Methods for enhancing neurostimulation during activity - Patents.com

Abstract

The disclosed systems and methods relate to stimulation of nerves via non-invasive sensory stimulation. The non-invasive sensory stimulation may include audio, visual, mechanical, or combinations thereof. One or more combinations and / or sequences of audio, visual, and mechanical brain stimulation may modulate, control, or otherwise manage the frequency of neural oscillations to provide beneficial effects on one or more cognitive states or functions of the brain, while mitigating or preventing deleterious effects on cognitive states or functions resulting from, for example, sleep deprivation, stress, hormonal imbalance, or other physical, physiological, or psychological conditions. In so doing, the present systems and methods may enhance a person's cognitive potential.

Description

[Technical field]

[0001] cross reference This application claims the benefit of U.S. Provisional Patent Application No. 63 / 248,880, filed September 27, 2021, which is incorporated by reference herein in its entirety.

[0002] Incorporation by Reference Each patent, publication, and non-patent literature cited in this application is incorporated herein by reference in its entirety, as if each was individually incorporated by reference. [Background technology]

[0003] Neural oscillations occur in humans or animals and include rhythmic or repetitive neural activity in the central nervous system. Neural tissue can generate oscillatory activity by mechanisms within individual neurons or by interactions between neurons. Oscillations can also appear as oscillations in membrane potentials or periodic patterns of action potentials, which can result in oscillatory activation of postsynaptic neurons. Synchronized activity of a group of neurons can give rise to macroscopic oscillations, which can be observed by electroencephalography ("EEG"). Neural oscillations can be characterized by their frequency, amplitude, and phase. Neural oscillations can give rise to electrical impulses that form brainwaves. These signal characteristics can be observed from neural recordings using time-frequency analysis. Summary of the Invention

[0004] In some embodiments, the present disclosure provides a method comprising identifying an activity being performed by a subject and administering a sensory stimulus to the subject during the activity to induce gamma oscillations in a brain region of the subject.

[0005] In some embodiments, the subject has a disease or disorder associated with cerebral white matter atrophy, demyelination, or a combination thereof. In some embodiments, the method further comprises administering one or more agents to treat the disease or disorder.

[0006] In some embodiments, the sensory stimulus comprises one or more of a mechanical stimulus, an auditory stimulus, and a visual stimulus, hi some embodiments, the sensory stimulus comprises a frequency between 10 and 100 Hertz.

[0007] In some embodiments, the activity involves a cognitive process. For example, in some cases, the cognitive process includes one or more executive functions. In some cases, the executive functions include emotion regulation, 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.

[0008] In certain embodiments, the activity performed includes one or more cognitive processes selected from memory encoding, memory consolidation, memory recall, perception, attention, knowledge formation, problem solving, concept formation, pattern recognition, association, decision-making, motor coordination, task planning, language expression, or language comprehension.

[0009] In some cases, the administering step includes slowing neurodegeneration.

[0010] In some cases, the administering step causes a change in the subject's neurological behavior, anxiety behavior, depression behavior, addictive behavior, food-seeking behavior, or sleep behavior. In some cases, the administering step improves cognitive skills. For example, in some cases, the cognitive skills include perceptual reasoning, sustained attention, selective attention, divided attention, long-term memory, working memory, logic and reasoning, auditory processing, visual processing, visuomotor planning and processing, visuospatial planning and processing, auditory memory, visual memory, task planning, task sequencing, task initiation, task completion, visual encoding and decoding, auditory encoding and decoding, sensory encoding and decoding, language expression, language comprehension, processing speed, cognitive control, cognitive inhibition, declarative memory, procedural memory, episodic memory, auditory memory, visual memory, semantic memory, or autobiographical memory. In some cases, the processing speed includes one or more of visual processing speed, language processing speed, auditory processing speed, and motor processing speed.

[0011] In some cases, the activity performed includes sleeping, reading, or ingesting a substance. In some cases, the ingested substance increases blood flow. In some cases, the substance increases blood flow. In some cases, the substance includes a stimulant or depressant.

[0012] In some cases, the activity performed includes physical activity. In some cases, the activity includes taking a bath or shower. For example, in some embodiments, the sensory stimulus includes an auditory stimulus and a mechanical stimulus, and administering the sensory stimulus includes opening a water source, which increases and decreases water pressure, thereby administering the sensory stimulus to the subject during the activity. In some cases, the activity includes operating heavy machinery. In some cases, the operating heavy machinery includes an automobile or an aircraft.

[0013] The present disclosure further provides a system for slowing neurodegeneration in a subject in need thereof, comprising a stimulation emission component and one or more processors configured to: a) receive instructions from the subject; b) generate an output signal based on the instructions; and c) provide the output signal to the stimulation emission component, causing the stimulation emission component to provide stimulation according to the generated output signal, thereby slowing neurodegeneration in the subject. In some embodiments, the stimulation emission component includes a display device. In some cases, slowing neurodegeneration includes reducing cerebral white matter atrophy experienced by the subject. In some embodiments, slowing neurodegeneration includes reducing the rate of demyelination experienced by the subject.

[0014] In some embodiments, the instructions are associated with an activity performed by the subject. In some embodiments, the activity is selected from the group consisting of learning, researching, presenting, speaking, concentrating, analyzing, or listening. In some cases, the activity includes rearranging a posture or position of the subject. In some cases, the activity includes walking, jogging, skipping, running, hopping, marching, swimming, or any combination thereof. In some cases, the activity includes engaging in mental effort, physical effort, or a combination thereof. In some embodiments, the activity includes playing a logic game, a board game, or a video game.

[0015] In some embodiments of the systems provided herein, the system further comprises a feedback monitor configured to provide subject instructions.In some embodiments of the systems provided herein, the system further comprises a profile manager configured to provide subject instructions. [Brief description of the drawings]

[0016] [Figure 1]FIG. 1 is a block diagram illustrating a system for performing neurostimulation via visual stimulation, according to one embodiment. [Figure 2A] 2A-2F show visual stimulation signals that trigger neural stimulation, according to some embodiments. [Figure 2B] 2A-2F show visual stimulation signals that trigger neural stimulation, according to some embodiments. [Figure 2C] 2A-2F show visual stimulation signals that trigger neural stimulation, according to some embodiments. [Figure 2D] 2A-2F show visual stimulation signals that trigger neural stimulation, according to some embodiments. [Figure 2E] 2A-2F show visual stimulation signals that trigger neural stimulation, according to some embodiments. [Figure 2F] 2A-2F show visual stimulation signals that trigger neural stimulation, according to some embodiments. [Figure 3A] 3A-3C illustrate fields of view to which visual signals may be transmitted for visual brain entrainment, according to some embodiments. [Figure 3B] 3A-3C illustrate fields of view into which visual signals may be transmitted for visual-brain entrainment, according to some embodiments. [Figure 3C] 3A-3C illustrate fields of view into which visual signals may be transmitted for visual-brain entrainment, according to some embodiments. [Figure 4A] 4A-4C illustrate a device configured to transmit a visual signal for neurostimulation, according to some embodiments. [Figure 4B] 4A-4C illustrate a device configured to transmit a visual signal for neurostimulation, according to some embodiments. [Figure 4C] 4A-4C illustrate a device configured to transmit a visual signal for neurostimulation, according to some embodiments. [Figure 5A]5A-5D illustrate a device configured to transmit a visual signal for neurostimulation, according to some embodiments. [Figure 5B] 5A-5D illustrate a device configured to transmit a visual signal for neurostimulation, according to some embodiments. [Figure 5C] 5A-5D illustrate a device configured to transmit a visual signal for neurostimulation, according to some embodiments. [Figure 5D] 5A-5D illustrate a device configured to transmit a visual signal for neurostimulation, according to some embodiments. [Figure 6A] 6A and 6B illustrate a device configured to receive feedback to facilitate neural stimulation, according to some embodiments. [Figure 6B] 6A and 6B illustrate a device configured to receive feedback to facilitate neural stimulation, according to some embodiments. [Figure 7A] 7A and 7B are block diagrams illustrating embodiments of computing devices useful in connection with the systems and methods described herein. [Figure 7B] 7A and 7B are block diagrams illustrating embodiments of computing devices useful in connection with the systems and methods described herein. [Figure 8] FIG. 1 is a flow diagram of a method for performing neurostimulation using visual stimulation, according to one embodiment. [Figure 9] FIG. 1 is a block diagram illustrating a system for neural stimulation via auditory stimulation, according to one embodiment. [Figure 10A] 10A-10I illustrate types of audio signals and modulations to audio signals used to induce neural oscillations via auditory stimulation, according to some embodiments. [Figure 10B]10A-10I illustrate types of auditory signals and modulations on auditory signals used to induce neural oscillations via auditory stimulation, according to some embodiments. [Figure 10C] 10A-10I illustrate types of auditory signals and modulations on auditory signals used to induce neural oscillations via auditory stimulation, according to some embodiments. [Figure 10D] 10A-10I illustrate types of auditory signals and modulations on auditory signals used to induce neural oscillations via auditory stimulation, according to some embodiments. [Figure 10E] 10A-10I illustrate types of auditory signals and modulations on auditory signals used to induce neural oscillations via auditory stimulation, according to some embodiments. [Figure 10F] 10A-10I illustrate types of auditory signals and modulations on auditory signals used to induce neural oscillations via auditory stimulation, according to some embodiments. [Figure 10G] 10A-10I illustrate types of auditory signals and modulations on auditory signals used to induce neural oscillations via auditory stimulation, according to some embodiments. [Figure 10H] 10A-10I illustrate types of auditory signals and modulations on auditory signals used to induce neural oscillations via auditory stimulation, according to some embodiments. [Figure 10I] 10A-10I illustrate types of auditory signals and modulations on auditory signals used to induce neural oscillations via auditory stimulation, according to some embodiments. [Figure 11A] FIG. 2 illustrates an auditory signal generated using binaural beats according to one embodiment. [Figure 11B] 1 illustrates an acoustic pulse having an isochronous tone according to one embodiment. [Figure 11C] 4 illustrates an audio signal having a modulation technique that includes an audio filter, according to one embodiment. [Figure 12A]12A-12C illustrate configurations of a system for neural stimulation via auditory stimulation, according to some embodiments. [Figure 12B] 12A-12C illustrate configurations of a system for neural stimulation via auditory stimulation, according to some embodiments. [Figure 12C] 12A-12C illustrate configurations of a system for neural stimulation via auditory stimulation, according to some embodiments. [Figure 13] 1 illustrates a system configuration of room-based auditory stimulation for neurostimulation, according to one embodiment. [Figure 14] 1 illustrates a device configured to receive feedback and facilitate neural stimulation via auditory stimulation, according to some embodiments. [Figure 15] FIG. 1 is a flow diagram of a method for performing auditory brain entrainment, according to one embodiment. [Figure 16A] FIG. 1 is a block diagram illustrating a system for nerve stimulation via peripheral nerve stimulation, according to one embodiment. [Figure 16B] FIG. 1 is a block diagram illustrating a system for neural stimulation via multiple stimulation modes, according to one embodiment. [Figure 17A] FIG. 1 is a block diagram illustrating a system for neurostimulation via visual and auditory stimuli, according to one embodiment. [Figure 17B] FIG. 1 illustrates waveforms used for neural stimulation via visual and auditory stimuli, according to one embodiment. [Figure 18] FIG. 1 is a flow diagram of a method for neurostimulation via visual and auditory stimuli, according to one embodiment. [Figure 19] FIG. 13 is an efficacy summary chart for the modified intention-to-treat (mITT) population, including p-values, differences, confidence intervals (CIs), and value-based standardized estimates of efficacy. [Figure 20]Individual mean analyses of Alzheimer's Disease Composite Score (ADCOMS) optimized for Moderate Alzheimer's Disease (MADCOMS) for sham and active treatment groups are shown on the left and linear model analyses are shown on the right. [Figure 21] Individual mean analyses of Alzheimer's Disease Assessment Scale-Cognitive Subscale 14 (ADAS-Cog14) scores for the sham and active treatment groups are shown on the left, and linear model analyses are shown on the right. [Figure 22] Individual mean analyses of Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) values ​​for sham and active treatment groups are shown on the left and linear model analyses are shown on the right. [Diagram 23] Individual mean analyses of Alzheimer's Disease Cooperative Study-ADL Scale (ADCS-ADL) Activities of Daily Living scores for the sham and active treatment groups are shown on the left and linear model analyses are shown on the right. [Figure 24] Linear model analysis of Mini-Mental State Examination (MMSE) scores measured 6 months after treatment (i.e., final time point) is shown. [Diagram 25] Magnetic resonance imaging (MRI) results for whole brain volume are shown on the left, and linear model analysis of hippocampal volume is shown on the right, after 6 months of treatment. [Figure 26] 1 is a table showing a summary of efficacy findings from human clinical trials, including p-values, treatment differences, CI values, and percentage of slowing of brain atrophy. [Figure 27] Figure 27 shows graphs demonstrating the observed improvement in sleep quality (Panels A and B) of an exemplary gamma stimulation treatment in mild to moderate AD subjects over a 24 week period during the first 12 week treatment period (indicated by the line closest to the white arrow) and the second 12 week treatment period (indicated by the line furthest from the white arrow), as measured by a reduction in sleep fragmentation, expressed as a higher frequency of longer pause durations. Panels C and D show the observed effect of a sham treatment on sleep quality, as measured by a reduction in sleep fragmentation. [Figure 28]FIG. 28 demonstrates power changes in response to (1 hour) 40Hz LED stimulation in an exemplary embodiment, showing 40Hz steady-state oscillations and enhanced alpha wave power during and after stimulation in a young healthy subject. Both panels show time-frequency domain decomposition of EEG activity recorded at the occipital pole before, during, and after 40Hz gamma stimulation (Oz, channel 64). The start and stop of gamma stimulation are marked with STIM ON and STIM OFF boundaries in both panels. The top panel shows enhanced 40Hz power during stimulation, showing steady-state visual evoked potentials (SSVEPs). The bottom panel shows alpha power dynamics during eyes open (EYO) and eyes closed (EYC), as well as enhanced alpha power both during gamma stimulation with eyes open and after 1 hour of 40Hz gamma stimulation. [Figure 29] Figure 1 provides an illustration of the composite global cognitive summary score as a function of mean sleep fragmentation (Panel A) and the combined expression of genes enriched in aged microglia (Panel B). Dashed lines indicate the 95% confidence interval of the estimate. [Diagram 30] 1 provides oscilloscope captures of visual (upper signal) and auditory (lower signal) signals of an exemplary non-invasive sensory stimulus with fs equal to 40 Hz, vd equal to 50%, VD equal to 50%, ft equal to 7,000 Hz, and AD equal to 0.57%. [Diagram 31] FIG. 31 shows a schematic diagram of some aspects and parameters characterizing the auditory and visual stimulation components of gamma oscillations delivered by the auditory stimulation module (110, FIG. 33) and the visual stimulation module (120, FIG. 33), respectively, of the stimulation delivery system (170, FIG. 33). The number and relative dimensions of the elements in FIG. 31 are adjusted for presentation purposes and do not represent the number and relative dimensions for an actual embodiment. [Diagram 32]Enrollment, treatment, and controls for an exemplary embodiment of non-invasive stimulation to improve sleep quality in mild to moderate AD subjects are outlined below. Treatment was delivered to two-thirds of subjects (12) using 40 Hz frequency audio, and to one-third of subjects (6, "controls") with alternative frequencies. [Diagram 33] FIG. 33 provides a block diagram of an exemplary stimulation delivery system, analysis and monitoring system including modules specific to sleep-related monitoring and / or analysis. [Diagram 34] Actigraphy data from 24-hour activity levels (gray bars, 1501 in FIG. 37 ) over two days for a single exemplary patient are provided, centered at 12:00 AM (indicated by double-sided arrows), along with a median filtering curve (labeled with a dotted arrow, 1507 in FIG. 37 ). The horizontal axis of FIG. 34 indicates time of day, and the vertical axis is relative activity (arbitrary log scale) recorded on a wrist-worn actigraphy measurement device. Calculated sleep periods (black horizontal lines, see 1508 in FIG. 37 ) are shown along with individual sample rest periods (yellow horizontal lines, see 1509 in FIG. 37 ), with the top panel (a) showing an exemplary pattern of frequent movements and short rest periods during sleep periods, and the bottom panel (b) showing an exemplary pattern of less frequent movements and long rest periods during sleep periods. [Diagram 35] An exemplary pattern of actigraphy over several days (arbitrary units, see FIG. 34) is provided, showing the actigraphy (grey; e.g., 1501 in FIG. 37) with a smooth curve superimposed. A cutoff line (black) separates active and resting periods (e.g., 1505 / FIG. 37). The black square represents an initial estimate of the midnight point (e.g., 1507 in FIG. 37). The final estimate of the midnight point is determined through an optimization algorithm (e.g., 1508 in FIG. 37). [Diagram 36]An exemplary cumulative distribution of rest periods from one patient (e.g., 1511 in FIG. 37) is shown. Data from a first exemplary 12-week treatment (solid points, weeks 0-12) and data from a second exemplary 12-week treatment (dashed points) are shown. In some embodiments, the distribution is characterized by an exponential distribution (e.g., 1512 in FIG. 37). In further embodiments, an increase in the exponential decay constant represents an improvement in sleep quality (e.g., 1513 in FIG. 37). In this example, tau2=45 min, tau1=40 min, and taudiff=5 min>0. [Figure 37] 36 provides a flow diagram of an exemplary analysis process responsive to actigraphy data, provided in some embodiments at least in part by the actigraphy monitoring module 130) FIG. 33). In some embodiments, the analysis is directed to determining a cumulative distribution of rest periods over a period of one or more nighttime sleep periods (1511) of one or more subjects. In some embodiments, the analysis is further directed to fitting an exponential distribution to the determined cumulative distribution (1512). In some embodiments, the analysis is further directed to calculating summary statistics or characteristic parameters for the fitted exponential distribution. In an exemplary embodiment, an exponential decay constant for the fitted exponential distribution is determined (1512 in FIG. 36). In FIG. 37, terms in italics and brackets refer to MATLAB (R2020a) APIs used in the corresponding steps in the exemplary embodiment, e.g., "medfilt1" refers to 1-D median filtering. In some embodiments, alternative APIs, methods, or processes with equivalent functionality may be employed (e.g., the Wolfram Language's "ButterworthFilterModel" may be used in place of "butter"). [Figure 38]Sample actigraphy recordings are provided for one patient, demonstrating the effect of gamma stimulation treatment on sleep over five consecutive nights recorded before and five consecutive nights recorded after gamma stimulation treatment. Dark grey horizontal bars below the x-axis indicate periods of continuous activity, which appear significantly higher in actigraphy recordings taken before treatment than in actigraphy recordings taken after treatment. [Figure 39] Figure 39 shows the cumulative distribution of nighttime resting and active periods based on pooled data from all participants. Black squares indicate active periods and grey squares indicate resting periods. Panel A of Figure 39 shows the cumulative distribution using a log-linear scale, and Panel B of Figure 39 shows the cumulative distribution using a log-log scale. [Diagram 40] Graphs comparing relative changes in active periods are shown, with the Y-axis showing the change from weeks 1-12 during weeks 13-24. FIG. 40 demonstrates a reduction in the duration of active periods in the treatment group, and therefore reduced sleep fragmentation leading to improved sleep quality. In contrast, an inverse effect was seen in the sham group, represented by the line closest to the grey arrow. Panel A of FIG. 40 shows the relative change based on active period duration, and Panel B of FIG. 40 shows the normalized nighttime activity duration calculated by dividing the duration of each active period by the duration of the total nighttime period it corresponds to. [Diagram 41] FIG. 1 shows the effect of gamma stimulation treatment on maintaining daytime activity as assessed by the Activities of Daily Living (ADCS-ADL) scope. The graph shows that the change in daytime activity was significantly improved in the treatment group and decreased in the sham treatment group. The X-axis compares the 1-12 week period with the 13-24 week period. The Y-axis shows the change in ADCS-ADL score during weeks 13-24 versus weeks 1-12. [Diagram 42]We provide a flow diagram illustrating the proposed relationship between Alzheimer's disease and sleep dysfunction. This diagram was 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. [Diagram 43] An exemplary embodiment of a handheld controller for adjusting parameters of stimulation delivered by an operably coupled stimulator is provided. [Diagram 44] Results are provided for % change in material volume from baseline for treatment and control groups receiving 40Hz gamma sensory stimulation and sham sensory stimulation treatments, respectively, over a 6-month period. Dark grey boxes represent treatment group participants and light grey boxes represent placebo group participants. Error bars indicate standard error (SE). [Diagram 45] Figure 1 shows the ratio of T1-weighted to T2-weighted (T1w / T2w) white matter change (% change from baseline) for placebo (light grey) and treatment (dark grey) participants after sham and 40 Hz gamma sensory stimulation treatment, respectively, over a 6-month period. [Figure 46A] Figure 46 provides measurements of volumetric changes in white matter structures as percent change relative to baseline. Treatment group participants are shown in dark grey, and placebo group participants' results are shown in light grey. Figure 46A provides results for the entorhinal region, left cingulate lobe, pars triangularis region, cuneus region, lateral occipital region, posterior central region, left occipital lobe, left frontal lobe, left parietal lobe, occipital lobe, left temporal lobe and caudal central frontal region (sorted in ascending order by p-value) for the treatment group after 6 months of treatment. [Figure 46B]Figure 46 provides measurements of volumetric changes in white matter structures as percent change relative to baseline. Treatment participants are shown in dark grey, and placebo participants' results are shown in light grey. Figure 46B provides results (sorted in ascending order by p-value) 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. [Figure 47A] Figure 47 shows the change in T1w / T2w ratios (% change from baseline) in white matter structures for placebo and treatment participants after sham and 40Hz gamma sensory stimulation treatments, respectively, over a 6-month period. Figure 47A provides results for the entorhinal region, parastriate region, posterior central region, left parietal lobe, lateral occipital region, paracentral region, rostral central frontal region, brachial region, precentral region, parietal lobe, right occipital lobe, fusiform region, occipital lobe, left frontal lobe, cuneate region, precorneal region, inferior parietal region, frontal lobe, lingual region, left occipital lobe, left temporal lobe, right parietal lobe, and paraorbital region, with white matter structures sorted in ascending order by p-value. [Figure 47B] Figure 47 shows the change in T1w / T2w ratios (% change from baseline) in white matter structures for placebo and treatment participants after sham and 40Hz gamma sensory stimulation treatments, respectively, over a 6-month period. Figure 47B provides results for the right frontal lobe, caudal central frontal region, rostral anterior cingulate region, superior frontal region, temporal lobe, medial orbitofrontal region, posterior cingulate region, superior parietal region, left cingulate lobe, superior temporal region, cingulate lobe, and temporal pole region, with white matter structures sorted in ascending order by p-value.

[0017] Features and advantages of the present solution will become apparent from the detailed description set forth below in conjunction with the drawings in which like reference numerals generally refer to similar elements and in which: DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] Described herein is a system and method for using non-invasive stimulation to a human subject and / or generating gamma wave oscillations in the brain of a human subject, which can improve one or more cognitive functions of the subject.In particular, the present disclosure uses non-invasive stimulation to generate sensory evoked potentials in at least one area of ​​the brain, thereby causing neuromodulatory effects in the brain of the subject.The present disclosure achieves improvements in mood, behavior, cognitive processing, memory, executive function, focus, and neurostimulation.

[0019] The systems and methods described herein may affect one or more of the cognitive processes. For example, the systems and methods described herein may cause improvements in emotion regulation, perceptual reasoning, cognitive flexibility, goal-directed persistence, metacognition, organization, planning / prioritization, response inhibition, stress resistance, sustained attention, task initiation, time management, working memory, or combinations thereof. Other cognitive processes that may benefit from the systems and methods described herein include sensory registration, short-term memory formation, long-term memory formation, memory encoding, memory consolidation, molecular or cellular memory consolidation, recall, cognition, attention, knowledge formation, problem solving, concept formation, pattern recognition, association, decision-making, motor coordination, decision-making, planning, language generation, or language comprehension. Additional mental processes that may benefit from the techniques described herein may further include mental arithmetic, visual encoding and decoding, auditory encoding 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, ordering, initiation, and completion.

[0020] The present disclosure is further directed to improving cognitive skills, which may include one or more of sustained attention, selective attention, divided attention, long-term memory, working memory, logic and reasoning, auditory processing, visual processing, processing speed, cognitive control, cognitive inhibition, declarative memory, procedural memory, episodic memory, semantic memory, and autobiographical memory.

[0021] The technical solution includes aspects covering the achievement of entrainment of gamma wave oscillations in the brain through various methods and systems, patient activity, motivation and feedback to the user and / or third parties, and monitoring and analysis of specific stimulation parameters targeted to improve cognition and cognitive function. Entrainment of gamma wave oscillations in the brain can be performed using non-invasive sensory stimulation, which can include tactile or mechanical stimulation, peripheral nerve stimulation, visual stimulation, auditory stimulation, or combinations thereof. The present disclosure further achieves improvements in brainwave coherence, as measured by increased power in alpha waves and other frequency bands, as well as other methods for assessing functional connectivity, and is associated with cognitive function, brain health, and overall health.

[0022] The systems and methods of the present disclosure may be directed to improving a person's cognitive capacity. In some embodiments, the present disclosure may improve or maintain an individual's cognitive function. Any individual may use the systems and methods of the present disclosure. The individual may be neurotypical or neurodiverse. In some embodiments, the individual suffers from a neurodegenerative disease. In some embodiments, the individual suffers from a physiological disorder, a psychological disorder, a psychosomatic disorder, or a psychiatric disorder.

[0023] In some embodiments, the present disclosure provides systems and methods for alleviating symptoms associated with microglia-mediated diseases or disorders associated with brain atrophy. For example, microglia-mediated diseases or disorders may include tauopathy-related neurodegenerative diseases, including but not limited to chronic traumatic encephalopathy, frontotemporal dementia, and corticobasal degeneration. Microglia-mediated diseases or disorders may include genetic disorders, such as hereditary ataxias associated with brain atrophy. Microglia-mediated diseases or disorders may further include neuropsychiatric disorders associated with brain atrophy, such as depression or schizophrenia, brain injuries, such as stroke, or demyelinating diseases, such as multiple sclerosis and acute disseminated encephalomyelitis.

[0024] Neurodegenerative diseases causing tauopathies: Alzheimer's disease, frontotemporal dementia, chronic traumatic encephalopathy, and corticobasal degeneration In some embodiments, the microglia-mediated disease or disorder may include neurodegenerative diseases associated with tauopathy, including, but not limited to, Alzheimer's disease, frontotemporal dementia, chronic traumatic encephalopathy (CTE), and corticobasal degeneration.

[0025] Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the decline of memory, orientation, and reasoning. AD may be characterized by the accumulation of amyloid plaques, including amyloid-β (Aβ) peptides and neurofibrillary tangles (NFTs) made of tau protein. Under normal conditions, soluble Aβ peptides are produced and secreted by neurons and then cleared from the brain via the cerebrospinal fluid (CSF) pathway. However, in subjects suffering from AD, Aβ peptides appear to aggregate into higher order species to form soluble oligomers and insoluble plaques in a concentration-dependent manner. This aggregation may initiate a number of neurotoxic events, including disruption of brain metabolism, neuroinflammation, reduced functional connectivity, loss of synapses and neurons, and / or formation of NFTs.

[0026] Frontotemporal dementia (FTD) is a group of disorders resulting from damage to the frontal and temporal lobes of the brain. Depending on the location of the damage, the disorder can cause social behavior, personality changes, and / or loss of language skills. In some people, FTD can also result in neuromuscular disorders such as Parkinsonism. Frontotemporal dementia occurs when abnormal proteins accumulate in the brain, causing brain cell death and atrophy of the frontal and temporal lobes of the brain. Frontotemporal dementia occurs in Alzheimer's disease, but can also be caused by other neurodegenerative diseases.

[0027] Chronic traumatic encephalopathy (CTE) is characterized by symptoms that may include memory loss, confusion, impaired judgment, impulse control problems, aggression, depression, anxiety, suicidal tendencies, parkinsonism, and progressive dementia. CTE caused by traumatic injury to the head induces microglia to phosphorylate tau protein at progressively higher rates, thus leading to the accumulation of hyperphosphorylated tau deposits. The accumulation of phosphorylated tau protein can cause axonal transport defects, neuroinflammation, and synaptic loss.

[0028] Corticobasal degeneration (CBD) is characterized by cell loss and deterioration in certain regions of the brain. In corticobasal degeneration, abnormal levels of tau accumulate in certain brain cells, eventually causing their deterioration. Symptoms often initially involve experiencing movement abnormalities in one limb, which gradually spreads to all limbs. Such movement abnormalities include, for example, progressive stiffening or tightening of the limb's muscles (progressive asymmetric rigidity), and the inability to perform purposeful or voluntary movements (ataxia). Speech and language troubles include aphasia, aphasia, dysarthria, and dysphagia. Symptoms may further be reflected in physical movements and tremors, such as experiencing motor tremors, postural tremors, bradykinesia, ataxia, 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.

[0029] Genetic Disorders: Hereditary Ataxias As mentioned above, the system and method can be used to alleviate the symptoms associated with hereditary ataxia.Hereditary ataxia is characterized by a slowly progressive incoordination of walking, often accompanied by poor coordination of hands, speech, and eye movements.Hereditary ataxia often causes cerebellar atrophy as a result of the circuitry and dysfunction of the cerebellar cortex, which is the result of neurodegeneration of cellular afferents and Purkinje cells, which have long axonal projections that comprise the only source of output from the cerebellar cortex to the deep cerebellar nuclei.

[0030] Neuropsychiatric disorders: schizophrenia, depression, chronic stress In other embodiments, the present disclosure provides systems and methods for treating neuropsychiatric disorders associated with brain atrophy mediated by microglial cells. For example, individuals suffering from schizophrenia often show a decrease in 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, neurogenesis disorders, and defects in synaptic plasticity are associated with depression. Chronic stress promotes microglial overcrowding and astrocyte atrophy. Thus, in some embodiments, the disclosed systems and methods can alleviate symptoms associated with chronic stress or depression by improving synaptic plasticity and stimulating neural networks, along with improving microglia-mediated clearance.

[0031] Brain trauma: stroke and related cerebrovascular diseases In some embodiments, the present disclosure provides systems and methods for alleviating symptoms associated with stroke. For example, the stroke can be an ischemic stroke, which triggers a neuroinflammatory response and activates microglia to aid in brain repair. Ischemic stroke is associated with loss of synaptic activity. As a result, during ischemic stroke, brain tissue within the penumbra is structurally intact but functionally silent. Failure to reperfuse this penumbra region or resupply glucose and oxygen in a timely manner can cause atrophy of brain cells located in the penumbra. In contrast, activation of synapses in this region can delay cell death and salvage brain tissue. The present systems and methods can alleviate brain atrophy and associated symptoms associated with ischemic stroke by improving synaptic plasticity and stimulating neural networking. Other forms of cerebrovascular disease with similar symptoms (e.g., neuroimmunomodulation, synaptic function) may also be treated by the present disclosure, including, but not limited to, transient ischemic attacks (TIA), hemorrhagic stroke, arteriovenous malformations, intracranial atherosclerosis (ICAD), and Moyamoya disease.

[0032] Demyelinating diseases: multiple sclerosis and acute disseminated encephalomyelitis In some embodiments, the present disclosure provides systems and methods for reducing symptoms of demyelinating diseases associated with brain atrophy. For example, demyelinating diseases may include 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. Extensive myelin damage occurs, causing damage to the myelin-rich white matter of the brain, as a result of multiple attacks that occur over time. In acute disseminated encephalomyelitis, similar symptoms are seen, but the onset of extensive myelin damage is often due to a single episode or attack. By reducing neuroinflammation and stimulating neural networks, the present disclosure provides systems and methods for slowing brain atrophy associated with demyelinating diseases and related conditions.

[0033] In some embodiments, the system and method are aimed at reducing interference in cognitive function. Cognitive interference has a significant impact on cognitive performance across a variety of functions, including perception, attention, and memory. People are susceptible to or exposed to interference in their daily lives. Thus, there are many populations that may benefit from a system or method that specifically aims to enhance the ability to deal with interference. Furthermore, many individuals who have not experienced a perceptible decline in cognitive function may wish to enhance their current cognitive abilities. One example is to improve performance in everyday tasks (e.g., multitasking, focus, memory, social skills such as conversation skills, decision-making abilities, creativity, or reaction times for specific tasks). Another example is to improve general measures of cognitive ability (e.g., "strengthen IQ").

[0034] The present disclosure may be directed to improving cognitive performance in people who do not necessarily experience cognitive decline or cognitive impairment.The secondary effect of improving cognitive function may also motivate the use of the present technology.For example, a group whose activities involve multitasking may improve their performance in performing their professional duties or hobbies through the use of the systems and methods described herein.Examples of such groups include, but are not limited to, athletes, airline pilots, military personnel, doctors, call center personnel, teachers, and vehicle operators.

[0035] In other embodiments, the present disclosure provides a method and system for improving the cognitive potential of a user. In some embodiments, the present disclosure provides a system and method for increasing the cognitive performance of the general population. In other embodiments, the systems and methods described herein can be used to improve cognitive processing during a time frame or activity. For example, the systems and methods may be used to momentarily increase a user's focus during a presentation, or the systems and methods may be used in a manner in which gamma therapy is administered one or more of before, during, and after learning the material to help reinforce the material being learned.

[0036] The systems and methods of the present disclosure may be used during a range of activities. They may also be used to improve performance of the activities. Improved performance may be achieved in activities, functions, or processes independent of the activities involving the use of the systems and methods. Alternatively, or additionally, the improvement in performance may be directly related to the activities during which the person engages in or that involve the systems and methods described herein. The activities may include leisure, work, physical effort, mental effort, or all of the above. Cognitive processes that may be involved in such activities include, but are not limited to, memory consolidation or recall, emotion regulation, cognitive flexibility, goal-directed persistence, metacognition, organization, planning / prioritization, response inhibition, stress tolerance, sustained attention, task initiation, time management, working memory, or combinations thereof.

[0037] In some embodiments, the disclosed system and method can improve cognitive performance by slowing brain atrophy.Subjects with brain atrophy can experience this as part of normal aging, or as a result of or due to various diseases, disorders, or disorders, including but not limited to Alzheimer's disease (AD), dementia, Parkinson's disease, stroke, cerebral palsy, senile dementia, Pick's disease, Huntington's disease, Krabbe's disease, leukodystrophy, multiple sclerosis, epilepsy, anorexia nervosa, aphasia, learning disability, frontotemporal dementia, expressive aphasia, receptive aphasia, Lewy body dementia, chronic traumatic encephalopathy (CTE), etc.

[0038] In some embodiments, the systems and methods of the present disclosure may improve cognitive performance by reducing symptoms of brain atrophy. Symptoms may include loss of neurons, memory loss, vision problems, aphasia, balance problems, paralysis, loss of cortical volume, increased CSF volume, loss of motor control, difficulty with speech, comprehension, reading comprehension, memory, loss of gray and / or white matter, loss of neuron size, loss of neuronal cytoplasmic proteins, or any combination thereof. In some embodiments, the present disclosure describes systems and methods that act to delay the onset of symptoms of brain atrophy. The present disclosure provides systems and methods for treating any of the above diseases and disorders by reducing any of the above symptoms associated with brain atrophy.

[0039] For example, the methods and systems described herein can alleviate symptoms of depression. Stress, neurogenesis disorders, and synaptic plasticity defects are associated with depression. Chronic stress promotes microglial overcrowding and astrocyte atrophy. Thus, in some embodiments, the disclosed systems and methods can alleviate symptoms associated with chronic stress or depression by improving synaptic plasticity and stimulating neural networks, along with improving microglial mediated clearance.

[0040] The system and method described herein can use sensory evoked potentials to slow down brain atrophy and thus alleviate symptoms associated with brain atrophy through various mechanisms.For example, the present disclosure describes systems and methods for reducing neuroinflammation, improving synaptic plasticity, stimulating neural networks, and improving microglia-mediated removal of brain damage, all of which can contribute to the progression of brain atrophy by inducing synchronous gamma oscillations in at least one region of the subject's brain.The at least one brain region can include, for example, the subject's visual cortex, somatosensory cortex, insular cortex, and / or hippocampus.The present disclosure further describes systems and methods for alleviating symptoms of diseases and disorders associated with brain atrophy through non-invasive stimulation of gamma oscillations.

[0041] Brain tissue atrophy represents the loss of volume within neurons, extracellular space, or glia. Atrophy may occur at different rates in different regions or areas of the brain and may be reflected by changes in the total brain volume. For adults, the total brain volume may be, for example, about 950ml to 1550ml. For adult women, the average total brain volume may be about 1130ml. For adult men, the average brain volume may be about 1260ml. For children aged about 4 to 16 years, the total brain volume may be, for example, 60ml to 120ml.

[0042] Brain volume can be measured using magnetic resonance imaging (MRI) or computed tomography (CT) scans. Brain volume loss can be measured by comparing brain volumes over time. Various methods can be used to measure brain volume or brain volume changes that indicate brain atrophy. Most commonly, brain volume or brain volume loss can be measured using cross-sectional or longitudinal methods. Cross-sectional methods can use a single MRI scan to segment specific 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 time points to calculate brain volume change or atrophy. Longitudinal methods attempt to align two MRI scans using warping techniques, and from this process, small changes in brain volume can be directly extracted.

[0043] Various tools and algorithms can be employed to determine brain volume through CT or MRI scans. Examples of various toolkits available for determining brain volume and brain volume changes based on scanned images include, but are not limited to, the following tools: Atropos, an open source tissue segmentation algorithm; CIVET, a web-based image processing tool for volumetric analysis using various human brain images; Structural Image Assessment (SIENA and SIENAX), a software that applies the Brain Extraction Tool (BET) to determine cross-sectional volumes; MSmetrix, a fully automated tool that detects brain lesions, calculates lesion volumes, and measures whole brain and gray matter atrophy; and Statistical Parametric Mapping (SPM) tools for the analysis of images in the MATLAB environment.

[0044] Subjects with brain atrophy may experience this as a cause or result of a variety of diseases, disorders, or conditions, including but not limited to the following: Alzheimer's disease (AD), dementia, Parkinson's disease, stroke, cerebral palsy, senile dementia, Pick's disease, Huntington's disease, Krabbe's disease, leukodystrophy, multiple sclerosis, epilepsy, anorexia nervosa, aphasia, learning disabilities, frontotemporal dementia, expressive aphasia, receptive aphasia, dementia with Lewy bodies, chronic traumatic encephalopathy (CTE), and the like.

[0045] The change in brain volume may be a decrease of 0.3 cm3 / month, 0.5 cm3 / month, 1 cm3 / month, 2 cm3 / month, 0.3 cm3 / year, 0.5 cm3 / year, 1 cm3 / year, 2 cm3 / year, 3 cm3 / year, 4 cm3 / year, 5 cm3 / year, 6 cm3 / year, 7 cm3 / year, 8 cm3 / year, 9 cm3 / year, 10 cm3 / year, 11 cm3 / year, 12 cm3 / year, 13 cm3 / year, 14 cm3 / year, or 15 cm3 / year, or 16 cm3 / year. The rate of brain atrophy may vary between individuals. Exemplary rates of brain atrophy include, but are not limited to, the following: -0.1% to 0.5% / year, 0.5% to 1.5% / year, 1.0% to 3.0% / year, or 3.0% to 6.0% / year. The rate of brain atrophy may vary based on the cause of atrophy. For example, healthy individuals may experience average brain atrophy rates of 0.1% and 0.4% per year. In contrast, for subjects suffering from multiple sclerosis (MS), the average brain atrophy rate may be 0.5%-1.3% per year. The average rate of total brain atrophy in Alzheimer's disease patients may be, for example, 1.0%-4.0% per year. Aging may further cause an increase in the rate of brain atrophy. For example, individuals in their 30s may experience a brain atrophy rate of about 0.2% / year, and individuals at about 60 years of age may experience a brain atrophy rate of about 0.5% / year.

[0046] The systems and methods of the present disclosure are further directed to alleviating symptoms of brain atrophy. Symptoms may include loss of neurons, memory loss, vision impairment, aphasia, balance disorder, loss of cortical volume, increase in CSF volume, loss of motor control, difficulty in speaking, understanding, reading comprehension, memory, loss of gray and / or white matter, loss of neuron size, loss of neuronal cytoplasmic protein, or any combination thereof. In some embodiments, the present disclosure describes systems and methods that act to delay the onset of symptoms of brain atrophy. The present disclosure provides systems and methods for treating any of the above diseases and disorders by reducing any of the above symptoms associated with brain atrophy.

[0047] The present disclosure is also directed to improving executive functions of the brain, which may include perception, attention, knowledge formation, problem solving, concept formation, pattern recognition, association, decision-making, comprehension, motor coordination, decision-making, planning, or language production.

[0048] In some embodiments, the disclosed system and method may improve cognitive performance by improving microglial clearance, reducing amyloid-β load, reducing tau tangles, or promoting other neuroprotective physiological responses. For example, the disclosed system and method may improve cognitive performance by reducing the level (e.g., amount or rate) of Aβ peptide in at least one brain region of a subject. In some embodiments, the disclosed system and method may reduce the production of Aβ peptide in at least one brain region of a subject, for example, by reducing the level (e.g., amount or rate) of C-terminal fragment (CTF) and / or N-terminal fragment (NTF) of APP in at least one brain region of a subject. Synchronized gamma oscillations may reduce the cleavage of APP into CTF and NTF by BACE1 and / or γ-secretase in at least one brain region of a subject. Synchronized gamma oscillations may reduce the level (e.g., number or percentage) of endosomes in at least one brain region of a subject. For example, the endosomes may be positive for early endosomal antigen 1 (EEA1) and / or Ras-associated protein (Rab5) encoded by the RAB5A gene. In some embodiments, synchronized gamma oscillations can improve cognitive performance by promoting the clearance of Aβ peptides in at least one brain region of the subject. Synchronized gamma oscillations can increase the uptake of Aβ peptides by microglia in at least one brain region of the subject.

[0049] The disclosed system and method may also improve cognitive performance by increasing the level (e.g., number or percentage) of microglial cells, morphological changes of microglial cells consistent with a neuroprotective state, and / or activity of microglial cells in at least one brain region of a subject, including generating synchronized gamma oscillations in at least one brain region of the subject. The synchronized gamma oscillations may upregulate at least one differentially expressed gene, such as Nr4a1, Arc, Npas4, Cd68, B2m, Bsr2, Icam1, Lyz2, Irf7, Spp1, Csf1r, and / or Csf2ra, involved in microglial activity in at least one brain region of the subject. The morphological changes of microglial cells consistent with a neuroprotective state may include an increase in cell body size and / or a decrease in process length.

[0050] In some embodiments, the disclosed system and method may improve cognitive performance by optogenetically stimulating FS-PV interneurons in the hippocampus with multiple light pulses, causing the FS-PV interneurons to express an optogenetic actuator, thereby injecting in vivo synchronous gamma oscillations measured in local field potentials in excitatory neurons (e.g., FS-PV-interneurons), which in turn reduces the level of Aβ peptides in the hippocampus of a subject, thereby reducing the level (e.g., amount or percentage) of Aβ peptides. The light pulses may have a pulse frequency of about 40 pulses / sec. Each light pulse may have a duration of about 1 ms. At least one light pulse may have a wavelength of about 473 nm. The optogenetic actuator may include channelrhodopsin, halorhodopsin, and / or arcarhodopsin. For example, the optogenetic actuator may be channelrhodopsin-2 (ChR2).

[0051] In some embodiments, the disclosed systems and methods can improve cognitive performance by reducing the level (e.g., amount or percentage) of soluble and / or insoluble Aβ peptides in the visual cortex of a subject, including stimulating the subject with multiple light pulses at a pulse frequency of about 40 pulses / s, thereby inducing synchronous gamma oscillations in the visual cortex in vivo to reduce the level of soluble and / or insoluble Aβ peptides in the visual cortex. In some embodiments, the disclosed systems and methods can also improve cognitive performance by reducing the level (e.g., amount or percentage) of tau phosphorylation in the visual cortex of a subject.

[0052] The disclosed method and system may include evaluating the likelihood that the subject responds successfully to the sensory stimulation that promotes the entrainment of gamma oscillations.For example, a successful response may include the subject showing a willingness to engage in the sensory stimulation that promotes the entrainment of gamma oscillations in one or more brain regions.In some embodiments, the neurostimulation system may identify a high probability of successful response and, in response, provide the subject with a prompt that asks the subject to accept or reject the administration of gamma stimulation.In some embodiments, a successful response may include that the degree of gamma oscillations in the brain region is higher than before the sensory stimulation is administered.

[0053] The present disclosure also describes techniques for monitoring a person's activity, identifying whether gamma stimulation may be administered during that activity, and if so, presenting the person with a prompt to initiate gamma stimulation. In some embodiments, the present disclosure describes techniques for monitoring a person's activity, identifying whether gamma stimulation may be administered during that activity, and providing gamma stimulation if identified as appropriate. In some embodiments, the described techniques involve a sensor operably coupled to a device. The device can include any device capable of input and output functions.

[0054] A sensor operably coupled to the device can inform whether the subject can benefit from administration of gamma stimulation. For example, the benefit from administration of gamma stimulation can be one or more of the following: (a) maintaining and / or reducing blood levels (e.g., amounts) of glucocorticoids involved in stress response in the subject; (b) preventing and / or reducing anxiety in the subject; (c) maintaining and / or enhancing memory associations in the subject; (d) maintaining and / or improving cognitive flexibility; (e) maintaining and / or reducing changes in anatomical structure and / or morphology in at least one brain region of the subject; (f) maintaining and / or reducing changes in the number of neurons, the quality of DNA in neurons, and / or synaptic puncta density. In some embodiments, a device that induces synchronous gamma oscillations in at least one brain region of the subject can prevent, reduce, and / or treat dementia and / or anxiety in the subject, maintain and / or enhance memory associations and / or cognitive flexibility in the subject, and / or maintain and / or reduce changes in anatomical structure, morphology, cells, and molecules in at least one brain region of the subject.

[0055] For example, the benefit may include (c) maintaining and / or enhancing memory associations in the subject. In one aspect, maintaining and / or enhancing memory associations includes maintaining and / or enhancing spatial memory. In one aspect, the benefit includes (d) maintaining and / or enhancing cognitive flexibility. In one aspect, the benefit includes (e) maintaining and / or reducing changes in at least one brain region. For example, the changes in anatomy and / or morphology may include changes in one or more of the following - brain weight, lateral ventricle size, cortical layer thickness, neural layer thickness, and / or blood vessel diameter. The at least one brain region may include, for example, the visual cortex, somatosensory cortex, and / or insular cortex. In another embodiment, the benefit includes (f) maintaining and / or reducing changes in the number of neurons, the quality of DNA in neurons, and / or synaptic puncta density in at least one brain region of the subject, such as the visual cortex, somatosensory cortex, insular cortex, and / or hippocampus of the subject.

[0056] In some embodiments, the technical solution provides methods and systems for monitoring and / or observing and / or recording conditions related to non-invasive sensory stimulation. In some embodiments, the monitoring and / or observing and / or recording is implemented and / or provided by the neurostimulation system. In some embodiments, the monitoring is provided via a separate, operably linked device, such as a personal tablet or mobile phone. In some embodiments, monitoring of the situation or setting in which the treatment is administered, or more generally, monitoring of the context of the user of the treatment or of others involved in the delivery of the treatment, may usefully inform the scheduling and selection of the device through which the treatment is delivered, the scheduling and dosing of the treatment, or other aspects of the management and delivery of the treatment and related activities and interactions. In such scenarios, monitoring of the context or setting may also usefully inform the configuration and management of other aspects of the treatment delivery and treatment outcome, including analysis of the effectiveness of the treatment and identification of more or less effective opportunities for treatment delivery, or participation and burden with respect to the treatment.

[0057] In some embodiments, aspects related to non-invasive sensory stimulation include, but are not limited to, one or more of the following: user context, social context, events, environment, ambient conditions, device environment, device capabilities, location, weather, activity. In some embodiments, the monitoring and / or observation and / or recording is directed to improving treatment efficacy and / or outcomes and / or engagement and / or compliance of one or more users and / or third parties. In some embodiments, the monitoring and / or observation and / or recording is directed to one or more of the following: stimulation delivery management, stimulation configuration, identification of opportunities for treatment delivery, scheduling of treatment delivery, configuration of treatment delivery. In some embodiments, one or more of the following: treatment dispatch, treatment distribution, treatment configuration, feedback, motivation, analysis, combinations thereof are responsive to the monitoring and / or observation and / or recording.

[0058] In some embodiments, the technical solution performs monitoring of social aspects. In some embodiments, the social aspects include, but are not limited to, one or more of the following: presence of one or more users and / or third parties, one or more relationships between one or more users and / or third parties, social calendar, social context, social events, social network information, social network activity, interactions between one or more users and / or third parties, propinquity, proximity between two or more users and / or third parties, contact and / or contact and / or proximity history between two or more users and / or third parties. In some embodiments, the monitoring of social aspects is directed to one or more of the following: identifying one or more social relationships, recording one or more social networks, verifying one or more social aspects, identifying one or more social aspects. In some embodiments, the monitoring of social aspects is directed to one or more of the following: identifying current and / or potential care partners, locating current and / or potential care partners, locating and / or identifying friends, relatives, caregivers, clinicians, or other third parties. In some embodiments, the monitoring of social aspects is performed by the neurostimulation system. In other embodiments, the monitoring of social aspects is performed by a computer processor. In some embodiments, the monitoring of social aspects is performed by operably linking a personal device, such as a tablet or smartphone, to the neurostimulation system. In other systems, a cloud-based system for transferring data and information is used.

[0059] In exemplary embodiments, the monitoring of social aspects is directed to one or more of the following: recording and / or characterizing the involvement and / or participation of one or more third parties in the administration of one or more of the non-invasive sensory stimuli. In exemplary embodiments, the monitoring of social aspects is directed to distributing and / or alleviating and / or allocating one or more burdens and / or workloads and / or tasks associated with the non-invasive sensory stimuli. For example, the monitoring of social aspects may include monitoring the distribution of the workload associated with the non-invasive sensory stimuli among care partners or caregivers over a period of time. In such examples, in some embodiments, scheduling or location or administration is developed or modified in response to such monitoring directed to distributing the workload more equally among the care partners or caregivers and / or identifying alternative or substitute care partners or caregivers. In some embodiments, the monitoring of social aspects identifies two or more caregivers or care partners characterized by a social relationship with one or more of each other, the user, or a third party. In some embodiments, the identification of two or more caregivers or care partners characterized by social relationships is directed to coordinating the treatment-related activities of the two or more caregivers or care partners. For example, the identification of relationships such as kinship, friendship, or frequent contact or communication between two or more people who participate in supporting the administration of non-invasive sensory stimulation or related activities may be used in part to schedule a treatment session so that two or more such people are available whenever care is administered, or to provide options for two or more such people to support treatment delivery. Conversely, in some embodiments, monitoring of social aspects, in particular monitoring of one or more individuals' contacts or contact history, is used in part (e.g., in combination with infection tests, epidemiological data, or other health information) to limit and / or select individuals and / or to restrict and / or exclude individuals' participation in the administration of non-invasive sensory stimulation.In some embodiments, the monitoring of social aspects is directed to reducing the chances that the user and / or individuals participating in the user's treatment will transmit the user's disease.

[0060] In some embodiments, the monitoring of social aspects is used at least in part to identify individuals who are participating or who may participate in the user's treatment, based at least in part on proximity and / or propensity. In some embodiments, the identification of one or more individuals who may participate in the user's treatment is directed to identifying individuals to replace individuals who have been excluded from participating in the treatment. In some embodiments, the social monitoring includes one or more communications with one or more users and / or third parties. In some embodiments, the communications with one or more users and / or third parties include one or more of messages, notifications, chats, interactions directed to determining one or more of the following: availability, willingness, ability of one or more users and / or third parties. In further exemplary embodiments, the scheduling and / or dispensing of one or more treatments is responsive to a determination of the availability and / or willingness and / or ability of one or more users and / or third parties. For example, a treatment delivery may be scheduled in response to a determination that a caregiver is willing and / or able to assist in the delivery of non-invasive stimulation.

[0061] In some embodiments, the technical solution monitors activity aspects. In some embodiments, the activity aspects include, but are not limited to, one or more of the following: classification and / or identification and / or recording and / or observation or one or more activities engaged in by one or more users and / or third parties. In some embodiments, the activity aspects include one or more of the following: workload and / or burden and / or projects and / or objectives and / or responsibilities associated with one or more users and / or third parties. In some embodiments, the monitoring of activity aspects targets one or more of the following: characterizing the burden and / or distraction and / or workload and / or responsibilities associated with one or more users and / or third parties.

[0062] In an exemplary embodiment, monitoring of activity aspects is directed to characterizing the suitability and / or compatibility of one or more activities involving one or more users and / or third parties to the administration of non-invasive sensory stimulation. In an exemplary embodiment, characterizing the suitability and / or compatibility with one or more activities is directed to improving the reliability of the engagement and / or involvement and / or effectiveness and / or contribution of one or more users and / or third parties to the delivery of non-invasive sensory stimulation.

[0063] For example, activity aspect monitoring can include monitoring or classifying a task or activity in which a user is engaged simultaneously or proximate to the provision of non-invasive sensory stimulation with respect to the level of burden or distraction it poses to the individual engaged in the task or to others present. In such examples, activity monitoring is directed to scheduling or structuring therapy such that the activity in which the user is engaged does not distract from, interfere with, or compromise therapy delivery. For example, a user may engage in a challenging or exhausting activity, or even a fun but distracting task, during which administration of non-invasive sensory stimulation is compromised. In such examples, therapy administration can be rescheduled to avoid periods during or proximate to such activities.

[0064] Similarly, activity aspect monitoring may include monitoring or classifying the type of tasks or activities that a caregiver or care partner is engaged in simultaneously or in close proximity to the delivery of non-invasive sensory stimulation, to avoid scheduling the delivery of the therapy in close proximity to caregiver or care partner activities that may compromise or disrupt the delivery of the therapy. Conversely, the therapy may be scheduled or configured to avoid disturbing activities in which the person is engaged. For example, in some scenarios, a care partner may be engaged in other tasks or activities that are important to themselves and their well-being, or activities that impact the effectiveness or sustainability of their participation in the patient's care. In such scenarios, activity monitoring may be directed to identifying and characterizing such activities so that the delivery of the therapy or the participation of the caregiver and / or care partner in the delivery of the therapy may be directed to disrupting or interfering with such activities.

[0065] In some embodiments, location monitoring of one or more users and / or third parties is performed. In some embodiments, location monitoring includes one or more of the following: tracking the location of one or more individuals, tracking the proximity of one or more first individuals to one or more second individuals, tracking the location history of one or more individuals, determining location or co-location history, contract tracing. In some embodiments, location monitoring includes receiving and / or requesting and / or incorporating and / or analyzing and / or processing location information, including but not limited to location and / or location-related information obtained from a system service or API or an external source.

[0066] In an exemplary embodiment, the scheduling of one or more treatments or sessions of non-invasive sensory stimulation or related treatments is responsive, at least in part, to location monitoring of one of the one or more users and / or third parties, including, but not limited to, location and / or co-location history. For example, treatments may be scheduled and / or distributed in response to identification of periods of co-location and / or proximity of one or more third parties with one or more users.

[0067] In some embodiments, scenario monitoring of one or more users and / or third parties and / or treatments is performed. Scenario monitoring may include, for example, one or more of the following: risk monitoring, scenario identification, scenario classification, scenario prioritization, scenario formulation. In some embodiments, scenario monitoring incorporates activities and / or social and / or other context information. In some embodiments, scenario monitoring includes predicting one or more of the following: activities, situations, roles, relationships, locations, responsibilities. In some embodiments, scenario monitoring incorporates and / or is responsive to analytics. In some embodiments, scenario monitoring is performed by a separate device operably coupled to the neural stimulation system. In other embodiments, the neural stimulation performs the scenario monitoring.

[0068] In an exemplary embodiment, scenario monitoring determines or evaluates the likelihood that a user is about to engage or has engaged in an activity or scenario in response to observing activity and / or social presence and / or location monitoring and / or other context monitoring and / or actigraphy. For example, scenario monitoring may determine that a user is about to go to bed in response to the departure of one or more care partners in conjunction with observing an activity associated with preparing for sleep. In some embodiments, the dispensing and / or issuing and / or configuring of a treatment is responsive to scenario monitoring. For example, in response to determining that a user is about to go to bed, in some embodiments a treatment may be scheduled or suggested to the user or configured for pre-sleep administration and administration.

[0069] In some embodiments, weather monitoring is performed in association with one or more users and / or third parties and / or therapies. In some embodiments, the weather monitoring includes one or more of the following: recording weather proximate to a treatment administration, recording weather proximate to a user and / or third party activity, recording weather proximate to an evaluation, recording weather proximate to other events, recording weather proximate to a disease-related event. In some embodiments, the weather monitoring includes correlating one or more weather conditions with one or more aspects of the context monitoring and / or one or more aspects of the user monitoring and / or one or more aspects of the stimulation signal and / or one or more evaluations and / or one or more analyses. In some embodiments, the weather monitoring includes receiving and / or requesting and / or incorporating and / or analyzing and / or processing weather information, including but not limited to weather and / or weather-related information obtained from a system service or API or an external source.

[0070] In some embodiments, stimulation opportunity monitoring of one or more users and / or third parties and / or contexts and / or scenarios is performed. In some embodiments, the stimulation opportunity monitoring includes one or more of the following: observing correlations between situation monitoring and / or user monitoring and / or other aspects directed to detecting and / or identifying opportunities to deliver stimulation and / or associated therapy. In some embodiments, the stimulation opportunity includes one or more of the following: available care partners, available devices, device capabilities, third party capabilities, candidate stimulation delivery settings, candidate delivery conditions, third party status, user status.

[0071] In some embodiments, the stimulation opportunity monitoring is directed to identifying and / or characterizing and / or classifying one or more routines of one or more users and / or third parties. In some embodiments, the stimulation opportunity monitoring is directed to identifying and / or characterizing and / or classifying one or more third party candidates to assist with therapy administration and / or support. In some embodiments, the stimulation opportunity monitoring is directed to identifying and / or characterizing and / or classifying one or more devices capable of and / or suitable for delivering therapy. In some embodiments, the stimulation opportunity monitoring is directed to identifying and / or characterizing and / or classifying one or more times suitable for therapy delivery. In some embodiments, the stimulation opportunity monitoring is directed to identifying and / or characterizing and / or classifying one or more environments suitable for therapy delivery.

[0072] In some embodiments, the monitoring of the routine is directed to avoiding interruptions to the routine. In an exemplary embodiment, the stimulation configuration and / or dispatch and / or distribution is directed to preserving the routine detected at least in part by the monitoring. For example, the monitoring can determine the times or locations at which the user or their caregiver engage in hobbies, chores, or other activities, and stimulation can be scheduled to occur at times other than those at which such engagements are observed to occur. Alternatively, the monitoring of the routine can be used to determine the best way to incorporate gamma stimulation therapy without interrupting the routine. For example, the neurostimulation system can determine that the subject routinely watches an hour of programming and stimulation can be administered during that hour.

[0073] In some embodiments, the systems and methods of the present disclosure may improve cognitive performance by improving the quality of a user's sleep. For example, the systems and methods of the present disclosure may improve cognitive performance by producing beneficial changes in actigraphy during sleep periods in one or more of subjects at risk for AD, subjects experiencing cognitive decline, subjects experiencing sleep disorders, subjects diagnosed with AD, subjects diagnosed with MCI, healthy subjects, subjects with sleep pathology, and subjects suffering from sleep disorders. In some embodiments, the beneficial changes in actigraphy include reduced sleep fragmentation. In embodiments, the beneficial changes in actigraphy may include one or more of an increase in the frequency of rest periods during a sleep period and / or a decrease in the frequency of sleep interruptions during a sleep period. In some embodiments, the present disclosure delivers non-invasive stimulation to produce reduced sleep fragmentation during nighttime sleep in patients with mild to moderate AD. In some embodiments, the present disclosure further describes techniques directed to increasing the length of rest periods during sleep and / or reducing the frequency of awakenings during sleep.

[0074] In some embodiments, the technology directed to producing beneficial changes in actigraphy is further directed to producing beneficial sleep-related health outcomes. Beneficial sleep-related health outcomes may include one or more of the following: removal of brain waste products, reduction of cognitive deficits, slowing or delaying AD progression, reduction of circadian rhythm disruption, reduction of microglial aging and activation, reduction of cognitive impairment, reduction of depressive symptoms, alleviation of appetite or eating disorders, reduction of agitation, reduction of apathy, reduction of psychotic symptoms (including delusions and hallucinations), reduction of aggression, reduction of behavioral and psychiatric symptoms of dementia, stabilization and / or prevention of decline in one or more indicators of performance. In some embodiments, the alleviated circadian rhythm disturbances include, but are not limited to, disturbances associated with AD, MCI, aging, eating disorders, irregular sleep-wake rhythm disorders, depression, anxiety, and stress.

[0075] In some embodiments, sleep, during sleep, or sleep periods may refer to nighttime periods of relative inactivity or periods of frequent pauses. In some further embodiments, such periods of relative inactivity or periods of frequent pauses refer to characterized patterns of actigraphy, including but not limited to patterns of actigraphy identified using methods described in embodiments of the present technical solution. Figure 32 provides examples of patterns of actigraphy identified using methods described herein. Figure 32 shows 24-hour activity levels (gray; 1501 in Figure 37) over two days for one example patient, centered at 12:00 a.m. (indicated by thick gray arrow), along with a median filtering curve (indicated by thin arrow, 1507 in Figure 37). The horizontal axis indicates time of day, and the vertical axis is the relative activity recorded on a wrist-worn actigraphy measurement device (arbitrary log scale). Calculated sleep periods (black horizontal lines, see 1508 in FIG. 37) are shown along with individual sample rest periods (yellow horizontal lines, see 1509 in FIG. 37): (a) shows an exemplary pattern of frequent movements and short rest periods during sleep periods, and (b) shows an exemplary pattern of less frequent movements and long rest periods during sleep periods. Similarly, FIG. 33 provides exemplary patterns of actigraphy (arbitrary units, see FIG. 34). FIG. 33 provides actigraphy data over several days (gray; e.g., 1501 in FIG. 37), with a smooth curve superimposed. A cutoff line (black line) separates active and rest periods (e.g., 1505 in FIG. 37). The black square represents an initial estimate of the midnight point (e.g., 1507 in FIG. 37), the final assessment of which is determined through an optimization algorithm (e.g., 1508 in FIG. 37).

[0076] Delivery Methods and Systems The present disclosure provides a method for improving cognitive function and / or inducing gamma oscillations in a subject, comprising non-invasively delivering a signal configured with stimulation program parameters for improving cognitive function and / or inducing gamma oscillations in a subject. In some embodiments, the present disclosure achieves improved sleep quality by enhancing the coherence or power of gamma oscillations in at least one brain region of the subject.

[0077] In some embodiments, the non-invasive signal is delivered through one or more of visual, auditory, tactile, olfactory stimulation, or bone conduction. In some embodiments, the combined auditory-visual stimulation is delivered for one hour daily for a period of three to six months or longer. In some embodiments, the stimulation is delivered for two hours daily. In some embodiments, the stimulation is delivered for multiple periods over a one day period. In some embodiments, the combined auditory-visual stimulation is delivered for an extended open-ended period. In some embodiments, the stimulation is delivered for periods of varying duration. In some embodiments, the stimulation is delivered in response to an opportunity to effectively deliver the stimulation, such opportunity being determined by one or more of monitoring, analysis, user or caregiver input, and clinician input. In some embodiments, the first stimulation period is delivered through a first device and the second stimulation period is delivered through a second device. In some embodiments, the first stimulation period and the second stimulation period are delivered through a single device.

[0078] In some embodiments, the non-invasive signal is delivered at least in part through glasses, goggles, a mask, or other wearable device capable of providing visual stimulation, hi some embodiments, the non-invasive signal induces gamma wave oscillations to improve sleep.

[0079] In some embodiments, the non-invasive signal is delivered at least in part through one or more devices in the user's environment, such as a speaker, a light fixture, a bed attachment, a wall-mounted screen, or other home device. In further embodiments, such devices are controlled by a further device, such as a phone, tablet, or home automation hub, configured to manage the delivery of the non-invasive signal through one or more devices in the user's environment. In some embodiments, such devices may additionally include a wearable device.

[0080] In some embodiments, the non-invasive signal is delivered, at least in part, through headphones that provide auditory stimulation. In some embodiments, the present disclosure induces gamma wave oscillations through headphones that provide auditory stimulation to improve sleep.

[0081] In some embodiments, the non-invasive signal is delivered through a combination of visual and auditory stimuli. In some embodiments, the present disclosure induces gamma oscillations to improve sleep through a combination of visual and auditory stimuli.

[0082] In some embodiments, the non-invasive signal is delivered through opaque or partially transparent glasses worn by the subject with lighting elements on the inside that provide a visual signal. In some embodiments, the non-invasive signal is delivered through headphones or earphones worn by the subject that provide an auditory signal. In some embodiments, a combined visual and auditory signal is provided by such headphones and glasses worn together at the same time. In some embodiments, the visual and auditory signals are delivered separately by glasses or headphones worn at different times. An exemplary embodiment includes glasses with LEDs inside the glasses that provide a visual stimulus and headphones that provide an auditory stimulus.

[0083] In some embodiments, the subject controls aspects of the stimulation signal to achieve one or more of the following: tolerance, comfort, efficacy, reduced fatigue, compliance, adherence. In some embodiments, the subject or a third party can pause, interrupt, or terminate the delivery of the stimulation. In an exemplary embodiment, the subject and / or a third party can adjust the peak audio volume and / or visual intensity of the stimulation within a predetermined safe operating range using a handheld controller operably coupled to the stimulation delivery device.

[0084] In some embodiments, the non-invasive signal is delivered by vibrotactile stimulation via clothing or body wear suitable for wearing in proximity to or during periods of sleep or rest. In some embodiments, such body wear may include a device that provides treatment of the user's ailments while sleeping, such as a CPAP machine. In some embodiments, the non-invasive signal may be delivered through the user's nostrils.

[0085] In some embodiments, the non-invasive signal is administered at least in part by a device specified in one or more of US Patents US10307611B2, US10293177B2, or US10279192B2.

[0086] In some embodiments, the present disclosure delivers non-invasive signals through a sleep mask worn over the subject's open or closed eyes. In some embodiments, the technical solution further provides visual stimulation through closed or partially closed eyelids. In some embodiments, the sleep mask is any device worn by the user in close proximity to a sleep period. In some embodiments, the sleep mask can be used in situations and times unrelated to a sleep period.

[0087] In an exemplary embodiment, a sleep mask with built-in or Bluetooth® paired, or other wireless technology paired, or physically paired headphones or earphones provides the ability to deliver visual stimuli, auditory stimuli, or a combination of the two. In a further exemplary embodiment, visual stimuli are provided automatically when the mask is over the eyes, and auditory stimuli are provided only when the headphones or earphones are placed or worn.

[0088] In some embodiments, the stimulation is delivered by a device (e.g., including but not limited to, a sleep mask embodiment) that may be worn throughout the subject's sleep period. In further embodiments, the stimulation may be delivered by the device in response to the user's detected sleep state and / or other information indicative of the user's activity. In an exemplary embodiment, the device delivers stimulation only during the period of the detected sleep interruption, or delivers stimulation during a particular sleep stage, including resting before the first sleep period, and / or waking at night or leaving the sleep area. In some embodiments, the stimulation parameters are adjusted in response to the detected sleep state or other monitoring. In an exemplary embodiment, the user is provided with auditory-only stimulation during the period of nighttime sleep interruption. In some embodiments, the sleep state is detected in response to one or more of the following: EEG, information about the subject's location or position, actigraphy.

[0089] In some embodiments, the stimulus is delivered to multiple subjects present within the space. In an exemplary embodiment, the stimulus is delivered to multiple subjects within the space through devices present within the space that deliver the same stimulus to all current subjects or deliver customized stimuli to individual subjects, or a combination thereof.

[0090] Monitoring, feedback and motivation In some embodiments, the present disclosure also provides one or more of monitoring improvements in cognitive function and / or neural entrainment, providing feedback to the user and third parties related to these aspects, and motivating the user or third parties for use of the stimulation device or other related activities or treatments. For example, Table 1 presents an exemplary testing and monitoring protocol. In Table 1, X indicates office assessment, P indicates telephone assessment, and A indicates home assessment. In some embodiments, the home assessment includes in-person assessment. In some embodiments, the home assessment includes video or telephone calls. In some embodiments, the present disclosure performs the exemplary protocol of FIG. 33 in assessing sleep-related conditions. In some embodiments, the present disclosure uses other measures of the effect of non-invasive stimulation. In some embodiments, for example, the present disclosure provides a system for assessing sleep-related conditions using the protocol presented in FIG. 32.

[0091] [Table 1]

[0092] monitoring In some embodiments, the systems and methods of the present disclosure perform sleep quality measurements. Sleep quality measurements may include one or more of the following: wake duration, bed out time, movement, body position, eye movement, eyelid state, breath sounds, snoring, respiration, heart rate, HRV, respiration rate, sleep fragmentation. Sleep quality measurements may include environmental aspects associated with sleep quality, including, but not limited to, one or more of the following: room noise, room temperature, air circulation, air chemistry, bed temperature, partner sleep attributes, room configuration. Sleep quality measurements may also include other aspects associated with sleep quality, including, but not limited to, one or more of the following: wake tests or self-reports, assessments, surveys, cognitive challenges, physical challenges, task performance, productivity, third-party assessments, daily activities, sports performance, appetite, weight gain or loss, hormone changes, drug use, or other aspects of user performance or health known to be or likely to be correlated with sleep quality. Sleep quality measurements may include measurements taken during sleep or at other times, as appropriate.

[0093] In some embodiments, the monitoring may include measuring the subject's electroencephalographic parameters, including, but not limited to, neural activity, gamma entrainment, power in specific frequency bands, resting state quantitative EEG attributes, sensory evoked potentials, steady state and induced oscillations, changes in coherence, cross-frequency amplitude coupling, and harmonics. In some embodiments, the measurement of the subject's electroencephalographic parameters is performed by a module incorporated into a component of the stimulation delivery apparatus. In some embodiments, the measurement of the subject's electroencephalographic parameters is performed by a module incorporated into a separate device. In some embodiments, gamma entrainment and / or entrainment at other frequencies is detected by one or more methods (e.g., FIG. 28) and at least partially by methods described in US10279192 B2 (e.g., by identifying multiple neurons in the subject's brain that oscillate at a specific frequency after or during application of stimulation, as illustrated in FIG. 39).

[0094] In some embodiments, an entrainment score is calculated that is at least partially responsive to the measurement of gamma entrainment. In some embodiments, measurements and calculations directed to entrainment detection activities are performed according to a schedule (e.g., Table 1), and in some embodiments, the scheduling, timing, and / or other attributes of the activities for entrainment detection are responsive to one or more of the following: user input, user state, third party input, third party state, user state, or environmental observation. In an exemplary embodiment, a monitoring module implemented in an application running on a device such as a mobile phone, tablet, or similarly functioning device aggregates such parameters from connected devices. In further embodiments, such connected devices include stimulus delivery devices. In some embodiments, the monitoring module is implemented on the stimulus delivery device. In further embodiments, these measurements are analyzed, possibly together with measures of sleep quality or other parameters that correlate with cognitive function. In an exemplary embodiment, the analysis of user aspects or context is used in combination with measures of sleep quality or other parameters that correlate with cognitive function to identify periods during which sleep quality may be affected by the context.

[0095] In some embodiments, measurements are taken during sleep, and in some embodiments, measurements are taken at other times. In further embodiments, measurements taken at other times may be specifically scheduled to provide the most relevant information (e.g., HRV during wakefulness resting for sleep quality, alpha wave measurements during and after stimulation, daytime cognitive assessment of productive wakefulness, etc.). In some embodiments, measurements of sleep quality related parameters may be taken passively, and in some embodiments, the user may be prompted or scheduled to provide information regarding sleep quality (e.g., by completing an assessment task or wearing a specific measurement device). In some embodiments, a third party, such as the user's caregiver, is prompted or scheduled to provide or facilitate the collection of measurements.

[0096] In some embodiments, the present disclosure provides for monitoring of sleep interruptions. In an exemplary embodiment, sleep interruptions are detected using actigraphy, where such actigraphy is provided from one or more devices associated with the user and worn or in proximity to the user during sleep. In further exemplary embodiments, such actigraphy is provided by sensors incorporated into a stimulus delivery device (see sleep mask) worn by the user throughout the sleep period. In an exemplary embodiment, actigraphy is continuously monitored using a wearable actigraphy device, such as a watch with actigraphy measurement capabilities.

[0097] In some embodiments, actigraphy observations include measuring, observing, and / or logging one or more of the following: acceleration, gravity, position, posture, orientation. In some embodiments, the measurements and / or observations are made of one or more body parts. In some embodiments, actigraphy measurements are calculated from the actigraphy observations. In some embodiments, actigraphy measurements are responsive, at least in part, to observed, transmitted, or recorded information regarding the environment, time of day, user self-report, history, demographic information, diagnostics, device interactions, online activity, and third party assessments.

[0098] In some embodiments, the technical solution employs monitoring of electroencephalogram parameters to determine stimulation parameters. In an exemplary embodiment, identification of the subject's dominant primary alpha wave frequency is used, at least in part, to determine the frequency of stimulation applied to the subject. In an exemplary embodiment, the stimulation is applied at four times the subject's dominant primary alpha wave frequency. In some embodiments, the stimulation is applied at an integer multiple of the subject's dominant primary alpha wave frequency. In some embodiments, the subject's dominant primary alpha wave frequency can be determined, at least in part, based on one or more of the following: observation or measurement of the subject's electroencephalogram parameters, demographic information associated with the subject, historical information associated with the subject, and profile information associated with the subject.

[0099] In some embodiments, the technical solution uses the monitoring of electroencephalogram parameters to classify a user's risk of developing a neurological disease or to diagnose a neurological disease or disorder. In one embodiment, the technical solution uses the monitoring of electroencephalogram parameters to classify a user's risk of developing a neurodegenerative disorder such as MCI or AD, to assess the progression of MCI or AD, or to diagnose MCI or AD. In further embodiments, such classification is based at least in part on a decrease in the amount of gamma electroencephalogram activity detected.

[0100] In some embodiments, the technical solution monitors one or more objects in the space, such monitoring includes one or more of the following: presence in the space, proximity to a stimulus delivery device, level, and values ​​of stimulus parameters associated with each object, activity, and behavior of the objects. In an exemplary embodiment, the presence of the objects in the space is observed and recorded. In an exemplary embodiment, the auditory or visual characteristics of the delivered stimulus are observed and recorded at one or more of the following: various locations in the space, the location of one or more objects in the space, one or more eyes of the objects, one or more ears of the objects. In some embodiments, such monitoring logs are employed to build a measure of each object's total exposure to the available stimuli while in the space.

[0101] In some embodiments, the monitoring information is communicated to a system that contributes to the operation of an automated interaction with a user or a third party. In an exemplary embodiment, the monitoring information is communicated to a system that operates a chatbot that interacts with a user or a caregiver.

[0102] In some embodiments, the monitored information includes or is responsive to an analysis of the monitored information, hi some embodiments, the monitored information includes or is at least partially responsive to a sleep fragmentation analysis from actigraphy and / or a comparison of two or more sleep fragmentation analyses from actigraphy.

[0103] feedback In some embodiments, the present disclosure provides feedback to the user and third parties regarding aspects of the user's sleep quality. In a further aspect, the present disclosure provides such feedback in response to delivery of gamma stimulation therapy or in response to monitoring or analysis of the monitoring. In some embodiments, the feedback includes feedback or information regarding the use of the stimulation device, with or without information regarding the monitoring or analysis.

[0104] In some embodiments, the feedback may include reporting to the user or a third party on aspects of the stimulation, including duration, parameters, schedule, etc.; in some embodiments, the feedback may include values ​​or summaries of values ​​of measurements or monitoring of sleep-related parameters; in some embodiments, the feedback may include information regarding sleep quality improvement, including frequency, duration, and distribution of rest periods. In some embodiments, the third party may include a caregiver, a medical professional, a provider, an insurer, or an employer. In some embodiments, the feedback may be provided on the stimulation device, on a secondary device (such as a phone or tablet), or remotely (e.g., on a console or other device associated with the third party). In some embodiments, one or more of the distributions, summary statistics of the distributions, or characteristic parameters of the fitted distributions are compared for one or more groups of one or more subjects and / or one or more time periods. In an exemplary embodiment (e.g., FIG. 37), the distributions of two groups of subjects are compared, and / or the distributions within both groups over a subsequent time period (e.g., 12 weeks) are compared. In some embodiments, the distributions of a single patient over two separate consecutive time periods (e.g., 12 weeks) are compared. In some embodiments, the difference between the exponential decay constants is calculated (e.g., 1513) as a measure of the difference in sleep quality between one or more subjects or time periods. In an exemplary embodiment, the exponential decay constant, tau for the first time period, 1 , and tau of the second period 2 In a further embodiment, tau is determined. diff =tau 2 -tau 1 In a further embodiment, tau is calculated. diff is used as a measure of improvement or deterioration in sleep quality, e.g., tau diff >0 reported as improved sleep quality and / or tau diff <0 is reported as poor sleep quality (e.g., FIG. 36). In some embodiments, one or more steps (1501-1513) are performed by actigraphy monitoring module 130 (FIG. 33).

[0105] In an exemplary embodiment, the user is presented with a summary of stimulation device usage (including one or more of duration of wearing, stimulation applied, parameters, parameters used, etc.) or a summary of changes in sleep quality, or a combination thereof, on a personal device (such as a phone or tablet) that is connected or paired with the stimulation device.

[0106] In an exemplary embodiment, the caregiver is presented with a summary of stimulation device usage (including one or more of duration of wear, stimulation applied, parameters used, etc.) or a summary of changes in sleep quality of one or more users, or a combination thereof, on a web dashboard linked to one or more stimulation devices of one or more users.

[0107] In some embodiments, monitoring of one or more objects in the space is utilized to provide guidance associated with one or more objects in the space with respect to location, position, behavior, or posture. In exemplary embodiments, the objects are provided with such guidance directed to improving one or more of the effectiveness of a received stimulus, characteristics of the received stimulus (e.g., light level, volume, intensity, frequency, duration, variability, etc.) for the one or more objects. In some embodiments, such guidance is provided to a third party. In some embodiments, such guidance is provided to the objects.

[0108] In some embodiments, monitoring of one or more subjects is used to diagnose the subject with disease, disorder or condition.For example, monitoring of subject can include evaluating cognitive decline or dementia characteristics, changes in fine motor skills, changes in EEG activity, sleep fragmentation, or voice or pitch analysis.

[0109] In some embodiments, the feedback is communicated or presented to one or more stimulus recipients. In some embodiments, the feedback is presented in the form of a diagnosis or prescription. In some embodiments, the feedback is communicated or presented to a third party, including, but not limited to, a clinician, delivery facility staff, device operator, device manufacturer, therapeutic component provider, caregiver, payer, provider, employer, family, researcher, health organization.

[0110] In some embodiments, the feedback communicated to the third party is modified, processed, filtered, selected, or presented to achieve one or more of the following: reducing recipient stress or concerns regarding the stimulation recipient, improving outcomes for one or more stimulation recipients, reducing costs associated with one or more stimulation recipients, or complying with regulations associated with stimulation delivery.

[0111] In some embodiments, the feedback is communicated or presented through programmatic interaction with a user or a third party, at least in part in response to the monitored information. In an exemplary embodiment, the feedback is communicated to a chatbot or chatbot component that interacts with the user or caregiver.

[0112] In some embodiments, the feedback incorporates or consists of processed or unprocessed monitored information or analysis, hi some embodiments, the feedback includes and / or consists of and / or is at least partially responsive to a sleep fragmentation analysis from actigraphy and / or a comparison of two or more sleep fragmentation analyses from actigraphy.

[0113] Motivation In some embodiments, the present disclosure facilitates motivating a user or third party to use a stimulation device or other related activity or treatment, hi further embodiments, the present disclosure provides such motivation in response to delivery of gamma stimulation therapy or in response to monitoring or analysis of the monitoring.

[0114] Motivations may include instructions for use (or links to instructions for use), reminders or notifications, calendar events, rewards, progress indicators, comparisons to goals or objectives, or comparisons to other users, or comparisons to target populations or demographic groups of the user. Motivations may also include evaluation of symptoms and signs of disease progression.

[0115] In an exemplary embodiment, when users go to bed or just before their usual bedtime, they are reminded of the progress they have made in the past using the stimulation device just before bedtime, with such reminders appearing on one or more personal devices (e.g., as a notification), on the stimulation device (e.g., as a flashing light or audio tone), or on other devices (e.g., a desktop calendar), and the content and timing of such reminders are further responsive to an analysis of the time and duration of device use associated with improved sleep quality.

[0116] In an exemplary embodiment, the user is presented with instructions, motivational rewards, prompts, or achievements on the stimulation device or a personal device associated with the user of the stimulation device that encourage use of the device in response to the user's history of device use that has resulted in improved sleep quality.

[0117] In an exemplary embodiment, the caregiver is presented with instructions or guidance on a web dashboard or console on how to encourage one or more users to use the stimulation device in usage or contexts (e.g., schedules, technology, environmental conditions, etc.) that are likely to result in improved sleep quality. In further exemplary embodiments, these methods are prioritized or selected based at least in part on monitoring or analysis of usage of the one or more users or other users that is associated with effective sleep quality improvement.

[0118] In some embodiments, the motivation is communicated or presented through programmatic interaction with the user or a third party, at least in part in response to the monitored information. In an exemplary embodiment, the feedback is communicated to a chatbot or chatbot component that interacts with the user or caregiver.

[0119] In some embodiments, the motivation incorporates or consists of feedback, hi some embodiments, the motivation includes and / or consists of and / or is at least partially responsive to a sleep fragmentation analysis from actigraphy and / or a comparison of two or more sleep fragmentation analyses from actigraphy.

[0120] analysis In some embodiments, beneficial changes in actigraphy are identified by calculating statistical measures related to the distribution of one or more of sleep fragmentation, rest periods during sleep periods, and sleep interruptions during sleep periods (FIG. 37). In exemplary embodiments, such analysis may include generating distributions of rest period durations or other measures of sleep fragmentation, and in further embodiments, such analysis may include comparing these distributions over time or in response to various treatment parameters or patterns of device use.

[0121] In some embodiments, the technical solution includes methods and systems for analyzing sleep fragmentation from actigraphy. In some embodiments, such methods and systems include collecting and / or receiving actigraphy data for one or more devices associated with one or more subjects over one or more time periods (1501 in FIG. 37), e.g., gray in FIG. 34). In some embodiments, such methods and systems may further include one or more of the following: bandpass filtering at least a portion of such actigraphy data (1502 in FIG. 37); extracting the amplitude of at least a portion of such actigraphy data at another reduced sampling frequency (1503 in FIG. 37). In some embodiments, such methods and systems further include determining a distribution of estimated accelerations (1504 in FIG. 37). In some embodiments, such methods and systems further include identifying one or more device-specific cutoffs that distinguish between active and inactive time based at least in part on device characteristics of actigraphy values ​​associated with device non-use (1505 in FIG. 37, e.g., black "cutoffs" in FIG. 35), and classifying the actigraphy data based on such distinction. In an exemplary embodiment, data points having actigraphy values ​​above a value associated with device non-use are assigned a score of 1, and all other data points are assigned a value of 0 (1506 in FIG. 375). In some embodiments, such methods and systems include generating a smoothed estimate of activity from the actigraphy data (1507 in FIG. 37, e.g., green in FIG. 34). In some embodiments, such methods and systems further include determining a time point of the first estimated midnight for each night from the smoothed estimate of activity (1507 in FIG. 37, e.g., black dot in FIG. 35). In some embodiments, the first estimated midnight time corresponds to the minimum of the smoothed estimates of activity over the period from 12:00 PM on consecutive days.

[0122] In some embodiments, the solution further includes methods and systems for determining the temporal extent of one or more nighttime sleep periods (black highlighted periods in FIG. 34), including optimization for determining an optimized midnight time point and surrounding time window, assigning credit to identified inactive data points (e.g., those assigned a value of 0) and assigning penalties to identified active data points (e.g., those assigned a value of 1) in the optimized time window around the optimized midnight time point, and assigning credit to identified active data points and assigning penalties to identified inactive data points outside such optimized time window (1508, FIG. 37). In some embodiments, the solution further includes methods and systems for identifying active and resting periods (e.g., gray bars in FIG. 34) within each nighttime sleep period (1509, FIG. 37). In an exemplary embodiment, periods having actigraphy values ​​above a value associated with non-use of the device are classified as active periods, while all other data points are classified as resting periods (1506, FIG. 37). In the exemplary embodiment, idle periods are assigned a value of one and active periods are assigned a value of zero.

[0123] In some embodiments, the solution further includes methods and systems for characterizing the distribution of identified rest periods, such methods including one or more of collecting and / or accumulating rest periods from one or more nights or other time periods for one or more subjects or groups of subjects (1510, FIG. 37), determining a cumulative distribution of the collected rest periods (1511, FIG. 37), fitting a statistical distribution to the distribution of collected rest periods. In some embodiments, such methods and systems further include fitting an exponential distribution to the distribution of collected rest periods and determining an exponential decay constant for the fitted exponential distribution (1512, FIG. 37). Some embodiments further include methods for determining and / or reporting and / or transmitting a value based at least in part on an exponential decay constant determined for an exponential distribution that fits the cumulative distribution of rest periods of one or more subjects over one or more days and / or other periods (1513, FIG. 37), and / or determining and / or reporting and / or transmitting a value based at least in part on a comparison between exponential decay constants for two or more exponential distributions that fit the cumulative distribution of rest periods of one or more subjects over one or more days and / or other periods (1513, FIG. 37).

[0124] In some embodiments, one or more such determined exponential decay constants, comparisons of such constants, functions of such constants, or values ​​responsive to such constants are reported, singly or in combination, as a measure of sleep quality, sleep improvement, sleep progression, treatment effectiveness, treatment results, disease progression, and / or other metrics of treatment success, failure, effectiveness, or outcome. In an exemplary embodiment, reports responsive to or incorporating values ​​based on differences between exponential decay constants for different users or different time periods are reported to a user or a third party.

[0125] In some embodiments, analysis of sleep fragmentation, including characterizing the distribution of identified rest periods, is used at least in part to identify and / or evaluate and / or report one or more of beneficial changes in actigraphy during a sleep period, an increase in the frequency of rest periods during a sleep period, a decrease in the frequency of sleep interruptions during a sleep period, improvement and / or maintenance prevention of worsening sleep-related health outcomes.

[0126] In some embodiments, the analysis of sleep fragmentation, including characterizing the distribution of identified rest periods, is used, at least in part, to determine, adjust, modify, and / or select one or more of the following: stimulation parameters, stimulation modalities, opportunities to deliver stimulation, goals for reducing sleep fragmentation, devices to use for stimulation, locations to use for stimulation, environmental adjustments related to stimulation, adjustments of user conditions related to stimulation, activities for use in conjunction with stimulation, and the role of third parties in stimulation. In some embodiments, such use of the analysis of sleep fragmentation to determine, adjust, modify, and / or select is used in conjunction with information that is responsive to one or more of the user's and / or third party's history, location, profile, preferences, diagnoses, tasks, activities, relationships, assessments, test results, feedback, observations, prognosis, reports, device usage history, and treatment history. In some embodiments, such use of the analysis of sleep fragmentation to determine, adjust, modify, and / or select is used in conjunction with information that is responsive to one or more of the following: available stimulation devices, stimulation or other characteristics of available stimulation devices, audio environment information, visual environment information, user context information, and third party context information. In an exemplary embodiment, devices and / or stimulation opportunities and / or parameters associated with effective and / or improved and / or mitigated outcomes as assessed at least in part by analyzed patterns of sleep fragmentation are presented and / or suggested to the user and / or a third party.

[0127] In some embodiments, the measured or observed sleep-related parameters are analyzed, either locally and / or on a server, to calculate a measure of sleep quality.

[0128] In some embodiments, comparison or analysis of sleep quality or sleep fragmentation measurements over time can be used to characterize the progression or risk of sleep-related diseases such as AD. In some embodiments, the sleep quality measure calculated by the analysis is used as a measure of AD disease progression, risk, or diagnosis. In an exemplary embodiment, detection of specific levels of sleep fragmentation determined by the analysis, or changes in those levels over time, is used to identify patients at risk of AD or in the early stages of AD.

[0129] In some embodiments, measured sleep-related and other parameters are aggregated from multiple users to identify population or demographic patterns associated with improved sleep and associations between program parameters or other aspects of stimulus delivery, In some embodiments, measured sleep-related and other parameters from a single user are used to identify user-specific patterns.

[0130] In some embodiments, the identified patterns are used to inform one or more of the following: selection of program parameters or values ​​for one or more users or populations of users, treatment schedules, motivation, communication with users, caregivers, or health care providers.

[0131] In some embodiments, the analysis or results of the analysis may be reported to a user, a caregiver, a health care provider, or other third party. In an exemplary embodiment, the disease progression analysis related to AD progression is reported to a health care provider or a caregiver.

[0132] Program parameters and parameter values In some embodiments, the stimulation program parameters consist of a stimulation frequency (e.g., fs in FIG. 31) of about 35 Hz to about 45 Hz for both the auditory and visual signals. In some embodiments, the auditory and visual signals are offset relative to each other by a delay time (e.g., td in FIG. 31). In an exemplary embodiment, the auditory and visual signals are synchronized (td=0s).

[0133] In some embodiments, the stimulation program parameters are configured with various timing and intensity parameters. In an exemplary embodiment, these parameters include those illustrated in FIG. 31. In some embodiments, these parameters are pre-configured, in some embodiments they are adjusted at least in part by a third party such as a caregiver or health care provider, and in some embodiments, one or more parameters are adjusted in response to a measurement or analysis of one or more of the following: user context, measured sleep quality related parameters associated with the user, observed or detected use of the stimulation device. In some embodiments, the stimulation parameters are adjusted in response to detected or analyzed progression of sleep-related AD symptoms.

[0134] In some embodiments, the present disclosure induces gamma wave oscillations via a variety of frequency and intensity parameters.

[0135] In some embodiments, the non-invasive stimulation comprises one or more of the following: non-invasive sensory stimulation, non-invasive gamma stimulation, non-invasive gamma sensory stimulation, gamma stimulation therapy, non-invasive gamma stimulation therapy. In some embodiments, the non-invasive stimulation is delivered as a non-invasive therapy.

[0136] In an exemplary embodiment, the subject receives one hour of non-invasive sensory gamma stimulation therapy per day. In some embodiments, the subject receives two hours of non-invasive sensory stimulation twice per day. In some embodiments, the subject receives multiple periods of non-invasive stimulation of various durations and total times throughout the day. In some embodiments, the timing, distribution of durations, and / or total duration throughout the day are responsive to one or more of the following: delivered stimulation value, environmental value, observed user state, observed or inferred efficacy. In an exemplary embodiment, the subject is delivered short periods of stimulation throughout the day at times determined to be appropriate for effective stimulation delivery, and the sum of the total periods is at least partially responsive to a cumulative measure of the efficacy of the stimulation. In some embodiments, the efficacy of the stimulation is responsive to an entrainment score.

[0137] In some embodiments, one or more stimulation parameters or other aspects are at least partially responsive to a sleep fragmentation analysis from actigraphy and / or a comparison of two or more sleep fragmentation analyses from actigraphy. In exemplary embodiments, different combinations of stimulation parameters are used during different time periods, with subsequent stimulation parameters being selected based at least in part on a comparison of sleep fragmentation analyses from actigraphy during at least some of those time periods. In some embodiments, the stimulation parameters are selected to optimize, improve, and / or enhance sleep improvement as assessed at least in part by the sleep fragmentation analysis from actigraphy.

[0138] In some embodiments, the present disclosure delivers non-invasive auditory, visual, or combined auditory-visual stimuli at 40 Hz. In some embodiments, the stimuli are delivered at one or more stimulation frequencies in the range of about 35-45 Hz (e.g., fs in FIG. 31). In some embodiments, "gamma" refers to a frequency in the range of 35-45 Hz. In some embodiments, the stimuli are delivered based at least in part on the user's detected, reported, or demographically or individually associated, or dominant alpha wave frequency.

[0139] In some embodiments, the specific visual parameters include one or more of the following: stimulation frequency, intensity (luminance), hue, visual pattern, spatial frequency, contrast, and duty cycle. In an exemplary embodiment, the visual stimulus is provided at a stimulation frequency of 40 Hz, a luminance of 0 μW / cm2 to 1120 μW / cm2, and a 50% visual signal duty cycle.

[0140] In some embodiments, the non-invasive stimulation is delivered as a combination of visual and auditory stimulation delivered at a 40Hz frequency. In some embodiments, the visual and auditory stimulation can be synchronized to start each cycle at the same time. In some embodiments, the start of each auditory and visual stimulation cycle is offset by a configured amount of time. In some embodiments, the visual and auditory signals are delivered at an intensity that is clearly perceived by the subject and adjusted to their tolerance level.

[0141] In some embodiments, at least some of the parameters or characteristics of the non-invasive signal administered to the subject correspond to those specified in one or more of the following US patents: US10307611B2, US10293177B2, or US10279192B2. In some embodiments, at least some of the parameters or characteristics of the non-invasive signal administered to the subject correspond to those specified in one or both of the following US patents: US10159816B2, or US10265497B2.

[0142] In some embodiments, the specific audio parameters include one or more of a stimulus frequency, intensity (volume), and duty cycle. In some embodiments, the audio frequency is adjusted in response to the subject's hearing characteristics, for example, to a frequency at which the subject is better at hearing. In an exemplary embodiment, the audio stimulus is provided at an audio tone frequency of 7,000 Hz, a volume level of 0 dBA to 80 dBA, and a 0.57% audio signal duty cycle.

[0143] In some embodiments, the non-invasive stimulation parameters are selected to induce gamma oscillations in the brain of the human subject. In some embodiments, the non-invasive stimulation parameters are selected to induce alpha waves in the human subject (FIG. 40). In some embodiments, the non-invasive stimulation parameters are directed to inducing beta waves in the human subject. In some embodiments, the non-invasive stimulation parameters are directed to inducing beta waves in the human subject. In some embodiments, the non-invasive stimulation parameters are directed to inducing gamma waves in the human subject.

[0144] In some embodiments, the light level and hue are adjusted to avoid tiring the subject. In some embodiments, the light level and hue are adjusted to provide motivation to the subject. In some embodiments, the parameters for each ear or eye are adjusted similarly. In some embodiments, the parameters for each ear or eye are adjusted differently. In an exemplary embodiment, audio and visual parameters such as tone and hue are varied to provide engagement or motivation to the subject to continue applying or monitoring the stimuli.

[0145] Neurostimulation via Visual Stimulation In some embodiments, the disclosed systems and methods relate to using visual signals to control the frequency of neural oscillations and, in so doing, promote improved sleep quality. Visual stimulation can modulate, control, or otherwise affect the frequency of neural oscillations to provide beneficial effects on one or more cognitive states or functions of the brain or immune system while mitigating or preventing detrimental consequences on cognitive states or functions. Visual stimulation can, for example, provide beneficial improvements in the quality of sleep experienced by a user. Visual stimulation can provide electroencephalographic entrainment that can provide beneficial effects on one or more cognitive states of the brain, cognitive functions of the brain, the immune system, or inflammation. In some cases, visual stimulation can provide localized effects, such as in the visual cortex and associated regions. In some cases, visual stimulation can provide more expansive effects, causing changes in physiology as well as the nervous system. EEG entrainment can, for example, treat sleep abnormalities. Sleep abnormalities, such as sleep fragmentation, have multiple effects on human physiology, including dysfunction that impairs not only the nervous system, but also the body's metabolism or immune defense system. Brainwave entrainment can treat disorders, illnesses, diseases, disabilities, injuries, or other problems related to the cognitive function, cognitive state, immune system, or inflammation of the brain.

[0146] Neural oscillations include rhythmic or repetitive neural activity in the central nervous system occurring in humans or animals. Neural tissue can generate oscillatory activity by mechanisms within individual neurons or by interactions between neurons. Oscillations can also appear as oscillations in membrane potentials or periodic patterns of action potentials, which can result in oscillatory activation of postsynaptic neurons. Synchronized activity of neuronal populations can give rise to macroscopic oscillations, which can be observed, for example, by electroencephalography ("EEG"), magnetoencephalography ("MEG"), functional magnetic resonance imaging ("fMRI"), or electrocorticography ("ECoG"). Neural oscillations can be characterized by their frequency, amplitude, and phase. These signal properties can be observed from neural recordings using time-frequency analysis.

[0147] For example, EEG can measure oscillatory activity in populations of neurons, which can be classified into frequency bands as follows: delta activity corresponds to the 1-4 Hz frequency band; theta activity corresponds to the 4-8 Hz frequency band; alpha activity corresponds to the 8-12 Hz frequency band; beta activity corresponds to the 13-30 Hz frequency band; and gamma activity corresponds to the 30-70 Hz frequency band.

[0148] The frequency and existence or activity of neural oscillations are associated with cognitive states or cognitive functions, such as information transfer, perception, motor control, and memory. Based on cognitive states or cognitive functions, the frequency of neural oscillations may change. Furthermore, a particular frequency of neural oscillations may have beneficial or detrimental effects on one or more cognitive states or cognitive functions. However, it may be difficult to synchronize neural oscillations using external stimuli to provide such beneficial effects or to reduce or prevent such detrimental effects.

[0149] Brainwave entrainment (e.g., neural entrainment or brain entrainment) occurs when an external stimulus of a specific frequency is perceived by the brain and causes neural activity in the brain that results in neurons oscillating at a frequency corresponding to the specific frequency of the external stimulus. Thus, brain entrainment can refer to using an external stimulus to synchronize the neural oscillations of the brain so that the neural oscillations occur at a frequency corresponding to the specific frequency of the external stimulus.

[0150] The disclosed system and method can provide external visual stimuli to achieve brain entrainment. For example, an external signal such as a light pulse or a high-contrast visual pattern can be perceived by the brain. The brain can regulate, manage, or control the frequency of neural oscillations in response to observing or sensing the light pulse. Light pulses generated at a predetermined frequency and sensed by visual means via direct or peripheral vision can initiate neural activity in the brain to induce brainwave entrainment. The frequency of neural oscillations can be at least partially influenced by the frequency of the light pulse. The brain can respond to visual stimuli at the sensory cortex while higher level cognitive functions can gate or hinder some areas that are entrained. Thus, the disclosed system and method can provide brainwave entrainment using external visual stimuli such as light pulses emitted at a predetermined frequency to synchronize electrical activity among a population of neurons based on the frequency of the light pulse. Entrainment of one or more parts or regions of the brain can be observed based on the total frequency of oscillations generated by synchronous electrical activity in an ensemble of cortical neurons. The frequency of the light pulses can cause this synchronous electrical activity in an ensemble of cortical neurons to oscillate or coordinate at a frequency corresponding to the frequency of the light pulses.

[0151] 1 is a block diagram illustrating a system for performing visual brain entrainment according to one embodiment. The system 100 can include a neurostimulation system ("NSS") 105. The NSS 105 can be referred to as a visual NSS 105 or an NSS 105. In brief overview, the NSS 105 can include, access, interface with, or otherwise communicate with one or more of a light generating module 110, a light adjusting module 115, an unwanted frequency filtering module 120, a profile manager 125, a side effect management module 130, a feedback monitor 135, a data repository 140, a visual signaling component 150, a filtering component 155, or a feedback component 160. Each of the light generating module 110, the light adjusting module 115, the unwanted frequency filtering module 120, the profile manager 125, the side effect management module 130, the feedback monitor 135, the visual signaling component 150, the filtering component 155, or the feedback component 160 may include at least one processing unit or other logic device, such as a programmable logic array engine, or a module configured to communicate with the database repository 150. Each of the light generating module 110, the light adjusting module 115, the unwanted frequency filtering module 120, the profile manager 125, the side effect management module 130, the feedback monitor 135, the visual signaling component 150, the filtering component 155, or the feedback component 160 may be a separate component, a single component, or part of the NSS 105. The system 100 and its components, such as the NSS 105, may include hardware elements, such as one or more processors, logic devices, or circuits. The system 100 and its components, such as the NSS 105, may include one or more hardware or interface components depicted in the system 700 of Figures 7A and 7B.For example, the components of the system 100 may include or execute one or more processors 721 , access storage devices 728 , or memory 722 , as well as communicate via a network interface 718 .

[0152] 1, in further detail, the NSS 105 may include at least one light-generating module 110. The light-generating module 110 may be designed and configured to interface with the visual signaling component 150 to command or otherwise cause or facilitate the generation of a visual signal, such as a light pulse or flash having one or more predefined parameters. The light-generating module 110 may include hardware or software to receive and process commands or data packets from one or more modules or components of the NSS 105. The light-generating module 110 may generate commands to cause the visual signal component 150 to generate a visual signal. The light-generating module 110 may control or enable the visual signal component 150 to generate a visual signal having one or more predefined parameters.

[0153] The light-generating module 110 can be communicatively coupled to the visual signaling component 150. The light-generating module 110 can communicate to the visual signaling component 150 via a circuit, wire, data port, network port, power line, ground, electrical contact, or pin. The light-generating 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 Communication ("NFC"), or other short, medium, or long range communication protocols. The light-generating module 110 can include or have access to a network interface 718 for wirelessly or wired communication with the visual signaling component 150.

[0154] The light-generating module 110 can interface with, control, or otherwise manage various types of visual signal components 150 to cause the visual signal components 150 to generate, block, control, or otherwise provide a visual signal having one or more predefined parameters. The light-generating module 110 can include a driver configured to drive a light source of the visual signal component 150. For example, the light source can include a light-emitting diode ("LED"), and the light-generating module 110 can include an LED driver, chip, microcontroller, operational amplifier, transistor, resistor, or diode configured to drive the LED light source by providing electrical power or power having specific voltage and current characteristics.

[0155] In some embodiments, the light-generating module 110 can command the visual signal component 150 to provide a visual signal including a light wave 200, as depicted in FIG. 2A. The light wave 200 can include or be made from electromagnetic waves. The electromagnetic waves of the light wave can travel orthogonally to each other, with respective amplitudes 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 further 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.

[0156] The light-generating module 110 can instruct the visual signal component 150 to generate light waves having one or more predetermined wavelengths or intensities. The wavelengths of the light waves can correspond to the visible spectrum, the ultraviolet spectrum, the infrared spectrum, or some other wavelength of light. For example, the wavelengths of light waves within the visible spectrum can range from 390 to 700 nanometers ("nm"). Within the visible spectrum, the light-generating module 110 can further specify one or more wavelengths corresponding to one or more colors. For example, the light generating module 110 can instruct the visual signal component 150 to generate a visual signal including one or more light waves having one or more wavelengths corresponding to one or more of ultraviolet (e.g., 10-380 nm), violet (e.g., 380-450 nm), blue (e.g., 450-495 nm), green (e.g., 495-570 nm), yellow (e.g., 570-590 nm), orange (e.g., 590-620 nm), red (e.g., 620-750 nm), or infrared (e.g., 750-1,000,000 nm). The wavelengths can range from 10 nm to 100 micrometers. In some embodiments, the wavelengths can range from 380-750 nm.

[0157] The light-generating module 110 can determine to provide a visual signal that includes a light pulse. The light-generating module 110 can command or otherwise cause the visual signal component 150 to generate a light pulse. A light pulse may refer to a burst of light waves. For example, FIG. 2B illustrates a burst of light waves. A burst of light waves may refer to a burst of an electric field 250 generated by the light waves. A burst of an electric field 250 may be referred to as a light pulse or a flash of light. For example, a light source that is turned on and off intermittently may generate a burst, flash, or pulse of light.

[0158] FIG. 2C illustrates pulses of light (235a-c), according to one embodiment. The pulses of light (235a-c) can be illustrated via a graph in a frequency spectrum, where the Y-axis represents the frequency of the light wave (e.g., the speed of the light wave divided by the wavelength) and the X-axis represents time. A visual signal is F a Frequency and F a For example, the NSS105 can include modulation of light waves between frequencies different from F. a The NSS 105 can modulate light waves between frequencies in the visible spectrum, such as 100 Hz, 100 Hz, 200 Hz, 300 Hz, 400 Hz, 500 Hz, 600 Hz, 700 Hz, 800 Hz, 900 Hz, 1000 Hz, 1200 Hz, 1400 Hz, 1600 Hz, 2000 Hz, 2200 Hz, 3000 Hz, 4000 Hz, 5000 Hz, 6000 Hz, 7000 Hz, 8000 Hz, 9000 Hz, 1000 Hz, 1200 Hz, 1400 Hz, 1600 Hz, 1800 Hz, 2000 Hz, 2200 Hz, 300

[0159] In some cases, the frequency of the light waves used to generate the light pulses is F a In some embodiments, each of the three pulses (235a-c) has the same frequency F a The light wave may include light waves having the following structure:

[0160] The width of each of the light pulses (e.g., the duration of a burst of light waves) may correspond to a pulse width (230a). The pulse width (230a) may refer to the length or duration of the burst. The pulse width (230a) may be measured in units of time or distance. In some embodiments, the pulses (235a-c) may have light waves with different frequencies from each other. In some embodiments, the pulses (235a-c) may have different pulse widths (230a) from each other, as illustrated in FIG. 2D. For example, the first pulse (235d) of FIG. 2D may have a pulse width (230a), while the second pulse (235e) has a second pulse width (230b) that is greater than the first pulse width (230a). The third pulse (235f) may have a third pulse width (230c) that is less than the second pulse width (230b). The third pulse width (230c) may also be less than the first pulse width (230a). Although the pulse widths (230a-c) of the pulses (235d-f) of the pulse train may vary, the light-generating module 110 may maintain a constant pulse rate interval 240 of the pulse train.

[0161] The pulses (235a-c) can form a pulse train having a pulse rate interval 240. The pulse rate interval 240 can be quantified using unit time. The pulse rate interval 240 can be based on a frequency of the pulses in the pulse train 201. The frequency of the pulses in the pulse train 201 can be referred to as a modulation frequency. For example, the light-generating module 110 can provide the pulse train 201 with a predetermined frequency corresponding to gamma radioactivity, such as 40 Hz. To do so, the light-generating module 110 can determine the pulse rate interval 240 by taking the multiplicative inverse (or reciprocal) of the frequency (e.g., by dividing 1 by the predetermined frequency of the pulse train). For example, the light-generating module 110 can obtain the multiplicative inverse of 40 Hz by dividing 1 by 40 Hz to determine the pulse rate interval 240 as 0.025 seconds. The pulse rate interval 240 can remain constant throughout the pulse train. In some embodiments, the pulse rate interval 240 may vary throughout the pulse train or from one pulse train to the next, In some embodiments, the number of pulses transmitted per second may be fixed while the pulse rate interval 240 varies.

[0162] In some embodiments, the light-generating module 110 can generate light pulses with light waves of different frequencies. For example, the light-generating module 110 can generate up-chirp pulses, in which the frequency of the light waves of the light pulse increases from the beginning of the pulse to the end of the pulse, as shown in FIG. 2E. For example, the frequency of the light waves at the beginning of the pulse (235g) is F a The frequency of the light wave in the pulse (235g) can be F a From F b and then at the end of the pulse, F c Therefore, the frequency of the light wave used to generate the pulse (235g) can be increased to a maximum of F a From F cThe frequency may increase linearly, exponentially, or based on some other rate or curve.

[0163] The light generating module 110 can generate a down-chirped pulse, as shown in FIG. 2F, in which the frequency of the light wave of the light pulse decreases from the start of the pulse to the end of the pulse. For example, the frequency of the light wave at the beginning of the pulse (235j) is F a The frequency of the light wave of the pulse (235j) can be F d From F e Then at the end of the pulse (235j) it increases to F f Therefore, the frequency of the light wave used to generate the pulse (235j) can be reduced to a minimum of F a From F f The frequency may decrease linearly, exponentially, or based on some other rate or curve.

[0164] The visual signal component 150 can be designed and constructed to generate light pulses in response to instructions from the light generating module 110. The instructions can include parameters of the light pulses, such as the frequency or wavelength of the light waves, the intensity, the duration of the pulses, the frequency of the pulse train, the pulse rate interval, or the duration of the pulse train (e.g., the number of pulses in a pulse train or the length of time to transmit a pulse train having a given frequency). The light pulses can be sensed, observed, or otherwise identified by the brain through visual means such as the eye. The light pulses can be transmitted to the eye directly or via peripheral vision.

[0165] FIG. 3A illustrates a horizontal direct field of view 310 and a horizontal peripheral field of view. FIG. 3B illustrates a vertical direct field of view 320 and a vertical peripheral field of view 325. FIG. 3C illustrates the angles of the direct and peripheral fields of view, including the relative distances at which visual signals may be sensed in the various fields of view. The visual signal component 150 may include a light source 305. The light source 305 may be positioned to transmit light pulses into the direct field of view 310 or 320 of the person's eye. The NS 105 may be configured to transmit light pulses into the direct field of view (310 or 320) so that the person can pay more attention to the light pulses to promote brain entrainment. The level of attention may be measured directly in the brain, indirectly through the person's eye movements, or quantitatively by active feedback (e.g., mouse tracking).

[0166] The light source 305 may be positioned to transmit light pulses to the peripheral vision 315 or 325 of the person's eye. For example, the NSS 105 may transmit light pulses to the peripheral vision 315 or 325, but these light pulses may be less intrusive to a person who may be performing other tasks, such as reading, walking, driving, etc. Thus, the NSS 105 may provide subtle, on-the-go visual brain stimulation by transmitting light pulses through the peripheral vision.

[0167] In some embodiments, the light source 305 is head-mounted, while in other embodiments, the light source 305 may be held by the subject's hand, placed on a stand, suspended from the ceiling, connected to a chair, or otherwise positioned to direct light into the subject's direct or peripheral visual field. For example, a chair or an externally supported system may contain or position the light source 305 to provide visual input while maintaining a fixed / pre-specified relationship between the subject's visual field and the visual stimuli. The system may provide an immersive experience. For example, the system may include an opaque or partially opaque dome that contains the light source. The dome may be positioned over the subject's head while the subject sits or leans back in the chair. The dome may cover a portion of the subject's visual field, thereby reducing external distractions and encouraging entrainment of brain regions.

[0168] The light source 305 may include any type of light source or light emitting device. The light source may include a coherent light source such as a laser. The light source 305 may include a light emitting diode (LED), an organic LED, a fluorescent light source, an incandescent light, or any other light emitting device. The light source may include a lamp, a light bulb, or one or more light emitting diodes of various colors (e.g., white, red, green, blue). In some embodiments, the light source may include 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, the light source 305 includes a hollow cathode lamp, a fluorescent tube light source, a neon lamp, an argon lamp, a plasma lamp, a xenon flash lamp, a mercury lamp, a metal halide lamp, or a sulfur lamp. In some embodiments, the light source 305 includes a laser or a laser diode. In some embodiments, the light source 305 includes an OLED, a PHOLED, a QDLED, or any other variation of a light source that utilizes organic materials. In some embodiments, the light source 305 includes a monochromatic light source. In some embodiments, light source 305 comprises a polychromatic light source. In some embodiments, light source 305 comprises a light source that emits light partially in the ultraviolet spectral range. In some embodiments, light source 305 comprises a device, product, or material that emits light partially in the visible spectral range. In some embodiments, light source 305 comprises a device, product, or material that emits or emits light partially in the infrared spectral range. In some embodiments, light source 305 comprises a device, product, or material that emits or emits light partially in the visible spectral range. In some embodiments, light source 305 comprises a light guide, optical fiber, or light guide through which light is emitted from the light source.

[0169] In some embodiments, the light source 305 includes one or more mirrors to reflect or redirect light. For example, the mirrors can reflect or redirect light toward the direct field of view 310 or 320 or the peripheral field of view 315 or 325. The light source 305 can include or interact with a microelectromechanical device ("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 and directed with one or more optical lenses into the direct field of view or the peripheral field of view. The ambient light or sunlight can be directed by one or more mirrors into the directed field of view or the peripheral field of view.

[0170] If the light source is ambient light, the ambient light is not positioned, but the ambient light can enter the eye via the direct or peripheral field of vision. In some embodiments, the light source 305 can be positioned to direct light pulses into the direct or peripheral field of vision. For example, as illustrated in FIG. 4A, one or more light sources 305 can be attached, coupled, mechanically coupled, or otherwise provided to a frame 400. In some embodiments, the visual signal component 150 can include a frame 400. Additional details of the operation of the NSS 105 in conjunction with a frame 400 including one or more light sources 305 are provided below in the section entitled "NSS Operating With a Frame." Thus, the light source can include any type of light source, such as an optical light source, a mechanical light source, or a chemical light source. The light source can include any material or object, reflective or opaque, such as a fan or bubble that rotates in front of the light, thereby generating, emitting, or reflecting an oscillating pattern of light. In some embodiments, the light source can include an invisible optical illusion, a physiological phenomenon inside the eye (e.g., pressing on the eyeball), or a chemical product that is applied to the eye.

[0171] Systems and devices configured for neurostimulation via visual stimuli - Patents.com Now, referring to FIG. 4A, the frame 400 may be designed and constructed to be placed or positioned on a person's head. The frame 400 may be configured to be worn by a person. The frame 400 may be designed and constructed to remain in place. The frame 400 may be configured to be worn and remain in place when a person sits, stands, walks, runs, or lies down. The light source 305 may be configured on the frame 400 to project light pulses to the person's eye in these various positions. In some embodiments, the light source 305 may be configured to project light pulses toward the person's eye such that when the person's eyelids are closed, the light pulses penetrate the eyelids and are perceived by the retina. The frame 400 may include a bridge 420. The frame 400 may include one or more eye wires 415 coupled to the bridge 420. The bridge 420 may be positioned between the eye wires 415. The frame 400 may include one or more temples extending from the one or more eye wires 415. In some embodiments, the eyewire 415 can include or hold a lens 425. In some embodiments, the eyewire 415 can include or hold a solid member 425 or a cover 425. The lens, solid member, or cover 425 can be transparent, translucent, opaque, or completely block outside light.

[0172] One or more light sources 305 may be located on or adjacent to the eye wire 415, the lens or other solid member 425, or the bridge 420. For example, the light source 305 may be located in the center of the eye wire 415, on the solid member 425, to transmit light pulses directly into the visual field. In some embodiments, the light source 305 may be located at a corner of the eye wire 415, such as a corner of the eye wire 415 coupled to the temple 410, to transmit light pulses into the peripheral visual field.

[0173] The NSS 105 can perform visual brain entrainment 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 be connected to a visual signaling component 150 that includes a frame 400 and two eye wires 415. However, the visual signaling component 150 may include a single light source 305 configured and arranged to direct light pulses to a first eye. The visual signaling component 150 may further include a light blocking component that blocks or blocks the light pulses generated from the light source 305 from entering the second eye. The visual signaling component 150 may block or prevent light from entering the second eye during the brain entrainment process.

[0174] In some embodiments, the visual signal component 150 can transmit or direct light pulses alternately to a first eye and a second eye. The visual signal component 150 can direct light pulses to a first eye for a first time interval. The visual signal component 150 can direct light pulses to a second eye for a second time interval. The first time interval and the second time interval can be the same time interval, overlapping time intervals, mutually exclusive time intervals, or consecutive time intervals.

[0175] 4B illustrates a frame 400 including a set of shutters 435 capable of blocking at least a portion of the light entering through the eye wire 415. The set of shutters 435 can intermittently block ambient or sunlight entering 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 the light entering through the eye wire 415. Additional details of the operation of the NSS 105 in conjunction with a frame 400 including one or more shutters 430 are provided below in the section entitled "NSS Operating with a Frame."

[0176] The set of shutters 435 may include one or more shutters 430 that are opened and closed by one or more actuators. The shutters 430 may be formed from one or more materials. The shutters 430 may include one or more materials. The shutters 430 may include or be formed from a material that can at least partially block or attenuate light.

[0177] The frame 400 may include one or more actuators configured to at least partially open or close the set of shutters 435 or individual shutters 430. The frame 400 may include one or more types of actuators to open and close the set of shutters 435. For example, the actuators may include mechanically driven actuators. The actuators may include magnetically driven actuators. The actuators may include pneumatic actuators. The actuators may include hydraulic actuators. The actuators may include piezoelectric actuators. The actuators may include microelectromechanical systems ("MEMS").

[0178] The set of shutters 435 may include one or more shutters 430 that are opened and closed via electrical or chemical techniques. For example, the shutter 430 or set of shutters 435 may be formed from one or more chemical products. The shutter 430 or set of shutters 435 may include one or more chemical products. The shutter 430 or set of shutters 435 may include or be formed from a material that can at least partially block or attenuate light.

[0179] For example, the shutter 430 or set of shutters 435 may include a photochromic lens configured to filter, attenuate, or block light. The photochromic lens may automatically darken when exposed to sunlight. The photochromic lens may include molecules configured to darken the lens. The molecules may be activated by light waves, such as ultraviolet light or other wavelengths of light. Thus, the photochromic molecules may be configured to darken the lens in response to a predetermined wavelength of light.

[0180] The shutter 430 or set of shutters 435 can include electrochromic glass or electrochromic plastic. Electrochromic glass or electrochromic plastic can change from light to dark (e.g., transparent to opaque) in response to a voltage or current. Electrochromic glass or electrochromic plastic can include a metal oxide coating deposited on the glass or plastic, multiple layers, and lithium ions that move between two electrodes between the layer that lightens the glass or the layer that darkens the glass.

[0181] The shutter 430 or set of shutters 435 may include micro-shutters. A micro-shutter may include a small window with dimensions of 100 x 200 microns. The micro-shutters may be arranged in a waffle-like grid on the eye frame 415. Individual micro-shutters may be opened and closed by an actuator. The actuator may include a magnetic arm that passes by the micro-shutter to open and close it. An open micro-shutter allows light to enter through the eye frame 415, while a closed micro-shutter may block, attenuate, or filter the light.

[0182] The NSS 105 can drive an actuator to open and close one or more shutters 430 or sets of shutters 435 at a predetermined frequency, such as 40 Hz. By opening and closing the shutters 430 at a predetermined frequency, the shutters 430 can pass flashes of light to the eyewire 415 at the predetermined frequency. Thus, a frame 400 that includes a set of shutters 435 may not include or use a separate light source coupled to the frame 400, such as the light source 305 coupled to the frame 400 shown in FIG. 4A.

[0183] In some embodiments, the visual signaling component 150 or the light source 305 may refer to or be included in a virtual reality headset 401, as shown in FIG. 4C. For example, the virtual reality headset 401 may be designed and constructed to receive the light source 305. The light source 305 may include a computing device having a display device, such as a smartphone or a mobile communication device. The virtual reality headset 401 may include a cover 440 that opens to receive the light source 305. The cover 440 may close to lock or hold the light source 305 in place. When closed, the cover 440 and the cases 450 and 445 may form an enclosure for the light source 305. This enclosure may provide an immersive experience that minimizes or eliminates unwanted visual distractions. The virtual reality headset may provide an environment that maximizes brainwave entrainment. The virtual reality headset may 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 from the surface towards the subject's eye (e.g., a head-up display that overlays a blinking object or an augmentation of reality onto the screen). Additional details of the operation of the NSS 105 in conjunction with the virtual reality headset 401 are provided below in the section entitled "Systems and Devices Configured for Neurostimulation With Visual Stimulation."

[0184] Virtual reality headset 401 includes straps 455 and 460 configured to secure virtual reality headset 401 to a person's head. Virtual reality headset 401 can be secured via straps 455 and 460 to minimize movement of worn headset 401 during physical activity, such as walking or running. Virtual reality headset 401 can include a skull cap formed from 460 or 455.

[0185] The feedback sensor 605 may include an electrode, a dry electrode, a gel electrode, a saline-soaked electrode, or an adhesive-based electrode.

[0186] 5A-5D show an embodiment of a visual signaling component 150 that may include a tablet computing device 500 or other computing device 500 having a display screen 305 as a light source 305. The visual signaling component 150 may transmit a light pulse, a light flash, or a pattern of light via the display screen 305 or the light source 305.

[0187] FIG. 5A illustrates a display screen 305 or light source 305 that transmits light. The light source 305 can transmit light including wavelengths in the visible spectrum. The NSS 105 can instruct the visual signaling component 150 to transmit light through the light source 305. The NSS 105 can instruct the visual signaling component 150 to transmit light flashes or light pulses having a predetermined pulse rate interval. For example, FIG. 5B illustrates a light source 305 that is turned off or disabled such that the light source does not emit light or emits only 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 the light flashes 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 light flashes or light pulses of a predetermined frequency.

[0188] In some embodiments, as shown in FIGS. 5C and 5D, the light generating module 110 can direct or cause the visual signaling component 150 to display a pattern of light via the display device 305 or light source 305. The light generating module 110 can cause the visual signaling component 150 to blink, toggle, or switch between two or more patterns to generate flashes of light or light pulses. The patterns can include, for example, alternating checkerboard patterns 510 and 515. The patterns can include symbols, characters, or images that can be toggled or adjusted from one state to another. For example, the color of the characters or text can be inverted relative to the background color to switch between a first state 510 and a second state 515. Inverting the foreground and background colors at a predetermined frequency can generate light pulses in a manner that displays a visual change that can facilitate regulating or managing the 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 entitled "NSS Operating with a Tablet."

[0189] In some embodiments, the light generation module 110 can command or cause the visual signaling component 150 to blink, toggle, or switch between images configured to stimulate specific or predetermined portions of the brain or a particular cortex. The presentation, form, color, movement, and other aspects of the light or image-based stimuli can dictate which cortex is 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 visual field, the color of the input, or the movement and speed of the light stimuli can dictate which areas of the cortex are stimulated.

[0190] For example, the brain can include at least two parts that process a given type of visual stimulus: the primary visual cortex on the left side of the brain and the calcarine sulcus on the right side of the brain. Each of these two parts can have one or more complex subparts that process a given type of visual stimulus. For example, the calcarine sulcus can include a subpart called area V5, which can include neurons that respond strongly to motion but may not register stationary objects. A subject with damage to area V5 can have motion blindness but otherwise normal vision. In another example, the primary visual cortex can include a subpart called area V4, which can include neurons specialized for color perception. A subject 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 subpart called area V1, which includes neurons that respond strongly to contrast edges and help segment an image into separate objects.

[0191] Thus, the light generation module 110 can command or cause the visual signaling component 150 to generate a type of still image or video, to blink, or to toggle between images configured to stimulate a specific or predetermined portion of the brain or a specific cortex. For example, the light generation module 110 can command or cause the visual signaling component 150 to generate an image of a fusiform human face to stimulate the face region, thereby promoting brain entrainment in a subject with prosopagnosia or face blindness. The light generation module 110 can command or cause the visual signaling component 150 to generate an image of a face that blinks to target this region of the subject's brain. In another example, the light generation module 110 can command the visual signaling component 150 to generate an image that includes edges or lines to stimulate neurons in the primary visual cortex that respond strongly to contrast edges.

[0192] The NSS 105 may include, access, interface with, or otherwise communicate with at least one light adjustment module 115. The light adjustment module 115 may be designed and constructed to measure or verify environmental variables (e.g., light intensity, timing, incident light, ambient light, eyelid state, etc.) to adjust parameters associated with the visual signal, such as the frequency, amplitude, wavelength, intensity pattern, or other parameters of the visual signal. The light adjustment module 115 may automatically change parameters of the visual signal based on profile information or feedback. The light adjustment module 115 may receive feedback information from a feedback monitor 135. The light adjustment module 115 may receive instructions or information from a side effect management module 130. The light adjustment module 115 may receive profile information from a profile manager 125.

[0193] The NSS 105 may include, access, interface with, or otherwise communicate with at least one unwanted frequency filtering module 120. The unwanted frequency filtering module 120 may be designed and constructed to block, moderate, reduce, or otherwise filter frequencies of undesirable visual signals to prevent or reduce a certain amount of such visual signals from being perceived by the brain. The unwanted frequency filtering module 120 may interface, command, control, or otherwise communicate with the filtering component 155 to cause the filtering component 155 to block, attenuate, or otherwise reduce the effects of unwanted frequencies on neural oscillations.

[0194] The NSS 105 may include, access, interface with, or otherwise communicate with at least one profile manager 125. The profile manager 125 may be designed or constructed to store, update, retrieve, or otherwise manage information related to one or more subjects related to visual brain entrainment. The profile information may include, for example, past treatment information, brain entrainment history information, medication information, light wave parameters, feedback, physiological information, environmental information, or other data related to the brain entrainment system and method.

[0195] The NSS 105 may include, access, interface with, or otherwise communicate with at least one side effect management module 130. The side effect management module 130 may be designed and constructed to provide information to the light adjustment module 115 or the light generation module 110 to modify one or more parameters of the visual signal to reduce side effects. Side effects may include, for example, nausea, migraines, fatigue, seizures, eye strain, or vision loss.

[0196] The side effect management module 130 can automatically instruct components of the NSS 105 to modify or change parameters of the visual signal. The side effect management module 130 can be configured with predefined thresholds to reduce side effects. For example, the side effect management module 130 can be configured with a maximum duration of a pulse train, a maximum intensity of light waves, a maximum amplitude, a maximum duty cycle of a pulse train (e.g., pulse width of a pulse train multiplied by frequency), a maximum number of treatments for brainwave entrainment over a period of time (e.g., 1 hour, 2 hours, 12 hours, or 24 hours).

[0197] The side effect management module 130 can vary a parameter of the visual signal in response to the feedback information. The side effect management module 130 can receive feedback from a feedback monitor 135. The side effect management module 130 can decide to adjust the parameter of the visual signal based on the feedback. The side effect management module 130 can compare the feedback to a threshold and decide to adjust the parameter of the visual signal.

[0198] The side effect management module 130 can be configured with or can include a policy engine that applies policies or rules to the current visual signal and feedback to determine adjustments to the visual signal. For example, if the feedback indicates that the patient receiving the visual signal has a heart rate or pulse rate above a threshold, the side effect 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 below the threshold.

[0199] The NSS 105 may include, access, interface with, or otherwise communicate with at least one feedback monitor 135. The feedback monitor may be designed and constructed to receive feedback information from a feedback component 160. The feedback component 160 may include, for example, a feedback sensor 605, such as a temperature sensor, a heart rate or pulse rate monitor, a physiological sensor, an ambient light sensor, an ambient temperature sensor, a sleep state via actigraphy, a blood pressure monitor, a respiration rate monitor, an electroencephalogram sensor, an EEG probe, an electro-oculogram ("EOG") probe configured to measure a corneal retinal standing potential present between the front and back of the human eye, an accelerometer, a gyroscope, a motion detector, a proximity sensor, a camera, a microphone, or a photodetector.

[0200] In some embodiments, the computing device 500 may include a feedback component 160 or a feedback sensor 605, as shown in Figures 5C and 5D. For example, the feedback sensor of the tablet 500 may include a front-facing camera that can capture an image of a person looking at the light source 305.

[0201] 6A shows one or more feedback sensors 605 disposed on the frame 400. In some embodiments, the frame 400 can include a single or multiple feedback sensors 605 disposed on a portion of the frame, such as a portion of the bridge 420 or the eye wire 415. The feedback sensor 605 can comprise or be coupled to the light source 305. The feedback sensor 605 can be separate from the light source 305.

[0202] The feedback sensor 605 can interact or communicate with the NSS 105. For example, the feedback sensor 605 can provide detected feedback information or data to the NSS 105 (e.g., the feedback monitor 135). The feedback sensor 605 can provide data to the NSS 105 in real time, for example, as the feedback sensor 605 detects or senses information. The feedback sensor 605 can provide feedback information to the NSS 105 based on a time interval, such as 1 minute, 2 minutes, 5 minutes, 10 minutes, 1 hour, 2 hours, 4 hours, 12 hours, or 24 hours. The feedback sensor 605 can provide feedback information to the NSS 105 in response to a condition or event, such as a feedback measurement exceeding or falling below a threshold. The feedback sensor 605 can provide feedback information in response to a change in a feedback parameter. In some embodiments, the NSS 105 can ping, query, or request information from the feedback sensor 605, and the feedback sensor 605 can provide feedback information in response to the ping, request, or query for network connectivity.

[0203] 6B shows a feedback sensor 605 placed or positioned on, on, or near a person's head. The feedback sensor 605 may include, for example, an EEG probe to detect brainwave activity.

[0204] The feedback monitor 135 can detect, receive, acquire, or otherwise identify feedback information from one or more feedback sensors 605. The feedback monitor 135 can provide the feedback information to one or more components of the NSS 105 for further processing or storage. For example, the profile manager 125 can update a profile data structure 145 stored in the data repository 140 with the feedback information. The profile manager 125 can associate the feedback information with an identifier of the patient or person receiving visual brain stimulation, as well as a timestamp and date stamp corresponding to the receipt or detection of the feedback information. The identifier can be indicative of a subject's activity, a subject's physiological or physical state, or a subject's mental state. The identifier can also be indicative of a disease, disorder, or condition.

[0205] The feedback monitor 135 can detect symptoms of a neurological disease or disorder. In this example, the feedback monitor can be used to evaluate changes in fine motor skills or changes in voice pitch or timbre over time. The profile manager 125 can update a profile data structure with the feedback information. The profile data structure can be used to evaluate whether a person is at risk for developing a neurological disorder, whether a person has a neurological disorder, or the progression of symptoms of a neurological disorder.

[0206] The feedback monitor 135 can determine the attention level. The attention level can refer to the focus provided to the light pulses used for brain stimulation. The feedback monitor 135 can determine the attention level using a variety of hardware and software techniques. The feedback monitor 135 can assign a score to the attention level (e.g., 1 to 10 where 1 is low attention and 10 is high attention, or vice versa; 1 to 100 where 1 is low attention and 100 is high attention, or vice versa; 0 to 1 where 0 is low attention and 1 is high attention, or vice versa), classify the attention level (e.g., low, medium, high), grade the attention (e.g., A, B, C, D, or F), or otherwise provide an indication of the attention level.

[0207] In some cases, the feedback monitor 135 can track the person's eye movements to determine attention levels. The feedback monitor 135 can interface with a feedback component 160 that includes an eye tracker. The feedback monitor 135 (e.g., via the feedback component 160) can detect and record the person's eye movements and analyze the recorded eye movements to determine attention span or attention levels. The feedback monitor 135 can measure gaze, which may indicate or provide information about hidden attention. For example, the feedback monitor 135 (e.g., via the feedback component 160) can be configured with electrooculography ("EOG") to measure skin potential around the eyes, which can indicate the direction the eyes are pointing relative to the head. In some embodiments, the EOG can include a system or device for stabilizing the head such that the head cannot move to determine the direction the eyes are pointing relative to the head. In some embodiments, the EOG can include or interface with a head tracker system to determine the position of the head and determine the direction the eyes are pointing relative to the head.

[0208] In some embodiments, feedback monitor 135 and feedback component 160 can use video detection of pupil or corneal reflexes to determine or track eye direction or eye movement. For example, feedback component 160 can include one or more cameras or video cameras. Feedback component 160 can include an infrared source that transmits light pulses toward the eye. The light can be reflected by the eye. Feedback component 160 can detect the location of the reflection. Feedback component 160 can capture or record the location of the reflection. Feedback component 160 can perform image processing on the reflection to determine or calculate eye direction or eye gaze direction.

[0209] The feedback monitor 135 can compare the eye direction or movement to the same person's eye direction or movement history, nominal eye movements, or other eye movement history information to determine the attention level. For example, if the eye is focused on the light pulses during the pulse train, the feedback monitor 135 can determine the attention level is high. If the feedback monitor 135 determines that the eye moves away from the pulse train for 25% of the pulse train, the feedback monitor 135 can determine the attention level is medium. If the feedback monitor 135 determines that eye movement occurs or the eye is unfocused for more than 50% of the pulse train, the feedback monitor 135 can determine the attention level is low.

[0210] In some embodiments, the system 100 may include a filter (e.g., filtering component 155) to control the spectral range of light emitted from the light source. In some embodiments, the light source includes a polarizer, filter, prism, or a light-reactive material that affects the emitted light, such as a photochromic material or electrochromic glass or plastic. The filtering component 155 may receive instructions from the unwanted frequency filtering module 120 to block or attenuate one or more frequencies of light.

[0211] The filtering component 155 may include optical filters that can selectively transmit light of a certain range of wavelengths or colors while blocking one or more other ranges of wavelengths or colors. Optical filters can change the magnitude or phase of an incident light wave for a range of wavelengths. Optical filters can include absorption filters, or interference or dichroic filters. Absorption filters can capture the energy of photons and convert the electromagnetic energy of the light wave into the internal energy of the absorber (e.g., thermal energy). The reduction in intensity of a light wave propagating through a medium due to the absorption of a portion of the photons can be referred to as attenuation.

[0212] An interference or dichroic filter may include an optical filter that reflects one or more spectral bands of light but transmits other spectral bands of light. An interference or dichroic filter may have an absorption coefficient of near zero for one or more wavelengths. An interference filter may be high-pass, low-pass, band-pass, or band-reject. An interference filter may include one or more thin layers of dielectric or metallic materials with different refractive indices.

[0213] In an example implementation, the NSS 105 may interface with a visual signaling component 150, a filtering component 155, and a feedback component 160. The visual signaling component 150 may include hardware or devices such as an eyeglass frame 400 and one or more light sources 305. The filtering component 155 may include hardware or devices such as a feedback sensor 605. The filtering component 155 may include hardware, materials, or chemicals such as polarized lenses, shutters, electrochromic or photochromic materials.

[0214] Computing Environment 7A and 7B depict a block diagram of a computing device 700. As shown in FIGS. 7A and 7B, the computing device 700 each includes a central processing unit 721 and a main memory 722. As shown in FIG. 7A, the computing device 700 can include a memory device 728, a mounting device 716, a network interface 718, an I / O controller 723, a display device (724a-724n), a keyboard 726, and a pointing device device 727 (e.g., a mouse). The memory device 728 can include, without limitation, an operating system, software, and software of a neurostimulation system ("NSS") 701. The NSS 701 can include or refer to one or more of the NSS 105, NSS 905, or NSOS (1605). As shown in FIG. 7B , each computing device 700 may also include additional optional elements, such as a memory port 703, a bridge 770, one or more I / O devices (730a-730n), generally referred to using the reference numeral 730, and a cache memory 740 in communication with the central processing unit 721.

[0215] 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 as a microprocessor unit, such as those manufactured by Intel Corporation (Mountain View, Calif.); those manufactured by Motorola Corporation (Schaumburg, Ill.); ARM processors (e.g., from ARM Holdings, and by ST, TI, ATMEL, etc.) and TEGRA systems-on-chips (SoCs) manufactured by Nvidia (Santa Clara, Calif.); those manufactured by IBM (White Plains, New York) as POWER7 processors; or those manufactured by Advanced Micro Devices (Sunnyvale, Calif.); or field programmable gate arrays ("FPGAs") from Altera (San Jose, Calif.), Xlinix (San Jose, Calif.), or MicroSemi (Aliso Viejo, Calif.), 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 caches, and multi-core processors. Multi-core processors 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.

[0216] The main memory unit 722 may include one or more memory chips that store data and allow any memory location to be directly accessed by the microprocessor 721. The main memory unit 722 may be volatile and faster than the memory of the storage 728. The main memory unit 722 may be dynamic random access memory (DRAM) or any variant including static random access memory (SRAM), burst SRAM or sync burst SRAM (BSRAM), fast page mode DRAM (FPM DRAM), enhanced DRAM (EDRAM), enhanced data output RAM (EDO RAM), enhanced 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 storage 728 may be non-volatile, such as non-volatile read access memory (NVRAM), flash memory non-volatile static RAM (nvSRAM), ferroelectric RAM (FeRAM), magnetoresistive RAM (MRAM), phase change memory (PRAM), conductive bridge RAM (CBRAM), silicon-oxide-nitride-oxide-silicon (SONOS), resistive RAM (RRAM), racetrack, nanoRAM (NRAM), or millipede memory. The main memory 722 may be based on any of the memory chips described above or other available memory chips capable of operating as described herein. In the embodiment shown in FIG. 7A, the processor 721 communicates with the 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 the main memory 722 via memory port 703. For example, in FIG. 7B, the main memory 722 may be a DRDRAM.

[0217] FIG. 7B illustrates an embodiment in which the main processor 721 communicates directly with the cache memory 740 through a secondary bus, sometimes referred to as a backside bus. In other embodiments, the main processor 721 communicates with the cache memory 740 using a system bus 750. The cache memory 740 typically has a faster response time than the main memory 722 and is typically provided by SRAM, BSRAM, or EDRAM. In the embodiment illustrated in FIG. 7B, the processor 721 communicates with various I / O devices 730 through a local system bus 750. Various buses, including a PCI bus, a PCI-X bus, or a PCI-Express bus, or a NuBus can be used to connect the central processing unit 721 to any of the I / O devices 730. In an embodiment in which the I / O device is a video display 724, the processor 721 can communicate with the display 724 or an I / O controller 723 for the display 724 using an Advanced Graphics Port (AGP). Figure 7B shows an embodiment of a computer 700 in which a main processor 721 communicates directly with I / O devices (730b) or other processors (721') via HYPERTRANSPORT, RAPIDIO, or INFINIBAND communications technologies. Figure 7B also depicts an embodiment in which local bus and direct communications are mixed, with processor 721 communicating with I / O devices (730a) using a local interconnect bus while also communicating directly with I / O devices (730b).

[0218] A wide variety of I / O devices (730a-730n) may be present in the computing device 700. Input devices may include keyboards, mice, trackpads, trackballs, touchpads, touch mice, multi-touch touchpads and touch mice, microphones (analog or MEMS), multi-array microphones, drawing tablets, cameras, single-lens reflex cameras (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, gyroscope sensors, or other sensors. Output devices may include video displays, graphical displays, speakers, headphones, inkjet printers, laser printers, and 3D printers.

[0219] The devices (730a-n) may include a combination of multiple input or output devices, including, for example, Microsoft KINECT, Nintendo Wiimote for the WII, Nintendo WII U GAMEPAD, or Apple IPHONE. Some devices (730a-n) allow gesture recognition input by combining some of the inputs and outputs. Some devices (730a-n) offer face recognition that may be used as input for different purposes, including authentication and other commands. Some devices (730a-n) offer voice recognition and input, including, for example, Microsoft KINECT, SIRI for the IPHONE by Apple, Google Now, or Google Voice Search.

[0220] Additional devices (730a-730n) have both input and output capabilities, including, for example, haptic feedback devices, touch screen displays, or multi-touch displays. Touch screens, multi-touch displays, touch pads, touch mice, or other touch sensing devices can use different technologies to sense touch, including, for example, capacitive, surface capacitive, projected capacitive touch (PCT), in-cell capacitive, resistive, infrared, waveguide, distributed 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 for two or more points of contact with a surface, allowing for advanced functionality including, for example, pinching, spreading, rotating, scrolling, or other gestures. Some touch screen devices, including, for example, the Microsoft PIXELSENSE or Multi-Touch Collaboration Wall, can have larger surfaces, such as on a tabletop or on a wall, and can also interact with other electronic devices. Some of the I / O devices (730a-730n), display devices (724a-724n), or groups of devices may be augmented reality devices. The I / O devices may be controlled by an I / O controller 721, as shown in FIG. 7A. The I / O controller 721 may control one or more I / O devices, such as, for example, a keyboard 126 and a pointing device 727, such as a mouse or optical pen. In addition, the I / O devices may also provide storage and / or installation medium 116 for the computing device 700. In yet other embodiments, the computing device 700 may provide a USB connection (not shown) for accepting a handheld USB storage device.In a further embodiment, the I / O device 730 may be a bridge between the system bus 750 and an external communication bus, such as a USB bus, a SCSI bus, a FireWire bus, an Ethernet bus, a Gigabit Ethernet bus, a Fibre Channel bus, or a Thunderbolt bus.

[0221] In some embodiments, the display devices (724a-n) can be connected to the I / O controller 721. The display devices can include, for example, a liquid crystal display (LCD), a thin film transistor LCD (TFT-LCD), a blue phase LCD, an electronic paper (e-ink) display, a flex display, a light emitting diode display (LED), a digital light processing (DLP) display, a liquid crystal on silicon (LCOS) display, an organic light emitting diode (OLED) display, an active matrix organic light emitting diode (AMOLED) display, a liquid crystal laser display, a time multiplexed optical shutter (TMOS) display, or a 3D display. Examples of 3D displays can use, for example, stereoscopic vision, polarizing filters, active shutters, or autostereoscopic vision. The display devices (724a-n) can also be head mounted displays (HMDs). In some embodiments, the display devices (724a-724n) or corresponding I / O controllers 723 may be controlled via an OPENGL or DIRECTX API or other graphics library, or may have hardware support for an OPENGL or DIRECTX API or other graphics library.

[0222] In some embodiments, the computing device 700 can include or be connected to multiple display devices (724a-724n), each of which can be the same or different types and / or forms. Thus, any of the I / O devices (730a-730n) and / or I / O 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, drivers, and / or libraries to interface with, communicate with, connect to, or otherwise use the display devices (724a-724n). In one embodiment, the video adapter can include multiple connectors for interfacing to multiple display devices (724a-724n). In other embodiments, computing device 700 may include multiple video adapters, each video adapter connected to one or more of the display devices (724a-724n). In some embodiments, any portion of the operating system of computing device 700 may be configured to use multiple displays (724a-724n). In other embodiments, one or more of the display devices (724a-724n) may be provided by one or more other computing devices (700a) or (700b) connected to computing device 700 via network 140. In some embodiments, software may be designed and constructed to use a display device of another computer as a second display device (724a) for computing device 700.For example, in one embodiment, an Apple iPad can connect to computing device 700 and use the display of device 700 as an additional display screen that can be used as an extended desktop.

[0223] Referring again to FIG. 7A, the computing device 700 may include a storage device 728) (e.g., one or more hard disk drives or a redundant array of independent disks) for storing an operating system or other related software, and for storing application software programs, such as any programs related to the software for the NS. Examples of storage devices 728 include, for example, hard disk drives (HDDs), optical drives, including CD drives, DVD drives, or BLU-RAY drives, solid state drives (SSDs), USB flash drives, or any other device suitable for storing data. Some storage devices may include multiple volatile and non-volatile memories, including, for example, solid state hybrid drives that combine a hard disk with a solid state cache. Some storage devices 728 may be non-volatile, alterable, or read-only. Some storage devices 728 may be internal and connected to the computing device 700 via a bus 750. Some storage devices 728 may be external and connected to the computing device 700 via an I / O device 730 that provides an external bus. Some storage devices 728 may be connected to the computing device 700 over a network via the network interface 718, including, for example, a remote disk for the MACBOOK AIR by Apple. Some client devices 700 may not require a non-volatile storage device 728 and may be thin clients or zero clients 202. Some storage devices 728 may also be used as installation devices 716 and may be suitable for installing software and programs. Additionally, the operating system and software may be executed from a bootable medium, for example, a bootable CD, for example, KNOPPIX, a bootable CD for GNU / Linux available as a GNU / Linux distribution from KNOPPIX.net.

[0224] The computing device 700 can also install software or applications from an application distribution platform. Examples of application distribution platforms include the App Store for iOS offered by Apple, Inc., the Mac App Store offered by Apple, Inc., Google PLAY for Android OS offered by Google Inc., CHROME Webstore for CHROME OS offered by Google Inc., and the Amazon Appstore for Android OS and KINDLE FIRE offered by Amazon.com, Inc.

[0225] Additionally, the computing device 700 may include a network interface 718 for interfacing to the network 140 through a variety of connections, including, but not limited to, standard telephone line LAN or WAN links (e.g., 802.11, T1, T3, Gigabit Ethernet, InfiniBand), broadband connections (e.g., ISDN, Frame Relay, ATM, Gigabit Ethernet, Ethernet-over-SONET, ADSL, VDSL, BPON, GPON, fiber optics including FiOS), wireless connections, or any combination of any or all of the above. Connections may 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, computing device 700 communicates with other computing devices 700' via any type and / or form of gateway or tunneling protocol, such as Secure Sockets Layer (SSL) or Transport Layer Security (TLS), or the Citrix Gateway protocol manufactured by Citrix Systems, Inc. of Ft. Lauderdale, Fla. Network interface 118 may include an internal network adapter, a network interface card, a PCMCIA network card, an EXPRESSCARD network card, a card bus network adapter, a wireless network adapter, a USB network adapter, a modem, or any other device suitable for interfacing computing device 700 to any type of network with which it is capable of communicating and performing the operations described herein.

[0226] A computing device 700 of the type shown in Figure 7A may operate under the control of an operating system that controls the scheduling of tasks and access to system resources. The computing device 700 may run any operating system, such as any version of the MICROSOFT WINDOWS operating system, different releases of the Unix and Linux operating systems, any version of MAC OS for Macintosh computers, any embedded operating system, any real-time operating system, any open source operating system, any proprietary operating system, any operating system for mobile computing devices, or any other operating system capable of running on a computing device and performing the operations described herein. Exemplary operating systems include, but are not limited to, WINDOWS 7000, WINDOWS Server 2012, WINDOWS CE, WINDOWS Phone, WINDOWS XP, WINDOWS VISTA, and WINDOWS 7, WINDOWS RT, and WINDOWS 8, all manufactured by Microsoft Corporation of Redmond, Washington; MAC OS and iOS manufactured by Apple, Inc. of Cupertino, California; and Linux, a freely available operating system such as the Linux Mint distribution ("distro") or Ubuntu distributed by Canonical Ltd. of London, England; or Unix or other Unix-like derived operating systems; and Android, designed by Google of Mountain View, California. Some operating systems, including, for example, CHROME OS by Google, can be used on zero or thin clients, including, for example, CHROMEBOOKS.

[0227] The computer system 700 may be any workstation, phone, desktop computer, laptop or notebook computer, netbook, ULTRABOOK, tablet, server, handheld computer, cell phone, smartphone or other portable telecommunications device, media playback device, gaming system, mobile computing device, or any other type and / or form of computing, telecommunications or media device capable of communication. The computer system 700 has sufficient processor power and memory capacity to perform the operations described herein. In some embodiments, the computing device 700 may have different processors, operating systems, and input devices consistent with the device. For example, the Samsung GALAXY smartphone operates under the control of the Android operating system developed by Google, Inc. The GALAXY smartphone receives input via a touch interface.

[0228] In some embodiments, computing device 700 is a gaming system. For example, computer system 700 may include a PLAYSTATION3, or a PERSONAL PLAYSTATION PORTABLE (PSP), or a PLAYSTATION VITA device manufactured by Sony Corporation of Tokyo, Japan, a NINTENDO DS, NINTENDO3DS, NINTENDO WII, or NINTENDO WII U device manufactured by Nintendo Co., Ltd. of Kyoto, Japan, an XBOX360 device manufactured by Microsoft Corporation of Redmond, Washington, or an OCULUS RIFT or OCULUS VR device manufactured by OCULUS VR, LLC of Menlo Park, California.

[0229] In some embodiments, the computing device 700 is a digital audio player, such as the Apple IPOD, IPOD Touch, and IPOD NANO device lines manufactured by Apple Computer of Cupertino, Calif. Some digital audio players may have other features, including, for example, gaming systems, or any features made available by applications from digital application distribution platforms. 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 that supports file formats, including, but not limited to, MP3, WAV, M4A / AAC, WMA Protected AAC, AIFF, Audible audiobooks, Apple Lossless audio file formats, and .mov, .m4v, and .mp4 MPEG-4 (H.264 / MPEG-4 AVC) video file formats.

[0230] In some embodiments, computing device 700 is a tablet, such as Apple's IPAD line of devices, Samsung's GALAXY TAB family of devices, or a KINDLE FIRE from Amazon.com, Inc. of Seattle, Wash. In other embodiments, computing device 700 is an eBook reader, such as the KINDLE family of devices from Amazon.com, or the NOOK family of devices from Barnes & Noble, Inc. of New York City, NY.

[0231] In some embodiments, the communication device 700 includes a combination of devices, such as a smartphone combined with a digital audio player or portable media player. For example, one of these embodiments is a smartphone, such as the IPHONE family of smartphones manufactured by Apple, Inc., the Samsung GALAXY family of smartphones manufactured by Samsung, Inc., or the Motorola DROID family of smartphones. In yet another embodiment, the communication device 700 is a laptop or desktop computer equipped with a web browser and a microphone and speaker system, such as a telephone headset. In these embodiments, the communication device 700 is web-enabled and can receive and initiate telephone calls. In some embodiments, the laptop or desktop computer is also equipped with a webcam or other video capture device that allows for video chat and video calling.

[0232] In some embodiments, the status of one or more machines 700 in a network is typically monitored as part of network management. In one of these embodiments, the status of a machine may include load information (e.g., the number of processes on the machine, CPU and memory utilization), port information (e.g., the number of available communication ports and port addresses), or session status (e.g., process duration and type, and whether the process is active or idle) identification. In another of these embodiments, this information may be identified by a number of metrics that may be applied at least in part to determining load distribution, network traffic management, and network failure recovery, as well as any aspect of the operation of the present solution described herein. The aspects of the operating environment and components described above will become apparent in the context of the systems and methods disclosed herein.

[0233] Methods for nerve stimulation FIG. 8 is a flow diagram of a method for visual brain entrainment according to an embodiment. Method 800 may be performed by one or more systems, components, modules, or elements shown in FIGS. 1-7B, including, for example, a neurostimulation system (NSS). In brief overview, the NSS may identify a visual signal to provide, at block 805. At block 810, the NSS may generate and send the identified visual signal. At 815, the NSS may receive or determine feedback related to neural activity, physiological activity, environmental parameters, or device parameters. At 820, the NSS may manage, control, or adjust the visual signal based on the feedback.

[0234] NSS working with frames The NSS 105 can operate in conjunction with a frame 400 including a light source 305, as shown in FIG 4A. The NSS 105 can operate in conjunction with a frame 400 including a light source 30 and a feedback sensor 605, as shown in FIG 6A. The NSS 105 can operate in conjunction with a frame 400 including at least one shutter 430, as shown in FIG 4B. The NSS 105 can operate in conjunction with a frame 400 including at least one shutter 430 and a feedback sensor 605.

[0235] In operation, a user of the frame 400 can wear the frame 400 on their head such that the eyewire 415 surrounds or substantially surrounds the eyes. In some cases, the user can indicate to the NSS 105 that the eyeglass frame 400 is worn and that the user is ready to undergo brainwave entrainment. The indication can include an instruction, command, selection, input, or other indication via an input / output interface, such as a keyboard 726, a pointing device 727, or other I / O devices 730a-n. The indication can be a motion-based indication, a visual indication, or an audio-based indication. For example, the user can give a voice command indicating that the user is ready to undergo brainwave entrainment.

[0236] In some cases, the feedback sensor 605 can determine that the user is ready to receive brainwave entrainment. The feedback sensor 605 can detect that the eyeglass frame 400 has been placed on the user's head. The NSS 105 can receive motion data, acceleration data, gyroscope data, temperature data, or capacitive touch data to determine that the frame 400 has been placed on the user's head. The received data, such as motion data, can indicate that the frame 400 has been picked up and placed on the user's head. The temperature data can measure a temperature at or near the frame 400 and can indicate that the frame is on the user's head. In some cases, the feedback sensor 605 can perform eye tracking to determine a level of attention that the user is paying to the light source 305 or the feedback sensor 605. The NSS 105 can sense the user's readiness in response to determining that the user is paying a high level of attention to the light source 305 or the feedback sensor 605. For example, gazing, gazing, or looking in the direction of the light source 305 or the feedback sensor 605 can provide an indication that the user is ready to receive brainwave entrainment.

[0237] Thus, the NSS 105 may detect or determine that the frame 400 is worn and the user is ready, or the NSS 105 may receive an indication or confirmation from the user that the user has worn the frame 400 and that the user is ready to undergo brainwave entrainment. Upon determining that the user is ready, the NSS 105 may initialize the brainwave entrainment process. In some embodiments, the NSS 105 may access the profile data structure 145. For example, the profile manager 125 may query the profile data structure 145 to determine one or more parameters for the external visual stimuli used in the brain entrainment process. The parameters may include, for example, a type of visual stimulus, an intensity of the visual stimulus, a frequency of the visual stimulus, a duration of the visual stimulus, or a wavelength of the visual stimulus. The profile manager 125 may query the profile data structure 145 to obtain historical information of the brain entrainment, such as previous visual stimulation sessions. The profile manager 125 may perform a search in the profile data structure 145. The profile manager 125 may perform a search using the user's name, a user identifier, location information, a fingerprint, a biometric identifier, a retina scan, voice recognition and authentication, or other identification techniques.

[0238] The NSS 105 can determine the type of external visual stimulus based on the hardware 400. The NSS 105 can determine the type of external visual stimulus based on the type of light source 305 available. For example, if the light source 305 includes a monochromatic LED that produces light waves in the red spectrum, the NSS 105 can determine that the type of visual stimulus includes pulses of light transmitted by the light source. However, if the frame 400 does not include an active light source 305, but instead includes one or more shutters 430, the NSS 105 can determine that the light source is sunlight or ambient light that is modulated as it enters the user's eye through the plane formed by the eye wire 415.

[0239] In some embodiments, the NSS 105 can determine the type of external visual stimulus based on past brainwave entrainment sessions. For example, the profile data structure 145 can be pre-configured with information regarding the type of visual signaling component 150.

[0240] The NSS 105 can determine the modulation frequency of the pulse train or the ambient light via the profile manager 125. For example, the NSS 105 can determine from the profile data structure 145 that the modulation frequency of the external visual stimulus should be set to 40 Hz. Depending on the type of visual stimulus, the profile data structure 145 can further indicate the pulse length, intensity, wavelength of the light waves forming the light pulse, or duration of the pulse train.

[0241] In some cases, the NSS 105 can determine or adjust one or more parameters of the external visual stimulus. For example, the NSS 105 (e.g., via the feedback component 160 or the feedback sensor 605) can determine the level or amount of ambient light. The NSS 105 (e.g., via the light adjustment module 115 or the side effect management module 130) can establish, initialize, set, or adjust the intensity or wavelength of the light pulses. For example, the NSS 105 can determine that there is a low level of ambient light. Because the level of ambient light is low, the user's pupils may be dilated. The NSS 105 can determine that the user's pupils are likely dilated based on the detection of the low level of ambient light. In response to determining that the user's pupils are likely dilated, the NSS 105 can set a lower level of intensity of the pulse train. Additionally, the NSS 105 can use light waves with a longer wavelength (e.g., red), which can reduce strain on the eyes.

[0242] In some embodiments, the NSS 105 can monitor the level of ambient light (e.g., via the feedback monitor 135 and the feedback component 160) throughout the brainwave entrainment process and automatically and periodically adjust the intensity or color of the light pulses. For example, if the user initiates the brainwave entrainment process when there is a high level of ambient light, the NSS 105 can initially set the intensity level of the light pulses higher and use a color that includes light waves with lower wavelengths (e.g., blue). However, in some embodiments where the level of ambient light decreases throughout the brainwave entrainment process, the NSS 105 can automatically detect the decrease in ambient light and, in response to the detection, adjust or decrease the intensity while increasing the wavelength of the light waves. The NSS 105 can adjust the light pulses to provide a high contrast ratio to facilitate brainwave entrainment.

[0243] In some embodiments, the NSS 105 can monitor or measure physiological conditions (e.g., via feedback monitor 135 and feedback component 160) to set or adjust parameters of the light waves. For example, the NSS 105 can monitor or measure the level of pupil dilation to adjust or set parameters of the light waves. In some embodiments, the NSS 105 can monitor or measure heart rate, pulse rate, blood pressure, body temperature, sweating, or brain activity to set or adjust parameters of the light waves.

[0244] In some embodiments, the NSS 105 can be pre-configured to initially send light pulses with the lowest light wave intensity setting (e.g., low amplitude of light waves or high wavelength of light waves) and gradually increase the intensity (e.g., increase the amplitude of light waves or decrease the wavelength of light waves) while monitoring feedback until an optimal light intensity is reached. The optimal light intensity can refer to the highest intensity without adverse physiological side effects such as blindness, stroke, heart attack, migraine, or other discomfort. The NSS 105 can monitor physiological symptoms (e.g., via side effect management module 130) to identify adverse side effects of the external visual stimulation and adjust the external visual stimulation accordingly (e.g., via light adjustment module 115) to reduce or eliminate the adverse side effects.

[0245] In some embodiments, the NSS 105 can adjust parameters of the light waves or light pulses (e.g., via the light adjustment module 115) based on the level of attention. For example, during the brainwave entrainment process, the user may become bored, lose focus, fall asleep, or otherwise not pay attention to the light pulses. Not paying attention to the light pulses can reduce the effectiveness of the brainwave entrainment process and result in neurons oscillating at a different frequency than the desired modulation frequency of the light pulses.

[0246] The NSS 105 can detect the level of attention the user is giving to the light pulse using the feedback monitor 135 and one or more feedback components 160. The NSS 105 can perform eye tracking to determine the level of attention the user is giving to the light pulse based on the gaze direction of the retina or pupil. The NSS 105 can measure eye movement to determine the level of attention the user is giving to the light pulse. The NSS 105 can present a survey or prompt asking for user feedback indicating the level of attention the user is giving to the light pulse. In response to determining that the user is not paying sufficient attention to the light pulse (e.g., a level of eye movement above a threshold or a gaze direction outside the direct field of view of the light source 305), the light adjustment module 115 can modify parameters of the light source to gain the user's attention. For example, the light adjustment module 115 can increase the intensity of the light pulse, adjust the color of the light pulse, or change the duration of the light pulse. The light adjustment module 115 can randomly vary one or more parameters of the light pulse. The light adjustment module 115 can initiate an attention-requesting light sequence configured to regain the user's attention. For example, the light sequence can include changes in color or intensity of the light pulses in a predetermined, random, or pseudo-random pattern. The attention-requesting light sequence can enable or disable different light sources if the visual signaling component 150 includes multiple light sources. Thus, the light adjustment module 115 can interact with the feedback monitor 135 to determine the level of attention the user pays to the light pulses and adjust the light pulses to regain the user's attention if the level of attention falls below a threshold.

[0247] In some embodiments, the light adjustment module 115 may modify or adjust one or more parameters of the light pulses or light waves at predetermined time intervals (e.g., every 5, 10, 15, or 20 minutes) to restore or maintain the user's level of attention.

[0248] In some embodiments, the NSS 105 can filter, block, attenuate, or remove undesired visual extraneous stimuli (e.g., via the unwanted frequency filtering module 120). Undesired visual extraneous stimuli can include, for example, undesired modulation frequencies of light waves, undesired intensities, or undesired wavelengths. The NSS 105 can consider a modulation frequency of a pulse train to be undesired if it differs or substantially differs (e.g., by 1%, 2%, 5%, 10%, 15%, 20%, 25%, or more than 25%) from a desired frequency.

[0249] For example, a desired modulation frequency for brainwave entrainment may be 40 Hz. However, a modulation frequency of 20 Hz or 80 Hz may interfere with brainwave entrainment. Therefore, the NSS 105 may filter out light pulses or light waves that correspond to a modulation frequency of 20 Hz or 80 Hz.

[0250] In some embodiments, the NSS 105 can detect, via the feedback component 160, that there is a light pulse from an ambient light source that corresponds to an undesired modulation frequency of 20 Hz. The NSS 105 can further determine the wavelength of the light wave of the light pulse that corresponds to the undesired modulation frequency. The NSS 105 can instruct the filtering component 155 to filter the wavelength that corresponds to the undesired modulation frequency. For example, the wavelength that corresponds to the undesired modulation frequency may correspond to the color blue. The filtering component 155 can include an optical filter that can selectively transmit light of a particular wavelength or color range while blocking one or more other ranges of wavelengths or colors. The optical filter can modulate the magnitude or phase of the light waves incident in a wavelength range. For example, the optical filter can be configured to block, reflect, or attenuate blue light waves that correspond to the undesired modulation frequency. The light conditioning module 115 can change the wavelength of the light waves generated by the light generating module 110 and the light source 305 so that the desired modulation frequency is not blocked or attenuated by the unwanted frequency filtering module 120.

[0251] NSS working with a virtual reality headset The NSS 105 can operate in conjunction with a virtual reality headset 401 that includes a light source 305 as shown in FIG. 4C. The NSS 105 can operate in conjunction with a virtual reality headset 401 that includes a light source 305 and a feedback sensor 605 as shown in FIG. 4C. In some embodiments, the NSS 105 can determine that the hardware of the visual signaling component 150 includes a virtual reality headset 401. In response to determining that the visual signaling component 150 includes a virtual reality headset 401, the NSS 105 can determine that the light source 305 includes a display screen of a smartphone or other mobile computing device.

[0252] The virtual reality headset 401 can provide an immersive and uninterrupted visual stimulation experience. The virtual reality headset 401 can provide an augmented reality experience. The feedback sensor 605 can capture pictures or videos of the physical real world to provide the augmented reality experience. The unwanted frequency filtering module 120 can filter out undesirable modulation frequencies before projecting, displaying, or presenting the augmented reality image via the display screen 305.

[0253] In operation, a user of the frame 401 can wear the frame 401 on their head such that the virtual reality headset's eye sockets 465 cover the user's eyes. The virtual reality headset's eye sockets 465 can encircle or substantially encircle the eyes. The user can secure the virtual reality headset 401 to the user's headset using one or more straps 455 or 460, a skull cap, or other fastening mechanism. In some cases, the user can provide an indication to the NSS 105 that the virtual reality headset 401 is positioned and secured on the user's head and that the user is ready to undergo brainwave entrainment. The indication can include an instruction, command, selection, input, or other indication via an input / output interface, such as the keyboard 726, pointing device 727, or other I / O devices 730a-n. The indication can be a motion-based indication, a visual indication, or an audio-based indication. For example, the user can give a voice command indicating that the user is ready to undergo brainwave entrainment.

[0254] In some cases, the feedback sensor 605 can determine that the user is ready to receive brainwave entrainment. The feedback sensor 605 can detect that the virtual reality headset 401 has been placed on the user's head. The NSS 105 can receive motion data, acceleration data, gyroscope data, temperature data, or capacitive touch data to determine that the virtual reality headset 401 has been placed on the user's head. The received data, such as the motion data, can indicate that the virtual reality headset 401 has been picked up and placed on the user's head. The temperature data can measure a temperature at or near the virtual reality headset 401 and can indicate that the virtual reality headset 401 is on the user's head. In some cases, the feedback sensor 605 can perform eye tracking to determine a level of attention that the user is paying to the light source 305 or the feedback sensor 605. The NSS 105 can detect that the user is ready in response to determining that the user is paying a high level of attention to the light source 305 or the feedback sensor 605. For example, gazing, gazing, or looking in the direction of the light source 305 or feedback sensor 605 may provide an indication that the user is ready to undergo brainwave entrainment.

[0255] In some embodiments, a sensor 605 in strap 455, strap 460, or eye socket 605 can detect when virtual reality headset 401 is secured, placed, or positioned on the user's head. Sensor 605 can be a touch sensor that senses or detects contact with the user's head.

[0256] Thus, the NSS 105 may detect or determine that the virtual reality headset 401 is donned and the user is ready, or the NSS 105 may receive an indication or confirmation from the user that the user has donned the virtual reality headset 401 and that the user is ready to undergo brainwave entrainment. Upon determining that the user is ready, the NSS 105 may initialize the brainwave entrainment process. In some embodiments, the NSS 105 may access the profile data structure 145. For example, the profile manager 125 may query the profile data structure 145 to determine one or more parameters for the external visual stimuli used in the brain entrainment process. The parameters may include, for example, a type of visual stimulus, an intensity of the visual stimulus, a frequency of the visual stimulus, a duration of the visual stimulus, or a wavelength of the visual stimulus. The profile manager 125 may query the profile data structure 145 to obtain historical information of the brain entrainment, such as previous visual stimulation sessions. The profile manager 125 may perform a search in the profile data structure 145. The profile manager 125 may perform a search using the user's name, a user identifier, location information, a fingerprint, a biometric identifier, a retina scan, voice recognition and authentication, or other identification techniques.

[0257] The NSS 105 can determine the type of external visual stimulus based on the hardware 401. The NSS 105 can determine the type of external visual stimulus based on the type of light source 305 available. For example, if the light source 305 includes a smartphone or a display device, the visual stimulus can include turning on and off a display screen of the display device. The visual stimulus can include displaying a pattern on the display device 305, such as a checkerboard, which can alternate according to a modulation of a desired frequency. The visual stimulus can include light pulses generated by a light source 305, such as an LED, disposed inside the enclosure of the virtual reality headset 401.

[0258] If the virtual reality headset 401 provides an augmented reality experience, the visual stimuli may include overlaying content on a display device and modulating the overlaid content at a desired modulation frequency. For example, the virtual reality headset 401 may include a camera 605 that captures the real physical world. The NSS 105 may also display content modulated at a desired modulation frequency while displaying a captured image of the real physical world. The NSS 105 may overlay content modulated at a desired modulation frequency. Otherwise, the NSS 105 may modify, manipulate, modulate, or adjust a portion of the display screen or a portion of the augmented reality to generate or effect the desired modulation frequency.

[0259] For example, the NSS 105 can modulate one or more pixels based on a desired modulation frequency. The NSS 105 can turn pixels on and off based on the modulation frequency. The NSS 105 can rotate pixels in any portion of the display device. The NSS 105 can turn pixels on and off in a pattern. The NSS 105 can turn pixels on and off in the direct field of view or the peripheral field of view. The NSS 105 can track or detect the gaze direction of the eye and turn on and off pixels in the gaze direction such that the light pulse (or modulation) is in the direct field of view. Thus, by modulating overlaid content or otherwise manipulating an augmented reality display or other image presented via the display device of the virtual reality headset 401, light pulses or flashes of light can be generated having a modulation frequency configured to promote brainwave entrainment.

[0260] The NSS 105 can determine the modulation frequency of the pulse train or the ambient light via the profile manager 125. For example, the NSS 105 can determine from the profile data structure 145 that the modulation frequency of the external visual stimulus should be set to 40 Hz. Depending on the type of visual stimulus, the profile data structure 145 can further indicate the number of pixels to modulate, the intensity of the pixels to modulate, the length of the pulse, the intensity, the wavelength of the light waves forming the light pulse, or the duration of the pulse train.

[0261] In some cases, the NSS 105 may determine or adjust one or more parameters of the external visual stimulus. For example, the NSS 105 (e.g., via the feedback component 160 or the feedback sensor 605) may determine a level or amount of light of the captured image used to provide the augmented reality experience. The NSS 105 (e.g., via the light adjustment module 115 or the side effect management module 130) may establish, initialize, set, or adjust the intensity or wavelength of the light pulses based on the level of light of the image data corresponding to the augmented reality experience. For example, the NSS 105 may determine that there is a low level of light in the augmented reality display because it may be dark outside. The low level of light in the augmented reality display may cause the user's pupils to dilate. The NSS 105 may determine that the user's pupils are likely dilated based on the detection of the low level of light. In response to determining that the user's pupils are likely dilated, the NSS 105 may set the intensity level of the light source or the light pulses providing the modulation frequency low. Furthermore, the NSS 105 can use light waves with longer wavelengths (eg, red), which can reduce strain on the eyes.

[0262] In some embodiments, the NSS 105 can monitor the light levels (e.g., via the feedback monitor 135 and the feedback component 160) throughout the brainwave entrainment process and automatically and periodically adjust the intensity or color of the light pulses. For example, if the user initiates the brainwave entrainment process when there is a high level of ambient light, the NSS 105 can initially set the intensity level of the light pulses higher and use a color that includes light waves with lower wavelengths (e.g., blue). However, as the light levels decrease throughout the brainwave entrainment process, the NSS 105 can automatically detect the decrease in light and, in response to the detection, adjust or decrease the intensity while increasing the wavelength of the light waves. The NSS 105 can adjust the light pulses to provide a high contrast ratio to facilitate brainwave entrainment.

[0263] In some embodiments, the NSS 105 can monitor or measure physiological conditions (e.g., via feedback monitor 135 and feedback component 160) to set or adjust parameters of the light pulses while the user is wearing the virtual reality headset 401. For example, the NSS 105 can monitor or measure a level of pupil dilation to adjust or set parameters of the light waves. In some embodiments, the NSS 105 can monitor or measure heart rate, pulse rate, blood pressure, body temperature, sweating, or brain activity via one or more feedback sensors in the virtual reality headset 401 or other feedback sensors to set or adjust parameters of the light waves.

[0264] In some embodiments, the NSS 105 can be pre-configured to initially send light pulses via the display device 305 with a lowest light wave intensity setting (e.g., low amplitude of the light waves or high wavelength of the light waves) and gradually increase the intensity (e.g., increase the amplitude of the light waves or decrease the wavelength of the light waves) while monitoring feedback until an optimal light intensity is reached. The optimal light intensity can refer to the highest intensity without adverse physiological side effects such as blindness, stroke, heart attack, migraine, or other discomfort. The NSS 105 (e.g., via the side effect management module 130) can monitor physiological symptoms to identify adverse side effects of the external visual stimulation and adjust the external visual stimulation accordingly (e.g., via the light adjustment module 115) to reduce or eliminate the adverse side effects.

[0265] In some embodiments, the NSS 105 can adjust parameters of the light waves or light pulses (e.g., via the light adjustment module 115) based on the level of attention. For example, during the brainwave entrainment process, the user may become bored, lose focus, fall asleep, or otherwise not pay attention to the light pulses generated via the display screen 305 of the virtual reality headset 401. Not paying attention to the light pulses can reduce the effectiveness of the brainwave entrainment process and result in neurons oscillating at a different frequency than the desired modulation frequency of the light pulses.

[0266] The NSS 105 can detect the level of attention the user is paying or directing to the light pulse using the feedback monitor 135 and one or more feedback components 160 (e.g., including the feedback sensor 605). The NSS 105 can perform eye tracking to determine the level of attention the user is directing to the light pulse based on the gaze direction of the retina or pupil. The NSS 105 can measure eye movement to determine the level of attention the user is directing to the light pulse. The NSS 105 can present a survey or prompt for user feedback indicating the level of attention the user is directing to the light pulse. In response to determining that the user is not paying sufficient attention to the light pulse (e.g., a level of eye movement above a threshold or a gaze direction outside the direct field of view of the light source 305), the light adjustment module 115 can modify parameters of the light source 305 or the display device 305 to gain the user's attention. For example, the light adjustment module 115 can increase the intensity of the light pulse, adjust the color of the light pulse, or modify the duration of the light pulse. The light adjustment module 115 can randomly vary one or more parameters of the light pulses. The light adjustment module 115 can initiate an attention-requesting light sequence configured to regain the user's attention. For example, the light sequence can include changes in color or intensity of the light pulses in a predetermined, random, or pseudo-random pattern. The attention-requesting light sequence can enable or disable different light sources if the visual signaling component 150 includes multiple light sources. Thus, the light adjustment module 115 can interact with the feedback monitor 135 to determine the level of attention the user pays to the light pulses and adjust the light pulses to regain the user's attention if the level of attention falls below a threshold.

[0267] In some embodiments, the light adjustment module 115 may modify or adjust one or more parameters of the light pulses or light waves at predetermined time intervals (e.g., every 5, 10, 15, or 20 minutes) to restore or maintain the user's level of attention.

[0268] In some embodiments, the NSS 105 can filter, block, attenuate, or remove undesired visual extraneous stimuli (e.g., via the unwanted frequency filtering module 120). Undesired visual extraneous stimuli can include, for example, undesired modulation frequencies of light waves, undesired intensities, or undesired wavelengths. The NSS 105 can consider a modulation frequency of a pulse train to be undesirable if it differs or substantially differs (e.g., by 1%, 2%, 5%, 10%, 15%, 20%, 25%, or more than 25%) from a desired frequency.

[0269] For example, a desired modulation frequency for brainwave entrainment may be 40 Hz. However, a modulation frequency of 20 Hz or 80 Hz may interfere with brainwave entrainment. Thus, the NSS 105 may filter light pulses or light waves corresponding to a modulation frequency of 20 Hz or 80 Hz. For example, the virtual reality headset 401 may detect undesirable modulation frequencies in the physical real world and eliminate, attenuate, filter, or otherwise remove the undesirable frequencies that arise to generate or bring about an augmented reality experience. The NSS 105 may include optical filters configured to perform digital signal processing or digital image processing to detect undesirable modulation frequencies in the real world captured by the feedback sensor 605. The NSS 105 may detect other content, images, or motions that have undesirable parameters (e.g., color, brightness, contrast ratio, modulation frequency) and remove it from the augmented reality experience projected to the user via the display screen 305. The NSS 105 may apply color filters to adjust the color of the augmented reality display or to remove the color. The NSS 105 may adjust, modify, or manipulate the brightness, contrast ratio, sharpness, tint, hue, or other parameters of the images or videos displayed via the display device 305 .

[0270] In some embodiments, the NSS 105 can detect, via the feedback component 160, that there is captured image or video content from the real physical world that corresponds to an undesired modulation frequency of 20 Hz. The NSS 105 can further determine the wavelength of the light waves of the light pulses that correspond to the undesired modulation frequency. The NSS 105 can instruct the filtering component 155 to filter the wavelengths that correspond to the undesired modulation frequency. For example, the wavelengths that correspond to the undesired modulation frequency may correspond to the color blue. The filtering component 155 can include digital optical filters that can digitally remove content or light of a particular wavelength or color range while allowing one or more other ranges of wavelengths or colors. The digital optical filters can change the magnitude or phase of the image in a wavelength range. For example, the digital optical filters can be configured to attenuate, eliminate, replace, or otherwise modify the blue light waves that correspond to the undesired modulation frequency. The light conditioning module 115 can change the wavelengths of the light waves generated by the light generating module 110 and the display device 305 such that the desired modulation frequency is not blocked or attenuated by the unwanted frequency filtering module 120.

[0271] NSS working with a tablet The NSS 105 can operate in conjunction with a tablet 500 as shown in Figures 5A-5D. In some embodiments, the NSS 105 can determine that the hardware of the visual signaling component 150 includes a tablet device 500 or other display screen that is not fixed to the user's head. The tablet 500 can include a display screen having one or more components or functions of the display screen 305 or the light source 305 shown in connection with Figures 4A and 4C. The light source 305 of the tablet can be a display screen. The tablet 500 can include one or more feedback sensors including one or more components or functions of the feedback sensor shown in connection with Figures 4B, 4C, and 6A.

[0272] The tablet 500 can communicate with the NSS 105 via a network, such as a wireless or cellular network. The NSS 105 can execute the NSS 105 or components thereof in some embodiments. For example, the tablet 500 can launch, open, or switch between applications or resources configured to effect at least one function of the NSS 105. The tablet 500 can execute applications as background or foreground processes. For example, a graphical user interface for the application can be in the background while the application overlays the tablet's display screen 305 with content or light that changes or modulates at a desired frequency (e.g., 40 Hz) for brain entrainment.

[0273] The tablet 500 may include one or more feedback sensors 605. In some embodiments, the tablet may use the one or more feedback sensors 605 to detect that a user is holding the tablet 500. The tablet may use the one or more feedback sensors 605 to determine the distance between the light source 305 and the user. The tablet may use the one or more feedback sensors 605 to determine the distance between the light source 305 and the user's head. The tablet may use the one or more feedback sensors 605 to determine the distance between the light source 305 and the user's eye.

[0274] In some embodiments, the tablet 500 can use a feedback sensor 605 including a receiver to determine distance. The tablet can send a signal and measure the amount of time it takes for the sent signal to leave the tablet 500, bounce off an object (e.g., the user's head), and be received by the feedback sensor 605. The tablet 500 or NSS 105 can determine distance based on the measured amount of time and the speed of the sent signal (e.g., the speed of light).

[0275] In some embodiments, the tablet 500 may include two feedback sensors 605 to determine distance. The two feedback sensors 605 may include a first feedback sensor 605 that is a transmitter and a second feedback sensor that is a receiver.

[0276] In some embodiments, the tablet 500 may include two or more feedback sensors 605 including two or more cameras that measure the angle and position of an object (e.g., a user's head) with each camera, and the measured angle and position can be used to determine or calculate the distance between the tablet 500 and the object.

[0277] In some embodiments, the tablet 500 (or an application thereof) can determine the distance between the tablet and the user's head by receiving a user's input. For example, the user's input can include an approximate size of the user's head. The tablet 500 can then determine the distance from the user's head based on the inputted approximate size.

[0278] The tablet 500, application, or NSS 105 may use the measured or determined distance to adjust the light pulse or flash of light emitted by the light source 305 of the tablet 500. The tablet 500, application, or NSS 105 may use the distance to adjust one or more parameters of the light pulse, flash of light, or other content emitted via the light source 305 of the tablet 500. For example, the tablet 500 may adjust the intensity of the light pulse emitted by the light source 305 based on the distance. The tablet 500 may adjust the intensity based on the distance to maintain a consistent or similar intensity at the eye regardless of the distance between the light source 305 and the eye. The tablet may increase the intensity in proportion to the square of the distance.

[0279] The tablet 500 can manipulate one or more pixels of the display screen 305 to generate light pulses or modulated frequencies for brainwave entrainment. The tablet 500 can superimpose light sources, light pulses or other patterns to generate modulated frequencies for brainwave entrainment. Similar to the virtual reality headset 401, the tablet can filter or modify undesirable frequencies, wavelengths or intensities.

[0280] Similar to the frame 400, the tablet 500 can adjust parameters of the pulses or flashes of light generated by the light source 305 based on ambient light, environmental parameters, or feedback.

[0281] In some embodiments, the tablet 500 can execute an application configured to generate light pulses or modulation frequencies for brainwave entrainment. The application can run in the background of the tablet such that all content displayed on the tablet's display screen is displayed as light pulses at the desired frequency. The tablet can be configured to detect the direction of the user's gaze. In some embodiments, the tablet can detect the direction of gaze by capturing an image of the user's eye via the tablet's camera. The tablet 500 can be configured to generate light pulses at specific locations on the display screen based on the direction of the user's gaze. In embodiments where a direct field of view is used, the light pulses can be displayed at a location on the display screen that corresponds to the user's gaze. In embodiments where a peripheral field of view is used, the light pulses can be displayed at a location that is outside of the portion of the display screen that corresponds to the user's gaze.

[0282] Neurostimulation via auditory stimulation 9 is a block diagram illustrating a system for neurostimulation by auditory stimulation, according to an embodiment. The system 900 can include a neurostimulation system ("NSS") 905. The NSS 905 can be referred to as an auditory NSS 905 or an NSS 905. In brief overview, the auditory neurostimulation system ("NSS") 905 can include, access, interface with, or otherwise communicate with one or more of an audio generation module 910, an audio conditioning module 915, an unwanted frequency filtering module 920, a profile manager 925, a side effect management module 930, a feedback monitor 935, a data repository 940, an auditory signaling component 950, a filtering component 955, or a feedback component 960. The audio generation module 910, the audio adjustment module 915, the unwanted frequency filtering module 920, the profile manager 925, the side effect management module 930, the feedback monitor 935, the auditory signaling component 950, the filtering component 955, or the feedback component 960 may each include a module configured to communicate with at least one processing unit, or other logic device, such as a programmable logic array engine, or the database repository 950. The audio generation module 910, the audio adjustment module 915, the unwanted frequency filtering module 920, the profile manager 925, the side effect management module 930, the feedback monitor 935, the auditory signaling component 950, the filtering component 955, or the feedback component 960 may be separate components, a single component, or part of the NSS 905. The system 100 and its components, such as the NSS 905, may include hardware elements, such as one or more processors, logic devices, or circuits. The system 100 and its components, such as the NSS 905, may include one or more hardware or interface components shown in the system 700 of FIG. 7A and FIG. 7B.For example, the components of the system 100 may include or run on one or more processors 721 , access a storage device 728 or memory 722 , and communicate via a network interface 718 .

[0283] 9, in further detail, the NSS 905 may include at least one audio generation module 910. The audio generation module 910 may be designed and constructed to interface with an auditory signal transmission component 950 to command or otherwise cause or facilitate the generation of an auditory signal, such as an audio burst, an audio pulse, an audio chirp, an audio sweep, or other acoustic wave having one or more predetermined parameters. The audio generation module 910 may include hardware or software for receiving and processing instructions or data packets from one or more modules or components of the NSS 905. The audio generation module 910 may generate instructions to cause the auditory signal transmission component 950 to generate an auditory signal. The audio generation module 910 controls or activates the auditory signal transmission component 950 to generate an auditory signal having one or more predetermined parameters.

[0284] The audio generation module 910 can be communicatively coupled to the auditory signaling component 950. The audio generation module 910 can communicate with the auditory signaling component 950 via a circuit, a wire, a data port, a network port, a power line, a ground, an electrical contact or a pin. The audio generation module 910 can wirelessly communicate with the auditory signaling component 950 using one or more wireless protocols, such as BlueTooth, BlueTooth Low Energy, Zigbee, Z-Wave, IEEE802, WIFI, 3G, 4G, LTE, Near Field Communication ("NFC"), or other short, medium or long range communication protocols. The audio generation module 910 can include or access a network interface 718 to communicate wirelessly or wired with the auditory signaling component 950.

[0285] The audio generation module 910 can interface, control, or otherwise manage various types of auditory signaling components 950 to cause the auditory signaling components 950 to generate, block, control, or otherwise provide an auditory signal having one or more predetermined parameters. The audio generation module 910 can include a driver configured to drive an audio source of the auditory signaling components 950. For example, the audio source can include a speaker, and the audio generation module 910 (or the auditory signaling components) can include a transducer that converts electrical energy into sound or acoustic waves. The audio generation module 910 can include a computing chip, microchip, circuit, microcontroller, operational amplifier, transistor, resistor, or diode configured to provide electricity or power having specific voltage and current characteristics to drive the speaker to generate an auditory signal having desired acoustic characteristics.

[0286] In some embodiments, the audio generating module 910 can instruct the auditory signal conveying component 950 to convey an auditory signal. For example, the auditory signal can include an acoustic wave 1000 as shown in FIG. 10A. The auditory signal can include multiple acoustic waves. The auditory signal can generate one or more acoustic waves. The acoustic wave 1000 can include or be formed from mechanical waves of pressure and displacement that travel through a medium such as a gas, liquid, and solid. The acoustic wave can travel through a medium to cause vibrations, sound, superacoustic waves, or sub-superacoustic waves. The acoustic wave can propagate as a longitudinal wave through air, water, or solids. The acoustic wave can propagate through a solid as a transverse wave.

[0287] Acoustic waves can be generated by the vibration of pressure, stress, particle displacement, particle velocity, or the superposition of such propagated vibrations propagating through a medium with internal forces (e.g., elastic or viscous). Sound can refer to the hearing sensation induced by this vibration. For example, sound can refer to the reception of acoustic waves and their perception by the brain.

[0288] The auditory signal transmission component 950 or its audio source can generate acoustic waves by vibrating a diaphragm of the audio source. For example, the audio source can include a diaphragm, such as a transducer configured to interconvert mechanical vibrations into sound. The diaphragm can include a thin membrane or sheet of various materials suspended at its edge. The varying pressure of the sound waves imparts mechanical vibrations to the diaphragm, which can then generate acoustic waves or sounds.

[0289] The acoustic wave 1000 shown in FIG. 10A includes a wavelength 1010. The wavelength 1010 can refer to the distance between successive peaks 1020 of the wave. The wavelength 1010 can be related to the frequency of the acoustic wave and the speed of the acoustic wave. For example, the wavelength can be determined as the speed of the acoustic wave divided by the frequency of the acoustic wave. The speed of the acoustic wave can be the product of the frequency and the wavelength. The frequency of the acoustic wave can be the speed of the acoustic wave divided by the wavelength of the acoustic wave. Thus, the frequency and wavelength of the acoustic wave can be inversely proportional. The speed of sound can vary based on the medium through which the acoustic wave propagates. For example, the speed of sound in air can be 343 meters per second.

[0290] Apex 1020 may refer to the point on a wave that has the crest or maximum value of the wave. The displacement of the medium is greatest at the wave crest 1020. Trough 1015 is opposite the crest 1020. Trough 1015 is the minimum or lowest point of the wave that corresponds to the smallest amount of displacement.

[0291] The acoustic wave 1000 can include an amplitude 1005. The amplitude 1005 can refer to the maximum degree of vibration or oscillation of the acoustic wave 1000 measured from an equilibrium position. The acoustic wave 1000 can be a longitudinal wave if it vibrates or oscillates in the same direction 1025 as it travels. In some cases, the acoustic wave 1000 can be a transverse wave, vibrating perpendicular to its direction of propagation.

[0292] The audio generation module 910 can instruct the auditory signaling component 950 to generate acoustic or sound waves having one or more predetermined amplitudes or wavelengths. The wavelengths of acoustic waves audible to the human ear range from approximately 17 meters to 17 millimeters (or 20 Hz to 20 kHz). The audio generation module 910 can further specify one or more characteristics of the acoustic waves within the audible spectrum or outside the audible spectrum. For example, the frequency of the acoustic waves can range from 0 to 50 kHz. In some embodiments, the frequency of the sound waves can range from 8 to 12 kHz. In some embodiments, the frequency of the sound waves can be 10 kHz.

[0293] The NSS 905 can modulate, modify, change, or otherwise alter the properties of the acoustic wave 1000. For example, the NSS 905 can modulate the amplitude or wavelength of the acoustic wave. As shown in Figures 10B and 10C, the NSS 905 can adjust, manipulate, or otherwise modify the amplitude 1005 of the acoustic wave 1000. For example, the NSS 905 can lower the amplitude 1005 to make the sound quieter, as shown in Figure 10B, or can increase the amplitude 1005 to make the sound louder, as shown in Figure 10C.

[0294] In some cases, the NSS 905 can tune, manipulate, or otherwise modify the wavelength (1010) of the acoustic wave. As shown in Figures 10D and 10E, the NSS 905 can tune, manipulate, or otherwise modify the wavelength (1010) of the acoustic wave (1000). For example, the NSS 905 can increase the wavelength (1010) to make the sound lower pitched, as shown in Figure 10D, or decrease the wavelength (1010) to make the sound higher pitched, as shown in Figure 10E.

[0295] The NSS 905 can modulate the acoustic wave. Modulating the acoustic wave can include modulating one or more properties of the acoustic wave. Modulating the acoustic wave can include filtering the acoustic wave, for example filtering undesired frequencies, or attenuating the acoustic wave to reduce amplitude. Modulating the acoustic wave can include adding one or more additional acoustic waves to the original acoustic wave. Modulating the acoustic wave can include combining acoustic waves such that there is constructive or destructive interference in the resulting combined acoustic wave corresponding to the modulated acoustic wave.

[0296] The NSS905 can modulate or change one or more characteristics of the acoustic wave based on a time interval. The NSS905 can change one or more characteristics of the acoustic at the end of the time interval. For example, the NSS905 can change the nature of the acoustic wave every 30 seconds, every 1 minute, every 2 minutes, every 3 minutes, every 5 minutes, every 7 minutes, every 10 minutes, or every 15 minutes. The NSS905 can change the modulation frequency of the acoustic wave, where the modulation frequency refers to the reciprocal of the repetitive modulation or pulse rate interval of the acoustic pulses. The modulation frequency can be a predetermined or desired frequency. The modulation frequency can correspond to a desired stimulation frequency of neural oscillations. The modulation frequency can be set to promote or cause brainwave entrainment. The NSS905 can set the modulation frequency to a frequency in the range of 0.1 Hz to 10,000 Hz. For example, the NSS905 can set the modulation frequency to 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.

[0297] The audio generation module 910 may determine to provide an auditory signal including a burst of acoustic waves, an audio pulse, or a modulation of an acoustic wave. The audio generation module 910 may command or cause the auditory signaling component 950 to generate an acoustic burst or pulse. An acoustic pulse may refer to a burst of acoustic waves, or a modulation to a characteristic of an acoustic wave that is perceived by the brain as a change in sound. For example, an audio source that is intermittently turned on and off may generate an audio burst or a change in sound. The audio source may 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 may be turned on and off to provide a pulse repetition frequency ranging from 0.1 Hz to 10 kHz or more.

[0298] For example, Figures 10F-10I show bursts of acoustic waves or bursts of modulation that can be applied to acoustic waves. The bursts of acoustic waves can include, for example, audio tones, beeps, or clicks. Modulation can refer to changing the amplitude of an acoustic wave, changing the frequency or wavelength of an acoustic wave, superimposing another acoustic wave on the original acoustic wave, or otherwise modifying or altering an acoustic wave.

[0299] 10F illustrates acoustic bursts 1035a-c (or modulated pulses 1035a-c) according to one embodiment. The acoustic bursts 1035a-c may be illustrated via a graph where the y-axis represents an acoustic wave parameter (e.g., frequency, wavelength, or amplitude) of the acoustic wave. The x-axis may represent time (e.g., seconds, milliseconds, or microseconds).

[0300] The auditory signal may include modulated acoustic waves modulated between different frequencies, wavelengths, or amplitudes. For example, the NSS905 may modulate acoustic waves between frequencies in the audio spectrum, such as Ma, and frequencies outside the audio spectrum, such as Mo. The NSS905 may modulate acoustic waves between two or more frequencies, between on and off states, or between high and low power states.

[0301] The acoustic bursts 1035a-c can have an acoustic wave parameter with a value Ma that is different from the value Mo of the elastic wave parameter. The modulation Ma can refer to frequency or wavelength, or amplitude. The pulses 1035a-c can be generated at a pulse rate interval (PRI) 1040.

[0302] For example, the acoustic wave parameter may be a frequency of the acoustic wave. The first value Mo may be a low frequency or carrier frequency of the acoustic wave, such as 10 kHz. The second value Ma may be different from the first frequency Mo. The second frequency Ma may be lower or higher than the first frequency Mo. For example, the second frequency Ma may be 11 kHz. The difference between the first frequency and the second frequency may be determined or set based on the level of sensitivity of the human ear. The difference between the first frequency and the second frequency may be determined or set based on the subject's profile information 945. The difference between the first frequency Mo and the second frequency Ma may be determined such that the modulation or change of the acoustic wave promotes brainwave entrainment.

[0303] In some cases, the parameters of the acoustic wave used to generate acoustic burst 1035a can be constant at Ma, thereby generating a square wave, as shown in Figure 10F. In some embodiments, each of the three pulses 1035a-1035c can include an acoustic wave having the same frequency Ma.

[0304] The width of each acoustic burst or pulse (e.g., the duration of a burst of acoustic waves having parameter Ma) can correspond to a pulse width 1030a. The pulse width 1030a can refer to the length or duration of the burst. The pulse width 1030a can be measured in units of time or distance. In some embodiments, the pulses 1035a-1035c can include acoustic waves having different frequencies from one another. In some embodiments, the pulses 1035a-c can have different pulse widths 1030a from one another, as shown in FIG. 10G. For example, the first pulse 1035d in FIG. 10G can have a pulse width 1030a, while the second pulse 1035e has a second pulse width 1030b that is greater than the first pulse width 1030a. The third pulse 1035f can have a third pulse width 1030c that is less than the second pulse width 1030b. The third pulse width 1030c may also be less than the first pulse width 1030a. Although the pulse widths 1030a-c of the pulses 1035d-f of the pulse train may vary, the audio generation module 910 may maintain a constant pulse rate interval 1040 for the pulse train.

[0305] The pulses 1035a-c can form a pulse train having a pulse rate interval 1040. The pulse rate interval 1040 can be quantified using units of time. The pulse rate interval 1040 can be based on a frequency of the pulses in the pulse train 201. The frequency of the pulses in the pulse train 201 can be referred to as a modulation frequency. For example, the audio generation module 910 can provide the pulse train 201 at a predetermined frequency, such as 40 Hz. To do so, the audio generation module 910 can determine the pulse rate interval 1040 by taking the multiplicative inverse (or reciprocal) of the frequency (e.g., dividing 1 by the predetermined frequency for the pulse train). For example, the audio generation module 910 can take the multiplicative inverse of 40 Hz by dividing 1 by 40 Hz to determine the pulse rate interval 1040 as 0.025 seconds. The pulse rate interval 1040 can remain constant throughout the pulse train. In some embodiments, the pulse rate interval 1040 may vary throughout the pulse train or from one pulse train to the next. In some embodiments, the number of pulses transmitted per second may be fixed while the pulse rate interval 1040 varies.

[0306] In some embodiments, the audio generation module 910 can generate audio bursts or audio pulses having acoustic waves that vary in frequency, amplitude, or wavelength. For example, the audio generation module 910 can generate an up-chirp pulse in which the frequency, amplitude, or wavelength of the acoustic waves of the audio pulse increases from the start of the pulse to the end of the pulse, as shown in FIG. 10H. For example, the frequency, amplitude, or wavelength of the acoustic waves at the start of the pulse 1035g can be Ma. The frequency, amplitude, or wavelength of the acoustic waves of the pulse 1035g can increase from Ma to Mb in the middle of the pulse 1035g, and then increase to a maximum Mc at the end of the pulse 1035g. Thus, the frequency, amplitude, or wavelength of the acoustic waves used to generate the pulse 1035g can range from Ma to Mc. The frequency, amplitude, or wavelength can increase linearly, exponentially, or based on some other rate or curve. One or more of the frequency, amplitude, or wavelength of the acoustic waves can vary from the start of the pulse to the end of the pulse.

[0307] The audio generating module 910 may generate a down-chirp pulse as shown in FIG. 10I, where the frequency, amplitude, or wavelength of the acoustic wave of the acoustic pulse decreases from the start of the pulse to the end of the pulse. For example, the frequency, amplitude, or wavelength of the acoustic wave at the start of the pulse 1035j may be Mc. The frequency, amplitude, or wavelength of the acoustic wave of the pulse 1035j may decrease from Mc to Mb in the middle of the pulse 1035j, and then decrease to a minimum value of Ma at the end of the pulse 1035j. Thus, the frequency, amplitude, or wavelength of the acoustic wave used to generate the pulse 1035j may range from Mc to Ma. The frequency, amplitude, or wavelength may decrease linearly, exponentially, or based on some other rate or curve. One or more of the frequency, amplitude, or wavelength of the acoustic wave may change from the start of the pulse to the end of the pulse.

[0308] In some embodiments, the audio generation module 910 can command or cause the auditory signaling component 950 to generate audio pulses to stimulate specific or predetermined portions of the brain or a particular cortex. The frequency, wavelength, modulation frequency, amplitude, and other aspects of the audio pulse, tone, or music-based stimulus can specify which cortex is recruited to process the stimulus. The auditory signaling component 950 can stimulate discrete portions of the cortex by modulating the presentation of the stimulus to target a specific or general region of interest. The modulation parameters or amplitude of the auditory stimulus can specify which areas of the cortex are stimulated. For example, different areas of the cortex are recruited to process sounds of different frequencies, referred to as their signature frequencies. Additionally, laterality of the stimulus can affect the cortical response, as some subjects may be treated by stimulating one ear rather than both ears.

[0309] The auditory signaling component 950 may be designed and constructed to generate audio pulses in response to instructions from the audio generation module 910. The instructions may include parameters of the audio pulses, such as, for example, frequency, wavelength, or acoustic wave, duration of the pulse, frequency of the pulse train, pulse rate interval, or duration of the pulse train (e.g., number of pulses in a pulse train or length of time for transmitting a pulse train having a given frequency). The audio pulses may be perceived, observed, or otherwise identified by the brain through cochlear means such as the ear. The audio pulses may be transmitted to the ear via an audio source speaker in close proximity to the ear, such as headphones, earphones, bone conduction transducers, or cochlear implants. The audio pulses may be transmitted to the ear via an audio source or speaker not in close proximity to the ear, such as a surround sound speaker system, bookshelf speakers, or other speakers not in direct or indirect contact with the ear.

[0310] 11A illustrates an auditory signal using binaural beats or binaural pulses, according to an embodiment. Briefly summarized, binaural beats refer to delivering a different tone to each ear of a subject. When the brain perceives two different tones, it mixes the two tones together to generate a pulse. The two different tones can be selected such that the sum of the tones produces a pulse train with a desired pulse rate interval 1040.

[0311] The auditory signal transmission component 950 may include a first audio source that transmits an auditory signal to a first ear of the subject and a second audio source that transmits a second auditory signal to a second ear of the subject. The first audio source and the second audio source may be different. The first ear may perceive only the first auditory signal from the first audio source, and the second ear may receive only the second auditory signal from the second audio source. The audio source may include, for example, headphones, earphones, or a bone conduction transducer. The audio source may include a stereo audio source.

[0312] The audio generation component 910 can select a first tone for the first ear and a different second tone for the second ear. The tone can be characterized by its duration, pitch, intensity (or volume), or timbre (or quality). In some cases, the first tone and the second tone can differ if they have different frequencies. In some cases, the first tone and the second tone can differ if they have different phase offsets. The first tone and the second tone can each be a pure tone. The pure tone can be a sound having a sinusoidal waveform of a single frequency.

[0313] As shown in FIG. 11A, the first tone or offset wave 1105 is slightly different from the second tone 1110 or carrier wave 1110. The first tone 1105 has a higher frequency than the second tone 1110. The first tone 1105 may be generated by a first earphone inserted in one ear of the subject, and the second tone 1110 may be generated by a second earphone inserted in the other ear of the subject. When the auditory cortex of the brain perceives the first tone 1105 and the second tone 1110, the brain can sum the two tones. The brain can sum the acoustic waveforms corresponding to the two tones. The brain can sum the two waveforms as shown by the waveform sum 1115. With the first and second tones having different parameters (such as different frequencies or phase offsets), portions of the wave can be added and subtracted from one another to result in a waveform 1115 having one or more pulses 1130 (or beats 1130). The pulses 1130 can be separated by a balanced portion 1125. By mixing these two different waveforms together, the pulses 1130 perceived by the brain can induce brainwave entrainment.

[0314] In some embodiments, the NSS 905 can generate binaural beats using pitch panning techniques. For example, the audio generation module 910 or the audio adjustment module 915 can include or use filters to modulate the pitch of an audio file or single tone up and down while simultaneously panning the modulation between stereo sides so that one side has a slightly higher pitch and the other side has a slightly lower pitch. A stereo side can refer to a first audio source that generates and delivers an auditory signal to a first ear of a subject, and a second audio source that generates and delivers an auditory signal to a second ear of the subject. An audio file can refer to a representation of an acoustic wave or a format of a file configured to store information. Exemplary audio file formats can include .mp3, .wav, .aac, .m4a, .smf, etc.

[0315] The NSS905 can use this pitch panning technique to create a type of spatial positioning that is perceived by the brain in a similar manner to binaural beats when heard through stereo headphones. Thus, the NSS905 can use this pitch panning technique to create a pulse or beat using a single tone or a single audio file.

[0316] In some cases, the NSS905 can generate a mono beat or a mono pulse. A mono beat or pulse is similar to a binaural beat in that it is also generated by combining two tones to form a beat. The NSS905 or components of the system 100 can form a mono beat by combining two tones using digital or analog techniques before the sound reaches the ears, as opposed to the brain combining the waveforms as in binaural beats. For example, the NSS905 (or the audio generation component 910) can identify and select two different waveforms that when combined generate a beat or pulse with a desired pulse rate interval. The NSS905 can identify a first digital representation of a first acoustic waveform and identify a second digital representation of a second acoustic waveform having different parameters than the first acoustic waveform. The NSS905 can combine the first digital waveform and the second digital waveform to generate a third digital waveform that is different from the first digital waveform and the second digital waveform. The NSS 905 can then send the third digital waveform in digital format to the auditory signaling component 950. The NSS 905 can convert the digital waveform to an analog format and send the analog format to the auditory signaling component 950. The auditory signaling component 950 can then generate, via the audio source, a sound that is perceived by one ear or both ears. The same sound may be perceived by both ears. The sound may include pulses or beats spaced apart by a desired pulse rate interval 1040.

[0317] FIG. 11B illustrates an acoustic pulse with isochronous tones, according to an embodiment. Isochronous tones are evenly spaced tone pulses. Isochronous tones can be created without the need to combine two different tones. The NSS 905 or other components of the system 100 can generate isochronous tones by turning tones on and off. The NSS 905 can generate isochronous tones or pulses by commanding the auditory signaling components on and off. The NSS 905 can modify the digital representation of the acoustic wave to remove or set the digital value of the acoustic wave so that sound is generated during the pulse 1135 and no sound is generated during the null portion 1140.

[0318] By turning acoustic waves on and off, the NSS 905 can establish acoustic pulses 1135 spaced apart by a pulse rate interval 1040 that corresponds to a desired stimulation frequency, such as 40 Hz. Isochronous pulses spaced apart by a desired PRI 1040 can induce brainwave entrainment.

[0319] 11C illustrates an audio pulse generated by the NSS 905 using an audio track, according to an embodiment. A sound track can include or refer to a complex acoustic wave that includes multiple different frequencies, amplitudes, or tones. For example, a sound track can include a voice track, an instrument track, a music track having both voice and instruments, nature sounds, or white noise.

[0320] The NSS905 can modulate the audio track to induce brainwave entrainment by rhythmically adjusting the components of the sound. For example, the NSS905 can adjust the volume by increasing or decreasing the amplitude of the acoustic waves or audio track to generate rhythmic stimulation corresponding to the stimulation frequency for inducing brainwave entrainment. Thus, the NSS905 can embed acoustic pulses in the audio track having a pulse rate interval corresponding to the desired stimulation frequency to induce brainwave entrainment. The NSS905 can manipulate the audio track to generate a new, modified audio track having acoustic pulses having a pulse rate interval corresponding to the desired stimulation frequency to induce brainwave entrainment.

[0321] As shown in FIG. 11C, the pulse 1135 is generated by modulating the volume from a first level Va to a second level Vb. During the portion 1140 of the acoustic wave 345, the NSS 905 can set or hold the volume at Va. The volume Va can refer to the amplitude of the wave, or the maximum amplitude or crest of the wave 345 during the portion 1140. The NSS 905 can then adjust, change, or increase the volume to Vb during the portion 1135. The NSS 905 can increase the volume by a predetermined amount, such as a percentage, a number of decibels, a subject-specified amount, or other amount. The NSS 905 can set or maintain the volume at Vb for a duration corresponding to the desired pulse length of the pulse 1135.

[0322] In some embodiments, the NSS 905 can include an attenuator to attenuate the volume from a level Vb to a level Va. In some embodiments, the NSS 905 can instruct an attenuator (e.g., an attenuator of the auditory signaling component 950) to attenuate the volume from a level Vb to a level Va. In some embodiments, the NSS 905 can include an amplifier to amplify or increase the volume from Va to Vb. In some embodiments, the NSS 905 can instruct an amplifier (e.g., an amplifier of the auditory signaling component 950) to amplify or increase the volume from Va to Vb.

[0323] Referring back to FIG. 9 , the NSS 905 may include, access, interface with, or otherwise communicate with at least one audio adjustment module 915. The audio adjustment module 915 may be designed and constructed to adjust parameters associated with the auditory signal, such as the frequency, amplitude, wavelength, pattern, or other parameters of the auditory signal. The audio adjustment module 915 may automatically modify parameters of the auditory signal based on profile information or feedback. The audio adjustment module 915 may receive feedback information from a feedback monitor 935. The audio adjustment module 915 may receive instructions or information from a side effect management module 930. The audio adjustment module 915 may receive profile information from a profile manager 925.

[0324] The NSS 905 may include, access, interface with, or otherwise communicate with at least one unwanted frequency filtering module 920. The unwanted frequency filtering module 920 may be designed and constructed to block, mitigate, reduce, or otherwise filter frequencies of undesirable auditory signals to prevent or reduce the amount of such auditory signals from being perceived by the brain. The unwanted frequency filtering module 920 may interface, command, control, or otherwise communicate with the filtering component 955 to cause the filtering component 955 to block, attenuate, or otherwise reduce the effect of unwanted frequencies on neural oscillations.

[0325] The unwanted frequency filtering module 920 may include an active noise control component (e.g., the active noise cancellation component 1215 shown in FIG. 12B). Active noise control may refer to or include active noise cancellation or active noise reduction. Active noise control may reduce an unwanted sound by adding a second sound with parameters specifically selected to cancel or attenuate the first sound. In some cases, the active noise control component may emit a sound wave with the same amplitude but inverse phase (or antiphase) to the original unwanted sound. The two waves may combine to form a new wave and effectively cancel each other out by destructive interference.

[0326] The active noise control component may include analog circuitry or digital signal processing. The active noise control component may include adaptive technology to analyze the waveform of background aural or non-aural noise. In response to background noise, the active noise control component may generate an auditory signal that may phase shift or invert the polarity of the original signal. This inverted signal may be amplified by a transducer or speaker to generate sound waves that are directly proportional to the amplitude of the original waveform, generating destructive interference. This may reduce the volume of the perceptible noise.

[0327] In some embodiments, the noise cancellation speaker may be co-located with the source speaker.In some embodiments, the noise cancellation speaker may be co-located with the source of sound to be attenuated.

[0328] The unwanted frequency filtering module 920 can remove undesirable frequencies that may adversely affect auditory electroencephalographic entrainment. For example, the active noise control component can identify that the auditory signal includes acoustic bursts having desired pulse rate intervals, as well as acoustic bursts having undesirable pulse rate intervals. The active noise control component can identify waveforms corresponding to acoustic bursts having undesirable pulse rate intervals, and generate inverted phase waveforms to cancel or attenuate the undesirable acoustic bursts.

[0329] The NSS 905 can include, access, interface with, or otherwise communicate with at least one profile manager 925. The profile manager 925 can be designed or constructed to store, update, retrieve, or otherwise manage information related to one or more subjects related to auditory brain entrainment. The profile information can include, for example, treatment history information, past brain entrainment information, medication information, acoustic wave parameters, feedback, physiological information, environmental information, or other data related to the brain entrainment system and method.

[0330] The NSS 905 may include, access, interface with, or otherwise communicate with at least one side effect management module 930. The side effect management module 930 may be designed and constructed to communicate information to the audio adjustment module 915 or the audio generation module 910 to modify one or more parameters of the auditory signal to reduce side effects. Side effects may include, for example, nausea, migraines, fatigue, seizures, ear tension, hearing loss, ringing in the ears, or tinnitus.

[0331] The side effect management module 930 can automatically instruct components of the NSS 905 to modify or change parameters of the auditory signal. The side effect management module 930 can be configured with predefined thresholds to reduce side effects. For example, the side effect management module 930 can be set to a maximum duration of a pulse train, a maximum amplitude of acoustic waves, a maximum volume, a maximum duty cycle of a pulse train (e.g., pulse width multiplied by the frequency of the pulse train), a maximum number of treatments for brainwave entrainment in a certain period of time (e.g., 1 hour, 2 hours, 12 hours, or 24 hours).

[0332] The side effect management module 930 can vary a parameter of the auditory signal in response to the feedback information. The side effect management module 930 can receive feedback from a feedback monitor 935. The side effect management module 930 can determine to adjust a parameter of the auditory signal based on the feedback. The side effect management module 930 can compare the feedback to a threshold to determine to adjust a parameter of the auditory signal.

[0333] The side effect management module 930 can be configured with or can include a policy engine that applies policies or rules to the current auditory signal and feedback to determine adjustments to the auditory signal. For example, if the feedback indicates that a patient receiving the auditory signal has a heart rate or pulse rate above a threshold, the side effect management module 930 can turn off the pulse train until the pulse rate stabilizes below the threshold or below a second threshold that is below the threshold.

[0334] The NSS 905 may include, access, interface with, or otherwise communicate with at least one feedback monitor 935. The feedback monitor may be designed and constructed to receive feedback information from a feedback component 960. The feedback component 960 may include, for example, a feedback sensor 1405, such as a temperature sensor, a heart rate or pulse monitor, a physiological sensor, an ambient noise sensor, a microphone, an ambient temperature sensor, a blood pressure monitor, an electroencephalogram sensor, an EEG probe, an electro-oculogram ("EOG") probe configured to measure corneal retinal orienting potentials present between the front and back of the human eye, an accelerometer, a gyroscope, a motion detector, a proximity sensor, a camera, a microphone, or a photodetector.

[0335] Systems and devices configured for neural stimulation via auditory stimulation - Patents.com 12A illustrates a system for auditory brain entrainment according to an embodiment. The system 1200 may include one or more speakers 1205. The system 1200 may include one or more microphones. In some embodiments, the system may include both a speaker 1205 and a microphone 1210. In some embodiments, the system 1200 may include a speaker 1205 and not include a microphone 1210. In some embodiments, the system 1200 may include a microphone 1210 and not include a speaker 1210.

[0336] The speaker 1205 can be integrated with the auditory signaling component 950. The auditory signaling component 950 can include the speaker 1205. The speaker 1205 can interact or communicate with the auditory signaling component 950. For example, the auditory signaling component 950 can instruct the speaker 1205 to generate a sound.

[0337] The microphone 1210 can be integrated with the feedback component 960. The feedback component 960 can include the microphone 1210. The microphone 1210 can interact or communicate with the feedback component 960. For example, the feedback component 960 can receive information, data, or signals from the microphone 1210.

[0338] In some embodiments, the speaker (1205) and the microphone (1210) can be integrated together or be the same device. For example, the speaker (1205) can be configured to function as the microphone (1210). The NSS 905 can switch the speaker (1205) from speaker mode to microphone mode.

[0339] In some embodiments, the system 1200 may include a single speaker 1205 located at one of the subject's ears. In some embodiments, the system 1200 may include two speakers. A first of the two speakers may be located at the first ear and a second of the two speakers may be located at the second ear. In some embodiments, an additional speaker may be located in front of the subject's head or behind the subject's head. In some embodiments, one or more microphones 1210 may be positioned at one or both ears, in front of the subject's head, or behind the subject's head.

[0340] The speaker 1205 may include a dynamic cone speaker configured to generate sound from an electrical signal. The speaker 1205 may include a full-range driver for generating acoustic waves having frequencies spanning some or all of the audible range (e.g., 60 Hz to 20,000 Hz). The speaker 1205 may include a driver for generating acoustic waves having frequencies outside the audible range, such as 0 to 60 Hz, or in the infrasonic range, such as 20 kHz to 4 GHz. The speaker 1205 may include one or more transducers or drivers for generating sound in various portions of the audible frequency range. For example, the speaker 1205 may include a tweeter for high frequencies (e.g., 2,000 Hz to 20,000 Hz), a mid-range driver for mid-range frequencies (e.g., 250 Hz to 2000 Hz), or a woofer for low frequencies (e.g., 60 Hz to 250 Hz).

[0341] The speaker 1205 may include one or more types of speaker hardware, components, or techniques for generating sound. For example, the speaker 1205 may include a diaphragm for generating sound. The speaker 1205 may include a moving iron loudspeaker that uses a stationary coil to vibrate a magnetized piece of metal. The speaker 1205 may include a piezoelectric speaker. A piezoelectric speaker may utilize the piezoelectric effect to generate sound by applying a voltage to a piezoelectric material to generate motion, which is converted into audible sound using a diaphragm and a resonator.

[0342] The speaker 1205 may include a variety of other types of hardware or technologies, such as a magnetostatic loudspeaker, a magnetostrictive speaker, an electrostatic loudspeaker, a ribbon speaker, a planar magnetic loudspeaker, a bending wave loudspeaker, a coaxial driver, a horn speaker, a Heil air motion transducer, or a transparent ion conduction speaker.

[0343] In some cases, the speaker 1205 may not have a diaphragm. For example, the speaker 1205 may be a plasma arc speaker using an electric plasma as the radiating element. The speaker 1205 may be a thermoacoustic speaker using carbon nanotube thin films. The speaker 1205 may be a rotating woofer that includes a fan with blades that constantly change their pitch.

[0344] In some embodiments, the speaker 1205 may include a headphone, or a pair of headphones, ear speakers, earphones, or earphones. A headphone may be a relatively small speaker compared to a loudspeaker. A headphone may be designed and constructed to be placed in, around, or otherwise near the ear or ear. A headphone may include an electroacoustic transducer that converts an electrical signal into a corresponding sound in the subject's ear. In some embodiments, the headphone 1205 may include or interface with a headphone amplifier, such as an integrated amplifier or a standalone unit.

[0345] In some embodiments, the speaker 1205 can include headphones that can include air jets that force air into the ear canal and press against the eardrum in a manner similar to sound waves. Compression and rarefaction of the eardrum with bursts of air (with or without any discernible sound) can control the frequency of neural vibrations similar to auditory signals. For example, the speaker 1205 can include air jets or devices similar to in-ear headphones that push, pull, or both push and pull air into the ear canal to compress or retract the eardrum and affect the frequency of neural vibrations. The NSS 905 can command, configure, or cause the air jets to generate bursts of air at a predetermined frequency.

[0346] In some embodiments, the headphones can be connected to the auditory signaling component 950 via a wired or wireless connection. In some embodiments, the auditory signaling component 950 can include 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 the system 100, such as the audio generation module 910, the audio conditioning module 915, the unwanted frequency filtering module 920, the profile manager 925, the side effect management module 930, the feedback monitor 935, the auditory signaling component 950, the filtering component 955, or the feedback component 960.

[0347] The speaker 1205 can include or be integrated into various types of headphones. For example, the headphones can include peri-aural headphones (e.g., full-sized headphones) that include, for example, circular or oval ear pads designed and constructed to seal against the head to attenuate external noise. Peri-aural headphones can facilitate the provision of an immersive auditory brainwave stimulation experience while reducing external distractions. In some embodiments, the headphones can include supra-aural headphones that include pads that press against the ears rather than around the ears. Supra-aural headphones may provide less attenuation of external noise.

[0348] Both circum-aural and supra-aural headphones can have an open back, closed back, or semi-open back. An open back allows more sound to leak out and more ambient sound to enter, but provides a more natural or speaker-like sound. Closed back headphones block out more ambient noise compared to open back headphones, thus providing a more immersive auditory brainwave stimulation experience while reducing external distractions.

[0349] In some embodiments, the headphones can include ear-fitting headphones, such as earbuds or in-ear headphones. Earbuds can refer to small headphones that are worn directly on the outer ear, facing the ear canal but not inserted. However, earbuds 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 can engage the ear canal and block more ambient noise compared to earbuds, thus providing a more immersive auditory EEG stimulation experience. In-ear headphones can include an ear canal plug made or formed from one or more materials, such as silicone rubber, elastomer, or foam. In some embodiments, the in-ear headphones can include a custom-made cast of the ear canal that creates a custom-molded plug that provides additional comfort and noise isolation to the subject, thereby further improving the immersion of the auditory EEG stimulation experience.

[0350] In some embodiments, one or more microphones 1210 can be used to detect sounds. The microphones 1210 can be integrated with the speaker 1205. The microphones 1210 can provide feedback information to the NSS 905 or other components of the system 100. The microphones 1210 can provide feedback to components of the speaker 1205 to cause the speaker 1205 to adjust parameters of the auditory signal.

[0351] The microphone 1210 may include a transducer that converts sound into an electrical signal. The microphone 1210 may generate an electrical signal from air pressure variations using electromagnetic induction, capacitance change, or piezoelectric. In some cases, the microphone 1210 may include or be connected to a preamplifier to amplify the signal before it is recorded or processed. The microphone 1210 may include one or more types of microphones, including, for example, a condenser microphone, an RF condenser microphone, an electret condenser, a dynamic microphone, a moving coil microphone, a ribbon microphone, a carbon microphone, a piezoelectric microphone, a crystal microphone, a fiber optic microphone, a laser microphone, a liquid or water microphone, a microelectromechanical system ("MEMS") microphone, or a speaker as a microphone.

[0352] The feedback component 960 can include or interface with a microphone 1210 to capture, identify, or receive audio. The feedback component 960 can capture ambient noise. The feedback component 960 can capture sound from the speaker 1205 to facilitate the NSS 905 adjusting characteristics of the auditory signal generated by the speaker 1205. The microphone 1210 can receive audio input from the subject, such as audio commands, instructions, requests, feedback information, or responses to survey questions.

[0353] 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 and can be located in a single enclosure, or the speaker 1205 and microphone 1210 can even be the same device, as they can be structurally designed to switch between sound generation and sound reception modes.

[0354] 12B illustrates a system configuration for auditory brain entrainment according to an embodiment. The system 1200 can include at least one speaker 1205. The system 1200 can include at least a 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.

[0355] The system 1200 can include a first speaker 1205 disposed at the first ear. The system 1200 can include a second speaker 1205 disposed at the second ear. The system 1200 can include a first active noise cancellation component 1215 communicatively coupled to the first microphone 1210. The system 1200 can include a second active noise cancellation component 1215 communicatively coupled to 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 to the active noise cancellation component 1215. The system 1200 may include a second microphone 1210 communicatively coupled to the active noise cancellation component 1215. In some embodiments, each of the microphone 1210, the speaker 1205, and the active noise cancellation component may communicate or interface with the NSS 905. In some embodiments, the system 1200 may include a feedback sensor 1225 and a second feedback sensor 1225 communicatively coupled to the NSS 905, the speaker 1205, the microphone 1210, or the active noise cancellation component 1215.

[0356] In operation, in some embodiments, the audio player 1220 can play a music track. The audio player 1220 can convey an auditory signal corresponding to the music track via a wired or wireless connection to the first and second speakers 1205. In some embodiments, the NSS 905 can intercept the auditory signal from the audio player. For example, the NSS 905 can receive a digital or analog auditory signal from the audio player 1220. The NSS 905 can mediate between the audio player 1220 and the speakers 1205. The NSS 905 can analyze the auditory signal corresponding to the music to embed an auditory EEG 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 shown in FIG. 11C. In some embodiments, the NSS 905 can convey different auditory signals to the first and second speakers using binaural beat techniques that combine to have a desired stimulation frequency when perceived by the brain.

[0357] In some embodiments, the NSS 905 can adjust any latency between the first speaker (1205) and the second speaker (1205) so that the brain perceives the audio signals at the same or substantially the same time (e.g., within 1 ms, 2 ms, 5 ms, or 10 ms). The NSS 905 can buffer the audio signals to account for latency so that the audio signals are transmitted from the speakers simultaneously.

[0358] In some embodiments, the NSS 905 may not mediate the audio player 1220 and the speaker. For example, the NSS 905 may receive a music track from a digital music repository. The NSS 905 may manipulate or modify the music track to embed acoustic pulses according to a desired PRI. The NSS 905 may then provide the modified music track to the audio player 1220 to provide a modified auditory signal to the speaker 1205.

[0359] In some embodiments, the active noise cancellation component 1215 can receive ambient noise information from the microphone 1210, identify undesirable frequencies or noise, and generate an anti-phase waveform to cancel or attenuate the undesirable waveform. 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 an additional speaker.

[0360] The feedback sensor 1225 of the system 1200 can detect feedback information, such as an environmental parameter or a physiological condition. The feedback sensor 1225 can provide the feedback information to the NSS 905. The NSS 905 can adjust or modify the auditory signal based on the feedback information. For example, the NSS 905 can reduce the volume of the auditory signal after determining that the subject's pulse rate exceeds a predetermined threshold. The NSS 905 can detect that the volume of the auditory signal exceeds the threshold and reduce the amplitude. The NSS 905 can determine that the pulse rate interval is below a threshold, which may indicate that the subject is losing focus or not paying a satisfactory level of attention to the auditory signal, and the NSS 905 can increase the amplitude of the auditory signal or change the tone or music track. In some embodiments, the NSS 905 can change the tone or music track based on the time interval. Changing the tone or music track can encourage the subject to pay a higher level of attention to the auditory stimuli and promote brainwave entrainment.

[0361] In some embodiments, the NSS 905 can receive neural oscillation information from the EEG probe 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 undesirable frequencies. The NSS 905 can then identify corresponding undesirable frequencies in the ambient noise using the microphone 1210. The NSS 905 can then instruct the active noise cancellation component 1215 to remove waveforms corresponding to the ambient noise having the undesirable frequencies.

[0362] In some embodiments, the NSS 905 can enable a passive noise filter. A pass noise filter can include a circuit having one or more resistors, capacitors, or inductors that filter undesirable frequencies of noise. In some cases, a passive filter can include a sound insulating material, a sound dampening material, or a sound absorbing material.

[0363] FIG. 4C illustrates a system configuration for auditory brain entrainment according to an embodiment. The system 401 can provide auditory brainwave stimulation using an ambient noise source 1230. For example, the system 401 can include a microphone 1210 that detects the ambient noise 1230. The microphone 1210 can transmit the detected ambient noise to the NSS 905. The NSS 905 can modify the ambient noise 1230 before transmitting it to the first speaker 1205 or the second speaker 1205. In some embodiments, the system 401 can be integrated or interfaced with a hearing aid device. A hearing aid can be a device designed to improve hearing.

[0364] The NSS 905 can increase or decrease the amplitude of the ambient noise 1230 to generate acoustic bursts having a desired pulse rate interval. The NSS 905 can provide modified auditory signals to the first and second speakers 1205 to facilitate auditory brainwave entrainment.

[0365] In some embodiments, the NSS 905 can overlay a click train, tone, or other acoustic pulse onto the ambient noise 1230. For example, the NSS 905 can receive ambient noise information from the microphone 1210, apply an auditory stimulus signal to the ambient noise information, and then present the combined ambient noise information and auditory stimulus signal to the first and second speakers 1205. In some cases, the NSS 905 can filter unwanted frequencies of the ambient noise 1230 before providing the auditory stimulus signal to the speaker 1205.

[0366] Thus, using ambient noise 1230 as part of the auditory stimulation, the subject can observe their surroundings or continue with their daily activities while receiving the auditory stimulation to promote brainwave entrainment.

[0367] FIG. 13 illustrates a system configuration for auditory brain entrainment according to an embodiment. The system 1300 can use a room environment to provide auditory stimuli for brainwave entrainment. 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, a right speaker 1315, a center speaker 1305, a right surround speaker 1325, and a left surround speaker 1330. The system 1300 includes a subwoofer 1320. The system 1300 can include a 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.

[0368] When providing auditory stimuli using a surround system, the NSS905 can provide the same or different audio signals to each of the speakers in the system (1300). The NSS905 can modify or adjust the audio signals provided to one or more of the speakers in the system (1300) to promote brainwave entrainment. For example, the NSS905 can receive feedback from the microphone (1210) and modify, manipulate, or otherwise adjust the audio signals to optimize the auditory stimuli provided to a subject located at a location in the room corresponding to the location of the microphone (1210). The NSS905 can optimize or improve the auditory stimuli perceived at the location corresponding to the microphone (1210) by analyzing the acoustic beams or waves generated by the speakers and propagating toward the microphone (1210).

[0369] The NSS 905 may be configured with information regarding the design and configuration of each speaker. For example, speaker 1305 may generate sound in a direction of angle 1335. speaker 1310 may generate sound traveling in a direction of angle 1340. speaker 1315 may generate sound traveling in a direction of angle 1345. speaker 1325 may generate sound traveling in a direction of angle 1355. speaker 1330 may generate sound traveling in a direction of angle 1350. These angles may be optimal or predetermined angles for each speaker. These angles are referred to as optimal angles for each speaker such that a person located at a location corresponding to microphone 1210 may receive optimal auditory stimulation. In this manner, the speakers of system 1300 may be oriented to transmit auditory stimulation toward a target.

[0370] 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 a speaker to facilitate brainwave entrainment. The NSS 905 can intercept music 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 send adjusted auditory signals to the speakers of the system 1300 to induce brainwave entrainment.

[0371] 14 shows a feedback sensor 1405 placed or positioned on, on, or near a person's head. The feedback sensor 1405 may include, for example, an EEG probe to detect brainwave activity.

[0372] The feedback monitor 935 may detect, receive, acquire, or otherwise identify feedback information from one or more feedback sensors (1405). The feedback monitor 935 may provide the feedback information to one or more components of the NSS 905 for further processing or storage. For example, the profile manager 925 may update a profile data structure 945 stored in the data repository 940 with the feedback information. The profile manager 925 may associate the feedback information with an identifier of the patient or person receiving auditory brain stimulation, as well as a timestamp and date stamp corresponding to the receipt or detection of the feedback information.

[0373] The feedback monitor 935 can determine the attention level. The attention level can refer to the focus provided to the acoustic pulses used for brain stimulation. The feedback monitor 935 can determine the attention level using a variety of hardware and software techniques. The feedback monitor 935 can assign a score to the attention level (e.g., 1 to 10, where 1 is low attention and 10 is high attention, or vice versa; 1 to 100, where 1 is low attention and 100 is high attention, or vice versa; 0 to 1, where 0 is low attention and 1 is high attention, or vice versa), classify the attention level (e.g., low, medium, high), grade the attention (e.g., A, B, C, D, or F), or otherwise provide an indication of the attention level.

[0374] In some cases, the feedback monitor 935 can track the person's eye movements to identify attention levels. The feedback monitor 935 can interface with a feedback component 960 that includes an eye tracker. The feedback monitor 935 (e.g., via the feedback component 960) can detect and record the person's eye movements and analyze the recorded eye movements to determine attention span or attention level. The feedback monitor 935 can measure gaze, which may indicate or provide information regarding hidden attention. For example, the feedback monitor 935 (e.g., via the feedback component 960) can be configured with electrooculography ("EOG") to measure skin potential around the eyes, which can indicate the direction the eyes are pointing relative to the head. In some embodiments,...

Claims

1. A system for altering neurological, anxiety, depressive, addictive, food-seeking, or sleep behavior in a subject, comprising: (a) a stimulus source programmed to emit stimuli to the subject having a pulse rate interval of about 0.014 seconds to about 0.03 seconds; and (b) one or more processors individually or collectively programmed to execute a set of instructions including instructing the stimulus source to emit the stimuli to the subject during an activity of the subject, thereby resulting in a change in the neurological, anxiety, depressive, addictive, food-seeking, or sleep behavior.

2. 10. The system of claim 1, wherein the subject has a disease or disorder associated with cerebral white matter atrophy, demyelination, or a combination thereof, and optionally, treatment of the disease or disorder is combined with the use of one or more agents.

3. The system described in claim 1, wherein the stimuli include one or more of mechanical stimuli, auditory stimuli, and visual stimuli, and optionally, the stimuli include frequencies between 10 Hz and 100 Hz.

4. The system of claim 1, wherein the activity involves a cognitive process, and optionally, the cognitive process includes one or more executive functions, and optionally, the executive functions include emotion regulation, cognitive flexibility, goal-oriented persistence, metacognition, organization, planning / prioritization, response inhibition, stress resilience, sustained attention, task initiation, time management, working memory, or a combination thereof.

5. The system of claim 1, wherein the activity includes one or more cognitive processes selected from memory encoding, memory consolidation, memory retrieval, perception, attention, knowledge formation, problem solving, concept formation, pattern recognition, association, decision-making, motor coordination, task planning, language expression, or language comprehension.

6. A system as described in claim 1 that slows neurodegeneration.

7. The system of claim 1, wherein the system improves cognitive skills, optionally wherein the cognitive skills include perceptual reasoning, sustained attention, selective attention, divided attention, long-term memory, working memory, logic and reasoning, auditory processing, visual processing, visuomotor planning and processing, visuospatial planning and processing, task planning, task sequencing, task initiation, task completion, visual encoding and decoding, auditory encoding and decoding, sensory encoding and decoding, language representation, language comprehension, processing speed, cognitive control, cognitive inhibition, declarative memory, procedural memory, episodic memory, auditory memory, visual memory, semantic memory, or autobiographical memory, and optionally wherein the processing speed includes one or more of visual processing speed, language processing speed, auditory processing speed, and motor processing speed.

8. The system of claim 1, wherein the activity includes meditating, sleeping, reading, or ingesting a substance, optionally wherein the substance promotes blood flow, and optionally wherein the substance includes a stimulant or depressant.

9. The system of claim 1, wherein the activity includes physical activity, and optionally, the activity includes bathing or showering.

10. The system described in claim 1, wherein the sensory stimuli include auditory and mechanical stimuli, and administering the sensory stimuli includes opening a water source, the water source being capable of creating increases and decreases in water pressure, thereby administering the sensory stimuli to the subject during the activity.

11. The system of claim 1, wherein the activity includes operating heavy machinery, and optionally, the operating heavy machinery includes an automobile or an aircraft.

12. A system for slowing neurodegeneration in a subject in need thereof, the system comprising: a stimulus-emitting component; and one or more processors, the processors: a. Receive a subject instruction; b. generating an output signal based on said instructions; and c. configured to provide the output signal to the stimulus-emitting component to cause the stimulus-emitting component to provide stimulation in accordance with the generated output signal, thereby slowing neurodegeneration in the subject; system.

13. The system described in claim 12, wherein the stimulated emission component includes a display device.

14. The system described in claim 12, wherein slowing neurodegeneration includes reducing cerebral white matter atrophy experienced by the subject, and optionally, slowing neurodegeneration includes reducing the rate of demyelination experienced by the subject.

15. The system of claim 12, wherein the instructions are associated with an activity to be performed by the subject.

16. The system of claim 15, wherein the activity is selected from the group consisting of learning, researching, presenting, speaking, concentrating, analyzing, or listening; optionally, the activity includes readjusting a posture or position of the subject; optionally, the activity includes walking, jogging, skipping, running, hopping, marching, swimming, or any combination thereof; optionally, the activity includes engaging in mental effort, physical effort, or a combination thereof; and optionally, the activity includes playing a logic game, a board game, or a video game.

17. The system of claim 12, further comprising a feedback monitor configured to provide the instruction to the subject.

18. The system of claim 12, further comprising a profile manager configured to provide the instructions to the subject.

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