Management of obstructive sleep apnea by upper airway dual nerve stimulation

Abstract

At least some embodiments of the present disclosure relate to systems and methods for managing sleep breathing disorders (e.g., obstructive sleep apnea) in a patient. The first implantable electrode delivers a first stimulation signal near a first nerve of the patient to stimulate the first nerve and activate at least one first muscle for upper airway dilation of the person. The second implantable electrode delivers a second stimulation signal proximate a second nerve to stimulate the second nerve and activate at least one second muscle for exhaust tube traction of the upper airway of the person. The stimulation signal generator generates first and second stimulation signals and coordinates delivery of the first stimulation signal with delivery of the second stimulation signal.

Description

[0001] Cross-references to related patent applications

[0002] This application claims priority to U.S. Provisional Application No. 63 / 519,463, filed on August 14, 2023, the disclosure of which is incorporated herein by reference in its entirety. Background Art

[0003] Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder. OSA may occur when the muscles in the back of the throat relax during sleep, causing partial or complete obstruction of the airway. Typical treatment options can include positive airway pressure (PAP) therapy, which uses devices such as continuous positive airway pressure (CPAP) to help keep the airway open during sleep, and oral appliances, which use a custom mouthpiece to reposition the jaw and tongue to prevent airway collapse. Summary of the invention

[0004] Certain embodiments of the present disclosure relate to medical systems, devices, and methods for managing sleep breathing disorders (e.g., obstructive sleep apnea) in patients. More specifically, some embodiments of the present disclosure relate to medical systems, devices, and methods for managing obstructive sleep apnea in patients through upper airway dual neural stimulation.

[0005] According to some embodiments, a system for managing obstructive sleep apnea in a person includes a first implantable electrode, which is configured to deliver a first stimulation signal to the vicinity of a first nerve of the person, thereby stimulating the first nerve and activating at least one first muscle for upper airway dilation of the person; a second implantable electrode, which is configured to deliver a second stimulation signal to the vicinity of a second nerve, thereby stimulating the second nerve and activating at least one second muscle for caudal tracheal traction of the upper airway of the person; and a stimulation signal generator, which is configured to deliver the first stimulation signal to the first implantable electrode and deliver the second stimulation signal to the second implantable electrode. The first stimulation signal has a series of first stimulation cycles, each of which includes a first stimulation period and a first non-stimulation period, and the second stimulation signal has a series of second stimulation cycles, each of which includes a second stimulation period and a second non-stimulation period, and the delivery of the first stimulation signal is coordinated with the delivery of the second stimulation signal. The second stimulation signal is modulated to activate at least one second muscle within a strain range from a first strain value to a second strain value, wherein a first stimulation level of the second stimulation signal corresponds to the first strain value and a second stimulation level of the second stimulation signal corresponds to the second strain value.

[0006] According to certain embodiments, a method for managing obstructive sleep apnea in a person includes providing a first implantable electrode configured to deliver a first stimulation signal to a vicinity of a first nerve, thereby stimulating the first nerve and activating at least one first muscle for upper airway dilation; providing a second implantable electrode configured to deliver a second stimulation signal to a vicinity of a second nerve, thereby stimulating the second nerve and activating at least one second muscle for tracheal traction of the person's upper airway; modulating the second stimulation signal to activate at least one second muscle within a strain range from a first strain value to a second strain value, wherein a first stimulation level of the second stimulation signal corresponds to the first strain value, and a second stimulation level of the second stimulation signal corresponds to the second strain value; delivering the first stimulation signal to the first implantable electrode; and delivering the second stimulation signal to the second implantable electrode. Coordinate the first stimulation signal with the second stimulation signal. The first stimulation signal has a series of first stimulation cycles, each of which includes a first stimulation period and a first non-stimulation period, and the second stimulation signal has a series of second stimulation cycles, each of which includes a second stimulation period and a second non-stimulation period.

[0007] Although multiple embodiments are disclosed, other embodiments of the present disclosure will be apparent to those skilled in the art from the following detailed description, which shows and describes illustrative embodiments of the present disclosure. Accordingly, the drawings and detailed description should be regarded as illustrative rather than restrictive. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1A A schematic diagram depicting a patient anatomy and an exemplary medical system for dual neural stimulation of the upper airway according to an embodiment of the present disclosure is shown.

[0009] Figure 1B Shows a depiction Figure 1A Schematic diagram of the patient's anatomy.

[0010] Figure 2 is a block diagram of an exemplary medical system for managing obstructive sleep apnea in a patient via upper airway dual neural stimulation according to an embodiment of the present disclosure.

[0011] Figure 3 is an exemplary flow chart of a medical method for managing obstructive sleep apnea in a patient via upper airway dual neural stimulation according to an embodiment of the present disclosure.

[0012] Figure 4A is a schematic diagram illustrating an exemplary timing cycle of dual neural stimulation in a first mode according to an embodiment of the present disclosure.

[0013] Figure 4B is a schematic diagram illustrating an exemplary timing cycle of dual neural stimulation in a second mode according to an embodiment of the present disclosure.

[0014] Figure 5A is a schematic diagram showing an exemplary neural entrainment with a natural breathing rhythm according to an embodiment of the present disclosure.

[0015] Figure 5B is an exemplary flow chart of a medical method for managing obstructive sleep apnea in a patient via upper airway dual neural stimulation according to an embodiment of the present disclosure.

[0016] Fig. 6A -C is an exemplary flow chart illustrating a titration method according to some embodiments of the present disclosure.

[0017] Fig. 7A Shown is a schematic diagram depicting a patient's anatomy and one or more exemplary target muscle locations for hypoglossal nerve stimulation in accordance with an embodiment of the present disclosure.

[0018] Figure 7B Shown is a schematic diagram depicting a patient's anatomy and one or more exemplary target muscle locations for ansa cervicalis stimulation, according to an embodiment of the present disclosure.

[0019] Figure 7C A schematic diagram depicting a patient's anatomy and one or more exemplary target nerve / muscle locations for dual nerve stimulation of the upper airway, including hypoglossal nerve stimulation and cervical loop stimulation, is shown in accordance with an embodiment of the present disclosure.

[0020] Fig.7D A schematic diagram depicting a patient's anatomy and one or more exemplary target nerve / muscle locations for cervical loop stimulation in upper airway dual neural stimulation is shown in accordance with an embodiment of the present disclosure.

[0021] Although the present disclosure is suitable for various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and described in detail below. However, it is not intended to limit the present disclosure to the specific embodiments described. On the contrary, the present disclosure is intended to cover all modifications, equivalents and alternatives within the scope of the present disclosure as defined by the appended claims. DETAILED DESCRIPTION

[0022] The following detailed description is exemplary in nature and is not intended to limit the scope, applicability or configuration of the present disclosure in any way. More specifically, the following description provides some practical examples for implementing the exemplary embodiments of the present disclosure. For selected elements, examples of construction, material and / or size are provided. Those skilled in the art will recognize that many examples in the examples have multiple suitable alternatives.

[0023] Unless otherwise stated, all numbers used in the specification and claims to represent feature sizes, quantities and physical properties should be understood to be modified by the term "about" in all cases. Therefore, unless otherwise stated, the numerical parameters set forth in the foregoing specification and the appended claims are approximate values, which can vary according to the desired properties sought to be obtained by those skilled in the art using the teachings disclosed herein. The numerical range using endpoints includes all numbers within the range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4 and 5) and any number within the range.

[0024] Although the illustrative method may be represented by one or more drawings (e.g., flow charts, communication flows, etc.), the drawings should not be interpreted as any requirement of the various steps disclosed herein or a specific order among or between the various steps disclosed herein. However, some embodiments may require certain steps and / or certain orders between certain steps, as can be clearly described herein and / or as can be understood according to the nature of the steps themselves (e.g., the execution of some steps may depend on the results of the previous steps). In addition, a "set", "subset" or "group" of an item (e.g., input, algorithm, data value, etc.) may include one or more items, and similarly, a subset or subgroup of an item may include one or more items. "Multiple" means more than one.

[0025] As used herein, the term "based on" is not intended to be restrictive, but rather to represent the determination, identification, prediction, calculation, and / or the like performed by using at least the term following "based on" as input. For example, predicting an outcome based on a particular piece of information can additionally or alternatively make the same determination based on another piece of information. In some embodiments, the term "receive" or "receiving" means obtaining from a data repository (e.g., a database), from another system or service, from another software, or from another software component in the same software. In certain embodiments, the term "access" or "accessing" means retrieving data or information, and / or generating data or information.

[0026] Typical treatment options for obstructive sleep apnea (OSA) of patients, such as positive airway pressure (PAP) therapy, may not be suitable for many patients. For OSA patients who are not suitable for PAP therapy, hypoglossal nerve stimulation (HNS) is considered to be an effective form of treatment. In a typical method of using hypoglossal nerve stimulation (HNS) to stimulate airway patency-related tissues, an implanted neurostimulator is used to generate a stimulation signal based on the patient's respiratory information sensed by the sensing wire to deliver it to the implanted stimulation wire. Hypoglossal nerve stimulation (HNS) therapy can work by protruding (protruding, protrude) and stiffening the tongue muscles (thereby reducing the obstruction from the tongue). However, HNS therapy may not reduce the obstruction from the side wall. It was found that about 35% of implanted patients did not respond to hypoglossal nerve stimulation (HNS). For example, it was found that patients with lateral wall collapse had a reduced response to HNS. Therefore, it is necessary to improve the method for the treatment of OSA. At least some embodiments of the present disclosure relate to medical systems, devices and methods for managing obstructive sleep apnea of ​​patients by dual nerve stimulation of the upper airway.

[0027] Figure 1AA schematic diagram depicting a patient anatomy and a system 100 for dual neural stimulation of the upper airway of a person according to an embodiment of the present disclosure is shown. The system 100 includes a first implantable electrode 102 configured to deliver a first stimulation signal to a vicinity of a first nerve of the person, thereby stimulating the first nerve and activating at least one muscle for upper airway dilation of the person. In some embodiments, the system 100 also includes a second implantable electrode 104 configured to deliver a second stimulation signal to a vicinity of a second nerve, thereby stimulating the second nerve and activating at least one muscle for tail airway traction of the upper airway of the person.

[0028] In some embodiments, the system 100 also includes a stimulation signal generator 106 configured to deliver a first stimulation signal to the first implanted electrode 102 and a second stimulation signal to the second implanted electrode 104. The stimulation signal generator 106 can be positioned (e.g., implanted) at any suitable location and connected to the implanted electrodes 102 and 104 wirelessly or via wires. In some embodiments, the stimulation signal generator 106 is implanted in or on the patient's body adjacent to the implanted electrodes 102 and 104, for example, in the chest. In some embodiments, the implanted electrodes 102 and 104 can be operably coupled to the same single stimulation signal generator 106. In some embodiments, the stimulation signal generator 106 can include a first stimulation signal generator coupled to the first implanted electrode 102 and a second stimulation signal generator coupled to the second implanted electrode 104. The first and second stimulation signal generators can be arranged in the same physical housing or in separate housings.

[0029] According to some embodiments, the stimulation signal generator 106 may be controlled to generate one or more stimulation signals and deliver the generated stimulation signals to one or more electrodes. In some embodiments, the stimulation signal generator 106 may be controlled to transmit various patterns of current and voltage to generate stimulation signals.

[0030] In some embodiments, the stimulation signal generator 106 can generate a first stimulation signal having a first set of stimulation parameters and a second stimulation signal having a second set of stimulation parameters. In some embodiments, the first stimulation signal has a series of first stimulation cycles, each of which includes a first stimulation period and a first non-stimulation period. In some embodiments, the second stimulation signal has a series of second stimulation cycles, each of which includes a second stimulation period and a second non-stimulation period.

[0031] In some embodiments, the stimulation signal generator 106 can be a pulse generator to generate a series of pulses in the stimulation period of each stimulation cycle. The stimulation signal generator 106 can control one or more stimulation parameters of the pulse signal, including one or more of amplitude, frequency, pulse width, amplitude change rate, duty cycle, etc.

[0032] In some embodiments, the stimulation signal generator 106 can coordinate the delivery of the first stimulation signal with the delivery of the second stimulation signal. In certain embodiments, the stimulation signal generator 106 includes an internal timer to provide timing of a series of first stimulation cycles of the first stimulation signal and a series of second stimulation cycles of the second stimulation signal. In some embodiments, the internal timer can synchronize the first stimulation period and the first non-stimulation period of the first stimulation signal with the second stimulation period and the second non-stimulation period of the second stimulation signal, respectively.

[0033] In some embodiments, the system 100 further includes a remote controller 110 that is functionally connected to the stimulation signal generator 106 to control the operation of the stimulation signal generator. In some embodiments, the remote controller 110 is configured to control or adjust one or more stimulation parameters of the stimulation signal generator 106, including, for example, the duration of the stimulation cycle, the duration of the stimulation period, the duration of the non-stimulation period, the coordination between the first stimulation signal and the second stimulation signal, the pulse amplitude, the pulse frequency, the pulse width, the duty cycle of the generated stimulation signal, etc. In some embodiments, the controller 110 allows the user to adjust the first amplitude of the first stimulation signal and the second amplitude of the second stimulation signal to obtain an optimized combination of the first amplitude and the second amplitude.

[0034] exist Figure 1A In the illustrated embodiment, the remote controller 110 includes a first controller 112 and a second controller 114. In some embodiments, the first controller 112 can be a patient remote controller for the patient to control the operation of the stimulation signal generator 106. For example, the patient can use the controller to turn the stimulation signal generator 106 on or off, adjust the respective amplitudes of one or more stimulation signals, switch the operation of the stimulation signal generator 106 between a first mode and a second mode, etc. In some embodiments, the controller 110 can automatically turn the stimulation signal generator 106 on or off based on the time of day. In some embodiments, the second controller 114 can be a clinician programmer for a physician or clinician to adjust one or more stimulation parameters of the stimulation signal generator 106.

[0035] In some embodiments, the first implantable electrode 102 is configured to deliver a first stimulation signal to the vicinity of the hypoglossal nerve to stimulate the hypoglossal nerve and activate at least one tongue muscle. In some embodiments, the second implantable electrode 104 is configured to deliver a second stimulation signal to the vicinity of the cervical nerve to stimulate the cervical nerve and activate at least one infrahyoid muscle.

[0036] Figure 1B Shows a depiction Figure 1A Schematic diagram of the patient's anatomy showing the therapeutic effect of dual nerve stimulation of the upper airway. In some embodiments, a first stimulation signal is delivered to activate one or more protrusor muscles of the tongue (e.g., genioglossus) to displace the tongue root forward (e.g., Figure 1B In some embodiments, a second stimulation signal is delivered to activate one or more infrahyoid muscles to lower the hyoid-thyroid complex, which results in caudal traction of the trachea, causing the lateral and posterior pharyngeal walls to stiffen downward (e.g., Figure 1B 124) for cervical plexus nerve stimulation (ACS).

[0037] Figure 2 is a block diagram of a medical system 200 for managing obstructive sleep apnea in a patient via upper airway neural stimulation according to an embodiment of the present disclosure.

[0038] In some embodiments, the medical system 200 includes: a first implantable electrode 202 configured to deliver a first stimulation signal to a vicinity of a first nerve 203 of a person to stimulate the first nerve 203; and a second implantable electrode 204 configured to deliver a second stimulation signal to a vicinity of a second nerve 205.

[0039] In some embodiments, the first implantable electrode 202 is configured to deliver a first stimulation signal to the vicinity of the hypoglossal nerve to stimulate the hypoglossal nerve and activate at least one tongue muscle. In some embodiments, the second implantable electrode 204 is configured to deliver a second stimulation signal to the vicinity of the loop cervical nerve to stimulate the loop cervical nerve and activate at least one infrahyoid muscle. In some embodiments, the medical system 200 may include a third implantable electrode configured to deliver a third stimulation signal to the vicinity of a third nerve to stimulate the third nerve. The third nerve may be, for example, a phrenic nerve.

[0040] In some embodiments, the medical system 200 also includes a stimulation signal generator 206, which is configured to deliver a first stimulation signal to the first implantable electrode 202 and a second stimulation signal to the second implantable electrode 204. The first stimulation signal has a series of first stimulation cycles, which include a first stimulation period and a first non-stimulation period. The second stimulation signal has a series of second stimulation cycles, which include a second stimulation period and a second non-stimulation period. The delivery of the first stimulation signal is coordinated with the delivery of the second stimulation signal.

[0041] In some embodiments, the stimulation signal generator 206 may include one or more pulse generators, each of which is configured to generate a stimulation signal, the stimulation signal including a series of stimulation cycles, which include a stimulation period and a non-stimulation period. The stimulation period of the stimulation cycle may include a series of stimulation pulses, which have one or more pulse parameters. Exemplary pulse parameters include pulse frequency, amplitude, pulse width, duty cycle, etc. The pulse frequency may be, for example, about 5 Hz to about 40 Hz (e.g., at or about 30 Hz). The pulse width may be, for example, about 10 microseconds to about 1000 microseconds (e.g., at or about 100 microseconds). The duty cycle may refer to the percentage of the duration of stimulation under a certain pulse amplitude to the duration of the stimulation cycle (e.g., the sum of the duration of stimulation and the duration of no stimulation). The duration of the stimulation cycle may be, for example, in the range of 2 seconds to 10 minutes. The duty cycle may be, for example, in the range of about 5% to 95%. The pulse amplitude may refer to the difference between a higher voltage level and a lower voltage level. The pulse amplitude may be, for example, in the range of 0.1 to 15 volts or 0.1 to 15 mA.

[0042] In some embodiments, the medical system 200 further includes a controller 210 that is functionally connected to the stimulation signal generator 206 to control the operation of the stimulation signal generator. In some embodiments, the controller 210 is a remote controller that is configured to control one or more stimulation parameters for the stimulation signal generator 106, including, for example, one or more of the amplitude, frequency, pulse width, amplitude change rate, duty cycle, etc. of the generated stimulation signal.

[0043] In some embodiments, the controller 210 may include a patient remote controller for the patient to control the operation of the stimulation signal generator 206, including, for example, turning the stimulation signal generator 206 on or off, adjusting the corresponding amplitude of one or more stimulation signals, switching the operation of the stimulation signal generator 106 from a first mode to a second mode, etc.

[0044] In some embodiments, the controller 210 may include a clinician programmer for a physician or clinician to pre-program the stimulation signal generator 206 with desired stimulation parameters. The stimulation parameters may be controllable to allow one or more stimulation signals to be remotely modulated to a desired setting without removing the corresponding electrodes from their target locations.

[0045] In some embodiments, the controller 210 may include one or more computing devices, each of which may include a bus that directly and / or indirectly couples the following devices: a processor, a memory, an input / output (I / O) port, an I / O component, and a power supply. Any number of additional components, different components, and / or combinations of components may also be included in the computing device. A bus representation may be one or more buses (such as, for example, an address bus, a data bus, or a combination thereof). Similarly, in some embodiments, a computing device may include multiple processors, multiple memory components, multiple I / O ports, multiple I / O components, and / or multiple power supplies. In addition, any number of these components or combinations thereof may be distributed and / or repeated on multiple computing devices.

[0046] In some embodiments, the medical system 200 also includes one or more sensors 214. In certain embodiments, the sensor 214 can be an external sensor configured to detect one or more physiological information of the patient, including, for example, an apnea-hypopnea index (AHI), an oxygen desaturation index (ODI), a respiratory disorder index (RDI), posture changes, sleep stages, restless body movements, etc. It should be understood that the external sensor can be any suitable type of sensor, including, for example, an acoustic sensor for snoring detection. In some embodiments, the apnea-hypopnea index (AHI) refers to a measure of the number of times a person or patient has upper airway obstruction during sleep. For example, an AHI of five to fifteen times can be mild sleep apnea. The patient's AHI can be monitored using any suitable sensor / device. Similarly, ODI and RDI measure oxygen saturation and respiratory flow changes caused by upper airway obstruction associated with sleep apnea.

[0047] According to certain embodiments, the sensor 214 may generate a sensor signal based on a physiological parameter or change and send the sensor signal to the controller 210. The controller 210 may process the sensor signal and control / adjust one or more stimulation parameters of the stimulation signal generator 206 based at least in part on one or more physiological parameters. In some instances, the sensor 214 may include a position sensor to sense body position or posture during sleep. In some instances, the sensor 214 may determine the sleep stage, for example, whether the patient is in deep sleep or light sleep. In some instances, multiple sensors may be combined to measure the AHI of the patient during sleep.

[0048] In some embodiments, the sensor 214 can send relevant sensing data to the controller 210 to determine whether the patient is entering a stable sleep. When the controller 210 determines that the patient is entering a stable sleep, the controller 210 can retrieve the stored therapy settings from the data storage library and send the therapy settings to the stimulation signal generator 206 to adjust the corresponding one or more first stimulation parameters of the first stimulation signal and / or one or more first stimulation parameters of the second stimulation signal.

[0049] In some embodiments, the sensor 214 can send relevant sensing data to the controller 210 to determine whether the patient is turning to the supine position. When the controller 210 determines that the patient is turning to the supine position, the controller 210 can retrieve the stored therapy settings from the data repository and send the therapy settings to the stimulation signal generator 206 to adjust the corresponding one or more first stimulation parameters of the first stimulation signal and / or one or more first stimulation parameters of the second stimulation signal.

[0050] In some embodiments, the sensor 214 can send relevant sensed data to the controller 210 to determine whether the patient is having an increased AHI. When the controller 210 determines that the patient is having an increased AHI, the controller 210 can retrieve the stored therapy settings from the data repository and send the therapy settings to the stimulation signal generator 206 to adjust the corresponding one or more first stimulation parameters of the first stimulation signal and / or one or more first stimulation parameters of the second stimulation signal.

[0051] In some embodiments, the medical system 200 also includes a data repository 212 to store data for the medical system 200. In some embodiments, the data repository 212 can be implemented using any of the memory or storage configurations described below. The data repository may include random access memory, flat files, XML files, and / or one or more database management systems (DBMS) executed on one or more database servers or data centers. The database management system may be a relational database management system (RDBMS), a hierarchical database management system (HDBMS), a multidimensional database management system (MDBMS), an object-oriented database management system (ODBMS or OODBMS), or an object-relational database management system (ORDBMS), etc. The data repository may be, for example, a single relational database. In some cases, the data repository may include multiple databases that may be exchanged and aggregated through a data integration process or software application. In an exemplary embodiment, at least a portion of the data repository may be stored in a cloud data center. In some cases, the data repository may be stored on a single computer, server, storage device, cloud server, etc. In some other cases, the data repository may be stored on a series of networked computers, servers, or devices. In some cases, data repositories may be stored on multiple layers of data storage, including local, regional, and central.

[0052] The various components of the medical system 200 can communicate or couple via a communication network or interface (e.g., a wired or wireless network or interface). The communication network or interface can be any suitable communication network or combination of communication networks. For example, the communication network can include a Wi-Fi network (which can include one or more wireless routers, one or more switches, etc.), a peer-to-peer network (e.g., a Bluetooth network), a cellular network (e.g., a 3G network, a 4G network, a 5G network, etc. that conforms to any suitable standard), a wired network, etc. In some instances, the communication network can be a local area network (LAN), a wide area network (WAN), a public network (e.g., the Internet), a private network or a semi-private network (e.g., a company or university intranet), any other suitable type of network, or any suitable combination of networks. The communication links (arrows) between the components of the medical system 200 can each be any suitable communication link or a combination of communication links (such as a wired link, a fiber optic link, a Wi-Fi link, a Bluetooth link, a cellular link, etc.).

[0053] Figure 3300 is a flow chart of a medical method 300 for managing obstructive sleep apnea (OSA) in a patient by upper airway neural stimulation according to an embodiment of the present disclosure. The method is described with respect to the stimulation signal generator and electrodes previously discussed herein. It should be understood that any stimulation signal generator and electrodes may be used with the method. Aspects of embodiments of the method may be provided, for example, by a medical system or controller (e.g., Figure 2 Medical system in 200 Figure 2 The controller 210 in the method is executed. One or more steps or blocks (boxes, blocks) of the method are optional and / or can be changed by one or more steps of other embodiments described herein. In addition, one or more steps of other embodiments described herein can be added to the method.

[0054] According to certain embodiments, at process 302, a first implantable electrode is provided near a first nerve of the patient. In some embodiments, the first implantable electrode may be implanted near the hypoglossal nerve of the patient. In some embodiments, the first implantable electrode may be implanted near one or more medial branches of the hypoglossal nerve (m-XII) to stimulate one or more medial branches and activate one or more protrusion muscles of at least one tongue muscle including the genioglossus. In some embodiments, the first electrode may be implanted percutaneously by insertion into the sublingual vein of the patient to be placed and fixed near the first nerve, which may be, for example, one or more medial branches of the hypoglossal nerve. In some embodiments, the first electrode may be implanted percutaneously by insertion through the skin and tissue of the patient to be placed and fixed near the first nerve, which may be, for example, one or more medial branches of the hypoglossal nerve. In some embodiments, the nerve may be located near a position that selectively recruits protrusion muscles and reduces retraction muscle recruitment. In some instances, the first electrode may include one or more percutaneous electrodes, one or more cuff electrodes (cuff electrodes), one or more wire electrodes, etc.

[0055] According to certain embodiments, at process 304, a second implantable electrode is provided near a second nerve of the patient. In some embodiments, the second implantable electrode may be implanted to stimulate the loop cervical nerve and activate one or more of the infrahyoid muscles (including, for example, the omohyoid muscle, the sternothyroid muscle, and the sternohyoid muscle, a combination of the omohyoid muscle, the sternothyroid muscle, and the sternohyoid muscle, or a combination of the sternothyroid muscle and the sternohyoid muscle). In some embodiments, the second implantable electrode may be implanted to deliver a second stimulation signal, thereby stimulating one or more specific nerve branches of the loop cervical and activating the sternothyroid muscle and the sternohyoid muscle simultaneously. In some embodiments, the second electrode may be implanted percutaneously by insertion into the patient's internal jugular vein to be placed and fixed to the second nerve, thereby stimulating the loop cervical nerve and activating one or more of the infrahyoid muscles (including, for example, the omohyoid muscle, the sternothyroid muscle, and the sternohyoid muscle, a combination of the omohyoid muscle, the sternothyroid muscle, and the sternohyoid muscle, or a combination of the sternothyroid muscle and the sternohyoid muscle). In some embodiments, the second electrode can be implanted percutaneously by insertion through the patient's skin and tissue to be placed and secured near the second nerve, thereby stimulating the loop cervical nerve and activating one or more of the infrahyoid muscles (including, for example, the omohyoid muscle, the sternothyroid muscle, and the sternohyoid muscle, a combination of the omohyoid muscle, the sternothyroid muscle, and the sternohyoid muscle, or a combination of the sternothyroid muscle and the sternohyoid muscle). In some examples, the second electrode can include one or more percutaneous leads, one or more paddle leads, one or more cuff leads, etc.

[0056] According to certain embodiments, at process 306, the stimulation signal generator 206 generates and / or delivers a first stimulation signal. In some embodiments, the first stimulation signal may include a series of first stimulation cycles, which include a first stimulation period and a first non-stimulation period. The first stimulation period of the stimulation cycle may include a series of first stimulation pulses having one or more first pulse parameters. Exemplary first pulse parameters include a first pulse frequency, a first pulse amplitude, a first pulse width, a first duty cycle, etc.

[0057] According to certain embodiments, at process 308, the stimulation signal generator 206 generates and / or delivers a second stimulation signal. In some embodiments, the second stimulation signal may include a series of second stimulation cycles, each second stimulation cycle including a second stimulation period and a second non-stimulation period. The second stimulation period of the stimulation cycle may include a series of first stimulation pulses having one or more second pulse parameters. Exemplary second pulse parameters include a second pulse frequency, a second pulse amplitude, a second pulse width, a second duty cycle, etc.

[0058] According to certain embodiments, at process 310, controller 210 coordinates delivery of a first stimulation signal through a first implantable electrode proximate a first nerve with delivery of a second stimulation signal through a second implantable electrode proximate a second nerve. In some embodiments, the first nerve is stimulated to activate at least one muscle for upper airway dilation of the patient. In some embodiments, the second nerve is stimulated to activate at least one muscle for tracheal traction of the upper airway of the patient. Method 300 proceeds to 312.

[0059] According to certain embodiments, at process 312, the controller 210 adjusts one or more first parameters of the first stimulation signal and one or more second parameters of the second stimulation signal. In some embodiments, the controller 210 can control or adjust one or more stimulation parameters for the stimulation signal generator 206 to generate the first and second stimulation signals. The stimulation parameters include, for example, the first / second duration of the first / second stimulation cycle of the first / second stimulation signal, the first / second duration of the first / second stimulation period of the first / second stimulation signal, the first / second duration of the first / second non-stimulation period of the first / second stimulation signal, the coordination between the first stimulation signal and the second stimulation signal, the first / second pulse amplitude of the first / second stimulation signal, the first / second pulse frequency of the first / second stimulation signal, the first / second pulse width of the first / second stimulation signal, the first / second duty cycle of the first / second stimulation signal, etc. In some embodiments, the controller 210 allows the user to adjust the first amplitude of the first stimulation signal and the second amplitude of the second stimulation signal to obtain an optimized combination of the first amplitude and the second amplitude while maintaining other stimulation parameters for the first and second stimulation signals.

[0060] Figure 4A is a schematic diagram showing an exemplary timing cycle of dual neural stimulation in a first mode according to an embodiment of the present disclosure. According to some embodiments, the stimulation signal generator operates in the first mode to synchronize a first stimulation period and a first non-stimulation period of a first stimulation signal with a second stimulation period and a second non-stimulation period of a second stimulation signal, respectively. Figure 4AAs shown in the embodiment, the first stimulation signal 410 includes a series of stimulation signal cycles, each stimulation signal cycle includes a first stimulation period 412 and a first non-stimulation period 414. The second stimulation signal 420 includes a series of stimulation signal cycles, each stimulation signal cycle includes a second stimulation period 422 and a second non-stimulation period 424. In some embodiments, the duration T1_on of the first stimulation period 412 and the duration T2_on of the second stimulation period 422 may be substantially the same. In other words, T1_on = T2_on. In some embodiments, the first stimulation signal 410 and the second stimulation signal 420 are substantially synchronized with each other. In some instances, the start of the first stimulation period 412 and the start of the second stimulation period 422 may be aligned with each other to occur simultaneously (e.g., at Figure 4A In some examples, the start of the first stimulation period 412 and the start of the second stimulation period 422 may be aligned with each other to have an offset T 偏移 For example, when the start of the first stimulation period 412 is at t1, the start of the second stimulation period 422 may be at t1′=t1±T 偏移 Place.

[0061] Figure 4B is a schematic diagram showing an exemplary timing cycle of dual neural stimulation in the second mode according to an embodiment of the present disclosure. According to some embodiments, when the stimulation signal generator is operated in the second mode, one or more first stimulation signals may be dominant (compared to one or more second stimulation signals). Figure 4B As shown in the embodiment of the present invention, the first stimulation signal 430 includes a series of stimulation signal cycles, each stimulation signal cycle includes a first stimulation period 432 and a first non-stimulation period 434. The second stimulation signal 440 includes a series of stimulation signal cycles, each stimulation signal cycle includes a second stimulation period 442 and a second non-stimulation period 444. In some embodiments, the duration T1_on of the first stimulation period 432 can be greater than the duration T2_on of the second stimulation period 442. The ratio of T1_on to T2_on can be in the range of, for example, about 1.0 to about 200.0, about 1.5 to about 200.0, or about 2.0 to about 200.0. In one example, T2_on is 3 seconds, and T1_on is 10 minutes or 600 seconds.

[0062] In some embodiments, the dominant first stimulation signal(s) may be delivered near the hypoglossal nerve to stimulate the hypoglossal nerve and activate at least one tongue muscle. In certain embodiments, the dominant first stimulation signal(s) may be delivered near one or more medial branches of the hypoglossal nerve (m-XII) to stimulate one or more medial branches and activate one or more protrusion muscles of at least one tongue muscle including the genioglossus muscle.

[0063] In some embodiments, one or more second stimulation signals can be delivered to the vicinity of the loop cervical nerve to stimulate the loop cervical nerve and activate one or more infrahyoid muscles. In some embodiments, one or more second stimulation signals can simultaneously stimulate two or more specific nerve branches of the loop cervical, for example, to simultaneously activate the sternothyroid and sternohyoid muscles. In certain embodiments, the stimulation to activate the tongue protrusion muscles can be longer than the stimulation to activate the infrahyoid muscles because the former may have a smaller load.

[0064] exist Figure 4B In the depicted embodiment, the duration T1_on of the first stimulation period 432 is substantially equal to the sum of three times the duration T2_on of the second stimulation period 442 and twice the duration T2_off of the second non-stimulation period 444. In other words, T1_on=3×T2_on+2×T2_off. In some embodiments, the duration T2_off of the second non-stimulation period 444 is substantially the same as the duration T1_off of the first non-stimulation period 434. The start of one first stimulation period 432 and the start T2_on of the second stimulation period 422 can be aligned with each other to occur simultaneously (e.g., at t1). The offset of one first stimulation period 432 in the first stimulation period is synchronized with the offset of another second stimulation period 442 in the second stimulation period (e.g., at t6).

[0065] Figure 5A is a schematic diagram illustrating neurally regulated synchronization with a natural breathing rhythm according to an embodiment of the present disclosure. An exemplary breathing waveform 502 includes a series of continuously repeated breathing cycles 504, each of which includes an inspiratory phase 503 and an expiratory phase 505. In some embodiments, the exemplary breathing waveform 502 can be pre-measured or pre-determined for a particular patient. The breathing waveform 502 can be stored as a historical breathing waveform in a data repository of the medical system described herein.

[0066] In some embodiments, the stimulation signal 512 may include a series of stimulation signal cycles 514, each stimulation signal cycle including a stimulation period 513 and a non-stimulation period 515. In some embodiments, the stimulation signal cycle 514 of the stimulation signal 512 may be controlled or adjusted to have a duration substantially the same as the duration of the respiratory cycle of the historical respiratory waveform 502. For example, the difference between the duration of the stimulation signal cycle 514 of the stimulation signal 512 and the duration of the respiratory cycle 504 of the respiratory waveform 502 may be no greater than 20%, no greater than 15%, or no greater than 10%. In some embodiments, the stimulation period 513 may have a duration substantially the same as the duration of the inspiratory phase 503 of the respiratory waveform 502. For example, the difference between the duration of the stimulation period 513 and the duration of the inspiratory phase 503 of the respiratory waveform 502 may be no greater than 20%, no greater than 15%, or no greater than 10%. In some embodiments, the non-stimulation period 515 may have a duration substantially the same as the duration of the expiratory phase 505 of the respiratory waveform 502. For example, the difference between the duration of the non-stimulation period 515 and the duration of the expiratory phase 505 of the respiratory waveform 502 may be no greater than 20%, no greater than 15%, or no greater than 10%.

[0067] In some embodiments, the medical system 200 does not require a sensor to detect the patient's respiratory waveform in real time. Instead, the controller 210 can access the historical respiratory waveform 502 stored in the data repository 212. The controller 210 can determine one or more stimulation parameters based at least in part on the historical respiratory waveform 502. For example, the controller 210 can determine one or more durations of the stimulation signal 512 based at least in part on one or more corresponding durations of the respiratory waveform 502. The controller 210 can send the determined stimulation parameters to the stimulation signal generator 206 to generate one or more stimulation signals and deliver them to one or more of the corresponding implanted electrodes.

[0068] In some embodiments, the stimulation signal generator 206 generates a first stimulation signal to be delivered to the first implantable electrode 202, thereby stimulating the first nerve and activating at least one muscle for the patient's upper airway dilation. Although not wanting to be bound by theory, it is believed that the duration of the upper airway patency can follow the first stimulation cycle of the first stimulation signal, which in turn can make the patient's natural breathing rhythm follow the first stimulation cycle of the first stimulation signal and synchronize with it, in other words, the patient's natural breathing rhythm is synchronized with the first stimulation signal. For example, in the embodiment depicted in Figure 5, the stimulation signal 512 can be the first stimulation signal. The stimulation signal cycle 513 of the first stimulation signal 512 is substantially synchronized with the respiratory cycle of the patient's respiratory waveform 502. The start of the stimulation cycle 513 of the first stimulation signal 512 is substantially aligned with the start of the inspiratory phase 503 of the patient's respiratory waveform 502.

[0069] In some embodiments, the stimulation signal generator 206 generates a second stimulation signal to be delivered to the second implantable electrode 204, thereby stimulating the second nerve and activating at least one muscle for the tail tracheal traction of the patient's upper airway. Although not wanting to be bound by theory, it is believed that the duration of the upper airway patency can follow the second stimulation cycle of the second stimulation signal, which in turn can make the patient's natural breathing rhythm follow the second stimulation cycle of the second stimulation signal and synchronize with it, in other words, the patient's natural breathing rhythm is synchronized with the second stimulation signal. For example, in the embodiment depicted in Figure 5, the stimulation signal 512 can be the second stimulation signal. The stimulation signal cycle 513 of the second stimulation signal 512 is substantially synchronized with the breathing cycle of the patient's breathing waveform 502. The start of the stimulation cycle 513 of the second stimulation signal 512 is substantially aligned with the start of the inspiratory phase 503 of the patient's breathing waveform 502.

[0070] Figure 5B is a flow chart of a medical method 500 for managing obstructive sleep apnea in a patient via upper airway dual neural stimulation in accordance with an embodiment of the present disclosure.

[0071] It should be understood that any stimulation signal generator and electrode can be used in the method. Aspects of the embodiments of the method can be implemented, for example, by a medical system or controller (e.g., Figure 2 Medical system in 200 Figure 2 The controller 210 in the method is executed. One or more steps or blocks of the method are optional and / or can be changed by one or more steps of other embodiments described herein. In addition, one or more steps of other embodiments described herein can be added to the method.

[0072] According to some embodiments, at process 522, the patient's natural breathing rhythm may be measured or received, such as Figure 5A502 of the respiratory waveform. It should be understood that the natural respiratory rhythm of the patient can be pre-measured or pre-determined for a specific patient. In some embodiments, the controller 210 can access the data repository 212 to obtain the historical respiratory waveform for a specific patient.

[0073] According to some embodiments, at process 524, a first stimulation signal period of the first stimulation signal may be determined based at least in part on the patient's breathing waveform. In some examples, the first stimulation signal period (e.g., Figure 5A The stimulation signal period 514 of the stimulation signal 512 is controlled or adjusted to have a duration substantially the same as the duration of the respiratory cycle of the historical respiratory waveform 502.

[0074] According to some embodiments, at process 526, a second stimulation signal period of the second stimulation signal may be determined based at least in part on the patient's breathing waveform and / or the first stimulation signal. In some examples, the second stimulation signal period of the second stimulation signal (e.g., Figure 5A The stimulation signal period 514 of the stimulation signal 512 is controlled or adjusted to have a duration substantially the same as the duration of the respiratory cycle of the historical respiratory waveform 502.

[0075] According to some embodiments, at process 528, the first stimulation signal can be coordinated with the second stimulation signal for delivery to the vicinity of the first nerve and the second nerve, respectively.

[0076] According to certain embodiments, at process 530, a first stimulation signal is delivered to stimulate a first nerve, and a second stimulation signal is delivered to stimulate a second nerve. In some embodiments, the first stimulation signal is delivered to stimulate the first hypoglossal nerve, thereby activating the tongue extensor muscles (e.g., the genioglossus muscle), and avoiding stimulation of certain nerve branches that may activate the suprahyoid muscles (e.g., the geniohyoid muscle) and avoiding stimulation of certain nerve branches that may activate the retractor muscles (e.g., the styloglossus muscle and / or the hyoglossus muscle) of the tongue muscles. In some embodiments, the second stimulation signal is delivered to stimulate the first cervical nerve, thereby activating the infrahyoid muscles (e.g., the sternothyroid muscle and / or the sternohyoid muscle), and avoiding stimulation of certain nerve branches that may activate the suprahyoid muscles (e.g., the geniohyoid muscle). In some embodiments, a second implantable electrode can be implanted to deliver a second stimulation signal to stimulate one or more specific nerve branches of the cervical loop and simultaneously activate the sternothyroid and sternohyoid muscles while avoiding stimulation of certain nerve branches that may activate the suprahyoid muscles (e.g., the geniohyoid muscle).

[0077] According to certain embodiments, at process 532, the patient's breathing rhythm may be synchronized with the first stimulation signal cycle and / or the second stimulation signal cycle to achieve synchronization of the patient's natural breathing rhythm with dual neural stimulation using coordinated first and second stimulation signals.

[0078] Fig. 6A -C is a flow chart illustrating various exemplary titration methods for developing stimulation therapies or settings for managing obstructive sleep apnea (OSA) in a person according to some embodiments of the present disclosure. In some embodiments, the obtained stimulation therapies or settings can be provided to the controller 210 or the stimulation signal generator 206 as programmable settings to modulate one or more stimulation signals.

[0079] In the first titration method 610, as Fig. 6A As shown, when it is detected that the patient enters stable sleep (at box 612), the first stimulation signal gradually increases from a lower level to a higher level (at box 614), and remains at the higher level for a first period of time (at box 615). The lower level can be, for example, a lower pulse amplitude, a lower pulse width, a lower duty cycle, a lower pulse frequency, etc. The higher level can be, for example, a higher pulse width, a higher pulse amplitude, a higher duty cycle, a higher pulse frequency, etc. In some embodiments, the lower level can be a functional or sensory threshold level when the patient begins to feel the stimulation. For example, the lower level can be the level at which the patient's tongue begins to extend through the stimulation of the first stimulation signal at a functional (bulk movement of the tongue or hyoid bone and thyroid cartilage complex) or sensory (the lowest stimulation level at which the patient perceives the stimulation) threshold level. In some embodiments, the higher level can be, for example, a saturation level when the patient's AHI begins to stabilize. In the case where the first stimulation signal remains at a saturation level, the second stimulation signal can be gradually increased from a lower level to a higher level (at box 616), and maintained at a higher level for a second period of time (at box 617). It will be appreciated that the lower / upper levels of the first stimulation signal may be different than the lower / upper levels of the second stimulation signal, possibly depending on the characteristics of the respective first and second nerves to be stimulated.

[0080] In the second titration method 620, as Figure 6BAs shown, when it is detected that the patient turns to a supine position (at box 622), the first stimulation signal gradually increases from a lower level to a higher level (at box 624), and remains at a higher level for a first time period (at box 625). The lower level can be, for example, a lower pulse amplitude, a lower pulse width, a lower duty cycle, etc. The higher level can be, for example, a higher pulse width, a higher pulse amplitude, a higher duty cycle, etc. In some embodiments, the lower level can be a functional or sensory threshold level when the patient begins to feel the stimulation. For example, the lower level can be the level when the patient's tongue begins to extend through the stimulation of the first stimulation signal at the functional or sensory threshold level. In some embodiments, the higher level can be, for example, a saturation level when the patient's AHI begins to stabilize. In the case where the first stimulation signal remains at a saturation level, the second stimulation signal can gradually increase from a lower level to a higher level (at box 626), and remain at a higher level for a second time period (at box 627). It should be understood that the corresponding lower and higher levels of the first and second stimulation signals can be different. When it is detected that the patient has turned to a non-supine posture (at box 628), the first stimulation signal and / or the second stimulation signal may be gradually reduced from the corresponding higher level to the corresponding second lower level (at box 629), and maintained at the corresponding second lower level for a third period of time (at box 631). The second lower level may be the same as or different from the previous lower level.

[0081] In the third titration method 630, as Figure 6C As shown, when the patient's AHI is detected to increase (at box 632), the first stimulation signal gradually increases from a lower level to a higher level (at box 634), and remains at the higher level for a first time period (at box 635). The lower level can be, for example, a lower pulse amplitude, a lower pulse width, a lower duty cycle, etc. The higher level can be, for example, a higher pulse width, a higher pulse amplitude, a higher duty cycle, etc. In some embodiments, the lower level can be a functional or sensory threshold level when the patient begins to feel the stimulation. For example, the lower level can be the level when the patient's tongue begins to extend by the stimulation of the first stimulation signal at the functional or sensory threshold level. In some embodiments, the higher level can be, for example, a saturation level when the patient's AHI begins to stabilize. In the case where the first stimulation signal remains at the saturation level, the second stimulation signal can be gradually increased from a lower level to a higher level (at box 636), and remain at the higher level for a second time period (at box 637). When it is detected that the patient's AHI drops to a predetermined range (e.g., below 5) (at box 638), the first stimulation signal and / or the second stimulation signal may be gradually reduced from the corresponding higher level to the corresponding second lower level (at box 639) and maintained at the corresponding second level for a fourth time period (at box 641).

[0082] According to certain embodiments, in any titration method (e.g., first, second, or third titration method 610, 620, 630), the patient's AHI may be measured by Figure 2 The sensor 214 is monitored in real time to adjust one or more first parameters of the first stimulation signal (e.g., first amplitude, first time period, etc.) and one or more second parameters of the second stimulation signal (e.g., second amplitude, second time period, etc.) to optimize the method and obtain an optimized therapy for managing the patient's obstructive sleep apnea (OSA).

[0083] Fig. 7A A schematic diagram depicting the patient's anatomical structure and one or more target muscle locations for hypoglossal nerve stimulation according to an embodiment of the present disclosure is shown. In some embodiments, one or more first implantable electrodes deliver a first stimulation signal to the vicinity of the first hypoglossal nerve to activate the tongue extensor muscles (e.g., the genioglossus 710). In some embodiments, the implantable electrode can be positioned to deliver the first stimulation signal to the vicinity of one or more medial branches of the hypoglossal nerve (m-XII) to stimulate the one or more medial branches and activate one or more extensor muscles of the tongue muscles including the genioglossus 710. In some embodiments, one or more first implantable electrodes deliver the first stimulation signal to avoid activating the suprahyoid muscles (e.g., the genioglossus 712). In some embodiments, one or more first implantable electrodes are positioned to avoid activating one or more retractor muscles of the tongue muscles including the styloglossus 711 and the hyoglossus 713.

[0084] Figure 7B A schematic diagram depicting the patient's anatomy and one or more target muscle locations for cervical loop stimulation according to an embodiment of the present disclosure is shown. In some embodiments, one or more second implantable electrodes deliver a second stimulation signal to the vicinity of the first cervical loop nerve to stimulate the first cervical loop nerve, thereby activating the infrahyoid muscles (including the sternothyroid muscle 722, the sternohyoid muscle 724, and the omohyoid muscle 721) located below the hyoid bone 723. In some embodiments, a second implantable electrode can be implanted to deliver a second stimulation signal to stimulate one or more specific nerve branches of the cervical loop and simultaneously activate the sternothyroid muscle 722 and the sternohyoid muscle 724. In some embodiments, one or more first implantable electrodes and second implantable electrodes are positioned to deliver the first and second stimulation signals to avoid activating the suprahyoid muscle 725 located above the hyoid bone 723 (see also, e.g., Fig. 7A Activation of the suprahyoid muscle 725 may counteract the effect of activation of the infrahyoid muscles (including the sternothyroid muscle 722 and the sternohyoid muscle 724), and it may be desirable to avoid activation of the suprahyoid muscle 725 by properly positioning the first implantable electrode.

[0085] It should be understood that when the first stimulation signal is used alone (i.e., not simultaneously with the second stimulation signal) to activate the tongue extensor muscles, it is acceptable for the first stimulation signal to also activate the suprahyoid muscles (e.g., the geniohyoid muscle). When dual nerve stimulation of the upper airway including both hypoglossal nerve stimulation and cervical loop stimulation is implemented as described herein, in some embodiments, it is desirable to avoid activating the suprahyoid muscles (e.g., the geniohyoid muscle) because such activation may counteract the effects of cervical loop stimulation.

[0086] Figure 7C A schematic diagram depicting the patient anatomy and one or more target nerve / muscle locations for upper airway dual neural stimulation (including hypoglossal nerve stimulation and cervical loop stimulation) according to an embodiment of the present disclosure is shown. In some embodiments, one or more target or desired nerve / muscle locations for upper airway dual neural stimulation may include, for example, one or more infrahyoid muscles (e.g., sternothyroid muscle 722, sternohyoid muscle 724, and omohyoid muscle 721). Figure 7C Also shown are related locations, such as the common trunk of the omohyoid, sternothyroid, and sternohyoid muscles 731, the common trunk of the sternothyroid and sternohyoid muscles 732, the nerve trunk of the sternothyroid muscle 733, the nerve trunk of the sternohyoid muscle 734, the first cervical (C1) spinal nerve, the second cervical (C2) spinal nerve, and the third cervical (C3) spinal nerve. In some embodiments, upper airway dual nerve stimulation can avoid stimulating or activating one or more nerve / muscle locations, including, for example, the styloglossus, hyoglossus, and geniohyoid muscles.

[0087] Fig.7D A schematic diagram depicting patient anatomy and one or more target nerve / muscle locations for cervical loop stimulation in upper airway dual neural stimulation is shown in accordance with an embodiment of the present disclosure. Fig.7D The locations of the various cervical nerves are shown, including the superior root (SR), superior omohyoid (OHs), superior sternohyoid (SHs), sternothyroid (ST), inferior sternohyoid (SHi), and inferior omohyoid (OHi). Fig.7DAlso shown are the locations of various muscles, including the sternohyoid muscle (SH), the sternothyroid muscle (ST), and the thyrohyoid muscle (TH). Also shown are the internal jugular vein (IJV) 71 and the cranial / caudal direction 73. The target stimulation locations may include one or more of location A 742, location B 743, location C 744, location D 745, and location E 746. In some embodiments, a single implanted stimulation lead may be arranged at or near one of locations A to E 742, 743, 744, 745, and 746. For example, a single implanted stimulation lead may be located at or near location A 742 to deliver a stimulation signal. In some embodiments, a stimulation signal may be delivered to or near location A 742 to simultaneously stimulate two or more related nerve branches of the cervical loop, for example, to simultaneously activate the sternothyroid muscle (ST) 722 and the sternohyoid muscle (SHi) 724. In certain embodiments, the stimulation lead may be arranged at (e.g., delivered to) or near a nerve segment connected to two or more nerve branches. For example, the stimulation lead may be arranged at or near position 742 where it is a nerve segment connected to branch 742A and branch 742B. In some embodiments, the stimulation signal may be delivered to or near a nerve segment connected to two or more nerve branches. In some embodiments, the first implanted stimulation lead may be located at or near one of position A 742, position B 743, and position C 744, and the second implanted stimulation lead may be located at or near position E 746 or position D 745. In some embodiments, position A 742 and position B 743 may be superior to position C 744 because the distance to the internal jugular vein (IJV) 741 is relatively close and / or the nerve size is relatively large (as indicated by the corresponding line thickness). In some embodiments, a first implanted stimulation lead can be located at or near position A 742 or position B 743 , and a second implanted stimulation lead can be located at or near position E 746 .

[0088] In some embodiments, the controller 210 is configured to modulate the second stimulation signal between a lower stimulation level and a higher stimulation level to activate one or more infrahyoid muscles within a strain range from a first strain value to a second strain value. In some embodiments, strain can be measured by displacement of the hyoid bone. The displacement can be, for example, an absolute displacement within a range of about 5 mm to about 20 mm, which can correspond to the first strain value and the second strain value, respectively. It should be understood that displacement or strain can be represented by a relative value (e.g., a percentage). The lower level of the second stimulation signal corresponds to the first strain value, and the higher level of the second stimulation signal corresponds to the second strain value. An optimal stimulation level can be determined between a lower stimulation level and a higher stimulation level to provide an optimal strain, thereby providing tail airway traction of the patient's upper airway. The optimal strain level can prevent possible upper airway collapse or flow limitation. In some embodiments, the optimal stimulation level can be determined by using the measured strain level (e.g., as indicated by the displacement of the hyoid bone) as feedback. For example, a series of stimulation levels can be applied, and the corresponding hyoid bone displacement can be measured to determine the optimal stimulation level.

[0089] Various changes and additions may be made to the exemplary embodiments discussed without departing from the scope of the present disclosure. For example, while the above-described embodiments relate to specific features, the scope of the present disclosure also includes embodiments having different combinations of features and embodiments that do not include all of the described features. Therefore, the scope of the present disclosure is intended to cover all such alternatives, changes and modifications that fall within the scope of the claims, together with all their equivalents.

[0090] According to some embodiments of the present disclosure, a system for managing obstructive sleep apnea in a person is provided. The system includes: a first implantable electrode configured to deliver a first stimulation signal to the vicinity of a first nerve of a person, thereby stimulating the first nerve and activating at least one first muscle for upper airway dilation of the person; a second implantable electrode configured to deliver a second stimulation signal to the vicinity of a second nerve, thereby stimulating the second nerve and activating at least one second muscle for tailpipe traction of the upper airway of the person; and a stimulation signal generator configured to deliver the first stimulation signal to the first implantable electrode and deliver the second stimulation signal to the second implantable electrode, the first stimulation signal having a series of first stimulation cycles, each of which includes a first stimulation period and a first non-stimulation period, the second stimulation signal having a series of second stimulation cycles, each of which includes a second stimulation period and a second non-stimulation period, and the delivery of the first stimulation signal is coordinated with the delivery of the second stimulation signal. The second stimulation signal is modulated to activate at least one second muscle within a strain range from a first strain value to a second strain value, wherein the first stimulation level of the second stimulation signal corresponds to the first strain value, and the second stimulation level of the second stimulation signal corresponds to the second strain value.

[0091] In certain embodiments, the system further includes a controller functionally connected to the stimulation signal generator to control the operation of the stimulation signal generator.

[0092] In certain embodiments, the controller is further configured to control one or more stimulation parameters for the stimulation signal generator.

[0093] In certain embodiments, the one or more stimulation parameters include one or more of amplitude, frequency, pulse width, rate of change of amplitude, and duty cycle.

[0094] In some embodiments, the first implantable electrode is configured to deliver a first stimulation signal proximate to the hypoglossal nerve to stimulate the hypoglossal nerve and activate at least one tongue muscle.

[0095] In some embodiments, the first implantable electrode is positioned to deliver a first stimulation signal proximate one or more medial branches of the hypoglossal nerve (m-XII) to stimulate the one or more medial branches and activate one or more protrusion muscles of at least one tongue muscle including the genioglossus muscle.

[0096] In some embodiments, the second implantable electrode is configured to deliver a second stimulation signal to the vicinity of the loop cervical nerve to stimulate the loop cervical nerve and activate one or more infrahyoid muscles. In some embodiments, the second stimulation signal can activate the sternothyroid muscle and the sternohyoid muscle simultaneously.

[0097] In some embodiments, the controller is configured to modulate the second stimulation signal to activate one or more infrahyoid muscles within a strain range from a first strain value to a second strain value, wherein a first amplitude level of the second stimulation signal corresponds to the first strain value and a second amplitude level of the second stimulation signal corresponds to the second strain value.

[0098] In some embodiments, the controller is configured to control the operation of the stimulation signal generator in a first mode, wherein the stimulation signal generator is configured to synchronize a first stimulation period and a first non-stimulation period of a first stimulation signal with a second stimulation period and a second non-stimulation period of a second stimulation signal, respectively.

[0099] In certain embodiments, the controller is configured to control operation of the stimulation signal generator in a second mode, wherein a first duration of the first stimulation session is greater than a second duration of the second stimulation session.

[0100] In some embodiments, in the second mode, a first duration of the first stimulation session is two or more times longer than a second duration of the second stimulation session.

[0101] In certain embodiments, the stimulation signal generator is configured to coordinate delivery of the first stimulation signal and delivery of the second stimulation signal based at least in part on the historical respiratory waveform.

[0102] In certain embodiments, the stimulation signal generator includes an internal timer to provide timing to coordinate a series of first stimulation cycles and a series of second stimulation cycles (independent of the person's respiratory state).

[0103] In certain embodiments, the system further comprises one or more sensors to detect one or more physiological parameters including apnea-hypopnea index (AHI), posture changes, sleep stage, and time of day.

[0104] In certain embodiments, the controller is configured to control one or more stimulation parameters of the stimulation signal generator based at least in part on one or more physiological parameters.

[0105] In certain embodiments, the controller further includes a patient controller to control the operation of the stimulation signal generator, including turning the stimulation signal generator on or off.

[0106] In some embodiments, the system also includes a third implantable electrode configured to deliver a third stimulation signal proximate to a third nerve to stimulate the third nerve.

[0107] According to certain embodiments of the present disclosure, a method for managing obstructive sleep apnea in a person is provided. The method includes: providing a first implantable electrode, which is configured to deliver a first stimulation signal to the vicinity of a first nerve, thereby stimulating the first nerve and activating at least one first muscle for upper airway dilation; providing a second implantable electrode, which is configured to deliver a second stimulation signal to the vicinity of a second nerve, thereby stimulating the second nerve and activating at least one second muscle for tailpipe traction of the upper airway of the person; modulating the second stimulation signal to activate at least one second muscle within a strain range from a first strain value to a second strain value, wherein the first stimulation level of the second stimulation signal corresponds to the first strain value, and the second stimulation level of the second stimulation signal corresponds to the second strain value; delivering the first stimulation signal to the first implantable electrode; and delivering the second stimulation signal to the second implantable electrode, wherein the first stimulation signal is coordinated with the second stimulation signal, and wherein the first stimulation signal has a series of first stimulation cycles, each of which includes a first stimulation period and a first non-stimulation period, and the second stimulation signal has a series of second stimulation cycles, each of which includes a second stimulation period and a second non-stimulation period.

[0108] In certain embodiments, the method further comprises controlling one or more first stimulation parameters for the first stimulation signal; and controlling one or more second stimulation parameters for the second stimulation signal.

[0109] In certain embodiments, the one or more first stimulation parameters and the one or more second stimulation parameters each include one or more of amplitude, frequency, pulse width, rate of change of amplitude, and duty cycle.

[0110] In some embodiments, the first implantable electrode is configured to deliver a first stimulation signal proximate to the hypoglossal nerve to stimulate the hypoglossal nerve and activate at least one tongue muscle.

[0111] In some embodiments, delivering the first stimulation signal also includes delivering the first stimulation signal near one or more medial branches of the hypoglossal nerve (m-XII) to stimulate the one or more medial branches and activate one or more protrusion muscles of at least one tongue muscle including the genioglossus muscle.

[0112] In some embodiments, the second implantable electrode is configured to deliver a second stimulation signal to the vicinity of the loop cervical nerve to stimulate the loop cervical nerve and activate one or more infrahyoid muscles (including the sternothyroid muscle and the sternohyoid muscle). In some embodiments, the second stimulation signal can activate the sternothyroid muscle and the sternohyoid muscle simultaneously.

[0113] In some embodiments, modulating the second stimulation signal to activate at least one second muscle also includes modulating the second stimulation signal to activate one or more infrahyoid muscles within a strain range from a first strain value to a second strain value, wherein the first amplitude level of the second stimulation signal corresponds to the first strain value and the second amplitude level of the second stimulation signal corresponds to the second strain value.

[0114] In some embodiments, the method also includes controlling the operation of the stimulation signal generator in a first mode, wherein the stimulation signal generator is configured to synchronize a first stimulation period and a first non-stimulation period of the first stimulation signal with a second stimulation period and a second non-stimulation period of the second stimulation signal, respectively.

[0115] In certain embodiments, the method further comprises controlling operation of the stimulation signal generator in a second mode, wherein a first duration of the first stimulation session is two or more times a second duration of the second stimulation session.

[0116] In certain embodiments, the method further comprises coordinating delivery of the first stimulation signal and delivery of the second stimulation signal based at least in part on a historical breathing waveform of the person.

[0117] In certain embodiments, the method further comprises synchronizing a series of first stimulation cycles of the first stimulation signal with a current breathing waveform of the person.

[0118] In certain embodiments, the method further comprises synchronizing a series of second stimulation cycles of the second stimulation signal with a current breathing waveform of the person.

[0119] In certain embodiments, the method further comprises coordinating the series of first stimulation cycles and the series of second stimulation cycles (independent of the person's respiratory state) by providing timing using an internal timer.

[0120] In certain embodiments, the method further comprises detecting one or more physiological parameters including apnea-hypopnea index (AHI), posture changes, sleep stage, and time of day.

[0121] In certain embodiments, the method further comprises controlling one or more stimulation parameters of the stimulation signal generator based at least in part on the one or more physiological parameters.

[0122] Various changes and additions may be made to the exemplary embodiments discussed without departing from the scope of the present disclosure. For example, while the above-described embodiments relate to specific features, the scope of the present invention also includes embodiments with different combinations of features and embodiments that do not include all of the described features. Therefore, the scope of the present invention is intended to cover all such alternatives, changes and modifications that fall within the scope of the claims, together with all their equivalents.

Claims

1. A system for managing obstructive sleep apnea in a person, the system comprising: a first implantable electrode configured to deliver a first stimulation signal proximate a first nerve of the person, thereby stimulating the first nerve and activating at least one first muscle for upper airway dilation of the person; a second implantable electrode configured to deliver a second stimulation signal proximate to a second nerve, thereby stimulating the second nerve and activating at least one second muscle for tailpipe traction of the upper airway of the person; as well as a stimulation signal generator configured to deliver the first stimulation signal to the first implanted electrode and to deliver the second stimulation signal to the second implanted electrode, the first stimulation signal having a series of first stimulation cycles, each of which includes a first stimulation period and a first non-stimulation period, the second stimulation signal having a series of second stimulation cycles, each of which includes a second stimulation period and a second non-stimulation period, the delivery of the first stimulation signal being coordinated with the delivery of the second stimulation signal, The second stimulation signal is modulated to activate the at least one second muscle within a strain range from a first strain value to a second strain value, wherein a first stimulation level of the second stimulation signal corresponds to the first strain value and a second stimulation level of the second stimulation signal corresponds to the second strain value.

2. The system of claim 1, further comprising a controller functionally connected to the stimulation signal generator to control the operation of the stimulation signal generator.

3. The system of claim 2, wherein the controller is further configured to control one or more stimulation parameters for the stimulation signal generator.

4. The system of claim 3, wherein the one or more stimulation parameters include one or more of amplitude, frequency, pulse width, amplitude change rate, and duty cycle.

5. The system of any one of claims 1 to 4, wherein the first implantable electrode is configured to deliver the first stimulation signal to the vicinity of the hypoglossal nerve to stimulate the hypoglossal nerve and activate at least one tongue muscle.

6. A system according to claim 5, wherein the first implantable electrode is positioned to deliver the first stimulation signal near one or more medial branches of the hypoglossal nerve (m-XII) to stimulate the one or more medial branches and activate one or more extensor muscles of at least one tongue muscle including the genioglossus muscle.

7. A system according to any one of claims 1 to 6, wherein: The second implantable electrode is configured to deliver the second stimulation signal proximate to the loop cervical nerve to stimulate the loop cervical nerve and activate one or more infrahyoid muscles.

8. The system of claim 7, wherein the second stimulation signal is further configured to activate the sternothyroid muscle and the sternohyoid muscle simultaneously.

9. A system according to claim 7 or 8, wherein: The controller is configured to modulate the second stimulation signal to activate the one or more infrahyoid muscles within a strain range from the first strain value to the second strain value, and A first amplitude level of the second stimulation signal corresponds to the first strain value, and a second amplitude level of the second stimulation signal corresponds to the second strain value.

10. A method for managing obstructive sleep apnea in a human, the method comprising: providing a first implantable electrode configured to deliver a first stimulation signal proximate to a first nerve, thereby stimulating the first nerve and activating at least one first muscle for upper airway dilation; providing a second implantable electrode configured to deliver a second stimulation signal proximate to a second nerve, thereby stimulating the second nerve and activating at least one second muscle for tail-tracheal traction of the upper airway of the person; modulating the second stimulation signal to activate the at least one second muscle within a strain range from a first strain value to a second strain value, wherein a first stimulation level of the second stimulation signal corresponds to the first strain value and a second stimulation level of the second stimulation signal corresponds to the second strain value; delivering the first stimulation signal to the first implantable electrode; as well as delivering the second stimulation signal to the second implantable electrode, wherein the first stimulation signal and the second stimulation signal are coordinated, and The first stimulation signal has a series of first stimulation cycles, each of which includes a first stimulation period and a first non-stimulation period, and the second stimulation signal has a series of second stimulation cycles, each of which includes a second stimulation period and a second non-stimulation period.

11. The method according to claim 10, further comprising: controlling one or more first stimulation parameters for the first stimulation signal; as well as One or more second stimulation parameters for the second stimulation signal are controlled.

12. The method of claim 10 or 11, wherein the first implantable electrode is configured to deliver the first stimulation signal to the vicinity of the hypoglossal nerve to stimulate the hypoglossal nerve and activate at least one tongue muscle.

13. The method according to any one of claims 10 to 12, wherein the second implantable electrode is configured to deliver a second stimulation signal to the vicinity of the loop cervical nerve to stimulate the loop cervical nerve and activate one or more infrahyoid muscles.

14. The method of claim 13, wherein the second stimulation signal is further configured to activate the sternothyroid muscle and the sternohyoid muscle simultaneously.

15. The method of any one of claims 10 to 14, further comprising coordinating delivery of the first stimulation signal and delivery of the second stimulation signal based at least in part on a historical breathing waveform of the person.

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