Combination therapy of gamma stimulation and neuromodulators

Abstract

In some embodiments, this disclosure describes methods for administering gamma-oscillating stimulation and agents to a target. In some embodiments, this disclosure describes methods for administering non-invasive gamma-oscillating stimulation and agents to a target. In some embodiments, this disclosure describes methods for treating neurodegeneration in subjects requiring treatment of neurodegeneration by administering gamma-oscillating stimulation and agents to a target.

Description

[Technical Field]

[0001] cross reference This application claims the benefits under U.S. Provisional Patent Application No. 63 / 499,534 filed 2 May 2023, U.S. Provisional Patent Application No. 63 / 517,211 filed 2 August 2023, and U.S. Provisional Patent Application No. 63 / 554,876 filed 16 February 2024, which are incorporated herein by reference to each of the above applications in their entirety. [Background technology]

[0002] Nerve oscillations occur in humans or animals and involve rhythmic or repetitive neural activity in the central nervous system. Neural tissue can generate oscillatory activity through mechanisms within individual neurons or through interactions between neurons. Oscillations can manifest as oscillations in membrane potential or as rhythmic patterns of action potentials that can lead to oscillatory activation of postsynaptic neurons. Synchronizing the activity of groups of neurons can produce macroscopic oscillations, which can then be non-invasively observed by electroencephalography ("EEG"). Nerve oscillations can be characterized by their frequency, amplitude, and phase. Nerve oscillations can generate electrical impulses that form electroencephalograms. These signal characteristics can be observed from neural recordings using time-frequency analysis. [Overview of the Initiative]

[0003] In some embodiments, the Disclosure describes a method of administering gamma oscillation-induced stimuli and one or more agents to subjects in need thereof, the one or more agents being amyloid-beta-specific monoclonal antibodies, N-methyl-D-aspartate (NMDA) receptor antagonists, cellular stress signaling blockers, chemical chaperones, glutamate regulators, sigma-1 receptor agonists, voltage-gated sodium channel blockers, NrF2 activators, vesicular monoamine transporter 2 (VMAT2) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, monoamine oxidase-B (MAO-B) inhibitors, dopamine reuptake inhibitors, adenosine 2A receptor (A2AR) antagonists, muscarinic receptor antagonists, antisense oligonucleotides, RNA splicing modifiers, stimulants (eugeroic The agents consist of serotonin 1A (5-hydroxytryptamine 1A, 5-HT1A) receptor agonists, 5-HT1F receptor agonists, 5-HT2A receptor inverse agonists, 5-HT2A receptor antagonists, dopamine and serotonin receptor antagonists, radiotracers or radiopharmaceutical compounds, free radical scavengers, GLP-1 receptor agonists, hallucinogens, GLP-1 receptor agonists, and sphingosine 1-phosphate (S1P) receptor modulators.

[0004] In some embodiments of the methods described herein, the amyloid-beta specific monoclonal antibody comprises aducanumab. In some embodiments of the methods described herein, the amyloid-beta specific monoclonal antibody comprises lecanemab. In some embodiments of the methods described herein, the amyloid-beta specific monoclonal antibody comprises donanemab. In some embodiments of the methods described herein, the amyloid-beta specific monoclonal antibody comprises remternetug.

[0005] In some embodiments of the methods described herein, the NMDA receptor antagonist includes memantine.

[0006] In some embodiments of the methods described herein, the cell stress signal blocker includes sodium phenylbutyrate and tauroursodeoxycholic acid. In some embodiments of the methods described herein, the chemical chaperone includes sodium phenylbutyrate.

[0007] In some embodiments of the methods described herein, the glutamate regulator includes riluzole.

[0008] In some embodiments of the methods described herein, the one or more agents include sigma-1 receptor and N-methyl-D-aspartate (NMDA) receptor antagonists. In certain embodiments, the one or more agents that include sigma-1 receptor and N-methyl-D-aspartate (NMDA) receptor antagonists include dextromethorphan and quinidine. In some embodiments of the methods described herein, the one or more agents include voltage-dependent sodium channel blockers. In certain embodiments, the one or more agents that include voltage-dependent sodium channel blockers include dextromethorphan and quinidine.

[0009] In some embodiments of the methods described herein, the NrF2 activator includes omaveloxolone.

[0010] In some embodiments of the methods described herein, the VMAT2 inhibitor includes tetrabenazine. In some embodiments of the methods described herein, the VMAT2 inhibitor includes valbenazine. In some embodiments of the methods described herein, the VMAT2 inhibitor includes dutetetrabenazine.

[0011] In some embodiments of the methods described herein, the COMT inhibitor includes entacapone. In some embodiments of the methods described herein, the COMT inhibitor includes tolcapone. In some embodiments of the methods described herein, the COMT inhibitor includes opicapone.

[0012] In some embodiments of the methods described herein, the MAO-B inhibitor comprises rasagiline. In some embodiments of the methods described herein, the MAO-B inhibitor comprises safinamide. In some embodiments of the methods described herein, the MAO-B inhibitor comprises selegiline.

[0013] In some embodiments of the methods described herein, the dopamine reuptake inhibitor includes amantadine.

[0014] In some embodiments of the methods described herein, the A2AR antagonist comprises istradefylline.

[0015] In some embodiments of the methods described herein, the muscarinic receptor antagonist comprises trihexyphenidyl. In some embodiments of the methods described herein, the muscarinic receptor antagonist comprises benztropine.

[0016] In some embodiments of the methods described herein, the antisense oligonucleotide comprises nusinersene.

[0017] In some embodiments of the methods described herein, the RNA splicing modifier includes risdiplam.

[0018] In some embodiments of the methods described herein, the stimulant comprises almodafinil.

[0019] In some embodiments of the methods described herein, 5-HT 1A The receptor agonist is caliprazine.

[0020] In some embodiments of the methods described herein, 5-HT 1F Receptor agonists include rasmiditane.

[0021] In some embodiments of the methods described herein, 5-HT 2A Receptor inverse agonists include pimavanserin.

[0022] In some embodiments of the methods described herein, 5-HT 2A The receptor antagonist is trazodone.

[0023] In some embodiments of the methods described herein, the dopamine and serotonin receptor antagonist includes olanzapine, brexpiprazole, lurasidone, lumateperone, or a combination thereof. In some specific embodiments, the dopamine and serotonin receptor antagonist includes olanzapine.

[0024] In some embodiments of the methods described herein, the radioactive tracer comprises a fluorine-18 (18F)-labeled stilbene derivative. In certain embodiments, the 18F-labeled stilbene derivative comprises fluorobetabene.

[0025] In some embodiments of the methods described herein, the free radical scavenger includes edaravone.

[0026] In some embodiments of the methods described herein, the hallucinogen comprises psilocybin. In some embodiments of the methods described herein, the hallucinogen comprises lysergic acid diethylamide (LSD).

[0027] In some embodiments of the methods described herein, the GLP-1 receptor agonist includes semaglutide, tilzepatide, dulaglutide, exenatide, liraglutide, or lixisenatide.

[0028] In some embodiments of the methods described herein, the S1P receptor modulator includes fingolimod hydrochloride, siponimod, or ozanimod hydrochloride.

[0029] In some embodiments of the methods described herein, the gamma vibration-induced stimulation includes electromagnetic stimulation, tactile or vibratory tactile stimulation, auditory stimulation, visual stimulation, or a combination thereof.

[0030] In some embodiments of the methods described herein, the gamma vibration-induced stimulation includes electromagnetic stimulation, tactile or vibratory tactile stimulation, auditory stimulation, visual stimulation, or a combination thereof.

[0031] In some embodiments, methods are described for administering non-invasive gamma oscillation-induced stimulation, as well as one or more agents selected from dopamine precursors, dopa-decarboxylase (DDC) inhibitors, and dopamine agonists, to subjects in need thereof.

[0032] In some embodiments of the methods described herein, the non-invasive gamma vibration-induced stimulation includes tactile or vibrotactile stimulation, auditory stimulation, visual stimulation, or a combination thereof.

[0033] In some embodiments of the methods described herein, the dopamine agonist comprises pramipexole. In some embodiments of the methods described herein, the dopamine agonist comprises ropinirole. In some embodiments of the methods described herein, the dopamine agonist comprises apomorphine. In some embodiments of the methods described herein, the dopamine agonist comprises rotigotine.

[0034] In some embodiments of the methods described herein, the DDC inhibitor includes carbidopa.

[0035] In some embodiments of the methods described herein, the DDC inhibitor includes benserazide.

[0036] In some embodiments of the methods described herein, the dopamine precursor includes levodopa.

[0037] In some embodiments of the methods described herein, one or more agents comprise a dopamine precursor and a dopa-decarboxylase inhibitor. In some specific embodiments, one or more agents comprise a dopamine precursor and a dopa-decarboxylase inhibitor, where the dopamine precursor comprises levodopa. In some specific embodiments, one or more agents comprise a dopamine precursor and a dopa-decarboxylase inhibitor, where the dopa-decarboxylase inhibitor comprises benserazide. In some specific embodiments, one or more agents comprise a dopamine precursor and a dopa-decarboxylase inhibitor, where the dopa-decarboxylase inhibitor comprises carbidopa.

[0038] In certain embodiments, the disclosure describes a method for treating neurodegeneration in subjects requiring treatment for neurodegeneration, the method comprising the steps of treating neurodegeneration in subjects requiring treatment for neurodegeneration by administering gamma oscillatory-induced stimulation and one or more agents selected from orexin receptor antagonists, selective serotonin reuptake inhibitors (SSRIs), and gamma-aminobutyric acid (GABA) receptor agonists.

[0039] In some embodiments of the methods described herein, the orexin receptor antagonist comprises suvorexant. In some embodiments of the methods described herein, the orexin receptor antagonist comprises remvorexant. In some embodiments of the methods described herein, the orexin receptor antagonist comprises dalidrexant.

[0040] In some embodiments of the methods described herein, the SSRI comprises escitalopram. In some embodiments of the methods described herein, the SSRI comprises citalopram. In some embodiments of the methods described herein, the SSRI comprises dapoxetine. In some embodiments of the methods described herein, the SSRI comprises fluvoxamine. In some embodiments of the methods described herein, the SSRI comprises paroxetine. In some embodiments of the methods described herein, the SSRI comprises sertraline. In some embodiments of the methods described herein, the SSRI comprises vortioxetine.

[0041] In some embodiments of the methods described herein, the GABA receptor agonist comprises baclofen. In some embodiments of the methods described herein, the GABA receptor agonist comprises propofol. In some embodiments of the methods described herein, the GABA receptor agonist comprises gamma-hydroxybutyrate (GHB).

[0042] In some embodiments, a method for treating neurodegeneration in a subject requiring treatment for neurodegeneration, comprising the step of treating the neurodegeneration in a subject requiring treatment for neurodegeneration by administering gamma-oscillating stimulation and one or more agents selected from orexin receptor antagonists, selective serotonin reuptake inhibitors (SSRIs), and gamma-aminobutyric acid (GABA) receptor agonists to the subject, wherein the gamma-oscillating stimulation includes electromagnetic stimulation, tactile or vibratory-tactile stimulation, auditory stimulation, visual stimulation, or a combination thereof.

[0043] In some embodiments, the disclosure describes a method comprising administering gamma-oscillating stimuli and acetylcholinesterase inhibitors selected from donepezil, rivastigmine, galantamine, and tacrine to subjects requiring them.

[0044] In certain embodiments, the disclosure describes administering gamma-oscillation-induced stimulation, as well as an orexin receptor antagonist selected from suvorexant, remvorexant, and dalidrexant, to subjects requiring them.

[0045] In some embodiments, the gamma-oscillating stimulation, along with an acetylcholinesterase inhibitor selected from donepezil, rivastigmine, galantamine, and tacrine, is administered to a subject requiring it. The gamma-oscillating stimulation includes electromagnetic stimulation, tactile or vibratory tactile stimulation, auditory stimulation, visual stimulation, or a combination thereof.

[0046] In certain embodiments, the Disclosure describes a method comprising the steps of administering (a) interferon beta-1b, interferon beta-1a, pegylated interferon beta-1a, or a combination thereof, and (b) gamma-oscillating stimulation to a subject requiring them.

[0047] In certain embodiments, the disclosure describes a method comprising the steps of administering (a) alemtuzumab, natalizumab, ocrelizumab, ofatumumab, or a combination thereof, and (b) gamma-oscillating stimulation to a subject requiring them.

[0048] In some embodiments, the Disclosure describes a method comprising the steps of administering (a) glatiramer acetate, teriflunomide, dimethyl fumarate, monomethyl fumarate, diloximel fumarate, or a combination thereof, and (b) a gamma-oscillating stimulus to a subject requiring them.

[0049] In certain embodiments, the disclosure describes a method comprising the steps of (a) identifying a subject as having amyloid plaques, (b) administering a gamma oscillation-induced stimulus, and (c) administering an amyloid-beta-specific monoclonal antibody to the subject.

[0050] In some embodiments of the methods described herein, the step of identifying a target includes obtaining an amyloid-positive PET scan of the target.

[0051] In some embodiments of the methods described herein, the subject is diagnosed with or suspected of having a prion disease. In some specific embodiments, the prion disease is Alzheimer's disease.

[0052] In certain embodiments of this specification, a method is described comprising the steps of (a) identifying a subject as having multiple sclerosis, (b) administering a gamma-oscillating stimuli, and (c) administering a therapeutic agent for the treatment of multiple sclerosis. In some embodiments, the therapeutic agent for the treatment of multiple sclerosis is selected from the list consisting of glatiramer acetate, interferon beta-1a, interferon beta-1b, ofatumumab, pegylated interferon beta-1a, fingolimod, cladribine, siponimod, dimethyl fumarate, diloximel fumarate, mitoxantrone, and natalizumab.

[0053] In some embodiments, the Disclosure provides a method for treating neurodegeneration in a subject requiring treatment for neurodegeneration, the method comprising the steps of treating the subject by (i) gamma oscillatory-induced stimulation and (ii) administering one or more agents selected from norepinephrine reuptake inhibitors, histamine receptor antagonists, GABAA subunit-selective negative allosteric modulators, muscarinic receptor agonists, or any combination thereof. In some embodiments, the norepinephrine reuptake inhibitor is atomoxetine. In some embodiments, the norepinephrine reuptake inhibitor is reboxetine. In some embodiments, the norepinephrine reuptake inhibitor is piroxazine. In some embodiments, the norepinephrine reuptake inhibitor is amedaline. In some embodiments, the norepinephrine reuptake inhibitor is daredarine. In some embodiments, the norepinephrine reuptake inhibitor is ediboxetine. In some embodiments, the norepinephrine reuptake inhibitor includes esreboxetine. In some embodiments, the norepinephrine reuptake inhibitor includes lortalamine. In some embodiments, the norepinephrine reuptake inhibitor includes nisoxetine. In some embodiments, the norepinephrine reuptake inhibitor includes talopram. In some embodiments, the norepinephrine reuptake inhibitor includes talspram. In some embodiments, the norepinephrine reuptake inhibitor includes tandamin. In some embodiments, the norepinephrine reuptake inhibitor includes bupropion. In some embodiments, the norepinephrine reuptake inhibitor includes desipramine. In some embodiments, the norepinephrine reuptake inhibitor includes maprotiline. In some embodiments, the norepinephrine reuptake inhibitor includes nortriptyline. In some embodiments, the norepinephrine reuptake inhibitor includes protriptyline. In some embodiments, the norepinephrine reuptake inhibitor includes tapentadol. In some embodiments, the norepinephrine reuptake inhibitor comprises teniroxazine. In some embodiments, the norepinephrine reuptake inhibitor comprises cyclazinedol. In some embodiments, the norepinephrine reuptake inhibitor comprises CP-39,332.In some embodiments, the norepinephrine reuptake inhibitor includes manifaxine. In some embodiments, the norepinephrine reuptake inhibitor includes radafaxine. In some embodiments, the GABAA subunit selective negative allosteric regulator includes basmisanil. In some embodiments, the GABAA subunit selective negative allosteric regulator includes α5IA. In some embodiments, the GABAA subunit selective negative allosteric regulator includes L-655,708. In some embodiments, the GABAA subunit selective negative allosteric regulator includes MRK-016. In some embodiments, the GABAA subunit selective negative allosteric regulator includes PWZ-029. In some embodiments, the GABAA subunit selective negative allosteric regulator includes Ro4938581. In some embodiments, the GABAA subunit selective negative allosteric regulator includes TB-21007. In some embodiments, the muscarinic receptor agonist includes xanomeline. In some embodiments, the muscarinic receptor agonist comprises xanomeline having throspium.

[0054] In some embodiments, the Disclosure provides a method for increasing synaptic plasticity in a subject, the method comprising the steps of increasing synaptic plasticity by (i) gamma oscillation-induced stimulation and (ii) administering one or more agents selected from SV2A agonists, HGF agonists, phosphodiesterase inhibitors, cannabinoid CB1 receptor negative allosteric modulators, or any combination thereof to the subject. In some embodiments, the SV2A agonist is brivalacetam. In some embodiments, the SV2A agonist is levetiracetam. In some embodiments, the HGF agonist is a MET kinase inhibitor (TKI). In some embodiments, the HGF agonist is an anti-HGF monoclonal antibody (anti-HGF Ab). In some embodiments, the HGF agonist is an anti-MET monoclonal antibody (anti-MET Ab). In some embodiments, the phosphodiesterase inhibitor is sildenafil. In some embodiments, the phosphodiesterase inhibitor is vardenafil. In some embodiments, the phosphodiesterase inhibitor is tadalafil. In some embodiments, the phosphodiesterase inhibitor includes avanafil. In some embodiments, the phosphodiesterase inhibitor includes one or more members selected from the group consisting of sildenafil, vardenafil, tadalafil, avanafil, cilostazol, dipyridamole, milrinone, amrinone, roflumilast, apremilast, crisabolol, rolipram, or theobromine. In some embodiments, the negative allosteric modulator of the cannabinoid CB1 receptor includes cannabidiol.

[0055] In some embodiments, the Disclosure provides a method for increasing remyelination of a subject, the method comprising the steps of increasing remyelination of the subject by (i) gamma oscillation-induced stimulation and (ii) administering one or more agents selected from histamine receptor modulators and S1P modulators, or any combination thereof. In some embodiments, the histamine receptor modulator includes betasol. In some embodiments, the histamine receptor modulator includes clemastine. In some embodiments, the histamine receptor modulator includes cetirizine. In some embodiments, the histamine receptor modulator includes terfenadine. In some embodiments, the histamine receptor modulator includes buclidine. In some embodiments, the histamine receptor modulator includes doxylamine. In some embodiments, the histamine receptor modulator includes mirtazapine. In some embodiments, the histamine receptor modulator includes profenamine. In some embodiments, the histamine receptor modulator includes dexbrompheniramine. In some embodiments, the histamine receptor modulator includes triprolidine. In some embodiments, the histamine receptor modulator includes cyproheptadine. In some embodiments, the histamine receptor modulator includes cimetidine. In some embodiments, the histamine receptor modulator includes hydroxyzine. In some embodiments, the histamine receptor modulator includes cinnarizine. In some embodiments, the histamine receptor modulator includes nizatidine. In some embodiments, the histamine receptor modulator includes astemizole. In some embodiments, the histamine receptor modulator includes azatadine. In some embodiments, the histamine receptor modulator includes meclizine. In some embodiments, the histamine receptor modulator includes carbinoxamine. In some embodiments, the histamine receptor modulator includes epinastine. In some embodiments, the histamine receptor modulator includes olopatadine. In some embodiments, the histamine receptor modulator includes tripellennamine. In some embodiments, the histamine receptor modulator includes brompheniramine. In some embodiments, the histamine receptor modulator includes pemirolast. In some embodiments, the histamine receptor modulator includes ketotifen.In some embodiments, the histamine receptor modulator includes famotidine. In some embodiments, the histamine receptor modulator includes fexofenadine. In some embodiments, the histamine receptor modulator includes desloratadine. In some embodiments, the histamine receptor modulator includes azelastine. In some embodiments, the histamine receptor modulator includes dimenhydrinate. In some embodiments, the histamine receptor modulator includes promethazine. In some embodiments, the histamine receptor modulator includes mequitazine. In some embodiments, the histamine receptor modulator includes diphenhydramine. In some embodiments, the histamine receptor modulator includes emedastine. In some embodiments, the histamine receptor modulator includes levocabastine. In some embodiments, the histamine receptor modulator includes chlorpheniramine. In some embodiments, the histamine receptor modulator includes doxepin. In some embodiments, the histamine receptor modulator includes cyclidine. In some embodiments, the histamine receptor modulator includes alimazine. In some embodiments, the histamine receptor modulator includes phenyndamine. In some embodiments, the histamine receptor modulator includes pheniramine. In some embodiments, the histamine receptor modulator includes flunarizine. In some embodiments, the histamine receptor modulator includes histamine. In some embodiments, the histamine receptor modulator includes mianserin. In some embodiments, the histamine receptor modulator includes levocetirizine. In some embodiments, the histamine receptor modulator includes mepyramine. In some embodiments, the histamine receptor modulator includes betahistine. In some embodiments, the histamine receptor modulator includes alkaftazine. In some embodiments, the histamine receptor modulator includes rhodoxamide. In some embodiments, the histamine receptor modulator includes antazoline. In some embodiments, the histamine receptor modulator includes dimethindene. In some embodiments, the histamine receptor modulator includes dimethothiazine. In some embodiments, the histamine receptor modulator includes acrivastine. In some embodiments, the histamine receptor modulator includes dexchlorpheniramine maleate.In some embodiments, the histamine receptor modulator includes tondilamine. In some embodiments, the histamine receptor modulator includes ebastine. In some embodiments, the histamine receptor modulator includes mizolastine. In some embodiments, the histamine receptor modulator includes oxatomide. In some embodiments, the histamine receptor modulator includes tritoqualin. In some embodiments, the histamine receptor modulator includes butyrate. In some embodiments, the histamine receptor modulator includes metapyrylene. In some embodiments, the histamine receptor modulator includes tesmirifene. In some embodiments, the histamine receptor modulator includes esmiltazapine. In some embodiments, the histamine receptor modulator includes SKF-91488. In some embodiments, the histamine receptor modulator includes tranilast. In some embodiments, the histamine receptor modulator includes chloropyramine. In some embodiments, the histamine receptor modulator includes isotipendyl. In some embodiments, the histamine receptor modulator includes methiaamide. In some embodiments, the histamine receptor modulator includes roxatidine acetate. In some embodiments, the histamine receptor modulator includes chlorphenoxamine. In some embodiments, the histamine receptor modulator includes ozagrel. In some embodiments, the histamine receptor modulator includes treforant. In some embodiments, the histamine receptor modulator includes lafutidine. In some embodiments, the histamine receptor modulator includes lavoltidine. In some embodiments, the histamine receptor modulator includes deptropine. In some embodiments, the histamine receptor modulator includes vamipine. In some embodiments, the histamine receptor modulator includes quifenadine. In some embodiments, the histamine receptor modulator includes a histamine receptor antagonist. In some embodiments, the histamine receptor antagonist includes famotidine. In some embodiments, the histamine receptor antagonist includes cimetidine. In some embodiments, the histamine receptor antagonist includes nizatidine.

[0056] In some embodiments, the S1P regulator includes GSK239512. In some embodiments, the S1P regulator includes siponimod. In some embodiments, the S1P regulator includes ponesimod.

[0057] Additional aspects and advantages of the present disclosure will be readily apparent to those skilled in the art from the following detailed description, which shows and describes only exemplary embodiments of the present disclosure. As will be understood, other embodiments and different embodiments are possible of the present disclosure, and some of its details can be modified in various obvious ways without departing from the present disclosure. Accordingly, the drawings and description are illustrative in nature and should not be considered limiting.

[0058] Reference All publications, patents, and patent applications referenced herein are incorporated by reference to the same extent as each individual publication, patent, or patent application is specifically and individually referenced. Where any publication or patent or patent application referenced herein conflicts with any disclosure contained herein, this specification is intended to supersede and / or take precedence over any such conflicting material. [Brief explanation of the drawing]

[0059] Novel features of the present invention are specifically stated in the appended claims. The features and advantages of the present invention will be better understood by referring to the following detailed description, which specifies exemplary embodiments in which the principles of the present invention are utilized, and to the appended drawings (also referred to herein as "Figure" and "FIG.").

[0060] [Figure 1] This is a block diagram showing a system that performs neural stimulation using visual stimuli, according to one embodiment. [Figure 2A] This figure shows a visual stimulus signal that produces nerve stimulation according to one embodiment. [Figure 2B]This figure shows a visual stimulus signal that produces nerve stimulation according to one embodiment. [Figure 2C] This figure shows a visual stimulus signal that produces nerve stimulation according to one embodiment. [Figure 2D] This figure shows a visual stimulus signal that produces nerve stimulation according to one embodiment. [Figure 2E] This figure shows a visual stimulus signal that produces nerve stimulation according to one embodiment. [Figure 2F] This figure shows a visual stimulus signal that produces nerve stimulation according to one embodiment. [Figure 3A] This figure shows a visual field through which visual signals can be transmitted to induce gamma oscillation visual stimuli in the brain, according to some embodiments. [Figure 3B] This figure shows a visual field through which visual signals can be transmitted to induce gamma oscillation visual stimuli in the brain, according to some embodiments. [Figure 3C] This figure shows a visual field through which visual signals can be transmitted to induce gamma oscillation visual stimuli in the brain, according to some embodiments. [Figure 4A] This figure shows a device configured to transmit visual signals for nerve stimulation, according to one embodiment. [Figure 4B] This figure shows a device configured to transmit visual signals for nerve stimulation, according to one embodiment. [Figure 4C] This figure shows a device configured to transmit visual signals for nerve stimulation, according to one embodiment. [Figure 5A] This figure shows a device configured to transmit visual signals for nerve stimulation, according to one embodiment. [Figure 5B] This figure shows a device configured to transmit visual signals for nerve stimulation, according to one embodiment. [Figure 5C] This figure shows a device configured to transmit visual signals for nerve stimulation, according to one embodiment. [Figure 5D]This figure shows a device configured to transmit visual signals for nerve stimulation, according to one embodiment. [Figure 6A] This figure shows a device configured to receive feedback to facilitate nerve stimulation, according to one embodiment. [Figure 6B] This figure shows a device configured to receive feedback to facilitate nerve stimulation, according to one embodiment. [Figure 7A] This is a block diagram showing embodiments of computing devices useful in relation to the systems and methods described herein. [Figure 7B] This is a block diagram showing embodiments of computing devices useful in relation to the systems and methods described herein. [Figure 8] This is a flowchart illustrating a method for performing neural stimulation using visual stimuli, according to one embodiment. [Figure 9] This is a block diagram showing a system for nerve stimulation using auditory stimulation according to one embodiment. [Figure 10A] This figure shows the types of audio signals and modulations applied to the audio signals used to induce neural oscillations by auditory stimulation, according to some embodiments. [Figure 10B] This figure shows the types of audio signals and modulations applied to the audio signals used to induce neural oscillations by auditory stimulation, according to some embodiments. [Figure 10C] This figure shows the types of audio signals and modulations applied to the audio signals used to induce neural oscillations by auditory stimulation, according to some embodiments. [Figure 10D] This figure shows the types of audio signals and modulations applied to the audio signals used to induce neural oscillations by auditory stimulation, according to some embodiments. [Figure 10E] This figure shows the types of audio signals and modulations applied to the audio signals used to induce neural oscillations by auditory stimulation, according to some embodiments. [Figure 10F]This figure shows the types of audio signals and modulations applied to the audio signals used to induce neural oscillations by auditory stimulation, according to some embodiments. [Figure 10G] This figure shows the types of audio signals and modulations applied to the audio signals used to induce neural oscillations by auditory stimulation, according to some embodiments. [Figure 10H] This figure shows the types of audio signals and modulations applied to the audio signals used to induce neural oscillations by auditory stimulation, according to some embodiments. [Figure 10I] This figure shows the types of audio signals and modulations applied to the audio signals used to induce neural oscillations by auditory stimulation, according to some embodiments. [Figure 11A] This figure shows an audio signal generated using binaural beats according to one embodiment. [Figure 11B] This figure shows an acoustic pulse having an isochronic tone according to one embodiment. [Figure 11C] This figure shows an audio signal having modulation technology including an audio filter, according to one embodiment. [Figure 12A] This figure shows the configuration of a system for neural stimulation using auditory stimulation, according to some embodiments. [Figure 12B] This figure shows the configuration of a system for neural stimulation using auditory stimulation, according to some embodiments. [Figure 12C] This figure shows the configuration of a system for neural stimulation using auditory stimulation, according to some embodiments. [Figure 13] This figure shows the configuration of a system for room-based auditory stimulation for nerve stimulation according to one embodiment. [Figure 14] This figure shows a device configured to receive feedback to facilitate auditory stimulation of nerves, according to one embodiment. [Figure 15] This is a flowchart illustrating a method for performing auditory induction of gamma oscillations on the brain according to one embodiment. [Figure 16A]This is a block diagram showing a system for nerve stimulation by peripheral nerve stimulation according to one embodiment. [Figure 16B] This is a block diagram showing a system for nerve stimulation using multiple stimulation modes according to one embodiment. [Figure 17A] This is a block diagram showing a system for nerve stimulation using visual and auditory stimuli according to one embodiment. [Figure 17B] This figure shows waveforms used for nerve stimulation by visual and auditory stimuli according to one embodiment. [Figure 18] This is a flowchart of a method for nerve stimulation using visual and auditory stimuli according to one embodiment. [Figure 19] This is an efficacy summary chart for a modified intent to treat (mITT) population, including p-values, differences, confidence intervals (CI), and efficacy estimates normalized based on the values. [Figure 20] This figure shows separate mean analyses (left) and linear model analyses (right) of the optimized Alzheimer's disease composite score (ADCOMS) for moderate and moderate Alzheimer's disease (MADCOMS) in the sham treatment group and the active treatment group. [Figure 21] This figure shows separate mean analyses (left) and linear model analyses (right) of Alzheimer's Disease Assessment Scale-Cognitive Subscale 14 (ADAS-Cog14) scores in the sham treatment group and the active treatment group. [Figure 22] This figure shows separate mean analysis (left) and linear model analysis (right) of the Clinical Dementia Rating Sale Sum of Boxes (CDR-SB) in the sham treatment group and the active treatment group. [Figure 23]This figure shows separate mean analyses (left) and linear model analyses (right) of the Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL) scores in the sham treatment group and the active treatment group. [Figure 24] This figure shows a linear model analysis of Mini-Mental State Examination (MMSE) scores measured 6 months after treatment (i.e., at the final point in time). [Figure 25] This figure shows a linear model analysis of magnetic resonance imaging (MRI) results for whole brain volume (left side) and hippocampal volume (right side) after 6 months of treatment. [Figure 26] This table summarizes efficacy findings from human clinical trials, including p-values, treatment differences, CI values, and percentages of slower brain atrophy. [Figure 27] ★These graphs demonstrate the observed improvement in sleep quality, measured by reduced sleep fragmentation, expressed as more frequent and longer rest periods, during the first 12-week treatment period (indicated by the line closest to the white arrow) and the second 12-week treatment period (indicated by the line furthest from the white arrow) in subjects with mild to moderate Alzheimer's disease (AD) after 24 weeks of non-invasive sensory stimulation treatment using exemplary gamma oscillations (panels a and b). Panels c and d show the impact on sleep quality observed in the sham treatment, measured by reduced sleep fragmentation. [Figure 28]This figure shows the output changes in response to a 40Hz LED stimulation (1 hour) in an exemplary embodiment demonstrating enhanced 40Hz steady-state oscillations and alpha output during and after stimulation in healthy young subjects. Both panels show the time-frequency domain resolution of EEG activity recorded across the occipital pole (Oz, channel-64) before, during, and after induced 40Hz stimulation by gamma oscillation. The start and stop of the 40Hz stimulation are marked at the STIM ON and STIM OFF boundaries in both panels. The upper panel shows the enhanced 40Hz output during stimulation, indicating steady-state visually evoked potentials (SSVEPs). The lower panel shows the alpha output dynamics during the open-eye (EYO) and closed-eye (EYC) states, as well as the enhanced alpha output during the open-eye 40Hz stimulation and 1 hour after induced 40Hz stimulation by gamma oscillation. [Figure 29] This figure shows the composite global cognitive summary score as a function of mean sleep fragmentation (Panel A) and composite expression of genes abundant in aging microglia (Panel B). The dashed line indicates the 95% confidence interval for the estimate. [Figure 30] This figure shows oscilloscope captures of visual signals (upper signal) and auditory signals (lower signal) of an exemplary non-invasive sensory stimulus, where fs is equal to 40 Hz, vd is equal to 50%, VD is equal to 50%, ft is equal to 7,000 Hz, and AD is equal to 0.57%. [Figure 31] This is a schematic diagram of some aspects and parameters characterizing the auditory and visual components of non-invasive stimuli delivered by the auditory stimulus module (110, Figure 33) and the visual stimulus module (120, Figure 33), respectively, of the stimulus delivery system (170, Figure 33). The number and relative dimensions of the elements in Figure 31 have been adjusted for presentation purposes and do not represent the number and relative dimensions in actual embodiments. [Figure 32]This figure outlines registration, treatment, and control for exemplary embodiments of non-invasive stimulation to improve sleep quality in subjects with mild to moderate Alzheimer's disease (AD). Two-thirds of subjects (12) were treated with a 40 Hz frequency voice, and one-third of subjects (6, "control") were treated with an alternative frequency. [Figure 33] This is an exemplary block diagram of a stimulus delivery system and an analysis / monitoring system, where the analysis / monitoring system includes modules specific to sleep-related monitoring and / or analysis. [Figure 34] This figure provides actigraphy data from a 24-hour activity level (gray bars, 1501, Figure 37) over two days for one patient, centered at 12:00 a.m. (indicated by a double-headed arrow), along with a median filtering curve (marked by a dashed arrow, 1507, Figure 37). The horizontal axis in Figure 34 represents time, and the vertical axis represents relative activity (on an arbitrary log scale) recorded by a wrist-worn actigraphy device. The calculated sleep duration (black horizontal line, see 1508, Figure 37) is shown along with individual sample rest periods (yellow horizontal line, see 1509, Figure 37). The upper panel (a) shows exemplary patterns of frequent movement and short rest periods during sleep, while the lower panel (b) shows exemplary patterns of infrequent movement and long rest periods during sleep. [Figure 35] This figure shows an exemplary pattern of actigraphy over several days (in arbitrary units, see Figure 34), illustrating the actigraphy (gray, e.g., 1501, Figure 37), with smoothed curves superimposed. Cutoff lines (black) separate periods of activity from periods of rest (e.g., 1505, Figure 37). Black squares represent initial estimates of midnight (e.g., 1507, Figure 37). The final evaluation of midnight is determined by an optimization algorithm (e.g., 1508, Figure 37). [Figure 36]This figure shows an exemplary cumulative distribution of rest periods from one patient (e.g., 1511 in Figure 37). Data from the first exemplary 12-week treatment (solid line time, weeks 0-12) and the second exemplary 12-week treatment (dashed line time) are shown. In some embodiments, the distribution is characterized by an exponential distribution (e.g., 1512, Figure 37). In further embodiments, an increase in the exponential decay constant represents an improvement in sleep quality (e.g., 1513, Figure 37). In this example, tau2 = 45 minutes, tau1 = 40 minutes, and taudiff = 5 minutes > 0. [Figure 37] This is a flowchart of an exemplary analysis process in response to actigraphy data provided at least partially by the actigraphy monitoring module 130 (Figure 33). In some embodiments, the analysis aims to determine the cumulative distribution of rest periods for one or more subjects over the duration of one or more nocturnal sleep periods (1511). In some embodiments, the analysis further aims to fit an exponential distribution to the determined cumulative distribution (1512). In some embodiments, the analysis further aims to calculate a general statistic or characteristic parameter relating to the fitted exponential distribution. In an exemplary embodiment, an exponential decay constant for the fitted exponential distribution is determined (1512, Figure 36). In Figure 37, italicized terms in parentheses refer to MATLAB® (R2020a) APIs employed in the corresponding processes in the exemplary embodiments, for example, “medfilt1” refers to 1-D median filtering. In some embodiments, an alternative API, method, or process with equivalent functionality may be employed (for example, Wolfram Language's "ButterworthFilterModel" may be used instead of "butter"). [Figure 38]This is a sample actigraphy recording from one patient. The recording, acquired five consecutive times during the night before treatment and five consecutive times during the night after treatment, demonstrates the effect of non-invasive sensory stimulation therapy inducing gamma oscillations on sleep. The dark gray horizontal bar below the X-axis indicates the duration of continuous activity, and the duration of continuous activity appears to be significantly higher in the actigraphy recordings acquired before treatment than in the actigraphy recordings acquired after treatment. [Figure 39] This figure shows the cumulative distribution of nighttime rest and activity periods based on pooled data from all participants. Black squares represent activity periods, and gray squares represent rest periods. Panel A of Figure 39 shows the cumulative distribution using a log-linear scale, and Panel B of Figure 39 shows the cumulative distribution using a log-log scale. [Figure 40] This graph compares the relative changes in activity duration, with the Y-axis showing the change from weeks 13 to 24 compared to weeks 1 to 12. Figure 40 demonstrates that the activity duration was shortened in the treatment group, resulting in a reduction in sleep fragmentation, which improves sleep quality. In contrast, the opposite effect was observed in the sham group, represented by the line closest to the gray arrow. Panel A of Figure 40 shows the relative changes based on activity duration, while Panel B of Figure 40 shows the normalized nighttime activity duration, calculated by dividing each activity duration by the total matched nighttime duration. [Figure 41] This graph shows the effect of non-invasive sensory stimulation therapy that induces gamma oscillations, as assessed by the Activities of Daily Living (ADCS-ADL) scale, on maintaining daytime activity. The graph indicates that changes in daytime activity significantly improved in the treatment group and decreased in the sham treatment group. The X-axis compares weeks 1–12 with weeks 13–24. The Y-axis demonstrates the change in ADCS-ADL scores between weeks 13–24 compared to weeks 1–12. [Figure 42]This flowchart demonstrates the proposed relationship between Alzheimer's disease and sleep dysfunction. It is based on "Bidirectional relationship between sleep and Alzheimer's disease: role of amyloid, tau, and other factors" by Wang, C. and D.M. Holtzman (2020), Neuropsychopharmacology 45(1): pp. 104-120. [Figure 43] This figure shows an exemplary embodiment of a handheld controller for adjusting the parameters of stimuli delivered by an operablely coupled stimulator. [Figure 44] This figure shows the results of the %) change in material volume from baseline in treatment and control groups that received sensory stimulation therapy and sham sensory stimulation therapy, respectively, inducing 40 Hz gamma oscillations over a 6-month period. Dark gray boxes represent participants in the treatment group, and light gray boxes represent participants in the placebo group. Error bars indicate the standard error (SE). [Figure 45] This figure shows the change in the ratio of T1-weighted to T2-weighted images (T1w / T2w) in white matter (percentage change from baseline) for participants in the placebo group (light gray) and the treatment group (dark gray) after receiving sham sensory stimulation therapy and sensory stimulation therapy inducing 40 Hz gamma oscillations, respectively, over a 6-month period. [Figure 46A] This figure shows the measured volume changes of white matter structure as a percentage change compared to baseline. Participants in the treatment group are shown in dark gray, and the results for participants in the placebo group are shown in light gray. Figure 46A provides results for the treatment group at 6 months of treatment for the entorhinal region, left cingulate lobe, amygdala region, cuneate region, lateral occipital region, posterior central region, left occipital lobe, left frontal lobe, left parietal lobe, occipital lobe, left temporal lobe, and caudal central frontal region (classified in ascending order by p-value). [Figure 46B]This figure shows the measured volume changes of white matter structure as percentage changes compared to baseline. Participants in the treatment group are shown in dark gray, and the results for participants in the placebo group are shown in light gray. Figure 46B provides results for the anterior central region, paracentral region, lingual region, fusiform region, frontal lobe, rostral anterior cingulate region, inferior temporal parietal region, right occipital lobe, parietal lobe, rostral midfrontal region, precorneal region, medial orbitofrontal region, and temporal lobe (classified in ascending order by p-value). [Figure 47A] Figure 47A shows the change in the T1w / T2w ratio (percentage change from baseline) of white matter structures in participants in the placebo and treatment groups after receiving sham sensory stimulation therapy and sensory stimulation therapy inducing 40 Hz gamma oscillations, respectively, over a 6-month period, with the treatment group showing a favorable outcome. Figure 47A provides results for the entorhinal region, paratriangular region, posterior central region, left parietal lobe, lateral occipital region, paracentral region, rostral central frontal region, supraboneal region, anterior central region, parietal lobe, right occipital lobe, fusiform region, occipital lobe, left frontal lobe, cuneate region, anterior apex region, inferior parietal region, frontal lobe, lingual region, left occipital lobe, left temporal lobe, right parietal lobe, and paraorbital region, with white matter structures classified in ascending order by p-value. [Figure 47B] Figure 47B shows the change in the T1w / T2w ratio (percentage change from baseline) of white matter structures in participants in the placebo and treatment groups after receiving sham sensory stimulation therapy and sensory stimulation therapy inducing 40 Hz gamma oscillations, respectively, over a 6-month period, with the treatment group showing a favorable outcome. Figure 47B provides results for the right frontal lobe, caudal central frontal region, rostral anterior cingulate region, superior frontal region, temporal lobe, medial orbitofrontal region, posterior cingulate region, superior parietal region, left cingulate lobe, superior temporal region, cingulate lobe, and temporal pole region, with white matter structures classified in ascending order by p-value. [Figure 48] This figure shows an example of participant use of a 40Hz auditory-visual stimulation device over a 6-month period. Participants selected different visual and auditory settings (first and second rows from the top), while setting the device frequency to 40Hz (third row from the top). The time of use on each day was recorded by the device (fourth row from the top). Independently, participants kept a diary of the number of treatment sessions (fifth row from the top). This participant demonstrated nearly 100% adherence (bottom row). [Figure 49] This figure shows the change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score as a function of baseline coherence after 6 months of active treatment with a 40Hz auditory-visual stimulation device. An overall negative correlation is observed between baseline coherence and ADAS-Cog score. [Figure 50] This figure shows the change in the Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL) score as a function of baseline coherence after 6 months of active treatment with a 40Hz auditory-visual stimulation device. An overall positive correlation is observed between baseline coherence and the ADCS-ADL score. [Figure 51] This figure shows the change in the Attentive Participation in Conversations score of the Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL) as a function of baseline coherence after 6 months of active treatment using a 40Hz auditory-visual stimulation device. An overall positive correlation is observed between baseline coherence and the ADCS-ADL Attentive Participation in Conversations score. [Figure 52] This figure shows the change in the Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL) item-finding score as a function of baseline coherence after 6 months of active treatment with a 40Hz auditory-visual stimulation device. An overall positive correlation is observed between baseline coherence and the ADCS-ADL item-finding score. [Figure 53]This figure shows the change in memory scores on the Clinical Dementia Assessment (CDR) as a function of baseline coherence after 6 months of active treatment using a 40Hz auditory-visual stimulation device. An overall negative correlation is observed between baseline coherence and CDR memory scores. [Figure 54] This figure shows the change in orientation score on the Clinical Dementia Assessment (CDR) as a function of baseline coherence after 6 months of active treatment using a 40Hz auditory-visual stimulation device. An overall negative correlation is observed between baseline coherence and the CDR orientation score. [Figure 55] This figure shows the change in the Clinical Dementia Rating Scale Total Score (CDR SB) score as a function of baseline coherence after 6 months of active treatment using a 40Hz auditory-visual stimulation device. An overall negative correlation is observed between baseline coherence and the CDR SB score. [Figure 56] This figure shows the change in Mini-Mental State Examination (MMSE) scores as a function of baseline coherence after 6 months of active treatment using a 40Hz auditory-visual stimulation device. An overall positive correlation is observed between baseline coherence and MMSE scores. [Figure 57] This figure shows the change in magnetic resonance imaging (MRI) lateral ventricular volume (vMRI-LV as a percentage of total intracranial volume) as a function of baseline coherence after 6 months of active treatment with a 40Hz auditory-visual stimulation device. An overall negative correlation is observed between baseline coherence and lateral ventricular (LV) volume. [Figure 58] This figure shows the change in MRI temporal cortical thickness (mm) as a function of baseline coherence after 6 months of active treatment with a 40Hz auditory-visual stimulation device. An overall positive correlation is observed between baseline coherence and temporal thickness. [Figure 59]This figure shows the change in Neuropsychiatric Inventory Questionnaire (NPIQ) severity score as a function of baseline coherence after 6 months of intensive treatment with a 40Hz auditory-visual stimulation device. An overall negative correlation is observed between baseline coherence and NPIQ severity score. [Figure 60] This figure shows the change in positron emission tomography (PET) composite amyloid normalized uptake (SUVR) as a function of baseline coherence after 6 months of aggressive treatment with a 40Hz auditory-visual stimulation device. An overall negative correlation is observed between baseline coherence and the PET composite SUVR score. [Figure 61] This figure shows the change in PET occipital amyloid SUVR as a function of baseline coherence after 6 months of aggressive treatment with a 40Hz auditory-visual stimulation device. An overall negative correlation is observed between baseline coherence and the PET occipital SUVR score. [Figure 62] This diagram illustrates a cyclical therapeutic agent and gamma-oscillating stimulation scheme. In this scheme, a therapeutic agent (e.g., a monoclonal antibody) and gamma-oscillating stimulation are delivered while the patient is amyloid-PET positive, and gamma-oscillating stimulation is delivered alone while the patient is amyloid-PET negative or when the PET status is unknown.

[0061] The features and advantages of this solution will become clearer from the detailed explanation provided below, along with drawings in which similar reference letters identify corresponding elements throughout. In the drawings, similar reference symbols generally indicate similar elements. [Modes for carrying out the invention]

[0062] Various embodiments of the present invention are shown and described herein, but it will be apparent to those skilled in the art that such embodiments are provided merely as examples. Numerous variations, modifications, and substitutions may be conceived by those skilled in the art without departing from the present invention. It should be understood that various alternatives to the embodiments of the present invention described herein may be adopted.

[0063] Neurological conditions affecting the nervous systems of humans and animals can be difficult to diagnose, treat, and evaluate due to overlapping or similar symptoms between diseases, the lack of accurate quantitative assays based on biomarkers, or long preclinical and prodromal phases.

[0064] Alzheimer's disease (AD) is a neurological condition with many associated problems. AD can progress for several years or even years before any symptoms appear. AD lacks widely available and accepted quantitative assays based on biomarkers that provide certainty in diagnosis. Diagnosis of AD may involve multidimensional analysis of the patient's and their family history, subjective reports of symptoms by the patient, MRI, laboratory work, and evaluations by multiple healthcare professionals. Furthermore, AD is associated with a high misdiagnosis rate (10%–20%). Some misdiagnoses may be due to various neurodegenerative or psychiatric disorders that are misdiagnosed as AD.

[0065] Some neurodegenerative diseases, such as Alzheimer's disease (AD), may be associated with a long preclinical and prodromal phase that can lead to symptoms such as cognitive impairment, behavioral abnormalities, and a decline in daily living activities. Symptoms from neurodegenerative diseases can also develop over a long period, and by the time they are detected, the underlying disease may have progressed significantly to a moderate or severe stage with little prospect of improvement. For example, the preclinical phase of Alzheimer's disease (before all physical symptoms appear) can last for several years or even decades.

[0066] Even when early symptoms begin to appear, the disease progresses slowly, making it easy for symptoms to be ignored or overlooked. Several stages of cognitive decline may exist before the onset of clinical dementia. In some cases, one of the first stages may be subjective cognitive decline (SCD). SCD may refer to self-reported experiences of worsening or more frequent confusion or memory loss. At this stage, individuals can be identified as “SCD plus,” meaning patients who have both cognitive impairment and co-occurring AD-related pathological changes. In some cases, patients classified as “SCD” may have the following high-risk features for further cognitive decline: subjective memory decline, onset of SCD within the past 5 years, being over 60 years old at the onset of SCD, concerns (worries) related to SCD, feeling that they are performing worse than others in their age group, or confirmation of cognitive decline by an informant. In some cases, the next stage of cognitive decline after SCD may be mild cognitive impairment (MCI). MCI can be characterized in patients who have problems with memory, language, thinking, or judgment. In some cases, it may be difficult to separate subjective elements (e.g., "self-reported") from the clinical evaluation of AD diagnosis and monitoring of AD progression.

[0067] Prion diseases are another set of neurological conditions in which problems exist. Prion diseases, also known as infectious spongiform encephalopathy, can refer to a group of fatal neurodegenerative diseases that may include Creutzfeldt-Jakob disease (CJD), variant Creutzfeldt-Jakob disease (vCJD), Gerstmann-Streussler-Scheinker syndrome, fatal familial insomnia, and Kuru disease. In some cases, prion diseases may present with other symptoms and / or symptoms similar to those of Alzheimer's disease (AD). In some cases, different types of prion diseases may cause brain damage that exhibits similar features, such as widespread spongiform degeneration, widespread nerve loss, synaptic alterations, atypical encephalitis, and accumulation of protein aggregates. In some cases, prion diseases such as CJD, Kuru disease, and Gerstmann-Streussler-Scheinker disease may form amyloid plaques similar to those observed in AD.

[0068] In some cases, treatment is for microglia-mediated diseases or disorders. Microglia-mediated diseases or disorders may include, but are not limited to, Alzheimer's disease, frontotemporal dementia, chronic traumatic encephalopathy (CTE), and tauopathic neurodegenerative diseases, including but not limited to cortical vascular degeneration. In some cases, the subject suffers from hereditary ataxia. Hereditary ataxia often results in cerebellar atrophy as a result of impaired cerebellar cortical circuitry and function, i.e., neurodegeneration of cellular afferent neurons and Purkinje cells, which have long axons containing the sole output source from the cerebellar cortex to the deep cerebellar nuclei.

[0069] In some cases, the treatment is for neuropsychiatric disorders associated with microglia-mediated brain atrophy. For example, individuals with schizophrenia often exhibit a reduction in postmortem cortical tissue. This phenomenon is caused by synaptic spruning, which reflects abnormalities in microglia-like cells and synaptic function. In other embodiments, the disclosure provides methods and systems for alleviating symptoms of depression. Stress, neurogenesis defects, and defects in synaptic plasticity are associated with depression. Chronic stress promotes excessive branching of microglia and astrocyte atrophy. Therefore, in some embodiments, the disclosed systems and methods may alleviate symptoms associated with chronic stress or depression by improving synaptic plasticity and stimulating neural networks, along with improving microglia-mediated clearance.

[0070] In some cases, treatment addresses symptoms associated with the stroke. For example, the stroke may be an ischemic stroke, which helps repair the brain by generating a neuroinflammatory response that activates microglia. Ischemic stroke is associated with a loss of synaptic activity. As a result, brain tissue in the penumbra during an ischemic stroke is structurally intact but functionally dormant.

[0071] In some cases, treatment is for demyelinating diseases. Demyelinating diseases may include multiple sclerosis or acute disseminated encephalomyelitis, both of which can cause neuroinflammation and brain atrophy. In multiple sclerosis (MS), brain or brain atrophy is often seen as a result of demyelination and destruction of nerve cells. Extensive myelinating damage occurs, damaging the myelin-rich white matter of the brain, and results from numerous seizures that occur over time. In acute disseminated encephalomyelitis, similar symptoms are seen, but the development of extensive myelinating damage is often due to a single episode or seizure.

[0072] The outcome may be one of several clinically relevant outcomes. In some cases, the outcome may be survival. In some cases, the outcome may be long-term survival. In some cases, the outcome may be improvement in symptoms associated with a disease or disorder, such as neurodegenerative disease. For example, in some cases, the outcome may include improvement in behavioral and psychological symptoms (BPSD) of dementia. For example, symptoms associated with a disease or disorder may include asymptomatic, anxiety, or depression. In some cases, the outcome may be an improvement in quality of life. In some cases, the outcome may be improvement in pathological processes, such as better sleep. In some cases, the outcome may be a decline in quality of life. In some cases, the outcome may be a cure. In some cases, the outcome may be a non-cure. In some cases, the outcome may be an improvement in cognitive function. In some cases, the outcome may be a deterioration in cognitive function. In some cases, the outcome may be an improvement in memory. In some cases, the outcome may be a deterioration in memory. In some cases, the outcome may be a feeling of well-being. In some cases, the outcome may be depression. In some cases, the outcome may be death. The outcome may be a value or condition that is quantitatively or qualitatively measurable or determinable for any of the aforementioned examples of clinically relevant outcomes. In some cases, the outcome may be a quantitative or qualitative assessment that can be performed by a healthcare professional. In some cases, the outcome may be a self-assessment, patient report, or report from a care partner prepared for the subject that can be performed by the subject. In some cases, the outcome may be the outcome of treatment for sleep fragmentation. In some cases, the result may be a quantitative or qualitative assessment that can be performed by an instrument or computer.

[0073] The subjects may be any animal with a nervous system. Depending on the circumstances, the subjects may be mammals. Depending on the circumstances, the subjects may be humans. The subjects may have a variety of ages, sexes, genders, heights, weights, or any other clinically relevant biometrics.

[0074] The subjects have been diagnosed with, are suspected of having, or are at risk of having any of the diseases disclosed herein. In some cases, the disease may be a neurodegenerative disorder associated with cognitive decline. In some cases, the subjects may have, are suspected of having, or are at risk of having, a prion disease or infectious spongiform encephalopathy. In some cases, the subjects may have, are suspected of having, or are at risk of having, Alzheimer's disease, Creutzfeldt-Jakob disease (CJD), variant CJD, Gerstmann-Streussler-Scheinker syndrome, fatal familial insomnia, Kuru disease, or any combination thereof. In some cases, the disease may be a psychiatric or neurological disorder associated with cognitive decline. Depending on the context, mental or neurological disorders include mood disorders, depression, bipolar disorder, anxiety, addiction, neurosis, anorexia, bulimia, dementia, mild cognitive impairment, subjective cognitive decline, Lewy body dementia, Parkinson's disease, sleep fragmentation, schizophrenia, or any combination thereof.

[0075] In some cases, the administration may be a non-invasive procedure. In some cases, the administration may be indirect (e.g., without physical contact) stimulation of the optic nerve. In some cases, the administration may use light. In some cases, the administration may be indirect stimulation of the auditory nerve. In some cases, the administration may be indirect stimulation of any one of the nerves disclosed herein. In some cases, the administration may use sound. In some cases, the administration may be direct stimulation. In some cases, the administration may be electricity delivered to a region within the subject's body. In some cases, the administration may be vibration delivered to a region within the subject's body. In some cases, the region within the subject's body may be the skin of the subject's head, the surface of the subject's skull, the surface of the membrane surrounding the subject's brain, the subject's brain, a region within the subject's brain, the subject's retinal nerve, or the subject's cochlear nerve. In some cases, the gamma-oscillation-induced non-invasive sensory stimulation may be visual stimulation, auditory stimulation, kinesthetic stimulation, or any combination thereof. Gamma vibration-induced non-invasive sensory stimulation may be provided using any one of the devices or methods disclosed herein.

[0076] In some cases, administration may be carried out continuously over a specified period. In some cases, the specified period may be between 10 minutes and 2 hours. In some cases, the specified period may be at least 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, or 60 minutes. In some cases, the specified period may be at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours. In some cases, the specified period may be at least 1, 2, 3, 4, 5, 6, or 7 days. In some cases, the specified period may be at most 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, or 60 minutes. Depending on the circumstances, the specified period may be at most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours. Depending on the circumstances, the specified period may be at most 1, 2, 3, 4, 5, 6, or 7 days.

[0077] In some cases, administration may be carried out at several discrete times. In some cases, administration may be carried out approximately once a day. In some cases, administration may be carried out at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times a day. In some cases, administration may be carried out at most approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times a day. In some cases, administration may be carried out multiple times over a period of time. In some cases, administration may be carried out over a period of at least approximately 1, 2, 3, 4, 5, 6, or 7 days. In some cases, administration may be carried out over a period of at least approximately 1, 2, 3, or 4 weeks. In some cases, administration may be carried out multiple times over a period of at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 months. In some cases, administration may be carried out approximately once a day over a period of 6 months. Depending on the circumstances, the drug may be administered multiple times over a period of at most approximately 1, 2, 3, or 4 weeks. Depending on the circumstances, the drug may be administered multiple times over a period of at most approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 months.

[0078] Gamma-oscillation-induced non-invasive stimulation can be any type of non-invasive stimulus having a component that induces gamma electroencephalograms (also referred to as neural activity). Gamma-oscillation-induced non-invasive sensory stimulation can be any stimulus that can be administered to a subject so that gamma oscillations are induced in the nerve of that subject. By choice, gamma-oscillation-induced non-invasive sensory stimulation can be a gamma-oscillation-induced non-invasive sensory stimulus. By choice, gamma-oscillation-induced non-invasive sensory stimulation can be a non-invasive sensory stimulus. In some embodiments, gamma-oscillation-induced non-invasive stimulation can induce neural oscillations in frequency ranges other than the gamma range. In some embodiments, gamma-oscillation-induced non-invasive stimulation can induce neural oscillations in the theta frequency range. In some embodiments, gamma-oscillation-induced non-invasive stimulation can induce neural oscillations in the gamma frequency range that alternate with neural oscillations in other frequency ranges (e.g., theta, alpha, or beta frequency ranges). Gamma-oscillation-induced non-invasive sensory stimulation can have any of the characteristics of stimuli disclosed herein.

[0079] Various machine learning algorithms may be used in this method. The machine learning algorithm may employ any one of the machine learning elements disclosed herein. The machine learning algorithm may be configured to receive a measured response from an object. The machine learning algorithm may be configured to receive one or more EEG signals measured from an object. The machine learning algorithm may be configured to receive one or more signals having frequencies between approximately 4 Hz and 400 Hz. The machine learning algorithm may be configured to receive one or more signals having frequencies between approximately 20 Hz and 200 Hz. The machine learning algorithm may be configured to receive one or more signals having frequencies between approximately 20 Hz and 80 Hz. The machine learning algorithm may be configured to output one or more values.

[0080] In some cases, adjustment of the therapeutic dose may involve adjusting the parameters of the gamma-oscillating non-invasive sensory stimulation administered in gamma-oscillating non-invasive sensory stimulation treatment. In some cases, adjustment of the therapeutic dose may involve adjusting the parameters of the gamma-oscillating non-invasive sensory stimulation administered in gamma-oscillating non-invasive sensory stimulation treatment with periodic elements. In some cases, adjustment of the therapeutic dose may involve adjusting the parameters of the gamma-oscillating non-invasive sensory stimulation administered in gamma-oscillating non-invasive sensory stimulation treatment with periodic elements. In some cases, adjustment of the therapeutic dose may involve adjusting the parameters of the gamma-oscillating non-invasive sensory stimulation administered in gamma-oscillating non-invasive sensory stimulation treatment with non-periodic elements. In some cases, adjustment of the therapeutic dose may involve adjusting the parameters of the gamma-oscillating non-invasive sensory stimulation administered in gamma-oscillating non-invasive sensory stimulation treatment with non-periodic elements. In some cases, adjustment of the therapeutic dose may involve adjusting the parameters of the gamma oscillatory-induced non-invasive sensory stimulation administered in the periodic or non-periodic elements of the gamma oscillatory-induced non-invasive sensory stimulation treatment. In some cases, adjustment of the parameters of the gamma oscillatory-induced non-invasive sensory stimulation may involve adjusting the duration of the stimulation. In some cases, adjustment of the parameters of the gamma oscillatory-induced non-invasive sensory stimulation may involve adjusting the intensity of the stimulation. In some cases, adjustment of the parameters of the gamma oscillatory-induced non-invasive sensory stimulation may involve adjusting the amplitude of the stimulation. In some cases, adjustment of the parameters of the gamma oscillatory-induced non-invasive sensory stimulation may involve adjusting the wavelength of the stimulation. In some cases, adjustment of the parameters of the gamma oscillatory-induced non-invasive sensory stimulation may involve adjusting the frequency of the stimulation. In some cases, adjustment of the parameters of the gamma oscillatory-induced non-invasive sensory stimulation may involve adjusting the waveform of the stimulation. In some cases, adjustment of the parameters of the gamma oscillatory-induced non-invasive sensory stimulation may involve adjusting the duty cycle of the stimulation. In some cases, adjusting the parameters of gamma-oscillating non-invasive sensory stimulation involves adjusting the stimulus interval. In some cases, adjusting the parameters of gamma-oscillating non-invasive sensory stimulation involves adjusting the stimulus spectrum. In some cases, adjusting the parameters of gamma-oscillating non-invasive sensory stimulation involves adjusting the stimulus envelope. In some cases, adjusting the parameters of gamma-oscillating non-invasive sensory stimulation involves adjusting the stimulus modulation.In some cases, adjusting the parameters of gamma-oscillating non-invasive sensory stimulation involves adjusting the modulation frequency of the stimulus. In some cases, adjusting the parameters of gamma-oscillating non-invasive sensory stimulation involves adjusting the modulation amplitude of the stimulus. In some cases, adjusting the parameters of gamma-oscillating non-invasive sensory stimulation involves adjusting the harmonic structure of the stimulus. In some cases, adjusting the parameters of gamma-oscillating non-invasive sensory stimulation involves adjusting the phase of the stimulus.

[0081] In some cases, adjusting the therapeutic dose may involve adjusting the parameters of unidirectional wave stimulation. In some cases, adjusting the therapeutic dose may involve adjusting the parameters of bidirectional wave stimulation. In some cases, adjusting the therapeutic dose may involve adjusting the parameters of square wave stimulation. In some cases, adjusting the therapeutic dose may involve adjusting the parameters of rectangular wave stimulation. In specific cases, adjusting the therapeutic dose may involve adjusting the parameters of pulsed stimulation. In some cases, adjusting the therapeutic dose may involve adjusting the parameters of sinusoidal wave stimulation. In some cases, adjusting the therapeutic dose may involve adjusting the parameters of triangular wave stimulation. In some cases, adjusting the therapeutic dose may involve adjusting the parameters of sawtooth wave stimulation. In some cases, adjusting the therapeutic dose may involve adjusting the parameters of ramp wave stimulation. In some cases, adjusting the therapeutic dose may involve adjusting the parameters of noise stimulation. In specific cases, adjusting the therapeutic dose may involve adjusting the parameters of white noise stimulation. In specific cases, adjusting the therapeutic dose may involve adjusting the parameters of pink noise stimulation. In certain cases, adjustment of the therapeutic dose may involve adjustment of the parameters of the red noise stimulus. In certain cases, adjustment of the therapeutic dose may involve adjustment of the parameters of the purple noise stimulus. In certain cases, adjustment of the therapeutic dose may involve adjustment of the parameters of the gray noise stimulus. In some cases, adjustment of the therapeutic dose may involve adjustment of the parameters of the sweep stimulus. In some cases, adjustment of the therapeutic dose may involve adjustment of the parameters of the chirp stimulus. In certain cases, adjustment of the therapeutic dose may involve adjustment of the parameters of the O-chirp stimulus. In certain cases, adjustment of the therapeutic dose may involve adjustment of the parameters of the linear chirp stimulus. In certain cases, adjustment of the therapeutic dose may involve adjustment of the parameters of the exponential chirp stimulus. In certain cases, adjustment of the therapeutic dose may involve adjustment of the parameters of the hyperbolic chirp stimulus. In some cases, adjustment of the therapeutic dose may involve adjustment of the parameters of the click stimulus. In certain cases, adjustment of the therapeutic dose may involve adjustment of the parameters of the frequency-modulated wave stimulus. In certain cases, adjusting the therapeutic dose may involve adjusting the parameters of the amplitude-modulated wave stimulation.

[0082] In some cases, adjustment of the therapeutic dose may involve adjusting the delivery parameters of the gamma-oscillating non-invasive sensory stimulation administered in gamma-oscillating non-invasive sensory stimulation treatment. In some cases, adjustment of the delivery parameters of gamma-oscillating non-invasive sensory stimulation may involve adjusting the time course of stimulation delivery. In some cases, adjustment of the delivery parameters of gamma-oscillating non-invasive sensory stimulation may involve adjusting the intensity of stimulation delivery. In some cases, adjustment of the delivery parameters of gamma-oscillating non-invasive sensory stimulation may involve adjusting the duration of stimulation delivery. In some cases, adjustment of the delivery parameters of gamma-oscillating non-invasive sensory stimulation may involve adjusting the modality of stimulation delivery.

[0083] Depending on the circumstances, the therapeutic dose may be any dose that can be prepared for the treatment of any one of the diseases disclosed herein.

[0084] Delivery method and system In some embodiments, gamma vibration-induced non-invasive sensory stimulation is delivered by one or more of the following: visual, auditory, tactile, olfactory, or bone conduction. In some embodiments, a combination of audiovisual stimuli is delivered for one hour daily over a period of 3 to 6 months or longer. In some embodiments, the stimulation is delivered for two hours daily. In some embodiments, the stimulation is delivered for multiple periods over the course of a day. In some embodiments, a combination of audiovisual stimuli is delivered over a long, unconstrained period. In some embodiments, the stimulation is delivered for various periods. In some embodiments, gamma vibration-induced non-invasive sensory stimulation is delivered at least partially by eyeglasses, goggles, a mask, or other wearable device that provides visual stimulation.

[0085] In some embodiments, gamma vibration-induced non-invasive sensory stimulation is delivered at least partially by one or more devices in the user environment, such as speakers, lighting fixtures, bed attachments, wall-mounted screens, or other home devices. In some embodiments, one or more devices are controlled by further devices, such as a telephone, tablet, or home automation hub, configured to manage the delivery of gamma vibration-induced non-invasive sensory stimulation by one or more devices in the user environment.

[0086] In some embodiments, gamma vibration-induced non-invasive sensory stimulation is delivered by opaque or partially transparent glasses worn by the subject, along with an internal lighting element that provides a visual signal. In some embodiments, gamma vibration-induced non-invasive sensory stimulation is delivered by headphones or earphones worn by the subject that provide an auditory signal. In some embodiments, a combination of visual and auditory signals is delivered simultaneously by headphones and glasses worn together. In some embodiments, visual and auditory signals are delivered separately at different times by glasses or headphones worn. An exemplary embodiment includes glasses having an LED inside the glasses that provides a visual stimulus and headphones that provide an auditory stimulus.

[0087] In some embodiments, gamma vibration-induced non-invasive sensory stimulation is delivered by vibratory tactile stimulation via clothing or body-worn devices. In some embodiments, gamma vibration-induced non-invasive sensory stimulation may be delivered through the user's nostrils.

[0088] In some embodiments, gamma-oscillation-induced non-invasive sensory stimulation is delivered by transcranial magnetic stimulation (TMS). In some embodiments, gamma-oscillation-induced non-invasive sensory stimulation is delivered by transcranial alternating current stimulation (tACS). In some embodiments, gamma-oscillation-induced non-invasive sensory stimulation is delivered by transcranial pulsed current stimulation (tPCS).

[0089] In some embodiments, gamma-oscillation-induced non-invasive sensory stimulation is administered at least partially by a device specified in one or more of U.S. Patent No. 1,0307611, U.S. Patent No. 1,0293177, or U.S. Patent No. 1,0279192.

[0090] In some embodiments, gamma vibration-induced non-invasive sensory stimulation is delivered to multiple objects present in space. In exemplary embodiments, gamma vibration-induced non-invasive sensory stimulation is delivered to multiple objects present in space through a device present in space, such a device either delivers the same stimulus to all present objects, or delivers customized stimuli to individual objects, or a combination of both.

[0091] Program parameters and parameter values In some embodiments, the gamma-oscillation-induced non-invasive sensory stimulation parameter consists of a stimulation frequency of approximately 30 Hz to approximately 50 Hz (e.g., fs in Figure 31) for both the auditory and visual signals. In some embodiments, the auditory and visual signals are offset from each other by a delay (e.g., td in Figure 31). In exemplary embodiments, the auditory and visual signals are synchronized (td=0s).

[0092] In some embodiments, gamma oscillatory-induced non-invasive sensory stimulation parameters consist of various timing and intensity parameters. In exemplary embodiments, these parameters include those shown in Figure 31. In some embodiments, these parameters are pre-configured. In some embodiments, these parameters are adjusted, at least in part, by a third party such as a caregiver or healthcare provider. In some embodiments, one or more parameters are adjusted in response to one or more measurements or analyses, including user context, measurements of user-related sleep quality parameters, and observed or detected use of the stimulation device. In some embodiments, gamma oscillatory-induced non-invasive sensory stimulation parameters are adjusted in response to the progression of detected or analyzed neurodegenerative disease symptoms. Various frequencies and intensities may be used as parameters for gamma oscillatory-induced non-invasive sensory stimulation.

[0093] In some embodiments, the Disclosure provides for the delivery of non-invasive auditory stimuli, visual stimuli, or a combination of audiovisual stimuli at 40 Hz. In some embodiments, the stimuli are delivered at one or more stimuli frequencies (e.g., fs in Figure 31). In some embodiments, the stimuli are delivered at one or more stimuli frequencies (e.g., fs in Figure 31) in the range of approximately 30–50 Hz. In some embodiments, “gamma” refers to frequencies in the range of 30–50 Hz. In some embodiments, the stimuli are periodic. In some embodiments, the stimuli are aperiodic. In some embodiments, the stimuli are periodic stimuli with aperiodic components. In some embodiments, the stimuli are intermittent. In some embodiments, the stimuli are delivered based at least in part on alpha wave frequencies detected, reported, or demographically or individually associated or dominant in the user.

[0094] In some embodiments, specific visual parameters include one or more of the following: stimulus frequency, intensity (luminance), hue, visual pattern, spatial frequency, contrast, and duty cycle. In an exemplary embodiment, the visual stimulus is provided with a stimulus frequency of 40 Hz, a luminance of 0 μW / cm² to 1120 μW / cm², and a visual signal duty cycle of 50%.

[0095] In some embodiments, the non-invasive stimulus is delivered as a combination of audiovisual stimuli delivered at a frequency of 40 Hz. In some embodiments, the visual and auditory stimuli are synchronized to start each cycle simultaneously. In some embodiments, the start of each auditory and visual stimulus cycle is offset by a set time. In some embodiments, the visual and auditory signals are delivered at an intensity that is clearly perceived by the subject and adjusted to their acceptable levels.

[0096] In some embodiments, at least some of the parameters or characteristics of the non-invasive signal administered to the subject correspond to those specified in one or more of U.S. Patent No. 1,0307611, U.S. Patent No. 1,0293177, or U.S. Patent No. 1,0279192. In some embodiments, at least some of the parameters or characteristics of the non-invasive signal administered to the subject correspond to those specified in one or more of U.S. Patent No. 1,0159816 or U.S. Patent No. 1,0265497.

[0097] In some embodiments, specific speech parameters include one or more of the following: stimulus frequency, intensity (volume), and duty cycle. In some embodiments, the audible frequency is adjusted in response to the auditory characteristics of the subject, for example, to a frequency that the subject can hear better. In an exemplary embodiment, the speech stimulus is provided with a speech tone frequency of 7,000 Hz, a volume level between 0 dBA and 80 dBA, and a speech signal duty cycle of 0.57%.

[0098] In some embodiments, non-invasive stimulation parameters are selected with the aim of inducing gamma wave oscillations in the brain of a human subject. In some embodiments, non-invasive stimulation parameters are selected with the aim of inducing alpha waves in a human subject (Figure 40). In some embodiments, non-invasive stimulation parameters are intended to induce beta waves in a human subject. In some embodiments, non-invasive stimulation parameters are intended to induce gamma waves in a human subject.

[0099] In some embodiments, light levels and hues are adjusted to avoid fatigue in the subject. In some embodiments, light levels and hues are adjusted to motivate the subject. In some embodiments, parameters for the ears or eyes are adjusted similarly. In some embodiments, parameters for the ears or eyes are adjusted differently. In exemplary embodiments, auditory and visual parameters such as timbre and hue are varied to give the subject engagement or motivation to continue the application of stimulation or monitoring.

[0100] Visual stimulation of nerves Visual stimuli can modulate, control, or otherwise influence the frequency of neural oscillations to mitigate or prevent adverse consequences to one or more cognitive states or functions of the brain, or to the immune system, while exerting beneficial effects on those states or functions. Visual stimuli can induce sensory-evoked neural oscillations that can generate detectable signals that may correlate with potentially beneficial effects on one or more cognitive states, cognitive functions of the brain, the immune system, or inflammation. In some cases, visual stimuli can produce local effects, such as in the visual cortex and related areas. In some cases, visual stimuli can produce broader effects, causing physiological changes in more nervous systems than just the nervous system alone.

[0101] Neural oscillations occur in humans or animals and involve rhythmic or repetitive neural activity in the central nervous system. Neural tissue can generate oscillatory activity through mechanisms within individual neurons or through interactions between neurons. Oscillations can manifest as oscillations in membrane potential or as rhythmic patterns of action potentials that can generate oscillatory activation of postsynaptic neurons. Macroscopic oscillations can be produced by synchronizing the activity of groups of neurons, and these oscillations can be observed, for example, by electroencephalography ("EEG"), magnetoencephalography ("MEG"), functional magnetic resonance imaging ("fMRI"), or electrocortical recording ("ECoG"). Neural oscillations can be characterized by their frequency, amplitude, and phase. These signal characteristics can be observed from neural recordings using time-frequency analysis.

[0102] For example, EEG can measure the oscillatory activity between groups of neurons, and the measured oscillatory activity can be classified into the following frequency bands: Delta activity corresponds to the frequency band of 0-4 Hz. Theta activity corresponds to the frequency band of 4-8 Hz. Alpha activity corresponds to the frequency band of 8-12 Hz. Beta activity corresponds to the frequency band of 13-30 Hz. Gamma activity corresponds to the frequency band of 30-100 Hz.

[0103] The frequency and presence or activity of nerve oscillations may be associated with cognitive states or functions such as information transmission, perception, motor control, and memory. In some cases, the frequency and presence or activity of nerve oscillations may be associated with deficiencies in cognitive states or functions. Based on cognitive states or functions, the frequency of nerve oscillations may vary. Furthermore, certain frequencies of nerve oscillations may have beneficial or harmful effects on one or more cognitive states or functions.

[0104] Sensory-evoked or sensory-induced neural oscillations occur when an external stimulus of a specific frequency is coded by neurons, inducing neural activity in the brain that results in neurons vibrating at frequencies corresponding to specific frequencies of the external stimulus. Therefore, sensory-evoked neural oscillations can refer to the synchronization of neural oscillations in the brain using an external stimulus so that the oscillations occur at frequencies corresponding to specific frequency components of the external stimulus. In some cases, sensory-evoked neural oscillations may include additional neural oscillations with frequencies different from those of the external stimulus. In some cases, these additional neural oscillations may correlate with the treatment outcome.

[0105] The systems and methods of this disclosure can achieve sensory induction of neural oscillations by applying external visual stimuli. For example, external signals such as light pulses or high-contrast visual patterns can be perceived by the brain. The brain can adjust, manage, or control the frequency of neural oscillations in response to the observation or perception of light pulses. Light pulses generated at a predetermined frequency and perceived by ocular means via the direct or peripheral visual field can induce neural activity in the brain and induce neural oscillations within a specific frequency range. The frequency of neural oscillations can be at least partially influenced by the frequency of the light pulse. High levels of cognitive function can gate or interfere with sensory induction of neural oscillations in some areas, but the brain can respond to visual stimuli in the sensory cortex. Thus, the systems and methods of this disclosure can synchronize the electrical activity between groups of neurons based on the frequency of the light pulse by bringing about sensory induction of neural oscillations using external visual stimuli such as light pulses emitted at a predetermined frequency. Sensory induction of neural oscillations in one or more parts or regions of the brain can be observed based on the total frequency of oscillations generated by the synchronized electrical activity in a collection of cortical neurons. The frequency of the light pulse can cause or adjust the synchronous electrical activity in this collection of cortical neurons to oscillate at a frequency corresponding to the frequency of the light pulse.

[0106] Figure 1 is a block diagram illustrating a system for performing visual stimulation induction of neural oscillations according to one embodiment. System 100 may include a neural stimulation system ("NSS") 105. The NSS 105 may also be referred to as the visual NSS 105 or NSS 105. In summary, the NSS 105 may be included in, access, interface with, or otherwise communicate with one or more of the following: a photogenerating module 110, a photomodulation module 115, an unwanted frequency filtering module 120, a profile manager 125, an adverse event management module 130, a feedback monitor 135, a data repository 140, a visual signal transmission component 150, a filtering component 155, or a feedback component 160. The light generation module 110, the light tuning module 115, the unwanted frequency filtering module 120, the profile manager 125, the side effect management module 130, the feedback monitor 135, the visual signal transmission component 150, the filtering component 155, or the feedback component 160 may each include at least one processing unit or other logical device, such as a programmable logic array engine, or a module configured to communicate with the database repository 150. The light generation module 110, the light tuning module 115, the unwanted frequency filtering module 120, the profile manager 125, the side effect management module 130, the feedback monitor 135, the visual signal transmission component 150, the filtering component 155, or the feedback component 160 may be separate components, single components, or part of NSS 105. System 100 and its components, such as NSS 105, may include one or more hardware elements such as processors, logic devices, or circuits. System 100 and its components, such as NSS 105, may include one or more hardware or interface components as shown in System 700 in Figures 7A and 7B.For example, the components of system 100 include, or run on, one or more processors 721, access storage 728, or memory 722, and can communicate via a network interface 718.

[0107] Continuing to refer to Figure 1 in more detail, the NSS 105 may include at least one photogenerating module 110. The photogenerating module 110 may be designed and constructed to interface with a visual signal transmission component 150 to instruct, or otherwise cause to occur or facilitate the generation of a visual signal, such as a light pulse or a flash of light, having one or more predetermined parameters. The photogenerating module 110 may include hardware or software for receiving and processing instructions or data packets from one or more modules or components of the NSS 105. The photogenerating module 110 may generate instructions for the visual signal transmission component 150 to generate a visual signal. The photogenerating module 110 may control or enable the visual signal component 150 to generate a visual signal having one or more predetermined parameters.

[0108] The light generation module 110 may be communicatively coupled to the visual signal component 150. The light generation module 110 can communicate with the visual signal transmission component 150 via circuits, wires, data ports, network ports, power lines, ground, electrical contacts, or pins. The light generation module 110 can wirelessly communicate with the visual signal transmission component 150 using one or more wireless protocols, such as Bluetooth, Bluetooth Low Energy, Zigbee, Z-Wave, IEEE 802.11, Wi-Fi, 3G, 4G, LTE, Near Field Communication ("NFC"), or other short-range, medium-range, or long-range communication protocols. The light generation module 110 can communicate wirelessly or via a wired connection with the visual signal transmission component 150 by including or accessing a network interface 718.

[0109] The photogenerating module 110 can interface with, control, or otherwise manage various types of visual signal transmission components 150 to cause the visual signal transmission components 150 to generate, block, control, or otherwise provide visual signals having one or more predetermined parameters. The photogenerating module 110 may include a driver configured to drive the light source of the visual signal transmission component 150. For example, the light source may include a light-emitting diode ("LED"), and the photogenerating module 110 may include an LED driver, chip, microcontroller, operational amplifier, transistor, resistor, or a diode configured to drive the LED light source by supplying electricity or power having specific voltage and current characteristics.

[0110] In some embodiments, the photogenerating module 110 can instruct the visual signal transmission component 150 to provide a visual signal including a light wave 200, as shown in Figure 2A. The light wave 200 may include or be formed from electromagnetic waves. The electromagnetic waves of the light wave have corresponding amplitudes and can propagate orthogonally to each other, as indicated by the amplitude-to-time of the electric field 205 and the amplitude-to-time of the magnetic field 210. The light wave 200 may have a wavelength 215. The light wave may also have a frequency. The product of the wavelength 215 and the frequency can be the speed of the light wave. For example, the speed of the light wave can be about 299,792,458 meters / second in a vacuum.

[0111] The photogenerating module 110 can instruct the visual signal component 150 to generate light waves having one or more predetermined wavelengths or intensities. The wavelengths of the light waves may correspond to the visible spectrum, the ultraviolet spectrum, the infrared spectrum, or any other wavelength of light. For example, the wavelengths of light waves within the visible spectrum may be in the range of 390 to 700 nanometers ("nm"). Within the visible spectrum, the photogenerating module 110 can further specify one or more wavelengths corresponding to one or more colors. For example, the photogenerating module 110 can instruct the visual signal transmission component 150 to generate a visual signal that includes one or more light waves having one or more wavelengths corresponding to one or more of the following: ultraviolet (e.g., 10-380 nm), violet (e.g., 380-450 nm), blue (e.g., 450-495 nm), green (e.g., 495-570 nm), yellow (e.g., 570-590 nm), orange (e.g., 590-620 nm), red (e.g., 620-750 nm), or infrared (e.g., 750-1,000,000 nm). The wavelengths can be in the range of 10 nm to 100 micrometers. In some embodiments, the wavelengths can be in the range of 380-750 nm.

[0112] The light generation module 110 may decide to provide a visual signal that includes light pulses. The light generation module 110 may instruct the visual signal transmission component 150 to generate light pulses, or otherwise cause it to do so. A light pulse may refer to a burst of light waves. For example, Figure 2B shows a burst of light waves. A burst of light waves may refer to a burst of the electric field 250 generated by the light waves. A burst of the electric field 250 of a light wave may be called a light pulse or a flash of light. For example, a light source that is intermittently turned on and off may produce bursts, flashes, or pulses of light.

[0113] Figure 2C shows pulses of light 235a-c according to one embodiment. The light pulses 235a-c can be shown as frequency spectra via a graph. The y-axis represents the frequency of the light wave (e.g., the speed of the light wave divided by the wavelength), and the x-axis represents time. The visual signal is at frequency F a And, F a This can include modulation of light waves between different frequencies. For example, the NSS105 can modulate light waves between frequencies in the visible spectrum, such as Fa, and frequencies outside the visible spectrum. The NSS105 can modulate light waves between two or more frequencies, between on and off states, or between high-power and low-power states.

[0114] In some cases, the frequency of the light wave used to generate the light pulse is F a This can be kept constant, thereby generating a square wave in the frequency spectrum. In some embodiments, each of the three pulses 235a to c has the same frequency F a It may include certain light waves.

[0115] The width of each optical pulse (e.g., the duration of a burst of light wave) may correspond to a pulse width 230a. The pulse width 230a may refer to the length or duration of the burst. The pulse width 230a can be measured in units of time or distance. In some embodiments, pulses 235a-c may include light waves having different frequencies from each other. In some embodiments, pulses 235a-c may have different pulse widths 230a from each other, as shown in Figure 2D. For example, the first pulse 235d in Figure 2D may have a pulse width 230a, while the second pulse 235e may have a second pulse width 230b that is larger than the first pulse width 230a. The third pulse 235f may have a third pulse width 230c that is smaller than the second pulse width 230b. The third pulse width 230c may also be less than the first pulse width 230a. Although the pulse widths 230a to c of pulses 235d to f of the pulse train may vary, the photogenerating module 110 can maintain a constant pulse rate interval 240 with respect to the pulse train.

[0116] Pulses 235a to c can form a pulse train having a pulse rate interval 240. The pulse rate interval 240 can be quantified using units of time. The pulse rate interval 240 can be based on the frequency of the pulses of the pulse train 201. The frequency of the pulses of the pulse train 201 can be referred to as a modulation frequency. For example, the optical generation module 110 can provide a pulse train 201 having a predetermined frequency corresponding to gamma activity, such as 40 Hz. To do so, the optical generation module 110 can determine the pulse rate interval 240 by taking the multiplicative inverse (or reciprocal) of the frequency (e.g., dividing 1 by the predetermined frequency of the pulse train). For example, the optical generation module 110 can take the multiplicative inverse of 40 Hz by dividing 1 by 40 Hz and determining the pulse rate interval 240 to be 0.025 seconds. The pulse rate interval 240 can be maintained constant throughout the pulse train. In some embodiments, the pulse rate interval 240 can vary throughout the pulse train or from one pulse train to a subsequent pulse train. In some embodiments, the number of pulses transmitted during a second period can be fixed, but the pulse rate interval 240 can vary.

[0117] In some embodiments, the optical generation module 110 can generate an optical pulse having a light wave with a varying frequency. For example, the optical generation module 110 can generate an up-chirp pulse, in which case the frequency of the light wave of the optical pulse increases from the start of the pulse to the end of the pulse, as shown in FIG. 2E. For example, the frequency of the light wave at the start of pulse 235g can be F a Let's say. The frequency of the light wave of pulse 235g is F at the middle of pulse 235g a from F b to F a and then increase to a maximum value Fc at the end of pulse 235g. Thus, the frequency of the light wave used to generate pulse 235g is F cThe frequency can be within this range. The frequency can increase linearly, exponentially, or based on some other velocity or curve.

[0118] The photogenerating module 110 can generate down chirp pulses as shown in Figure 2F, in which case the frequency of the light wave in the light pulse decreases from the start of the pulse to the end of the pulse. For example, the frequency of the light wave at the start of pulse 235j is F d This can be done. The frequency of the light wave of pulse 235j is F in the middle of pulse 235j. d From F e It increases to a minimum value of F at the end of pulse 235j. f It can be reduced to this. Therefore, the frequency of the light wave used to generate pulse 235j is F d ~F f The frequency can be within this range. The frequency can decrease linearly, exponentially, or based on some other velocity or curve.

[0119] The visual signal transmission component 150 can be designed and constructed to generate light pulses in response to commands from the light generation module 110. The commands may include parameters of the light pulse, such as the frequency or wavelength of the light wave, the intensity and duration of the pulse, the frequency of the pulse train, the pulse rate interval, or the duration of the pulse train (e.g., the number of pulses in the pulse train, or the length of time for transmitting a pulse train having a given frequency). The light pulses may be perceived, observed, or otherwise identified by the brain via ocular means such as the eyes. The light pulses may be transmitted to the eyes via the direct or peripheral vision.

[0120] Figure 3A shows the horizontal direct field of view 310 and the horizontal peripheral field of view. Figure 3B shows the vertical direct field of view 320 and the vertical peripheral field of view 325. Figure 3C shows the extent of the direct and peripheral fields of view, including the relative distances at which visual signals can be perceived in different fields of view. The visual signal transmission component 150 may include a light source 305. The light source 305 can be positioned to transmit light pulses to the direct field of view 310 or 320 of the individual's eye. The NSS 105 can be configured to transmit light pulses into the direct field of view 310 or 320, as this may facilitate sensory induction of neural oscillations when more attention can be paid to the light pulses by the individual. Attention levels can be measured quantitatively directly in the brain, indirectly through the individual's eye movements, or by active feedback (e.g., mouse tracking).

[0121] The light source 305 can be positioned to transmit light pulses to the peripheral field of vision 315 or 325 of the individual's eye. For example, the NSS 105 can transmit light pulses to the peripheral field of vision 315 or 325 because these light pulses may not interfere with the concentration of an individual who may be performing other tasks such as reading, walking, or driving. Therefore, the NSS 105 can provide subtle and continuous visual brain stimulation by transmitting light pulses through the peripheral field of vision.

[0122] In some embodiments, the light source 305 may be head-mounted, while in other embodiments, the light source 305 may be held by the subject's hand, mounted on a stand, suspended from the ceiling, connected to a chair, or otherwise positioned to direct light directly into the field of vision or peripheral vision. For example, a chair or external support system may include or position the light source 305 to maintain a fixed / pre-defined relationship between the subject's field of vision and visual stimuli while providing visual input. The system can provide an immersive experience. For example, the system may include an opaque or partially opaque dome containing the light source. This dome may be positioned above the subject's head while the subject is sitting or leaning in a chair. By partially covering the subject's field of vision, the dome can reduce external distractions and facilitate sensory induction of neural oscillations in brain regions.

[0123] The light source 305 can include any type of light source or light-emitting device. The light source can include a coherent light source such as a laser. The light source 305 can include light-emitting diodes (LEDs), organic LEDs, fluorescent light sources, incandescent light, or any other light-emitting device. The light source can include lamps, light bulbs, or one or more light-emitting diodes of various colors (e.g., white, red, green, blue). In some embodiments, the light source includes semiconductor light-emitting devices such as light-emitting diodes of any spectral or wavelength range. In some embodiments, the light source 305 includes a broadband lamp or broadband light source. In some embodiments, the light source includes a black light. In some embodiments, the light source 305 includes a hollow cathode lamp, a fluorescent tube light source, a neon lamp, an argon lamp, a plasma lamp, a xenon flash lamp, a mercury lamp, a metal halide lamp, or a sulfur lamp. In some embodiments, the light source 305 includes a laser or laser diode. In some embodiments, the light source 305 includes an OLED, PHOLED, QDLED, or any other variation of a light source utilizing organic materials. In some embodiments, the light source 305 includes a monochromatic light source. In some embodiments, the light source 305 includes a multicolor light source. In some embodiments, the light source 305 includes a light source that emits light partially within the ultraviolet spectrum. In some embodiments, the light source 305 includes a device, product, or material that emits light partially within the visible spectrum. In some embodiments, the light source 305 is a device, product, or material that partially emits or emits light within the infrared spectrum. In some embodiments, the light source 305 includes a device, product, or material that emits or emits light within the visible spectrum. In some embodiments, the light source 305 includes an optical guide, optical fiber, or waveguide through which light is emitted from the light source.

[0124] In some embodiments, the light source 305 includes one or more mirrors for reflecting or redirecting light. For example, the mirrors can reflect or redirect light toward the direct field of view 310 or 320, or the peripheral field of view 315 or 325. The light source 305 may include interaction with microelectromechanical devices ("MEMS"). The light source 305 may include or interact with a digital light projector ("DLP"). In some embodiments, the light source 305 may include ambient light or sunlight. The ambient light or sunlight can be focused by one or more optical lenses and directed toward the direct field of view or the peripheral field of view. The ambient light or sunlight can be directed toward the direct field of view or the peripheral field of view by one or more mirrors.

[0125] When the light source is ambient light, the ambient light is not localized, but it can enter the eye through the direct or peripheral field of vision. In some embodiments, the light source 305 can be positioned to direct light pulses into the direct or peripheral field of vision. For example, one or more light sources 305 can be mounted, fixed, coupled, mechanically coupled, or otherwise provided on the frame 400 as shown in Figure 4A. In some embodiments, the visual signal transmission component 150 may include the frame 400. Further details of the operation of the NSS 105 in relation to the frame 400 including one or more light sources 305 are provided below in a section titled “NSS Operating with the Frame”. For this purpose, the light source can include any type of light source, such as an optical light source, a mechanical light source, or a chemical light source. The light source can include any reflective or opaque material or object that can generate, emit, or reflect patterns of light vibration, such as a fan or bubble rotating in front of the light. In some embodiments, the light source can include invisible optical illusions, physiological phenomena in the eye (e.g., eye pressure), or chemicals applied to the eye.

[0126] In some embodiments, visual gamma-oscillating stimuli can be used to induce neural stimulation. Figure 28 shows output changes in response to a 40Hz LED stimulus (over 1 hour) in an exemplary embodiment demonstrating 40Hz steady-state oscillation and alpha output enhancement during and after stimulation in a healthy young subject. Both panels show time-frequency domain resolution of EEG activity recorded across the occipital pole (Oz, channel-64) before, during, and after 40Hz stimulation induced by gamma oscillation. The start and stop of the 40Hz stimulation are marked at the STIM ON and STIM OFF boundaries in both panels. The upper panel shows the 40Hz output enhanced during stimulation, indicating steady-state visual evoked potentials (SSVEPs). The lower panel shows alpha output dynamics during the open-eye (EYO) and closed-eye (EYC) states, as well as the alpha output enhanced during the open-eye 40Hz stimulation and 1 hour after induced 40Hz stimulation by gamma oscillation.

[0127] Systems and devices configured for neural stimulation using visual stimuli Referring here to Figure 4A, the frame 400 can be designed and constructed to be placed or positioned on an individual's head. The frame 400 can be configured to be worn by the individual. The frame 400 can be designed and constructed to remain in place. Once worn, the frame 400 can be configured to remain in place when the individual sits, stands, walks, runs, or lies down. A light source 305 can be configured on the frame 400 to project light pulses toward the individual's eyes while in these various positions. In some embodiments, the light source 305 can be configured to project light pulses toward the individual's eyes when the eyelids are closed, so that the light pulses penetrate the eyelids and are perceived by the retina. The frame 400 may include a bridge 420. The frame 400 may include one or more eye wires 415 coupled to the bridge 420. The bridge 420 may be positioned between the eye wires 415. The frame 400 may include one or more temples extending from one or more eye wires 415. In some embodiments, the eye wire 415 may include or hold a lens 425. In some embodiments, the eye wire 415 may include or hold a solid material 425 or a cover 425. The lens, solid material, or cover 425 may be transparent, translucent, opaque, or completely block external light.

[0128] One or more light sources 305 can be positioned on or adjacent to the eye wire 415, lens or other solid material 425, or bridge 420. For example, a light source 305 can be positioned in the center of the eye wire 415 on the solid material 425 to transmit light pulses directly into the field of view. In some embodiments, a light source 305 can be positioned at a corner of the eye wire 415, such as the corner of the eye wire 415 connected to the temple 410, to transmit light pulses toward the peripheral field.

[0129] The NSS105 can perform visual stimulation induction of neural oscillatory through one or both eyes. For example, the NSS105 can direct light pulses to one or both eyes. The NSS105 can interface with a visual signal transmission component 150 which includes a frame 400 and two eye wires 415. However, the visual signal transmission component 150 may include a single light source 305 configured and positioned to direct light pulses to the first eye. The visual signal transmission component 150 may further include a light blocking component that prevents or blocks light pulses generated from the light source 305 from entering the second eye. The visual signal transmission component 150 can block or prevent light from entering the second eye during sensory induction of neural oscillatory.

[0130] In some embodiments, the visual signal transmission component 150 can alternatively transmit or direct light pulses to a first eye and a second eye. For example, the visual signal transmission component 150 can direct light pulses to the first eye over a first time interval. The visual signal transmission component 150 can direct light pulses to the second eye over a second time interval. The first and second time intervals can be the same time interval, overlapping time intervals, mutually exclusive time intervals, or successive time intervals.

[0131] Figure 4B shows a frame 400 with a pair of shutters 435 that can block at least a portion of the light entering through the eye wire 415. The pair of shutters 435 can intermittently block ambient light or sunlight entering through the eye wire 415. The pair of shutters 435 can open to allow light to enter through the eye wire 415 and close to block at least a portion of the light entering through the eye wire 415. Further details of the operation of the NSS 105 in relation to the frame 400 including one or more shutters 430 are provided below in a section titled “NSS in Operation with the Frame”.

[0132] A set of shutters 435 may include one or more shutters 430 that are opened and closed by one or more actuators. The shutters 430 may be formed from one or more materials. The shutters 430 may include, or be formed from, a material capable of blocking or attenuating light at least partially.

[0133] The frame 400 may include one or more actuators configured to open or close a set of shutters 435 or individual shutters 430 at least partially. The frame 400 may include one or more types of actuators for opening and closing the shutters 435. For example, the actuator may include a mechanically driven actuator. The actuator may include a magnetically driven actuator. The actuator may include a pneumatic actuator. The actuator may include a hydraulic actuator. The actuator may include a piezoelectric actuator. The actuator may include a micro-electromechanical system ("MEMS").

[0134] A set of shutters 435 may include one or more shutters 430 that are opened and closed by electrical or chemical techniques. For example, a shutter 430 or a set of shutters 435 may be formed from one or more chemical substances. A shutter 430 or a set of shutters may include, or be formed from, a chemical substance capable of blocking or attenuating light at least partially.

[0135] For example, shutter 430 or a pair of shutters 435 may include a photochromic lens configured to filter, attenuate, or block light. The photochromic lens may automatically darken when exposed to sunlight. The photochromic lens may include a molecule configured to darken the lens. This molecule may be activated by light waves such as ultraviolet light or other light wavelengths. For this reason, the photochromic molecule may be configured to darken the lens in response to a given light wavelength.

[0136] The shutter 430 or a pair of shutters 435 may include electrochromic glass or plastic. The electrochromic glass or plastic can change from a light state to a dark state (e.g., transparent to opaque) in response to a voltage or current. The electrochromic glass or plastic may include a metal oxide coating deposited on the glass or plastic, multiple layers, and lithium ions moving between two electrodes between the layers to lighten or darken the glass.

[0137] A shutter 430 or a pair of shutters 435 may include microshutters. Microshutters may include small windows measuring 100 × 200 microns. Microshutters may be arranged within the eye frame 415 in a waffle grid. Individual microshutters may be opened and closed by actuators. Actuators may include magnetic arms that pass through the microshutters to open and close them. An open microshutter can allow light to enter through the eye frame 415, while a closed microshutter can block, attenuate, or filter light.

[0138] The NSS105 can drive an actuator to open and close one or more shutters 430 or a pair of shutters 435 at a predetermined frequency, such as 40 Hz. By opening and closing the shutters 430 at a predetermined frequency, the shutters 430 can allow a flash of light to pass through the eye wire 415 at that frequency. For this reason, a frame 400 containing a pair of shutters 435 may or may not include or use a separate light source coupled to the frame 400, such as the light source 305 coupled to the frame 400 shown in Figure 4A.

[0139] In some embodiments, the visual signal transmission component 150 or light source 305 may point to or be included in the virtual reality headset 401, as shown in Figure 4C. For example, the virtual reality headset 401 may be designed and constructed to house the light source 305. The light source 305 may include a computing device having a display device, such as a smartphone or mobile communication device. The virtual reality headset 401 may include a cover 440 that opens to house the light source 305. The cover 440 can be closed to lock or hold the light source 305 in place. When closed, the cover 440, case 450, and 445 can form a housing for the light source 305. This housing can provide an immersive experience that minimizes or eliminates unwanted visual distractions. The virtual reality headset can provide an environment that maximizes sensory induction of neurovibrations. The virtual reality headset can provide an augmented reality experience. In some embodiments, the light source 305 can project an image onto another surface so that the image is reflected from the surface and directed towards the target's eye (for example, a head-up display that overlays a flashing object or an augmented portion of reality onto a screen). Further details of the operation of the NSS 105 in conjunction with the virtual reality headset 401 are provided below in the section titled "Systems and Devices Configured for Neural Stimulation by Visual Stimuli".

[0140] The virtual reality headset 401 includes straps 455 and 460 configured to secure the virtual reality headset 401 to an individual's head. The virtual reality headset 401 may be secured by straps 455 and 460 to minimize movement of the headset 401 when worn during physical activities such as walking or running. The virtual reality headset 401 may include a skull cap formed from 460 or 455.

[0141] The feedback sensor 605 may include an electrode, a dry electrode, a gel electrode, a saline-immersed electrode, or an adhesive-based electrode.

[0142] Figures 5A to 5D show embodiments of a visual signal transmission component 150, which may include a tablet computing device 500 or other computing device 500 having a display screen 305 as a light source 305. The visual signal transmission component 150 can transmit light pulses, light flashes, or light patterns via the display screen 305 or the light source 305.

[0143] Figure 5A shows a display screen 305 or light source 305 that transmits light. The light source 305 can transmit light containing wavelengths of the visible spectrum. The NSS 105 can instruct the visual signal transmission component 150 to transmit light through the light source 305. The NSS 105 can instruct the visual signal transmission component 150 to transmit flashes or pulses of light having a predetermined pulse rate interval. For example, Figure 5B shows the light source 305 being turned off or disabled so that it emits no light or only a minimal or small amount of light. The visual signal transmission component 150 can cause the tablet computing device 500 to enable (e.g., Figure 5A) or disable (e.g., Figure 5B) the light source 305 so that the flashes of light have a predetermined frequency, such as 40 Hz. The visual signal transmission component 150 can generate flashes or pulses of light having a predetermined frequency by switching the light source 305 between two or more states.

[0144] In some embodiments, the light generation module 110 can instruct or cause the visual signal transmission component 150 to display a pattern of light via the display device 305 or light source 305, as shown in Figures 5C and 5D. The light generation module 110 can generate a flash of light or a pulse of light by causing the visual signal transmission component 150 to blink, switch, or toggle between two or more patterns. Examples of patterns include alternating checkerboard patterns 510 and 515. Patterns may include symbols, characters, or images that can be switched or adjusted from one state to another. For example, the color of a character or text can be inverted against a background color to create a switch between a first state 510 and a second state 515. A pulse of light can be generated by inverting the foreground and background colors at a predetermined frequency to show a visual change that facilitates the adjustment or control of the frequency of nerve oscillations. Further details of the operation of the NSS 105 in relation to the tablet 500 are provided below in a section titled “NSS Operating with a Tablet”.

[0145] In some embodiments, the photogenerating module 110 can instruct or cause the visual signaling component 150 to flash, switch, or toggle images configured to stimulate specific or predetermined parts of the brain or a particular cortex. The presentation, form, color, motion, and other aspects of the light or image-based stimulus can determine which cortex is mobilized to process the stimulus. The visual signaling component 150 can target specific or whole regions of interest by stimulating distinct parts of the cortex by modulating the presentation of the stimulus. The relative position in the visual field, the color of the input, or the motion and speed of the light stimulus can determine which areas of the cortex are stimulated.

[0146] For example, the brain may contain at least two parts that process a given type of visual stimulus: the primary visual cortex on the left side of the brain and the calcaneal sulcus on the right side. Each of these two parts may have one or more subparts that process a given type of visual stimulus. For example, the calcaneal sulcus may contain a subpart called area V5, which may contain neurons that respond strongly to motion but do not register stationary objects. A subject with damage to area V5 may have motor blindness but otherwise may have normal vision. In another example, the primary visual cortex may contain a subpart called area V4, which may contain neurons specialized in color perception. A subject with damage to area V4 may have color blindness and may only perceive objects in shades of gray. In yet another example, the primary visual cortex may contain a subpart called area VI, which may contain neurons that respond strongly to contrast edges and help separate images into distinct objects.

[0147] Therefore, the photogenerating module 110 can instruct or cause the visual signaling component 150 to form a type of still image or video, generate flicker, or switch between images configured to stimulate a specific or predetermined part of the brain or a particular cortex. For example, the photogenerating module 110 can instruct or cause the visual signaling component 150 to generate an image of a human face to stimulate a spindle-shaped facial region, thereby facilitating the sensory induction of neural oscillations for subjects with prosopagnosia or facial recognition impairment. The photogenerating module 110 can instruct or cause the visual signaling component 150 to generate a flickering image of a face to target this region of the subject's brain. In another example, the photogenerating module 110 can instruct the visual signaling component 150 to generate an image containing edges or line drawings to stimulate neurons in the primary visual cortex that respond strongly to contrast edges.

[0148] NSS105 may include, access, interface with, or otherwise communicate with at least one optical adjustment module 115. The optical adjustment module 115 may be designed and built to measure or verify environment variables (e.g., light intensity, timing, incident light, ambient light, eyelid state, etc.) to adjust parameters related to the visual signal, such as frequency, amplitude, wavelength, intensity pattern, or other parameters of the visual signal. The optical adjustment module 115 may automatically vary the parameters of the visual signal based on profile information or feedback. The optical adjustment module 115 may receive feedback information from the feedback monitor 135. The optical adjustment module 115 may receive commands or information from the side effect management module 130. The optical adjustment module 115 may receive profile information from the profile manager 125.

[0149] The NSS105 includes, accesses, interfaces with, or otherwise communicates with at least one unwanted frequency filtering module 120. The unwanted frequency filtering module 120 may be designed and constructed to block, mitigate, reduce, or otherwise remove frequencies of visual signals that are undesirable in order to prevent or reduce the amount of such visual signals perceived by the brain. The unwanted frequency filtering module 120 may interface with, command, control, or otherwise communicate with the filtering component 155 to cause the filtering component 155 to block, attenuate, or reduce the effect of unwanted frequencies on nerve oscillations.

[0150] The NSS105 may include, access, interface with, or otherwise communicate with at least one profile manager 125. The profile manager 125 may be designed or constructed to store, update, retrieve, or otherwise manage information relating to one or more subjects related to visual stimulus-induced nerve vibration. The profile information may include, for example, treatment history information, nerve vibration sensory induction history information, medication information, light wave parameters, feedback, physiological information, environmental information, or other data relating to the system and method of nerve vibration sensory induction.

[0151] The NSS105 includes, can access, interface with, or otherwise communicate with at least one adverse event management module 130. The adverse event management module 130 may be designed and constructed to provide information to the light adjustment module 115 or the light generation module 110 to modify one or more parameters of the visual signal in order to reduce adverse events. Adverse events may include, for example, nausea, migraine, fatigue, seizures, eye strain, or vision loss.

[0152] The adverse event management module 130 can automatically instruct the components of the NSS 105 to modify or change the parameters of the visual signal. The adverse event management module 130 can be configured to reduce adverse events at a predetermined threshold. For example, the adverse event management module 130 can be configured using the maximum duration of the pulse train, the maximum intensity and amplitude of the light wave, the maximum duty cycle of the pulse train (e.g., pulse width multiplied by the frequency of the pulse train), and the maximum number of treatments in sensory induction of nerve oscillations over a period of time (e.g., 1 hour, 2 hours, 12 hours, or 24 hours).

[0153] The adverse event management module 130 can cause changes in the parameters of the visual signal in response to feedback information. The adverse event management module 130 can receive feedback from the feedback monitor 135. The adverse event management module 130 can decide to adjust the parameters of the visual signal based on the feedback. The adverse event management module 130 can decide to adjust the parameters of the visual signal by comparing the feedback with a threshold.

[0154] The adverse event management module 130 may consist of, or include, a policy engine that applies policies or rules to the current visual signal and feedback to determine adjustments to the visual signal. For example, if feedback indicates that the heart rate or pulse rate of the patient receiving the visual signal is above a threshold, the adverse event management module 130 may turn off the pulse train until the pulse rate stabilizes and falls below the threshold, or below a second threshold below the threshold.

[0155] The NSS105 may include, access, interface with, or otherwise communicate with at least one feedback monitor 135. The feedback monitor may be designed and constructed to receive feedback information from a feedback component 160. The feedback component 160 may include, for example, a feedback sensor 605 such as a temperature sensor, a heart rate or pulse rate monitor, a physiological sensor, an ambient light sensor, an ambient temperature sensor, a sleep state via actigraphy, a blood pressure monitor, a respiratory rate monitor, an electroencephalogram ("EOG") probe configured to measure the corneal retinal standing potential present between the anterior and posterior segments of the human eye, an accelerometer, a gyroscope, a motion detector, a proximity sensor, a camera, a microphone, or a photodetector.

[0156] In some embodiments, the computing device 500 may include a feedback component 160 or a feedback sensor 605, as shown in Figures 5C and 5D. For example, the feedback sensor on the tablet 500 may include a front-facing camera capable of capturing an image of an individual viewing the light source 305.

[0157] Figure 6A shows one or more feedback sensors 605 mounted on the frame 400. In some embodiments, the frame 400 may include one or more feedback sensors 605 mounted on a portion of the frame, such as part of the bridge 420 or the eye wire 415. The feedback sensors 605 may be mounted on or coupled to the light source 305. The feedback sensors 605 may be separated from the light source 305.

[0158] The feedback sensor 605 can interact with or communicate with the NSS 105. For example, the feedback sensor 605 can provide detected feedback information or data to the NSS 105 (e.g., the feedback monitor 135). The feedback sensor 605 can provide data to the NSS 105 in real time, for example, when the feedback sensor 605 detects or senses information. The feedback sensor 605 can provide feedback information to the NSS 105 based on time intervals such as 1 minute, 2 minutes, 5 minutes, 10 minutes, 1 hour, 2 hours, 4 hours, 12 hours, or 24 hours. The feedback sensor 605 can provide feedback information to the NSS 105 in response to conditions or events such as feedback measurements exceeding or falling below a threshold. The feedback sensor 605 can provide feedback information in response to changes in feedback parameters. In some embodiments, the NSS 105 can ping, query, or send requests for information to the feedback sensor 605, and the feedback sensor 605 can provide feedback information in response to the ping, request, or query.

[0159] Figure 6B shows a feedback sensor 605 positioned on or near an individual's head. The feedback sensor 605 may include, for example, an EEG probe for detecting electroencephalogram (EEG) activity.

[0160] The feedback monitor 135 can detect, receive, acquire, or otherwise identify feedback information from one or more feedback sensors 605. The feedback monitor 135 can provide the feedback information to one or more components of the NSS 105 for further processing or storage. For example, the profile manager 125 can update the profile data structure 145 stored in the data repository 140 using the feedback information. The profile manager 125 can associate the feedback information with an identifier for the patient or individual receiving visual brain stimulation, as well as a timestamp and date stamp corresponding to the reception or detection of the feedback information.

[0161] The feedback monitor 135 can determine the attention level. The attention level can refer to the focus given to the light pulse used for brain stimulation. The feedback monitor 135 can determine the attention level using various hardware and software technologies. The feedback monitor 135 can assign a score to the attention level (e.g., 1 to 10, where 1 is low attention, 10 is high attention, or vice versa; 1 to 100, where 1 is low attention, 100 is high attention, or vice versa; 0 to 1, where 0 is low attention, 1 is high attention, or vice versa), classify the attention level (e.g., low, moderate, high), grade the attention (e.g., A, B, C, D, or F), or otherwise provide an index of the attention level.

[0162] Depending on the circumstances, the feedback monitor 135 may track an individual's eye movements to determine their attention level. The feedback monitor 135 may interface with a feedback component 160, which may include an eye tracker. The feedback monitor 135 (e.g., via the feedback component 160) may detect and record an individual's eye movements and analyze the recorded eye movements to determine an attention span or attention level. The feedback monitor 135 may measure gaze directions that can display or provide information related to potential attention. For example, the feedback monitor 135 (e.g., via the feedback component 160) may be configured to measure skin potentials around the eyes using electrooculography ("EOG"), which can indicate the direction in which the eyes are facing relative to the head. In some embodiments, the EOG may include a system or device to stabilize the head so that it cannot move in order to determine the direction of the eyes relative to the head. In some embodiments, the EOG may include or interface with a head tracker system that determines the position of the head and then the direction of the eyes relative to the head.

[0163] In some embodiments, the feedback monitor 135 and feedback component 160 can determine or track eye direction or eye movement using video detection of pupil or corneal reflection. For example, the feedback component 160 may include one or more cameras or video cameras. The feedback component 160 may include an infrared source that transmits light pulses toward the eye. The light may be reflected by the eye. The feedback component 160 can detect the location of the reflection. The feedback component 160 can capture or record the location of the reflection. The feedback component 160 can determine or calculate eye direction or gaze direction by performing image processing on the reflection.

[0164] The feedback monitor 135 can determine the attention level by comparing the direction or movement of the eyes with the same individual's eye direction or movement history, nominal eye movement, or other eye movement history information. For example, if the eyes are focused on a light pulse during the pulse train, the feedback monitor 135 can determine that the attention level is high. If the feedback monitor 135 determines that the eyes have moved away from the pulse train for 25% of the pulse train, the feedback monitor 135 can determine that the attention level is moderate. If the feedback monitor 135 determines that eye movement occurred for more than 50% of the pulse train, or that the eyes were not focused on the pulse train for more than 50% of the pulse train, the feedback monitor 135 can determine that the attention level is low.

[0165] In some embodiments, the system 100 may include a filter (e.g., a filtering component 155) that controls the spectral range of light emitted from the light source. In some embodiments, the light source includes a polarizer, filter, prism, or photochromic material, or a photoreactive material that affects the emitted light, such as electrochromic glass or plastic. The filtering component 155 can receive commands from the unwanted frequency filtering module 120 to block or attenuate one or more frequencies of light.

[0166] The filtering component 155 may include an optical filter that can selectively transmit light of a specific range of wavelengths or colors while blocking one or more other ranges of wavelengths or colors. The optical filter can modify the magnitude or phase of the incident light wave in a certain wavelength range. The optical filter may include an absorption filter, or an interference or dichroic filter. An absorption filter can capture the energy of photons and convert the electromagnetic energy of the light wave into internal energy (e.g., thermal energy) of the absorber. The reduction in the intensity of a light wave propagating through a medium by absorbing some of the photons of the light wave may be called attenuation.

[0167] Interference filters or dichroic filters may include optical filters that transmit light in other spectral bands while reflecting light in one or more spectral bands. Interference filters or dichroic filters may have an absorption coefficient of nearly zero for one or more wavelengths. Interference filters may be high-pass, low-pass, band-pass, or band-stopping. Interference filters may include one or more thin layers of dielectric or metallic materials having varying refractive indices.

[0168] In an exemplary implementation, the NSS105 can interface with a visual signal transmission component 150, a filtering component 155, and a feedback component 160. The visual signal transmission component 150 may include hardware or devices such as a glass frame 400 and one or more light sources 305. The filtering component 155 may include hardware or devices such as a feedback sensor 605. The filtering component 155 may include hardware, materials, or chemicals such as a polarizing lens, shutter, electrochromic material, or photochromic material.

[0169] computing environment Figures 7A and 7B show block diagrams of computing devices 700. As shown in Figures 7A and 7B, each computing device 700 includes a central processing unit 721 and a main memory unit 722. As shown in Figure 7A, computing devices 700 may include a storage device 728, an installation device 716, a network interface 718, an I / O controller 723, display devices 724a-724n, a keyboard 726, and a pointing device 727, such as a mouse. The storage device 728 may include, but is not limited to, an operating system, software, and software for a neural stimulation system ("NSS") 701. NSS 701 may include or refer to one or more of NSS 105, NSS 905, or NSOS 1605. As shown in Figure 7B, each computing device 700 may also include additional optional elements, such as a memory port 703, a bridge 770, one or more input / output devices 730a-730n (collectively referred to by reference numeral 730), and a cache memory 740 that communicates with a central processing unit 721.

[0170] The central processing unit 721 is any logic circuit that responds to and processes instructions fetched from the main memory unit 722. In many embodiments, the central processing unit 721 is provided by a microprocessor unit, for example, an ARM processor from Intel Corporation (Mountain View, California), Motorola Corporation (Schaumburg, Illinois), or Nvidia (Santa Clara, California) (e.g., from ARM Holdings, and those manufactured by ST, TI, ATMEL, etc.), as well as a TEGRA system-on-a-chip (SoC) from Nvidia (Santa Clara, California), a POWER7 processor from International Business Machines (White Plains, New York), or from Advanced Micro Devices (Sunnyvale, California), or a field-programmable gate array ("FPGA") from Altera (San Jose, California), Intel Corporation, Xlinix (San Jose, California), or MicroSemi (Aliso Viejo, California), etc. The computing device 700 may be based on any of these processors, or any other processor capable of operating as described herein. The central processing unit 721 can utilize instruction-level parallelism, thread-level parallelism, various levels of caching, and multi-core processors. A multi-core processor can contain two or more processing units on a single computing component. Examples of multi-core processors include the AMD PHENOM IIX2, Intel Core i5, and Intel Core i7.

[0171] The main memory unit 722 may include one or more memory chips that store data and allow any storage location to be directly accessed by the microprocessor 721. The main memory unit 722 is volatile and may be faster than the memory of the storage 728. The main memory unit 722 can be any variation including dynamic random access memory (DRAM), static random access memory (SRAM), burst SRAM or sync-burst SRAM (BSRAM), fast page mode DRAM (FPM DRAM), extended DRAM (EDRAM), extended data output RAM (EDO RAM), extended data output DRAM (EDO DRAM), burst extended data output DRAM (BEDO DRAM), single data rate synchronous DRAM (SDR SDRAM), double data rate SDRAM (DDR SDRAM), direct rhombus DRAM (DRDRAM), or extreme data rate DRAM (XDR DRAM). In some embodiments, the main memory 722 or storage 728 may be non-volatile, such as non-volatile read-access memory (NVRAM), flash memory non-volatile static RAM (nvSRAM), ferroelectric RAM (FeRAM), magnetoresistive RAM (MRAM), phase-change memory (PRAM), conductive bridge RAM (CBRAM), silicon oxide-nitride-oxide-silicon (SONOS), resistive RAM (RRAM), racetrack, nanoRAM (NRAM), or millipede memory. The main memory 722 may be based on any of the memory chips described above, or any other available memory chip capable of operating as described herein. In the embodiment shown in Figure 7A, the processor 721 communicates with the main memory 722 via the system bus 750 (described in more detail below). Figure 7B shows an embodiment of a computing device 700 in which the processor communicates directly with the main memory 722 via a memory port 703. For example, in Figure 7B, the main memory 722 may be DRDRAM.

[0172] Figure 7B shows an embodiment in which the main processor 721 communicates directly with the cache memory 740 via a secondary bus, sometimes referred to as the backside bus. In other embodiments, the main processor 721 communicates with the cache memory 740 using the system bus 750. The cache memory 740 typically has a faster response time than the main memory 722 and is typically provided by SRAM, BSRAM, or EDRAM. In the embodiment shown in Figure 7B, the processor 721 communicates with various I / O devices 730 via the local system bus 750. The central processing unit 721 can be connected to any of the I / O devices 730 using various buses, including the PCI bus, PCI-X bus, PCI-Express bus, or NuBus. In embodiments where the I / O device is a video display 724, the processor 721 can communicate with the display 724 or the I / O controller 723 for the display 724 using an Advanced Graphics Port (AGP). Figure 7B shows an embodiment of computer 700 in which the main processor 721 communicates directly with I / O device 730b or other processor 721' via HYPERTRANSPORT, RAPIDIO, or INFINIBAND communication technology. Figure 7B also shows an embodiment in which local bus and direct communication are mixed, in which processor 721 communicates directly with I / O device 730b while communicating with I / O device 730a using the local interconnect bus.

[0173] Computing device 700 can include a wide variety of I / O devices 730a to 730n. Input devices may include keyboards, mice, trackpads, trackballs, touchpads, touch mice, multi-touch touchpads and touch mice, microphones (analog or MEMS), multi-array microphones, drawing tablets, cameras, single-lens reflex cameras (SLRs), digital SLRs (DSLRs), CMOS sensors, CCDs, accelerometers, inertial measurement units, infrared optical sensors, pressure sensors, magnetometers, angular velocity sensors, depth sensors, proximity sensors, ambient light sensors, gyroscopes, or other sensors. Output devices may include video displays, graphical displays, speakers, headphones, inkjet printers, laser printers, and 3D printers.

[0174] Devices 730a–730n may include combinations of multiple input / output devices, such as Microsoft Kinect, Nintendo Wiimote for the Wii, Nintendo Wii U GamePad, or Apple iPhone®. Some devices 730a–730n enable gesture recognition input by combining some of the inputs and outputs. Some devices 730a–730n provide facial recognition that can be used as input for various purposes, including authentication and other commands. Some devices 730a–730n provide voice recognition and input, such as Microsoft Kinect, Siri for Apple iPhone®, Google Now, or Google Voice Search.

[0175] Additional devices 730a–730n have both input and output capabilities, including, for example, haptic feedback devices, touchscreen displays, or multi-touch displays. Touchscreens, multi-touch displays, touchpads, touch mice, or other touch-sensing devices can use a variety of touch-sensing technologies, including, for example, capacitive, surface capacitive, projected capacitive touch (PCT), in-cell capacitive, resistive, infrared, waveguide, dispersed signal touch (DST), in-cell optics, surface acoustic wave (SAW), bent wave touch (BWT), or force-based sensing technologies. Some multi-touch devices allow for two or more contact points with a surface, enabling advanced functionality, such as pinching, spreading, rotating, scrolling, or other gestures. Some touchscreen devices, such as Microsoft PIXELSENSE or Multi-Touch Collaboration Wall, can have larger surfaces, such as on a tabletop or wall, and can also interact with other electronic devices. Some I / O devices 730a-730n, display devices 724a-724n, or a collection of devices can be an augmented reality device. The I / O devices can be controlled by an I / O controller 721, as shown in Figure 7A. The I / O controller 721 can control one or more I / O devices, such as a keyboard 126 and a pointing device 727, such as a mouse or optical pen. Furthermore, the I / O devices can also provide storage and / or installation media 116 for the computing device 700. In yet another embodiment, the computing device 700 can provide a USB connection (not shown) for housing a handheld USB storage device. In a further embodiment, the I / O device 730 can be a bridge between the system bus 750 and an external communication bus, such as a USB bus, SCSI bus, FireWire bus, Ethernet bus, Gigabit Ethernet bus, Fibre Channel bus, or Thunderbolt bus.

[0176] In some embodiments, the display devices 724a to 724n can be connected to the I / O controller 721. Examples of display devices include liquid crystal displays (LCDs), thin-film transistor LCDs (TFT-LCDs), blue-phase LCDs, e-ink displays, flexible displays, light-emitting diode displays (LEDs), digital light-processing (DLP) displays, liquid crystal on silicon (LCOS) displays, organic light-emitting diode (OLED) displays, active-matrix organic light-emitting diode (AMOLED) displays, liquid crystal laser displays, time-multiplexed optical shutter (TMOS) displays, or 3D displays. Examples of 3D displays may utilize, for example, stereoscopic viewing, polarizing filters, active shutters, or automatic stereoscopic viewing. The display devices 724a to 724n can also be head-mounted displays (HMDs). In some embodiments, the display devices 724a to 724n or the corresponding I / O controller 723 may be controlled via the OPENGL or DIRECTX API or other graphics libraries, or may have hardware support for them.

[0177] In some embodiments, the computing device 700 may include or connect to a plurality of display devices 724a-724n, each of which may be of the same or different types and / or forms. Therefore, either the I / O devices 730a-730n and / or the I / O controller 723 may include any type and / or form of suitable hardware, software, or combination of hardware and software that supports, enables, or provides the connection and use of the plurality of display devices 724a-724n by the computing device 700. For example, the computing device 700 may include any type and / or form of video adapters, video cards, drivers, and / or libraries that interface, communicate, connect, or otherwise use the display devices 724a-724n. In one embodiment, the video adapter may include multiple connectors that interface to the plurality of display devices 724a-724n. In other embodiments, the computing device 700 may include multiple video adapters, each video adapter connected to one or more of the display devices 724a-724n. In some embodiments, any part of the operating system of the computing device 700 can be configured to use a plurality of displays 724a to 724n. In other embodiments, one or more of the display devices 724a to 724n can be provided by one or more other computing devices 700a or 700b connected to the computing device 700 via the network 140. In some embodiments, the software can be designed and constructed to use the display device of another computer as a second display device 724a for the computing device 700. For example, in one embodiment, an Apple iPad® can be connected to the computing device 700 and can use the display of the device 700 as an additional display screen that can be used as an extended desktop.

[0178] Referring again to Figure 7A, the computing device 700 may include storage devices 728 (e.g., one or more hard disk drives or redundant arrays of independent disks) for storing the operating system or other related software, and application software programs such as any programs related to the software for NSS. Examples of storage devices 728 include, for example, hard disk drives (HDDs), optical drives (including CD drives, DVD drives, or Blu-ray drives), solid-state drives (SSDs), USB flash drives, or any other devices suitable for storing data. Some storage devices may include multiple volatile and non-volatile memories, such as a solid-state hybrid drive that combines a hard disk with a solid-state cache. Some storage devices 728 may be non-volatile, modifiable, or read-only. Some storage devices 728 may be internal and connected to the computing device 700 via the bus 750. Some storage devices 728 may be external and connected to the computing device 700 via an I / O device 730 providing an external bus. Some storage devices 728 can connect to computing devices 700 via a network interface 718 over a network, for example, including a remote disk for Apple's MacBook Air. Some client devices 700 do not require non-volatile storage devices 728 and can be thin clients or zero clients 202. Some storage devices 728 can also be used as installation devices 716 and may be suitable for installing software and programs. In addition, the operating system and software can be run from bootable media, for example, a bootable CD, such as KNOPPIX, a bootable CD for GNU / Linux® available as a GNU / Linux® distribution from KNOPPIX.net.

[0179] Computing device 700 can also install software or applications from application distribution platforms. Examples of application distribution platforms include the App Store for iOS, provided by Apple, Inc.; the Mac App Store, also provided by Apple, Inc.; Google Play for Android OS, provided by Google Inc.; the Chrome Webstore for Chrome OS, provided by Google Inc.; and the Amazon Appstore for Android OS and Kindle Fire, provided by Amazon.com, Inc.

[0180] Furthermore, the computing device 700 may include a network interface 718 for interface connection to the network 140 through various connections, including but not limited to standard telephone line LAN or WAN links (e.g., 802.11, T1, T3, Gigabit Ethernet, Infiniband), broadband connections (e.g., optical fiber including ISDN, Frame Relay, ATM, Gigabit Ethernet, Ethernet-over-SONET, ADSL, VDSL, BPON, GPON, FiOS), wireless connections, or any combination of any or all of the above. Connections can be established using various communication protocols (e.g., TCP / IP, Ethernet, ARCNET, SONET, SDH, Fiber Distributed Data Interface (FDDI), IEEE 802.11a / b / g / n / ac CDMA, GSM, WiMax, and direct asynchronous connections). In one embodiment, computing device 700 communicates with other computing devices 700' via any type and / or form of gateway or tunneling protocol, such as Secure Sockets Layer (SSL) or Transport Layer Security (TLS), or the Citrix Gateway protocol from Citrix Systems, Inc. (Fort Lauderdale, Florida). The network interface 118 may comprise an internal network adapter, a network interface card, a PCMCIA network card, an Expresscard network card, a Cardbus network adapter, a wireless network adapter, a USB network adapter, a modem, or any other device suitable for interface computing device 700 to any type of network capable of communication and performing the operations described herein.

[0181] The type of computing device 700 shown in Figure 7A can operate under the control of an operating system that controls task scheduling and access to system resources. The computing device 700 can run any operating system, including any version of the MICROSOFT WINDOWS® operating system, various releases of the Unix and Linux® operating systems, any version of MAC OS® for Macintosh computers, any embedded operating system, any real-time operating system, any open-source operating system, any proprietary operating system, any operating system for mobile computing devices, or any other operating system capable of running on the computing device and performing the operations described herein. Typical operating systems include, but are not limited to, Windows® 7000, Windows® Server 2012, Windows® CE, Windows® Phone, Windows® XP, Windows® Vista, and Windows® 7, Windows® RT, and Windows® 8 (all manufactured by Microsoft Corporation (Redmond, Washington)), Mac OS® and iOS manufactured by Apple, Inc. (Cupertino, California), and Linux®, such as the Linux® Mint distribution ("distro") or Ubuntu sold by Canonical Ltd. (London, UK), or Unix or other Unix-like derivative operating systems, as well as Android designed by Google (Mountain View, California).For example, some operating systems, including Google's Chrome OS, can be used on zero clients or thin clients, such as Chromebooks.

[0182] The computer system 700 can be any workstation, telephone, desktop computer, laptop or notebook computer, netbook, ultrabook, tablet, server, handheld computer, mobile phone, smartphone or other portable telecommunications device, media playback device, game system, mobile computing device, or any other type and / or form of computing, telecommunications, or media device capable of communication. The computer system 700 has sufficient processor power and memory capacity to perform the operations described herein. In some embodiments, the computing device 700 may have various processors, operating systems, and input devices compatible with the device. For example, the Samsung GALAXY smartphone operates under the control of the Android operating system developed by Google, Inc. The GALAXY smartphone receives input via a touch interface.

[0183] In some embodiments, the computing device 700 is a game system. For example, the computer system 700 may include a PLAYSTATION 3, or PERSONAL PLAYSTATION PORTABLE (PSP), or a PLAYSTATION VITA device manufactured by SONY (Tokyo), a Nintendo DS, Nintendo 3DS, Nintendo Wii, or Nintendo Wii U device manufactured by Nintendo Co., Ltd. (Kyoto, Japan), an XBOX® 360 device manufactured by Microsoft Corporation (Redmond, Washington), or an OCULUS RIFT or OCULUS VR device manufactured by BY OCULUS VR, LLC (Menlo Park, California).

[0184] In some embodiments, the computing device 700 is a digital audio player such as the Apple iPod, iPod Touch, and iPod Nano line of devices manufactured by Apple Computer (Cupertino, California). Some digital audio players may have other functions, including, for example, any functionality made available by a game system or an application from a digital application distribution platform. For example, the iPod Touch may have access to the Apple App Store. In some embodiments, the computing device 700 is a portable media player or digital audio player that supports file formats including, but not limited to, MP3, WAV, M4A / AAC, WMA Protected AAC, AIFF, Audible audiobook, Apple Lossless audio file format, and .mov, .m4v, and .MP4 MPEG-4 (H.264 / MPEG-4 AVC) video file format.

[0185] In some embodiments, the computing device 700 is a tablet, for example, Apple's iPad line of devices, Samsung's GALAXY TAB family of devices, or Amazon.com, Inc.'s (Seattle, Washington) Kindle Fire. In other embodiments, the computing device 700 is an eBook reader, for example, Amazon.com's Kindle family of devices, or Barnes & Noble, Inc.'s (New York, New York) NOOK family of devices.

[0186] In some embodiments, the communication device 700 includes a combination of devices, such as a smartphone combined with a digital audio player or portable media player. For example, one of these embodiments is a smartphone, such as the iPhone® family of smartphones from Apple, Inc., the Samsung Galaxy family of smartphones from Samsung, Inc., or the Motorola DROID family of smartphones. In another embodiment, the communication device 700 is a laptop or desktop computer equipped with a web browser and a microphone and speaker system, such as a telephone headset. In these embodiments, the communication device 700 is web-enabled and can receive and initiate telephone calls. In some embodiments, the laptop or desktop computer is also equipped with a webcam or other video capture device that enables video chat and video calls.

[0187] In some embodiments, the status of one or more machines 700 in the network is generally monitored as part of network management. In one of these embodiments, the status of a machine may include identification of load information (e.g., the number of processes, CPUs, and memory utilization on the machine), port information (e.g., the number of available communication ports and port addresses), or session status (e.g., the duration and type of a process, and whether the process is active or idle). In another embodiment of these embodiments, this information may be identified by multiple metrics, which can be applied at least partially to decisions in load balancing, network traffic management, and network fault recovery, as well as to all aspects of the operation of the solutions described herein. The above-described operating environments and component configurations will become apparent in the context of the systems and methods disclosed herein.

[0188] Methods for nerve stimulation Figure 8 is a flowchart of a method for inducing visual stimulation of neural oscillations according to one embodiment. Method 800 can be carried out by one or more systems, components, modules, or elements shown in Figures 1 to 7B, for example, a neural stimulation system (NSS). In a brief overview, the NSS can identify the visual signals provided in block 805. In block 810, the NSS can generate and transmit the identified visual signals. In 815, the NSS can receive or determine feedback related to neural activity, physiological activity, environmental parameters, or device parameters. In 820, the NSS can manage, control, or adjust the visual signals based on the feedback.

[0189] NSS that works with frames The NSS105 can operate with a frame 400 including a light source 305, as shown in Figure 4A. The NSS105 can operate with a frame 400 including a light source 30 and a feedback sensor 605, as shown in Figure 6A. The NSS105 can operate with a frame 400 including at least one shutter 430, as shown in Figure 4B. The NSS105 can operate with a frame 400 including at least one shutter 430 and a feedback sensor 605.

[0190] During operation, the user of frame 400 can wear frame 400 on their head so that the eye wires 415 surround or substantially surround their eyes. Optionally, the user can give instructions to NSS 105 that the glass frame 400 is fitted and that the user is ready to receive sensory induction of neural vibrations. This instruction may include commands, selections, inputs, or other instructions via an input / output interface such as a keyboard 726, a pointing device 727, or other I / O devices 730a-n. The instructions may be motion-based, visual, or voice-based. For example, the user may give a voice command indicating that the user is ready to receive sensory induction of electroencephalogram vibrations.

[0191] Depending on the circumstances, the feedback sensor 605 may determine that the user is ready to receive neurovibrational sensory induction. The feedback sensor 605 may detect that the glass frame 400 is positioned on the user's head. The NSS 105 may determine that the frame 400 is positioned on the user's head by receiving motion data, acceleration data, gyroscope data, temperature data, or capacitive touch data. Received data, such as motion data, may indicate that the frame 400 has been picked up and positioned on the user's head. Temperature data may measure the temperature of the frame 400 or its vicinity, which may indicate that the frame is on the user's head. Depending on the circumstances, the feedback sensor 605 may perform eye-tracking to determine the level of attention the user is paying to the light source 305 or the feedback sensor 605. In response to a determination that the user is paying a high level of attention to the light source 305 or the feedback sensor 605, the NSS 105 may detect that the user is ready. For example, looking, gazing at, or looking in the direction of the light source 305 or the feedback sensor 605 may indicate that the user is ready to receive neurovibrational sensory induction.

[0192] Thus, the NSS 105 can detect or determine that the frame 400 is attached and the user is ready, or the NSS 105 can receive instructions or confirmation from the user that the user has attached the frame 400 and is ready to receive sensory induction of neurovibration. Once it is determined that the user is ready, the NSS 105 can initialize the sensory induction of the neurovibration process. In some embodiments, the NSS 105 can access the profile data structure 145. For example, the profile manager 125 can query the profile data structure 145 to determine one or more parameters of the external visual stimulus used for sensory induction of the neurovibration process. Parameters may include, for example, the type of visual stimulus, the intensity of the visual stimulus, the frequency of the visual stimulus, the duration of the visual stimulus, or the wavelength of the visual stimulus. The profile manager 125 can query the profile data structure 145 to retrieve the sensory induction history of neurovibration information, such as past visual stimulus sessions. The profile manager 125 can perform a lookup in the profile data structure 145. Profile Manager 125 can perform lookups using username, user identifier, location information, fingerprint, biometric identifier, retinal scan, voice recognition and authentication, or other identification techniques.

[0193] The NSS105 can determine the type of external visual stimulus based on the hardware 400. The NSS105 can determine the type of external visual stimulus based on the type of available light source 305. For example, if the light source 305 includes a monochromatic LED that generates light waves of the red spectrum, the NSS105 can determine that the type of visual stimulus includes pulses of light transmitted by the light source. However, if the frame 400 does not include an active light source 305 but instead includes one or more shutters 430, the NSS105 can determine that the light source is sunlight or ambient light that will be modulated as it enters the user's eye through the plane formed by the eye wire 415.

[0194] In some embodiments, the NSS 105 can determine the type of external visual stimulus based on the sensory induction history of the neural oscillatory session. For example, the profile data structure 145 can be pre-configured using information about the type of visual signal transmission component 150.

[0195] The NSS105 can determine the modulation frequency of a pulse train or ambient light via the profile manager 125. For example, the NSS105 can determine from the profile data structure 145 that the modulation frequency for an external visual stimulus may be set to 40 Hz. Depending on the type of visual stimulus, the profile data structure 145 may further indicate the pulse length, intensity, wavelength of the light wave forming the light pulse, or duration of the pulse train.

[0196] Depending on the circumstances, the NSS105 can determine or adjust one or more parameters of an external visual stimulus. For example, the NSS105 (e.g., via the feedback component 160 or the feedback sensor 605) can determine the level or amount of ambient light. The NSS105 (e.g., via the light adjustment module 115 or the side effect management module 130) can establish, initialize, set, or adjust the intensity or wavelength of a light pulse. For example, the NSS105 can determine that a low level of ambient light is present. Due to the low level of ambient light, the user's pupils may dilate. Based on the detection of low-level ambient light, the NSS105 can determine that the user's pupils are likely to be dilated. In response to the determination that the user's pupils are likely to be dilated, the NSS105 can set a low intensity for the pulse train. The NSS105 can further use light waves with longer wavelengths (e.g., red) that can reduce distortion to the eye.

[0197] In some embodiments, the NSS 105 can monitor the ambient light level through sensory induction of the neurooscillating process (e.g., via the feedback monitor 135 and feedback component 160) to automatically and periodically adjust the intensity or color of the light pulse. For example, if the user initiates sensory induction of the neurooscillating process when a high level of ambient light is present, the NSS 105 can first set a higher intensity level for the light pulse and use a color (e.g., blue) that includes light waves with lower wavelengths. However, in some embodiments where the ambient light level decreases through sensory induction of the neurooscillating process, the NSS 105 can automatically detect the decrease in ambient light and, in response to this detection, increase the wavelength of the light wave while adjusting or decreasing the intensity. The NSS 105 can adjust the light pulse to provide a high contrast ratio and facilitate the induction of neurooscillating processes.

[0198] In some embodiments, the NSS105 (e.g., via the feedback monitor 135 and feedback component 160) can monitor or measure physiological conditions to set or adjust the parameters of the light wave. For example, the NSS105 can monitor or measure the level of pupil dilation to adjust or set the parameters of the light wave. In some embodiments, the NSS105 can monitor or measure heart rate, pulse rate, blood pressure, body temperature, sweating, or brain activity to set or adjust the parameters of the light wave.

[0199] In some embodiments, the NSS105 can be pre-configured to initially transmit an optical pulse with a minimum setting of optical intensity (e.g., a low-amplitude or high-wavelength optical wave) and gradually increase the intensity while monitoring feedback until an optimal optical intensity is reached (e.g., increasing the amplitude of the optical wave or decreasing the wavelength of the optical wave). The optimal optical intensity may refer to the highest intensity that does not result in adverse physiological side effects such as blindness, seizures, heart attacks, migraines, or other discomforts. The NSS105 (e.g., via the side effect management module 130) can monitor physiological symptoms to identify adverse side effects of external visual stimuli and adjust the external visual stimuli accordingly (e.g., via the optical adjustment module 115) to reduce or eliminate adverse side effects.

[0200] In some embodiments, the NSS105 (e.g., via the optical adjustment module 115) can adjust the parameters of the light wave or light pulse based on the level of attention. For example, during sensory induction of a neural oscillatory process, the user may become bored, lose focus, fall asleep, or otherwise fail to pay attention to the light pulse. Failure to pay attention to the light pulse reduces the effectiveness of sensory induction of the neural oscillatory process, and as a result, neurons may vibrate at a frequency different from the desired modulation frequency of the light pulse.

[0201] The NSS105 can detect the level of attention the user is paying to the light pulse using the feedback monitor 135 and one or more feedback components 160. The NSS105 can track the eyes and determine the level of attention the user is paying to the light pulse based on the direction of gaze of the retina or pupil. The NSS105 can measure eye movements to determine the level of attention the user is paying to the light pulse. The NSS105 can provide a survey or prompt to request user feedback indicating the level of attention the user is paying to the light pulse. In response to a determination that the user is not paying sufficient attention to the light pulse (e.g., the level of eye movement is greater than a threshold, or the line of sight is outside the direct field of view of the light source 305), the light adjustment module 115 can change the parameters of the light source to gain the user's attention. For example, the light adjustment module 115 can increase the intensity of the light pulse, adjust the color of the light pulse, or change the duration of the light pulse. The light adjustment module 115 can randomly change one or more parameters of the light pulse. The light adjustment module 115 can initiate an attention-seeking light sequence configured to restore the user's attention. For example, the light sequence may include changes in the color or intensity of light pulses in a predetermined, random, or pseudo-random pattern. If the visual signal transmission component 150 includes multiple light sources, the attention-seeking light sequence can enable or disable different light sources. In this way, the light adjustment module 115 can interact with the feedback monitor 135 to determine the level at which the user is paying attention to the light pulses, and if the level of attention falls below a threshold, it can adjust the light pulses to restore the user's attention.

[0202] In some embodiments, the light adjustment module 115 can change or adjust one or more parameters of a light pulse or light wave at predetermined time intervals (for example, every 5 minutes, every 10 minutes, every 15 minutes, or every 20 minutes) to restore or maintain the user's attention level.

[0203] In some embodiments, the NSS105 (e.g., via the unwanted frequency filtering module 120) can filter, block, attenuate, or remove unwanted visual stimuli. Unwanted visual stimuli may include, for example, unwanted modulation frequencies, unwanted intensities, or unwanted wavelengths of light waves. The NSS105 may consider a modulation frequency to be undesirable if the modulation frequency of a pulse train differs from or substantially differs from a desired frequency (e.g., by 1%, 2%, 5%, 10%, 15%, 20%, 25%, or more than 25%).

[0204] For example, a desirable modulation frequency for sensory induction of nerve vibrations may be 40 Hz. However, modulation frequencies of, for example, 15 Hz or 90 Hz may interfere with sensory induction of nerve vibrations. For this reason, the NSS105 can filter out optical pulses or light waves corresponding to modulation frequencies of 15 Hz or 90 Hz.

[0205] In some embodiments, the NSS 105 can detect, via the feedback component 160, the presence of light pulses from an ambient light source corresponding to an unwanted modulation frequency of 20 Hz. The NSS 105 can further determine the wavelength of the light wave of the light pulse corresponding to the unwanted modulation frequency. The NSS 105 can instruct the filtering component 155 to filter out the wavelength corresponding to the unwanted modulation frequency. For example, the wavelength corresponding to the unwanted modulation frequency may correspond to blue light. The filtering component 155 may include an optical filter that can selectively transmit light of a specific range of wavelengths or colors while blocking one or more other ranges of wavelengths or colors. The optical filter can modify the magnitude or phase of the incident light wave in a certain wavelength range. For example, the optical filter can be configured to block, reflect, or attenuate blue light waves corresponding to the unwanted modulation frequency. The light adjustment module 115 can modify the wavelength of the light waves generated by the light generation module 110 and the light source 305 so that a desired modulation frequency is not blocked or attenuated by the unwanted frequency filtering module 120.

[0206] NSS works with virtual reality headsets. The NSS105 can operate with a virtual reality headset 401 that includes a light source 305, as shown in Figure 4C. The NSS105 can operate with a virtual reality headset 401 that includes a light source 305 and a feedback sensor 605, as shown in Figure 4C. In some embodiments, the NSS105 can determine that the hardware of the visual signal transmission component 150 includes a virtual reality headset 401. In response to the determination that the visual signal transmission component 150 includes a virtual reality headset 401, the NSS105 can determine that the light source 305 includes a display screen of a smartphone or other mobile computing device.

[0207] The virtual reality headset 401 can provide an immersive and non-destructive visual stimulation experience. The virtual reality headset 401 can provide an augmented reality experience. The feedback sensor 605 can capture a photograph or video of the physical real world to provide an augmented reality experience. The unwanted frequency filtering module 120 can remove unwanted modulation frequencies before projecting, displaying, or providing augmented reality images via the display screen 305.

[0208] During operation, the user of frame 401 can wear frame 401 on their head so that the eye sockets 465 of the virtual reality headset cover the user's eyes. The eye sockets 465 of the virtual reality headset can surround or substantially surround the user's eyes. The user can secure the virtual reality headset 401 to their headset using one or more straps 455 or 460, a skull cap, or other fastening mechanisms. Optionally, the user can give instructions to NSS 105 indicating that the virtual reality headset 401 is positioned and secured on the user's head and that the user is ready to receive sensory induction of neurovibrations. These instructions may include commands, selections, inputs, or other instructions via an input / output interface such as a keyboard 726, a pointing device 727, or other I / O devices 730a-n. The instructions may be motion-based, visual, or voice-based. For example, the user may give a voice command indicating that the user is ready to receive sensory induction of neurovibrations.

[0209] Depending on the circumstances, the feedback sensor 605 may determine that the user is ready to receive sensory induction of neural vibration. The feedback sensor 605 may detect that the virtual reality headset 401 is positioned on the user's head. The NSS 105 may determine that the virtual reality headset 401 is positioned on the user's head by receiving motion data, acceleration data, gyroscope data, temperature data, or capacitive touch data. Received data, such as motion data, may indicate that the virtual reality headset 401 has been picked up and positioned on the user's head. Temperature data may measure the temperature of the virtual reality headset 401 or its vicinity, which may indicate that the virtual reality headset 401 is on top of the user's head. Depending on the circumstances, the feedback sensor 605 may perform eye-tracking to determine the level of attention the user is paying to the light source 305 or the feedback sensor 605. In response to a determination that the user is paying a high level of attention to the light source 305 or the feedback sensor 605, the NSS 105 may detect that the user is ready. For example, looking, gazing at, or seeing in the direction of the light source 305 or the feedback sensor 605 can signal that the user is ready to receive sensory induction of neural vibrations.

[0210] In some embodiments, a sensor 605 on strap 455, strap 460, or eye socket 605 can detect that the virtual reality headset 401 is secured, positioned, or located on the user's head. Sensor 605 may be a touch sensor that senses or detects touches on the user's head.

[0211] In this way, NSS105 can detect or determine that the virtual reality headset 401 is worn and the user is in a ready state, or NSS105 can receive an instruction or confirmation from the user that the user is wearing the virtual reality headset 401 and is ready to receive sensory induction of neural oscillations. When it is determined that the user is ready, NSS105 can initialize the sensory induction of the neural oscillation process. In some embodiments, NSS105 can access the profile data structure 145. For example, the profile manager 125 can query the profile data structure 145 to determine one or more parameters of the external visual stimuli used for the sensory induction of the neural oscillation process. The parameters can include, for example, the type of visual stimulus, the intensity of the visual stimulus, the frequency of the visual stimulus, the duration of the visual stimulus, or the wavelength of the visual stimulus. The profile manager 125 can query the profile data structure 145 to obtain a history of sensory-induced neural oscillation information such as past visual stimulus sessions. The profile manager 125 can perform a lookup in the profile data structure 145. The profile manager 125 can perform the lookup using the user name, user identifier, location information, fingerprint, biometric identifier, retinal scan, voice recognition and authentication, or other identification techniques.

[0212] NSS105 can determine the type of external visual stimulus based on the hardware 401. NSS105 can determine the type of external visual stimulus based on the type of available light source 305. For example, if the light source 305 includes a smartphone or a display device, the visual stimulus may include turning on and off the display screen of the display device. The visual stimulus may include displaying a pattern such as a checkerboard pattern on the display device 305 that can be alternated according to a desired frequency modulation. The visual stimulus can include light pulses generated by a light source 305 such as an LED disposed within the housing of the virtual reality headset 401.

[0213] When the virtual reality headset 401 provides an augmented reality experience, the visual stimulus may include overlaying the content on the display device and modulating the overlaid content at a desired modulation frequency. For example, the virtual reality headset 401 can include a camera 605 that captures the real physical world. While displaying the captured image of the real physical world, the NSS 105 can also display content modulated at a desired modulation frequency. The NSS 105 can overlay the content modulated at the desired modulation frequency. The NSS 105 can modify, manipulate, modulate, or adjust a portion of the display screen or a portion of the augmented reality in a different manner so as to generate or provide the desired modulation frequency.

[0214] For example, the NSS 105 can modulate one or more pixels based on the desired modulation frequency. The NSS 105 can turn pixels on and off based on the modulation frequency. The NSS 105 can rotate the pixels of any part of the display device. The NSS 105 can turn pixels on and off in a certain pattern. The NSS 105 can turn pixels on and off in the direct field of view or the peripheral field of view. The NSS 105 can track or detect the eye's gaze direction and turn pixels on and off in the gaze direction so that the light pulse (or modulation) is within the direct field of view. Thus, by modulating the overlaid content or otherwise manipulating the augmented reality display or other images provided via the display device within the virtual reality headset 401, a light pulse or light flash having a modulation frequency configured to facilitate the sensory induction of neural oscillations can be generated. <​​The NSS105 can determine the modulation frequency of a pulse train or ambient light via the profile manager 125. For example, the NSS105 can determine from the profile data structure 145 that the modulation frequency for an external visual stimulus may be set to 40 Hz. Depending on the type of visual stimulus, the profile data structure 145 may further indicate the number of pixels to modulate, the intensity of the pixels to modulate, the pulse length, the intensity, the wavelength of the light wave forming the light pulse, or the duration of the pulse train.

[0216] Depending on the circumstances, the NSS105 can determine or adjust one or more parameters of the external visual stimulus. For example, the NSS105 (e.g., via the feedback component 160 or feedback sensor 605) can determine the level or amount of light in the captured image used to provide the augmented reality experience. The NSS105 (e.g., via the light adjustment module 115 or side effect management module 130) can establish, initialize, set, or adjust the intensity or wavelength of the light pulse based on the light level in the image data corresponding to the augmented reality experience. For example, the NSS105 may determine that there is a low level of light present in the augmented reality display because the outside may be dark. The user's pupils may dilate as a result of the low level of light in the augmented reality display. Based on the detection of low level of light, the NSS105 may determine that the user's pupils are likely to be dilated. In response to the determination that the user's pupils are likely to be dilated, the NSS105 may set a low intensity for the light pulse or light source that results in a modulation frequency. NSS105 can further utilize light waves with longer wavelengths (e.g., red) that can reduce distortion for the eye.

[0217] In some embodiments, the NSS105 can monitor the level of light through sensory induction of the neurovibration process (e.g., via the feedback monitor 135 and feedback component 160) to automatically and periodically adjust the intensity or color of the light pulse. For example, if the user initiates sensory induction of the neurovibration process when a high level of ambient light is present, the NSS105 can first set a higher intensity level for the light pulse and use a color (e.g., blue) that includes light waves with lower wavelengths. However, as the light level decreases through sensory induction of the neurovibration process, the NSS105 can automatically detect the decrease in light and, in response to this detection, increase the wavelength of the light wave while adjusting or decreasing the intensity. The NSS105 can adjust the light pulse to provide a high contrast ratio and facilitate sensory induction of neurovibration.

[0218] In some embodiments, the NSS 105 (e.g., via the feedback monitor 135 and feedback component 160) can monitor or measure physiological states to set or adjust light pulse parameters while the user is wearing the virtual reality headset 401. For example, the NSS 105 can monitor or measure the level of pupil dilation to adjust or set light wave parameters. In some embodiments, the NSS 105 can monitor or measure heart rate, pulse rate, blood pressure, body temperature, sweating, or brain activity via one or more feedback sensors of the virtual reality headset 401 to set or adjust light wave parameters.

[0219] In some embodiments, the NSS105 can be pre-configured to first transmit a light pulse with a minimum light wave intensity setting (e.g., a low-amplitude or high-wavelength light wave) via a display device, and then gradually increase the intensity (e.g., increase the amplitude of the light wave or decrease the wavelength of the light wave) while monitoring feedback until an optimal light intensity is reached. The optimal light intensity may refer to the highest intensity that does not result in adverse physiological side effects such as blindness, seizures, heart attacks, migraines, or other discomforts. The NSS105 (e.g., via the side effect management module 130) can monitor physiological symptoms to identify adverse side effects of external visual stimuli and adjust the external visual stimuli accordingly (e.g., via the light adjustment module 115) to reduce or eliminate adverse side effects.

[0220] In some embodiments, the NSS 105 (e.g., via the light adjustment module 115) can adjust the parameters of the light wave or light pulse based on the level of attention. For example, during sensory induction of a neuro-oscillating process, the user may become bored, lose focus, fall asleep, or otherwise fail to pay attention to the light pulses generated via the display screen 305 of the virtual reality headset 401. Failure to pay attention to the light pulses reduces the effectiveness of sensory induction of the neuro-oscillating process, and as a result, neurons may vibrate at a frequency different from the desired modulation frequency of the light pulses.

[0221] The NSS105 can detect the level to which the user is paying attention to or providing attention to the light pulses using the feedback monitor 135 and one or more feedback components 160 (including, for example, a feedback sensor 605). The NSS105 can perform eye tracking and determine the level to which the user is paying attention to the light pulses based on the gaze direction of the retina or pupil. The NSS105 can measure eye movements to determine the level to which the user is paying attention to the light pulses. The NSS105 can provide a survey or prompt to request user feedback indicating the level to which the user is paying attention to the light pulses. In response to a determination that the user is not paying sufficient attention to the light pulses (e.g., the level of eye movement is greater than a threshold, or the gaze direction is outside the direct field of view of the light source 305), the light adjustment module 115 can change the parameters of the light source 305 or the display device 305 to gain the user's attention. For example, the light adjustment module 115 can increase the intensity of the light pulses, adjust the color of the light pulses, or change the duration of the light pulses. The light adjustment module 115 can randomly change one or more parameters of the light pulse. The light adjustment module 115 can initiate an attention-seeking light sequence configured to restore the user's attention. For example, the light sequence may include changes in the color or intensity of the light pulse in a predetermined, random, or pseudo-random pattern. If the visual signal transmission component 150 includes multiple light sources, the attention-seeking light sequence can enable or disable different light sources. In this way, the light adjustment module 115 can interact with the feedback monitor 135 to determine the level of attention the user is paying to the light pulse, and if the level of attention falls below a threshold, it can adjust the light pulse to restore the user's attention.

[0222] In some embodiments, the light adjustment module 115 can change or adjust one or more parameters of a light pulse or light wave at predetermined time intervals (for example, every 5 minutes, every 10 minutes, every 15 minutes, or every 20 minutes) to restore or maintain the user's attention level.

[0223] In some embodiments, the NSS105 (e.g., via the unwanted frequency filtering module 120) can filter, block, attenuate, or remove unwanted visual stimuli. Unwanted visual stimuli may include, for example, unwanted modulation frequencies, unwanted intensities, or unwanted wavelengths of light waves. The NSS105 may consider a modulation frequency to be undesirable if the modulation frequency of a pulse train differs from or substantially differs from a desired frequency (e.g., by 1%, 2%, 5%, 10%, 15%, 20%, 25%, or more than 25%).

[0224] For example, a desirable modulation frequency for sensory induction of nerve vibrations may be 40 Hz. However, modulation frequencies of, for example, 15 Hz or 90 Hz may interfere with sensory induction of nerve vibrations. For this reason, the NSS 105 can filter out light pulses or light waves corresponding to modulation frequencies of 15 Hz or 90 Hz. For example, a virtual reality headset 401 can generate or provide an augmented reality experience by detecting unwanted modulation frequencies in the physical real world and eliminating, attenuating, filtering out, or otherwise removing the unwanted frequencies. The NSS 105 may include an optical filter configured to perform digital signal processing or digital image processing to detect unwanted modulation frequencies in the real world captured by the feedback sensor 605. The NSS 105 can detect other content, images, or motion with unwanted parameters (e.g., color, brightness, contrast ratio, modulation frequency) and remove them from the augmented reality experience projected to the user via the display screen 305. The NSS 105 can apply a color filter to adjust or remove colors from the augmented reality display. The NSS105 can adjust, modify, or manipulate the brightness, contrast ratio, sharpness, hue, color, or other parameters of an image or video displayed via the display device 305.

[0225] In some embodiments, the NSS 105 can detect, via the feedback component 160, the presence of image or video content captured from the real physical world corresponding to an unwanted modulation frequency of 20 Hz. The NSS 105 can further determine the wavelength of the light wave in the optical pulse corresponding to the unwanted modulation frequency. The NSS 105 can instruct the filtering component 155 to filter out the wavelength corresponding to the unwanted modulation frequency. For example, the wavelength corresponding to the unwanted modulation frequency may correspond to blue. The filtering component 155 may include a digital optical filter that allows one or more other ranges of wavelengths or colors while digitally removing content or light of a specific range of wavelengths or colors. The digital optical filter can alter the scale or phase of the image in a certain wavelength range. For example, the digital optical filter can be configured to attenuate, erase, replace, or otherwise modify the blue light wave corresponding to the unwanted modulation frequency. The optical adjustment module 115 can change the wavelength of the light waves generated by the light generation module 110 and the display device 305 so that the desired modulation frequency is not blocked or attenuated by the unwanted frequency filtering module 120.

[0226] NSS that works with tablets The NSS105 can operate with the tablet 500 shown in Figures 5A to 5D. In some embodiments, the NSS105 can determine that the hardware of the visual signal transmission component 150 includes a tablet device 500 or other display screen, whether fixed to the user's head or not. The tablet 500 may include a display screen having one or more components or functions of a display screen 305 or a light source 305, as shown in conjunction with Figures 4A and 4C. The light source 305 in the tablet may be a display screen. The tablet 500 may include one or more feedback sensors, including one or more components or functions of a feedback sensor, as shown in conjunction with Figures 4B, 4C, and 6A.

[0227] The tablet 500 can communicate with the NSS 105 via a network such as a wireless network or a cellular network. In some embodiments, the NSS 105 can run the NSS 105 or its components. For example, the tablet 500 can launch, open, or switch an application or resource configured to provide at least one function of the NSS 105. The tablet 500 can run the application as a background process or a foreground process. For example, the graphical user interface for the application may be in the background while the application overlays content or light on the tablet's display screen 305 that changes or modulates at a frequency (e.g., 40 Hz) desired for sensory induction of nerve vibrations.

[0228] The tablet 500 may include one or more feedback sensors 605. In some embodiments, the tablet can use one or more feedback sensors 605 to detect that a user is holding the tablet 500. The tablet can use one or more feedback sensors 605 to determine the distance between the light source 305 and the user. The tablet can use one or more feedback sensors 605 to determine the distance between the light source 305 and the user's head. The tablet can use one or more feedback sensors 605 to determine the distance between the light source 305 and the user's eyes.

[0229] In some embodiments, the tablet 500 can determine distance using a feedback sensor 605 which includes a receiver. The tablet can transmit a signal and measure the time it takes for the transmitted signal to leave the tablet 500, bounce off an object (e.g., the user's head), and be received by the feedback sensor 605. The tablet 500 or NSS 105 can determine the distance based on the measured amount of time and the speed of the transmitted signal (e.g., the speed of light).

[0230] In some embodiments, the tablet 500 may include two feedback sensors 605 for determining distance. The two feedback sensors 605 may include a first feedback sensor 605 which is a transmitter and a second feedback sensor which is a receiver.

[0231] In some embodiments, the tablet 500 may include two or more feedback sensors 605, each containing two or more cameras. The two or more cameras can measure the angle and position of an object (e.g., the user's head) above each camera, and the measured angle and position can be used to determine or calculate the distance between the tablet 500 and the object.

[0232] In some embodiments, the tablet 500 (or its application) can determine the distance between the tablet and the user's head by receiving user input. For example, the user input may include the approximate size of the user's head. Then, the tablet 500 can determine the distance from the user's head based on the input approximate size.

[0233] The tablet 500, application, or NSS 105 can use the measured or determined distance to adjust the pulse or flash of light emitted by the light source 305 of the tablet 500. The tablet 500, application, or NSS 105 can use this distance to adjust one or more parameters of the light pulse, light flash, or other content emitted through the light source 305 of the tablet 500. For example, the tablet 500 can adjust the intensity of the light pulse emitted by the light source 305 based on the distance. The tablet 500 can adjust the intensity based on the distance to maintain a consistent or similar intensity in the eye regardless of the distance between the light source 305 and the eye. The tablet can increase the intensity in proportion to the square of the distance.

[0234] The tablet 500 can operate one or more pixels on the display screen 305 to generate a light pulse or modulation frequency for the sensory induction of neural oscillations. The tablet 500 can superimpose light sources, light pulses, or other patterns to generate a modulation frequency for the sensory induction of neural oscillations. Similar to the virtual reality headset 401, the tablet can filter or correct unwanted frequencies, wavelengths, or intensities.

[0235] Similar to the frame 400, the tablet 500 can adjust the parameters of the pulse or flash of light generated by the light source 305 based on ambient light, environmental parameters, or feedback.

[0236] In some embodiments, the tablet 500 can run an application configured to generate light pulses or modulation frequencies for sensory induction of nerve vibrations. The application can run in the background of the tablet so that all content displayed on the tablet's display screen is displayed as light pulses at a desired frequency. The tablet can be configured to detect the user's gaze direction. In some embodiments, the tablet can detect the gaze direction by capturing an image of the user's eyes via the tablet's camera. The tablet 500 can be configured to generate light pulses at specific locations on the display screen based on the user's gaze direction. In embodiments employing a direct field of view, the light pulses can be displayed at locations on the display screen corresponding to the user's gaze. In embodiments employing a peripheral field of view, the light pulses can be displayed at locations on the display screen outside the portion of the display screen corresponding to the user's gaze.

[0237] Auditory stimulation of nerves Figure 9 is a block diagram illustrating a system for auditory nerve stimulation according to one embodiment. System 900 may include a nerve stimulation system ("NSS") 905. The NSS 905 may be referred to as auditory NSS 905 or NSS 905. In summary, the auditory nerve stimulation system ("NSS") 905 includes, can access, interface with, or otherwise communicate with one or more of the following: a speech generation module 910, a speech adjustment module 915, an unwanted frequency filtering module 920, a profile manager 925, an adverse effect management module 930, a feedback monitor 935, a data repository 940, a speech signal transmission component 950, a filtering component 955, or a feedback component 960. The voice generation module 910, voice adjustment module 915, unwanted frequency filtering module 920, profile manager 925, side effect management module 930, feedback monitor 935, voice signal transmission component 950, filtering component 955, or feedback component 960 may each include a module configured to communicate with at least one processing unit or other logical device, such as a programmable logic array engine, or with the database repository 950. The voice generation module 910, voice adjustment module 915, unwanted frequency filtering module 920, profile manager 925, side effect management module 930, feedback monitor 935, voice signal transmission component 950, filtering component 955, or feedback component 960 may be separate components, single components, or part of the NSS905. System 100 and its components, such as the NSS905, may include one or more hardware elements such as processors, logic devices, or circuits. System 100 and its components, such as the NSS905, may include one or more hardware or interface components shown in System 700 in Figures 7A and 7B.For example, the components of system 100 include, or run on, one or more processors 721, access storage 728, or memory 722, and can communicate via a network interface 718.

[0238] Continuing to refer to Figure 9 in more detail, the NSS905 may include at least one voice generation module 910. The voice generation module 910 may be designed and constructed to interface with the voice signal transmission component 950 to facilitate the generation of voice signals, such as voice bursts, voice pulses, voice chirps, voice sweeps, or other acoustic waves having one or more predetermined parameters, or to cause generation to occur in other ways. The voice generation module 910 may include hardware or software for receiving and processing commands or data packets from one or more modules or components of the NSS905. The voice generation module 910 may generate commands that cause the voice signal transmission component 950 to generate voice signals. The voice generation module 910 may control or enable the voice signal component 950 to generate voice signals having one or more predetermined parameters.

[0239] The voice generation module 910 may be communicatively coupled to the voice signal component 950. The voice generation module 910 can communicate with the voice signal transmission component 950 via circuits, wires, data ports, network ports, power lines, ground, electrical contacts, or pins. The voice generation module 910 can wirelessly communicate with the voice signal transmission component 950 using one or more wireless protocols, such as Bluetooth, Bluetooth Low Energy, Zigbee, Z-Wave, IEEE802, Wi-Fi, 3G, 4G, LTE, Near Field Communication ("NFC"), or other short-range, medium-range, or long-range communication protocols. The voice generation module 910 can communicate wirelessly or via a wired connection with the voice signal transmission component 950 by including or accessing the network interface 718.

[0240] The voice generation module 910 can interface with, control, or otherwise manage various types of voice signal transmission components 950 to cause the voice signal transmission components 950 to generate, interrupt, control, or otherwise provide voice signals having one or more predetermined parameters. The voice generation module 910 may include a driver configured to drive the sound source of the voice signal transmission components 950. For example, the sound source may include a speaker, and the voice generation module 910 (or the voice signal transmission component) may include a transducer that converts electrical energy into sound waves or acoustic waves. The voice generation module 910 may include a computing chip, microchip, circuit, microcontroller, operational amplifier, transistor, resistor, or diode, which are configured to drive a speaker by supplying electricity or power having specific voltage and current characteristics to generate a voice signal having desired acoustic characteristics.

[0241] In some embodiments, the voice generation module 910 can instruct the voice signal transmission component 950 to provide a voice signal. For example, the voice signal may include an acoustic wave 1000 as shown in Figure 10A. The voice signal may include multiple sound waves. The voice signal may generate one or more acoustic waves. The acoustic wave 1000 may include, or be formed from, a mechanical wave of pressure and displacement that propagates through a medium such as a gas, liquid, or solid. As the acoustic wave propagates through a medium, it may produce vibration, sound, ultrasound, or infrared radiation. The acoustic wave may propagate as a longitudinal wave through air, water, or a solid. The acoustic wave may propagate as a transverse wave through a solid.

[0242] Acoustic waves can generate sound through vibrations at pressure, stress, particle displacement, or particle velocity propagated within a medium along with internal forces (e.g., elastic or viscous), or through a superposition of such propagated vibrations. Sound can refer to the auditory sensation induced by these vibrations. For example, sound can refer to the reception of sound waves and the perception of sound waves by the brain.

[0243] The audio signal transmission component 950 or its sound source can generate acoustic waves by vibrating the diaphragm of the sound source. For example, the sound source may include a diaphragm such as a transducer configured to interconvert mechanical vibrations into sound. The diaphragm may include a thin membrane or sheet of various materials suspended at its edges. Pressure fluctuations of sound waves can impart mechanical vibrations to the diaphragm, which in turn can produce sound waves or sound.

[0244] The acoustic wave 1000 shown in Figure 10A includes a wavelength 1010. The wavelength 1010 may refer to the distance between the continuous crests 1020 of the wave. The wavelength 1010 may be related to the frequency and speed of the acoustic wave. For example, the wavelength can be determined as the quotient obtained by dividing the speed of the acoustic wave by the frequency of the acoustic wave. The speed of the sound wave can be the product of the frequency and the wavelength. The frequency of the acoustic wave can be the quotient obtained by dividing the speed of the acoustic wave by the wavelength of the acoustic wave. This allows the frequency and wavelength of the acoustic wave to be inversely proportional. The speed of sound can vary depending on the medium through which the acoustic wave propagates. For example, the speed of sound in air can be 343 meters / second.

[0245] The crest 1020 can refer to the peak of the wave, or the point on the wave that has the maximum value. The displacement of the medium is greatest at the crest 1020 of the wave. The trough 1015 is on the opposite side of the crest 1020. The trough 1015 is the minimum or lowest point of the wave, corresponding to the minimum displacement.

[0246] The acoustic wave 1000 may include an amplitude 1005. The amplitude 1005 may refer to the maximum range of oscillation or vibration of the acoustic wave 1000 as measured from the equilibrium position. The acoustic wave 1000 may be a longitudinal wave if it vibrates or oscillates in the same direction of propagation 1025. In some cases, the acoustic wave 1000 may be a transverse wave that oscillates perpendicular to its direction of propagation.

[0247] The voice generation module 910 can instruct the voice signal transmission component 950 to generate one or more acoustic waves or sound waves having a predetermined amplitude or wavelength. The wavelength of acoustic waves audible to the human ear is in the range of approximately 17 meters to 17 millimeters (or 20 Hz to 20 kHz). The voice generation module 910 can further specify one or more characteristics of the acoustic waves that are within or outside the audible spectrum. For example, the frequency of the acoustic wave can be in the range of 0 to 50 kHz. In some embodiments, the frequency of the acoustic wave can be in the range of 8 to 12 kHz. In some embodiments, the frequency of the acoustic wave can be 10 kHz.

[0248] The NSS905 can modulate, modify, change, or otherwise alter the characteristics of the acoustic wave 1000. For example, the NSS905 can modulate the amplitude or wavelength of the acoustic wave. As shown in Figures 10B and 10C, the NSS905 can adjust, manipulate, or otherwise modify the amplitude 1005 of the acoustic wave 1000. For example, the NSS905 can decrease the amplitude 1005 to make the sound quieter, as shown in Figure 10B, or increase the amplitude 1005 to make the sound louder, as shown in Figure 10C.

[0249] Depending on the circumstances, the NSS905 can adjust, manipulate, or otherwise modify the wavelength 1010 of the acoustic wave. As shown in Figures 10D and 10E, the NSS905 can adjust, manipulate, or otherwise modify the wavelength 1010 of the acoustic wave 1000. For example, the NSS905 can increase the wavelength 1010 to lower the pitch of the sound, as shown in Figure 10D, or decrease the wavelength 1010 to raise the pitch of the sound, as shown in Figure 10E.

[0250] The NSS905 can modulate acoustic waves. Acoustic wave modulation may include modulating one or more characteristics of a sound wave. Acoustic wave modulation may include filtering an acoustic wave, such as filtering out unwanted frequencies or attenuating an acoustic wave to reduce its amplitude. Acoustic wave modulation may include adding one or more additional acoustic waves to an original acoustic wave. Acoustic wave modulation may include combining acoustic waves such that the combined acoustic waves have a constructive or canceling interference corresponding to the modulated acoustic wave.

[0251] The NSS905 can modulate or change one or more characteristics of an acoustic wave based on time intervals. The NSS905 can change one or more characteristics of the acoustic wave at the end of the time interval. For example, the NSS905 can change the characteristics of the acoustic wave every 30 seconds, 1 minute, 2 minutes, 3 minutes, 5 minutes, 7 minutes, 10 minutes, or 15 minutes. The NSS905 can change the modulation frequency of the acoustic wave, in which case the modulation frequency refers to the repetitive modulation or reciprocal of the pulse rate interval of the acoustic pulse. The modulation frequency can be a predetermined frequency or a desired frequency. The modulation frequency may correspond to a desired stimulation frequency of nerve oscillation. The modulation frequency can be set to facilitate or produce sensory induction of nerve oscillation. The NSS905 can set the modulation frequency to a frequency in the range of 0.1 Hz to 10,000 Hz. For example, the NSS905 modulates frequencies of approximately 0.1Hz, 1Hz, 5Hz, 10Hz, 20Hz, 25Hz, 30Hz, 31Hz, 32Hz, 33Hz, 34Hz, 35Hz, 36Hz, 37Hz, 38Hz, 39Hz, 40Hz, 41Hz, 42Hz, 43Hz, 44Hz, 45Hz, 46Hz, 47Hz, 48Hz, 49Hz, 50Hz, 60Hz, 70Hz, 80Hz, and 90Hz. It can be set to 100Hz, 150Hz, 160Hz, 200Hz, 240Hz, 250Hz, 300Hz, 320Hz, 400Hz, 480Hz, 500Hz, 640Hz, 1000Hz, 1,280Hz, 2000Hz, 3000Hz, 4,000Hz, 5000Hz, 6,000Hz, 7,000Hz, 8,000Hz, 9,000Hz, or 10,000Hz.

[0252] The voice generation module 910 may determine to provide an audio signal that includes bursts of acoustic waves, audio pulses, or modulation to acoustic waves. The voice generation module 910 may instruct the audio signal transmission component 950 to generate acoustic bursts or pulses, or cause it to generate them in other ways. An acoustic pulse may refer to a burst of sound waves or modulation to the characteristics of an acoustic wave that is perceived by the brain as a change in sound. For example, a sound source that is intermittently switched on and off can produce audio bursts or changes in sound. The sound source may be switched on and off based on a predetermined or fixed pulse rate interval, such as every 0.025 seconds, to provide a pulse repetition frequency of 40 Hz. The sound source may be switched on and off to give a pulse repetition frequency in the range of 0.1 Hz to 10 kHz or higher.

[0253] For example, Figures 10F to 10I show bursts of acoustic waves, or bursts of modulation that may be applied to acoustic waves. Examples of bursts of acoustic waves include vocal tones, beeps, or clicks. Modulation may refer to changes in the amplitude of an acoustic wave, changes in the frequency or wavelength of an acoustic wave, superimposing another acoustic wave on top of an original acoustic wave, presenting an acoustic wave at a desired frequency interval, or otherwise modifying or altering an acoustic wave.

[0254] For example, Figure 10F shows acoustic bursts 1035a-c (or modulated pulses 1035a-c) according to one embodiment. Acoustic bursts 1035a-c can be represented by a graph where the y-axis represents the parameters of the acoustic wave (e.g., frequency, wavelength, or amplitude). The x-axis can represent time (e.g., seconds, milliseconds, or microseconds).

[0255] Audio signals can include modulated acoustic waves that are modulated between different frequencies, wavelengths, or amplitudes. For example, the NSS905 can modulate acoustic waves between frequencies within the audio spectrum, such as Ma, and frequencies outside the audio spectrum, such as Mo. The NSS905 can modulate acoustic waves between two or more frequencies, between on and off states, or between high-power and low-power states.

[0256] Acoustic bursts 1035a-c may have acoustic wave parameters where value Ma differs from the value Mo of the acoustic wave parameter. Modulation Ma may refer to frequency, wavelength, or amplitude. Pulses 1035a-c can be generated with a pulse rate interval (PRI) 1040.

[0257] For example, the acoustic wave parameter can be the frequency of the acoustic wave. The first value Mo can be a low frequency or carrier frequency of the acoustic wave, such as 10 kHz. The second value Ma can be different from the first frequency Mo. The second frequency Ma can be lower or higher than the first frequency Mo. For example, the second frequency Ma can be 11 kHz. The difference between the first frequency and the second frequency can be determined or set based on the sensitivity level of the human ear. The difference between the first frequency and the second frequency can be determined or set based on the target profile information 945. The difference between the first frequency Mo and the second frequency Ma can be determined so that the modulation or change of the acoustic wave facilitates sensory induction of nerve oscillations.

[0258] In some cases, the parameters of the acoustic wave used to generate the acoustic burst 1035a can be kept constant at Ma, thereby generating a square wave as shown in Figure 10F. In some embodiments, each of the three pulses 1035a-c may contain an acoustic wave having the same frequency Ma.

[0259] The width of each acoustic burst or pulse (e.g., the duration of a burst of an acoustic wave having parameter Ma) may correspond to a pulse width 1030a. The pulse width 1030a may refer to the length or duration of the burst. The pulse width 1030a can be measured in units of time or distance. In some embodiments, pulses 1035a-c may include acoustic waves having different frequencies from each other. In some embodiments, pulses 1035a-c may have different pulse widths 1030a from each other, as shown in Figure 10G. For example, the first pulse 1035d in Figure 10G may have a pulse width 1030a, while the second pulse 1035e may have a second pulse width 1030b that is larger than the first pulse width 1030a. The third pulse 1035f may have a third pulse width 1030c that is smaller than the second pulse width 1030b. The third pulse width 1030c can also be less than the first pulse width 1030a. The pulse widths 1030a to c of pulses 1035d to f of the pulse train may vary, but the voice generation module 910 can maintain a constant pulse rate interval 1040 for the pulse train.

[0260] Pulses 1035a to 1035c can form a pulse train having a pulse rate interval of 1040. The pulse rate interval 1040 can be quantified using units of time. The pulse rate interval 1040 can be based on the frequency of the pulses in the pulse train 201. The frequency of the pulses in the pulse train 201 can be called the modulation frequency. For example, the speech generation module 910 can provide a pulse train 201 having a predetermined frequency such as 40 Hz. To do this, the speech generation module 910 can determine the pulse rate interval 1040 by taking the reciprocal (or multiplicative reciprocal) of the frequency (for example, dividing 1 by the predetermined frequency of the pulse train). For example, the speech generation module 910 can take the reciprocal of 40 Hz by dividing 1 by 40 Hz to determine the pulse rate interval 1040 to be 0.025 seconds. The pulse rate interval 1040 can remain constant throughout the entire pulse train. In some embodiments, the pulse rate interval 1040 may vary across the entire pulse train or from one pulse train to a subsequent pulse train. In some embodiments, the number of pulses transmitted during the second period may be fixed, but the pulse rate interval 1040 may vary.

[0261] In some embodiments, the voice generation module 910 can generate voice bursts or voice pulses having acoustic waves with varying frequency, amplitude, or wavelength. For example, the voice generation module 910 can generate an up-chirp pulse, in which case the frequency, amplitude, or wavelength of the acoustic wave of the voice pulse increases from the start to the end of the pulse, as shown in Figure 10H. For example, the frequency, amplitude, or wavelength of the acoustic wave at the start of pulse 1035g may be Ma. The frequency, amplitude, or wavelength of the acoustic wave of pulse 1035g may increase from Ma to Mb in the middle of pulse 1035g, and then increase to a maximum value Me at the end of pulse 1035g. Therefore, the frequency, amplitude, or wavelength of the acoustic wave used to generate pulse 1035g may be in the range of Ma to Me. The frequency, amplitude, or wavelength may increase linearly, exponentially, or based on some other velocity or curve. One or more of the frequency, amplitude, or wavelength of the acoustic wave may change from the start to the end of the pulse.

[0262] The voice generation module 910 can generate a down chirp pulse as shown in Figure 10I, in which case the frequency, amplitude, or wavelength of the acoustic wave of the acoustic pulse decreases from the start to the end of the pulse. For example, the frequency, amplitude, or wavelength of the acoustic wave at the start of pulse 1035j may be Mc. The frequency, amplitude, or wavelength of the acoustic wave of pulse 1035j may decrease from Me to Mb in the middle of pulse 1035j, and then decrease to a minimum value Ma at the end of pulse 1035j. Therefore, the frequency, amplitude, or wavelength of the acoustic wave used to generate pulse 1035j may be in the range of Mc to Ma. The frequency, amplitude, or wavelength may decrease linearly, exponentially, or based on some other speed or curve. One or more of the frequency, amplitude, or wavelength of the acoustic wave may change from the start to the end of the pulse.

[0263] In some embodiments, the speech generation module 910 can instruct or cause the speech signaling component 950 to generate or generate speech pulses that stimulate specific or predetermined parts of the brain or a particular cortex. The frequency, wavelength, modulation frequency, amplitude, and other aspects of the speech pulses, tone, or music-based stimulus can determine which cortex is recruited to process the stimulus. The speech signaling component 950 can target specific or whole regions of interest by stimulating individual parts of the cortex by modulating the presentation of the stimulus. The modulation parameters or amplitude of the speech stimulus can determine which cortical regions are stimulated. For example, different cortical regions are recruited to process sounds of different frequencies, known as their intrinsic frequencies. Furthermore, since some subjects may be treated by stimulating one ear rather than both, the laterality of the stimulus to the ear can affect the cortical response.

[0264] The audio signal transmission component 950 can be designed and constructed to generate audio pulses in response to commands from the audio generation module 910. The commands may include parameters of the audio pulse, such as the frequency, wavelength, pulse duration, pulse train frequency, pulse rate interval, or pulse train duration (e.g., the number of pulses in the pulse train, or the length of time for transmitting a pulse train having a given frequency). The audio pulses may be perceived, observed, or otherwise identified by the brain via cochlear means, such as both ears. The audio pulses may be transmitted to the ears via sound source speakers located near the ears, such as headphones, earphones, bone conduction transducers, or cochlear implants. Alternatively, the audio pulses may be transmitted to the ears via sound sources or speakers not located near the ears, such as surround sound speaker systems, bookshelf speakers, or other speakers that do not directly or indirectly contact the ears.

[0265] Figure 11A shows an audio signal using binaural beats or binaural pulses according to one embodiment. In short, binaural beats refer to giving each ear of the subject a different tone. When the brain perceives two different tones, the brain mixes the two tones to create a pulse. The two different tones can be selected such that summing the tones generates a pulse train with a desired pulse rate interval of 1040.

[0266] The audio signal transmission component 950 may include a first sound source that provides an audio signal to a target's first ear and a second sound source that provides a second audio signal to a target's second ear. The first and second sound sources may be different. The first ear may perceive only the first audio signal from the first sound source, and the second ear may receive only the second audio signal from the second sound source. The sound sources may include, for example, headphones, earphones, or bone conduction transducers. The sound sources may include stereo sound sources.

[0267] The speech generation component 910 can select a first tone for the first ear and a different second tone for the second ear. Tones can be characterized by their duration, pitch, intensity (i.e., loudness), or timbre (i.e., timbre). In some cases, the first and second tones may be different if they have different frequencies. In some cases, the first and second tones may be different if they have different phase offsets. The first and second tones may each be pure tones. A pure tone may be a tone with a single-frequency sine wave.

[0268] As shown in Figure 11A, the first tone or offset wave 1105 is slightly different from the second tone 1110 or carrier wave 1110. The first tone 1105 has a higher frequency than the second tone 1110. The first tone 1105 can be generated by a first earphone inserted into one ear of the subject, and the second tone 1110 can be generated by a second earphone inserted into the other ear of the subject. When the auditory cortex of the brain perceives the first tone 1105 and the second tone 1110, the brain can combine the two tones. The brain can combine the acoustic waveforms corresponding to the two tones. The brain can combine the two waveforms as shown by the waveform sum 1115. Since the first and second tones have different parameters (such as different frequencies or phase offsets), the parts of the waves can be added and subtracted from each other to obtain a waveform 1115 having one or more pulses 1130 (or beats 1130). The pulse 1130 can be separated by the equilibrium portion 1125. By mixing these two different waveforms together, the pulse 1130 perceived by the brain can generate sensory induction of neural oscillations.

[0269] In some embodiments, the NSS905 can generate binaural beats using pitch panning techniques. For example, the voice generation module 910 or voice adjustment module 915 may include, or use, a filter for modulating the pitch of a sound file or a single tone up or down, and simultaneously panning the modulation between the stereo sides such that the pitch on one side is slightly higher and the pitch on the other side is slightly lower. The stereo sides may refer to a first sound source that generates an audio signal and provides it to the target's first ear, and a second sound source that generates an audio signal and provides it to the target's second ear. A sound file may refer to a file format configured to store a representation of an acoustic wave or information about an acoustic wave. Exemplary sound file formats include .mp3, .wav, .aac, .m4a, .smf, and the like.

[0270] The NSS905 can use this pitch-panning technique to generate a type of spatial positioning that, when listened to through stereo headphones, is perceived by the brain similarly to binaural beats. Therefore, the NSS905 can use this pitch-panning technique to generate pulses or beats using a single tone or a single sound file.

[0271] Depending on the circumstances, the NSS905 can generate a monaural beat or monaural pulse. A monaural beat or monaural pulse is similar to a binaural beat in that it can also be generated by combining two tones to form a beat. The NSS905 or components of system 100 can form a monaural beat by combining two tones using digital or analog techniques before the sound reaches the ear, in contrast to the brain combining waveforms as in binaural beats. For example, the NSS905 (or sound generation component 910) can identify and select two different waveforms that, when combined, produce a beat or pulse with a desired pulse rate interval. The NSS905 can identify a first digital representation of a first acoustic waveform, and can also identify a second digital representation of a second acoustic waveform having different parameters from the first acoustic waveform. The NSS905 can combine the first and second digital waveforms to generate a third digital waveform that is different from the first and second digital waveforms. Next, the NSS905 can transmit the third digital waveform in digital format to the audio signal transmission component 950. The NSS905 can convert the digital waveform to analog format and transmit the analog format to the audio signal transmission component 950. The audio signal transmission component 950 can then generate a sound that is perceived by one or both ears via the sound source. The same sound may also be perceived by both ears. This sound may contain pulses or beats spaced at a desired pulse rate interval 1040.

[0272] Figure 11B shows an acoustic pulse having an isochronic tone according to one embodiment. An isochronic tone is a tone pulse with equal intervals. An isochronic tone can be created without the need to combine two different tones. The NSS905 or other components of System 100 can create an isochronic tone by switching the tone on and off. The NSS905 can generate an isochronic tone or isochronic pulse by commanding an audio signal transmission component to switch on and off. The NSS905 can modify the digital representation of the acoustic wave to remove or set the digital value of the acoustic wave so that sound is generated in pulse 1135 and not in null portion 1140.

[0273] By switching the acoustic wave on and off, the NSS905 can establish acoustic pulses 1135 spaced at pulse rate intervals 1040 corresponding to a desired stimulation frequency such as 40 Hz. Partially spaced isochronic pulses at a desired PRI 1040 can generate sensory induction of nerve oscillations.

[0274] Figure 11C shows an audio pulse generated by the NSS905 using a soundtrack according to one embodiment. The soundtrack may include, or refer to, a composite acoustic wave containing multiple different frequencies, amplitudes, or tones. For example, the soundtrack may include a voice track, an instrument track, a music track containing both voice and instrument, a nature sound, or white noise.

[0275] The NSS905 can generate sensory induction of neural oscillations by modulating a soundtrack and rhythmically adjusting the components within the sound. For example, the NSS905 can create rhythmic stimuli corresponding to the stimulation frequency necessary to generate sensory induction of neural oscillations by adjusting the volume by increasing or decreasing the amplitude of an acoustic wave or soundtrack. Therefore, the NSS905 can generate sensory induction of neural oscillations by embedding acoustic pulses with pulse rate intervals corresponding to a desired stimulation frequency into a soundtrack. The NSS905 can generate sensory induction of neural oscillations by manipulating a soundtrack to generate a new modified soundtrack containing acoustic pulses with pulse rate intervals corresponding to a desired stimulation frequency.

[0276] As shown in Figure 11C, pulse 1135 is generated by adjusting the volume from a first level Va to a second level Vb. During section 1140 of the acoustic wave 345, NSS905 can set or maintain the volume at Va. Volume Va may refer to the amplitude of the wave during section 1140, or the maximum amplitude or crest of wave 345. NSS905 can then adjust, change, or increase the volume to Vb during section 1135. NSS905 can increase the volume by a predetermined amount, such as a percentage, decibels, a specified amount, or other amount. NSS905 can set or maintain the volume at Vb for a duration corresponding to a desired pulse length of pulse 1135.

[0277] In some embodiments, the NSS905 may include an attenuator that reduces the volume from level Vb to level Va. In some embodiments, the NSS905 can instruct an attenuator (e.g., an attenuator in the audio signal transmission component 950) to reduce the volume from level Vb to level Va. In some embodiments, the NSS905 may include an amplifier that amplifies or increases the volume from Va to Vb. In some embodiments, the NSS905 can instruct an attenuator (e.g., an attenuator in the audio signal transmission component 950) to amplify or increase the volume from Va to Vb.

[0278] Referring again to Figure 9, the NSS905 includes, accesses, interfaces with, or otherwise communicates with at least one voice adjustment module 915. The voice adjustment module 915 can be designed and built to adjust parameters related to the voice signal, such as the frequency, amplitude, wavelength, pattern, or other parameters of the voice signal. The voice adjustment module 915 can automatically vary the parameters of the voice signal based on profile information or feedback. The voice adjustment module 915 can receive feedback information from the feedback monitor 935. The PVC adjustment module 915 can receive commands or information from the side effect management module 930. The voice adjustment module 915 can receive profile information from the profile manager 925.

[0279] The NSS905 includes, accesses, interfaces with, or otherwise communicates with at least one unwanted frequency filtering module 920. The unwanted frequency filtering module 920 may be designed and constructed to block, mitigate, reduce, or otherwise remove frequencies of unwanted audio signals in order to prevent or reduce the amount of such audio signals perceived by the brain. The unwanted frequency filtering module 920 may interface with, command, control, or otherwise communicate with the filtering component 955 to cause the filtering component 955 to block, attenuate, or reduce the effect of unwanted frequencies on neural oscillations.

[0280] The unwanted frequency filtering module 920 may include an active noise control component (for example, the active noise rejection component 1215 shown in Figure 12B). Active noise control may be referred to as, or include, active noise rejection or active noise reduction. Active noise control can reduce unwanted noise by adding a second sound with parameters specifically selected to remove or attenuate a first sound. In some cases, the active noise control component may emit a sound wave having the same amplitude but in opposite phase (i.e., antiphase) to the original unwanted sound. The two waves can combine to form a new wave, which can effectively remove each other through canceling interference.

[0281] Active noise control components may include analog circuitry or digital signal processing. Active noise control components may include adaptive techniques for analyzing the waveform of background auditory or non-auditory noise. In response to background noise, active noise control components can generate an audio signal whose polarity can be phase-shifted or inverted. This inverted signal can be amplified by a transducer or speaker to produce a sound wave directly proportional to the amplitude of the original waveform, causing canceling interference. This can reduce the perceived volume of the noise.

[0282] In some embodiments, the noise-canceling speaker can be placed in the same location as the sound source speaker. In some embodiments, the noise-canceling speaker can be placed in the same location as the sound source to be attenuated.

[0283] The unwanted frequency filtering module 920 can filter out unwanted frequencies that may adversely affect the auditory induction of neural oscillations. For example, the active noise control component can identify that the audio signal contains acoustic bursts with unwanted pulse rate intervals as well as acoustic bursts with desired pulse rate intervals. The active noise control component can identify the waveform corresponding to the acoustic bursts with unwanted pulse rate intervals and generate an inverted phase waveform to remove or attenuate the unwanted acoustic bursts.

[0284] The NSS905 may include, access, interface with, or otherwise communicate with at least one profile manager 925. The profile manager 925 may be designed or constructed to store, update, retrieve, or otherwise manage information relating to one or more subjects related to the sensory induction of nerve vibrations. The profile information may include, for example, treatment history information, brain sensory induction history information for nerve vibrations, medication information, acoustic wave parameters, feedback, physiological information, environmental information, or other data relating to the system and method of sensory induction of nerve vibrations.

[0285] The NSS905 includes, can access, interface with, or otherwise communicate with at least one adverse event management module 930. The adverse event management module 930 may be designed and constructed to provide information to the voice adjustment module 915 or the voice generation module 910 to modify one or more parameters of the voice signal in order to reduce adverse events. Adverse events may include, for example, nausea, migraine, fatigue, seizures, ear strain, hearing loss, ringing, or tinnitus.

[0286] The adverse event management module 930 can automatically instruct the components of the NSS 905 to modify or change the parameters of the audio signal. The adverse event management module 930 can be configured to reduce adverse events at predetermined thresholds. For example, the adverse event management module 930 can be configured using the maximum duration of the pulse train, the maximum amplitude of the acoustic wave, the maximum volume, the maximum duty cycle of the pulse train (e.g., pulse width multiplied by the frequency of the pulse train), and the maximum number of treatments in sensory induction of nerve oscillations over a period of time (e.g., 1 hour, 2 hours, 12 hours, or 24 hours).

[0287] The side effect management module 930 can cause changes in the parameters of the audio signal in response to feedback information. The side effect management module 930 can receive feedback from the feedback monitor 935. The side effect management module 930 can decide to adjust the parameters of the audio signal based on the feedback. The side effect management module 930 can decide to adjust the parameters of the audio signal by comparing the feedback with a threshold.

[0288] The adverse event management module 930 may consist of, or include, a policy engine that applies policies or rules to the current voice signal and feedback to determine adjustments to the voice signal. For example, if feedback indicates that the heart rate or pulse rate of the patient receiving the voice signal is above a threshold, the adverse event management module 930 may turn off the pulse train until the pulse rate stabilizes and falls below the threshold, or below a second threshold below the threshold.

[0289] NSS905 may include, access, interface with, or otherwise communicate with at least one feedback monitor 935. The feedback monitor may be designed and constructed to receive feedback information from the feedback component 960. The feedback component 960 may include, for example, feedback sensors 1405 such as a temperature sensor, a heart rate or pulse rate monitor, a physiological sensor, an ambient noise sensor, a mobile phone, an ambient temperature sensor, a blood pressure monitor, an electroencephalogram ("EOG") probe configured to measure the corneal retinal standing potential present between the anterior and posterior segments of the human eye, an accelerometer, a gyroscope, a motion detector, a proximity sensor, a camera, a microphone, or a photodetector.

[0290] Systems and devices configured for auditory nerve stimulation Figure 12A shows a system for auditory induction of neural vibration according to one embodiment. System 1200 may include one or more speakers 1205. System 1200 may include one or more microphones. In some embodiments, the system may include both speakers 1205 and microphones 1210. In some embodiments, system 1200 may include speakers 1205 but not microphones 1210. In some embodiments, system 1200 may include microphones 1210 but not speakers 1210.

[0291] The speaker 1205 can be integrated with the audio signal transmission component 950. The audio signal transmission component 950 may include the speaker 1205. The speaker 1205 can interact with or communicate with the audio signal transmission component 950. For example, the audio signal transmission component 950 can command the speaker 1205 to generate sound.

[0292] The microphone 1210 can be integrated with the feedback component 960. The feedback component 960 may include the microphone 1210. The microphone 1210 can interact with or communicate with the feedback component 960. For example, the feedback component 960 may receive information, data, or signals from the microphone 1210.

[0293] In some embodiments, the speaker 1205 and microphone 1210 can be integrated together or be the same device. For example, the speaker 1205 can be configured to function as a microphone 1210. The NSS905 can switch the speaker 1205 from speaker mode to microphone mode.

[0294] In some embodiments, the system 1200 may include a single speaker 1205 positioned over one ear of the subject. In some embodiments, the system 1200 may include two speakers. The first speaker of the two speakers may be positioned over the first ear, and the second speaker of the two speakers may be positioned over the second ear. In some embodiments, an additional speaker may be positioned in front of or behind the subject's head. In some embodiments, one or more microphones 1210 may be positioned over one or both ears, in front of or behind the subject's head.

[0295] Speaker 1205 may include a dynamic cone speaker configured to generate sound from an electrical signal. Speaker 1205 may include a full-range driver that generates acoustic waves having frequencies across a portion or all of the audible range (e.g., 60 Hz to 20,000 Hz). Speaker 1205 may include a driver that generates sound waves having frequencies outside the audible range, such as 0 to 60 Hz, or within the ultrasonic range, such as 20 kHz to 4 GHz. Speaker 1205 may include one or more transducers or drivers that generate sound at various points in the audible frequency range. For example, speaker 1205 may include a tweeter for high-frequency ranges (e.g., 2,000 Hz to 20,000 Hz), a mid-range driver for intermediate frequencies (e.g., 250 Hz to 2,000 Hz), or a woofer for low frequencies (e.g., 60 Hz to 250 Hz).

[0296] Speaker 1205 may include one or more types of speaker hardware, components, or technical products that produce sound. For example, Speaker 1205 may include a diaphragm that produces sound. Speaker 1205 may include a moving iron loudspeaker that vibrates a magnetized metal piece using a fixed coil. Speaker 1205 may include a piezoelectric speaker. A piezoelectric speaker can produce sound by using the piezoelectric effect to generate motion by applying a voltage to a piezoelectric material, which is then converted into an audible sound using a diaphragm and a resonator.

[0297] Speaker 1205 can include various other types of hardware or technology products, such as magnetostatic loudspeakers, magnetostrictive speakers, electrostatic loudspeakers, ribbon speakers, planar magnetic loudspeakers, bent-wave loudspeakers, coaxial drivers, horn loudspeakers, Heil air motion transducers, or transparent ion conduction speakers.

[0298] In some cases, speaker 1205 may not include a diaphragm. For example, speaker 1205 can be a plasma arc speaker that uses electric plasma as a radiating element. Speaker 1205 can be a thermoacoustic speaker that uses a carbon nanotube thin film. Speaker 1205 can be a rotating woofer that includes a fan with blades that constantly change their pitch.

[0299] In some embodiments, speaker 1205 may include headphones or a pair of headphones, ear speakers, earphones, or earbuds. Headphones may be relatively small speakers compared to loudspeakers. Headphones may be designed and constructed to be positioned inside, around, or otherwise near the ear. Headphones may include electroacoustic transducers that convert electrical signals into corresponding sounds in the target ear. In some embodiments, headphones 1205 may include or interface with a headphone amplifier, such as an integrated amplifier or a standalone unit.

[0300] In some embodiments, speaker 1205 may include headphones that include an air jet that pushes air into the ear canal to move the eardrum in a similar manner to sound waves. Compression and thinning of the eardrum by bursts of air (with or without discernible sound) can control the frequency of nerve vibrations similar to auditory signals. For example, speaker 1205 may include an air jet or device similar to an in-ear headphone that pushes, pulls, or pushes air in and out of the ear canal to influence the frequency of nerve vibrations by compressing or pulling the eardrum. NSS905 can instruct, configure, or cause the air jet to generate bursts of air at a predetermined frequency.

[0301] In some embodiments, headphones can be connected to the audio signal transmission component 950 via a wired or wireless connection. In some embodiments, the audio signal transmission component 950 may include headphones. In some embodiments, headphones 1205 can interface with one or more components of the NSS905 via a wired or wireless connection. In some embodiments, headphones 1205 may include one or more components of the NSS905 or system 100, such as a voice generation module 910, a voice adjustment module 915, an unwanted frequency filtering module 920, a profile manager 925, an adverse event management module 930, a feedback monitor 935, an audio signal transmission component 950, a filtering component 955, or a feedback component 960.

[0302] Speaker 1205 can include or integrate with various types of headphones. For example, the headphones may include circumaural headphones (e.g., full-size headphones) that include, for example, circular or oval ear pads designed and constructed to protect the head and attenuate external noise. Circumaural headphones can facilitate the delivery of an immersive auditory-electroencephalography (EEG) experience while reducing external distractions. In some embodiments, the headphones may include supraaural headphones that include pads that press against the ears rather than around them. Supraaural headphones may offer less attenuation of external noise.

[0303] Both circumaural and supraaural headphones can be open-back, closed-back, or semi-open-back. Open-back headphones allow more ambient noise to enter, but provide a more natural or speaker-like sound. Closed-back headphones block out more ambient noise compared to open-back headphones, thus providing a more immersive auditory-electroencephalography (EEG) experience while reducing external distractions.

[0304] In some embodiments, headphones may include ear-fitting headphones such as earphones or in-ear headphones. Earphones (i.e., earbuds) may refer to small headphones that are worn directly on the outer ear, facing the ear canal but not inserted. However, earphones offer only minimal acoustic isolation, allowing ambient noise to enter. In-ear headphones (or in-ear monitors or canal headphones) may refer to small headphones that can be designed and constructed to be inserted into the ear canal. In-ear headphones engage with the ear canal and can block out more ambient noise compared to earphones, thus providing a more immersive auditory-electroencephalography (EEG) experience. In-ear headphones may include ear canal plugs made or formed from one or more materials such as silicone rubber, elastomer, or foam. In some embodiments, in-ear headphones may include custom-made castings of the ear canal to create custom-molded plugs that provide the subject with greater comfort and noise isolation, thereby further improving the immersion of the AEG experience.

[0305] In some embodiments, one or more microphones 1210 can be used to detect sound. The microphones 1210 can be integrated with the speaker 1205. The microphones 1210 can provide feedback information to the NSS 905 or other components of the system 100. The microphones 1210 can provide feedback to the components of the speaker 1205, causing the speaker 1205 to adjust the parameters of the audio signal.

[0306] Microphone 1210 may include a transducer that converts sound into an electrical signal. Microphone 1210 can generate an electrical signal from air pressure fluctuations using electromagnetic induction, capacitance change, or piezoelectricity. Optionally, microphone 1210 may include or be connected to a preamplifier to amplify the signal before recording or processing it. Microphone 1210 may include one or more types of microphones, such as condenser microphones, RF condenser microphones, electret condensers, dynamic microphones, moving coil microphones, ribbon microphones, carbon microphones, piezoelectric microphones, crystal microphones, fiber optic microphones, laser microphones, liquid or water microphones, micro-electromechanical system ("MEMS") microphones, or speakers as microphones.

[0307] The feedback component 960 can acquire, identify, or receive sound by including or interfaceing with the microphone 1210. The feedback component 960 can acquire ambient noise. The feedback component 960 can acquire sound from the speaker 1205, facilitating the NSS 905 to adjust the characteristics of the audio signal generated by the speaker 1205. The microphone 1210 can receive audio input from the subject, such as voice commands, instructions, requests, feedback information, or responses to survey questions.

[0308] In some embodiments, one or more speakers 1205 can be integrated with one or more microphones 1210. For example, the speakers 1205 and microphones 1210 may be structurally designed to switch between sound generation mode and sound reception mode, so that they can form a headset, be housed in a single housing, or be the same device.

[0309] Figures 12B and 12C show a system configuration for auditory induction of neural vibrations according to an embodiment. System 1200 may include at least one speaker 1205. System 1200 may include at least one microphone 1210. System 1200 may include at least one active noise cancellation component 1215. System 1200 may include at least one feedback sensor 1225. System 1200 may include or interface with an NSS905. System 1200 may include or interface with an audio player 1220.

[0310] System 1200 may include a first speaker 1205 positioned in the first ear. System 1200 may include a second speaker 1205 positioned in the second ear. System 1200 may include a first noise cancellation component 1215 communicatively coupled to a first microphone 1210. System 1200 may include a second noise cancellation component 1215 communicatively coupled to a second microphone 1210. Optionally, the active noise cancellation component 1215 may communicate with both the first speaker 1205 and the second speaker 1205, or with both the first microphone 1210 and the second microphone 1210. System 1200 may include a first microphone 1210 communicatively coupled to the active noise cancellation component 1215. System 1200 may include a second microphone 1210 communicatively coupled to the active noise cancellation component 1215. In some embodiments, the microphone 1210, speaker 1205, and active noise cancellation component can each communicate with or interface with the NSS 905. In some embodiments, the system 1200 may include a feedback sensor 1225 and a second feedback sensor 1225 that is communicatively coupled to the NSS 905, speaker 1205, microphone 1210, or active noise cancellation component 1215.

[0311] During operation, in some embodiments, the audio player 1220 can play a music track. The audio player 1220 can provide audio signals corresponding to the music track via wired or wireless connections to the first and second speakers 1205. In some embodiments, the NSS 905 can intercept the audio signals from the audio player. For example, the NSS 905 can receive digital or analog audio signals from the audio player 1220. The NSS 905 can act as an intermediary between the audio player 1220 and the speakers 1205. The NSS 905 can analyze the audio signals corresponding to the music in order to embed auditory-electroencephalogram (EEG) stimulation signals. For example, the NSS 905 can adjust the volume of the auditory signals from the audio player 1220 to generate acoustic pulses with pulse rate intervals as shown in Figure 11C. In some embodiments, the NSS 905 can use binaural beat techniques to provide the first and second speakers with different auditory signals that are combined to have a desired stimulation frequency when perceived by the brain.

[0312] In some embodiments, the NSS905 can adjust any latency between the first speaker 1205 and the second speaker 1205 so that the brain perceives the audio signals in the same or substantially the same amount of time (e.g., within 1 millisecond, 2 milliseconds, 5 milliseconds, or 10 milliseconds). The NSS905 can buffer the audio signals to account for latency so that the audio signals are transmitted from the speakers simultaneously.

[0313] In some embodiments, the NSS905 may not be located between the audio player 1220 and the speaker. For example, the NSS905 can receive music tracks from a digital music repository. The NSS905 can manipulate or modify the music tracks to embed acoustic pulses according to a desired PRI. The NSS905 can then provide the modified music track to the audio player 1220, which in turn can provide the modified audio signal to the speaker 1205.

[0314] In some embodiments, the active noise cancellation component 1215 can receive ambient noise information from the microphone 1210, identify unwanted frequencies or noise, and cancel or attenuate unwanted waveforms by generating an inverted phase waveform. In some embodiments, the system 1200 may include an additional speaker to generate the noise cancellation waveform provided by the noise cancellation component 1215. The noise cancellation component 1215 may include an additional speaker.

[0315] The feedback sensor 1225 of system 1200 can detect feedback information such as environmental parameters or physiological conditions. The feedback sensor 1225 can provide feedback information to the NSS 905. The NSS 905 can adjust or modify the audio signal based on the feedback information. For example, the NSS 905 can lower the volume of the audio signal after determining that the subject's pulse rate exceeds a predetermined threshold. The NSS 905 can detect that the volume of the auditory signal exceeds a threshold and reduce its amplitude. The NSS 905 can determine that the pulse rate interval falls below a threshold, indicating that the subject is out of focus or not paying sufficient attention to the audio signal, and the NSS 905 can increase the amplitude of the audio signal or change the tone or music track. In some embodiments, the NSS 905 can change the tone or music track based on a time interval. By changing the tone or music track, the subject can pay a greater level of attention to the auditory stimulus, thereby facilitating sensory induction of neural oscillations.

[0316] In some embodiments, the NSS905 can receive neural oscillation information from the EEG probe 1225 and adjust auditory stimuli based on the EEG information. For example, the NSS905 can determine from the probe information that a neuron is oscillating at an undesirable frequency. The NSS905 can then use the microphone 1210 to identify the corresponding undesirable frequency in the ambient noise. The NSS905 can then instruct the active noise cancellation component 1215 to cancel the waveform corresponding to the ambient noise having the undesirable frequency.

[0317] In some embodiments, the NSS905 can enable passive noise filtering. Passive noise filtering may include a circuit having one or more resistors, capacitors, or inductors that filter out undesirable frequencies of noise. In some cases, passive filtering may include sound-insulating, sound-blocking, or sound-absorbing materials.

[0318] Figure 4C shows a system configuration for auditory induction of neural oscillations according to one embodiment. System 401 can provide auditory electroencephalogram stimulation using an ambient noise source 1230. For example, system 401 may include a microphone 1210 that detects the ambient noise 1230. The microphone 1210 can provide the detected ambient noise to an NSS 905. The NSS 905 can modify the ambient noise 1230 and then provide it to a first speaker 1205 or a second speaker 1205. In some embodiments, system 401 can be integrated with or interfaced with a hearing aid device. The hearing aid may be a device designed to improve hearing.

[0319] The NSS905 can increase or decrease the amplitude of ambient noise 1230 to generate acoustic bursts with a desired pulse rate interval. The NSS905 can then supply the modified audio signal to the first and second speakers 1205 to facilitate auditory induction of neural oscillations.

[0320] In some embodiments, the NSS905 can superimpose click trains, tones, or other acoustic pulses on top of the ambient noise 1230. For example, the NSS905 can receive ambient noise information from the microphone 1210, apply an auditory stimulus signal to the ambient noise information, and then present the combined ambient noise information and auditory stimulus signal to the first and second speakers 1205. Optionally, the NSS905 can filter out unwanted frequencies in the ambient noise 1230 before providing the auditory stimulus signal to the speakers 1205.

[0321] In this way, by using ambient noise 1230 as part of the auditory stimulus, the subject can receive the auditory stimulus while observing their surroundings or continuing their daily activities, which facilitates sensory induction of neural oscillations.

[0322] Figure 13 shows a system configuration for auditory induction of neural vibration according to one embodiment. System 1300 can provide auditory stimuli for sensory induction of neural vibration using an indoor environment. System 1300 may include one or more speakers. System 1300 may include a surround sound system. For example, System 1300 includes a left speaker 1310, a right speaker 1315, a center speaker 1305, a right surround speaker 1325, and a left surround speaker 1330. System 1300 includes a subwoofer 1320. System 1300 may include a microphone 1210. System 1300 may include or refer to a surround system. In some embodiments, System 1300 may have one, two, three, four, five, six, seven, or more speakers.

[0323] When providing auditory stimulation using a surround sound system, the NSS905 can provide the same or different audio signals to each speaker in the system 1300. The NSS905 can modify or adjust the audio signals provided to one or more of the speakers in the system 1300 to facilitate sensory induction of neural vibrations. For example, the NSS905 can receive feedback from microphone 1210 and modify, manipulate, or otherwise adjust the audio signal to optimize the auditory stimulation provided to an object located in the room corresponding to the location of microphone 1210. The NSS905 can optimize or improve the auditory stimulation perceived at the location corresponding to microphone 1210 by analyzing the acoustic beam or wave generated by the speakers and propagating toward microphone 1210.

[0324] The NSS905 can be configured using information about the design and configuration of each speaker. For example, speaker 1305 can generate sound in a direction with an angle of 1335. Speaker 1310 can generate sound traveling in a direction with an angle of 1340. Speaker 1315 can generate sound traveling in a direction with an angle of 1345. Speaker 1325 can generate sound traveling in a direction with an angle of 1355. Speaker 1330 can generate sound traveling in a direction with an angle of 1350. These angles can be the optimal or predetermined angles for each speaker. These angles may refer to the optimal angles for each speaker so that an individual positioned at the location corresponding to microphone 1210 can receive the optimal auditory stimulus. In this way, the speakers in system 1300 can be oriented to transmit auditory stimuli toward an object.

[0325] In some embodiments, the NSS905 can enable or disable one or more speakers. In some embodiments, the NSS905 can increase or decrease the volume of the speakers to facilitate sensory induction of neurovibrations. The NSS905 can intercept music tracks, television audio, movie audio, internet audio, audio output from a set-top box, or other sound sources. The NSS905 can adjust or manipulate the received audio and transmit the adjusted audio signal to the speakers in the system 1300 to generate sensory induction of neurovibrations.

[0326] Figure 14 shows a feedback sensor 1405 positioned on or near an individual's head. The feedback sensor 1405 may include, for example, an EEG probe for detecting electroencephalogram (EEG) activity.

[0327] The feedback monitor 935 can detect, receive, acquire, or otherwise identify feedback information from one or more feedback sensors 1405. The feedback monitor 935 can provide the feedback information to one or more components of the NSS 905 for further processing or storage. For example, the profile manager 925 can update the profile data structure 945 stored in the data repository 940 using the feedback information. The profile manager 925 can associate the feedback information with an identifier for the patient or individual receiving auditory brain stimulation, as well as a timestamp and date stamp corresponding to the reception or detection of the feedback information.

[0328] The Feedback Monitor 935 can determine the level of attention. The level of attention can refer to the focus given to the acoustic pulse used for brain stimulation. The Feedback Monitor 935 can determine the level of attention using various hardware and software technologies. The Feedback Monitor 935 can assign a score to the level of attention (e.g., 1-10, where 1 is low attention, 10 is high attention, or vice versa; 1-100, where 1 is low attention, 100 is high attention, or vice versa; 0-1, where 0 is low attention, 1 is high attention, or vice versa), classify the level of attention (e.g., low, moderate, high), grade the attention (e.g., A, B, C, D, or F), or otherwise provide an index of the level of attention.

[0329] Depending on the circumstances, the feedback monitor 935 may track an individual's eye movements to determine their attention level. The feedback monitor 935 may interface with a feedback component 960, which may include an eye tracker. The feedback monitor 935 (e.g., via the feedback component 960) may detect and record an individual's eye movements and analyze the recorded eye movements to determine an attention span or attention level. The feedback monitor 935 may measure gaze directions that can display or provide information related to potential attention. For example, the feedback monitor 935 (e.g., via the feedback component 960) may be configured to measure skin potentials around the eyes using electrooculography ("EOG"), which can indicate the direction in which the eyes are facing relative to the head. In some embodiments, the EOG may include a system or device to stabilize the head so that it cannot move in order to determine the direction of the eyes relative to the head. In some embodiments, the EOG may include or interface with a head tracker system that determines the position of the head and then the direction of the eyes relative to the head.

[0330] In some embodiments, the feedback monitor 935 and feedback component 960 can determine the level of attention an object is paying to an auditory stimulus based on eye movements. For example, increased eye movements may indicate that the object is focusing on a visual stimulus in contrast to an auditory stimulus. To determine the level of attention an object is paying to a visual stimulus in contrast to an auditory stimulus, the feedback monitor 935 and feedback component 960 can determine or track the direction or movement of the eyes using video detection of pupil or corneal reflections. For example, the feedback component 960 may include one or more cameras or video cameras. The feedback component 960 may include an infrared source that transmits light pulses toward the eyes. The light may be reflected by the eyes. The feedback component 960 can detect the location of the reflection. The feedback component 960 can capture or record the location of the reflection. The feedback component 960 can determine or calculate the direction or gaze direction of the eyes by performing image processing on the reflection.

[0331] The feedback monitor 935 can determine the level of attention by comparing the direction or movement of the eyes with the same individual's eye direction or movement history, nominal eye movements, or other eye movement history information. For example, the feedback monitor 935 can determine the history of the amount of eye movements during an auditory stimulus session. The feedback monitor 935 can identify deviations by comparing the current eye movements with the eye movement history. Based on this comparison, the NSS 905 can determine an increase in eye movements and, further, determine that the subject is not paying much attention to the current auditory stimulus based on the increase in eye movements. In response to the detection of decreased attention, the feedback monitor 935 can instruct the speech adjustment module 915 to change the parameters of the audio signal to capture the subject's attention. The speech adjustment module 915 can change the volume, tone, pitch, or music track to supplement the subject's attention or increase the level at which the subject is paying attention to the auditory stimulus. After changing the audio signal, the NSS 905 can continue to monitor the level of attention. For example, by changing the audio signal, the NSS905 can detect a decrease in eye movements, which may indicate an increased level of attention provided to the audio signal.

[0332] The feedback sensor 1405 can interact with or communicate with the NSS 905. For example, the feedback sensor 1405 can provide detected feedback information or data to the NSS 905 (e.g., the feedback monitor 935). The feedback sensor 1405 can provide data to the NSS 905 in real time, for example, when the feedback sensor 1405 detects or senses information. The feedback sensor 1405 can provide feedback information to the NSS 905 based on time intervals such as 1 minute, 2 minutes, 5 minutes, 10 minutes, 1 hour, 2 hours, 4 hours, 12 hours, or 24 hours. The feedback sensor 1405 can provide feedback information to the NSS 905 in response to conditions or events such as feedback measurements exceeding or falling below a threshold. The feedback sensor 1405 can provide feedback information in response to changes in feedback parameters. In some embodiments, the NSS905 can ping, query, or send information requests to the feedback sensor 1405, and the feedback sensor 1405 can provide feedback information in response to the ping, request, or query.

[0333] Methods for nerve stimulation using auditory stimulation Figure 15 is a flowchart of a method for auditory induction of neural oscillations according to one embodiment. Method 800 can be carried out by one or more systems, components, modules, or elements shown in Figures 7A, 7B, and Figures 9 to 14, including, for example, a neural stimulation system (NSS). In a brief overview, the NSS can identify the audio signal provided in block 1505. In block 1510, the NSS can generate and transmit the identified audio signal. In 1515, the NSS can receive or determine feedback related to neural activity, physiological activity, environmental parameters, or device parameters. In 1520, the NSS can manage, control, or adjust the audio signal based on the feedback.

[0334] NSS works with headphones The NSS905 can operate with the speaker 1205 as shown in Figure 12A. The NSS905 can also operate with an earphone or in-earphone that includes the speaker 1205 and the feedback sensor 1405.

[0335] During operation, the subject using the headphones may wear them on their head so that the speakers are positioned in or within the ear canal. If necessary, the subject may give instructions to the NSS905 indicating that the headphones are worn and that the subject is ready to receive sensory induction of nerve vibrations. These instructions may include commands, selections, inputs, or other instructions via an input / output interface such as the keyboard 726, pointing device 727, or other I / O devices 730a-n. The instructions may be motion-based, visual, or voice-based. For example, the subject may give a voice command indicating that the subject is ready to receive sensory induction of nerve vibrations.

[0336] Depending on the circumstances, the feedback sensor 1405 may determine that the subject is ready to receive sensory induction of neural vibrations. The feedback sensor 1405 may detect that the headphones are placed on the subject's head. The NSS 905 may determine that the headphones are placed on the subject's head by receiving motion data, acceleration data, gyroscope data, temperature data, or capacitive touch data. Received data, such as motion data, may indicate that the headphones have been picked up and placed on the subject's head. Temperature data may measure the temperature of the headphones or their vicinity, which may indicate that the headphones are on the subject's head. In response to a determination that the subject is paying a high level of attention to the headphones or the feedback sensor 1405, the NSS 905 may detect that the subject is ready.

[0337] Thus, the NSS905 can detect or determine that headphones are being worn and the subject is ready, or the NSS905 can receive instructions or confirmation from the subject that the subject is wearing headphones and is ready to receive sensory induction of neurovibration. If the NSS905 determines that the subject is ready, it can initialize the sensory induction of the neurovibration process. In some embodiments, the NSS905 can access the profile data structure 945. For example, the profile manager 925 can query the profile data structure 945 to determine one or more parameters of the external auditory stimulus used for sensory induction of the neurovibration process. Parameters may include, for example, the type of auditory stimulation technique, the intensity or volume of the auditory stimulus, the frequency of the auditory stimulus, the duration of the auditory stimulus, or the wavelength of the auditory stimulus. The profile manager 925 can query the profile data structure 945 to retrieve a history of sensory-induced neurovibration information, such as past auditory stimulation sessions. The profile manager 925 can perform a lookup in the profile data structure 945. Profile Manager 925 can perform lookups using username, user identifier, location information, fingerprint, biometric identifier, retinal scan, voice recognition and authentication, or other identification techniques.

[0338] The NSS905 can determine the type of external auditory stimulus based on the components connected to the headphones. The NSS905 can also determine the type of external auditory stimulus based on the type of available speaker 1205. For example, if the headphones are connected to an audio player, the NSS905 can decide to embed acoustic pulses. If the headphones are not connected to an audio player and are only connected to a microphone, the NSS905 can decide to inject a pure tone or correct ambient noise.

[0339] In some embodiments, the NSS905 can determine the type of external auditory stimulus based on the sensory induction history of the neural oscillatory session. For example, the profile data structure 945 can be pre-configured using information about the type of auditory signal transmission component 950.

[0340] The NSS905 can determine the modulation frequency of a pulse train or audio signal via the profile manager 925. For example, the NSS905 can determine from the profile data structure 945 that the modulation frequency for an external auditory stimulus should be set to 40 Hz. Depending on the type of auditory stimulus, the profile data structure 945 may further indicate the pulse length, intensity, wavelength of the acoustic wave forming the audio signal, or duration of the pulse train.

[0341] Depending on the circumstances, the NSS905 can determine or adjust one or more parameters of an external auditory stimulus. For example, the NSS905 (e.g., via the feedback component 960 or feedback sensor 1405) can determine the amplitude of an acoustic wave or the volume level of a sound. The NSS905 (e.g., via the sound adjustment module 915 or side effect management module 930) can establish, initialize, set, or adjust the amplitude or wavelength of an acoustic wave or acoustic pulse. For example, the NSS905 can determine that a low level of ambient noise is present. Because the ambient noise is at a low level, the subject's hearing may not be impaired, nor may their attention be distracted. Based on the detection of low-level ambient noise, the NSS905 can determine that it may not be necessary to increase the volume, or that it may be possible to decrease the volume to maintain the effectiveness of sensory induction of the neural oscillator.

[0342] In some embodiments, the NSS905 can monitor the level of ambient noise through sensory induction of the neurooscillating process (e.g., via the feedback monitor 935 and feedback component 960) to automatically and periodically adjust the amplitude of the acoustic pulse. For example, if the subject initiates the electroencephalogram (EEG) synchronization process when a high level of ambient noise is present, the NSS905 can initially set a high amplitude for the acoustic pulse and use a tone that includes easily perceptible frequencies such as 10 kHz. However, in some embodiments where the ambient noise level decreases through sensory induction of the neurooscillating process, the NSS905 can automatically detect the decrease in ambient noise and, in response to this detection, reduce the frequency of the acoustic wave while adjusting or reducing the volume. The NSS905 can facilitate sensory induction of the neurooscillating process by adjusting the acoustic pulse to provide a high contrast ratio against ambient noise.

[0343] In some embodiments, the NSS905 (e.g., via the feedback monitor 935 and feedback component 960) can monitor or measure physiological conditions to set or adjust acoustic wave parameters. In some embodiments, the NSS905 can monitor or measure heart rate, pulse rate, blood pressure, body temperature, sweating, or brain activity to set or adjust acoustic wave parameters.

[0344] In some embodiments, the NSS905 can be pre-configured to initially transmit an acoustic pulse with a minimum acoustic wave intensity setting (e.g., a low-amplitude or high-wavelength acoustic wave) and gradually increase the intensity (e.g., increase the amplitude or decrease the wavelength) while monitoring feedback until an optimal voice intensity is reached. The optimal voice intensity may refer to the highest intensity that does not result in adverse physiological side effects such as hearing loss, seizures, heart attacks, migraines, or other discomforts. The NSS905 (e.g., via the side effect management module 930) can monitor physiological symptoms to identify adverse side effects of external auditory stimuli and adjust the external auditory stimuli accordingly (e.g., via the voice adjustment module 915) to reduce or eliminate adverse side effects.

[0345] In some embodiments, the NSS905 (e.g., via the sound adjustment module 915) can adjust the parameters of the sound waves or acoustic pulses based on the level of attention. For example, during sensory induction of a neuro-oscillating process, the subject may become bored, lose focus, fall asleep, or otherwise fail to pay attention to the acoustic pulse. Failure to pay attention to the acoustic pulse reduces the effectiveness of sensory induction of the neuro-oscillating process, and as a result, neurons may vibrate at a frequency different from the desired modulation frequency of the acoustic pulse.

[0346] The NSS105 can detect the level at which an object is paying attention to an acoustic pulse using the feedback monitor 935 and one or more feedback components 960. In response to a determination that the object is not paying sufficient attention to the acoustic pulse, the voice adjustment module 915 can modify the parameters of the voice signal to gain the object's attention. For example, the voice adjustment module 915 can increase the amplitude of the acoustic pulse, adjust the tone of the acoustic pulse, or change the duration of the acoustic pulse. The voice adjustment module 915 can randomly change one or more parameters of the acoustic pulse. The voice adjustment module 915 can initiate an attention-seeking acoustic sequence configured to return the object's attention. For example, the acoustic sequence may include changes in frequency, tone, or amplitude, or the insertion of words or music in a predetermined pattern, random pattern, or pseudo-random pattern. If the voice signal transmission component 950 includes multiple sound sources or speakers, the attention-seeking acoustic sequence can enable or disable different sound sources. In this way, the sound adjustment module 915 interacts with the feedback monitor 935 to determine the level at which the subject is paying attention to the acoustic pulse, and if the level of attention falls below a threshold, it can adjust the acoustic pulse to restore the subject's attention.

[0347] In some embodiments, the sound adjustment module 915 can change or adjust one or more parameters of an acoustic pulse or acoustic wave at predetermined time intervals (for example, every 5 minutes, every 10 minutes, every 15 minutes, or every 20 minutes) to restore or maintain the attention level of the subject.

[0348] In some embodiments, the NSS905 (e.g., via the unwanted frequency filtering module 920) can filter, block, attenuate, or remove unwanted auditory stimuli. Unwanted auditory stimuli may include, for example, unwanted modulation frequencies, unwanted intensities, or unwanted wavelengths of sound waves. The NSS905 may consider a modulation frequency to be undesirable if the modulation frequency of a pulse train differs from or substantially differs from a desired frequency (e.g., by 1%, 2%, 5%, 10%, 15%, 20%, 25%, or more than 25%).

[0349] For example, a desirable modulation frequency for sensory induction of nerve oscillations may be 40 Hz. However, modulation frequencies of 20 Hz or 80 Hz may reduce the beneficial effects on brain cognitive function, brain cognitive state, the immune system, or inflammation that may result from sensory induction of nerve oscillations at other frequencies such as 40 Hz. For this reason, the NSS905 can filter out acoustic pulses corresponding to modulation frequencies of 20 Hz or 80 Hz.

[0350] In some embodiments, the NSS905 can detect, via the feedback component 960, the presence of an acoustic pulse from an ambient noise source corresponding to an unwanted modulation frequency of 20 Hz. The NSS905 can further determine the wavelength of the acoustic wave of the acoustic pulse corresponding to the unwanted modulation frequency. The NSS905 can instruct the filtering component 955 to filter out the wavelength corresponding to the unwanted modulation frequency.

[0351] Nerve stimulation by peripheral nerve stimulation In some embodiments, the systems and methods of the present disclosure can be used to stimulate peripheral nerves to produce or induce nerve oscillations. For example, tactile stimulation to the skin surrounding a sensory nerve that forms part of or is connected to the peripheral nervous system can produce or induce electrical activity in the sensory nerve, resulting in transmission to the brain via the central nervous system, which may produce or induce electrical and neural activity in the brain that can be perceived by the brain or that produces nerve oscillations. Similarly, passing an electric current through or to the skin surrounding a sensory nerve that forms part of or is connected to the peripheral nervous system can produce or induce electrical activity in the sensory nerve, resulting in transmission to the brain via the central nervous system, which may produce or induce electrical and neural activity in the brain that can be perceived by the brain or that produces nerve oscillations. The brain can adjust, manage, or control the frequency of nerve oscillations in response to the reception of peripheral nerve stimulation. Electrical currents, such as time-varying pulses, can cause depolarization of nerve cells. Current pulses may also directly induce depolarization. Secondary effects on other areas of the brain may be gated or controlled by the brain in response to depolarization. Peripheral nerve stimulation generated at a predetermined frequency can induce or generate neural oscillations by inducing neural activity in the brain. The frequency of the neural oscillations may be based on or corresponding to the frequency of the peripheral nerve stimulation, or a modulation frequency associated with the peripheral nerve stimulation. Therefore, the systems and methods of this disclosure can synchronize electrical activity among groups of neurons based on the frequency of peripheral nerve stimulation by generating or inducing neural oscillations using peripheral nerve stimulation, such as current pulses modulated at a predetermined frequency. Sensory induction of neural oscillations can be observed from the total frequency of the neural oscillations produced by the synchronous electrical activity in a group of cortical neurons. The modulation of the current, or the frequency of its pulse, can cause or adjust the synchronous electrical activity in this group of cortical neurons to oscillate at a frequency corresponding to the frequency of the peripheral nerve stimulation pulse.

[0352] Figure 16A is a block diagram illustrating a system, according to one embodiment, that generates or induces nerve oscillations, such as electroencephalogram (EEG) synchronization, by performing peripheral nerve stimulation. System 1600 may include a peripheral nerve stimulation system 1605. Briefly outlined, the peripheral nerve stimulation system (or peripheral nerve stimulation system) ("NSS") 1605 includes, accesses, interfaces with, or can otherwise communicate with one or more of the following: a nerve stimulation generation module 1610, a nerve stimulation adjustment module 1615, a profile manager 1625, an adverse event management module 1630, a feedback monitor 1635, a data repository 1640, a nerve stimulation generator component 1650, a shielding component 1655, a feedback component 1660, or a nerve stimulation amplification component 1665. The nerve stimulation generation module 1610, nerve stimulation adjustment module 1615, profile manager 1625, side effect management module 1630, feedback monitor 1635, nerve stimulation generator component 1650, shielding component 1655, feedback component 1660, or nerve stimulation amplification component 1665 may each include at least one processing unit or other logical device, such as a programmable logic array engine, or a module configured to communicate with the database repository 1650. The nerve stimulation generation module 1610, nerve stimulation adjustment module 1615, profile manager 1625, side effect management module 1630, feedback monitor 1635, nerve stimulation generator component 1650, shielding component 1655, feedback component 1660, or nerve stimulation amplification component 1665 may be separate components, single components, or part of NSS 1605. The system 1600 and its components, such as NSS 1605, may include one or more hardware elements such as processors, logical devices, or circuits.System 1600 and its components, such as NSS 1605, may include one or more hardware or interface components, as shown in System 700 in Figures 7A and 7B. For example, the components of System 1600 may include, or run on, one or more processors 721, access storage 728, or memory 722, and communicate via the network interface 718.

[0353] Nerve stimulation using multiple stimulation modes Figure 16B is a block diagram illustrating a system for neural stimulation with multiple stimulation modes according to one embodiment. System 1600 may include a neural stimulation orchestration system ("NSOS") 1605. The NSOS 1605 can provide multiple stimulation modes. For example, the NSOS 1605 may provide a first stimulation mode including visual stimulation and a second stimulation mode including auditory stimulation. In each stimulation mode, the NSOS 1605 may provide one type of signal. For example, in the visual stimulation mode, the NSOS 1605 may provide the following types of signals: light pulses, image patterns, ambient light flicker, or augmented reality. The NSOS 1605 can be coordinated, managed, controlled, or otherwise facilitated in providing multiple stimulation modes and types of stimulation.

[0354] In summary, NSOS1605 includes, can access, interface with, or otherwise communicate with one or more of the following: a stimulus orchestration component 1610, a target evaluation module 1650, a data repository 1615, one or more signaling components 1630a-n, one or more filtering components 1635a-n, one or more feedback components 1640a-n, and one or more neural stimulation systems ("NSS") 1645a-n. The data repository 1615 includes or can store a profile data structure 1620 and a policy data structure 1625. The stimulus orchestration component 1610 and the target evaluation module 1650 may include at least one processing unit or other logical device, such as a programmable logic array engine, or a module configured to communicate with the database repository 1615. The stimulus orchestration component 1610 and the target evaluation module 1650 may be a single component, include separate components, or be part of NSOS1605. System 1600 and its components, such as NSOS 1605, may include one or more hardware elements such as processors, logic devices, or circuits. System 1600 and its components, such as NSOS 1605, may include one or more hardware or interface components shown in System 700 in Figures 7A and 7B. For example, the components of System 1600 may include, or run on, one or more processors 721, access storage 728, or memory 722, which can communicate via a network interface 718. System 1600 may include one or more components or functionalities shown in Figures 1 to 15, such as System 100, System 900, Visual NSS 105, or Auditory NSS 905.For example, at least one of the signal transmission components 1630a to n may include one or more components or functions of the visual signal transmission component 150 or the audio signal transmission component 950. At least one of the filtering components 1635a to n may include one or more components or functions of the filtering component 155 or the filtering component 955. At least one of the feedback components 1640a to n may include one or more components or functions of the feedback component 160 or the feedback component 960. At least one of the NSS 1645a to n may include one or more components or functions of the visual NSS 105 or the auditory NSS 905.

[0355] Continuing to refer to Figure 16B in more detail, NSOS1605 may include at least a stimulus orchestration component 1610. The stimulus orchestration component 1610 can be designed and constructed to perform neural stimulation using multiple stimulus modalities. The stimulus orchestration component 1610 or NSOS1605 can interface with at least one of the signaling components 1630a-n, at least one of the filtering components 1635a-n, or at least one of the feedback components 1640a-n. One or more of the signaling components 1630a-n may be of the same type or different types. The type of signaling component can correspond to the stimulus mode. For example, multiple types of signaling components 1630a-n may correspond to visual signaling components or auditory signaling components. In some cases, at least one of the signaling components 1630a-n may include a visual signaling component 150 such as a light source, LED, laser, tablet computing device, or virtual reality headset. At least one of the signal transmission components includes an audio signal transmission component 950 such as headphones, a speaker, a cochlear implant, or an air jet.

[0356] One or more of the filtering components 1635a to n may be of the same type or different types. One or more of the feedback components 1640a to n may be of the same type or different types. For example, feedback components 1640a to n may include electrodes, dry electrodes, gel electrodes, saline-immersed electrodes, adhesive-based electrodes, temperature sensors, heart rate or pulse rate monitors, physiological sensors, ambient light sensors, ambient temperature sensors, sleep state via actigraphy, blood pressure monitors, respiratory rate monitors, electroencephalogram sensors, EEG probes configured to measure angular retinal standing potentials present between the anterior and posterior parts of the human eye, accelerometers, gyroscopes, motion detectors, proximity sensors, cameras, microphones, or photodetectors.

[0357] The stimulus orchestration component 1610 may include, or be configured with, interfaces for communicating with different types of signal transmission components 1630a-n, filtering components 1635a-n, or feedback components 1640a-n. The NSOS 1605 or the stimulus orchestration component 1610 may interface with a system intermediary to one of the signal transmission components 1630a-n, filtering components 1635a-n, or feedback components 1640a-n. For example, the stimulus orchestration component 1610 may interface with the visual NSS 105 shown in Figure 1 or the auditory NSS 905 shown in Figure 9. Thus, in some embodiments, the stimulus orchestration component 1610 or the NSOS 1605 may indirectly interface with at least one of the signal transmission components 1630a-n, filtering components 1635a-n, or feedback components 1640a-n.

[0358] The stimulus orchestration component 1610 (e.g., via an interface) can ping each of the signal transmission components 1630a-n, filtering components 1635a-n, and feedback components 1640a-n to determine information about the components. This information may include the type of component (e.g., visual, auditory, attenuator, optical filter, temperature sensor, or light sensor), the configuration of the component (e.g., frequency range, amplitude range), or status information (e.g., standby, ready, online, enabled, error, fault, offline, disabled, warning, service required, available, or battery level).

[0359] The stimulus orchestration component 1610 can instruct or cause at least one of the signaling components 1630a to n to generate, transmit, or otherwise provide a signal that may be perceived, received, or observed by the brain and may affect the frequency of neural oscillations in at least one region or part of the brain in question. The signal may be perceived through various means, for example, including optic nerves or cochlear cells.

[0360] The stimulus orchestration component 1610 can access the data repository 1615 to retrieve profile information 1620 and policy 1625. Profile information 1620 may include profile information 145 or profile information 945. Policy 1625 may include a multimodal stimulus policy. Policy 1625 may indicate a multimodal stimulus program. The stimulus orchestration component 1610 can apply policy 1625 to the profile information to determine the type of stimulus (e.g., visual or auditory) and the parameter values ​​for each type of stimulus (e.g., amplitude, frequency, wavelength, color, etc.). The stimulus orchestration component 1610 can apply policy 1625 to the profile information 1620 and feedback information received from one or more feedback components 1640a~n to determine or adjust the type of stimulus (e.g., visual or auditory) and determine or adjust the parameter values ​​for each type of stimulus (e.g., amplitude, frequency, wavelength, color, etc.). The stimulus orchestration component 1610 can apply policy 1625 to profile information to determine the type of filter (e.g., an audio filter or a visual filter) applied by at least one of the filtering components 1635a to n, and determine the parameter values ​​for each filter type (e.g., frequency, wavelength, color, sound attenuation, etc.). The stimulus orchestration component 1610 can apply policy 1625 to profile information and feedback information received from one or more feedback components 1640a to n to determine or adjust the type of filter (e.g., an audio filter or a visual filter) applied by at least one of the filtering components 1635a to n, and determine or adjust the parameter values ​​for the filter (e.g., frequency, wavelength, color, sound attenuation, etc.).

[0361] NSOS1605 can acquire profile information 1620 via the subject assessment module 1650. The subject assessment module 1650 can be designed and constructed to determine information that can facilitate neural stimulation via one or more stimulation modes for one or more subjects. The subject assessment module 1650 can receive, acquire, detect, determine, or otherwise identify statistics, queries, questionnaires, prompts, network-accessible remote profile information, diagnostic tests, or treatment history via feedback components 1640a-n.

[0362] The target evaluation module 1650 can receive information before, during, or after nerve stimulation. For example, the target evaluation module 1650 can prompt for information before starting a nerve stimulation session. The target evaluation module 1650 can prompt for information during a nerve stimulation session. The target evaluation module 1650 can receive feedback from feedback components 1640a-n (e.g., EEG probes) during a nerve stimulation session. The target evaluation module 1650 can prompt for information after the end of a nerve stimulation session. The target evaluation module 1650 can receive feedback from feedback components 1640a-n after the end of a nerve stimulation session.

[0363] The subject evaluation module 1650 can use the above information to determine the effectiveness of the modality of the stimulus (e.g., visual or auditory stimulus) or the type of signal (e.g., light pulses from a laser or LED source, ambient light flicker, or image patterns displayed by a tablet computing device). For example, the subject evaluation module 1650 can determine that the desired nerve stimulation resulted from a first stimulation mode or a first type of signal, but did not result from a second stimulation mode or a second type of signal, or took a long time to occur. Based on feedback information from feedback components 1640a-n, the subject evaluation module 1650 can determine that the desired nerve stimulation was less pronounced in the second stimulation mode or a second type of signal compared to the first stimulation mode or a first type of signal.

[0364] The target evaluation module 1650 can determine the effectiveness level of each stimulation mode or type of stimulation independently or based on a combination of stimulation modes or types. A combination of stimulation modes may refer to the transmission of signals from different stimulation modes at the same or substantially similar time. A combination of stimulation modes may refer to the superimposed transmission of signals from different stimulation modes. A combination of stimulation modes may refer to the transmission of signals from different stimulation modes within a certain time interval without superimposing them (for example, transmitting a signal pulse train from a second stimulation mode within 0.5 seconds, 1 second, 1.5 seconds, 2 seconds, 2.5 seconds, 3 seconds, 5 seconds, 7 seconds, 10 seconds, 12 seconds, 15 seconds, 20 seconds, 30 seconds, 45 seconds, 60 seconds, 1 minute, 2 minutes, 3 minutes, 5 minutes, 10 minutes, or within other time intervals in which the effect of the first mode on the frequency of nerve oscillations may overlap with that of the second mode).

[0365] The target evaluation module 1650 can aggregate or compile information and update the profile data structure 1620 stored in the data repository 1615. If necessary, the target evaluation module 1650 can update or generate a policy 1625 based on the received information. The policy 1625 or profile information 1620 may indicate which modes or types of stimulation are likely to have the desired effect on nerve stimulation while reducing side effects.

[0366] The stimulus orchestration component 1610 can instruct or cause multiple signal transmission components 1630a to n to generate, transmit, or otherwise provide different types of stimuli or signals according to policy 1625, profile information 1620, or feedback information detected by feedback components 1640a to n. The stimulus orchestration component 1610 can cause multiple signal transmission components 1630a to n to generate, transmit, or otherwise provide different types of stimuli or signals simultaneously or nearly simultaneously. For example, the first signal transmission component 1630a can transmit a first type of stimulus at the same time that the second signal transmission component 1630b transmits a second type of stimulus. The first signal transmission component 1630a can transmit or provide a first set of signals, pulses, or stimuli at the same time that the second signal transmission component 1630b transmits or provides a second se...

Claims

1. A method comprising the steps of administering gamma oscillation-induced stimulation and one or more drugs to a subject in need thereof, wherein the one or more drugs are a. Amyloid-beta specific monoclonal antibody, b. N-methyl-D-aspartate (NMDA) receptor antagonists, c. Cellular stress signaling blockers, d. Chemical chaperones, e. Glutamate regulators, f. Sigma-1 receptor agonists, g. Voltage-gated sodium channel blockers, h. NrF2 activator, i. Vesicular monoamine transporter 2 (VMAT2) inhibitors, j. Catechol-O-methyltransferase (COMT) inhibitors, k. Monoamine oxidase-B (MAO-B) inhibitors, l. Dopamine reuptake inhibitors, m. Adenosine 2A receptor (A2AR) antagonist, n. Muscarinic receptor antagonists, o. Antisense oligonucleotides, p. RNA splicing modifiers, Q. Stimulants (eugeroic agents), r. Serotonin 1A (5-hydroxytryptamine 1A, 5-HT １Ａ ) Receptor agonist, s. 5-HT １Ｆ Receptor agonists, t. 5-HT ２Ａ Receptor inverse agonist, u. 5-HT ２Ａ Receptor antagonist, v. Dopamine and serotonin receptor antagonists, w. Radioactive tracers or radiopharmaceutical compounds, x. Free radical scavengers, y. GLP-1 receptor agonist, hallucinogen, z. GLP-1 receptor agonists, and aa. Sphingosine-1-phosphate (S1P) receptor regulator A method selected from the group consisting of the following.

2. The method according to claim 1, wherein the amyloid-beta specific monoclonal antibody comprises aducanumab.

3. The method according to claim 1, wherein the amyloid-beta specific monoclonal antibody comprises lecanemab.

4. The method according to claim 1, wherein the amyloid-beta specific monoclonal antibody comprises donanemab.

5. The method according to claim 1, wherein the amyloid-beta specific monoclonal antibody comprises remternetug.

6. The method according to claim 1, wherein the NMDA receptor antagonist comprises memantine.

7. The method according to claim 1, wherein the cell stress signal blocker comprises sodium phenylbutyrate and taursodiol.

8. The method according to claim 1, wherein the chemical chaperone comprises sodium phenylbutyrate.

9. The method according to claim 1, wherein the glutamate regulator comprises riluzole.

10. The method according to claim 1, wherein the one or more agents include a sigma-1 receptor and an N-methyl-D-aspartate (NMDA) receptor antagonist.

11. The method according to claim 10, wherein the one or more drugs include dextromethorphan and quinidine.

12. The method according to claim 1, wherein the one or more agents include a voltage-gated sodium channel blocker.

13. The method according to claim 12, wherein the one or more drugs include dextromethorphan and quinidine.

14. The method according to claim 1, wherein the NrF2 activator comprises omaberoxolone.

15. The method according to claim 1, wherein the VMAT2 inhibitor comprises tetrabenazine.

16. The method according to claim 1, wherein the VMAT2 inhibitor comprises valbenazine.

17. The method according to claim 1, wherein the VMAT2 inhibitor comprises deutetrabenazine.

18. The method according to claim 1, wherein the COMT inhibitor comprises entacapone.

19. The method according to claim 1, wherein the COMT inhibitor comprises tolcapone.

20. The method according to claim 1, wherein the COMT inhibitor comprises opicapone.

21. The method according to claim 1, wherein the MAO-B inhibitor comprises rasagiline.

22. The method according to claim 1, wherein the MAO-B inhibitor comprises safinamide.

23. The method according to claim 1, wherein the MAO-B inhibitor comprises selegiline.

24. The method according to claim 1, wherein the dopamine reuptake inhibitor comprises amantadine.

25. The method according to claim 1, wherein the A2AR antagonist comprises istradefylline.

26. The method according to claim 1, wherein the muscarinic receptor antagonist comprises trihexyphenidyl.

27. The method according to claim 1, wherein the muscarinic receptor antagonist comprises benztropin.

28. The method according to claim 1, wherein the antisense oligonucleotide comprises nusinersene.

29. The method according to claim 1, wherein the RNA splicing modifier comprises risdiplam.

30. The method according to claim 1, wherein the stimulant comprises almodafinil.

31. The aforementioned 5-HT １Ａ The method according to claim 1, wherein the receptor agonist is caliprazine.

32. The aforementioned 5-HT １Ｆ The method according to claim 1, wherein the receptor agonist comprises rasmiditane.

33. The aforementioned 5-HT ２Ａ The method according to claim 1, wherein the receptor inverse agonist comprises pimavanserin.

34. The aforementioned 5-HT ２Ａ The method according to claim 1, wherein the receptor antagonist is trazodone.

35. The method according to claim 1, wherein the dopamine and serotonin receptor antagonist includes olanzapine, brexpiprazole, lurasidone, lumateperone, or a combination thereof.

36. The method according to claim 35, wherein the dopamine and serotonin receptor antagonist comprises olanzapine.

37. The method according to claim 1, wherein the radioactive tracer comprises a fluorine-18 (18F) labeled stilbene derivative.

38. The method according to claim 37, wherein the 18F-labeled stilbene derivative comprises florbetabene.

39. The method according to claim 1, wherein the free radical scavenger comprises edaravone.

40. The method according to claim 1, wherein the hallucinogen comprises psilocybin.

41. The method according to claim 1, wherein the hallucinogen comprises lysergic acid diethylamide (LSD).

42. The method according to claim 1, wherein the GLP-1 receptor agonist comprises semaglutide, tylzepatide, dulaglutide, exenatide, liraglutide, or lixisenatide.

43. The method according to claim 1, wherein the SIP receptor modulator comprises fingolimod hydrochloride, siponimod, or ozanimod hydrochloride.

44. The method according to claim 1, wherein the gamma vibration induction stimulus includes electromagnetic stimulation, tactile or vibratory tactile stimulation, auditory stimulation, visual stimulation, or a combination thereof.

45. The method according to any one of claims 1 to 44, wherein the subject is identified as amyloid PET positive.

46. A method comprising the steps of providing non-invasive gamma oscillation-induced stimulation, and administering one or more agents selected from dopamine precursors, doper-decarboxylase (DDC) inhibitors, and dopamine agonists to a subject in need thereof.

47. The method according to claim 46, wherein the non-invasive gamma vibration-induced stimulation includes tactile or vibrotactile stimulation, auditory stimulation, visual stimulation, or a combination thereof.

48. The method according to claim 46, wherein the dopamine agonist comprises pramipexole.

49. The method according to claim 46, wherein the dopamine agonist comprises ropinirole.

50. The method according to claim 46, wherein the dopamine agonist comprises apomorphine.

51. The method according to claim 46, wherein the dopamine agonist comprises rotigotine.

52. The method according to claim 46, wherein the DDC inhibitor comprises carbidopa.

53. The method according to claim 46, wherein the DDC inhibitor comprises benserazide.

54. The method according to claim 46, wherein the dopamine precursor comprises levodopa.

55. The method according to claim 46, wherein the one or more agents include the dopamine precursor and the doper-decarboxylase inhibitor.

56. The method according to claim 55, wherein the dopamine precursor comprises levodopa.

57. The method according to claim 55, wherein the doper decarboxylase inhibitor comprises benserazide.

58. The method according to claim 55, wherein the doper-decarboxylase inhibitor comprises carbidopa.

59. A method for treating neurodegeneration in a subject requiring treatment for neurodegeneration, comprising the step of administering gamma oscillation-induced stimulation and one or more agents selected from orexin receptor antagonists, selective serotonin reuptake inhibitors (SSRIs), and gamma-aminobutyric acid (GABA) receptor agonists to the subject, thereby treating the neurodegeneration in the subject requiring treatment for neurodegeneration.

60. The method according to claim 59, wherein the orexin receptor antagonist comprises suvorexant.

61. The method according to claim 59, wherein the orexin receptor antagonist comprises remborexant.

62. The method according to claim 59, wherein the orexin receptor antagonist comprises dalidrexant.

63. The method according to claim 59, wherein the SSRI comprises escitalopram.

64. The method according to claim 59, wherein the SSRI comprises citalopram.

65. The method according to claim 59, wherein the SSRI comprises dapoxetine.

66. The method according to claim 59, wherein the SSRI comprises fluvoxamine.

67. The method according to claim 59, wherein the SSRI comprises paroxetine.

68. The method according to claim 59, wherein the SSRI comprises sertraline.

69. The method according to claim 59, wherein the SSRI comprises vortioxetine.

70. The method according to claim 59, wherein the GABA receptor agonist comprises baclofen.

71. The method according to claim 59, wherein the GABA receptor agonist comprises propofol.

72. The method according to claim 59, wherein the GABA receptor agonist comprises gamma-hydroxybutyrate (GHB).

73. The method according to claim 59, wherein the gamma-oscillating stimulation includes electromagnetic stimulation, tactile or vibratory tactile stimulation, auditory stimulation, visual stimulation, or a combination thereof.

74. A method comprising the steps of administering gamma-oscillating stimulation and an acetylcholinesterase inhibitor selected from donepezil, rivastigmine, galantamine, and tacrine to a subject requiring them.

75. A method comprising the steps of administering gamma-oscillating stimulation, and an orexin receptor antagonist selected from suvorexant, remvorexant, and dalidrexant, to a subject requiring them.

76. The method according to claim 74 or 75, wherein the gamma-oscillating induced stimulus includes electromagnetic stimulation, tactile or vibratory tactile stimulation, auditory stimulation, visual stimulation, or a combination thereof.

77. A method comprising the steps of (a) administering interferon beta-1b, interferon beta-1a, pegylated interferon beta-1a, or a combination thereof, and (b) gamma-oscillating stimulation to a subject requiring the same.

78. A method comprising the steps of (a) administering alemtuzumab, natalizumab, ocrelizumab, ofatumumab, or a combination thereof, and (b) gamma-oscillating stimulation to a subject in need thereof.

79. A method comprising the steps of (a) administering glatiramer acetate, teriflunomide, dimethyl fumarate, monomethyl fumarate, diloximel fumarate, or a combination thereof, and (b) a gamma-oscillating stimulus to a subject requiring them.

80. A method comprising: (a) identifying a subject as having amyloid plaques; (b) administering gamma oscillation-induced stimulation; and (c) administering an amyloid-beta-specific monoclonal antibody to the subject.

81. The method according to claim 80, wherein the step of identifying the target includes obtaining an amyloid-positive PET scan of the target.

82. The method according to any one of claims 1 to 81, wherein the subject has been diagnosed with a prion disease or is suspected of having a prion disease.

83. The method according to claim 82, wherein the prion disease includes Alzheimer's disease.

84. A method comprising: (a) identifying a subject as having multiple sclerosis; (b) administering gamma oscillation-induced stimulation; and (c) administering a therapeutic agent for the treatment of multiple sclerosis.

85. The method according to claim 84, wherein the therapeutic agent for treating the multiple sclerosis is selected from the list consisting of glatiramer acetate, interferon beta-1a, interferon beta-1b, ofatumumab, pegylated interferon beta-1a, fingolimod, cladribine, siponimod, dimethyl fumarate, diroximel fumarate, mitoxantrone, and natalizumab.

86. A method of treating neurodegeneration in a subject that requires treatment of neurodegeneration, comprising administering to the subject (i) gamma oscillation-induced stimulation and (ii) one or more agents selected from a norepinephrine reuptake inhibitor, a histamine receptor antagonist, a GABA Ａ subunit selective negative allosteric modulator, a muscarinic receptor agonist, or any combination thereof, thereby treating the neurodegeneration in the subject.

87. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises atomoxetine.

88. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises reboxetine.

89. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises biloxazine.

90. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises amedaline.

91. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises daredarin.

92. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises ediboxetine.

93. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises esreboxetine.

94. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises lortalamine.

95. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises nisoxetine.

96. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises talopram.

97. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises talspram.

98. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises tandamine.

99. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises bupropion.

100. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises desipramine.

101. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises maprotiline.

102. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises nortriptyline.

103. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises protriptyline.

104. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises tapentadol.

105. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises teniroxazine.

106. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises cyclazindol.

107. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises CP-39,332.

108. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises manifaxine.

109. The method according to claim 86, wherein the norepinephrine reuptake inhibitor comprises radafaxine.

110. The aforementioned GABA Ａ The method according to claim 86, wherein the subunit-selective negative allosteric regulator comprises basmisanil.

111. The aforementioned GABAA subunit selective negative allosteric regulator is α ５ The method according to claim 86, including IA.

112. The aforementioned GABA Ａ The method according to claim 86, wherein the subunit-selective negative allosteric regulators include L-655,708.

113. The method according to claim 86, wherein the GABAA subunit selective negative allosteric regulator comprises MRK-016.

114. The aforementioned GABA Ａ The method according to claim 86, wherein the subunit-selective negative allosteric regulator comprises PWZ-029.

115. The method according to claim 86, wherein the GABAA subunit selective negative allosteric regulator comprises Ro4938581.

116. The aforementioned GABA Ａ The method according to claim 86, wherein the subunit-selective negative allosteric regulator comprises TB-21007.

117. The method according to claim 86, wherein the muscarinic receptor agonist comprises xanomeline.

118. The method according to claim 86, wherein the muscarinic receptor agonist comprises xanomeline having throspium.

119. A method for increasing synaptic plasticity of a target, comprising the step of increasing synaptic plasticity by (i) gamma oscillation-inducing stimulation and (ii) administering to the target one or more agents selected from an SV2A agonist, an HGF agonist, a phosphodiesterase inhibitor, a negative allosteric modulator of the cannabinoid CB1 receptor, or any combination thereof.

120. The method according to claim 119, wherein the SV2A agonist comprises brivalacetam.

121. The method according to claim 119, wherein the SV2A agonist comprises levetiracetam.

122. The method according to claim 119, wherein the HGF agonist comprises a MET kinase inhibitor (TKI).

123. The method according to claim 119, wherein the HGF agonist comprises an anti-HGF monoclonal antibody (anti-HGF Ab).

124. The method according to claim 119, wherein the HGF agonist comprises an anti-MET monoclonal antibody (anti-MET Ab).

125. The method according to claim 119, wherein the phosphodiesterase inhibitor comprises sildenafil.

126. The method according to claim 119, wherein the phosphodiesterase inhibitor comprises vardenafil.

127. The method according to claim 119, wherein the phosphodiesterase inhibitor comprises tadalafil.

128. The method according to claim 119, wherein the phosphodiesterase inhibitor comprises avanafil.

129. The cannabinoid CB １ The method according to claim 119, wherein the negative allosteric regulator of the receptor comprises cannabidiol.

130. A method for increasing the remyelination of the subject, comprising the step of increasing the remyelination of the subject by administering to the subject (i) gamma oscillation-induced stimulation and (ii) one or more agents selected from histamine receptor modulators and SIP modulators, or any combination thereof.

131. The method according to claim 130, wherein the histamine receptor modulator comprises betasol.

132. The method according to claim 130, wherein the histamine receptor modulator comprises clemastine.

133. The method according to claim 130, wherein the histamine receptor modulator comprises cetirizine.

134. The method according to claim 130, wherein the histamine receptor modulator comprises terfenadine.

135. The method according to claim 130, wherein the histamine receptor modulator comprises buclidine.

136. The method according to claim 130, wherein the histamine receptor modulator comprises doxylamine.

137. The method according to claim 130, wherein the histamine receptor modulator comprises mirtazapine.

138. The method according to claim 130, wherein the histamine receptor modulator comprises profenamine.

139. The method according to claim 130, wherein the histamine receptor modulator comprises dexbrompheniramine.

140. The method according to claim 130, wherein the histamine receptor modulator comprises triprolidine.

141. The method according to claim 130, wherein the histamine receptor modulator comprises cyproheptadine.

142. The method according to claim 130, wherein the histamine receptor modulator comprises cimetidine.

143. The method according to claim 130, wherein the histamine receptor modulator comprises hydroxyzine.

144. The method according to claim 130, wherein the histamine receptor modulator comprises cinnaridine.

145. The method according to claim 130, wherein the histamine receptor modulator comprises nizatidine.

146. The method according to claim 130, wherein the histamine receptor modulator comprises astemizole.

147. The method according to claim 130, wherein the histamine receptor modulator comprises azatadine.

148. The method according to claim 130, wherein the histamine receptor modulator comprises meclizine.

149. The method according to claim 130, wherein the histamine receptor modulator comprises carbinoxamine.

150. The method according to claim 130, wherein the histamine receptor modulator comprises epinastine.

151. The method according to claim 130, wherein the histamine receptor modulator comprises olopatadine.

152. The method according to claim 130, wherein the histamine receptor modulator comprises tripellennamine.

153. The method according to claim 130, wherein the histamine receptor modulator comprises brompheniramine.

154. The method according to claim 130, wherein the histamine receptor modulator comprises pemirolast.

155. The method according to claim 130, wherein the histamine receptor modulator comprises ketotifen.

156. The method according to claim 130, wherein the histamine receptor modulator comprises famotidine.

157. The method according to claim 130, wherein the histamine receptor modulator comprises fexofenadine.

158. The method according to claim 130, wherein the histamine receptor modulator comprises desloratadine.

159. The method according to claim 130, wherein the histamine receptor modulator comprises azelastine.

160. The method according to claim 130, wherein the histamine receptor modulator comprises dimenhydrinate.

161. The method according to claim 130, wherein the histamine receptor modulator comprises promethazine.

162. The method according to claim 130, wherein the histamine receptor modulator comprises mequitazine.

163. The method according to claim 130, wherein the histamine receptor modulator comprises diphenhydramine.

164. The method according to claim 130, wherein the histamine receptor modulator comprises emedastine.

165. The method according to claim 130, wherein the histamine receptor modulator comprises levocabastine.

166. The method according to claim 130, wherein the histamine receptor modulator comprises chlorpheniramine.

167. The method according to claim 130, wherein the histamine receptor modulator includes doxepin.

168. The method according to claim 130, wherein the histamine receptor modulator comprises cyclidine.

169. The method according to claim 130, wherein the histamine receptor modulator comprises alimazine.

170. The method according to claim 130, wherein the histamine receptor modulator comprises phenyndamine.

171. The method according to claim 130, wherein the histamine receptor modulator comprises pheniramine.

172. The method according to claim 130, wherein the histamine receptor modulator comprises flunarizine.

173. The method according to claim 130, wherein the histamine receptor modulator includes histamine.

174. The method according to claim 130, wherein the histamine receptor modulator comprises mianserin.

175. The method according to claim 130, wherein the histamine receptor modulator comprises levocetirizine.

176. The method according to claim 130, wherein the histamine receptor modulator comprises mepyramine.

177. The method according to claim 130, wherein the histamine receptor modulator comprises betahistine.

178. The method according to claim 130, wherein the histamine receptor modulator comprises alkafatazine.

179. The method according to claim 130, wherein the histamine receptor modulator comprises rhodoxamide.

180. The method according to claim 130, wherein the histamine receptor modulator comprises antazoline.

181. The method according to claim 130, wherein the histamine receptor modulator comprises dimethindene.

182. The method according to claim 130, wherein the histamine receptor modulator comprises dimethothiazine.

183. The method according to claim 130, wherein the histamine receptor modulator comprises acribastin.

184. The method according to claim 130, wherein the histamine receptor modulator comprises dexchlorpheniramine maleate.

185. The method according to claim 130, wherein the histamine receptor modulator comprises tondylamine.

186. The method according to claim 130, wherein the histamine receptor modulator comprises ebastine.

187. The method according to claim 130, wherein the histamine receptor modulator comprises mizolastin.

188. The method according to claim 130, wherein the histamine receptor modulator comprises oxatomide.

189. The method according to claim 130, wherein the histamine receptor modulator comprises tritoqualin.

190. The method according to claim 130, wherein the histamine receptor modulator comprises butyrate.

191. The method according to claim 130, wherein the histamine receptor modulator comprises metapyrylene.

192. The method according to claim 130, wherein the histamine receptor modulator comprises tesmirifen.

193. The method according to claim 130, wherein the histamine receptor modulator comprises esmirtazapine.

194. The method according to claim 130, wherein the histamine receptor modulator includes SKF-91488.

195. The method according to claim 130, wherein the histamine receptor modulator comprises tranilast.

196. The method according to claim 130, wherein the histamine receptor modulator comprises chloropyramine.

197. The method according to claim 130, wherein the histamine receptor modulator comprises isotipendyl.

198. The method according to claim 130, wherein the histamine receptor modulator comprises methiaamide.

199. The method according to claim 130, wherein the histamine receptor modulator comprises roxatidine acetate.

200. The method according to claim 130, wherein the histamine receptor modulator comprises chlorphenoxamine.

201. The method according to claim 130, wherein the histamine receptor modulator comprises ozagrel.

202. The method according to claim 130, wherein the histamine receptor modulator comprises treforant.

203. The method according to claim 130, wherein the histamine receptor modulator comprises lafutidine.

204. The method according to claim 130, wherein the histamine receptor modulator comprises lavortidine.

205. The method according to claim 130, wherein the histamine receptor modulator comprises deptropin.

206. The method according to claim 130, wherein the histamine receptor modulator comprises vamipine.

207. The method according to claim 130, wherein the histamine receptor modulator comprises kifenadine.

208. The method according to claim 130, wherein the histamine receptor modulator includes a histamine receptor antagonist.

209. The method according to claim 208, wherein the histamine receptor antagonist comprises famotidine.

210. The method according to claim 208, wherein the histamine receptor antagonist comprises cimetidine.

211. The method according to claim 208, wherein the histamine receptor antagonist comprises nizatidine.

212. The method according to claim 130, wherein the SIP regulatory factor includes GSK239512.

213. The method according to claim 130, wherein the SIP regulator comprises siponimod.

214. The method according to claim 130, wherein the SIP regulator includes ponesimod.

215. The method according to claim 119, wherein the phosphodiesterase inhibitor comprises one or more members selected from the group consisting of sildenafil, vardenafil, tadalafil, avanafil, cilostazol, dipyridamole, milrinone, amrinone, roflumilast, apremilast, crisabolol, rolipram, or theobromine.

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