Systems and methods for improving sleep disordered breathing

Abstract

Systems and methods for improving sleep disordered breathing include delivering a stimulating neuromodulation signal to a neck loop to stimulate activation of the neck loop governing one or more sublingual muscles. A blocking neuromodulation signal may be delivered to the neck loop to block activation of outgoing fibers that govern one or more supralingual muscles. The blocking neuromodulation signal may mitigate undesired reverse outgoing activation of one or more supralingual muscles.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Application No. 63 / 357,137, filed on June 30, 2022, the entire contents of which are incorporated herein by reference. Technical Field

[0003] The present disclosure relates to systems and methods for improving sleep-disordered breathing via neuromodulation by applying a combination of blocking neuromodulation signals and stimulatory neuromodulation signals. Background Art

[0004] Sleep disordered breathing (SDB) occurs when there are multiple episodes of partial or complete cessation of breathing throughout the night. Obstructive sleep apnea (OSA) is a type of SDB that involves the cessation or significant reduction of airflow in the presence of respiratory effort. This is the most common type of SDB and is characterized by recurrent episodes of upper airway collapse during sleep, causing repeated pauses in breathing followed by decreased oxygen saturation or neural arousals. The pathophysiology of OSA may involve factors such as craniofacial anatomy, airway collapsibility, and neuromuscular control of the upper airway dilator musculature. Electromyographic studies have shown that the tone and phasic activity of the pharyngeal airway dilator muscles (such as the genioglossus) gradually decrease from wakefulness to non-rapid eye movement to rapid eye movement.

[0005] Continuous positive airway pressure (CPAP) therapy is the first-line treatment for OSA. CPAP therapy utilizes a machine designed to deliver a constant flow of air pressure to keep the airway open continuously in patients with OSA, which typically includes an airflow generator, a catheter, and a mask. However, the success of CPAP therapy is limited by reported compliance rates ranging from 50% to 70%. Hypoglossal nerve stimulation (HNS) has now been established as an effective form of therapy for patients with obstructive sleep apnea (OSA) who cannot tolerate positive airway pressure. This therapy works by protruding and stiffening the tongue muscles to expand the pharyngeal airway. However, only a small portion of patients with OSA have an anatomical structure suitable for hypoglossal nerve stimulation therapy, because many patients continue to suffer from airway collapse even when the hypoglossal nerve musculature is stimulated. Summary of the invention

[0006] The present disclosure provides a neuromodulation system and method for improving SDB by applying various combinations of stimulatory neuromodulation signals and blocking neuromodulation signals to various neural target sites. In one aspect, a neuromodulation system for improving sleep-disordered breathing may include a processor and a non-transitory computer-readable medium storing executable instructions that can be executed by the processor. Such executable instructions may include directing the delivery of stimulatory neuromodulation signals to the cervical loop to stimulate activation of the cervical loop that innervates one or more infrahyoid muscles, and directing the delivery of blocking neuromodulation signals to the cervical loop to block activation of efferent fibers that innervate one or more suprahyoid muscles, the blocking neuromodulation signal relieving undesired reverse efferent activation of one or more suprahyoid muscles.

[0007] In another aspect, the present disclosure provides a method for improving SDB in a patient with SDB. This method may include delivering a stimulatory neuromodulation signal to the cervical loop to stimulate activation of the cervical loop that innervates one or more infrahyoid muscles. The method may also include delivering a blocking neuromodulation signal to the cervical loop to block activation of efferent fibers innervating one or more suprahyoid muscles, the blocking neuromodulation signal relieving undesired reverse efferent activation of one or more suprahyoid muscles. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 is a block diagram depicting illustrative components of a neuromodulation system according to one aspect of the present disclosure.

[0009] Figure 2 is a block diagram depicting illustrative components of a neuromodulation system according to one aspect of the present disclosure.

[0010] Figure 3 A flow chart depicting illustrative steps for a method of improving SDB in a patient suffering from SDB. DETAILED DESCRIPTION

[0011] The present disclosure relates to a neuromodulation system and method for improving SDB. In particular, the system and method include delivering a neuromodulation signal that activates a neural target site and delivering a neuromodulation signal that blocks a neural target site. Blocking a neural target site refers to inhibiting neuronal action potentials. For example, the present disclosure provides a system and method for directional stimulation of the cervical loop, the hypoglossal nerve, the glossopharyngeal nerve, the pharyngeal plexus and / or its branches, or a suitable combination thereof to activate a desired target muscle. In addition, the present disclosure provides a system and method for directional blocking of an undesirable motor target of the cervical loop, a motor target of the hypoglossal nerve, an afferent sensory component of the glossopharyngeal nerve, or a suitable combination thereof. Non-limiting examples of SDB are increased upper airway resistance, including snoring, upper airway resistance syndrome (UARS), sleep apnea, and combinations thereof. Sleep apnea may include OSA, central sleep apnea (CSA), and complex sleep apnea. Mentioning "improving" a patient's SDB includes treating SDB, reducing the symptoms of SDB, alleviating SDB, or preventing SDB. In some aspects, the system and method for improving the SDB of the patient are preventive, rather than reactive. In other words, the system or method for improving the SDB of the patient according to some aspects relates to preventing SDB, rather than detecting, for example, apnea or hypopnea events and responding to such detected events. By preventing SDB, the treatment system or method can reduce the possibility of airway collapse, rather than reacting to the recorded events. Patients with SDB include mammals such as humans. As used herein with respect to the elements described, unless otherwise stated, the terms "one", "an" and "the" include at least one or more of the elements described. In addition, unless otherwise stated, the terms "or" and "and" refer to "and / or" and combinations thereof. As used herein, "patient" includes mammals such as humans. The term "machine learning" may refer to one or more statistical techniques (or algorithms) to gradually improve the performance of a specific task without explicit programming. Instructions that can be executed by a processor may be executed by the same processor or multiple processors.

[0012] refer to Figure 1In one aspect, the present disclosure provides a neuromodulation system for improving SDB in a patient, the neuromodulation system having at least one neuromodulation device having at least one electrical contact implanted or positioned in the patient's body. The system 10 may include a processor 12 and a non-transitory memory 14 storing computer-readable instructions 16, which, when executed by the processor 12, causes the at least one neuromodulation device to perform various functions. The computer-readable instructions may include algorithms for performing the functions, and machine learning 18 may be employed. The instructions may include directing the delivery of stimulatory neuromodulation signals to the cervical loop to stimulate activation of the cervical loop innervating one or more infrahyoid muscles. The delivery may be directed to, for example, one or both of the superior and inferior roots of the cervical loop, and efferent / motor fibers may be activated to activate one or more infrahyoid muscles. Without wishing to be bound by a particular mechanism of action, it is believed that activation of the infrahyoid muscles (e.g., tightening these muscles) may reduce upper airway compliance (e.g., stiffening the upper airway) by pulling the thyroid cartilage and / or hyoid bone caudally along with their respective pharyngeal muscle attachments. Upper airway compliance may indicate the likelihood of airway collapse and may be relevant to treating SDB.The processor may directionally deliver stimulatory neuromodulation signals to activate one or more infrahyoid muscles, including the sternohyoid muscle, the sternothyroid muscle, the omohyoid muscle, the thyrohyoid muscle, or a suitable combination thereof.

[0013] The instructions may also include directing the delivery of blocking neuromodulation signals to the cervical loop to block the activation of the efferent fibers that innervate one or more suprahyoid muscles to relieve the undesired retrograde efferent activation of one or more suprahyoid muscles that pull the hyoid bone and thyroid cartilage forward and / or upward. The delivery may be directed to, for example, the upper root of the cervical loop. In some aspects, the instructions include directing the delivery of blocking neuromodulation signals to the cervical loop to block the activation of the efferent fibers that innervate the geniohyoid muscle. Relieving the undesired retrograde efferent activation of one or more suprahyoid muscles is advantageous because their contraction can inhibit or counteract the desired caudal movement of the thyroid cartilage and / or hyoid bone achieved by the activation of the infrahyoid muscle.

[0014] The processor may also execute instructions to deliver stimulatory neuromodulation signals to the hypoglossal nerve in a directed manner to stimulate the genioglossus muscle. In particular, the stimulatory neuromodulation signals may activate the efferent / motor fibers of the hypoglossal nerve to activate the genioglossus muscle. Activation of the hypoglossal nerve may cause contraction of the desired tongue musculature, thereby reducing or eliminating pharyngeal obstruction caused by posterior collapse of the tongue root by displacing the tongue forward. Such obstruction may not be treatable by cervical loop stimulation alone.

[0015] In some aspects, the processor may execute instructions to deliver blocking neuromodulation signals to the hypoglossal nerve to block activation of efferent fibers innervating the styloglossus muscle, the hyoglossus muscle, or both. The blocking neuromodulation signals may alleviate undesirable efferent activation of the styloglossus muscle, the hyoglossus muscle, or both. Alleviating undesirable efferent activation of the styloglossus muscle, the hyoglossus muscle, or both may be advantageous because they retract the tongue toward the posterior pharyngeal wall, thereby counteracting the desired anterior displacement.

[0016] The processor can also execute instructions to deliver stimulatory neuromodulation signals to the glossopharyngeal nerve to stimulate the activation of the efferent fibers of the glossopharyngeal nerve. Such efferent fibers can control one or more pharyngeal contractile muscles or stylopharyngeal muscles to activate one or more pharyngeal contractile muscles, stylopharyngeal muscles or both. For example, the processor can deliver stimulatory neuromodulation signals to the pharyngeal plexus or its branches. When activated, such one or more pharyngeal contractile muscles can increase the firmness of the pharyngeal muscles by hardening the pharyngeal wall, thereby reducing pharyngeal airway collapse. Pharyngeal wall hardening without complete contraction may make the stimulation of the cervical loop and hypoglossal nerve more effective. Regarding the stylopharyngeal muscle, when it is activated, the stylopharyngeal muscle can move the pharyngeal wall laterally, and can increase the airway caliber, and can also offset the pharyngeal narrowing component (pharyngeal narrowing component) of contractile muscle activation that may occur when the muscle activation exceeds the initial pharyngeal wall hardening.

[0017] In some aspects, the processor may execute instructions to deliver a blocking neuromodulatory signal to the glossopharyngeal nerve to block activation of afferent fibers of the glossopharyngeal nerve. The blocking neuromodulatory signal may alleviate undesirable afferent / sensory effects. Alleviating undesirable afferent activation is advantageous because afferent activation of central nervous system receptors may cause neural arousal during sleep or may cause undesirable muscle activation through an afferent / efferent reflex arc, such as activation of the pharyngeal gag reflex.

[0018] In some aspects, the processor can execute instructions to deliver stimulatory neuromodulation signals to a neural site, such as the pharyngeal plexus or its branches, to stimulate activation of the palatoglossus, palatopharyngeus, or both. Electrical stimulation of the neural sites innervating the palatoglossus and / or palatopharyngeus during sleep can expand the retropalatal space, thereby opening the patient's upper airway without causing sleep arousals. Such a system can be used for patients with isolated palate collapse, or in combination with hypoglossal nerve stimulation, cervical loop stimulation, phrenic nerve stimulation, and other neuromodulation systems as part of a multi-stage airway therapy for SDB such as OSA.

[0019] In certain aspects, the processor may execute instructions to deliver stimulatory neuromodulation signals to the phrenic nerve in a directed manner to stimulate activation of the phrenic nerve to activate the diaphragm. Phrenic nerve stimulation may affect upper airway collapse, or may be used to treat central sleep apnea. Stimulating the phrenic nerve in isolation may cause airway collapse, rather than prevent it, because the descent of the diaphragm may essentially create a negative pressure gradient within the pharyngeal lumen, which may cause collapse before a stabilizing effect is achieved. Simultaneous stimulation of the cervical loop and phrenic nerve may provide a greater degree of ability to control airway collapse than either stimulation in isolation by providing personalized control of tail traction and chest expansion during the respiratory cycle.

[0020] In some aspects, the processor may execute instructions to utilize suitable neuromodulation parameters to directionally deliver any suitable combination of the stimulatory neuromodulation signals and / or blocking signals described above. Non-limiting examples of neuromodulation parameters include electrical contact selection (such as which electrical contacts of the neuromodulation device provide stimulatory neuromodulation signals and which electrical contacts provide blocking neuromodulation signals), stimulation mode, signal pulse waveform, signal pulse width, signal pulse frequency, signal pulse phase, signal pulse polarity, signal pulse amplitude, signal pulse intensity, signal pulse duration, duty cycle, and combinations thereof. The process may continue until a therapeutic effect with minimal side effects is achieved.

[0021] The process may also be assisted by machine learning 18. Machine learning 18 may include algorithms that can be trained to recognize certain effects from the delivery of neuromodulation signals. Machine learning 18 may allow for active adjustment of neuromodulation parameters of the neuromodulation signal to provide a therapeutic effect with minimal side effects. Machine learning may employ one or more machine learning algorithms, such as decision tree learning, association rule learning, artificial neural networks, deep learning, inductive logic programming, support vector machines, clustering, Bayesian networks, reinforcement learning, representation learning, similarity and metric learning, sparse dictionary learning, genetic algorithms, rule-based machine learning, learning classifier systems, feature selection, and the like.

[0022] Regarding the specific details of the systems provided herein, the processor may include one or more microprocessors controlled by a suitable software program. The processor may control various neuromodulation parameters of the neuromodulation device, such as stimulation mode, electrical contact selection, signal pulse waveform, signal pulse width, signal pulse frequency, signal pulse phase, signal pulse polarity, signal pulse amplitude, signal pulse intensity, signal pulse duration, duty cycle, and combinations thereof. The processor may be programmed to transmit various currents and voltages to the electrical contacts to modulate the activity of a neural target site such as a nerve, neuron, or nerve fiber. The processor may be programmed to control multiple electrical contacts independently or in various combinations as needed to provide neuromodulation therapy.

[0023] The electrical neuromodulation signal can be constant, intermittent, variable and / or modulated with respect to current, voltage, pulse width, waveform, duty cycle, frequency, amplitude, etc. The waveform can be a sine wave, square wave, triangle wave, etc. The type of neuromodulation can vary and involve different waveforms. The optimal stimulation pattern may require delaying the activation of one electrical contact before activating another electrical contact, or delaying the activation of one electrical contact in another coordinated manner to improve the patient's SDB, whether this involves staggering the activation of the electrical contacts in a coordinated, adjustable manner or activating the electrical contacts simultaneously. With respect to the stimulatory signal, illustratively, the signal can have an amplitude ranging from about 0.1 mA to about 5 mA, a pulse width between about 30 μs to about 250 μs, a pulse frequency between about 30 Hz to about 50 Hz, a queue length between about 0.1 s to about 5 s, and a queue interval encoded as a time ranging from about 0.1 s to about 5 s or a queue interval encoded as a percentage of the queue length. With respect to the blocking signal, illustratively, the signal can have an amplitude ranging from about 0.1 mA to about 5 mA, a pulse width between about 100 μs and 1000 μs, a frequency ranging from about 1 Hz to about 60 kHz, and timing parameters between 1 μs and 250 μs so that the blocking signal is synchronized with the appropriate phase of a complementary stimulation signal delivered simultaneously to the same target nerve.

[0024] A neuromodulation system may include electronic circuits, such as one or more electronic circuits for delivering neuromodulation signals, enclosed in a sealed housing and coupled to a neuromodulation device, such as a cuff electrode, electrical leads, or other form factor neuromodulation device having electrical contacts. Figure 2 is a block diagram of a neuromodulation system 20 according to one aspect of the present disclosure. The neuromodulation system 20 may include a housing 22 enclosing a processor 24 and associated memory 26, a telemetry module 28, and a pulse generator 30 in electrical communication with electrical contacts 32A and 32B of the neuromodulation device. The neuromodulation system 20 may also include a power source 34.

[0025] The neuromodulation device can have different form factors, such as an injectable microstimulator, a nerve cuff electrode, a cylindrical lead, a paddle lead, or a transcutaneous patch. In addition, as described above, multiple target sites can be stimulated by the same neuromodulation device, or a single target site can be stimulated by a single neuromodulation device. Neuromodulation can be unilateral neuromodulation of these neural target sites, or bilateral neuromodulation of these neural target sites.

[0026] The electrical contacts 32 of the neuromodulatory device can be positioned along the outer surface of the housing 22 and can be coupled to the pulse generator 30 via an insulated feedthrough or other connection. In other embodiments, the electrical contacts 32 can be carried by the neuromodulatory device, which is a wire or insulated tether that is electrically coupled to the processor via an appropriate insulated feedthrough or other electrical connection through the sealed housing. In other embodiments, the electrical contacts can be incorporated into the housing, with the externally exposed surface adapted to be operably positioned near a target site proximate to a neural target site and electrically coupled to the processor. The electrical contacts can be controllable to provide an electrical signal that can be varied, for example, in voltage, frequency, amplitude, waveform, pulse width, current, intensity, duty cycle, polarity, duration, and combinations thereof. The electrical contacts can also provide positive and negative current from the electrical contacts, or can block current from the electrical contacts, or change the direction of current from the electrical contacts.

[0027] As described above, neuromodulatory devices (e.g., nerve cuff electrodes) can be placed on the same or different target sites. For example, if the target site includes two independent nerves or nerve segments, independent nerve cuff electrodes or other neuromodulatory devices can be placed on each nerve or nerve segment, wherein each nerve cuff electrode has its own cathode and anode, but is connected to the same processor, or independent nerve cuff electrodes are connected to the same processor, but one nerve cuff electrode is used as the cathode and the other nerve cuff electrode is used as the anode, wherein the generated electric field captures both nerves or nerve segments. In some embodiments, a neuromodulatory device configured to stimulate a nerve or nerve segment can be combined with a neuromodulatory device configured to stimulate another nerve or nerve segment. Alternatively, a neuromodulatory device configured to stimulate a nerve or nerve segment can be part of a device separate from a neuromodulatory device configured to stimulate another nerve or nerve segment.

[0028] The processor may include any one or more of a microprocessor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field-programmable gate array (FPGA), or an equivalent discrete or integrated logic circuit. In some examples, the processor may include multiple components, such as any combination of one or more microprocessors, one or more controllers, one or more DSPs, one or more ASICs, or one or more FPGAs, as well as other discrete or integrated logic circuits. The functions attributed to the processor herein may be embodied as software, firmware, hardware, or any combination thereof. The processor may be programmed to deliver electrical signals with various characteristics. As described above, the electrical signal may be constant, intermittent, variable, or modulated with respect to current, voltage, pulse width, waveform, period, frequency, amplitude, etc. The waveform may be a sine wave, a square wave, etc. The type of stimulation may vary and involve different waveforms. The optimal activation mode may require delaying one electrode before activating another electrode, or delaying one electrode in another coordinated manner to optimally open the airway, whether this involves staggered activation or simultaneous activation in a coordinated, adjustable manner.

[0029] Non-limiting examples of blocking neuromodulation signals include direct current (DC) blocking, kilohertz frequency alternating current block (kHFACb), anode blocking, collision blocking, quasi-trapezoidal stimulation, and low frequency alternating current block (LFACb). In the case of DC blocking, a ramp or DC current passes through a blocking electrical contact. However, this approach is associated with the possibility of producing toxic electrochemical byproducts, which may damage nerves. Alternatively or additionally, kHFACb is a method using a sinusoidal charged balanced waveform with a frequency range of from about 1 kHz to about 40 kHz that can be delivered. Because the waveform is a zero mean with a short cycle duration, the charge reverses itself and there is no net accumulated charge to avoid the possibility of nerve damage. In order to mitigate the effects from DC blocking and kHFACb, a blocking waveform composed of two blocking combinations can be generated. Charged balanced direct current (CBDC) carousal block is a method to mitigate initial activation, where blocking is achieved using ramped DC pulses or trapezoidal pulses that balance charge through long but equal charge discharging phases. In addition, high capacitance materials (e.g., Pt black) can be used to prevent the generation of reactive species. LFACb is a pure tone sinusoidal waveform modification of kHFACb distinguished by its amplitude and frequency. Phase blocking of the action potential can be achieved by reducing the frequency of the sinusoidal waveform to less than about 10 Hz and having a total current delivery amount less than that required for kHFACb.

[0030] The processor can be programmed to control the multiple electrical contacts independently or in various combinations as needed to provide neuromodulation. In one example, a neuromodulation therapy protocol for improving a patient's SDB can be stored or encoded as instructions in a memory that are executed by the processor to cause the pulse generator to deliver therapy via the electrical contacts in accordance with the programmed protocol. Thus, the neuromodulation device can be pre-programmed with the desired stimulation parameters. Although Figure 2 The processor shown in FIG. 1 is located internal to the neuromodulation device, but alternatively it may be an external controller such that the neuromodulation parameters are remotely modulated to the desired settings.

[0031] The memory 26 may include computer-readable instructions that, when executed by the processor 24, cause the neuromodulation device to perform various functions attributed to the neuromodulation device throughout the present disclosure. The computer-readable instructions may be encoded in the memory 26. The memory may include non-transitory computer-readable storage media, including any volatile, non-volatile, magnetic, optical, or electrical computer-readable storage media, such as random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically-erasable programmable ROM (EEPROM), flash memory, or any other digital media, with the sole exception of transitory propagating signals.

[0032] A telemetry module 28 and an associated antenna 36 may be provided for establishing two-way communication with an external device including, for example, a patient programmer and / or a physician programmer. Examples of communication technologies used by the neuromodulation system and the external device include low frequency or radio frequency (RF) telemetry, which may be, for example, an RF link established via Bluetooth, WiFi, or MICS. Antenna 36 may be located within, along, or extending outwardly from housing 22.

[0033] The power source 46 may be a battery or other power source. The battery may be recharged via inductive coupling. The power source may be internal to the neuromodulation device (e.g., Figure 2 ), in a remote location within or on the patient's body, or at a remote location remote from the patient's body. When located remote from the body, the neuromodulation device can be powered by bringing a power source external to the patient's body into contact with the patient's skin or at a location remote from the patient's body (e.g., where the power is first delivered through another medium). When the neuromodulation device is configured as an externally powered device, the power source can be worn by the patient during sleep to provide the power required to generate the stimulation pulses, or can be adjacent to the patient (e.g., one on the patient's bed, under the patient's pillow, one on the patient's nightstand, etc.). For example, the power source can be a battery-powered device including a primary coil for inductively transmitting power to a secondary coil included in the neuromodulation device. The power source can include one or more primary batteries or rechargeable batteries, and thus, illustratively, it can include a power adapter and plug for recharging in a standard 110V or 220V wall outlet. In some embodiments, when the neuromodulation device is embodied as a rechargeable or externally powered device, the functions required to transmit power to the neuromodulation device and the functions required to program the neuromodulation device to control therapy delivery can be implemented in a single external device.

[0034] The neuromodulation system may include other components such as an analog front end or analog-to-digital converter, multiplexers, and other components.

[0035] In another aspect, the neuromodulation system may include one or more sensors (not shown) to allow for open-loop or closed-loop control. For example, in an open-loop system, the system may include one or more sensors so that a patient can manage (e.g., preventively) improvements in SDB based on feedback (e.g., detected signals) from the sensors. Such detected signals may indicate the onset of SDB, such as changes in muscle or nerve electrical activity, tongue position, oropharyngeal airflow, etc. Once the signal is noticed, the patient can trigger or activate the neuromodulation device to prevent or alleviate SDB.

[0036] In another aspect, the neuromodulation system can include one or more sensors to allow closed-loop control, illustratively by automatically responding (e.g., by activating a neuromodulation device) in response to a sensed physiological parameter, or an associated symptom or sign indicative of the extent or presence of SDB. Physiological parameters include changes in muscle or nerve electrical activity, tongue position, changes in heart rate or blood pressure, changes in pressure in response to respiratory effort, oropharyngeal airflow, etc. Sensors used as part of a closed-loop or open-loop system can be placed at any appropriate anatomical location on the patient, including on the surface of the skin, in the oral cavity, nasal cavity, on a mucosal surface, or at a subcutaneous location.

[0037] refer to Figure 3 In one aspect, a method 100 of treating SDB in a patient suffering from SDB includes delivering a stimulatory neuromodulation signal to the cervical loop to stimulate activation of the cervical loop innervating one or more infrahyoid muscles 102, and delivering a blocking neuromodulation signal to the cervical loop to block activation of efferent fibers innervating one or more suprahyoid muscles 104. The blocking neuromodulation signal can alleviate undesirable antidromic efferent activation of one or more suprahyoid muscles (e.g., including the geniohyoid muscle).

[0038] Regarding the stimulatory neuromodulation signal, such a signal can be delivered to stimulate the activation of motor fibers of the cervical loop to activate, for example, the sternothyroid muscle. The stimulatory neuromodulation signal can also be delivered to the cervical loop that innervates the upper belly of the sternohyoid muscle and / or the lower belly of the sternohyoid muscle to activate part or all of the sternohyoid muscle. For example, an exemplary target site for delivering the stimulatory neuromodulation signal can be the upper root of the cervical loop, or near the branch point of the upper root that innervates the sternohyoid muscle or at the branch point of the upper root that innervates the sternohyoid muscle, so that the sternohyoid muscle and the sternothyroid muscle are activated. In some aspects, the stimulatory neuromodulation signal can be delivered to the upper root of the cervical loop or close to the upper root to activate part or all of the omohyoid muscle.

[0039] In some aspects, the stimulatory neuromodulation signal can be delivered to a target site near the cervical loop (e.g., near the lower root of the cervical loop), which also innervates the sternothyroid muscle, the sternohyoid muscle, and the omohyoid muscle to activate one or more innervated muscles. In some aspects, the stimulatory neuromodulation signal can be delivered to the cervical loop simultaneously to stimulate nerve branches from the upper and lower roots of the cervical loop that innervate the sternothyroid muscle and the sternohyoid muscle and the omohyoid muscle. In some aspects, delivering the stimulatory neuromodulation signal to a target site (e.g., near or located at a branch point of a nerve or common trunk nerve arising from the cervical loop, which combines nerve fibers from the upper and lower roots and innervates at least the sternothyroid muscle and variably innervates the sternohyoid muscle and the omohyoid muscle) can at least activate the sternothyroid muscle, in some aspects activate the sternohyoid muscle, and in some aspects activate the omohyoid muscle. In certain aspects, delivering a stimulatory neuromodulation signal to a target site (e.g., near or at a branch point of a nerve from a common trunk of the cervical loop or the sternothyroid nerve) can activate the sternothyroid muscle. The branches of the sternothyroid muscle can be a single nerve fiber or several nerve fibers closely distributed together. It should be noted that the above-mentioned target sites are merely exemplary, and the neuromodulation device can be placed in other parts of the cervical loop including its branches. In addition, stimulation can be applied to any combination of the sites and branches described above. For example, the neuromodulation device can be placed proximal or distal to the branches of the omohyoid muscle so that the stimulation captures only the sternothyroid / sternohyoid muscle fibers. As another example, one or more cuff electrodes can surround a single fiber or multiple fibers that innervate the sternothyroid muscle.

[0040] With respect to blocking neuromodulatory signals, such signals may be delivered to the superior root of the cervical loop, for example, to reduce or eliminate antidromic motor efferent activation of the suprahyoid muscle target in situations where activation of only the infrahyoid muscle is desired.

[0041] In some aspects, the method for improving SDB includes additionally delivering an electrical signal to a target site of the hypoglossal nerve close to the innervation of the genioglossus muscle to activate the genioglossus muscle. The target site can be close to the hypoglossal nerve so that the delivery of the electrical signal activates the motor fibers of the hypoglossal nerve to activate the genioglossus muscle. In some aspects, the electrical signal is not delivered to the hypoglossal nerve close to its branch point because it is believed that an independent neuromodulation device may be required to potentially provide stimulation of different intensities or times to the cervical loop and the hypoglossal nerve. In other aspects, the hypoglossal nerve can be stimulated proximal or distal to the branch point of the retractor muscle (retrusormuscle) branch of the styloglossus muscle and / or the hyoglossus muscle. The activation of the hypoglossal nerve can stiffen the tongue muscle tissue, thereby reducing or eliminating the pharyngeal obstruction produced by the posterior collapse of the tongue root, which, illustratively, may not be treated by the cervical loop.

[0042] In some aspects, the method also includes delivering a blocking neuromodulation signal to the hypoglossal nerve to block activation of efferent fibers that innervate the styloglossus muscle, the hyoglossus muscle, or both. Such a blocking neuromodulation signal can avoid undesirable efferent activation of the styloglossus muscle, the hyoglossus muscle, or both. When the upstream electrical contacts activate multiple efferent motor targets, it may be desirable to block undesirable motor efferents.

[0043] In certain aspects, the method for improving SDB includes additionally delivering a stimulatory neuromodulatory signal to the efferent fibers of the glossopharyngeal nerve that innervates one or more pharyngeal constrictors or stylopharyngeus muscles to activate one or more pharyngeal constrictors or stylopharyngeus muscles. Exemplarily, the neural target site may include the pharyngeal plexus or its branches. When activated, such one or more pharyngeal constrictors can increase pharyngeal muscle firmness to reduce pharyngeal airway collapse. When activated, the stylopharyngeus muscle can move the pharyngeal wall laterally.

[0044] The lateral wall of the pharynx is composed of pharyngeal constrictor muscles, which are innervated by a pharyngeal plexus that includes fibers from cranial nerves IX and X. The nerves that innervate these muscles form a plexus on the outer surface of the pharyngeal constrictor muscles and then penetrate the pharyngeal constrictor muscles to reach the palatoglossus and palatopharyngeus muscles. The motor branch of cranial nerve IX may be responsible for respiratory control of the constrictor muscles and can be identified in the region of the stylopharyngeus muscle. Increased constrictor muscle firmness during respiration can reduce pharyngeal collapse by stiffening the pharyngeal wall. Stiffening the pharyngeal wall without complete contraction can make stimulation of the cervical loop and hypoglossal nerve more effective. Stimulating the stylopharyngeus muscle can increase airway caliber by moving the pharyngeal wall laterally and can also counteract the pharyngeal constriction component of constrictor muscle activation that may occur if muscle activation exceeds the initial pharyngeal wall stiffening.

[0045] Stimulation of the efferent fibers of the glossopharyngeal nerve innervating one or more pharyngeal constrictors or the stylopharyngeus muscle can be combined with stimulation of other neural target sites as described herein. Stimulation of the cervical loop can anchor the lower end of the pharynx by preventing upward movement of the thyroid cartilage and hyoid bone, which can allow contraction of the pharyngeal constrictors and palatopharyngeus muscles to oppose a solid anchor point rather than a mobile insertion point, thereby increasing the effectiveness of co-stimulation of the cervical loop with stimulation of the efferent fibers of the glossopharyngeal nerve or stimulation of the palatopharyngeus muscle.

[0046] In some embodiments, the method includes delivering a neuromodulation signal to the efferent fibers of the glossopharyngeal nerve that is independent of a sensory or input signal detected or sensed regarding the neuromuscular state of the airway. For example, the electrical signal may be delivered on a tonic basis, or at a duty cycle that is independent of a sensory or input signal detected or sensed regarding the neuromuscular state of the airway. In other words, even if a sensory or input signal regarding the neuromuscular state of the airway can be measured, in some embodiments, such sensory information may not determine the stimulation parameters of the electrical signal delivered to the target site. In some aspects, the electrical signal is not delivered to the sensory fibers of the mucosal layer that innervates the pharyngeal wall.

[0047] In some aspects, the method includes delivering a blocking neuromodulatory signal to the glossopharyngeal nerve to block activation of afferent fibers of the glossopharyngeal nerve. The blocking neuromodulatory signal can avoid undesirable sensory effects. For example, the blocking neuromodulatory signal can be delivered upstream of the main glossopharyngeal nerve.

[0048] In certain aspects, the method for improving SDB includes additionally delivering a neuromodulatory signal to the nerves that control the palatal muscles (such as palatoglossus, palatopharyngeal muscles or both) to improve SDB in patients with SDB. Palatoglossus and palatopharyngeal muscles are muscles of the soft palate (also referred to as "palatine muscles"). The palatoglossus originates from the palatine aponeurosis (palatine aponeurosis) at the rear of the hard palate. It descends to the lower side to insert into the posterior lateral surface of the tongue. During its process through the rear of the oral cavity, its inner side is covered by mucous membrane tissue (mucous membrane), thereby forming a palatoglossus arch (palatoglossus arch). The effect of the palatoglossus is to separate the oral cavity from the oropharynx (oropharynx) by raising the back tongue and pulling the soft palate downward. The muscle is innervated by the branches of the pharyngeal plexus, which works independently of the hypoglossal nerve and the remaining intrinsic and extrinsic tongue muscle tissues. The palatopharyngeal muscle forms a palatopharyngeal arch (palatopharyngeal arch). It is attached to the hard palate and palatine aponeurosis on the upper side, and attached to the side wall and thyroid cartilage of the pharynx on the lower side. During swallowing, it acts to tension the soft palate and pull the pharyngeal walls upward, forward, and inward, effectively separating the nasopharynx from the oropharynx.

[0049] This method of delivering electrical signals to the nerves that innervate the palatal muscles to improve SDB is different from indirect methods of muscle stimulation, such as transcutaneous electrical pacing, which has been found to be uncoordinated and poorly tolerated by sleeping patients. Directed intramuscular stimulation via fine-wire electrode placement or other techniques is impractical for daily use because it requires uncomfortable daily punctures of the skin or the inner wall of the mouth to access the muscle tissue. During sleep, electrical stimulation of the nerves that innervate the palatoglossus and / or palatopharyngeus muscles can expand the retropalatal space, thereby opening the patient's upper airway, without causing sleep arousals. Such an approach can be used for patients with isolated palate collapse, or used in combination with hypoglossal nerve stimulation, cervical loop stimulation, and / or phrenic nerve stimulation as part of a multi-stage airway treatment for SDB such as OSA.

[0050] In certain embodiments, the target site of the nerve innervating the palatoglossus and / or palatopharyngeal muscle is the pharyngeal plexus or its branches.Preferably, the electrical signal delivered to the target site of the nerve innervating the palatoglossus and / or palatopharyngeal muscle stimulates the motor fibers of the pharyngeal plexus innervating the patient's soft palate.

[0051] In certain embodiments, the target site of stimulation is not the cranial root of the patient's accessory nerve, because targeting the cranial root of the accessory nerve or the root of the vagus nerve can result in diffuse, nonspecific stimulation. For example, activation of the vagus nerve root can simultaneously activate the levator veli palatini muscle, thereby opposing the action of the palatoglossus and palatopharyngeus muscles. Stimulating the cranial root of the spinal accessory nerve can similarly cause nonspecific activation of the pharyngeal plexus musculature. In addition, in all patients, the connection of the cranial root of the accessory nerve to the vagus nerve is unknown. If the cranial root of the accessory nerve is not connected to the pharyngeal plexus, it will remain on the spinal root of the accessory nerve. Therefore, stimulating the cranial root of the accessory nerve can result in unintentional stimulation of the spinal root of the accessory nerve, resulting in undesired activation of the sternocleidomastoid and trapezius muscles.

[0052] In certain aspects, a method of improving SDB includes stimulating the cervical loop to activate one or more infrahyoid strap muscles while stimulating the phrenic nerve to activate the diaphragm. Phrenic nerve stimulation can affect upper airway collapse. Stimulating the phrenic nerve in isolation can cause airway collapse rather than prevent it because the descent of the diaphragm inherently creates a negative pressure gradient within the pharyngeal cavity, which can cause collapse before a stabilizing effect is achieved. Simultaneous stimulation of the cervical loop and phrenic nerve can provide a greater degree of ability to control airway collapse than stimulating either in isolation by providing personalized control of caudal traction and chest expansion during the respiratory cycle.

[0053] By placing one or more electrical contacts near the target site, delivery of neuromodulation signals to any one or more of the above target sites can be achieved. The electrical contacts can be placed near the target site in a variety of different ways, such as by transcutaneously, percutaneously, subcutaneously, intramuscularly, intraluminally, transvascularly, intravascularly, or via direct open surgery. Neuromodulation (stimulatory and / or blocking) can be unilateral neuromodulation or bilateral neuromodulation.

[0054] In certain aspects, rather than delivering blocking neuromodulatory signals to the above-described neural target sites, the stimulation intensity of a portion of any desired motor target of these nerves can be reduced to better balance or alter the ratio of recruitment in the desired muscles.

[0055] The methods disclosed herein can be used as part of a closed-loop system (as described in more detail below). Such methods can include sensing a physiological parameter associated with SDB, generating a sensor signal based on the physiological parameter, and activating an electrode in response to the sensor signal to regulate the application of an electrical signal to a target site to improve the patient's SDB.

[0056] Each disclosed aspect and embodiment of the present disclosure may be considered separately or in combination with other aspects, embodiments and variations of the present disclosure. Unless otherwise specified, any step of the disclosed method is not limited to any particular order of execution. In addition, although the above is described with respect to electrical stimulation, other forms of energy may also be used, such as ultrasound, magnetic energy or light energy.

Claims

1. A neural modulation system for improving sleep-disordered breathing, comprising: processor; as well as A non-transitory computer-readable medium storing executable instructions executable by the processor to: Directly delivering stimulatory neuromodulation signals to the cervical loop to stimulate activation of the cervical loop innervating one or more infrahyoid muscles; and A blocking neuromodulatory signal is directed to the cervical loop, which blocks activation of efferent fibers innervating one or more suprahyoid muscles, the blocking neuromodulatory signal mitigating undesirable retrograde efferent activation of the one or more suprahyoid muscles.

2. The neural modulation system of claim 1 , further comprising the following instructions: Stimulatory neuromodulatory signals are directed to the hypoglossal nerve, which stimulates activation of the genioglossus muscle.

3. The neural modulation system of claim 1 , further comprising the following instructions: A blocking neuromodulatory signal is directed to the hypoglossal nerve, which blocks activation of efferent fibers innervating the styloglossus muscle, the hyoglossus muscle, or both, and the blocking neuromodulatory signal relieves undesirable efferent activation of the styloglossus muscle, the hyoglossus muscle, or both.

4. The neural modulation system of claim 1 , further comprising the following instructions: A stimulatory neuromodulatory signal is directed to the glossopharyngeal nerve, which stimulates activation of the efferent fibers of the glossopharyngeal nerve.

5. The neural modulation system of claim 1 , further comprising the following instructions: A blocking neuromodulatory signal is directed to the glossopharyngeal nerve, which blocks activation of afferent fibers of the glossopharyngeal nerve, the blocking neuromodulatory signal mitigating the undesirable sensory effect.

6. The neural modulation system of claim 1 , further comprising the following instructions: Directing the delivery of stimulatory neuromodulatory signals to the hypoglossal nerve, which stimulates the genioglossus muscle; and A blocking neuromodulatory signal is directedly delivered to the hypoglossal nerve, which blocks activation of efferent fibers innervating the styloglossus muscle, the hyoglossus muscle, or both, and the blocking neuromodulatory signal relieves unwanted efferent activation of the styloglossus muscle, the hyoglossus muscle, or both.

7. The neural modulation system of claim 1 , further comprising the following instructions: Directly delivering a stimulatory neuromodulatory signal to the glossopharyngeal nerve, which stimulates activation of efferent fibers of the glossopharyngeal nerve; and A blocking neuromodulatory signal is directed to the glossopharyngeal nerve, which blocks activation of afferent fibers of the glossopharyngeal nerve, the blocking neuromodulatory signal mitigating the undesirable sensory effect.

8. The neural modulation system of claim 1 , further comprising the following instructions: Directed delivery of stimulatory neuromodulatory signals to the hypoglossal nerve, which stimulates activation of the genioglossus muscle; Directly delivering a blocking neuromodulatory signal to the hypoglossal nerve, which blocks activation of efferent fibers innervating the styloglossus muscle, the hyoglossus muscle, or both, the blocking neuromodulatory signal alleviating undesirable efferent activation of the styloglossus muscle, the hyoglossus muscle, or both; Directly delivering a stimulatory neuromodulatory signal to the glossopharyngeal nerve, which stimulates activation of efferent fibers of the glossopharyngeal nerve; and A blocking neuromodulatory signal is directed to the glossopharyngeal nerve, which blocks activation of afferent fibers of the glossopharyngeal nerve, the blocking neuromodulatory signal mitigating the undesirable sensory effect.

9. The neural modulation system of claim 1 , further comprising the following instructions: Stimulatory neuromodulatory signals are delivered to the neural site in a targeted manner, which stimulates activation of the palatoglossus muscles, the palatopharyngeal muscles, or both.

10. The neural modulation system of claim 1, further comprising the following instructions: Stimulatory neuromodulatory signals are directed to the phrenic nerve, which stimulates activation of the diaphragm.

11. A method for improving sleep-disordered breathing in a patient suffering from sleep-disordered breathing, comprising: delivering a stimulatory neuromodulation signal to the cervical loop that stimulates activation of the cervical loop innervating one or more infrahyoid muscles; and A blocking neuromodulatory signal is delivered to the cervical loop that blocks activation of efferent fibers innervating one or more suprahyoid muscles, the blocking neuromodulatory signal mitigating undesirable retrograde efferent activation of the one or more suprahyoid muscles.

12. The method according to claim 11, further comprising: A stimulatory neuromodulatory signal is delivered to the hypoglossal nerve, which stimulates activation of the genioglossus muscle.

13. The method according to claim 11, further comprising: A blocking neuromodulatory signal is delivered to the hypoglossal nerve that blocks activation of efferent fibers innervating the styloglossus muscle, the hyoglossus muscle, or both, the blocking neuromodulatory signal avoiding undesired efferent activation of the styloglossus muscle, the hyoglossus muscle, or both.

14. The method according to claim 11, further comprising: A stimulatory neuromodulatory signal is delivered to the glossopharyngeal nerve, which stimulates activation of the efferent fibers of the glossopharyngeal nerve.

15. The method according to claim 11, further comprising: A blocking neuromodulatory signal is delivered to the glossopharyngeal nerve which blocks activation of afferent fibers of the glossopharynx, the blocking neuromodulatory signal avoiding undesirable sensory effects.

16. The method according to claim 11, further comprising: delivering a stimulatory neuromodulatory signal to the hypoglossal nerve which stimulates activation of the genioglossus muscle; and A blocking neuromodulatory signal is delivered to the hypoglossal nerve, which blocks activation of efferent fibers innervating the styloglossus muscle, the hyoglossus muscle, or both, the blocking neuromodulatory signal mitigating undesirable efferent activation of the styloglossus muscle, the hyoglossus muscle, or both.

17. The method according to claim 11, further comprising: delivering a stimulatory neuromodulatory signal to the glossopharyngeal nerve that stimulates activation of efferent fibers of the glossopharyngeal nerve; and A blocking neuromodulatory signal is delivered to the glossopharyngeal nerve which blocks activation of afferent fibers of the glossopharyngeal nerve, the blocking neuromodulatory signal mitigating the undesirable sensory effect.

18. The method according to claim 11, further comprising: delivering a stimulatory neuromodulatory signal to the hypoglossal nerve, which stimulates activation of the genioglossus muscle; delivering a blocking neuromodulatory signal to the hypoglossal nerve that blocks activation of efferent fibers innervating the styloglossus muscle, the hyoglossus muscle, or both, the blocking neuromodulatory signal mitigating undesirable efferent activation of the styloglossus muscle, the hyoglossus muscle, or both; delivering a stimulatory neuromodulatory signal to the glossopharyngeal nerve that stimulates activation of efferent fibers of the glossopharyngeal nerve; and A blocking neuromodulatory signal is delivered to the glossopharyngeal nerve which blocks activation of afferent fibers of the glossopharyngeal nerve, the blocking neuromodulatory signal mitigating the undesirable sensory effect.

19. The method according to claim 11, further comprising: A stimulatory neuromodulatory signal is delivered to the neural site, which stimulates activation of the palatoglossus muscle, the palatopharyngeal muscle, or both.

20. The method according to claim 11, further comprising: A stimulatory neuromodulatory signal is delivered to the phrenic nerve, which stimulates activation of the diaphragm.

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