US20230083643A1 - Detection and Treatment of Obstructive Sleep Apnea - Google Patents

Abstract

A treatment for obstructive sleep apnea (“OSA”) of a user includes affixing a patch externally on a dermis of the user, the patch including a flexible substrate, an adhesive on a first side adapted to adhere to the dermis of the user, a processor directly coupled to the substrate, and electrodes directly coupled to the substrate. The treatment includes detecting an occurrence of OSA and activating the patch in response to the detecting, the activating including generating an electrical stimuli via the electrodes to activate the genioglossus muscle of the user.

Description

CROSS REFERENCE TO RELATED APPLICATIONS
• This application is a continuation of U.S. patent application Ser. No. 17/016,734, filed on Sep. 10, 2020, which claims priority to U.S. Provisional Patent Application Ser. No. 62/898,506, filed Sep. 10, 2019, and U.S. Provisional Patent Application Ser. No. 62/907,514 filed Sep. 27, 2019, and is a continuation-in-part of U.S. patent application Ser. No. 16/823,476, filed on Mar. 19, 2020, which claims priority to U.S. Provisional Patent Application Ser. No. 62/822,252, filed Mar. 22, 2019, and U.S. Provisional Patent Application Ser. No. 62/860,010, filed Jun. 11, 2019. The disclosure of each of these applications is hereby incorporated by reference.
FIELD
• This invention is directed to obstructive sleep apnea, and more particularly to the detection and treatment, using externally applied electrical stimulation, of obstructive sleep apnea.
BACKGROUND INFORMATION
• Obstructive sleep apnea (OSA) affects the quality of sleep. Obstructive sleep apnea is the intermittent occlusion of the upper airway (UAW), resulting in the reduction of airflow through the throat. This may be due to neuromuscular factors or anatomical causes. The muscles that keep the airway open when active can allow it to close when relaxed. An obstructed airflow causes imbalances in oxygen exchange, measurable in the hemoglobin of the blood.
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG.1 is a depiction of a neuron activating a muscle by electrical impulse.
• FIG.2 is a representation of the electrical potential activation time of an electrical impulse in a nerve.
• FIG.3 is a cross section of a penis.
• FIG.4 is an illustration of a Topical Nerve Stimulator/Sensor (TNSS) component configuration including a system on a chip (SOC).
• FIG.5 is an illustration of the upper side of a Smart Band Aid implementation of a TNSS showing location of battery, which may be of various types.
• FIG.6 is an illustration of the lower side of the SBA ofFIG.5.
• FIG.7 is TNSS components incorporated into a SBA.
• FIG.8 is examples of optional neural stimulator and sensor chip sets incorporated into a SBA.
• FIG.9 is examples of optional electrode configurations for a SBA.
• FIG.10 is an example of the use of TNSS with a Control Unit as a System, in a population of Systems and software applications.
• FIG.11 shows a method for forming and steering a beam by the user of a plurality of radiators.
• FIG.12 is an exemplary beam forming and steering mechanism.
• FIG.13 illustrates exemplary Control Units for activating a nerve stimulation device.
• FIG.14 are exemplary software platforms for communicating between the Control Units and the TNSS, gathering data, networking with other TNSSs, and external communications.
• FIG.15 represents TNSS applications for patients with spinal cord injury.
• FIG.16 shows an example TNSS system.
• FIG.17 shows communications among the components of the TNSS system ofFIG.16 and a user.
• FIG.18 shows an example electrode configuration for electric field steering and sensing.
• FIG.19 shows an example of stimulating and sensing patterns of signals in a volume of tissue.
• FIG.20 is a graph showing pulses applied to the skin.
• FIG.21 is a graph showing symmetrical and asymmetrical pulses applied to the skin.
• FIG.22 is a cross-sectional diagram showing a field in underlying tissue produced by application of two electrodes to the skin.
• FIG.23 is a cross-sectional diagram showing a field in underlying tissue produced by application of two electrodes to the skin, with two layers of tissue of different electrical resistivity.
• FIG.24 is a cross-sectional diagram showing a field in underlying tissue when the stimulating pulse is turned off.
• FIG.25A is a system diagram of an example software and hardware components showing an example of a Topical Nerve Stimulator/Sensor (TNSS) interpreting a data stream from a control device in accordance with one example.
• FIG.25B is a flow chart showing an example of a function of a master control program in accordance with one example.
• FIG.26 is a block diagram of an example TNSS component configuration including a system on a chip (SOC) in accordance with one example.
• FIG.27 is a flow diagram of the protocol for adaptive current control in accordance with one example.
• FIG.28 is a Differential Integrator Circuit used in the Adaptive Current Protocol in accordance with one example.
• FIG.29 is a table relating charge duration vs. frequency to provide feedback to the Adaptive Current Protocol in accordance with one example.
• FIG.30 is an obstructive sleep apnea suppression and detection system in accordance with one example.
• FIG.31A illustrates a user with a neck, a jaw line, and an area behind the mandible.
• FIG.31B illustrates the user and a submental triangle below the chin.
• FIG.31C illustrates the user and an internal view of the hypoglossal nerve and the sublingual nerve.
• FIG.31D illustrates the user and an internal view of the hypoglossal nerve, and the genioglossus muscle under the tongue.
• FIG.32 illustrates an example placement of a patch and other elements of the system in accordance with one example.
• FIG.33 illustrates a conventional polysomnography (PSG) system.
• FIG.34 illustrates an example of signals captured during a sleep period.
• FIG.35 illustrates measurements showing biometric data during a sleep study.
• FIG.36 illustrates measurements showing biometric data during a sleep study.
• FIG.37 illustrates measurements showing biometric data during a sleep study.
• FIG.38 illustrates measurements showing biometric data during a sleep study.
• FIG.39 illustrates functionality of the system when repeatedly measuring one or more physiological metrics on a user and then passing this measurement data to a smart controller.
• FIG.40 illustrates anatomical features that are related to the placement ofpatch3010 in accordance to example inventions.
• FIG.41A illustrates a placement of one of a set of neck relatedpatches3010 in accordance to example inventions.
• FIG.41B illustrates a single patch, with multiple electrodes, singly or in pairs, to activate one or more nerves in accordance to example inventions.
• FIGS.42A and42B illustrate the anatomical features related to the placement of the patch at the mandible in accordance to example inventions.
• FIGS.43A and43B illustrate the orientation related to the placement of a chin based patch at the chin in accordance to example inventions.
• FIGS.43C and43D illustrate the orientation related to the placement of a mandible based patch at the mandible in accordance to example inventions.
• FIG.44 illustrates example stimulation waveforms for treating OSA in accordance with example inventions.
• FIGS.45A and45B illustrate the use of the patch on the sural nerve of the leg to treat OSA in accordance to example inventions.
• FIGS.46A and46B illustrate the use of the patch on the masseter nerve in the jaw, and on the temporal nerve and muscle in the head to treat OSA in accordance to example inventions.
DETAILED DESCRIPTION
• Example inventions can be used to detect and treat obstructive sleep apnea (“OSA”). Examples provide a method and system to address the effects of OSA without the discomfort and complexity of continuous positive airway pressure (“CPAP”) machines or the use of surgically implanted devices. Further, examples are directed to a method for electrical, mechanical, chemical and/or optical interaction with a human or mammal nervous system to stimulate and/or record body functions using small electronic devices attached to the skin and capable of being wirelessly linked to and controlled by a cellphone, activator or computer network
• The body is controlled by a chemical system and a nervous system.
• Nerves and muscles produce and respond to electrical voltages and currents. Electrical stimulation of these tissues can restore movement or feeling when these have been lost, or can modify the behavior of the nervous system, a process known as neuro modulation. Recording of the electrical activity of nerves and muscles is widely used for diagnosis, as in the electrocardiogram, electromyogram, electroencephalogram, etc. Electrical stimulation and recording require electrical interfaces for input and output of information. Electrical interfaces between tissues and electronic systems are usually one of three types:
• a. Devices implanted surgically into the body, such as pacemakers. These are being developed for a variety of functions, such as restoring movement to paralyzed muscles or restoring hearing, and can potentially be applied to any nerve or muscle. These are typically specialized and somewhat expensive devices.
• b. Devices inserted temporarily into the tissues, such as needles or catheters, connected to other equipment outside the body. Health care practitioners use these devices for diagnosis or short-term treatment.
• c. Devices that record voltage from the surface of the skin for diagnosis and data collection, or apply electrical stimuli to the surface of the skin using adhesive patches connected to a stimulator. Portable battery-powered stimulators have typically been simple devices operated by a patient, for example for pain relief. Their use has been limited by;
• i. The inconvenience of chronically managing wires, patches and stimulator, particularly if there are interfaces to more than one site, and
• ii. The difficulty for patients to control a variety of stimulus parameters such as amplitude, frequency, pulse width, duty cycle, etc.
• Nerves can also be stimulated mechanically to produce sensation or provoke or alter reflexes; this is the basis of touch sensation and tactile feedback. Nerves can also be affected chemically by medications delivered locally or systemically and sometimes targeted to particular nerves on the basis of location or chemical type. Nerves can also be stimulated or inhibited optically if they have had genes inserted to make them light sensitive like some of the nerves in the eye. The actions of nerves also produce electrical, mechanical and chemical changes that can be sensed.
• The topical nerve stimulator/sensor (TNSS) is a device to stimulate nerves and sense the actions of the body that can be placed on the skin of a human or mammal to act on and respond to a nerve, muscle or tissue. One implementation of the TNSS is the Smart Band Aid™ (SBA). A system, incorporating a SBA, controls neuro modulation and neuro stimulation activities. It consists of one or more controllers or Control Units, one or more TNSS modules, software that resides in Control Units and TNSS modules, wireless communication between these components, and a data managing platform. The controller hosts software that will control the functions of the TNSS. The controller takes inputs from the TNSS of data or image data for analysis by said software, The controller provides a physical user interface for display to and recording from the user, such as activating or disabling the TNSS, logging of data and usage statistics, generating reporting data. Finally, the controller provides communications with other Controllers or the Internet cloud.
• The controller communicates with the Neurostim module, also called TNSS module or SBA or patch, and also communicates with the user. In at least one example, both of these communications can go in both directions, so each set of communications is a control loop. Optionally, there may also be a control loop directly between the TNSS module and the body. So the system optionally may be a hierarchical control system with at least four control loops. One loop is between the TNSS and the body; another loop is between the TNSS and the controller; another loop is between the controller and the user; and another loop is between the controller and other users via the cloud. Each control loop has several functions including: (1) sending activation or disablement signals between the controller and the TNSS via a local network such as Bluetooth; (2) driving the user interface, as when the controller receives commands from the user and provides visual, auditory or tactile feedback to the user; (3) analyzing TNSS data, as well as other feedback data such as from the user, within the TNSS, and/or the controller and/or or the cloud; (4) making decisions about the appropriate treatment; (5) system diagnostics for operational correctness; and (6) communications with other controllers or users via the Internet cloud for data transmission or exchange, or to interact with apps residing in the Internet cloud.
• The control loop is closed. This is as a result of having both stimulating and sensing. The sensing provides information about the effects of stimulation, allowing the stimulation to be adjusted to a desired level or improved automatically.
• Typically, stimulation will be applied. Sensing will be used to measure the effects of stimulation. The measurements sensed will be used to specify the next stimulation. This process can be repeated indefinitely with various durations of each part. For example (where “a” is applying stimulation, “b” is sensing the results of stimulation, and “c” is correcting or revising the stimulation based on the applying and sensing): rapid cycling through the process (a-b-c-a-b-c-a-b-c); prolonged stimulation, occasional sensing (aaaa-b-c-aaaa-b-c-aaaa-b-c); or prolonged sensing, occasional stimulation (a-bbbb-c-a-bbbb-c-a-bbbb). The process may also start with sensing, and when an event in the body is detected this information is used to specify stimulation to treat or correct the event, for example, (bbbbbbbbb-c-a-bbbbbbbb-c-a-bbbbbbbbb). Other patterns are possible and contemplated within the scope of the application.
• The same components can be used for stimulating and sensing alternately, by switching their connection between the stimulating circuits and the sensing circuits. The switching can be done by standard electronic components. In the case of electrical stimulating and sensing, the same electrodes can be used for both. An electronic switch is used to connect stimulating circuits to the electrodes and electric stimulation is applied to the tissues. Then the electronic switch disconnects the stimulating circuits from the electrodes and connects the sensing circuits to the electrodes and electrical signals from the tissues are recorded.
• In the case of acoustic stimulating and sensing, the same ultrasonic transducers can be used for both (as in ultrasound imaging or radar). An electronic switch is used to connect circuits to the transducers to send acoustic signals (sound waves) into the tissues. Then the electronic switch disconnects these circuits from the transducers and connects other circuits to the transducers (to listen for reflected sound waves) and these acoustic signals from the tissues are recorded.
• Other modalities of stimulation and sensing may be used (e.g. light, magnetic fields, etc.) The closed loop control may be implemented autonomously by an individual TNSS or by multiple TNSS modules operating in a system such as that shown below inFIG.16. Sensing might be carried out by some TNSSs and stimulation by others.
• Stimulators are protocol controlled initiators of electrical stimulation, where such protocol may reside in either the TNSS and/or the controller and/or the cloud. Stimulators interact with associated sensors or activators, such as electrodes or MEMS devices.
• The protocol, which may be located in the TNSS, the controller or the cloud, has several functions including:
• (1) Sending activation or disablement signals between the controller and the TNSS via a local network such as Bluetooth. The protocol sends a signal by Bluetooth radio waves from the smartphone to the TNSS module on the skin, telling it to start or stop stimulating or sensing. Other wireless communication types are possible.
• (2) Driving the user interface, as when the controller receives commands from the user and provides visual, auditory or tactile feedback to the user. The protocol receives a command from the user when the user touches an icon on the smartphone screen, and provides feedback to the user by displaying information on the smartphone screen, or causing the smartphone to beep or buzz.
• (3) Analyzing TNSS data, as well as other feedback data such as from the user, within the TNSS, and/or the controller and/or or the cloud. The protocol analyzes data sensed by the TNSS, such as the position of a muscle, and data from the user such as the user's desires as expressed when the user touches an icon on the smartphone; this analysis can be done in the TNSS, in the smartphone, and/or in the cloud.
• (4) Making decisions about the appropriate treatment. The protocol uses the data it analyzes to decide what stimulation to apply.
• (5) System diagnostics for operational correctness. The protocol checks that the TNSS system is operating correctly.
• (6) Communications with other controllers or users via the Internet cloud for data transmission or exchange, or to interact with apps residing in the Internet cloud. The protocol communicates with other smartphones or people via the internet wirelessly; this may include sending data over the internet, or using computer programs that are operating elsewhere on the internet.
• A neurological control system, method and apparatus are configured in an ecosystem or modular platform that uses potentially disposable topical devices to provide interfaces between electronic computing systems and neural systems. These interfaces may be direct electrical connections via electrodes or may be indirect via transducers (sensors and actuators). It may have the following elements in various configurations: electrodes for sensing or activating electrical events in the body; actuators of various modalities; sensors of various modalities; wireless networking; and protocol applications, e.g. for data processing, recording, control systems. These components are integrated within the disposable topical device. This integration allows the topical device to function autonomously. It also allows the topical device along with a remote control unit (communicating wirelessly via an antenna, transmitter and receiver) to function autonomously.
• Referring toFIG.1, nerve cells are normally electrically polarized with the interior of the nerve being at an electric potential 70 mV negative relative to the exterior of the cell. Application of a suitable electric voltage to a nerve cell (raising the resting potential of the cell from −70 mV to above the firing threshold of −55 mV) can initiate a sequence of events in which this polarization is temporarily reversed in one region of the cell membrane and the change in polarization spreads along the length of the cell to influence other cells at a distance, e.g. to communicate with other nerve cells or to cause or prevent muscle contraction.
• Referring toFIG.2, a nerve impulse is graphically represented from a point of stimulation resulting in a wave of depolarization followed by a repolarization that travels along the membrane of a neuron during the measured period. This spreading action potential is a nerve impulse. It is this phenomenon that allows for external electrical nerve stimulation.
• Referring toFIG.3, the dorsal genital nerve on the back of the penis or clitoris just under the skin is a purely sensory nerve that is involved in normal inhibition of the activity of the bladder during sexual activity, and electrical stimulation of this nerve has been shown to reduce the symptoms of the Over Active Bladder. Stimulation of the underside of the penis may cause sexual arousal, erection, ejaculation and orgasm.
• A Topical nerve stimulator/sensor (TNSS) is used to stimulate these nerves and is convenient, unobtrusive, self-powered, controlled from a smartphone or other control device. This has the advantage of being non-invasive, controlled by consumers themselves, and potentially distributed over the counter without a prescription.
• Referring toFIG.4, the TNSS has one or more electronic circuits or chips that perform the functions of: communications with the controller, nerve stimulation via electrodes408 that produce a wide range of electric field(s) according to treatment regimen, one ormore antennae410 that may also serve as electrodes and communication pathways, and a wide range ofsensors406 such as, but not limited to, mechanical motion and pressure, temperature, humidity, chemical and positioning sensors. One arrangement would be to integrate a wide variety of these functions into an SOC, system onchip400. Within this is shown acontrol unit402 for data processing, communications and storage and one or more stimulators404 andsensors406 that are connected to electrodes408. Anantenna410 is incorporated for external communications by the control unit. Also present is aninternal power supply412, which may be, for example, a battery. An external power supply is another variation of the chip configuration. It may be necessary to include more than one chip to accommodate a wide range of voltages for data processing and stimulation. Electronic circuits and chips will communicate with each other via conductive tracks within the device capable of transferring data and/or power.
• In one or more examples, a Smart Band Aid™ incorporating a battery and electronic circuit and electrodes in the form of adhesive conductive pads may be applied to the skin, and electrical stimuli is passed from the adhesive pads into the tissues. Stimuli may typically be trains of voltage-regulated square waves at frequencies between 15 and 50 Hz with currents between 20 and 100 mA. In other examples, the stimuli includes square waves having an amplitude between 10 and 100 volts, pulse widths between 100 and 500 microseconds, and a pulse repetition rate of between 3 and 30 pulses per second. The trains of stimuli are controlled from a smartphone operated by the user. Stimuli may be either initiated by the user when desired, or programmed according to a timed schedule, or initiated in response to an event detected by a sensor on the Smart Band Aid™ or elsewhere. Another implementation for males may be a TNSS incorporated in a ring that locates a stimulator conductively to selected nerves in a penis to be stimulated.
• Referring toFIG.5, limited lifetime battery sources will be employed asinternal power supply412, to power the TNSS deployed in this illustration as a Smart Band Aid™. These may take the form of Lithium Ion technology or traditional non-toxic Mn02 ™ technologies.FIG.5 illustrates different battery options such as a printable Manganese Oxide battery516 and a button battery518. A TNSS of different shapes may require different battery packaging.
• FIG.6 shows an alternate arrangement of these components where the batteries616-618 are positioned on the bottom side of the SBA between theelectrodes610 and620. In this example,battery616 is a lithium ion battery, battery617 is a Mn02 battery and battery618 is a button battery. Other types of batteries and other battery configurations are possible within the scope of this application in other examples.
• Aside from the Controller, the Smart Band Aid™ Packaging Platform (also referred to as a “smart patch” or “patch”) consists of an assembly of an adhesive patch capable of being applied to the skin and containing the TNSS Electronics, protocol, and power described above.
• Referring toFIG.7 is a TNSS deployed as a Smart Band Aid™414. The Smart Band Aid™ has a substrate with adhesive on a side for adherence to skin, theSOC400 previously described inFIG.4, or electronic package, and electrodes408 disposed between the dermis and the adhesive surface. The electrodes provide electrical stimuli through the dermis to nerves and other tissue and in turn may collect electrical signals from the body, such as the electrical signals produced by muscles when they contract (the electromyogram) to provide data about body functions such as muscle actions.
• Referring toFIG.8, different chips may be employed to design requirements. Shown are sample chips for packaging in a TNSS in this instance deployed as a SBA. For example, neural stimulator800,sensor802, processor/communications804 are represented. The chips can be packaged separately on a substrate, including a flexible material, or as a system-on-chip (SOC)400. The chip connections and electronics package are not shown but are known in the art.
• Referring toFIG.9, SBAs with variations on arrangements of electrodes are shown. Each electrode may consist of a plurality of conductive contacts that give the electrode abilities to adjust the depth, directionality, and spatial distribution of the applied electric field. For all the example electrode configurations shown,901-904, the depth of the electrical stimulation can be controlled by the voltage and power applied to the electrode contacts. Electric current can be applied to various electrode contacts at opposite end of the SBA, or within a plurality of electrode contacts on a single end of the SBA. The phase relationship of the signals applied to the electrode contacts can vary the directionality of the electric field. For all configurations of electrodes, the applied signals can vary over time and spatial dimensions. The configuration on the left,901, shows a plurality of concentric electrode contacts at either end of the SBA. This configuration can be used to apply an electric stimulating field at various tissue depths by varying the power introduced to the electrode contacts. The next configuration,902, shows electrodes404 that are arranged in a plurality of parallel strips of electrical contacts. This allows the electric field to be oriented perpendicular or parallel to the SBA. The next configuration,903, shows an example matrix of electrode contacts where the applied signal can generate a stimulating field between any two or more electrode contacts at either end of the SBA, or between two or more electrode contacts within a single matrix at one end of the SBA. Finally, the next configuration on the far right,904, also shows electrodes that are arranged in a plurality of parallel strips of electrical contacts. As with the second configuration, this allows the electric field to be oriented perpendicular or parallel to the SBA. There may be many other arrangements of electrodes and contacts.
• One or more TNSSs with one or more Controllers form a System. Systems can communicate and interact with each other and with distributed virtualized processing and storage services. This enables the gathering, exchange, and analysis of data among populations of systems for medical and non-medical applications.
• Referring toFIG.10, a system is shown with two TNSS units1006, with one on the wrist, one on the leg, communicating with its controller, asmartphone1000 or other control device. The TNSS units can be both sensing and stimulating and can act independently and also work together in a Body Area Network (BAN). Systems communicate with each other over a communication bridge or network such as a cellular network. Systems also communicate with applications running in a distributed virtualized processing and storage environment generally via theInternet1002. The purpose for communications with the distributed virtualized processing and storage environment is to communicate large amounts of user data for analysis and networking with other third parties such as hospitals, doctors, insurance companies, researchers, and others. There are applications that gather, exchange, and analyze data frommultiple Systems1004. Third party application developers can access TNSS systems and their data to deliver a wide range of applications. These applications can return data or control signals to the individual wearing the TNSS unit1006. These applications can also send data or control signals to other members of the population who employsystems1008. This may represent an individual's data, aggregated data from a population of users, data analyses, or supplementary data from other sources.
• Referring toFIG.11, shown is an example of an electrode array to affect beam forming and beam steering. Beam forming and steering allows a more selective application of stimulation energy by a TNSS to nerves and tissue. Beam steering also provides the opportunity for lower power for stimulation of cells including nerves by applying the stimulating mechanism directionally to a target. In the use of an electrical beam lower power demand lengthens battery life and allows for use of low power chip sets. Beam steering may be accomplished in multiple ways for instance by magnetic fields and formed gates.FIG.11 shows a method for forming and steering a beam by the use of a plurality ofradiators1102 which are activated out of phase with each other by a plurality ofphase shifters1103 that are supplied power from a common source1104. Because the radiated signals are out of phase they produce aninterference pattern1105 that results in the beam being formed and steered in varying controlleddirections1106. Electromagnetic radiation like light shows some properties of waves and can be focused on certain locations. This provides the opportunity to stimulate tissues such as nerves selectively. It also provides the opportunity to focus the transmission of energy and data on certain objects, including topical or implanted electronic devices, thereby not only improving the selectivity of activating or controlling those objects but also reducing the overall power required to operate them.
• FIG.12 is another example of agating structure1200 used for beam shaping andsteering1202. Thegating structure1200 shows an example of an interlocked pair of electrodes that can be used for simple beam forming through the application of time-varying voltages. Thesteering1202 shows a generic picture of the main field lobes and how such beam steering works in this example.FIG.12 is illustrative of a possible example that may be used.
• The human and mammal body is an anisotropic medium with multiple layers of tissue of varying electrical properties. Steering of an electric field may be accomplished using multiple electrodes, or multiple SBAs, using the human or mammal body as an anisotropic volume conductor. Electric field steering will discussed below with reference toFIGS.18 and19.
• Referring toFIG.13, the controller is an electronics platform that is asmartphone1300,tablet1302,personal computer1304, ordedicated module1306 that hosts wireless communications capabilities, such as Near Field Communications, Bluetooth, or Wi-Fi technologies as enabled by the current set of communications chips, e.g. Broadcom BCM4334,TI WiLink 8 and others, and a wide range of protocol apps that can communicate with the TNSSs. There may be more than one controller, acting together. This may occur, for example, if the user has both a smartphone control app running, and a key fob controller in his/her pocket/purse.
• TNSS protocol performs the functions of communications with the controller including transmitting and receiving of control and data signals, activation and control of the neural stimulation, data gathering from on board sensors, communications and coordination with other TNSSs, and data analysis. Typically the TNSS may receive commands from the controller, generate stimuli and apply these to the tissues, sense signals from the tissues, and transmit these to the controller. It may also analyze the signals sensed and use this information to modify the stimulation applied. In addition to communicating with the controller it may also communicate with other TNSSs using electrical or radio signals via a body area network.
• Referring toFIG.14, controller protocol executed and/or displayed on asmartphone1400,tablet1402 or other computing platform or mobile device, will perform the functions of communications with TNSS modules including transmitting and receiving of control and data signals, activation and control of the neuro modulation regimens, data gathering from on board sensors, communications and coordination with other controllers, and data analysis. In some cases local control of the neuro modulation regimens may be conducted by controller protocol without communications with the user.
• FIG.15 shows potential applications of electrical stimulation and sensing for the body, particularly for users who may suffer from paralysis or loss of sensation or altered reflexes such as spasticity or tremor due to neurological disorders and their complications, as well as users suffering from incontinence, pain, immobility and aging. Different example medical uses of the present system are discussed below.
• FIG.16 shows the components of one example of a typical TNSS system1600. TNSS devices1610 are responsible for stimulation of nerves and for receiving data in the form of electrical, acoustic, imaging, chemical and other signals which then can be processed locally in the TNSS or passed to the Control Unit1620. TNSS devices1610 are also responsible for analysis and action. The TNSS device1610 contain a plurality of electrodes for stimulation and for sensing. The same electrodes may be used for both functions, but this is not required. The TNSS device1610 contain an imaging device, such as an ultrasonic transducer to create acoustic images of the structure beneath the electrodes or elsewhere in the body that may be affected by the neural stimulation.
• In this example TNSS system, most of the data gathering and analysis is performed in the Control Unit1620. The Control Unit1620 may be a cellular telephone or a dedicated hardware device. The Control Unit1620 runs an app that controls the local functions of the TNSS System1600. The protocol app also communicates via the Internet orwireless networks1630 with other TNSS systems and/or with 3rd party software applications.
• FIG.17 shows the communications among the components of the TNSS system1600 and the user. In this example, TNSS1610 is capable of applying stimuli to nerves1640 to produce action potentials in the nerves1640 to produce actions inmuscles1670 or other organs such as the brain1650. These actions may be sensed by the TNSS1610, which may act on the information to modify the stimulation it provides. This closed loop constitutes the first level of the system1600 in this example.
• The TNSS1610 may also be caused to operate by signals received from a Control Unit1620 such as a cellphone, laptop, key fob, tablet, or other handheld device and may transmit information that it senses back to the Control Unit1620. This constitutes the second level of the system1600 in this example.
• The Control Unit1620 is caused to operate by commands from a user, who also receives information from the Control Unit1620. The user may also receive information about actions of the body via natural senses such as vision or touch via sensory nerves and the spinal cord, and may in some cases cause actions in the body via natural pathways through the spinal cord to the muscles.
• The Control Unit1620 communicate information to other users, experts, or application programs via theInternet1630, and receive information from them via theInternet1630.
• The user may choose to initiate or modify these processes, sometimes using protocol applications residing in the TNSS1610, the Control Unit1620, theInternet1630, or wireless networks. This software may assist the user, for example by processing the stimulation to be delivered to the body to render it more selective or effective for the user, and/or by processing and displaying data received from the body or from theInternet1630 or wireless networks to make it more intelligible or useful to the user.
• FIG.18 shows anexample electrode configuration1800 for Electric Field Steering. The application of an appropriate electric field to the body can cause a nerve to produce an electrical pulse known as an action potential. The shape of the electric field is influenced by the electrical properties of the different tissue through which it passes and the size, number and position of the electrodes used to apply it. The electrodes can therefore be designed to shape or steer or focus the electric field on some nerves more than on others, thereby providing more selective stimulation.
• An example 10×10 matrix ofelectrical contacts1860 is shown. By varying the pattern ofelectrical contacts1860 employed to cause anelectric field1820 to form and by time varying the applied electrical power to this pattern ofcontacts1860, it is possible to steer thefield1820 across different parts of the body, which may includemuscle1870, bone, fat, and other tissue, in three dimensions. Thiselectric field1820 can activate specific nerves ornerve bundles1880 while sensing the electrical and mechanical actions produced1890, and thereby enabling the TNSS to discover more effective or the most effective pattern of stimulation for producing the desired action.
• FIG.19 shows an example of stimulating and sensing patterns of signals in a volume of tissue.Electrodes1910 as part of a cuff arrangement are placed around limb1915. Theelectrodes1910 are external to a layer ofskin1916 onlimb1915. Internal components of thelimb1915 includemuscle1917,bone1918,nerves1919, and other tissues. By using electric field steering for stimulation, as described with reference toFIG.18, theelectrodes1910 can activatenerves1919 selectively. An array of sensors (e.g., piezoelectric sensors or micro-electro-mechanical sensors) in a TNSS can act as a phased array antenna for r6eceiving ultrasound signals, to acquire ultrasonic images of body tissues.Electrodes1910 may act as an array of electrodes sensing voltages at different times and locations on the surface of the body, with software processing this information to display information about the activity in body tissues, e.g., which muscles are activated by different patterns of stimulation.
• The SBA's ability to stimulate and collect organic data has multiple applications including bladder control, reflex incontinence, sexual stimulations, pain control and wound healing among others. Examples of SBA's application for medical and other uses follow.
Medical uses
• Bladder Management
• Overactive bladder: When the user feels a sensation of needing to empty the bladder urgently, he or she presses a button on the Controller to initiate stimulation via a Smart Band Aid™ applied over the dorsal nerve of the penis or clitoris. Activation of this nerve would inhibit the sensation of needing to empty the bladder urgently, and allow it to be emptied at a convenient time.
• Incontinence: A person prone to incontinence of urine because of unwanted contraction of the bladder uses the SBA to activate the dorsal nerve of the penis or clitoris to inhibit contraction of the bladder and reduce incontinence of urine. The nerve could be activated continuously, or intermittently when the user became aware of the risk of incontinence, or in response to a sensor indicating the volume or pressure in the bladder.
• Erection, ejaculation and orgasm: Stimulation of the nerves on the underside of the penis by a Smart Band Aid™ (electrical stimulation or mechanical vibration) can cause sexual arousal and might be used to produce or prolong erection and to produce orgasm and ejaculation.
• Pain control: A person suffering from chronic pain from a particular region of the body applies a Smart Band Aid™ over that region and activates electrically the nerves conveying the sensation of touch, thereby reducing the sensation of pain from that region. This is based on the gate theory of pain.
• Wound care: A person suffering from a chronic wound or ulcer applies a Smart Band Aid™ over the wound and applies electrical stimuli continuously to the tissues surrounding the wound to accelerate healing and reduce infection.
• Essential tremor: A sensor on a Smart Band Aid™ detects the tremor and triggers neuro stimulation to the muscles and sensory nerves involved in the tremor with an appropriate frequency and phase relationship to the tremor. The stimulation frequency would typically be at the same frequency as the tremor but shifted in phase in order to cancel the tremor or reset the neural control system for hand position.
• Reduction of spasticity: Electrical stimulation of peripheral nerves can reduce spasticity for several hours after stimulation. A Smart Band Aid™ operated by the patient when desired from a smartphone could provide this stimulation.
• Restoration of sensation and sensory feedback: People who lack sensation, for example as a result of diabetes or stroke use a Smart Band Aid™ to sense movement or contact, for example of the foot striking the floor, and the SBA provides mechanical or electrical stimulation to another part of the body where the user has sensation, to improve safety or function. Mechanical stimulation is provided by the use of acoustic transducers in the SBA such as small vibrators. Applying a Smart Band Aid™ to the limb or other assistive device provides sensory feedback from artificial limbs. Sensory feedback can also be used to substitute one sense for another, e.g. touch in place of sight.
• Recording of mechanical activity of the body: Sensors in a Smart Band Aid™ record position, location and orientation of a person or of body parts and transmit this data to a smartphone for the user and/or to other computer networks for safety monitoring, analysis of function and coordination of stimulation.
• Recording of sound from the body or reflections of ultrasound waves generated by a transducer in a Smart Band Aid™ could provide information about body structure, e.g., bladder volume for persons unable to feel their bladder. Acoustic transducers may be piezoelectric devices or MEMS devices that transmit and receive the appropriate acoustic frequencies. Acoustic data may be processed to allow imaging of the interior of the body.
• Recording of Electrical Activity of the Body
• Electrocardiogram: Recording the electrical activity of the heart is widely used for diagnosing heart attacks and abnormal rhythms. It is sometimes necessary to record this activity for 24 hours or more to detect uncommon rhythms. A Smart Band Aid™ communicating wirelessly with a smartphone or computer network achieves this more simply than present systems.
• Electromyogram: Recording the electrical activity of muscles is widely used for diagnosis in neurology and also used for movement analysis. Currently this requires the use of many needles or adhesive pads on the surface of the skin connected to recording equipment by many wires. Multiple Smart Band Aids™ record the electrical activity of many muscles and transmit this information wirelessly to a smartphone.
• Recording of optical information from the body: A Smart Band Aid™ incorporating a light source (LED, laser) illuminates tissues and senses the characteristics of the reflected light to measure characteristics of value, e.g., oxygenation of the blood, and transmit this to a cellphone or other computer network.
• Recording of chemical information from the body: The levels of chemicals or drugs in the body or body fluids is monitored continuously by a Smart Band Aid™ sensor and transmitted to other computer networks and appropriate feedback provided to the user or to medical staff. Levels of chemicals may be measured by optical methods (reflection of light at particular wavelengths) or by chemical sensors.
• Special Populations of Disabled Users
• There are many potential applications of electrical stimulation for therapy and restoration of function. However, few of these have been commercialized because of the lack of affordable convenient and easily controllable stimulation systems. Some applications are shown in theFIG.15.
• Limb Muscle stimulation: Lower limb muscles can be exercised by stimulating them electrically, even if they are paralyzed by stroke or spinal cord injury. This is often combined with the use of a stationary exercise cycle for stability. Smart Band Aid™ devices could be applied to the quadriceps muscle of the thigh to stimulate these, extending the knee for cycling, or to other muscles such as those of the calf. Sensors in the Smart Band Aid™ could trigger stimulation at the appropriate time during cycling, using an application on a smartphone, tablet, handheld hardware device such as a key fob, wearable computing device, laptop, or desktop computer, among other possible devices. Upper limb muscles can be exercised by stimulating them electrically, even if they are paralyzed by stroke of spinal cord injury. This is often combined with the use of an arm crank exercise machine for stability. Smart Band Aid™ devices are applied to multiple muscles in the upper limb and triggered by sensors in the Smart Band Aids™ at the appropriate times, using an application on a smartphone.
• Prevention of osteoporosis: Exercise can prevent osteoporosis and pathological fractures of bones. This is applied using Smart Band Aids™ in conjunction with exercise machines such as rowing simulators, even for people with paralysis who are particularly prone to osteoporosis.
• Prevention of deep vein thrombosis: Electric stimulation of the muscles of the calf can reduce the risk of deep vein thrombosis and potentially fatal pulmonary embolus. Electric stimulation of the calf muscles is applied by a Smart Band Aid™ with stimulation programmed from a smartphone, e.g., during a surgical operation, or on a preset schedule during a long plane flight.
• Restoration of Function (Functional Electrical Stimulation) Lower Limb
• 1) Foot drop: People with stroke often cannot lift their forefoot and drag their toes on the ground. A Smart Band Aid™ is be applied just below the knee over the common peroneal nerve to stimulate the muscles that lift the forefoot at the appropriate time in the gait cycle, triggered by a sensor in the Smart Band Aid™.
• 2) Standing: People with spinal cord injury or some other paralyses can be aided to stand by electrical stimulation of the quadriceps muscles of their thigh. These muscles are stimulated by Smart Band Aids™ applied to the front of the thigh and triggered by sensors or buttons operated by the patient using an application on a smartphone. This may also assist patients to use lower limb muscles when transferring from a bed to a chair or other surface.
• 3) Walking: Patients with paralysis from spinal cord injury are aided to take simple steps using electrical stimulation of the lower limb muscles and nerves. Stimulation of the sensory nerves in the common peroneal nerve below the knee can cause a triple reflex withdrawal, flexing the ankle, knee and hip to lift the leg, and then stimulation of the quadriceps can extend the knee to bear weight. The process is then repeated on the other leg. Smart Band Aids™ coordinated by an application in a smartphone produce these actions.
• Upper Limb
• Hand grasp: People with paralysis from stroke or spinal cord injury have simple hand grasp restored by electrical stimulation of the muscles to open or close the hand. This is produced by Smart Band Aids™ applied to the back and front of the forearm and coordinated by sensors in the Smart Band Aids™ and an application in a smartphone.
• Reaching: Patients with paralysis from spinal cord injury sometimes cannot extend their elbow to reach above the head. Application of a Smart Band Aid™ to the triceps muscle stimulates this muscle to extend the elbow. This is triggered by a sensor in the Smart Band Aid™ detecting arm movements and coordinating it with an application on a smartphone.
• Posture: People whose trunk muscles are paralyzed may have difficulty maintaining their posture even in a wheelchair. They may fall forward unless they wear a seatbelt, and if they lean forward they may be unable to regain upright posture. Electrical stimulation of the muscles of the lower back using a Smart Band Aid™ allows them to maintain and regain upright posture. Sensors in the Smart Band Aid™ trigger this stimulation when a change in posture was detected.
• Coughing: People whose abdominal muscles are paralyzed cannot produce a strong cough and are at risk for pneumonia. Stimulation of the muscles of the abdominal wall using a Smart Band Aid™ could produce a more forceful cough and prevent chest infections. The patient using a sensor in a Smart Band Aid™ triggers the stimulation.
• Essential Tremor: It has been demonstrated that neuro stimulation can reduce or eliminate the signs of ET. ET may be controlled using a TNSS. A sensor on a Smart Band Aid™ detects the tremor and trigger neuro stimulation to the muscles and sensory nerves involved in the tremor with an appropriate frequency and phase relationship to the tremor. The stimulation frequency is typically be at the same frequency as the tremor but shifted in phase in order to cancel the tremor or reset the neural control system for hand position.
Non-Medical Applications
• Sports Training
• Sensing the position and orientation of multiple limb segments is used to provide visual feedback on a smartphone of, for example, a golf swing, and also mechanical or electrical feedback to the user at particular times during the swing to show them how to change their actions. The electromyogram of muscles could also be recorded from one or many Smart Band Aids™ and used for more detailed analysis.
• Gaming
• Sensing the position and orientation of arms, legs and the rest of the body produces a picture of an onscreen player that can interact with other players anywhere on the Internet. Tactile feedback would be provided to players by actuators in Smart Band Aids on various parts of the body to give the sensation of striking a ball, etc.
• Motion Capture for Film and Animation
• Wireless TNSS capture position, acceleration, and orientation of multiple parts of the body. This data may be used for animation of a human or mammal and has application for human factor analysis and design.
Sample Modes of Operation
• An SBA system consists of at least a single Controller and a single SBA. Following application of the SBA to the user's skin, the user controls it via the Controller's app using Near Field Communications. The app appears on a smartphone screen and can be touch controlled by the user; for ‘key fob’ type Controllers. The SBA is controlled by pressing buttons on the key fob.
• When the user feels the need to activate the SBA s/he presses the “go” button two or more times to prevent false triggering, thus delivering the neuro stimulation. The neuro stimulation may be delivered in a variety of patterns of frequency, duration, and strength and may continue until a button is pressed by the user or may be delivered for a length of time set in the application.
• Sensor capabilities in the TNSS, are enabled to start collecting/analyzing data and communicating with the controller when activated.
• The level of functionality in the protocol app, and the protocol embedded in the TNSS, will depend upon the neuro modulation or neuro stimulation regimen being employed.
• In some cases there will be multiple TNSSs employed for the neuro modulation or neuro stimulation regimen. The basic activation will be the same for each TNSS.
• However, once activated multiple TNSSs will automatically form a network of neuro modulation/stimulation points with communications enabled with the controller.
• The need for multiple TNSSs arises from the fact that treatment regimens may need several points of access to be effective.
Controlling the Stimulation
• In general, advantages of a wireless TNSS system as disclosed herein over existing transcutaneous electrical nerve stimulation devices include: (1) fine control of all stimulation parameters from a remote device such as a smartphone, either directly by the user or by stored programs; (2) multiple electrodes of a TNSS can form an array to shape an electric field in the tissues; (3) multiple TNSS devices can form an array to shape an electric field in the tissues; (4) multiple TNSS devices can stimulate multiple structures, coordinated by a smartphone; (5) selective stimulation of nerves and other structures at different locations and depths in a volume of tissue; (6) mechanical, acoustic or optical stimulation in addition to electrical stimulation; (7) the transmitting antenna of TNSS device can focus a beam of electromagnetic energy within tissues in short bursts to activate nerves directly without implanted devices; (8) inclusion of multiple sensors of multiple modalities, including but not limited to position, orientation, force, distance, acceleration, pressure, temperature, voltage, light and other electromagnetic radiation, sound, ions or chemical compounds, making it possible to sense electrical activities of muscles (EMG, EKG), mechanical effects of muscle contraction, chemical composition of body fluids, location or dimensions or shape of an organ or tissue by transmission and receiving of ultrasound.
• Further advantages of the wireless TNSS system include: (1) TNSS devices are expected to have service lifetimes of days to weeks and their disposability places less demand on power sources and battery requirements; (2) the combination of stimulation with feedback from artificial or natural sensors for closed loop control of muscle contraction and force, position or orientation of parts of the body, pressure within organs, and concentrations of ions and chemical compounds in the tissues; (3) multiple TNSS devices can form a network with each other, with remote controllers, with other devices, with the Internet and with other users; (4) a collection of large amounts of data from one or many TNSS devices and one or many users regarding sensing and stimulation, collected and stored locally or through the internet; (5) analysis of large amounts of data to detect patterns of sensing and stimulation, apply machine learning, and improve algorithms and functions; (6) creation of databases and knowledge bases of value; (7) convenience, including the absence of wires to become entangled in clothing, showerproof and sweat proof, low profile, flexible, camouflaged or skin colored, (8) integrated power, communications, sensing and stimulating inexpensive disposable TNSS, consumable electronics; (9) power management that utilizes both hardware and software functions will be critical to the convenience factor and widespread deployment of TNSS device.
• Referring again toFIG.1, a nerve cell normally has a voltage across the cell membrane of 70 millivolts with the interior of the cell at a negative voltage with respect to the exterior of the cell. This is known as the resting potential and it is normally maintained by metabolic reactions which maintain different concentrations of electrical ions in the inside of the cell compared to the outside. Ions can be actively “pumped” across the cell membrane through ion channels in the membrane that are selective for different types of ion, such as sodium and potassium. The channels are voltage sensitive and can be opened or closed depending on the voltage across the membrane. An electric field produced within the tissues by a stimulator can change the normal resting voltage across the membrane, either increasing or decreasing the voltage from its resting voltage.
• Referring again toFIG.2, a decrease in voltage across the cell membrane to about 55 millivolts opens certain ion channels, allowing ions to flow through the membrane in a self-catalyzing but self-limited process which results in a transient decrease of the trans membrane potential to zero, and even positive, known as depolarization followed by a rapid restoration of the resting potential as a result of active pumping of ions across the membrane to restore the resting situation which is known as repolarization. This transient change of voltage is known as an action potential and it typically spreads over the entire surface of the cell. If the shape of the cell is such that it has a long extension known as an axon, the action potential spreads along the length of the axon. Axons that have insulating myelin sheaths propagate action potentials at much higher speeds than those axons without myelin sheaths or with damaged myelin sheaths.
• If the action potential reaches a junction, known as a synapse, with another nerve cell, the transient change in membrane voltage results in the release of chemicals known as neuro-transmitters that can initiate an action potential in the other cell. This provides a means of rapid electrical communication between cells, analogous to passing a digital pulse from one cell to another.
• If the action potential reaches a synapse with a muscle cell it can initiate an action potential that spreads over the surface of the muscle cell. This voltage change across the membrane of the muscle cell opens ion channels in the membrane that allow ions such as sodium, potassium and calcium to flow across the membrane, and can result in contraction of the muscle cell.
• Increasing the voltage across the membrane of a cell below −70 millivolts is known as hyper-polarization and reduces the probability of an action potential being generated in the cell. This can be useful for reducing nerve activity and thereby reducing unwanted symptoms such as pain and spasticity
• The voltage across the membrane of a cell can be changed by creating an electric field in the tissues with a stimulator. It is important to note that action potentials are created within the mammalian nervous system by the brain, the sensory nervous system or other internal means. These action potentials travel along the body's nerve “highways”. The TNSS creates an action potential through an externally applied electric field from outside the body. This is very different than how action potentials are naturally created within the body.
• Electric Fields that Can Cause Action Potentials
• Referring toFIG.2, electric fields capable of causing action potentials can be generated by electronic stimulators connected to electrodes that are implanted surgically in close proximity to the target nerves. To avoid the many issues associated with implanted devices, it is desirable to generate the required electric fields by electronic devices located on the surface of the skin. Such devices typically use square wave pulse trains of the form shown inFIG.20. Such devices may be used instead of implants and/or with implants such as reflectors, conductors, refractors, or markers for tagging target nerves and the like, so as to shape electric fields to enhance nerve targeting and/or selectivity.
• Referring toFIG.20, the amplitude of the pulses “A”, applied to the skin, may vary between 1 and 100 Volts, pulse width “t”, between 100 microseconds and 10 milliseconds, duty cycle (t/T) between 0.1% and 50%, the frequency of the pulses within a group between 1 and 100/sec, and the number of pulses per group “n”, between 1 and several hundred. Typically, pulses applied to the skin will have an amplitude of up to 60 volts, a pulse width of 250 microseconds and a frequency of 20 per second, resulting in a duty cycle of 0.5%. In some cases balanced-charge biphasic pulses will be used to avoid net current flow. Referring toFIG.21, these pulses may be symmetrical, with the shape of the first part of the pulse similar to that of the second part of the pulse, or asymmetrical, in which the second part of the pulse has lower amplitude and a longer pulse width in order to avoid canceling the stimulatory effect of the first part of the pulse.
• Formation of Electric Fields by Stimulators
• The location and magnitude of the electric potential applied to the tissues by electrodes provides a method of shaping the electrical field. For example, applying two electrodes to the skin, one at a positive electrical potential with respect to the other, can produce a field in the underlying tissues such as that shown in the cross-sectional diagram ofFIG.22.
• The diagram inFIG.22 assumes homogeneous tissue. The voltage gradient is highest close to the electrodes and lower at a distance from the electrodes. Nerves are more likely to be activated close to the electrodes than at a distance. For a given voltage gradient, nerves of large diameter are more likely to be activated than nerves of smaller diameter. Nerves whose long axis is aligned with the voltage gradient are more likely to be activated than nerves whose long axis is at right angles to the voltage gradient.
• Applying similar electrodes to a part of the body in which there are two layers of tissue of different electrical resistivity, such as fat and muscle, can produce a field such as that shown inFIG.23. Layers of different tissue may act to refract and direct energy waves and be used for beam aiming and steering. An individual's tissue parameters may be measured and used to characterize the appropriate energy stimulation for a selected nerve.
• Referring toFIG.24, when the stimulating pulse is turned off the electric field will collapse and the fields will be absent as shown. It is the change in electric field that will cause an action potential to be created in a nerve cell, provided sufficient voltage and the correct orientation of the electric field occurs. More complex three-dimensional arrangements of tissues with different electrical properties can result in more complex three-dimensional electric fields, particularly since tissues have different electrical properties and these properties are different along the length of a tissue and across it, as shown in Table 1.

• 	TABLE 1
  	Electrical
  	Conductivity
  	(siemens/m)	Direction	Average

  	Blood		.65
  	Bone	Along	.17
  	Bone	Mixed	.095
  	Fat		.05
  	Muscle	Along	.127
  	Muscle	Across	.45
  	Muscle	Mixed	.286
  	Skin (Dry)		.000125
  	Skin (Wet)		.00121

• Modification of Electric Fields by Tissue
• An important factor in the formation of electric fields used to create action potentials in nerve cells is the medium through which the electric fields must penetrate. For the human body this medium includes various types of tissue including bone, fat, muscle, and skin. Each of these tissues possesses different electrical resistivity or conductivity and different capacitance and these properties are anisotropic. They are not uniform in all directions within the tissues. For example, an axon has lower electrical resistivity along its axis than perpendicular to its axis. The wide range of conductivities is shown in Table 1. The three-dimensional structure and resistivity of the tissues will therefore affect the orientation and magnitude of the electric field at any given point in the body.
• Modification of Electric Fields by Multiple Electrodes
• Applying a larger number of electrodes to the skin can also produce more complex three-dimensional electrical fields that can be shaped by the location of the electrodes and the potential applied to each of them. Referring toFIG.20, the pulse trains can differ from one another indicated by A, t/T, n, and f as well as have different phase relationships between the pulse trains. For example with an 8×8 array of electrodes, combinations of electrodes can be utilized ranging from simple dipoles, to quadripoles, to linear arrangements, to approximately circular configurations, to produce desired electric fields within tissues.
• Applying multiple electrodes to a part of the body with complex tissue geometry will thus result in an electric field of a complex shape. The interaction of electrode arrangement and tissue geometry can be modeled using Finite Element Modeling, which is a mathematical method of dividing the tissues into many small elements in order to calculate the shape of a complex electric field. This can be used to design an electric field of a desired shape and orientation to a particular nerve.
• High frequency techniques known for modifying an electric field, such as the relation between phases of a beam, canceling and reinforcing by using phase shifts, may not apply to application of electric fields by TNSSs because they use low frequencies. Instead, examples use beam selection to move or shift or shape an electric field, also described as field steering or field shaping, by activating different electrodes, such as from an array of electrodes, to move the field. Selecting different combinations of electrodes from an array may result in beam or field steering. A particular combination of electrodes may shape a beam and/or change the direction of a beam by steering. This may shape the electric field to reach a target nerve selected for stimulation.
• Activation of Nerves by Electric Fields
• Typically, selectivity in activating nerves has required electrodes to be implanted surgically on or near nerves. Using electrodes on the surface of the skin to focus activation selectively on nerves deep in the tissues, as with examples of the invention, has many advantages. These include avoidance of surgery, avoidance of the cost of developing complex implants and gaining regulatory approval for them, and avoidance of the risks of long-term implants.
• The features of the electric field that determine whether a nerve will be activated to produce an action potential can be modeled mathematically by the “Activating Function” disclosed in Rattay F., “The basic mechanism for the electrical stimulation of the nervous system”,NeuroscienceVol. 89, No. 2, pp. 335-346 (1999). The electric field can produce a voltage, or extracellular potential, within the tissues that varies along the length of a nerve. If the voltage is proportional to distance along the nerve, the first order spatial derivative will be constant and the second order spatial derivative will be zero. If the voltage is not proportional to distance along the nerve, the first order spatial derivative will not be constant and the second order spatial derivative will not be zero. The Activating Function is proportional to the second-order spatial derivative of the extracellular potential along the nerve. If it is sufficiently greater than zero at a given point it predicts whether the electric field will produce an action potential in the nerve at that point. This prediction may be input to a nerve signature.
• In practice, this means that electric fields that are varying sufficiently greatly in space or time can produce action potentials in nerves. These action potentials are also most likely to be produced where the orientation of the nerves to the fields change, either because the nerve or the field changes direction. The direction of the nerve can be determined from anatomical studies and imaging studies such as MRI scans. The direction of the field can be determined by the positions and configurations of electrodes and the voltages applied to them, together with the electrical properties of the tissues. As a result, it is possible to activate certain nerves at certain tissue locations selectively while not activating others.
• To accurately control an organ or muscle, the nerve to be activated must be accurately selected. This selectivity may be improved by using examples disclosed herein as a nerve signature, in several ways, as follows:
• • (1) Improved algorithms to control the effects when a nerve is stimulated, for example, by measuring the resulting electrical or mechanical activity of muscles and feeding back this information to modify the stimulation and measuring the effects again. Repeated iterations of this process can result in optimizing the selectivity of the stimulation, either by classical closed loop control or by machine learning techniques such as pattern recognition and artificial intelligence;
  • (2) Improving nerve selectivity by labeling or tagging nerves chemically; for example, introduction of genes into some nerves to render them responsive to light or other electromagnetic radiation can result in the ability to activate these nerves and not others when light or electromagnetic radiation is applied from outside the body;
  • (3) Improving nerve selectivity by the use of electrical conductors to focus an electric field on a nerve; these conductors might be implanted, but could be passive and much simpler than the active implantable medical devices currently used;
  • (4) The use of reflectors or refractors, either outside or inside the body, is used to focus a beam of electromagnetic radiation on a nerve to improve nerve selectivity. If these reflectors or refractors are implanted, they may be passive and much simpler than the active implantable medical devices currently used;
  • (5) Improving nerve selectivity by the use of feedback from the person upon whom the stimulation is being performed; this may be an action taken by the person in response to a physical indication such as a muscle activation or a feeling from one or more nerve activations;
  • (6) Improving nerve selectivity by the use of feedback from sensors associated with the TNSS, or separately from other sensors, that monitor electrical activity associated with the stimulation; and
  • (7) Improving nerve selectivity by the combination of feedback from both the person or sensors and the TNSS that may be used to create a unique profile of the user's nerve physiology for selected nerve stimulation.
• Potential applications of electrical stimulation to the body, as previously disclosed, are shown inFIG.15.
• Referring toFIG.25A, a TNSS934 human and mammalian interface and its method of operation and supporting system are managed by a Master Control Program (“MCP”)910 represented in function format as block diagrams. It provides the logic for the nerve stimulator system in accordance to one example.
• In one example, MCP910 and other components shown inFIG.25A are implemented by one or more processors that are executing instructions. The processor may be any type of general or specific purpose processor. Memory is included for storing information and instructions to be executed by the processor. The memory can be comprised of any combination of random access memory (“RAM”), read only memory (“ROM”), static storage such as a magnetic or optical disk, or any other type of computer readable media.
• Master Control Program
• The primary responsibility of MCP910 is to coordinate the activities and communications among the various control programs, a Data Manager920, a User932, and the external ecosystem and to execute the appropriate response algorithms in each situation. The MCP910 accomplishes electric field shaping and/or beam steering by providing an electrode activation pattern to TNSS device934 to selectively stimulate a target nerve. For example, upon notification by a Communications Controller930 of an external event or request, the MCP910 is responsible for executing the appropriate response, and working with the Data Manager920 to formulate the correct response and actions. It integrates data from various sources such as Sensors938 and external inputs such as TNSS devices934, and applies the correct security and privacy policies, such as encryption and HIPAA required protocols. It will also manage the User Interface (UI)912 and the various Application Program Interfaces (APIs)914 that provide access to external programs.
• MCP910 is also responsible for effectively managing power consumption by TNSS device934 through a combination of software algorithms and hardware components that may include, among other things: computing, communications, and stimulating electronics, antenna, electrodes, sensors, and power sources in the form of conventional or printed batteries.
• Communications Controller
• Communications controller930 is responsible for receiving inputs from the User932, from a plurality of TNSS devices934, and from 3rd party apps936 via communications sources such as the Internet or cellular networks. The format of such inputs will vary by source and must be received, consolidated, possibly reformatted, and packaged for the Data Manager920.
• User inputs may include simple requests for activation of TNSS devices934 to status and information concerning the User's932 situation or needs. TNSS devices934 will provide signaling data that may include voltage readings, TNSS934 status data, responses to control program inquiries, and other signals. Communications Controller930 is also responsible for sending data and control requests to the plurality of TNSS devices934.3rd party applications936 can send data, requests, or instructions for the Master Control Program910 or User932 via the Internet or cellular networks. Communications Controller930 is also responsible for communications via the cloud where various software applications may reside.
• In one example, a user can control one or more TNSS devices using a remote fob or other type of remote device and a communication protocol such as Bluetooth. In one example, a mobile phone is also in communication and functions as a central device while the fob and TNSS device function as peripheral devices. In another example, the TNSS device functions as the central device and the fob is a peripheral device that communicates directly with the TNSS device (i.e., a mobile phone or other device is not needed).
• Data Manager
• The Data Manager (DM)920 has primary responsibility for the storage and movement of data to and from the Communications Controller930, Sensors938, Actuators940, and the Master Control Program910. The DM920 has the capability to analyze and correlate any of the data under its control. It provides logic to select and activate nerves. Examples of such operations upon the data include: statistical analysis and trend identification; machine learning algorithms; signature analysis and pattern recognition, correlations among the data within the Data Warehouse926, the Therapy Library922, the Tissue Models924, and the Electrode Placement Models928, and other operations. There are several components to the data that is under its control as disclosed below.
• The Data Warehouse (DW)926 is where incoming data is stored; examples of this data can be real-time measurements from TNSS devices934 or from Sensors (938), data streams from the Internet, or control and instructional data from various sources. The DM920 will analyze data, as described above, that is held in the DW926 and cause actions, including the export of data, under MCP910 control. Certain decision making processes implemented by the DM920 will identify data patterns both in time, frequency, and spatial domains and store them as signatures for reference by other programs. Techniques such as EMG, or multi-electrode EMG, gather a large amount of data that is the sum of hundreds to thousands of individual motor units and the typical procedure is to perform complex decomposition analysis on the total signal to attempt to tease out individual motor units and their behavior. The DM920 will perform big data analysis over the total signal and recognize patterns that relate to specific actions or even individual nerves or motor units. This analysis can be performed over data gathered in time from an individual, or over a population of TNSS Users.
• The Therapy Library922 contains various control regimens for the TNSS devices934. Regimens specify the parameters and patterns of pulses to be applied by the TNSS devices934. The width and amplitude of individual pulses may be specified to stimulate nerve axons of a particular size selectively without stimulating nerve axons of other sizes. The frequency of pulses applied may be specified to modulate some reflexes selectively without modulating other reflexes. There are preset regimens that may be loaded from the Cloud942 or 3rd party apps936. The regimens may be static read-only as well as adaptive with read-write capabilities so they can be modified in real-time responding to control signals or feedback signals or software updates. Referring to
• FIG.3, one such example of a regimen has parameters A=40 volts, t=500 microseconds, T=1 Millisecond, n=100 pulses per group, and f=20 per second. Other examples of regimens will vary the parameters within ranges previously specified.
• The Tissue Models924 is specific to the electrical properties of particular body locations where TNSS devices934 may be placed. As previously disclosed, electric fields for production of action potentials will be affected by the different electrical properties of the various tissues that they encounter. Tissue Models924 are combined with regimens from the Therapy Library922 and Electrode Placement Models928 to produce desired actions. Tissue Models924 be developed by MRI, Ultrasound or other imaging or measurement of tissue of a body or particular part of a body. This may be accomplished for a particular User932 and/or based upon a body norm. One such example of a desired action is the use of a Tissue Model924 together with a particular Electrode Placement Model928 to determine how to focus the electric field from electrodes on the surface of the body on a specific deep location corresponding to the pudendal nerve in order to stimulate that nerve selectively to reduce incontinence of urine. Other examples of desired actions may occur when a Tissue Model924 in combination with regimens from the Therapy Library22 and Electrode Placement Models928 produce an electric field that stimulates a sacral nerve. Many other examples of desired actions follow for the stimulation of other nerves.
• Electrode Placement Models928 specify electrode configurations that the TNSS devices934 may apply and activate in particular locations of the body. For example, a TNSS device934 may have multiple electrodes and the Electrode Placement Model928 specifies where these electrodes should be placed on the body and which of these electrodes should be active in order to stimulate a specific structure selectively without stimulating other structures, or to focus an electric field on a deep structure. An example of an electrode configuration is a 4 by 4 set of electrodes within a larger array of multiple electrodes, such as an 8 by 8 array. This 4 by 4 set of electrodes may be specified anywhere within the larger array such as the upper right corner of the 8 by 8 array. Other examples of electrode configurations may be circular electrodes that may even include concentric circular electrodes. The TNSS device934 may contain a wide range of multiple electrodes of which the Electrode Placement Models928 will specify which subset will be activated. The Electrode Placement Models928 complement the regimens in the Therapy Library922 and the Tissue Models924 and are used together with these other data components to control the electric fields and their interactions with nerves, muscles, tissues and other organs. Other examples may include TNSS devices934 having merely one or two electrodes, such as but not limited to those utilizing a closed circuit.
• Sensor/Actuator Control
• Independent sensors938 and actuators940 can be part of the TNSS system. Its functions can complement the electrical stimulation and electrical feedback that the TNSS devices934 provide. An example of such a sensor938 and actuator940 include, but are not limited to, an ultrasonic actuator and an ultrasonic receiver that can provide real-time image data of nerves, muscles, bones, and other tissues. Other examples include electrical sensors that detect signals from stimulated tissues or muscles. The Sensor/Actuator Control module950 provides the ability to control both the actuation and pickup of such signals, all under control of the MCP910.
• Application Program Interfaces
• The MCP910 is also responsible for supervising the various Application Program Interfaces (APIs) that will be made available for 3rd party developers. There may exist more than one API914 depending upon the specific developer audience to be enabled. For example many statistical focused apps will desire access to the Data Warehouse926 and its cumulative store of data recorded from TNSS934 and User932 inputs. Another group of healthcare professionals may desire access to the Therapy Library922 and Tissue Models924 to construct better regimens for addressing specific diseases or disabilities. In each case a different specific API914 may be appropriate.
• The MCP910 is responsible for many software functions of the TNSS system including system maintenance, debugging and troubleshooting functions, resource and device management, data preparation, analysis, and communications to external devices or programs that exist on the smart phone or in the cloud, and other functions. However, one of its primary functions is to serve as a global request handler taking inputs from devices handled by the Communications Controller930, external requests from the Sensor Control Actuator Module (950), and 3rd party requests936. Examples of High Level Master Control Program (MCP) functions are disclosed below.
• The manner in which the MCP handles these requests is shown inFIG.25B. The Request Handler (RH)960 accepts inputs from the User932, TNSS devices934, 3rd party apps936, sensors938 and other sources. It determines the type of request and dispatches the appropriate response as set forth in the following paragraphs.
• User Request: The RH960 will determine which of the plurality of User Requests961 is present such as: activation; display status, deactivation, or data input, e.g. specific User condition. Shown inFIG.25B is the RH's960 response to an activation request. As shown in block962, RH960 will access the Therapy Library922 and cause the appropriate regimen to be sent to the correct TNSS934 for execution, as shown at block964 labeled “Action.”
• TNSS/Sensor Inputs: The RH960 will perform data analysis over TNSS934 or Sensor inputs965. As shown at block966, it employs data analysis, which may include techniques ranging from DSP decision-making processes, image processing algorithms, statistical analysis and other algorithms to analyze the inputs. InFIG.25B two such analysis results are shown; conditions which cause a User Alarm970 to be generated and conditions which create an Adaptive Action980 such as causing a control feedback loop for specific TNSS934 functions, which can iteratively generate further TNSS934 or Sensor inputs965 in a closed feedback loop.
• 3rd Party Apps: Applications can communicate with the MCP910, both sending and receiving communications. A typical communication would be to send informational data or commands to a TNSS934. The RH960 will analyze the incoming application data, as shown at block972.FIG.25B shows two such actions that result. One action, shown at block974 would be the presentation of the application data, possibly reformatted, to the User932 through the MCP User Interface912. Another result would be to perform a User932 permitted action, as shown at976, such as requesting a regimen from the Therapy Library922.
• Referring toFIG.26, an example TNSS in accordance to one example is shown. The TNSS has one or more electronic circuits orchips2600 that perform the functions of: communications with the controller, nerve stimulation viaelectrodes2608 that produce a wide range of electric field(s) according to treatment regimen, one ormore antennae2610 that may also serve as electrodes and communication pathways, and a wide range ofsensors2606 such as, but not limited to, mechanical motion and pressure, temperature, humidity, chemical and positioning sensors. In another example, TNSS interfaces totransducers2614 to transmit signals to the tissue or to receive signals from the tissue.
• One arrangement is to integrate a wide variety of these functions into an SOC, system onchip2600. Within this is shown acontrol unit2602 for data processing, communications, transducer interface and storage and one ormore stimulators2604 andsensors2606 that are connected toelectrodes2608. Anantenna2610 is incorporated for external communications by the control unit. Also present is aninternal power supply2612, which may be, for example, a battery. An external power supply is another variation of the chip configuration. It may be necessary to include more than one chip to accommodate a wide range of voltages for data processing and stimulation. Electronic circuits and chips will communicate with each other via conductive tracks within the device capable of transferring data and/or power.
• The TNSS interprets a data stream from the control device, such as that shown inFIG.25A, to separate out message headers and delimiters from control instructions. In one example, control instructions contain information such as voltage level and pulse pattern. The TNSS activates thestimulator2604 to generate a stimulation signal to theelectrodes2608 placed on the tissue according to the control instructions. In another example the TNSS activates atransducer2614 to send a signal to the tissue. In another example, control instructions cause information such as voltage level and pulse pattern to be retrieved from a library stored in the TNSS.
• The TNSS receives sensory signals from the tissue and translates them to a data stream that is recognized by the control device, such as the example inFIG.25A. Sensory signals include electrical, mechanical, acoustic, optical and chemical signals among others. Sensory signals come to the TNSS through theelectrodes2608 or from other inputs originating from mechanical, acoustic, optical, or chemical transducers. For example, an electrical signal from the tissue is introduced to the TNSS through theelectrodes2608, is converted from an analog signal to a digital signal and then inserted into a data stream that is sent through theantenna2610 to the control device. In another example an acoustic signal is received by atransducer2614 in the TNSS, converted from an analog signal to a digital signal and then inserted into a data stream that is sent through theantenna2610 to the control device. In certain examples sensory signals from the tissue are directly interfaced to the control device for processing.
• An open loop protocol to control current to electrodes in known neural stimulation devices does not have feedback controls. It commands a voltage to be set, but does not check the actual Voltage. Voltage control is a safety feature. A stimulation pulse is sent based on preset parameters and cannot be modified based on feedback from the patient's anatomy. When the device is removed and repositioned, the electrode placement varies. Also the humidity and temperature of the anatomy changes throughout the day. All these factors affect the actual charge delivery if the voltage is preset.
• In contrast, examples of the TNSS stimulation device have features that address these shortcomings using the Nordic Semiconductor nRF52832 microcontroller to regulate charge in a TNSS. The High Voltage Supply is implemented using a LED driver chip combined with a Computer controlled Digital Potentiometer to produce a variable voltage. A 3-1 step up Transformer then provides the desired High Voltage, “VBOOST”, which is sampled to assure that no failure causes an incorrect Voltage level as follows. The nRF52832 Microcontroller samples the voltage of the stimulation waveform providing feedback and impedance calculations for an adaptive protocol to modify the waveform in real time. The Current delivered to the anatomy by the stimulation waveform is integrated using a differential integrator and sampled and then summed to determine actual charge delivered to the user for a Treatment. After every pulse in a Stimulation event, this measurement is analyzed and used to modify, in real time, subsequent pulses.
• This hardware adaptation allows a firmware protocol to implement the adaptive protocol. This protocol regulates the charge applied to the body by changing VBOOST. A treatment is performed by a sequence of periodic pulses, which insert charge into the body through the electrodes. Some of the parameters of the treatment are fixed and some are user adjustable. The strength, duration and frequency may be user adjustable. The user may adjust these parameters as necessary for comfort and efficacy. The strength may be lowered if there is discomfort and raised if nothing is felt. The duration will be increased if the maximum acceptable strength results in an ineffective treatment.
• A flow diagram in accordance with one example of the Adaptive Protocol disclosed above is shown inFIG.27. The Adaptive Protocol strives to repeatedly and reliably deliver a target charge (“Q_target”) during a treatment and to account for any environmental changes. Therefore, the functionality ofFIG.27 is to adjust the charge level applied to a user based on feedback, rather than use a constant level.
• The mathematical expression of this protocol is as follows:
• 
  Q_target=Q_target(A*dS+B*dT), whereAis the Strength Coefficient13 determined empirically, dS is the user change in Strength, B is the Duration Coefficient—determined empirically, and dT is the user change in Duration.
• The Adaptive Protocol includes two phases in one example:Acquisition2700 andReproduction2720. Any change in user parameters places the Adaptive Protocol in the Acquisition phase. When the first treatment is started, a new baseline charge is computed based on the new parameters. At a new acquisition phase at2702, all data from the previous charge application is discarded. In one example,2702 indicates the first time for the current usage where the user places the TNSS device on a portion of the body and manually adjusts the charge level, which is a series of charge pulses, until it feels suitable, or any time the charge level is changed, either manually or automatically. The treatment then starts. The mathematical expression of this function of the application of a charge is as follows:
• The charge delivered in a treatment is
• $Q_{\mathrm{target}}=\sum _{i=1}^{T*f}{Q}_{\mathrm{pulse}}\left(i\right)$
• Where T is the duration; f is the frequency of “Rep Rate”; Q_pulse(i) is the measured charge delivered by Pulse (i) in the treatment pulse train provided as a voltage MON_CURRENT that is the result of a Differential Integrator circuit shown inFIG.28 (i.e., the average amount of charge per pulse). The Nordic microcontroller ofFIG.28 is an example of an Analog to Digital Conversion feature used to quantify voltage into a number representing the delivered charge and therefore determine the charge output. The number of pulses in the treatment is T*f.
• At2704 and2706, every pulse is sampled. In one example, the functionality of2704 and2706 lasts for 10 seconds with a pulse rate of 20 Hz, which can be considered a full treatment cycle. The result ofphase2700 is the target pulse charge of Q_target.
• FIG.29 is a table in accordance with one example showing the number of pulses per treatment measured against two parameters, frequency and duration. Frequency is shown on the Y-axis and duration on the X-axis. The Adaptive Current protocol in general performs better when using more pulses. One example uses a minimum of 100 pulses to provide for solid convergence of charge data feedback. Referring to theFIG.29, a frequency setting of 20 Hz and duration of 10 seconds produces 200 pulses, which is desirable to allow the Adaptive Current Protocol to reproduce a previous charge.
• Thereproduction phase2720 begins in one example when the user initiates another subsequent treatment afteracquisition phase2700 and the resulting acquisition of the baseline charge, Q_target. For example, a full treatment cycle, as discussed above, may take 10 seconds. After, for example, a two-hour pause as shown atwait period2722, the user may then initiate another treatment. During this phase, the Adaptive Current Protocol attempts to deliver Q_targetfor each subsequent treatment. The functionality ofphase2720 is needed because, during thewait period2722, conditions such as the impedance of the user's body due to sweat or air humidity may have changed. The differential integrator is sampled at the end of each Pulse in the Treatment. At that point, the next treatment is started and the differential integrator is sampled for each pulse at2724 for purposes of comparison to the acquisition phase Q_target. Sampling the pulse includes measuring the output of the pulse in coulombs. The output of the integrator ofFIG.28 in voltage, referred to asMon_Current2801, is a direct linear relationship to the delivered charge in micro-coulombs and provides a reading of how much charge is leaving the device and entering the user. At2726, each single pulse is compared to the charge value determined in phase2700 (i.e., the target charge) and the next pulse will be adjusted in the direction of the difference.
• 
  NUM_PULSES=(T*f)
• After each pulse, the observed charge, Q_pulse(i), is compared to the expected charge per pulse.
• 
  Q_pulse(i)>Q_targetNUM_PULSES?
• The output charge or “VBOOST” is then modified at either2728 (decreasing) or2730 (increasing) for the subsequent pulse by:
• 
  dV(i)=G[Q_target/NUM_PULSES−Q_pulse(i)]
• where G is the Voltage adjustment Coefficient—determined empirically. The process continues until the last pulse at2732.
• A safety feature assures that the VBOOST will never be adjusted higher by more than 10%. If more charge is necessary, then the repetition rate or duration can be increased.
• In one example, in general, the current is sampled for every pulse duringacquisition phase2700 to establish target charge for reproduction. The voltage is then adjusted via a digital potentiometer, herein referred to as “Pot”, duringreproduction phase2720 to achieve the established target_charge.
• The digital Pot is calibrated with the actual voltage at startup. A table is generated with sampled voltage for each wiper value. Tables are also precomputed storing the Pot wiper increment needed for 1v and 5v output delta at each pot level. This enables quick reference for voltage adjustments during the reproduction phase. The tables may need periodic recalibration due to battery level.
• In one example, duringacquisition phase2700, the minimum data set=100 pulses and every pulse is sampled and the average is used as the target_charge forreproduction phase2720. In general, less than 100 pulses may provide an insufficient data sample to use as a basis forreproduction phase2720. In one example, the default treatment is 200 pulses (i.e., 20 Hz for 10 seconds). In one example, a user can adjust both duration and frequency manually.
• In one example, duringacquisition phase2700, the maximum data set =1000 pulses. The maximum is used to avoid overflow of 32bit integers in accumulating the sum of samples. Further, 1000 pulses in one example is a sufficiently large data set and collecting more is likely unnecessary.
• After 1000 pulses for the above example, the target_charge is computed. Additional pulses beyond 1000 in the acquisition phase do not contribute to the computation of the target charge.
• In one example, the first 3-4 pulses are generally higher than the rest so these are not used inacquisition phase2700. This is also accounted for inreproduction phase2720. Using these too high values can result in target charge being set too high and over stimulating on the subsequent treatments inreproduction phase2720. In other examples, more advanced averaging algorithms could be applied to eliminating high and low values.
• In an example, there may be a safety concern about automatically increasing the voltage. For example, if there is poor connection between the device and the user's skin, the voltage may auto-adjust at2730 up to the max. The impedance may then be reduced, for example by the user pressing the device firmly, which may result in a sudden high current. Therefore, in one example, if the sample is 500 mv or more higher than the target, it immediately adjusts to the minimum voltage. This example then remains inreproduction phase2720 and should adjust back to the target current/charge level. In another example, the maximum voltage increase is set for a single treatment (e.g., 10V). More than that should not be needed in normal situations to achieve the established target_charge. In another example, a max is set for VBOOST (e.g., 80V).
• In various examples, it is desired to have stability duringreproduction phase2720. In one example, this is accomplished by adjusting the voltage by steps. However, a relatively large step adjustment can result in oscillation or over stimulation. Therefore, voltage adjustments may be made in smaller steps. The step size may be based on both the delta between the target and sample current as well as on the actual VBOOST voltage level. This facilitates a quick and stable/smooth convergence to the target charge and uses a more gradual adjustments at lower voltages for more sensitive users.
• The following are the conditions that may be evaluated to determine the adjustment step.
• 
  delta-mon_current=abs(sample_mon_current−target_charge)
• If delta_mon_current>500 mv and VBOOST>20V then step=5V for increase adjustments
• (For decrease adjustments a 500 mv delta triggers emergency decrease to minimum Voltage)
• 
  If delta_mon_current>200 mv then step=1V
• 
  If delta_mon_current>100 mv and delta_mon_current>5%*sample_mon_current then step=1V
• In other examples, new treatments are started with voltage lower than target voltage with a voltage buffer of approximately 10%. The impedance is unknown at the treatment start. These examples save the target_voltage in use at the end of a treatment. If the user has not adjusted the strength parameter manually, it starts a new treatment with saved target_voltage with the 10% buffer. This achieves target current quickly with the 10% buffer to avoid possible over stimulation in case impedance has been reduced. This also compensates for the first 3-4 pulses that are generally higher.
• As disclosed, examples apply an initial charge level, and then automatically adjust based on feedback of the amount of current being applied. The charge amount can be varied up or down while being applied. Therefore, rather than setting and then applying a fixed voltage level throughout a treatment cycle, implementations of the invention measure the amount of charge that is being input to the user, and adjust accordingly throughout the treatment to maintain a target charge level that is suitable for the current environment.
• Obstructive Sleep Apnea
• In addition to the applications of the patch in accordance to example inventions disclosed above, in other example inventions, the patch is used to detect and then reduce/treat the number of apnea or hypopnea episodes during sleep, thereby improving the sleep architecture of individuals with obstructive sleep apnea (OSA) or obstructive sleep hypopnea. The behavior of these individuals is changed to provide better quality sleep, which in turn affects their behavior during daytime activities. In other example inventions, the patch is used for a diagnostic method and system to allow an individual to determine whether they exhibit symptoms of OSA, without having to consult a physician. Similarly, example inventions provide a method and system that physicians may offer to their patients to diagnose OSA without the complex and intrusive system of a conventional sleep study in a clinic
• In general, example inventions provide an integrated system in the form of the patch which may be placed on the skin of the user and be automatically activated and used with or without the help of a medical professional. The integrated system includes hardware and software to selectively stimulate nerves in the neck or lower jaw related to OSA, while also monitoring biometrics related to breathing, and also optionally measuring respiration or acoustic measurements using oximetry in some examples, and stimulating the hypoglossal nerve to relieve apnea to provide a closed-loop system.
• The hypoglossal nerve (HN) is the 12^thcranial nerve (CXII) that controls the muscles of the tongue, excepting the palatoglossus muscle. Two hypoglossal nerves descend from the brain through the hypoglossal canals, with one hypoglossal nerve lying along the underside of the tongue on each of the left and right sides of the tongue.
• The genioglossus is the muscle that controls the protrusion of the tongue and is innervated by the HN. It has a left and a right component. When components are stimulated, the center of the back of the tongue is depressed and the tongue protrudes forward. This opens the airway. When the muscle is relaxed, the airway may be obstructed. The two medial branches of the hypoglossal nerve innervate the two sides of the genioglossus muscle.
• Insufficient activation of the upper airway muscles leads to upper airway obstruction in individuals with obstructive sleep apnea. Increasing the activity in these muscles can reduce the obstructive air pressure, relieving restrictions on breathing, and improving sleep, while also reducing the severity of oxyhemoglobin desaturations.
• Known solutions to OSA include using implanted nerve stimulation to increases muscle activity related to OSA. This stimulation is applied to one or both of the hypoglossal nerves. In contrast, example inventions avoid implanted stimulation and implanted breathing monitoring in favor of transcutaneous monitoring of breathing and stimulation of the hypoglossal nerve, therefore avoiding any surgical procedures.
• FIG.30 is an obstructive sleep apnea suppression anddetection system3000 in accordance with one example.System3000 includes a Neck Topical Nerve Activator (TNA) device3010 (or “patch”3010) that includes a securing mechanism3012 (e.g., adhesive layer), and one ormore electrode pairs3014 with each pair having a positive electrode and a negative electrode, asensor3015, atag3017, apower source3016 and a processor/controller3018.System3000 further includes arespiration monitoring device3020, aposture indication device3030, asmart controller3040 with adisplay3042, and anacknowledgment button3044 and afob3050 with one ormore buttons3052.
• FIG.31A illustrates auser3100 with aneck3110, ajaw line3120, and anarea3130 behind the mandible.
• FIG.31B illustrates theuser3100 and asubmental triangle3140 below the chin.
• FIG.31C illustrates theuser3100 and an internal view of thehypoglossal nerve3150 and thesublingual nerve3160.
• FIG.31D illustrates theuser3100 and an internal view of thehypoglossal nerve3150, and thegenioglossus muscle3180 under thetongue3170.
• FIG.32 illustrates an example placement ofpatch3010 and other elements ofsystem3000 in accordance with one example. As shown inFIG.32,patch3010 is configured to be placed on either side of the neck, or on the jaw in one of several locations, such as thesubmental triangle3140, below thejawline3120, or behind themandible3130 and is situated to be able to accurately monitor biometrics related to breathing.Patch3010 is situated such that electrical stimulation may activate one or more branches of thehypoglossal nerve3140 on one or both sides of theneck3110 using electrical fields. Sensors may assist in placement, which can be the same sensors for detection/measurement of biometrics (e.g., ultrasound). Electrodes may be used to assist in placement. In embodiments,patch3010 is implemented using elements shown in the patch ofFIGS.4-9 above.
• Referring again toFIG.30,patch3010 is designed and configured in a shape to conform to the skin when affixed to the skin to be electronically effective at stimulating thehypoglossal nerve3140 and monitoring breathing.Patch3010 can be used for apnea detection as well as for delivering electrical stimulation.Patch3010 is electronically most effective for stimulation when the positive and negative electrodes are placed axially along the path of the nerve in contrast to transversely across the path of the nerve, which is not as electronically effective. The shape ofpatch3010 is designed to minimize discomfort for theuser3100 when affixed in the target location.
• In some examples,patch3010 uses oneelectrode pair3014 to activate thehypoglossal nerve3140 on one of the distal or lateral sides of theneck3110. In some examples,patch3010 uses twoelectrode pairs3014 to activate both the distal and lateral branches of thehypoglossal nerve3140 on theneck3110.
• In some examples,patch3010 uses multiple positive electrodes and one or more negative electrodes to activate one or both of the distal and lateral branches of thehypoglossal nerve3140, modifying the waveshapes or timings or both of the activation pulses from the multiple electrodes to direct the waveform energy at one or more specific points on the hypoglossal nerves. Various arrays of electrodes as disclosed above can be controlled to generate optimized stimulation. The stimulation can be adaptive based on feedback from sensors as disclosed above. The stimulation, in the form of electrical stimuli generated by the electrodes whenpatch3010 is activated, in examples include square waves having an amplitude between 10 and 100 volts, pulse widths between 100 and 500 microseconds, and a pulse repetition rate of between 2 and 60 pulses per second.
• In some examples,patch3010 uses adhesive surfaces to attach to the skin. In some examples, thepatch3010 is affixed to the underside of thejaw line3120 on one or both sides of the jaw, using its electrodes to activate thehypoglossal nerve3150 on one or both sides as the nerve enters the underside of thetongue3170 into thegenioglossus muscle3180.
• In some examples,patch3010 is affixed on the throat, in thesubmental triangle3140 which overlies the submental muscle, which lies below the mylohyoid, geniohyoid, and genioglossus muscles, using its electrodes to activate the innervation of thegenioglossus muscle3180, to cause thetongue3170 to push forward, opening the upper airway. Multiple negative and positive electrodes can be used, and beam steering, beam selection, and interferential stimulation can be used to select the targeted nerve deep inside the tissue.
• In some examples,patch3010 is affixed on the back of the jaw, behind themandible3130, using its electrodes to activate thehypoglossal nerve3150 before it is occluded by the muscles of the neck, the activations proceeding down the nerve into thegenioglossus muscle3180.
• In some examples,patch3010 is affixed to one of the left and right sides of the jaw line or back of the jaw, alternating to the opposite side of the jaw line or jaw on succeeding nights, or to a similar schedule, in order to activate the genioglossus muscle on both sides of the tongue to an equal degree when averaged across a series of days, while using apatch3010 that is small enough in dimensions to fit on one side of the body.
• The individual components of thesystem3000 may be connected as peer devices in a Body Area Network, passing each other signals and sharing the tasks of data recording, real-time analysis, and closed-loop monitoring of the user.
• In examples, activatingpatch3010 generates electrical charges on the electrodes to stimulate the genioglossus muscle, with the hypoglossal nerve, with the result being causing unconscious movement of the user's tongue, and “treating” the sleep apnea condition. In other examples, other nerves can be stimulated that cause movement of the tongue through a reflex (i.e., a rapid, involuntary response to a stimulus) and/or a reflex arc (i.e., the pathway traveled by the nerve impulses during a reflex). For example, the following reflexes cause the tongue to move in response to electrical stimulation:
• Glossopharyngeal/Hypoglossal reflex: Stimulation of the glossopharyngeal and superior laryngeal nerves results in the excitation of the genioglossus muscles. This reflex results in a protrusion of the tongue.
• Jaw/tongue reflexes: Opening of the jaw results in reflexive activity of the genioglossus muscle.
• Masseter Reflex: Stimulation of masseter afferents excites muscles which protrude the tongue, (primarily the genioglossus) and inhibits opposing muscles.
• Temporalis Reflex: Light pressure on temporalis muscle activates hypoglossal motoneurons that innervate the tongue muscles.
• Pharyngeal Reflex: Sensory mechanoreceptors located within the pharyngeal mucosa play an important role in the reflex which maintains upper airway patency. For example, pharyngeal negative pressure sensors activate dilatory muscles of the upper airway and help stabilize the airway.
• In some examples,patch3010 includes one or more sensors which measure internal features or biometrics of the user in the neck area, these measurements used to help the user to orient andplace patch3010 most accurately in the target location. The sensor data is communicated to one or more ofsmart controller3040,fob3050 andpatch3010, and an indication such as an LED or vibration is sent to the user to assist them in placing the device.
• For example, the orientation vertically or horizontally of thepatch3010 itself can be determined by a 9-axis accelerometer on the patch. The smart phone app can tell the user in real-time to rotate the patch to the proper orientation before sticking it to the skin. The shape ofpatch3010 can be designed in a shape to assist the user in orienting it properly. Further, a marking (e.g., an arrow meant to be vertical) could be printed on the patch or on a removable paper liner (so that the arrow is removed when the patch is actually applied).
• Further,patch3010 can be designed to accommodate multiple orientations. For example, the electrodes could be an array or series or matrix of sub-electrodes, and the patch could select which to use for effective stimulation based on the position and orientation of the patch. Similarly,patch3010 can include two microphones which could have their roles reversed if the patch were placed “upside down” on the skin.
• Further, the position ofpatch3010 on the neck/throat/submental region could be deduced after the patch is affixed to the skin by sensing through the skin with the on-board sensors, then notifying the user through the app that the patch is good or that it needs to be re-positioned. For example, the sound of the jugular vein could be detected; or the sound of air in the pharynx positioned between the 2 microphones.
• Further,patch3010 includeselectronic sensor3015, in a fixed placement onpatch3010 relative toelectrodes3014.Sensors3015 are used to detect the strength of the activation pulse at the target nerve through the use oftag3017 previously placed on or near the target nerve.Tag3017 responds to the activation signal fromelectrodes3014 to a degree proportional to the strength of the activation signal coupled into the target nerve, and sends this response topatch3010. The strength of this response is then used by the user to re-orient or movepatch3010 on the neck for optimum performance of the activation on the target nerve.Tag3017 may also reflect and/or absorb energy from thepatch3010 to activate a selected nerve.
• Respiration monitoring device3020 detects occurrences of interrupted breathing due to an apnea episode or hypopnea episode, and notifies one or more ofpatch3010, orsmart controller3040, orfob3050 of such an episode. In some examples,respiration monitoring device3020 measures the airflow during inspiration or expiration or both. In some examples,respiration monitoring device3020 measures other biometric attributes of theuser3100 to determine the beginning of an apnea episode. Examples of these measurements may be blood oxygenation level, oximetry; or cessation of motion in the airway or lungs; or change in the audio signal from movement of air into and out of the lungs.
• OSA has traditionally been diagnosed through a sleep study, or polysomnography, usually performed in a clinic setting with multiple electrodes monitoring multiple body parameters, including attaching multiple wired sensors and equipment such as thoracic belts, nasal flow meters to the body which interfere with natural sleep and thus the accuracy of true sleep measurements. However, requests for home screening tests are rising because of comfort and cost issues. The “STOPBANG” scale has been used to provide guidance to those individuals assumed to be at high risk for moderate to severe OSA, with the acronym defined as Snoring; Tiredness in daytime; Observation by third party of stopped breathing; high blood Pressure; Body Mass Index (BMI) greater than 35; Age over 50; Neck circumference greater than 16 inches; and male Gender. A STOPBANG score of 3 or more indicates a home test or sleep study should be performed, especially since up to 80% of people with OSA do not know they have apnea.
• In some examples, OSA suppression anddetection System3000 includespatch3010 and respiration monitoring device (RMD)3020.RMD3020 includes one or more accelerometers, a CO2 sensor, an oximeter, and an audio sensing device. The accelerometer detects rhythmic movements of respiration, or the lack of such movement. The CO2 sensor detects the carbon dioxide content airflow due to inspiration or exhalation. The oximeter monitors the saturation of peripheral oxygen (SpO2). The audio sensing device detects the sounds of snoring, body motion in bed, and background noise. Measuring airflow may include use of Doppler by laser, or ultrasonically, which could measure through the trachea rather than nasally.
• RMD3020 can be positioned at various locations on the body, depending upon which sensor and which body parameters are measured. For example, anRMD3020 that includes an accelerometer can be positioned on the chest to detect rhythmic breathing patterns, or on the neck in the submental region, or on the lower neck at the suprasternal notch; whereas anRMD3020 including a CO2 sensor or an audio sensor can be positioned near the outside of the nasal passageway.
• In some examples,RMD3020 is a separate unit frompatch3010, which can be positioned at various anatomical locations around the body away frompatch3010. In some examples,RMD3020 is integrated withinpatch3010, with all elements coupled to a common substrate, and can monitor specific body signals at the same location aspatch3010. In some examples,RMD3020 is a separate patch-like device with all elements coupled to a common substrate that is a different substrate than withpatch3010.
• In some examples,RMD3020 may send data related to respiration tosmart controller3040 during the user's sleep period while the stimulation function ofpatch3010 is not activated, this data being collected to determine if the user exhibits signs of obstructive sleep apnea. In someexamples RMD3020 is a separate unit, attached to one or more of the user's chest, or abdomen, or nasal opening, and detects breathing status with one or more sensors, such as accelerometers, and communicates data tosmart controller3040. In some examples,RMD3020 is a part of an integratedOSA suppression system3000, co-located withinpatch3010 and coupled to the same substrate as the other components.
• Posture indication device3030, worn by the user, detects changes in the user's body position as the position relates to sleeping or not sleeping, such as standing, or sitting, or prone, using one or more sensors, such as accelerometers, and notifies one or more ofpatch3010, orsmart controller3040, orfob3050 of such position change, thereby indicating the start or end of a sleep period. The specification of a sleep period may also be determined by other signals such as time of day, location of the user, amount of activity, posture, and other signals.
• In some examples,user3100 indicates explicitly their position as prone versus non-prone onsmart controller3040 through the use ofdisplay3042 oracknowledgment button3044, or withfob3050, or other means. When smart controller is informed of the user's prone position, such as at bedtime,smart controller3040 putspatch3010 andrespiration monitoring device3020 into a state of monitoring apnea episodes. Whensmart controller3040 is informed of the user's non-prone position or awake position, such as during daylight activities,smart controller3040 puts patch and respiration monitoring device into a state of standby, no longer monitoring apnea episodes.
• In some examples, whenuser3100 indicates explicitly their position tosmart controller3040,posture indication device3030 is not used, or the decision ofposture indication device3030 is overridden by the user's explicit input, such as when intending to sleep in a sitting position in a chair.
• In some examples,smart controller3040 determines the prone position ofuser3100 without the use of theposture indication device3030, such as through the use of a GPS, an accelerometer and other sensors attached to the user or separate from the user such as in the bed, analyzing data from these features internal tosmart controller3040. For example, the location ofsmart controller3040 orfob3050, or both, at the bedside or in the bed for longer than a pre-set time limit may be used as an indicator that the user is in the bed and in a prone position.
• In some examples,user3100 is prompted by and indicates tosmart controller3040 the locations in which the user sleeps, such as a bed in a bedroom, such that the data on locations collected in this manner bysmart controller3040 allowssmart controller3040 to determine when the user is in those new locations at a later time, such as when visiting another home or traveling.
• In examples, the monitoring performed byRMD3020, or any other elements, includingpatch3010 itself, may detect the “trailing edge” of an apnea event, or the “leading edge” of an apnea event. The latter is preferred in order to trigger a stimulation to cut short or eliminate that apnea event.
• InFIG.32,OSA suppression system3000 includespatch3010 and respiration monitoring device (RMD)3020.RMD3020 may be a separate unit or integrated withinpatch3010. It may also includesmart controller3040 orfob3050.OSA system3000 may or may not includeposture indication device3030.User3100 may indicate to patch3010 orsmart controller3040 orfob3050 directly when the user is beginning a sleep period and again when the user is ending a sleep period. During the sleep period, whenRMD3020 senses an OSA episode,RMD3020 then signals3012 tosmart controller3040 orfob3050 that the apnea should be suppressed usingpatch3010.Smart controller3040 then signals3214 patch to activate the nerve via electrodes.Smart controller3040 can also optionally signal3216 to fob3050 to record such an activation event that the apnea is suppressed for a period of time. In other examples,patch3010, withintegrated RMD3020, can detect and automatically activate the nerve without needing any other components.
• In some examples,smart controller3040, orfob3050, or both, is in control of a second person, such as a sleep partner, or a person sleeping in or near the user, or a caregiver, or a medical service provider such as in a nursing home. Whenrespiration monitoring device3020 detects an apnea episode, a notification is sent tosmart controller3040 orfob3050, whereupon the second person may activate the user'spatch3010 to address the apnea episode.
• In some examples, the second person may activate the stimulator based upon visual and auditory clues arising from the sleeping individual. The second person can also observe the effects of stimulation upon the user, and record reactions, either electronically insmart controller3040 or infob3050, or manually such as in a sleep diary.
• In some examples, multiple other persons may be notified of an apnea episode byrespiration monitoring device3020, such as in a skilled nursing facility with multiple medical personnel or a personal physician or a research clinician.
• In some examples, the second person may monitor and respond to the signals from multiple users' OSA suppression and detection systems, or from a database of historical recordings of the user's sleep patterns, or a database of a large population of anonymized user sleep recordings that have been analyzed with pattern recognition or artificial intelligence (AI) techniques including machine learning and deep learning techniques.
• In some examples, OSA suppression anddetection systems3000 use AI techniques such as correlation analysis to correlate real-time data recordings of the user with larger population databases to produce comparative or predictive analyses. In some examples, machine-learning algorithms are employed to build up the user's sleep history and provide specific predictors of sleep apnea severity and associated conditions.
• In some examplesOSA suppression system3000 may use electrocardiogram (ECG), or encephalogram (EEG), or other means to detect the user is in the state of rapid eye movement (REM) sleep, or in non-REM sleep, and the system may apply apnea treatments in a manner appropriate to each type of sleep.
• In some examples,respiration monitoring device3020 may signal directly topatch3010 to automatically suppress the apnea episode, bypassingsmart controller3040.Patch3010,respiration monitoring device3020,posture indication device3030,smart controller3040, andfob3050 may be combined in a variety of ways to implement anOSA suppression system3000. In some examples, theuser3100 usesfob3050 to send data and controls tosmart controller3040.
• In some examples,user3100 usesfob3050 to send data and controls to patch3010. In some examples,user3100 usessmart controller3040 directly, and afob3050 is not used. In some examples,fob3050 communicates data and controls withsmart controller3040 or to patch3010, or both, through wireless means. In some examples,smart controller3040 is implemented by a smartphone with functionality and apps as described above.
• In some examples,user3100 does not wearpatch3010, orrespiration monitoring device3020, or both, when in the non-prone or waking state. In some examples, analysis ofrespiration monitoring device3020 measurements andposture indication device3030 measurements is performed by one or both ofpatch3010 andsmart controller3040.
• In some examples, the communication of data and control amongsmart controller3040,patch3010,respiration monitoring device3020, andposture indicator device3030 may be by wireless means through the use of Bluetooth Low Energy (BLE), Wi-Fi, or other means.
• In some examples,respiration monitoring device3020 andposture indicator device3030 may be combined into one unit with a common processor and common power source, data and control betweenrespiration monitoring device3020 andposture indicator device3030 being in this case through wired or wireless means. This combined unit may communicate data and control withsmart controller3040 andpatch3010 through wireless means.
• In some examples,respiration monitoring device3020 andposture indicator device3030 andsmart controller3040 may be combined into one unit with a common processor and common power source, data and control betweenrespiration monitoring device3020 andposture indicator device3030 andsmart controller3040 being in this case through wired or wireless means. This combined unit may communicate data and control withpatch3010 through wireless means.
• In some examples,respiration monitoring device3020 andposture indicator device3030,smart controller3040, andpatch3010 may be combined into one unit with a common processor and common power source, data and control between respiration monitoring device and the Posture Indicator Device and the Smart Controller andpatch3010 being in this case through wired means.
• Thepatch power source3016,respiration monitoring device3020 andposture indicator device3030,smart controller3040 andfob3050 may be powered by battery or rechargeable means.
• In some examples,patch3010 sends an activation signal to the relevant nerve and repeats this signal according to a timer preset by theuser3100, the interval between electrode activations being selected to effectively suppress apnea episodes according to the user's preference.
• In some examples, analysis of measurements from one or both of thesmart controller3040 andrespiration monitoring device3020 may be performed by processing in a remote server, in the cloud, or on a computer separate fromsmart controller3040 but local to the user, such as a personal computer.
• In some examples, theOSA suppression system3000 measures the user's sleep schedule over a period of days or weeks or longer, noting the clock time when the user begins the sleep period and the clock time when the user wakes during or at the end of the sleep period. The system analyzes this data and determines the most effective clock times to activateOSA suppression system3000.
• In some examples,OSA suppression system3000 collects time-based records of a user's sleep. These records are used to build a database of anonymized sleep period information from large populations ofOSA suppression system3000 users, or with recordings of sleep periods from other detection systems.
• In some examples, the time-based records of sleep periods are supplemented with data entered manually by one or more observers of the user's sleep. The data recorded in the time-based database is sent to the cloud through a local network, such as a home mesh network, or directly over the Internet.
• Sleep Studies
• Sleep studies that employ polysomnography are typically used to diagnose sleep disorders. Polysomnography monitors brain waves (EEG), blood oxygen levels, heart rate, breathing, and eye and leg movements. These tests are generally conducted in sleep clinics and require overnight observation by trained sleep technicians as well as physicians. During the sleep study, if apnea is observed, the patient is awakened and a continuous positive airway pressure (CPAP) device is applied to the patient to continue to observe and record the same biometric signals while under the CPAP treatment.
• FIG.33 illustrates a conventional polysomnography (PSG)system3300.System3300 includes a number of sensors and wires attached touser3301 while sleeping, including a set ofleg movement sensors3310 with wires, asnoring sensor microphone3320, anambient noise microphone3322, anEEG electrode3330, one or morebreathing detection belts3340, and anairway sensor3350. As shown inFIG.33, the wires connecting the sensors toPSG Controller3360 may interfere with the user's sleep, or the measurements may be adversely affected by user movement, or the measurements may be stopped due to disconnection of one or more sensor due to User movement.
• FIG.34 illustrates an example of signals captured during a sleep period. Snoring is detected alongsnoring signal3410; Breathing is detected alongnasal flow signal3420, andthermistor signal3430; User movement is detected alongabdomen signal3440, andthorax signal3442; respiratory airflow volume is detected alongXFlow signal3450, and SpO2oxygen saturation signal3460.
• FIG.35 illustrates measurements showing biometric data during a sleep study. The graph shows how only the nasal/oral airflow signal3530 indicates a sleep apnea event without trailing the sleep apnea event, such as is shown by theoxygen saturation signal3560 and theEMG signal3520 which are trailing signals. The other signals include: theEEG3510, thethoracic movement signal3540, and theabdominal movement signal3550—do not distinctively indicate a sleep apnea event.
• FIG.36 illustrates measurements showing biometric data during a sleep study. The graph shows how airflow, measured by the nasal and oralair flow signal3620, the nasalair flow signal3622, thethorax chest effort3630, theabdominal effort3632, and thecalculated air flow3640 all indicate a sleep apnea event without trailing the sleep apnea event as is shown by theEEG signal3610. The other signals: the bloodoxygen saturation signal3650, and theheart rhythm signal3660—do not distinctively indicate a sleep apnea event.
• FIG.37 illustrates measurements showing biometric data during a sleep study. Apnea events are strongly indicated coincident by breathing airflow measurements3750, and somewhat indicated coincident by breathing effort measurements3760; but either are not clearly indicated or only indicated after the onset of a sleep apnea event byEEG measurements3710, Electroculogram (EOG)measurements3720,Electromyelogram measurements3730, andpulse oximetry measurements3740.
• FIG.38 illustrates measurements showing biometric data during a sleep study. Apnea events are only indicated after the event byEMG measurements3810,EEG measurements3820,EKG measurements3830, andblood chemistry measurements3860. Thethermocouple measurements3840, from which air flow is calculated, andCO2 levels3850 correlate with coincident timing to sleep apnea events.
• A novel discovery/conclusion in embodiments that is deduced from the graphs shown inFIGS.34-38 is that measurement of breathing air flow is sufficient to indicate a sleep apnea event at a time coincident with the event and not trailing in time after the event has begun.
• In embodiments,system3000measures user3100 and analyzes the measured data and detects sleep apnea events in a manner which allowspatch3010 to stimulateuser3100 and limit the duration of the sleep apnea event. The physiological impact of OSA onuser3100 is reduced by shortening or eliminating sleep apnea events.
• FIG.39 illustrates functionality ofsystem3000 when repeatedly measuring one or more physiological metrics onuser3100, and then passing thismeasurement data3910 tosmart controller3040.Smart controller3040 manipulatesmeasurement data3910 usingOSA analysis module3920, which mathematically assesses the pattern of breathing (or “breathing parameters”) and determines if an expected breath has not been performed by the user.Smart controller3040 continues to collectmeasurement data3910 while executingOSA analysis module3920.
• In some examples,OSA analysis module3920 compares the times of breaths and missed breaths against one or more breath limits3922. If breathing is not detected before the limit or limits have been reached, thenOSA analysis module3920 sets anapnea event flag3930.
• In some examples,OSA analysis module3920 compares the formats of breaths against abreath template3924 that stores “normal” non OSA breathing patterns of the user. If the format of breathing falls outside of the bounds ofbreath template3924, thenOSA analysis module3920 sets anapnea event flag3930.
• Usingbreath template3924, example analysis can detect an OSA event on the occurrence of a first breath which is not a normal breath. For example, the upper airway begins to close during the end of a breath, preceding the obstruction of air flow which will prevent the next breath from occurring. When this closure begins, usually by lapse of tone in the genioglossus, the measurement values of the present breath begin to diverge from the normal measured values. The divergence may be measured as a “whistle” (i.e., change in frequency content), or reduction in amplitude (i.e., change in energy content) during the exhalation phase of this last breath.
• OSA system3000 detects this divergence and concludes that an OSA event is about to begin (i.e., that the next breath will be blocked).OSA system3000 can then stimulate the user immediately, to re-open the airway by movement of the genioglossus. The OSA event is therefore avoided. The Apnea Hypopnea Index (AHI) number for the user will therefore not count an OSA event at this time and the AHI will be lowered. The anatomical effect of OSA will be reduced. AsOSA3000 system detects multiple imminent OSA events and prevents them, the AHI and anatomical effect is significantly reduced. AHI is a key parameter calculated to show the severity of obstructive sleep apnea in a person
• Example inventions reduce AHI. Specifically, the breathing tempo for many users is 12-20 breaths per minute; the time gap from one breath to the next may be 3-5 seconds. Concluding that an OSA event is occurring only after the first missed breath may mean that 3 seconds or more may have already passed. Therefore, example inventions, as disclosed, can detect an apnea event generally before a first breath is missed.
• However, by detecting an imminent OSA event during the last normal breath and/or at the first missing breath,OSA system3000 can reduce the stopped breathing interval to less than 10 seconds, thereby disqualifying it as an “apnea event”, and therefore not counting toward the AHI. Reducing the duration of an event will also reduce the effect on SpO2, thereby disqualifying the event as a “hypopnea” event, and therefore not counting toward the AHI.
• In some examples,OSA analysis module3920 compares the times of breaths and missed breaths against data from apopulation pattern3926 of other users ofpatch3010.Population pattern3926 may be assembled from previous use data fromuser3100; orpopulation pattern3926 may be assembled from previous use data across a group of users, in some examples also including in the derivation ofpopulation pattern3926 an analysis of user metrics separate from breathing such as age, weight, body mass index, and the like. If breathing falls outside the boundaries ofpopulation pattern3926, thenOSA analysis module3920 setsapnea event flag3930.
• In some examples,OSA analysis module3920 includes a combination ofbreath limits3922,breath template3924 andpopulation pattern3926 to perform the analysis ofmeasurement data3910.
• System3000 monitorsapnea event flag3930. Whenapnea event flag3930 is set, then OSAevent notification module3940 sends one or more control signals or notifications topatch3010.Patch3010 reacts by initiating a nerve stimulation onuser3100 such thatuser3100 resumes inhalation and exhalation.
• In some examples, whensystem3000 detects that breathing has not resumed after a nerve stimulation,system3000 sends additional signals or notifications to patch3010, to initiate a second or subsequent stimulation event.
• In some examples,system3000 uses adata logging module3950 to log the preceding apnea event with at least a time stamp and an indication of whether the apnea event was curtailed or not. The information in the log of events may be used bysmart controller3040 to modify the choice of mathematical analyses from among the set of analytic processes insystem3000, to improve performance.
• OSA analysis module3920 includes software or firmware processes which may be executed by one or more ofpatch3010,smart controller3040, a computer separate fromsmart controller3040, or in the cloud.
• In some examples, some or all ofbreath limits3922,breath template3924 andpopulation pattern3926 are derived using machine learning. Training data sets can also be assembled from large numbers of user recordings of their nightly sleeping signals and patterns.
• In some examples, some or all ofbreath limits3922,breath template3924 andpopulation pattern3926 are derived using artificial intelligence algorithms.
• Breath limits3922,breath template3924 andpopulation pattern3926 or any other analytics can take as inputs data from other biometric devices such as smartwatches, smart patches or medical devices (either implanted or topical). The data can be acquired either directly in a point-to-point manner using wireless or wired means, or over BAN (Body Area Networks). Further, data from other devices can be acquired via the cloud or through the device's own data repositories.
• Further, embodiments can implement adaptive control, as disclosed above, of the detection-stimulation closed loop, where the control is adapted continuously based onbreath limits3922,breath template3924 and/orpopulation pattern3926. This control can be based upon real-time analytics and/or a “Behavior Library” which originates from the control unit or the cloud, and is similar to the libraries and models shown inFIG.25A. The libraries can either be resident onpatch3010, or dynamically downloaded from the controller or cloud. The libraries include a Treatment Library, a Tissue Library and a Placement (location on the body) Library. The “Behavior Library” is the result of the AI/ML algorithms over large training sets or from other data analysis approaches. The Behavior Library is used in the predictive identification of oncoming apnea events, both obstructive as well as hypopnea events.
• UsingOSA system3000, when an apnea event is observed by the system, stimulation can immediately be provided by the system and monitored throughRMD3020. Use ofOSA system3000 avoids awakening the user to administer CPAP to observe the effects of treatment. Thus, a sleep study with recording of basic OSA signals such as with theRMD3020 can be done at home without the artifacts possibly introduced by a sleep clinic.
• Further, the convenient and comfortable use ofOSA system3000 allows the system to collect data over a longer period of time without undue interference with sleep or other inconvenience when compared to conventional PSG systems.
• As disclosed, examples allow OSA to be detected using only breathing parameters rather than additional non-breathing parameters used by more traditional testing. The detection of OSA using only breathing parameters can be done at the leading edge of an OSA event, thus leading to automatic treatment through stimulation. Analytics allows an individual's breathing parameters to be measured and identified and compared to a signature to provide a tailored treatment (i.e., by varying stimulation time and amount). Further, examples monitor OSA to determine the effectiveness of a stimulation treatment and this feedback can be used to modify the stimulation parameters.
• Placement of the Patch for OSA Treatment
• FIG.40 illustrates anatomical features that are related to the placement ofpatch3010 in accordance to example inventions. Thetongue3170 is shown protruding beyondmandible3130. Thegenioglossus muscle3180 is anchored to the anterior mandible and produces tongue protrusion when activated by pulling forward. Thegeniohyoid muscle4010 opens the mouth when activated, if thehyoid bone4020 remains stationary. Thestyloglossus muscle4050 retractstongue3170 toward the airway when activated, which is not an effect useful for treating OSA. Themylohyoid muscle4030 pulls on the hyoid bone when activated, pulling the mandible down.
• FIG.41A illustrates a placement of one of a set of neck relatedpatches3010 in accordance to example inventions. As shown, eachpatch3010 is placed on or nearsubmental triangle3140 to affect specific nerves and muscles.Patch3010 is placed axially along the hypoglossal nerve that innervatesgenioglossus muscle3180, either bilaterally with two or more pairs of electrodes, or as a single pair of electrodes. Placement is at the anterior end ofhypoglossal nerve3150, to avoid activation ofstyloglossus muscle4050.
• In one example,patch3010 placement is on thesubmental triangle4130 at the front or back of the median4110 and4112, or both, to activategenioglossus muscle3180.
• In another example,patch3010 placement is to the left or right of median4120 and4122, or both, to activatemylohyoid muscle4030.
• In another example,patch3010 placement is to the left or right margins ofsubmental triangle4130, or both, to activategenioglossus muscle3180 through thesmaller digastric muscles4020, which do not affect the shape oftongue3170.
• FIG.41B illustrates asingle patch3010, withmultiple electrodes4110, singly or in pairs, to activate one or more nerves in accordance to example inventions.
• FIGS.42A and42B illustrate the anatomical features related to the placement ofpatch3010 atmandible3130 in accordance to example inventions. As disclosed,genioglossus muscle3180 contracts when activated byhypoglossal nerve3150.Genioglossus muscle3180 andgeniohyoid muscle4010 are anchored to the mandible at themental spine4250.Geniohyoid muscle4010 is attached at the twoinferior spines4240.Genioglossus muscle3180 is attached at the twosuperior spines4242.
• FIGS.43A and43B illustrate the orientation related to the placement of a chin based patch at thechin4320 in accordance to example inventions. In the example ofFIGS.43A and B,patch3010 has been designed as a “chin patch”device4310 to extend from theneck3110, undermandible3130, abovehyoid4020; up acrosschin4320, ending at thelower lip4330, to affect specific nerves and muscles.
• Chin patch4310 uses aprimary electrode4312 and asecondary electrode4314 to create an electrical field which is oriented to cross axially alonggeniohyoid muscle4010, and to intersect the anterior end ofgenioglossus muscle3180, to avoid activation ofstyloglossus muscle4050.
• In one example, one or both ofprimary electrode4312 andsecondary electrode4314 are divided into multiple sub-electrodes, these sub-electrodes being energized using voltages, timings and waveform shapes to refine the direction of the electric field.
• FIGS.43C and43D illustrate the orientation related to the placement of a mandible based patch atmandible3130 in accordance to example inventions.Patch3010 has been designed as amandibular patch device4310 to extend fromneck3110, undermandible3130, abovehyoid4020, up acrosschin4320; overlower lip4330, ending atinner gum line4250 of the mandible after crossing overlower teeth4352 to affect specific nerves and muscles.
• FIG.43C illustrates a view looking forward through the tissues of the right side of the face in accordance to example inventions.FIG.43C illustratesgenioglossus muscle3180,genioglossal nerve3150, and other nearby structures, withprimary electrode4312 between thelower gum line4250 and thelower teeth4252. InFIG.43C, thesecondary electrode4314 is partially hidden behind the curve of the jaw.
• FIG.43D illustrates the view looking outward from inside the mouth, through the tissues of the lower jaw, limited at the top by thelower teeth4352 in accordance to example inventions.FIG.43D illustratesprimary electrode4312 inside the lower jaw at the inner gum line, behind the main body of thepatch4310, and showssecondary electrode4314 on the posterior surface ofpatch4310, facing the skin at theneck3110.
• Patch4310 usesprimary electrode4312 andsecondary electrode4314 to create an electrical field which is oriented to cross axially alonggeniohyoid muscle4010, and to intersect the anterior end ofgenioglossus muscle3180, to avoid activation ofstyloglossus muscle4050.
• An example, one or both ofprimary electrode4312 andsecondary electrode4314 are divided into multiple sub-electrodes, these sub-electrodes being energized using voltages, timings and waveform shapes to refine the direction of the electric field.
• The use of sub-electrodes couples energy efficiently into the target tissues, such asgenioglossus muscle3180 andgeniohyoid muscle4010, while passing effectively through or around other tissues, such asmandible3130 andlower teeth4352, these tissues being obstructive to electrical energy due to their higher electrical impedances than the impedances of the target nerves and muscles.
• As an example,mandibular patch4310 has an interior stiffening element extending through the curved portion overlower teeth4352, this stiffener holdingmandibular patch4310 securely tolower teeth4352 while worn byuser3100 by using a clasping force directed to one or both of the anterior and posterior sideslower teeth4250.
• In another example,mandibular patch4310 has an adhesive surface extending through the curved portion overlower teeth4250, this adhesive holdingmandibular patch4310 securely tolower teeth4250 while worn byuser3100 by using an adhesive selected to resist the moisture and movement in this area of user's3100 mouth while also being temporary, such thatuser3100 can removemandibular patch4310 after use.
• In examples,patch3010 is applied to the skin from 1 to 5 centimeters below the user's3100jaw line3120. In examples,patch3010 is designed in a shape to appear as a shape of equal size on the left and right sides on the neck when properly affixed to the skin, so that the electrical stimulation is effective through the tissue.
• In examples,patch3010 is designed in a shape to appear as a shape with unequal size on the left and right sides on the neck when properly affixed to the skin, the underlying design ofpatch3010 arrangingelectrode pairs3014 so that the stimulation is effective through the tissue.
• Placement ofpatch3010 ontojaw line3120 may be difficult for some users due to the angle of view to that part of their anatomy. For some users, aligning the device to one or more specific anatomical features, such as the tip of the chin, may provide sufficient guidance to properly position the device. For some users, additional prompts may be required.
• In examples, a separate device, such as a smart phone or camera, is mounted on a surface or held by the user or held by a second person, and provides a view of the target area forpatch3010 such that the user or a second person may accurately placepatch3010 on the skin.
• In examples, a mark or indicator onpatch3010 is used by the user to align the device properly on the neck. In examples, a template is provided touser3100, including markings or indicators on the template to simplify positioning of the template in the prescribed position on the neck. The template is used to provide a marked location for proper positioning ofpatch3010. The template is removed from the skin after proper placing ofpatch3010.
• In examples, the template is disposable and used one time byuser3100. In examples, the template is reusable and saved byuser3100 for repeated use in aligning andpositioning patch3010 on the neck.
• In examples,patch3010 initiates a low-intensity stimulation intended to trigger a perceptible sensation in the user if and only if the device is properly positioned on the skin. This sensation may be a muscle twitch, a tingling, or similar, which provides no purpose except as a confirmation of positioning. The user may, after affixing the device to the skin and feeling no sensation, pull the device off of the skin and reposition it, repeating this process until the sensation is felt and the device is properly positioned.
• OSA Treatment
• FIG.44 illustrates example stimulation waveforms for treating OSA in accordance with example inventions.Patch3010 stimulates the one or more nerves using a series of electrical pulses in a pattern ofpulse sequence4400 with a specific frequency, waveform, intensity and duration.Pulses4410 are applied at an intensity below that level which stimulates a painful sensation and below that level which wakesuser3100.
• In examples, each pulse has a pulsehigh time4420, a pulselow time4422, apulse period4424, and apulse amplitude4426.Pulses4410 may be monopolar pulses orbipolar pulses4440. For monopolar pulses, thepulse period4424 is the sum of the pulsehigh time4420 and the pulselow time4422. Bipolar pulses have anegative pulse width4442 and anegative pulse amplitude4444, for the purpose of balancing the DC bias of the sequence of stimulation pulses, and for the purpose of balancing for zero net energy into the tissues. The negative pulse width may differ from the pulse high time. The negative pulse amplitude may differ from the pulse amplitude. Pulse shapes are affected by the impedance coupling to the user's tissues and by thepatch3010 output impedance, internal drive strength, and other factors, such that the pulses, whether monopolar or bipolar, may not be square waves.
• One or more of the pulsehigh time4420, the pulselow time4422, thepulse period4424, and thepulse amplitude4426 may be adjusted. Forbipolar pulses4440, thenegative pulse width4442 andnegative pulse amplitude4444 may be adjusted from one user to another user, or from one application of a device to another on the same user. The pulse pattern may be adjusted during the course of a treatment.
• Pulses may be output inbursts4430. Each burst has two ormore pulses4410, orbipolar pulses4440. Each burst has a burstpulse count4432 and aburst period4434. One or both of the burst pulse count and the burst period are adjustable for each user, or from one application of a device to another on the same user. The pulse frequency is the inverse of the pulse period. The burst frequency is the inverse of the burst period.
• Pulses or bursts may be adjusted by each user each time apatch3010 is applied, since effective intensity may be different according to skin condition, dampness, dryness, weight change, specific location of placement and other factors. In this manner, the electrical pattern of stimulation pulses is adjusted for each application/treatment.
• As an example, the applied frequency of thestimulation pulses4410 may be in the range of 2 Hz to 50 Hz, and the current applied may be up to 10 milliamps. Further,pulses4410 singly or inbursts4430 may have pulsehigh times4420 in the range of 100 to 500 microseconds, and pulselow times4422 in the range of 100 to 500 microseconds, with burst frequency and pulse frequency for single pulses in the range of 2 Hz to 50 Hz, and the current applied is in the range 0.1-10 mA.
• In examples, the pulses within one burst may all be of equal width. In examples, the pulses within one burst may be of varying widths, the width adjusted to optimize the stimulation for effectiveness.
• In examples, the pulses within one burst may be evenly spaced. In examples, the pulses within one burst may be unevenly spaced.
• In examples, the pulses within one burst may have consistent amplitude. In examples, the pulses within one burst may have unequal amplitudes.
• As such, the intensity of the applied pulses is adjusted for each user and may be adjusted and applied by each user each time patch3010 (or any other patches disclosed herein) is applied, since effective intensity may be different according to skin condition, dampness, dryness, weight change, specific location of placement and other factors. In this manner, the electrical pattern of stimulation pulses is adjusted for each application.
• As an example,processor3018 adjusts the intensity of applied pulses, or the duration of application, or both, using data from the monitoring device or devices, such asRMD3020, included in OSA detection andstimulation system3000 ofFIG.30.
• As another example,smart controller3040 adjusts the intensity of applied pulses, or the duration of application, or both, using data exchanged withpatch3010 and itsprocessor3018. The exchanged data includes data from the monitoring device or devices included in OSA detection andstimulation system3000 ofFIG.30.
• As another example, one or both ofpatch3010 andsmart controller3040 adjusts the intensity or the duration of the applied pulses, or both, anduser3100 adjusts the intensity and the duration of the applied pulses, or both, with all adjustments limited to preset ranges.
• In an example, one or more of the intensity, the pulse high time, the pulse low time, the pulse count per burst, and the burst count are adjusted by one or more ofpatch3010,smart controller3040 anduser3100.
• In an example, one or more of pulse rise time, pulse fall time, pulse overshoot, and pulse undershoot are adjusted by one or both ofpatch3010 andsmart controller3040. Changes in pulse shape, including one or more of rise time, fall time, overshoot and undershoot, allow the patch to optimize use of power during the application of a treatment protocol. Optimizing the power used in a treatment allows a patch with a given design to apply more stimulation when compared to a patch without the means to optimize power delivery. Pulse shape is limited by one or both of patch and smart controller such that delivered energy, rate of energy delivery, magnitude of currents and/or voltages all meet the requirements for effective nerve stimulation at the applied position.
• In an example, one or both ofpatch3010 andsmart controller3040 operate to select one of a variety of hardware configurations, each hardware configuration on the patch specified to limit one or more of pulse rise time, pulse fall time, pulse overshoot, and pulse undershoot. One example uses a bank of capacitors, switched into the pulse application circuit under control of the patch, to optimize the load and its effect on the driven pulse voltage and current. A second example uses a bank of inductive loads. A third example uses a bank of resistive loads.
• Nerve Pathway Placement and Stimulation
• In example inventions, instead of applying electrical stimuli in the neck or jaw area to treat OSA, one or more of several nerves in different locations on the body may be stimulated to activate a reflex arc or other nerve pathway which activates the hypoglossal nerve to suppress the apnea event. Reflex arcs can be monosynaptic or polysynaptic. In a monosynaptic reflex arc, the afferent neuron synapses directly on the efferent neuron. In a polysynaptic reflex arc, there are one or more intermediate neurons that transmit either inhibitory or excitatory signals to the efferent neuron that innervates the target muscle.
• The reflex arcs or other nerve pathways of interest in example inventions are those that cause excitatory signals to be transmitted to the efferent neuron, the hypoglossal nerve, that controls the movement of the tongue, the genioglossus muscle. Many reflex arcs are processed in the spinal cord where the afferent neuron enters through the dorsal horn of the vertebrae and synapses directly or indirectly on a peripheral efferent neuron.
• Similar monosynaptic or polysynaptic reflex arcs extend from sensory nerves, through the spinal column, to the midbrain, then to efferent cranial nerves. Stimulation of the glossopharyngeal and superior laryngeal nerves results in the excitation ofgenioglossus muscle3180, causing tongue protrusion.
• FIGS.45A and45B illustrate the use ofpatch3010 on the sural nerve of the leg to treat OSA in accordance to example inventions. Stimulation of the sciatic nerve, particularly in theleg4510 at thesural nerve4520, either by way of direct stimulation of afferent fibers or by continuous leg muscle contractions, activates central neurons of the respiratory midbrain, which integrates and further processes the neural signals to affect tongue movement.
• FIGS.46A and46B illustrate the use ofpatch3010 on the masseter nerve in the jaw, and on the temporal nerve and muscle in the head to treat OSA in accordance to example inventions. The temporomandibular joint (“TMJ”)4620 is innervated withsensory nerves4610, consisting of branches of the trigeminal (mandibular nerve) and masseteric nerves. Jaw movement is highly regulated by numerous sensory receptors in the TMJ. A jaw/hypoglossal reflex causes the opening of the jaw, which increases activity of thegenioglossus muscle3180 and results in tongue protrusion. Light pressure on theanterior temporalis muscle4630 activates mechanoreceptors in the temporalis muscles, which activate the hypoglossal motoneurons that innervate the tongue muscles, resulting in protrusion of the tongue. The sensory nerves may also be activated by electrical stimulation.
• FIG.46B showspatch3010 placed on the same location to activate thesensory nerves4610.
• As disclosed, examples detect and then treat OSA using electrical stimulation that is generated and applied viapatch3010. In general, for a neck oriented treatment, patch is placed on or nearsubmental triangle3140 and axially along the hypoglossal nerve. In other examples, the patch is placed on a user's chin or on a user's mandible. In other examples, other locations can be used with reflex arc. The electrical stimulation applies pulses having an intensity that is automatically adjusted for each user and each application by the user due to changing conditions.
• Several examples are specifically illustrated and/or described herein. However, it will be appreciated that modifications and variations of the disclosed examples are covered by the above teachings and within the purview of the appended claims without departing from the spirit and intended scope of the invention.

Claims (1)

What is claimed is:

1. A method of treatment for obstructive sleep apnea (OSA) of a user, the method comprising:

affixing a patch externally on a dermis of the user, the patch comprising a flexible substrate, a processor directly coupled to the substrate, and electrodes directly coupled to the substrate;

detecting an occurrence of OSA;

activating the patch in response to the detecting, the activating comprising generating an electrical stimuli via the electrodes in a first shape and a first direction and applying the electrical stimuli to a first portion of a nerve of the user; and

the activating comprising, based on sensing, generating the electrical stimuli in a second shape different than the first shape and/or a second direction different then the first direction and applying the electrical stimuli to a second portion of the nerve different than the first portion of the user.

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