Methods and devices for optimizing human performance

Abstract

Provided herein are methods and systems for improving a physiological and / or psychological state in a subject. The methods and systems comprise top-down and bottom-up modulation of a subject's biological state. Biofeedback protocols can be used with neurostimulation to improve a subject's physiological state, psychological state, or combined physiological state and psychological state.

Description

WSGR Docket No.68475-701.601 METHODS AND DEVICES FOR OPTIMIZING HUMAN PERFORMANCE CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This PCT application claims the benefit of U.S. Provisional Patent Application No. 63 / 664,109, filed June 25, 2024, the entire contents of which is incorporated herein by reference. BACKGROUND

[0002] In recent years, there has been an increased understanding of the neurophysiological factors related to sustaining and enhancing human performance. Human performance, whether it be exemplified within athletics and / or education, places high psychophysiological demands on an individual driven to create optimal results quite often under suboptimal and / or competitive conditions. New solutions are needed to address these psychophysiological demands and provide novel mechanisms for improving physiological and / or psychological states of an individual. These conditions may arise exogenously from the environment (such as unexpected changes in gameplay or battlefield dynamics) or endogenously within the individual (such as irregular respiration rate or pre-competitive stress). The enhancement of endogenous neurophysiological factors, whether they be psychological or physiological, have shown to be the most promising means of optimizing performance before, during, and after performance-related endeavors. The effective manipulation of psychological variables such as attention, self-confidence, stress control, anxiety, motivation, cohesion, self-control, perceived effort, or emotional self-regulation, moods, and interpersonal skills can have a significant influence on an individual’s performance. Furthermore, the effective manipulation of physiological variables such as heart rate variability (HRV), pulse respiratory quotient (PRQ), energy expenditure, psychomotor function, neurocognitive flexibility, muscle relaxation, and respiratory dynamics can result in considerable performance optimization. Development of methods and systems for simultaneous modulation of top-down (psychological) and bottom-up (physiological) factors at the same time would be the ideal means of holistically developing performance within the individual. SUMMARY

[0003] Recognized herein are methods and system for modulation of top-down and bottom-up processes to improve at least one state of a subject. The methods and systems can provide for exercise and neurostimulation protocols to enhance a subject’s health, wellbeing, athletic performance, or any combination thereof. 1WSGR Docket No.68475-701.601

[0004] In an aspect, the present disclosure provides a method of improving a state of a subject, the method comprising: (a) providing to the subject, by way of a computing device, instructions to the subject to proceed through an exercise protocol, the exercise protocol comprising one or more of a physical exercise, a psychological exercise, or a breathing exercise; (b) stimulating a nerve of the subject according to a stimulation program in response to the subject proceeding through the exercise protocol; (c) measuring at least one physiological or psychological parameter of the subject; and (d) modifying the stimulation program, the exercise protocol, or any combination thereof in response to the measured at least one physiological or psychological parameter to improve at least one biometric of the subject related to the state of the subject.

[0005] In some embodiments, the state is a physical state, a mental state, or any combination thereof.

[0006] In some embodiments, the physical state is an epigenetic age, a cardiovascular fitness capacity, a sleep quality, at least one metabolic health biomarker, a heart rate, a resting heart rate, a heart rate variability, a VO2 max, a pulse respiratory quotient, a breath hold time, a velocity, an energy expenditure, a functional threshold power, a force output, a pulse rate variability, a VCO2, a metabolic rate, a perceived effort, a fatigue management, or any combination thereof. In some embodiments, the physical state is a physical condition comprising cardiovascular disease, a respiratory disease, musculoskeletal disease, autonomic dysfunction and / or dysregulation, consciousness disruption, inflammatory disease, or any combination thereof. In some embodiments, the mental state is memory, attention, cognitive flexibility, interoception, executive function, cardiorespiratory, psycho-behavioral, neurochemical, cognitive-affective, or any combination thereof. In some embodiments, the state is performance of a physical activity.

[0007] In some embodiments, the nerve comprises a peripheral nerve. In some embodiments, the nerve comprises a median nerve, a vagal nerve, a trigeminal nerve, a tibial nerve, or any combination thereof. In some embodiments, the nerve is a median nerve.

[0008] In some embodiments, the stimulating occurs at the subject’s arm, wrist, hand, neck, head, leg, torso, or any combination thereof. In some embodiments, the physiological parameter comprises a heart rate, a resting heart rate, a heart rate variability, a VO2 max, a pulse respiratory quotient, a blood-oxygen content, a blood pressure, an electrodermal activity, electrocardiogram (EEG) information, a body position, a sleep cycle, a body temperature, a mile-split time, a respiratory pattern, or any combination thereof. In some embodiments, the respiratory pattern comprises a respiratory rate, an inhalation, an exhalation, a breath-hold time, a tidal volume, or any combination thereof.

[0009] In some embodiments, the measuring at least one physiological or psychological parameter of the subject occurs prior to the subject proceeding through the exercise protocol, while the 2WSGR Docket No.68475-701.601 subject is proceeding through the exercise protocol, while the nerve of the subject is stimulated, or any combination thereof.

[0010] In some embodiments, the nerve is stimulated via vibratory stimulation, electrical stimulation, thermal stimulation, acoustic stimulation, infrasound stimulation, ultrasound stimulation, pulse laser, transient optical neural stimulation, or any combination thereof. In some embodiments, the nerve is stimulated via vibratory stimulation, electrical stimulation, or any combination thereof. In some embodiments, one or more biosensors measure the at least one physiological or psychological parameter of the subject.

[0011] In some embodiments, the one or more biosensors comprise a electroencephalogram (EEG) sensor, and a photoplethysmographic (PPG) sensor, an electromyographic (EMG) sensors, an electrooculographic (EOG) sensor, an electrocardiogram (ECG) sensor, a pulse-oximeter, a chest monitor, a PPG biosensor ring, a PPG biosensor patch, a biosensor tattoo, a blood pressure sensor, a perspiration sensor, a skin conductivity sensor, an accelerometer, a location sensor, a gyroscope, or any combination thereof.

[0012] In some embodiments, the stimulation program comprises one or more parameters comprising: a frequency, a pulse width, a pulse pattern, a current, a voltage, a pulse duration, a repetition rate, a current intensity, or any combination thereof. In some embodiments, the frequency comprises a range from about 1-1000 Hz. In some embodiments, the frequency comprises a range from about 10-120 Hz. In some embodiments, the current intensity comprises a range from about 100 μA to about 10 mA. In some embodiments, the pulse width comprises a range from about 1 μs to about 100 milliseconds (ms). In some embodiments, the pulse pattern is a cyclical or sinusoidal pulse pattern. In some embodiments, the pulse pattern is rhythmic. In some embodiments, the pulse pattern is arrhythmic.

[0013] In some embodiments, the pulse patten is paired with cardiovascular activity of the subject. In some embodiments, the pulse pattern is not paired from cardiovascular activity of the subject.

[0014] In some embodiments, the stimulating of the nerve is by non-invasive neurostimulation. In some embodiments, the non-invasive stimulation is via a transcutaneous neurostimulator. In some embodiments, the transcutaneous neurostimulator comprises one or more electrodes, wherein the electrodes are configured to administer stimulation to the nerve of the subject. In some embodiments, the method further comprises monitoring sympathetic and / or parasympathetic activity of the subject.

[0015] In some embodiments, the method further comprises stimulating a second nerve of the subject according to the stimulation program. In some embodiments, the second nerve is at a same location of the body as the nerve of the subject. In some embodiments, the second nerve is at a different location of the body as the nerve of the subject. In some embodiments, the second nerve 3WSGR Docket No.68475-701.601 comprises a median nerve, a vagal nerve, a trigeminal nerve, a tibial nerve, or any combination thereof.

[0016] In some embodiments, the breathing exercise comprises inhalation and / or exhalation dynamics to increase sympathetic nervous system activity, parasympathetic nervous system activity, or any combination thereof. In some embodiments, the breathing exercise comprises inhalation and / or exhalation dynamics to decrease sympathetic nervous system activity, parasympathetic nervous system activity, or any combination thereof. In some embodiments, the breathing exercise comprises inhalation and / or exhalation dynamics to increase sympathetic nervous system activity and decrease parasympathetic nervous system activity. In some embodiments, the breathing exercise comprises inhalation and / or exhalation dynamics to decrease sympathetic nervous system activity and increase parasympathetic nervous system activity. In some embodiments, the breathing exercise regulates an equal ration of sympathetic and / or parasympathetic activity.

[0017] In some embodiments, the method further comprises administering a secondary signal. In some embodiments, the secondary signal comprises an audio signal, a visual signal, or an audiovisual signal. In some embodiments, the secondary signal is administered prior to stimulating the nerve of the subject, after stimulating the nerve of the subject, or concurrently with stimulating the nerve of the subject.

[0018] In some embodiments, stimulating the nerve of the subject occurs concurrently with the subject proceeding through the exercise protocol. In some embodiments, the stimulating the nerve of the subject occurs after the subject proceeds through the exercise protocol.

[0019] In some embodiments, the method further comprises ceasing stimulation of the nerve in response to improvement of the at least one biometric. In some embodiments, the method further comprises prolonging stimulation of the nerve in response to improvement of the at least one biometric.

[0020] In some embodiments, the computing device comprises a mobile electronic device. In some embodiments, the mobile electronic device comprises a smartwatch. In some embodiments, the stimulation program comprises one or more stimulation profiles, wherein each of the one or more stimulation profiles comprises a different stimulation parameter. In some embodiments, modifying the stimulation program in response to the measured at least one physiological or psychological parameter comprises selecting a second stimulation profile that is different from a first stimulation profile. In some embodiments, the method further comprises, prior to (a), determining a baseline physiological or psychological parameter of the subject, wherein the baseline physiological or psychological parameter is the same type of physiological or psychological parameter as the measured physiological or psychological parameter of (c). 4WSGR Docket No.68475-701.601

[0021] In another aspect, the present disclosure provides a method of improving a state of a subject, the method comprising: (a) establishing a baseline cardiovascular parameter, baseline respiratory parameter, a baseline biomechanical parameter, a baseline biochemical parameter, or any combination thereof; (b) detecting an inhalation or exhalation of the subject; (c) measuring a physiological state of the subject based on the inhalation or exhalation; (d) comparing the physiological state to the baseline cardiovascular parameter, baseline respiratory parameter, baseline biomechanical parameter, baseline biochemical parameter, or any combination thereof; and (e) administering a stimulation to a nerve of the subject based on the comparison of (d); and wherein the stimulation improves the state of the subject.

[0022] In another aspect, the present disclosure provides a method for improving a state of a subject, the method comprising: (a) receiving from: (i) one or more first sensors, at least one signal indicative of a baseline cardiovascular parameter; and (ii) one or more second sensors, at least one signal indicative of a baseline respiratory parameter; (b) determining an inhalation or exhalation of the subject; (c) measuring a physiological state of the subject; (d) comparing the physiological state to the baseline cardiovascular parameter, the baseline respiratory parameter, or any combination thereof to determine a cardiorespiratory dynamic and / or neurocardiac dynamic; and (e) administering a stimulation via one or more electrodes to a nerve of the subject, wherein the stimulation is based on the cardiorespiratory dynamic and / or neurocardiac dynamic.

[0023] In some embodiments, the state is a physical state, a mental state, or any combination thereof.

[0024] In some embodiments, the physical state is an epigenetic age, a cardiovascular fitness capacity, a sleep quality, at least one metabolic health biomarker, a heart rate, a resting heart rate, a heart rate variability, a VO2 max, a pulse respiratory quotient, a breath hold time, a velocity, an energy expenditure, a functional threshold power, a force output, a pulse rate variability, a VCO2, a metabolic rate, a perceived effort, a fatigue management, or any combination thereof.

[0025] In some embodiments, the physical state is a physical condition comprising cardiovascular disease, a respiratory disease, musculoskeletal disease, autonomic dysfunction and / or dysregulation, consciousness disruption, inflammatory disease, or any combination thereof.

[0026] In some embodiments, the mental state is memory, attention, cognitive flexibility, interoception, executive function, cardiorespiratory, psycho-behavioral, neurochemical, cognitive-affective, or any combination thereof. In some embodiments, the state is performance of a physical activity. In some embodiments, the nerve comprises a peripheral nerve. In some embodiments, the nerve comprises a median nerve, a vagal nerve, a trigeminal nerve, a tibial nerve, or any combination thereof. In some embodiments, the nerve is a median nerve. In some 5WSGR Docket No.68475-701.601 embodiments, the stimulating occurs at the subject’s arm, wrist, hand, neck, head, leg, torso, or any combination thereof.

[0027] In some embodiments, the baseline cardiovascular parameter comprises a heart rate, a resting heart rate, a heart rate variability, a VO2max, a pulse respiratory quotient, a blood-oxygen content, a blood pressure, an electrodermal activity, electrocardiogram (EEG) information, a body position, a sleep cycle, a body temperature, a velocity, an energy expenditure, a functional threshold power, a force output, a pulse rate variability, a VCO2, a metabolic rate, a perceived effort, a fatigue management, or any combination thereof. In some embodiments, the baseline respiratory parameter comprises a respiratory rate, an inhalation, an exhalation, a breath-hold time, a tidal volume, or any combination thereof.

[0028] In some embodiments, the nerve is stimulated via vibratory stimulation, electrical stimulation, thermal stimulation, acoustic stimulation, infrasound stimulation, ultrasound stimulation, pulse laser, transient optical neural stimulation, or any combination thereof. In some embodiments, the nerve is stimulated via vibratory stimulation, electrical stimulation, or any combination thereof. In some embodiments, one or more biosensors measure the physiological state of the subject.

[0029] In some embodiments, the one or more biosensors comprise a electroencephalogram (EEG) sensor, and a photoplethysmographic (PPG) sensor, an electromyographic (EMG) sensors, an electrooculographic (EOG) sensor, an electrocardiogram (ECG) sensor, a pulse-oximeter, a chest monitor, a PPG biosensor ring, a PPG biosensor patch, a biosensor tattoo, a blood pressure sensor, a perspiration sensor, a skin conductivity sensor, an accelerometer, a location sensor, a gyroscope, or any combination thereof.

[0030] In some embodiments, the stimulation comprises one or more parameters comprising: a frequency, a pulse width, a pulse pattern, a current, a voltage, a pulse duration, a repetition rate, a current intensity, or any combination thereof. In some embodiments, the frequency comprises a range from about 1-1000 Hz. In some embodiments, the frequency comprises a range from about 10-120 Hz. In some embodiments, the current intensity comprises a range from about 100 μA to about 10 mA. In some embodiments, the pulse width comprises a range from about 1 μs to about 100 ms. In some embodiments, the pulse pattern is a cyclical or sinusoidal pulse pattern. In some embodiments, the pulse pattern is rhythmic. In some embodiments, the pulse pattern is arrhythmic.

[0031] In some embodiments, the pulse pattern is paired with cardiovascular activity of the subject. In some embodiments, the pulse pattern is not paired with cardiovascular activity of the subject.

[0032] In some embodiments, stimulation of the nerve is by non-invasive neurostimulation. In some embodiments, the non-invasive stimulation is via a transcutaneous neurostimulator. In some 6WSGR Docket No.68475-701.601 embodiments, the transcutaneous neurostimulator comprises one or more electrodes, wherein the electrodes are configured to administer stimulation to the nerve of the subject. In some embodiments, the method further comprises monitoring sympathetic and / or parasympathetic activity of the subject.

[0033] In some embodiments, the method further comprises stimulating a second nerve of the subject according to the stimulation program. In some embodiments, the second nerve is at a same location of the body as the nerve of the subject. In some embodiments, the second nerve is at a different location of the body as the nerve of the subject. In some embodiments, the second nerve comprises a median nerve, a vagal nerve, a trigeminal nerve, a tibial nerve, or any combination thereof.

[0034] In some embodiments, the inhalation or exhalation increases sympathetic nervous system activity, parasympathetic nervous system activity, or any combination thereof. In some embodiments, the inhalation or exhalation decreases sympathetic nervous system activity, parasympathetic nervous system activity, or any combination thereof. In some embodiments, the inhalation or exhalation increases sympathetic nervous system activity and decreases parasympathetic nervous system activity. In some embodiments, the inhalation or exhalation decreases sympathetic nervous system activity and increases parasympathetic nervous system activity. In some embodiments, the inhalation or exhalation regulates an equal ration of sympathetic and / or parasympathetic activity.

[0035] In some embodiments, the method further comprises administering a secondary signal. In some embodiments, the secondary signal comprises an audio signal, a visual signal, or an audiovisual signal. In some embodiments, the secondary signal is administered prior to stimulating the nerve of the subject, after stimulating the nerve of the subject, or concurrently with stimulating the nerve of the subject.

[0036] In some embodiments, the method further comprises (f) providing to the subject, by way of a computing device, instructions to the subject to proceed through an exercise protocol, the exercise protocol comprising one or more of a physical exercise, a psychological exercise, or a breathing exercise.

[0037] In some embodiments, stimulation to the nerve of the subject occurs concurrently with the subject proceeding through the exercise protocol. In some embodiments, the stimulation to the nerve of the subject occurs after the subject proceeds through the exercise protocol.

[0038] In some embodiments, the method further comprises ceasing stimulation of the nerve in response to improvement of the state of the subject. In some embodiments, the method further comprises prolonging stimulation of the nerve in response to improvement of the state of the subject. 7WSGR Docket No.68475-701.601

[0039] In some embodiments, the computing device comprises a mobile electronic device. In some embodiments, stimulation to the nerve of subject occurs according to a stimulation program in response to the comparing of (d). In some embodiments, the stimulation program comprises one or more stimulation profiles, wherein each of the one or more stimulation profiles comprises a different stimulation parameter.

[0040] In an aspect, the present disclosure provides a method of improving a state of a subject, the method comprising: (a) receiving from: (i) one or more sensors, at least one signal indicative of a baseline respiratory parameter; (b) determining an inhalation or exhalation; (c) measuring a respiratory pattern of the subject; (d) comparing the respiratory pattern with the baseline respiratory parameter; and (e) applying a stimulation to a nerve of the subject based on the comparison of the respiratory pattern the baseline respiratory parameter.

[0041] In an aspect, the present disclosure provides a system for modulating a respiratory function of a subject, said system comprising: (i) a flexible carrier configured to be worn by the subject; (ii) a transcutaneous neurostimulator, the transcutaneous neurostimulator comprising at least one electrode coupled to the flexible carrier; (iii) one or more sensors configured to retrieve at least one signal indicative of the subject’s respiratory pattern; and (iv) a controller configured to communicate with the transcutaneous neurostimulator and comprising a memory-storing biofeedback program, wherein the memory-storing biofeedback program is configured to compare the at least one signal indicative of the subject’s respiratory pattern with a baseline respiratory pattern of the subject; and wherein the transcutaneous neurostimulator is configured to generate one or more stimulation to a nerve of the subject.

[0042] In some embodiments, the method further comprises (v) a power source coupled to the flexible carrier.

[0043] In some embodiments, the transcutaneous neurostimulator is in electrical communication with the power source. In some embodiments, the memory-storing biofeedback program is disposed on a mobile electronic device.

[0044] In some embodiments, the one or more sensors comprise a electroencephalogram (EEG) sensor, and a photoplethysmographic (PPG) sensor, an electromyographic (EMG) sensors, an electrooculographic (EOG) sensor, an electrocardiogram (ECG) sensor, a pulse-oximeter, a chest monitor, a PPG biosensor ring, a PPG biosensor patch, a biosensor tattoo, a blood pressure sensor, a perspiration sensor, a skin conductivity sensor, an accelerometer, a location sensor, or any combination thereof.

[0045] In some embodiments, the stimulation comprises vibratory stimulation, electrical stimulation, thermal stimulation, acoustic stimulation, infrasound stimulation, ultrasound stimulation, pulse laser, transient optical neural stimulation, or any combination thereof. In some 8WSGR Docket No.68475-701.601 embodiments, the stimulation comprises vibratory stimulation, electrical stimulation, or any combination thereof.

[0046] In some embodiments, the controller is further configured to adjust one or more stimulation based on the comparison of the at least one signal indicative of the subject’s respiratory pattern and the baseline respiratory pattern of the subject.

[0047] In some embodiments, the nerve comprises a peripheral nerve. In some embodiments, the nerve comprises a median nerve, a vagal nerve, a trigeminal nerve, a tibial nerve, or any combination thereof. In some embodiments, the nerve is a median nerve. In some embodiments, the flexible carrier is disposed on the subject’s arm, wrist, hand, neck, head, leg, or torso.

[0048] In some embodiments, the at least one signal indicative of the subject’s respiratory pattern comprises a respiratory rate, an inhalation, an exhalation, a breath-hold time, a tidal volume, a heart rate variability, a pulse respiratory quotient, or any combination thereof.

[0049] In some embodiments, the one or more sensors is disposed on the subject’s arm, wrist, hand, neck, head, leg, or torso. In some embodiments, the one or more sensors is further configured to retrieve at least one signal indicative of the subject’s cardiovascular health.

[0050] In some embodiments, the at least one signal indicative of the subject’s cardiovascular health comprises a heart rate, a resting heart rate, a VO2max, a blood-oxygen content, a blood pressure, an electrodermal activity, electrocardiogram (EEG) information, a body position, a sleep cycle, a body temperature, a mile-split time, or any combination thereof.

[0051] In some embodiments, the one or more stimulation is applied as continuous stimulation to the nerve of the subject. In some embodiments, the one or more stimulation is applied as a burst stimulation to the nerve of the subject. In some embodiments, the one or more stimulation comprise one or more parameters comprising: a frequency, a pulse width, a pulse pattern, a current, a voltage, a pulse duration, a repetition rate, a current intensity, or any combination thereof.

[0052] In some embodiments, the frequency comprises a range from about 1-1000 Hz. In some embodiments, the frequency comprises a range from about 10-120 Hz. In some embodiments, the current intensity comprises a range from about 100 μA to about 10 mA. In some embodiments, the pulse width comprises a range from about 1 μs to about 100 ms. In some embodiments, the pulse pattern is a cyclical or sinusoidal pulse pattern. In some embodiments, the pulse pattern is rhythmic. In some embodiments, the pulse pattern is arrhythmic.

[0053] In some embodiments, the pulse patten is paired with cardiovascular activity of the subject. In some embodiments, the pulse pattern is not paired from cardiovascular activity of the subject.

[0054] In some embodiments, the system is further configured to monitor a level of sympathetic nervous system activity and / or parasympathetic nervous system activity of the subject. 9WSGR Docket No.68475-701.601

[0055] In some embodiments, the transcutaneous neurostimulator is configured to generate at least a first stimulation to a first nerve of the subject and a second stimulation to a second nerve of the subject. In some embodiments, the second nerve is at a same location of the body as the first nerve of the subject. In some embodiments, the second nerve is at a different location of the body as the first nerve of the subject.

[0056] In some embodiments, the second nerve comprises a median nerve, a vagal nerve, a trigeminal nerve, or a tibial nerve. In some embodiments, the memory-storing biofeedback program comprises one or more stimulation profile.

[0057] In some embodiments, the one or more stimulation profile is configured to define parameters of the generated one or more stimulation. In some embodiments, the system further comprises an audio generator, wherein the audio generator is configured to provide an auditory stimulus. In some embodiments, the memory-storing biofeedback program is in electrical communication with a smartphone. In some embodiments, the memory-storing biofeedback program is in electrical communication with a virtual reality program. In some embodiments, the memory-storying biofeedback program is in electrical communication with a VO2 mask.

[0058] Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in this art from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive. INCORPORATION BY REFERENCE

[0059] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such contradictory material. BRIEF DESCRIPTION OF THE DRAWINGS

[0060] The novel features of the present disclosure are set forth with particularity in the appended claims. A better understanding of the features and the disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles 10WSGR Docket No.68475-701.601 of the present disclosure are utilized, and the accompanying drawings (also “Figure” and “FIG.” herein), of which:

[0061] FIG. 1 shows a flow chart of an exemplary method for optimizing performance using a stimulation device or system of the present disclosure.

[0062] FIG.2 shows a schematic diagram of an exemplary system for optimizing performance.

[0063] FIGs. 3A-3E show exemplary schematics of the systems and device described herein. FIG. 3A depicts a front view of example body regions of stimulation interest. FIG. 3B shows a schematic view of an example device setup that can be attached to an area of a subject. FIG. 3C shows a bottom front isometric view of the device that can be strapped onto a left and / or right wrist. FIG.3D shows a side elevation view of the device comprising a personal computing device and accompanying biometric sensors. FIG. 3E depicts a bottom view of the underside of the device which can make topical contact upon the wearer´s skin. The device can have one or more integrated biometric sensors and at least one neuromodulation unit.

[0064] FIG. 4 depicts a flow chart of the processes of an application described herein. The application can assist in data collection, user feedback, and development of the systems and methods provided herein.

[0065] FIG. 5 shows a schematic representation of a system described herein in electrical communication with a mobile electronic device (e.g., Apple Watch). The system comprises a main control unit (MCU) comprising firmware and Bluetooth. The MCU is in electrical communication with the other electrical components of the system.

[0066] FIGs.6A-6F show exemplary schematics of the system and device described herein. FIG. 6A depicts a top-down view of the device. FIG. 6B depicts a side elevation view of the device. FIG.6C depicts a bottom-up view of the device. FIG.6D depicts bottom front isometric view of the device. FIG.6E depicts a front view of the device. FIG.6F depicts a cross-sectional view of the device, illustrating internal components.

[0067] FIG.7 shows an image of an example location of the device described herein. The image depicts adjustments of the stimulator. Wrist circumference adjustment is denoted by “A” and stimulator placement is denoted as “B”.

[0068] FIG. 8 depicts an image showing an exemplary configuration of electrodes and vibrator of a system described herein.

[0069] FIGs. 9A-9B show images of exemplary configurations of the device on a subject. FIG. 9A shows an arrangement of electrodes and vibrator, in which all three components are aligned. FIG.9B shows an arrangement of electrodes and vibrator, in which the two electrodes are offset from the vibrator. 11WSGR Docket No.68475-701.601

[0070] FIGs. 10A-10B show graphs depicting exemplary effects of the device, methods, and / or systems described herein. FIG. 10A depicts effects on heart rate following introduction of the methods and systems, with modulation of autonomic behavior before, during, and after performance, training and / or competition. FIG. 10B shows autonomic activity (e.g., parasympathetic and sympathetic activity) following instruction of the system described herein across a time period (e.g., from 8:00 AM to 6:00AM).

[0071] FIG. 11 shows a computer system that is programmed or otherwise configured to implement methods provided herein.

[0072] FIG.12 shows a graphical representation of performance over increasing energy levels. DETAILED DESCRIPTION

[0073] While various embodiments of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions can occur to those skilled in the art without departing from the present disclosure. It should be understood that various alternatives to the embodiments of the present disclosure described herein can be employed.

[0074] An objective of the present disclosure may be to provide methods and systems for enhancing the effects of biofeedback in combination with neurostimulation. This combination can offer a holistic approach to enhancing human performance (e.g., improving a state of a subject). Interdisciplinary theories such as the neurovisceral integration model, the polyvagal theory, the biological behavioral model, the resonance frequency (RF) model, and the psychophysiological coherence model all propose that the vagus nerve (VN) can play a vital role in sustaining and optimizing both top-down and bottom-up psychophysiological regulatory function. The VN is the largest of the twelve cranial nerves and is considered the main nerve of the parasympathetic nervous system (PNS). The VN connects the brain to our viscera (below the neck) and innervates various organs and organ systems throughout the body. It is composed of both afferent (80%) and efferent (20%) fibers which can both receive and convey sensory information between the brain and the body respectively. Due to its unique position between the brain and the body, the VN plays a vital role in regulating and mediating a variety of performance-related physiological functions regarding heart rate and heart rate variability (HRV), cardiovascular function, cardiorespiratory function, and autonomic function along with performance-related psychological functions pertaining to reward seeking behavior, emotional regulation, prosocial behavior, sustained focus, interoceptive awareness, executive functions, and positive goal expectancy. The system and methods described herein can provide a performance training system for high performance individuals (e.g., professionals and / or students) to advance neurological 12WSGR Docket No.68475-701.601 performance, cardiovascular performance, autonomic performance, psychophysiological performance, or any combination thereof.

[0075] The heart, brain, and lungs have a tri-directional influence on one another. This tri- directional electrical and hemodynamic connection between the heart, the brain, and the lungs supports a wide variety of performance-related physiological, psychological, and cognitive parameters that have a significant impact on our physical, mental, and social health. Heart rate variability (HRV)—a measure of the variability of beat-to-beat interval (R-R interval) resulting from the dynamic interactions between sympathetic and parasympathetic activities—can be a reliable parameter of autonomic function and vagal tone within human performance science. While autonomic neurocardiac function can be evaluated by HRV regarding human performance, cardiorespiratory function can be evaluated with the pulse respiratory quotient (PRQ = HR / RR)— a nonlinear dynamical system that indexes phase synchrony during rest and regulatory capacity during performance that can be linked to both the cardiovascular and autonomic nervous system. Both HRV and PRQ are performance parameters that directly influence psychological performance states.

[0076] Peak performance can be characterized by having feelings of self-confidence and expectations of success, being energized but also feeling relaxed, in control, focused, positive, determined and committed to achieving a goal. In addition to its role as a proxy of autonomic function, HRV can be associated with peak performance-related psychological states including executive functions, decision-making, and emotional regulation, as well as peak performance- related physiological states such as stamina, energy expenditure, oxidative stress, and pain tolerance. Optimal human functioning during peak performance in a variety of domains (e.g., sports, education, combat, etc.,) can be described by the experience and achievement of one of either two psychophysiological states: flow or clutch. Flow can be described as “letting it happen”—a harmonious and intrinsically rewarding state characterized by an effortlessness automaticity of task completion, absorption in a specific activity, and the exclusion of irrelevant thoughts and critical emotions accompanied by a sense of task cohesion. In contrast, clutch can be often described as “making it happen”—a more intense and effortful state of performing under pressure where there can be a heightened concentration and awareness that can be absent from negative thoughts. Flow could occur at any stage of performance involving a gradual buildup of confidence whereas clutch could occur in more acute instances of appraising situational demands towards the end of competition. One of the most promising means of significantly altering psychophysiological performance in real-time can be the deliberate modulation of respiration.

[0077] The neurobiology of breath has been extensively studied in both animals and in humans. Recent explorations in the neurobiology of breath have explored how specific breathing exercises 13WSGR Docket No.68475-701.601 can significantly impact human performance in a variety of performance-related domains (such as athletics, medicine, education, music and combat training among others). The pattern, frequency, and depth of breathing have direct physiological impacts on neurological, pulmonary, cardiovascular, and autonomic function. Altering the depth and frequency of the breath can produce different emotional and cognitive states in part by the regulation of carbon dioxide levels. Brain-body states related to performance that are modulated by respiratory dynamics, ranging from enhanced recovery to building stress tolerance, can help individuals within a performance context inhibit and / or facilitate specific performance related states at will. One of the main differentiators of common breathing techniques can be the emphasis on relative duration and intensity of inhales versus exhales.

[0078] A diverse range of breathing techniques exist, such as slow breathing that can be typically utilized to increase relaxation by enhancing parasympathetic nervous system (PNS) activity (i.e., cardiac vagal high-frequency HRV) or hyperventilation that can be typically utilized to achieve psychophysiological arousal by increasing autonomic stress (as indicated by increases in low- frequency HRV). Breathing techniques can be classified into five main categories: slow paced breathing, fast-paced breathing, hyperventilation, breath holding, and nostril or mouth breathing. Slow-paced breathing decreases respiratory frequency and prolongs the exhalation phase to increase cardiac vagal activity which relates positively to adaptability, resilience, recovery rates and optimal interactions of neurocardiac processes to meet the physiological and psychological demands of performance. Fast-paced breathing increases respiratory activity, heart rate (HR), oxygen uptake, carbon dioxide elimination, and decreases cardiac vagal HRV activity—a series of processes that activates the sympathetic nervous system (SNS) and places an athlete in a higher state of arousal. Hyperventilation can be deep breathing at either a normal or fast breathing frequency where blood oxygen levels increase and carbon dioxide levels decreases—the increase in blood pH (e.g., respiratory alkalosis) can delay fatigue and rapid decreases in blood pH induced by intense exercise. This can provide a rationale for training hyperventilation during a pre-exercise routine to improve high-intensity short-duration sport performance, such as sprinting, and enhances anaerobic energy supply and muscle function. Breath-holding (also referred to as hypoventilation training) can be exercised by exhaling to residual volume, performing cognitive or physical exercises without breathing, and exhaling again. By mirroring hypoxic (e.g., oxygen deficient) conditions, hypoventilation at low pulmonary volumes can trigger physiological adaptations via delayed metabolic acidosis can improve buffer capacity during performance. Nasal breathing can affect the central nervous system by synchronizing electrical activity in the olfactory cortex as well as amygdala and hippocampus, which has implications for optimizing performance- related stress. 14WSGR Docket No.68475-701.601

[0079] Inhaling has been shown to increase alertness levels and learning while exhaling increases relaxation and reappraisal in humans. Slow-paced breathing techniques may increase cardiac vagal HRV and have been shown to improve fine and gross motor function as well as executive functions (a robust predictor of enhanced performance in elite soccer players regarding the number of goals and assists executed in-game), emotion regulation, and self-regulation. Fast paced breathing exercises can improve information processing, elicit faster responses to environmental changes, and improve attention by increasing sympathetic tone and elevating norepinephrine secretion. But despite these effects breathing techniques may impart on human performance and the vagus nerve, the degree to which these techniques can significantly alter long-term autonomic function and cardiovascular fitness can be quite limited. Neurostimulation via nerve stimulation has shown to result in significant alterations in neurocognitive, neurocardiac, psychomotor, and autonomic function that can support and drive long-term positive changes in psychophysiology.

[0080] Transcutaneous vagus nerve stimulation (tVNS), which predominantly uses electrical impulses sent through the skin (transcutaneously) to innervate afferent (80%) vagal function can regulate both psychological and physiological parameters that may be relevant for advancing human performance. However, tVNS can be predominantly used for the treatment of epilepsy, treatment-resistant chronic pain, major depressive disorder, and other psychophysiological ailments and not for advancing performance parameters in healthy individuals such as athletes. Due to the clinical purpose of use and intention to treat, tVNS devices are often costly, not user friendly, have adverse side effects, and have a narrow clinical user profile. Prior-art tVNS devices typically cannot be given to those receiving other types of recreational neurostimulation (such as transcranial magnetic stimulation) or those who may have sub-clinical irregular autonomic and / or cardiovascular function. Furthermore, devices of the prior-art force users (i.e., patients) to passively receive treatment (stimulation) without any active training for advancing cognitive and affective function (i.e., biofeedback)—users do not learn how to optimize vagal function on their own without artificial intervention.

[0081] Healthy individuals interested in benefiting from VN stimulation but who do not meet the clinical requirements as patients to receive such neurostimulation techniques (i.e., high performance athletes, armed forces personnel, students, etc.,) are left with few innovative biotech solutions to advancing performance-related health. It can also be important to note that stimulating the VN results exclusively in an increase in cardiac vagal activity (i.e., parasympathetic nervous system, PNS, activity) which only drives relaxation and recovery. Healthy athletes interested in utilizing nerve stimulation to drive significant long-term changes in performance psychophysiology also need ways to stimulate the sympathetic nervous system (SNS) for arousal, focus, and muscle contraction. Currently market available sports wearables, biofeedback devices, 15WSGR Docket No.68475-701.601 and applications within human performance science are designed to predominantly monitor cardiac vagal HRV with the intention of increasing HRV over time. However, high levels of vagal HRV may not always be favorable to competitors within human performance. In fact, acute decreases in HRV (i.e., pre-competitive sympathetic arousal) prior to competition can often indicate an increase in HR, arousal, preparedness, focus, and improve the control of specific muscle contractions that can engage optimally during a stressful event. In addition, longitudinal data indicates that low levels of vagal HRV as a result of fatigue and high training load could improve performance markers (e.g. VO2 max, single-legged counter-movement jump, and drop jump index) in high-level tennis players.

[0082] Recent research investigating the median nerve (MN) has indicated that median nerve stimulation (MNS) may be a viable means of modulating autonomic nervous system (ANS) function and regulatory capacity both regarding the PNS and SNS via the VN. The median nerve originates from the brachial plexus and mostly innervates muscles of the anterior compartment of the forearm where both myelinated and unmyelinated afferents contribute to the observable effects of MNS on cardiovascular excitatory reflexes. In addition, the median nerve can indirectly innervate the VN through activation of vagal brainstem nuclei such as the nucleus tractus solitarius, dorsal motor nucleus, and associated regions in the brain such as the hypothalamus, insula, and amygdala. MNS using a variety of stimulation parameters can have significantly different effects on the autonomic nervous system (ANS). Among all of the parameters, frequency seems to be one of the most significant means of modulating HRV—lower stimulation frequencies have shown to exert a greater cardiac vagal (parasympathetic) dominance whereas higher stimulation frequencies exert a greater sympathetic activation. Laterality of MNS—stimulating the median nerve on the left and / or right wrists—could potentially instigate distinct neuromodulatory effects of HRV, with bilateral stimulation increasing sympathetic dominance whereas unilateral left-sided stimulation seems to increase parasympathetic dominance via VN network influences.

[0083] The median nerve, through activation of brainstem nuclei such as the nucleus tractus solitarius, can be associated with the stimulation of the 10th cranial nerve, also known as the vagus nerve (VN). The VN can be strongly linked to the autonomic nervous system (ANS) and associated measures of heart rate variability (HRV). HRV can be a standard for measuring autonomic modulation. Low HRV may be associated with various cardiovascular diseases (CVDs) and psychological distress. If present in healthy young individuals, HRV may be an indicator of over-training, competitive stress, sleep loss, or combination thereof.

[0084] Despite the noticeable shifts in autonomic tone, the precise network of cortical and subcortical activation responsible for the effectiveness of MNS on HRV, its potential beneficial 16WSGR Docket No.68475-701.601 effects on overall cardiovascular health, and its possible implications for performance enhancement are still unknown. A problem with MNS devices can be that they are typically not designed or developed for performance enhancement, have no integrated closed-loop biofeedback systems to personalize stimulation to a user’s own biometrics, and / or are not paired with any respiratory breathing techniques associated with altering autonomic tone in the competitive setting. Smart phone applications that deliver breathwork training programs are often simplistic, promise “performance enhancement” without any concern for effectiveness and have possible adverse effects for users regarding false performance expectations, placebo-driven effects, and unmeasurable physiological results. Furthermore, psychological-based performance applications which include audio for guided meditations, coaching, timers, reminders, and mood assessment tracking programs cannot interact with, or be reactive to, a user´s specific respiratory dynamics, cardiovascular, neurological, and nerve function during practice. Users are therefore forced to practice “passive” forms of psycho-behavioral interventions that are not based on their specific physiological state and have little means of optimizing their practice based on their own objective neurological (electroencephalogram), pulmonary (respiration rate and volume), autonomic, and / or cardiovascular performance-related parameters.

[0085] To ensure that breathing techniques have an impact on human performance by modulating respiratory sinus arrhythmia, the baroreflex, pulmonary afferents, the vagus nerve, and relevant brain networks, a practitioner must utilize the correct respiratory dynamics (i.e., respiratory frequency, depth, and intensity). The biofeedback programs employed may not only monitor respiratory dynamics but may also actively aid in driving psychophysiological state changes in the field by showcasing real-time changes in physiology. Deliberate patterns of breathing as trained during biofeedback-enhanced breathwork exercises provides direct control over one’s physiology as opposed to passively attending to the presence of one’s breath during mindfulness meditation and / or following simple audio / visual guidance. To achieve harmonic coupling between HRV, respiration, peripheral blood pressure (BP), and skin blood flow in a 0.15 Hz rhythm band (e.g., a range of 0.01-0.30 Hz or 0.12–0.18 Hz) users must engage in dynamic biofeedback training regimens with a device that can not only monitor but also actively drive neurocardiac function.

[0086] More work may be needed to determine what frequencies and intensities are useful for driving health and performance especially in nonclinical populations. Furthermore, there may be needs for a system which includes a closed-loop biofeedback system wherein the stimulation can be delivered in relation to, or in conjunction with, the subject´s own neuro-cardiovascular activity. This combination can be advantageous for personalizing such stimulation for the augmentation and regulation of the nervous system to drive and sustain improved health and performance states. These states can be achieved spontaneously and may be “trainable” due to a lack of tools and 17WSGR Docket No.68475-701.601 methods used to interface such a system in real-time. Acute stress prior to engaging in a performance demanding task (e.g., with low HRV) can increase neurocognitive and psychomotor performance within that task. For example, sympathetic stimulation prior to competition (e.g., an elite sport) may enhance neurocognitive and psychomotor performance during the competition. In addition, a user (e.g., athlete) may face spontaneous demands of performance, for example a period in which the user may be demanded to be calm and / or relaxed (e.g., having parasympathetic tone) and period in which the user may be demanded to be focused and attentive (e.g., having sympathetic tone). These spontaneous demands may facilitate a nervous system that can be flexible, and regulation may be practical during these periods. Efficiently recovering after such high performance demands may be difficult for a user (e.g., an elite athlete). Regular high intensity training sessions leading up to competition may result in low baseline heart rate recovery (HRR) and / or HRV. The systems and methods described herein can stimulate a nerve (e.g., the median nerve) in combination with biofeedback (e.g., cardiorespiratory biofeedback training regimens) to improve HRV, HRR, and other biometrics. Users of the systems and methods described herein can actively modulate HRV and may see positive effects of nerve stimulation (e.g., MNS) and breathing techniques on autonomic balance and health.

[0087] The goal of devices and approaches, whether they be mind-body applications or neurostimulators, may be to decrease pain, distress, or psychophysiological suffering (passive coping). However, the system and method described herein can be designed to increase psychophysiological tolerance, flexibility, and fitness in response to stress for a user (e.g., active coping). Elite athletes, corporate managers, academics, and working-class professionals in various high-performance segments of society continually encounter stressful situations throughout the entirety of their career and can be therefore seen as a natural part of their high-demanding professions; seeking acute solutions to stress reduction may not be as sustainable as seeking solutions that increase fitness, regulation, and tolerance which allow individuals to operate optimally and sustainably under frequent high stress situations. The lack of personalization, applicability, and integrative approach in the prior-art of performance applications and nerve stimulators respectively sets the stage for the device and methods of use herein described. The distinct processes and contexts in which a competitor could be trained to accomplish and experience peak performance states and transition from one state to another during training or competition relies on a dynamic interplay of endogenous psychophysiological skills and strategies. To reliably enhance human performance, one must develop better state-specific psychophysiological strategies for entering important competitions, develop the skills necessary to create and maintain such states, and to prepare those skills for use in each context. 18WSGR Docket No.68475-701.601

[0088] The novel wearable device can be designed to be worn on multiple locations of the body to innervate multiple peripheral nerves at various locations. The corresponding application described herein can deliver real-time state-specific psychophysiological strategies to enhance a user´s propensity to: (i) create the context both in mind and body in which flow and / or clutch can be engaged during particular stages of human performance; (ii) engage in the process of building flow and / or clutch during performance (setting open-ended goals and receiving positive feedback for flow and setting fixed goals in relation to task demands to increase effort for clutch); (iii) train targeted styles of self-regulation in which certain psychological skills (i.e., attention regulation) in conjunction with certain physiological states (shifts in autonomic tone) can aid in managing and sustaining optimal performance; or (iv) any combinations thereof. Embodiments of the present disclosure can comprise a first median nerve stimulator with an adaptable usability designed specifically for advancing human performance by delivering closed-loop cardiovascular neuromodulation. An embodiment of the present disclosure can comprise a wearable biofeedback system with an integrated vibro-electrotactile neurostimulator that 1) employs a method of ensuring optimal resonance (harmonic coupling) between cardiovascular, autonomic, and neurological functions and 2) stimulates nerve ramifications (namely median and vagal) which produces significant shifts in cardiovascular and autonomic activity before, during, and after performance that can be effective, efficient, safe, and adaptable to each user´s goals and requirements. In some embodiments, the methods and systems described herein may be used to optimize human performance by optimizing the functionality and selectivity of both afferent and efferent nerve fibers (e.g., vagal and median nerve) pathways during biofeedback sessions. The integrated neurostimulation device in combination with a personal computing device (e.g., smart phone and / or smart watch) application can combine specific vibro-electrotactile nerve stimulation methods with biofeedback training protocols (e.g., respiratory-based breathing techniques) to enhance human performance based upon a user´s own physiological output (e.g., HRV, PRQ, etc.,) and psychological state (e.g., sustained focus, motivation, cognitive functioning, or any combination thereof). Methods for Improving a Subject’s State

[0089] In an aspect, provided herein are methods of improving a state of a subject. A computing device may be provided to the subject. The computing device can comprise instructions to the subject. The instructions can be visual instructions, audio instructions, or audiovisual instructions. The instructions can instruct to proceed through one or more exercise protocols. In some cases, the one or more exercise protocols can comprise a physical exercise, a psychological exercise, a breathing exercise, or any combination thereof. The methods described herein can further 19WSGR Docket No.68475-701.601 comprise stimulating a nerve of a subject. The stimulation may be according to a stimulation program. In some cases, the stimulation program can be selected in response to the subject proceeding through the one or more exercise protocols. The methods described herein can further comprise measuring at least one physiological parameter, at least one psychological parameter, or any combination thereof of the subject. In some cases, one or more physiological parameters are measured in the subject. In some cases, one or more psychological parameters are measured in the subject. The methods described herein can further comprise modifying the stimulation program, the one or more exercise protocols, or any combination thereof. The stimulation program and / or the one or more exercise protocols may be modified in response to the measured physiological parameter and / or psychological parameter of the subject. The stimulation program and / or the one or more exercise protocols may be modified to improve a biometric of the subject. A “biometric” can refer to any measurable physiological (e.g., anatomical or biological) or psychological (e.g., behavioral) characteristic of a subject. A biometric described herein can be related to the state of the subject. In some embodiments, the stimulation program and / or the one or more exercise protocols may be modified to improve multiple biometrics of the subject. For example, at least about 1, 2, 3, 4, 5, 6, 7, 8, or greater than 8 biometrics may be improved in a subject. In some cases, at most about 8, 7, 6, 5, 4, 3, 2, 1, or less than 1 biometric may be improved in a subject.

[0090] As an example, a method of the present disclosure can comprise: (a) providing to the subject, by way of a computing device, instructions to the subject to proceed through an exercise protocol, the exercise protocol comprising one or more of a physical exercise, a psychological exercise, or a breathing exercise; (b) stimulating a nerve of the subject according to a stimulation program in response to the subject proceeding through the exercise protocol; (c) measuring at least one physiological or psychological parameter of the subject; and (d) modifying the stimulation program, the exercise protocol, or any combination thereof in response to the measured at least one physiological or psychological parameter to improve at least one biometric of the subject related to the state of the subject.

[0091] In some embodiments, a state of the subject can be a physical state, a mental state (e.g., a psychological state), or any combination thereof. The physical state can comprise an epigenetic age, a cardiovascular fitness capacity, a sleep quality, an at least one metabolic health biomarker, a heart rate, a resting heart rate, a heart rate variability, a VO2 max, a pulse respiratory quotient, a breath hold time, a velocity, an energy expenditure, a functional threshold power, a force output, a pulse rate variability, a VCO2, a metabolic rate, a perceived effort, a fatigue management, or any combination thereof. The psychological state can comprise of any cognitive and / or affective capacity regarding attention, attention regulation, sustained focus, task switching, cognitive flexibility, executive function, emotion regulation, motivation, perceived effort, grit, resiliency, 20WSGR Docket No.68475-701.601 or any combination thereof. The term “epigenetic age” can refer to a measure of biological aging related to cognitive functioning. The term “cardiovascular fitness capacity” can refer to cardiovascular endurance (e.g., aerobic fitness). Cardiovascular fitness capacity can provide a measure of how well a subject’s body supplies oxygen to organs, muscles, or any combination thereof. For example, a subject with good cardiovascular fitness capacity may be capable of longer durations of physical exercise. The term “sleep quality” can refer to a measure of how well a subject sleep’s during a period of rest. For example, sleep quality may be quantified by a number of disruptions during a period of rest. Sleep quality may be measured by sleep latency (e.g., how long a subject takes to fall asleep), sleep duration (e.g., a total time period a subject can be asleep), wake after sleep onset (e.g., a total amount of time a subject stays awake following onset of sleep), or any combination thereof. The term “metabolic health biomarker” can refer to any measure of metabolic health of a subject, including, but not limited to, blood pressure, waist circumference, blood sugar levels, cholesterol levels, weight, and triglyceride levels. The term “pulse respiratory quotient” can refer to a measure of cardiorespiratory interaction, wherein a heart rate can be divided by respiratory rate. The term “pulse rate variability” can refer to the change in the interval between pulses in blood volume pulse (BVP) acquired using a biosensor (e.g., a PPG sensor).

[0092] A physical state can comprise a physical condition. The physical condition may comprise a cardiovascular disease. The cardiovascular disease can comprise coronary artery disease, high blood pressure, cardiac arrest, congestive heart failure, arrhythmia, peripheral artery disease, cardiomyopathy, pericardial disease, heart valve disease, or any combination thereof. The physical condition may comprise a respiratory disease. The respiratory disease may comprise asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pneumonia, or any combination thereof.

[0093] The physical condition may comprise a musculoskeletal disease. The musculoskeletal disease can comprise a disease that affects a muscle, joint, nerve, tendon, or cartilage of the subject. For example, the musculoskeletal disease can comprise back pain (e.g., chronic back pain), arthritis (e.g., osteoarthritis or rheumatoid arthritis), osteoporosis, tendinitis, rotator cuff, carpal tunnel syndrome, or any combination thereof. The physical condition may comprise an autonomic dysfunction and / or dysregulation. The autonomic dysfunction and / or dysregulation can comprise an injury to one or more nerves of the autonomic nervous system and / or impairment of sympathovagal balance. For example, the autonomic dysfunction and / or dysregulation can comprise autonomic neuropathy, dysautonomia, or disruption of the hypothalamic-pituitary- adrenal axis. The physical condition may comprise an inflammatory disease. The inflammatory disease can comprise ankylosing spondylitis, antiphospholipid antibody syndrome, autoimmune encephalitis, chronic recurrent multifocal osteomyelitis, gout, Henoch-Schoenlein purpura, 21WSGR Docket No.68475-701.601 juvenile dermatomyositis, juvenile idiopathic arthritis, juvenile lupus (SLE), juvenile scleroderma, juvenile vasculitis, Kawasaki disease, lupus (systemic lupus erythematosus), mixed connective tissue disease, myositis, poststreptococcal inflammatory syndrome, psoriatic arthritis, reactive arthritis, rheumatoid arthritis, scleroderma, Sjogren's syndrome, Spondylarthritis and / or spondyloarthropathy, systemic juvenile idiopathic arthritis, undifferentiated connective tissue disease, uveitis, vasculitis, or any combination thereof.

[0094] In some embodiments, the methods described herein can improve a physical condition comprising a cardiovascular disease, a respiratory disease, musculoskeletal disease, autonomic dysfunction and / or dysregulation, consciousness disruption, inflammatory disease, or any combination thereof. In some embodiments, the methods described herein can improve a psychological condition comprising psychological distress (i.e., anxiety and / or depression), angst, low-mood, trauma, attention deficit disorder, cognitive fog, cognitive fatigue, migraine, social- isolation, cognitive impairment, avolition, or any combination thereof. A consciousness disruption can comprise a psychological distress or mental health condition (e.g., anxiety disorder, bipolar affective disorder, depression, dissociative disorder, obsessive compulsive disorder, post- traumatic stress disorder, or any combination thereof). The psychological distress may be insomnia.

[0095] In some embodiments, the methods described herein can improve a mental state. The mental state can comprise cognition or behavioral characteristic. In some embodiments, the mental state can comprise a cardiorespiratory state, psycho-behavioral state, neurochemical state, cognitive-affective state, or any combination thereof. In some embodiments, the methods described herein can improve one or more of memory, attention, cognitive flexibility, interoception, or executive function of the subject.

[0096] The state of the subject may comprise physical activity. The physical activity can comprise any exercise or fitness. The exercise may be aerobic exercise or anaerobic exercise. The physical activity may comprise strength training exercise, stretching exercise, balance exercise, or any combination thereof. The physical activity may comprise a sport (e.g., swimming, running, walking, cycling, golf, rowing, dance, soccer, skiing, basketball, football, boxing, tennis, hiking, or any combination thereof).

[0097] In some embodiments, the nerve (e.g., the stimulated nerve) can comprise a peripheral nerve. In some embodiments, the nerve can be of the somatic nervous system or the autonomic nervous system (e.g., the sympathetic nervous system, the parasympathetic nervous system, or the enteric nervous system). The nerve may be a plexus of nerves. The nerve can be a collection of nerves. In some embodiments, the nerve can be a median nerve, a vagus nerve, a trigeminal nerve, a tibial nerve, or any combination thereof. In some embodiments, the methods described herein 22WSGR Docket No.68475-701.601 may comprise stimulating one or more nerves. In some embodiments, the methods described herein may comprise stimulating at least about 1 nerve, at least about 2 nerves, at least about 3 nerves, at least about 4 nerves, at least about 5 nerves, or greater than about 5 nerves. In some embodiments, the methods described herein may comprise stimulating at most about 5 nerves, at most about 4 nerves, at most about 3 nerves, at most about 2 nerves, at most about 1 nerve, or less than about 1 nerve. In some embodiments, the nerve can be a median nerve. In some embodiments, the stimulating can occur at an area of the body of the subject. For example, stimulating may occur at the subject’s arm, wrist, hand, neck, head, leg, torso, or any combination thereof. A subject may be stimulated at two or more locations of the body. In some embodiments, a subject may be stimulated at a left wrist and a right wrist. In some embodiments, a subject may be stimulated at a wrist (e.g., a left wrist or a right wrist) and a torso. In some embodiments, a subject may be stimulated at a wrist (e.g., a left wrist or a right wrist) and a head (e.g., a forehead). In some embodiments, a subject may be stimulated at a torso and a head (e.g., a forehead). In some embodiments, a subject may be stimulated at a wrist (e.g., a left wrist or a right wrist) and neck.

[0098] The subject can be instructed by a computing device to proceed through a physical exercise, a psychological exercise, or a breathing exercise. In some embodiments, the physical exercise can comprise any aerobic fitness or anaerobic fitness. In some embodiments, the psychological exercise can comprise any activity involving cognitive functioning (e.g., memory, attention, executive function, cognitive flexibility, or any combination thereof). In some embodiments, the breathing exercise can comprise an activity involving use of the respiratory system (e.g., inhalation, exhalation, or holding one’s breath).

[0099] The measured physiological parameter can comprise any biological response of a subject. In some cases, a measured physiological parameter can comprise a heart rate, a resting heart rate, a heart rate variability, a maximum heart rate, a heart rate recovery, a VO2 max, a pulse respiratory quotient, a blood-oxygen content, a blood pressure, a baroreflex sensitivity, an electrodermal activity, electrocardiogram (EEG) information, a body position, a sleep cycle, a body temperature, a mile-split time, a respiratory pattern, or any combination thereof. In some cases, one or more physiological parameters may be measured (e.g., at least about 1, 2, 3, 4, 5, 6, 7, 8, or more physiological parameters). In some embodiments, one or more psychological parameters may be measured. The psychological parameter can comprise a measure of any mental process of a subject. For example, the psychological parameter may comprise a result of a memory, attention, cognitive flexibility, or executive function test. The psychological parameter may measure memory, attention, cognitive flexibility, executive function, or any combination thereof. In some embodiments, one or more physiological parameters may be measured and one or more psychological parameters may be measured in the subject. 23WSGR Docket No.68475-701.601

[0100] The measuring of the one or more physiological parameters and / or one or more psychological parameters may occur prior to the subject proceeding through the exercise protocol (e.g., the physical exercise, psychological exercise, or breathing exercise). The measuring of the one or more physiological parameters and / or one or more psychological parameters may occur concurrently with the subject proceeding through the exercise protocol (e.g., the physical exercise, psychological exercise, or breathing exercise). The measuring of the one or more physiological parameters and / or one or more psychological parameters may occur concurrently with nerve stimulation.

[0101] In some embodiments, one or more sensors (e.g., biosensors) may measure the physiological parameter, psychological parameter, or any combination thereof. The one or more sensors (e.g., biosensors) may comprise a electroencephalogram (EEG) sensor, and a photoplethysmographic (PPG) sensor, an electromyographic (EMG) sensors, an electrooculographic (EOG) sensor, an electrocardiogram (ECG) sensor, a pulse-oximeter, a chest monitor, a PPG biosensor ring, a PPG biosensor patch, a biosensor tattoo, a blood pressure sensor, a perspiration sensor, a skin conductivity sensor, an accelerometer, a location sensor, a gyroscope, or any combination thereof.

[0102] The nerve may be stimulated by vibratory stimulation, electrical stimulation, thermal stimulation, acoustic stimulation, infrasound stimulation, ultrasound stimulation, pulse laser, transient optical neural stimulation, or any combination thereof. In some embodiments, the nerve may be stimulated only with vibratory stimulation. In some embodiments, the nerve may be stimulated with vibratory stimulation and electrical stimulation at the same time. In some embodiments, the nerve may be stimulated with vibratory stimulation prior to electrical stimulation. In some embodiments, the nerve may be stimulated with vibratory stimulation subsequent to electrical stimulation.

[0103] Stimulation of the nerve of the subject may be according to a stimulation program. The stimulation program can comprise one or more parameters. The parameters can comprise a frequency, a pulse width, a pulse pattern, a current, a voltage, a pulse duration, a repetition rate, a current intensity, or any combination thereof. In some embodiments, a frequency can comprise at least about 1 Hz, 2 Hz, 3 Hz, 4 Hz, 5 Hz, 10 Hz, 20 Hz, 30 Hz, 40 Hz, 50 Hz, 60 Hz, 70 Hz, 80 Hz, 90 Hz, 100 Hz, 110 Hz, 120 Hz, 130 Hz, 140 Hz, 150 Hz, 200 Hz, 250 Hz, 500 Hz, 750 Hz, 1000 Hz, or greater than about 1000 Hz. In some embodiments, a frequency can comprise at most about 1000 Hz, 750 Hz, 500 Hz, 250 Hz, 200 Hz, 150 Hz, 140 Hz, 130 Hz, 120 Hz, 110 Hz, 100 Hz, 90 Hz, 80 Hz, 70 Hz, 60 Hz, 50 Hz, 40 Hz, 30 Hz, 20 Hz, 10 Hz, 5 Hz, 4 Hz, 3 Hz, 2 Hz, 1 Hz, or less than about 1 Hz. In some embodiments, a frequency can comprise a range between about 5 Hz to about 200 Hz. In some embodiments, a frequency can comprise a range between 24WSGR Docket No.68475-701.601 about 5 Hz to about 10 Hz, about 5 Hz to about 25 Hz, about 5 Hz to about 50 Hz, about 5 Hz to about 60 Hz, about 5 Hz to about 70 Hz, about 5 Hz to about 80 Hz, about 5 Hz to about 90 Hz, about 5 Hz to about 100 Hz, about 5 Hz to about 120 Hz, about 5 Hz to about 150 Hz, about 5 Hz to about 200 Hz, about 10 Hz to about 25 Hz, about 10 Hz to about 50 Hz, about 10 Hz to about 60 Hz, about 10 Hz to about 70 Hz, about 10 Hz to about 80 Hz, about 10 Hz to about 90 Hz, about 10 Hz to about 100 Hz, about 10 Hz to about 120 Hz, about 10 Hz to about 150 Hz, about 10 Hz to about 200 Hz, about 25 Hz to about 50 Hz, about 25 Hz to about 60 Hz, about 25 Hz to about 70 Hz, about 25 Hz to about 80 Hz, about 25 Hz to about 90 Hz, about 25 Hz to about 100 Hz, about 25 Hz to about 120 Hz, about 25 Hz to about 150 Hz, about 25 Hz to about 200 Hz, about 50 Hz to about 60 Hz, about 50 Hz to about 70 Hz, about 50 Hz to about 80 Hz, about 50 Hz to about 90 Hz, about 50 Hz to about 100 Hz, about 50 Hz to about 120 Hz, about 50 Hz to about 150 Hz, about 50 Hz to about 200 Hz, about 60 Hz to about 70 Hz, about 60 Hz to about 80 Hz, about 60 Hz to about 90 Hz, about 60 Hz to about 100 Hz, about 60 Hz to about 120 Hz, about 60 Hz to about 150 Hz, about 60 Hz to about 200 Hz, about 70 Hz to about 80 Hz, about 70 Hz to about 90 Hz, about 70 Hz to about 100 Hz, about 70 Hz to about 120 Hz, about 70 Hz to about 150 Hz, about 70 Hz to about 200 Hz, about 80 Hz to about 90 Hz, about 80 Hz to about 100 Hz, about 80 Hz to about 120 Hz, about 80 Hz to about 150 Hz, about 80 Hz to about 200 Hz, about 90 Hz to about 100 Hz, about 90 Hz to about 120 Hz, about 90 Hz to about 150 Hz, about 90 Hz to about 200 Hz, about 100 Hz to about 120 Hz, about 100 Hz to about 150 Hz, about 100 Hz to about 200 Hz, about 120 Hz to about 150 Hz, about 120 Hz to about 200 Hz, or about 150 Hz to about 200 Hz.

[0104] In some embodiments, the stimulation program can comprise a current. Current through the electrodes can follow Ohm’s law: I=V / R, where R is the skin resistance and V is the voltage across the electrodes. The current generator can adjust the voltage across the electrodes to maintain a desired current level. In some embodiments, a current intensity may comprise at least about 10 μA, 20 μA, 30 μA, 40 μA, 50 μA, 100 μA, 150 μA, 200 μA, 250 μA, 500 μA, 750 μA, 1 mA, 2 mA, 3 mA, 4 mA, 5 mA, 10 mA, 15 mA, 20 mA, or greater than about 20 mA. In some embodiments, a current intensity may comprise at most about 20 mA, 15 mA, 10 mA, 5 mA, 4 mA, 3 mA, 2 mA, 1 mA, 750 μA, 500 μA, 250 μA, 200 μA, 150 μA, 100 μA, 50 μA, 40 μA, 30 μA, 20 μA, 10 μA, or less than about 10 μA. In some embodiments, a current intensity of a stimulation system and / or device described herein may comprise a range between about 0.01 mA to about 20 mA. In some embodiments, a current intensity of a stimulation system and / or device described herein may comprise a range between about 0.01 mA to about 0.05 mA, about 0.01 mA to about 0.1 mA, about 0.01 mA to about 0.5 mA, about 0.01 mA to about 1 mA, about 0.01 mA to about 2 mA, about 0.01 mA to about 3 mA, about 0.01 mA to about 4 mA, about 0.01 mA to 25WSGR Docket No.68475-701.601 about 5 mA, about 0.01 mA to about 10 mA, about 0.01 mA to about 15 mA, about 0.01 mA to about 20 mA, about 0.05 mA to about 0.1 mA, about 0.05 mA to about 0.5 mA, about 0.05 mA to about 1 mA, about 0.05 mA to about 2 mA, about 0.05 mA to about 3 mA, about 0.05 mA to about 4 mA, about 0.05 mA to about 5 mA, about 0.05 mA to about 10 mA, about 0.05 mA to about 15 mA, about 0.05 mA to about 20 mA, about 0.1 mA to about 0.5 mA, about 0.1 mA to about 1 mA, about 0.1 mA to about 2 mA, about 0.1 mA to about 3 mA, about 0.1 mA to about 4 mA, about 0.1 mA to about 5 mA, about 0.1 mA to about 10 mA, about 0.1 mA to about 15 mA, about 0.1 mA to about 20 mA, about 0.5 mA to about 1 mA, about 0.5 mA to about 2 mA, about 0.5 mA to about 3 mA, about 0.5 mA to about 4 mA, about 0.5 mA to about 5 mA, about 0.5 mA to about 10 mA, about 0.5 mA to about 15 mA, about 0.5 mA to about 20 mA, about 1 mA to about 2 mA, about 1 mA to about 3 mA, about 1 mA to about 4 mA, about 1 mA to about 5 mA, about 1 mA to about 10 mA, about 1 mA to about 15 mA, about 1 mA to about 20 mA, about 2 mA to about 3 mA, about 2 mA to about 4 mA, about 2 mA to about 5 mA, about 2 mA to about 10 mA, about 2 mA to about 15 mA, about 2 mA to about 20 mA, about 3 mA to about 4 mA, about 3 mA to about 5 mA, about 3 mA to about 10 mA, about 3 mA to about 15 mA, about 3 mA to about 20 mA, about 4 mA to about 5 mA, about 4 mA to about 10 mA, about 4 mA to about 15 mA, about 4 mA to about 20 mA, about 5 mA to about 10 mA, about 5 mA to about 15 mA, about 5 mA to about 20 mA, about 10 mA to about 15 mA, about 10 mA to about 20 mA, or about 15 mA to about 20 mA.

[0105] In some embodiments, the stimulation program can comprise a pulse width. The pulse width may comprise at least about 0.5 μs, 1 μs, 2 μs, 3 μs, 4 μs, 5 μs, 10 μs, 20 μs, 30 μs, 40 μs, 50 μs, 100 μs, 250 μs, 500 μs, 1000 μs, 5 ms, 10 ms, 25 ms, 50 ms, 100 ms, 250 ms, 500 ms, or greater than about 500 ms. The pulse width may comprise at most about 500 ms, 250 ms, 100 ms, 50 ms, 25 ms, 10 ms, 5 ms, 1000 μs, 500 μs, 250 μs, 100 μs, 50 μs, 40 μs, 30 μs, 20 μs, 10 μs, 5 μs, 4 μs, 3 μs, 2 μs, 1 μs, 0.5 μs, or less than about 0.5 μs. The pulse width may comprise a range between about 0.01 ms to about 100 ms. The pulse width may comprise a range between about 0.01 ms to about 0.05 ms, about 0.01 ms to about 0.1 ms, about 0.01 ms to about 0.5 ms, about 0.01 ms to about 1 ms, about 0.01 ms to about 5 ms, about 0.01 ms to about 10 ms, about 0.01 ms to about 25 ms, about 0.01 ms to about 50 ms, about 0.01 ms to about 75 ms, about 0.01 ms to about 100 ms, about 0.05 ms to about 0.1 ms, about 0.05 ms to about 0.5 ms, about 0.05 ms to about 1 ms, about 0.05 ms to about 5 ms, about 0.05 ms to about 10 ms, about 0.05 ms to about 25 ms, about 0.05 ms to about 50 ms, about 0.05 ms to about 75 ms, about 0.05 ms to about 100 ms, about 0.1 ms to about 0.5 ms, about 0.1 ms to about 1 ms, about 0.1 ms to about 5 ms, about 0.1 ms to about 10 ms, about 0.1 ms to about 25 ms, about 0.1 ms to about 50 ms, about 0.1 ms to about 75 ms, about 0.1 ms to about 100 ms, about 0.5 ms to about 1 ms, about 0.5 ms to about 5 26WSGR Docket No.68475-701.601 ms, about 0.5 ms to about 10 ms, about 0.5 ms to about 25 ms, about 0.5 ms to about 50 ms, about 0.5 ms to about 75 ms, about 0.5 ms to about 100 ms, about 1 ms to about 5 ms, about 1 ms to about 10 ms, about 1 ms to about 25 ms, about 1 ms to about 50 ms, about 1 ms to about 75 ms, about 1 ms to about 100 ms, about 5 ms to about 10 ms, about 5 ms to about 25 ms, about 5 ms to about 50 ms, about 5 ms to about 75 ms, about 5 ms to about 100 ms, about 10 ms to about 25 ms, about 10 ms to about 50 ms, about 10 ms to about 75 ms, about 10 ms to about 100 ms, about 25 ms to about 50 ms, about 25 ms to about 75 ms, about 25 ms to about 100 ms, about 50 ms to about 75 ms, about 50 ms to about 100 ms, or about 75 ms to about 100 ms.

[0106] The stimulation program may comprise a voltage, wherein the voltage level can be optimized for the size of the electrode. In some embodiments, a voltage may comprise at least about 25V, at least about 50V, at least about 75V, at least about 100V, at least about 125V, at least about 150V, at least about 175V, at least about 200V, at least about 250V, at least about 300V, at least about 350V, at least about 400V, at least about 450V, at least about 500V, or greater than about 500V. In some embodiments, a voltage may comprise at most about 500V, at most about 450V, at most about 400V, at most about 350V, at most about 300V, at most about 250V, at most about 200V, at most about 175V, at most about 150V, at most about 125V, at most about 100V, at most about 75V, at most about 50V, at most about 25V, or less than about 25V. In some embodiments, a voltage may comprise a range between about 25 V to about 400 V. In some embodiments, a voltage may comprise a range between about 25 V to about 50 V, about 25 V to about 75 V, about 25 V to about 100 V, about 25 V to about 125 V, about 25 V to about 150 V, about 25 V to about 175 V, about 25 V to about 200 V, about 25 V to about 250 V, about 25 V to about 300 V, about 25 V to about 350 V, about 25 V to about 400 V, about 50 V to about 75 V, about 50 V to about 100 V, about 50 V to about 125 V, about 50 V to about 150 V, about 50 V to about 175 V, about 50 V to about 200 V, about 50 V to about 250 V, about 50 V to about 300 V, about 50 V to about 350 V, about 50 V to about 400 V, about 75 V to about 100 V, about 75 V to about 125 V, about 75 V to about 150 V, about 75 V to about 175 V, about 75 V to about 200 V, about 75 V to about 250 V, about 75 V to about 300 V, about 75 V to about 350 V, about 75 V to about 400 V, about 100 V to about 125 V, about 100 V to about 150 V, about 100 V to about 175 V, about 100 V to about 200 V, about 100 V to about 250 V, about 100 V to about 300 V, about 100 V to about 350 V, about 100 V to about 400 V, about 125 V to about 150 V, about 125 V to about 175 V, about 125 V to about 200 V, about 125 V to about 250 V, about 125 V to about 300 V, about 125 V to about 350 V, about 125 V to about 400 V, about 150 V to about 175 V, about 150 V to about 200 V, about 150 V to about 250 V, about 150 V to about 300 V, about 150 V to about 350 V, about 150 V to about 400 V, about 175 V to about 200 V, about 175 V to about 250 V, about 175 V to about 300 V, about 175 V to about 350 V, about 175 V to about 400 V, about 27WSGR Docket No.68475-701.601 200 V to about 250 V, about 200 V to about 300 V, about 200 V to about 350 V, about 200 V to about 400 V, about 250 V to about 300 V, about 250 V to about 350 V, about 250 V to about 400 V, about 300 V to about 350 V, about 300 V to about 400 V, or about 350 V to about 400 V.

[0107] In some embodiments, a maximum voltage may comprise about 150V. Without wishing to be bound by theory, the higher voltage a circuit operates on, the isolation distance between components and traces may be larger on the printed circuit board. Components themselves may also get larger with a higher voltage rating.

[0108] A pulse pattern of the stimulation program may be cyclical or sinusoidal. In some cases, the pulse pattern may be rhythmic. In some cases, the pulse pattern may be arrhythmic. In some cases, the pulse pattern may be constant. In some embodiments, the pulse pattern can be paired with a cardiovascular activity of the subject. For example, a pulse pattern may be paired (e.g., synced) with a heart rate of a subject. In some embodiments, the pulse pattern may not be paired with a cardiovascular activity of the subject.

[0109] In some embodiments, stimulation of the subject’s nerve may be by non-invasive stimulation (e.g., non-invasive neurostimulation). In some embodiments, stimulation of the subject’s nerve may be by invasive stimulation. The non-invasive stimulation (e.g., non-invasive neurostimulation) can be achieved via transcutaneous stimulation. A transcutaneous neurostimulator can comprise one or more electrodes. In some embodiments, a stimulation device described herein (e.g., transcutaneous neurostimulator) can comprise at least about 1, 2, 3, 4, 5, or more electrodes. The electrodes can be configured to administer stimulation to the subject (e.g., to a nerve of the subject).

[0110] The methods described herein can further comprise monitoring sympathetic activity, parasympathetic activity, or any combination thereof of the subject. Monitoring sympathetic activity and / or parasympathetic activity can comprise measuring heart rate variation (e.g., coefficient of heart rate variation (HRV)), pulse rate variability (PRV), pulse rate quotient (PRQ), functional threshold power (FTP), velocity, power management, perceived rate of exertion, VO2 Max, EEG bandwidth, or any combination thereof.

[0111] In some embodiments, the methods described herein can further comprise stimulating a second nerve of subject. In some embodiments, the second nerve can be the same as the first nerve. In some embodiments, the second nerve can be different than the first nerve. In some embodiments, the second nerve can be at a same location of the body as the nerve (e.g., first nerve) of the subject. For example, the nerve (e.g., first nerve) may be located at a subject’s left wrist, and a second nerve may be located at a subject’s left wrist or right wrist. The second nerve can comprise a median nerve, a vagal nerve, a trigeminal nerve, a tibial nerve, or any combination thereof. In some embodiments, a first nerve may be stimulated as a priming stimulation for a 28WSGR Docket No.68475-701.601 second nerve of the subject. In some embodiments, the nerve (e.g., first nerve) and the second are stimulated concurrently. In some embodiments, the nerve of the subject (e.g., first nerve) can be stimulated prior to the second nerve. In some embodiments, the nerve of the subject (e.g., first nerve) can be stimulated subsequent to the second nerve.

[0112] In some embodiments, the subject may proceed through a breathing exercise. The breathing exercise can comprise inhalation and / or exhalation (e.g., inhalation and / or exhalation dynamics). The inhalation and / or exhalation dynamics may increase both sympathetic activity and parasympathetic activity. The inhalation and / or exhalation dynamics may decrease both sympathetic activity and parasympathetic activity. The inhalation and / or exhalation dynamics may increase sympathetic activity and decrease parasympathetic activity. The inhalation and / or exhalation dynamics may decrease sympathetic activity and increase parasympathetic activity. The breathing exercise can regulate an equal ratio of sympathetic / parasympathetic activity. For example, the breath exercise can regulate a low frequency (LF) to high frequency (HF) ratio (LF / HF ratio). The LF / HF ratio can be a metric of heart rate variability (HRV) and provide an indication of sympathetic / parasympathetic balance.

[0113] In some embodiments, the methods described herein can further comprise administering a secondary signal. The secondary signal can comprise an audio signal, a visual signal, or an audiovisual signal. In some embodiments, the secondary signal can be administered prior to stimulating a nerve of the subject. In some embodiments, the secondary signal can be administered subsequent to stimulating a nerve of the subject. In some embodiments, the secondary signal can be administered concurrently with stimulating a nerve of the subject. Stimulating a nerve of a subject (e.g., a first nerve and / or a second nerve) can occur concurrently with the subject proceeding through the exercise protocol (e.g., the physical exercise, psychological exercise, or breathing exercise). Stimulating a nerve of a subject (e.g., a first nerve and / or a second nerve) can occur after the subject proceeds through the exercise protocol (e.g., the physical exercise, psychological exercise, or breathing exercise).

[0114] In response to the stimulation, the physiological parameter and / or psychological parameter may be measured. In some embodiments, the physiological parameter and / or psychological parameter may be measured at least about 1 second, 5 seconds, 10 seconds, 15 seconds, 30 seconds, 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 10 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 24 hours, or greater than 24 hours after stimulation of the nerve. In some embodiments, the physiological parameter and / or psychological parameter may be measured at most about 24 hours, 12 hours, 6 hours, 5 hours, 4 hours, 3 hours, 2 hours, 1 hour, 45 minutes, 30 minutes, 15 minutes, 10 minutes, 29WSGR Docket No.68475-701.601 5 minutes, 4 minutes, 3 minutes, 2 minutes, 1 minute, 30 seconds, 15 seconds, 10 seconds, 5 seconds, 1 second, or less than 1 second after stimulation of the nerve.

[0115] Based on the measured physiological parameter and / or psychological parameter, the stimulation program can be modified. For example, based on the measured physiological parameter and / or psychological parameter a frequency, a pulse width, a pulse pattern, a current, a voltage, a pulse duration, a repetition rate, a current intensity, or any combination thereof may be modified to adjust the stimulation. Stimulation of the nerve can improve at least one biometric of the subject. In some embodiments, the methods described herein may comprise ceasing stimulation in response to improvement of the at least one biometric. In some embodiments, the methods described herein may comprise prolonging stimulation in response to improvement of the at least one biometric.

[0116] The stimulation device (e.g., transcutaneous neurostimulator) can be in electronic communication with the computing device described herein. The computing device may comprise a mobile electronic device. The mobile electronic device can be a smartwatch. In some embodiments, the mobile electronic device can be a smartphone. The secondary signal administered to the subject may be on the mobile electronic device. For example, a secondary signal may comprise an audio signal emitted from the mobile electronic device (e.g., smartwatch). As another example, the secondary signal may comprise a visual signal (e.g., a flashing screen) emitted from the mobile electronic device (e.g., smartwatch). The stimulation program may further comprise one or more stimulation profiles. The one or more stimulation profiles may each comprise at least one different stimulation parameter (e.g., a frequency, a pulse width, a pulse pattern, a current, a voltage, a pulse duration, a repetition rate, or a current intensity). The stimulation profile may depend on the exercise protocol. For example, one stimulation profile may be selected for a breathing exercise and a different stimulation profile may be selected for a psychological exercise. In some embodiments, modifying the stimulation program in response to the measured physiological parameter and / or psychological parameter can comprise selecting a different stimulation profile. In some embodiments, the methods described herein can comprise a subject selecting at least two or more stimulation profiles. In some embodiments, the methods described herein can further comprise determining a baseline physiological and / or psychological parameter of the subject. The baseline physiological and / or psychological parameter can be the same type of physiological and / or psychological parameter as the measured physiological and / or psychological parameter. In some embodiments, the baseline physiological and / or psychological parameter can be different than the measured physiological and / or psychological parameter. In some embodiments, a stimulation may be modified based on comparison of the baseline 30WSGR Docket No.68475-701.601 physiological and / or psychological parameter and the measured physiological and / or psychological parameter.

[0117] As an example, a method of improving a state of a subject can comprise: (a) establishing a baseline cardiovascular parameter, baseline respiratory parameter, a baseline biomechanical parameter, a baseline biochemical parameter, or any combination thereof; (b) detecting an inhalation or exhalation of the subject; (c) measuring a physiological state of the subject based on the inhalation or exhalation; (d) comparing the physiological state to the baseline cardiovascular parameter, baseline respiratory parameter, baseline biomechanical parameter, baseline biochemical parameter, or any combination thereof; and (e) administering a stimulation to a nerve of the subject based on the comparison of (d); and wherein the stimulation improves the state of the subject.

[0118] In some embodiments, a cardiovascular parameter can comprise a neurocardiovascular parameter.

[0119] As another example, a method of improving a state of a subject, the method comprising: (a) receiving from: one or more first sensors, at least one signal indicative of a baseline cardio- vascular parameter; and one or more second sensors, at least one signal indicative of a baseline respiratory parameter; (b) determining an inhalation or exhalation of the subject; (c) measuring a physiological state of the subject; (d) comparing the physiological state to the baseline cardiovascular parameter, the base-line respiratory parameter, or any combination thereof to determine a cardiorespiratory dynamic and / or neurocardiac dynamic; and (e) administering a stimulation via one or more electrodes to a nerve of the subject, wherein the stimulation can be based on the cardiorespiratory dynamic and / or neurocardiac dynamic.

[0120] In some embodiments, the methods provided herein may further comprise providing instruction to the subject. The instructions can comprise proceeding through an exercise protocol. The instructions can be provided by way of a computing device. In some embodiments, an exercise protocol can comprise a biofeedback-based exercise. In some embodiments, the exercise protocol can comprise a physical exercise, a psychological exercise, or a breathing exercise.

[0121] As another example, a method of improving a state of a subject can comprise: (a) receiving from: one or more sensors, at least one signal indicative of a baseline respiratory parameter; (b) determining an inhalation or exhalation; (c) measuring a respiratory pattern of the subject; (d) comparing the respiratory pattern with the baseline respiratory parameter; and (e) applying a stimulation to a nerve of the subject based on the comparison of the respiratory state pattern the baseline respiratory parameter. In some embodiments, the baseline respiratory parameter can comprise any measure of brain, heart, or lung function (e.g., a neuro-cardiorespiratory parameter). 31WSGR Docket No.68475-701.601

[0122] An exemplary embodiment of the methods described herein is shown in FIG.1. The flow chart depicts a method 100 for assisting performance-based breathing and / or neurostimulation programs during one or more user sessions. In some embodiments, a practice protocol can be selected in a step 101. Following selection of the training protocol (e.g., exercise protocol), stimulation types can be selected in steps 102, 103. A user can initiate a breathing session with a desired or predetermined breathing rate in a step 104. In some embodiments, the user can initiate a physiological exercise. In some embodiments, the user can initiate a psychological exercise. A biological state indicator may indicate a level (e.g., state) of a subject’s biological function. A measured physiological and / or psychological parameter may be measured in a step 105. A biological state indicator indicating a state of one of the user’s biological functions may be measured. The biological state indicator may be heart rate variability (HRV) as utilized in the respiratory-based biofeedback (BF) protocols. The HRV may provide real-time physiological information. The real-time physiological information can comprise respiratory rate, average heart rate, an increase and / or decrease of heart rate, a lung capacity, an oxygen content, a pulse rate variability, a pulse respiratory quotient, or any combination thereof. One or more biosensors described herein may be used to assess and / or monitor a subject’s psychophysiology. A neurostimulation device described herein can comprise one or more sensors (e.g., biosensors). For example, the neurostimulation device can comprise an integrated photoplethysmographic (PPG) that calculates at least one of the heart rate, the heart rate variability (HRV), blood-oxygen content, or blood pressure of the subject. The one or more sensors of the neurostimulation device can detect the breathing phase (exhalation and / or inhalation) of the subject through a wrist, a leg, a neck, a forehead, or any combination thereof. A neurostimulation device of the present disclosure can comprise at least one dry-contact electrodes (e.g., 1, 2, 3, 4, 5, or more dry-contact electrodes). The electrodes may be placed within the neurostimulation unit. The electrodes may be placed along the band. The neurostimulation unit and / or band can record neurological activity from the subject before, during, and / or after stimulation (e.g., vibratory stimulation, electrical stimulation, or vibro-electrotactile stimulation). The stimulation sessions can be conducted in real-time to run one or more EEG-based biofeedback protocols. The biofeedback protocol may be based upon the user’s respiration data, heart rate variability (HRV) data, electroencephalogram (EEG) data, or any combination thereof.

[0123] The subject’s biological functions (e.g., pulmonary functions, for example respiratory rate and depth) can be measured using various methods including, but not limited to, an accelerometer placed upon a user’s torso above the user’s diaphragm (which measures the undulations of the user’s diaphragm during inhalation and exhalation) and via plethysmography (PPG) as measured by an integrated biosensor or compatible wearable device. The subject’s cardiovascular or 32WSGR Docket No.68475-701.601 autonomic function can be measured using plethysmography (PPG) or can be recorded with compatible heart-rate sensors. A cardiovascular measure can comprise blood pressure and an autonomic measure can comprise heart rate variability. A subject’s EEG data can be recorded from the scalp of a subject to evaluate vagal activation, mental performance state indications, and / or autonomic efficacy of the stimulation sessions by analyzing various bandwidths (e.g., alpha, beta, gamma, or any combination thereof). A selection of bandwidth may provide increased efficacy for a system session. For example, selection of alpha band may provide advantages for focused attention training.

[0124] At step 106, it may be determined whether a biological state indicator of the subject can be in resonance or in an association with the predetermined physiological and / or psychological parameter (e.g., a baseline physiological and / or psychological parameter, for example a breathing rate and phase). As an example, resonance can occur when the subject’s respiratory frequency aligns with a baseline breathing rate (e.g., predetermined breathing rate), and / or when a cardiovascular, autonomic, or neurological parameters of interest are associated with, or correlated to, a predetermined or selected breathing rate, depth, and pattern. In some embodiments, resonance between the subject’s predetermined breathing rate and one or more biological state indicators can result in an equilibrium. The equilibrium can be achieved between one or more functions of the body (e.g., cardiovascular and / or respiratory states). The equilibrium may lead to a harmonious effect for more effective performance enhancement. It may be determined that the biological state of the subject can be in resonance with the predetermined breathing rate in a step 107. If resonance can be achieved, there may be no active correction during the subject’s biofeedback session as noted in a step 108. If resonance is not achieved (e.g., one or more biological states of the subject is not in resonance with the predetermined breathing rate) as noted in a step 109, then active correction may be used to correct the subject’s state in a step 110.

[0125] At step 110, a corrective input (e.g., audiovisual, proprioceptive, and / or other secondary signal described herein) can be delivered to the subject. The secondary signal can assist in harmonizing the measured physiological and / or psychological parameter and the baseline physiological and / or psychological parameter (e.g., predetermined breathing rate).

[0126] The signals to indicate a correct breathing rate during system correction in the step 110 can be audiovisual cues such as a note, tone, line of text, color, or shape. For example, the signal may be one that reacts accordingly to a subject’s breathing performance / accuracy. The signal may be tailored to the specific performance enhancement biofeedback and / or neurostimulation program types (e.g., stimulation profiles). The audiovisual cue may be pre-recorded verbal and / or visual instruction. The signal may also be vibrations or electrical pulses delivered to any part of a user’s body whether as a form of guidance and / or actual stimulation. 33WSGR Docket No.68475-701.601

[0127] The system correction step 110 delivered to the subject could also occur during performance related hypnosis which can be delivered in conjunction with respiratory-gated vibro- electrotactile nerve stimulation. Hypnosis can involve one or more auditory, visual, or other perceptible cues that deliver suggestive instructions to put the user into a performance ready state. During hypnosis, the user´s behavioral and emotional state can be influenced and malleable for positive psycho-behavioral change before, during, and after performance. Hypnosis can enhance parasympathetic activity and increases vagal tone (i.e., increasing levels of cardiac vagal HRV) while reducing sympathetic tone (i.e., low-frequency HRV). There can be a positive correlation between hypnotic susceptibility, autonomic responsiveness, and / or vagal efferent activity during hypnosis. Hypnosis delivery can be personalized by a subject. For example, a hypnotic protocol can be administered during one or more vibro-electrotactile stimulation sessions. The combination of hypnotic protocol with neurostimulation may gate to a subject’s inhalation, breath-hold, and / or exhalation phase.

[0128] At step 111, the method can return to step 105 of measuring a biological state indicator and / or step 106 to determine an effect of the performance program. The performance program may have resulted in the biological state now being in resonance (in association to or in correlation) with the baseline physiological and / or psychological parameter (e.g., the predetermined breathing technique, rate, depth, or phase of the subject). The subject may be undergoing biofeedback training paired or unpaired with neurostimulation. The methods described herein may cycle through 105 to 110 continuously monitoring for resonance and / or correcting the physiological and / or psychological parameter(s) (e.g., breathing rate) of the subject if needed.

[0129] The method 100 can further include stimulating a subject’s nerve (e.g., a subject’s median nerve, vagal nerve, and / or trigeminal nerve). The method 100 can further include stimulating a subject’s brain region (e.g., prefrontal cortical region) at predetermined intervals in a step 112. For example, the nerve may be stimulated by vibrations and / or electricity on the subject’s viscera (e.g., area below the subject’s neck). As another example, the brain region may be electrically stimulated on the subject’s forehead. The predetermined intervals for stimulation may be in line with the predetermined physiological and / or psychological parameter (e.g., breathing dynamics) and stimulation parameters (e.g., frequency, depth, and / or pulse pattern). For example, at the predetermined physiological and / or psychological parameter (e.g., respiration rate and inhale / exhale ratio), the nerve stimulator can be activated to deliver stimulation to the nerve (e.g., respiratory-gated stimulation). As another example, the nerve stimulator can be activated only when it may be determined that the subject’s breathing rate may be out of synchronization with the predetermined physiological and / or psychological parameter (e.g., predetermined breathing 34WSGR Docket No.68475-701.601 rate). In an exemplary embodiment, the nerve stimulator can be activated at the predetermined respiratory frequency and when the user’s exhalation or inhalation may not be in synchronization. Stimulation of the activated nerve can provide the one or more signals to indicate a correct breathing rate and exhalation / inhalation duration.

[0130] In some examples, the predetermined breathing rate determined by the step 104 can be a fixed biometric parameter (e.g., at the resonance frequency). In some embodiments, a breathing rate may be fixed at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, or 20 breaths per minute (bpm). For example, the breathing rate (resonance frequency) may be fixed at 6 breaths per minute (bpm). In another example, the method can further comprise gathering information on a particular subject and determining a breathing rate specific to the individual subject. This personalized breathing rate may account for a subject’s experience with performance. For example, a subject who may be new to priming (pre-competitive / training preparation) before a performance endeavor may have a breathing rate set at a higher number of inhalations per minute. The breathing rate may be increased over time such that, as a user becomes more experienced in preparing for performance states, their preset time between breaths can be increased or decreased dependent on their physiological output and desired state.

[0131] A technical solution of the present disclosure provides a subject with a means of maintaining and / or optimizing adaptive emotional self-regulatory and cognitive performance factors, including, but not limited to, psychological functions (e.g., memory, attention, and / or executive functions), athletic performance, and / or biological states. Systems for Modulating Functions

[0132] In an aspect, the present disclosure provides a system for modulating a function of a subject. The function may be a respiratory function, a cardiovascular function, a neurological function, or any combination thereof. The system can comprise a flexible carrier. The flexible carrier can be configured to be worn by the subject. The flexible carrier can comprise electronic components. The system can comprise a stimulator (e.g., a neurostimulator). The neurostimulator can be non-invasive, wherein the stimulator can comprise a transcutaneous neurostimulator. The neurostimulator can comprise one or more electrodes (e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more electrodes). The electrodes can be coupled to the flexible carrier. The system can further comprise one or more sensors (e.g., biosensors). The biosensors may retrieve at least one signal from the subject. The signal may be indicative of a biological pattern of the subject. In some cases, the signal may be indicative of a subject’s respiratory pattern (e.g., an inhalation and / or exhalation). The system can comprise a controller configured to communicate with the transcutaneous neurostimulator. The controller may comprise a memory-storing biofeedback program. In some embodiments, the 35WSGR Docket No.68475-701.601 memory-storing biofeedback program may be configured to compare a signal and a biological pattern of the subject. For example, the memory-storing biofeedback program can be configured to compare at least one signal indicative of the subject’s respiratory pattern with a baseline respiratory pattern of the subject.

[0133] As an example, a system for modulating a respiratory function of a subject can comprise: (i) a flexible carrier configured to be worn by the subject; (ii) a transcutaneous neurostimulator, the transcutaneous neurostimulator comprising at least one electrode coupled to the flexible carrier; (iii) one or more sensors configured to retrieve at least one signal indicative of the subject’s respiratory pattern; and (iv) a controller configured to communicate with the transcutaneous neurostimulator and comprising a memory-storing biofeedback program, wherein the memory- storing biofeedback program may be configured to compare the at least one signal indicative of the subject’s respiratory pattern with a baseline respiratory pattern of the subject; and wherein the transcutaneous neurostimulator may be configured to generate one or more stimulation to a nerve of the subject.

[0134] As another example, the present disclosure provides a device (e.g., a cardiovascular neuromodulation biotech device) that can be embodied within a smartphone / smartwatch compatible wearable band. The neuromodulation device may be placed mainly upon a subject’s left wrist and / or right wrist. The system can be configured to noninvasively modulate autonomic activity and associated neurological functions by combining peripheral nerve stimulation with biofeedback to enhance human performance. The device can comprise at least one vibro- electrotactile stimulator. The at least one vibro-electrotactile stimulator can be located on a left and / or right wrist or forearm. The stimulator can be located at or around pericardium meridian of acupuncture point 6, PC6, located roughly 5 cm from the palmar wrist crease (in addition to PC5 and PC3) (e.g., directly above the median nerve). The device provided herein can be placed at the heart meridian / ulnar nerve location (such as HT3 and HT4) for transcutaneous ulnar stimulation. In some embodiments, the device provided herein can be placed around the neck for cervical transcutaneous vagus nerve stimulation (tVNS). In some embodiments, the device provided herein can be placed around the forehead for trigeminal nerve stimulation (i.e., electrical stimulation). The vibro-electrotactile stimulator can use an entire area of the wrist and / or forearm to stimulate the median nerve when a vibratory, electrical or a combined vibro-electrical pulse stimulus may be applied to it. A stimulation pulse can be delivered at a particular frequency, pattern (e.g., rhythmic, arrhythmic, or constant), and / or intensity within a pulse-paired or unpaired proprioceptive feedback protocol. The neurostimulator can be attached, integrated, and / or in communication with one or more biosensors that monitor and / or record a subject’s physiological output. The one or more biosensors can monitor the subject’s physiological output before, during, 36WSGR Docket No.68475-701.601 and / or after performance. Biometric data can be sent to a mobile electronic device (e.g., a subject’s personal computing device application). An application (e.g., app) on a subject’s mobile electronic device may program and / or run one or more human performance biofeedback training sessions. As another example, a system and / or device provided herein may be strapped onto a left and / or right wrist and connected to an external personal computing operating system containing a biological state indicator measuring module and determination module.

[0135] The system provided herein may further comprise a power source. The power source can be coupled to the flexible carrier. The memory-storing feedback program can be disposed on a mobile electronic device (e.g., an application on a smartwatch and / or smartphone).

[0136] In some embodiments, the nerve stimulated by the transcutaneous stimulator can comprise a peripheral nerve. In some embodiments, the nerve can be of the somatic nervous system or the autonomic nervous system (e.g., the sympathetic nervous system, the parasympathetic nervous system, or the enteric nervous system). The nerve may be a plexus of nerves. The nerve can be a collection of nerves. In some embodiments, the nerve can be a median nerve, a vagus nerve, a trigeminal nerve, a tibial nerve, or any combination thereof. In some embodiments, the methods described herein may comprise stimulating one or more nerves. In some embodiments, the methods described herein may comprise stimulating at least about 1 nerve, at least about 2 nerves, at least about 3 nerves, at least about 4 nerves, at least about 5 nerves, or greater than about 5 nerves. In some embodiments, the methods described herein may comprise stimulating at most about 5 nerves, at most about 4 nerves, at most about 3 nerves, at most about 2 nerves, at most about 1 nerve, or less than about 1 nerve.

[0137] In some embodiments, the one or more sensors (e.g., biosensors) may measure a physiological parameter, psychological parameter, or any combination thereof. The one or more sensors (e.g., biosensors) of the system described herein may comprise a electroencephalogram (EEG) sensor, and a photoplethysmographic (PPG) sensor, an electromyographic (EMG) sensors, an electrooculographic (EOG) sensor, an electrocardiogram (ECG) sensor, a pulse-oximeter, a chest monitor, a PPG biosensor ring, a PPG biosensor patch, a biosensor tattoo, a blood pressure sensor, a perspiration sensor, a skin conductivity sensor, an accelerometer, a location sensor, a gyroscope, or any combination thereof.

[0138] The nerve may be stimulated by vibratory stimulation, electrical stimulation, thermal stimulation, acoustic stimulation, infrasound stimulation, ultrasound stimulation, pulse laser, transient optical neural stimulation, or any combination thereof. In some embodiments, the nerve may be stimulated only with vibratory stimulation. In some embodiments, the nerve may be stimulated with vibratory stimulation and electrical stimulation at the same time. In some embodiments, the nerve may be stimulated with vibratory stimulation prior to electrical 37WSGR Docket No.68475-701.601 stimulation. In some embodiments, the nerve may be stimulated with vibratory stimulation subsequent to electrical stimulation.

[0139] The flexible carrier may be disposed on a subject’s body (e.g., on a subject’s skin). In some embodiments, the flexible carrier may be disposed on a subject’s arm, wrist, hand, neck, head, leg, torso, or any combination thereof. The at least one signal indicative of a subject’s respiratory pattern can comprise a respiratory rate, an inhalation, an exhalation, a breath-hold time, a tidal volume, a heart rate variability, a pulse respiratory quotient, or any combination thereof. In some embodiments, the one or more sensors can be disposed on a subject’s body. In some embodiments, the one or more sensors can be disposed on a subject’s arm, wrist, hand, neck, head, leg, torso, or any combination thereof. In some cases, the flexible carrier and the one or more sensors are disposed on the same area of the subject’s body (e.g., on a left wrist). The one or more sensors may measure at least one signal indicative of a subject’s cardiovascular health. In some embodiments, the at least one signal indicative of the subject’s cardiovascular health comprises a heart rate, a resting heart rate, a VO2 max, a blood-oxygen content, a blood pressure, an electrodermal activity, electrocardiogram (EEG) information, a body position, a sleep cycle, a body temperature, a mile-split time, or any combination thereof. In some cases, one biosensor may measure at least one signal indicative of the subject’s cardiovascular health and at least one signal indicative of the subject’s respiratory pattern.

[0140] Stimulation of the subject’s nerve may be achieved by continuous stimulation or burst stimulation. In some embodiments, one or more stimulation administered to the subject can comprise one or more parameters (e.g., stimulation parameters). The parameters may comprise a frequency, a pulse width, a pulse pattern, a current, a voltage, a pulse duration, a repetition rate, a current intensity, or any combination thereof. In some embodiments, a frequency can comprise at least about 1 Hz, 2 Hz, 3 Hz, 4 Hz, 5 Hz, 10 Hz, 20 Hz, 30 Hz, 40 Hz, 50 Hz, 60 Hz, 70 Hz, 80 Hz, 90 Hz, 100 Hz, 110 Hz, 120 Hz, 130 Hz, 140 Hz, 150 Hz, 200 Hz, 250 Hz, 500 Hz, 750 Hz, 1000 Hz, or greater than about 1000 Hz. In some embodiments, a frequency can comprise at most about 1000 Hz, 750 Hz, 500 Hz, 250 Hz, 200 Hz, 150 Hz, 140 Hz, 130 Hz, 120 Hz, 110 Hz, 100 Hz, 90 Hz, 80 Hz, 70 Hz, 60 Hz, 50 Hz, 40 Hz, 30 Hz, 20 Hz, 10 Hz, 5 Hz, 4 Hz, 3 Hz, 2 Hz, 1 Hz, or less than about 1 Hz. In some embodiments, a frequency can comprise a range between about 5 Hz to about 200 Hz. In some embodiments, a frequency can comprise a range between about 5 Hz to about 10 Hz, about 5 Hz to about 25 Hz, about 5 Hz to about 50 Hz, about 5 Hz to about 60 Hz, about 5 Hz to about 70 Hz, about 5 Hz to about 80 Hz, about 5 Hz to about 90 Hz, about 5 Hz to about 100 Hz, about 5 Hz to about 120 Hz, about 5 Hz to about 150 Hz, about 5 Hz to about 200 Hz, about 10 Hz to about 25 Hz, about 10 Hz to about 50 Hz, about 10 Hz to about 60 Hz, about 10 Hz to about 70 Hz, about 10 Hz to about 80 Hz, about 10 Hz to about 90 Hz, 38WSGR Docket No.68475-701.601 about 10 Hz to about 100 Hz, about 10 Hz to about 120 Hz, about 10 Hz to about 150 Hz, about 10 Hz to about 200 Hz, about 25 Hz to about 50 Hz, about 25 Hz to about 60 Hz, about 25 Hz to about 70 Hz, about 25 Hz to about 80 Hz, about 25 Hz to about 90 Hz, about 25 Hz to about 100 Hz, about 25 Hz to about 120 Hz, about 25 Hz to about 150 Hz, about 25 Hz to about 200 Hz, about 50 Hz to about 60 Hz, about 50 Hz to about 70 Hz, about 50 Hz to about 80 Hz, about 50 Hz to about 90 Hz, about 50 Hz to about 100 Hz, about 50 Hz to about 120 Hz, about 50 Hz to about 150 Hz, about 50 Hz to about 200 Hz, about 60 Hz to about 70 Hz, about 60 Hz to about 80 Hz, about 60 Hz to about 90 Hz, about 60 Hz to about 100 Hz, about 60 Hz to about 120 Hz, about 60 Hz to about 150 Hz, about 60 Hz to about 200 Hz, about 70 Hz to about 80 Hz, about 70 Hz to about 90 Hz, about 70 Hz to about 100 Hz, about 70 Hz to about 120 Hz, about 70 Hz to about 150 Hz, about 70 Hz to about 200 Hz, about 80 Hz to about 90 Hz, about 80 Hz to about 100 Hz, about 80 Hz to about 120 Hz, about 80 Hz to about 150 Hz, about 80 Hz to about 200 Hz, about 90 Hz to about 100 Hz, about 90 Hz to about 120 Hz, about 90 Hz to about 150 Hz, about 90 Hz to about 200 Hz, about 100 Hz to about 120 Hz, about 100 Hz to about 150 Hz, about 100 Hz to about 200 Hz, about 120 Hz to about 150 Hz, about 120 Hz to about 200 Hz, or about 150 Hz to about 200 Hz.

[0141] In some embodiments, a current intensity may comprise at least about 10 μA, 20 μA, 30 μA, 40 μA, 50 μA, 100 μA, 150 μA, 200 μA, 250 μA, 500 μA, 750 μA, 1 mA, 2 mA, 3 mA, 4 mA, 5 mA, 10 mA, 15 mA, 20 mA, or greater than about 20 mA. In some embodiments, a current intensity may comprise at most about 20 mA, 15 mA, 10 mA, 5 mA, 4 mA, 3 mA, 2 mA, 1 mA, 750 μA, 500 μA, 250 μA, 200 μA, 150 μA, 100 μA, 50 μA, 40 μA, 30 μA, 20 μA, 10 μA, or less than about 10 μA. In some embodiments, a current intensity of a stimulation system and / or device described herein may comprise a range between about 0.01 mA to about 20 mA. In some embodiments, a current intensity of a stimulation system and / or device described herein may comprise a range between about 0.01 mA to about 0.05 mA, about 0.01 mA to about 0.1 mA, about 0.01 mA to about 0.5 mA, about 0.01 mA to about 1 mA, about 0.01 mA to about 2 mA, about 0.01 mA to about 3 mA, about 0.01 mA to about 4 mA, about 0.01 mA to about 5 mA, about 0.01 mA to about 10 mA, about 0.01 mA to about 15 mA, about 0.01 mA to about 20 mA, about 0.05 mA to about 0.1 mA, about 0.05 mA to about 0.5 mA, about 0.05 mA to about 1 mA, about 0.05 mA to about 2 mA, about 0.05 mA to about 3 mA, about 0.05 mA to about 4 mA, about 0.05 mA to about 5 mA, about 0.05 mA to about 10 mA, about 0.05 mA to about 15 mA, about 0.05 mA to about 20 mA, about 0.1 mA to about 0.5 mA, about 0.1 mA to about 1 mA, about 0.1 mA to about 2 mA, about 0.1 mA to about 3 mA, about 0.1 mA to about 4 mA, about 0.1 mA to about 5 mA, about 0.1 mA to about 10 mA, about 0.1 mA to about 15 mA, about 0.1 mA to about 20 mA, about 0.5 mA to about 1 mA, about 0.5 mA to about 2 mA, about 0.5 mA to about 3 mA, 39WSGR Docket No.68475-701.601 about 0.5 mA to about 4 mA, about 0.5 mA to about 5 mA, about 0.5 mA to about 10 mA, about 0.5 mA to about 15 mA, about 0.5 mA to about 20 mA, about 1 mA to about 2 mA, about 1 mA to about 3 mA, about 1 mA to about 4 mA, about 1 mA to about 5 mA, about 1 mA to about 10 mA, about 1 mA to about 15 mA, about 1 mA to about 20 mA, about 2 mA to about 3 mA, about 2 mA to about 4 mA, about 2 mA to about 5 mA, about 2 mA to about 10 mA, about 2 mA to about 15 mA, about 2 mA to about 20 mA, about 3 mA to about 4 mA, about 3 mA to about 5 mA, about 3 mA to about 10 mA, about 3 mA to about 15 mA, about 3 mA to about 20 mA, about 4 mA to about 5 mA, about 4 mA to about 10 mA, about 4 mA to about 15 mA, about 4 mA to about 20 mA, about 5 mA to about 10 mA, about 5 mA to about 15 mA, about 5 mA to about 20 mA, about 10 mA to about 15 mA, about 10 mA to about 20 mA, or about 15 mA to about 20 mA.

[0142] The pulse width may comprise at least about 0.5 μs, 1 μs, 2 μs, 3 μs, 4 μs, 5 μs, 10 μs, 20 μs, 30 μs, 40 μs, 50 μs, 100 μs, 250 μs, 500 μs, 1000 μs, 5 ms, 10 ms, 25 ms, 50 ms, 100 ms, 250 ms, 500 ms, or greater than about 500 ms. The pulse width may comprise at most about 500 ms, 250 ms, 100 ms, 50 ms, 25 ms, 10 ms, 5 ms, 1000 μs, 500 μs, 250 μs, 100 μs, 50 μs, 40 μs, 30 μs, 20 μs, 10 μs, 5 μs, 4 μs, 3 μs, 2 μs, 1 μs, 0.5 μs, or less than about 0.5 μs. The pulse width may comprise a range between about 0.01 ms to about 100 ms. The pulse width may comprise a range between about 0.01 ms to about 0.05 ms, about 0.01 ms to about 0.1 ms, about 0.01 ms to about 0.5 ms, about 0.01 ms to about 1 ms, about 0.01 ms to about 5 ms, about 0.01 ms to about 10 ms, about 0.01 ms to about 25 ms, about 0.01 ms to about 50 ms, about 0.01 ms to about 75 ms, about 0.01 ms to about 100 ms, about 0.05 ms to about 0.1 ms, about 0.05 ms to about 0.5 ms, about 0.05 ms to about 1 ms, about 0.05 ms to about 5 ms, about 0.05 ms to about 10 ms, about 0.05 ms to about 25 ms, about 0.05 ms to about 50 ms, about 0.05 ms to about 75 ms, about 0.05 ms to about 100 ms, about 0.1 ms to about 0.5 ms, about 0.1 ms to about 1 ms, about 0.1 ms to about 5 ms, about 0.1 ms to about 10 ms, about 0.1 ms to about 25 ms, about 0.1 ms to about 50 ms, about 0.1 ms to about 75 ms, about 0.1 ms to about 100 ms, about 0.5 ms to about 1 ms, about 0.5 ms to about 5 ms, about 0.5 ms to about 10 ms, about 0.5 ms to about 25 ms, about 0.5 ms to about 50 ms, about 0.5 ms to about 75 ms, about 0.5 ms to about 100 ms, about 1 ms to about 5 ms, about 1 ms to about 10 ms, about 1 ms to about 25 ms, about 1 ms to about 50 ms, about 1 ms to about 75 ms, about 1 ms to about 100 ms, about 5 ms to about 10 ms, about 5 ms to about 25 ms, about 5 ms to about 50 ms, about 5 ms to about 75 ms, about 5 ms to about 100 ms, about 10 ms to about 25 ms, about 10 ms to about 50 ms, about 10 ms to about 75 ms, about 10 ms to about 100 ms, about 25 ms to about 50 ms, about 25 ms to about 75 ms, about 25 ms to about 100 ms, about 50 ms to about 75 ms, about 50 ms to about 100 ms, or about 75 ms to about 100 ms. 40WSGR Docket No.68475-701.601

[0143] In some embodiments, a voltage may comprise at least about 25V, at least about 50V, at least about 75V, at least about 100V, at least about 125V, at least about 150V, at least about 175V, at least about 200V, at least about 250V, at least about 300V, at least about 350V, at least about 400V, at least about 450V, at least about 500V, or greater than about 500V. In some embodiments, a voltage may comprise at most about 500V, at most about 450V, at most about 400V, at most about 350V, at most about 300V, at most about 250V, at most about 200V, at most about 175V, at most about 150V, at most about 125V, at most about 100V, at most about 75V, at most about 50V, at most about 25V, or less than about 25V. In some embodiments, a voltage may comprise a range between about 25 V to about 400 V. In some embodiments, a voltage may comprise a range between about 25 V to about 50 V, about 25 V to about 75 V, about 25 V to about 100 V, about 25 V to about 125 V, about 25 V to about 150 V, about 25 V to about 175 V, about 25 V to about 200 V, about 25 V to about 250 V, about 25 V to about 300 V, about 25 V to about 350 V, about 25 V to about 400 V, about 50 V to about 75 V, about 50 V to about 100 V, about 50 V to about 125 V, about 50 V to about 150 V, about 50 V to about 175 V, about 50 V to about 200 V, about 50 V to about 250 V, about 50 V to about 300 V, about 50 V to about 350 V, about 50 V to about 400 V, about 75 V to about 100 V, about 75 V to about 125 V, about 75 V to about 150 V, about 75 V to about 175 V, about 75 V to about 200 V, about 75 V to about 250 V, about 75 V to about 300 V, about 75 V to about 350 V, about 75 V to about 400 V, about 100 V to about 125 V, about 100 V to about 150 V, about 100 V to about 175 V, about 100 V to about 200 V, about 100 V to about 250 V, about 100 V to about 300 V, about 100 V to about 350 V, about 100 V to about 400 V, about 125 V to about 150 V, about 125 V to about 175 V, about 125 V to about 200 V, about 125 V to about 250 V, about 125 V to about 300 V, about 125 V to about 350 V, about 125 V to about 400 V, about 150 V to about 175 V, about 150 V to about 200 V, about 150 V to about 250 V, about 150 V to about 300 V, about 150 V to about 350 V, about 150 V to about 400 V, about 175 V to about 200 V, about 175 V to about 250 V, about 175 V to about 300 V, about 175 V to about 350 V, about 175 V to about 400 V, about 200 V to about 250 V, about 200 V to about 300 V, about 200 V to about 350 V, about 200 V to about 400 V, about 250 V to about 300 V, about 250 V to about 350 V, about 250 V to about 400 V, about 300 V to about 350 V, about 300 V to about 400 V, or about 350 V to about 400 V.

[0144] A pulse pattern of the stimulation program may be cyclical or sinusoidal. In some cases, the pulse pattern may be rhythmic. In some cases, the pulse pattern may be arrhythmic. In some cases, the pulse pattern may be constant. In some embodiments, the pulse pattern can be paired with a cardiovascular activity of the subject. For example, a pulse pattern may be paired (e.g., synced) with a heart rate of a subject. In some embodiments, the pulse pattern may not be paired with a cardiovascular activity of the subject. In some embodiments, the pulse pattern can be set 41WSGR Docket No.68475-701.601 based on the at least one signal indicative of the subject’s cardiovascular health measured by the one or more biosensor.

[0145] FIG. 8 depicts an image showing an exemplary configuration of one or more electrodes 805 and vibrator 810 of a system described herein. Electrodes may be spaced apart at a dimension measured from an interior side of each electrode (e.g., closer to the center of the system), for example as shown in FIG. 8. As another example, the electrodes may be spaced apart at a dimension measured from an exterior side of the electrode (e.g., away from the center of the system). The system may comprise at least about 1 electrode, at least about 2 electrodes, at least about 3 electrodes, at least about 4 electrodes, at least about 5 electrodes, or greater than about 5 electrodes. The system may comprise at most about 5 electrodes, at most about 4 electrodes, at most about 3 electrodes, at most about 2 electrodes, at most about 1 electrode, or less than 1 electrode. The system may comprise at least about 1 vibrator, at least about 2 vibrators, at least about 3 vibrators, at least about 4 vibrators, at least about 5 vibrators, or greater than about 5 vibrators. The system may comprise at most about 5 vibrators, at most about 4 vibrators, at most about 3 vibrators, at most about 2 vibrators, at most about 1 vibrator, or less than 1 vibrator. In some cases, as shown in FIG.8, the system may comprise about 2 electrodes and about 1 vibrator.

[0146] Electrodes of the system may comprise an anode and cathode. In some embodiments, the anode and cathode can be separated by at least about 0.5 centimeters (cm), 0.6 cm, 0.7 cm, 0.8 cm, 0.9 cm, 1.0 cm, 1.5 cm, 2.0 cm, 2.5 cm, 3.0 cm, 3.5 cm, 4.0, or greater than about 4.0 cm apart. In some embodiments, the anode and cathode can be separated by at most about 4.0 cm, 3.5 cm, 3.0 cm, 2.5 cm, 2.0 cm, 1.5 cm, 1.0 cm, 0.9 cm, 0.8 cm, 0.7 cm, 0.6 cm, 0.5 cm, or less than about 0.5 cm apart. In some embodiments, the anode and cathode can be separated between about 0.5 cm to about 4 cm apart. In some embodiments, the anode and cathode can be separated between about 0.5 cm to about 0.6 cm, about 0.5 cm to about 0.7 cm, about 0.5 cm to about 0.8 cm, about 0.5 cm to about 0.9 cm, about 0.5 cm to about 1 cm, about 0.5 cm to about 1.5 cm, about 0.5 cm to about 2 cm, about 0.5 cm to about 2.5 cm, about 0.5 cm to about 3 cm, about 0.5 cm to about 3.5 cm, about 0.5 cm to about 4 cm, about 0.6 cm to about 0.7 cm, about 0.6 cm to about 0.8 cm, about 0.6 cm to about 0.9 cm, about 0.6 cm to about 1 cm, about 0.6 cm to about 1.5 cm, about 0.6 cm to about 2 cm, about 0.6 cm to about 2.5 cm, about 0.6 cm to about 3 cm, about 0.6 cm to about 3.5 cm, about 0.6 cm to about 4 cm, about 0.7 cm to about 0.8 cm, about 0.7 cm to about 0.9 cm, about 0.7 cm to about 1 cm, about 0.7 cm to about 1.5 cm, about 0.7 cm to about 2 cm, about 0.7 cm to about 2.5 cm, about 0.7 cm to about 3 cm, about 0.7 cm to about 3.5 cm, about 0.7 cm to about 4 cm, about 0.8 cm to about 0.9 cm, about 0.8 cm to about 1 cm, about 0.8 cm to about 1.5 cm, about 0.8 cm to about 2 cm, about 0.8 cm to about 2.5 cm, about 0.8 cm to about 3 cm, about 0.8 cm to about 3.5 cm, about 0.8 cm to about 4 cm, about 0.9 cm to 42WSGR Docket No.68475-701.601 about 1 cm, about 0.9 cm to about 1.5 cm, about 0.9 cm to about 2 cm, about 0.9 cm to about 2.5 cm, about 0.9 cm to about 3 cm, about 0.9 cm to about 3.5 cm, about 0.9 cm to about 4 cm, about 1 cm to about 1.5 cm, about 1 cm to about 2 cm, about 1 cm to about 2.5 cm, about 1 cm to about 3 cm, about 1 cm to about 3.5 cm, about 1 cm to about 4 cm, about 1.5 cm to about 2 cm, about 1.5 cm to about 2.5 cm, about 1.5 cm to about 3 cm, about 1.5 cm to about 3.5 cm, about 1.5 cm to about 4 cm, about 2 cm to about 2.5 cm, about 2 cm to about 3 cm, about 2 cm to about 3.5 cm, about 2 cm to about 4 cm, about 2.5 cm to about 3 cm, about 2.5 cm to about 3.5 cm, about 2.5 cm to about 4 cm, about 3 cm to about 3.5 cm, about 3 cm to about 4 cm, or about 3.5 cm to about 4 cm apart.

[0147] FIGs.9A-9B show images of exemplary configurations of the device on a subject. In some embodiments, a length of the device may be greater than a width of the device. In some embodiments, a width of the device may be greater than a length of the device. FIG. 9A shows an arrangement of one or more electrodes and one or more vibrators, in which all three components are aligned. For example, the device may have a first electrode 905 adjacent to a vibrator 910. The vibrator may be adjacent to a second electrode 915. In some embodiments, one or more electrodes of the device may be adjacent to one another. For example, a first electrode may be adjacent to a second electrode. In some embodiments, one or more electrodes of the device may not be adjacent to one another (e.g., another component may be between one or more electrodes). An electrode (e.g., a first electrode 905 and / or second electrode 915) may be arranged vertically along a longitudinal axis of the device. An electrode (e.g., a first electrode 905 and / or second electrode 915) may be arranged horizontally along a longitudinal axis of the device. An electrode described herein may comprise any shape, for example an electrode may have a square shape, rectangular shape, circular shape, or ovular shape. FIG.9B shows an arrangement of electrodes and vibrator, in which the two electrodes are offset from the vibrator.

[0148] In some embodiments, an area of the device described herein may be at least about 5 cm2, at least about 10 cm2, at least about 11 cm2, at least about 12 cm2, at least about 13 cm2, at least about 14 cm2, at least about 15 cm2, or greater than about at least about 15 cm2. In some embodiments, an area of the device described herein may be at most about 15 cm2, at most about 14 cm2, at most about 13 cm2, at most about 12 cm2, at most about 11 cm2, at most about 10 cm2, at most about 5 cm2, or less than about 5 cm2. In some embodiments, a weight of the device described herein may be at least about 20 grams (g), at least about 25 g, at least about 30 g, at least about 35 g, at least about 40 g, at least about 45 g, at least about 50 g, or greater than about 50 g. In some embodiments, a weight of the device described herein may be at most about 50 g, at most about 45 g, at most about 40 g, at most about 35 g, at most about 30 g, at most about 25 g, at most about 20 g, or less than about 20 g. 43WSGR Docket No.68475-701.601

[0149] In some embodiments, the methods described herein can further comprise stimulating a second nerve of subject. In some embodiments, the second nerve may be the same as the first nerve. In some embodiments, the second nerve may be different than the first nerve. In some embodiments, the second nerve can be at a same location of the body as the nerve (e.g., first nerve) of the subject. For example, the nerve (e.g., first nerve) may be located at a subject’s left wrist, and a second nerve may be located at a subject’s left wrist or right wrist. The second nerve can comprise a median nerve, a vagal nerve, a trigeminal nerve, a tibial nerve, or any combination thereof. In some embodiments, a first nerve may be stimulated as a priming stimulation for a second nerve of the subject. In some embodiments, the nerve (e.g., first nerve) and the second are stimulated concurrently. In some embodiments, the nerve of the subject (e.g., first nerve) may be stimulated prior to the second nerve. In some embodiments, the nerve of the subject (e.g., first nerve) may be stimulated subsequent to the second nerve. In some embodiments, the system comprises one electrode that may provide at least two stimulations. In some embodiments, the system comprises two or more electrodes that provide stimulation.

[0150] FIG.7 shows an image of an example location of the device described herein. The image depicts adjustments of the stimulator. Wrist circumference adjustment can be denoted by “A” and stimulator placement can be denoted as “B”. A stimulator 705 may be any location on the body, and FIG. 7 shows an embodiment of a wrist placement. The device may be worn such that the stimulator may be on a user’s bottom-side of the wrist (e.g., facing the floor). In some cases, the device may be worn such that the stimulator may be on a user’s top-side of the wrist (e.g., facing away from the floor).

[0151] In some embodiments, the memory-storing biofeedback program of the systems described herein can comprise one or more stimulation profiles. The one or more stimulation profiles may each comprise at least one different stimulation parameter (e.g., a frequency, a pulse width, a pulse pattern, a current, a voltage, a pulse duration, a repetition rate, or a current intensity). The one or more stimulation profiles can define parameters of the one or more stimulation generated by the system. The system can further comprise an audio generator. The audio generator may be configured to provide an auditory stimulus. The auditory stimulus may be provided prior to a nerve stimulation. The auditory stimulus may be provided after a nerve stimulation. The auditory stimulus may be provided concurrently with a nerve stimulation.

[0152] The memory-storying biofeedback program can be in electrical communication with a mobile electronic device. In some embodiments, the memory-storying biofeedback program can be in electrical communication with a smartphone and / or smartwatch. In some embodiments, the memory-storying biofeedback program can be in electrical communication with a virtual reality 44WSGR Docket No.68475-701.601 program. In some embodiments, the memory-storying biofeedback program can be in electrical communication with a VO2 mask.

[0153] When properly attached by a user, the wrist-worn device can stimulate nerve endings (namely that of the median, cervical vagal, or trigeminal) that respond to various forms of electrical, mechanical, thermal, or laser-based stimuli. The device can be designed to work in sync with a user´s respiratory dynamics before, during, and / or after training or competition. Stimulation intensity, type, and frequency can be adjusted accordingly to: 1) deliver low frequency stimulation during the exhalation phase to increase cardiac vagal HRV (i.e., increase parasympathetic tone via increases in high-frequency HRV or rMSSD); 2) deliver high frequency stimulation during the inhalation phase to decrease cardiac vagal HRV (i.e., increase sympathetic tone via increases in low-frequency HRV), or ; 3) deliver moderate stimulation during equal inhale and exhale respiratory cycles to regulate both parasympathetic and sympathetic tone (i.e., sympathovagal index). Afferent (bottom-up) parasympathetic activity to the heart increases during expiration relative to inspiration when there may be an increase in sympathetic activity (heart rate increases). The method and system may therefore work as a sympatho-vagal modulator before, during, or after performance with or without biofeedback training which can cause significant changes in HRV across the entire respiratory cycle.

[0154] In conjunction with afferent (bottom-up) nerve stimulation, efferent (top-down) transcranial direct current stimulation (tDCS) can be delivered to increase cognitive processes, psychomotor function, and sensorimotor activity associated with human performance before, during, or after training, learning, and / or competition. Audio-visual guidance and efferent biofeedback regulatory training are applied to augment the efficacy of the afferent stimulation described, simultaneously or separately. Through audiovisual guidance, a user can be trained in positive efferent (top-down) predictions concerning their psychophysiological performance state (i.e., such as in clutch states-- “I will become more resilient and focused during performance stress”). Positive outcome expectancy which can be used commonly by athletes and can be driven in-part by the autonomic nervous system can beneficially affect a user´s peripheral physiology.

[0155] In a non-limiting embodiment, a chargeable internal battery within the wearable neurostimulation device provides operational power for the incorporated vibro-electrotactile stimulator(s) and dry-contact electroencephalogram (EEG) sensor(s), and photoplethysmographic (PPG) biosensor(s), whether incorporated within the neurostimulation device or located separately within the user´s personal computing device (i.e., smartphone or smartwatch). Data captured by the integrated and / or separate PPG biosensor(s) before, during and / or after stimulation can be sent to a dedicated cloud-based platform and / or personal computing device (i.e., smart phone) so each user can be provided with real-time as well as pre and post data output that can 1) be integrated 45WSGR Docket No.68475-701.601 with data collected from other e-health and m-health wearable devices and / or 2) shared remotely with coaches and instructors to monitor treatment progress and results of the respective user(s) (i.e., athletes, students, military personnel, etc.).

[0156] The different stimulation protocols can be grouped into the following four non-limiting practice protocols to be delivered before (prime), during (perform), or after (recovery) performance and outside of performance (life).

[0157] Examples of the protocols can be: (i) biofeedback sessions without vibro-electrotactile stimulation OR vibro-electrotactile stimulation delivered without considering a user´s pulmonary (respiratory cycle), neurological activity (EEG), cardiovascular (e.g., HR, blood pressure, etc.), or autonomic, (HRV) biometric data; (ii) biofeedback sessions with vibro-electrotactile stimulation that can be pre-set to a particular respiratory ratio, pattern, and / or frequency (such as the user´s particular resonance frequency) or neurological activity (EEG), cardiovascular (e.g., HR, blood pressure, etc.), autonomic, (HRV), or cardiorespiratory (PRQ) biometric data for the user to match their respiratory cycle to; (iii) biofeedback sessions where the system automatically detects the users’ inspiration and exhalation and delivers vibro-electrotactile stimulation only during exhalation, only during inhalation, or stimulates upon detection of neurological or biometric (cardiovascular or autonomic) information (i.e., pulse paired stimulation); or any combinations thereof.

[0158] The vibro-electrotactile stimulation delivered by the device with or without the biofeedback sessions can be variable regarding intensity, pattern, and vibratory frequency and can be personalized by the user in all the above protocol embodiments within a personal computer application. The vibratory mechanical stimulus and / or electrical pulse stimulus may have a sinusoidal or other waveform stimulation pattern that could be rhythmic, arrhythmic, or constant. The vibratory mechanical stimulus and / or electrical stimulus can be delivered according to a presubscribed programmed pattern, which may include delivering the stimulus either continuously or intermittently in on / off bursts.

[0159] The stimulation delivered by the neurostimulation device can be synchronized with the respiratory phase (exhalation and / or inhalation phase) and / or pulse (HR) of the user only in stimulation protocols 2 and 3 (Protocol 1 could be understood as a somewhat “passive” stimulation session). Low frequency median and / or vagal afferent stimulation delivered during the exhalation phase of a user can be delivered with the intention to enhance parasympathetic tone. Conversely, high frequency median and / or vagal afferent stimulation delivered during the inhalation phase of a user can be delivered with the intention to enhance sympathetic tone. Taken together, the system herein described delivers sympatho-vagal modulation and overall autonomic regulation in real time to users. 46WSGR Docket No.68475-701.601

[0160] In Protocol 2, the user inhales or exhales during stimulation at a pre-determined respiratory rate / rhythm (such as 6 breadths per minute or the users own unique resonance frequency rate). The neurovisceral integration model employed in the system described can modulate neurocardiac function for each user at particular respiratory rates to either increase or decrease HRV.

[0161] In Protocol 3, the biosensor(s) located within the device itself and / or paired personnel computing device detects the user’s pulmonary, cardiac, or neurological data and delivers vibro- electrotactile stimulation upon initiation of a cardiorespiratory phase (inhalation phase, exhalation phase, respiratory rate, or PRQ change), cardiac output (high or low HRV or pulse detection), or neurological activity (increase or decreases in regional brain activity) before, during, after or outside of performance.

[0162] To operate biofeedback (BF) modalities whether they be neuro BF, respiratory BF or heart rate (HR) / heart rate variability (HRV) BF before, during or after performance, the neurostimulation device can use the biosensor(s) to read biometric signal(s) (e.g., HRV, EEG, respiratory dynamics, etc.) and control the delivery of the vibro-electrotactile stimulus and corresponding software application program based at least in part on the sensed signal(s) under consideration. The sensed signal may be any of the various types of biometric signals sensed with the biosensor. The delivery of the stimulus may be based on at least one of the sensed signals which includes initiating and / or arresting the delivery of the stimulus in response to the sensed biometric signal(s).

[0163] The vibro-electrotactile stimulus can also be delivered in response to the detection of brain-related cognitive-motor or cognitive-learning performance states (i.e., sustained focus, task switching, cognitive flexibility, etc.,) based directly on data received by the electrode(s) and biosensor(s) or indirectly via self-report behavioral questionnaires in the user´s personal computer application. This activity may include associated levels of HRV, respiratory dynamics, or hemodynamic / neural-electrical signals.

[0164] A user can wear the device throughout the day in a monitor and stimulation mode (i.e., life mode) where the system (application and device) monitors the cardiovascular, autonomic, pulmonary, and / or neurological state of the user and delivers performance-based breathing sessions and / or neurostimulation in response to unfavored or favored psychophysiological homeostatic perturbances. The performance-based breathing sessions and / or neurostimulation can be delivered until the unfavored psycho-physiological state may be no longer detected or the favored psycho-physiological state may be no longer required (flow state, clutch state, reward seeking behavior, acute focus, or any combination thereof). In some embodiments, a subject can wear the device described herein for at least about 10 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 24 hours, 2 days, 3 days, 4 days, 5 47WSGR Docket No.68475-701.601 days, 6 days, 7 days, or longer than 7 days. In some embodiments, a subject can wear the device described herein for at most about 7 days, 6 days, 5 days, 4 days, 3 days, 2 days, 24 hours, 12 hours, 6 hours, 5 hours, 4 hours, 3 hours, 2 hours, 1 hour, 45 minutes, 30 minutes, 15 minutes, 10 minutes, or less than about 10 minutes.

[0165] Compatible sensors that can be paired to the neurostimulation device to integrate a user´s performance health data can, for example, originate from electromyographic (EMG) sensors, electrooculographic (EOG) sensors, other heart rate sensors (including, but not limited to, EKG, pulse-oximeter based heart rate sensors, chest monitors / belts, PPG biosensor rings, etc.), blood pressure sensors, temperature sensors, perspiration sensors, skin conductivity sensors, and other respiration sensors. Other types of sensors for providing information regarding the state of the subject and his or her environment may be used, without limitation, including motion sensors (i.e. accelerometers, gyroscopes) or location sensors. In various aspects of operating the neurostimulator, secondary integrative or paired stimulators or devices may include a mechanical stimulator, other bioelectronic and / or brain stimulators, an audio player, an auditory stimulus source, a virtual reality system, an augmented reality system, a visual stimulus source, a tactile stimulator, a haptic stimulator, an odorant source, or a virtual coach, for example.

[0166] The system of the present disclosure comprises of a smartphone application that allows the user to personalize, adjust, and interact with the integrated neurostimulator device to augment the effects of the performance-based breathing and psycho-behavioral audiovisual training programs. The neurostimulator device may be able to charge within a charging case (or pad) to charge an internal battery which may supply the energy needed to run all stimulation and recording (EEG and biosensor) procedures. Data obtained from the device 206 can also be integrated with e-health wearables and / or monitors such as smart watches and / or virtual reality goggles, for example, to account for other psychophysiological health-related variables which can have significant impacts on the performance (sport or cognitive) effect of the device (such as memory retention, physical fitness, and sleep).

[0167] In an exemplary embodiment, the present disclosure provides methods for the performance-based biofeedback sessions and accompanying vibro-electrotactile stimulation system comprising of the following non-limiting steps: (a) placing device on a wrist; (b) selecting one or more operational protocols (e.g., operational protocols 1, 2, 3, or 4) for before performance, during performance, after performance or outside of performance (life); (c) selecting corresponding performance-based breathwork techniques to increase, decrease, and / or regulate heart rate variability; (d) selecting vibratory, electrical, or vibro-electrotactile stimulation types; (e) selecting or determining respiration rate (e.g., desired respiration rate, the breathing rate at which heart rate variability, blood pressure oscillations, and other biological state indicators may 48WSGR Docket No.68475-701.601 be optimized for the subject in response to their breathing); and (f) commencing biofeedback session dependent on practice protocol, additive neurostimulation involvement and type, audiovisual psycho-behavioral training program, corrective adjustment procedures and predictive performance modeling, chosen biological state indicator, or any combination thereof.

[0168] Before, during, or after performance with or without additive vibro-electrotactile stimulation and corrective system adjustment, PPG biosensor(s) integrated within the user´s personal computer device, neurostimulation device, or compatible e-health wearable (smart watch, ring, cardiac monitor, etc.) may record data and send it to a user´s personal computer device (smart phone) system application before, after, or in real-time during the training session. Data can be stored within the user´s personal computer device (smart phone) system application and can be sent to a secure cloud for data and integration storage with data from other paired devices which may include smart watches, cardiac monitors, etc. This data can either be kept by the user and / or shared securely and remotely with a corresponding professional for further performance monitorization and evaluation.

[0169] Verbal, pre-recorded instructions may be in the form of guided breathing to deliver and ensure accurate various breathing technique (whether fast-paced to increase sympathetic tone or slow-paced to increase parasympathetic tone). Deep breathing can be instigated with awareness of the in and out breaths. More specifically, deep breathing, or diaphragmatic breathing, can be defined as an efficient integrative mind-body training regimen that involves contraction of the diaphragm, expansion of the belly, and deepening of inhalation and exhalation; this consequently decreases the respiration frequency and maximizes the amount of blood flow. Benefits of diaphragmatic breathing have been investigated in association with performance in psychomotor and cognitive domains. These benefits contribute to emotional balance, social adaptation, and have been found to be very effective in regulating the stress response before, during, and after performance endeavors. Deep breathing at various rates can also increase or decrease blood pressure, increase blood-oxygen concentration (at higher rates) and alter baroreflex functionality. Advantageously, with the novel system and device described herein, this technically demanding technique can be practiced anywhere at any time during particular autonomic states driven by neurostimulation within the performance environment (classroom, arena, battlefield, etc.,).

[0170] Breathwork paired with attentional training regimens encompass a broad family of complex emotional and attentional regulatory training interventions that can be broadly categorized into three groups based upon the specific types of attention being practiced.

[0171] The guided sessions provided by the personal computer application may include but are not limited to, Focused Attention (FA) training regimens, Open Monitoring (OM) training regimens, and / or Nondirective (ND) training regimens. FA training entails the voluntary focusing 49WSGR Docket No.68475-701.601 of attention on a chosen object, word, idea, or stimulus (usually the breath) by a user. As attention wanders away from the breath, the user detects mind wandering and brings their attention back to the physical sensation of the breath. In OM training, a user monitors the content of their inner and outer experiences from moment to moment paying careful attention to whatever comes into and out of awareness without changing it. Non-directive attention training guides the user to accept spontaneously occurring thoughts, images, sensations, memories, and emotions without actively directing attention toward them (FA) or away from them (OM). In ND training, a practitioner effortlessly places a relaxed focus of attention on a mental or audible sound while non- judgmentally allowing their attention to shift toward spontaneously occurring thoughts, images, sensations, or emotions.

[0172] Various breathwork programs can be employed before, during, and after performance such as box-breathing, resonance frequency breathing, cyclic hyperventilation, slow paced breathing, breath retention, and cyclic sighing, among others, as selected in the step 102 during neurostimulation and corrective guidance step 110. Furthermore, meditative-based breathing sessions may also be employed such as a body scan practice (i.e. non-sleep deep rest, NSDR), guided seated meditation, walking / movement meditation (such as during yoga sessions), loving kindness meditation, or thoughts and emotions meditation wherein the user acknowledges thoughts and emotions non-judgmentally, as they come and go, during performance (i.e., chess game).

[0173] FIG.2 shows a schematic diagram of a system 200 for assisting performance. The system 200 can be suitable for carrying out the method 100. The system 200 can have a biological state indicator measuring module 204 for analyzing pulmonary, autonomic, cardiovascular, and / or neurological data, a determination module 203 for analyzing the biological state indicator data and determining if there may be at least one biological state in resonance with the predetermined breathing rate of the user, and a psycho-behavioral delivery module 205 configured to deliver a biofeedback program to the user to encourage resonance (in association to or in correlation with) and / or any desired performance relation between the biological state of a user and the predetermined breathing rate of the user. The system 200 can also have an integrated peripheral nerve stimulation module and / or transcranial stimulation module 202.

[0174] As demonstrated by dotted lines, the biological state indicator measuring module 204, the determination module 203, the biofeedback delivery module 205, and the peripheral nerve stimulation module 202 can all in data communication with each other and may be separated and / or integrated within one or several functional embodiments. The data communication functionality among the various facets of the system 200 may be provided directly via electronic 50WSGR Docket No.68475-701.601 circuits or by short-range wireless communication technology, such as near field communication (NFC), and / or low-energy Bluetooth communication.

[0175] The biological state indicator measuring module 204, the determination module 203, and the peripheral nerve stimulation module 202 may be housed in the same device 206 and connected wirelessly to the biofeedback delivery module 205. In another possible embodiment, the nerve stimulator device 202 comprises the biofeedback delivery device 205. In other examples, there can be a separate biofeedback delivery device 205 to the nerve stimulator device 202.

[0176] FIG.3A depicts a diagram of the human body in which various regions are of stimulation interest. The diagram in FIG. 3A depicts the device 206 (D) and system described placed upon the left and right wrist for median nerve stimulation, on the neck for cervical vagal nerve stimulation, and on the forehead for delivering trigeminal nerve stimulation. A nerve of stimulation interest can be the median nerve (MN) and its indirect influence on the vagus nerve (VN) and associated brain regions. The area of stimulating the MN can be via innervation of the pericardium meridian of acupuncture point 6, PC6, located roughly 5 cm (e.g., at least about or at most about 1, 2, 3, 4, 5, 6, 7, or 8 cm) from the palmar wrist crease. Due to the novel strap design and adjustability of the nerve stimulation unit, other areas and nerves which may be of interest in various non-limiting embodiments that can be stimulated via vibration, electricity, or both, to modulate autonomic function may be of interest.

[0177] FIG.3B shows an example performance enhancement device 206 embedded into an entire system 200. In the example of FIG.3B, the device 206 can be strapped on the underside of a User U’s left wrist containing the nerve stimulation module 202 that can be wirelessly connected and strapped to a biological state indicator measuring module 204 and determination module 203. In some examples, the nerve stimulation module 202 provides electrical-based stimulation or at least an electrical-based stimulation element alongside vibro-electrotactile stimulation. The vibro- electrotactile nerve stimulator module 202 can be housed within a first housing 301. The first housing 301 can be malleable, sweatproof, waterproof, flexible, impact resistant, biocompatible and / or a thermoelastic polymer which can be molded to a specific shape and adjusted via the strap. This may ensure that the entire stimulation region of interest can be accommodated, and that optimal contact can be made between the vibro-electrotactile nerve stimulator module 202 and the skin. The biological state indicator measuring module 204 and determination module 203 can be located within a first housing 301 or separately within a second housing 302 which contains or can be integrated with a personal computer operating system 205 and secured to the strap 303 which can be placed on the top-side or underside of a user’s wrist. A clasp 304 can connect the first housing 301 to the second housing 302 and can also be used to connect the first housing 301 to the performance training module application located on a user´s smartwatch 205. 51WSGR Docket No.68475-701.601

[0178] The device 206 can be integrated and / or compatible with commercially available audio devices (e.g., Bose®, AirPods®, Bang & Olufsen®, Sony®, etc.,) such that psycho-behavioral coaching and nerve stimulation can be simultaneously or separately delivered during biofeedback performance sessions. Both the device 206 and integrated or compatible audio device of choice can be paired to the application on the personal computer operating system 205 (i.e., smart watch).

[0179] FIG. 3C and FIG. 3D show a first vibro-electrotactile stimulation device, without a personal computer operating system 205 in FIG.3C and with personal computer operating system 205 in FIG. 3D, that can be mounted on a user’s left and / or right wrist. The device depicted can be composed of a robust, sweat and water-proof material that can be adjusted on strap 303. This can allow the device to be relocated to the user´s placement to achieve optimal direct contact between the vibro-electrotactile output source, possible integrated biosensor(s) 305 (whether within the first housing unit 301, strap 303, and / or second housing 302), and dry-contact electrode(s) 306 with the nerve or brain stimulation and recording areas of interest. The device can be comprised of a waterproof material to prevent liquid damage to the device. This can allow the device to be used in environments in which the device may be exposed to liquid such as during watersports such as swimming or diving. The device can be comprised of a non-allergenic material to prevent the user having an allergic reaction to the device and causing discomfort.

[0180] FIG. 3E depicts an embodiment of the present disclosure wherein the first housing 301 contains both the neuromodulation unit 202 and the biometric sensor(s) 305 (i.e., PPG sensors) for recording relevant biometric data to user U. The internal components of the device 206a may comprise an LED light diode 308 which indicates power consumption and charge, a USB-C connector 307 for charging, an internal electromagnetically rechargeable battery or other power source (e.g., non-electromagnetically rechargeable battery, a non-rechargeable battery, a capacitor or capacitor assembly, etc.) for providing operational power to the device, an internal board to hold the battery and Bluetooth functionality, an internal board to hold the vibrator unit 309 and electrode, 2 silver electrodes 306 for stimulation bolts 308 to hold the casing in place, a vibrator unit 309, and an internal electrode driver board. The PPG biosensor(s) or electroencephalogram (EEG) sensor(s) which could be either housed within the first housing unit 301, strap 303, and / or second housing 302 can measure several biometric variables, some of which include oxygen saturation, heart rate, heart rate variability, blood-oxygen saturation, blood pressure, and detects breathing phase (exhalation or inhalation) of the user.

[0181] The device also has at least one electronic chip and or electrode driver board embedded within the flexible hardware housing 301. The at least one electronic chip can be programable to: 1) generate stimulation patterns delivered by the vibro-electrotactile stimulation system with variable duration, intensity, frequency, and pulse (e.g. bursts of vibratory and / or electrical output 52WSGR Docket No.68475-701.601 as compared to one continuous line of high-frequency vibrations or electrical pulses); 2) generate stimulation patterns synchronized with a user´s U exhalation, inhalation, or breath hold phase; 3) exchange data with external devices (whether it be with a compatible wearable or the personal computing device) through wireless connections, and; 4) enable wireless electromagnetic charging of device. A central circuit may be placed within the hardware housing 301 to control the functioning of the device and can be configured to communicate wirelessly with the performance state training module 205 located within the user´s computer device.

[0182] The device 206 can have a wireless connection Bluetooth module such that the device can communicate with the rest of the system 200. In another example, the device 206a may be configured to be positioned entirely within the secondary biosensor housing 302. The components of these configurations are of the same kind as in the configuration shown in FIG.3D an but are placed differently to accommodate to the respective housing requirements.

[0183] FIG. 5 shows a schematic representation of a system described herein in electrical communication with a mobile electronic device (e.g., Apple Watch). The system comprises a main control unit (MCU) comprising firmware and Bluetooth. The MCU may be in electrical communication with the other electrical components of the system. A wristband 505 of the system described herein may have one or more structural or electrical features. The wristband 505 may comprise a microcontroller unit (MCU) 510. The MCU can have a firmware 545, a Bluetooth component 540, or combinations thereof. The Bluetooth 540 can communicate with one or more additional devices that have a Bluetooth component. The MCU 510 can communicate with one or more other components of the wristband 505. For example, the MCU may communicate with a vibrator driver 515. The vibrator driver may connect with a vibrator 520 of the device. The MCU may communicate with an electrode driver 530. The electrode driver 530 may connect with one or more electrodes 525 of the device. The wristband may also comprise one or more batteries 535. The MCU may communicate with the one or more batteries 535. The battery 535 may be connected to one or more drivers of the device (e.g., vibrator driver, electrode driver, or combinations thereof). The wristband 505 may communicate with a mobile electronic device 550. For example, the wristband 505 may communicate with a mobile electronic device 550 via Bluetooth. A Bluetooth component of the wristband 540 may communicate with a Bluetooth component of the mobile electronic device 555. The mobile electronic device 550 can comprise one or more applications 565. The application 565 can execute any of the protocols and / or programs described herein. For example, the application 565 may execute a program 560 with instructions for a user.

[0184] Electrical stimulation protocols delivered by the vibro-electrotactile nerve stimulation module 202 which receive stimulation protocol guidance from electronic chip 309 includes a 53WSGR Docket No.68475-701.601 rhythmic sequence, or train, of pulse bursts typically between 1 and 10 burst per second. The intensity of the electric current intensity (mA), the width of the pulses and their frequency (Hz) are also variable in the stimulation protocols via the personal computer (smart phone and or smart watch) application 205 where the user U can vary the intensity to 1) sufficiently produce an effective stimulation of peripheral nerve endings and 2) can be comfortable for the user during biofeedback sessions. The pulse width can determine the type of fibers that are innervated—short pulses stimulate thick fibers while elongated pulses excite both thick and thin fibers. The median nerve (MN) can be composed of myelinated and unmyelinated afferents that when stimulated contribute to cardiovascular excitatory reflexes; stimulation of group III and group IV MN fibers activates nociceptive receptors in the rostral ventrolateral medulla which can be associated with inhibition of the sympathetic outflow and reduces cardiovascular metabolic demands.

[0185] The nerve stimulation module 202 which may include the electrodes 206 and / or vibratory unit 309 among other nerve stimuli apparatuses (i.e., pressure, laser, etc.,) may deliver high- frequency (around 50 - 80 Hz) MN stimulation to increase sympathetic tone monitored by the PPG biosensor(s) during the inhalation phase of breathwork techniques (i.e., cyclic hyperventilation) delivered during biofeedback to increase focus and arousal before and during performance. Conversely, the nerve stimulation module 202 may deliver low-frequency (around 10 - 25 Hz) MN stimulation to increase parasympathetic tone during the exhalation phase of breathwork techniques (i.e., resonance frequency breathing) delivered during biofeedback to increase relaxation and recovery before during, and after performance. The nerve stimulation module 202 may also deliver moderate frequency (around 25 – 50 Hz) MN stimulation to regulate both sympathetic and parasympathetic tone before, during, and after performance to create a relaxed yet focused state during breathwork techniques (i.e., boxed breathing) delivered during biofeedback. The nerve stimulation module 202 may also deliver low, moderate, and high frequency MN stimulation throughout the day and / or evening to preserve natural and / or desirable autonomic regulatory activity.

[0186] Mechanoreceptors and thermoreceptors located within the nerves of interest (e.g. median, vagal, and trigeminal) may react to mechanical and thermal stimuli, respectively, which makes it possible to activate these nerve endings with mechanical stimuli such as vibration via the vibratory unit 309. The vibratory mechanical stimulation unit 309 delivered and housed by the nerve stimulation module 202 may produce a vibratory stimulus with a sufficient amplitude and frequency to innervate these receptors. The stimulator can deliver continuous or transient vibratory stimulation in a cyclical or sinusoidal stimulus pattern with a general frequency range of 1 Hz to 1000 Hz—Pacinian corpuscles are often most responsive to vibratory mechanical stimuli with frequencies of 200 Hz-300 Hz, while Meissner's Corpuscles are typically most 54WSGR Docket No.68475-701.601 responsive to vibratory stimuli with frequencies of 30-40 Hz. The exhaustive operational heat and pressure the device may exert when placed upon the user may also contribute to mechanoreceptor stimulation (indentation of the skin by a few micrometers to a few millimeters can stimulate mechanoreceptors).

[0187] The system 200 shown in FIG.2 can be suitable for carrying out the method 100 before, during, and after performance. In FIG. 3A, the user U may wear the vibro-electrotactile stimulation device 206 integrated with or separate to the biological state indicator module 204 and determination module 203 around various parts of their body. If the system 200 can be worn around only the left wrist, this can have a more significant effect on upregulating cardiac vagal parasympathetic tone (root mean square of successive differences, rMSSD). However, the user U can place the system 200 on their left wrist and in addition a separate nerve stimulation module 202 on their right wrist to upregulate sympathetic tone (low frequency HRV, lfHRV). Wearing the system 200 on either the left or right wrist in addition to wearing a separate nerve stimulation module 202 attached to strap 303 below the left or right knee may be utilized to increase psychomotor function of the user U. Placing system 200 on the left wrist in addition to wearing a separate nerve stimulation module 202 attached to strap 303 around the neck to deliver cervical vagal nerve stimulation can be exercised to augment cardiac vagal activity and drive relaxation and recovery. Placing system 200 on the head of the user U and moving the nerve stimulation module 202 along strap 303 to the correct area to stimulate particular brain regions in conjunction with any of the aforementioned peripheral nerve stimulation applications can upregulate certain neurovisceral and neurocognitive functions associated with high performance in user U to nurture neuroplasticity.

[0188] When the user U begins their biofeedback session, they can launch an application 205 on their personal computer device as depicted for example in FIG.3B as a smartwatch 302. The user U’s smartwatch housing 302 may also contain the performance training module (such as an app) 205 as part of the system 200. The application (app) may contain audiovisual / computer readable instructions that, when executed on the smartwatch’s processor, first retrieves the predetermined breathing rate. Then, instructions can be sent to the biological state indicator module 204 to gather the cardiovascular, autonomic, and / or neurological data from the biological state indicator measuring module composed of biometric sensors. The pertinent biometric data can be then sent back to the integrated determination module 203 composed of the electronic chips(s) and circuit(s) which can be sent wirelessly to the smart watch 302 and application 205 for further processing.

[0189] Using the gathered data, the application runs an algorithm to determine whether there can be resonance (i.e., desired and / or ideal relations) between the predetermined breathing rate and the biological state of the user U. If there may be resonance, the application 205 may or may not 55WSGR Docket No.68475-701.601 choose to perform any further corrective intervention during the user’s biofeedback session. However, if it can be established by the algorithm within the smart watch 302 that resonance may not be occurring, corrective instructions 110 can be sent to the performance training module 205 to deliver a stimulus to encourage resonance. Whilst the application 205 is open, the application 205 can be configured to continuously run the algorithm to check for resonance and determine whether the intervention may be desirable. Corrective training 110 may comprise of one or more multisensory signals to indicate a correct breathing rate such as audiovisual cues from the smart watch 302 or audio from a compatible earphone, pre-recorded verbal or visual instructions and / or additive vibrations or electrical pulses delivered to any part of a user’s U body as seen in FIG. 3A.

[0190] If the application 205 is not receiving any data in the form of biological state indicators from the biological state indicator module 204 the application 205 may be configured to push a notification to alert the user, for example, via a graphical user interface (GUI) on the smartwatch 302.

[0191] Any compatible respiratory belt placed upon the diaphragm and / or chest area with integrated accelerometer or means of measuring mechanical movement can be used to work in- sync with the device 206 and / or smartwatch 302. Even though an integrated PPG biosensor located within device 206 or located within a smartwatch 302 could register respiratory rate and inhalation / exhalation of the user U as described in an embodiment of device in FIG.3B, placing an accelerometer, ultra-sonic sensor, or other sensor capable of measuring spatial differentials on the user´s U diaphragm ensures that the user U may be using the diaphragm instead of the chest to achieve the same desired respiration rate. Diaphragmatic breathing at the same rate as chest or upper clavicle breathing could stimulate afferent nerve signals differently.

[0192] An alternative method to obtaining biological state indicator information could be by placing a finger, for example the index finger, in front of an LED light and a camera of the personal computing device such as a smartphone. Using a flash function of a smart phone to deliver light pulses to the user U’s finger and recording images of the user’s finger under said light pulses in combination with a second algorithm stored on the application to analyze said images, plethysmography (PPG) can be achieved and used to collect pertinent biometric information. Compatible e-health wearables including, but not limited to, devices such as rings or smart watches 302 can be worn by the user U to collect and integrate more data via PPG regarding cardiovascular and autonomic function which can be integrated with data collected from the device 206 itself and application 205 hosted on personal computing device 401.

[0193] Other reported lifestyle factors commonly collected by such wearables such as sleep quality, alcohol consumption, caffeine consumption, and physical fitness regimen—all factors 56WSGR Docket No.68475-701.601 which may affect the performance enhancement efficacy of the system 200—can also be integrated by a user U with data collected from the device 206 and / or application 205. A smart ring, smart watch, or other wearable sensor device of choice could provide the biological state indicator(s) for use in the method 100 alone or in combination with biosensor(s) 204. The smart watch 302 or other wearable sensor device (such as a ring or smart phone) may also be in wireless data communication with the device and its ongoing use as depicted in FIG.3C and FIG.3D for data integration, machine learning, and predictive training model development as driven by artificial intelligence.

[0194] The vibro-electrotactile neurostimulation device can work as a fully integrated device that can be specifically designed to optimize the effectiveness of the specific respiratory-based biofeedback sessions delivered to a user by stimulating peripheral nerves (namely the median and vagal nerves) as well as brain regions (via transcranial direct and / or indirect stimulation) for top- down and bottom-up integrated performance enhancement. The device can innervate afferent nerve signals via vibro-electrotactile stimulation of the MN paired or unpaired with biofeedback exercises and stimulates efferent nerve signals via attentional regulatory / modulatory practices and neuro stimulation. The system can provide a novice with the means to noninvasively and effectively initiate, sustain, or optimize their psychophysiological performance and wellbeing within and outside of the competitive setting. Due to the automatic personalization and adaptability of the system, it can be also an effective tool for more advanced professionals and / or other applicable users as mentioned. The system can be autonomous, portable, and demands no prior knowledge from the user.

[0195] The system may be connectable to the internet, for example, to access audio files stored on the web via streaming or may be useable in an offline mode. The application of the system may be configured to interact with other applications stored on a user’s smart device (e.g.,TrainingPeaks , Strava , Garmin Connect , Apple Health , etc.,), for example, or it may beconfigured to access audio file applications from a third provider (i.e., Spotify , Apple Music ,etc.,). Biometric data collected from the device whether they be neural signals, physiological signals, or other secondary signals (e.g., obtained from compatible e-health wearables such as a smart watch or virtual reality system) in addition to biofeedback session performance information and subjective self-report performance questionnaires provided by the smart phone application can be correlated with a psychophysiological performance state of the user, reported to a teacher, coach, healthcare professional and / or other party, and / or securely stored in the subject's own performance database. Any parameters that are indicative of worsening performance status or overall dysfunction of the user can be reported to a coach so that an appropriate intervention can be made, if needed, and / or used as a basis for further modulating the delivery of the system. The 57WSGR Docket No.68475-701.601 application associated with the system may include a reminder function and / or tracking function to encourage the user to use the system to maximum effect.

[0196] FIG. 4 depicts a flow chart 400 of the processes of an application described herein. The application can assist in data collection, user feedback, and development of the systems and methods provided herein. Connection information 405 can be relayed to a user. The connection information may inform a user that the device is connected, a power level of the battery, or any combination thereof. For example, the connection information 405 can inform a user that the battery may be low. The application may comprise one or more different stimulation protocols 410. The one or more protocols 410 may be delivered during different time periods during a use by the user. For example, the protocols (e.g., practice protocols) may be delivered before (prime), during (perform), or after (recovery) performance and outside of performance (life). Each protocol can comprise a number of programs. The programs may comprise stimulation instructions, feedback for the user, or combinations thereof. A protocol (e.g., a prime protocol, perform protocol, recover protocol, and / or life protocol) 410 can comprise at least about 1 program, at least about 2 programs, at least about 3 programs, at least about 4 programs, at least about 5 programs, or greater than about 5 programs. A protocol (e.g., a prime protocol, perform protocol, recover protocol, and / or life protocol) can comprise at most about 5 programs, at most about 4 programs, at most about 3 programs, at most about 2 programs, at most about 1 program, or less than 1 programs.

[0197] When a protocol starts, a screen 415 may appear to inform the user that the protocol (e.g., a program of the protocol) may be starting. The protocol indicator screen 415 may have a countdown until the program may be initiated. In some cases, the protocol may not have a countdown. The protocol may have an introduction 420, to provide instructions to a user. For example, the introduction 420 may have text to tell a user about the program (e.g., the exercise). The text may be instructions of how the program (e.g., exercise) may be performed. The text may be an explanation of why the program (e.g., exercise) may be done. The application may also have one or more settings 425 which can be varied. For example, the one or more settings can be varied from program to program of a protocol. The setting may comprise a program length (e.g., an exercise length), a frequency (e.g., a vibration frequency and / or an auditory frequency), an intensity (e.g., a vibratory intensity and / or an auditory intensity), a discard rate, or any combinations thereof. The protocol can comprise a screen 430 with the program initiated (e.g., the exercise screen). The application may have visual guidance for the user. The application may have auditory guidance for the user. The application may have visual and auditory guidance for the user. The application can comprise a completion screen 435. The completion may inform the user that the program (e.g., the exercise) may be completed. 58WSGR Docket No.68475-701.601

[0198] FIGs.6A-6F show exemplary schematics of the system and device described herein. FIG. 6A depicts a top-down view of the device. In some cases, the device may have curved edges. In some cases, the device may not have curved edges. FIG. 6B depicts a side elevation view of the device. The device may have one or more charge ports. The charge port may be on a side of the device as shown in FIG.6B. In some cases, the charge port may be on a bottom of a device. FIG. 6C depicts a bottom-up view of the device. As shown in FIG. 6C, the device may comprise one or more fixtures (e.g., screws) to hold the electrical components of the device. FIG. 6D depicts bottom front isometric view of the device. FIG.6E depicts a front view of the device. The device may have a height (e.g., a dimension measured from “A” to “A” of FIG. 6E). A height of the device may be at least about 1 centimeter (cm), at least about 2 cm, at least about 3 cm, at least about 4 cm, at least about 5 cm, at least about 6 cm, at least about 7 cm, at least about 8 cm, at least about 9 cm, at least about 10 cm, at least about 15 cm, at least about 20 cm, or greater than about 20 cm. A height of the device may be at most about 20 cm, at most about 15 cm, at most about 10 cm, at most about 9 cm, at most about 8 cm, at most about 7 cm, at most about 6 cm, at most about 5 cm, at most about 4 cm, at most about 3 cm, at most about 2 cm, at most about 1 cm, or less than about 1 cm. FIG.6F depicts a cross-sectional view of the device, illustrating internal components. The device may comprise one or more electrical components, for example as shown in FIG.5. For example, the internal components of the device as shown in FIG.6F may comprise Bluetooth, firmware, battery, drivers (e.g., vibrator driver and / or electrode driver), vibrator, electrode, or any combinations thereof.

[0199] Furthermore, the system can be designed to integrate a first level of passive performance training (such as guided visual and audio coaching) with a second level of active training (such as biofeedback and gated respiratory training) for effective performance enhancement.

[0200] FIG. 12 shows a schematic depicting performance dynamics over energy levels. The schematic is based off of the Yerkes-Dodson Law of Performance (1908) which originally suggested that performance and arousal can be associated in the following manner: (i) low arousal may lead to poor performance due to under-engagement; (ii) optimal arousal may lead to peak performance; and (iii) high arousal may lead to poor performance due to stress or overload.

[0201] The methods and systems described herein for optimizing human performance can help further define performance tasks. For example, the methods and systems may refine performance tasks in an activity like golf (e.g., refine fine-motor skills). The methods and systems may refine one or more performance states and / or drive cardiorespiratory, neurocardiovascular, or autonomic actions. The wearable device described herein can modulate energy (e.g., arousal) in a plurality of ways. For example, as shown in FIG. 12, the wearable device, systems, and / or methods described herein can (i) prime for upregulation (e.g., for under-arousal), (ii) recover for 59WSGR Docket No.68475-701.601 downregulation (e.g., for over-arousal), perform for regulation (e.g., maintain and / or sustain arousal and psychophysiological energy management), or (iv) any combination thereof. The wearable device, systems, and / or methods described herein can improve the grit of a user, thereby reinforcing resilience and / or adaptability. Grit may be enhanced prior to an activity, during an activity, after an activity, or any combination thereof. Computer Systems

[0202] The present disclosure provides computer systems that are programmed to implement methods of the disclosure. FIG. 11 shows a computer system 1101 that is programmed or otherwise configured to direct operation of the system of the present disclosure (e.g., the sensing device, the reference device, the article of furniture, other devices, computer processor, etc.). In some embodiments, the computer system 1101 can be programmed or otherwise configured to monitor, project and / or regulate a parameter (e.g., temperature) of a bed device, a user, or both in accordance with any of the methods provided herein. The computer system 1101 can regulate various aspects of the methods as provided herein, such as, for example, directing the regulator to adjust at least one sleep-related parameter for the bed device to enhance sleep of the user, directing the projector to project the optical pattern to the wall or the ceiling adjacent the bed device, or both. The computer system 1101 can be an electronic device of a user or a computer system that is remotely located with respect to the electronic device. The electronic device can be a mobile electronic device.

[0203] The computer system 1101 includes a central processing unit (CPU, also “processor” and “computer processor” herein) 1105, which can be a single core or multi core processor, or a plurality of processors for parallel processing. The computer system 1101 also includes memory or memory location 1110 (e.g., random-access memory, read-only memory, flash memory), electronic storage unit 1115 (e.g., hard disk), communication interface 1120 (e.g., network adapter) for communicating with one or more other systems, and peripheral devices 1125, such as cache, other memory, data storage and / or electronic display adapters. The memory 1110, storage unit 1115, interface 1120 and peripheral devices 1125 are in communication with the CPU 1105 through a communication bus (solid lines), such as a motherboard. The storage unit 1115 can be a data storage unit (or data repository) for storing data. The computer system 1101 can be operatively coupled to a computer network (“network”) 1130 with the aid of the communication interface 1120. The network 1130 can be the Internet, an internet and / or extranet, or an intranet and / or extranet that is in communication with the Internet. The network 1130 in some cases is a telecommunication and / or data network. The network 1130 can include one or more computer servers, which can enable distributed computing, such as cloud computing. The network 1130, in 60WSGR Docket No.68475-701.601 some cases with the aid of the computer system 1101, can implement a peer-to-peer network, which may enable devices coupled to the computer system 1101 to behave as a client or a server.

[0204] The CPU 1105 can execute a sequence of machine-readable instructions, which can be embodied in a program or software. The instructions may be stored in a memory location, such as the memory 1110. The instructions can be directed to the CPU 1105, which can subsequently program or otherwise configure the CPU 1105 to implement methods of the present disclosure. Examples of operations performed by the CPU 1105 can include fetch, decode, execute, and writeback.

[0205] The CPU 1105 can be part of a circuit, such as an integrated circuit. One or more other components of the system 1101 can be included in the circuit. In some cases, the circuit is an application specific integrated circuit (ASIC).

[0206] The storage unit 1115 can store files, such as drivers, libraries and saved programs. The storage unit 1115 can store user data, e.g., user preferences and user programs. The computer system 1101 in some cases can include one or more additional data storage units that are external to the computer system 1101, such as located on a remote server that is in communication with the computer system 1101 through an intranet or the Internet.

[0207] The computer system 1101 can communicate with one or more remote computer systems through the network 1130. For instance, the computer system 1101 can communicate with a remote computer system of a user. Examples of remote computer systems include personal computers (e.g., portable PC), slate or tablet PC’s (e.g., Apple® iPad, Samsung® Galaxy Tab), telephones, Smart phones (e.g., Apple® iPhone, Android-enabled device, Blackberry®), or personal digital assistants. The user can access the computer system 1101 via the network 1130.

[0208] Methods as described herein can be implemented by way of machine (e.g., computer processor) executable code stored on an electronic storage location of the computer system 1101, such as, for example, on the memory 1110 or electronic storage unit 1115. The machine executable or machine readable code can be provided in the form of software. During use, the code can be executed by the processor 1105. In some cases, the code can be retrieved from the storage unit 1115 and stored on the memory 1110 for ready access by the processor 1105. In some situations, the electronic storage unit 1115 can be precluded, and machine-executable instructions are stored on memory 1110.

[0209] The code can be pre-compiled and configured for use with a machine having a processer adapted to execute the code, or can be compiled during runtime. The code can be supplied in a programming language that can be selected to enable the code to execute in a pre-compiled or as- compiled fashion. 61WSGR Docket No.68475-701.601

[0210] Aspects of the systems and methods provided herein, such as the computer system 1101, can be embodied in programming. Various aspects of the technology may be thought of as “products” or “articles of manufacture” typically in the form of machine (or processor) executable code and / or associated data that is carried on or embodied in a type of machine readable medium. Machine-executable code can be stored on an electronic storage unit, such as memory (e.g., read- only memory, random-access memory, flash memory) or a hard disk. “Storage” type media can include any or all of the tangible memory of the computers, processors or the like, or associated modules thereof, such as various semiconductor memories, tape drives, disk drives and the like, which may provide non-transitory storage at any time for the software programming. All or portions of the software may at times be communicated through the Internet or various other telecommunication networks. Such communications, for example, may enable loading of the software from one computer or processor into another, for example, from a management server or host computer into the computer platform of an application server. Thus, another type of media that may bear the software elements includes optical, electrical and electromagnetic waves, such as used across physical interfaces between local devices, through wired and optical landline networks and over various air-links. The physical elements that carry such waves, such as wired or wireless links, optical links or the like, also may be considered as media bearing the software. As used herein, unless restricted to non-transitory, tangible “storage” media, terms such as computer or machine “readable medium” refer to any medium that participates in providing instructions to a processor for execution.

[0211] Hence, a machine readable medium, such as computer-executable code, may take many forms, including but not limited to, a tangible storage medium, a carrier wave medium or physical transmission medium. Non-volatile storage media include, for example, optical or magnetic disks, such as any of the storage devices in any computer(s) or the like, such as may be used to implement the databases, etc. shown in the drawings. Volatile storage media include dynamic memory, such as main memory of such a computer platform. Tangible transmission media include coaxial cables; copper wire and fiber optics, including the wires that comprise a bus within a computer system. Carrier-wave transmission media may take the form of electric or electromagnetic signals, or acoustic or light waves such as those generated during radio frequency (RF) and infrared (IR) data communications. Common forms of computer-readable media therefore include for example: a floppy disk, a flexible disk, hard disk, magnetic tape, any other magnetic medium, a CD-ROM, DVD or DVD-ROM, any other optical medium, punch cards paper tape, any other physical storage medium with patterns of holes, a RAM, a ROM, a PROM and EPROM, a FLASH-EPROM, any other memory chip or cartridge, a carrier wave transporting data or instructions, cables or links transporting such a carrier wave, or any other medium from which a computer may read 62WSGR Docket No.68475-701.601 programming code and / or data. Many of these forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to a processor for execution.

[0212] The computer system 1101 can include or be in communication with an electronic display 1135 (e.g., the projector as provided herein) that comprises a user interface (UI) 1140 for providing, for example, at least one of (a) status information for the bed device, local environment, or both or (b) at least one control option to direct operation of the sleep enhancement device. Examples of UI’s include, without limitation, a graphical user interface (GUI) and web-based user interface.

[0213] Methods and systems of the present disclosure can be implemented by way of one or more algorithms. An algorithm can be implemented by way of software upon execution by the central processing unit 1105. The algorithm can, for example, assist in comparison of the sensing data and control data as provided herein. The algorithm can, for example, analyze data collected from the bed device, the user, or both, for implementing any of the methods provided herein. EXAMPLES

[0214] The following examples are provided to further illustrate some embodiments of the present disclosure, but are not intended to limit the scope of the disclosure; it will be understood by their exemplary nature that other procedures, methodologies, or techniques known to those skilled in the art may alternatively be used.

[0215] The examples below are illustrative and non-limiting. Example 1. Methods for Instigating, Improving, And Sustaining Elite Athletic Performance And Lifestyle

[0216] The user may furthermore perform the method prior to, during, after, or outside of various performance sessions to modulate the stress response within and outside of competition in relation to autonomic regulatory function (such as during pre-testing for students, during performances for musicians, and / or during recovery for athletes). Unhealthy human stress can be defined as the negative psychophysiological reaction of a person who confronts a situation in which there is an imbalance between the demands, be it real or imagined, and the ability to fulfill them. The ability to fulfill these demands are quite often dependent upon the optimal function and regulatory behavior of the nervous system and its impact on the brain, heart, and lungs. A stressor is an internal or external, physical, or psychological factor, which can create disequilibrium or in fact drive positive performance states. In elite extreme athletes (i.e., snowboarders), increases in pre- competitive sympathetic tone are positively associated with competitive performance outcomes. The device and system described herein may therefore be utilized to upregulate pre-competitive sympathetic tone through high-frequency nerve stimulation with or without biofeedback. Pre- 63WSGR Docket No.68475-701.601 competitive performance anxiety, also commonly found in both novice and professional performers, can also be downregulated via low-frequency nerve stimulation with or without biofeedback. Athletes (i.e., elite golfers) who are able to perform under stress (clutch performers) as compared to chokers (athletes whose performance degrades during stressful performance) exhibit no changes in lfHRV—an indicator of stressful mental workload and attentional focus in performers. Due to the challenge of training the clutch state, the device and system described herein may therefore be utilized to aid in sustaining lfHRV during performance to instigate and support clutch. As competition progresses, quite often sympathetic tone increases gradually and may become overreactive (as seen quite often in male elite skiers) which could instigate sympathetic over reactivity and atrial fibrillation. The device and system described herein may therefore be utilized to send low-frequency nerve stimulation with or without biofeedback in order to preserve vagal parasympathetic function during performance sessions. The user may perform the method 100 in response to performance related stress whether it is self-reported by the user (self-addressed through questionnaires, for example) or automatically detectable by the biosensor(s) integrated within the neurostimulation device itself or personal computing device (such as a smartphone or smartwatch). Acute episodes of performance stress and autonomic regulatory function correlate with acute changes in HR, HRV and PRQ that can be detectable by the biosensor(s) without the user self-reporting stress. Quite often, due to sympathetic drive, high performers typically find it difficult to initiate the recovery and restitution phase as indexed by parasympathetic drive, high-frequency HRV, and heart rate recovery (HRR), which may take hours to initiate after training and / or competition. The device and system described herein may therefore be utilized to more efficiently and directly upregulate parasympathetic tone and increase the rate of HRR and associated decreases in PRQ during recovery. High performers in a variety of sectors (i.e., police and security forces) showcase daily increases in stress and somatization that are associated with decreases in HRV over the long-term and display abnormal daily fluctuations of autonomic function outside of normal ranges. Due to the fact that daily (lifestyle) autonomic regulation outside of training and competition impacts performance, the device and system described herein may therefore be utilized to more efficiently and directly upregulate and downregulate accordingly sympathetic and / or parasympathetic tone during the daytime and / or nighttime. FIG. 2 shows a schematic diagram of a system 200 for assisting performance. FIG. 10A shows exemplary effects of the system 200 and method 100 before during and after performance and FIG. 10B shows exemplary effects of the system 200 and method 100 during daily lifestyle use. 64WSGR Docket No.68475-701.601 Example 2. Exploratory Observational Case Series Presentation of Elite Athletes Using Median Nerve Stimulation: Preliminary Reported Effects on Autonomic Regulation, Heart Rate Variability, Recovery and Associated Subjective Metrics

[0217] This case series aimed to describe the outcomes observed in a small cohort of elite athletes utilizing a wearable neuro-cardiovascular device and corresponding biofeedback system during athletic activities.

[0218] This exploratory observational case series investigated the physiological and subjective performance-related effects of a novel peripheral nerve stimulation (PNS) closed-loop biofeedback wearable targeting the median nerve in elite athletes. A sample of seven individuals (N = 7) from diverse high-performance sports (e.g., boxing, tennis, golf, alpine skiing, sport climbing, crossfit, and track and field) used the device before, during, and after training and competition. Quantitative metrics, including heart rate variability (HRV), autonomic nervous system (ANS) markers, pulse respiratory quotient (PRQ), and heart rate recovery (HRR), alongside subjective ratings of perceived effort and recovery, were assessed. Results indicate consistent enhancements in autonomic regulation, competitive preparedness, rapid cardiovascular recovery, and improved perceived exertion and recovery metrics across the sample. Below are a series of three select case presentations which outline preliminary case reports collected from the athletes when testing and using the device described herein.

[0219] Seven elite athletes (4 male, 3 female; mean age 33.0 ± 8.8 years) from boxing (n=1), tennis (n=1), golf (n=1), alpine skiing (n=1), sport climbing (n=1), crossfit (n=1), and track and field (n=1) participated. All athletes were free of cardiovascular or neurological disorders, had no history of any psychiatric condition, and were not taking any cardioactive medications. All subjects provided informed consent for preliminary testing and use of the device.

[0220] Participants were fitted with a prototype of the device comprising a wrist-worn neuro- cardiovascular biofeedback device with smartwatch designed to deliver patterned and personalized electrical stimulation to the median nerve. The system included embedded sensors for HRV tracking (via a plethysmographic sensor), respiration tracking, energy expenditure, time of practice, cardiorespiratory biofeedback guidance, proprioceptive tactile feedback (via an embedded vibrator) and provided real-time feedback during use. Athletes used the device across an average of 10–14 sessions over an average of 3-weeks during a variety of typical daily training and competitive scenarios. Physiological data were recorded at three time points: pre-activity (baseline), during activity, and post-activity (recovery phase). Subjective ratings of perceived exertion (RPE) were also collected. Exploratory outcome measures included: heart rate variability (HRV); time-domain metrics (RMSSD and SDNN); autonomic regulation index (ARI), inferred from HRV; pulse respiratory quotient (PRQ), defined as the PR interval-to-respiration ratio; heart 65WSGR Docket No.68475-701.601 rate recovery (HRR), defined as the heart rate drop at 1 minute post-exercise; and perceived exertion and recovery, visual analog recovery scale. Table 1 shows metrics and the corresponding observations in the study. Table 1. Recorded metrics

[0221] All athletes demonstrated and reported improvements across key physiological domains during the intervention phase compared to their baseline training metrics. One athlete showed acute HRR gains post high-intensity sparring. Athletes also reported decreased muscle fatigue and improved breathing synchrony. Two athletes also displayed improved pre-competition HRV and reduced pre-performance anxiety. The use and application of the human performance wearable device enhanced autonomic recovery dynamics and subjective perceived effort. Significant changes in both preparedness and effort in elite athletes across multiple sports domains were observed. Possible mechanisms included increased sympathovagal balance, parasympathetic tone, and improved cardiovagal regulation. The observed acute PRQ improvements suggested possible enhancement of cardio-respiratory coupling. Peripheral median nerve stimulation combined with biofeedback as delivered and operated with the wearable device offered benefits in autonomic regulation, readiness, recovery, and subjective effort in elite athletes. Case Presentation 1: Tennis Player

[0222] The elite tennis player reported a subjective experience of feeling more focused, calm, and competitively prepared after using the wearable device described herein. Mechanisms may involve modulation of the autonomic nervous system (ANS) and related psychophysiological pathways.

[0223] Table 2 provides an overview of the measures and benefits following application of the wearable device described herein. Table 2. Neurophysiological mechanisms, cardiovascular mechanisms, and other regulatory functions66WSGR Docket No.68475-701.601

[0224] Table 3 shows the observed benefit and corresponding underlying mechanism for the case study. Table 3. Observed benefits and mechanisms67WSGR Docket No.68475-701.601

[0225] The tennis player’s self-reported effects of enhanced psychological readiness, calm, and sustained focus may have resulted from central and peripheral autonomic regulation, driven by the device’s means of combining median nerve stimulation with biofeedback-induced guided self- regulation. This combination optimizes neuro-cardiovascular integration, balances the stress response, and primes the athlete both mentally and physically for elite performance. Case Presentation 2: Elite Male Hurdle Runner

[0226] The elite men’s hurdle runner achieved his personal-best time during 50m flying sprints after using the wearable device under a specific cyclic hyperventilation biofeedback program (i.e., Clutch). Effects can be attributed to potential acute upregulation of sympathetic nervous system (SNS) activity, combined with neurocardiovascular priming and psychophysiological readiness. The protocol induces a highly optimized arousal-performance state—characterized by heightened alertness, neuromuscular drive, cardiorespiratory efficiency, and focused mental engagement— all practical for short-duration, explosive events like sprint hurdling.

[0227] Table 4 provides an overview of the measures and benefits following application of the wearable device described herein. Table 4. Neurophysiological mechanisms, cardiovascular mechanisms, and other regulatory functions68WSGR Docket No.68475-701.601

[0228] Table 5 shows the target domain, underlying mechanisms, and possible performance effects for the case study. Table 5. Observed benefits and mechanisms

[0229] The elite hurdler’s personal-best sprint times could be a result from combined activations of neurophysiological readiness, autonomic priming, neuromuscular optimization, and psychological focus. These characteristics are enhanced by the combined use of median nerve stimulation and cyclic hyperventilation biofeedback as delivered by the wearable device. This 69WSGR Docket No.68475-701.601 protocol induces a controlled high-arousal state, maximizing output while preserving focus and coordination, which are useful for executing sprint hurdling. Case Presentation 3: Elite Female Boxer

[0230] The elite female boxer reported enhanced post-training recovery and improved digestive comfort after using the wearable device described herein. Results of the post-training recovery and improved digestive comfort may be attributed to integrated neuro-cardiovascular, autonomic, gastrointestinal, and psychophysiological mechanisms. The wearable device and training protocols combine nerve stimulation with biofeedback to promote parasympathetic nervous system (PNS) dominance which has shown significant impacts on facilitating recovery, gut function, and emotional regulation.

[0231] Table 6 provides an overview of the measures and benefits following application of the wearable device described herein. Table 6. Neuro-autonomic mechanisms, gastrointestinal regulation, and other regulatory functions70WSGR Docket No.68475-701.601

[0232] Table 7 shows the target domain, underlying mechanisms, and possible outcomes for the case study. Table 7. Observed benefits and mechanisms

[0233] The elite boxer’s improved post-training recovery and digestion may be attributed to restoration of parasympathetic dominance via the wearable device, which delivered nerve stimulation and slow deep breathing exercises by utilizing specific stimulation parameters. The device and methods may have not only accelerated cardiovascular and neuromuscular recovery but also rebalanced gut-brain axis function. The improved gut-brain axis function resolves common post-training GI discomfort as reported previously by the user. Psychologically, the intervention supports a state of relaxed focus, which are practical benefits for day-to-day performance consistency in elite combat sports.

[0234] A graphical model, as shown in FIG. 12, demonstrates the above findings in Example 2 and observed performance dynamics in the case studies. The model is based on the Yerkes-Dodson Law of Performance which originally suggested that performance and arousal are roughly associated in the following manner: low arousal can lead to poor performance due to under- engagement; optimal arousal can lead to peak performance; and high arousal can lead to poor 71WSGR Docket No.68475-701.601 performance due to stress or overload. The methods and systems described herein for optimizing human performance during activity further evolve the model.

[0235] While preferred embodiments of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. It is not intended that the present disclosure be limited by the specific examples provided within the specification. While the present disclosure has been described with reference to the aforementioned specification, the descriptions and illustrations of the embodiments herein are not meant to be construed in a limiting sense. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the present disclosure. Furthermore, it shall be understood that all aspects of the present disclosure are not limited to the specific depictions, configurations or relative proportions set forth herein which depend upon a variety of conditions and variables. It should be understood that various alternatives to the embodiments of the present disclosure described herein can be employed in practicing the present disclosure. It is therefore contemplated that the present disclosure shall also cover any such alternatives, modifications, variations or equivalents. It is intended that the following claims define the scope of the present disclosure and that methods and structures within the scope of these claims and their equivalents be covered thereby. 72

Claims

WSGR Docket No.68475-701.601 CLAIMS WHAT IS CLAIMED IS:

1. A method of improving a state of a subject, the method comprising: (a) providing to the subject, by way of a computing device, instructions to the subject to proceed through an exercise protocol, the exercise protocol comprising one or more of a physical exercise, a psychological exercise, or a breathing exercise; (b) stimulating a nerve of the subject according to a stimulation program in response to the subject proceeding through the exercise protocol; (c) measuring at least one physiological or psychological parameter of the subject; and (d) modifying the stimulation program, the exercise protocol, or any combination thereof in response to the measured at least one physiological or psychological parameter to improve at least one biometric of the subject related to the state of the subject.

2. The method of claim 1, wherein the state is a physical state, a mental state, or any combination thereof.

3. The method of claim 2, wherein the physical state is an epigenetic age, a cardiovascular fitness capacity, a sleep quality, an at least one metabolic health biomarker, a heart rate, a resting heart rate, a heart rate variability, a VO2max, a pulse respiratory quotient, a breath hold time, a velocity, an energy expenditure, a functional threshold power, a force output, a pulse rate variability, a VCO2, a metabolic rate, a perceived effort, a fatigue management, or any combination thereof.

4. The method of claim 2, wherein the physical state is a physical condition comprising cardiovascular disease, a respiratory disease, musculoskeletal disease, autonomic dysfunction and / or dysregulation, consciousness disruption, inflammatory disease, or any combination thereof.

5. The method of claim 2, wherein the mental state is memory, attention, cognitive flexibility, interoception, executive function, cardiorespiratory, psycho-behavioral, neurochemical, cognitive-affective, or any combination thereof.

6. The method of claim 1, wherein the state is performance of a physical activity.

7. The method of any one of claims 1-6, wherein the nerve comprises a peripheral nerve.

8. The method of any one of claims 1-7, wherein the nerve comprises a median nerve, a vagal nerve, a trigeminal nerve, a tibial nerve, or any combination thereof.

9. The method of any one of claims 1-8, wherein the nerve is a median nerve. 73WSGR Docket No.68475-701.601 10. The method of any one of claims 1-9, wherein the stimulating occurs at the subject’s arm, wrist, hand, neck, head, leg, torso, or any combination thereof.

11. The method of any one of claims 1-10, wherein the physiological parameter comprises a heart rate, a resting heart rate, a heart rate variability, a VO2max, a pulse respiratory quotient, a blood-oxygen content, a blood pressure, an electrodermal activity, electrocardiogram (EEG) information, a body position, a sleep cycle, a body temperature, a mile-split time, a respiratory pattern, or any combination thereof.

12. The method of claim 11, wherein the respiratory pattern comprises a respiratory rate, an inhalation, an exhalation, a breath-hold time, a tidal volume, or any combination thereof.

13. The method of any one of claims 1-12, wherein the measuring at least one physiological or psychological parameter of the subject occurs prior to the subject proceeding through the exercise protocol, while the subject is proceeding through the exercise protocol, while the nerve of the subject is stimulated, or any combination thereof.

14. The method of any one of claims 1-13, wherein the nerve is stimulated via vibratory stimulation, electrical stimulation, thermal stimulation, acoustic stimulation, infrasound stimulation, ultrasound stimulation, pulse laser, transient optical neural stimulation, or any combination thereof.

15. The method of any one of claims 1-14, wherein the nerve is stimulated via vibratory stimulation, electrical stimulation, or any combination thereof.

16. The method of any one of claims 1-15, wherein one or more biosensors measure the at least one physiological or psychological parameter of the subject.

17. The method of claim 16, wherein the one or more biosensors comprise a electroencephalogram (EEG) sensor, and a photoplethysmographic (PPG) sensor, an electromyographic (EMG) sensors, an electrooculographic (EOG) sensor, an electrocardiogram (ECG) sensor, a pulse-oximeter, a chest monitor, a PPG biosensor ring, a PPG biosensor patch, a biosensor tattoo, a blood pressure sensor, a perspiration sensor, a skin conductivity sensor, an accelerometer, a location sensor, a gyroscope, or any combination thereof.

18. The method of any one of claims 1-17, wherein the stimulation program comprises one or more parameters comprising: a frequency, a pulse width, a pulse pattern, a current, a voltage, a pulse duration, a repetition rate, a current intensity, or any combination thereof.

19. The method of claim 18, wherein the frequency comprises a range from about 1-1000 Hz. 74WSGR Docket No.68475-701.601 20. The method of claim 18 or 19, wherein the frequency comprises a range from about 10- 120 Hz.

21. The method of any one of claims 18-20, wherein the current intensity comprises a range from about 100 μA to about 10 mA.

22. The method of any one of claims 18-21, wherein the pulse width comprises a range from about 1 μs to about 100 ms.

23. The method of any one of claims 18-22, wherein the pulse pattern is a cyclical or sinusoidal pulse pattern.

24. The method of claim 23, wherein the pulse pattern is rhythmic.

25. The method of claim 23, wherein the pulse pattern is arrhythmic.

26. The method of claim 23, wherein the pulse patten is paired with cardiovascular activity of the subject.

27. The method of claim 23, wherein the pulse pattern is not paired from cardiovascular activity of the subject.

28. The method of any one of claims 1-27, wherein the stimulating of the nerve is by non- invasive neurostimulation.

29. The method of claim 28, wherein the non-invasive stimulation is via a transcutaneous neurostimulator.

30. The method of claim 29, wherein the transcutaneous neurostimulator comprises one or more electrodes, wherein the electrodes are configured to administer stimulation to the nerve of the subject.

31. The method of any one of claims 1-30, further comprising monitoring sympathetic and / or parasympathetic activity of the subject.

32. The method of any one of claims 1-31, further comprising stimulating a second nerve of the subject according to the stimulation program.

33. The method of claim 32, wherein the second nerve is at a same location of the body as the nerve of the subject.

34. The method of claim 32, wherein the second nerve is at a different location of the body as the nerve of the subject.

35. The method of any one of claims 32-34, wherein the second nerve comprises a median nerve, a vagal nerve, a trigeminal nerve, a tibial nerve, or any combination thereof.

36. The method of any one of claims 1-35, wherein the breathing exercise comprises inhalation and / or exhalation dynamics to increase sympathetic nervous system activity, parasympathetic nervous system activity, or any combination thereof. 75WSGR Docket No.68475-701.601 37. The method of any one of claims 1-35, wherein the breathing exercise comprises inhalation and / or exhalation dynamics to decrease sympathetic nervous system activity, parasympathetic nervous system activity, or any combination thereof.

38. The method of any one of claims 1-35, wherein the breathing exercise comprises inhalation and / or exhalation dynamics to increase sympathetic nervous system activity and decrease parasympathetic nervous system activity.

39. The method of any one of claims 1-35, wherein the breathing exercise comprises inhalation and / or exhalation dynamics to decrease sympathetic nervous system activity and increase parasympathetic nervous system activity.

40. The method of any one of claims 1-35, wherein the breathing exercise regulates an equal ration of sympathetic and / or parasympathetic activity.

41. The method of any one of claims 1-40, further comprising administering a secondary signal.

42. The method of claim 41, wherein the secondary signal comprises an audio signal, a visual signal, or an audiovisual signal.

43. The method of claim 40 or 41, wherein the secondary signal is administered prior to stimulating the nerve of the subject, after stimulating the nerve of the subject, or concurrently with stimulating the nerve of the subject.

44. The method of any one of claims 1-43, wherein stimulating the nerve of the subject occurs concurrently with the subject proceeding through the exercise protocol.

45. The method of any one of claims 1-43, wherein the stimulating the nerve of the subject occurs after the subject proceeds through the exercise protocol.

46. The method of any one of claims 1-45, further comprising ceasing stimulation of the nerve in response to improvement of the at least one biometric.

47. The method of any one of claims 1-45, further comprising prolonging stimulation of the nerve in response to improvement of the at least one biometric.

48. The method of any one of claims 1-47, wherein the computing device comprises a mobile electronic device.

49. The method of claim 48, wherein the mobile electronic device comprises a smartwatch.

50. The method of any one of claims 1-49, wherein the stimulation program comprises one or more stimulation profiles, wherein each of the one or more stimulation profiles comprises a different stimulation parameter.

51. The method of claim 50, wherein modifying the stimulation program in response to the measured at least one physiological or psychological parameter comprises selecting a second stimulation profile that is different from a first stimulation profile. 76WSGR Docket No.68475-701.601 52. The method of claim 1-51, further comprising, prior to (a), determining a baseline physiological or psychological parameter of the subject, wherein the baseline physiological or psychological parameter is the same type of physiological or psychological parameter as the measured physiological or psychological parameter of (c).

53. A method of improving a state of a subject, the method comprising: (a) establishing a baseline cardiovascular parameter, baseline respiratory parameter, a baseline biomechanical parameter, a baseline biochemical parameter, or any combination thereof; (b) detecting an inhalation or exhalation of the subject; (c) measuring a physiological state of the subject based on the inhalation or exhalation; (d) comparing the physiological state to the baseline cardiovascular parameter, baseline respiratory parameter, baseline biomechanical parameter, baseline biochemical parameter, or any combination thereof; and (e) administering a stimulation to a nerve of the subject based on the comparison of (d); and wherein the stimulation improves the state of the subject.

54. A method for improving a state of a subject, the method comprising: (a) receiving from: (i) one or more first sensors, at least one signal indicative of a baseline cardiovascular parameter; and (ii) one or more second sensors, at least one signal indicative of a baseline respiratory parameter; (b) determining an inhalation or exhalation of the subject; (c) measuring a physiological state of the subject; (d) comparing the physiological state to the baseline cardiovascular parameter, the baseline respiratory parameter, or any combination thereof to determine a cardiorespiratory dynamic and / or neurocardiac dynamic; and (e) administering a stimulation via one or more electrodes to a nerve of the subject, wherein the stimulation is based on the cardiorespiratory dynamic and / or neurocardiac dynamic.

55. The method of claim 53 or 54, wherein the state is a physical state, a mental state, or any combination thereof. 77WSGR Docket No.68475-701.601 56. The method of claim 55, wherein the physical state is an epigenetic age, a cardiovascular fitness capacity, a sleep quality, an at least one metabolic health biomarker, a heart rate, a resting heart rate, a heart rate variability, a VO2max, a pulse respiratory quotient, a breath hold time, a velocity, an energy expenditure, a functional threshold power, a force output, a pulse rate variability, a VCO2, a metabolic rate, a perceived effort, a fatigue management, or any combination thereof.

57. The method of claim 55, wherein the physical state is a physical condition comprising cardiovascular disease, a respiratory disease, musculoskeletal disease, autonomic dysfunction and / or dysregulation, consciousness disruption, inflammatory disease, or any combination thereof.

58. The method of claim 55, wherein the mental state is memory, attention, cognitive flexibility, interoception, executive function, cardiorespiratory, psycho-behavioral, neurochemical, cognitive-affective, or any combination thereof.

59. The method of claim 53 or 54, wherein the state is performance of a physical activity.

60. The method of any one of claims 53-59, wherein the nerve comprises a peripheral nerve.

61. The method of any one of claims 53-60, wherein the nerve comprises a median nerve, a vagal nerve, a trigeminal nerve, a tibial nerve, or any combination thereof.

62. The method of any one of claims 53-61, wherein the nerve is a median nerve.

63. The method of any one of claims 53-62, wherein the stimulating occurs at the subject’s arm, wrist, hand, neck, head, leg, torso, or any combination thereof.

64. The method of any one of claims 53-63, wherein the baseline cardiovascular parameter comprises a heart rate, a resting heart rate, a heart rate variability, a VO2max, a pulse respiratory quotient, a blood-oxygen content, a blood pressure, an electrodermal activity, electrocardiogram (EEG) information, a body position, a sleep cycle, a body temperature, a velocity, an energy expenditure, a functional threshold power, a force output, a pulse rate variability, a VCO2, a metabolic rate, a perceived effort, a fatigue management, or any combination thereof.

65. The method of any one of claims 53-64, wherein the baseline respiratory parameter comprises a respiratory rate, an inhalation, an exhalation, a breath-hold time, a tidal volume, or any combination thereof.

66. The method of any one of claims 53-65, wherein the nerve is stimulated via vibratory stimulation, electrical stimulation, thermal stimulation, acoustic stimulation, infrasound stimulation, ultrasound stimulation, pulse laser, transient optical neural stimulation, or any combination thereof. 78WSGR Docket No.68475-701.601 67. The method of any one of claims 53-66, wherein the nerve is stimulated via vibratory stimulation, electrical stimulation, or any combination thereof.

68. The method of any one of claims 53-67, wherein one or more biosensors measure the physiological state of the subject.

69. The method of claim 68, wherein the one or more biosensors comprise a electroencephalogram (EEG) sensor, and a photoplethysmographic (PPG) sensor, an electromyographic (EMG) sensors, an electrooculographic (EOG) sensor, an electrocardiogram (ECG) sensor, a pulse-oximeter, a chest monitor, a PPG biosensor ring, a PPG biosensor patch, a biosensor tattoo, a blood pressure sensor, a perspiration sensor, a skin conductivity sensor, an accelerometer, a location sensor, a gyroscope, or any combination thereof.

70. The method of any one of claims 53-69, wherein the stimulation comprises one or more parameters comprising: a frequency, a pulse width, a pulse pattern, a current, a voltage, a pulse duration, a repetition rate, a current intensity, or any combination thereof.

71. The method of claim 70, wherein the frequency comprises a range from about 1-1000 Hz.

72. The method of claim 70 or 71, wherein the frequency comprises a range from about 10- 120 Hz.

73. The method of any one of claims 70-72, wherein the current intensity comprises a range from about 100 μA to about 10 mA.

74. The method of any one of claim 70-73, wherein the pulse width comprises a range from about 1 μs to about 100 ms.

75. The method of any one of claims 70-74, wherein the pulse pattern is a cyclical or sinusoidal pulse pattern.

76. The method of claim 75, wherein the pulse pattern is rhythmic.

77. The method of claim 75, wherein the pulse pattern is arrhythmic.

78. The method of claim 75, wherein the pulse pattern is paired with cardiovascular activity of the subject.

79. The method of claim 75, wherein the pulse pattern is not paired with cardiovascular activity of the subject.

80. The method of any one of claims 70-79, wherein stimulation of the nerve is by non- invasive neurostimulation.

81. The method of claim 80, wherein the non-invasive stimulation is via a transcutaneous neurostimulator. 79WSGR Docket No.68475-701.601 82. The method of claim 81, wherein the transcutaneous neurostimulator comprises one or more electrodes, wherein the electrodes are configured to administer stimulation to the nerve of the subject.

83. The method of any one of claims 53-82, further comprising monitoring sympathetic and / or parasympathetic activity of the subject.

84. The method of any one of claims 53-83, further comprising stimulating a second nerve of the subject according to the stimulation program.

85. The method of claim 84, wherein the second nerve is at a same location of the body as the nerve of the subject.

86. The method of claim 84, wherein the second nerve is at a different location of the body as the nerve of the subject.

87. The method of any one of claims 84-86, wherein the second nerve comprises a median nerve, a vagal nerve, a trigeminal nerve, a tibial nerve, or any combination thereof.

88. The method of any one of claims 53-87, wherein the inhalation or exhalation increases sympathetic nervous system activity, parasympathetic nervous system activity, or any combination thereof.

89. The method of any one of claims 53-87, wherein the inhalation or exhalation decreases sympathetic nervous system activity, parasympathetic nervous system activity, or any combination thereof.

90. The method of any one of claims 53-87, wherein the inhalation or exhalation increases sympathetic nervous system activity and decreases parasympathetic nervous system activity.

91. The method of any one of claims 53-87, wherein the inhalation or exhalation decreases sympathetic nervous system activity and increases parasympathetic nervous system activity.

92. The method of any one of claims 53-87, wherein the inhalation or exhalation regulates an equal ration of sympathetic and / or parasympathetic activity.

93. The method of any one of claims 53-92, further comprising administering a secondary signal.

94. The method of claim 93, wherein the secondary signal comprises an audio signal, a visual signal, or an audiovisual signal.

95. The method of claim 93 or 94, wherein the secondary signal is administered prior to stimulating the nerve of the subject, after stimulating the nerve of the subject, or concurrently with stimulating the nerve of the subject. 80WSGR Docket No.68475-701.601 96. The method of any one of claims 53-95, further comprising (f) providing to the subject, by way of a computing device, instructions to the subject to proceed through an exercise protocol, the exercise protocol comprising one or more of a physical exercise, a psychological exercise, or a breathing exercise; 97. The method of claim 96, wherein the stimulation to the nerve of the subject occurs concurrently with the subject proceeding through the exercise protocol.

98. The method of claim 96, wherein the stimulation to the nerve of the subject occurs after the subject proceeds through the exercise protocol.

99. The method of any one of claims 53-98, further comprising ceasing stimulation of the nerve in response to improvement of the state of the subject.

100. The method of any one of claims 53-98, further comprising prolonging stimulation of the nerve in response to improvement of the state of the subject 101. The method of any one of claims 96-98, wherein the computing device comprises a mobile electronic device.

102. The method of any one of claims 53-101, wherein stimulation to the nerve of subject occurs according to a stimulation program in response to the comparing of (d).

103. The method of claim 102, wherein the stimulation program comprises one or more stimulation profiles, wherein each of the one or more stimulation profiles comprises a different stimulation parameter.

104. A method of improving a state of a subject, the method comprising: (a) receiving from: (i) one or more sensors, at least one signal indicative of a baseline respiratory parameter; (b) determining an inhalation or exhalation; (c) measuring a respiratory pattern of the subject; (d) comparing the respiratory pattern with the baseline respiratory parameter; and (e) applying a stimulation to a nerve of the subject based on the comparison of the respiratory pattern the baseline respiratory parameter.

105. A system for modulating a respiratory function of a subject, said system comprising: (i) a flexible carrier configured to be worn by the subject; (ii) a transcutaneous neurostimulator, the transcutaneous neurostimulator comprising at least one electrode coupled to the flexible carrier; (iii) one or more sensors configured to retrieve at least one signal indicative of the subject’s respiratory pattern; and 81WSGR Docket No.68475-701.601 (iv) a controller configured to communicate with the transcutaneous neurostimulator and comprising a memory-storing biofeedback program, wherein the memory- storing biofeedback program is configured to compare the at least one signal indicative of the subject’s respiratory pattern with a baseline respiratory pattern of the subject; and wherein the transcutaneous neurostimulator is configured to generate one or more stimulation to a nerve of the subject.

106. The system of claim 105, further comprising (v) a power source coupled to the flexible carrier.

107. The system of claim 106, wherein the transcutaneous neurostimulator is in electrical communication with the power source.

108. The system of any one of claims 105-107, wherein the memory-storing biofeedback program is disposed on a mobile electronic device.

109. The system of any one of claims 105-108, wherein the one or more sensors comprise a electroencephalogram (EEG) sensor, and a photoplethysmographic (PPG) sensor, an electromyographic (EMG) sensors, an electrooculographic (EOG) sensor, an electrocardiogram (ECG) sensor, a pulse-oximeter, a chest monitor, a PPG biosensor ring, a PPG biosensor patch, a biosensor tattoo, a blood pressure sensor, a perspiration sensor, a skin conductivity sensor, an accelerometer, a location sensor, or any combination thereof.

110. The system of any one of claims 105-109, wherein the stimulation comprises vibratory stimulation, electrical stimulation, thermal stimulation, acoustic stimulation, infrasound stimulation, ultrasound stimulation, pulse laser, transient optical neural stimulation, or any combination thereof.

111. The system of any one of claims 105-110, wherein the stimulation comprises vibratory stimulation, electrical stimulation, or any combination thereof.

112. The system of any one of claims 105-111, wherein the controller is further configured to adjust one or more stimulation based on the comparison of the at least one signal indicative of the subject’s respiratory pattern and the baseline respiratory pattern of the subject.

113. The system of any one of claims 105-112, wherein the nerve comprises a peripheral nerve.

114. The system of any one of claims 105-113, wherein the nerve comprises a median nerve, a vagal nerve, a trigeminal nerve, a tibial nerve, or any combination thereof.

115. The system of any one of claims 105-114, wherein the nerve is a median nerve. 82WSGR Docket No.68475-701.601 116. The system of any one of claims 105-115, wherein the flexible carrier is disposed on the subject’s arm, wrist, hand, neck, head, leg, or torso.

117. The system of any one of claims 105-116, wherein the at least one signal indicative of the subject’s respiratory pattern comprises a respiratory rate, an inhalation, an exhalation, a breath-hold time, a tidal volume, a heart rate variability, a pulse respiratory quotient, or any combination thereof.

118. The system of any one of claims 105-117, wherein the one or more sensors is disposed on the subject’s arm, wrist, hand, neck, head, leg, or torso.

119. The system of any one of claims 105-118, wherein the one or more sensors is further configured to retrieve at least one signal indicative of the subject’s cardiovascular health.

120. The system of any one of claims 105-119, wherein the at least one signal indicative of the subject’s cardiovascular health comprises a heart rate, a resting heart rate, a VO2 max, a blood-oxygen content, a blood pressure, an electrodermal activity, electrocardiogram (EEG) information, a body position, a sleep cycle, a body temperature, a mile-split time, or any combination thereof.

121. The system of any one of claims 105-120, wherein the one or more stimulation is applied as continuous stimulation to the nerve of the subject.

122. The system of any one of claims 105-120, wherein the one or more stimulation is applied as a burst stimulation to the nerve of the subject.

123. The system of any one of claims 105-122, wherein the one or more stimulation comprise one or more parameters comprising: a frequency, a pulse width, a pulse pattern, a current, a voltage, a pulse duration, a repetition rate, a current intensity, or any combination thereof.

124. The system of claim 123, wherein the frequency comprises a range from about 1-1000 Hz.

125. The system of claim 123 or 124, wherein the frequency comprises a range from about 10-120 Hz.

126. The system of any one of claims 123-125, wherein the current intensity comprises a range from about 100 μA to about 10 mA.

127. The system of any one of claim 123-126, wherein the pulse width comprises a range from about 1 μs to about 100 ms.

128. The system of any one of claims 123-127, wherein the pulse pattern is a cyclical or sinusoidal pulse pattern.

129. The system of claim 128, wherein the pulse pattern is rhythmic.

130. The system of claim 128, wherein the pulse pattern is arrhythmic. 83WSGR Docket No.68475-701.601 131. The system of claim 128, wherein the pulse patten is paired with cardiovascular activityof the subject.

132. The system of claim 128, wherein the pulse pattern is not paired from cardiovascularactivity of the subject 133. The system of any one of claims 105-132, wherein the system is further configured tomonitor a level of sympathetic nervous system activity and / or parasympathetic nervous system activity of the subject.

134. The system of any one of claims 105-133, wherein the transcutaneous neurostimulatoris configured to generate at least a first stimulation to a first nerve of the subject and a second stimulation to a second nerve of the subject.

135. The system of claim 134, wherein the second nerve is at a same location of the body asthe first nerve of the subject.

136. The system of claim 134, wherein the second nerve is at a different location of the bodyas the first nerve of the subject.

137. The system of any one of claims 134-136, wherein the second nerve comprises amedian nerve, a vagal nerve, a trigeminal nerve, or a tibial nerve.

138. The system of any one of claims 105-137, wherein the memory-storing biofeedbackprogram comprises one or more stimulation profile.

139. The system of claim 138, wherein the one or more stimulation profile is configured todefine parameters of the generated one or more stimulation.

140. The system of any one of claims 105-139, wherein the system further comprises anaudio generator, wherein the audio generator is configured to provide an auditory stimulus.

141. The system of any one of claims 105-140, wherein the memory-storing biofeedbackprogram is in electrical communication with a smartphone.

142. The system of any one of claims 105-140, wherein the memory-storing biofeedbackprogram is in electrical communication with a virtual reality program.

143. The system of any one of claims 105-140, wherein the memory-storying biofeedbackprogram is in electrical communication with a VO2 mask. 84

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