Systems and methods for inverse binocular type stimulation

Abstract

Systems and methods for inverted binocular stimulation may include a device that determines a target frequency of a stimulation response. The device may output a first visual stimulus of a first frequency and a first phase to a first eye. The device may output a second visual stimulus of a second frequency and a second phase to a second eye. The first visual stimulus and the second visual stimulus together may produce a stimulus response at a target frequency.

Description

Cross Reference to Related Applications

[0001] This application claims priority to and the benefit of U.S. Patent Application No. 18 / 132,852, filed April 10, 2023, and granted as U.S. Patent No. 11,730,975, the contents of which are incorporated by reference in their entirety. Field of Disclosure

[0002] The present disclosure relates generally to neural stimulation. BACKGROUND

[0003] Neural oscillations occur in humans and animals, including rhythmic or repetitive neural activity in the central nervous system. Neural tissue can generate oscillatory activity through mechanisms within individual neurons or through interactions between neurons. Oscillations can manifest as periodic fluctuations in membrane potential or rhythmic patterns of action potentials, which can produce oscillatory activation of post-synaptic neurons. Synchronous activity of a group of neurons can give rise to macroscopic oscillations, which can be observed in the brain by using techniques such as electroencephalography (EEG), intracranial EEG (iEEG) (also known as electrocorticography (ECoG)), and magnetoencephalography (MEG) to sense electric or magnetic fields in the brain. SUMMARY

[0004] According to the systems and methods described herein, neural stimulation can be provided via counter-phased or interleaved binocular (e.g., dual eye) stimulation, where separate fields or stimuli are presented or provided to each eye. The systems and methods described herein can use counter-phased binocular (or dual eye) stimulation at a frequency less than a target frequency to produce or provide stimulation at the target frequency. To provide stimulation at a target frequency, some systems would simply output stimulation at the target frequency. For example, to provide stimulation at a target frequency of 40 Hz, some systems would output stimulation at 40 Hz. In contrast to such systems, it has been observed that providing counter-phased or interleaved dual eye stimulation at a reduced frequency, such as half of the target frequency, produces a greater stimulation response at the target frequency than providing stimulation at the target frequency, depending on the target frequency and other parameters of the stimulation. The stimulation can adjust, control, or otherwise affect the frequency of neural oscillations to provide beneficial effects to one or more cognitive states, cognitive functions, immune systems, or inflammation while mitigating or preventing adverse consequences to cognitive states or cognitive functions. For example, the stimulation response to the systems and methods of the present technology can treat, prevent, protect, or otherwise affect Alzheimer’s disease or other cognitive or neurological disorders.

[0005] In various cases where a patient is undergoing treatment or otherwise undergoing audio or visual stimulation (as described herein), often the stimulation is at a target or specific frequency or band (e.g., in the delta, theta, and / or gamma band) to stimulate a particular response in the patient’s brain (e.g., at a particular frequency and / or in a particular portion, region, or area of the patient’s brain). As described below, rather than producing stimulation at the target or specific frequency, the systems and methods described herein can provide anti-phase stimulation at a related or reduced frequency, which provides a combined effect of stimulating the brain at the target frequency due to the nonlinear response of neurons and networks in the brain. Such implementations and embodiments can produce a greater stimulation response in the patient’s brain at the target frequency, which can increase the efficacy of the treatment.

[0006] In one aspect, the disclosure relates to a method. The method includes determining, by a device, a target frequency of a stimulation response. The method includes outputting, by the device, a first visual stimulus of a first frequency and a first phase to a first eye. The method includes outputting, by the device, a second visual stimulus of a second frequency and a second phase to a second eye. The first visual stimulus and the second visual stimulus can together produce the stimulation response at the target frequency.

[0007] In some embodiments, the first frequency is half of the target frequency and the second frequency is half of the target frequency. In some embodiments, the second phase is anti-phase of the first phase. In some embodiments, the target frequency is between 35 Hz and 40 Hz. In some embodiments, the sum of the first frequency and the second frequency is equal to the target frequency. In some embodiments, the target frequency is equal to 38 Hz, the first frequency is equal to 19 Hz, and the second frequency is equal to 19 Hz.

[0008] In some embodiments, the device includes one or more first light sources to stimulate the first eye and one or more second light sources to stimulate the second eye. Outputting the first visual stimulus can include controlling the one or more first light sources to output light at the first frequency and the first phase. Outputting the second visual stimulus can include controlling the one or more second light sources to output light at the second frequency and the second phase. In some embodiments, the device includes a head-mounted device having the one or more first light sources located at a first location of the head-mounted device and the one or more second light sources located at a second location of the head-mounted device. The first location can correspond to stimulating the first eye when the head-mounted device is worn, and the second location can correspond to stimulating the second eye when the head-mounted device is worn.

[0009] In another aspect, the disclosure relates to a device. The device includes one or more light sources. The device includes one or more processors configured to determine a target frequency of a stimulus response, output a first visual stimulus to a first eye at a first frequency and a first phase, and output a second visual stimulus to a second eye at a second frequency and a second phase. The first visual stimulus and the second visual stimulus together can produce the stimulus response at the target frequency.

[0010] In some embodiments, the first frequency is half of the target frequency, the second frequency is half of the target frequency, and the second phase is an inverse of the first phase. In some embodiments, the target frequency is equal to 38 Hz, the first frequency is equal to 19 Hz, and the second frequency is equal to 19 Hz.

[0011] In yet another aspect, the disclosure relates to a system. The system includes one or more light sources. The system includes one or more processors configured to determine a target frequency of a stimulus response, output a first visual stimulus to a first eye at a first frequency and a first phase, and output a second visual stimulus to a second eye at a second frequency and a second phase. The first visual stimulus and the second visual stimulus together can produce the stimulus response at the target frequency. BRIEF DESCRIPTION OF DRAWINGS

[0012] The accompanying drawings are not intended to be drawn to scale. Wherever possible, the same reference numbers and designations are used throughout the various figures and the drawings. Not every component can be labeled in every figure. In some embodiments, the same reference numbers and designations are used throughout the various figures and drawings.

[0013] Figure 1 is a block diagram of a system for anti-phase binocular stimulation according to example embodiments of the disclosure.

[0014] Figure 2 depicts a first graph showing a target frequency and a second graph showing an oscillatory state for providing the target frequency according to example embodiments of the disclosure.

[0015] Figure 3 depicts an example of a head-mounted device for providing visual stimulation according to example embodiments of the disclosure.

[0016] Figure 4 depicts an example of a system for providing visual stimulation according to example embodiments of the disclosure.

[0017] Figure 5 depicts an illumination system that can be implemented in a system of Figure 4 according to example embodiments of the disclosure.

[0018] Figure 6A series of images are depicted that illustrate measured stimulus responses (actual) according to different visual stimulus inputs in patients, according to example embodiments of the present disclosure.

[0019] Figure 7 Another series of images are depicted that illustrate average stimulus responses across multiple patients according to different visual stimulus inputs, according to example embodiments of the present disclosure.

[0020] Figures 8A-8F A series of plots are depicted that illustrate power spectral density and gain for different types of input stimuli shown in Figure 6 and Figure 7 according to example embodiments of the present disclosure.

[0021] Figure 9 is a flowchart illustrating an example method of providing anti-biocular stimulation, according to example embodiments of the present disclosure.

[0022] Figure 10 is a block diagram of an example computer system, according to example embodiments of the present disclosure. DETAILED DESCRIPTION

[0023] Before turning to the drawings, it is understood that the disclosure is not limited to the details or methodology set forth in the description or illustrated in the figures. It is also understood that the terminology used herein is for the purpose of description only and should not be regarded as limiting.

[0024] According to the systems and methods described herein, neural stimulation can be provided via anti-biocular (or inverse, interleaved, etc.) binocular stimulation. The systems and methods described herein can use anti-biocular stimulation at a frequency different from (e.g., less than or greater than) a target frequency to produce or provide stimulation at the target frequency. To provide stimulation at a target frequency, some systems will simply output stimulation at the target frequency. For example, to provide stimulation at a target frequency of 40 Hz, some systems will output stimulation at 40 Hz. In contrast to such systems, it has been observed that providing anti-biocular or binocular stimulation at a related frequency (e.g., half of the target frequency) can produce a greater constructive stimulus response at the target frequency (e.g., when the binocular stimulation is constructive or combined) than providing stimulation at the target frequency (e.g., when the target frequency is close to the flicker fusion threshold). The stimulation can modulate, control, or otherwise affect the frequency of neural oscillations to provide beneficial effects to one or more cognitive states, cognitive functions, immune systems, or inflammation while mitigating or preventing adverse consequences to cognitive states or cognitive functions. For example, the stimulus response to the systems and methods of the present technology can treat, prevent, protect, or otherwise affect Alzheimer’s disease or other cognitive diseases.

[0025] In various cases where a patient is undergoing treatment or otherwise undergoing audio stimulation (as described herein), generally the stimulation is in a target or specific frequency or band (e.g., in the delta, theta, and / or gamma band) to stimulate a response in the patient’s brain and / or a particular portion of the patient’s brain. Rather than generating stimulation at a target or specific frequency as can be performed by some systems or solutions, the systems and methods described herein can provide stimulation at a related frequency that, due to the nonlinear response of neurons and networks in the brain, provides a combined effect of stimulation response at the target frequency. Such implementations and embodiments can produce a greater stimulation response at the target frequency in the patient’s brain, which can increase the efficacy of the treatment.

[0026] Neural oscillations can be characterized by their frequency, amplitude, and phase. These signal properties can be observed from neural recordings using time-frequency analysis. For example, EEG can measure oscillatory activity among a group of neurons, and the measured oscillatory activity can be classified into frequency bands as follows: delta activity corresponds to a frequency band of 0.5 Hz - 4 Hz; theta activity corresponds to a frequency band of 4 Hz - 8 Hz; alpha activity corresponds to a frequency band of 8 Hz - 13 Hz; beta activity corresponds to a frequency band of 13 Hz - 30 Hz; and gamma activity corresponds to a frequency band of 30 Hz and above.

[0027] Neural oscillations in different frequency bands can be associated with cognitive states or cognitive functions such as perception, action, attention, reward, learning, and memory. Based on the cognitive state or cognitive function, neural oscillations in one or more frequency bands can be involved. Furthermore, neural oscillations in one or more frequency bands can have a beneficial impact or adverse consequences on one or more cognitive states or functions.

[0028] Neural entrainment occurs when the brain perceives an external stimulus of a particular frequency or combination of frequencies and triggers neural activity in the brain that causes neurons to oscillate at a frequency related to the particular frequency of the external stimulus. Thus, neural entrainment can refer to the use of an external stimulus to synchronize neural oscillations in the brain such that the neural oscillations occur at a frequency corresponding to the particular frequency of the external stimulus. Neural entrainment can also refer to the use of an external stimulus to synchronize neural oscillations in the brain such that the neural oscillations occur at a frequency corresponding to a harmonic, subharmonic, integer ratio, and combination of the particular frequency of the external stimulus. In response to a set of external stimulus frequencies, a particular neural oscillation frequency can be observed. The neural oscillation frequency can arise from the nonlinear response of neurons and networks in the brain and can be predicted by models of neural oscillations and neural entrainment. The models can be based in part on Equation 1 below, which describes how a stimulus frequency relates to a target response frequency: Equation 1: , where m and k are equal to positive (or negative) integers, is equal to the response frequency, and to is equal to the stimulation frequency.

[0029] Cognitive functions such as learning and memory involve coordinated activity across distributed subcortical and cortical brain regions, including the hippocampus, cortical and subcortical association areas, sensory areas, and prefrontal cortex. At different brain regions, behaviorally relevant information is encoded, maintained, and retrieved through transient increases in the power of neural oscillations reflecting multiple activity frequencies and synchronization between these neural oscillations.

[0030] In particular, oscillatory neural activity in the theta and gamma bands is associated with encoding, maintenance, and retrieval processes during short-term memory, working memory, and long-term memory. Induced gamma activity is related to working memory, with increased occurrence of gamma-band activity recorded on the scalp and intracranially during working-memory maintenance. Increases in gamma activity power dynamically track the number of items maintained in working memory. Using electrocorticography (ECoG), one study found that working memory load, tracked by gamma power, was enhanced in the hippocampus and medial temporal lobe when participants maintained sequences of letters or faces in working memory. Finally, other evidence suggests that hippocampal gamma activity contributes to episodic memory, using different sub-gamma bands corresponding to encoding and retrieval phases.

[0031] Oscillations (4 Hz - 8 Hz) are related to working memory and episodic memory processes. Intracranial electroencephalography (iEEG) recordings indicate that theta oscillations gate on and gate off (i.e., increase and maintain amplitude, followed by a rapid decrease in amplitude) during encoding, maintenance, and retrieval phases during working memory. Other work observed an increase in scalp-recorded theta activity during working-memory maintenance. Some studies concluded that scalp-recorded theta activity from midline frontal electrodes is the strongest neural correlate of language working memory maintenance. In addition, midline frontal theta activity tracks working memory load, increasing and maintaining power according to the number of items maintained in working memory.

[0032] Some studies have found that gamma frequency auditory-visual stimulation can improve dementia or Alzheimer’s Disease (AD) related biomarkers and pathophysiology, and if administered during the early stages of disease progression, can provide neuroprotection. The systems and methods described herein can produce or provide frequency responses or oscillatory neural activity at various target frequencies, as described in more detail below. Such responses or oscillatory neural activity can provide treatment for or otherwise improve the effects of various cognitive diseases, such as any of those set forth herein (or any other cognitive disease).

[0033] Referring to Figure 1 A block diagram of a system 100 for anti-phase binocular stimulation, in accordance with example embodiments of the present disclosure, is depicted. The system 100 can include a control system 102 communicatively coupled to a plurality of light sources 104 (e.g., first and second light sources 104(1) and 104(2)) and an audio output device 106. The control system 102 can include an oscillation selection module (OSM) 108 and a brain rhythm stimulator (BRS) 110. As described in more detail below, the control system 102 can be configured to determine to output visual stimuli at target frequencies. The control system 102 can be configured to output a first visual stimulus at a first frequency and phase to a first eye (e.g., via the first light source 104(1)) and a second visual stimulus at a second frequency and phase to a second eye (e.g., via the second light source 104(2)).

[0034] The control system 102 can include an oscillation selection module (OSM) 108. The OSM 310 can be communicatively coupled to various other components or elements of the control system 102, such as various input / output devices, user interface devices, user profiles, processing components, or other components / elements / devices / hardware of the system, such as those described in more detail below. The OSM 310 can be configured to determine, select, or otherwise identify various oscillatory states for stimulating a patient. The oscillatory states can be or include target frequencies and various sub-oscillatory states for providing or implementing the target frequencies.

[0035] The OSM 108 can be configured to receive, detect, identify, or otherwise determine to output a visual stimulus at a target frequency. The target frequency can be or include a frequency within a frequency band, such as a delta, theta, and / or gamma frequency range or band. In some embodiments, the OSM 108 can be configured to receive user input (e.g., from a patient, from a therapy professional associated with the patient, etc.) that specifies, selects, or otherwise identifies the target frequency. In some embodiments, the OSM 108 can be configured to identify the target frequency based on a setting in a patient profile (e.g., a therapy plan that defines or sets a schedule of particular target frequencies at particular times of day). In some embodiments, the OSM 108 can be configured to identify the target frequency based on or from simulated responses to a given frequency (e.g., simulated brain responses to different input frequencies). For example, the OSM 108 can be configured to select the target frequency from among input frequencies based on which of the input frequencies results in the strongest simulated brain response.

[0036] The OSM 108 can be configured to determine, detect, or otherwise identify an oscillatory state for providing the target frequency. The oscillatory state can be defined as or include a frequency, amplitude, and phase that produces the visual stimulus at the corresponding frequency. In some embodiments, the OSM 108 can be configured to determine, select, or otherwise define an oscillatory state to provide a stimulus response at the target frequency. The frequency of the oscillatory state can be less than the target frequency. The OSM 108 can be configured to define an oscillatory state for a stimulus provided to each eye of the patient. The OSM 108 can be configured to define a first oscillatory state for providing a visual stimulus to one eye of the patient and a second oscillatory state for providing a visual stimulus to the other eye of the patient. The OSM 108 can be configured to define the oscillatory states to specify respective frequencies, amplitudes, and phases to produce the stimulus response at the target frequency. In this regard, the OSM 108 can be configured to select, determine, or otherwise define different oscillatory states for the respective eyes to produce the stimulus response in the patient’s brain based on a combined effect of the different oscillatory states.

[0037] Referring now to Figure 1 and Figure 2 together, the OSM 108 can be configured to define or set the oscillatory states to provide the target frequency response. Specifically, Figure 2 a first plot 200 showing a target frequency 202 and a second plot 204 showing oscillatory states 206, 208 of a stimulus waveform that provides a stimulus response at the target frequency. As shown, the oscillatory states 206, 208 can include one oscillatory state for one stimulus waveform provided to one eye and another oscillatory state for another stimulus waveform provided to the other eye.Figure 2 The target frequency shown is 40 Hz; however, it should be noted that the system and method described herein can be used for multiple frequencies in various frequency bands. For example, the target frequency can be 40 Hz (as shown in the figure), between 30 Hz and 40 Hz (such as between 35 Hz and 40 Hz or 38 Hz), between 13 Hz and 30 Hz, between 8 Hz and 13 Hz, between 4 Hz and 8 Hz, between 0.5 Hz and 4 Hz, or greater than 40 Hz.

[0038] like Figure 2 As shown, the OSM 108 can be configured to determine the oscillatory state of a first visual stimulus and the oscillatory state of a second visual stimulus different from the first visual stimulus, based on or according to an expected or target stimulus. The OSM 108 can be configured to determine the oscillatory state by selecting frequency, amplitude, and phase according to a target frequency (e.g., for each oscillatory state). The OSM 108 can be configured to determine the phase of the oscillatory states such that the oscillatory states are out of phase (or opposite to each other). The OSM 108 can be configured to determine the phase such that the oscillatory state of the first visual stimulus is out of phase / interleaved / opposite to the oscillatory state of the second visual stimulus. Figure 2 As shown, although the oscillation state 206 for the first visual stimulus and the oscillation state 208 for the second visual stimulus may have the same frequency, the corresponding signals may be out of phase / interleaved / opposite to each other, thereby producing a complementary combined effect.

[0039] In some embodiments, the OSM 108 can be configured to determine the frequency and amplitude of each oscillation state based on or according to a target frequency. The OSM 108 can be configured to determine the frequency and amplitude such that, when combined, the stimulus response is at the target frequency. Therefore, the frequency of each oscillation state can be less than the target frequency. The frequency of each oscillation state can be half the target frequency. For example, the OSM 108 can be configured to determine the frequency of one oscillation state to be equal to half the target frequency, and to determine the frequency of another oscillation state to be equal to half the target frequency. For example, in the case where the target frequency is between 35 Hz and 40 Hz, the OSM 108 can be configured to determine the frequency of each oscillation state to be equal to a frequency between 17.5 Hz and 20 Hz.

[0040] The control system 102 can include a brain rhythm stimulator (BRS) 110. The BRS 110 can be configured to generate, produce, or otherwise provide control signals for output devices (e.g., the light source 104 and / or the audio output device 106) based on the oscillatory state determined by the OSM 108 to provide audio and / or visual stimulation. The BRS 110 can be configured to use the oscillatory state to produce or provide visual stimulation at a selected frequency (or range of frequencies) via one or more output devices (e.g., the light source 104, the audio output device 106, etc.). In some embodiments, the BRS 110 can output rhythmic visual stimulation to the user. The BRS 110 can include a pattern buffer, a generation module, an adjustment module, and a filtering component, and can be operatively connected to the output devices for outputting the stimulation to the patient.

[0041] In some embodiments, the OSM 108 and the BRS 110 can be configured to determine, identify, or otherwise provide audio signals for synchronization with the visual stimulation. For example, the control system 102 can be configured to pre-process an auditory stimulus, auditory input, or audio signal to provide a multi-channel rhythmic input (e.g., a note onset). In some embodiments, the auditory input or audio signal is provided by the control system 102, such as by or via a built-in audio playback system that has access to a library of songs and / or other musical works. In some embodiments, the system 102 can also include a graphical display and input / output accessible to the user (e.g., the patient or a therapist) to allow the user to select from the library for playback. In other embodiments, in addition to or as an alternative to the built-in audio playback system, the control system 102 can include an auxiliary audio input to allow the system to receive input from a secondary playback system, such as a personal music playback device (e.g., an iPod, an MP3 player, a smart phone, etc.). In some embodiments, in addition to or as an alternative to the above-described auditory input, the system 102 can include a microphone or similar device to allow the system 102 to receive auditory input from ambient sounds, such as a live music performance or a broadcast of music from an auxiliary speaker (such as a user's home stereo system). In embodiments in which the system receives the audio signal through a built-in playback system or an auxiliary input (e.g., through an MP3 player), the system can also include headphones or integrated speakers to allow the listener to hear the audio signal 102 in real time.

[0042] The OSM 108 can be configured to select the most salient oscillations from the audio signal for configuring, selecting, or otherwise determining the oscillatory state of the visual stimulus for synchronization with the audio stimulus. In some embodiments, the OSM 108 can couple the visual frequency stimulus to the beat and rhythmic structure of the music. The OSM 108 can select variable, music-based frequencies in the delta, theta, and gamma ranges for visual stimulation of the user that is synchronized to the audio stimulus described herein. In some embodiments, the OSM 108 can modulate a visual signal at a particular frequency to produce a visual stimulus that is synchronized to the audio signal. For example, the OSM 108 can amplitude modulate a beta or gamma frequency visual signal at a theta frequency (and / or at various other frequencies, such as a delta frequency) derived or determined from the music rhythm. The BRS 110 can be configured to generate, produce, or otherwise provide control signals for the output devices (e.g., Figure 1 light source 104 and / or audio output device 106) based on data from the OSM 108 to provide the audio and / or visual stimulus. In some embodiments, the BRS 110 can be configured to use simulated neural oscillations to synchronize visual stimuli in selected frequency ranges with the rhythm of the music via the output devices (e.g., the audio output device 106). In some embodiments, the BRS 110 can also interface with a profile manager that stores data related to one or more users or patients. Thus, in some embodiments, the information stored by the profile manager can also include preferences for previously captured or user-selected patterns, waveforms, or other stimulus parameters, such as a user / patient preferred color.

[0043] Reference is now made to Figures 3-5 FIG. 1 depicts an example of an output device for providing visual stimulation in accordance with example embodiments of the present disclosure. Specifically, in accordance with example embodiments of the present disclosure, the output device 100 can be configured to provide visual stimulation to a user in synchronization with an audio stimulus. In some embodiments, the output device 100 can be configured to provide visual stimulation to a user in synchronization with an audio stimulus that is music. In some embodiments, the output device 100 can be configured to provide visual stimulation to a user in synchronization with an audio stimulus that is music and / or a voice. Figure 3 FIG. 2 depicts an example of a head-mounted device 300 for providing visual stimulation in accordance with example embodiments of the present disclosure, Figure 4 FIG. 3 depicts an example of a system 400 for providing visual stimulation in accordance with example embodiments of the present disclosure, and Figure 5 FIG. 4 depicts Figure 4The output device can be communicatively coupled to the control system 102 described above. In some embodiments, the control system 102 can be implemented on or incorporated into the output device. For example, the control system 102 can reside on the head-mounted device 300 and communicate with the light sources 104(1), 104(2) and / or the audio output device 106 to deliver the audio / visual stimuli locally to the patient. In some embodiments, the control system 102 can be remotely located and communicatively (e.g., wirelessly) coupled to the output device. For example, the control system 102 can reside on a cloud-based server, a computing device (e.g., a remote or local device), etc., and deliver wireless signals to the light sources 104 and / or the audio output device 106.

[0044] With specific reference now to Figure 3 The output device for providing the audio / visual stimuli can include a head-mounted device. The head-mounted device can include augmented reality glasses, virtual reality goggles, etc. The display of the head-mounted device can present the visual pattern to the user. For example, in the case that the head-mounted device includes augmented reality glasses, the augmented reality glasses can augment the user's environment visible through the glasses with the visual pattern. As another example, in the case that the head-mounted device includes virtual reality goggles (or other non-AR goggles), the goggles can display the visual pattern on a display proximate to the patient's eyes. In some embodiments, the display of the head-mounted device can display separate visual patterns on each of the patient's eyes and at different angles to provide the visual stimuli to the patient.

[0045] The head-mounted device 300 can include light sources 104(1), 104(2) for delivering light into each of the patient's respective eyes. The light sources 104 can be light sources corresponding to various displays (or display devices) of the head-mounted device 300. For example, the display devices can include a plurality of light sources, at least some of which are used to deliver light into each of the patient's respective eyes. The head-mounted device 300 can include a light source 104 for each eye. For example, one light source 104(1) can be dedicated to a particular eye (e.g., a first light source 104(1) can be dedicated to the patient's right eye, and a second light source 104(2) can be dedicated to the patient's left eye). The light sources 104 can be disposed on or along an interior-facing portion of the head-mounted device 300 to deliver, direct, or otherwise output light toward and / or at the patient's eyes (when the head-mounted device 300 is worn by the patient). In some embodiments, the light sources 104 can include light-emitting diodes (LEDs) or other types or forms of lights. The light sources 104 can be configured or capable of outputting light of various colors / brightness / rhythmic frequencies, etc.

[0046] The head-mounted device 300 can include one or more audio output devices 106. In some embodiments, the head-mounted device 300 can include a single audio output device 106 arranged to produce or output a binaurally perceptible audio signal. For example, the audio output device 106 can include a speaker or speaker system. In some embodiments, the head-mounted device 300 can include multiple audio output devices 106 arranged at various locations of the head-mounted device 300. For example, the head-mounted device 300 can include earbuds, positioning speakers, etc. arranged to produce or output respective audio signals perceptible by one of the patient’s ears (e.g., a left speaker or earbud for the left ear, and a right speaker or earbud for the right ear).

[0047] With specific reference Figure 4 and Figure 5 , in accordance with example implementations of the present disclosure, the output device for providing audio / visual stimuli can include an audio / visual system 400 including separate illumination systems 402(1), 402(2). The illumination systems 402 can be or include a visual stimulus ring 500 as shown in Figure 5 , where the visual stimulus ring includes a plurality of LED lights 702 operably connected to the system 100. In some embodiments, as shown in Figure 4 , the system 400 can include a dedicated illumination system 400 (or visual stimulus ring 500) for each eye of the patient. For example, the illumination systems 402(1), 402(2) can be positioned in front of the participant or patient (e.g., on respective sides of the participant or patient). The patient can focus in the center of the respective illumination system 402 (indicated by a cross 501 in Figure 5 ). To receive the counter-phase stimuli, the patient can be asked to focus between the centers of the respective illumination systems (e.g., shown as a median 404 in Figure 4 ). In some embodiments, the illumination systems 402 can be placed at an appropriate distance to stimulate the retina at a particular viewing angle. For example, the illumination systems 402 can be placed at an appropriate distance to stimulate the retina at a viewing angle between 0 and 15 degrees, or between 10 and 60 degrees, or between 15 and 50 degrees, or between 15 and 25 degrees, or between 18 and 22 degrees, or between 19 and 21 degrees. In some embodiments, the illumination systems 402 can be placed at an appropriate distance to stimulate the retina at a viewing angle of 20 degrees, at which the maximum density of rods is found in the retina.

[0048] While shown as a stimulus ring 500, various other output devices can be used as part of the system 100, with or in addition to the stimulus ring 500. For example, and in some embodiments, the vision system 402 can include a separate display, a single wide display with dedicated portions for the patient's left and right eyes, etc.

[0049] Reference is now made to Figure 6 and Figure 7 , Figure 6 a series of images depicting stimulus responses measured according to different visual stimulus inputs in a patient, Figure 7 a further series of images depicting average stimulus responses across multiple patients according to different visual stimulus inputs. In the leftmost column, stimulus responses measured at 20 Hz and 40 Hz, respectively, are depicted based on input visual stimulus of 40 Hz on both eyes. As shown, at 20 Hz, the measured response gain (in dB, e.g., 10log 10 (µV 2 ) is close to zero across the patient's entire brain. At 40 Hz, the measured stimulus response across the patient's entire brain is strong in many parts of the patient's brain (e.g., the front and back).

[0050] In the center column, stimulus responses measured at 20 Hz and 40 Hz, respectively, are depicted based on input visual stimulus of 20 Hz anti-phase (or inverse phase or interlaced) binocular split visual stimulus. As shown in the center column, the interlaced binocular split visual input stimulus produces a stronger response at 40 Hz across the brain when compared to the stimulus response to the 40 Hz input stimulus. In addition, as shown in the right column, due to the nonlinear response of neurons and networks in the brain, applying a 20 Hz stimulus to one eye (e.g., stimulus response depicted to 20 Hz applied to the right eye) produces a weak stimulus response at the 40 Hz harmonic. However, the 40 Hz response to the interlaced stimulus (middle) is much stronger than the simple harmonic response to the 20 Hz monocular stimulus (indicating constructive interaction between the interlaced binocular split visual stimulus), and the 20 Hz response to the interlaced stimulus (middle) is weaker than the response to the 20 Hz monocular stimulus (indicating some interference between the 20 Hz interlaced binocular split visual stimulus). These results are achieved on an individual basis (as shown in Figure 6 ) and across the entire patient population (as shown in Figure 7 ). Thus, it has been observed that 20 Hz interlaced stimulus produces a stronger stimulus response than 40 Hz stimulus.

[0051] Reference is now made to Figures 8A-8F a series of plots showing the above referenced Figure 6 and Figure 7Power spectral densities and gains of different types of input stimuli are shown and described. For electrodes posterior to the Cz electrode, the plots show the log power (in dB, e.g., 10 log 10 （µV 2 ） ) and gain (relative to the local mean) averaged over subjects, where the strongest responses to visual stimuli are expected to occur. Specifically, Figures 8A-8C Plots of power spectral densities of stimulus responses to 40 Hz (both eyes) input stimuli, 20 Hz interlaced (binocular split) input stimuli, 20 Hz input stimuli to one eye, respectively, are shown. Figures 8D-8F Plots of gains of stimulus responses to the same respective input stimuli shown in Figures 8A-8C are shown. As shown in Figure 8B and Figure 8E , the 20 Hz interlaced produces the strongest stimulus response at 40 Hz (as measured by both log power and gain) when compared to other input stimuli, but produces a weaker response at 20 Hz when compared to monocular stimuli. In addition, the 20 Hz interlaced (binocular split stimuli) has about 4 dB more power in the response than the 40 Hz stimuli (as shown in Figure 8B compared to Figure 8A ) and about 2.5 dB more gain than the 40 Hz stimuli (as shown in Figure 8F compared to Figure 8E ). Thus, the interlaced stimuli has been shown to produce a stronger stimulus response at the target frequency than providing a visual stimulus at the target frequency itself.

[0052] Referring now to Figure 9 , a flowchart showing an example method 900 of providing anti-phase binocular or binocular split stimuli according to example embodiments of the present disclosure is depicted. The method 900 can be performed and / or implemented by components, elements, and / or hardware described herein, such as those described above with reference to Figures 1 to 8F As a brief overview, at 902, a device can determine a target frequency. At 904, the device can determine a frequency and a phase. At 906, the device can determine an output visual stimulus. At 908, the device can output a first visual stimulus and a second visual stimulus.

[0053] At 902, a device can determine a target frequency. The device can be or include a Figure 1The device can determine the target frequency based on or from various received, detected, and / or identified inputs. For example, the device can determine the target frequency in response to receiving user input via an input / output device (e.g., from a patient, from a therapy professional, etc.). As another example, the device can determine the target frequency in response to identifying the target frequency in a therapy schedule of a patient profile (e.g., maintained by the profile manager 1306). As yet another example, the device can determine the target frequency based on feedback from a simulation (e.g., via the otocoustic simulator 1308). The target frequency can be a frequency at which stimulation of the patient’s brain is to be received. Thus, the target frequency can not be a frequency of visual stimulation, but rather a frequency of stimulation response.

[0054] At 904, the device can determine a frequency and a phase. In some embodiments, the device can determine, derive, calculate, or otherwise identify a frequency and a phase of the visual stimulation to achieve, produce, request, or otherwise provide a frequency response of the target frequency. In some embodiments, the device can determine an oscillatory state for each eye of the patient, where the oscillatory state includes a frequency and a phase of an oscillation for the visual stimulation. The oscillatory state of each eye together can provide the frequency response of the target frequency. In other words, the oscillatory state of a first eye (e.g., a left eye) (e.g., including a first frequency and a first phase) and the oscillatory state of a second eye (e.g., a right eye) (e.g., including a second frequency and a second phase) together can provide the frequency response of the target frequency in the patient’s brain.

[0055] In some embodiments, the device can determine the oscillatory states based on or from the target frequency. For example, the device can determine the frequency of the oscillatory states from the target frequency. In some embodiments, a sum of the first frequency and the second frequency (e.g., of the respective oscillatory states) can equal the target frequency. For example, the first frequency can equal half of the target frequency, and the second frequency can equal half of the target frequency. Additionally, the phases of the respective oscillatory states can be out of phase with each other (e.g., the oscillatory states can be out of phase). In other words, the first phase and the second phase (e.g., of the respective oscillatory states) can be opposite each other.

[0056] In one example, the target frequency determined at 902 can be equal to a frequency between 35 Hz and 40 Hz. For example, the target frequency can be determined to be 38 Hz. The device can determine the first and second frequencies and the first and second phases from the target frequency. For example, the device can determine that the first phase is opposite / anti-phase / inverse phase to the second phase, such that the resulting visual stimulus produces a constructive effect. The device can determine that the first and second frequencies are equal to half of the target frequency, such that the resulting visual stimulus (when combined) produces a stimulus response of the target frequency. Continuing the example above, the device can determine that the first and second frequencies are equal to each other and between 17.5 Hz and 20 Hz (e.g., 19 Hz).

[0057] At 906, the device can determine an output visual stimulus. In some embodiments, the device can determine the output visual stimulus to produce a stimulus response of the target frequency. The device can determine the output visual stimulus in response to determining the frequencies and phases that together produce a stimulus response of the target frequency. The device can determine the output visual stimulus according to a schedule (e.g., a treatment schedule for a session). The device can determine the output visual stimulus in response to receiving a signal (e.g., from an input device) to begin visual stimulation of the patient.

[0058] At 908, the device can output a first visual stimulus and a second visual stimulus. In some embodiments, the device can output a first visual stimulus of the first frequency and phase to a first eye and a second visual stimulus of the second frequency and phase to a second eye. The first visual stimulus can include or correspond to a first oscillatory state and the second visual stimulus can include or correspond to a second oscillatory state. In other words, the first visual stimulus can have the first frequency and phase and the second visual stimulus can have the second frequency and phase, both of which are described above with reference to 904. The first and second visual stimuli together can provide a stimulus response of the target frequency. In other words, the first and second frequencies can be different from the target frequency. However, because the first and second visual stimuli are constructive (due to the first and second phases being opposite or interleaved with each other), the first and second visual stimuli together can provide a stimulus response of the target frequency.

[0059] In some embodiments, the device can output the first and second visual stimuli by controlling one or more light sources (e.g., light sources 104) to output light at the first and second frequencies and the first and second phases. For example, the device can transmit a signal (e.g., via a wired or wireless connection) to the light sources 104 to output the visual stimuli. The device can transmit a first signal to a first set of light sources 104 (e.g., first light sources 104(1)) to output the first visual stimuli to one eye of the patient and a second signal to a second set of light sources 104 (e.g., second light sources 104(2)) to output the second visual stimuli to the other eye of the patient.

[0060] In some embodiments, the device performing 902-908 can include a lamp that outputs the visual stimuli. For example, the device can include the light sources 104 described above with reference to Figure 1 In some embodiments, the device performing 902-908 can not include a lamp. For example, the device can be communicatively coupled to the light sources 104 and output the first and second visual stimuli by sending / transmitting / communicating signals that cause the light sources 104 to output the visual stimuli.

[0061] In some embodiments, the device can output an audio signal while outputting the first and second visual stimuli. As described above, the audio signal can be synchronized with the first and second visual stimuli. In some embodiments, the audio signal can be or correspond to music. The device can output the audio signal by transmitting the audio signal to an audio output device to output the music. The device can modify the audio signal and / or coordinate the first and second visual stimuli such that the first and second visual stimuli are synchronized with the music corresponding to the audio signal.

[0062] Figure 10 An example block diagram of an example computer system 1000 is depicted. Various components, elements, and / or hardware described herein, such as with reference to Figure 1Those described can be implemented by a computer system 1000 that includes the components of the computer system 1000, via the computer system 1000, and / or on the computer system 1000. The computer system or computing device 1000 can comprise or be used in a data processing system or component thereof. The computing system 1000 includes at least one bus 1005 or other communication means for communicating information and at least one processor 1010 or processing circuit coupled to the bus 1005 for processing information. The computing system 1000 can also include one or more processors 1010 or processing circuits coupled to the bus for processing information. The computing system 1000 also includes at least one main memory 1015, such as a random access memory (RAM) or other dynamic storage device, coupled to the bus 1005 for storing information and instructions to be executed by the processor 1010. Main memory 1015 can be used for storing information during processing by the processor 1010. The computing system 1000 can further include at least one read only memory (ROM) 1020 or other static storage device coupled to the bus 1005 for storing static information and instructions for the processor 1010. A storage device 1025, such as a solid state device, magnetic disk or optical disk, can be coupled to the bus 1005 for persistently storing information and instructions.

[0063] The computing system 1000 can be coupled via the bus 1005 to a display 1035, such as a liquid crystal display or active matrix display, for displaying information to a user. An input device 1030, such as a keyboard or voice interface, can be coupled to the bus 1005 for communicating information and commands to the processor 1010. The input device 1030 can include a touch screen display 1035. The input device 1030 can also include a cursor control, such as a mouse, a trackball, or cursor direction keys, for communicating direction information and command selections to the processor 1010 and for controlling cursor movement on the display 1035.

[0064] The processes, systems and methods described herein can be implemented by the computing system 1000 in response to the processor 1010 executing an arrangement of instructions contained in main memory 1015. Such instructions can be read into the main memory 1015 from another computer-readable medium, such as the storage device 1025. Execution of the arrangement of instructions contained in the main memory 1015 causes the computing system 1000 to perform the illustrative processes described herein. One or more processors in multiple processing arrangement can also be used to execute the instructions contained in the main memory 1015. Hard-wired circuitry can be used in place of or in combination with software instructions for implementation of the systems and methods described herein. The systems and methods described herein are not limited to any specific combination of hardware circuitry and software.

[0065] Although the systems and methods described herein can be embodied in software, hardware, or a combination of both, the disclosure is not limited to particular Figure 10Example computing systems are described in the detailed description that follows, but the subject matter including the operations described in this specification can be implemented in other types of digital electronic circuitry, or in computer software, firmware, or hardware, including the structures disclosed in this specification and their structural equivalents, or in combinations of one or more of the same.

[0066] Having now described some illustrative implementations, it is apparent that the foregoing implementation is illustrative rather than limiting, and that numerous modifications and other implementations are possible in light of the foregoing. Specifically, although many examples presented herein involve particular combinations of method actions or system elements, those actions and those elements can be combined or implemented in other combinations, or in conjunction with other actions or elements, without departing from the scope of the present disclosure. It will be appreciated that some implementations of the described implementations can be comprised of one or more generic or specialized processors (or "processing devices") programmed with specific software instructions (or "computer code") stored in memory to perform the various functions described above, and that the various hardware elements identified in the figures can be provided in various combinations of hardware and / or software to achieve the functions described. It will also be appreciated that the various functions implemented by the various elements identified in the figures can be combined or split among different hardware or software elements, without departing from the scope of the present disclosure.

[0067] The hardware and data processing components for carrying out various processes, operations, illustrative logics, logical blocks, modules, and circuits that are described in connection with the embodiments disclosed herein can be implemented or performed with a general purpose single- or multi-chip processor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA) or other programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein. A general purpose processor can be a microprocessor, or any conventional processor, controller, microcontroller, or state machine. A processor can also be implemented as a combination of computing devices, such as a combination of a DSP and a microprocessor, a plurality of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration. In some embodiments, the specific processes and methods can be performed by circuitry that is specific to a given function. Memory (e.g., memory, memory units, memory devices, etc.) can include one or more devices (e.g., RAM, ROM, Flash memory, hard disk storage, etc.) for storing data and / or computer code for completing or facilitating the various processes, layers and modules described in the present disclosure. Memory can be or include volatile memory or non-volatile memory, and can include database components, object code components, script components, or any other type of information structures for supporting the various activities and information structures described in the present disclosure. According to an exemplary embodiment, the memory is communicably connected to the processor via the processing circuitry and includes computer code for executing (e.g., by the processing circuitry and / or the processor) one or more processes described herein.

[0068] The present disclosure contemplates methods, systems, and program products on any machine-readable media for accomplishing various operations. The embodiments of the present disclosure can be implemented using existing computer processors, or by a special purpose computer processor for an appropriate system, or by a hardwired system. Embodiments within the scope of the present disclosure include program products comprising machine-readable media for carrying or having machine-executable instructions or data structures stored thereon. Such machine-readable media can be any available media that can be accessed by a general purpose or special purpose computer or other machine with a processor. By way of example, such machine-readable media can include RAM, ROM, EPROM, EEPROM, or other optical disk storage, magnetic disk storage or other magnetic storage devices, or any other medium which can be used to carry or store desired program codes in the form of machine-executable instructions or data structures and which can be accessed by a general purpose or special purpose computer or other machine with a processor. Combinations of the above are also included within the scope of machine-readable media. Machine-executable instructions include, for example, instructions and data which cause a general purpose computer, special purpose computer, or special purpose processing devices to perform a certain function or group of functions.

[0069] The phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of "including," "comprising," "having," "containing," "involving," "characterized by," "characterized in that," "characterized by," "characterized in that," variations thereof and like terms are used herein to mean and convey that an item, feature, structure, or act, either express or implied, that was included in or with another item, feature, structure, or act, or a group thereof, is included also in the present disclosure. In one implementation, the systems and methods described herein consist of one, each combination of more than one, or all of the described elements, acts, or components.

[0070] Any reference to implementations or elements or acts of the system and method, in the singular, plural, or proximate can be meant to include one or more implementations of the described items, and any reference to implied or explicit "consisting of" can be meant to include one or more implementations of the described items. References in the singular or plural form are not intended to limit the presently disclosed systems or methods, their components, acts, or elements to a single configuration or multiple configurations. Any reference to an action or element based on any information, act, or element can include implementations where the action or element is based at least in part on any information, act, or element.

[0071] Any implementation disclosed herein can be combined with any other implementation or embodiment, and references to “implementation,” “some implementations,” “one implementation,” etc. need not necessarily be mutually exclusive, and intended to indicate that a particular feature, structure, or characteristic described in connection with the implementation can be included in at least one implementation or embodiment. The referring terms used herein are not necessarily all referring to the same implementation. Any implementation can be included in any combination of other implementations or embodiments in a manner consistent with the aspects and implementations disclosed herein, including in an inclusive or exclusive combination with any other implementation.

[0072] Where a technical feature is followed by reference signs, the reference signs are included for the sole purpose of increasing the intelligibility of the drawings, detailed description, and claims. Accordingly, neither the reference signs nor their absence have any limiting influence on the scope of any claim element.

[0073] The systems and methods described herein can be embodied in other specific forms without departing from the characteristics thereof. Unless otherwise expressly stated, references to any degree term include variations as + / - 10% from a given measured value, unit, or range. Coupled elements can be directly electrically, mechanically, or physically coupled to one another, or electrically, mechanically, or physically coupled to one another with intervening elements. Accordingly, the scope of the systems and methods described herein is indicated by the appended claims, rather than by the foregoing description, and changes that come within the meaning and range of equivalents of the claims are to be embraced within their scope.

[0074] The term “coupled” and variations thereof, include the joining of two members directly or indirectly to one another. Such joining can be stationary (e.g., permanent or fixed) or moveable (e.g., removable or releasable). Such joining can be achieved with the two members coupled directly to each other, with the two members coupled to each other using a separate intervening member, with the two members coupled to each other using any additional intervening members, or with the two members coupled to each other using an intervening member that is integral with one of the two members as a single unitary body. If “coupled” or variations thereof are modified by an additional term (e.g., directly coupled), the generic definition of “coupled” provided above is modified by the plain language meaning of the additional term (e.g., “directly coupled” means the joining of two members without any separate intervening member), resulting in a narrower definition of “coupled” than the generic definition provided above. Such coupling can be mechanical, electrical, or fluidic.

[0075] References to “or” can be construed as inclusive so that any terms described using “or” can indicate any of a single, more than one, and all of the described terms. A reference to “at least one of’ A and B can include only A, only B, as well as both A and B. Such references used in conjunction with “comprising” or other open terminology can include additional items.

[0076] Modifications can be made to the described elements and acts to provide the disclosed subject matter in its entirety within the intended scope of the teachings and advantages of the subject matter disclosed herein. For example, the sizes, shapes, and relative positions of the various elements can be changed as appropriate, and other changes can be made to the elements and acts described herein. Other substitutions, modifications, changes, and omissions can also be made in the design, operating conditions, and arrangement of the disclosed elements and operations without departing from the scope of the present disclosure.

Claims

1. A method comprising: determining, by a device, a target frequency of a stimulus response; outputting, by the device, a first visual stimulus of a first frequency and a first phase to a first eye; and outputting, by the device, a second visual stimulus of a second frequency and a second phase to a second eye, the first visual stimulus and the second visual stimulus together producing a stimulus response of the target frequency. the first frequency is half the target frequency and the second frequency is half the target frequency.

2. The method of claim 1, wherein, the second phase is an inverse of the first phase.

3. The method of claim 1, wherein, the target frequency is between 35 Hz and 40 Hz.

4. The method of claim 1, wherein, the sum of the first frequency and the second frequency is equal to the target frequency.

5. The method of claim 4, wherein, the target frequency is equal to 38 Hz, the first frequency is equal to 19 Hz, and the second frequency is equal to 19 Hz.

6. The method of claim 4, wherein, the device comprises one or more first light sources for stimulating the first eye and one or more second light sources for stimulating the second eye, 7. The method of claim 1, wherein, wherein outputting the first visual stimulus comprises controlling the one or more first light sources to output light of the first frequency and the first phase, and wherein outputting the second visual stimulus comprises controlling the one or more second light sources to output light of the second frequency and the second phase. the device comprises a head-mounted device, the head-mounted device comprising the one or more first light sources at a first location of the head-mounted device and the one or more second light sources at a second location of the head-mounted device, the first location corresponding to stimulating the first eye when the head-mounted device is worn and the second location corresponding to stimulating the second eye when the head-mounted device is worn.

8. The method of claim 7, wherein, outputting the first visual stimulus and the second visual stimulus comprises:

9. The method of claim 1, wherein, outputting, by the device, an audio signal at the same time as outputting the first visual stimulus; and outputting, by the device, the audio signal at the same time as outputting the second visual stimulus, the audio signal being synchronized with the first visual stimulus and the second visual stimulus. the target frequency is in a frequency band that is one of between 30 hertz and 40 hertz, between 13 hertz and 30 hertz, between 8 hertz and 13 hertz, between 4 hertz and 8 hertz, or between 0.5 hertz and 4 hertz.

10. The method of claim 1, wherein, 11. A device comprising: one or more light sources; and one or more processors configured to: determine a target frequency of a stimulus response; output a first visual stimulus of a first frequency and a first phase to a first eye; and output a second visual stimulus of a second frequency and a second phase to a second eye, the first visual stimulus and the second visual stimulus together producing a stimulus response of the target frequency. the first frequency is half the target frequency, the second frequency is half the target frequency, and the second phase is inverse to the first phase. the target frequency is equal to 38 Hz, the first frequency is equal to 19 Hz, and the second frequency is equal to 19 Hz. ​ 12. The apparatus of claim 11, wherein, ​ 13. The apparatus of claim 11, wherein, ​ 14. The apparatus of claim 11, wherein, The one or more processors are configured to output an audio signal concurrently with the first and second visual stimuli.

15. The apparatus of claim 11, wherein, The audio signal is synchronized with the first and second visual stimuli.

16. A system comprising: one or more light sources; and one or more processors configured to: determine a target frequency of a stimulus response; output a first visual stimulus to a first eye at a first frequency and a first phase; and output a second visual stimulus to a second eye at a second frequency and a second phase, the first and second visual stimuli together producing a stimulus response at the target frequency.

17. The system of claim 16, wherein, The one or more processors and the one or more processors are implemented on a head-mounted device.

18. The system of claim 16, wherein, The first frequency is half the target frequency and the second frequency is half the target frequency.

19. The system of claim 16, wherein, The second phase is an inverse of the first phase.

20. The system of claim 16, wherein, The target frequency is equal to 38 Hz, the first frequency is equal to 19 Hz, and the second frequency is equal to 19 Hz.

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