Methods and systems for slowing brain atrophy

Abstract

The disclosed system and method are directed to neurostimulation via non-invasive sensory stimulation.Non-invasive sensory stimulation can reduce neuroinflammation by inducing synchronous gamma oscillations in at least one region of the subject's brain, improve synaptic plasticity and stimulate neural networks, and improve microglia-mediated clearance of brain damage that would otherwise lead to the progression of brain atrophy.The stimulation can regulate, control, or otherwise manage the frequency of neural oscillations to provide beneficial effects to one or more cognitive states or functions of the brain, while mitigating or preventing the adverse effects on cognitive state or function resulting from the progression of brain atrophy.

Description

[Technical field]

[0001] (cross reference) This application claims the benefit of U.S. Provisional Patent Application No. 63 / 158,779, filed March 9, 2021, and U.S. Provisional Patent Application No. 63 / 244,522, filed September 15, 2021, each of which is incorporated by reference in its entirety. [Background technology]

[0002] 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 appear as oscillations in membrane potentials or as rhythmic patterns of action potentials that can produce oscillatory activation of postsynaptic neurons. Synchronized activity of neuronal groups 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.

[0003] (Incorporated by reference) Each patent, publication, and non-patent literature cited in this application is incorporated by reference in its entirety, as if each was individually incorporated by reference. Summary of the Invention

[0004] In some embodiments, disclosed herein is a method for reducing the rate of brain atrophy in one or more regions of a subject's brain, the method comprising administering a non-invasive stimulation to a subject to induce synchronous gamma oscillations in at least one region of the subject's brain, thereby reducing the rate of brain atrophy in one or more regions of the subject's brain.

[0005] In some embodiments, the non-invasive stimulation includes one or more stimulation waveforms.

[0006] The one or more stimulus waveforms may include a visual stimulus waveform, an auditory stimulus waveform, a tactile stimulus waveform, a mechanical stimulus waveform, or a combination thereof.

[0007] In some embodiments, the one or more stimulation waveforms have a synchronous phase. In some embodiments, the one or more stimulation waveforms include a first stimulation waveform and a second stimulation waveform. In some embodiments, the first stimulation waveform includes a visual stimulation waveform. In some embodiments, the first stimulation waveform includes an auditory stimulation waveform. In some embodiments, the first stimulation waveform includes a mechanical stimulation waveform. In some cases, the first stimulation waveform includes a vibrotactile stimulation waveform or a tactile stimulation waveform.

[0008] In some embodiments, the second stimulus waveform comprises an auditory stimulus waveform. In some embodiments, the second stimulus waveform comprises a mechanical stimulus waveform. In some embodiments, the second stimulus waveform comprises a vibrotactile stimulus waveform or a tactile stimulus waveform. In some embodiments, the first stimulus waveform comprises a square wave function. In some embodiments, the first stimulus waveform comprises a sine wave function. In some embodiments, the second stimulus waveform comprises a square wave function. In some embodiments, the second stimulus waveform comprises a sine wave function.

[0009] In some embodiments, administering the non-invasive stimulus includes administering the non-invasive stimulus for a first duration. In some cases, the method further includes measuring the subject's response to the non-invasive stimulus for a second duration. In some cases, the first duration and the second duration are separated by a third duration.

[0010] In many embodiments described herein, the non-invasive stimulation is delivered via a wearable device. In some cases, the wearable device includes glasses. In some cases, the glasses include an illumination source. In some cases, the glasses include opaque glasses. In some cases, the glasses include clear glasses. In some cases, the wearable device further includes headphones.

[0011] In some embodiments, the methods and systems described herein further include measuring the subject's response to the non-invasive stimulation. In some cases, measuring the response is performed for a first duration. In some cases, measuring the response is performed for a second duration. In some cases, measuring the response is performed for a first duration. In some cases, measuring the response is performed for a third duration. In some cases, measuring the response is performed for the first duration and the second duration. In some cases, measuring the response is performed for a third duration.

[0012] The one or more regions of the brain include the visual cortex, the somatosensory cortex, the insular cortex, or any combination thereof. In some embodiments, reducing the rate of brain atrophy includes reducing the rate of brain volume shrinkage. In some cases, the rate of brain volume shrinkage is about 0.3 cm per month. 3 Approximately 2cm per month 3 In some cases, the rate of brain volume reduction is approximately 0.3 cm per year. 3 Approximately 2cm per year 3 Includes.

[0013] In some cases, the reduction in brain volume includes a reduction in hippocampal volume, lateral lobe volume, lateral ventricle volume, temporal lobe volume, occipital lobe volume, temporal cortical thickness, occipital cortical thickness, or a combination thereof.

[0014] The present disclosure further provides systems and methods for treating a disease, disorder, or condition associated with brain atrophy in a subject, the method comprising administering a non-invasive stimulus to the subject to generate synchronous gamma oscillations in at least one brain region, wherein the administering reduces a rate of brain atrophy experienced by the subject, thereby treating the disease, disorder, or condition associated with brain atrophy in the subject. In some cases, the disease, disorder, or condition comprises a microglia-mediated disease. In some cases, the disease, disorder, or condition comprises a neurodegenerative disorder. In some cases, the neurodegenerative disorder comprises Alzheimer's disease, Creutzfeldt-Jakob disease (CJD), variant CJD, Gerstmann-Straussler-Scheinker disease, fatal familial insomnia, kuru, or any combination thereof. In some cases, the disease, disorder, or condition comprises aging.

[0015] In some embodiments described herein, the brain atrophy rate is decreased from a first rate to a second rate, the first rate comprises at least 0.5% brain atrophy per year, and the second rate comprises less than the first rate. In some cases, the first rate comprises at least 0.6% brain atrophy per year. In some cases, the first rate comprises at least 0.7% brain atrophy per year. In some cases, the first rate comprises at least 0.8% brain atrophy per year. In some cases, the first rate comprises at least 0.9% brain atrophy per year. In some cases, the first rate comprises at least 1.0% brain atrophy per year. In some cases, the first rate comprises at least 1.1% brain atrophy per year. In some cases, the first rate comprises at least 1.2% brain atrophy per year. In some cases, the first rate comprises at least 1.3% brain atrophy per year. In some cases, the first rate comprises at least 2.0% brain atrophy per year. In some cases, the first rate comprises at least 3.0% brain atrophy per year. In some cases, the first rate comprises at least 4.0% brain atrophy per year.

[0016] Further provided herein are methods and systems for reducing cognitive decline linked to brain atrophy, the methods comprising administering a non-invasive stimulus to a subject in need of reducing cognitive decline linked to brain atrophy to induce synchronous gamma oscillations in at least one region of the brain, wherein the administering reduces the rate of atrophy experienced by the brain, thereby reducing the cognitive decline linked to brain atrophy.

[0017] Also disclosed herein are systems and methods for reducing one or more symptoms or diseases associated with brain atrophy, the methods including (a) identifying a subject experiencing brain atrophy, and (b) administering to the subject a non-invasive stimulation that causes one or more brain wave synchronization, thereby reducing one or more symptoms associated with brain atrophy. In some cases, the one or more symptoms or diseases include neuronal loss, memory loss, vision impairment, aphasia, balance impairment, paralysis, cortical volume loss, CSF volume increase, motor skills loss, speech difficulties, reading comprehension difficulties, gray matter volume loss, white matter volume loss, neuronal size loss, neuronal cytoplasmic protein loss, or any combination thereof. In some embodiments, identifying the subject includes assessing the subject's disease, performing an assessment on the subject, or measuring the subject's neuronal activity.

[0018] In some embodiments, the systems and methods disclosed herein further include evaluating the subject's response to the non-invasive sensory stimulation. In some embodiments, the systems and methods further include adjusting the non-invasive sensory stimulation to enhance synchronization.

[0019] In some embodiments, the non-invasive stimulation comprises a frequency of about 20 Hz to about 70 Hz. In some embodiments, the non-invasive stimulation comprises a frequency of about 30 Hz to about 60 Hz. In some embodiments, the non-invasive stimulation comprises a frequency of about 35 Hz to about 45 Hz.

[0020] In some embodiments, the adjusting includes switching the non-invasive sensory stimulation from a square wave function to a sine wave function. In some cases, the adjusting includes switching the non-invasive sensory stimulation from a square wave function to a sine wave function. In some cases, the adjusting includes adjusting an intensity of the non-invasive stimulation. In some cases, the adjusting includes adjusting a frequency of the non-invasive stimulation. In some cases, the adjusting includes adjusting a waveform of the non-invasive stimulation. In some cases, the adjusting includes switching a source of the non-invasive sensory stimulation.

[0021] Also provided herein is a non-transitory computer-readable storage medium encoded with instructions executable by one or more processors, the instructions performing any one of the above systems and methods. Further provided is a computer-implemented system including at least one digital processing device including at least one processor and instructions executable by the at least one processor, where the instructions perform any one of the methods described herein.

[0022] The present disclosure further provides a system for reducing the rate of brain atrophy in a subject, the system including: a) a stimulus emitting component capable of providing neural, auditory, or visual stimuli to the subject; b) a processor; c) a memory device; and d) a feedback sensor, wherein the processor (i) receives via the feedback sensor an indication of the subject's physiological assessment, cognitive assessment, neural assessment, physical assessment, or any combination thereof; and (ii) based on the indication, instructs the stimulus emitting component to adjust at least one parameter associated with the neural, auditory, or visual stimulation to bring about an improvement in the degree of neural entrainment exhibited by neurons in at least one brain region of the subject, thereby causing a reduction in the rate of brain atrophy. [Brief description of the drawings]

[0023] [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 illustrate visual stimulation signals that induce neural stimulation, according to some embodiments. [Figure 2B] 2A-2F illustrate visual stimulation signals that induce neural stimulation, according to some embodiments. [Figure 2C] 2A-2F illustrate visual stimulation signals that induce neural stimulation, according to some embodiments. [Figure 2D] 2A-2F illustrate visual stimulation signals that induce neural stimulation, according to some embodiments. [Figure 2E] 2A-2F illustrate visual stimulation signals that induce neural stimulation, according to some embodiments. [Figure 2F] 2A-2F illustrate visual stimulation signals that induce 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 to which visual signals may be transmitted for visual brain entrainment, according to some embodiments. [Figure 3C] 3A-3C illustrate fields of view to which visual signals may be transmitted for visual brain entrainment, according to some embodiments. [Figure 4A] 4A-4C illustrate a device configured to deliver a visual signal for neurostimulation, according to some embodiments. [Figure 4B] 4A-4C illustrate a device configured to deliver a visual signal for neurostimulation, according to some embodiments. [Figure 4C]4A-4C illustrate a device configured to deliver a visual signal for neurostimulation, according to some embodiments. [Figure 5A] 5A-5D illustrate a device configured to deliver a visual signal for neurostimulation according to some embodiments. [Figure 5B] 5A-5D illustrate a device configured to deliver a visual signal for neurostimulation according to some embodiments. [Figure 5C] 5A-5D illustrate a device configured to deliver a visual signal for neurostimulation according to some embodiments. [Figure 5D] 5A-5D illustrate a device configured to deliver a visual signal for neurostimulation according to some embodiments. [Figure 6A] 6A and 6B show a device configured to receive feedback to facilitate neural stimulation according to some embodiments. [Figure 6B] 6A and 6B show 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. 8 is a flow diagram of a method for performing neurostimulation using visual stimulation according to one embodiment. [Figure 9] FIG. 9 is a block diagram illustrating a system for neural stimulation via auditory stimulation in accordance with one embodiment. [Figure 10A]10A-10I illustrate audio signals and types of modulations on audio signals used to induce neural oscillations via auditory stimulation, according to some embodiments. [Figure 10B] 10A-10I illustrate audio signals and types of modulations on audio signals used to induce neural oscillations via auditory stimulation, according to some embodiments. [Figure 10C] 10A-10I illustrate audio signals and types of modulations on audio signals used to induce neural oscillations via auditory stimulation, according to some embodiments. [Figure 10D] 10A-10I illustrate audio signals and types of modulations on audio signals used to induce neural oscillations via auditory stimulation, according to some embodiments. [Figure 10E] 10A-10I illustrate audio signals and types of modulations on audio signals used to induce neural oscillations via auditory stimulation, according to some embodiments. [Figure 10F] 10A-10I illustrate audio signals and types of modulations on audio signals used to induce neural oscillations via auditory stimulation, according to some embodiments. [Figure 10G] 10A-10I illustrate audio signals and types of modulations on audio signals used to induce neural oscillations via auditory stimulation, according to some embodiments. [Figure 10H] 10A-10I illustrate audio signals and types of modulations on audio signals used to induce neural oscillations via auditory stimulation, according to some embodiments. [Figure 10I] 10A-10I illustrate audio signals and types of modulations on audio signals used to induce neural oscillations via auditory stimulation, according to some embodiments. [Figure 11A]FIG. 11A illustrates an audio signal generated using binaural beats according to one embodiment. [Figure 11B] FIG. 11B illustrates an acoustic pulse having isochronic tones according to one embodiment. [Figure 11C] FIG. 11C 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] FIG. 13 illustrates a system configuration for room-based auditory stimulation for neurostimulation, according to one embodiment. [Figure 14] FIG. 14 illustrates a device configured to receive feedback to facilitate neural stimulation via auditory stimulation according to some embodiments. [Figure 15] FIG. 15 is a flow diagram of a method for performing auditory brain entrainment, according to one embodiment. [Figure 16] FIG. 16 is a block diagram illustrating a system for neural stimulation via multiple stimulation modes, according to one embodiment. [Figure 17A] FIG. 17A is a block diagram illustrating a system for neurostimulation via visual and auditory stimuli according to one embodiment. [Figure 17B] FIG. 17B illustrates waveforms used for neurostimulation via visual and auditory stimuli, according to one embodiment. [Figure 18]FIG. 18 is a flow diagram of a method for neurostimulation via visual and auditory stimuli according to one embodiment. [Figure 19] FIG. 19 is an efficacy summary chart for the modified ITT population, including p-values, differences, confidence intervals (CIs), and standardized estimates of efficacy based on values. [Figure 20] FIG. 20 shows separate mean analyses (left) and linear model analyses (right) of the Optimized Alzheimer's Disease Composite Score (ADCOMS) for mid and moderate Alzheimer's Disease (ADCOMS) for sham and treatment groups. [Figure 21] FIG. 21 shows separate means analysis (left) and linear model analysis (right) of Alzheimer's Disease Assessment Scale-Cognitive Subscale 14 (ADAS-Cogl4) values ​​for sham and treatment groups. [Figure 22] FIG. 22 shows separate means analysis (left) and linear model analysis (right) of Clinical Dementia Rating Sale Sum of Boxes (CDR-SB) values ​​for the sham and treatment groups. [Figure 23] FIG. 23 shows separate mean analyses (left) and linear model analyses (right) of Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scores for sham and treatment groups. [Figure 24] FIG. 24 shows a linear model analysis of Mini-Mental State Examination (MMSE) scores measured after 6 months of treatment (ie, the final time point). [Diagram 25] FIG. 25 shows a linear model analysis of magnetic resonance imaging (MRI) results of whole brain volume values ​​(left side) and hippocampal volume (right side) after 6 months of treatment. [Figure 26]FIG. 26 is a table showing a summary of efficacy findings from human clinical trials, including p-values, treatment differences, CI values, and percentage slowing of brain atrophy. [Figure 27A] Figure 27A and Figure 27B summarize the findings of the ITT population primary analysis. Figure 27A shows summary findings for the ITT population primary analysis of occipital cortex volume change in cm3 from human clinical trials, including the least squares mean change (±SE) from baseline for both sham and treatment arms and p-values ​​at 0, 3, and 6 months. Figure 27B shows summary findings for the ITT population primary analysis of occipital cortex thickness in mm from human clinical trials, including the least squares mean change (±SE) from baseline for both sham and treatment arms and p-values ​​at 0, 3, and 6 months. [Figure 27B] Figure 27A and Figure 27B summarize the findings of the ITT population primary analysis. Figure 27A shows summary findings for the ITT population primary analysis of occipital cortex volume change in cm3 from human clinical trials, including the least squares mean change (±SE) from baseline for both sham and treatment arms and p-values ​​at 0, 3, and 6 months. Figure 27B shows summary findings for the ITT population primary analysis of occipital cortex thickness in mm from human clinical trials, including the least squares mean change (±SE) from baseline for both sham and treatment arms and p-values ​​at 0, 3, and 6 months.

[0024] The features and advantages of the present solution will become more 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

[0025] Use of neurostimulation to slow brain atrophy and alleviate associated disorders

[0026] Described herein is a system and method for using sensory evoked potentials to slow brain atrophy and thus mediate the symptoms of brain atrophy in subjects.In particular, the present disclosure describes a system and method for reducing neuroinflammation, improving synaptic plasticity, stimulating neural network, and improving microglia-mediated clearance of brain damage that would otherwise contribute to the progression of brain atrophy by inducing synchronous gamma oscillation in at least one region of the brain of a subject.The at least one brain region can include, for example, the visual cortex, somatosensory cortex, insular cortex, and / or hippocampus of the subject.

[0027] Brain atrophy and volume When used herein to refer to measurable values ​​such as quantity, time duration, etc., it is meant to include an open-ended variation of ±40% or ±20% or ±10%, ±5%, ±1%, or ±0.1% from the stated value. Such variations are appropriate. The term "about" is used herein to provide literal support for the exact number it precedes, as well as a number that is close to or approximately the number it precedes. When determining whether a number is close to or approximately a number specifically recited, the close or approximately unrecited number may be a number that provides a substantial equivalent to the specifically recited number in the context in which it is presented.

[0028] It should be noted that, as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. It should be further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as a predicate for using exclusive terminology such as "solely," "only," or "negative" limitations in connection with the recitation of claim elements.

[0029] Brain atrophy can be present as a change in brain volume. Brain atrophy, or atrophy of brain tissue, represents a loss of volume within neurons, extracellular space, or glia. Atrophy can occur at different rates in different regions or areas of the brain and can be reflected by a change in total brain volume. In adults, total brain volume is, for example, approximately 950 cm 3 ~1550cm 3 For adult women, the average total brain volume is about 1130 cm 3 For an adult male, the average brain volume is about 1260 cm 3 For children aged between about 4 and 16 years, the total brain volume can be, for example, about 60 cm 3 ~Approx. 120cm 3 It could be.

[0030] The present disclosure provides systems and methods directed to slowing brain volume changes associated with brain atrophy. 3 / month, 0.5cm 3 / month, 1cm 3 / month, 2cm 3 / month, 0.3cm 3 / year, 0.5cm 3 / year, 1cm 3 / year, 2cm 3 / year, 3cm 3 / year, 4cm 3 / year, 5cm 3 / year, 6cm 3 / year, 7cm 3 / year, 8cm 3 / year, 9cm 3 / year, 10cm 3 / year, 11cm 3 / year, 12cm 3 / year, 13cm 3 / year, 14cm 3 / year or 15cm 33 / year, or 16 cm3 / year. Brain atrophy rates may vary between individuals. Exemplary rates of brain atrophy include, but are not limited to, 0.1%-0.5% / year, 0.5%-1.5% / year, 1.0%-3.0% / year, or 3.0%-6.0% / year. Brain atrophy rates 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 with 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 also cause an increase in the rate of brain atrophy. For example, a middle-aged individual may experience a brain atrophy rate of about 0.2% / year, and an individual about 60 years old may experience a brain atrophy rate of about 0.5% / year.

[0031] 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 the two MRI scans using warping techniques, and from this process, small changes in brain volume can be directly extracted.

[0032] Various tools and algorithms may be employed to determine brain volume through CT or MRI scans. Of the various toolkits available for determining brain volume and brain volume changes based on scanned images, examples include, but are not limited to, Atropos, an open source tissue segmentation algorithm; CIVET, a web-based image processing tool for volumetric analysis using different human brain images; Structural Image Assessment with Atrophy Normalization (SIENA and SIENAX), a software that applies the Brain Extraction Tool (BET) to determine cross-sectional volume; MSmetrix, a fully automated tool that detects brain lesions, calculates lesion volume, and measures whole brain and gray matter atrophy; and tools such as Statistical Parameter Mapping (SPM) for the analysis of images in the MATLAB environment.

[0033] Source of brain atrophy The systems and methods described herein can reduce brain atrophy or symptoms thereof due to normal aging of a subject.The systems and methods described herein can also reduce brain atrophy or symptoms thereof due to disease, disorder, or illness.In addition, the systems and methods of the present disclosure can help slow the progression of diseases, disorders, or illnesses associated with brain atrophy through non-invasive stimulation of gamma oscillations.

[0034] The disclosed system and method may slow brain atrophy and alleviate symptoms of brain atrophy through non-invasive stimulation of gamma oscillations.Subjects with brain atrophy may experience this as a result of or as a result of various diseases, disorders, or disorders, including but not limited to normal aging, 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, Lewy body dementia, chronic traumatic encephalopathy (CTE), etc.

[0035] The system and method of the present disclosure are also directed to alleviating symptoms of brain atrophy. The system and method described herein can reduce brain atrophy or symptoms thereof caused by normal aging of a subject. The system and method described herein can also reduce brain atrophy or symptoms thereof caused by disease, disorder, or illness. In addition, the system and method of the present disclosure can help slow the progression of diseases, disorders, or illnesses associated with brain atrophy through non-invasive stimulation of gamma oscillations.

[0036] Symptoms may include loss of neurons, memory loss, vision problems, aphasia, balance problems, paralysis, reduced cortical volume, increased CSF volume, loss of motor control, difficulty speaking, comprehension, reading, memory, reduced gray and / or white matter, reduced 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.

[0037] The disclosed system and method may slow brain atrophy and alleviate symptoms of brain atrophy through non-invasive stimulation of gamma oscillations.Subjects with brain atrophy may experience this as a result of or as a result of various diseases, disorders, or disorders, including but not limited to normal aging, 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, Lewy body dementia, chronic traumatic encephalopathy (CTE), etc.

[0038] Thus, in some embodiments, the present disclosure provides systems and methods for alleviating symptoms associated with microglia-mediated disease or disorder associated with brain atrophy.For example, microglia-mediated disease or disorder may include tauopathy-related neurodegenerative diseases, including but not limited to chronic traumatic encephalopathy, frontotemporal dementia, and cortical vascular degeneration.Microglia-mediated disease or disorder may include genetic disorders, such as hereditary ataxias, associated with brain atrophy.Microglia-mediated disease or disorder may also include neuropsychiatric disorders associated with brain atrophy, such as depression or schizophrenia; brain injury, such as stroke; or demyelinating diseases, such as multiple sclerosis and acute disseminated encephalomyelitis.

[0039] 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 cortical vascular degeneration.

[0040] Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the decline of memory, orientation, and reasoning. AD can be characterized by the accumulation of amyloid plaques containing multiple neurofibrillary tangles (NFTs) made of amyloid-β (Aβ) peptides and tau protein. Under normal conditions, soluble Aβ peptides are produced and secreted by neurons and subsequently removed from the brain via the cerebrospinal fluid (CSF) pathway. However, in subjects with AD, Aβ peptides appear to aggregate into higher order species to form soluble oligomers and insoluble plaques in a concentration-dependent manner. This aggregation can 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.

[0041] 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 causes 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, leading to the death of brain cells 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.

[0042] Chronic traumatic encephalopathy (CTE) is characterized by symptoms that may include memory loss, confusion, impaired judgment, impulse control problems, aggression, depression, anxiety, suicide, 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 lead to axonal transport defects, neuroinflammation, and synaptic loss.

[0043] Corticobasal degeneration (CBD) is characterized by cell loss and deterioration of certain regions of the brain. In corticobasal degeneration, abnormal levels of tau accumulate in certain brain cells, eventually causing their deterioration. Symptoms often include initially experiencing motor abnormalities in one limb, which gradually spreads to all limbs. Such motor 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, including aphasia, aphasia, dysarthria, and dysphagia. Symptoms may also 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.

[0044] Genetic Disorders: Hereditary Ataxias As described above, the present system and method can be used to alleviate symptoms associated with hereditary ataxia.Hereditary ataxia is characterized by slowly progressing gait coordination, and is 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.

[0045] 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 with 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 hyperfibrosis 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.

[0046] Brain Injury: Stroke and Related Cerebrovascular Diseases In some embodiments, the present disclosure provides a system and method for reducing 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, brain tissue in the penumbra during ischemic stroke is structurally intact but functionally silent. Failure to reperfuse this penumbra region or to resupply glucose and oxygen in a timely manner can result in atrophy of brain cells located in the penumbra. In contrast, activation of synapses in this region can delay cell death and salvage brain tissue. By improving synaptic plasticity and stimulating neural networking, the present system and method can reduce brain atrophy and associated symptoms associated with ischemic stroke. 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.

[0047] 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 brain atrophy. In multiple sclerosis (MS), brain or brain 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.

[0048] Transmissible spongiform encephalopathies (prion diseases) In some embodiments, the present disclosure provides systems and methods for reducing symptoms of prion diseases associated with brain atrophy. Prion diseases, also known as transmissible spongiform encephalopathies, include a group of fatal neurodegenerative diseases including, for example, Creutzfeldt-Jakob disease (CJD), variant Creutzfeldt-Jakob disease (vCJD), Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, Kuru, and others. In some cases, prion diseases may have similar symptoms to other and / or AD. In some cases, different types of prion diseases may cause brain damage that exhibits similar characteristics such as widespread spongiform degeneration, widespread neuronal loss, synaptic changes, atypical brain inflammation, and accumulation of protein aggregates. In some cases, prion diseases such as CJD, Kuru, and Gerstmann-Straussler-Scheinker disease may form amyloid plaques similar to those observed in AD.

[0049] Delivery Methods and Systems The present disclosure provides a method for reducing the progression of brain atrophy by inducing gamma oscillations in a subject, the method comprising delivering a gamma oscillation inducing waveform and / or inducing gamma oscillations in a subject. In some cases, the gamma oscillation inducing waveform is provided as a visual signal. In some embodiments, the gamma oscillation inducing waveform induces a signal indicative of an expected outcome associated with a condition or disease associated with brain atrophy.

[0050] Provided herein is a system and method for reducing the brain atrophy rate in one or more regions of a subject's brain, the method includes administering a non-invasive stimulation to a subject to induce synchronous gamma oscillation in at least one region of the subject's brain, thereby reducing the brain atrophy rate in one or more regions of the subject's brain.In some embodiments, the non-invasive stimulation includes one or more stimulation waveforms.The one or more stimulation waveforms may include a visual stimulation waveform, an auditory stimulation waveform, a tactile stimulation waveform, a mechanical stimulation waveform, or a combination thereof.

[0051] In some embodiments, the one or more stimulation waveforms have a synchronous phase. In some embodiments, the one or more stimulation waveforms comprise a first stimulation waveform and a second stimulation waveform. In some embodiments, the first stimulation waveform includes a visual stimulation waveform. In some embodiments, the first stimulation waveform includes an auditory stimulation waveform. In some embodiments, the first stimulation waveform includes a mechanical stimulation waveform. In some embodiments, the first stimulation waveform includes a vibrotactile or tactile stimulation waveform.

[0052] In some embodiments, the second stimulus waveform comprises an auditory stimulus waveform. In some embodiments, the second stimulus waveform comprises a mechanical stimulus waveform. In some embodiments, the second stimulus waveform comprises a vibrotactile or tactile stimulus waveform. In some embodiments, the first stimulus waveform comprises a square wave function. In some embodiments, the first stimulus waveform comprises a sine wave function. In some embodiments, the second stimulus waveform comprises a square wave function. In some embodiments, the second stimulus waveform comprises a sine wave function.

[0053] In some embodiments, administering the non-invasive stimulation includes administering the non-invasive stimulation for a first duration. Optionally, the method further includes measuring the subject's response to the non-invasive stimulation for a second duration. Optionally, the first duration and the second duration are separated by a third duration.

[0054] The systems and methods provided herein may provide gamma vibration-inducing waveforms through a variety of stimulation sources. For example, in some embodiments, the gamma vibration-inducing waveforms are delivered through one or more of visual stimulation, auditory stimulation, tactile or haptic stimulation, olfactory stimulation, or bone conduction.

[0055] In some embodiments, the gamma vibration inducing waveform is delivered at least in part through one or more devices in the user's environment. For example, in some cases, the gamma vibration inducing waveform is delivered at least in part through one or more of a speaker, a light fixture, a bed attachment, a wall screen, or other home device. In some embodiments, the one or more devices are controlled by a further device, such as a phone, tablet, or home automation hub, that is configured to manage the delivery of the gamma vibration inducing waveform through one or more devices in the user's environment. In some embodiments, the gamma vibration inducing waveform is delivered through multiple devices in the user's environment.

[0056] In some embodiments, the gamma oscillation inducing waveform is delivered to a plurality of subjects present in the space. In an exemplary embodiment, the gamma oscillation inducing waveform is delivered to a plurality of subjects present in the space through one or more devices present in the space. In some cases, the one or more devices deliver the same stimulus to all subjects present in the space. In some cases, the one or more devices deliver the same stimulus to a subset of subjects present in the space. In some cases, the one or more devices deliver a customized stimulus to each individual subject.

[0057] In some embodiments, the gamma oscillation inducing waveform is delivered via clothing or a body attachment worn by the subject. In some cases, the gamma oscillation inducing waveform is delivered, at least in part, through glasses, goggles, a mask, or other wearable device that provides the stimulation.

[0058] In some embodiments, the gamma vibration inducing waveform is delivered through vibrotactile or tactile (touch) stimulation. For example, the gamma vibration inducing waveform can be delivered via a device that vibrates at a frequency sufficient to entrain gamma oscillations. Vibrotactile stimulation can be delivered via clothing or body attachments.

[0059] In some embodiments, the gamma vibration inducing waveform provides a visual signal. In some embodiments, the visual signal is delivered through a light source, such as a light bulb or an LED screen. In some embodiments, the gamma vibration inducing waveform includes a visual stimulus provided as a visual signal delivered through glasses worn by the subject. In some embodiments, the gamma vibration inducing waveform is delivered through opaque or partially transparent glasses. Such glasses may include internal lighting elements or other light sources that provide the visual signal. In some embodiments, the wearable device further comprises headphones. In some embodiments, the waveform is provided as an audio signal. In some embodiments, the gamma vibration inducing waveform is delivered through an audio source, such as a set of headphones, speakers, or a set of earphones. In some embodiments, the gamma vibration inducing waveform is delivered at least in part through the headphones or earphones. For example, in some embodiments, the visual and auditory signals are provided by such headphones and glasses worn together at the same time. In some embodiments, the combined visual and auditory signals are delivered through one device.

[0060] In some embodiments, the methods and systems described herein further include measuring a response of the subject to the non-invasive stimulation. In some cases, the response measurement is performed for a first duration. In some cases, the response measurement is performed for a second duration. In some cases, the response measurement is performed for the first duration. In some cases, the response measurement is performed for a third duration. In some cases, the response measurement is performed for the first duration and the second duration. In some cases, the response measurement is performed for the third duration.

[0061] The one or more regions of the brain may comprise the visual cortex, the somatosensory cortex, the insular cortex, or any combination thereof. In some embodiments, reducing the rate of brain atrophy comprises reducing the rate of brain volume loss. In some cases, the rate of brain volume loss is about 0.3 cm 3 / month ~ approx. 2cm 3 / month. In some cases, the rate of brain volume loss is approximately 0.3 cm 3 / year ~ approx. 2cm 3 / Including year.

[0062] In some cases, the rate of brain volume reduction includes a rate of reduction in hippocampal volume, lateral lobe volume, lateral ventricular volume, temporal lobe volume, occipital lobe volume, temporal cortical thickness, occipital cortical thickness, or a combination thereof.

[0063] The present disclosure further provides a system and method for treating a disease, disorder, or condition associated with brain atrophy in a subject, the method comprising administering a non-invasive stimulus to the subject to generate synchronous gamma oscillations in at least one brain region, the administration reducing the rate of brain atrophy experienced by the subject, thereby treating the disease, disorder, or condition associated with brain atrophy in the subject. In some cases, the disease, disorder, or condition comprises a microglia-mediated disease. In some cases, the disease, disorder, or condition comprises a neurodegenerative disorder. In some cases, the neurodegenerative disorder comprises Alzheimer's disease, Creutzfeldt-Jakob disease (CJD), variant CJD, Gerstmann-Straussler Scheinker syndrome, fatal familial insomnia, Kuru, or any combination thereof. In some cases, the disease, disorder, or condition comprises aging.

[0064] In some embodiments described herein, the brain atrophy rate is reduced from a first rate to a second rate, the first rate comprising at least about 0.5% brain atrophy per year, and the second rate comprising less than the first rate. In some cases, the first rate comprises at least 0.6% brain atrophy per year. In some cases, the first rate comprises at least 0.7% brain atrophy per year. In some cases, the first rate comprises at least 0.8% brain atrophy per year. In some cases, the first rate comprises at least 0.9% brain atrophy per year. In some cases, the first rate comprises at least 1.0% brain atrophy per year. In some cases, the first rate comprises at least 1.1% brain atrophy per year. In some cases, the first rate comprises at least 1.2% brain atrophy per year. In some cases, the first rate comprises at least 1.3% brain atrophy per year. In some cases, the first rate comprises at least 2.0% brain atrophy per year. In some cases, the first rate comprises brain atrophy of at least 3.0% per year. In some cases, the first rate comprises brain atrophy of at least 4.0% per year.

[0065] Further provided herein are methods and systems for reducing cognitive decline associated with brain atrophy, the methods comprising administering to a subject in need thereof non-invasive stimulation to induce synchronous gamma oscillations in at least one region of the brain, wherein administration causes a reduction in the rate at which the brain experiences atrophy, thereby reducing the cognitive decline associated with brain atrophy.

[0066] Also disclosed herein are systems and methods for reducing one or more symptoms or diseases associated with brain atrophy, the methods including (a) identifying a subject experiencing brain atrophy, and (b) administering non-invasive sensory stimulation to the subject, the non-invasive sensory stimulation causing one or more brain wave synchronizations, thereby reducing one or more symptoms associated with brain atrophy. In some cases, the one or more symptoms or diseases include loss of neurons, memory loss, vision impairment, aphasia, balance impairment, paralysis, reduced cortical volume, increased CSF volume, loss of motor control, difficulty speaking, difficulty reading, reduced gray matter volume, reduced white matter volume, reduced neuronal size, reduced neuronal cytoplasmic protein, or any combination thereof. In some embodiments, identifying the subject includes assessing the disease of the subject, performing an assessment of the subject, or measuring the neuronal activity of the subject.

[0067] In some embodiments, the systems and methods disclosed herein further include evaluating the subject's response to the non-invasive sensory stimulation. In some embodiments, the systems and methods further include modulating the non-invasive sensory stimulation to enhance synchronization.

[0068] In some embodiments, the non-invasive stimulation comprises a frequency of about 20 Hz to about 70 Hz. In some embodiments, the non-invasive stimulation comprises a frequency of about 30 Hz to about 60 Hz. In some embodiments, the non-invasive stimulation comprises a frequency of about 35 Hz to about 45 Hz.

[0069] In some embodiments, the adjusting includes alternating the non-invasive sensory stimulation from a square wave function to a sine wave function. In some cases, the adjusting includes alternating the non-invasive sensory stimulation from a square wave function to a sine wave function. In some cases, the adjusting includes adjusting an intensity of the non-invasive stimulation. In some cases, the adjusting includes adjusting a frequency of the non-invasive stimulation. In some cases, the adjusting includes a waveform of the non-invasive stimulation. In some cases, the adjusting includes changing a source of the non-invasive sensory stimulation.

[0070] Also provided herein is a non-transitory computer-readable storage medium encoded with instructions executable by one or more processors, the instructions implementing any one of the systems and methods described above. Further provided is a computer-implemented system including at least one digital processing device comprising at least one processor and instructions executable by the at least one processor, the instructions implementing any one of the methods described herein.

[0071] The present disclosure further provides a system for reducing a rate of brain atrophy in a subject, the system comprising: a) a stimulation emitting component capable of providing neural, auditory, or visual stimulation to the subject; b) a processor; c) a memory device; and d) a feedback sensor, wherein the processor (i) receives through the feedback sensor an indication of the subject's physiological assessment, cognitive assessment, neurological assessment, physical assessment, or any combination thereof; and (ii) instructs the stimulation emitting component based on the instructions to adjust at least one parameter associated with the neural, auditory, or visual stimulation to result in an improvement in a degree of neural entrainment exhibited by neurons in at least one brain region of the subject, thereby causing a reduction in the rate of brain atrophy.

[0072] Program parameters and parameter values The systems and methods herein may include administration of the stimulation for a particular duration or at a particular frequency. For example, in some cases, the gamma oscillation inducing waveform is delivered for about 5 minutes, about 10 minutes, about 20 minutes, about 30 minutes, about 40 minutes, about 50 minutes, or about 1 hour. In some embodiments, the gamma oscillation inducing waveform is delivered for less than 30 minutes. In some embodiments, the gamma oscillation inducing waveform is delivered for up to 30 minutes. In some embodiments, the gamma oscillation inducing waveform is delivered for 30 minutes or more. In some embodiments, the gamma oscillation inducing waveform is delivered for up to 1 hour. In some embodiments, the gamma oscillation inducing waveform is delivered for 10-20 minutes, 20-40 minutes, or 30-60 minutes. The stimulation may be delivered for a period of up to 1 week. The stimulation may be delivered for 1-3 months. The stimulation may be delivered for 3-6 months. Additionally, the stimulation may be delivered for a period of more than 6 months. The stimulation may be delivered for more than 1 week, more than 1 month, or more than 1 year.

[0073] In some embodiments, the stimulation is delivered over an open-ended period such that the subject receiving the gamma oscillation inducing waveform determines the period by choosing to receive the stimulation. In some embodiments, the stimulation is delivered for periods of varying duration. For example, the stimulation may be delivered over a first duration and a second duration. The first duration may be 0-5 minutes, 5-10 minutes, 10-20 minutes, 20-30 minutes, 30-40 minutes, 40-50 minutes, or 50-60 minutes. The first duration may be greater than 60 minutes. The second duration may be 0-5 minutes, 5-10 minutes, 10-20 minutes, 20-30 minutes, 30-40 minutes, 40-50 minutes, or 50-60 minutes. The second duration may be greater than 60 minutes. The second duration may be the same as the first duration. The second duration may be different from the first duration.

[0074] In some cases, the stimulation is provided on an hourly basis. In some cases, the stimulation is provided daily. In some embodiments, the stimulation is delivered for multiple periods per day. In some cases, the stimulation is provided at least once per week. In some cases, the frequency of the stimulation is changed over a given period. In some cases, the duration of the stimulation varies over a given period. In other cases, both the frequency of the stimulation and the duration of the stimulation are changed over a given period.

[0075] The stimulation may be provided, for example, at least daily, at least weekly, at least every other week, or at least monthly. In some cases, the stimulation is delivered for at least 1 hour each day. In other cases, the stimulation is delivered for at least 2 hours each day. In some embodiments, the stimulation is delivered for less than 1 hour each day. In some embodiments, the stimulation is delivered for at least 3 hours each day. In some embodiments, the stimulation is delivered for more than 3 hours each day.

[0076] In some embodiments, delivery of the gamma vibration inducing waveform is performed such that a first signal (e.g., a visual, audio, or tactile signal) and a second signal (e.g., a visual, audio, or tactile signal) are offset with respect to each other by a delay. In some embodiments, such signals are delivered such that the first signal and the second signal are synchronized. For example, in some embodiments, the first signal has a frequency having a first value and the second signal has a frequency having a second value. The first value and the second value may be different. The first value and the second value may be substantially the same. In some embodiments, the first signal and the second signal are provided via multiple stimulation sources.

[0077] In some embodiments, the gamma oscillation inducing waveform parameters are configured with various timing and intensity parameters. In some embodiments, these parameters are preconfigured, 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 a user context, a measured sleep quality related parameter associated with the user, and an observed or detected use of the stimulation device. In some embodiments, the gamma oscillation inducing waveform is adjusted in response to a progression of symptoms of a detected or analyzed neurodegenerative disease. Various frequencies and various intensities may be used as parameters for the gamma oscillation inducing waveform.

[0078] In some embodiments, one or more stimulation parameters are based at least in part on various clinical measures of cognitive outcome as disclosed herein. In some embodiments, different combinations of stimulation parameters are used during different time periods, and subsequent stimulation parameters are selected at least in part based on a comparison of the clinical measures of cognitive outcome during at least some of those time periods.

[0079] In some embodiments, the present disclosure delivers non-invasive auditory, visual, or combined audio-visual stimulation at 40 Hz. In some embodiments, the stimulation is delivered at one or more stimulation frequencies within the range of about 35-45 Hz. In some embodiments, "gamma" refers to frequencies in the range of 35-45 Hz.

[0080] In some embodiments, the specific visual parameters include one or more of a 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 about 20 Hz, about 30 Hz, about 40 Hz, about 50 Hz, about 60 Hz, or about 70 Hz. In some embodiments, the stimulation waveform has a duty cycle of less than 50%. In some embodiments, the stimulation waveform has a duty cycle of more than 50%. In some embodiments, the stimulation waveform has a duty cycle of 50%.

[0081] In some embodiments, the non-invasive stimulation is delivered as a combined visual and auditory stimulation delivered at a frequency that provides a gamma oscillation-inducing waveform. In some embodiments, the visual and auditory stimulation are 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 set time. In some embodiments, the visual and auditory signals are delivered at an intensity that is clearly perceived by the subject and adjusted to their tolerance level.

[0082] In some embodiments, the specific audio parameters include one or more of the stimulation frequency, intensity (volume), and duty cycle. In some embodiments, the audio frequency is adjusted in response to the hearing characteristics of the subject, for example, to a frequency at which the subject is better at hearing.

[0083] In some embodiments, the non-invasive stimulation parameters are directed to inducing gamma oscillations in the brain of the human subject. In some embodiments, the non-invasive stimulation parameters are directed to inducing alpha 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, thereby reducing brain atrophy in the subject.

[0084] Visually mediated neural stimulation The disclosed system and method is directed to using visual signals to control the frequency of neural oscillations, and in so doing, slow brain atrophy in a subject. Visual stimulation can regulate, control, or otherwise affect the frequency of neural oscillations to provide beneficial effects to one or more cognitive states or functions of the brain or immune system, while mitigating or preventing adverse consequences to cognitive states or functions. Visual stimulation can provide electroencephalographic entrainment that can provide beneficial effects to one or more cognitive states, functions of the brain, immune system, or inflammation of the brain. In some cases, visual stimulation can provide localized effects, such as within the visual cortex and associated regions. Electroencephalographic entrainment can treat disorders, ailments, diseases, inefficiencies, damage, or other problems associated with cognitive functions, cognitive states, immune system, or inflammation of the brain.

[0085] 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 appear as oscillations in membrane potentials or as rhythmic patterns of action potentials that can result in oscillatory activation of postsynaptic neurons. Synchronized activity of neuronal groups 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.

[0086] For example, EEG can measure oscillatory activity between groups of neurons, and the measured oscillatory activity can be categorized into frequency bands: delta activity corresponds to a frequency range of 1-4 Hz; theta activity corresponds to a frequency range of 4-8 Hz; alpha activity corresponds to a frequency range of 8-12 Hz; beta activity corresponds to a frequency range of 13-30 Hz; and gamma activity corresponds to a frequency range of 30-70 Hz, etc.

[0087] The frequency and existence or activity of neural oscillations can be related to cognitive states or cognitive functions, such as information transmission, perception, motor control and memory. Based on cognitive states or cognitive functions, the frequency of neural oscillations can change. Furthermore, certain frequencies of neural oscillations can have beneficial or detrimental effects on one or more cognitive states or functions. However, it can be difficult to synchronize neural oscillations using external stimuli to provide such beneficial effects or reduce or prevent such detrimental effects.

[0088] Brainwave entrainment (e.g., neural entrainment or brain entrainment) occurs when an external stimulus of a particular frequency is perceived by the brain and induces neural activity in the brain that results in neurons oscillating at a frequency corresponding to the particular frequency of the external stimulus. Thus, brain entrainment can refer to synchronizing neural oscillations in the brain using an external stimulus so that the neural oscillations occur at a frequency corresponding to the particular frequency of the external stimulus.

[0089] The disclosed systems and methods 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 adjust, manage, or control the frequency of neural oscillations in response to observing or perceiving the light pulse. Light pulses generated at a predetermined frequency and perceived by the eyeball through direct or peripheral vision can induce neural activity in the brain and induce electroencephalographic 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 in the sensory cortex, while high-level cognitive functions can gate or interfere with some areas that are engaged. Thus, the disclosed systems and methods can provide electroencephalographic entrainment using external visual stimuli, such as light pulses emitted at a predetermined frequency, to synchronize electrical activity between groups 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 a collection of cortical neurons. The frequency of the light pulses can cause this synchronous electrical activity in a population of cortical neurons to oscillate or coordinate at a frequency corresponding to the frequency of the light pulses.

[0090] FIG. 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 summary, the NSS (105) can include, access, interface with, or otherwise communicate with one or more of a light generation module (110), a light adjustment 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). The light generation module (110), the light adjustment 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 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 (150). The light generation module (110), the light adjustment 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 separate components, 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 shown in the system (700) of Figures 7A and 7B.For example, the components of the system (100) may include or execute on one or more processors (721), access storage (728), or memory (722), and communicate via a network interface (718).

[0091] Continuing to refer to FIG. 1, in further detail, the NSS (105) can include at least one light-generating module (110). The light-generating module (110) can be designed and constructed to interface with the visual signaling component (150) to provide instructions or otherwise cause or facilitate the generation of a visual signal, such as a light pulse or a flash of light, having one or more predetermined parameters. The light-generating module (110) can include hardware or software for receiving and processing instructions or data packets from one or more modules or components of the NSS (105). The light-generating module (110) can generate instructions to cause the visual signaling component (150) to generate a visual signal. The light-generating module (110) can control or enable the visual signaling component (150) to generate a visual signal having one or more predetermined parameters.

[0092] The light-generating module (110) can be communicatively coupled to the visual signaling component (150). The light-generating module (110) can communicate with the visual signaling component (150) via a circuit, a wire, a data port, a network port, a power line, a ground, an electrical contact, or a 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) to communicate with the visual signaling component (150) wirelessly or via wires.

[0093] The light-generating module (110) can interface, control, or otherwise manage various types of visual signaling components (150) to cause the visual signaling components (150) to generate, block, control, or otherwise provide a visual signal having one or more predetermined parameters. The light-generating module (110) can include a driver configured to drive a light source of the visual signaling components (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 electricity or power having specific voltage and current characteristics.

[0094] In some embodiments, the light-generating module (110) can instruct the visual signaling component (150) to provide a visual signal including a light wave (200), as shown in FIG. 2A. The light wave (200) can include or be formed of an electromagnetic wave. The electromagnetic waves of the light wave can have respective amplitudes and travel orthogonally to each other, as shown by the amplitude vs. time of the electric field (205) and the amplitude vs. time of the magnetic field (210). The light wave (200) can have a wavelength (215). The light wave can also have a frequency. The product of the wavelength (215) and the frequency can be the speed of the light wave. For example, the speed of the light wave can be about 299,792,458 meters per second in a vacuum.

[0095] The light-generating module (110) can instruct the visual signaling 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 that correspond to one or more colors. For example, the light generating module (110) can instruct the visual signaling 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 be in the range of 10 nm to 100 micrometers. In some embodiments, the wavelengths can be in the range of 380-750 nm.

[0096] The light generating module (110) can determine to provide a visual signal including a light pulse. The light generating module (110) can command or otherwise cause the visual signal transmission component (150) to generate a light pulse. A light pulse can refer to a burst of light waves. For example, FIG. 2B shows a burst of light waves. A burst of light waves can refer to a burst of an electric field (250) generated by a light wave. A burst of an electric field (250) of a light wave can be referred to as a pulse or flash of light. For example, a light source that is intermittently turned on and off can generate a burst, flash, or pulse of light.

[0097] FIG. 2C illustrates pulses of light (235a-c) according to one embodiment. The light pulses (235a-c) can be illustrated by a graph of 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 represented by F a Frequency and F a For example, the NSS (105) can modulate light waves between a frequency within the visible spectrum, such as Fa, and a frequency outside the visible spectrum. The NSS (105) can modulate light waves between two or more frequencies, between on and off states, or between high and low power states.

[0098] 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:

[0099] The width of each of the light pulses (e.g., the duration of a burst of light waves) can correspond to a pulse width (230a). The pulse width (230a) can refer to the length or duration of the burst. The pulse width (230a) can be measured in units of time or distance. In some embodiments, the pulses (235a-c) can include light waves having different frequencies from one another. In some embodiments, the pulses (235a-c) can have different pulse widths (230a) from one another, as shown in FIG. 2D. For example, the first pulse (235d) of FIG. 2D can have a pulse width (230a) and the second pulse (235e) has a second pulse width (230b) that is greater than the first pulse width (230a). The third pulse (235f) can have a third pulse width (230c) that is less than the second pulse width (230b). The third pulse width (230c) can also be less than the first pulse width (230a). Although the pulse widths (230a-c) of the pulses (235d-f) of the pulse train can vary, the light-generating module (110) can maintain a constant pulse rate interval (240) for the pulse train.

[0100] The pulses (235a-c) can form a pulse train having a pulse rate interval (240). The pulse rate interval (240) can be quantified using units of time. The pulse rate interval (240) can be based on a frequency of the pulses 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 a pulse train (201) having a predetermined frequency corresponding to gamma activity, 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., 1 divided by the predetermined frequency of the pulse train). For example, the light-generating module (110) can take 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) can vary throughout the pulse train or from one pulse train to a subsequent pulse train, hi some embodiments, the number of pulses delivered during the second period can be fixed and the pulse rate interval (240) varies.

[0101] In some embodiments, the light generating module (110) can generate light pulses having light waves with varying frequencies. For example, the light generating module (110) can generate up-chirped pulses, where the frequency of the light waves of the light pulses increases from the start of the pulse to the end of the pulse, as shown in FIG. 2E. For example, the frequency of the light waves at the start 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 to a maximum value of Fc at the end of the pulse (235g). Thus, the frequency of the light wave used to generate the pulse (235g) is F a ~F cThe frequency may range from 0 to 100 Hz. The frequency may increase linearly, exponentially, or based on some other rate or curve.

[0102] The light generating module (110) can generate down-chirped pulses, as shown in FIG. 2F, where 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 start of the pulse (235j) is F d The frequency of the light wave of the pulse (235j) can decrease from Fd to Fe in the middle of the pulse (235j) and then to a minimum of Ff at the end of the pulse (235j). Thus, the frequency of the light wave used to generate the pulse (235j) can be F d ~F f The frequency may range from 0 to 100 Hz. The frequency may decrease linearly, exponentially, or based on some other rate or curve.

[0103] The visual signaling 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 of the pulses, the duration, 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 perceived, observed, or otherwise identified by the brain visually, such as via the eye. The light pulses can be transmitted to the eye via the direct visual field or the peripheral visual field.

[0104] FIG. 3A shows a horizontal direct field of view (310) and a horizontal peripheral field of view. FIG. 3B shows a vertical direct field of view (320) and a vertical peripheral field of view (325). FIG. 3C illustrates the extent of the direct field of view and the peripheral field of view, including the relative distances at which visual signals can be perceived in different fields of view. The visual signal transmission component (150) can include a light source (305). The light source (305) can be positioned to transmit a light pulse to the direct field of view (310 or 320) of the person's eye. The NSS (105) can be configured to transmit a light pulse to the direct field of view (310) or (320) because this can promote brain entrainment as the person may pay more attention to the light pulse. The attention level can be measured directly in the brain, indirectly through the person's eye behavior, or quantitatively by active feedback (e.g., mouse tracking).

[0105] The light source (305) can be positioned to deliver light pulses to the peripheral vision (315 or 325) of the person's eye. For example, the NSS (105) can deliver light pulses to the peripheral vision (315 or 325) because these light pulses may not be distracting to a person who may be performing other tasks, such as reading, walking, driving, etc. Thus, the NSS (105) can provide subtle ongoing visual brain stimulation by delivering light pulses through the peripheral vision.

[0106] In some embodiments, the light source (305) can be head-mounted, while in other embodiments, the light source (305) can be held by the subject's hand, mounted on a stand, suspended from the ceiling, or connected to a chair, or positioned to direct light toward the subject's direct or peripheral vision. For example, a chair or external support system can include or be positioned to provide visual input while maintaining a fixed / given relationship between the subject's field of vision and the visual stimulus. The system can provide an immersive experience. For example, the system can include an opaque or partially opaque dome that includes the light source. The dome can be placed over the subject's head while the subject sits or sits in the chair. The dome can cover a portion of the subject's field of vision, thereby reducing external distraction and promoting entrainment of brain regions.

[0107] 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 an 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 includes a semiconductor light emitting device such as a light emitting diode of any spectrum 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 light sources that utilize organic materials. In some embodiments, the light source (305) comprises a monochromatic light source. In some embodiments, the light source (305) comprises a polychromatic light source. In some embodiments, the light source (305) comprises a light source that emits light partially within the ultraviolet spectral range. In some embodiments, the light source (305) comprises a device, product, or material that emits light partially within the visible spectral range. In some embodiments, the light source (305) is a device, product, or material that emits or radiates light partially within the infrared spectral range. In some embodiments, the light source (305) comprises a device, product, or material that emits or radiates light partially within the visible spectral range. In some embodiments, the light source (305) comprises a light guide, optical fiber, or wave guide through which light is emitted from the light source.

[0108] 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 a direct field of view (310 or 320) or a peripheral field of view (315 or 325). The light source (305) can include interacting 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 by one or more optical lenses toward a direct field of view or a peripheral field of view. The ambient light or sunlight can be directed by one or more mirrors toward a directed field of view or a peripheral field of view.

[0109] If the light source is an ambient light, the ambient light is not positioned, but the ambient light can enter the eye via the direct or peripheral vision. In some embodiments, the light source (305) can be positioned to direct light pulses into the direct or peripheral vision. For example, the one or more light sources (305) can be attached, affixed, coupled, mechanically coupled, or otherwise provided to a frame (400), as illustrated in FIG. 4A. In some embodiments, the visual signaling component (150) can include a frame (400). Further 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 labeled "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, that can generate, emit, or reflect an oscillating pattern of light, such as a fan or air bubble rotating in front of the light. In some embodiments, the light source may include an invisible optical illusion, a physiological phenomenon that occurs within the eye (eg, pressing on the eyeball), or a chemical that is applied to the eye.

[0110] Systems and devices configured for neurostimulation via visual stimulation - Patents.com Now referring to FIG. 4A, the frame (400) can be designed and constructed to be placed or positioned on a person's head. The frame (400) can be configured to be worn by a person. The frame (400) can be designed and constructed to remain in a fixed position. The frame (400) can be configured to be worn and remain in a fixed position when a person sits, stands, walks, runs, or lies flat. The light source (305) can be configured on the frame (400) to project light pulses toward the person's eye during these various positions. In some embodiments, the light source (305) can be configured to project light pulses toward the person's eye when the eyelids are closed such that the light pulses penetrate the eyelids to be perceived by the retina. The frame (400) can include a bridge (420). The frame (400) can include one or more eye wires (415) coupled to the bridge (420). The bridge (420) can be positioned between the eye wires (415). The frame (400) can include one or more temples extending from one or more eye wires (415). In some embodiments, the eye wire (415) can include or hold a lens (425). In some embodiments, the eye wire (415) can include or hold a solid material (425) or a cover (425). The lens, solid material, or cover (425) can be transparent, translucent, opaque, or completely block outside light.

[0111] One or more light sources (305) can be positioned on or adjacent to the eye wire (415), the lens or other solid material (425), or the bridge (420). For example, the light source (305) can be located in the center of the eye wire (415) on the solid material (425) to deliver a light pulse into the direct field of view. In some embodiments, the light source (305) can be positioned at a corner of the eye wire (415), such as a corner of the eye wire (415) that is coupled to the temple (410), to transmit a light pulse toward the peripheral field of view.

[0112] The NSS (105) can perform visual brain entrainment via one or both eyes. For example, the NSS (105) can direct light pulses to one or both eyes. The NSS (105) can interface with a visual signaling component (150) that includes a frame (400) and two eye wires (415). However, the visual signaling component (150) may include a single light source (305) that is configured and positioned to direct light pulses to a first eye. The visual signaling component (150) can further include a light blocking component that blocks or blocks light pulses generated from the light source (305) from entering the second eye. The visual signaling component (150) can block or prevent light from entering the second eye during the brain entrainment process.

[0113] In some embodiments, the visual signaling component (150) can alternatively transmit or direct light pulses to a first eye and a second eye. For example, the visual signaling component (150) can direct light pulses to a first eye for a first time interval. The visual signaling 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 subsequent time intervals.

[0114] 4B shows a frame (400) with 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). In an open state, the set of shutters (435) can allow light to enter through the eye wire (415) and in a closed state, can at least partially block the light entering through the eye wire (415). Further 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 labeled "NSS Operating With A Frame."

[0115] The set of shutters (435) can include one or more shutters (430) that are opened and closed by one or more actuators. The shutters (430) can be formed from one or more materials. The shutters (430) can include one or more materials. The shutters (430) can include or be formed from a material that can at least partially block or attenuate light.

[0116] The frame (400) can include one or more actuators configured to at least partially open and close the set of shutters (435) or individual shutters (430). The frame (400) can include one or more types of actuators for opening and closing the shutters (435). For example, the actuators can include mechanically driven actuators. The actuators can include magnetically driven actuators. The actuators can include pneumatic actuators. The actuators can include hydraulic actuators. The actuators can include piezoelectric actuators. The actuators can include microelectromechanical systems ("MEMS").

[0117] The set of shutters (435) can include one or more shutters (430) that are opened and closed via electrical or chemical techniques. For example, the shutters (430) or the set of shutters (435) can be formed from one or more chemicals. The shutters (430) or the set of shutters can include one or more chemicals. The shutters (430) or the set of shutters (435) can include or be formed from chemicals that can at least partially block or attenuate light.

[0118] For example, the shutter (430) or set of shutters (435) can include a photochromic lens configured to filter, attenuate, or block light. The photochromic lens can automatically darken upon exposure to sunlight. The photochromic lens can include molecules configured to darken the lens. The molecules can be activated by light waves, such as ultraviolet light or other wavelengths of light. Thus, the photochromic molecules can be configured to darken the lens in response to a predetermined wavelength of light.

[0119] The shutter (430) or set of shutters (435) can include electrochromic glass or plastic. Electrochromic glass or plastic can change from a light state to a dark state (e.g., transparent to opaque) in response to a voltage or current. Electrochromic glass or plastic can include a metal oxide coating that is deposited on the glass or plastic, multiple layers, and lithium ions that migrate between two electrodes between the layers to make the glass lighter or darker.

[0120] The shutter (430) or set of shutters (435) may include micro-shutters. The micro-shutters may include small windows of 100 x 200 microns. The micro-shutters may be arranged within the eye frame (415) in a waffle-like grid. Individual micro-shutters may be opened and closed by actuators. The actuators may include magnetic arms that sweep across the micro-shutters to open and close them. An open micro-shutter may allow light to enter through the eye frame (415), while a closed micro-shutter may block, attenuate, or filter light.

[0121] The NSS (105) can drive an actuator to open and close one or more shutters (430) or a set 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 the flash light to the eye wire (415) at the predetermined frequency. Thus, a frame (400) including 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.

[0122] In some embodiments, the visual signaling component (150) or the light source (305) can refer to or be included in a virtual reality headset (401), as shown in FIG. 4C. For example, the virtual reality headset (401) can be designed and constructed to receive the light source (305). The light source (305) can include a computing device having a display device, such as a smartphone or a mobile communication device. The virtual reality headset (401) can include a cover (440) that opens to receive the light source (305). The cover (440) can be closed to lock or hold the light source (305) in place. In the closed state, the cover (440) and the case (450 and 445) can form an enclosure for the light source (305). This enclosure can provide an immersive experience that minimizes or eliminates unwanted visual distractions. The virtual reality headset can provide an environment that maximizes brainwave entrainment. The virtual reality headset can provide an augmented reality experience. In some embodiments, the light source (305) can form an image on another surface such that the image is reflected from the surface toward the eye (e.g., a head-up display that overlays a flickering object or an augmentation of reality on a screen). Further details of the operation of the NSS (105) in conjunction with the virtual reality headset (401) are provided below in the section labeled "Systems and Devices Configured for Neurostimulation Via Visual Stimulation."

[0123] The virtual reality headset (401) includes straps (455 and 460) configured to secure the virtual reality headset (401) to a person's head. The virtual reality headset (401) can be secured via the straps (455 and 460) to minimize movement of the headset (401) worn during physical activity, such as walking or running. The virtual reality headset (401) can include a skull cap formed from (460 or 455).

[0124] The feedback sensor (605) may include an electrode, a dry electrode, a gel electrode, a saline-soaked electrode, or an adhesive-based electrode.

[0125] 5A-5D show embodiments 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, light flash, or pattern of light via the display screen (305) or the light source (305).

[0126] FIG. 5A shows 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 flashes of light or light pulses having a predetermined pulse rate interval. For example, FIG. 5B illustrates the light source (305) being turned off or disabled such that the light source does not emit light or emits a minimal or reduced amount of light. The visual signaling component (150) can cause the tablet computing device (500) to enable (e.g., FIG. 5A) and disable (e.g., FIG. 5B) the light source (305) such that the light flashes have a predetermined frequency, for example, 40 Hz. The visual signaling component (150) can toggle or switch the light source (305) between two or more states to generate flashes of light or light pulses having a predetermined frequency.

[0127] In some embodiments, the light generating module (110) can command or cause the visual signaling component (150) to display a pattern of light via the display device (305) or light source (305), as shown in Figures 5C and 5D. The light generating module (110) can cause the visual signaling component (150) to flicker, 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 switched or adjusted from one state to another. For example, the color of the characters or text relative to the background color can be inverted to cause a switch between a first state (510) and a second state (515). The foreground and background colors can be inverted at a predetermined frequency to generate light pulses by exhibiting a visual change that can facilitate the adjustment or management of the frequency of neural oscillations. Further details regarding the operation of the NSS (105) in conjunction with the tablet (500) are provided below in the section labeled "NSS Operating with a Tablet."

[0128] In some embodiments, the light generation module (110) can command or cause the visual signaling component (150) to flash, 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 determine which cortex or cortex is recruited to process the stimuli. The visual signaling component (150) can stimulate individual portions of the cortex by modulating the presentation of the stimuli to target specific or general areas of interest. The relative position within the visual field, the color of the input, or the movement and speed of the light stimuli can determine which areas of the cortex are stimulated.

[0129] For example, the brain may include at least two portions that process a given type of visual stimulus, with the primary visual cortex being on the left side of the brain and the calcarine fissure being on the right side of the brain. Each of these two portions may have one or more multiple sub-portions that process a given type of visual stimulus. For example, the calcarine fissure may include a sub-portion called area V5, which may include neurons that respond strongly to motion but do not register stationary objects. A subject with damage to area V5 may have motion blindness but otherwise normal vision. In another example, the primary visual cortex may include a sub-portion called area V4, which may include neurons specialized for color perception. A subject with damage to area V4 may have color blindness and only perceive objects in shades of gray. In another example, the primary visual cortex may include a sub-portion called area VI, which includes neurons that respond strongly to contrast edges and help segment an image into separate objects.

[0130] Thus, the light generation module (110) can instruct or cause the visual signaling component (150) to generate a type of still image or video, or to generate a flicker, or to toggle between images configured to stimulate a particular or predetermined portion of the brain or a particular cortex. For example, the light generation module (110) can instruct or cause the visual signaling component (150) to generate an image of a human face to stimulate the fusiform face region, which can facilitate brain entrainment for subjects with hematopoietic disorders or face blindness. The light generation module (110) can instruct or cause the visual signaling component (150) to generate a blinking face image to target this region of the subject's brain. In another example, the light generation module (110) can instruct 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.

[0131] The NSS (105) can include, access, interface with, or otherwise communicate with at least one light adjustment module (115). The light adjustment module (115) can be designed and constructed to measure or verify environmental variables (e.g., light intensity, timing, incident light, ambient light, eyelid condition, 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) can automatically modify parameters of the visual signal based on profile information or feedback. The light adjustment module (115) can receive feedback information from a feedback monitor (135). The light adjustment module (115) can receive instructions or information from a side effect management module (130). The light adjustment module (115) can receive profile information from a profile manager (125).

[0132] 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, attenuate, reduce, or otherwise remove frequencies of visual signals that are undesirable to prevent or reduce the amount of such visual signals from being perceived by the brain. The unwanted frequency filtering module (120) may interface, direct, control, or otherwise communicate with the filtering component (155) to cause the filtering component (155) to block, attenuate, or reduce the effect of undesirable frequencies on neural oscillations.

[0133] The NSS (105) can include, access, interface with, or otherwise communicate with at least one profile manager (125). The profile manager (125) can be designed or constructed to store, update, retrieve, or manage information related to one or more subjects related to visual brain entrainment. The profile information can include, for example, historical treatment information, historical brain entrainment information, administration information, light wave parameters, feedback, physiological information, environmental information, or other data related to the brain entrainment system and method.

[0134] 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 loss of vision.

[0135] The side effect management module (130) can automatically instruct components of the NSS (105) to change or modify 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 the pulse train, a maximum intensity of the light waves, a maximum amplitude, a maximum duty cycle of the pulse train (e.g., pulse width multiplied by the frequency of the pulse train), a maximum number of treatments for brainwave entrainment in a period of time (e.g., 1 hour, 2 hours, 12 hours, or 24 hours).

[0136] The side effect management module (130) can cause a change in 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.

[0137] The side effect management module (130) may consist of or include a policy engine that applies policies or rules to the current visual signal and feedback to determine adjustments to the visual signal. For example, if the feedback indicates that a patient receiving the visual signal has a heart rate or pulse rate above a threshold, the side effect management module (130) may turn off the pulse train until the pulse rate stabilizes below the threshold or below a second threshold that is below the threshold.

[0138] The NSS (105) can include, access, interface with, or otherwise communicate with at least one feedback monitor (135). The feedback monitor can be designed and constructed to receive feedback information from a feedback component (160). The feedback component (160) can include feedback sensors (605), such as, for example, 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 electroencephalography sensor, an EEG probe, an electro-oculography ("EOG") probe configured to measure a corneal-retinal orthostatic 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.

[0139] In some embodiments, the computing device (500) may include a feedback component (160) or a feedback sensor (605), as shown in Figures 5C and 5D. For example, the feedback sensor on the tablet (500) may include a front-facing camera that can capture an image of a person looking at the light source (305).

[0140] 6A shows one or more feedback sensors (605) disposed on the frame (400). In some embodiments, the frame (400) can include one or more feedback sensors (605) disposed on a portion of the frame, such as a portion of the bridge (420) or eye wire (415). The feedback sensors (605) can be disposed on or coupled to the light source (305). The feedback sensors (605) can be separate from the light source (305).

[0141] 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, when 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 value 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) may ping, query, or send a request for information to the feedback sensor (605), and the feedback sensor (605) may provide feedback information in response to the ping, request, or query.

[0142] 6B shows a feedback sensor (605) placed or disposed at, on, or near a person's head. The feedback sensor (605) may include, for example, an EEG probe to detect brainwave activity.

[0143] The feedback monitor (135) may detect, receive, acquire, or otherwise identify feedback information from one or more feedback sensors (605). The feedback monitor (135) may provide the feedback information to one or more components of the NSS (105) for further processing or storage. For example, the profile manager (125) may update a profile data structure (145) stored in the data repository (140) with the feedback information. The profile manager (125) may 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.

[0144] 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., 1-10 where 1 is low attention and 10 is high attention, 1-100 where 1 is low attention and 100 is high attention, or vice versa, 0-1 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.

[0145] In some cases, the feedback monitor (135) can track the person's eye movements to identify attention levels. The feedback monitor (135) can interface with a feedback component (160) that includes an eye tracker. The feedback monitor (135) can detect and record the person's eye movements (e.g., via the feedback component (160)) and analyze the recorded eye movements to determine attention span or attention level. The feedback monitor (135) can measure gaze, which can indicate or provide information related to hidden attention. For example, the feedback monitor (135) can be configured (e.g., via the feedback component (160)) 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 so that it cannot move to determine the direction of the eyes 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 then the direction of the eyes relative to the head.

[0146] In some embodiments, the feedback monitor (135) and the feedback component (160) can use video detection of the pupil or corneal reflex to determine or track eye direction or eye movement. For example, the feedback component (160) can include one or more cameras or video cameras. The feedback component (160) can include an infrared source that transmits light pulses toward the eye. The light can be reflected by the eye. The feedback component (160) can detect the location of the reflection. The feedback component (160) can capture or record the location of the reflection. The feedback component (160) can perform image processing on the reflection to determine or calculate eye direction or eye gaze direction.

[0147] The feedback monitor (135) can compare the eye direction or movement to historical eye direction or movement, nominal eye movements, or other historical eye movement information for the same person to determine the level of attention. For example, if the eye is focused on the light pulses during the pulse train, the feedback monitor (135) can determine a high level of attention. 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 a medium level of attention. If the feedback monitor (135) determines that eye movement occurs for more than 50% of the pulse train or that the eye is not focused on the pulse train for more than 50% of the pulse train, the feedback monitor (135) can determine a low level of attention.

[0148] In some embodiments, the system (100) can 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 an electrochromic glass or plastic. The filtering component (155) can receive instructions from the unwanted frequency filtering module (120) to block or attenuate one or more frequencies of light.

[0149] The filtering component (155) may include an optical filter that can selectively transmit light of a certain range of wavelengths or colors while blocking one or more other ranges of wavelengths or colors. An optical filter may change the magnitude or phase of an incident light wave for a range of wavelengths. An optical filter may include an absorption filter, or an interference or dichroic filter. An absorption filter may 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 the intensity of a light wave propagating through a medium due to the absorption of a portion of the medium's photons may be referred to as attenuation.

[0150] An interface filter 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 interface filter or dichroic filter may have a near-zero absorption coefficient for one or more wavelengths. An interface filter may be high-pass, low-pass, band-pass, or band-reject. An interface filter may include one or more thin layers of dielectric or metallic materials with different refractive indices.

[0151] In an exemplary implementation, the NSS (105) can interface with a visual signaling component (150), a filtering component (155), and a feedback component (160). The visual signaling component (150) can include hardware or devices such as a glass frame (400) and one or more light sources (305). The filtering component (155) can include hardware or devices such as a feedback sensor (605). The filtering component (155) can include hardware, materials, or chemicals such as polarized lenses, shutters, electrochromic or photochromic materials.

[0152] Computing Environment 7A and 7B show block diagrams of a computing device (700). As shown in FIGS. 7A and 7B, each computing device (700) includes a central processing unit (721) and a main memory unit (722). As shown in FIG. 7A, the computing device (700) may include a storage device (728), an installation device (716), a network interface (718), an I / O controller (723), a display device (724a-724n), a keyboard (726), and a pointing device (727), such as a mouse. The storage device (728) may include, but is not limited to, an operating system, software, and software of a neurostimulation system ("NSS") (701). The NSS (701) may include or reference one or more of an NSS (105), an NSS (905), or an 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 input / output devices (730a-730n) (generally referred to using the reference numeral (730)), and a cache memory (740) in communication with the central processing unit (721).

[0153] The central processing unit (721) is any logic circuit that responds to and processes instructions fetched from the main memory unit (722). In many embodiments, the central processing unit (721) is provided by a microprocessor unit, examples of which include those manufactured by Intel (Mountain View, Calif.); those manufactured by Motorola Corporation (Schaumburg, Ill.); ARM processors (e.g., from ARM Holdings and those manufactured by ST, TI, ATMEL, etc.) and TEGRA system-on-chips (SoCs) manufactured by Nvidia (Santa Clara, Calif.); POWER7 processors, manufactured by IBM (White Plains, New York), or manufactured by AMD (Sunnyvale, Calif.); Field Programmable Gate Arrays ("FPGAs") from Altera (San Jose, Calif.), Intel (Xlinix, San Jose, Calif.), 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 cache, 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.

[0154] 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; for example, it may be a 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 mentioned above or any other available memory chip 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 illustrates an embodiment of a computing device (700) in which the processor communicates directly with the main memory (722) via a memory port (703). For example, in FIG. 7B, the main memory (722) may be a DRDRAM.

[0155] FIG. 7B illustrates an embodiment in which the main processor (721) communicates directly with the cache memory (740) via 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 the various EO devices (730) via 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 EO devices (730). In an embodiment in which the EO device is a video display (724), the processor (721) can communicate with the display (724) or an EO 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 communication technologies. Figure 7B also shows an embodiment in which local bus and direct communication are mixed: the processor (721) communicates with EO devices (730a) using a local interconnect bus while communicating directly with EO devices (730b).

[0156] A wide variety of EO devices (730a-730n) may be present in the computing device (700). Input devices may include keyboards, mice, track pads, track balls, touch pads, touch mice, multi-touch touch pads 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.

[0157] 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 facial recognition that may be utilized 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 on the Apple IPHONE, Google Now, or Google Voice Search.

[0158] 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 EO 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 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 media (116) for the computing device (700). In yet other embodiments, the computing device (700) may provide a USB connection (not shown) for receiving 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 communications 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.

[0159] In some embodiments, the display devices (724a-n) can be connected to the EO 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-n) or corresponding EO 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.

[0160] 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 EO devices (730a-730n) and / or the EO controller (723) can include any type and / or form of suitable hardware, software, or combination of hardware and software to support, enable, or provide for the connection and use of the 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 the multiple display devices (724a-724n). In other embodiments, the computing device (700) may include multiple video adapters, each connected to one or more of the display devices (724a-724n). In some embodiments, any portion of the operating system of the computing device (700) 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 the computing device (700) via the network (140). In some embodiments, the software may be designed and constructed to use the display device of another computer as a second display device (724a) for the computing device (700). For example, in one embodiment, an Apple iPad may connect to the computing device (700) and use the display of the device (700) as an additional display screen that may be used as an extended desktop.

[0161] Referring again to FIG. 7A, the computing device (700) may include storage (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 (728) include optical drives, including CD drives, DVD drives, or BLU-RAY drives; solid state drives (SSD); 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 EO device (730) that provides an external bus. Some storage devices (728) may be connected to the computing device (700) through a network interface (718), including, for example, a remote disk for an Apple MACBOOK AIR. Some client devices (700) may not require non-volatile storage devices (728) and may be thin 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 run 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.

[0162] 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.

[0163] 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, Infraband), broadband connections (e.g., ISDN, Frame Relay, ATM, Gigabit Ethernet, Ethernet over SONET, ADSL, VDSL, BPON, GPON, fiber optic 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, the 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 Florida. The network interface (118) may comprise 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 the computing device (700) to any type of network capable of communicating and performing the operations described herein.

[0164] 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, as well as WINDOWS 7, WINDOWS RT, and WINDOWS 8, all of which are manufactured by Microsoft Corporation (Redmond, Washington); MAC OS and iOS manufactured by Apple, Inc. (Cupertino, California); or Linux, a freely available operating system, such as the Linux Mint distribution ("distro") or Ubuntu sold by Canonical Ltd. (London, UK); or Unix or other Unix-like derived operating systems; and Android, designed by Google (Mountain View, California), among others. Some operating systems, including, for example, Google's CHROME OS, can be used on zero or thin clients, including, for example, CHROMEBOOKS.

[0165] The computer system (700) may be any workstation, phone, desktop computer, laptop or notebook computer, netbook, ULTRABOOK, tablet, server, handheld computer, mobile phone, smartphone or other portable telecommunication device, media playback device, gaming system, mobile computing device, or any other type and / or form of computing, telecommunication, 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 that are compatible with the device. The Samsung GALAXY smartphone, for example, operates under the control of the Android operating system developed by Google, Inc.

[0166] In some embodiments, the computing device (700) is a gaming system. For example, the computer system (700) may comprise a PLAYSTATION 3, or a PERSONAL PLAYSTATION PORTABLE (PSP), or a PLAYSTATION VITA device manufactured by SONY, Tokyo, Japan, a NINTENDO DS, NINTENDO 3DS, NINTENDO WII, or NINTENDO WII U device manufactured by NINTENDO Co., Ltd., Kyoto, Japan, or an XBOX 360 device manufactured by Microsoft Corporation, Redmond, Washington, Japan, or an OCULUS RIFT or OCULUS VR device manufactured by BY OCULUS VR, LLC, Menlo Park, California.

[0167] In some embodiments, the computing device (700) is a digital audio player, such as the Apple IPOD, IPOD Touch, and IPOD NANO line of devices manufactured by Apple Computer (Cupertino, Calif.). Some digital audio players may have other features, including, for example, gaming systems, or any functionality made available by applications from a digital application distribution platform. For example, the IPOD Touch can access Apple's App Store. In some embodiments, the computing device (700) is a portable media player or digital audio player that supports file formats, including, but not limited to, MP3, WAV, M4A / AAC, WMA Protected AAC, AIFF, Audible audiobook, Apple Lossless audio file formats, and .mov, m4v, and .MP4 MPEG-4 (H.264 / MPEG-4 AVC) video file formats.

[0168] In some embodiments, the computing device (700) is a tablet, such as Apple's IPAD line of devices, Samsung's GALAXY TAB family of devices, or Amazon.com, Inc.'s (Seattle, Wash.) KINDLE FIRE. In other embodiments, the computing device (700) is an eBook reader, such as Amazon.com's KINDLE family of devices, or Barnes & Noble, Inc.'s (New York, NY) NOOK family of devices.

[0169] In some embodiments, the communication device (700) includes a combination of devices, such as a smartphone combined with a digital audio player or a 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.

[0170] In some embodiments, the status of one or more machines (700) in a network is generally monitored as part of network management. In one of these embodiments, the state of the 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 identification of session state (e.g., the duration and type of process, and whether the process is active or idle). In another of these embodiments, this information may be identified by a number of metrics, which may be applied at least in part to decisions in load balancing, 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.

[0171] Methods of nerve stimulation FIG. 8 is a flow diagram of a method for performing visual-brain entrainment, according to an embodiment. The 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 in block (805). In block (810), the NSS may generate and transmit the identified visual signal. In (815), the NSS may receive or determine feedback related to neural activity, physiological activity, environmental parameters, or device parameters. In (820), the NSS may manage, control, or adjust the visual signal based on the feedback.

[0172] NSS operation using frames The NSS (105) can operate with a frame (400) including a light source (305), as shown in FIG 4A. The NSS (105) can operate with a frame (400) including a light source (30) and a feedback sensor (605), as shown in FIG 6A. The NSS (105) can operate 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).

[0173] In operation, a user of the frame (400) can wear the frame (400) on their head such that the eyewires (415) surround or substantially surround their eyes. In some cases, the user can provide an indication to the NSS (105) that the glass frame (400) is worn and that the user is ready to undergo brainwave entrainment. The indication can include a command, a selection, an 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 provide a voice command indicating that the user is ready to undergo brainwave entrainment.

[0174] 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 glass 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), which 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 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, directing, gazing, or looking in the direction of the light source (305) or feedback sensor (605) can provide an indication that the user is ready to undergo brainwave entrainment.

[0175] Thus, the NSS (105) can detect or determine that the frame (400) is worn and the user is in a ready state, or the NSS (105) can 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) can initialize the brainwave entrainment process. In some embodiments, the NSS (105) can access the profile data structure (145). For example, the profile manager (125) can query the profile data structure (145) to determine one or more parameters for the external visual stimulation to be used in the brain entrainment process. The parameters can include, for example, a type of visual stimulation, an intensity of the visual stimulation, a frequency of the visual stimulation, a duration of the visual stimulation, or a wavelength of the visual stimulation. The profile manager (125) can query the profile data structure (145) to obtain historical brain entrainment information, such as previous visual stimulation sessions. The profile manager (125) can perform searches in the profile data structure (145). The profile manager (125) can perform searches using a user name, a user identifier, location information, a fingerprint, a biometric identifier, a retina scan, voice recognition and authentication, or other identification techniques.

[0176] 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 available light source (305). 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 should be modulated as it enters the user's eye via the plane formed by the eye wire (415).

[0177] In some embodiments, the NSS (105) can determine the type of external visual stimulus based on historical electroencephalographic entrainment sessions. For example, the profile data structure (145) can be pre-configured with information about the type of visual signaling component (150).

[0178] 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 for 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.

[0179] 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 feedback sensor (605)) can determine a level or amount of ambient light. The NSS (105) (e.g., via the light adjustment module (115) or side effect management module (130)) can establish, initialize, set, or adjust an intensity or wavelength of the light pulses. For example, the NSS (105) can determine that there is a low level of ambient light. Due to the low level of ambient light, the user's pupils may be dilated. The NSS (105) can determine that the user's pupils are likely dilated based on detecting the low level of ambient light. In response to determining that the user's pupils are likely dilated, the NSS (105) can set a low level of intensity for the pulse train. The NSS (105) can also use light waves having a longer wavelength (e.g., red), which can reduce strain on the eye.

[0180] In some embodiments, the NSS (105) can monitor ambient light levels (e.g., via the feedback monitor (135) and feedback component (160)) throughout the brainwave entrainment process to 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 a higher intensity level for the light pulses and use a color that includes light waves with lower wavelengths (e.g., blue). However, in some embodiments where the ambient light levels decrease 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.

[0181] In some embodiments, the NSS (105) (e.g., via the feedback monitor (135) and feedback component (160)) can monitor or measure a physiological condition to set or adjust parameters of the light waves. 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 to set or adjust parameters of the light waves.

[0182] In some embodiments, the NSS (105) can be pre-configured to initially transmit light pulses having a lowest setting of light wave intensity (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 may refer to the highest intensity that is not accompanied by 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.

[0183] In some embodiments, the NSS (105) (e.g., via the light adjustment module (115)) can adjust parameters of the light waves or light pulses based on attention level. 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.

[0184] The NSS (105) can detect the level of attention the user is paying to the light pulse using the feedback monitor (135) and one or more feedback components (160). The NSS (105) can perform eye tracking to determine the level of attention the user is paying 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 paying to the light pulse. The NSS (105) can provide a survey or prompt for user feedback indicating the level of attention the user is paying to the light pulse. In response to determining that the user is not paying a sufficient amount of attention to the light pulse (e.g., a level of eye movement greater than a threshold or a gaze direction that is outside the direct field of view of the light source (305)), the light adjustment module (115) can alter parameters of the light source to capture 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 alter 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-seeking light sequence configured to restore 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-seeking 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 is paying to the light pulses and adjust the light pulses to restore the user's attention if the level of attention falls below a threshold.

[0185] In some embodiments, the light adjustment module (115) may modify or adjust one or more parameters of the light pulses or waves at predetermined time intervals (e.g., every 5 minutes, 10 minutes, 15 minutes, or 20 minutes) to restore or maintain the user's attention level.

[0186] In some embodiments, the NSS (105) (e.g., via the unwanted frequency filtering module (120)) can filter, block, attenuate, or remove undesired visual extraneous stimuli. 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 differs substantially (e.g., by 1%, 2%, 5%, 10%, 15%, 20%, 25%, or more than 25%) from a desired frequency.

[0187] 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.

[0188] 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 change the magnitude or phase of the incoming light waves 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).

[0189] Works with NSS Virtual Reality Headsets 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.

[0190] 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).

[0191] 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 indicate 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 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.

[0192] 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 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 the user is paying to the light source (305) or the feedback sensor (605). The NSS (105) can detect 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 feedback sensor (605) may provide an indication that the user is ready to undergo brainwave entrainment.

[0193] In some embodiments, a sensor (605) in the strap (455), strap (460), or eye socket (605) can detect when the virtual reality headset (401) is secured, placed, or positioned on the user's head. The sensor (605) can be a touch sensor that senses or detects contact with the user's head.

[0194] Thus, the NSS (105) can detect or determine that the virtual reality headset (401) is worn and the user is ready, or the NSS (105) can receive an indication or confirmation from the user that the user has worn 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) can initialize the brainwave entrainment process. In some embodiments, the NSS (105) can access the profile data structure (145). For example, the profile manager (125) can query the profile data structure (145) to determine one or more parameters for the external visual stimuli used in the brain entrainment process. The parameters can 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) can query the profile data structure (145) to obtain brain entrainment history information, such as previous visual stimulation sessions. The profile manager (125) can perform searches in the profile data structure (145). The profile manager (125) can perform searches 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.

[0195] 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 available light source (305). 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 within an enclosure of the virtual reality headset (401).

[0196] 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 provide the desired modulation frequency.

[0197] 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.

[0198] 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.

[0199] 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 a level or amount of light in 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)) can establish, initialize, set, or adjust the intensity or wavelength of the light pulses based on the level of light in the image data corresponding to the augmented reality experience. For example, the NSS (105) can 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) can 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) can 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.

[0200] In some embodiments, the NSS (105) can monitor the light levels (e.g., via the feedback monitor (135) and 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.

[0201] In some embodiments, the NSS (105) (e.g., via the feedback monitor (135) and feedback component (160)) can monitor or measure physiological conditions 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.

[0202] In some embodiments, the NSS (105) can be preconfigured via the display device (305) to initially send light pulses having 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 the 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.

[0203] In some embodiments, the NSS (105) (e.g., via the light adjustment module (115)) can adjust parameters of the light waves or light pulses based on a 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.

[0204] The NSS (105) can use the feedback monitor (135) and one or more feedback components (160) (e.g., including the feedback sensor (605)) to detect the level of attention the user is paying or directing to the light pulse. 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 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-seeking light sequence configured to regain the user's attention. For example, the light sequence can include changes in color or intensity of the light pulse in a predetermined, random, or pseudo-random pattern. The attention-seeking light sequence can enable or disable different light sources when 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 is providing to the light pulse and adjust the light pulse to regain the user's attention if the level of attention falls below a threshold.

[0205] In some embodiments, the light adjustment module (115) may modify or adjust one or more parameters of the light pulses or waves at predetermined time intervals (e.g., every 5, 10, 15, or 20 minutes) to restore or maintain the user's level of attention.

[0206] In some embodiments, the NSS (105) (e.g., via the unwanted frequency filtering module (120)) can filter, block, attenuate, or remove undesired visual extraneous stimuli. 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 differs substantially (e.g., by 1%, 2%, 5%, 10%, 15%, 20%, 25%, or more than 25%) from a desired frequency.

[0207] 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 effect 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 eliminate 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 an image or video displayed via the display device (305).

[0208] 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 a digital optical filter 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 filter can modify the magnitude or phase of the image in a wavelength range. For example, the digital optical filter 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 wavelength of the light waves generated by the light generating module (110) and the display device (305) so that the desired modulation frequency is not blocked or attenuated by the unwanted frequency filtering module (120).

[0209] NSS running on 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 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.

[0210] The tablet (500) can communicate with the NSS (105) via a network, such as a wireless network or a cellular network. The NSS (105), in some embodiments, can execute the NSS (105) or components thereof. For example, the tablet (500) can launch, open, or switch between applications or resources configured to provide 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.

[0211] The tablet (500) may include one or more feedback sensors (605). In some embodiments, the tablet may use one or more feedback sensors (605) to detect when a user is holding the tablet (500). The tablet may use one or more feedback sensors (605) to determine a distance between the light source (305) and a user. The tablet may use one or more feedback sensors (605) to determine a distance between the light source (305) and a user's head. The tablet may use one or more feedback sensors (605) to determine a distance between the light source (305) and a user's eye.

[0212] 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).

[0213] In some embodiments, the tablet (500) can include two feedback sensors (605) to determine distance. The two feedback sensors (605) can include a first feedback sensor (605) that is a transmitter and a second feedback sensor that is a receiver.

[0214] 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) in contact 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.

[0215] In some embodiments, the tablet (500) (or an application thereof) can determine the distance between the tablet and the user's head by receiving user input. For example, the user 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.

[0216] The tablet (500), application, or NSS (105) can 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) can 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) can adjust the intensity of the light pulse emitted by the light source (305) based on the distance. The tablet (500) can adjust the intensity based on the distance to maintain a consistent or similar intensity at the eye regardless of the distance between the light source (305) and the eye. The tablet can increase the intensity in proportion to the square of the distance.

[0217] The tablet (500) can manipulate one or more pixels of the display screen (305) to generate light pulses or modulation frequencies for brainwave entrainment. The tablet (500) can superimpose light sources, light pulses or other patterns to generate modulation frequencies for brainwave entrainment. Similar to the virtual reality headset (401), the tablet can filter or modify undesirable frequencies, wavelengths or intensities.

[0218] Similar to the frame 400, the tablet (500) can adjust parameters of the light pulses or flashes of light generated by the light source (305) based on ambient light, environmental parameters, or feedback.

[0219] 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 a 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 on the display screen that is outside of the portion of the display screen that corresponds to the user's gaze.

[0220] Nerve stimulation by 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 audio signal transmission 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 audio 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 a 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 audio 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 of the hardware or interface components shown in the system (700) of Figures 7A and 7B. For example, the components of the system (100) may include or execute on one or more processors (721), access storage (728) or memory (722), and communicate via a network interface (718).

[0221] Still referring to FIG. 9, in more detail, the NSS (905) can include at least one audio generation module (910). The audio generation module (910) can be designed and constructed to provide instructions or otherwise interface with an audio signal transmission component (950) to cause or facilitate the generation of an audio 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) can 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) can generate instructions to cause the audio signal transmission component (950) to generate an audio signal. The audio generation module (910) can control or enable the audio signal transmission component (950) to generate an audio signal having one or more predetermined parameters.

[0222] The audio generation module (910) can be communicatively coupled to the audio signal transmission component (950). The audio generation module (910) can communicate with the audio signal transmission 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 audio signal transmission 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 have access to a network interface (718) for wireless or wired communication with the audio signal transmission component (950).

[0223] The audio generation module (910) can interface, control, or otherwise manage various types of audio signal conveying components (950) to generate, block, control, or otherwise communicate to the audio signal conveying components (950) an audio signal having one or more predefined parameters. The audio generation module (910) can include a driver configured to drive an audio source of the audio signal conveying components (950). For example, the audio source can include a speaker, and the audio generation module (910) (or the audio signal conveying 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 audio signal having desired acoustic characteristics.

[0224] In some embodiments, the audio generating module (910) can instruct the audio signal conveying component (950) to convey an audio signal. For example, the audio signal can include an acoustic wave (1000) as shown in FIG. 10A. The audio signal can include multiple acoustic waves. The audio 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 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.

[0225] 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.

[0226] The audio signal transmission component (950) or its sound source can generate acoustic waves by vibrating a diaphragm of the sound source. For example, the sound 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.

[0227] The acoustic wave (1000) shown in FIG. 10A includes a wavelength (1010). The wavelength (1010) can refer to the distance between successive crests (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 quotient of 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 quotient of 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.

[0228] A crest (1020) can refer to the crest of a wave or the point of a wave that has a maximum value. The displacement of the medium is greatest at the crest (1020) of the wave. A trough (1015) is opposite the crest (1020). The trough (1015) is the minimum or lowest point of the wave that corresponds to the smallest amount of displacement.

[0229] The acoustic wave (1000) can include an amplitude (1005). The amplitude (1005) can refer to the maximum range of oscillation of the acoustic wave (1000) measured from an equilibrium position. The acoustic wave (1000) can be a longitudinal wave if it oscillates in the same traveling direction (1025). In some cases, the acoustic wave (1000) can be a transverse wave, oscillating perpendicular to its direction of propagation.

[0230] The audio generation module (910) can instruct the audio signal transmission 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 acoustic waves can range from 8 to 12 kHz. In some embodiments, the frequency of the acoustic waves can be 10 kHz.

[0231] 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.

[0232] 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.

[0233] 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.

[0234] The NSS (905) can modulate or change one or more characteristics of the acoustic wave based on a time interval. The NSS (905) can change one or more characteristics of the acoustic at the end of the time interval. For example, the NSS (905) can change the properties 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 NSS (905) 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 NSS (905) can set the modulation frequency to a frequency in the range of 0.1 Hz to 10,000 Hz. For example, the NSS (905) 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.

[0235] The audio generation module (910) can determine to convey an audio signal including a burst of acoustic waves, an audio pulse, or a modulation of an acoustic wave. The audio generation module (910) can command or otherwise cause the audio signal conveying component (950) to generate an acoustic burst or pulse. An acoustic pulse can 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, a sound source that is intermittently turned on and off can generate the audio burst or change in sound. The sound source can be turned on and off based on a predetermined or fixed pulse rate interval, such as every 0.025 seconds, to provide a pulse repetition frequency of 40 Hz. The sound source can be turned on and off to provide a pulse repetition frequency ranging from 0.1 Hz to 10 kHz or more.

[0236] 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 the acoustic wave, changing the frequency or wavelength of the acoustic wave, superimposing another acoustic wave on the original acoustic wave, or otherwise modifying or altering the acoustic wave.

[0237] For example, FIG. 10F illustrates acoustic bursts (1035a-c) (or modulated pulses (1035a-c)) according to an 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).

[0238] The audio signal may include modulated acoustic waves modulated between different frequencies, wavelengths, or amplitudes. For example, the NSS (905) may modulate acoustic waves between frequencies in the audio spectrum, such as Ma, and frequencies outside the audio spectrum, such as Mo. The NSS (905) may modulate acoustic waves between two or more frequencies, between on and off states, or between high and low power states.

[0239] The acoustic bursts (1035a-c) can have an acoustic wave parameter with a value Ma that is different from the value Mo of the acoustic 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).

[0240] For example, the acoustic wave parameter can be a frequency of the acoustic wave. The first value Mo can be a low frequency or carrier frequency of the acoustic wave, such as 10 kHz. The second value Ma can be different from the first frequency Mo. The second frequency Ma can be lower or higher than the first frequency Mo. For example, the second frequency Ma can be 11 kHz. The difference between the first frequency and the second frequency can be determined or set based on the level of sensitivity of the human ear. The difference between the first frequency and the second frequency can be determined or set based on the subject's profile information (945). The difference between the first frequency Mo and the second frequency Ma can be determined such that the modulation or change of the acoustic wave promotes brainwave entrainment.

[0241] In some cases, the parameters of the acoustic wave used to generate the 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.

[0242] 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) of 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) can also be less than the first pulse width (1030a). Although the pulse widths (1030a-c) of the pulses (1035d-f) of the pulse train can vary, the audio generation module (910) can maintain a constant pulse rate interval (1040) for the pulse train.

[0243] The pulses (1035a-c) may form a pulse train having a pulse rate interval (1040). The pulse rate interval (1040) may be quantified using units of time. The pulse rate interval (1040) may be based on a frequency of the pulses in the pulse train (201). The frequency of the pulses in the pulse train (201) may be referred to as a modulation frequency. For example, the audio generation module (910) may provide a pulse train (201) of a predetermined frequency, such as 40 Hz. To do so, the audio generation module (910) may determine the pulse rate interval (1040) by taking a 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) may 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) may 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 pulse rate interval (1040) varies but the number of pulses delivered during the second can be fixed.

[0244] In some embodiments, the audio generation module (910) can generate audio bursts or audio pulses having acoustic waves of varying 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 wave may vary from the start of the pulse to the end of the pulse.

[0245] The audio generating module (910) can 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) can be Mc. The frequency, amplitude, or wavelength of the acoustic wave of the pulse (1035j) can 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) can range from Mc to Ma. The frequency, amplitude, or wavelength can decrease linearly, exponentially, or based on some other rate or curve. One or more of the frequency, amplitude, or wavelength of the acoustic wave can change from the start of the pulse to the end of the pulse.

[0246] In some embodiments, the audio generation module (910) can command or cause the audio 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 determine which cortex is recruited to process the stimulus. The audio signaling component (950) can stimulate individual 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 determine which area of ​​the cortex is stimulated. For example, different areas of the cortex are recruited to process sounds of different frequencies, referred to as their signature frequency. Additionally, the unilateral nature of the stimulation can affect the cortical response, since some subjects can be treated by stimulating one ear rather than both ears.

[0247] The audio signal transmission component (950) can be designed and constructed to generate audio pulses in response to instructions from the audio generation module (910). The instructions can include parameters of the audio pulses, such as the 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., the number of pulses in the pulse train or the length of time to send a pulse train having a given frequency). The audio pulses can be sensed, observed, or otherwise identified by the brain through cochlear means such as the ear. The audio pulses can be sent to the ear via a source speaker in close proximity to the ear, such as a headphone, earphone, bone conduction transducer, or cochlear implant. The audio pulses can be sent to the ear via a source or speaker not in close proximity to the ear, such as a surround sound speaker system, bookshelf speaker, or other speaker not in direct or indirect contact with the ear.

[0248] FIG. 11A illustrates an audio 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).

[0249] The audio signal transmission component (950) may include a first sound source that transmits an audio signal to a first ear of the subject and a second sound source that transmits a second audio signal to a second ear of the subject. The first sound source and the second sound source may be different. The first ear may perceive only the first audio signal from the first sound source, and the second ear may receive only the second audio signal from the second sound source. The sound source may include, for example, headphones, earphones, or a bone conduction transducer. The sound source may include a stereo sound source.

[0250] 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.

[0251] 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 sum of the waveforms (1115). With first and second tones having different parameters (such as different frequencies or phase offsets), portions of the wave can be added and subtracted from another resulting in a waveform (1115) having one or more pulses (1130) (or beats (1130)). The pulses (1130) can be separated by portions (1125) that are in equilibrium. The pulses (1130) perceived by the brain by mixing these two different waveforms together can induce brainwave entrainment.

[0252] In some embodiments, the NSS (905) can generate binaural beats using pitch panning techniques. For example, the audio generation module (910) or 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 audio signal to a first ear of a subject, and a second audio source that generates and delivers an audio signal to a second ear of the subject. An audio file can refer to a format of a file configured to store representations or information of acoustic waves. Exemplary audio file formats can include .mp3, .wav, .aac, .m4a, .smf, etc.

[0253] The NSS (905) can use this pitch panning technique to generate a type of spatial positioning that is perceived by the brain in a manner similar to binaural beats when heard through stereo headphones. Thus, the NSS (905) can use this pitch panning technique to generate a pulse or beat using a single tone or a single audio file.

[0254] In some cases, the NSS (905) can generate a monaural beat or a monaural pulse. A monaural beat or pulse is similar to a binaural beat in that it is also generated by combining two tones to form a beat. The NSS (905) or components of the system (100) can form a monaural beat by combining two tones using digital or analog techniques before the sound reaches the ear, as opposed to the brain combining the waveforms as in binaural beats. For example, the NSS (905) (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 NSS (905) 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 NSS (905) 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 audio signal transmission component (950). The NSS (905) can convert the digital waveform to an analog format and send the analog format to the audio signal transmission component (950). The audio signal transmission component (950) can then generate, via a sound 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 at a desired pulse rate interval (1040).

[0255] FIG. 11B illustrates an acoustic pulse with an isochronous tone, according to an embodiment. An isochronous tone is an evenly spaced tone pulse. An isochronous tone can be created without the need to combine two different tones. The NSS (905) or other components of the system (100) can generate the isochronous tone by turning a tone on and off. The NSS (905) can generate the isochronous tone or pulse by commanding an audio signal conveying component 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).

[0256] 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 at a desired PRI (1040) can induce brainwave entrainment.

[0257] 11C illustrates an audio pulse generated by the NSS (905) using an audio track, according to an embodiment. A soundtrack can include or refer to a complex acoustic wave that includes multiple different frequencies, amplitudes, or tones. For example, a soundtrack can include a voice track, an instrument track, a music track having both voice and instruments, nature sounds, or white noise.

[0258] The NSS (905) can modulate the audio track to induce brainwave entrainment by rhythmically adjusting the components of the sound. For example, the NSS (905) can adjust the volume by increasing or decreasing the amplitude of the acoustic waves or audio track to generate rhythmic stimulation corresponding to a stimulation frequency for inducing brainwave entrainment. Thus, the NSS (905) can embed acoustic pulses in the audio track having a pulse rate interval corresponding to a desired stimulation frequency to induce brainwave entrainment. The NSS (905) can manipulate the audio track to generate a new modified audio track having acoustic pulses having a pulse rate interval corresponding to a desired stimulation frequency to induce brainwave entrainment.

[0259] 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 specified amount of interest, 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).

[0260] In some embodiments, the NSS (905) can include an attenuator that attenuates 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 audio signal conveying components (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 audio signal conveying components (950)) to amplify or increase the volume from Va to Vb.

[0261] 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 an audio signal, such as the frequency, amplitude, wavelength, pattern, or other parameters of the audio signal. The audio adjustment module (915) may automatically modify parameters of the audio 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).

[0262] The NSS (905) can include, access, interface with, and otherwise communicate with at least one unwanted frequency filtering module (920). The unwanted frequency filtering module (920) can be designed and constructed to block, mitigate, reduce, or otherwise filter frequencies of the audio signal that are undesirable to prevent or reduce the amount of such audio signal from being perceived by the brain. The unwanted frequency filtering module (920) can 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.

[0263] The unwanted frequency filtering module (920) may include an active noise control component (e.g., an 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.

[0264] 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 audio 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.

[0265] 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.

[0266] 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 audio signal includes acoustic bursts having intervals of a desired pulse rate, as well as acoustic bursts having intervals of an undesirable pulse rate. The active noise control component can identify waveforms corresponding to the acoustic bursts having intervals of an undesirable pulse rate, and generate an inverted phase waveform to cancel or attenuate the undesirable acoustic bursts.

[0267] 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, past treatment 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.

[0268] 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 audio signal to reduce side effects. Side effects may include, for example, nausea, migraines, fatigue, seizures, ear strain, hearing loss, ringing in the ears, or tinnitus.

[0269] The side effect management module (930) can automatically instruct components of the NSS (905) to modify or change parameters of the audio 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 configured with 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 period of time (e.g., 1 hour, 2 hours, 12 hours, or 24 hours).

[0270] The side effect management module (930) can vary a parameter of the audio 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 audio signal based on the feedback. The side effect management module (930) can compare the feedback to a threshold to determine to adjust the parameter of the audio signal.

[0271] The side effect management module (930) can be configured with or can include a policy engine that applies policies or rules to the current audio signal and feedback to determine adjustments to the audio signal. For example, if the feedback indicates that a patient receiving the audio 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 to a value below the threshold or below a second threshold that is below the threshold.

[0272] 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.

[0273] Systems and devices configured for neurostimulation via auditory stimulation - Patents.com 12A illustrates a system for auditory brain entrainment, according to an embodiment. The system (1200) can include one or more speakers (1205). The system (1200) can include one or more microphones. In some embodiments, the system can include both a speaker (1205) and a microphone (1210). In some embodiments, the system (1200) can include a speaker (1205) and not include a microphone (1210). In some embodiments, the system (1200) can include a microphone (1210) and not include a speaker (1210).

[0274] The speaker (1205) can be integrated with the audio signal transmission component (950). The audio signal transmission component (950) can include a speaker (1205). The speaker (1205) can interact or communicate with the audio signal transmission component (950). For example, the audio signal transmission component (950) can instruct the speaker (1205) to generate sound.

[0275] 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).

[0276] In some embodiments, the speaker (1205) and the microphone (1210) may be integrated together or in the same device. For example, the speaker (1205) may be configured to function as the microphone (1210). The NSS (905) may switch the speaker (1205) from speaker mode to microphone mode.

[0277] In some embodiments, the system (1200) can include a single speaker (1205) located at one of the subject's ears. In some embodiments, the system (1200) can include two speakers. A first of the two speakers can be located at the first ear and a second of the two speakers can be located at the second ear. In some embodiments, an additional speaker can be located in front of the subject's head or behind the subject's head. In some embodiments, the one or more microphones (1210) can be located at one or both ears, in front of the subject's head, or behind the subject's head.

[0278] 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 parts 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).

[0279] The speaker (1205) can include one or more types of speaker hardware, components, or technologies for generating sound. For example, the speaker (1205) can include a diaphragm for generating sound. The speaker (1205) can include a moving ferrous loudspeaker that uses a stationary coil to vibrate a magnetized piece of metal. The speaker (1205) can include a piezoelectric speaker. A piezoelectric speaker can generate sound by utilizing the piezoelectric effect to apply a voltage to a piezoelectric material to generate motion, which is converted into audible sound using a diaphragm and a resonator.

[0280] 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.

[0281] 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.

[0282] 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 stand-alone unit.

[0283] 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, retract, 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.

[0284] In some embodiments, the headphones can be connected to the audio signal transmission component (950) via a wired or wireless connection. In some embodiments, the audio signal transmission component (950) 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 system (100), such as 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), an audio signal transmission component (950), a filtering component (955), or a feedback component (960).

[0285] 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 EEG 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 can provide less attenuation of external noise.

[0286] Both circum-aural and supra-aural headphones can have an open back, closed back, or semi-open back. Open backs allow more sound to leak out and more ambient sound to enter, but provide a more natural or speaker-like sound. Closed back headphones block out more ambient noise compared to open back headphones, thus providing a more immersive auditory brainwave stimulation experience while reducing external distractions.

[0287] 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 out 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, creating a custom-molded plug that adds comfort and noise isolation to the subject, thereby further improving the immersion of the auditory EEG stimulation experience.

[0288] In some embodiments, one or more microphones (1210) may be used to detect sound. The microphones (1210) may be integrated with the speakers (1205). The microphones (1210) may provide feedback information to the NSS (905) or other components of the system (100). The microphones (1210) may provide feedback to components of the speaker (1205) to cause the speaker (1205) to adjust parameters of the audio signal.

[0289] 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 quartz microphone, a fiber optic microphone, a laser microphone, a liquid or water microphone, a microelectromechanical system ("MEMS") microphone, or a speaker as a microphone.

[0290] The feedback component (960) may include or interface with a microphone (1210) to capture, identify, or receive audio. The feedback component (960) may capture ambient noise. The feedback component (960) may capture sound from the speaker (1205) to facilitate the NSS (905) adjusting characteristics of the audio signal generated by the speaker (1205). The microphone (1210) may receive audio input from the subject, such as audio commands, instructions, requests, feedback information, or responses to survey questions.

[0291] In some embodiments, one or more speakers (1205) may be integrated with one or more microphones (1210). For example, the speaker (1205) and microphone (1210) may form a headset and be located in a single enclosure, or the speaker (1205) and microphone (1210) may even be the same device, as they may be structurally designed to switch between sound generating and sound receiving modes.

[0292] FIG. 12B shows 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 an NSS (905). The system (1200) can include or interface with an audio player (1220).

[0293] The system (1200) can include a first speaker (1205) disposed at a first ear. The system (1200) can include a second speaker (1205) disposed at a 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 with 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) can 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 can communicate or interface with the NSS (905). In some embodiments, the system (1200) can include a feedback sensor (1225) and a second feedback sensor (1225) communicatively coupled to the NSS (905), the speaker (1205), the microphone (1210), or the active noise cancellation component (1215).

[0294] In operation, in some embodiments, the audio player (1220) can play a music track. The audio player (1220) can communicate an audio 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 audio signal from the audio player. For example, the NSS (905) can receive a digital or analog audio signal from the audio player (1220). The NSS (905) can mediate the audio player (1220) and the speakers (1205). The NSS (905) can analyze the audio signal corresponding to 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 use binaural beat technology to deliver different auditory signals to the first and second speakers that combine to have the desired stimulation frequency when perceived by the brain.

[0295] In some embodiments, the NSS (905) can adjust the latency between either the first and second speakers (1205) so that the brain perceives the audio signals simultaneously or substantially simultaneously (e.g., within 1 ms, 2 ms, 5 ms, or 10 ms). The NSS (905) can buffer the audio signals to account for the latency so that the audio signals are sent from the speakers simultaneously.

[0296] 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 communicate the modified music track to the audio player (1220) for communicating the modified audio signal to the speaker (1205).

[0297] 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.

[0298] 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 audio signal based on the feedback information. For example, the NSS (905) can reduce the volume of the audio signal after determining that the subject's pulse rate exceeds a predetermined threshold. The NSS (905) can detect that the volume of the auditory signal exceeds a threshold and reduce the amplitude. The NSS (905) can determine that the pulse rate interval is below a threshold, which can indicate that the subject is losing focus or not paying a satisfactory level of attention to the audio signal, and the NSS (905) can increase the amplitude of the audio signal or modify the tone or music track. In some embodiments, the NSS (905) can vary the tone or music track based on the time interval. Changing the tone or music track can enable the subject to pay a higher level of attention to the auditory stimuli and promote brainwave entrainment.

[0299] 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 use the microphone (1210) to identify corresponding undesirable frequencies in the ambient noise. The NSS (905) can then instruct the active noise cancellation component (1215) to remove waveforms corresponding to the ambient noise having the undesirable frequencies.

[0300] 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 sound insulating, sound damping, or sound absorbing materials.

[0301] FIG. 4C shows 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.

[0302] 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 audio signals to the first and second speakers (1205) to facilitate auditory brainwave entrainment.

[0303] 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 conveying the auditory stimulus signal to the speakers (1205).

[0304] 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.

[0305] FIG. 13 shows 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.

[0306] When a surround system is used to provide auditory stimuli, the NSS (905) can convey the same or different audio signals to each of the speakers of the system (1300). The NSS (905) can modify or adjust the audio signals provided to one or more of the speakers of the system (1300) to facilitate brainwave entrainment. For example, the NSS (905) 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 NSS (905) can optimize or improve the auditory stimuli perceived at a location corresponding to the microphone (1210) by analyzing an acoustic beam or wave generated by the speaker that propagates toward the microphone (1210).

[0307] The NSS (905) may be configured with information regarding the design and configuration of each speaker. For example, the speaker (1305) may generate a sound in a direction of an angle (1335). The speaker (1310) may generate a sound traveling in a direction of an angle (1340). The speaker (1315) may generate a sound traveling in a direction of an angle (1345). The speaker (1325) may generate a sound traveling in a direction of an angle (1355). The speaker (1330) may generate a sound traveling in a direction of an angle (1350). These angles may be optimal or predetermined angles for each speaker. These angles may refer to the optimal angle for each speaker such that a person located at a location corresponding to the microphone (1210) may receive optimal auditory stimulation. Thus, the speakers of the system (1300) may be oriented to transmit auditory stimulation toward a target.

[0308] 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 condition or manipulate the received audio and send the conditioned audio signal to the speakers of the system (1300) to induce brainwave entrainment.

[0309] 14 shows a feedback sensor (1405) placed or positioned on, on, or near a person's head. The feedback sensor (1405) can include, for example, an EEG probe to detect brainwave activity.

[0310] 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 use the feedback information to update a profile data structure (945) stored in the data repository (940). The profile manager (925) may associate the feedback information with an identifier of the patient or person receiving the audio brain stimulation, as well as a timestamp and date stamp corresponding to the receipt or detection of the feedback information.

[0311] The feedback monitor (935) can determine the level of attention. The level of attention can refer to the focus placed on the acoustic pulses used for brain stimulation. The feedback monitor (935) can determine the level of attention using a variety of hardware and software techniques. The feedback monitor (935) can assign a score to the level of attention (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), can classify the level of attention (e.g., low, medium, high), can grade the attention (e.g., A, B, C, D, or F), or can otherwise provide an indication of the level of attention.

[0312] In some cases, the feedback monitor (935) can track the person's eye movements to identify a level of attention. The feedback monitor (935) can interface with a feedback component (960) that includes an eye tracker. The feedback monitor (935) (e.g., via the feedback component (960)) can detect and record the person's eye movements and analyze the recorded eye movements to determine an attention span or level of attention. The feedback monitor (935) can measure gaze, which can indicate or convey information related to covert attention. For example, the feedback monitor (935) (e.g., via the feedback component (960)) can be configured with an electro-oculogram ("EOG") to measure skin potential around the eye, which can indicate the direction the eye is pointing relative to the head. In some embodiments, the EOG can include a system or device for stabilizing the head so that the head does not move in order to determine the direction of the eye relative to the head. In some embodiments, the EOG can include or interface with a head tracker system to determine the position of the head and then the direction of the eye relative to the head.

[0313] In some embodiments, the feedback monitor (935) and the feedback component (960) can determine the level of attention the subject is paying to the auditory stimulus based on the eye movement. For example, increased eye movement may indicate that the subject is focusing on the visual stimulus as opposed to the auditory stimulus. To determine the level of attention the subject is paying to the visual stimulus as opposed to the auditory stimulus, the feedback monitor (935) and the feedback component (960) can use video detection of the pupil or corneal reflection to determine or track the direction of the eye or eye movement. For example, the feedback component (960) can include one or more cameras or video cameras. The feedback component (960) can include an infrared source that sends light pulses toward the eye. The light can be reflected by the eye. The feedback component (960) can detect the location of the reflection. The feedback component (960) can capture or record the location of the reflection. The feedback component (960) can perform image processing on the reflection to determine or calculate the direction of the eye or the direction of the eye's gaze.

[0314] The feedback monitor (935) can compare the eye direction or movement to past eye direction or movement of the same person, public eye movements, or other past eye movement information to determine the level of attention. For example, the feedback monitor (935) can determine the past amount of eye movement during past auditory stimulation sessions. The feedback monitor (935) can compare the current eye movement to the past eye movements to identify deviations. The NSS (905) can determine an increase in eye movement based on the comparison, and further determine that the subject is paying relatively less attention to the current auditory stimulation based on the increase in eye movement. In response to detecting the decrease in attention, the feedback monitor (935) can instruct the audio adjustment module (915) to modify parameters of the audio signal to direct the subject's attention. The audio adjustment module (915) can modify the volume, tone, pitch, or music track to direct the subject's attention or increase the level of attention the subject is paying to the auditory stimulation. As the audio signal is modified, the NSS (905) can continue to monitor the level of attention. For example, when modifying an audio signal, the NSS (905) can detect a decrease in eye movement, which can indicate an increase in the level of attention being given to the audio signal.

[0315] The feedback sensor (1405) can interact or communicate with the NSS (905). For example, the feedback sensor (1405) can communicate detected feedback information or data to the NSS (905) (e.g., feedback monitor (935)). The feedback sensor (1405) can communicate data to the NSS (905) in real time, for example, when the feedback sensor (1405) detects or senses or notifies. The feedback sensor (1405) can provide feedback information to the NSS (905) 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 (1405) can provide feedback information to the NSS (905) in response to a condition or event, such as a feedback measurement value exceeding or falling below a threshold value. The feedback sensor (1405) can provide feedback information in response to a change in a feedback parameter. In some embodiments, the NSS (905) may send a ping, query, or request to the feedback sensor (1405) for information, and the feedback sensor (1405) may provide feedback information in response to the ping, request, or query.

[0316] Method for nerve stimulation by auditory stimulation FIG. 15 is a flow diagram of a method for auditory brain entrainment according to an embodiment. The method (800) may be performed by one or more systems, components, modules or elements shown in FIGS. 7A, 7B, and 9-14, including, for example, a neurostimulation system (NSS). In brief overview, the NSS may identify an audio signal for presentation at block (1505). At block (1510), the NSS may generate and send the identified audio signal. At (1515), the NSS may receive or determine feedback related to neural activity, physiological activity, environmental parameters, or device parameters. At (1520), the NSS may manage, control, or adjust the audio signal based on the feedback.

[0317] NSS works with headphones The NSS (905) can operate in conjunction with a speaker (1205) as shown in Figure 12A. The NSS (905) can operate in conjunction with an earphone or in-ear phone that includes the speaker (1205) and a feedback sensor (1405).

[0318] In operation, a subject using headphones can place the headphones on their head so that the speaker is placed at or within the ear canal. In some cases, the subject can indicate to the NSS (905) that the headphones are placed and that the subject is ready to receive 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 subject can give a voice command indicating that the subject is ready to receive brainwave entrainment.

[0319] In some cases, the feedback sensor (1405) can determine that the subject is ready to receive brainwave entrainment. The feedback sensor (1405) can detect that the headphones have been placed on the subject's head. The NSS (905) can receive motion data, acceleration data, gyroscope data, temperature data, or capacitive touch data to determine that the headphones have been placed on the subject's head. The received data, such as motion data, can indicate that the headphones have been picked up and placed on the subject's head. The temperature data can measure a temperature at or near the headphones and can indicate that the headphones are on the subject's head. The NSS (905) can detect that the subject is ready in response to determining that the subject is paying a high level of attention to the headphones or the feedback sensor (1405).

[0320] Thus, the NSS (905) can detect or determine that the headphones are worn and the subject is ready, or the NSS (905) can receive an indication or confirmation from the subject that the subject has worn the headphones and that the subject is ready to undergo brainwave entrainment. Upon determining that the subject is ready, the NSS (905) can initialize the brainwave entrainment process. In some embodiments, the NSS (905) can access a profile data structure (945). For example, the profile manager (925) can query the profile data structure (945) to determine one or more parameters for the outer ear stimulation used in the brain entrainment process. The parameters can include, for example, a type of auditory stimulation technology, an intensity or volume of the auditory stimulation, a frequency of the auditory stimulation, a duration of the auditory stimulation, or a wavelength of the auditory stimulation. The profile manager (925) can query the profile data structure (945) to obtain information of the brain entrainment history, such as previous auditory stimulation sessions. The profile manager (925) can perform a search in the profile data structure (945). The profile manager (925) can perform searches using the user's name, a user identifier, location information, fingerprints, biometric identifiers, retina scans, voice recognition and authentication, or other identification technologies.

[0321] The NSS (905) can determine the type of outer ear stimulation based on the components connected to the headphones. The NSS (905) can determine the type of outer ear stimulation based on the type of speakers (1205) available. For example, if the headphones are connected to an audio player, the NSS (905) can determine to embed an acoustic pulse. If the headphones are not connected to an audio player and are only connected to a microphone, the NSS (905) can determine to inject a pure tone or to modify the ambient noise.

[0322] In some embodiments, the NSS (905) can determine the type of outer ear stimulation based on past electroencephalographic entrainment sessions. For example, the profile data structure (945) can be pre-configured with information regarding the type of audio signal conveying component (950).

[0323] The NSS (905) can determine the modulation frequency of the pulse train or audio signal via the profile manager (925). For example, the NSS (905) can determine from the profile data structure (945) that the modulation frequency of the outer ear stimulus should be set to 40 Hz. Depending on the type of auditory stimulus, the profile data structure (945) can further indicate the pulse length, intensity, wavelength of the acoustic waves forming the audio signal, or duration of the pulse train.

[0324] In some cases, the NSS (905) can determine or adjust one or more parameters of the outer ear stimulation. For example, the NSS (905) (e.g., via the feedback component (960) or feedback sensor (1405)) can determine the amplitude of the acoustic waves or the level of the volume of the sound. The NSS (905) (e.g., via the audio adjustment module (915) or the side effect management module (930)) can establish, initialize, set, or adjust the amplitude or wavelength of the acoustic waves or acoustic pulses. For example, the NSS (905) can determine that there is a low level of ambient noise. The level of ambient noise is low so that the subject's hearing may not be impaired or distracted. The NSS (905) can determine that there may be no need to increase the volume or that the volume may be reduced to maintain the effectiveness of the brainwave entrainment based on detecting a low level of ambient noise.

[0325] In some embodiments, the NSS (905) can monitor the level of ambient noise (e.g., via the feedback monitor (935) and feedback component (960)) throughout the brainwave entrainment process and automatically and periodically adjust the amplitude of the acoustic pulse. For example, if the subject begins the brainwave entrainment process when there is a high level of ambient noise, the NSS (905) can initially set the amplitude of the acoustic pulse higher and use a tone that includes an easily perceptible frequency, such as 10 kHz. However, in some embodiments where the level of ambient noise decreases throughout the brainwave entrainment process, the NSS (905) can automatically detect the decrease in ambient noise and, in response to the detection, adjust or lower the volume while decreasing the frequency of the acoustic waves. The NSS (905) can adjust the acoustic pulse to provide a high contrast ratio to the ambient noise to facilitate brainwave entrainment.

[0326] In some embodiments, the NSS (905) (e.g., via the feedback monitor (935) and feedback component (960)) can monitor or measure physiological conditions to set or adjust parameters of the acoustic waves. In some embodiments, the NSS (905) can monitor or measure heart rate, pulse rate, blood pressure, body temperature, sweating, or brain activity to set or adjust parameters of the acoustic waves.

[0327] In some embodiments, the NSS (905) can be pre-configured to initially send acoustic pulses with the lowest setting of acoustic wave intensity (e.g., low amplitude or high wavelength) and gradually increase the intensity (e.g., increase the amplitude or decrease the wavelength) while monitoring feedback until an optimal audio intensity is reached. The optimal audio intensity can refer to the highest intensity without adverse physiological side effects such as hearing loss, seizures, heart attacks, migraines, or other discomforts. The NSS (905) (e.g., via the side effect management module (930)) can monitor physiological symptoms to identify adverse side effects of the outer ear stimulation and adjust the outer ear stimulation accordingly (e.g., via the audio adjustment module (915)) to reduce or eliminate the adverse side effects.

[0328] In some embodiments, the NSS (905) (e.g., via the audio adjustment module (915)) can adjust parameters of the acoustic waves or acoustic pulses based on the level of attention. For example, during the brainwave entrainment process, the subject may become bored, lose focus, fall asleep, or otherwise not pay attention to the acoustic pulses. Not paying attention to the acoustic pulses may reduce the effectiveness of the brainwave entrainment process and result in neurons oscillating at a different frequency than the desired modulation frequency of the acoustic pulses.

[0329] The NSS (905) can detect the level of attention that the subject is directing to the acoustic pulse using the feedback monitor (935) and one or more feedback components (960). In response to determining that the subject is not paying a sufficient amount of attention to the acoustic pulse, the audio adjustment module (915) can modify parameters of the audio signal to attract the subject's attention. For example, the audio adjustment module (915) can increase the amplitude of the acoustic pulse, adjust the tone of the acoustic pulse, or change the duration of the acoustic pulse. The audio adjustment module (915) can randomly vary one or more parameters of the acoustic pulse. The audio adjustment module (915) can initiate an attention-seeking audio sequence configured to restore the subject's attention. For example, the audio sequence can include changes in frequency, tone, amplitude, or the insertion of words or music in a predetermined, random, or pseudo-random pattern. The attention-seeking audio sequence can enable or disable different audio sources if the audio signaling component (950) includes multiple audio sources or speakers. Thus, the audio adjustment module (915) can interact with the feedback monitor (935) to determine the level of attention the subject is giving to the acoustic pulse, and adjust the acoustic pulse to regain the subject's attention if the level of attention falls below a threshold.

[0330] In some embodiments, the audio adjustment module (915) can modify or adjust one or more parameters of the acoustic pulses or waves at predetermined time intervals (e.g., every 5, 10, 15, or 20 minutes) to restore or maintain the subject's level of attention.

[0331] In some embodiments, the NSS (905) (e.g., via the unwanted frequency filtering module (920)) can filter, block, attenuate, or remove unwanted auditory extraneous stimuli. Unwanted auditory extraneous stimuli can include, for example, undesirable modulation frequencies, undesirable intensities, or undesirable wavelengths of sound waves. The NSS (905) can consider a modulation frequency of a pulse train to be undesirable if it differs or differs substantially (e.g., by 1%, 2%, 5%, 10%, 15%, 20%, 25%, or more than 25%) from a desired frequency.

[0332] For example, a desired modulation frequency for EEG entrainment may be 40 Hz. However, a modulation frequency of 20 Hz or 80 Hz may reduce the beneficial effects on brain cognitive function, brain cognitive state, immune system, or inflammation that may result from EEG entrainment at other frequencies, such as 40 Hz. Thus, the NSS (905) may filter acoustic pulses corresponding to a modulation frequency of 20 Hz or 80 Hz.

[0333] In some embodiments, the NSS (905) can detect, via the feedback component (960), that there is an acoustic pulse from an ambient noise source that corresponds to an undesired modulation frequency of 20 Hz. The NSS (905) can further determine a wavelength of an acoustic wave of the acoustic pulse that corresponds to the undesired modulation frequency. The NSS (905) can instruct the filtering component (955) to filter the wavelength that corresponds to the undesired modulation frequency.

[0334] Nerve stimulation with multiple stimulation modes FIG. 16 is a block diagram illustrating a system for neural stimulation with multiple stimulation modes, according to an embodiment. The system (1600) can include a neural stimulation orchestration system ("NSOS") (1605). The NSOS (1605) can provide multiple stimulation modes. For example, the NSOS (1605) can provide a first stimulation mode including visual stimulation and a second stimulation mode including auditory stimulation. For each stimulation mode, the NSOS (1605) can convey certain types of signals. For example, for a visual mode of stimulation, the NSOS (1605) can convey the following types of signals: light pulse, image pattern, ambient light flicker, or augmented reality. The NSOS (1605) can facilitate integrating, managing, controlling, or otherwise providing multiple stimulation modes and stimulation types.

[0335] In a brief overview, the NSOS (1605) may include, access, interface with, or otherwise communicate with one or more of a stimulus orchestration component (1610), a subject evaluation module (1650), a data repository (1615), one or more signaling components (1630a-n), one or more filtering components (1635a-n), one or more feedback components (1640a-n), and one or more neural stimulation systems ("NSS") (1645a-n). The data repository (1615) may include or store a profile data structure (1620) and a policy data structure (1625). The stimulus orchestration component (1610) and the subject evaluation module (1650) may include modules configured to communicate with at least one processing unit or other logic device, such as a programmable logic array engine, or a database repository (1615). The stimulus orchestration component (1610) and the subject evaluation module (1650) may be a single component, may comprise separate components, or may be part of the NSOS (1605). The system (1600) and its components, such as the NSOS (1605), may comprise hardware elements, such as one or more processors, logic devices, or circuits. The system (1600) and its components, such as the NSOS (1605), may comprise one or more hardware or interface components shown in the system (700) of Figures 7A and 7B. For example, the components of the system (1600) may include or execute on one or more processors (721), access a storage device (728) or memory (722), and communicate via a network interface (718). The system (1600) may include one or more components or functions shown in Figures 1-15, including, for example, the system (100), the system (900), the visual NSS (105), or the auditory NSS (905).For example, at least one of the signaling components (1630a-n) may include one or more components or functions of a visual signaling component (150) or an audio signaling component (950). At least one of the filtering components (1635a-n) may include one or more components or functions of a filtering component (155) or a filtering component (955). At least one of the feedback components (1640a-n) may include one or more components or functions of a feedback component (160) or a feedback component (960). At least one of the NSSs (1645a-n) may include one or more components or functions of a visual NSS (105) or an auditory NSS (905).

[0336] Further referring to FIG. 16, in more detail, the NSOS (1605) can include at least a stimulation orchestration component (1610). The stimulation orchestration component (1610) can be designed and constructed to perform neural stimulation using multiple stimulation modalities. The stimulation orchestration component (1610) or the NSOS (1605) can interface with at least one of the signaling components (1630a-n), at least one of the filtering components (1635a-n), or at least one of the feedback components (1640a-n). One or more of the signaling components (1630a-n) can be the same type of signaling component or different types of signaling components. The type of signaling component can correspond to a mode of stimulation. For example, the multiple types of signaling components (1630a-n) can correspond to visual signaling components or auditory signaling components. In some cases, at least one of the signaling components (1630a-n) includes a visual signaling component (150), such as a light source, an LED, a laser, a tablet computing device, or a virtual reality headset. At least one of the signaling components includes an audio signaling component (950), such as a headphone, a speaker, a cochlear implant, or an air jet.

[0337] One or more of the filter components (1635a-n) may be the same type of filter components or different types of filter components. One or more of the feedback components (1640a-n) may be the same type of feedback components or different types of feedback components. For example, the feedback components (1640a-n) may include an electrode, a dry electrode, a gel electrode, a saline-soaked electrode, an adhesive-based electrode, 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 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.

[0338] The stimulus orchestration component (1610) may include or be configured with interfaces for communicating with different types of signaling components (1630a-n), filtering components (1635a-n), or feedback components (1640a-n). The NSOS (1605) or the stimulus orchestration component (1610) may interface with a system intermediary to one of the signaling components (1630a-n), filtering components (1635a-n), or feedback components (1640a-n). For example, the stimulus orchestration component (1610) may interface with the visual NSS (105) shown in FIG. 1 or the auditory NSS (905) shown in FIG. 9. Thus, in some embodiments, the stimulus orchestration component (1610) or the NSOS (1605) may indirectly interface with at least one of the signaling components (1630a-n), the filtering components (1635a-n), or the feedback components (1640a-n).

[0339] The stimulus orchestration component (1610) (e.g., via an interface) can ping each of the signaling components (1630a-n), filtering components (1635a-n), and feedback components (1640a-n) to determine information about the component. The information can include the type of component (e.g., visual, auditory, attenuator, optical filter, temperature sensor, or light sensor), the configuration of the component (e.g., frequency range, amplitude range), or status information (e.g., standby, ready, online, enabled, error, fault, offline, disabled, warning, service needed, availability, or battery level).

[0340] The stimulus orchestration component (1610) can command or cause at least one of the signaling components (1630a-n) to generate, send, or otherwise convey a signal that can be perceived, received, or observed by the brain and affect the frequency of neural oscillations in at least one region or portion of the subject's brain. The signal can be perceived through a variety of means, including, for example, the optical nerve or cochlear cells.

[0341] The stimulus orchestration component (1610) can access the data repository (1615) to obtain profile information (1620) and policies (1625). The profile information (1620) can include profile information (145) or profile information (945). The policies (1625) can include multimodal stimulation policies. The policies (1625) can indicate a multimodal stimulation program. The stimulus orchestration component (1610) can apply the policies (1625) to the profile information to determine a type of stimulation (e.g., visual or auditory) and values ​​for parameters of each type of stimulation (e.g., amplitude, frequency, wavelength, color, etc.). The stimulus orchestration component (1610) can apply a policy (1625) to the profile information (1620) and feedback information received from one or more feedback components (1640a-n) to determine or adjust a type of stimulus (e.g., visual or auditory) and to determine or adjust a parameter value for each type of stimulus (e.g., amplitude, frequency, wavelength, color, etc.). The stimulus orchestration component (1610) can apply a policy (1625) to the profile information to determine a type of filter to be applied by at least one of the filtering components (1635a-n) (e.g., an audio filter or a visual filter) and to determine a parameter value for the type of filter (e.g., frequency, wavelength, color, sound attenuation, etc.). The stimulus orchestration component (1610) can apply a policy (1625) to the profile information and feedback information received from one or more feedback components (1640a-1640n) to determine or adjust the type of filter applied by at least one of the filtering components (1635a-1635n) (e.g., an audio filter or a visual filter) and to determine or adjust the value of a parameter of the filter (e.g., frequency, wavelength, color, sound attenuation, etc.).

[0342] The NSOS (1605) can obtain profile information (1620) via a subject evaluation module (1650). The subject evaluation module (1650) can be designed and constructed to determine information about one or more subjects that can facilitate neural stimulation via one or more stimulation modes. The subject evaluation module (1650) can receive, obtain, detect, determine, or otherwise identify information via feedback components (1640a-n), surveys, queries, questionnaires, prompts, remote profile information accessible via a network, diagnostic tests, or past treatments.

[0343] The subject evaluation module (1650) can receive information before initiating the neurostimulation, during the neurostimulation, or after the neurostimulation. For example, the subject evaluation module (1650) can prompt a request for information before initiating a neurostimulation session. The subject evaluation module (1650) can prompt a request for information during a neurostimulation session. The subject evaluation module (1650) can receive feedback from the feedback components (1640a-n) (e.g., an EEG probe) during the neurostimulation session. The subject evaluation module (1650) can prompt a request for information after the neurostimulation session is completed. The subject evaluation module (1650) can receive feedback from the feedback components (1640a-n) after the neurostimulation session is completed.

[0344] The subject evaluation module (1650) can use the information to determine the effectiveness of a stimulation modality (e.g., visual or auditory stimulation) or a type of signal (e.g., light pulses from a laser or LED light source, ambient light flicker, or an image pattern displayed by a tablet computing device). For example, the subject evaluation module (1650) can determine that a desired neural stimulation resulted from a first stimulation mode or first type of signal, but that the desired neural stimulation did not result or took longer to result from a second stimulation mode or second type of signal. The subject evaluation module (1650) can determine that the desired neural stimulation was less pronounced from the second stimulation mode or second type of signal compared to the first stimulation mode or first type of signal based on feedback information from the feedback components (1640a-n).

[0345] The subject evaluation module (1650) can determine the level of effectiveness of each stimulation mode or type independently or based on a combination of stimulation modes or types. A combination of stimulation modes can refer to sending signals from different stimulation modes at the same or substantially similar times. A combination of stimulation modes can refer to sending signals from different stimulation modes in an overlapping manner. A combination of stimulation modes can refer to sending signals from different stimulation modes in a non-overlapping manner but within a time interval of each other (e.g., sending a signal pulse train from a second stimulation mode within 0.5 seconds, 1 second, 1.5 seconds, 2 seconds, 2.5 seconds, 3 seconds, 5 seconds, 7 seconds, 10 seconds, 12 seconds, 15 seconds, 20 seconds, 30 seconds, 45 seconds, 60 seconds, 1 minute, 2 minutes, 3 minutes, 5 minutes, 10 minutes, or other time interval in which the effect of the first mode on the frequency of neural oscillations may overlap with the second mode).

[0346] The subject assessment module (1650) may aggregate or compile the information and update a profile data structure (1620) stored in the data repository (1615). In some cases, the subject assessment module (1650) may update or generate a policy (1625) based on the received information. The policy (1625) or profile information (1620) may indicate which mode or type of stimulation is likely to have a desired effect on the neurostimulation while reducing side effects.

[0347] The stimulus orchestration component (1610) can command or cause the multiple signaling components (1630a-n) to generate, transmit, or otherwise communicate different types of stimuli or signals according to the policy (1625), the profile information (1620), or feedback information detected by the feedback components (1640a-n). The stimulus orchestration component (1610) can cause the multiple signaling components (1630a-n) to generate, transmit, or communicate different types of stimuli or signals simultaneously or substantially simultaneously. For example, a first signaling component (1630a) can send a first type of stimulus at the same time that a second signaling component (1630b) sends a second type of stimulus. The first signaling component (1630a) can send or provide a first set of signals, pulses, or stimuli while the second signaling component (1630b) sends or sends a second set of signals, pulses, or stimuli. For example, a first pulse from a first signaling component (1630a) can begin simultaneously or substantially simultaneously (e.g., 1%, 2%, 3%, 4%, 5%, 6%, 7%, 10%, 15%, 20%) with a second pulse from a second signaling component (1630b). The first and second pulses can end simultaneously or substantially simultaneously. In another example, a first pulse train can be sent by a first signaling component (1630a) at the same or substantially similar time as a second pulse train sent by a second signaling component (1630b).

[0348] The stimulus orchestration component (1610) can cause multiple signaling components (1630a-n) to generate, transmit, or convey different types of stimuli or signals in an overlapping manner. The different pulses or pulse trains may overlap each other, but do not necessarily exist or terminate at the same time. For example, at least one pulse of a first set of pulses from a first signaling component (1630a) may at least partially overlap in time with at least one pulse of a second set of pulses from a second signaling component (1630b). For example, the pulses can straddle each other. In some cases, a first pulse train transmitted or sent by a first signaling component (1630a) may at least partially overlap with a second pulse train transmitted or sent by a second signaling component (1630b). The first pulse train can straddle the second pulse train.

[0349] The stimulus orchestration component (1610) can cause multiple signal transmission components (1630a-n) to generate, transmit or otherwise convey different types of stimuli or signals that are received, perceived or otherwise observed by one or more regions or portions of the brain simultaneously, contemporaneously or substantially simultaneously. The brain can receive different stimulation modes or signal types at different times. The duration between the transmission of a signal by the signal transmission components (1630a-n) and the reception or perception of the signal by the brain can vary based on the type of signal (e.g., visual, auditory), the parameters of the signal (e.g., wave speed or velocity, amplitude, frequency, wavelength), or the distance between the signal transmission components (1630a-n) and the nerve or cell of the subject configured to receive the signal (e.g., eye or ear). The stimulus orchestration component (1610) can offset or delay the transmission of the signals so that the brain perceives the different signals at desired times. The stimulus orchestration component (1610) can offset or delay the transmission of a first signal sent by a first signal transmission component (1630a) relative to the transmission of a second signal sent by a second signal transmission component (1630b). The stimulus orchestration component (1610) can determine the amount of offset of each type of signal or each signal transmission component (1630a-n) relative to a reference clock or signal. The stimulus orchestration component (1610) can be pre-configured or calibrated with the offset of each signal transmission component (1630a-n).

[0350] The stimulus orchestration component (1610) can determine to enable or disable an offset based on the policy (1625). For example, the policy (1625) can indicate to send multiple signals simultaneously, in which case the stimulus orchestration component (1610) can disable or not use an offset. In another example, the policy (1625) can indicate to send multiple signals such that multiple signals are perceived by the brain simultaneously, in which case the stimulus orchestration component (1610) can enable or use an offset.

[0351] In some embodiments, the stimulus orchestration component (1610) can stagger the signals sent by the different signaling components (1630a-n). For example, the stimulus orchestration component (1610) can stagger the signals such that pulses from the different signaling components (1630a-n) do not overlap. The stimulus orchestration component (1610) can stagger pulse trains from the different signaling components (1630a-n) such that they do not overlap. The stimulus orchestration component (1610) can set parameters for each mode of the stimulation or signaling components (1630a-n) such that the signals do not overlap.

[0352] Thus, the stimulus orchestration component (1610) can set parameters of signals sent by one or more signaling components (1630a-n) so that the signals are sent synchronously or asynchronously or perceived by the brain synchronously or asynchronously. The stimulus orchestration component (1610) can apply a policy (1625) to the available signaling components (1630a-n) to determine the parameters to be set for each signaling component (1630a-n) for synchronous or asynchronous transmission. The stimulus orchestration component (1610) can adjust parameters such as time delay, phase offset, frequency, pulse rate interval, or amplitude to synchronize the signals.

[0353] In some embodiments, the NSOS (1605) can adjust or change the mode of stimulation or the type of signal based on feedback received from the feedback components (1640a-n). The stimulation orchestration component (1610) can adjust the mode of stimulation or the type of signal based on feedback to the subject, feedback to the environment, or a combination of feedback to the subject and the environment. Feedback to the subject can include, for example, physiological information, temperature, level of attention, level of fatigue, activity (e.g., sitting, lying, walking, biking, or driving), visual ability, hearing ability, side effects (e.g., pain, migraine, tinnitus, or blindness), or frequency of neural oscillations in an area or portion of the brain (e.g., EEG probe). Feedback information regarding the environment can include, for example, ambient temperature, ambient light, ambient sound, battery information, or power source.

[0354] The stimulus orchestration component (1610) can determine to maintain or modify aspects of the stimulation therapy based on the feedback. For example, the stimulus orchestration component (1610) can determine that the neuron is not oscillating at a desired frequency in response to a first stimulation mode. In response to determining that the neuron is not oscillating at a desired frequency, the stimulus orchestration component (1610) can disable the first stimulation mode and enable a second stimulation mode. The stimulus orchestration component (1610) can also determine that the neuron is not oscillating at a desired frequency in response to a second stimulation mode (e.g., via the feedback component (1640a)). In response to determining that the neuron is still not oscillating at a desired frequency, the stimulus orchestration component (1610) can increase the amplitude of a signal corresponding to the second mode of stimulation. In response to the increase in the amplitude of the signal corresponding to the second mode of stimulation, the stimulus orchestration component (1610) can determine that the neuron is oscillating at a desired frequency.

[0355] The stimulus orchestration component (1610) can monitor the frequency of neural oscillations in a region or portion of the brain. The stimulus orchestration component (1610) can determine that neurons in a first region of the brain are oscillating at a desired frequency, but neurons in a second region of the brain are not oscillating at the desired frequency. The stimulus orchestration component (1610) can perform a search in the profile data structure (1620) to determine a mode of stimulation or a type of signal that maps to the second region of the brain. The stimulus orchestration component (1610) can compare the results of the search to a currently enabled stimulation mode and determine that a third mode of stimulation is more likely to cause neurons in the second region of the brain to oscillate at the desired frequency. In response to the determination, the stimulus orchestration component (1610) can identify a signaling component (1630a-n) configured to generate and send a signal corresponding to the selected third mode of stimulation, and can command or cause the identified signaling component (1630a-n) to send the signal.

[0356] In some embodiments, the stimulation orchestration component (1610) can determine, based on the feedback information, that a stimulation mode is likely to affect the frequency of neural oscillations or is unlikely to affect the frequency of neural oscillations. The stimulation orchestration component (1610) can select a stimulation mode from a plurality of stimulation modes that is most likely to affect the frequency of neural stimulation or is most likely to result in a desired frequency of neural oscillations. If the stimulation orchestration component (1610) determines, based on the feedback information, that a mode of stimulation is unlikely to affect the frequency of neural oscillations, the stimulation orchestration component (1610) can disable the mode of stimulation for a predetermined period of time or until the feedback information indicates that the mode of stimulation is enabled.

[0357] The stimulus orchestration component (1610) can select one or more modes of stimulation to conserve resources or minimize resource utilization. For example, the stimulus orchestration component (1610) can select one or more modes of stimulation to reduce or minimize power consumption when the power source is a battery or when the battery level is low. In another example, the stimulus orchestration component (1610) can select one or more modes of stimulation to reduce heating when the ambient temperature is above a threshold or the temperature of the subject is above a threshold. In another example, the stimulus orchestration component (1610) can select one or more modes of stimulation to increase the level of attention when the stimulus orchestration component (1610) determines that the subject is not focusing on the stimulation (e.g., based on eye tracking or undesirable frequencies of neural oscillations).

[0358] Visual and auditory neurostimulation 17A is a block diagram illustrating an embodiment of a system for neural stimulation by visual and auditory stimuli. The system (1700) may include an NSOS (1605). The NSOS (1605) may interface with a visual NSS (105) and an auditory NSS (905). The visual NSS (105) may interface or communicate with a visual signaling component (150), a filtering component (155), and a feedback component (160). The auditory NSS (905) may interface or communicate with an audio signaling component (950), a filtering component (955), and a feedback component (960).

[0359] To provide neurostimulation via visual and audio stimuli, the NSOS (1605) can identify the types of components available for a neurostimulation session. The NSOS (1605) can identify the type of visual signal that the visual signaling component (150) is configured to generate. The NSOS (1605) can also identify the type of audio signal that the audio signaling component (950) is configured to generate. The NSOS (1605) can be configured with respect to the types of visual and audio signals that the components (150 and 950) are configured to generate. The NSOS (1605) can ping the components (150 and 950) for information about the components (150 and 950). The NSOS (1605) can query the components, send SNMP requests, broadcast queries, or otherwise determine information about the available visual signaling components (150) and audio signaling components (950).

[0360] For example, the NSOS (1605) can determine that the following components are available for neural stimulation: the visual signaling component (150) includes a virtual reality headset 401 as shown in FIG. 4C; the audio signaling component (950) includes a speaker (1205) as shown in FIG. 12B; the feedback component (160) includes an ambient light sensor (605), an eye tracking device (605), and an EEG probe as shown in FIG. 4C; the feedback component (960) includes a microphone (1210) and a feedback sensor (1225) as shown in FIG. 12B; and the filtering component (955) includes a noise cancellation component (1215). The NSOS (1605) can further determine the absence of a filtering component (155) communicatively coupled to the visual NSS (105). The NSOS (1605) can determine the presence (available or online) or absence (offline) of components via the visual NSS (105) or the auditory NSS (905). The NSOS (1605) can further obtain an identifier for each of the available or online components.

[0361] The NSOS (1605) can perform a search in a profile data structure (1620) using an identifier of the subject to identify one or more types of visual and audio signals to communicate to the subject. The NSOS (1605) can perform a search in a profile data structure (1620) using an identifier of the subject and each online component to identify another type of visual and audio signals to communicate to the subject. The NSOS (1605) can perform a search in a policy data structure (1625) using an identifier of the subject to obtain a policy for the subject. The NSOS (1605) can perform a search in a policy data structure (1625) using an identifier of the subject and each online component to identify a policy of a type of visual and audio signals to communicate to the subject.

[0362] FIG. 17B illustrates waveforms used for neural stimulation via visual and auditory stimuli, according to an embodiment. FIG. 17B illustrates an example sequence or set of sequences (1701) that can be generated by the stimulus orchestration component (1610) or can be generated by one or more visual signaling components (150) or audio signaling components (950). The stimulus orchestration component (1610) can retrieve the sequences from a data structure stored in the data repository (1615) of the NSOS (1605) or a data repository corresponding to the NSS (105) or NSS (905). The sequences can be stored in a tabular format, such as Table 1 below. In some embodiments, the NSOS (1605) can select predefined sequences to generate a set of sequences for a therapy session or period, such as the set of sequences in Table 1. In some embodiments, the NSOS (1605) can obtain a set of predefined or preconfigured sequences. In some embodiments, the NSOS (1605) can construct or generate a set of sequences or each sequence based on information obtained from the subject evaluation module (1650). In some embodiments, the NSOS (1605) can remove or delete sequences from the set of sequences based on feedback, such as adverse side effects. The NSOS (1605), via the subject evaluation module (1650), can include sequences that are more likely to stimulate neurons in a given region of the brain to oscillate at a desired frequency.

[0363] Based on the profile information, policies, and available components, the NSOS (1605) can determine to provide neural stimulation using both visual and auditory signals using the following sequence shown in exemplary Table 1:

[0364] [Table 1]

[0365] Each waveform sequence can include one or more characteristics such as a sequence identifier, a mode, a type of signal, one or more signal parameters, a modulation or stimulation frequency, and a timing schedule, as shown in Table 1. As shown in FIG. 17B and Table 1, the sequence identifiers are (1755, 1760, 1765, 1765, 1770, 1775, and 1760).

[0366] The stimulus orchestration component (1610) can receive characteristics of each sequence. The stimulus orchestration component (1610) can send, configure, load, command, or otherwise communicate the sequence characteristics to the signaling components (1630a-n). In some embodiments, the stimulus orchestration component (1610) can provide the sequence characteristics to the visual NSS (105) or the auditory NSS (905), while in some cases, the stimulus orchestration component (1610) can provide the sequence characteristics directly to the visual signaling component (150) or the audio signaling component (950).

[0367] The NSOS (1605) can determine from the data structure of Table 1 that the mode of stimulation for the sequences (1755, 1760, and 1765) is visual by parsing the table to identify the mode. In response to determining that the mode is visual, the NSOS (1605) can communicate information or characteristics associated with the sequences (1755, 1760, and 1765) to the visual NSS (105). The NSS (105) (e.g., via the light generation module (110)) can analyze the sequence characteristics and then instruct the visual signaling component (150) to generate and send a corresponding visual signal. In some embodiments, the NSOS (1605) can directly instruct the visual signaling component (150) to generate and send a visual signal corresponding to the sequences (1755, 1760, and 1765).

[0368] The NSOS (1605) can determine from the data structure of Table 1 that the mode of stimulation of the sequences (1770, 1775, and 1780) is audio by parsing the table to identify the mode. In response to determining that the mode is audio, the NSOS (1605) can communicate information or characteristics associated with the sequences (1770, 1775, and 1780) to the auditory NSS (905). The NSS (905) (e.g., via the light generation module (110)) can analyze the sequence characteristics and then instruct the audio signaling component (950) to generate and send a corresponding audio signal. In some embodiments, the NSOS (1605) can directly instruct the visual signaling component (150) to generate and send a visual signal corresponding to the sequences (1770, 1775, and 1780).

[0369] For example, the first sequence (1755) may include a visual signal. The type of signal may include a light pulse (235) generated by a light source (305) including a laser. The light pulse may include a light wave having a wavelength corresponding to the red color of the visible spectrum. The intensity of the light may be set low. The low intensity level may correspond to a low contrast ratio (e.g., relative to the ambient light level) or a low absolute intensity. The pulse width of the light burst may correspond to the pulse width (230a) shown in FIG. 2C. The stimulation frequency may be 40 Hz or may correspond to a pulse rate interval ("PRI") of 0.025 seconds. The first sequence (1655) may run from t0 to t8. The first sequence (1655) may run for the duration of a session or treatment. The first sequence (1655) may run while one or more other sequences are running others. The time interval may refer to an absolute time, a period, a number of cycles, or other events. The time interval from t0 to t8 can be, for example, 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 7 minutes, 10 minutes, 12 minutes, 15 minutes, 20 minutes, or more or less. The time interval can be shortened or terminated by the subject or in response to feedback information. The time interval can be adjusted by the subject based on profile information or via an input device.

[0370] The second sequence (1760) can be another visual signal beginning at t1 and ending at t4. The second sequence (1760) can include a signal type of a checkerboard image pattern presented by a display screen of the tablet. The signal parameters can include black and white colors such that the checkerboard pattern alternates between black and white squares. The intensity can be high, which can correspond to a high contrast ratio to the ambient light. Or, there can be high contrast between objects in the checkerboard pattern. The pulse width of the checkerboard pattern can be the same as the pulse width (230a) as in sequence (1755). The sequence (1760) can start and end at different times than the sequence (1755). For example, the sequence (1760) can start at t1, which can be offset by more or less than 5 seconds, 10 seconds, 15 seconds, 20 seconds, 20 seconds, 30 seconds, 1 minute, 2 minutes, or 3 minutes from t0. The visual signaling component (150) can begin a second sequence (1760) at t1 and end the second sequence at t4, such that the second sequence (1760) can overlap with the first sequence (1755).

[0371] Pulse trains or sequences 1755 and 1760 can overlap one another, but the pulses (235) of the second sequence (1760) do not have to overlap with the pulses (235) of the first sequence (1755). For example, the pulses (235) of the second sequence (1760) can be offset from the pulses (235) of the first sequence (1755) so that they do not overlap.

[0372] The third sequence (1765) can include a visual signal. The type of signal can include ambient light modulated by an actuated shutter configured in a frame (e.g., frame (400) shown in FIG. 4B). The pulse width can vary from 230c to 230a in the third sequence (1765). The stimulation frequency can still be 40Hz, such that the PRI is the same as the PRI of sequences (1760 and 1755). The pulse (235) of the third sequence (1765) can at least partially overlap with the pulse (235) of sequence (1755), but may not overlap with the pulse (235) of sequence (1760). Furthermore, the pulse (235) can refer to blocking ambient light or allowing ambient light to be perceived by the eye. In some embodiments, the pulse (235) can correspond to blocking ambient light, in which case the laser light pulse (1755) can appear to have a higher contrast ratio. In some cases, pulse (235) of sequence (1765) may correspond to allowing ambient light to enter the eye, in which case the contrast ratio of pulse (235) of sequence (1755) may be lower, reducing adverse side effects.

[0373] The fourth sequence (1770) can include an auditory stimulation mode. The fourth sequence (1770) can include an up-chirp pulse (1035). The audio pulse can be provided through headphones or speakers (1205) of FIG. 12B. For example, the pulse (1035) can correspond to modulating music played by an audio player (1220) as shown in FIG. 12B. The modulation can include an M a ~M c The modulation can refer to modulating the amplitude of the music. The amplitude can refer to the volume. Thus, the NSOS (1605) modulates the volume level M for the duration PW1030a. a From volume level M cThe audio signaling component (950) can be instructed to increase the volume at t3 during the pulse (1035) and then return the volume to a baseline or mute level during the pulse (1035). The PRI (240) can be 025 or can correspond to a stimulation frequency of 40 Hz. The NSOS (1605) can instruct the fourth sequence (1770) to begin at t3, which overlaps with the visual stimulation sequences (1755, 1760, and 1765).

[0374] The fifth sequence (1775) can include another auditory stimulation mode. The fifth sequence (1775) can include an acoustic burst. The acoustic burst can be provided by the headphones or speaker (1205) of FIG. 12B. The sequence (1775) can include a pulse (1035). The pulse (1035) can vary from one pulse to another in the sequence. The fifth waveform (1775) can be configured to refocus the subject to increase the subject's level of attention to the neural stimulation. The fifth sequence (1775) can increase the subject's level of attention by varying a parameter of the signal from one pulse to the other. The fifth sequence (1775) can vary the frequency from one pulse to the other. For example, the first pulse (1035) of the sequence (1775) can have a higher frequency than the previous sequence. The second pulse can be an up-chirp pulse with a frequency that increases from a low frequency to a high frequency. The third pulse can be a sharper up-chirp pulse with a frequency that increases from an even lower frequency to the same high frequency. The fifth pulse can have a low stable frequency. The sixth pulse can be a down-chirp pulse that goes from a high frequency to the lowest frequency. The seventh pulse can be a high frequency pulse with a small pulse width. The fifth sequence (1775) can be at t4 and end at t7. The fifth sequence can overlap with sequence (1755) and partially overlap with sequences (1765 and 1770). The fifth sequence can be non-overlapping with sequence (1760). The stimulation frequency can be 39.8 Hz.

[0375] The sixth sequence (1780) can include an auditory stimulation mode. The type of signal can include pressure or air delivered by an air jet. The sixth sequence can begin at t6 and end at t8. The sixth sequence (1780) can overlap with sequence (1755) and can partially overlap with sequences (1765 and 1775). The sixth sequence (1780) can end the neurostimulation session with the first sequence (1755). The air jet can be a high pressure M c From low pressure M a A pulse (1035) having a pressure in the range of 1000 Hz may be applied. The pulse width may be 1030a and the stimulation frequency may be 40 Hz.

[0376] The NSOS (1605) can adjust, change, or otherwise modify the sequence or pulses based on the feedback. In some embodiments, the NSOS (1605) can determine to provide neural stimulation using both visual and audio signals based on the profile information, policies, and available components. The NSOS (1605) can determine to synchronize the transmission times of the first visual pulse train and the first audio pulse train. The NSOS (1605) can send the first visual pulse train and the first audio pulse train for a first duration (e.g., 1 minute, 2 minutes, or 3 minutes). At the end of the first duration, the NSOS (1605) can ping the EEG probe to determine the frequency of neural oscillations in the brain region. If the oscillation frequency is not the desired oscillation frequency, the NSOS (1605) can select an out-of-order sequence or change the timing schedule of the sequence.

[0377] For example, the NSOS (1605) may ping the feedback sensor at t1. The NSOS (1605) may determine that the neurons of the primary visual cortex are oscillating at a desired frequency at t1. Thus, the NSOS (1605) may determine to cease transmitting sequences (1760 and 1765) because the neurons of the primary visual cortex are already oscillating at a desired frequency. The NSOS (1605) may determine to disable sequences (1760 and 1765). The NSOS (1605) may disable sequences (1760 and 1765) in response to the feedback information. The NSOS (1605) may modify flags in a data structure corresponding to Table 1 to indicate that sequences (1760 and 1765) have been disabled in response to the feedback information.

[0378] The NSOS (1605) can receive feedback information at t2. At t2, the NSOS (1605) can determine that a frequency of neural oscillations in the primary visual cortex differs from a desired frequency. In response to determining the difference, the NSOS (1605) can enable or re-enable a sequence (1765) to stimulate neurons in the primary visual cortex such that the neurons may oscillate at a desired frequency.

[0379] Similarly, the NSOS (1605) can enable or disable the auditory stimulation sequences (1770, 1775, and 1780) based on feedback related to the auditory cortex. In some cases, the NSOS (1605) can determine to disable all audio stimulation sequences if the visual sequences (1755) are normally affecting the frequency of neural oscillations in the brain at each time period t1, t2, t3, t4, t5, t6, t7, and t8. In some cases, the NSOS (1605) can determine that the subject is not paying attention at t4 and proceed from only directly enabling the visual sequences (1755) to enabling the audio sequences (1755) and refocus the user using a different stimulation mode.

[0380] Method for neurostimulation by visual and auditory stimuli - Patent Application 20070123333 FIG. 18 is a flow diagram of a method for neural stimulation with visual and auditory stimuli, according to an embodiment. The method (180) may be performed by one or more systems, components, modules, or elements shown in FIGS. 1-17B, including, for example, a neural stimulation orchestration component or a neural stimulation system. In brief overview, the NSOS may identify a plurality of signal modes to provide in block (1805). In block (1810), the NSOS may generate and send identified signals corresponding to the plurality of modes. In (1815), the NSOS may receive or determine feedback related to neural activity, physiological activity, environmental parameters, or device parameters. In (1820), the NSOS may manage, control, or adjust one or more signals based on the feedback.

[0381] Although the present specification contains many specific implementation details, these should not be construed as limitations on the scope of any of the present disclosure or what may be claimed, but rather as descriptions of features specific to certain embodiments of certain aspects. Certain features described herein in the context of separate embodiments can also be implemented in combination in a single embodiment. Conversely, various features described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable subcombination. Furthermore, although features may be described above as acting in a particular combination, and even initially claimed as such, one or more features from a claimed combination may, in some cases, be deleted from the combination, and the claimed combination may be subject to a subcombination or a variation of the subcombination.

[0382] Similarly, although operations are shown in the figures in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown, or in sequential order, or that all of the operations shown be performed, to achieve desirable results. In certain situations, multitasking and parallel processing may be advantageous. Furthermore, the separation of various system components in the above-described embodiments should not be understood as requiring such separation in all embodiments, and it should be understood that the program components and systems described may generally be integrated into a single software product or packaged into multiple software products.

[0383] References to "or" may be construed as inclusive, such that any term listed using "or" may indicate either one, more than one, and all of the listed terms. Reference to at least one of a conjunctive list of terms may be construed as an inclusive OR, indicating either one, more than one, and all of the listed terms. For example, a reference to "at least one of 'A' and 'B'" may include only 'A', only 'B', and both 'A' and 'B'.

[0384] Thus, specific embodiments of the subject matter have been described. In some cases, the actions recited in the claims can be performed in a different order and still achieve desirable results. Further, the processes depicted in the accompanying figures do not necessarily require the particular order shown, or sequential order, to achieve desirable results.

[0385] The present technology, including any systems, methods, devices, components, modules, elements or functions described or illustrated in or associated with the drawings, can...

Claims

1. 1. A system for reducing the rate of brain atrophy in one or more regions of a subject's brain, the system comprising: a wearable device including one or more processors individually or collectively programmed to execute instructions including administering non-invasive stimulation to the subject to induce synchronous gamma oscillations in at least one region of the subject's brain, wherein administering reduces the rate of brain atrophy in one or more regions of the subject's brain, and wherein the reducing the rate of brain atrophy comprises reducing a rate of brain volume shrinkage in the brain of the subject.

2. The system of claim 1 , wherein the non-invasive stimulation comprises one or more stimulation waveforms.

3. The system of claim 2 , wherein the one or more stimulus waveforms include a visual stimulus waveform, an auditory stimulus waveform, a tactile stimulus waveform, a mechanical stimulus waveform, or a combination thereof.

4. The system of claim 2 or 3, wherein the one or more stimulation waveforms have synchronous phases.

5. The system of any one of claims 1 to 4, wherein administering the non-invasive stimulation includes administering the non-invasive stimulation for a first duration.

6. The system of claim 5, wherein the instructions further include measuring the subject's response to the non-invasive stimulus for a second duration.

7. The system of claim 6, wherein the first duration and the second duration are separated by a third duration.

8. A system described in any one of claims 1 to 7, wherein the non-invasive stimulation is delivered via a wearable device.

9. The system described in claim 8, wherein the wearable device includes glasses.

10. The system described in claim 8 or 9, wherein the wearable device includes a stimulation source.

11. The system described in claim 9 or 10, wherein the glasses include transparent glasses.

12. A system described in any one of claims 8 to 11, wherein the wearable device includes headphones.

13. A system described in any one of claims 1 to 12, wherein the instructions further include measuring the subject's response to the non-invasive stimulation.

14. The system of claim 13, wherein measuring the response is performed for a first duration.

15. The system of claim 13, wherein measuring the response is performed for a second duration.

16. The system described in claim 13, wherein measuring the response is performed for a third duration.

17. The system described in any one of claims 1 to 16, wherein the one or more regions of the brain include the visual cortex, the somatosensory cortex, the insular cortex, or any combination thereof.

18. A system described in any one of claims 1 to 17, wherein reducing the rate of brain atrophy includes reducing the rate of brain volume reduction.

19. The system of claim 18, wherein the rate of brain volume reduction comprises from about 0.3 cm 3 per year to about 2 cm 3 per year.

20. The system of claim 19, wherein the rate of reduction in brain volume includes the rate of change of total brain volume, white matter volume, gray matter volume, hippocampal volume, lateral ventricle volume, temporal lobe volume, occipital lobe volume, cerebral cortical volume, temporal cortical thickness, occipital cortical thickness, or any combination thereof.

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