Devices and systems for neural, visual, auditory, or haptic stimulation and methods of using the same

Abstract

The present disclosure describes systems, devices, and methods of benefiting a cognitive state or function of a brain of a subject. The systems can include a portable system comprising a single headset device to be worn by a subject, comprising a pair of glasses configured to provide a visual stimulus to the subject, and a pair of supra-aural headphones configured to provide an auditory stimulus to the subject.

Description

CROSS-REFERENCE

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 618,268 filed on January 5, 2024, which is incorporated by reference in its entirety. BACKGROUND

[0002] Neural oscillation occurs in humans or animals and includes rhythmic or repetitive neural activity in the central nervous system. Neural oscillations can be characterized by their frequency, amplitude, and phase. Neural oscillations of the gamma waveform frequency specifically control the connectivity between different brain regions, which is crucial for perception, movement, memory, and emotion. Studies have linked abnormal gamma oscillations to conditions of the central nervous system, including Alzheimer's disease, Parkinson's disease, and schizophrenia. The present disclosure provides systems, devices, and methods of restoring normal gamma oscillations in brain regions of a subject by applying a non-invasive therapeutic stimulus with a gamma waveform frequency, thereby benefiting a cognitive state or function of a brain of a subject. SUMMARY

[0003] The present disclosure provides systems, methods, and devices for neurostimulation.

[0004] In one aspect, provided herein is a portable neurostimulation system for use by a subject in need thereof, said portable system comprising: a) a first stimulus emitting component comprising a visual source configured to emit a visual stimulus having a frequency of about 20 Hz to about 60 Hz; and b) a second stimulus emitting component comprising an audio source configured to emit an auditory stimulus having a frequency of about 20 Hz to about 60 Hz, wherein said visual source and said audio source are operatively connected and comprised in a single headset device, and wherein said visual source is rotatable about said audio source. In some embodiments, use of said system induces gamma oscillations in a brain region of said subject, thereby slowing progression of a mild cognitive impairment or dementia in said subject. In some embodiments, said visual source comprises a light emitting diode that projects said visual stimulus towards a screen, wherein the visual stimulus comprises light pulses. In some embodiments, said visual source comprises a light emitting diode driver. In some embodiments, said audio source comprises a set of headphones. In some embodiments, said audio source comprises supra-aural headphones. In some embodiments, said supra-aural headphones further comprise a removable headband configured to secure said portable system to said head of said subject. In some embodiments, said light pulses have a frequency of about 40 Hz to about 60 Hz. In some embodiments, said light pulses have a frequency of about 35 Hz to about 45 Hz. In some embodiments, said light pulses have a frequency of about 40 Hz. In some embodiments, said auditory stimulus has a frequency of about 40 Hz to about 60 Hz. In some embodiments, said auditory stimulus has a frequency of about 35 Hz to about 45 Hz. In some embodiments, said auditory stimulus has a frequency of about 40 Hz. In some embodiments, said visual source comprises glasses. In some embodiments, said glasses comprise a lens that is not opaque. In some embodiments, said lens comprises a translucent lens. In some embodiments, said lens comprises a transmittance of about 0% to about 100%. In some embodiments, said portable system further comprises a third stimulus emitting component comprising a haptic source, wherein said haptic source produces a haptic stimulus. In some embodiments, said haptic stimulus has a frequency of about 40 Hz to about 60 Hz. In some embodiments, said haptic stimulus has a frequency of about 35 Hz to about 45 Hz. In some embodiments, said haptic stimulus has a frequency of about 40 Hz. In some embodiments, said haptic stimulus comprises a vibration. In some embodiments, said portable system further comprises an input device comprising a hand-held controller. In some embodiments, said hand-held controller receives and transmits a signal dictating a dosing parameter corresponding to a frequency of said visual stimulus, a duration of said visual stimulus, a brightness of said visual stimulus, a color of said visual stimulus, a duration of said audio or haptic stimulus, an intensity of said audio or haptic stimulus, a frequency of said audio or haptic stimulus, or any combination thereof. In some embodiments, said hand-held controller further comprises an independent power supply comprising batteries. In some embodiments, said hand-held controller further comprises a rechargeable battery. In some embodiments, said hand-held controller is operably connected to receive and transmit said signal to said portable system using Wi-Fi or Bluetooth signals. In some embodiments, said portable system further comprises adjustable inputs. In some embodiments, said adjustable input for said portable system comprises an input for powering on and powering off said portable system. In some embodiments, said adjustable input for said portable system comprises an input for pausing said visual, haptic, or audio stimulus. In some embodiments, said portable system further comprises adjustable inputs for said audio source. In some embodiments, said adjustable inputs for said audio source comprise an adjustable volume input. In some embodiments, said portable system further comprises adjustable inputs for said haptic source. In some embodiments, said adjustable inputs for said haptic source comprise an adjustable intensity input. In some embodiments, said portable system further comprises adjustable inputs for said visual source. In some embodiments, said adjustable inputs for said visual source comprise an adjustable brightness input. In some embodiments, said hand-held controller comprises said adjustable inputs. In some embodiments, said visual source comprises said adjustable inputs. In some embodiments, said visual source comprising said adjustable inputs comprises a pair of glasses. In some embodiments, said single headset device provides improved comfort, portability, patient adherence, ease of use, or cognitive function of said subject's brain as compared to a portable system for benefiting a cognitive state or function of a brain of a subject comprising a visual source and an audio source that are not operatively configured to comprise a single headset device. In some embodiments, said portable system further comprises a rechargeable battery. In some embodiments, said portable system further comprises a base. In some embodiments, said base is configured to house said portable system and a hand-held controller. In some embodiments, said base is configured to provide a charge for said rechargeable battery of said portable system and a hand-held controller. In some embodiments, use of said system slows progression of a neurological disease. In some embodiments, said neurological disease is Alzheimer’s disease. In some embodiments, said neurological disease is Parkinson’s disease. In some embodiments, said neurological disease is dementia. In some embodiments, said portable system is configured to transmit data to a clinician. In some embodiments, said data comprises records of said subject’s use of the portable system, dosing parameters used by said subject, said subject’s cognitive state or function, or a combination thereof. In some embodiments, said system further comprises: c) a processor; d) a memory device; and e) a feedback sensor, wherein said processor receives an indication of a physiological assessment, cognitive assessment, neural assessment, or physical assessment of said subject through said feedback sensor and instructs said first stimulus-emitting component, said second stimulus-emitting component, or said third stimulus-emitting component based on said indication to adjust at least one parameter associated with said auditory, visual, or haptic stimulus. In some embodiments, said adjustment of at least one parameter associated with said auditory, visual, or haptic stimulus comprises an adjustment that induces gamma oscillations in a brain region of said subject. In some embodiments, said physical assessment of said subject involves ascertaining at least one of said subject's: compliance with proper use and positioning of said system, eye status, alert or sleep status, or environment and surroundings. In some embodiments, said neural assessment of said subject is received using brain wave sensors, an electroencephalography (EEG) device, an electrooculography (EOG) devices, or a magnetoencephalography (MEG) device. In some embodiments, said cognitive assessment of said subject is obtained through questions posed to said subject, activities and tasks performed by said subject in response to a prompt, or behaviors exhibited by said subject. In some embodiments, said processor further instructs said stimulus-emitting component to lengthen or shorten a duration of stimulation in response to said indication of said physiological, cognitive, neural, and / or physical assessment. In some embodiments, said physical assessment of said subject is performed to determine hearing of said subject. In some embodiments, said system is used to treat, prevent, or mitigate cognitive dysfunction in said subject. In some embodiments, use of said portable system comprises inducing one or more improvements in said brain region of said subject. In some embodiments, said one or more improvements comprises maintaining or improving cognitive function in said brain region of said subject. In some embodiments, said maintaining or improving cognitive function comprises maintaining or improving recognition, discrimination, spatial memory, working memory, attention, or a combination thereof. In some embodiments, said one or more improvements comprises maintaining or reducing tau phosphorylation in said brain region of said subject. In some embodiments, said one or more improvements comprises maintaining or reducing an amount of amyloid-P (AP) peptide in said brain region of said subject. In some embodiments, said one or more improvements comprises maintaining or reducing an amount of C-terminal fragments (CTFs) of amyloid precursor protein (APP) in said brain region of said subject. In some embodiments, said one or more improvements comprises maintaining or reducing cleavage of APP into CTFs and NTFs by P-secretase (BACE1) in said brain region of said subject. In some embodiments, said one or more improvements comprises maintaining or reducing cleavage of APP into CTFs and NTFs by y-secretase in said brain region of said subject. In some embodiments, said one or more improvements comprises maintaining or reducing a number of endosomes in said brain region of said subject. In some embodiments, said one or more improvements comprises promoting clearance of Ap peptide in said brain region of said subject. In some embodiments, said one or more improvements comprises increasing uptake of Ap peptide by microglia in said brain region of said subject. In some embodiments, said dementia comprises Alzheimer’s disease, vascular dementia, Lewy body dementia, Pick's disease, fronto-temporal dementia (FTD), AIDS dementia, age-related cognitive impairments, and age-related memory impairments. In some embodiments, said one or more improvements are increased by about 1% to about 100% in said subject as compared to a subject that does not use said portable system. In some embodiments, said brain region comprises an entorhinal cortex, a hippocampus, a cerebral cortex, a visual association cortex, an auditory association cortex, a cingulate lobe, an amygdala, a thalamic nucleus, a cingulate lobe, a pons, a brainstem, a cerebellum, a lateral ventricle, an occipital lobe, a parietal lobe, a temporal lobe, a midbrain, a striatum, a basal ganglia, a globus pallidus, a substantia nigra, or any combination thereof.

[0005] In one aspect, provided herein is a method comprising stimulating a subject with a visual, auditory, or haptic stimulus as disclosed herein generated by a portable system as disclosed herein, thereby inducing gamma oscillations in a brain region of said subject. In some embodiments, said gamma oscillations comprise synchronized gamma oscillations. In some embodiments, said visual, auditory, or haptic stimulus is administered at a frequency of about 20 Hz to about 60 Hz, about 30 Hz to about 60 Hz, about 30 Hz to about 50 Hz, or about 40 Hz. In some embodiments, said visual, auditory, or haptic stimulus is administered to said subject for about 10 minutes, about 30 minutes, about 45 minutes, about 1 hour, or more than about 1 hour per day. In some embodiments, said visual, auditory, or haptic stimulus is administered to said subject at least once, twice, three times, or more than three times per day. In some embodiments, said subject comprises a mammal. In some embodiments, said mammal comprises a non-human primate. In some embodiments, said mammal comprises a human. In some embodiments, said method further comprises a) identifying an activity being performed by a subject; and b) administering said visual, auditory, or haptic stimulus to said subject during said activity to induce a gamma oscillation in a brain region of said subject.

[0006] In one aspect, provided herein is a method of benefiting a cognitive state or function of a brain of a subject, comprising providing a subject a portable system as disclosed herein, and stimulating said subject with a visual, auditory, or haptic stimulus as disclosed herein, wherein use of said system induces gamma oscillations in at least one brain region of said subject and causes an improvement in one or more cognitive functions of said subject's brain, thereby slowing progression of mild cognitive impairment or Alzheimer's disease in said subject. In some embodiments, said gamma oscillations comprise synchronized gamma oscillations. In some embodiments, said visual, auditory, or haptic stimulus is administered at a frequency of about 20 Hz to about 60 Hz, about 30 Hz to about 60 Hz, about 30 Hz to about 50 Hz, or about 40 Hz. In some embodiments, said visual, auditory, or haptic stimulus is administered to said subject for about 10 minutes, about 30 minutes, about 45 minutes, about 1 hour, or more than about 1 hour per day. In some embodiments, said visual, auditory, or haptic stimulus is administered to said subject at least once, twice, three times, or more than three times per day. In some embodiments, said subject comprises a mammal. In some embodiments, said mammal comprises a non-human primate. In some embodiments, said mammal comprises a human. In some embodiments, said method further comprises a) identifying an activity being performed by a subject; and b) administering said visual, auditory, or haptic stimulus to said subject during said activity to induce a gamma oscillation in a brain region of said subject. INCORPORATION BY REFERENCE

[0007] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede or take precedence over any such contradictory material. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also “Figure” and “FIG.” herein), of which:

[0009] FIGURE 1 illustrates a block diagram depicting a system for performing neuromodulation using a visual stimulus, in accordance with an embodiment.

[0010] FIGURES 2A-2F illustrate visual stimulus signals for neuromodulation, in accordance with some embodiments.

[0011] FIGURES 3A-3C illustrate fields of vision in which visual stimulus can be transmitted for brain entrainment, in accordance with some embodiments.

[0012] FIGURES 4A-4C illustrate devices configured to display visual stimulus for neuromodulation, in accordance with some embodiments.

[0013] FIGURES 5A-5D illustrate devices configured to display visual stimulus for neuromodulation, in accordance with some embodiments.

[0014] FIGURES 6A AND 6B illustrate devices configured to receive feedback to facilitate neuromodulation, in accordance with some embodiments.

[0015] FIGURES 7A and 7B schematically illustrate depict block diagrams of computing devices that can be operatively coupled to various embodiments disclosed herein.

[0016] FIGURE 8 schematically illustrates a method for neuromodulation using a visual stimulus, in accordance with some embodiments.

[0017] FIGURE 9 schematically illustrates a block diagram depicting a system for neuromodulating a subject using an auditory stimulus, in accordance with some embodiments.

[0018] FIGURE 10A-10I illustrate auditory stimuli for neuromodulation, in accordance with some embodiments.

[0019] FIGURE 11A illustrates an auditory stimulus generated using binaural beats, in accordance with some embodiments.

[0020] FIGURE 11B illustrates an auditory stimulus having isochronic tones, in accordance with some embodiments.

[0021] FIGURE 11C illustrates an auditory stimulus having a modulation technique including audio filters, in accordance with some embodiments.

[0022] FIGURES 12A-12C illustrate configurations of systems for neuromodulation using auditory stimulus, in accordance with some embodiments. WO 2025 / 147596                                   PCT / US2025 / 010218

[0023] FIGURE 13 illustrates a configuration for a system for room-based auditory stimulation for neuromodulation, in accordance with some embodiments.

[0024] FIGURE 14 illustrates devices configured to receive feedback to facilitate neuromodulation using auditory stimulus, in accordance with some embodiments.

[0025] FIGURE 15 schematically illustrates a method for performing brain entrainment using auditory stimulus, in accordance with some embodiments.

[0026] FIGURE 16A schematically illustrates a system for neuromodulation through peripheral nerve stimulation, in accordance with some embodiments.

[0027] FIGURE 16B schematically illustrates a system for neuromodulation using multiple modes of neuromodulating stimulus, in accordance with some embodiments.

[0028] FIGURE 17A schematically illustrates a system for neuromodulation using visual stimulus and auditory stimulus, in accordance with some embodiments.

[0029] FIGURE 17B schematically illustrates gamma oscillation inducing waveforms used for neuromodulation using visual stimulus and auditory stimulus, in accordance with some embodiments.

[0030] FIGURE 18 schematically illustrates a method for neuromodulation using visual stimulus and auditory stimulus, in accordance with some embodiments.

[0031] FIGURE 19 is an efficacy summary chart for the modified intent to treat (mITT) population, including p-values, difference, confidence intervals (CI), and a standardized estimate of efficacy based on the values.

[0032] FIGURE 20 shows the separate means analysis, on the left, and the linear model analysis, on the right, of the Alzheimer’s Disease composite score (ADCOMS) as optimized for mid and moderate Alzheimer’s Disease (MADCOMS) for the sham and active treatment groups.

[0033] FIGURE 21 shows the separate means analysis, on the left, and a linear model analysis, on the right, of the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 14 (ADAS-Cogl4) values for the sham and active treatment groups.

[0034] FIGURE 22 shows the separate means analysis, on the left, and a linear model analysis, on the right, of the Clinical Dementia Rating Sale Sum of Boxes (CDR-SB) values for the sham and active treatment groups.

[0035] FIGURE 23 shows the separate means analysis, on the left, and a linear model analysis, on the right, of the Alzheimer’s Disease Cooperative Study - Activities of Daily Living Scale (ADCS-ADL) scores for the sham and active treatment groups.

[0036] FIGURE 24 shows the linear model analysis of the Mini-Mental State Examination (MMSE) score, as measured after six months of neuromodulation treatment (i.e., at the last time point). WO 2025 / 147596                                   PCT / US2025 / 010218

[0037] FIGURE 25 shows the linear model analysis of magnetic resonance imaging (MRI) results of whole brain volume value, on the left, and hippocampal volume, on the right, after six months of neuromodulation treatment.

[0038] FIGURE 26 is a table depicting a summary of efficacy findings resulting from the human clinical trial, including p-values, treatment differences, CI values and the percentage of slowing of brain atrophy.

[0039] FIGURE 27 shows graphs that demonstrate the observed improvement (panels a and b) in sleep quality as measured by a reduction in sleep fragmentation, expressed as a higher frequency longer rest durations, over a 24 week period of exemplary neuromodulation treatment for a first 12-week period of treatment (indicated by the line closest to the white arrow), and second 12-week period of treatment (indicated by the line furthest from the white arrow), in mild to moderate AD subjects. Panels c and d demonstrate the observed impact of the sham treatment on sleep quality as measured by a reduction in sleep fragmentation.

[0040] FIGURES 28A-B demonstrate power changes responsive to ( 40 Hz LED stimulus for 1 hour in an example embodiment showing 40 Hz steady state oscillation and enhanced alpha power during and following neuromodulation stimulus in a young healthy subject. FIGs. 28A-B both illustrate the time-frequency domain decomposition of EEG activity recorded over the occipital pole (Oz, channel-64) before, during and after 40 Hz gamma stimulation. The start and stop of gamma stimulation are marked with STIM ON and STIM OFF boundaries in FIGs. 28A-B. The FIG. 28A illustrates enhanced 40 Hz power during stimulation indicating steady-state visually evoked potential (SSVEP). The FIG. 28B shows alpha-power dynamics during eyes-open (EYO) and eyes-closed (EYC) conditions, and the enhanced alpha power both during eyes-open gamma stimulation, as well as following the one-hour 40 Hz gamma stimulation.

[0041] FIGURES 29A-B depict the composite global cognitive summary score as a function of average sleep fragmentation (FIG. 29A), and composite expression of genes enriched in aged microglia (FIG. 29B). The dotted lines show 95% confidence intervals of estimate.

[0042] FIGURE 30 provides an oscilloscope capture of the visual (upper signal) and audio (lower signal) signals of an example gamma oscillation inducing waveform with fs equal to about 40 Hz, vd equal to about 50%, VD equal to about 50%; ft equal to about 7,000 Hz, and AD equal to about 0.57%.

[0043] FIGURE 31 shows a schematic of some aspects and parameters characterizing stimulus audio and visual components of gamma oscillation inducing waveform as delivered respectively by Audio Stimulus Module (110; FIG. 33) and Visual Stimulus Module (120; FIG. 33) of Stimulus Delivery System (170; FIG. 33). WO 2025 / 147596                                   PCT / US2025 / 010218

[0044] FIGURE 32 demonstrates an overview of enrollment, treatment, and control for an example embodiment of neuromodulation treatment for improving sleep quality in mild to moderate AD subjects. Treatment was delivered to two thirds of the subjects (12) using 40 Hz frequency audio, and one third of subjects (6, “control”) at an alternate frequency.

[0045] FIGURE 33 schematically illustrates a stimulus delivery system and analysis and monitoring system, said analysis and monitoring system comprising modules specific to sleep-related monitoring and / or analysis, in accordance with some embodiments.

[0046] FIGURE 34 provides actigraphy data from 24 hours of activity levels (gray bar) over two days for a single example patient. This corresponds to 1501 in FIG. 37. The data was centered around 12 AM (indicated by double-sided arrow) along with a median filtered curve was generated. This corresponds to 1507 in FIG. 37 (labeled with dotted arrows in FIG. 34). The horizontal axis of FIG. 34 shows time of day, and the vertical axis is relative activity recorded on a wrist-worn actigraphic measuring device (arbitrary log scale). Calculated sleep periods (corresponding to 1508 in FIG. 37) along with individual sample rest periods (corresponding to 1509in FIG. 37) are shown: with the top panel (a) showing an example pattern for frequent movements and short rest periods during sleep periods, and the bottom panel (b) showing an example pattern of less frequent movements and longer rest periods during sleep periods.

[0047] FIGURE 35 provides example patterns of actigraphy (arbitrary units, see FIG. 34) over several days showing actigraphy (see gray lines; corresponding to 1501 in FIG. 37), and a smooth curve is superposed. A cutoff line (black) separates active versus rest periods (corresponding to 1505 in FIG. 37). Black squares represent initial estimation for the mid-night point (corresponding tol507 in FIG. 37). The final assessment of the mid-night points is determined through optimization algorithm (corresponding to 1508 in FIG. 37).

[0048] FIGURE 36 provides example cumulative distribution of rest periods from a single patient (corresponding to 1511 in FIG. 37). Data from a first example 12 weeks of neuromodulation treatment (dark gray, weeks 0-12) and a second example 12 weeks of neuromodulation treatment (light gray, weeks 12-24) is shown. In some embodiments, the distribution is characterized by an exponential distribution (corresponding to 1512 in FIG. 37). In some embodiments, an increase in the exponential decay constant represents an improvement in sleep quality (corresponding to 1513 in FIG. 37). In the present example, tau2 = 45 min, taul = 40 min, and tauaiir = 5 min > 0.

[0049] FIGURE 37 schematically illustrates analysis steps responsive to actigraphy data, provided in some embodiments at least in part by Actigraphy Monitoring Module 130 (FIG. 33), in accordance with some embodiments. In some embodiments, analysis is directed at determining the cumulative distribution of rest periods for one or more subjects over a period of one or more nighttime sleep periods (1511). In some embodiments, analysis is further directed at fitting an exponential distribution to the determined cumulative distribution (1512). In some embodiments, analysis is further directed at computing summary statistics or characteristic parameters for the fitted exponential distribution. In an exemplary embodiment, the exponential decay constant for the fitted exponential distribution is determined (1512; FIG. 36). In FIG. 37, terms in italics and in brackets refer to MATLAB (R2020a) APIs employed in the corresponding steps in an example embodiment, e.g., “medfiltl” refers to 1-D median filtering. In some embodiments, alternate APIs, methods, or processes, with equivalent function can be employed (e.g., Wolfram Language’s “ButterworthFilterModel” can be substituted for “butter”).

[0050] FIGURE 38 provides sample actigraphy recordings from a single patient, said sample actigraphy recording demonstrating the effect of neuromodulation treatment on sleep through recordings taken five consecutive nights prior to neuromodulation treatment, and five consecutive nights following neuromodulation treatment. The dark gray, horizontal bars below the X axis indicate continuous activity periods, with the continuous activity periods appearing significantly higher in the actigraphy recordings taken prior to neuromodulation treatment than the actigraphy recordings taken following neuromodulation treatment.

[0051] FIGURES 39A-B provides a cumulative distribution of rest and active durations in nighttime based on data pooled from all participants. The black squares indicate active periods, and the gray squares indicate rest periods. FIG. 39A shows the cumulative distribution using a log-linear scale, and FIG. 39B shows the cumulative distribution using a log-log scale.

[0052] FIGURES 40A-B shows graphs comparing the relative change in active durations, with the Y-axis indicating change relative to Weeks 1-12 during Weeks 13-24. The figures demonstrates a reduction in duration of active periods for the neuromodulation treatment group and, consequently, a reduction in sleep fragmentation leading to increased sleep quality. In contrast, the opposite effect was seen with the sham group, which is represented by the line closest to the gray arrow. FIG. 40A shows the relative change based on the duration of active periods, and FIG. 40B shows the normalized nighttime active durations, calculated by dividing the duration of each active period by the duration of the matching entire nighttime period.

[0053] FIGURE 41 shows the effect of neuromodulation treatment on maintenance of daytime activities, assessed by Activities of Daily Living (ADCS-ADL) scope. The graph shows that changes in daytime activities significantly improved in the neuromodulation treatment group and declined in the sham group. The X-axis compares the period from Week 1-12 and the period from Week 13-24. The Y-axis demonstrates the change in ADCS-ADL score during Weeks 1324 relative to Weeks 1-12.

[0054] FIGURE 42 schematically illustrates a proposed relationship between Alzheimer’s disease and sleep dysfunction, in accordance with some embodiments. This figure is adapted from Wang, C. and D. M. Holtzman (2020). "Bidirectional relationship between sleep and Alzheimer's disease: role of amyloid, tau, and other factors." Neuropsychopharmacology 45(1): 104-120.

[0055] FIGURE 43 provides a hand-held controller for adjusting parameters of the stimulus delivered by an operably coupled stimulus apparatus, in accordance with some embodiments. The features and advantages of the present solution will become more apparent from the detailed description set forth below when taken in conjunction with the drawings, in which like reference characters identify corresponding elements throughout. In the drawings, like reference numbers generally indicate like elements.

[0056] FIGURE 44 provides the results on matter volume change from baseline (%) for treatment and control groups who received 40Hz gamma sensory stimulation therapy and sham sensory stimulation therapy, respectively, for a 6-month period. The dark gray boxes correspond to the Treatment group participants, and the light gray boxes correspond to the Placebo group participants. Error bars indicate standard error (SE).

[0057] FIGURE 45 provides the Tl-weighted image to T2-weighted images (Tlw / T2w) ratio change in white matter (% change from baseline) for Placebo group participants (light gray) and Treatment group participants (dark gray) after receiving sham and 40Hz gamma sensory stimulation therapy, respectively, for a 6-month period.

[0058] FIGURES 46A and 46B provides measurements of volume change in white matter structures as a percent change relative to baseline. The Treatment group participants are indicated by dark gray, and the Placebo group participants’ results are indicated in light gray. FIGURE 46A provides the results for entorhinal region, left cingulate lobe, parstriangularis region, cuneus region, lateral occipital region, postcentral region, left occipital lobe, left frontal lobe, left parietal lobe, occipital lobe, left temporal lobe and caudal middle frontal region (sorted in ascending order by p value) for the treatment group after 6 months of treatment. FIGURE 46B provides the results for the precentral region, paracentral region, lingual region, fusiform region, frontal lobe, rostral anterior cingulate region, inferior temporal region, right occipital lobe, parietal lobe, rostral middle frontal, precuneus region, medial orbitofrontal region and temporal lobe (sorted in ascending order by p value).

[0059] FIGURES 47A and 47B provides the Tlw / T2w ratio change in white matter structures (% change from baseline) for Placebo and Treatment group participants after receiving sham and 40Hz gamma sensory stimulation therapy, respectively, for a 6-month period favors the treatment group. FIGURE 47A provides the results for the entorhinal region, parstriangularis region, postcentral region, left parietal lobe, lateral occipital region, paracentral region, rostral middle frontal region, supramarginal region, precentral region, parietal lobe, right occipital lobe, fusiform region, occipital lobe, left frontal lobe, cuneus region, precuneus region, inferior parietal region, frontal lobe, lingual region, left occipital lobe, left temporal lobe, right parietal lobe and parsorbitalis region, with white matter structures sorted in ascending order by p value. FIGURE 47B provides the results for the right frontal lobe, caudal middle 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 sorted in ascending order by p value.

[0060] FIGURE 48 is a block diagram depicting a system for selecting dosing parameters of stimulation signals to induce synchronized neural oscillations in the brain of a subject in accordance with an embodiment.

[0061] FIGURE 49 is a block diagram of a subject profile that can be included in the system shown in FIG. 26 in accordance with an embodiment.

[0062] FIGURE 50 is a graphical representation of adjusting a therapy session based on feedback collected during the therapy session.

[0063] FIGURE 51A is a flow diagram of a method for selecting dosing parameters of stimulation signals to induce synchronized neural oscillations in the brain of a subject in accordance with an embodiment.

[0064] FIGURE 51B is a flow diagram of a method for conducting a therapy session in accordance with an embodiment.

[0065] FIGURE 51C is a flow diagram of a method for counteracting distractions while applying a neural stimulus in accordance with an embodiment.

[0066] FIGURE 52 is a block diagram depicting a system for providing assessments for neural stimulation, in accordance with an embodiment.

[0067] FIGURE 53 is a block diagram depicting a system for providing assessments for neural stimulation on a subject in response to stimulation, in accordance with an embodiment.

[0068] FIGURE 54 is a flow diagram depicting a method of providing assessments for neural stimulation on a subject in response to stimulation.

[0069] FIGURE 55 is a flow diagram depicting a method of providing assessments for neural stimulation on a subject in response to stimulation.

[0070] FIGURE 56 is a flow diagram depicting a method of providing assessments for neural stimulation on a subject in response to iterative stimulation.

[0071] FIGURE 57 is a flow diagram depicting a method for generating therapy regimens based on comparison of assessments for different stimulation modalities. WO 2025 / 147596                                   PCT / US2025 / 010218

[0072] FIGURE 58 illustrates graphs depicting frequency-domain measurements of various states of neural stimulation, in accordance with an embodiment.

[0073] FIGURE 59 is a flow diagram illustrating a method of sensing neural oscillations induced by an external stimulus and subject attentiveness during application of the external stimuli, in accordance with an embodiment.

[0074] FIGURE 60 is a flow diagram of a method for evaluating neural responses to different stimulation modalities for subjects, in accordance with an embodiment.

[0075] FIGURE 61 shows an embodiment of an illustrative portable system (Combinatorial Neurostimulation System).

[0076] FIGURE 62 is a rendering of an embodiment of a controller of the portable system (Combinatorial Neurostimulation System).

[0077] FIGURE 63 illustratively depicts a process for a personalized and patient-specific therapeutic use of the Combinatorial Neurostimulation System any embodiment of the device described herein. A physician prescribes at-home therapeutic Combinatorial Neurostimulation System settings for a patient, which include adjusting any parameters of which the device is configured to emit a visual stimulus or an auditory stimulus to the eyes and ears of the patient. The physician confirms that patient’s neurological response to by cortical EEG recordings in order to identify the optimal stimulation frequency of the visual stimulus and the auditory stimulus. The patient then uses the device at home with the settings prescribed by the physician. The patient’s adherence to using the device as prescribed is monitored throughout the course of treatment.

[0078] FIGURE 64 depicts an embodiment of the portable system (Combinatorial Neurostimulation System) having a hand-held controller, headphones for delivering the auditory stimulation, and eyeglasses for visual stimulation. The Combinatorial Neurostimulation System device setting encryption, enhanced device connectivity with daily upload of device usage and actigraphy data. The patient can use an actigraphy watch for generating and tracking the patient’s actigraphy data. The Combinatorial Neurostimulation System can also interface with an electronic tablet for, as a nonlimiting example, integrating patient surveys and cognitive and linguistic home assessments. The Combinatorial Neurostimulation System automatically generated daily reports to track treatment and patient activities to measure adherence to the prescribed treatment regimen. The daily reports can also include information and / or data to detect baseline response evaluation and re-assessment. Any embodiments of the portable system (Combinatorial Neurostimulation System) described herein can be used for the treatment of neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. WO 2025 / 147596                                   PCT / US2025 / 010218

[0079] FIGURE 65 depicts an embodiment of a portable system as described herein (Combinatorial Neurostimulation System). The Combinatorial Neurostimulation System integrated data flow is used to monitor and support adherence to the prescribed neural stimulation treatment regimen by the patient.

[0080] FIGURE 66 depicts an embodiment of a portable system as described herein (Combinatorial Neurostimulation System). This embodiment depicts a single headset device with integrated stimulation eyeglasses and stimulation headphones. The stimulation eyeglasses can include transparent Ganz frames, so that the patient can engage in routine daily activities during the prescribed neural stimulation treatment regimen. The Combinatorial Neurostimulation System has accessibility updates, wireless and Bluetooth connectivity capabilities.

[0081] FIGURE 67 depicts an embodiment of a portable system as described herein (Combinatorial Neurostimulation System). This embodiment depicts a single headset device with integrated stimulation eyeglasses and stimulation headphones. Each headphone of the single headset device possesses a connector configured to fasten to a detachable headband via a removable-attachment mechanism. FIGURE 67 depicts a “female” connector in the housing of each headphone for attaching to a detachable headband equipped with “male” connectors positioned at each end (see also FIGURE 70).

[0082] FIGURE 68 depicts an embodiment of a portable system as disclosed herein (Combinatorial Neurostimulation System). This embodiment depicts a single headset device with integrated stimulation eyeglasses and stimulation headphones having user control hardware structurally and functionally integrated into the device. The external housing of a headphone speaker includes a button control for turning on or off the emission of the auditory stimulus from the device. The button user control hardware can have the share of a circle, a rhombus, a triangle, a parallelogram, or any other known regular or irregular shape.

[0083] FIGURE 69 depicts an embodiment of a portable system as disclosed herein (Combinatorial Neurostimulation System). This embodiment depicts a single headset device with integrated stimulation eyeglasses and stimulation headphones having user control hardware structurally and functionally integrated into the device. The frame of the eyeglasses houses a button switch control for adjusting the brightness of the visual stimulus. The button switch control integrated in the frame has functions to: (1) increase light intensity of the visual stimulus, decrease light intensity of the visual stimulus, (3) turn on or activate emission of the visual stimulus, and (4) turn off or stop emission of the visual stimulus. The external housing of a headphone speaker includes a horizontal button switch control for adjusting the volume of the auditory stimulus emitted by the device. The button switch control has a position setting to: (1) increase the volume of the auditory stimulus, (2) decrease volume of the auditory stimulus, (3) WO 2025 / 147596                                   PCT / US2025 / 010218 turn on or activate emission of the auditory stimulus, and (4) turn off or stop emission of the auditory stimulus. Any of the button switch user control hardware can be oriented vertically or horizontally.

[0084] FIGURE 70 depicts an embodiment of a portable system as disclosed herein (Combinatorial Neurostimulation System). This embodiments depicts a single headset device with integrated stimulation eyeglasses and stimulation headphones having user control hardware structurally and functionally integrated into the device as described in FIGURE 69. This embodiment of the single headset device further includes a detachable headband, which can be inserted into the housing of each headphone speaker. The detachable headband can be made of a malleable or flexible material. The headband can also comprise a synthetic material or a natural material. The detachable headband has an elongated shape and is configured to have an adjustable length to achieve a secure fit on a user’s head. A “male’ connecting member is affixed to each end of the detachable headband and is configured to fasten to a “female” connecting member that is housed within the slit on each headphone housing (see FIGURE 67). As depicted on the right, the material of the headband can be affixed or joined by any structural, physical, or chemical means to a second material as a means to achieve greater user comfort or accommodate any aspect of user wearability (e.g,. head size, head shape). The second material can be a soft fabric or material.

[0085] FIGURE 71 depicts another embodiment of a portable system as disclosed herein (Combinatorial Neurostimulation System). This embodiment depicts a single headset device with integrated stimulation eyeglasses and stimulation headphones having user control hardware structurally and functionally integrated into the single headset device as described in FIGURE 69. The detachable headband can be made of a rigid or semi-rigid material, such as a metal or plastic, to limit malleability and to substantially preserve the general shape and arch of the detachable headband of the single headset device, regardless of whether a user is wearing the single headset device. The headband can also comprise a synthetic material or a natural material. As depicted, the detachable headband is configured to have an adjustable length to achieve a secure fit on a user’s head and to position the headphones over each ear of the user. As depicted, each end of the primary rigid material of the detachable headband is molded into a connecting member, such as a “male” or “female” connecting member”, for the purpose of fastening to a complementary connecting member that is housed on each headphone housing (e.g., a “female” or “male” connecting member). In some cases, the connecting members at each end of the detachable headband can be made of a metal that magnetically connects to the housing of or a component within each headphone. In some cases, the As depicted on the right, the material of the headband can be affixed or joined by any structural, physical, or chemical means to a second WO 2025 / 147596                                   PCT / US2025 / 010218 material as a means to achieve greater user comfort or accommodate any aspect of user wearability (e.g., head size, head shape). The second material can be a soft fabric or material. Additionally, the single headset device can have vertically oriented user button, switch, or button switch controllers to enhance the user experience.

[0086] FIGURE 72 depicts an embodiment of portable system as disclosed herein (Combinatorial Neurostimulation System). This embodiment depicts a single headset device e, a hand-held controller, and a charging station that can recharge the rechargeable battery of the single headset device for continued use of the Combinatorial Neurostimulation System. The charging station can be powered via a direct wired connection to an electrical power supply. The hand-held controller can transmit wireless commands to the single headset device to activate or de-activate emission of the visual stimulation or the auditory stimulation from the eyeglasses or headphones of the single headset device. The hand-held controller can also adjust the brightness of the light stimulus or the volume of the sound stimulus emitted from the single headset device.

[0087] FIGURE 73 depicts another embodiment of a portable system as disclosed herein (Combinatorial Neurostimulation System). This embodiment depicts a single headset, a handheld controller, and a charging station that can recharge the rechargeable battery of the single headset device for continued use of the Combinatorial Neurostimulation System. As previously described, the charging station can be powered via a direct wired connection to an electrical power supply. The hand-held controller can transmit wireless commands to the single headset device to activate or de-activate emission of the visual stimulation or the auditory stimulation from the eyeglasses or headphones of the single headset device. The hand-held controller can also adjust the brightness of the light stimulus or the volume of the sound stimulus emitted from the single headset device via switches, buttons, or button switch mechanisms. The hand-held controller can also be equipped with a digital display to indicate the assigned user settings (e.g., brightness, volume, stimulus emission activation, stimulus emission de-activation, treatment duration, time remaining of a current treatment session). The digital display can be configured to display settings or information as numeric and / or alphabetic characters (as shown), as a percentage of a maximal value, or as a digital scale indicating an adjustable row of digital dots or shapes or, alternatively, an adjustable length of a digital line.

[0088] FIGURE 74 depicts an embodiment of a charging station of a portable system as disclosed herein (Combinatorial Neurostimulation System). In additional to the characteristics described in FIGURE 72 and FIGURE 73, the charging station can also have wireless connection capabilities, including establishing a connection to a Wi-Fi or Bluetooth™ device. The charging station can also include a charging pin housing. The charging station can be equipped with a “locate” button which, when pressed, triggers emission of a sound alert from the single headset device to aid the user in identifying the current location of the single headset device paired with the user’s Combinatorial Neurostimulation System. As depicted, the charging station can also be equipped with a digital display to indicate current settings of the single headset device or other component of the Combinatorial Neurostimulation System settings (e.g., light stimulus brightness, sound stimulus volume, stimulus emission activation, stimulus emission deactivation, treatment duration, time remaining of a current treatment session, charging status of the single headset device, estimation of time remaining for single headset device to be fully charged). The digital display on the charging station can be configured to display settings or information as numeric and / or alphabetic characters (as shown), as a percentage of a maximal value, or as a digital scale indicating an adjustable row of digital dots or shapes or, alternatively, an adjustable length of a digital line.

[0089] FIGURE 75A-75D provide exemplary embodiments of hand-held controllers for systems provided herein. FIG. 75A provides one embodiment with a volume display at the top, a pause / play button below, and brightness (right) and volume (left) up / down toggles below the pause / play button. FIG. 75B shows an embodiment of a hand-held controller with a brightness level indicated at the top, a pause / play button below, and volume (left) and brightness (right) up / down toggles below the pause / play button. FIG. 75C provides an embodiment of a hand-held controller with a timer indicated at the top, a pause / play button below, and volume (left) and brightness (right) up / down toggles below the pause / play button. FIG. 75D provides a smaller, condensed version of a remote, with the pause play button directly between the volume (left) and brightness panels (right). In FIG. 75D, there are small lights at the top of the hand-held controller, which extend upward from the volume and brightness button panels, respectively. In this exemplary embodiment, these number of lights indicate a level of brightness (right) or volume (left). For example, four lights on the left side of the remote would be a lower volume than five lights on the left side of the hand-held controller. Four lights on the right side of the hand-held controller indicate a lower brightness than five lights on the right side of the hand-held controller.

[0090] FIGURE 76 depicts an empty case for a portable system as disclosed herein (or Combinatorial Neurostimulation System). This embodiment has on-ear headphones and wearable glasses as provided herein. The center of the case has a button with Bluetooth capabilities. The case can fit the portable, wearable system and a remote control for the system.

[0091] FIGURE 77 depicts a case for a portable system as disclosed herein. This embodiment has on-ear headphones and wearable glasses as provided herein. As shown in FIG. 77, the case is holding the portable, wearable system comprising the glasses with on-ear headphones and a remote control for the system. WO 2025 / 147596                                   PCT / US2025 / 010218

[0092] FIGURE 78 depicts details of an exemplary embodiment of a portable system as provided herein. The top panel provides a portable system comprising glasses with a light source in the rim of the glasses and off-ear speakers. The temple arms of the glasses are folded at the rims and enclosed in an open case.

[0093] FIGURE 79 depicts a front view of an exemplary embodiment of a portable system as provided herein. As shown in FIG. 79, the portable systems comprise glasses, with foldable temple arms 8002. An off-ear speaker 8001 is built into the temple arms 8002 of the glasses, proximal to the temple tips 8006.

[0094] FIGURE 80 depicts a rear-facing view of an exemplary embodiment of a portable systems as provided herein. As shown in FIG. 80, the portable systems provide glasses, with foldable temple arms 8002. A hinge 8005 is provided for folding the temple arms. An off-ear speaker 8001 is built into the temple arm of the glasses, proximal to the temple tips 8006. A play / pause button 8004 is located on the top of the temple arms.

[0095] FIGURES 81A-B depict corpus callosum area and group level changes in the brains of subjects administered stimulation using a portable system via methods as disclosed herein versus control subjects.

[0096] FIGURES 82A-F depict corpus callosum subregion area and group level changes in the brains of subjects administered stimulation using a portable system via methods as disclosed herein versus control subjects.

[0097] The features and advantages of the present solution will become more apparent from the detailed description set forth below when taken in conjunction with the drawings, in which like reference characters identify corresponding elements throughout. In the drawings, like reference numbers generally indicate like elements. DETAILED DESCRIPTION

[0098] Devices, systems, and methods of the present disclosure are directed to neurostimulation via neural, visual, auditory, haptic stimulation, or any combination thereof. Neural, visual, auditory, or haptic stimulation, including neural, visual, auditory, or haptic signals, or any combination thereof can affect frequencies of neural oscillations. The neural, visual, auditory, or haptic stimulation can elicit brainwave effects via neural, visual, auditory, or haptic input, or any combination thereof. Devices, systems, and methods disclosed herein can adjust, control, or otherwise manage the frequency of the neural, visual, auditory, or haptic stimulation, or any combination thereof, to provide beneficial effects to one or more cognitive states or cognitive functions of a subject, such as beneficial effects within a brain region or the immune system, while mitigating or preventing adverse consequences of a cognitive state or cognitive function. For example, devices, systems, and methods of the present technology can treat, prevent, protect against, or otherwise affect diseases or conditions such as dementia or Alzheimer's Disease.

[0099] External signals, e.g., stimuli, such as visual signals, audio signals or haptic signals, can be observed or perceived by the brain. The brain, in response to perceiving the signals, can adjust, manage, or control the frequency of neural oscillations within a region or regions of the brain. This stimulation can result in repeated activation of portions of the brain which are known to process input, such as the visual or auditory cortex. For example, visual signals having a predetermined modulation frequency and perceived by the visual cortex or other brain regions can trigger neural activity in the brain to cause a predetermined or resulting frequency of neural oscillations. The frequency of neural oscillations can be affected by or correspond to the modulation frequency of the signals. Thus, devices, systems, and methods of the present disclosure can induce brainwave oscillations via neural, visual, auditory, or haptic stimulation, or any combination thereof.

[0100] Devices, systems, and methods of the present disclosure can induce brainwave oscillations using a non-invasive external stimulus, such as a visual, auditory, or haptic stimulus, or any combination thereof, including stimuli such as visual, visual, audio, or haptic signals forming visual, acoustic, or vibratory pulses emitted at a predetermined modulation frequency to synchronize electrical activity among groups of neurons based on the modulation frequency of the visual, audio, or haptic signals. Brainwave oscillations can be observed based on the aggregate frequency of oscillations produced by the synchronous electrical activity in ensembles of cortical neurons which the visual, acoustic, or haptic vibratory pulses can adjust to synchronize with frequency of the acoustic or haptic vibratory pulses.

[0101] The present disclosure provides devices, and systems for stimulation via neural, visual, auditory, or haptic stimulation, or any combination thereof. In some embodiments, the system comprises a portable neurostimulation system comprising stimulus emitting components. In some embodiments, the stimulus emitting components comprise a visual source, an audio source, a haptic source, or a combination thereof. In some embodiments, a portable system comprises a visual source and an audio source that are operatively connected and comprise a single headset device wherein said device comprises one or more rotatable elements. A rotatable element as described herein may comprise one module of the device that rotates relative to an axis of another module of the device. The rotatable element may comprise an auditory module that rotates relative to a visual module of the device. The rotatable element may comprise a visual module that rotates relative to an auditory module of the device. A rotatable element as described herein may be as depicted in any one of FIGS. 66-73. In some embodiments, a portable system WO 2025 / 147596                                   PCT / US2025 / 010218 comprises a visual source and an audio source that are operatively connected and comprise a single headset device wherein said visual source is rotatable about said audio source.

[0102] In some embodiments, a portable system comprises a visual source, wherein the visual source comprises glasses. The visual source can comprise a lens that is opaque, or not opaque, e.g., a translucent lens. In some embodiments, a device or system, e.g., a portable system or single headset device as disclosed herein provides a visual stimulus to a subject using a visual source with an opaque or transparent lens. In some embodiments, a portable system comprises an audio source, wherein the audio source comprises headphones. In some embodiments, the audio source comprises supra-aural headphones. The visual source and the audio source can be operatively connected as a single headset device that can be worn by a subject. The single headset device can be a wireless device. The portable system can comprise a haptic source. In some embodiments, a haptic source comprises wireless bone conduction headphones, wireless bone conduction protheses, or wireless bone conduction hearing aid devices. In some embodiments, a portable system comprises a single headset device comprising a visual source, an audio source, and a haptic source, wherein the visual source is rotatable about the audio source.

[0103] The devices or systems can be configured to emit a neural, visual, auditory, or haptic stimulus, or any combination thereof. In some embodiments, the stimulus comprises a gamma frequency. In some embodiments, the gamma frequency is about 20 Hertz (Hz) to about 140 Hz, about 30 Hz to about 60 Hz, about 40 Hz to about 60 Hz, about 35 Hz to about 45 Hz, or about 40 Hz. I. Portable Systems

[0104] In some embodiments, disclosed herein are portable systems capable of delivering a stimulus to a subject. In some embodiments, a portable system includes one or more stimulus emitting components comprising one or more visual, audio, or haptic sources, or any combination thereof. In some embodiments, a portable system comprises a single headset device comprising one or more visual, audio, or haptic sources, capable of transmitting a visual, audio, and / or haptic stimulus, or any combination thereof. In some embodiments, a single headset device comprises an audio source operatively connected to a visual source, and / or a haptic source, wherein the visual source is rotatable about said audio source and wherein said single headset device is capable of being worn by a subject. In some embodiments, a portable system can further comprise a hand-held controller capable of receiving and transmitting a signal dictating a dosing parameter corresponding to a frequency of said visual stimulus, a duration of said visual stimulus, a brightness of said visual stimulus, a color of said visual stimulus, a WO 2025 / 147596                                   PCT / US2025 / 010218 duration of said audio or haptic stimulus, an intensity of said audio or haptic stimulus, a frequency of said audio or haptic stimulus, or any combination thereof.

[0105] In some embodiments, a portable system further comprises a processor, a memory device, and a feedback sensor.

[0106] In some embodiments, a portable system as described herein is referred to as a Combinatorial Neurostimulation System.

[0107] In some embodiments, a portable system as disclosed herein comprises a Neural Stimulation System (NSS) as disclosed herein, and / or comprises a component of an NSS as disclosed herein, or can be configured to implement a method of an NSS as disclosed herein. A. Stimulus Emitting Components

[0108] In some embodiments, a portable system comprises one or more stimulus emitting components, wherein the stimulus emitting components comprises a visual source, an audio source, and / or a haptic source, or any combination thereof. i. Visual Source

[0109] In some embodiments, the stimulus emitting component comprises a visual source. In some embodiments, said visual source comprises a pair of glasses worn by the subject with a visual source capable of providing a visual stimulus. The visual source can comprise a lens, e.g., a translucent lens. In some embodiments, a visual source as disclosed herein provides a visual stimulus to a subject using a visual source with an opaque or transparent lens. In some embodiments, a visual source comprises a portable system visual source. In some embodiments, the glasses comprise one or more lenses. In some embodiments, the lenses comprise transparent lenses. In some embodiments, a lens comprises a transmittance of about 0% to about 100%. In some embodiments, the visual source is operatively coupled to one or more processors.

[0110] In some embodiments, a portable system visual source comprises a frame that can be designed and constructed to be placed or positioned on a subject’s head. The frame can be configured to be worn by the person. The frame can be designed and constructed to stay in place. The frame can be configured to be worn and stay in place as a person sits, stands, walks, runs, or lays down flat. In some embodiments, a portable system visual source comprises a visual source operatively connected to one or more processors that can be configured on the frame to project light pulses towards the person’s eyes in various positions. In some embodiments, the visual source can be configured to project light pulses towards the person’s eyes if their eyelids are closed such that the light pulse penetrates the eyelid to be perceived by the retina. The frame can include a bridge. The frame can include one or more eye wires coupled to the bridge. The bridge can be positioned in between the eye wires. The frame can include one or more temples extending from the one or more eye wires. In some embodiments, the portable system visual source can include or hold a lens. In some embodiments, the portable system visual source can include or hold a solid material or cover. The lens, solid material, or cover can be transparent, semi-transparent, opaque, or completely block out external light.

[0111] One or more visual sources can be positioned on or adjacent to the eye wire, lens or other solid material, or bridge. For example, a visual source can be positioned in the middle of the eye wire on a solid material in order to transmit light pulses into the direct visual field. In some embodiments, a visual source can be positioned at a comer of the eye wire, such as a comer of the eye wire coupled to the temple, in order to transmit light pulses towards a peripheral field.

[0112] The portable system visual source can perform visual stimulation via a single eye or both eyes. For example, the portable system visual source can direct light pulses to a single eye or both eyes. The visual signaling component can include a single visual source configured and positioned to direct light pulses to a first eye. The visual signaling component can further include a light blocking component that keeps out or blocks the light pulses generated from the visual source from entering a second eye. The visual signaling component can block or prevent light from entering the second eye during the brain stimulation process.

[0113] In some embodiments, the visual source can alternatively transmit or direct light pulses to the first eye and the second eye. For example, the visual source can direct light pulses to the first eye for a first time interval. The visual source can direct light pulses to the second eye for a second time interval. The first time interval and the second time interval can be a same time interval, overlapping time intervals, mutually exclusive time intervals, or subsequent time intervals.

[0114] The lens can include electrochromic glass or plastic. Electrochromic glass or plastic can change from light to dark (e.g., clear to opaque) in response to an electrical voltage or current. Electrochromic glass or plastic can include metal-oxide coatings that are deposited on the glass or plastic, multiple layers, and lithium ions that travel between two electrodes between a layer to lighten or darken the lens.

[0115] In some embodiments, a portable system visual source can include a tablet computing visual source or other computing visual source having a display screen.

[0116] In some embodiments, the visual source can display a pattern of light. The light can flicker, toggle or switch between two or more patterns to generate flashes of light or light pulses. Patterns can include, for example, alternating checkerboard patterns. The pattern can include symbols, characters, or images that can be toggled or adjusted from one state to another state. For example, the color of a character or text relative to a background color can be inverted to cause a WO 2025 / 147596                                   PCT / US2025 / 010218 switch between a first state and a second state. Inverting a foreground color and background color at a predetermined frequency can generate light pulses by way of indicating visual changes that can facilitate adjusting or managing a frequency of neural oscillations.

[0117] In some embodiments, the visual source can instruct or cause a visual stimulus to flicker, toggle, or switch between images configured to stimulate specific or predetermined portions of the brain or a specific cortex. The presentation, form, color, motion and other aspects of the light or an image based stimuli can dictate which cortex or cortices are recruited to process the stimuli. The visual source can stimulate discrete portions of the cortex by modulating the presentation of the stimuli to target specific or general regions of interest. The relative position in the field of view, the color of the input, or the motion and speed of the light stimuli can dictate which region of the cortex is stimulated. For example, the brain can include at least two portions that process predetermined types of visual stimuli: the primary visual cortex on the left side of the brain, and the calcarine fissure on the right side of the brain. Each of these two portions can have one or more multiple sub-portions that process predetermined types of visual stimuli. For example, the calcarine fissure can include a sub-portion referred to as area V5 that can include neurons that respond strongly to motion but cannot register stationary objects. Subjects with damage to area V5 can have motion blindness, but otherwise normal vision. In another example, the primary visual cortex can include a sub-portion referred to as area V4 that can include neurons that are specialized for color perception. Subjects with damage to area V4 can have color blindness and only perceive objects in shades of gray. In another example, the primary visual cortex can include a sub-portion referred to as area VI that includes neurons that respond strongly to contrast edges and helps segment the image into separate objects. Thus, the visual source can instruct or cause a visual stimulus to form a type of still image or video, or generate a flicker, or toggle between images that configured to stimulate specific or predetermined portions of the brain or a specific cortex. For example, the visual source can generate images of human faces to stimulate a fusiform face area, which can facilitate brain stimulation for subjects having prosopagnosia or face blindness. In some embodiments, the visual source can generate images of faces flickering to target this area of the subject’s brain. In another example, the visual source can generate images that include edges or line drawings to stimulate neurons of the primary visual cortex that respond strongly to contrast edges.

[0118] The portable system visual source can include, access, interface with, or otherwise communicate with at least one visual source. The visual source can be designed and constructed to measure or verify an environmental variable (e.g., light intensity, timing, incident light, ambient light, eye lid status, etc.) to adjust a parameter associated with the visual signal, such as a frequency, amplitude, wavelength, intensity pattern or other parameter of the visual signal, or any combination thereof. The visual source can automatically vary a parameter of the visual signal based on profile information or feedback. The visual source can receive the feedback information from a feedback monitor. The visual source can receive instructions or information from a side effects management module. The visual source can receive profile information from a profile manager. The visual source can include an LED.

[0119] The portable system visual source can include, access, interface with, or otherwise communicate with at least one unwanted frequency filtering module. The unwanted frequency filtering module can be designed and constructed to block, mitigate, reduce, or otherwise filter out frequencies of visual signals that are undesired to prevent or reduce an amount of such visual signals from being perceived by the brain. The unwanted frequency filtering module can interface, instruct, control, or otherwise communicate with a filtering component to cause the filtering component to block, attenuate, or otherwise reduce the effect of the unwanted frequency on the neural oscillations.

[0120] The portable system visual source can include, access, interface with, or otherwise communicate with at least one profile manager. The profile manager can be designed or constructed to store, update, retrieve or otherwise manage information associated with one or more subjects associated with the portable system. Profile information can include, for example, historical treatment information, historical brain stimulation information, dosing information, parameters of light waves, feedback, physiological information, environmental information, or other data associated with the systems and methods of brain stimulation.

[0121] The portable system visual source can include, access, interface with, or otherwise communicate with at least one side effects management module. The side effects management module can be designed and constructed to provide information to the visual source to change one or more parameter of the visual signal in order to reduce a side effect. Side effects can include, for example, nausea, migraines, fatigue, seizures, eye strain, or loss of sight.

[0122] The side effects management module can automatically instruct a component of the portable system visual source to alter or change a parameter of the visual signal. The side effects management module can be configured with predetermined thresholds to reduce side effects. For example, the side effects management module can be configured with a maximum duration of a pulse train, maximum intensity of light waves, maximum amplitude, maximum duty cycle of a pulse train (e.g., the pulse width multiplied by the frequency of the pulse train), maximum number of treatments for brainwave stimulation in a time period (e.g., 1 hour, 2 hours, 12 hours, or 24 hours).

[0123] The side effects management module can cause a change in the parameter of the visual signal in response to feedback information. The side effect management module can receive WO 2025 / 147596                                   PCT / US2025 / 010218 feedback from the feedback monitor. The side effects management module can determine to adjust a parameter of the visual signal based on the feedback. The side effects management module can compare the feedback with a threshold to determine to adjust the parameter of the visual signal.

[0124] The side effects management module can be configured with or include a policy engine that applies a policy or a rule to the current visual signal and feedback to determine an adjustment to the visual signal. For example, if feedback indicates that a patient receiving visual signals has a heart rate or pulse rate above a threshold, the side effects management module can turn off the pulse train until the pulse rate stabilizes to a value below the threshold, or below a second threshold that is lower than the threshold.

[0125] The portable system visual source can include, access, interface with, or otherwise communicate with at least one feedback monitor. The feedback monitor can be designed and constructed to receive feedback information from a feedback component. The feedback component can include, for example, a feedback sensor such as a temperature sensor, heart or pulse rate monitor, physiological sensor, ambient light sensor, ambient temperature sensor, sleep status via actigraphy, blood pressure monitor, respiratory rate monitor, brain wave sensor, EEG probe, electrooculography (“EOG”) probes configured to measure the comeo-retinal standing potential that exists between the front and the back of the human eye, accelerometer, gyroscope, motion detector, proximity sensor, camera, microphone, or photo detector, or any combination thereof.

[0126] In some embodiments, a computing visual source can include the feedback component or feedback sensor. For example, the feedback sensor can be placed on a tablet and can include a front-facing camera that can capture images of a person viewing the visual source.

[0127] The feedback sensor can interact with or communicate with portable system visual source. For example, the feedback sensor can provide detected feedback information or data to the portable system visual source. The feedback sensor can provide data to the portable system visual source in real-time, for example as the feedback sensor detects or senses or information. The feedback sensor can provide the feedback information to the portable system visual source based on a time interval, such as 1 minute, 2 minutes, 5 minutes, 10 minutes, hourly, 2 hours, 4 hours, 12 hours, or 24 hours. The feedback sensor can provide the feedback information to the portable system visual source responsive to a condition or event, such as a feedback measurement exceeding a threshold or falling below a threshold. The feedback sensor can provide feedback information responsive to a change in a feedback parameter. In some embodiments, the portable system visual source can ping, query, or send a request to the feedback sensor for information, and the feedback sensor can provide the feedback information WO 2025 / 147596                                   PCT / US2025 / 010218 in response to the ping, request, or query. Feedback sensors can include, for example, EEG probes that detect brain wave activity.

[0128] The feedback monitor can detect, receive, obtain, or otherwise identify feedback information from the one or more feedback sensors . The feedback monitor can provide the feedback information to one or more component of the portable system visual source for further processing or storage. For example, the profile manager can update profile data structure stored in data repository with the feedback information. Profile manager can associate the feedback information with an identifier of the patient or person undergoing the visual brain stimulation, as well as a time stamp and date stamp corresponding to receipt or detection of the feedback information. The identifier can be indicative of an activity of a subject, a physiological or physical condition of a subject, or a mental condition of a subject. The identifier can also be indicative of a disease, disorder, or condition.

[0129] The feedback monitor can detect symptoms of a neurological disease or disorder. For the example, the feedback monitor can be used to evaluate changes in fine motor skills over time or changes in voice pitch or tone. The profile manager can update profile data structure with the feedback information. The profile data structure can be used to assess whether a person is at risk of developing a neurological disorder, whether a person has a neurological disorder, or progression of symptoms of a neurological disorder.

[0130] The feedback monitor can determine a level of attention. The level of attention can refer to the focus provided to the light pulses used for brain stimulation. The feedback monitor can determine the level of attention using various hardware and software techniques. The feedback monitor can assign a score to the level of attention (e.g., 1 to 10 with 1 being low attention and 10 being high attention, or vice versa, 1 to 100 with 1 being low attention and 100 being high attention, or vice versa, 0 to 1 with 0 being low attention and 1 being high attention, or vice versa), categorize the level of attention (e.g., low, medium, high), grade the attention (e.g., A, B, C, D, or F), or otherwise provide an indication of a level of attention.

[0131] In some cases, the feedback monitor can track a person’s eye movement to identify a level of attention. The feedback monitor can interface with a feedback component that includes an eye-tracker. The feedback monitor can detect and record eye movement of the person and analyze the recorded eye movement to determine an attention span or level of attention. The feedback monitor can measure eye gaze which can indicate or provide information related to covert attention. For example, the feedback monitor can be configured with electro-oculography (“EOG”) to measure the skin electric potential around the eye, which can indicate a direction the eye faces relative to the head. In some embodiments, the EOG can include a system or visual source to stabilize the head so it cannot move in order to determine the direction of the eye WO 2025 / 147596                                   PCT / US2025 / 010218 relative to the head. In some embodiments, the EOG can include or interface with a head tracker system to determine the position of the heads, and then determine the direction of the eye relative to the head.

[0132] In some embodiments, the feedback monitor and feedback component can determine or track the direction of the eye or eye movement using video detection of the pupil or corneal reflection. For example, the feedback component can include one or more camera or video camera. The feedback component can include an infra-red source that sends light pulses towards the eyes. The light can be reflected by the eye. The feedback component can detect the position of the reflection. The feedback component can capture or record the position of the reflection. The feedback component can perform image processing on the reflection to determine or compute the direction of the eye or gaze direction of the eye.

[0133] The feedback monitor can compare the eye direction or movement to historical eye direction or movement of the same person, nominal eye movement, or other historical eye movement information to determine a level of attention. For example, if the eye is focused on the light pulses during the pulse train, then the feedback monitor can determine that the level of attention is high. If the feedback monitor determines that the eye moved away from the pulse train for 25% of the pulse train, then the feedback monitor can determine that the level of attention is medium. If the feedback monitor determines that the eye movement occurred for more than 50% of the pulse train or the eye was not focused on the pulse train for greater than 50%, then the feedback monitor can determine that the level of attention is low.

[0134] In some embodiments, the portable system visual source can include a filter to control the spectral range of the light emitted from the visual source. In some embodiments, the visual source includes a light reactive material affecting the light emitted, such as a polarizer, filter, prism or a photochromic material, or electrochromic glass or plastic. The filtering component can receive instructions from the unwanted frequency filtering module to block or attenuate one or more frequencies of light.

[0135] The filtering component can include an optical filter that can selectively transmit light in a particular 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 incoming light wave for a range of wavelengths. The optical filter can include an absorptive filter, or an interference or dichroic filter. An absorptive filter can take energy of a photon to transform the electromagnetic energy of a light wave into internal energy of the absorber (e.g., thermal energy). The reduction in intensity of a light wave propagating through a medium by absorption of a part of its photons can be referred to as attenuation.

[0136] An interference filter or dichroic filter can include an optical filter that reflects one or more spectral bands of light, while transmitting other spectral bands of light. An interference filter or dichroic filter can have a nearly zero coefficient of absorption for one or more wavelengths. Interference filters can be high-pass, low-pass, bandpass, or band-rejection. An interference filter can include one or more thin layers of a dielectric material or metallic material having different refractive indices. 1. Visual Stimulus

[0137] In some embodiments, a portable system visual source is configured to generate a visual stimulus such as such as a light pulse or flash of light. In some embodiments, the visual stimulus comprises a light pulse or flash of light with amplitude or intensity, a frequency, a pulse rate, a tone, a signal delay, an offset, a duration, or any combination thereof. In some embodiments, the visual source comprises a light emitting diode (LED) capable of producing a light pulse or flash of light.

[0138] In some embodiments, the visual stimulus comprises one or more light waves. In some embodiments, the visual stimulus is perceptible to the subject. In some embodiments, the visual stimulus is imperceptible to the subject. In some embodiments, the visual stimulus comprises a frequency from about 0 Hz to about 50 kHz. In some embodiments, the visual stimulus comprises a frequency from about 20 Hz to about 20 kHz.

[0139] In some embodiments, the visual stimulus comprises a frequency capable of modulating a gamma waveform in a brain region of the subject. In some embodiments, the frequency capable of modulating a gamma waveform in the subject comprises a waveform of. 1 Hz, 1 Hz, 5 Hz, 10 Hz, 20 Hz, 25 Hz, 30 Hz, 31 Hz, 32 Hz, 33 Hz, 34 Hz, 35 Hz, 36 Hz, 37 Hz, 38 Hz, 39 Hz, 40 Hz, 41 Hz, 42 Hz, 43 Hz, 44 Hz, 45 Hz, 46 Hz, 47 Hz, 48 Hz, 49 Hz, 50 Hz, 60 Hz, 70 Hz, 80 Hz, 90 Hz, 100 Hz, 150 Hz, 200 Hz, 250 Hz, 300 Hz, 400 Hz, 500 Hz, 1000 Hz, 2000 Hz, 3000 Hz, 4,000 Hz, 5000 Hz, 6,000 Hz, 7,000 Hz, 8,000 Hz, 9,000 Hz, or 10,000 Hz.

[0140] The visual stimulus can be turned 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 visual source can be turned on and off to provide a pulse repetition frequency in the range of about 20 Hertz (Hz) to about 140 Hz, about 30 Hz to about 60 Hz, about 40 Hz to about 60 Hz, about 35 Hz to about 45 Hz, or about 40 Hz, in accordance with methods disclosed herein.

[0141] In some embodiments, the present disclosure describes systems and devices for providing a gamma-oscillation inducing waveform that is imperceptible to a subject. In some cases, a display device can be configured to output the gamma oscillation inducing waveform. In some cases, a stimulation source can be configured to be operatively configured to another device, such that the stimulation source outputs the gamma oscillation inducing waveform in association with the output of the device. In some cases, a device can comprise a filter, wherein the filter is capable of masking one or more waveforms of a waveform source such that a subject using the filter receives a gamma oscillation inducing waveform. In some cases, a device can comprise a cover, wherein the cover is configured to add a gamma-oscillation inducing waveform to one or more waveforms of a waveform source such that a subject using the cover receives a gamma oscillation inducing waveform. ii. Audio Source

[0142] Devices and systems as disclosed herein may comprise an audio source. By way of example, a portable system audio source can comprise headphones worn by a subject. In some embodiments, the headphones can be worn about the head of a subject. The headphones can comprise wireless over-ear headphones or wireless in-ear headphones suitable for delivering an auditory stimulus to the subject.

[0143] In some embodiments, wireless headphones can include, for example, circumaural headphones (e.g., full size / over-ear headphones) that include circular or ellipsoid earpads that are designed and constructed to seal against the head to attenuate external noise. Circumaural headphones can facilitate providing an immersive auditory brainwave wave stimulation experience, while reducing external distractions. In some embodiments, headphones can include supra-aural headphones, which include pads that press against the ears rather than around them. Supra-aural headphones can provide less attenuation of external noise.

[0144] Both circumaural headphones and supra-aural headphones can have an open back, closed back, or semi-open back. An open back can leak more sound and allow more ambient sounds to enter, but can provide a more natural or speaker-like sound. Closed back headphones can block more of the ambient noise as compared to open back headphones, thus providing a more immersive auditory brainwave stimulation experience while reducing external distractions.

[0145] In some embodiments, headphones include ear-fitting headphones, such as earphones or in-ear headphones. Earphones (or earbuds) can refer to small headphones that are fitted directly in the outer ear, facing but not inserted in the ear canal. In-ear headphones (or in-ear monitors or canalphones) can refer to small headphones that can be designed and constructed for insertion into the ear canal. In-ear headphones engage the ear canal and can block out more ambient noise as compared to earphones, thus providing a more immersive auditory brainwave stimulation experience. In-ear headphones can include ear canal plugs made or formed from one or more material, such as silicone rubber, elastomer, or foam. In some embodiments, in-ear headphones can include custom-made castings of the ear canal to create custom-molded plugs that provide WO 2025 / 147596                                   PCT / US2025 / 010218 added comfort and noise isolation to the subject, thereby further improving the immersion of a subject.

[0146] In some embodiments, a portable system audio source comprises a signal emitter. In some embodiments, a signal emitter includes a speaker, wherein the speaker can include one or more types of speaker hardware, components, or technology to generate an auditory stimulus such as an audio tone, beep, or click disclosed herein.

[0147] The speaker can include a diaphragm to produce sound. The speaker can include a moving-iron loudspeaker that uses a stationary coil to vibrate a magnetized piece of metal. The speaker can include a piezoelectric speaker. A piezoelectric speaker can use the piezoelectric effect to generate sound by applying a voltage to a piezoelectric material to generate motion, which is converted into audible sound using diaphragms and resonators.

[0148] The speaker can include various other types of hardware or technology, such as magnetostatic loudspeakers, magnetostrictive speakers, electrostatic loudspeakers, a ribbon speaker, planar magnetic loudspeakers, bending wave loudspeakers, coaxial drivers, horn loudspeakers, Heil air motion transducers, or transparent ionic conductions speaker.

[0149] In some embodiments, the speaker may not include a diaphragm. For example, the speaker can be a plasma arc speaker that uses electrical plasma as a radiating element. The speaker can be a thermoacoustic speakers that uses carbon nanotube thin film. The speaker can be a rotary woofer that includes a fan with blades that constantly change their pitch.

[0150] In some embodiments, the portable system audio source comprises one or more microphones. The microphones can be used to detect sound. A microphone can be integrated with a speaker. The microphone can provide feedback information to an audio source or system as disclosed herein. The microphone can provide feedback to a component of the speaker to cause the speaker to adjust a parameter of an auditory stimulus.

[0151] The microphone can include a transducer that converts sound into an electrical signal. The microphone can use electromagnetic induction, capacitance change, or piezoelectricity to produce the electrical signal from air pressure variations. In some embodiments, the microphone can include or be connected to a pre-amplifier to amplify the signal before it is recorded or processed. The microphone can include one or more type of microphone, including, for example, a condenser microphone, RF condenser microphone, electret condenser, dynamic microphone, moving-coil microphone, ribbon microphone, carbon microphone, piezoelectric microphone, crystal microphone, fiber optic microphone, laser microphone, liquid or water microphone, microelectromechanical systems (“MEMS”) microphone, or speakers as microphones.

[0152] In some embodiments, a portable system audio source comprises one or more feedback components. The feedback component can include or interface with the microphone to obtain, identify, or receive sound. The feedback component can obtain ambient noise. The feedback component can obtain sound from the speakers to facilitate the audio source adjusting a characteristic of the auditory stimulus generated by the speaker. The microphone can receive voice input from a subject, such as audio commands, instructions, requests, feedback information, or responses to survey questions.

[0153] In some embodiments, a portable system audio source also includes at least one memory for storing processor executable instructions and at least one processor communicatively connected to the audio source and the at least one memory. Upon execution of the processor executable instructions, the at least one processor can control the audio source such that device emits the auditory stimulus at a frequency that activates neural, visual, oscillations, e.g., gamma oscillations, in a brain region of the subject corresponding to the audio frequency generated by the audio source. In some embodiments, the at least one processor can control the audio source such that the device actuates the auditory stimulus at the frequency that activates neural, visual, oscillations, e.g., gamma oscillations, in at least one of the auditory cortex and the hippocampus at the frequency corresponding to the audio frequency generated by the audio source.

[0154] In some embodiments, the audio source includes a data interface that enables data communication between the audio source and an external control device or system. The external device can be external device such as a fitting system, PDA, computer, mobile phone, or any other suitable device. Preferably, the interface allows two-way or bidirectional communication. That is, interface data can be sent from both the audio source and the external device. For example, in one embodiment, the interface can be adapted to receive control signals from the external device for generating an auditory stimulus at predetermined frequencies, and receive control settings for the audio source for storing in the memory unit. In some embodiments, however, the interface is a one-way interface, allowing only data to be forwarded from the external device to the audio source. In other embodiments, communication is a one-way interface with data being forwarded from the audio source to any type of receiving device. The data can include measured control signals or any type of status information or other suitable data. This information can be used to merely monitor the audio source or be used with a control device that can be a separate device or be integrated into the audio source or be any other suitable device.

[0155] In some embodiments, the processor is configured to receive an indication of a physiological, cognitive, neural, visual, auditory, or physical assessment, or any combination thereof of the subject wearing the audio source. In some embodiments, when the processor receives the indication of the physiological, cognitive, neural, visual, auditory, or physical assessment, or any combination thereof of the subject, the processor instructs the stimulus emitter to emit the auditory stimulus. In some embodiments, the physical assessment of the subject comprises ascertaining at least one of the subject's: compliance with proper use and positioning of the system, eye status, alert or sleep status, or environment and surroundings. In some embodiments, the physical assessment of the subject is performed to determine hearing of the subject, the indication of the physiological, cognitive, neural, visual,, or physical assessment, or any combination thereof of the subject comprises a biosignal. In some embodiments, the biosignal comprises an electroencephalography (EEG).

[0156] In some embodiments, the cognitive assessment of the subject is obtained through questions posed to the subject, activities and tasks performed by the subject in response to a prompt, or behaviors exhibited by the subject.

[0157] In some embodiments, an audio source as disclosed herein is provided with or operatively connected to a computer system as disclosed herein. The computer system can communicate with one or more remote computer systems through the network. For instance, the computer system can communicate with a remote computer system of a user. Examples of remote computer systems include personal computers (e.g., portable PC), slate or tablet PC’s (e.g., Apple® iPad, Samsung® Galaxy Tab), telephones, Smart phones (e.g., Apple® iPhone, Android-enabled device, Blackberry®), or personal digital assistants. The user can access the computer system via the network. In some embodiments, the computer systems are programmed to implement the function of an audio source, such as implementing an auditory stimulus delivered to a subject by the audio source as described herein. l.Auditory Stimulus

[0158] In some embodiments, a portable system audio source is configured to generate an auditory stimulus such as an audio tone, a beep, a click, or a similar audio stimulus, or any combination thereof. In some embodiments, the auditory stimulus comprises a sound with amplitude or intensity, a frequency, a pulse rate, a tone, a signal delay, an offset, a duration, a sinusoidal grating, a dynamic sound, a perceived direction of motion, or any combination thereof.

[0159] In some embodiments, the auditory stimulus comprises one or more acoustic waves. In some embodiments, the sound comprises an ultrasound or an infrasound. In some embodiments, the sound comprises a tone or frequency perceptible to the subject. In some embodiments, the sound comprises a tone or frequency imperceptible to the subject. In some embodiments, the sound comprises an acoustic frequency from about 0 Hz to about 50 kHz. In some embodiments, the sound comprises an acoustic frequency from about 20 Hz to about 20 kHz. In some embodiments, the sound comprises an acoustic frequency from about 8 Hz to about 12 kHz. In some embodiments, the sound comprises an acoustic frequency of 10 kHz.

[0160] In some embodiments, the dynamic sound comprises a tone or acoustic frequency perceptible to the subject. In some embodiments, the dynamic sound comprises a tone or acoustic frequency imperceptible to the subject. In some embodiments, the dynamic sound comprises an acoustic frequency from about 20 Hz to about 20 kHz. In some embodiments, the auditory stimulus comprises an acoustic frequency capable of modulating a gamma waveform in the subject. In some embodiments, the acoustic frequency capable of modulating a gamma waveform in the subject comprises an acoustic waveform of. 1 Hz, 1 Hz, 5 Hz, 10 Hz, 20 Hz, 25 Hz, 30 Hz, 31 Hz, 32 Hz, 33 Hz, 34 Hz, 35 Hz, 36 Hz, 37 Hz, 38 Hz, 39 Hz, 40 Hz, 41 Hz, 42 Hz, 43 Hz, 44 Hz, 45 Hz, 46 Hz, 47 Hz, 48 Hz, 49 Hz, 50 Hz, 60 Hz, 70 Hz, 80 Hz, 90 Hz, 100 Hz, 150 Hz, 200 Hz, 250 Hz, 300 Hz, 400 Hz, 500 Hz, 1000 Hz, 2000 Hz, 3000 Hz, 4,000 Hz, 5000 Hz, 6,000 Hz, 7,000 Hz, 8,000 Hz, 9,000 Hz, or 10,000 Hz.

[0161] The auditory stimulus can be turned 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 audio source can be turned on and off to provide a pulse repetition frequency in the range of about 20 Hertz (Hz) to about 140 Hz, about 30 Hz to about 60 Hz, about 40 Hz to about 60 Hz, about 35 Hz to about 45 Hz, or about 40 Hz, in accordance with methods disclosed herein. iii. Haptic Source

[0162] In a fully functional human hearing anatomy, the outer ear comprises an auricle and an ear canal. A sound wave or acoustic pressure is collected by the auricle and channeled into and through the ear canal. Disposed across the distal end of the ear canal is a tympanic membrane which vibrates in response to acoustic wave. This vibration is coupled to the oval window or fenestra ovalis through three bones of middle ear, collectively referred to as the ossicles and comprising the malleus, the incus, and the stapes. The ossicles of the middle ear serve to filter and amplify an acoustic wave, causing the oval window to vibrate. Such vibration sets up waves of fluid motion within the cochlea. Such fluid motion, in turn, activates hair cells that line the inside of cochlea. Activation of the hair cells causes appropriate nerve impulses to be transferred through the spiral ganglion cells and auditory nerve to the brain, where they are perceived as sound. In some embodiments, such as in damaged or dysfunctional hearing, this process is disrupted. A haptic source, such as a wireless bone conduction device, works by transmitting vibrations through the bones of the skull to the inner ear's cochlea, bypassing the outer and middle ear. In some embodiments, a haptic source can improve hearing perception, such as in damaged or dysfunctional hearing and can be useful in activating neural, visual, oscillations, e.g., gamma oscillations, in a brain region of a subject corresponding to the haptic frequency generated by the haptic device.

[0163] By way of example, a portable system can comprise a haptic source. The haptic source can comprise headphones worn about the head of a subject. The wireless headphones can comprise wireless bone conduction headphones suitable for delivering a haptic vibration gamma stimulus to the subject. The wireless bone conduction headphones can include, for example, circumaural headphones (e.g., full size / over-ear headphones) designed to sit above the ear of a user. The haptic source can be integrated into the audio source, i.e., wherein the haptic source located within an audio source as disclosed herein.

[0164] In some embodiments, bone conduction headphones include ear-fitting headphones, such as earphones or in-ear headphones. Earphones (or earbuds) can refer to small headphones that are fitted directly in the outer ear, facing but not inserted in the ear canal. In-ear headphones (or inear monitors or canalphones) can refer to small headphones that can be designed and constructed for insertion into the ear canal. In-ear headphones engage the ear canal and can block out more ambient noise as compared to earphones, thus providing a more immersive auditory brainwave stimulation experience. In-ear headphones can include ear canal plugs made or formed from one or more material, such as silicone rubber, elastomer, or foam. In some embodiments, in-ear headphones can include custom-made castings of the ear canal to create custom-molded plugs that provide added comfort and noise isolation to the subject, thereby further improving the immersion of a subject during the non-invasive stimulation .

[0165] In some embodiments, the haptic device can include an implanted bone conduction prosthesis, or a bone conduction hearing aid device. 1. Haptic Stimulus

[0166] In some embodiments, a haptic source is configured to generate a haptic stimulus such as a vibration, or a similar haptic stimulus. In some embodiments, the haptic stimulus can include any means that induces the perception of vibration through touch. In some embodiments, a haptic stimulus can be any stimulus that activates the somatosensory system.

[0167] In some embodiments, the frequency of the haptic stimulus comprises a haptic stimulus of 1 Hertz (Hz), 1 Hz, 5 Hz, 10 Hz, 20 Hz, 25 Hz, 30 Hz, 31 Hz, 32 Hz, 33 Hz, 34 Hz, 35 Hz, 36 Hz, 37 Hz, 38 Hz, 39 Hz, 40 Hz, 41 Hz, 42 Hz, 43 Hz, 44 Hz, 45 Hz, 46 Hz, 47 Hz, 48 Hz, 49 Hz, 50 Hz, 60 Hz, 70 Hz, 80 Hz, 90 Hz, 100 Hz, 150 Hz, 200 Hz, 250 Hz, 300 Hz, 400 Hz, 500 Hz, 1000 Hz, 2000 Hz, 3000 Hz, 4,000 Hz, 5000 Hz, 6,000 Hz, 7,000 Hz, 8,000 Hz, 9,000 Hz, or 10,000 Hz.

[0168] In some embodiments, the haptic stimulus can be turned 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 haptic source can be turned on and off to provide a pulse WO 2025 / 147596                                   PCT / US2025 / 010218 repetition frequency in the range of 20 Hertz (Hz) to about 140 Hz, about 30 Hz to about 60 Hz, about 40 Hz to about 60 Hz, about 35 Hz to about 45 Hz, or about 40 Hz, in accordance with methods disclosed herein. B. Additional Portable System Components i. Single Headset Device

[0169] In some embodiments, a portable system as disclosed herein comprises a single headset device. In some embodiments, the single headset device comprises a visual, audio, or haptic source, or any combination thereof as described herein. In some embodiments, the single headset device comprises an audio source and a visual source, wherein the visual source is rotatable about the audio source. In some embodiments, a module of any device or system as disclosed herein is rotatable about an axis of another module of the device of system. For instance, a visual module may be rotatable about an auditory module of a device or system as disclosed herein. In some embodiments, the single headset device comprises an audio source comprising headphones, and a visual source comprising glasses wherein the glasses are rotatable about the headphones, e.g., as shown and described in FIGs. 66-73.

[0170] In some embodiments, the single headset device comprises an audio source and a visual source, wherein the visual source is rotatable about the audio source, wherein the visual source is rotatable by about 0 degrees to about 360 degrees about the audio source. In some embodiments, the visual source is rotatable by about 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270,, 280, 290, 300, 310, 320, 330, 340, 350, or 360 degrees about the audio source. In some embodiments, the visual source is rotatable by more than 360 degrees about the audio source.

[0171] In some embodiments, a portable system as disclosed herein comprises a single headset device wherein the single headset device comprises a visual source and an audio source, wherein the visual source is rotatable about the audio source and audio source comprises a headband, e.g., as shown and described in FIGs. 70 and 71. In some embodiments the headband comprises a detachable headband. ii. Processor, Memory, and Feedback Sensor

[0172] In some embodiments, a portable system also includes at least one memory for storing processor executable instructions and at least one processor communicatively connected one or more additional component of the portable system. In some embodiments, a portable system also includes at least one memory for storing processor executable instructions and at least one processor communicatively connected to a stimulus emitting component of the portable system WO 2025 / 147596                                   PCT / US2025 / 010218 and the at least one memory. Upon execution of the processor executable instructions, the at least one processor may control the portable system such that system emits a stimulus at a frequency that activates neural oscillations, e.g., gamma oscillations, in a brain region of the subject corresponding to the frequency generated by the stimulus emitting component.

[0173] In some embodiments, the portable system includes a data interface that enables data communication between the system and an external control device or system. The external device may be external device such as a fitting system, PDA, computer, mobile phone, or any other suitable device. Preferably, the interface allows two-way or bidirectional communication. That is, interface data may be sent from both the open view visual stimulation device and the external device. For example, in one embodiment, the interface may be adapted to receive control signals from the external device for generating a visual stimulus at predetermined frequencies, and receive control settings for the portable system for storing in the memory unit. In some embodiments, however, the interface is a one-way interface, allowing only data to be forwarded from the external device to the portable system. In other embodiments, communication is a oneway interface with data being forwarded from the open view visual stimulation device to any type of receiving device. The data may include measured control signals or any type of status information or other suitable data. This information may be used to merely monitor the portable system or be used with a control device that may be a separate device or be integrated into the portable system or any other suitable device.

[0174] In some embodiments, the processor is configured to receive an indication of a physiological, cognitive, neural, visual, or physical assessment of the subject wearing portable system, e.g., as a single headset device embodiment. In some embodiments, when the processor receives the indication of the physiological, cognitive, neural, visual, or physical assessment of the subject, the processor instructs the stimulus emitting component to emit a visual, auditory, and / or haptic stimulus, or any combination thereof. In some embodiments, the physical assessment of the subject comprises ascertaining at least one of the subject's: compliance with proper use and positioning of the system, eye status, alert or sleep status, or environment and surroundings. In some embodiments, the physical assessment of the subject is performed to determine hearing of the subject, the indication of the physiological, cognitive, neural, visual, or physical assessment of the subject comprises a biosignal. In some embodiments, the biosignal comprises an electroencephalography (EEG).

[0175] In some embodiments, the cognitive assessment of the subject is obtained through questions posed to the subject, activities and tasks performed by the subject in response to a prompt, or behaviors exhibited by the subject.

[0176] In some embodiments, a portable system as disclosed herein is provided with or operatively connected to a computer system as disclosed herein. The computer system can communicate with one or more remote computer systems through the network. For instance, the computer system can communicate with a remote computer system of a user. Examples of remote computer systems include personal computers (e.g., portable PC), slate or tablet PC’s (e.g., Apple® iPad, Samsung® Galaxy Tab), telephones, Smart phones (e.g., Apple® iPhone, Android-enabled device, Blackberry®), or personal digital assistants. The user can access the computer system via the network. In some embodiments, the computer systems are programmed to implement the function of a portable system, such as implementing a stimulus delivered to a subject by the portable system as described herein.

[0177] In some embodiments, a portable system comprises one or more feedback components. The feedback component can include or interface with the microphone to obtain, identify, or receive sound. The feedback component can obtain ambient noise. The feedback component can obtain sound from the speakers to facilitate the audio device adjusting a characteristic of the auditory stimulus generated by the speaker. The microphone can receive voice input from a subject, such as audio commands, instructions, requests, feedback information, or responses to survey questions. iii. Hand-held Controller

[0178] In some embodiments, the portable system further comprises a hand-held controller. In some embodiments, said hand-held controller receives and transmits a signal dictating a dosing parameter corresponding to a frequency, a duration, a brightness, or a color of said visual stimulus, or a combination thereof, or a duration, an intensity, or a frequency of said audio stimuli, or a combination thereof, or a duration, frequency, intensity, or combination thereof of said haptic stimulus. In some embodiments, said hand-held controller further comprises an independent power supply comprising batteries or a rechargeable battery.

[0179] In some embodiments, the hand-held controller further comprises adjustable inputs for said single headset device, said audio source, said haptic source, and / or said visual source, wherein said adjustable inputs for said audio source comprise an adjustable volume input, and said adjustable inputs for said visual source comprise an adjustable brightness input and wherein said adjustable input for said single headset device comprises an input for powering on and powering off said single headset device, or for pausing said visual, haptic, or audio stimulus. In some embodiments, said hand-held controller comprises a device as shown and described in FIGs. 72, FIG. 73, FIG. 75A, FIG. 75B, FIG. 75C, or FIG. 75D WO 2025 / 147596                                   PCT / US2025 / 010218 iv. Neural Stimulation System (NSS)

[0180] In some embodiments, disclosed herein is a neural stimulation system. In some cases, a portable system or single headset device as disclosed herein comprises a neural stimulation system as disclosed herein. In some embodiments, a portable system or single headset device comprises a visual source, an audio source, and / or a haptic source as disclosed herein, wherein the visual, audio, or haptic source comprises an NSS as disclosed herein. The following describe illustrative embodiments, of a NSS that can be integrated into a portable system or single headset device as disclosed herein.

[0181] FIG. 1 is a block diagram depicting a system to perform visual brain stimulation in accordance with an embodiment. The system 100 can include a neural stimulation system (“NSS”) 105. The NSS 105 can be referred to as visual NSS 105 or NSS 105. In some embodiments, the visual NSS or NSS comprise a visual source, audio source, or a haptic source as described herein and can be included in a portable system as disclosed herein, wherein the visual source, audio source, or haptic source is configured to deliver a visual, auditory, or haptic stimulus, or a combination thereof. In brief overview, the NSS 105 can include, access, interface with, or otherwise communicate with one or more of a light generation module 110, light adjustment module 115, unwanted frequency filtering module 120, profile manager 125, side effects management module 130, feedback monitor 135, data repository 140, visual signaling component 150, filtering component 155, or feedback component 160. The light generation module 110, light adjustment module 115, unwanted frequency filtering module 120, profile manager 125, side effects management module 130, feedback monitor 135, visual signaling component 150, filtering component 155, or feedback component 160 can each include at least one processing unit or other logic device such as programmable logic array engine, or module configured to communicate with the database repository 150. The light generation module 110, light adjustment module 115, unwanted frequency filtering module 120, profile manager 125, side effects management module 130, feedback monitor 135, visual signaling component 150, filtering component 155, or feedback component 160 can be separate components, a single component, or part of the NSS 105. The system 100 and its components, such as the NSS 105, can include hardware elements, such as one or more processors, logic devices, or circuits. The system 100 and its components, such as the NSS 105, can include one or more hardware or interface component depicted in system 700 in FIGs. 7A and 7B. For example, a component of system 100 can include or execute on one or more processors 721, access storage 728 or memory 722, and communicate via network interface 718.

[0182] Still referring to FIG. 1, and in further detail, the NSS 105 can include at least one light generation module 110. The light generation module 110 can be designed and constructed to interface with a visual signaling component 150 to provide instructions or otherwise cause or facilitate the generation of a visual signal, such as a light pulse or flash of light, having one or more predetermined parameter. The light generation module 110 can include hardware or software to receive and process instructions or data packets from one or more module or component of the NSS 105. The light generation module 110 can generate instructions to cause the visual signaling component 150 to generate a visual signal. The light generation module 110 can control or enable the visual signaling component 150 to generate the visual signal having one or more predetermined parameters.

[0183] The light generation module 110 can be communicatively coupled to the visual signaling component 150. The light generation module 110 can communicate with the visual signaling component 150 via a circuit, electrical wire, data port, network port, power wire, ground, electrical contacts or pins. The light generation module 110 can wirelessly communicate with the visual signaling component 150 using one or more wireless protocols such as BlueTooth, BlueTooth Low Energy, Zigbee, Z-Wave, IEEE 802.11, WIFI, 3G, 4G, LTE, near field communications (“NFC”), or other short, medium or long range communication protocols, etc. The light generation module 110 can include or access network interface 718 to communicate wirelessly or over a wire with the visual signaling component 150.

[0184] The light generation module 110 can interface, control, or otherwise manage various types of visual signaling components 150 in order to cause the visual signaling component 150 to generate, block, control, or otherwise provide the visual signal having one or more predetermined parameters. The light generation module 110 can include a driver configured to drive a light source of the visual signaling component 150. For example, the light source can include a light emitting diode (“LED”), and the light generation module 110 can include an LED driver, chip, microcontroller, operational amplifiers, transistors, resistors, or diodes configured to drive the LED light source by providing electricity or power having certain voltage and current characteristics.

[0185] In some embodiments, the light generation module 110 can instruct the visual signaling component, e.g., the visual source, 150 to provide a visual signal that include a light wave 200 as depicted in FIG. 2A. The light wave 200 can include or be formed of electromagnetic waves. The electromagnetic waves of the light wave can have respective amplitudes and travel orthogonal to one another as depicted by the amplitude of the electric field 205 versus time and the amplitude of the magnetic field 210 versus time. The light wave 200 can have a wavelength 215. The light wave can 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 approximately 299,792,458 meters per second in a vacuum.

[0186] The light generation module 110 can instruct the visual signaling component 150 to generate light waves having one or more predetermined wavelength or intensity. The wavelength of the light wave can correspond to the visible spectrum, ultraviolet spectrum, infrared spectrum, or some other wavelength of light. For example, the wavelength of the light wave within the visible spectrum range can range from 390 to 700 nanometers (“nm”). Within the visible spectrum, the light generation module 110 can further specify one or more wavelengths corresponding to one or more colors. For example, the light generation module 110 can instruct the visual signaling component 150 to generate visual signals comprising one or more light waves having one or more wavelength corresponding to one or more of ultra-violet (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 -1000000 nm). The wavelength can range from 10 nm to 100 micrometers. In some embodiments, the wavelength can be in the range of 380 to 750 nm.

[0187] The light generation module 110 can determine to provide visual signals that include light pulses. The light generation module 110 can instruct or otherwise cause the visual signaling component 150 to generate light pulses. A light pulse can refer to a burst of light waves. For example, FIG. 2B illustrates a burst of a light wave. The burst of light wave can refer to a burst of an electric field 250 generated by the light wave. The burst of the electric field 250 of the light wave can be referred to as a light pulse or a flash of light. For example, a light source that is intermittently turned on and off can create bursts, flashes or pulses of light.

[0188] FIG. 2C illustrates pulses of light 235a-c in accordance with an embodiment. The light pulses 235a-c can be illustrated via a graph in the frequency spectrum where the y-axis represents 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 can include modulations of light wave between a frequency of Fa and frequency different from Fa. For example, the NSS 105 can modulate a light wave between a frequency in the visible spectrum, such as Fa, and a frequency outside the visible spectrum. The NSS 105 can modulate the light wave between two or more frequencies, between an on state and an off state, or between a high power state and a low power state.

[0189] In some cases, the frequency of the light wave used to generate the light pulse can be constant at Fa, thereby generating a square wave in the frequency spectrum. In some embodiments, each of the three pulses 235a-c can include light waves having a same frequency Fa.

[0190] The width of each of the light pulses (e.g., the duration of the burst of the light wave) can correspond to a pulse width 230a. The pulse width 230a can 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, the pulses 235a-c can include lights waves having different frequencies from one another. In some embodiments, the pulses 235a-c can have different pulse widths 230a from one another, as illustrated in FIG. 2D. For example, a first pulse 23 5d of FIG. 2D can have a pulse width 230a, while a second pulse 235e has a second pulse width 230b that is greater than the first pulse width 230a. A third pulse 235f can have a third pulse width 230c that is less than the second pulse width 230b. The third pulse width 230c can also be less than the first pulse width 230a. While the pulse widths 230a-c of the pulses 235d-f of the pulse train can vary, the light generation module 110 can maintain a constant pulse rate interval 240 for the pulse train.

[0191] The pulses 235a-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 a 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 light generation module 110 can provide a pulse train 201 with a predetermined frequency corresponding to gamma activity, such as 40 Hz. To do so, the light generation module 110 can determine the pulse rate interval 240 by taking the multiplicative inverse (or reciprocal) of the frequency (e.g., 1 divided by the predetermined frequency for the pulse train). For example, the light generation module 110 can take the multiplicative inverse of 40 Hz by dividing 1 by 40 Hz to determine the pulse rate interval 240 as .025 seconds. The pulse rate interval 240 can remain 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 can be fixed, while the pulse rate interval 240 varies.

[0192] In some embodiments, the light generation module 110 can generate a light pulse having a light wave that varies in frequency. For example, the light generation module 110 can generate up-chirp pulses where the frequency of the light wave of the light pulse increases from the beginning of the pulse to the end of the pulse as illustrated in FIG. 2E. For example, the frequency of a light wave at the beginning of pulse 235g can be Fa. The frequency of the light wave of the pulse 235g can increase from Fa to Fb in the middle of the pulse 235g, and then to a maximum of Fc at the end of the pulse 235g. Thus, the frequency of the light wave used to generate the pulse 235g can range from Fa to Fc. The frequency can increase linearly, exponentially, or based on some other rate or curve.

[0193] The light generation module 110 can generate down-chirp pulses, as illustrated in FIG. 2F, where the frequency of the light wave of the light pulse decreases from the beginning of the pulse to the end of the pulse. For example, the frequency of a light wave at the beginning of pulse 23 5j can be Fd. The frequency of the light wave of the pulse 23 5j can decrease from Fd to Fe in the middle of the pulse 23 5j, and then to a minimum of Ff at the end of the pulse 23 5j. Thus, the WO 2025 / 147596                                   PCT / US2025 / 010218 frequency of the light wave used to generate the pulse 23 5j can range from Fd to Ff. The frequency can decrease linearly, exponentially, or based on some other rate or curve.

[0194] A visual signaling component 150 can be designed and constructed to generate the light pulses responsive to instructions from the light generation module 110. The instructions can include, for example, parameters of the light pulse such as a frequency or wavelength of the light wave, intensity, duration of the pulse, frequency of the pulse train, pulse rate interval, or duration of the pulse train (e.g., a number of pulses in the pulse train or the length of time to transmit a pulse train having a predetermined frequency). The light pulse can be perceived, observed, or otherwise identified by the brain via ocular means such as eyes. The light pulses can be transmitted to the eye via direct visual field or peripheral visual field.

[0195] FIG. 3A illustrates a horizontal direct visual field 310 and a horizontal peripheral visual field. FIG. 3B illustrates a vertical direct visual field 320 and a vertical peripheral visual field 325. FIG. 3C illustrates degrees of direct visual fields and peripheral visual fields, including relative distances at which visual signals might be perceived in the different visual fields. The visual signaling component 150 can include a light source 305. The light source 305 can be positioned to transmit light pulses into the direct visual field 310 or 320 of a person’s eyes. The NSS 105 can be configured to transmit light pulses into the direct visual field 310 or 320 because this can facilitate brain entrainment as the person can pay more attention to the light pulses. The level of attention can be quantitatively measured directly in the brain, indirectly through the person’s eye behavior, or by active feedback (e.g., mouse tracking).

[0196] The light source 305 can be positioned to transmit light pulses into a peripheral visual field 315 or 325 of a person’s eyes. For example, the NSS 105 can transmit light pulses into the peripheral visual field 315 or 325 as these light pulses can be less distracting to the person who might be performing other tasks, such as reading, walking, driving, etc. Thus, the NSS 105 can provide subtle, on-going visual brain stimulation by transmitting light pulses via the peripheral visual field.

[0197] In some embodiments, the light source 305 can be head-worn, while in other embodiments the light source 305 can be held by a subject’s hands, placed on a stand, hung from a ceiling, or connected to a chair or otherwise positioned to direct light towards the direct or peripheral visual fields. For example, a chair or externally supported system can include or position the light source 305 to provide the visual input while maintaining a fixed / pre-specified relationship between the subject’s visual field and the visual stimulus. The system can provide an immersive experience. For example, the system can include an opaque or partially opaque dome that includes the light source. The dome can positioned over the subject’s head while the subject WO 2025 / 147596                                   PCT / US2025 / 010218 sits or reclines in chair. The dome can cover portions of the subject’s visual field, thereby reducing external distractions and facilitating entrainment of regions of the brain.

[0198] 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 a light emitting diode (LED), Organic LED, fluorescent light source, incandescent light, or any other light emitting device. The light source can include a lamp, light bulb, or one or more light emitting diodes of various colors (e.g., white, red, green, blue). In some embodiments, the light source includes a semiconductor light emitting device, such as a light emitting diode of any spectral or wavelength range. In some embodiments, the light source 305 includes a broadband lamp or a broadband light source. In some embodiments, the light source includes a black light. In some embodiments, 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 a laser diode. In some embodiments, light source 305 includes an OLED, PHOLED, QDLED, or any other variation of a light source utilizing an organic material. In some embodiments, light source 305 includes a monochromatic light source. In some embodiments, light source 305 includes a polychromatic light source. In some embodiments, the light source 305 includes a light source emitting light partially in the spectral range of ultraviolet light. In some embodiments, light source 305 includes a device, product or a material emitting light partially in the spectral range of visible light. In some embodiments, light source 305 is a device, product or a material partially emanating or emitting light in the spectral range of the infrared light. In some embodiments, light source 305 includes a device, product or a material emanating or emitting light in the visible spectral range. In some embodiments, light source 305 includes a light guide, an optical fiber or a waveguide through which light is emitted from the light source.

[0199] In some embodiments, light source 305 includes one or more mirrors for reflecting or redirecting of light. For example, the mirrors can reflect or redirect light towards the direct visual field 310 or 320, or the peripheral visual field 315 or 325. The light source 305 can include interact with microelectromechanical devices (“MEMS”). The light source 305 can include or interact with a digital light projector (“DLP”). In some embodiments, the light source 305 can include ambient light or sunlight. The ambient light or sunlight can be focused by one or more optical lenses and directed towards the direct visual field or peripheral field. The ambient light or sunlight can be directed by one or more mirrors towards the directed visual field or peripheral visual field.

[0200] In cases where the light source is ambient light, the ambient light is not positioned but the ambient light can enter the eye via a direct visual field or peripheral visual field. In some embodiments, the light source 305 can be positioned to direct light pulses towards the direct visual field or peripheral field. For example, one or more light sources 305 can be attached, affixed, coupled, mechanically coupled, or otherwise provided with a frame 400 as illustrated in FIG. 4A. In some embodiments, the visual signaling component 150 can include the frame 400. Additional details of the operation of the NSS 105 in conjunction with the frame 400 including one or more light sources 305 are provided below, in the section labelled as “NSS Operating With A Frame”. Thus, the light source can include any type of light source such as an optical light source, mechanical light source, or chemical light source. The light source can include any material or object that is reflective or opaque that can generate, emit, or reflect oscillating patterns of light, such as a fan rotating in front of a light, or bubbles. In some embodiments, the light source can include optical illusions that are invisible, physiological phenomena that are within the eye (e.g., pressing the eyeball), or chemicals applied to the eye. 1. Systems and Devices Configured for Neural Stimulation via Visual Stimulation

[0201] Referring now to FIG. 4A, the frame 400 can be designed and constructed to be placed or positioned on a person’s head. The frame 400 can be configured to be worn by the person. The frame 400 can be designed and constructed to stay in place. The frame 400 can be configured to be worn and stay in place as a person sits, stands, walks, runs, or lays down flat. The light source 305 can be configured on the frame 400 to project light pulses towards the person’s eyes during these various positions. In some embodiments, the light source 305 can be configured to project light pulses towards the person’s eyes if their eyelids are closed such that the light pulse penetrates the eyelid to be perceived by the retina. The frame 400 can include a bridge 420. The frame 400 can include one or more eye wires 415 coupled to the bridge 420. The bridge 420 can be positioned in between the eye wires 415. The frame 400 can include one or more temples extending from the one or more eye wires 415. In some embodiments, the eye wires 415 can include or hold a lens 425. In some embodiments, the eye wires 415 can include or hold a solid material 425 or cover 425. The lens, solid material, or cover 425 can be transparent, semitransparent, opaque, or completely block out external light.

[0202] 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 middle of the eye wire 415 on a solid material 425 in order to transmit light pulses into the direct visual field. In some embodiments, a light source 305 can be positioned at a comer of the eye wire 415, such as a comer of the eye wire 415 coupled to the temple 410, in order to transmit light pulses towards a peripheral field.

[0203] The NSS 105 can perform visual brain stimulation via a single eye or both eyes. For example, the NSS 105 can direct light pulses to a single eye or both eyes. The NSS 105 can interface with a visual signaling component 150 that includes a frame 400 and two eye wires 415. However, the visual signaling component 150 can include a single light source 305 configured and positioned to direct light pulses to a first eye. The visual signaling component 150 can further include a light blocking component that keeps out or blocks the light pulses generated from the light source 305 from entering a second eye. The visual signaling component 150 can block or prevent light from entering the second eye during the brain entrainment process.

[0204] In some embodiments, the visual signaling component 150 can alternatively transmit or direct light pulses to the first eye and the second eye. For example, the visual signaling component 150 can direct light pulses to the first eye for a first time interval. The visual signaling component 150 can direct light pulses to the second eye for a second time interval. The first time interval and the second time interval can be a same time interval, overlapping time intervals, mutually exclusive time intervals, or subsequent time intervals.

[0205] FIG. 4B illustrates a frame 400 comprising a set of shutters 435 that can block at least a portion of light that enters through the eye wire 415. The set of shutters 435 can intermittently block ambient light or sunlight that enters through the eye wire 415. The set of shutters 435 can open to allow light to enter through the eye wire 415, and close to at least partially block light that enters through the eye wire 415. Additional details of the operation of the NSS 105 in conjunction with the frame 400 including one or more shutters 430 are provided below, in the section labelled as “NSS Operating With A Frame”.

[0206] The set of shutters 435 can include one or more shutter 430 that is opened and closed by one or more actuator. The shutter 430 can be formed from one or more materials. The shutter 430 can include one or more materials. The shutter 430 can include or be formed from materials that are capable of at least partially blocking or attenuating light.

[0207] The frame 400 can include one or more actuators configured to at least partially open or close the set of shutters 435 or an individual shutter 430. The frame 400 can include one or more types of actuators to open and close the shutters 435. For example, the actuator can include a mechanically driven actuator. The actuator can include a magnetically driven actuator. The actuator can include a pneumonic actuator. The actuator can include a hydraulic actuator. The actuator can include a piezoelectric actuator. The actuator can include a micro-electromechanical systems (“MEMS”).

[0208] The set of shutters 435 can include one or more shutter 430 that is opened and closed via electrical or chemical techniques. For example, the shutter 430 or set of shutters 435 can be formed from one or more chemicals. The shutter 430 or set of shutters can include one or more WO 2025 / 147596                                   PCT / US2025 / 010218 chemicals. The shutter 430 or set of shutters 435 can include or be formed from chemicals that are capable of at least partially blocking or attenuating light.

[0209] For example, the shutter 430 or set of shutters 435 can include photochromic lenses configured to filter, attenuate or block light. The photochromic lenses can automatically darken when exposed to sunlight. The photochromic lens can include molecules that are configured to darken the lens. The molecules can be activated by light waves, such as ultraviolet radiation or other light wavelengths. Thus, the photochromic molecules can be configured to darken the lens in response to a predetermined wavelength of light.

[0210] The shutter 430 or set of shutters 435 can include electrochromic glass or plastic. Electrochromic glass or plastic can change from light to dark (e.g., clear to opaque) in response to an electrical voltage or current. Electrochromic glass or plastic can include metal-oxide coatings that are deposited on the glass or plastic, multiple layers, and lithium ions that travel between two electrodes between a layer to lighten or darken the glass.

[0211] The shutter 430 or set of shutters 435 can include micro shutters. Micro shutters can include tiny windows that measure 100 by 200 microns. The micro shutters can be arrayed in the eye frame 415 in a waffle-like grid. The individual micro shutters can be opened or closed by an actuator. The actuator can include a magnetic arm that sweeps past the micro shutter to open or close the micro shutter. An open micro shutter can allow light to enter through the eye frame 415, while a closed micro shutter can block, attenuate, or filter the light.

[0212] The NSS 105 can drive the actuator to open and close one or more shutters 430 or the set of shutters 435 at a predetermined frequency such as 40 Hz. By opening and closing the shutter 430 at the predetermined frequency, the shutter 430 can allow flashes of light to pass through the eye wire 415 at the predetermined frequency. Thus, the frame 400 including a set of shutters 435 may not include or use separate light source coupled to the frame 400, such as a light source 305 coupled to frame 400 depicted in FIG. 4A.

[0213] In some embodiments, the visual signaling component 150 or light source 305 can refer to or be included in a virtual reality headset 401, as depicted in FIG. 4C. For example, the virtual reality headset 401 can be designed and constructed to receive a light source 305. The light source 305 can include a computing device having a display device, such as a smartphone or mobile telecommunications device. The virtual reality headset 401 can include a cover 440 that opens to receive the light source 305. The cover 440 can close to lock or hold the light source 305 in place. When closed, the cover 440 and case 450 and 445 can form an enclosure for the light source 305. This enclosure can provide an immersive experience that minimize or eliminates unwanted visual distractions. The virtual reality headset can provide an environment to maximize brainwave entrainment. The virtual reality headset can provide an augmented reality experience. In some embodiments, the light source 305 can form an image on another surface such that the image is reflected off the surface and towards a subject’s eye (e.g., a heads up display that overlays on the screen a flickering object or an augmented portion of reality). Additional details of the operation of the NSS 105 in conjunction with the virtual reality headset 401 are provided below.

[0214] The virtual reality headset 401 includes straps 455 and 460 configured to secure the virtual reality headset 401 to a person’s head. The virtual reality headset 401 can be secured via straps 455 and 460 such to minimize movement of the headset 401 worn during physical activity, such as walking or running. The virtual reality headset 401 can include a skull cap formed from 460 or 455.

[0215] The feedback sensor 605 can include an electrode, dry electrode, gel electrode, saline soaked electrode, or adhesive-based electrodes.

[0216] FIGs. 5A-5D illustrate embodiments of the visual signaling component 150 that can include a tablet computing device 500 or other computing device 500 having a display screen 305 as the light source 305. The visual signaling component 150 can transmit light pulses, light flashes, or patterns of light via the display screen 305 or light source 305.

[0217] FIG. 5A illustrates a display screen 305 or light source 305 that transmits light. The light source 305 can transmit light comprising a wavelength in the visible spectrum. The NSS 105 can instruct the visual signaling component 150 to transmit light via the light source 305. The NSS 105 can instruct the visual signaling component 150 to transmit flashes of light or light pulses having a predetermined pulse rate interval. For example, FIG. 5B illustrates the light source 305 turned off or disabled such that the light source does not emit light, or emits a minimal or reduced amount of light. The visual signaling component 150 can cause the tablet computing device 500 to enable (e.g., FIG. 5A) and disable (e.g., FIG. 5B) the light source 305 such that flashes of light have a predetermined frequency, such as 40 Hz. The visual signaling component 150 can toggle or switch the light source 305 between two or more states to generate flashes of light or light pulses with the predetermined frequency.

[0218] In some embodiments, the light generation module 110 can instruct or cause the visual signaling component 150 to display a pattern of light via display device 305 or light source 305, as depicted in FIGs. 5C and 5D. The light generation module 110 can cause the visual signaling component 150 can flicker, toggle or switch between two or more patterns to generate flashes of light or light pulses. Patterns can include, for example, alternating checkerboard patterns 510 and 515. The pattern can include symbols, characters, or images that can be toggled or adjusted from one state to another state. For example, the color of a character or text relative to a background color can be inverted to cause a switch between a first state 510 and a second state 515. Inverting WO 2025 / 147596                                   PCT / US2025 / 010218 a foreground color and background color at a predetermined frequency can generate light pulses by way of indicating visual changes that can facilitate adjusting or managing a frequency of neural oscillations. Additional details of the operation of the NSS 105 in conjunction with the tablet 500 are provided below, in the section labeled as “NSS Operating With a Tablet”.

[0219] In some embodiments, the light generation module 110 can instruct or cause the visual signaling component 150 to flicker, toggle, or switch between images configured to stimulate specific or predetermined portions of the brain or a specific cortex. The presentation, form, color, motion and other aspects of the light or an image based stimuli can dictate which cortex or cortices are recruited to process the stimuli. The visual signaling component 150 can stimulate discrete portions of the cortex by modulating the presentation of the stimuli to target specific or general regions of interest. The relative position in the field of view, the color of the input, or the motion and speed of the light stimuli can dictate which region of the cortex is stimulated.

[0220] For example, the brain can include at least two portions that process predetermined types of visual stimuli: the primary visual cortex on the left side of the brain, and the calcarine fissure on the right side of the brain. Each of these two portions can have one or more multiple subportions that process predetermined types of visual stimuli. For example, the calcarine fissure can include a sub-portion referred to as area V5 that can include neurons that respond strongly to motion but may not register stationary objects. Subjects with damage to area V5 can have motion blindness, but otherwise normal vision. In another example, the primary visual cortex can include a sub-portion referred to as area V4 that can include neurons that are specialized for color perception. Subjects with damage to area V4 can have color blindness and only perceive objects in shades of gray. In another example, the primary visual cortex can include a sub-portion referred to as area VI that includes neurons that respond strongly to contrast edges and helps segment the image into separate objects.

[0221] Thus, the light generation module 110 can instruct or cause the visual signaling component 150 to form a type of still image or video, or generate a flicker, or toggle between images that configured to stimulate specific or predetermined portions of the brain or a specific cortex. For example, the light generation module 110 can instruct or cause the visual signaling component 150 to generate images of human faces to stimulate a fusiform face area, which can facilitate brain entrainment for subjects having prosopagnosia or face blindness. The light generation module 110 can instruct or cause the visual signaling component 150 to generate images of faces flickering to target this area of the subject’s brain. In another example, the light generation module 110 can instruct the visual signaling component 150 to generate images that include edges or line drawings to stimulate neurons of the primary visual cortex that respond strongly to contrast edges.

[0222] The NSS 105 can include, access, interface with, or otherwise communicate with at least one light adjustment module 115. The light adjustment module 115 can be designed and constructed to measure or verify an environmental variable (e.g., light intensity, timing, incident light, ambient light, eye lid status, etc.) to adjust a parameter associated with the visual signal, such as a frequency, amplitude, wavelength, intensity pattern or other parameter of the visual signal. The light adjustment module 115 can automatically vary a parameter of the visual signal based on profile information or feedback. The light adjustment module 115 can receive the feedback information from the feedback monitor 135. The light adjustment module 115 can receive instructions or information from a side effects management module 130. The light adjustment module 115 can receive profile information from profile manager 125.

[0223] The NSS 105 can include, access, interface with, or otherwise communicate with at least one unwanted frequency filtering module 120. The unwanted frequency filtering module 120 can be designed and constructed to block, mitigate, reduce, or otherwise filter out frequencies of visual signals that are undesired to prevent or reduce an amount of such visual signals from being perceived by the brain. The unwanted frequency filtering module 120 can interface, instruct, control, or otherwise communicate with a filtering component 155 to cause the filtering component 155 to block, attenuate, or otherwise reduce the effect of the unwanted frequency on the neural oscillations.

[0224] The NSS 105 can include, access, interface with, or otherwise communicate with at least one profile manager 125. The profile manager 125 can be designed or constructed to store, update, retrieve or otherwise manage information associated with one or more subjects associated with the visual brain entrainment. Profile information can include, for example, historical treatment information, historical brain entrainment information, dosing information, parameters of light waves, feedback, physiological information, environmental information, or other data associated with the systems and methods of brain entrainment.

[0225] The NSS 105 can include, access, interface with, or otherwise communicate with at least one side effects management module 130. The side effects management module 130 can be designed and constructed to provide information to the light adjustment module 115 or the light generation module 110 to change one or more parameter of the visual signal in order to reduce a side effect. Side effects can include, for example, nausea, migraines, fatigue, seizures, eye strain, or loss of sight.

[0226] The side effects management module 130 can automatically instruct a component of the NSS 105 to alter or change a parameter of the visual signal. The side effects management module 130 can be configured with predetermined thresholds to reduce side effects. For example, the side effects management module 130 can be configured with a maximum duration of a pulse WO 2025 / 147596                                   PCT / US2025 / 010218 train, maximum intensity of light waves, maximum amplitude, maximum duty cycle of a pulse train (e.g., the pulse width multiplied by the frequency of the pulse train), maximum number of treatments for brainwave entrainment in a time period (e.g., 1 hour, 2 hours, 12 hours, or 24 hours).

[0227] The side effects management module 130 can cause a change in the parameter of the visual signal in response to feedback information. The side effect management module 130 can receive feedback from the feedback monitor 135. The side effects management module 130 can determine to adjust a parameter of the visual signal based on the feedback. The side effects management module 130 can compare the feedback with a threshold to determine to adjust the parameter of the visual signal.

[0228] The side effects management module 130 can be configured with or include a policy engine that applies a policy or a rule to the current visual signal and feedback to determine an adjustment to the visual signal. For example, if feedback indicates that a patient receiving visual signals has a heart rate or pulse rate above a threshold, the side effects management module 130 can turn off the pulse train until the pulse rate stabilizes to a value below the threshold, or below a second threshold that is lower than the threshold.

[0229] The NSS 105 can include, access, interface with, or otherwise communicate with at least one feedback monitor 135. The feedback monitor can be designed and constructed to receive feedback information from a feedback component 160. Feedback component 160 can include, for example, a feedback sensor 605 such as a temperature sensor, heart or pulse rate monitor, physiological sensor, ambient light sensor, ambient temperature sensor, sleep status via actigraphy, blood pressure monitor, respiratory rate monitor, brain wave sensor, EEG probe, electrooculography (“EOG”) probes configured to measure the comeo-retinal standing potential that exists between the front and the back of the human eye, accelerometer, gyroscope, motion detector, proximity sensor, camera, microphone, or photo detector.

[0230] In some embodiments, a computing device 500 can include the feedback component 160 or feedback sensor 605, as depicted in FIGS. 5C and 5D. For example, the feedback sensor on tablet 500 can include a front-facing camera that can capture images of a person viewing the light source 305.

[0231] FIG. 6A depicts one or more feedback sensors 605 provided on a frame 400. In some embodiments, a frame 400 can include one or feedback sensors 605 provided on a portion of the frame, such as the bridge 420 or portion of the eye wire 415. The feedback sensor 605 can be provided with or coupled to the light source 305. The feedback sensor 605 can be separate from the light source 305.

[0232] The feedback sensor 605 can interact with or communicate with NSS 105. For example, the feedback sensor 605 can provide detected feedback information or data to the NSS 105 (e.g., feedback monitor 135). The feedback sensor 605 can provide data to the NSS 105 in real-time, for example as the feedback sensor 605 detects or senses or information. The feedback sensor 605 can provide the feedback information to the NSS 105 based on a time interval, such as 1 minute, 2 minutes, 5 minutes, 10 minutes, hourly, 2 hours, 4 hours, 12 hours, or 24 hours. The feedback sensor 605 can provide the feedback information to the NSS 105 responsive to a condition or event, such as a feedback measurement exceeding a threshold or falling below a threshold. The feedback sensor 605 can provide feedback information responsive to a change in a feedback parameter. In some embodiments, the NSS 105 can ping, query, or send a request to the feedback sensor 605 for information, and the feedback sensor 605 can provide the feedback information in response to the ping, request, or query.

[0233] FIG. 6B illustrates feedback sensors 605 placed or positioned at, on, or near a person’s head. Feedback sensors 605 can include, for example, EEG probes that detect brain wave activity.

[0234] The feedback monitor 135 can detect, receive, obtain, or otherwise identify feedback information from the one or more feedback sensors 605. The feedback monitor 135 can provide the feedback information to one or more component of the NSS 105 for further processing or storage. For example, the profile manager 125 can update profile data structure 145 stored in data repository 140 with the feedback information. Profile manager 125 can associate the feedback information with an identifier of the patient or person undergoing the visual brain stimulation, as well as a time stamp and date stamp corresponding to receipt or detection of the feedback information. The identifier can be indicative of an activity of a subject, a physiological or physical condition of a subject, or a mental condition of a subject. The identifier can also be indicative of a disease, disorder, or condition.

[0235] The feedback monitor 135 can detect symptoms of a neurological disease or disorder. For the example, the feedback monitor can be used to evaluate changes in fine motor skills over time or changes in voice pitch or tone. The profile manager 125 can update profile data structure with the feedback information. The profile data structure can be used to assess whether a person is at risk of developing a neurological disorder, whether a person has a neurological disorder, or progression of symptoms of a neurological disorder.

[0236] The feedback monitor 135 can determine a level of attention. The level of attention can refer to the focus provided to the light pulses used for brain stimulation. The feedback monitor 135 can determine the level of attention using various hardware and software techniques. The feedback monitor 135 can assign a score to the level of attention (e.g., 1 to 10 with 1 being low WO 2025 / 147596                                   PCT / US2025 / 010218 attention and 10 being high attention, or vice versa, 1 to 100 with 1 being low attention and 100 being high attention, or vice versa, 0 to 1 with 0 being low attention and 1 being high attention, or vice versa), categorize the level of attention (e.g., low, medium, high), grade the attention (e.g., A, B, C, D, or F), or otherwise provide an indication of a level of attention.

[0237] In some cases, the feedback monitor 135 can track a person’s eye movement to identify a level of attention. The feedback monitor 135 can interface with a feedback component 160 that includes an eye-tracker. The feedback monitor 135 (e.g., via feedback component 160) can detect and record eye movement of the person and analyze the recorded eye movement to determine an attention span or level of attention. The feedback monitor 135 can measure eye gaze which can indicate or provide information related to covert attention. For example, the feedback monitor 135 (e.g., via feedback component 160) can be configured with electro-oculography (“EOG”) to measure the skin electric potential around the eye, which can indicate a direction the eye faces relative to the head. In some embodiments, the EOG can include a system or device to stabilize the head so it cannot move in order to determine the direction of the eye relative to the head. In some embodiments, the EOG can include or interface with a head tracker system to determine the position of the heads, and then determine the direction of the eye relative to the head.

[0238] In some embodiments, the feedback monitor 135 and feedback component 160 can determine or track the direction of the eye or eye movement using video detection of the pupil or corneal reflection. For example, the feedback component 160 can include one or more camera or video camera. The feedback component 160 can include an infra-red source that sends light pulses towards the eyes. The light can be reflected by the eye. The feedback component 160 can detect the position of the reflection. The feedback component 160 can capture or record the position of the reflection. The feedback component 160 can perform image processing on the reflection to determine or compute the direction of the eye or gaze direction of the eye.

[0239] The feedback monitor 135 can compare the eye direction or movement to historical eye direction or movement of the same person, nominal eye movement, or other historical eye movement information to determine a level of attention. For example, if the eye is focused on the light pulses during the pulse train, then the feedback monitor 135 can determine that the level of attention is high. If the feedback monitor 135 determines that the eye moved away from the pulse train for 25% of the pulse train, then the feedback monitor 135 can determine that the level of attention is medium. If the feedback monitor 135 determines that the eye movement occurred for more than 50% of the pulse train or the eye was not focused on the pulse train for greater than 50%, then the feedback monitor 135 can determine that the level of attention is low.

[0240] In some embodiments, the system 100 can include a filter (e.g., filtering component 155) to control the spectral range of the light emitted from the light source. In some embodiments, WO 2025 / 147596                                   PCT / US2025 / 010218 light source includes a light reactive material affecting the light emitted, such as a polarizer, filter, prism or a photochromic material, or electrochromic glass or plastic. The filtering component 155 can receive instructions from the unwanted frequency filtering module 120 to block or attenuate one or more frequencies of light.

[0241] The filtering component 155 can include an optical filter that can selectively transmit light in a particular 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 incoming light wave for a range of wavelengths. The optical filter can include an absorptive filter, or an interference or dichroic filter. An absorptive filter can take energy of a photon to transform the electromagnetic energy of a light wave into internal energy of the absorber (e.g., thermal energy). The reduction in intensity of a light wave propagating through a medium by absorption of a part of its photons can be referred to as attenuation.

[0242] An interference filter or dichroic filter can include an optical filter that reflects one or more spectral bands of light, while transmitting other spectral bands of light. An interference filter or dichroic filter can have a nearly zero coefficient of absorption for one or more wavelengths. Interference filters can be high-pass, low-pass, bandpass, or band-rejection. An interference filter can include one or more thin layers of a dielectric material or metallic material having different refractive indices.

[0243] In an illustrative implementation, the NSS 105 can interface with a visual signaling component 150, a filtering component 155, and a feedback component 160. The visual signaling component 150 can include hardware or devices, such as glass frames 400 and one or more light sources 305. The filtering component 155 can include hardware or devices, such as a feedback sensor 605. The filtering component 155 can include hardware, materials or chemicals, such as a polarizing lens, shutters, electrochromic materials or photochromic materials. 2. Systems and Devices Configured for Neural Stimulation via Auditory Stimulation

[0244] FIG. 12A illustrates a system for auditory stimulation in accordance with an embodiment. The system 1200 can include one or more speakers 1205. The system 1200 can include one or more microphones. In some embodiments, the system can include both speakers 1205 and microphones 1210. In some embodiments, the system 1200 includes speakers 1205 and may not include microphones 1210. In some embodiments, the system 1200 includes microphones 1210 and may not include speakers 1210.

[0245] The speakers 1205 can be integrated with the audio signaling component 950. The audio signaling component 950 can include speakers 1205. The speakers 1205 can interact or WO 2025 / 147596                                   PCT / US2025 / 010218 communicate with audio signaling component 950. For example, the audio signaling component 950 can instruct the speaker 1205 to generate sound.

[0246] The microphones 1210 can be integrated with the feedback component 960. The feedback component 960 can include microphones 1210. The microphones 1210 can interact or communicate with feedback component 960. For example, the feedback component 960 can receive information, data or signals from microphone 1210.

[0247] In some embodiments, the speaker 1205 and the microphone 1210 can be integrated together or a same device. For example, the speaker 1205 can be configured to function as the microphone 1210. The NSS 905 can toggle the speaker 1205 from a speaker mode to a microphone mode.

[0248] In some embodiments, the system 1200 can include a single speaker 1205 positioned at one of the ears of the subject. In some embodiments, the system 1200 can include two speakers. A first speaker of the two speakers can be positioned at a first ear, and the second speaker of the two speakers can be positioned at the second ear. In some embodiments, additional speakers can be positioned in front of the subject’s head, or behind the subject’s head. In some embodiments, one or more microphones 1210 can be positioned at one or both ears, in front of the subject’s head, or behind the subject’s head.

[0249] The speaker 1205 can include a dynamic cone speaker configured to produce sound from an electrical signal. The speaker 1205 can include a full-range driver to produce acoustic waves with frequencies over some or all of the audible range (e.g., 60 Hz to 20,000 Hz). The speaker 1205 can include a driver to produce acoustic waves with frequencies outside the audible range, such as 0 to 60 Hz, or in the ultrasonic range such as 20 kHz to 4 GHz. The speaker 1205 can include one or more transducers or drivers to produce sounds at varying portions of the audible frequency range. For example, the speaker 1205 can include tweeters for high range frequencies (e.g., 2,000 Hz to 20,000 Hz), mid-range drivers for middle frequencies (e.g., 250 Hz to 2000 Hz), or woofers for low frequencies (e.g., 60 Hz to 250 Hz).

[0250] The speaker 1205 can include one or more types of speaker hardware, components or technology to produce sound. For example, the speaker 1205 can include a diaphragm to produce sound. The speaker 1205 can include a moving-iron loudspeaker that uses a stationary coil to vibrate a magnetized piece of metal. The speaker 1205 can include a piezoelectric speaker. A piezoelectric speaker can use the piezoelectric effect to generate sound by applying a voltage to a piezoelectric material to generate motion, which is converted into audible sound using diaphragms and resonators.

[0251] The speaker 1205 can include various other types of hardware or technology, such as magnetostatic loudspeakers, magnetostrictive speakers, electrostatic loudspeakers, a ribbon WO 2025 / 147596                                   PCT / US2025 / 010218 speaker, planar magnetic loudspeakers, bending wave loudspeakers, coaxial drivers, hom loudspeakers, Heil air motion transducers, or transparent ionic conductions speaker.

[0252] In some cases, the speaker 1205 may not include a diaphragm. For example, the speaker 1205 can be a plasma arc speaker that uses electrical plasma as a radiating element. The speaker 1205 can be a thermoacoustic speakers that uses carbon nanotube thin film. The speaker 1205 can be a rotary woofer that includes a fan with blades that constantly change their pitch.

[0253] In some embodiments, the speaker 1205 can include a headphone or a pair of headphones, earspeakers, earphones, or earbuds. Headphones can be relatively small speakers as compared to loudspeakers. Headphones can be designed and constructed to be placed in the ear, around the ear, or otherwise at or near the ear. Headphones can include electroacoustic transducers that convert an electrical signal to a corresponding sound in the subject’s ear. In some embodiments, the headphones 1205 can include or interface with a headphone amplifier, such as an integrated amplifier or a standalone unit.

[0254] In some embodiments, the speaker 1205 can include headphones that can include an air jet that pushes air into the auditory canal, pushing the tympanum in a manner similar to that of a sound wave. The compression and rarefaction of the tympanic membrane through bursts of air (with or without any discernible sound) can control frequencies of neural oscillations similar to auditory signals. For example, the speaker 1205 can include air jets or a device that resembles inear headphones that either push, pull or both push and pull air into and out of the ear canal in order to compress or pull the tympanic membrane to affect the frequencies of neural oscillations. The NSS 905 can instruct, configure or cause the air jets to generate bursts of air at a predetermined frequency.

[0255] In some embodiments, the headphones can connect to the audio signaling component 950 via a wired or wireless connection. In some embodiments, the audio signaling component 950 can include the headphones. In some embodiments, the headphones 1205 can interface with one or more components of the NSS 905 via a wired or wireless connection. In some embodiments, the headphones 1205 can include one or more components of the NSS 905 or system 100, such as the audio generation module 910, audio adjustment module 915, unwanted frequency filtering module 920, profile manager 925, side effects management module 930, feedback monitor 935, audio signaling component 950, filtering component 955, or feedback component 960.

[0256] The speaker 1205 can include or be integrated into various types of headphones. For example, the headphones can include, for example, circumaural headphones (e.g., full size headphones) that include circular or ellipsoid earpads that are designed and constructed to seal against the head to attenuate external noise. Circumaural headphones can facilitate providing an immersive auditory brainwave wave stimulation experience, while reducing external distractions. WO 2025 / 147596                                   PCT / US2025 / 010218 In some embodiments, headphones can include supra-aural headphones, which include pads that press against the ears rather than around them. Supra-aural headphones can provide less attenuation of external noise.

[0257] Both circumaural headphones and supra-aural headphones can have an open back, closed back, or semi open back. An open back leaks more sound and allows more ambient sounds to enter, but provides a more natural or speaker-like sound. Closed back headphones block more of the ambient noise as compared to open back headphones, thus providing a more immersive auditory brainwave stimulation experience while reducing external distractions.

[0258] In some embodiments, headphones can include ear-fitting headphones, such as earphones or in-ear headphones. Earphones (or earbuds) can refer to small headphones that are fitted directly in the outer ear, facing but not inserted in the ear canal. Earphones, however, provide minimal acoustic isolation and allow ambient noise to enter. In-ear headphones (or in-ear monitors or canalphones) can refer to small headphones that can be designed and constructed for insertion into the ear canal. In-ear headphones engage the ear canal and can block out more ambient noise as compared to earphones, thus providing a more immersive auditory brainwave stimulation experience. In-ear headphones can include ear canal plugs made or formed from one or more material, such as silicone rubber, elastomer, or foam. In some embodiments, in-ear headphones can include custom-made castings of the ear canal to create custom-molded plugs that provide added comfort and noise isolation to the subject, thereby further improving the immersiveness of the auditory brainwave stimulation experience.

[0259] In some embodiments, one or more microphones 1210 can be used to detect sound. A microphone 1210 can be integrated with a speaker 1205. The microphone 1210 can provide feedback information to the NSS 905 or other component of system 100. The microphone 1210 can provide feedback to a component of the speaker 1205 to cause the speaker 1205 to adjust a parameter of audio signal.

[0260] The microphone 1210 can include a transducer that converts sound into an electrical signal. The Microphone 1210 can use electromagnetic induction, capacitance change, or piezoelectricity to produce the electrical signal from air pressure variations. In some cases, the microphone 1210 can include or be connected to a pre-amplifier to amplify the signal before it is recorded or processed. The microphone 1210 can include one or more type of microphone, including, for example, a condenser microphone, RF condenser microphone, electret condenser, dynamic microphone, moving-coil microphone, ribbon microphone, carbon microphone, piezoelectric microphone, crystal microphone, fiber optic microphone, laser microphone, liquid or water microphone, microelectromechanical systems (“MEMS”) microphone, or speakers as microphones.

[0261] The feedback component 960 can include or interface with the microphone 1210 to obtain, identify, or receive sound. The feedback component 960 can obtain ambient noise. The feedback component 960 can obtain sound from the speakers 1205 to facilitate the NSS 905 adjusting a characteristic of the audio signal generated by the speaker 1205. The microphone 1210 can receive voice input from the subject, such as audio commands, instructions, requests, feedback information, or responses to survey questions.

[0262] In some embodiments, one or more speakers 1205 can be integrated with one or more microphones 1210. For example, the speaker 1205 and microphone 1210 can form a headset, be placed in a single enclosure, or can even be the same device since the speaker 1205 and the microphone 1210 can be structurally designed to toggle between a sound generation mode and a sound reception mode.

[0263] FIG. 12B illustrates a system configuration for auditory brain entrainment in accordance with an embodiment. The system 1200 can include at least one speaker 1205. The system 1200 can include at least microphone 1210. The system 1200 can include at least one active noise cancellation component 1215. The system 1200 can include at least one feedback sensor 1225. The system 1200 can include or interface with the NSS 905. The system 1200 can include or interface with an audio player 1220.

[0264] The system 1200 can include a first speaker 1205 positioned at a first ear. The system 1200 can include a second speaker 1205 positioned at a second year. The system 1200 can include a first active noise cancellation component 1215 communicatively coupled with the first microphone 1210. The system 1200 can include a second active noise cancellation component 1215 communicatively coupled with the second microphone 1210. In some cases, the active noise cancellation component 1215 can communicate with both the first speaker 1205 and the second speaker 1205, or both the first microphone 1210 and the second microphone 1210. The system 1200 can include a first microphone 1210 communicatively coupled with the active noise cancellation component 1215. The system 1200 can include a second microphone 1210 communicatively coupled with the active noise cancelation component 1215. In some embodiments, each of the microphone 1210, speaker 1205 and active noise cancellation component can communicate or interface with the NSS 905. In some embodiments, the system 1200 can include a feedback sensor 1225 and a second feedback sensor 1225 communicatively coupled to the NSS 905, the speaker 1205, microphone 1210, or active noise cancellation component 1215.

[0265] In operation, and in some embodiments, the audio player 1220 can play a musical track. The audio player 1220 can provide the audio signal corresponding to the musical track via a wired or wireless connection to the first and second speakers 1205. In some embodiments, the NSS 905 can intercept the audio signal from the audio player. For example, the NSS 905 can receive the digital or analog audio signal from the audio player 1220. The NSS 905 can be intermediary to the audio player 1220 and a speaker 1205. The NSS 905 can analyze the audio signal corresponding to the music in order to embed an auditory brainwave stimulation signal. For example, the NSS 905 can adjust the volume of the auditory signal from the audio player 1220 to generate acoustic pulses having a pulse rate interval as depicted in FIG. 11C. In some embodiments, the NSS 905 can use a binaural beats technique to provide different auditory signals to the first and second speakers that, when perceived by the brain, is combined to have the desired stimulation frequency.

[0266] In some embodiments, the NSS 905 can adjust for any latency between first and second speakers 1205 such that the brain perceives the audio signals at the same or substantially same time (e.g., within 1 milliseconds, 2 milliseconds, 5 milliseconds, or 10 milliseconds). The NSS 905 can buffer the audio signals to account for latency such that audio signals are transmitted from the speakers at the same time.

[0267] In some embodiments, the NSS 905 may not be intermediary to the audio player 1220 and the speaker. For example, the NSS 905 can receive the musical track from a digital music repository. The NSS 905 can manipulate or modify the musical track to embed acoustic pulses in accordance with the desired PRI. The NSS 905 can then provide the modified musical track to the audio player 1220 to provide the modified audio signal to the speaker 1205.

[0268] In some embodiments, an active noise cancellation component 1215 can receive ambient noise information from the microphone 1210, identify unwanted frequencies or noise, and generate an inverted phase waveform to cancel out or attenuate the unwanted waveforms. In some embodiments, the system 1200 can include an additional speaker that generates the noise canceling waveform provided by the noise cancellation component 1215. The noise cancellation component 1215 can include the additional speaker.

[0269] The feedback sensor 1225 of the system 1200 can detect feedback information, such as environmental parameters or physiological conditions. The feedback sensor 1225 can provide the feedback information to NSS 905. The NSS 905 can adjust or change the audio signal based on the feedback information. For example, the NSS 905 can determine that a pulse rate of the subject exceeds a predetermined threshold, and then lower the volume of the audio signal. The NSS 905 can detect that the volume of the auditory signal exceeds a threshold, and decrease the amplitude. The NSS 905 can determine that the pulse rate interval is below a threshold, which can indicate that a subject is losing focus or not paying a satisfactory level of 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 vary the tone or the music track based on WO 2025 / 147596                                   PCT / US2025 / 010218 a time interval. Varying the tone or the music track can cause the subject to pay a greater level of attention to the auditory stimulation, which can facilitate brainwave entrainment.

[0270] In some embodiments, the NSS 905 can receive neural oscillation information from EEG probes 1225, and adjust the auditory stimulation based on the EEG information. For example, the NSS 905 can determine, from the probe information, that neurons are oscillating at an undesired frequency. The NSS 905 can then identify the corresponding undesired frequency in ambient noise using the microphone 1210. The NSS 905 can then instruct the active noise cancellation component 1215 to cancel out the waveforms corresponding to the ambient noise having the undesired frequency.

[0271] In some embodiments, the NSS 905 can enable a passive noise filter. A pass noise filter can include a circuit having one or more or a resistor, capacitor or an inductor that filters out undesired frequencies of noise. In some cases, a passive filter can include a sound insulating material, sound proofing material, or sound absorbing material.

[0272] FIG. 4C illustrates a system configuration for auditory brain entrainment in accordance with an embodiment. The system 401 can provide auditory brainwave stimulation using ambient noise source 1230. For example, system 401 can include the microphone 1210 that detects the ambient noise 1230. The microphone 1210 can provide the detected ambient noise to NSS 905. The NSS 905 can modify the ambient noise 1230 before providing it to the first speaker 1205 or the second speaker 1205. In some embodiments, the system 401 can be integrated or interface with a hearing aid device. A hearing aid can be a device designed to improve hearing.

[0273] The NSS 905 can increase or decrease the amplitude of the ambient noise 1230 to generate acoustic bursts having the desired pulse rate interval. The NSS 905 can provide the modified audio signals to the first and second speakers 1205 to facilitate auditory brainwave entrainment.

[0274] In some embodiments, the NSS 905 can overlay a click train, tones, or other acoustic pulses over the ambient noise 1230. For example, the NSS 905 can receive the ambient noise information from the microphone 1210, apply an auditory stimulation signal to the ambient noise information, and then present the combined ambient noise information and auditory stimulation signal to the first and second speakers 1205. In some cases, the NSS 905 can filter out unwanted frequencies in the ambient noise 1230 prior to providing the auditory stimulation signal to the speakers 1205.

[0275] Thus, using the ambient noise 1230 as part of the auditory stimulation, a subject can observe the surroundings or carry on with their daily activities while receiving auditory stimulation to facilitate brainwave entrainment.

[0276] FIG. 13 illustrates a system configuration for auditory brain entrainment in accordance with an embodiment. The system 1300 can provide auditory stimulation forbrainwave entrainment using a room environment. The system 1300 can include one or more speakers. The system 1300 can include a surround sound system. For example, the system 1300 includes a left speaker 1310, right speaker 1315, center speaker 1305, right surround speaker 1325, and left surround speaker 1330. System 1300 an include a sub-woofer 1320. The system 1300 can include the microphone 1210. The system 1300 can include or refer to a 5.1 surround system. In some embodiments, the system 1300 can have 1, 2, 3, 4, 5, 6, 7 or more speakers.

[0277] When providing auditory stimulation using a surround system, the NSS 905 can provide the same or different audio signals to each of the speakers in the system 1300. The NSS 905 can modify or adjust audio signals provided to one or more of the speakers in system 1300 in order to facilitate brainwave entrainment. For example, the NSS 905 can receive feedback from microphone 1210 and modify, manipulate or otherwise adjust the audio signal to optimize the auditory stimulation provided to a subject located at a position in the room that corresponds to the location of the microphone 1210. The NSS 905 can optimize or improve the auditory stimulation perceived at the location corresponding to microphone 1210 by analyzing the acoustic beams or waves generated by the speakers that propagate towards the microphone 1210.

[0278] The NSS 905 can be configured with information about the design and construction of each speaker. For example, speaker 1305 can generate sound in a direction that has an angle of 1335; speaker 1310 can generate sound that travels in a direction having an angle of 1340; speaker 1315 can generate sound that travels in a direction having an angle of 1345; speaker 1325 can generate sound that travels in a direction having an angle of 1355; and speaker 1330 can generate sound that travels in a direction having an angle of 1350. These angles can be the optimal or predetermined angles for each of the speakers. These angles can refer to the optimal angle of each speaker such that a person positioned at location corresponding to microphone 1210 can receive the optimum auditory stimulation. Thus, the speakers in system 1300 can be oriented to transmit auditory stimulation towards the subject.

[0279] In some embodiments, the NSS 905 can enable or disable one or more speakers. In some embodiments, the NSS 905 can increase or decrease the volume of the speakers to facilitate brainwave entrainment. The NSS 905 can intercept musical tracks, television audio, movie audio, internet audio, audio output from a set top box, or other audio source. The NSS 905 can adjust or manipulate the received audio, and transmit the adjusted audio signals to the speakers in system 1300 to induce brainwave entrainment. WO 2025 / 147596                                   PCT / US2025 / 010218

[0280] FIG. 14 illustrates feedback sensors 1405 placed or positioned at, on, or near a person’s head. Feedback sensors 1405 can include, for example, EEG probes that detect brain wave activity.

[0281] The feedback monitor 935 can detect, receive, obtain, or otherwise identify feedback information from the one or more feedback sensors 1405. The feedback monitor 935 can provide the feedback information to one or more component of the NS S 905 for further processing or storage. For example, the profile manager 925 can update profile data structure 945 stored in data repository 940 with the feedback information. Profile manager 925 can associate the feedback information with an identifier of the patient or person undergoing the auditory brain stimulation, as well as a time stamp and date stamp corresponding to receipt or detection of the feedback information.

[0282] The feedback monitor 935 can determine a level of attention. The level of attention can refer to the focus provided to the acoustic pulses used for brain stimulation. The feedback monitor 935 can determine the level of attention using various hardware and software techniques. The feedback monitor 935 can assign a score to the level of attention (e.g., 1 to 10 with 1 being low attention and 10 being high attention, or vice versa, 1 to 100 with 1 being low attention and 100 being high attention, or vice versa, 0 to 1 with 0 being low attention and 1 being high attention, or vice versa), categorize the level of attention (e.g., low, medium, high), grade the attention (e.g., A, B, C, D, or F), or otherwise provide an indication of a level of attention.

[0283] In some cases, the feedback monitor 935 can track a person’s eye movement to identify a level of attention. The feedback monitor 935 can interface with a feedback component 960 that includes an eye-tracker. The feedback monitor 935 (e.g., via feedback component 960) can detect and record eye movement of the person and analyze the recorded eye movement to determine an attention span or level of attention. The feedback monitor 935 can measure eye gaze which can indicate or provide information related to covert attention. For example, the feedback monitor 935 (e.g., via feedback component 960) can be configured with electro-oculography (“EOG”) to measure the skin electric potential around the eye, which can indicate a direction the eye faces relative to the head. In some embodiments, the EOG can include a system or device to stabilize the head so it cannot move in order to determine the direction of the eye relative to the head. In some embodiments, the EOG can include or interface with a head tracker system to determine the position of the heads, and then determine the direction of the eye relative to the head.

[0284] In some embodiments, the feedback monitor 935 and feedback component 960 can determine a level of attention the subject is paying to the auditory stimulation based on eye movement. For example, increased eye movement can indicate that the subject is focusing on visual stimuli, as opposed to the auditory stimulation. To determine the level of attention the subject is paying to visual stimuli as opposed to the auditory stimulation, the feedback monitor 935 and feedback component 960 can determine or track the direction of the eye or eye movement using video detection of the pupil or corneal reflection. For example, the feedback component 960 can include one or more camera or video camera. The feedback component 960 can include an infra-red source that sends light pulses towards the eyes. The light can be reflected by the eye. The feedback component 960 can detect the position of the reflection. The feedback component 960 can capture or record the position of the reflection. The feedback component 960 can perform image processing on the reflection to determine or compute the direction of the eye or gaze direction of the eye.

[0285] The feedback monitor 935 can compare the eye direction or movement to historical eye direction or movement of the same person, nominal eye movement, or other historical eye movement information to determine a level of attention. For example, the feedback monitor 935 can determine a historical amount of eye movement during historical auditory stimulation sessions. The feedback monitor 935 can compare the current eye movement with the historical eye movement to identify a deviation. The NSS 905 can determine, based on the comparison, an increase in eye movement and further determine that the subject is paying less attention to the current auditory stimulation based on the increase in eye movement. In response to detecting the decrease in attention, the feedback monitor 935 can instruct the audio adjustment module 915 to change a parameter of the audio signal to capture the subject’s attention. The audio adjustment module 915 can change the volume, tone, pitch, or music track to capture the subject’s attention or increase the level of attention the subject is paying to the auditory stimulation. Upon changing the audio signal, the NSS 905 can continue to monitor the level of attention. For example, upon changing the audio signal, the NSS 905 can detect a decrease in eye movement which can indicate an increase in a level of attention provided to the audio signal.

[0286] The feedback sensor 1405 can interact with or communicate with NSS 905. For example, the feedback sensor 1405 can provide detected feedback information or data to the NSS 905 (e.g., feedback monitor 935). The feedback sensor 1405 can provide data to the NSS 905 in real-time, for example as the feedback sensor 1405 detects or senses or information. The feedback sensor 1405 can provide the feedback information to the NSS 905 based on a time interval, such as 1 minute, 2 minutes, 5 minutes, 10 minutes, hourly, 2 hours, 4 hours, 12 hours, or 24 hours. The feedback sensor 1405 can provide the feedback information to the NSS 905 responsive to a condition or event, such as a feedback measurement exceeding a threshold or falling below a threshold. The feedback sensor 1405 can provide feedback information responsive to a change in a feedback parameter. In some embodiments, the NSS 905 can ping, query, or send a request to WO 2025 / 147596                                   PCT / US2025 / 010218 the feedback sensor 1405 for information, and the feedback sensor 1405 can provide the feedback information in response to the ping, request, or query. 3. Computing Environment

[0287] In some embodiments, a portable system or single headset device as disclosed herein can comprise a computing system and / or a computing device. In some embodiments, a portable system as disclosed herein can comprise an NSS as disclosed herein, wherein the NSS comprises a computing system.

[0288] FIGs. 7A and 7B depict block diagrams of a computing device 700. As shown in FIGs. 7A and 7B, each computing device 700 includes a central processing unit 721, and a main memory unit 722. As shown in FIG. 7A, a computing device 700 can 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, e.g., a mouse. The storage device 728 can include, without limitation, an operating system, software, and software of a neural stimulation system (“NSS”) 701. The NSS 701 can include or refer to one or more of NSS 105, NSS 905, or NSOS 1605. As shown in FIG. 7B, each computing device 700 can also include additional optional elements, e.g., a memory port 703, a bridge 770, one or more input / output devices 730a-73On (generally referred to using reference numeral 730), and a cache memory 740 in communication with the central processing unit 721.

[0289] The central processing unit 721 is any logic circuitry 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, e.g.: those manufactured by Intel Corporation of Mountain View, California; those manufactured by Motorola Corporation of Schaumburg, Illinois; the ARM processor (from, e.g., ARM Holdings and manufactured by ST, TI, ATMEL, etc.) and TEGRA system on a chip (SoC) manufactured by Nvidia of Santa Clara, California; the POWER7 processor, those manufactured by International Business Machines of White Plains, New York; or those manufactured by Advanced Micro Devices of Sunnyvale, California; or field programmable gate arrays (“FPGAs”) from Altera in San Jose, CA, Intel Corporation, Xlinix in San Jose, CA, or MicroSemi in Aliso Viejo, CA, etc. The computing device 700 can 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, different levels of cache, and multi-core processors. A multi-core processor can include 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.

[0290] Main memory unit 722 can include one or more memory chips capable of storing data and allowing any storage location to be directly accessed by the microprocessor 721. Main memory unit 722 can be volatile and faster than storage 728 memory. Main memory units 722 can be Dynamic random access memory (DRAM) or any variants, including static random access memory (SRAM), Burst SRAM or SynchBurst SRAM (BSRAM), Fast Page Mode DRAM (FPM DRAM), Enhanced 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 Rambus DRAM (DRDRAM), or Extreme Data Rate DRAM (XDR DRAM). In some embodiments, the main memory 722 or the storage 728 can be non-volatile, e.g., non-volatile read access memory (NVRAM), flash memory non-volatile static RAM (nvSRAM), Ferroelectric RAM (FeRAM), Magnetoresistive RAM (MRAM), Phase-change memory (PRAM), conductive-bridging RAM (CBRAM), Silicon-Oxide-Nitride-Oxide-Silicon (SONOS), Resistive RAM (RRAM), Racetrack, Nano-RAM (NRAM), or Millipede memory. The main memory 722 can be based on any of the above described memory chips, or any other available memory chips capable of operating as described herein. In the embodiment shown in FIG. 7A, the processor 721 communicates with main memory 722 via a system bus 750 (described in more detail below). FIG. 7B depicts an embodiment of a computing device 700 in which the processor communicates directly with main memory 722 via a memory port 703. For example, in FIG. 7B the main memory 722 can be DRDRAM.

[0291] FIG. 7B depicts an embodiment in which the main processor 721 communicates directly with cache memory 740 via a secondary bus, sometimes referred to as a backside bus. In other embodiments, the main processor 721 communicates with cache memory 740 using the system bus 750. Cache memory 740 typically has a faster response time than main memory 722 and is typically provided by SRAM, BSRAM, or EDRAM. In the embodiment shown in FIG. 7B, the processor 721 communicates with various VO devices 730 via a local system bus 750. Various buses can be used to connect the central processing unit 721 to any of the VO devices 730, including a PCI bus, a PCI-X bus, or a PCI-Express bus, or a NuBus. For embodiments in which the I / O device is a video display 724, the processor 721 can use an Advanced Graphics Port (AGP) to communicate with the display 724 or the VO controller 723 for the display 724. FIG. 7B depicts an embodiment of a computer 700 in which the main processor 721 communicates directly with VO device 730b or other processors 721’ via HYPERTRANSPORT, RAPIDIO, or INFINIBAND communications technology. FIG. 7B also depicts an embodiment in which local busses and direct communication are mixed: the processor 721 communicates with VO device 730a using a local interconnect bus while communicating with VO device 730b directly.

[0292] A wide variety of I / O devices 730a-730n can be present in the computing device 700. Input devices can include keyboards, mice, trackpads, trackballs, touchpads, touch mice, multitouch touchpads and touch mice, microphones (analog or MEMS), multi-array microphones, drawing tablets, cameras, single-lens reflex camera (SLR), digital SLR (DSLR), CMOS sensors, CCDs, accelerometers, inertial measurement units, infrared optical sensors, pressure sensors, magnetometer sensors, angular rate sensors, depth sensors, proximity sensors, ambient light sensors, gyroscopic sensors, or other sensors. Output devices can include video displays, graphical displays, speakers, headphones, inkjet printers, laser printers, and 3D printers.

[0293] Devices 730a-730n can include a combination of multiple input or output devices, including, e.g., Microsoft KINECT, Nintendo Wiimote for the WII, Nintendo WIIU GAMEPAD, or Apple IPHONE. Some devices 730a-730n allow gesture recognition inputs through combining some of the inputs and outputs. Some devices 730a-730n provides for facial recognition which can be utilized as an input for different purposes including authentication and other commands. Some devices 730a-730n provides for voice recognition and inputs, including, e.g., Microsoft KINECT, SIRI for IPHONE by Apple, Google Now or Google Voice Search.

[0294] Additional devices 730a-730n have both input and output capabilities, including, e.g., haptic feedback devices, touchscreen displays, or multi-touch displays. Touchscreen, multi-touch displays, touchpads, touch mice, or other touch sensing devices can use different technologies to sense touch, including, e.g., capacitive, surface capacitive, projected capacitive touch (PCT), incell capacitive, resistive, infrared, waveguide, dispersive signal touch (DST), in-cell optical, surface acoustic wave (SAW), bending wave touch (BWT), or force-based sensing technologies. Some multi-touch devices can allow two or more contact points with the surface, allowing advanced functionality including, e.g., pinch, spread, rotate, scroll, or other gestures. Some touchscreen devices, including, e.g., Microsoft PIXELSENSE or Multi-Touch Collaboration Wall, can have larger surfaces, such as on a table-top or on a wall, and can also interact with other electronic devices. Some EO devices 730a-730n, display devices 724a-724n or group of devices can be augmented reality devices. The EO devices can be controlled by an EO controller 721 as shown in FIG. 7A. The EO controller 721 can control one or more EO devices, such as, e.g., a keyboard 126 and a pointing device 727, e.g., a mouse or optical pen. Furthermore, an EO device can also provide storage and / or an installation medium 116 for the computing device 700. In still other embodiments, the computing device 700 can provide USB connections (not shown) to receive handheld USB storage devices. In further embodiments, an EO device 730 can be a bridge between the system bus 750 and an external communication bus, e.g., a USB bus, a SCSI bus, a FireWire bus, an Ethernet bus, a Gigabit Ethernet bus, a Fibre Channel bus, or a Thunderbolt bus.

[0295] In some embodiments, display devices 724a-724n can be connected to I / O controller 721. Display devices can include, e.g., liquid crystal displays (LCD), thin film transistor LCD (TFT-LCD), blue phase LCD, electronic papers (e-ink) displays, flexile displays, light emitting diode displays (LED), 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 can use, e.g., stereoscopy, polarization filters, active shutters, or autostereoscopy. Display devices 724a-724n can also be a head-mounted display (HMD). In some embodiments, display devices 724a-724n or the corresponding EO controllers 723 can be controlled through or have hardware support for OPENGL or DIRECTX API or other graphics libraries.

[0296] In some embodiments, the computing device 700 can include or connect to multiple display devices 724a-724n, which each can be of the same or different type and / or form. As such, any of the EO devices 730a-730n and / or the EO controller 723 can include any type and / or form of suitable hardware, software, or combination of hardware and software to support, enable or provide for the connection and use of multiple display devices 724a-724n by the computing device 700. For example, the computing device 700 can include any type and / or form of video adapter, video card, driver, and / or library to interface, communicate, connect or otherwise use the display devices 724a-724n. In one embodiment, a video adapter can include multiple connectors to interface to multiple display devices 724a-724n. In other embodiments, the computing device 700 can include multiple video adapters, with each video adapter connected to one or more of the display devices 724a-724n. In some embodiments, any portion of the operating system of the computing device 700 can be configured for using multiple displays 724a-724n. In other embodiments, one or more of the display devices 724a-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, software can be designed and constructed to use another computer’s display device as a second display device 724a for the computing device 700. For example, in one embodiment, an Apple iPad can connect to a computing device 700 and use the display of the device 700 as an additional display screen that can be used as an extended desktop.

[0297] Referring again to FIG. 7A, the computing device 700 can comprise a storage device 728 (e.g., one or more hard disk drives or redundant arrays of independent disks) for storing an operating system or other related software, and for storing application software programs such as any program related to the software for the NSS. Examples of storage device 728 include, e.g., hard disk drive (HDD); optical drive including CD drive, DVD drive, or BLU-RAY drive; solidstate drive (SSD); USB flash drive; or any other device suitable for storing data. Some storage devices can include multiple volatile and non-volatile memories, including, e.g., solid state hybrid drives that combine hard disks with solid state cache. Some storage devices 728 can be non-volatile, mutable, or read-only. Some storage devices 728 can be internal and connect to the computing device 700 via a bus 750. Some storage devices 728 can be external and connect to the computing device 700 via a I / O device 730 that provides an external bus. Some storage devices 728 can connect to the computing device 700 via the network interface 718 over a network, including, e.g., the Remote Disk for MACBOOK AIR by Apple. Some client devices 700 may not require a non-volatile storage device 728 and can be thin clients or zero clients 202. Some storage devices 728 can also be used as an installation device 716, and can be suitable for installing software and programs. Additionally, the operating system and the software can be run from a bootable medium, for example, a bootable CD, e.g., KNOPPIX, a bootable CD for GNU / Linux that is available as a GNU / Linux distribution from knoppix.net.

[0298] Computing device 700 can also install software or application from an application distribution platform. Examples of application distribution platforms include the App Store for iOS provided by Apple, Inc., the Mac App Store provided by Apple, Inc., GOOGLE PLAY for Android OS provided by Google Inc., Chrome Webstore for CHROME OS provided by Google Inc., and Amazon Appstore for Android OS and KINDLE FIRE provided by Amazon.com, Inc.

[0299] Furthermore, the computing device 700 can include a network interface 718 to interface to the network 140 through a variety of connections including, but not limited to, standard telephone lines LAN or WAN links (e.g., 802.11, Tl, T3, Gigabit Ethernet, Infiniband), broadband connections (e.g., ISDN, Frame Relay, ATM, Gigabit Ethernet, Ethernet-over-SONET, ADSL, VDSL, BPON, GPON, fiber optical including FiOS), wireless connections, or some combination of any or all of the above. Connections can be established using a variety of 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, the computing device 700 communicates with other computing devices 700’ via any type and / or form of gateway or tunneling protocol e.g., Secure Socket Layer (SSL) or Transport Layer Security (TLS), or the Citrix Gateway Protocol manufactured by Citrix Systems, Inc. of Ft. Lauderdale, Florida. The network interface 118 can comprise a built-in network adapter, network interface card, PCMCIA network card, EXPRESSCARD network card, card bus network adapter, wireless network adapter, USB network adapter, modem or any other device suitable for interfacing the computing device 700 to any type of network capable of communication and performing the operations described herein.

[0300] A computing device 700 of the sort depicted in FIG. 7A can operate under the control of an operating system, which controls scheduling of tasks and access to system resources. The computing device 700 can be running any operating system such as any of the versions of the MICROSOFT WINDOWS operating systems, the different releases of the Unix and Linux operating systems, any version of the 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 systems 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 of which are manufactured by Microsoft Corporation of Redmond, Washington; MAC OS and iOS, manufactured by Apple, Inc. of Cupertino, California; and Linux, a freely-available operating system, e.g.,Linux Mint distribution (“distro”) or Ubuntu, distributed by Canonical Ltd. of London, United Kingdom; or Unix or other Unix-like derivative operating systems; and Android, designed by Google, of Mountain View, California, among others. Some operating systems, including, e.g., the CHROME OS by Google, can be used on zero clients or thin clients, including, e.g., CHROMEBOOKS.

[0301] The computer system 700 can be any workstation, telephone, desktop computer, laptop or notebook computer, netbook, ULTRABOOK, tablet, server, handheld computer, mobile telephone, smartphone or other portable telecommunications device, media playing device, a gaming system, mobile computing device, or any other type and / or form of computing, telecommunications or media device that is 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 can have different processors, operating systems, and input devices consistent with the device. The Samsung GALAXY smartphones, e.g., operate under the control of Android operating system developed by Google, Inc. GALAXY smartphones receive input via a touch interface.

[0302] In some embodiments, the computing device 700 is a gaming system. For example, the computer system 700 can comprise a PLAYSTATION 3, or PERSONAL PLAYSTATION PORTABLE (PSP), or a PLAYSTATION VITA device manufactured by the Sony Corporation of Tokyo, Japan, a NINTENDO DS, NINTENDO 3DS, NINTENDO WII, or a NINTENDO WII U device manufactured by Nintendo Co., Ltd., of Kyoto, Japan, or an XBOX 360 device manufactured by the Microsoft Corporation of Redmond, Washington, or an OCULUS RIFT or OCULUS VR device manufactured BY OCULUS VR, LLC of Menlo Park, California.

[0303] In some embodiments, the computing device 700 is a digital audio player such as the Apple IPOD, IPOD Touch, and IPOD NANO lines of devices, manufactured by Apple Computer of Cupertino, California. Some digital audio players can have other functionality, including, e.g., a gaming system or any functionality made available by an application from a digital application distribution platform. For example, the IPOD Touch can access the Apple App Store. In some embodiments, the computing device 700 is a portable media player or digital audio player supporting file formats including, but not limited to, MP3, WAV, M4A / AAC, WMA Protected AAC, AIFF, Audible audiobook, Apple Lossless audio file formats and .mov, ,m4v, and .mp4 MPEG-4 (H.264 / MPEG-4 AVC) video file formats.

[0304] In some embodiments, the computing device 700 is a tablet e.g.,the IPAD line of devices by Apple; GALAXY TAB family of devices by Samsung; or KINDLE FIRE, by Amazon.com, Inc. of Seattle, Washington. In other embodiments, the computing device 700 is an eBook reader, e.g.,the KINDLE family of devices by Amazon.com, or NOOK family of devices by Barnes & Noble, Inc. of New York City, New York.

[0305] In some embodiments, the communications device 700 includes a combination of devices, e.g.,a smartphone combined with a digital audio player or portable media player. For example, one of these embodiments is a smartphone, e.g.,the IPHONE family of smartphones manufactured by Apple, Inc.; a Samsung GALAXY family of smartphones manufactured by Samsung, Inc.; or a Motorola DROID family of smartphones. In yet another embodiment, the communications device 700 is a laptop or desktop computer equipped with a web browser and a microphone and speaker system, e.g.,a telephony headset. In these embodiments, the communications devices 700 are web-enabled and can receive and initiate phone calls. In some embodiments, a laptop or desktop computer is also equipped with a webcam or other video capture device that enables video chat and video call.

[0306] In some embodiments, the status of one or more machines 700 in the network are monitored, generally as part of network management. In one of these embodiments, the status of a machine can include an identification of load information (e.g., the number of processes on the machine, CPU and memory utilization), of port information (e.g., the number of available communication ports and the port addresses), or of session status (e.g., the duration and type of processes, and whether a process is active or idle). In another of these embodiments, this information can be identified by a plurality of metrics, and the plurality of metrics can be applied at least in part towards decisions in load distribution, network traffic management, and network failure recovery as well as any aspects of operations of the present solution described herein. Aspects of the operating environments and components described above will become apparent in the context of the systems and methods disclosed herein. v. Computing Devices and Systems for Portable Systems WO 2025 / 147596                                   PCT / US2025 / 010218

[0307] The present disclosure provides computer systems that are programmed to implement systems, devices and methods of the disclosure. The computer system can be an electronic device of a user or a computer system that is remotely located with respect to the electronic device. The electronic device can be a mobile electronic device.

[0308] The computer system includes a central processing unit (CPU, also “processor” and “computer processor” herein), which can be a single core or multi core processor, or a plurality of processors for parallel processing. The computer system also includes memory or memory location (e.g., random-access memory, read-only memory, flash memory), electronic storage unit (e.g., hard disk), communication interface (e.g., network adapter) for communicating with one or more other systems, and peripheral devices, such as cache, other memory, data storage or electronic display adapters. The memory, storage unit, interface, and peripheral devices are in communication with the CPU through a communication bus, such as a motherboard. The storage unit can be a data storage unit (or data repository) for storing data. The computer system can be operatively coupled to a computer network (“network”) with the aid of the communication interface. The network can be the Internet, an internet or extranet, or an intranet or extranet that is in communication with the Internet. In some embodiments, the network is a telecommunication or data network. The network can include one or more computer servers, which can enable distributed computing, such as cloud computing. In some embodiments, the network, with the aid of the computer system, can implement a peer-to-peer network, which may enable devices coupled to the computer system to behave as a client or a server.

[0309] The CPU can execute a sequence of machine-readable instructions, which can be embodied in a program or software. The instructions may be stored in a memory location, such as the memory. The instructions can be directed to the CPU, which can subsequently program or otherwise configure the CPU to implement methods of the present disclosure. Examples of operations performed by the CPU can include fetch, decode, execute, and writeback.

[0310] The CPU can be part of a circuit, such as an integrated circuit. One or more other components of the system can be included in the circuit. In some embodiments, the circuit is an application specific integrated circuit (ASIC).

[0311] The storage unit can store files, such as drivers, libraries, and saved programs. The storage unit can store user data, e.g., user preferences and user programs. The computer system In some embodiments can include one or more additional data storage units that are external to the computer system, such as located on a remote server that is in communication with the computer system through an intranet or the Internet.

[0312] The computer system can communicate with one or more remote computer systems through the network. For instance, the computer system can communicate with a remote WO 2025 / 147596                                   PCT / US2025 / 010218 computer system of a user. Examples of remote computer systems include personal computers (e.g., portable PC), slate or tablet PC’s (e.g., Apple® iPad, Samsung® Galaxy Tab), telephones, Smart phones (e.g., Apple® iPhone, Android-enabled device, Blackberry®), or personal digital assistants. The user can access the computer system via the network.

[0313] Methods as described herein can be implemented by way of machine (e.g., computer processor) executable code stored on an electronic storage location of the computer system, such as, for example, on the memory or electronic storage unit. The machine executable or machine-readable code can be provided in the form of software. During use, the code can be executed by the processor. In some embodiments, the code can be retrieved from the storage unit and stored on the memory for ready access by the processor. In some situations, the electronic storage unit can be precluded, and machine-executable instructions are stored on memory.

[0314] The code can be pre-compiled and configured for use with a machine having a processer adapted to execute the code, or can be compiled during runtime. The code can be supplied in a programming language that can be selected to enable the code to execute in a pre-compiled or as-compiled fashion.

[0315] Aspects of the systems and methods provided herein, such as the computer system, can be embodied in programming. Various aspects of the technology may be thought of as “products” or “articles of manufacture” typically in the form of machine (or processor) executable code or associated data that is carried on or embodied in a type of machine readable medium. Machineexecutable code can be stored on an electronic storage unit, such as memory (e.g., read-only memory, random-access memory, flash memory) or a hard disk. “Storage” type media can include any or all of the tangible memory of the computers, processors or the like, or associated modules thereof, such as various semiconductor memories, tape drives, disk drives and the like, which may provide non-transitory storage at any time for the software programming. All or portions of the software may at times be communicated through the Internet or various other telecommunication networks. Such communications, for example, may enable loading of the software from one computer or processor into another, for example, from a management server or host computer into the computer platform of an application server. Thus, another type of media that may bear the software elements includes optical, electrical, and electromagnetic waves, such as used across physical interfaces between local devices, through wired and optical landline networks and over various air-links. The physical elements that carry such waves, such as wired or wireless links, optical links or the like, also may be considered as media bearing the software. As used herein, unless restricted to non-transitory, tangible “storage” media, terms such as computer or machine “readable medium” refer to any medium that participates in providing instructions to a processor for execution.

[0316] Hence, a machine readable medium, such as computer-executable code, may take many forms, including but not limited to, a tangible storage medium, a carrier wave medium or physical transmission medium. Non-volatile storage media include, for example, optical or magnetic disks, such as any of the storage devices in any computer(s) or the like, such as may be used to implement the databases, etc., as shown in the drawings. Volatile storage media include dynamic memory, such as main memory of such a computer platform. Tangible transmission media include coaxial cables; copper wire and fiber optics, including the wires that comprise a bus within a computer system. Carrier-wave transmission media may take the form of electric or electromagnetic signals, or acoustic or light waves such as those generated during radio frequency (RF) and infrared (IR) data communications. Common forms of computer-readable media therefore include for example: a floppy disk, a flexible disk, hard disk, magnetic tape, any other magnetic medium, a CD-ROM, DVD or DVD-ROM, any other optical medium, punch cards paper tape, any other physical storage medium with patterns of holes, a RAM, a ROM, a PROM and EPROM, a FLASH-EPROM, any other memory chip or cartridge, a carrier wave transporting data or instructions, cables or links transporting such a carrier wave, or any other medium from which a computer may read programming code or data. Many of these forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to a processor for execution.

[0317] The computer system can include or be in communication with an electronic display that comprises a user interface (UI). Examples of Ui’s include, without limitation, a graphical user interface (GUI) and web-based user interface.

[0318] Methods and systems of the present disclosure can be implemented by way of one or more algorithms. An algorithm can be implemented by way of software upon execution by the central processing unit. II. Methods of Using Portable System or Devices as disclosed herein A. Methods of Using Portable Systems or Devices as Disclosed Herein

[0319] In some embodiments, methods of using a device, e.g., a single headset device, or portable system as disclosed herein are provided below.

[0320] In some embodiments, the method comprises administering to a subject a visual, auditory, or haptic stimulus, or a combination thereof generated by a device or portable system as disclosed herein. In some embodiments, the stimulation induces neural, visual, oscillations in a brain region of the subject, wherein the frequency of the induced neural, visual, oscillations corresponds to the frequency of the haptic stimulus that is administered to the subject.

[0321] In some embodiments, the stimulus is administered at a frequency of 1 Hertz (Hz), 2 Hz, 5 Hz, 10 Hz, 20 Hz, 25 Hz, 30 Hz, 31 Hz, 32 Hz, 33 Hz, 34 Hz, 35 Hz, 36 Hz, 37 Hz, 38 Hz, 39 Hz, 40 Hz, 41 Hz, 42 Hz, 43 Hz, 44 Hz, 45 Hz, 46 Hz, 47 Hz, 48 Hz, 49 Hz, 50 Hz, 60 Hz, 70 Hz, 80 Hz, 90 Hz, 100 Hz, 150 Hz, 200 Hz, 250 Hz, 300 Hz, 400 Hz, 500 Hz, 1000 Hz, 2000 Hz, 3000 Hz, 4,000 Hz, 5000 Hz, 6,000 Hz, 7,000 Hz, 8,000 Hz, 9,000 Hz, or 10,000 Hz.

[0322] In some embodiments, the stimulus is administered at a frequency of about 20 Hertz (Hz) to about 140 Hz, about 30 Hz to about 60 Hz, about 40 Hz to about 60 Hz, about 35 Hz to about 45 Hz, or about 40 Hz. In some embodiments, the stimulus is administered at a gamma frequency. In some embodiments, administration of the gamma frequency results in the induction of synchronized gamma oscillations within a brain region of the subject. i. Stimulus Exposure, Session duration, Session frequency, and Regimen Duration

[0323] In some embodiments, administering the stimulus comprises a stimulus exposure. In some embodiments, the stimulus exposure comprises a session duration, a session frequency, a regimen duration, or a combination thereof. In some embodiments, the stimulus exposure may comprise more than one regimen duration. In some embodiments, administering may be performed continuously for a session duration. In some embodiments, the session duration may be between 10 minutes and 2 hours. In some embodiments, the session duration may be at least 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, or 60 minutes. In some embodiments, the session duration 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 embodiments, the session duration may be at least 1, 2, 3, 4, 5, 6, or 7 days. In some embodiments, the session duration may be at most 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, or 60 minutes. In some embodiments, the session duration 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. In some embodiments, the session duration may be at most 1, 2, 3, 4, 5, 6, or 7 days.

[0324] In some embodiments, the session frequency may occur at least once, at least twice, at least 3 times, at least 4 times, or at least 5 times per day. In some embodiments, the session frequency may occur at least once, at least twice, at least 3 times, at least 4 times, at least 5 times, at least 6 times, or at least 7 times per week. In some embodiments, the session frequency may occur at least once, at least twice, at least 3 times, at least 4 times, or at least 5 times, at least 8 times, at least 10 times, at least 20 times, at least 28 times, at least 30 times, or at least 31 times per month. In some embodiments, the session frequency may occur at least once, at least twice, at least 3 times, at least 4 times, or at least 5 times, at least 10 times, at least 20 times, at least 30 times, at least 50 times, at least 100 times, at least 150 times, at least 200 times, at least 300 WO 2025 / 147596                                   PCT / US2025 / 010218 times, at least 365 times, at least 400 times, at least 500 times, at least 600 times, at least 700 times, at least 800 times, at least 900 times, or at least one thousand times per year.

[0325] The regimen duration refers to the length of time over which all session durations and session frequencies for the administering of the non-invasive stimulus occur. For example, a regimen duration can refer to a total length of an experimental study period, a total length of a therapeutic treatment, or a total length of a diagnostic period. In some embodiments, the regimen duration comprises at least one day, at least one week, at least one month, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least one year, at least 2 years, at least 3 years, at least 4 years, at least 5 years, at least 10 years, at least 15 years, or at least 20 years. In some embodiments, the regimen duration comprises the reminder of the life expectancy of the subject. In some embodiments, the regimen duration comprises the remainder of the subject’s life.

[0326] In some embodiments, the regimen duration and session frequency comprises about once a day for 6 months. In some embodiments, the regimen duration and session frequency comprises at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times a day. In some embodiments, the regimen duration and session frequency comprises at most about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times a day. ii. Methods of Verifying Administration of a Stimulus

[0327] In some embodiments, the administration of a stimulus to a subject is confirmed or verified within the subject by evaluating and measuring the stimulus. In some embodiments, the stimulus is measured in the brain of the subject. In some embodiments, a stimulus is measured in at least one, at least two, at least three, at least 4, at least 5, at least 8, at least 10, at least 15, at least 20 specific brain regions of the subject. In some embodiments, a stimulus is measured simultaneously in at least one, at least two, at least three, at least 4, at least 5, at least 8, at least 10, at least 15, at least 20 specific brain regions of the subject.

[0328] In some embodiments, the measuring comprises analyzing the brain or a specific brain region of the subject. In some embodiments, the measuring comprises analyzing the stimulus in the brain or a specific brain region of the subject.

[0329] In some embodiments, the specific brain region comprises an entorhinal cortex, a hippocampus, a cerebral cortex, a visual association cortex, an auditory association cortex, a cingulate lobe, an amygdala, a thalamic nucleus, a cingulate lobe, a pons, a brainstem, a cerebellum, a lateral ventricle, an occipital lobe, a parietal lobe, a temporal lobe, a midbrain, a striatum, a basal ganglia, a globus pallidus, a substantia nigra, or any combination thereof.

[0330] In some embodiments, the measuring comprises neuroimaging. In some embodiments, the measuring comprises neuroimaging of the brain of the subject. In some embodiments, the measuring comprises neuroimaging of the whole brain of the subject. In some embodiments, the measuring comprises neuroimaging of the specific brain regions of the subject. In some embodiments, the measuring comprises neuroimaging of an entorhinal cortex, a hippocampus, a cerebral cortex, a visual association cortex, an auditory association cortex, a cingulate lobe, an amygdala, a thalamic nucleus, a cingulate lobe, a pons, a brainstem, a cerebellum, a lateral ventricle, an occipital lobe, a parietal lobe, a temporal lobe, a midbrain, a striatum, a basal ganglia, a globus pallidus, a substantia nigra, or any combination thereof.

[0331] In some embodiments, the measuring comprises neuroimaging techniques. In some embodiments, the neuroimaging comprises magnetic resonance imaging (MRI), computer tomography, positron emission tomography (PET) imaging, diffusion-weighted MRI imaging, or any combination thereof in a brain region of a subject, wherein a brain region an entorhinal cortex, a hippocampus, a cerebral cortex, a visual association cortex, an auditory association cortex, a cingulate lobe, an amygdala, a thalamic nucleus, a cingulate lobe, a pons, a brainstem, a cerebellum, a lateral ventricle, an occipital lobe, a parietal lobe, a temporal lobe, a midbrain, a striatum, a basal ganglia, a globus pallidus, a substantia nigra, or any combination thereof. iii. Closed Loop Therapy

[0332] In some embodiments, the present disclosure provides methods of administering a closed-loop therapy to a subject with a system or device as disclosed herein. For example, in some embodiments, a subject may be monitored during a therapy session using a variety of sensors, such as ECG sensors, heart rate sensors, or galvanic skin response sensors, or a combination thereof, and the dosing parameters for the session may be updated in real time based on the outputs of the sensors. Such a therapy session can be referred to as a closed loop therapy session. FIG. 50 is a graphical representation of adjusting a therapy session based on feedback collected during the therapy session, i.e., a closed loop therapy session. A graph 2805 shows a series of scheduled stimulation pulses included in a single therapy session along a time axis. As shown, the pulses occur during intervals labeled as Tl, T2, T3, T4, T5, and T6. In this example, the intervals T5 and T6 do not include any scheduled stimulation pulses. It should be understood that the graph 2805 may represent pulses of any modality (e.g., visual stimulation pulses or auditory stimulation pulses). It should also be understood that the amplitude of the pulses, the duration of the pulse intervals, and the frequency of the pulses is illustrative only, and that in some implementations, these factors may be varied without departing from the scope of this disclosure.

[0333] A graph 2810 shows the attention level of the subject over time. Higher values indicate that the subject is more attentive, and lower values indicate that the subject is less attentive. In some implementations, subject attention level may be correlated with quality of a therapy session, such as when the subject's attention is required for the stimulation pulses to be delivered effectively. For example, if the stimulation pulses are delivered via a video display screen, it may be necessary for the subject to focus his or her attention on the video display screen in order to receive the benefit of the stimulation pulses. Thus, the graph 2810 includes a threshold L for user attention level. In this example, it can be assumed that the user's attention level must be greater than or equal to the threshold L in order for the therapy to be effectively delivered. As shown in the graph 2810, the subject's attention level varies over time, and is sometimes below the threshold L. If the subject's attention level is below the threshold L during any of the pulse intervals, the subject may not receive the benefit of the pulses delivered during those intervals.

[0334] In some implementations, the subject's attention level can be monitored by a sensor. For example, one or more camera sensors can be configured to track the subject's eyes to determine whether they are aligned in a particular orientation that allows the subject to perceive the stimulation pulses (e.g., whether the subject's eyes are focused on a video screen that delivers the stimulation pulses). During time periods in which the subject's eyes are appropriately focused, the subject's attention level may be recorded as relatively high (e.g., above the threshold L). During time periods in which the subject's eyes are not appropriately focused, the subject's attention level may be recorded as relatively low (e.g., below the threshold L).

[0335] The graphs 2815, 2820, and 2825 show adjusted stimulation pulses that may be delivered to the subject based on the attention level of the subject over time.

[0336] Referring now to the graph 2815, two additional stimulation pulses are delivered to the subject during intervals T5 and T6, which originally did not include any schedule pulses as shown in the graph 2805. In some implementations, the additional pulses delivered during the intervals T5 and T6 can be useful because the subject's attention level was below the threshold L for portions of the time periods during which the scheduled pulses were delivered (i.e., intervals T2 and T4). Because the subject may not receive the benefits of the pulses delivered during the intervals T2 and T4 as a result of the relatively low attention level during portions of these intervals, the overall effect of the therapy session may be reduced. Thus, the additional pulses delivered during the intervals T5 and T6 can be administered to compensate for the subjects low attention level during some of the scheduled pulses.

[0337] The graph 2820 shows stimulation pulses that are intended to refocus the subject's attention when it appears that the subject's attention level may be below the threshold L during certain time intervals. For example, the subject's attention level falls at the end of the interval T2. Thus, the graph 2820 includes a pulse that occurs just before the beginning of the interval T3, which is intended to recapture the subject's attention so that the subject's attention level will be above the threshold L during the interval T3. As shown in the graph 2810, the subject's attention level increases just before the beginning of the interval T3 as a result of the pulse shown on the left-hand side of the graph 2820. Before the time period T4, the subject's attention level again drops below the threshold L. As a result, the graph 2820 shows a second pulse that occurs before the interval T4 in order to refocus the subject's attention. However, the second pulse shown in the graph 2820 appears to be ineffective, as the subject's attention level does not rise above the threshold L for the beginning of the interval T4. It should be understood that the modality associated with the graph 2820 need not be the same as the modality associated with the graph 2805. For example, the scheduled pulses shown in the graph 2805 may be visual stimulation pulses, and the pulses shown in the graph 2820 may be auditory pulses that are intended to remind the subject to refocus his attention appropriately.

[0338] The graph 2825 shows adjusted stimulation pulses that are intended to combat the subject's inattention during certain time intervals. For example, the subject's attention level drops at the end of the interval T2. As a result, the graph 2825 includes a pulse that occurs simultaneous with the subject's attention dropping during the interval T2, and continues until the end of the interval T2. It should be noted that the amplitude of the adjusted pulses shown in the graph 2825 is larger than the amplitude of the scheduled pulses shown in the graph 2805. Such a larger amplitude can serve to refocus the subject's attention, or can be used to increase the

[0339] effectiveness of pulses that the user is not sufficiently focused on. In some implementations, the larger amplitude of the pulses shown in the graph 2825 may correspond to a brighter visual stimulation signal or a louder auditory stimulation signal, relative to the signals used to generate the scheduled pulses shown in the graph 2805. As shown in the graph 2825, a second adjusted pulse having a high amplitude occurs during the beginning of the interval T4, when the subject's attention level is relatively low. However, when the subject's attention level changes to exceed the threshold level L towards the end of the time interval T4, the adjusted pulse is terminated, as it is no longer necessary.

[0340] In some implementations, adjusted pulses different from those shown in FIG. 28 may be used. Furthermore, adjusted pulses may be delivered to the subject in other scenarios not illustrated in FIG. 50. In some implementations, adjusted pulses may be delivered in order to increase the subject's comfort level during a therapy session. For example, if sensor data (e.g., heart rate sensor data or galvanic skin response sensor data) indicates that the subject is experiencing stress during a therapy session, and adjusted pulse having an amplitude lower than that of a scheduled pulse may be delivered to the subject, in order to reduce the discomforting effect that the scheduled pulses may have on the subject. iv. Additional Methods

[0341] In some embodiments, the present disclosure provides devices, systems and methods for improving one or more patient outcomes or treating a disease. The device or system may comprise any device or system as disclosed herein. In some embodiments, the gamma oscillation inducing waveform is delivered through one or more of: visual stimulus, auditory stimulus, tactile stimulus, haptic stimulus, olfactory stimulus, or bone conduction, or a combination thereof. In some embodiments, combined audio-visual stimulus is delivered for an hour each day for a 3 to 6 month or longer period. In some embodiments, stimulus is delivered for two hours each day. In some embodiments, a stimulus is delivered for multiple periods over the course of a day. In some embodiments, combined audio-visual stimulus is delivered over an extended open-ended period of time. In some embodiments, stimulus is delivered in periods of varying durations. In some embodiments, the gamma oscillation inducing waveform is delivered at least in part through glasses, goggles, a mask, or other worn apparatus that can provide visual stimulus.

[0342] In some embodiments, the systems, devices, and methods for benefiting a cognitive state or function of a brain of a subject, comprises a portable system comprising a first stimulus emitting component comprising a visual source comprising a pair of glasses configured to project light pulses towards said subject's eyes, said light pulses having a frequency of about 30 Hz to about 60 Hz and producing a square-wave duty cycle of about 50%, wherein said pair of glasses comprises: a light emitting diode and a light emitting diode driver, said light emitting diode projecting said light pulses towards a screen which flickers at about 30 Hz to about 60 Hz and reflects said light pulses to redirect said light pulses towards said subject's eyes; and a display device configured to provide a visual stimulus to said subject and a second stimulus emitting component comprising an audio source comprising a set of supra-aural headphones, wherein said set of supra-aural headphones produces an auditory stimulus with a frequency of about 30 Hz to about 60 Hz and a duty cycle of 50% wherein said glasses and said supra-aural headphones are operatively configured to comprise a single headset device to be worn by said subject, and wherein use of said system promotes synchronized gamma oscillations in at least one brain region of said subject and causes an improvement in one or more cognitive functions of said subject's brain, thereby slowing progression of mild cognitive impairment or Alzheimer's disease in said subject.

[0343] In some embodiments, the systems, methods, and devices of the present disclosure can be implemented as shown and described in FIG. 48- FIG. 61.

[0344] In some embodiments, said portable system can be used as shown in FIG. 63 which illustratively depicts a process for a personalized and patient-specific therapeutic use of a portable system and / or any embodiment of a device described herein. In some embodiments, a physician prescribes at-home therapeutic portable system settings for a patient, which include adjusting any parameters of which the portable system is configured to emit a visual stimulus, a haptic stimulus, or an auditory stimulus to the eyes and ears, or brain of the patient. The physician can confirm that a patient’s neurological response is elicited by analyzing cortical EEG recordings in order to identify the optimal stimulation frequency of the visual stimulus, haptic stimulus, or the auditory stimulus delivered by the portable system. The patient can then use the device at home with the settings prescribed by the physician. The patient’s adherence to using the device as prescribed is monitored throughout the course of treatment.

[0345] In some embodiments, a rendering of an embodiment of a controller of the portable system (Combinatorial Neurostimulation System) is shown in FIG. 62.

[0346] In some embodiments, said portable system comprises a device as shown and described in FIG. 64 and FIG. 65

[0347] In some embodiments, a single headset device as disclosed herein comprises a device as shown and described in FIG. 66-FIG. 80.

[0348] In some embodiments, the portable system (or Combinatorial Neurostimulation System) further comprises a hand-held controller. In some embodiments, said portable system comprises a portable neurostimulation system. In some embodiments, said hand-held controller receives and transmits a signal dictating a dosing parameter corresponding to a frequency, a duration, a brightness, or a color of said visual stimulus, or a duration, an intensity, or a frequency of said audio stimuli. In some embodiments, said hand-held controller further comprises an independent power supply comprising batteries or a rechargeable battery.

[0349] In some embodiments, the hand-held controller further comprises adjustable inputs for said single headset device, said audio source, and said visual source, wherein said adjustable inputs for said audio source comprise an adjustable volume input, and said adjustable inputs for said visual source comprise an adjustable brightness input and wherein said adjustable input for said single headset device comprises an input for powering on and powering off said single headset device, or for pausing said visual or audio stimulus. In some embodiments, said handheld controller comprises a device as shown and described in FIG. 72, FIG. 73, FIG. 75A, FIG. 75B, FIG. 75C, or FIG. 75D

[0350] In some embodiments, said portable system is configured to induce gamma oscillation inducing waveforms in a subject.

[0351] In some embodiments, said portable system comprises a stimulus first stimulus emitting component comprising a visual source comprising a pair of glasses and a second stimulus WO 2025 / 147596                                   PCT / US2025 / 010218 emitting component comprising an audio source comprising an audio speaker within the temple arm of the glasses, as shown and described in FIG. 79 and FIG. 80.

[0352] In some embodiments, said supra-aural headphones of said portable system further comprise said adjustable inputs for said system, including said adjustable inputs for said visual source, said audio source, and said single headset device.

[0353] In some embodiments, the gamma oscillation inducing waveform is delivered by a visual stimulus through a visual source. In some embodiments, said visual source comprises a pair of glasses worn by the subject with illuminating elements on the interior providing a visual stimulus. In some embodiments, the gamma oscillation inducing waveform is delivered through supra-aural headphones or earbuds worn by the subject providing an auditory signal. In some embodiments, combined visual and auditory signals are provided by such supra-aural headphones and glasses worn together at the same time comprising said single headset device.

[0354] In some embodiments said single headset device comprises a neurostimulation device as disclosed and described herein.

[0355] In some embodiments, said gamma oscillation inducing waveform comprises a visual stimulus with a frequency of about 30 Hz to about 60 Hz and / or an auditory stimulus with a frequency of about 30 Hz to about 60 Hz.

[0356] In some embodiments, the gamma oscillation inducing waveform is delivered as vibrotactile stimulus via an article of clothing or body attachment. In some embodiments, such body attachment can include a device providing treatment for a condition of a user during sleep, such as a CPAP device. In some embodiments, the gamma oscillation inducing waveform can be delivered through the user's nostrils. 1. Program parameters and parameter values

[0357] In some embodiments, gamma oscillation inducing waveform parameters are configured with a stimulus frequency (e.g., fs in FIG. 31) of about 30 Hz to about 60 Hz for both audio and visual signals. In some embodiments, audio and visual stimulus are offset relative to each other by a delay (e.g., td in FIG. 31). In an example embodiment, audio and visual signals are synchronized (td = 0 s).

[0358] In some embodiments, gamma oscillation inducing waveform parameters are configured with a variety of timing and intensity parameters. In an example embodiment, these parameters include those illustrated in FIG. 31. In some embodiments, these parameters are preconfigured; they can be adjusted at least in part by a third party such as a caregiver or healthcare provider. In some embodiments, one or more parameters of the stimulus can be adjusted responsive to measurements or analysis of one or more of: user context, measured parameters associated with WO 2025 / 147596                                   PCT / US2025 / 010218 the user, observed or detected use of the stimulation device. In some embodiments, gamma oscillation inducing waveform are adjusted responsive to detected or analyzed symptom progression related to an affliction impacting cognitive function. Various frequencies and various intensities can be used as parameters for the gamma oscillation inducing waveform.

[0359] In some embodiments, one or more stimulus parameters are based at least partially on various clinical measures of cognitive function disclosed herein. In some embodiments, varying combinations stimulus parameters are used during different time periods and subsequent stimulus parameters are selected at least in part based on comparison of clinical measures of cognitive function among at least some of those periods. In some embodiments, stimulus parameters are selected to optimize, improve, and / or enhance sleep improvement as assessed at least in part by clinical measures of cognitive function.

[0360] In some embodiments, the present disclosure delivers about 30 Hz to about 60 Hz gamma oscillation inducing waveform as an auditory stimulus, a visual stimulus, or combined audiovisual stimulus. In some embodiments stimulus is delivered at one or more stimulus frequencies (e.g., fs in FIG. 31) in the approximate range of about 30 Hz to about 60 Hz In some embodiments, “gamma” can refer to frequencies in the range of 30-60Hz, 30-50Hz, 30-40Hz, or 35-45 Hz. In some embodiments, stimulus can be delivered based at least in part on a user’s detected, reported, or demographically or individually associated or dominant alpha wave frequency.

[0361] In some embodiments, specific parameters for a visual stimulus can include one or more of: stimulus frequency, intensity (brightness), hue, visual patterns, spatial frequency, contrast, and duty-cycle. In an exemplary embodiment, visual stimulus is provided at a stimulus frequency of 40 Hz, brightness between 0 pW / cm2 to 1120 pW / cm2, and 50% duty-cycle.

[0362] In some embodiments, gamma oscillation inducing waveform can be delivered as combined visual stimulus and auditory stimulus, delivered at about 35-45 Hz frequency. In some embodiments, visual stimulus and auditory stimulus can be synchronized to begin each cycle simultaneously. In some embodiments, the beginning of each auditory stimulus and visual stimulus cycle is offset by a configured amount of time. In some embodiments, visual and auditory signals are delivered at an intensity clearly recognized by subjects and adjusted to their tolerance level. In some embodiments, visual and auditory signals are delivered at an intensity imperceptible by subjects.

[0363] In some embodiments, at least some of the parameters or characteristics of the gamma oscillation inducing waveform administered to a subject correspond to those specified in one or more of US Patents US 10307611 B2, US 10293177 B2, or US 10279192 B2. In some embodiments, at least some of the parameters or characteristics of the gamma oscillation WO 2025 / 147596                                   PCT / US2025 / 010218 inducing waveform administered to a subject correspond to those specified in one or more of US Patents US 10159816 B2 or US 10265497 B2.

[0364] In some embodiments, parameters of an auditory stimulus include one or more of: stimulus frequency, intensity (volume), and duty-cycle. In some embodiments, frequency is adjusted responsive to a subject’s hearing characteristics, for example to frequencies that a subject is better at hearing. In an example embodiment, audio stimulus is provided at an audio tone frequency of 7,000 Hz, volume level between 0 dBA to 80 dBA, and 0.57% duty-cycle.

[0365] In some embodiments, gamma oscillation inducing waveform parameters are directed at evoking gamma wave oscillations in the nervous systems of human subjects. In some embodiments, the gamma oscillation inducing waveform parameters can be configured to induce beta waves in human subjects. In some embodiments, the gamma oscillation inducing waveform parameters can be configured to induce alpha waves in human subjects.

[0366] In some embodiments, light levels and hue can be adjusted to avoid fatiguing the subject. In some embodiments, light levels and hue can be adjusted to provide motivation to the subject. In some embodiments, light levels and hue can be adjusted to be imperceptible to the subject. In some embodiments, parameters to each ear or eye of the subject are adjusted in a similar manner. In some embodiments, parameters to each ear or eye of the subject are adjusted differently. In some embodiments, audio and visual parameters such as tone and hue are varied to provide engagement or motivation to the subject to continue applying the stimulus or monitoring. In some embodiments, audio and visual parameters such as tone and hue can be varied to be imperceptible to the subject.

[0367] The embodiments of the portable system described herein can allow for personalization and patient user-specific therapeutic treatment regimens, as prescribed and determined by a physician or healthcare provider. In some embodiments, the devices and systems provided herein allow for connectivity to patient and care partner support networks (e.g., online, phone, group, telemedicine, telehealth). In some embodiments, the portable system comprises feedback sensors. In some embodiments, the feedback sensors comprise a sensor configured to track the eyes of the user or patient, measure adherence to the prescribed stimulation treatment regimen, or the health status of the user or patient. In some embodiments, the feedback sensors are configured to determine if the eyes of the user or patient are open during the visual and auditory stimulation. In some embodiments, the health status of the user or patient comprises homeostatic eye movement to determine if the user or patient is experiencing a seizure or significant atypical or detrimental neurological event.

[0368] In some embodiments, the portable neurostimulation system comprises feedback loops configured to execute routines and adapt to patient-relevant biometric data for allowing the portable neurostimulation device to establish a patient-specific or user-specific treatment regimen. In some embodiments, the portable neurostimulation system comprises feedback loops configured to automate transfer of data pertaining to or in the form of patient surveys, selfassessments, healthcare provider assessments, caregiver assessments, biometric data, actigraphy data, and / or treatment adherence between the portable neurostimulation system and a receiving device, data network, or cloud storage system for subsequent analysis. In some embodiments, the devices and systems described herein can be structurally and / or functionally integrated with third-party activity sensors or monitoring sensors. In some embodiments, the data obtained by the device sensors, feedback sensors, and feedback loops can be used to identify additional health or disease indications, including new biomarkers (e.g., changes in neurological activity, cognitive status, cognitive function, treatment adherence). In some embodiments, data analytics obtained via the portable system or devices associated therewith can be enhanced by artificial intelligence.

[0369] The portable system (or Combinatorial Neurostimulation System) described herein is a therapeutic sensory stimulation system that is a portable system, which, in some embodiments, includes a handheld controller, eyeglasses for visual stimulation, and headphones for auditory stimulation that work together to deliver precisely timed, non-invasive stimulation to induce steady-state gamma brainwave activity. In some embodiments, the eyeglasses and headphones are integrated into a single headset device.

[0370] In some embodiments, the visual stimulation generated by the portable system (or Combinatorial Neurostimulation System) comprises precisely timed flashes of visible white light from light-emitting diodes (LEDs), and the auditory stimulation comprises short-duration clicks. The stimuli typically occur at a pulse repetition frequency of about 20 Hz to about 60 Hz. The on-off periods of the visual stimulation are perceivable by the patient but not disruptive; an individual remains aware of their surroundings and can converse with a care partner during the use of the system. In some embodiments, the light pulses of the light-emitting diodes (LEDs) are emitted from the device or system in a manner that is in-phase with the emission of the shortduration clicks from the device or system. In some embodiments, the light pulses of the lightemitting diodes (LEDs) are emitted from the device or system in a manner that is out-of-phase with the emission of the short-duration clicks from the device or system. In some embodiments, the light pulses of the light-emitting diodes (LEDs) are emitted from the device or system in a manner that is in-phase and staggered in time with respect to the emission of the short-duration clicks from the device or system. In some embodiments, the light pulses of the light-emitting diodes (LEDs) are emitted from the device at a time consistently staggered with respect to the emission of the short-duration clicks from the device or system. In some embodiments, the light pulses are staggered by no more than 25 milliseconds with respect to the emission of the short- WO 2025 / 147596                                   PCT / US2025 / 010218 duration clicks from the device or system. In some embodiments, the onset of the light pulses are staggered by no more than 25 milliseconds with respect to the emission of the onset of the shortduration clicks from the device or system.

[0371] In some embodiments, the portable system (or Combinatorial Neurostimulation System) is designed to be a prescription device intended for use under the direction of a clinician in the AD population. In some embodiments, the customized stimulation output is determined and verified by a clinician based on both patient-reported comfort information and the patient’s quantitative electroencephalography (EEG) response to the stimulation. In some embodiments, the portable system (or Combinatorial Neurostimulation System) is then configured to the determined settings, and all subsequent use will be within this predefined operating range. In some embodiments, once a physician has prescribed a patient’s use of the portable system, the patient uses the device at home for daily sessions lasting one hour. In some embodiments, a patient can adjust the brightness of the visual stimulation and the volume of the auditory stimulation within this predefined operating range via push buttons on the controller, and pause / resume a treatment session with assistance from a care partner as needed. In some embodiments, the system logs device usage and stimulation output settings for adherence monitoring; this information is uploaded to a “cloud” storage or a physical media storage device for remote monitoring.

[0372] In some embodiments,, the system is designed for ease of use for older adults: the controller user interface has a limited number of controls with no requirements for high dexterity manipulation, the device is accompanied by simple visual instructions in large print, and auditory (voice) prompts of a patient’s progress during a treatment session are delivered through the headphones. In some embodiments, from a patient’s perspective, the flashing light and auditory click stimulation result in the desired induced gamma brainwave activity without interruption of normal functioning. In some embodiments, the individual wearing the device remains oriented to the surrounding environment; s / he is readily able to converse and perform voluntary movements such as holding the hand of their care partner while remaining seated throughout the treatment session. In some embodiments, the flashing light and auditory click stimulation are administered to the user or patient while the user or patient is in a state of wakefulness. In some embodiments, the flashing light and auditory click stimulation are administered to the user or patient while the user or patient is attentive to the flashing light and auditory click stimulation. v. Physical or Cognitive Assessment

[0373] In some embodiments, methods of using a device or system as disclosed herein comprise receiving an indication of a physiological, cognitive, neural, visual, or physical assessment of a subject wearing a device or system as disclosed herein and emitting a stimulus in response to the indication. In some embodiments, a physiological, cognitive, neural, visual, or physical assessment is performed using a portable system as disclosed herein. In some embodiments, a physiological, cognitive, neural, visual, or physical assessment is performed using a portable system or single headset device as disclosed herein, wherein the system or single headset device comprises a processor and a feedback sensor, wherein the feedback sensor receives an indication of a physiological assessment, cognitive assessment, neural assessment, or physical assessment of a subject through said feedback sensor and transmits the a signal to the processor, wherein the processor instructs a stimulus-emitting component, to adjust at least one parameter associated with a auditory, visual, or haptic stimulus. In some embodiments, the adjustment of at least one parameter associated with said stimulus comprises an adjustment that induces gamma oscillations in a brain region of said subject. In some embodiments, the physical assessment of the subject involves ascertaining at least one of said subject's: compliance with proper use and positioning of said system, eye status, alert or sleep status, or environment and surroundings. In some embodiments, the neural assessment of said subject is received using brain wave sensors, an electroencephalography (EEG) device, an electrooculography (EOG) devices, or a magnetoencephalography (MEG) device. In some embodiments, the cognitive assessment of the subject is obtained through questions posed to said subject, activities and tasks performed by said subject in response to a prompt, or behaviors exhibited by said subject. In some embodiments, the processor further instructs the stimulus-emitting component to lengthen or shorten a duration of stimulation in response to the indication of the physiological, cognitive, neural, and / or physical assessment.

[0374] In some embodiments, the indication of the physical assessment of the subject comprises ascertaining at least one of the subject's: compliance with proper use and positioning of the system, eye status, alert or sleep status, or environment and surroundings.

[0375] In some embodiments, the indication of the cognitive assessment of the subject is obtained through questions posed to the subject, activities and tasks performed by the subject in response to a prompt, or behaviors exhibited by the subject.

[0376] In some embodiments, methods comprise instructing the device or system to lengthen or shorten a duration of stimulation in response to the indication of the physiological, cognitive, neural, visual,, or physical assessment. In some embodiments, the physical assessment of the subject is performed to determine hearing of the subject. vi. Methods of Treating Diseases or Conditions WO 2025 / 147596                                   PCT / US2025 / 010218

[0377] In some embodiments, methods of using a device or system as disclosed herein include using the device or system to treat, prevent, or mitigate cognitive dysfunction in a subject.

[0378] In some embodiments, the device or system is used to treat Alzheimer's disease or dementia in a subject in need thereof. In some embodiments, the dementia comprises, vascular dementia, Lewy body dementia, Pick's disease, fronto-temporal dementia (FTD), AIDS dementia, age-related cognitive impairments, and age-related memory impairments.

[0379] In some embodiments, the disease or condition comprises Parkinson’s disease.

[0380] In some embodiments, the method of treatment comprises stimulating a subject with a stimulus generated by a device or system disclosed herein, thereby inducing gamma oscillations in brain region of the subject.

[0381] In some embodiments, the brain region comprises an entorhinal cortex, a hippocampus, a cerebral cortex, a visual association cortex, an auditory association cortex, a cingulate lobe, an amygdala, a thalamic nucleus, a cingulate lobe, a pons, a brainstem, a cerebellum, a lateral ventricle, an occipital lobe, a parietal lobe, a temporal lobe, a midbrain, a striatum, a basal ganglia, a globus pallidus, a substantia nigra, or any combination thereof.

[0382] In some embodiments, the induced gamma oscillations correspond to the frequency of the stimulus generated by a wireless audio or haptic device, or system used to administer the stimulus. 1. Additional Diseases and Conditions

[0383] In some embodiments, the systems, devices, and methods of the present disclosure can be useful for treating or benefiting a cognitive state or function of a brain of a subject including the following diseases and conditions.

[0384] In some embodiments, the disease or disorder can comprise a neurodegenerative disease associated with tauopathy, including but not limited to Alzheimer’s disease, frontotemporal dementia, chronic traumatic encephalopathy (CTE), and corticobasilar degeneration.

[0385] Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by a decline in memory, orientation, and reasoning. AD can be characterized by the accumulation of amyloid plaques comprising the amyloid-3 (A3) peptide and neurofibrillary tangles (NFTs) made of the tau protein. Under normal conditions, the soluble A3 peptide is produced and secreted by neurons and subsequently cleared from the brain via cerebral spinal fluid (CSF) pathways. However, in subjects with AD, the Ap peptide appears to aggregate into higher-order species to form soluble oligomers and insoluble plaques in a concentration-dependent manner. This aggregation can initiate many neurotoxic events including disrupted brain metabolism, WO 2025 / 147596                                   PCT / US2025 / 010218 neuroinflammation, reduced functional connectivity, synaptic and neuronal loss, and / or formation of NFTs.

[0386] Frontotemporal dementia (FTD) is a group of disorders that result from damage to the frontal and temporal lobes of the brain. Depending on the location of the damage, the disorder causes changes in social behavior, personality, and / or loss of language skills. In some people, FTD can also lead to neuromuscular disorder, such as parkinsonism. Frontotemporal dementia occurs where abnormal proteins build up in the brain, leading to death of brain cells and atrophy of the frontal and temporal lobes of the brain. Frontotemporal dementia occurs in Alzheimer’s disease, although it can be caused by other neurodegenerative diseases as well.

[0387] Chronic traumatic encephalopathy (CTE) is characterized by symptoms that can include memory loss, confusion, impaired judgment, impulse control problems, aggression, depression, anxiety, suicidality, parkinsonism, and progressive dementia. CTE results from traumatic injury to the head triggers microglia, leading to tau proteins becoming phosphorylated at progressively higher rates and, accordingly, accumulation of hyperphosphorylated tau deposits. The buildup of phosphorylated tau proteins can lead to axonal transport defects, neuroinflammation, and synapse loss.

[0388] Corticobasal degeneration (CBD) is characterized by cell loss and deterioration of specific areas of the brain. In corticobasal degeneration, abnormal levels of tau accumulate in certain brain cells, eventually causing their deterioration. Symptoms often initially include experiencing motor abnormalities in one limb that progressively spreads to all limbs. Such motor abnormalities include, for example, progressive stiffening or tightening of muscles in the limb (progressive asymmetric rigidity) and the inability to perform purposeful or voluntary movements (apraxia). Trouble with speech and language, including aphasia, apraxia of speech, dysarthria, dysphagia. Symptoms can also be reflected in physical movements and tremors, such as experiencing action tremor, postural tremor, bradykinesia, akinesia, myoclonus, and ataxic gait. The severity and type of symptoms depend on the area of the brain affected by the disease, which is most commonly the cerebral cortex and basal ganglia. a) Genetic Disorders: Inherited Ataxias

[0389] Hereditary ataxias are characterized by slowly progressive incoordination of gait and are often associated with poor coordination of hands, speech, and eye movements. Hereditary ataxias frequently cause atrophy of the cerebellum as a result of impaired circuitry and function of the cerebellar cortex, a result of neurodegeneration of cellular afferents and the Prukinje cells, which have long axonal projections that comprise the only sources of output from the cerebellar cortex to deep cerebellar nuclei. b) Neuropsychiatric Disorders: Schizophrenia, Depression, Chronic Stress

[0390] In other embodiments, the present disclosure provides system and methods for treating neuropsychiatric disorders associated with brain atrophy, which is mediated by microglial cells. For example, individuals with schizophrenia often show reduced postmortem cortical tissue. This phenomenon is caused by synaptic pruning, which reflects abnormalities in microglia-like cells and synaptic function. In other embodiments, the present disclosure provides methods and systems for alleviating symptoms of depression. Stress, impaired neurogenesis, and defects in synaptic plasticity are associated with depression. Chronic stress promotes microglial hyperramification and astroglial atrophy. Thus, in some embodiments, the system and methods disclosed can alleviate symptoms associated with chronic stress or depression by improving synaptic plasticity and stimulating neural networking, along with improving microglial-mediated clearance. c) Brain Injury: Stroke and Related Cerebrovascular Diseases

[0391] In some embodiments, the present disclosure provides systems, devices, and methods for alleviating symptoms associated with a stroke. For example, the stroke can be an ischemic stroke, which causes a neuroinflammatory response and activates microglia to help repair the brain. Ischemic stroke is associated with disappearance of synaptic activity. As a result, brain tissue within the penumbra during an ischemic stroke is structurally intact, but functionally silent. Failure to reperfuse this penumbral region or resupply glucose and oxygen in time can lead to atrophy of brain cells located in the penumbra. In contrast, activating synapses in this region can delay cell death and salvage brain tissue. By improving synaptic plasticity and stimulating neural networking, the present systems, devices, and methods can reduce brain atrophy and related symptoms associated with ischemic stroke. Other forms cerebrovascular diseases with similar symptoms— e.g., neuroimmune modulation, synaptic function—can also be treated by the present disclosure, including but not limited to: transient ischemic attack (TIA), hemorrhagic stroke, arteriovenous malformation, intracranial atherosclerosis (ICAD), and Moyamoya. d) Demyelinating Diseases: Multiple Sclerosis and Acute Disseminated Encephalomyelitis

[0392] In some embodiments, the present disclosure provides systems, devices, and methods for alleviating symptoms of demyelinating diseases associated with brain atrophy. For example, the demyelinating disease can comprise Multiple Sclerosis or Acute disseminated encephalomyelitis, both of which can cause neuroinflammation and cerebral atrophy. In multiple sclerosis (MS), brain or cerebral atrophy is common due to demyelination and destruction of nerve cells. Widespread myelin damage occurs, causing damage to the myelin-rich white matter of the brain, occurs as a result of a number of attacks which occur over time. In acute disseminated encephalomyelitis, similar symptoms are seen, but the onset of widespread myelin damage is often due to a single episode or attack. By reducing neuroinflammation and stimulating neural networking, the present disclosure provides systems, devices, and methods for slowing brain atrophy associated with demyelinating diseases and related symptoms. e) Sleep

[0393] In some embodiments, the systems, devices, and methods of the present disclosure are also directed towards improvement in sleep quality, including reduced sleep fragmentation and increased nighttime restful periods as assessed from actigraphy data, through non-invasive, convenient, and easily tolerated treatment, in mild to moderate AD subjects, with applications to wider populations of users. Moreover, the present solution, i.e., use of a portable system as disclosed herein, provides a method that can be easily administered in the home or other familiar setting by the patient or caregiver, thus avoiding transportation between home and clinical facility. In some cases, the present solution, i.e., use of a portable system as disclosed herein, can improve sleep quality and potentially prevent, mitigate, and / or treat dementia, in particular AD, along with other sleep-related benefits.

[0394] Sleep fragmentation is associated with increased expression of genes characteristic of aged microglia and the proportion of morphologically activated microglia, which are in turn correlated with, and can underlie, sleep-fragmentation associated cognitive deficits. Based on these and other clinical observations, reducing sleep fragmentation and / or improving sleep quality in MCI and AD patients can provide multiple benefits: better sleep can enhance patients’ daytime performance, including cognitive function, and reduce behavioral pathologies and daytime sleepiness. Furthermore, improved sleep quality as a result of reduced sleep fragmentation can also positively modify disease progression.

[0395] In some embodiments, the present disclosure describes systems, devices, and methods for delivering gamma oscillation inducing waveform directed at producing a reduction in sleep fragmentation during night-time sleep of mild to moderate AD patients. In some embodiments, the present disclosure describes systems, devices, and methods for increasing the length of restful periods during sleep and / or reducing the frequency of awakenings during sleep.

[0396] In some embodiments, the present disclosure describes systems, devices, and methods for delivering a gamma oscillation inducing waveform directed at producing beneficial changes in actigraphy during night-time sleep of mild to moderate AD patients. In some embodiments, the present disclosure describes systems, devices, and methods for delivering gamma oscillation inducing waveform directed at producing beneficial changes in actigraphy during sleep periods in mild to moderate AD patients. In some embodiments, the present disclosure describes systems, devices, and methods for producing changes in actigraphy during sleep in mild to moderate AD patients through the application of audio-visual gamma wave stimulation. In some embodiments, the present disclosure describes systems, devices, and methods for producing beneficial changes in sleep of mild to moderate AD patients through the application of audio-visual gamma wave stimulation.

[0397] In some embodiments, the present disclosure describes systems, devices, and methods for delivering gamma oscillation inducing waveform directed at producing beneficial changes in actigraphy during sleep periods in one or more of: subjects at risk of AD, subjects experiencing cognitive decline, subjects experiencing sleep disruption, subjects diagnosed with AD, subjects diagnosed with MCI, healthy subjects, subjects with sleep pathologies, and subjects with sleep disruptions. In some embodiments, beneficial changes in actigraphy includes reduction in sleep fragmentation. In some embodiments, beneficial changes in actigraphy includes one or more of: increases the frequency of restful periods during sleep periods and / or reduction in the frequency of sleep interruptions during sleep periods. In some embodiments, the present disclosure delivers gamma oscillation inducing waveform directed at producing a reduction in sleep fragmentation during night-time sleep of mild to moderate AD patients. In some embodiments, the present disclosure further describes technologies directed at increasing the length of restful periods during sleep and / or reducing the frequency of awakenings during sleep.

[0398] In some embodiments, systems, devices, and methods directed at producing beneficial changes in actigraphy are further directed at producing beneficial sleep-related health outcomes. In some embodiments, beneficial sleep-related health outcomes include one or more of: clearance of brain waste products, mitigation of various afflictions that negatively affect cognitive function, slowing or delay of AD progression, reduction of circadian rhythm disruptions, reduction of microglial aging and activation, reduction in cognitive impairment, reduction in depression symptoms, mitigation of appetite or eating disorders, reduction in agitation, reduction in apathy, reduction in psychosis symptoms (including delusions and hallucinations), reduction in aggression, reduction in behavioral and psychiatric symptoms of dementia, stabilizing and / or preventing the degradation of one or more measures of performance. In some embodiments, mitigated circadian rhythm disruptions include but are not limited to disruptions associated with: AD, MCI, ageing, eating disorders, irregular sleep wake rhythm disorder, depression, anxiety, stress.

[0399] In some embodiments, sleep, during sleep, or sleep periods can refer to nighttime periods of relative inactivity or periods of frequent rest. In some further embodiments, such periods of relative inactivity or frequent rest refer to those characterized patterns of actigraphy, including but not limited to patterns of actigraphy identified using the methods described in embodiments of the present technological solution. FIGs. 34 and 35 provides an example of a pattern of actigraphy identified using the methods described herein. FIGs. 34 and 35 shows twenty-four (24) hours of activity levels (gray; 1501, FIG. 37) over two days for a single example patient, centered around 12 AM (indicated by the thick, gray arrows) along with a median filtered curve (labelled by thin arrows; 1507, FIG. 37). The horizontal axis shows time of day; the vertical axis is relative activity recorded on a wrist-worn actigraphic measuring device (arbitrary log scale). Calculated sleep periods (black horizontal lines; see 1508, FIG. 37) along with individual sample rest periods (yellow horizontal lines; see 1509, FIG. 37) are shown: with (a) showing an example pattern for frequent movements and short rest periods during sleep periods, and (b) showing an exemplary pattern of less frequent movements and longer rest periods during sleep periods. Similarly, FIG. 33 provides example patterns of actigraphy (arbitrary units, see FIG. 34). FIG. 33 provides actigraphy data for over several days (gray; e.g., 1501, FIG. 37), and a smooth curve is superposed. The cutoff line (black line) separates active vs rest periods (e.g., 1505, FIG. 37). The black squares represent initial estimation for the mid-night point (e.g., 1507, FIG. 37), of which a final assessment of the mid-night points will be determined through optimization algorithm e.g., 1508, FIG. 37). f) Brain Atrophy

[0400] In some embodiments, systems, devices, and methods described herein can also be used to slow brain atrophy, and thus mediate symptoms associated with brain atrophy through a variety of mechanisms. For example, the present disclosure describes systems, devices, and methods for reducing neuroinflammation, improving synaptic plasticity and stimulating neural networking, and improving microglial-mediated clearance of cerebral insults, all of which can contribute to the progression of brain atrophy, by inducing synchronized gamma oscillations in at least one region of a brain in a subject. The at least one brain region, for example, can include a visual cortex, a somatosensory cortex, an insular cortex, and / or a hippocampus of the subject. The present disclosure also describes systems, devices, and methods for alleviating symptoms of diseases and disorders associated with brain atrophy through non-invasive stimulation of gamma oscillations.

[0401] Atrophy of brain tissue describes the loss of volume within neurons, extracellular space, or glia. Atrophy can occur at different rates in different areas or regions of the brain, and it can be reflected by changes in whole brain volume. For an adult, whole brain volume can be, for example, between around 950 ml and 1550 ml. For an adult female, average whole brain volume can be around 1130 ml. For an adult male, average brain volume can be around 1260 ml. WO 2025 / 147596                                   PCT / US2025 / 010218

[0402] For a child of an age between around 4 years old and 16 years old, whole brain volume can be, for example, between 60 ml and 120 ml.

[0403] Brain volume can be measured using magnetic resonance imaging (MRI) or computerized tomography (CT) scans. Loss of brain volume can be measured by comparing brain volume over time. Various methods can be used to measure brain volume or changes in brain volume, which indicate brain atrophy. Most commonly, brain volume or brain volume loss can be measured using cross-sectional methods or longitudinal methods. Cross-sectional methods can use a single MRI scan to segment particular tissues or structures and calculate the volume of these tissue types and / or structures. Longitudinal methods can use at least two MRI scans of the same subject at different points in time to calculate brain volume changes or atrophy. Longitudinal methods can seek to match the two MRI scans using warping techniques and, from this process, directly extract small changes in brain volume.

[0404] Various tools and algorithms can be employed to determine brain volume through CT or MRI scans. Of the various toolkits available for determining brain volume and changes in brain volume based on the scanned images, examples include, but are not limited to, the following tools: Atropos, an opensource tissue segmentation algorithm; CIVET, a web-based imageprocessing tool for volumetric analysis with different human brain images; the Structural Image Evaluation using Normalization of Atrophy (SIENA and SIENAX), a software that applies a Brain Extraction Tool (BET) to determine cross-sectional volumes; MSmetrix, a fully-automatic tool that detects brain lesions and calculates lesion volume and measures whole-brain and gray matter atrophy; and Statistical Parametric Mapping (SPM), which for analysis of images in a MATLAB environment.

[0405] A subject with brain atrophy can experience this as a cause or result of a variety of conditions, disorders, or diseases, including but not limited to: Alzheimer’s Disease (AD), dementia, Parkinson’s disease, seizure, cerebral palsy, senile dementia, pick’s disease, Huntington’s disease, Krabbe disease, leukodystrophies, multiple sclerosis, epilepsy, anorexia nervosa, aphasia, learning disability, frontotemporal dementia, expressive aphasia, receptive aphasia, Lewy body dementia, chronic traumatic encephalopathy (CTE), and others.

[0406] The change in brain volume can be a reduction of around: 0.3 cm3 per month, 0.5 cm3 per month, 1 cm3 per month, 2 cm3 per month, 0.3 cm3 per year, 0.5 cm3 per year, 1 cm3 per year, 2 cm3 per year, 3 cm3 per year, 4 cm3 per year, 5 cm3 per year, 6 cm3 per year, 7 cm3 per year, 8 cm3 per year, 9 cm3 per year, 10 cm3 per year, 11 cm3 per year, 12 cm3 per year, 13 cm3 per year, 14 cm3 per year, or 15 cm3 per year, or 16 cm3 per year. The rate of brain atrophy can differ between individuals. Exemplary rates of brain atrophy can include, but are not limited to, rates around: between 0.1% and 0.5% per year, between 0.5% and 1.5% per year, between 1.0% and 3.0% per year, or between 3.0% and 6.0% per year. The rate of brain atrophy can vary based on the cause of atrophy. For example, a healthy individual can experience an average brain atrophy rate of 0.1% and 0.4% per year. In contrast, for subjects with Multiple Sclerosis (MS), the average brain atrophy rate can be between 0.5% and 1.3% per year. The average rate of whole brain atrophy for a patient with Alzheimer’s Disease can be, for example, between 1.0% and 4.0% per year. Aging can also cause brain atrophy rates to increase. For example, an individual in their mid-thirties can experience a rate of brain atrophy that is around 0.2% per year, and an individual at around age sixty can experience a rate of brain atrophy that is around 0.5% per year.

[0407] The systems, devices, and methods of the present disclosure are also directed to alleviating symptoms of brain atrophy. Symptoms can include a loss of neurons, memory loss, blurred vision, aphasia, impaired balance, paralysis, decreases in cortical volume, increases in CSF volume, loss of motor control, difficulty speaking, comprehension, reading comprehension, memory, decrease in gray and / or white matter, decrease in neuronal size, loss of neuronal cytoplasmic proteins, or any combination thereof. In some embodiments, the present disclosure describes systems, devices, and methods which act to slow the onset of symptoms of brain atrophy. The present disclosure provides systems, devices, and methods for treating any of the above-listed diseases and disorders by reducing any of the above-listed symptoms associated with brain atrophy. In some embodiments, brain atrophy is reduced or maintained in the corpus callosum. In some embodiments, the brain region comprises an entorhinal cortex, a hippocampus, a cerebral cortex, a visual association cortex, an auditory association cortex, a cingulate lobe, an amygdala, a thalamic nucleus, a cingulate lobe, a pons, a brainstem, a cerebellum, a lateral ventricle, an occipital lobe, a parietal lobe, a temporal lobe, a midbrain, a striatum, a basal ganglia, a globus pallidus, a substantia nigra, or any combination thereof. In some embodiments, a level of atrophy in a brain region of a subject stimulated by a portable system or device as disclosed herein is about 1% to about 100% reduced as compared to a subject not stimulated by a portable system or device as disclosed herein. vii. Methods of Inducing Gamma Oscillations During Daily Activities

[0408] Also described herein are systems, devices, and methods for providing a gamma oscillation inducing waveform to a subject, wherein the gamma oscillation inducing waveform is imperceptible to the subject. An imperceptible waveform can be integrated into various activities in the daily life of the subject, for instance, watching television, working on a computer, listening to music, playing video games, and other aspects of life.

[0409] When the gamma oscillation inducing waveform is imperceptible to the subject, the subject can enjoy various daily activities while benefiting from the therapeutic effects of the gamma-oscillation inducing waveform without feeling the intrusion of the gamma oscillation inducing waveform into the daily activities. An advantage of providing the gamma oscillation inducing waveform in an imperceptible manner can be that various daily activities (e.g., work or pleasure) that a subject takes part in will not be disrupted by the gamma oscillation inducing waveform.

[0410] Furthermore, if the daily activity is social in nature, for instance, watching television with family, playing video games with a friend, etc., providing the gamma-oscillation inducing waveform in an imperceptible manner can bring additional benefits. A family member, a husband or spouse, a friend, and other acquaintances important to the subject may not feel disrupted, annoyed, or bothered by the gamma oscillation inducing waveform when it is imperceptible to them. B. Methods of Inducing Improvements in a Brain Region via Use of Portable Systems and Devices as Disclosed Herein i. Cognition

[0411] The present technological solution achieves the induction of gamma wave oscillations in the brain through a variety of methods and systems, and includes aspects covering the monitoring and analysis of patient activity, motivation and feedback to users and / or third parties, and specific stimulation parameters targeted at improving cognition and cognitive functioning. Induction of gamma wave oscillations in the brain can be done using non-invasive sensory stimulation, which can include haptic or mechanical stimulation, peripheral nerve stimulation, visual stimulation, auditory stimulation, or a combination thereof. The disclosure further achieves improved brain wave coherence, measured through increased power in alpha and other frequency bands and other methods for assessing functional connectivity, which are associated with cognitive function, brain health, and general wellbeing.

[0412] In some embodiments, the present disclosure describes systems, devices, and methods for benefiting a cognitive state or function of a brain of a subject, by delivering a gamma oscillation inducing waveform to improve cognitive function and / or to evoke gamma wave oscillations in a subject. In some embodiments, the gamma oscillation inducing waveform achieves cognitive function improvement by inducing gamma oscillations in at least one brain region of the subject.

[0413] Systems, devices, and methods of the present disclosure can be directed to improving the cognitive capacity of a person. In some embodiments, the present disclosure can improve or maintain cognitive functioning of an individual. Any individual can use the systems, devices, and methods of the present disclosure. The individual can be neurotypical or neurodivergent. In some embodiments, the individual has a neurodegenerative disease. In some embodiments, the individual has a physiological disorder, a psychological disorder, a psychosomatic disorder, or a psychiatric disorder.

[0414] In some embodiments, stimulating a subject with the stimulus according to the methods disclosed herein comprises inducing one or more improvements in a brain region of the subject. In some embodiments, the one or more improvements comprises maintaining or improving cognitive function in said brain region of said subject. In some embodiments, said maintaining or improving cognitive function comprises maintaining or improving recognition, discrimination, spatial memory, working memory, attention, or a combination thereof. Systems, devices, and methods described herein can influence one or more of a cognitive process in order to cause a therapeutic improvement. For example, systems, devices, and methods described herein can cause an improvement in emotional control, perceptual reasoning, cognitive flexibility, goal-directed persistence, metacognition, organization, planning / prioritization, response inhibition, stress tolerance, sustained attention, task initiation, time management, working memory, or a combination thereof. Other cognitive processes that can benefit from the systems, devices, and methods described herein include sensory register, short-term memory formation, long-term memory formation, memory encoding, memory consolidation, molecular or cellular memory consolidation, memory recall, perception, attention, knowledge formation, problem solving, concept formation, pattern recognition, association, decision making, motor coordination, decision making, planning, language production, or language comprehension. Further mental processes that can benefit from the technology described herein can also comprise mental calculation, visual encoding and decoding, auditory coding and decoding, sensory encoding and decoding, visual processing, visual-motor planning and processing, visual-spatial planning and processing, auditory memory, visual memory, and task planning, sequencing, initiation, and completion.

[0415] The present disclosure is also directed towards improving cognitive skills. Cognitive skills can include one or more of sustained attention, selective attention, divided attention, longterm memory, working memory, logic and reasoning, auditory processing, visual processing, processing speed, cognitive control, cognitive inhibition, declarative memory, procedural memory, episodic memory, semantic memory, autobiographical memory. WO 2025 / 147596                                   PCT / US2025 / 010218 ii. Additional Improvements

[0416] In some embodiments, the one or more improvements comprise the maintenance or reduction of a level of tau phosphorylation in a brain region of the subject. In some embodiments, a level of tau phosphorylation in a brain region of a subject stimulated by a portable system or device as disclosed herein is about 1% to about 100% reduced as compared to a subject not stimulated by a portable system or device as disclosed herein.

[0417] In some embodiments, stimulating a subject with a portable system or device results in the maintenance or reduction of punctate localization of phosphorylated tau protein in a brain region of the subject. In some embodiments, punctate localization of phosphorylated tau protein in a brain region of a subject stimulated by a portable system or device as disclosed herein is about 1% to about 100% reduced as compared to a subject not stimulated by a portable system or device as disclosed herein.

[0418] In some embodiments, stimulating a subject with a portable system or device according to the methods disclosed herein results in maintaining or improving cognitive function in the subject. In some embodiments, the maintaining or improving cognitive function comprises maintaining or improving recognition, discrimination, spatial memory, working memory, attention, or a combination thereof.

[0419] In some embodiments, a level of cognitive function in a subject stimulated by a portable system or device as disclosed herein is about 1% to about 100% improved as compared to a subject not stimulated by a portable system or device as disclosed herein.

[0420] In some embodiments, a level of cognitive function in a subject stimulated by a portable system or device as disclosed herein is at least 1% to at least 100% improved as compared to a subject not stimulated by a portable system or device as disclosed herein.

[0421] In some embodiments, stimulating a subject with a portable system or device according to the methods disclosed herein results in maintaining or reducing an amount of amyloid-P (AP) peptide in a brain region of a subject.

[0422] In some embodiments, a level of amyloid-P (AP) peptide in a subject stimulated by a portable system or device as disclosed herein is about 1% to about 100% improved as compared to a subject not stimulated by a portable system or device as disclosed herein.

[0423] In some embodiments, a level of amyloid-P (AP) peptide in a subject stimulated by a portable system or device as disclosed herein is at least 1% to at least 100% improved as compared to a subject not stimulated by a portable system or device as disclosed herein.

[0424] In some embodiments, stimulating a subject with a portable system or device according to the methods disclosed herein results in maintaining or reducing an amount of C-terminal WO 2025 / 147596                                   PCT / US2025 / 010218 fragments (CTFs) and N-terminal fragments (NTFs) of amyloid precursor protein (APP) in a brain region of a subject.

[0425] In some embodiments, a level of C-terminal fragments (CTFs) and N-terminal fragments (NTFs) of amyloid precursor protein (APP) in a subject stimulated by a portable system or device as disclosed herein is about 1% to about 100% reduced as compared to a subject not stimulated by a portable system or device as disclosed herein.

[0426] In some embodiments, a level of C-terminal fragments (CTFs) and N-terminal fragments (NTFs) of amyloid precursor protein (APP) in a subject stimulated by a portable system or device as disclosed herein is at least 1% to at least 100% reduced as compared to a subject not stimulated by a portable system or device as disclosed herein.

[0427] In some embodiments, stimulating a subject with a portable system or device according to the methods disclosed herein results in maintaining or reducing an amount of cleavage of APP into CTFs and NTFs by at least one of P-secretase (BACE1) and y-secretase in a brain region of a subject.

[0428] In some embodiments, a level of cleavage of APP into CTFs and NTFs by at least one of P-secretase (BACE1) and y-secretase in a subject stimulated by a portable system or device as disclosed herein is about 1% to about 100% reduced as compared to a subject not stimulated by a portable system or device as disclosed herein.

[0429] In some embodiments, a level of cleavage of APP into CTFs and NTFs by at least one of P-secretase (BACE1) and y-secretase in a subject stimulated by a portable system or device as disclosed herein is at least 1% to at least 100% reduced as compared to a subject not stimulated by a portable system or device as disclosed herein.

[0430] In some embodiments, stimulating a subject with a portable system or device according to the methods disclosed herein results in maintaining or reducing an amount of a number of endosomes in a brain region of a subject.

[0431] In some embodiments, a number of endosomes in a subject stimulated by a portable system or device as disclosed herein is about 1% to about 100% reduced as compared to a subject not stimulated by a closed view visual stimulation device as disclosed herein.

[0432] In some embodiments, a number of endosomes in a subject stimulated by a portable system or device as disclosed herein is at least 1% to at least 100% reduced as compared to a subject stimulated by a portable system or device as disclosed herein.

[0433] In some embodiments, stimulating a subject with a portable system or device according to the methods disclosed herein results in clearance of Ap peptide in a brain region of the subject. WO 2025 / 147596                                   PCT / US2025 / 010218

[0434] In some embodiments, clearance of Ap peptide in a brain region of a subject stimulated by a portable system or device as disclosed herein is about 1% to about 100% increased as compared to a subject not stimulated by a portable system or device as disclosed herein.

[0435] In some embodiments, clearance of Ap peptide in a brain region of a subject stimulated by a portable system or device as disclosed herein is at least 1% to at least 100% increased as compared to a subject not stimulated by a portable system or device as disclosed herein.

[0436] In some embodiments, stimulating a subject with a portable system or device according to the methods disclosed herein results in increasing uptake of Ap peptide by microglia in a brain region of the subject.

[0437] In some embodiments, increasing uptake of Ap peptide by microglia in a brain region of the subject stimulated by a portable system or device as disclosed herein is about 1% to about 100% increased uptake as compared to a subject not stimulated by a portable system or device as disclosed herein.

[0438] In some embodiments, increasing uptake of Ap peptide by microglia in a brain region of the subject stimulated by a portable system or device as disclosed herein is at least 1% to at least 100% increased uptake as compared to a subject not stimulated by a portable system or device as disclosed herein.

[0439] In some embodiments, stimulating a subject with a portable system or device according to the methods disclosed herein results in inducing a change in microglial cells in a brain region of a subject, thereby improving the cognitive function of the subject, or preventing, reducing, or treating cognitive decline in the subject.

[0440] In some embodiments, also described herein are systems, devices, and methods for providing a gamma oscillation inducing waveform to a subject via stimulus emitting components, for benefiting a cognitive state or function of a brain of a subject. Gamma oscillation inducing waveforms delivered to the subject can produce gamma wave oscillations in various regions in the nervous system of the subject, and bring about therapeutic benefits to the subject as a result, thereby slowing progression of mild cognitive impairment or Alzheimer's disease in said subject.

[0441] By integrating the delivery of the gamma oscillation inducing waveform with a portable system as disclosed herein, or a neurostimulation device (e.g., a single headset device through a visual source, a haptic source, and / or an auditory source), the subject can experience therapeutic benefits of receiving the gamma oscillation inducing waveform in various daily activities. Integrating the delivery of the gamma oscillation inducing waveform with a portable system or a neurostimulation device can bring therapeutic benefits to the subject with little intrusion into and / or disruption of the daily life of the subject.

[0442] In some cases, the gamma oscillation can lead to a therapeutic improvement in one or more cognitive functions. For example, the gamma oscillation inducing waveform can generate sensory-evoked potentials in at least one region of the nervous system and, as a result, bring about therapeutic improvements in one or more cognitive functions of the subject, for instance, improvements in neurotic behavior, anxious behavior, depressive behavior, addictive behavior, food-seeking behavior, or sleeping behavior.

[0443] In some embodiments, the present disclosure provides systems, devices, and methods for alleviating symptoms associated with a microglial-mediated disease or disorder associated with brain atrophy. For example, the microglial-mediated disease or disorder can comprise a neurodegenerative disease associated with tauopathy, including but not limited to chronic traumatic encephalopathy, frontotemporal dementia, and corticobasilar degeneration. The microglial-mediated disease or disorder can comprise a genetic disorder, such as an inherited ataxia associated with brain atrophy. The microglial-mediated disease or disorder can also comprise a neuropsychiatric disorder associated with brain atrophy, such as depression or schizophrenia; brain injury, such as stroke; or demyelinating diseases, such as Multiple Sclerosis and Acute disseminated encephalomyelitis. C. Methods for Neural Stimulation with an NSS via Visual Stimulation In some aspects, described herein are methods of neural stimulation via visual stimulation. In some embodiments, a method of visual neurostimulation comprises a method of using a portable system or single headset device as disclosed herein. In some embodiments, a method of visual neurostimulation comprises a method of using a portable system as disclosed herein, wherein the portable system comprises an NSS. Illustrative embodiments are described as follows.

[0444] In FIG. 8 is a flow diagram of a method of performing visual brain stimulation in accordance with an embodiment. The method 800 can be performed by one or more systems, component, modules or elements depicted in FIGS. 1-7B, including, for example, a neural stimulation system (NSS). In brief overview, the NSS can identify a visual signal to provide at block 805. At block 810, the NSS can generate and transmit the identified visual signal. At 815 the NSS can receive or determine feedback associated with neural activity, physiological activity, environmental parameters, or device parameters. At 820 the NSS can manage, control, or adjust the visual signal based on the feedback. i. NSS Operating With A Frame

[0445] The NSS 105 can operate in conjunction with the frame 400 including a light source 305 as depicted in FIG. 4A. The NSS 105 can operate in conjunction with the frame 400 including a WO 2025 / 147596                                   PCT / US2025 / 010218 light source 30 and a feedback sensor 605 as depicted in FIG. 6A. The NSS 105 can operate in conjunction with the frame 400 including at least one shutter 430 as depicted in FIG. 4B. The NSS 105 can operate in conjunction with the frame 400 including at least one shutter 430 and a feedback sensor 605. ...

Claims

1. A portable neurostimulation system for use by a subject in need thereof, said portable system comprising:a. a first stimulus emitting component comprising a visual source configured to emit a visual stimulus having a frequency of about 20 Hz to about 60 Hz; andb. a second stimulus emitting component comprising an audio source configured to emit an auditory stimulus having a frequency of about 20 Hz to about 60 Hz, wherein said visual source and said audio source are operatively connected and comprised in a single headset device, and wherein said visual source is rotatable about said audio source.

2. The portable system of claim 1, wherein use of said system induces gamma oscillations in a brain region of said subject, thereby slowing progression of a mild cognitive impairment or dementia in said subject.

3. The portable system of claim 1 or 2, wherein said visual source comprises a light emitting diode that projects said visual stimulus towards a screen, wherein said visual stimulus comprises light pulses.

4. The portable system of any one of the preceding claims, wherein said visual source comprises a light emitting diode driver.

5. The portable system of any one of the preceding claims, wherein said audio source comprises a set of headphones.

6. The portable system of claim 5, wherein said audio source comprises supra-aural headphones.

7. The portable system of claim 6, wherein said supra-aural headphones further comprise a removable headband configured to secure said portable system to said head of said subject.

8. The portable system of claim 1, wherein said light pulses have a frequency of about 40 Hz to about 60 Hz.

9. The portable system of claim 8, wherein said light pulses have a frequency of about 35 Hz to about 45 Hz.

10. The portable system of claim 9, wherein said light pulses have a frequency of about 40 Hz.

11. The portable system of claim 1, wherein said auditory stimulus has a frequency of about 40 Hz to about 60 Hz.

12. The portable system of claim 11, wherein said auditory stimulus has a frequency of about 35 Hz to about 45 Hz.WO 2025 / 147596                                   PCT / US2025 / 01021813. The portable system of claim 12, wherein said auditory stimulus has a frequency of about40 Hz.

14. The portable system of any one of the preceding claims, wherein said visual source comprises glasses.

15. The portable system of claim 14, wherein said glasses comprise a lens that is not opaque.

16. The portable system of claim 15, wherein said lens comprises a translucent lens.

17. The portable system of claim 16, wherein said lens comprises a transmittance of about 0% to about 100%.

18. The portable system of claim any one of the preceding claims, further comprising a third stimulus emitting component comprising a haptic source, wherein said haptic source produces a haptic stimulus.

19. The portable system of claim 18, wherein said haptic stimulus has a frequency of about 40 Hz to about 60 Hz.

20. The portable system of claim 19, wherein said haptic stimulus has a frequency of about 35 Hz to about 45 Hz.

21. The portable system of claim 20, wherein said haptic stimulus has a frequency of about40 Hz.

22. The portable system of any one of claims 18-21, wherein said haptic stimulus comprises a vibration.

23. The portable system of any one of claims 1-22, further comprising an input device comprising a hand-held controller.

24. The portable system of claim 23, wherein said hand-held controller receives and transmits a signal dictating a dosing parameter corresponding to a frequency of said visual stimulus, a duration of said visual stimulus, a brightness of said visual stimulus, a color of said visual stimulus, a duration of said audio or haptic stimulus, an intensity of said audio or haptic stimulus, a frequency of said audio or haptic stimulus, or any combination thereof.

25. The portable system of claim 24, wherein said hand-held controller further comprises an independent power supply comprising batteries.

26. The portable system of claim 25, wherein said hand-held controller further comprises a rechargeable battery.

27. The portable system of any one of claims 23-26, wherein said hand-held controller is operably connected to receive and transmit said signal to said portable system using WiFi or Bluetooth signals.

28. The portable system of any one of claims 23-27, wherein said portable system further comprises adjustable inputs.WO 2025 / 147596                                   PCT / US2025 / 01021829. The portable system of claim 28, wherein said adjustable input for said portable system comprises an input for powering on and powering off said portable system.

30. The portable system of claim 28 or 29, wherein said adjustable input for said portable system comprises an input for pausing said visual, haptic, or audio stimulus.

31. The portable system of any one of the preceding claims, wherein said portable system further comprises adjustable inputs for said audio source.

32. The portable system of claim 31, wherein said adjustable inputs for said audio source comprise an adjustable volume input.

33. The portable system of any one of the preceding claims, wherein said portable system further comprises adjustable inputs for said haptic source.

34. The portable system of claim 33, wherein said adjustable inputs for said haptic source comprise an adjustable intensity input.

35. The portable system of any one of the preceding claims, wherein said portable system further comprises adjustable inputs for said visual source.

36. The portable system of claim 35, wherein said adjustable inputs for said visual source comprise an adjustable brightness input.

37. The portable system of any one of claims 28-36, wherein said hand-held controller comprises said adjustable inputs.

38. The portable system of any one of claims 28-36, wherein said visual source comprises said adjustable inputs.

39. The portable system of claim 38, wherein said visual source comprises a pair of glasses.

40. The portable system of any one of the preceding claims, wherein said single headset device provides improved comfort, portability, patient adherence, ease of use, or cognitive function of said subject's brain as compared to a portable system for benefiting a cognitive state or function of a brain of a subject comprising a visual source and an audio source that are not operatively configured to comprise a single headset device.

41. The portable system of any one of the preceding claims, wherein said portable system further comprises a rechargeable battery.

42. The portable system of any one of the preceding claims, wherein said portable system further comprises a base.

43. The portable system of claim 42, wherein said base is configured to house said portable system and a hand-held controller.

44. The portable system of claim 43, wherein said base is configured to provide a charge for said rechargeable battery of said portable system and a hand-held controller.WO 2025 / 147596                                   PCT / US2025 / 01021845. The portable system of any one of the preceding claims, wherein use of said system slowsprogression of a neurological disease.

46. The portable system of claim 45, wherein said neurological disease is Alzheimer’s disease.

47. The portable system of claim 45, wherein said neurological disease is Parkinson’s disease.

48. The portable system of claim 45, wherein said neurological disease is dementia.

49. The portable system of any one of the preceding claims, wherein said portable system is configured to transmit data to a clinician.

50. The portable system of claim 49, wherein said data comprises records of said subject’s use of the portable system, dosing parameters used by said subject, said subject’s cognitive state or function, or a combination thereof.

51. The portable system of any one of the preceding claims, wherein said portable system further comprises:c. a processor;d. a memory device; ande. a feedback sensor,wherein said processor receives an indication of a physiological assessment, cognitive assessment, neural assessment, or physical assessment of said subject through said feedback sensor and instructs said first stimulus-emitting component, said second stimulus-emitting component, or said third stimulus-emitting component based on said indication to adjust at least one parameter associated with said auditory, visual, or haptic stimulus.

52. The portable system of claim 51, wherein said adjustment of at least one parameter associated with said auditory, visual, or haptic stimulus comprises an adjustment that induces gamma oscillations in a brain region of said subject.

53. The portable system of claim 51 or 52, wherein said physical assessment of said subject involves ascertaining at least one of said subject's: compliance with proper use and positioning of said system, eye status, alert or sleep status, or environment and surroundings.

54. The portable system of any one of claims 51-53, wherein said neural assessment of said subject is received using brain wave sensors, an electroencephalography (EEG) device, an electrooculography (EOG) devices, or a magnetoencephalography (MEG) device.WO 2025 / 147596                                   PCT / US2025 / 01021855. The portable system of any one of claims 51-54, wherein said cognitive assessment of said subject is obtained through questions posed to said subject, activities and tasks performed by said subject in response to a prompt, or behaviors exhibited by said subject.

56. The portable system of any one of claims 51-55, wherein said processor further instructs said stimulus-emitting component to lengthen or shorten a duration of stimulation in response to said indication of said physiological, cognitive, neural, and / or physical assessment.

57. The portable system of any one of claims 51-56, wherein said physical assessment of said subject is performed to determine hearing of said subject.

58. The portable system of any one of claims 51-57, wherein said system is used to treat, prevent, or mitigate cognitive dysfunction in said subject.

59. The portable system of any one of the preceding claims, wherein use of said portable system comprises inducing one or more improvements in said brain region of said subject.

60. The portable system of claim 59, wherein said one or more improvements comprises maintaining or improving cognitive function in said brain region of said subject.

61. The portable system of claim 60, wherein said maintaining or improving cognitive function comprises maintaining or improving recognition, discrimination, spatial memory, working memory, attention, or a combination thereof.

62. The portable system of claim 60 or 61, wherein said one or more improvements comprises maintaining or reducing tau phosphorylation in said brain region of said subject.

63. The portable system of any one of claims 60-62, wherein said one or more improvements comprises maintaining or reducing an amount of amyloid-P (AP) peptide in said brain region of said subject.

64. The portable system of any one of claims 60-63, wherein said one or more improvements comprises maintaining or reducing an amount of C-terminal fragments (CTFs) of amyloid precursor protein (APP) in said brain region of said subject.

65. The portable system of any one of claims 60-64, wherein said one or more improvements comprises maintaining or reducing cleavage of APP into CTFs and NTFs by P-secretase (BACE1) in said brain region of said subject.

66. The portable system of any one of claims 60-65, wherein said one or more improvements comprises maintaining or reducing cleavage of APP into CTFs and NTFs by y-secretase in said brain region of said subject.WO 2025 / 147596                                   PCT / US2025 / 01021867. The portable system of any one of claims 60-66, wherein said one or more improvements comprises maintaining or reducing a number of endosomes in said brain region of said subject.

68. The portable system of any one of claims 60-67, wherein said one or more improvements comprises promoting clearance of Ap peptide in said brain region of said subject.

69. The portable system of any one of claims 60-68, wherein said one or more improvements comprises increasing uptake of Ap peptide by microglia in said brain region of said subject.

70. The portable system of any one of claims 60-69, wherein said dementia comprises Alzheimer’s disease, vascular dementia, Lewy body dementia, Pick's disease, frontotemporal dementia (FTD), AIDS dementia, age-related cognitive impairments, and age-related memory impairments.

71. The portable system of any one of claims 60-70, wherein said one or more improvements are increased by about 1% to about 100% in said subject as compared to a subject that does not use said portable system.

72. The portable system of claim 2, wherein said brain region comprises an entorhinal cortex, a hippocampus, a cerebral cortex, a visual association cortex, an auditory association cortex, a cingulate lobe, an amygdala, a thalamic nucleus, a cingulate lobe, a pons, a brainstem, a cerebellum, a lateral ventricle, an occipital lobe, a parietal lobe, a temporal lobe, a midbrain, a striatum, a basal ganglia, a globus pallidus, a substantia nigra, or any combination thereof.

73. A method comprising: stimulating a subject with said visual, auditory, or haptic stimulus generated by said portable system of any one of claims 1-72, thereby inducing gamma oscillations in a brain region of said subject.

74. A method of benefiting a cognitive state or function of a brain of a subject, comprising providing a subject said portable system of any one of claims 1-73, and stimulating said subject with said visual, auditory, or haptic stimulus, wherein use of said system induces gamma oscillations in at least one brain region of said subject and causes an improvement in one or more cognitive functions of said subject's brain, thereby slowing progression of mild cognitive impairment or Alzheimer's disease in said subject.

75. The method of claim 73 or 74, wherein said gamma oscillations comprise synchronized gamma oscillations.

76. The method of any one of claims 73-75, wherein said visual, auditory, or haptic stimulus is administered to said subject for about 10 minutes, about 30 minutes, about 45 minutes, about 1 hour, or more than about 1 hour per day.WO 2025 / 147596                                   PCT / US2025 / 01021877. The method of any one of claims 73-76, wherein said visual, auditory, or haptic stimulus is administered to said subject at least once, twice, three times, or more than three times per day.

78. The method of any one of claims 73-77, wherein said subject comprises a mammal.

79. The method of claim 78, wherein said mammal comprises a non-human primate.

80. The method of claim 78, wherein said mammal comprises a human.

81. The method of any one of claims 73-80, wherein said method further comprises a) identifying an activity being performed by a subject; and b) administering said visual, auditory, or haptic stimulus to said subject during said activity to induce a gamma oscillation in a brain region of said subject.

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