EP4735107A1

EP4735107A1 - Systems and methods for aiding a user in breathing using implantable devices

Info

Publication number: EP4735107A1
Application number: EP24829625.3A
Authority: EP
Inventors: Michael James DENT; Matthew Robin WELLS; Ross William Deas
Original assignee: Resmed Pty Ltd
Current assignee: Resmed Pty Ltd
Priority date: 2023-06-28
Filing date: 2024-06-27
Publication date: 2026-05-06
Also published as: WO2025000032A1; CN121443351A

Abstract

A neurostimulation system disclosed herein comprises a stimulation device including a stimulator that is configured to provide electrical stimulation to one or more branches of a nerve of the user or one or more muscles of the user, a memory storing machine-readable instructions; and a control system including one or more processors configured to execute the machine-readable instructions to implement an acclimatization process. The acclimatization process is configured to acclimatize the user to a neurostimulation therapy for aiding the user in breathing, prior to commencement of a therapy period, by: setting a stimulation profile of the system to a starting stimulation profile configured so that a level of electrical stimulation applied under the starting stimulation profile is weaker than required for providing the neurostimulation therapy; causing the stimulation device to provide the electrical stimulation under the starting stimulation profile to the one or more branches of the nerve or the one or more muscles; receiving a response data from, or measured from a physiological output of, the user; processing the response data to determine a stimulation response; changing the stimulation profile to increase a level of electrical stimulation applied under the profile, while the stimulation response is within a tolerance threshold; and stopping stimulation when the stimulation response is not within the tolerance threshold or the stimulation profile is at a predefined limit.

Description

SYSTEMS AND METHODS FOR AIDING A USER IN BREATHING USING IMPLANTABLE DEVICES

TECHNICAL FIELD

[0001] The present disclosure relates generally to systems and methods for aiding a user in breathing, and more particularly, to systems and methods for aiding in preventing an apnea from occurring by stimulating one or more nerve branches at a determined stimulation time.

BACKGROUND

[0002] Many individuals suffer from sleep-related respiratory disorders such as, for example, Sleep-Disordered Breathing (SDB), Obstructive Sleep Apnea (OSA), Cheyne- Stokes Respiration (CSR). These disorders are characterized event such as apneas, hypopneas, hyperpnea, and hypercapnia where the individual’s breathing stops or is disrupted/restricted during sleep. Various systems exist for aiding users experiencing sleep apnea and related respiratory disorders. Some such systems require the user to wear an interface (e.g., mask) that aids in suppling pressurized air to the airway of the user (e.g., a continuous positive airway pressure (CPAP) system). Some users find such systems to be uncomfortable, difficult to use, expensive, aesthetically unappealing, etc. Other systems rely on an implanted respiration monitoring sensor and/or stimulator that stimulates nerves/muscles to open the airway. In such systems, electrical stimulation provided to the nerves or muscles may cause discomfort to the users, particularly when the user is still awake. The stimulation may also cause the users to awaken from their sleep, when the therapy is performed while the user is asleep, thus defeating the purpose for providing a sleep aid. However, although applying lower stimulation levels decreases the possibility of discomfort to the users or waking the users, this may impact the effectiveness in the therapy in aiding to open the airway. The present disclosure is directed to solving or ameliorating, at least in part, these and other problems. SUMMARY

[0003] According to some implementations of the present disclosure, there is provided a neurostimulation system, comprising: a stimulation device including a stimulator that is configured to provide electrical stimulation to one or more branches of a nerve of the user or one or more muscles of the user; a memory storing machine-readable instructions; and a control system including one or more processors. The one or more processors are configured to execute the machine-readable instructions to implement an acclimatization process to acclimatize the user to a neurostimulation therapy for aiding the user in breathing, prior to commencement of a therapy period, by: setting a stimulation profile of the system to a starting stimulation profile configured so that a level of electrical stimulation applied under the starting stimulation profile is weaker than required for providing the neurostimulation therapy; causing the stimulation device to provide the electrical stimulation under the starting stimulation profile to the one or more branches of the nerve or the one or more muscles; receiving a response data from, or measured from a physiological output of, the user; processing the response data to determine a stimulation response; changing the stimulation profile to increase a level of electrical stimulation applied under the profile, while the stimulation response is within a tolerance threshold; and stopping stimulation when the stimulation response is not within the tolerance threshold or the stimulation profile is at a predefined limit.

[0004] In some embodiments, the stimulation profile is characterized by one or more parameters, and the electrical stimulation strength associated with the stimulation profile is determined at least in part by values of the one or more parameters.

[0005] In some embodiments, the the plurality of parameters comprise parameters selected from: an amplitude, a frequency, and a duty cycle of the stimulation.

[0006] In some embodiments, the changing the stimulation profile comprises increasing the value or values of one or more of the parameters.

[0007] In some embodiments, the parameters comprise one or more nonquantitative parameters selected from: stimulation channel and user position. [0008] In some embodiments, the control system is further configured to output a highest level of stimulation which the user is able to tolerate within a tolerance threshold and/or an acclimatized stimulation profile associated with the highest level of stimulation.

[0009] In some embodiments, the highest stimulation level and/or the acclimatized stimulation profile is used as a basis to set a therapy stimulation level for the neurostimulation therapy.

[0010] In some embodiments, the user’s tolerance is determined from a threshold framework.

[0011] In some embodiments, the control system is further configured to output an acclimatized stimulation profile associated with the highest stimulation level.

[0012] In some embodiments, the control system is further configured to output a period of time which has elapsed from a time when stimulation at a last stimulation level is applied to a time when the response data indicating the stimulation response outside the tolerance threshold is received.

[0013] In some embodiments, the control system is configured to change the stimulation profile based on a comparison between the stimulation response and the tolerance threshold.

[0014] In some embodiments, the response data comprises self-reported data provided by the user or a third-party via an external device.

[0015] In some embodiments, the self-reported data indicates a pain or discomfort, or pain or discomfort level, experienced by the user during application of electrical stimulation.

[0016] In some embodiments, the response data includes sensor data gathered by one or more sensors.

[0017] In some embodiments, the system comprises one or more sensors configured to do one or more of: measure one or more physiological outputs from the user, measure an acoustic output from the user, acquire a camera or thermal image of the user, sense motion. [0018] In some embodiments, the one or more physiological outputs comprises one or more of: heart rate, breathing rate, a force or strain caused by a muscle twitch, a respiratory flow rate, electrocardiogram, electroencephalogram.

[0019] In some embodiments, the system further comprises an output device configured to provide an acoustic, visual, or video output, wherein the control system is configured to cause the output device to provide an additional therapy to the user, the additional therapy being delivered using one or more of an acoustic, visual, or video signals, while causing the stimulation device to provide the electrical stimulation.

[0020] In some embodiments, the additional therapy is configured to trigger or aid in triggering a parasympathetic nervous response in the user.

[0021] In some embodiments, the additional therapy is provided in response to the control system determining that user has a negative response to the electrical stimulation wherein the stimulation response is not within the tolerance threshold.

[0022] In some embodiments, the output device is configured to provide additional therapy from a time which precedes a start time when the stimulation provides the electrical stimulation.

[0023] In some embodiments, the system further comprises a respiration monitoring device including a sensor configured to generate data associated with respiration of the user.

[0024] In some embodiments, the nerve is a hypoglossal nerve.

[0025] According to some implementations of the present disclosure, there is provided a method of determining a starting stimulation level for a stimulation therapy. The method comprises implementing an acclimatization process to acclimatize the user to a neurostimulation therapy for aiding the user in breathing, prior to commencement of a therapy period, by: setting a stimulation profile to a starting stimulation profile configured so that a level of electrical stimulation applied under the starting stimulation profile is weaker than required for the neurostimulation therapy; providing electrical stimulation under the stimulation profile to the one or more branches of the nerve or the one or more muscles; receiving a response data from, or measured from a physiological output of, the user; processing the response data to determine a stimulation response; changing the stimulation profile to increase a level of electrical stimulation while the stimulation response is within a tolerance threshold; stopping stimulation when the stimulation response is not within the tolerance threshold or when the stimulation profile has reached a predefined limit; establishing a highest level of stimulation which the user is able to tolerate within a tolerance threshold and/or an acclimatized stimulation profile associated with the highest level of stimulation; and setting the starting therapy level at a level using a maximum tolerable stimulation level derived from the highest level of stimulation and/or the acclimatized stimulation profile.

[0026] In some embodiments, the starting therapy level is less than the maximum tolerable stimulation level.

[0027] In some embodiments, the method comprises performing implementing the acclimatization multiple times, where a different stimulation channel is used each time, to obtain maximum tolerable stimulation levels associated with each stimulation channel, wherein the maximum tolerable stimulation level for the user is selected from the maximum tolerable stimulation levels associated with the stimulation channels.

[0028] In some embodiments, the acclimatization process is implemented while the user is in one or more sleep positions.

[0029] According to some implementations of the present disclosure, there is provided a stimulation system for aiding opening of a user’s airway. The stimulation system includes a stimulation device, a memory, and a control system configured to control a stimulation level applied by the stimulation device. The stimulation device includes a stimulator that is configured to provide electrical stimulation to one or more branches of a nerve of the user innervating or adjacent to a muscle of the user, where movement of the muscle causes an opening of the user’s airway. The control system includes one or more processors configured to execute machine-readable instructions to determine a stimulation level applied by the stimulation device. The stimulation level is controllable on the basis of a response input which is indicative of the user’s response to a current level of stimulation. [0030] The response input may indicate a level of pain or discomfort.

[0031] The response input may be provided by the user or may be measured by a sensor. [0032] The response input may be a user input indicating pain or discomfort.

[0033] The response input may include a heart rate or breathing rate of the user.

[0034] The response input may be the Apnea-Hypopnea Index (AHI).

[0035] The response input may be an asleep or awake status of the user.

[0036] A method of determining the stimulation level may include: adjusting the stimulation level over a first period of time on the basis of the input, in order to determine a stimulation level which is to be applied during a subsequent period when breathing aid is provided to the user.

[0037] The method may include, during the first period of time, setting the stimulation level to a starting level, and then adjusting the stimulation level from the starting level on the basis of the response input. For example, the stimulation level is lowered from the starting level if the response input indicates the user has transitioned from being asleep to being awake. In further examples, the stimulation level is additionally or alternatively, lowered from the starting level if the response input indicates the user is experiencing a pain or discomfort which is over a threshold. In cases where the threshold is zero, this means the stimulation level is lowered if the response input indicates that the user is experiencing any discomfort or pain.

[0038] The control system may be configured to adjust the stimulation level by increasing it from the starting level to a second, higher, level after a period of time.

[0039] The stimulation system may be provided as part of a system for aiding a user in breathing. Therefore, according to some implementations of the present disclosure, there can be provided a system for aiding a user in breathing, which includes a respiration monitoring device, and a stimulation device, a memory, and a control system. The respiration monitoring device includes a sensor configured to generate data associated with respiration of the user. The stimulation device includes a stimulator that is configured to provide electrical stimulation to one or more branches of a nerve of the user innervating or adjacent to a muscle of the user, where movement of the muscle will cause an opening of the user’s airway. The memory stores machine-readable instructions. The control system includes one or more processors configured to execute the machine-readable instructions to determine, based at least in part on the generated data associated with the respiration of the user, a respiration signal for the user.

[0040] The muscle may be a muscle of the tongue of the user or may be a muscle at least partially responsible for moving the jaw of the user.

[0041] According to some implementations of the present disclosure, there is provided a neurostimulation system, comprising: a stimulation device including a stimulator that is configured to provide electrical stimulation to one or more branches of a nerve of the user or one or more muscles of the user; a memory storing machine-readable instructions; and a control system. The control system includes one or more processors configured to execute the machine-readable instructions to implement an acclimatization process to acclimatize the user to a neurostimulation therapy for aiding the user in breathing, prior to commencement of a therapy period, by: setting a stimulation profile of the system to a starting stimulation profile configured so that a level of electrical stimulation applied under the starting stimulation profile is weaker than required for providing the neurostimulation therapy; causing the stimulation device to provide the electrical stimulation under the starting stimulation profile to the one or more branches of the nerve or the one or more muscles; changing the stimulation profile to an updated stimulation profile, to increase a level of electrical stimulation applied under the updated profile, wherein changes are made in accordance with a stimulation profile adjustment model; and causing the stimulation device to provide the electrical stimulation under the updated stimulation profile.

[0042] The control system may be configured to: receive a response data from, or measured from a physiological output of, the user; and process the response data to determine a stimulation response; wherein the stimulation profile adjustment model is configured to determine changes to be made to the stimulation profile, based at least in part on the determined stimulation response.

[0043] The predetermined stimulation profile model may be configured to determine a change to the stimulation profile to apply a predetermined rate of increase to the level of stimulation.

[0044] The stimulation profile adjustment model may be configured to cause the stimulation device to provide the electrical stimulation under an updated stimulation profile after a period of time has elapsed from when the stimulation device is caused to apply the electrical stimulation under the preceding stimulation profile.

[0045] Application of electrical stimulation under the updated stimulation profile and application of electrical stimulation under the preceding stimulation profile may occur within a therapy session.

[0046] Application of electrical stimulation under the updated stimulation profile and application of electrical stimulation under the preceding stimulation profile may occur in different therapy sessions. Application of electrical stimulation under the preceding stimulation profile may occurs in a therapy session and application of electrical stimulation under the updated stimulation profile may occur in a subsequent therapy session.

[0047] The above summary is not intended to represent each implementation or every aspect of the present disclosure. Additional features and benefits of the present disclosure are apparent from the detailed description and figures set forth below.

BRIEF DESCRIPTION OF THE DRAWINGS

[0048] FIG. 1 A is a diagram that illustrates an overview of a respiratory system of a user;

[0049] FIG. IB is a diagram that illustrates an upper airway of the user of FIG. 1 A;

[0050] FIG. 2A is a block diagram of a system for providing neurostimulation in aiding a user (e.g., in breathing), according to some implementations of the present disclosure;

[0051] FIG. 2B is a block diagram of another system for providing neurostimulation, including a sensor arrangement, according to some implementations of the present disclosure;

[0052] FIG. 2C is a block diagram of another system for providing neurostimulation, including a sensor arrangement and a respiration monitoring device, according to some implementations of the present disclosure;

[0053] FIG. 3A illustrates a method for acclimatizing a user for stimulation therapy, according to some implementations of the present disclosure;

[0054] FIG. 3B illustrates a method for determining the user’s stimulation response, according to some implementation of the present disclosure;

[0055] FIG. 3C illustrates a method of providing stimulation therapy, including adjusting the therapy stimulation level after commencement of the therapy;

[0056] FIG.4A is a schematic illustration of an acclimatization process in which an adjustment applied to the stimulation is made on the basis of stimulation response determined from stimulation response data, according to some implementations of the present disclosure;

[0057] FIG. 4B is a schematic illustration of an acclimatization process in which an adjustment applied to the stimulation is made on the basis of stimulation response determined from stimulation response data, and where the process also involves providing additional therapy input, according to some implementations of the present disclosure;

[0058] While the present disclosure is susceptible to various modifications and alternative forms, specific implementations and embodiments thereof have been shown by way of example in the drawings and will herein be described in detail. It should be understood, however, that it is not intended to limit the present disclosure to the particular forms disclosed, but on the contrary, the present disclosure is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure as defined by the appended claims.

DETAILED DESCRIPTION

[0059] Referring to FIG. 1A, an overview of a respiratory system 12 of a user 10 (e.g., patient) is shown, which generally includes a nasal cavity, an oral cavity, a larynx, vocal folds, an esophagus, a trachea, a bronchus, lungs, alveolar sacs, a heart, and a diaphragm. More generally, the user 10 has a throat 20, which includes a region(s) of the respiratory system 12 of the user 10 generally in the neck area of the user 10. The diaphragm of the user 10 is a sheet of muscle that extends across the bottom of the rib cage of the user 10. The diaphragm generally separates the thoracic cavity 40 of the user 10, which contains the heart, lungs, and ribs, from the abdominal cavity 40 of the user 10. As the diaphragm contracts, the volume of the thoracic cavity 40 increases and air is drawn into the lungs.

[0060] As is described herein, one or more stimulators of the present disclosure can be placed (e.g., implanted via surgery, injected via syringe, etc.) inside the user 10 to aid the user 10, for example, in breathing while sleeping. For example, one or more stimulators can be positioned inside the user 10 adjacent to a tongue 16 of the user 10. In another example, one or more stimulators can be positioned inside the user 10 adjacent to a nerve (e.g., hypoglossal nerve 18) and/or nerve branches. The hypoglossal nerve 18 is generally involved in controlling movement of the tongue 16 and includes a plurality of nerve branches distributed to the extrinsic and intrinsic muscles of the tongue 16.

[0061] Referring to FIG. IB, a view of an upper airway 14 of the user 10 is shown, which includes the nasal cavity, nasal bone, lateral nasal cartilage, greater alar cartilage, nostrils (one shown), a lip superior, a lip inferior, the larynx, a hard palate, a soft palate, an oropharynx, a tongue, an epiglottis, the vocal folds, the esophagus, and the trachea.

[0062] The respiratory system 12 of the user 10 facilitates gas exchange. The nose 50 and mouth 60 of the user 10 form the entrance to the airways of the user 10. As best shown in FIG. 1 A, the airways include a series of branching tubes, which become narrower, shorter, and more numerous as they penetrate deeper into the lungs of the user 10. The prime function of the lungs is gas exchange, allowing oxygen to move from the inhaled air into the venous blood and carbon dioxide to move in the opposite direction. The trachea divides into right and left main bronchi, which further divide eventually into terminal bronchioles. The bronchi make up the conducting airways, and do not take part in gas exchange. Further divisions of the airways lead to the respiratory bronchioles, and eventually to the alveoli. The alveolated region of the lungs is where the gas exchange takes place, and is referred to as the respiratory zone.

[0063] A range of respiratory disorders exist that can impact the user 10. Certain disorders are characterized by particular events (e.g., apneas, hypopneas, hyperpneas, or any combination thereof). Examples of sleep-related and/or respiratory disorders include Periodic Limb Movement Disorder (PLMD), Restless Leg Syndrome (RLS), Sleep- Disordered Breathing (SDB), Obstructive Sleep Apnea (OSA), Cheyne-Stokes Respiration (CSR), respiratory insufficiency, Obesity Hyperventilation Syndrome (OHS), Chronic Obstructive Pulmonary Disease (COPD), Neuromuscular Disease (NMD), and chest wall disorders.

[0064] Obstructive Sleep Apnea (OSA) is a form of Sleep Disordered Breathing (SDB), and is characterized by events including occlusion or obstruction of the upper air passage during sleep resulting from a combination of an abnormally small upper airway and the normal loss of muscle tone in the region of the tongue, soft palate and posterior oropharyngeal wall. More generally, an apnea generally refers to the cessation of breathing caused by blockage of the air (Obstructive Sleep Apnea) or the stopping of the breathing function (often referred to as central apnea). Other types of apneas include hypopnea, hyperpnea, and hypercapnia. Hypopnea is generally characterized by slow or shallow breathing caused by a narrowed airway, as opposed to a blocked airway. Hyperpnea is generally characterized by an increase depth and/or rate of breathing. Hypercapnia is generally characterized by elevated or excessive carbon dioxide in the bloodstream, typically caused by inadequate respiration.

[0065] Cheyne-Stokes Respiration (CSR) is another form of sleep disordered breathing. CSR is a disorder of a user's respiratory controller in which there are rhythmic alternating periods of waxing and waning ventilation known as CSR cycles. CSR is characterized by repetitive de-oxygenation and re-oxygenation of the arterial blood. It is possible that CSR is harmful because of the repetitive hypoxia. In some users, CSR is associated with repetitive arousal from sleep, which causes severe sleep disruption, increased sympathetic activity, and increased afterload. [0066] Respiratory failure is an umbrella term for respiratory disorders in which the lungs are unable to inspire sufficient oxygen or exhale sufficient CO2 to meet the user’s needs. Respiratory failure may encompass some or all of the following disorders. A user with respiratory insufficiency (a form of respiratory failure) may experience abnormal shortness of breath on exercise.

[0067] Obesity Hyperventilation Syndrome (OHS) is defined as the combination of severe obesity and awake chronic hypercapnia, in the absence of other known causes for hypoventilation. Symptoms include dyspnea, morning headache and excessive daytime sleepiness.

[0068] Chronic Obstructive Pulmonary Disease (COPD) encompasses any of a group of lower airway diseases that have certain characteristics in common, such as increased resistance to air movement, extended expiratory phase of respiration, and loss of the normal elasticity of the lung. Examples of COPD are emphysema and chronic bronchitis. COPD is caused by chronic tobacco smoking (primary risk factor), occupational exposures, air pollution and genetic factors. Symptoms include: dyspnea on exertion, chronic cough and sputum production.

[0069] Neuromuscular Disease (NMD) encompasses many diseases and ailments that impair the functioning of the muscles either directly via intrinsic muscle pathology, or indirectly via nerve pathology. Some users suffering from NMD are characterized by progressive muscular impairment leading to loss of ambulation, being wheelchair-bound, swallowing difficulties, respiratory muscle weakness and, eventually, death from respiratory failure. Neuromuscular disorders can be divided into rapidly progressive and slowly progressive: (i) rapidly progressive disorders: characterized by muscle impairment that worsens over months and results in death within a few years (e.g. amyotrophic lateral sclerosis (ALS) and duchenne muscular dystrophy (DMD) in teenagers); (ii) variable or slowly progressive disorders: characterized by muscle impairment that worsens over years and only mildly reduces life expectancy (e.g. limb girdle, Facioscapulohumeral and myotonic muscular dystrophy). Symptoms of respiratory failure in NMD include: increasing generalized weakness, dysphagia, dyspnea on exertion and at rest, fatigue, sleepiness, morning headache, and difficulties with concentration and mood changes.

[0070] Chest wall disorders are a group of thoracic deformities that result in inefficient coupling between the respiratory muscles and the thoracic cage. The disorders are usually characterized by a restrictive defect and share the potential of long term hypercapnic respiratory failure. Scoliosis and/or kyphoscoliosis may cause severe respiratory failure. Symptoms of respiratory failure include: dyspnea on exertion, peripheral edema, orthopnea, repeated chest infections, morning headaches, fatigue, poor sleep quality and loss of appetite.

[0071] These other disorders are characterized by particular events (e.g., snoring, an apnea, a hypopnea, a restless leg, a sleeping disorder, choking, an increased heart rate, labored breathing, an asthma attack, an epileptic episode, a seizure, or any combination thereof) that occur when the individual is sleeping. While these other sleep-related disorders may have similar symptoms as insomnia, distinguishing these other sleep-related disorders from insomnia is useful for tailoring an effective treatment plan distinguishing characteristics that may call for different treatments. For example, fatigue is generally a feature of insomnia, whereas excessive daytime sleepiness is a characteristic feature of other disorders (e.g., PLMD) and reflects a physiological propensity to fall asleep unintentionally.

[0072] The Apnea-Hypopnea Index (AHI) is an index used to indicate the severity of sleep apnea during a sleep session. The AHI is calculated by dividing the number of apnea and/or hypopnea events experienced by the user during the sleep session by the total number of hours of sleep in the sleep session. The event can be, for example, a pause in breathing that lasts for at least 10 seconds. An AHI that is less than 5 is considered normal. An AHI that is greater than or equal to 5, but less than 15 is considered indicative of mild sleep apnea. An AHI that is greater than or equal to 15, but less than 40 is considered indicative of moderate sleep apnea. An AHI that is greater than or equal to 40 is considered indicative of severe sleep apnea. In children, an AHI that is greater than 1 is considered abnormal. Sleep apnea can be considered “controlled” when the AHI is normal, or when the AHI is normal or mild. The AHI can also be used in combination with oxygen desaturation levels to indicate the severity of Obstructive Sleep Apnea.

[0073] One of more of the disorders described herein can be treated using electrical stimulation. For example, a stimulator can provide electrical and/or magnetic stimulation to the user (e.g., a nerve, nerve branch, a muscle, etc.) to aid in preventing an apnea event about to be experienced by the user. The electrical stimulation is able to aid in preventing apneas by, for example, causing the one or more muscles to move (e.g., contract) and open the airway of the user prior to an apnea occurring. For example, the stimulator can electrically stimulate the hypoglossal nerve 18 (FIG. IB) to move the tongue 16 to aid in opening the airway to allow more inspiration and prevent apneas from occurring. In some embodiments, the stimulator is alternatively configured to stimulate the fibre(s) of another muscle where the movement of the muscle will aid in the opening if the airway.

[0074] In typical stimulation systems, the stimulator is placed (e.g., implanted) in the user. However external stimulation via transdermal stimulation or intraoral stimulation may be used instead. For example, the stimulator can be affixed to a location on the user’s body whereby activation of the stimulator will innervate the nerve or nerve branches from an external location, or stimulate muscle movement such as by triggering a reflex or triggering a contraction or lengthening of muscle fibres whose movements may aid in the opening of the airway. As another example, the stimulator may be affixed to an intra-oral position to stimulate muscle fibre(s) in the tongue, or stimulate elsewhere in the mouth such as a portion of the pallet so as to elicit a reflex from the user to move his or her tongue to touch the stimulated portion.

[0075] A respiratory sensor may also placed in or on the user and measures the respiration of the user. The timing of the stimulation is determined based on the respiration data. In other words, the system needs to determine when to stimulate in substantially real-time based on the respiration data. Thus, in these systems, the stimulator and the respiratory sensor are electrically coupled via one or more leads and/or wires for communication (e.g., so the respiratory sensor can signal the simulator when to stimulate) and for power (e.g., to provide power to the respiratory sensor and/or the stimulator). These leads/wires are often embedded or tunneled in the skin of the user and are therefore often painful or bothersome to the user. The leads/wires are also susceptible to breaking (e.g., the wires can get stuck in the tissue or pull apart if there is not enough slack), potentially necessitating another procedure/surgery to repair the connection. The wired connection also imposes a practical limitation on the number of sensors and/or simulators (e.g., for redundancy) that can be used because this would require additional wires/leads embedded in the user’s skin.

[0076] Referring to FIG. 2 A, a system 100, according to some implementations of the present disclosure, is illustrated. The system 100 includes a control system 110, a memory device 114, a stimulation device 130, one or more transmitters 140 (hereinafter, transmitter 140), and one or more receivers 142 (hereinafter, receiver 142), a magnetic field generator 144. The system also includes an external device 180 configured receive data signal from the transmitter 140 and send data signal to the receiver 142. The transmitter 140 and the receiver 142 can be implemented by one or more transceivers (hereinafter, transceiver), or it can be implemented by a communication module configured to be in data communication with the external device 180 via mobile data such as 3G, 4G, or 5G, Wifi, or Bluetooth®. The external device 180 may be configured to include a user interface to allow the user to operate or adjust the operation of the system 100, or include data storage and/or processing components to store and/or analyze data gathered by the system 100. It may further include communication hardware so that information such as one or more of the gathered data, analysis result, or records of therapy applied, can be transmitted to a remote computing system such as a server. The external device 180 can be a purpose-built device or it can be provided by a mobile device such as a mobile phone, tablet, or laptop.

[0077] FIG. 2B depicts an embodiment which differs from that shown in FIG. 2A by including a sensor arrangement 150.

[0078] Referring to FIGs. 2A and 2B, the control system 110 includes one or more processors 112 (hereinafter, processor 112). The control system 110 is generally used to control (e.g., actuate) the various components of the system 100 and/or analyze data obtained and/or generated by the components of the system 100. The processor 112 can be a general or special purpose processor or microprocessor. While one processor 112 is shown in FIG. 1, the control system 110 can include any suitable number of processors (e.g., one processor, two processors, five processors, ten processors, etc.) that can be in a single housing, or located remotely from each other. The control system 110 can be coupled to and/or positioned within, for example, a housing of the external device 180, within a housing 124 of a respiration monitoring device 120 (in embodiments where one is provided, such as that shown in FIG. 2B or FIG. 2C), a housing 136 of the stimulation device 130, or any combination thereof. The control system 110 can be centralized (within one such housing) or decentralized (within two or more of such housings, which are physically distinct). In such implementations including two or more housings containing the control system 110, such housings can be located proximately and/or remotely from each other. [0079] The memory device 114 stores machine-readable instructions that are executable by the processor 112 of the control system 110. The memory device 114 can be any suitable computer readable storage device or media, such as, for example, a random or serial access memory device, a hard drive, a solid state drive, a flash memory device, etc. While one memory device 114 is shown in FIG. 1, the system 100 can include any suitable number of memory devices 114 (e.g., one memory device, two memory devices, five memory devices, ten memory devices, etc.). The memory device 114 can be coupled to and/or positioned within the housing of the respiration monitoring device 120 (if included), within the housing 136 of the stimulation device 130, or any combination thereof. Like the control system 110, the memory device 114 can be centralized (within one such housing) or decentralized (within two or more of such housings, which are physically distinct).

[0080] In some implementations, the memory device 114 (FIG. 1) stores a user profile associated with the user. The user profile can include one or more of, for example, demographic information associated with the user, biometric information associated with the user, medical information associated with the user, self-reported user feedback, sleep parameters associated with the user (e.g., sleep-related parameters recorded from one or more earlier sleep sessions. The demographic information can include, for example, information indicative of an age of the user, a gender of the user, a race of the user, a family history of insomnia or sleep apnea, an employment status of the user, an educational status of the user, a socioeconomic status of the user, or any combination thereof. The medical information can include, for example, information indicative of one or more medical conditions associated with the user, medication usage by the user, or both. The medical information data can further include a multiple sleep latency test (MSLT) result or score and/or a Pittsburgh Sleep Quality Index (PSQI) score or value. The self-reported user feedback can include information indicative of a self-reported subjective sleep score (e.g., poor, average, excellent), a self-reported subjective stress level of the user, a self-reported subjective fatigue level of the user, a self-reported subjective health status of the user, a recent life event experienced by the user, or any combination thereof. One or more of the information may be used to adjust a level of stimulation applied by the stimulation device. Thus, in some embodiments, such information is not necessarily stored against a profile, and may instead be retained only temporarily, e.g., for the purpose of using it as input to control or adjust the stimulation level.

[0081] While the control system 110 and the memory device 114 are described and shown in FIG. 2 as being a separate and distinct component of the system 100, in some implementations, the control system 110 and/or the memory device 114 are integrated in the external device 180, the respiration monitoring device 120 (if provided) and/or the stimulation device 130. Alternatively, in some implementations, the control system 110 or a portion thereof (e.g., the processor 112) can be located in a cloud (e.g., integrated in a server, integrated in an Internet of Things (loT) device, connected to the cloud, be subject to edge cloud processing, etc.), located in one or more servers (e.g., remote servers, local servers, etc., or any combination thereof.

[0082] Some of the elements of the system 100 are positioned in the user 10 (e.g., implanted in the user 10) and others of the elements of the system 100 are positioned outside the user 10 (e.g., wom/donned or affixed onto by the user 10). One or more of the elements of the system 100 that are positioned in the user 10 can be so positioned by being injected into the user 10 using, for example, a syringe with a hypodermic needle attached thereto. Alternatively or additionally, one or more of the elements of the system 100 that are positioned in the user 10 can be so positioned by being surgically placed therein (e.g., cutting open the skin and positioning the element(s) therein and suturing the skin closed). However, in less invasive systems, the components may all be positioned outside or on the user, such as by applying stimulation intra-orally or trans-dermally, or using sensing arrangements to gather the required data for monitoring purposes, that are not implanted medical devices.

[0083] FIG.2C depicts an embodiment of the system 100 which differs from that shown in FIG. 2B by including a respiratory system 120. The respiration monitoring device 120 includes one or more sensors 122, a housing 124, and a power supply 126. As described herein, the respiration monitoring device 120 can be placed (e.g., surgically) inside the user (e.g., in or adjacent to a thoracic cavity of the user), or outside the user, and the one or more sensors 122 generate data associated with respiration of the user for determining a respiration signal for the user.

[0084] The one or more sensors 122 can include any suitable sensor(s) for generated data from which a respiration signal of the user can be determined (e.g., a signal indicative of inhalation and/or exhalation of the user). In some implementations, the one or more sensors 122 includes an air pressure sensor (e.g., barometric pressure sensor, gauge, absolute transducer, etc.) that generates data indicative of the respiration (e.g., inhaling and/or exhaling) of the user. The pressure sensor can be, for example, a capacitive sensor, an electromagnetic sensor, a piezoelectric sensor, a strain-gauge sensor, an optical sensor, a potentiometric sensor, or any combination thereof. In some implementations, the one or more sensors 122 includes an air flow sensor that generates data indicative the respiration (e.g., inhaling and/or exhaling) of the user. In some implementations, the one or more sensors 122 includes a motion sensor that generates motion data indicative the respiration (e.g., inhaling and/or exhaling) of the user. In some implementations, the one or more sensors 122 includes an acoustic sensor (e.g., including a microphone and/or a speaker) that generates data indicative of the respiration (e.g., inhaling and/or exhaling) of the user. In other implementations, the one or more sensors 122 includes an electromyography (EMG) sensor that generates data indicative of the respiration (e.g., inhaling and/or exhaling) of the user. In some implementations, the one or more sensors 122 includes a photoplethysomgram (PPG) sensor that generates data indicative of the respiration (e.g., inhaling and/or exhaling) of the user. In other implementations, the one or more sensors 122 includes an oxygen sensor that generates data indicative of a blood oxygen level or oxygen saturation (SpCh), which in turn are indicative of respiration (e.g., inhaling and/or exhaling) of the user.

[0085] In some implementations, the one or more sensors 122 of the respiration monitoring device 120 are directly positioned in the user 10. In such implementations, the housing 124 is not required. Alternatively, the sensor(s) 122 or a portion thereof are coupled to the housing 124 (e.g., positioned at least partially therein) and the housing 124 (with the sensor(s) 122 coupled thereto) is positioned in the user 10. The housing 124 can have the shape of an elongated pill (or any other shape) that is conducive to being injected into the user 10 using, for example, a syringe with a hypodermic needle attached thereto. In some implementations, the housing 124 electrically insulates at least a portion of the sensor(s) 122 from surrounding tissue of the user 10.

[0086] The sensor(s) 122 can be powered by the power supply 126. The power supply 126 can be, for example, a battery (e.g., a rechargeable battery). In some implementations, the power supply 126 can be recharged by the magnetic field generator 144 and/or the external device 180. Alternatively to the respiration monitoring device 120 including the power supply 126, in some implementations, power for the sensor(s) is supplied wirelessly by the magnetic field generator 144 (which can be included in the external device 180) directly to the electrical sensor(s).

[0087] In addition to the sensor(s) 122 and power supply 126 being coupled to or integrated in the housing 124, a number of other elements of the system 100 can be coupled to the housing 124 and placed into the user 10. By coupled to the housing 124 it is meant that the element coupled to the housing 124 is completely incased within the housing 124, attached to an exterior surface of the housing 124, partially protruding from one or more openings in the housing 124, directly or indirectly attached to the housing 124, or any combination thereof. For example, in some implementations, one or more of the transmitters 140 and/or one or more of the receivers 142 can be coupled to or integrated in the housing 124.

[0088] In such implementations, the transmitter 140 and/or receiver 142 allow the respiration monitoring device 120 to wirelessly communicate (e.g., using a Bluetooth communication protocol, a WiFi communication protocol, or any other suitable RF communication protocol) with the control system 110, the stimulation device 130, the external device 180 or any combination thereof (e.g., to transmit data generated by the sensor(s) 122 for analysis by the control system 110). If Bluetooth is used the wireless communication frequency is in the MHz range, whereas breaching frequency is about 15 Hz. Thus, the data the respiration monitoring device 120 can be wirelessly transmitted (e.g., to the control system 110) before the next inhalation and/or exhalation of the user.

[0089] The stimulation device 130 includes a simulator 132, a housing 136, and a power supply 138. As described herein, the stimulation device 130 can be placed (e.g., surgically) inside the user (e.g., adjacent to a tongue of the user) to stimulate one or more branches of a nerve (e.g., a hypoglossal nerve) at a determined stimulation time.

[0090] The stimulator 132 is positioned in the user 10 such that one or more electrical leads 134 of the stimulator 132 are positioned adjacent to one or more muscles of the user 10 and/or one or more nerves of the user 10 that are connected to the one or more muscles of the user 10. In some implementations, the one or more electrical leads 134 includes a first electrical lead that is positioned to stimulate a first one of the one or more muscles and/or a first one of the one or more nerves. Similarly, a second electrical lead is positioned to stimulate a second one of the one or more muscles and/or a second one of the one or more nerves. In some implementations, the first electrical lead provides the electrical stimulation at a first frequency and the second electrical lead provides the electrical stimulation at a second frequency that is different from the first frequency. In some implementations, the first electrical lead provides the electrical stimulation at a first intensity and the second electrical lead provides the electrical stimulation at a second intensity that is different from the first intensity. Alternatively, the stimulator 132 may be leadless, with the stimulator body being conductive and the ends of the body acting as electrodes.

[0091] Once the stimulation device 130 is positioned in or on the user 10, the stimulator 132 is capable of delivering electrical and/or magnetic stimulation to the user 10 to aid in causing the one or more muscles of the user 10 to contract. The contraction of the one or more muscles of the user 10 can aid in opening an airway of the user 10. The contraction can alternatively or additionally aid in causing the user 10 to have breathing effort (e.g., causing the diaphragm to draw/suck in air). The electrical stimulation can be applied directly to the one or more muscles of the user 10 (e.g., muscles in the tongue of the user 10, muscles surrounding and/or adjacent to the tongue of the user 10, neck muscles, throat muscles, the palate, other soft issue generally in or around the airway of the user, etc.) and/or directly to the one or more nerves that are connected to the one or more muscles. Directing the electrical stimulation to the one or more nerves (as opposed to the one or more muscles directly) allows for a relatively lower intensity (e.g., voltage, amperage, etc. or any combination thereof) of the electrical stimulation to be applied to cause the one or more muscles (connected to the one or more nerves) to contract.

[0092] The stimulator 132 includes or is an electrical conductor (e.g., one or more electrically conductive wires with or without a portion being electrically insulated). The stimulator 132 includes the one or more electrical leads 134, which are capable of carrying and/or flowing and delivering electrical current to the one or more muscles and/or one or more nerves of the user 10. The electrical current can be supplied by the power supply 138. The power supply 138 can be, for example, a battery (e.g., a rechargeable battery). In some implementations, the power supply 138 can be recharged or energized by the magnetic field generator 144 and/or the external device 180. Alternatively to the stimulator 132 including the power supply 138, in some implementations, the electrical current is supplied wirelessly by the magnetic field generator 144 (which can be included in the external device 180) directly to the electrical conductor(s).

[0093] In some implementations, the stimulator 132 only includes one or more electrically conductive wires, with or without a portion being electrically insulated. In some such implementations, the stimulator 132 has a length between about 1 millimeter and about 100 centimeters; between about 1 millimeter and about 100 millimeters; between about 1 millimeter and about 10 millimeters; or any length therebetween. Further, in some such implementations, the stimulator 132/wire has a diameter between about 0.01 millimeters and about 5 millimeters; between about 0.1 millimeter and about 2 millimeters; between about 0.1 millimeter and about 1 millimeter; or any diameter therebetween. The size and shape of the stimulator 132 can be selected to permit the injection of the stimulation device 130 into the user 10 via a syringe with an attached hypodermic needle.

[0094] In some implementations, the stimulator 132 is directly positioned in the user 10. In such implementations, the housing 136 is not required. Alternatively, the stimulator 132 or a portion thereof is coupled to the housing 136 (e.g., positioned at least partially therein) and the housing 136 (with the stimulator 132 coupled thereto) is positioned in the user 10. The housing 136 can have the shape of an elongated pill (or any other shape) that is conducive to being injected into the user 10 using, for example, a syringe with a hypodermic needle attached thereto. In some implementations, the housing 136 electrically insulates at least a portion of the stimulator 132 (e.g., the entire stimulator 132 except for the one or more electrical leads 134 or conductive ends) from surrounding tissue of the user 10.

[0095] In addition to the stimulator 132 being coupled to the housing 136, a number of other elements of the system 100 can be coupled to the housing 136 and placed into the user 10. By coupled to the housing 136 it is meant that the element coupled to the housing 136 is completely incased within the housing 136, attached to an exterior surface of the housing 136, partially protruding from one or more openings in the housing 136, directly or indirectly attached to the housing 136, or any combination thereof. For example, in some implementations, one or more of the transmitters 140 and/or one or more of the receivers 142 can be coupled to or integrated in the housing 136. In such implementations, the transmitter 140 and/or receiver 142 allow the respiration monitoring device 120 to wirelessly communicate (e.g., using a Bluetooth communication protocol, a WiFi communication protocol, or any other suitable RF communication protocol) with the control system 110, the respiration monitoring device 120, or any combination thereof (e.g., to transmit a signal to actuate the stimulator 132 to deliver electrical stimulation). In other implementations, the transmitter 140 and the receiver 142 are combined as a transceiver.

[0096] While the system 100 has been described herein as including one respiration monitoring device 120, the system 100 more generally can include any suitable number of respiration monitoring devices that are the same as, or similar to, the respiration monitoring device 120 (e.g., 2, 3, 5, 10, etc.). Having multiple respiration monitoring devices can be advantageous, for example, to provide redundancy in case another respiration monitoring device fails (e.g., runs out of battery or power) and to provide more respiration data for more accurate determinations of the respiration signal. The respiration monitoring devices can be positioned in the user together in the same implant or implanted separately in the same area.

[0097] In embodiments, the system 100 may include wearable(s) 146 which can be worn by the user and can be generally used to position the magnetic field generator 144 adjacent one or more of the other components of the system, such as the stimulation device 130 to provide power as described herein. The wearable(s) 146 can include a belt, a collar, a patch (e.g., an adhesive patch), clothing, a sleeve, a bracelet, a necklace, a watch, or any combination thereof. The magnetic field generator 144 can be embedded in the wearable 146 and/or removable from the wearable 146.

[0098] The one or more external sensors 150 of the system 100 can be used to generate or obtain different physiological data associated with the user. In some implementations, the one or more external sensors 150 can be used to generate data associated with respiration of the user. In these and other implementations, the one or more sensors 150 can be used to generate data associated with a pain response or stress indicators in the user. The one or more external sensors 150 can include one or more of: an oxygen sensor 152, a motion sensor 154, a camera 156, an acoustic sensor 158, a radio-frequency (RF) sensor 164, a PPG sensor 170, a capacitive sensor 172, a force sensor 174, a strain gauge sensor 176, an EMG sensor 178, and an electrocardiogram (ECG) sensor 179, or any combination thereof. Data from the sensor(s) 150 can be received and stored in the memory device 114 or one or more other memory devices. [0099] The oxygen sensor 152 outputs oxygen data indicative of an oxygen concentration of gas (e.g., in the blood of the user). The oxygen sensor 152 can be, for example, a pulse oximeter sensor an ultrasonic oxygen sensor, an electrical oxygen sensor, a chemical oxygen sensor, an optical oxygen sensor, or any combination thereof.

[0100] The motion sensor 154 outputs motion data that is indicative of movement of the user. The motion data from the motion sensor 154 can be used by the control system 110 to determine movement of the user (e.g., respiration). The camera 156 outputs image data reproducible as one or more images (e.g., still images, video images, thermal images, or a combination thereof) that can be stored in the memory device 114. The image data from the camera 156 can be used by the control system 110 to determine movement of the user (e.g., respiration). The motion data may be indicative convulsions of the user as a response to the stimulation.

[0101] The microphone 160 outputs sound data that can be stored in the memory device 114 and/or analyzed by the processor 112 of the control system 110. The microphone 160 can be used to record sound(s) to determine (e.g., using the control system 110) a respiration signal or a pain response such as moaning, for the user. The speaker 162 outputs sound waves that are audible to a user of the system 100. The speaker 162 can be used, for example, as an alarm clock or to play an alert or message to the user.

[0102] In some implementations, the microphone 160 and the speaker 162 can be combined into an acoustic sensor 158, as described in, for example, WO 2018/050913, which is hereby incorporated by reference herein in its entirety. In such implementations, the speaker 162 generates or emits sound waves at a predetermined interval and the microphone 160 detects the reflections of the emitted sound waves from the speaker 162. The sound waves generated or emitted by the speaker 162 have a frequency that is not audible to the human ear (e.g., below 20 Hz or above around 18 kHz). Based at least in part on the data from the microphone 160 and/or the speaker 162, the control system 110 can determine movement of the user (e.g., respiration).

[0103] The RF transmitter 168 generates and/or emits radio waves having a predetermined frequency and/or a predetermined amplitude (e.g., within a high frequency band, within a low frequency band, long wave signals, short wave signals, etc.). The RF receiver 166 detects the reflections of the radio waves emitted from the RF transmitter 168, and this data can be analyzed by the control system 110 to determine movement of the user. While the RF receiver 166 and RF transmitter 168 are shown as being separate and distinct elements in FIG. 2, in some implementations, the RF receiver 166 and RF transmitter 168 are combined as a part of an RF sensor 164. In some such implementations, the RF sensor 164 includes a control circuit. The specific format of the RF communication could be WiFi, Bluetooth, etc.

[0104] In some implementations, the RF sensor 164 is a part of a mesh system. One example of a mesh system is a WiFi mesh system, which can include mesh nodes, mesh router(s), and mesh gateway(s), each of which can be mobile/movable or fixed. In such implementations, the WiFi mesh system includes a WiFi router and/or a WiFi controller and one or more satellites (e.g., access points), each of which include an RF sensor that the is the same as, or similar to, the RF sensor 164. The WiFi router and satellites continuously communicate with one another using WiFi signals. The WiFi mesh system can be used to generate motion data based on changes in the WiFi signals (e.g., differences in received signal strength) between the router and the satellite(s) due to an object or person moving partially obstructing the signals. The motion data can be indicative of motion, breathing, heart rate, gait, falls, behavior, etc., or any combination thereof.

[0105] The PPG sensor 170 outputs physiological data associated with the user that can be used to determine, for example, a heart rate, a heart rate variability, a cardiac cycle, respiration rate, an inspiration amplitude, an expiration amplitude, an inspirationexpiration ratio, estimated blood pressure parameter(s), or any combination thereof.

[0106] The capacitive sensor 172, the force sensor 174, and the strain gauge sensor 176 output data that can be stored in the memory device 114 and used by the control system 110 to determine movement of the user (e.g., respiration, convulsion, twitching). The EMG sensor 178 outputs physiological data associated with electrical activity produced by one or more muscles. The ECG sensor 179 outputs physiological data associated with electrical activity of the heart of the user. In some implementations, the ECG sensor 179 includes one or more electrodes that are positioned on or around a portion of the user.

[0107] While shown separately in FIG. 2B, and FIG. 2C, any combination of the one or more sensors 130 can be integrated in and/or coupled to any one or more of the components of the system 100, including the respiration monitoring device 120 where provided, the stimulation device 130, the control system 110, the external device 180, or any combination thereof. [0108] In some implementations, the one or more external sensors 150 also include one or more of a temperature sensor, an EEG sensor, an analyte sensor, a moisture sensor, and a Light Detection and Ranging (LiDAR) sensor. The LiDAR sensor can be used for depth sensing. This type of optical sensor (e.g., laser sensor) can be used to detect objects and build three dimensional (3D) maps of the surroundings, such as of a living space. LiDAR can generally utilize a pulsed laser to make time of flight measurements. LiDAR is also referred to as 3D laser scanning. In an example of use of such a sensor, a fixed or mobile device (such as a smartphone) having a LiDAR sensor can measure and map an area extending 5 meters or more away from the sensor. The LiDAR data can be fused with point cloud data estimated by an electromagnetic RADAR sensor, for example. The LiDAR sensor(s) can also use artificial intelligence (Al) to automatically geofence RADAR systems by detecting and classifying features in a space that might cause issues for RADAR systems, such a glass windows (which can be highly reflective to RADAR). LiDAR can also be used to provide an estimate of the height of a person, as well as changes in height when the person sits down, or falls down, for example. LiDAR may be used to form a 3D mesh representation of an environment. In a further use, for solid surfaces through which radio waves pass (e.g., radio-translucent materials), the LiDAR may reflect off such surfaces, thus allowing a classification of different type of obstacles.

[0109] The external device 180 (FIG. 2A, 2B, 2C) includes a display device 182 and a speaker device 184. Multiple display and/or speaker devices may be included. The external device 180 can be, for example, a mobile device such as a smart phone, a tablet, a laptop, or the like. Alternatively, the external device 180 can be an external sensing system, a television (e.g., a smart television) or another smart home device (e.g., a smart speaker(s) such as Google Home, Amazon Echo, Alexa etc.). In some implementations, the external device 180 is a wearable device (e.g., a smart watch). The display device 182 is generally used to display image(s) including still images, video images, or both. In some implementations, the display device 182 acts as a human-machine interface (HMI) that includes a graphical user interface (GUI) configured to display the image(s) and an input interface. The display device 182 can be an LED display, an OLED display, an LCD display, or the like. The input interface can be, for example, a touchscreen or touch- sensitive substrate, a mouse, a keyboard, or any sensor system configured to sense inputs made by a human user interacting with the external device 180. In some implementations, one or more external devices can be used by and/or included in the system 100.

[0110] While system 100 is shown as including all of the components described above, more or fewer components can be included in a system for aiding a user (e.g., in breathing) according to implementations of the present disclosure. For example, a first alternative system includes the control system 110, the memory device 114, the respiration monitoring device, and the stimulation device. As another example, a second alternative system includes the control system 110, the memory device 114, the respiration monitoring device 120, the stimulation device 130, and the external device 180. As yet another example, a third alternative system includes the respiration monitoring device 120 and the stimulation device 130. Thus, various systems can be formed using any portion or portions of the components shown and described herein and/or in combination with one or more other components.

Method of acclimatizing user to stimulation therapy, using response feedback

[OHl] In embodiments of the stimulation system descried herein, the memory device 114 is configured to store data acquired by sensors included in the system (if any), and/or selfreported data provided by the user or an observation data provided by a third-party such as a clinician. The user input can include a self-reported observation of a side effect which may be undesirable, and the third-party observation data can include the third-party’s observation of any side effect. An undesirable effect may be, e.g., an unintended cross talk between the stimulation target and another branch of nerve or muscle, whereby the electrical stimulation manifested in a movement or contraction in an incorrect muscle, rather than the muscle which corresponds to the stimulation target. Other undesirable effects may be muscle cramps, muscle twitching or spasms, dry mouth, or another side effect associated with experiencing the stimulation when the user is awake. The user input can include a self-reported pain and/or discomfort level associated with one or more of the undesirable effects. The self-reported response data or third-party observation data, or both, can be provided as a quantitative input (e.g., on a scale of 1 to 10), but in other implementations may be provided as a descriptive input or as a selection from available options. The descriptive input may be interpreted using language processing and then assigned a quantitative equivalent input (e.g., score). One or more of the sensor data, the user input data, and the third-party observation data, may instead or additionally be stored in a temporary memory storage or cache in the control system 110. Hereinafter, “stimulation response data” refers to data which will be processed to ascertain the user’s response to the stimulation. Thus, the response data may comprise one or more of the measured data, the self-reported data, and the third-party observation data. The measured data may be data from one or more of the sensors which are arranged to sense physiological signal or output of the user, or data indicative of the user’ s physiological output, or the user input data providing self-reported data, or both. The measured data may also be a nerve response data, measurable as a physiologic response of the nerve to the stimulation. The nerve response may be, e.g., an action potential of the nerve. Therefore, it would be expected that whilst the user is asleep, the response data will include only the measured data or the third-party observation data, or both.

[0112] The stimulation response data may be received via a user interface in the external device 180, whereby user provides self-reported data which indicates whether the stimulation causes pain or is acceptable. The measured data may be gathered using one or more sensors, such as but not limited to, one or more of: a heart rate sensor, a flow sensor which provides breathing flow data such as flow rate or breathing rate, sensors or electrodes which measure the user’s eye movements or EEG, or sensors or electrodes which detect muscle twitches or movements, such as those indicating a pain-related muscle response, e.g., a grimace, or a nerve response to the stimulation as mentioned above. Accordingly, a negative response may be determined from whether one or more of the following are detected: an increased heart rate, an increased heart rate variability, an increased flow rate at the airway indicating harder breathing, an increased breathing rate, muscle twitching or contraction indicating a pain response, a change in EEG or eye movements indicating restlessness or sleep disturbance, or a combination of one or more of these, and other types of data as corresponding to the sensor type. The different types of response data of which the stimulation is comprised, are part of a response framework. The response framework defines the data which is processed to provide the feedback to the stimulation system, to enable an automated adjustment of the stimulation profile on the basis of the feedback. The response data within the framework may be adjusted on the basis of a learning model. For example, weights determined from the learning model may be applied to the response data in order to compute an overall score. The computation may be made on the basis of the weighted data values. The computation may be performed using, e.g., a matrix calculation involving a response matrix comprised of the data, and a weight matrix. In some cases, the score may be significantly influenced by one or more of the values of the response data. For example, if the data value for one of the response data types is above a particular threshold, e.g., when the amount of muscle twitching or spasm indicates pain, then the score may be at a value which indicates a negative response which would be sufficient to trigger the stimulation to be stopped or interrupted. A combination of the approaches may be adopted.

[0113] As described herein the stimulation system 100 is configured to implement an acclimatization process to condition the user so that he or she can get used to a neurostimulation therapy providing a breathing aid. Embodiments of the acclimatization process will provide an automated system which adjusts the profile of the stimulation on the basis of the feedback from the stimulation (i.e., stimulation response data). As will be further described, depending on the embodiment(s) of the acclimatization process which is implemented, the stimulation system 100 may also be used to determine the profile of the stimulation to be applied to the user, during therapy.

[0114] The acclimatization may be implemented over a period of time. For instance, the acclimatization process may be performed over two or more separate sessions. This allows time between the sessions, for the stimulated part(s) of the nervous or muscular system to adapt to being stimulated, and for any inflammatory processes of the body to settle. The profile of the applied stimulation of a session may be determined on the basis of the data of the response framework obtained from a previous session. Also, the application of stimulation during an acclimatization session may cause portion(s) of the nervous or muscular system of the user to continue acclimatize afterwards. Therefore, the response framework, obtained from two or more separate sessions with the same or similar stimulation profiles, may still be different. The user’s overall “conditioned” response to an acclimatization process performed over multiple sessions may be described by the data of the response framework obtained during the last session. At the end of the overall acclimatization process, the stimulation profile which provides the strongest stimulation which the user is able to tolerate, i.e., the user’s response as determined from the response framework is not negative, can be considered the “acclimatized” stimulation profile.

[0115] Referring to FIG. 3 A, a method 300 for acclimatizing a user for stimulation therapy acceptance and for determining a maximum tolerable stimulation level for the user, according to some implementations of the present disclosure is illustrated. The method is performed during an acclimatization session. It may be performed at each of a series of acclimatization sessions. In the depicted acclimatization process 300, the stimulation is applied with a starting profile (302). The stimulation profile may include various parameters including stimulation level and duration, stimulation channels (dictated by electrode positioning and activation), and user position. This profile may be selected from “preset” profile or based on user characteristics. For a stimulation profile parameter which is quantifiable within a range, e.g., amplitude, frequency, duty cycle, the starting profile includes a starting level which may be a level lower than that which is known to be sufficient in triggering a muscle contraction. During or after the stimulation, response data indicative of the user’s response to the stimulation is gathered, and the gathered response data is analyzed to determine the user’s response to the stimulation (304). Stimulation at increasingly higher stimulation levels which are under a predefined threshold (e.g., as allowed under stimulation safety requirements) and/or by variation of other parameters of the stimulation profile will be applied, to acclimatize the user to the increasingly higher levels or other changes in the stimulation profile towards a therapy stimulation profile. This may continue whilst the response has not reached a tolerance threshold (306). The tolerance threshold is a threshold indicating the upper limit of a pain or discomfort response. When a stop condition occurs, the stimulation is stopped (308). There may be one or more “stop conditions” which will trigger the stimulation to stop during the acclimatization. These can include, but are not limited to: a response indicative of a response which is below a tolerance threshold; the maximum allowable stimulation level has been reached; the user decides to stop; the current stimulation level is already at a lowest threshold value (would prevent decreasing of level); the response data indicates a strongly negative response, such as pain or discomfort response which is above a threshold; the user awakes from sleep. The last stimulation profile threshold applied where the user response is below the tolerance threshold may be set as the “maximum tolerance threshold” for the user (310). This may be saved in the data storage for the stimulation system to be accessible later, and/or against the user’s profile. The tolerance threshold may be defined within a tolerance framework, comprising one or more predefined tolerance limits associated with at least one or more of the parameters characterizing the stimulation profile. E.g., if the limits associated with three different parameters are used to define the tolerance framework, then the tolerance threshold will delimit a range defined by a trivariable space bound by the respective limits for the parameters.

[0116] One or more of the parameters characterizing the stimulation profile may be nonquantitative, i.e., not defined by a quantity. An example is the stimulation channel, the stimulation may be applied at a first channel as the starting value, and then switched to a subsequent channel as a second value, etc. The acclimatization process may be performed by switching between the different channels, to identify an optimal stimulation channel. The optimal stimulation channel may be one via which the applied stimulation can cause the most prominent response - meaning a weaker stimulation pulses are sufficient to elicit the required response if the stimulation applied via this channel, while stronger stimulation pulses (pulses having e.g., higher amplitude, frequency, higher ramping speed, or longer duty cycle) may be needed if applied via another channel. The optimal stimulation channel may be the channel where the user response shows the least negative effect.

[0117] Another example of a non-quantitative parameter characterizing the stimulation profile may be a position of the user while the stimulation is applied. In performing the acclimatization process(es) as described in any of the embodiments encompassed herein, the user may be asked to assume different positions, which may include at least one or more sleep positions. For example, the user may be asked to lie down in a supine position, on the side, or on the stomach, with his or her head resting on differently profiled pillows, turned to the side or not, with the neck more or less stretched, etc. The acclimatization process may comprise applying the electrical stimulation with the user assuming a particular position, so that acclimatization can occur, e.g., when the user is in a position in which he or she typically sleeps. The acclimatization process may be performed multiple times, each time with the user being in a different one of a plurality of different positions, so that a stimulation response associated with each position may be ascertained. If a negative response is consistently obtained, or even with repeated acclimatization sessions, in a position in which the user normally sleeps, then further aids can be utilized, e.g., a pillow or another device that adjusts the user’s sleep position, to help the user sleep in a position in which he or she does not have a negative response to the stimulation.

[0118] In embodiments, the acclimatization may involve adjusting both at least one quantitative parameter, and at least one non-quantitative parameter. [0119] For instance, there may be multiple stimulation channels available for applying the electrical stimulation. The channels may each have a different orientation. The process 300 may involve applying electrical stimulation at a starting level (302) at each available channel in turn, and then gathering and analyzing the response data to obtain user response to stimulation at each channel (304). An optimal channel is selected and then the stimulation process continues via the selected stimulation channel. The continuation of the stimulation process may be performed some time after the identification of the optimal channel, e.g., at a subsequent session, to allow the user time to rest or to give his or her nervous system time to self-acclimatize to being stimulated.

[0120] Example embodiments of processes for implementing the step (304) of acclimatizing the user to increasingly higher levels of stimulation are discussed later, for example with reference to FIGs 4 A and 4B.

[0121] FIG. 3B illustrates how to determine a user response, according to some implementation of the present disclosure. First, response data is gathered (312). The gathering of the response data may be performed during the electrical stimulation, particularly if the response are measured or gathered by sensors. Additionally or alternatively, the response data may be gathered after the electrical stimulation has been applied for a period, by the user entering a self-reported response data. The gathered data analyzed by the processor or processor(s) of the system (314). The analysis may comprise reading the response data where the response data comprises a quantitative, self-reported pain or discomfort indication, e.g., on a scale of 0 to 10. The analysis may be made during the stimulation so that the control system monitors the user’s response during the stimulation, and/or may be made after the aforementioned period of stimulation. The analysis result or results are compared against indicators of pain or discomfort (316). The result of the comparison, and/or any self-reported quantitative pain or discomfort response data, will be used to determine a stimulation response (318). The determined stimulation response may be a quantitative value. The combination of the various comparisons and any self-reported data to provide the stimulation response may be performed by a machine learning model.

[0122] The acclimatization can be performed during an acclimatization period, before the user starts the neurostimulation therapy, in order to help acclimatize the user to the therapy. The adjustment can instead or additionally be performed some time after the commencement of the therapy, when the therapy starts to lose effectiveness and needs to become more intensive or adjusted in other ways, in order to effectively open the user’s airway and aid sleep, to help acclimatize the user to the higher required intensity.

[0123] For example, in embodiments where the acclimatization method outputs the “maximum tolerable stimulation level”, this output may be used to set the stimulation level to be applied during a therapy period. FIG. 3C illustrates a method of adjusting therapy stimulation levels during the neurostimulation therapy, according to some implementations of the disclosure. To commence the therapy, the stimulation device will be controlled to obtain from the user profile or a memory location, or receive from a remote data storage where data associated with the user are stored, the maximum tolerable stimulation level (320). The commencing or starting therapy level will be set to be a level which is lower than the maximum tolerable stimulation level (322). Once the therapy has commenced, the system will receive therapy feedback (324). The feedback may be in the form of data from sensors configured to sense respiration of the user, and/or sleep quality indicative parameter such as the AHI, and/or self-reported data from the user indicating fatigue, day time tiredness, etc. The feedback data is processed or analysed to determine whether it is indicative of therapy inefficacy (326). If therapy inefficacy is determined, then the therapy stimulation level is set to be an increased level, between the starting therapy level and the previously determined maximum tolerable stimulation level (328). Optionally, the acclimatization process will be performed again to acclimatize the user up to the set therapy stimulation level (330), and the therapy recommences at the set therapy stimulation level (332).

[0124] In the above, the application of the stimulation may be accompanied by the provision of additional therapy signal(s) to the user or all or a part of each stimulation period. The additional therapy input is intended to aid the user in modulating his or her discomfort/pain or sympathetic response to the stimulation therapy, and thus optimizing his or her tolerance to the stimulation. The additional therapy may include audio, video, or audio-video outputs known to elicit or help elicit relaxation responses, or parasympathetic responses. Examples include, but are not limited to, music or audible signals which trigger the parasympathetic nervous system, such as by including sounds at particular frequencies, cognitive behaviour therapy, coaching to direct the user how to breathe to help activate the parasympathetic response, providing meditation input, or displaying visual inputs of calming colours or scenes. Some of these inputs will only be provided whilst the acclimatization process is performed on a user who is awake. Optionally, the start of the additional therapy input may precede the start of the stimulation, to allow the user time to be in a relaxed state.

[0125] Alternatively or additionally, the additional therapy signal(s) may be provided after a series of one or more periods of stimulation have been applied to find a maximum tolerable level. For instance, after a process such as that depicted in FIG. 3A has been applied, the additionally therapy signal(s) may be provided to the user for a period of time, and then the process 300 is reapplied. The maximum output tolerance level determined from the first application of the process 300 can be compared with that determined from the second application of the process 300. This comparison will help to provide a measure of the effectiveness of the additional therapy signal(s) in helping the user acclimatize to higher level(s) of stimulation.

[0126] The controller may be configured to cause the external device 180, or another device such as a mobile device of the user, to output the additional therapy. In some embodiments, the external device 180 is provided by the mobile device. For example, the control system of the stimulation system may be configured to communicate with a mobile device via a mobile application, where control data from the control system will cause the mobile device to output the additional therapy. The user-interface required for the selfreported response data to be provided to the control system, and also the output which provides the additional therapy signal(s) to the user, may be provided in the form of a mobile application. The determination of the additional therapy signals to be provided can be made on the basis of a pre-set program, a pre-set program which is tailored to user’s preferences, or it may be set automatically. The automatically setting of the additional therapy program may be done taking into account user’s specific acclimatization parameters and stimulation response. For example, someone with a mild negative response profile when the stimulation is considered to be too strong may be given only one type of additional therapy input such as a sound therapy or a breathing coaching input. The automatic setting again can be a pre-set program, or it can be determined by a self-learning artificial intelligence program.

[0127] To implement the processes described herein, the control system 110 is configured to control the operation of the stimulation device 140. It is configured to execute machine code to implement a method of adjusting one or more aspects of the stimulation profile which is or which will be applied by the stimulation device 140. The stimulation profile is at least partially characterized by parameters including at least the duty cycle, amplitude, frequency, , stimulation ramping rate, etc. The adjustment may be made to one or more of the parameters characterizing the stimulation profile. The adjustment may be made to the parameter to which the user’s nervous system is determined to be most sensitive, i.e., the parameter where the least amount of adjustment is able to elicit a predefined amount of change in the nervous response or in the muscle movement.

[0128] In the above and elsewhere in this document, an increase or a decrease in the stimulation “level” will refer to an increase or a decrease in the value of a quantitative parameter of the stimulation profile, such as stimulation amplitude, frequency, or duty cycle, depending on which one or ones of the parameters are being adjusted. It will also be appreciated that during the acclimatization process as well as the actual therapy, the values for the various parameters will be kept no more than the predefined safety value. This safety value can be established based on previous therapy, research or any available product testing or use results. Preferably, the values for the various parameters will be no more than threshold values corresponding to stimulation levels that have been known to be associated with user fatigue. For non-quantitative parameters, a change in the parameter will involve switching to a different value, e.g., a different position or a different channel, as mentioned above.

[0129] Example processes for acclimatizing up to a threshold level

[0130] In some embodiments, the parameters are adjusted in turns, where the value of one parameter is adjusted while the values for the other parameters remain at pre-set values or values determined from one or more previously performed acclimatization sessions. For example, during an acclimatization period, the adjustment is made to the value of a first parameter of the waveform such as the amplitude, with values of the parameters of the waveform set to pre-set minima. The amplitude is adjusted so that the stimulation pulses applied initially have a minimum amplitude, and then progressively increased to an upper threshold. The threshold may be an amplitude with an amplitude range for waveforms known for sufficiently enervating the nerve or muscle in the user so as to open the airway, or it may be determined on the basis of a previously determined maximum tolerable stimulation level. During a subsequent acclimatization period, the adjustment of the waveform is made to another parameter such as the frequency, and so on. The acclimatization may be configured to acclimatize the user up to a stimulation level which is a minimum level (e.g., amplitude, frequency, duty cycle, etc) known to be sufficient in stimulating the nerve or muscle in order to cause a muscle contraction or elicit a minimum amount of nerve response. Or it can be configured to acclimatize the user up to a stimulation level which is a pre-determined minimum level required to cause the user’s stimulated muscle to contract.

[0131] In some embodiments, after acclimatizing the user to the minimum required stimulation levels or minimum required values for the parameters, the value for one parameter will be set at the minimum required value, while one or more of the values of the other parameters are decreased, in order to find a waveform of an overall lower intensity whilst still being sufficient to stimulate the nerve or muscle to open the airway. The parameter whose value is kept at the minimum required value may be the parameter to which the user has shown the most sensitivity to change. The identification of the parameter to which the user is most sensitive may be determined via repeated applications of process 300 where different parameters are being tuned during each run of the process 300. This can help to determine an optimal waveform which will most effectively provide stimulation for the user.

[0132] In some embodiments, the adjustment is made on the basis of an output from the processing configured to analyse the response data. The controller is configured to process the response data to determine whether the stimulation response has reached or exceeds a tolerance threshold as mentioned with respect to FIG. 3A and 3B.

[0133] Optionally, in embodiments of the acclimatization process, the increments and reduction to the parameter values may be at discrete levels, and/or may be tunable. For instance, the amount by which the stimulation response obtained from analysing the response data exceeds the tolerance threshold will affect the amount of decrease. The response exceeding the tolerance threshold by a higher amount will cause the simulation level to be decreased further.

[0134] Figure 4A depicts an example embodiment of an acclimatization process 400 during which the stimulation level is adjusted on the basis of response data gathered from the user, where the stimulation level is not always incremented. During a time period which will be referred to as an “acclimatizing period”, the value of the stimulation parameter, i.e., “stimulation level” will be adjusted on the basis of the response data indicative of the user’ s response to the stimulation. The user or a clinical staff overseeing the acclimatization process, will cause the controller to initiate the stimulation device to apply stimulation (402). The stimulation will initially be applied at a starting level. In an embodiment, the starting level is lower than the minimum therapy level required to stimulate the nerve or muscle fibre(s) to open the airway. This starting level may be applied for a pre-set period of time, or until the user’s response indicates the stimulation causes a negative response.

[0135] The control system 110 is configured to process the response data obtained while the stimulation is applied at the starting level, to ascertain the stimulation response of the user (404). If the stimulation response is a negative response, then the controller will check that no “stop condition” has occurred (406), and then adjust the stimulation level by decreasing it (408) and apply the stimulation at the adjusted level (402). If a stop condition has occurred, the highest stimulation level which was considered tolerable (i.e., analysis result from response data indicates response is within tolerance threshold), is output as the maximum tolerable stimulation level (414). It will be understood that some variations of the process will be considered to be within the scope of the disclosure. For example, after the determination that there is no adverse or negative response from the user at step 404, the stimulation level can be first increased (412), before the control system checks whether or not a stop condition has occurred (410), and then the stimulation applied at the increased level if no stop condition has occurred.

[0136] Here and in other embodiments, the tolerance threshold for the pain, discomfort, or disturbance (e.g., sleep disturbance) experienced can be a “zero” threshold, meaning that any discomfort, pain, or sleep disturbance will trigger the controller to try to decrease the stimulation level.

[0137] Referring again to Figure 4A, if the results from analysing the response data indicates a stimulation response which is still lower than the tolerance threshold, then the controller will check no stop condition has been reached (410), and then cause the stimulation level to be increased (412). The control system 110 causes the stimulation to be applied at the increased level (402), and continues to monitor and process the response data (404). This process is repeated, until the user or patient reports discomfort or the stimulation level has reached the minimum required therapy level. At the completion of the process 400, the controller will be able to ascertain what the user’s initial tolerance to neurostimulation is, i.e., the maximum level of stimulation which the user will tolerate, up to the minimum required therapy level. Further, by slowly building up the stimulation level applied to the user, this helps to acclimatize the user to the stimulation. Optionally, the stimulation is applied together with an additional therapy Input to the user, for at least a part of the duration that the stimulation is applied.

[0138] There can be variants of the process 400 shown in FIG 4A. An example is the process 450 depicted in FIG 4B. Here, the initial stimulation is applied at a “starting level”, and the stimulation is applied for a pre-set period of time (452). The controller processes the response data in order to determine whether the response data is indicative of a stimulation response not within (i.e., exceeding or reaching) the tolerance threshold, considered a “negative response” (454). If no negative response is detected, then the control system checks that no stop condition has been reached (456). If no stop condition has occurred, the stimulation level is increased (462), and then stimulation applied again (452). On the other hand, if the response data indicates a negative response, then the control system will check whether a stop condition has occurred (460). If no process stop condition has occurred, stimulation is applied again with a decreased stimulation level, applied with additional therapy input, or both (462). If a stop condition has occurred, then the last (i.e., highest) stimulation level to which the stimulation response was within the tolerance threshold (i.e., not negative) will be set as the maximum tolerable threshold (464).

[0139] One or more elements or aspects or steps, or any portion(s) thereof, from one or more of any of the embodiments described can be combined with one or more elements or aspects or steps, or any portion(s) thereof, from one or more of any of the other embodiments or combinations thereof, to form one or more additional implementations and/or claims of the present disclosure.

[0140] While the present disclosure has been described with reference to one or more particular embodiments or implementations, those skilled in the art will recognize that many changes may be made thereto without departing from the spirit and scope of the present disclosure. Each of these implementations and obvious variations thereof is contemplated as falling within the spirit and scope of the present disclosure. It is also contemplated that additional implementations according to aspects of the present disclosure may combine any number of features from any of the implementations described herein.

Claims

1. A neurostimulation system, comprising: a stimulation device including a stimulator that is configured to provide electrical stimulation to one or more branches of a nerve of the user or one or more muscles of the user; a memory storing machine-readable instructions; and a control system including one or more processors configured to execute the machine-readable instructions to implement an acclimatization process to acclimatize the user to a neurostimulation therapy for aiding the user in breathing, prior to commencement of a therapy period, by: setting a stimulation profile of the system to a starting stimulation profile configured so that a level of electrical stimulation applied under the starting stimulation profile is weaker than required for providing the neurostimulation therapy; causing the stimulation device to provide the electrical stimulation under the starting stimulation profile to the one or more branches of the nerve or the one or more muscles; receiving a response data from, or measured from a physiological output of, the user; processing the response data to determine a stimulation response; changing the stimulation profile to increase a level of electrical stimulation applied under the profile, while the stimulation response is within a tolerance threshold; and stopping stimulation when the stimulation response is not within the tolerance threshold or the stimulation profile is at a predefined limit.

2. The system of claim 1, wherein the stimulation profile is characterized by one or more parameters, and the electrical stimulation strength associated with the stimulation profile is determined at least in part by values of the one or more parameters.

3. The system of claim 2, wherein the plurality of parameters comprise parameters selected from: an amplitude, a frequency, and a duty cycle of the stimulation.

4. The system of claim 3, wherein changing the stimulation profile comprises increasing the value or values of one or more of the parameters.

5. The system of any one of claims 2 to 4, wherein the parameters comprise one or more nonquantitative parameters selected from; stimulation channel and user position.

6. The system of any preceding claim, wherein the control system is further configured to output a highest level of stimulation which the user is able to tolerate within a tolerance threshold and/or an acclimatized stimulation profile associated with the highest level of stimulation.

7. The system of claim 6, wherein the highest stimulation level and/or the acclimatized stimulation profile is used as a basis to set a therapy stimulation level for the neurostimulation therapy.

8. The system of claim 6 or 7, wherein the user’s tolerance is determined from a threshold framework.

9. The system of any preceding claim, wherein the control system is further configured to output an acclimatized stimulation profile associated with the highest stimulation level.

10. The system of any preceding claim, wherein the control system is further configured to output a period of time which has elapsed from a time when stimulation at a last stimulation level is applied to a time when the response data indicating the stimulation response outside the tolerance threshold is received.

11. The system of any preceding claim, wherein the control system is configured to change the stimulation profile based on a comparison between the stimulation response and the tolerance threshold.

12. The system of any preceding claim, wherein the response data comprises selfreported data provided by the user or a third-party via an external device.

13. The system of claim 12, wherein the self-reported data indicates a pain or discomfort, or pain or discomfort level, experienced by the user during application of electrical stimulation.

14. The system of claim 12 or 13, wherein the response data includes sensor data gathered by one or more sensors.

15. The system of claim 14, comprising one or more sensors configured to do one or more of: measure one or more physiological outputs from the user, measure an acoustic output from the user, acquire a camera or thermal image of the user, sense motion.

16. The system of claim 15, wherein the one or more physiological outputs comprises one or more of: heart rate, breathing rate, a force or strain caused by a muscle twitch, a respiratory flow rate, electrocardiogram, electroencephalogram.

17. The system of any preceding claim, further comprising an output device configured to provide an acoustic, visual, or video output, wherein the control system is configured to cause the output device to provide an additional therapy to the user, the additional therapy being delivered using one or more of an acoustic, visual, or video signals, while causing the stimulation device to provide the electrical stimulation.

18. The system of claim 17, wherein the additional therapy is configured to trigger or aid in triggering a parasympathetic nervous response in the user.

19. The system of claim 17 or 18, wherein the additional therapy is provided in response to the control system determining that user has a negative response to the electrical stimulation wherein the stimulation response is not within the tolerance threshold.

20. The system of any one of claims 17 to 19, wherein the output device is configured to provide additional therapy from a time which precedes a start time when the stimulation provides the electrical stimulation.

21. The system of any preceding claim, further comprising a respiration monitoring device including a sensor configured to generate data associated with respiration of the user.

22. The system of any preceding claim, wherein the nerve is a hypoglossal nerve.

23. A method of determining a starting stimulation level for a stimulation therapy, comprising: implementing an acclimatization process to acclimatize the user to a neurostimulation therapy for aiding the user in breathing, prior to commencement of a therapy period, by: setting a stimulation profile to a starting stimulation profile configured so that a level of electrical stimulation applied under the starting stimulation profile is weaker than required for the neurostimulation therapy; providing electrical stimulation under the stimulation profile to the one or more branches of the nerve or the one or more muscles; and receiving a response data from, or measured from a physiological output of, the user; processing the response data to determine a stimulation response; changing the stimulation profile to increase a level of electrical stimulation while the stimulation response is within a tolerance threshold; stopping stimulation when the stimulation response is not within the tolerance threshold or when the stimulation profile has reached a predefined limit; establishing a highest level of stimulation which the user is able to tolerate within a tolerance threshold and/or an acclimatized stimulation profile associated with the highest level of stimulation; and setting the starting therapy level at a level using a maximum tolerable stimulation level derived from the highest level of stimulation and/or the acclimatized stimulation profile.

24. The method of claim 23, wherein the starting therapy level is less than the maximum tolerable stimulation level.

25. The method of claim 23 or 24, comprising performing implementing the acclimatization multiple times, where a different stimulation channel is used each time, to obtain maximum tolerable stimulation levels associated with each stimulation channel, wherein the maximum tolerable stimulation level for the user is selected from the maximum tolerable stimulation levels associated with the stimulation channels.

26. The method of any one of claims 23 to 25, wherein the acclimatization process is implemented while the user is in one or more sleep positions.

27. A neurostimulation system, comprising: a stimulation device including a stimulator that is configured to provide electrical stimulation to one or more branches of a nerve of the user or one or more muscles of the user; a memory storing machine-readable instructions; and a control system including one or more processors configured to execute the machine-readable instructions to implement an acclimatization process to acclimatize the user to a neurostimulation therapy for aiding the user in breathing, prior to commencement of a therapy period, by: setting a stimulation profile of the system to a starting stimulation profile configured so that a level of electrical stimulation applied under the starting stimulation profile is weaker than required for providing the neurostimulation therapy; causing the stimulation device to provide the electrical stimulation under the starting stimulation profile to the one or more branches of the nerve or the one or more muscles; changing the stimulation profile to an updated stimulation profile, to increase a level of electrical stimulation applied under the updated profile, wherein changes are made in accordance with a stimulation profile adjustment model; causing the stimulation device to provide the electrical stimulation under the updated stimulation profile.

28. The system of claim 27, wherein the control system is further configured to: receive a response data from, or measured from a physiological output of, the user; and process the response data to determine a stimulation response; wherein the stimulation profile adjustment model is configured to determine changes to be made to the stimulation profile, based at least in part on the determined stimulation response.

29. The system of claim 29, wherein the predetermined stimulation profile adjustment model is configured to determine a change to the stimulation profile to apply a predetermined rate of increase to the level of stimulation.

30. The system of any one of claims 27 to 29, wherein the stimulation profile adjustment model is configured to cause the stimulation device to provide the electrical stimulation under an updated stimulation profile after a period of time has elapsed from when the stimulation device is caused to apply the electrical stimulation under the preceding stimulation profile.

31. The system of claim 30, wherein application of electrical stimulation under the updated stimulation profile and application of electrical stimulation under the preceding stimulation profile occur within a therapy session.

32. The system of claim 30, wherein application of electrical stimulation under the preceding stimulation profile occurs in a therapy session and application of electrical stimulation under the updated stimulation profile occurs in a subsequent therapy session.