WO2025042826A1

WO2025042826A1 - Systems and methods for evaluating efficacy of treatment for improvement of sleep disordered breathing

Info

Publication number: WO2025042826A1
Application number: PCT/US2024/042907
Authority: WO
Inventors: Anthony V. Caparso; Travis M. SPOOR; Bhavesh Patel; Rabih Nassif
Original assignee: XII Medical Inc
Current assignee: XII Medical Inc
Priority date: 2023-08-21
Filing date: 2024-08-19
Publication date: 2025-02-27
Anticipated expiration: 2026-02-21

Abstract

Methods and systems for treating sleep disordered breathing and assessing and improving efficacy of treatment of sleep disordered breathing re disclosed herein. According to some embodiments, the present technology includes a method of treating sleep disordered breathing with a neuromodulation system at least partially implanted in a patient having an airway compromised by an obstruction. The method includes delivering stimulation energy to a target nerve in the patient using an electrode of the neuromodulation system, wherein the target nerve is associated with patency of the airway, receiving sensor data from a sensor arrangement of the neuromodulation system, wherein the sensor data is indicative of airflow in the airway proximal to the obstruction, and assessing efficacy of the stimulation energy based at least in part on the received sensor data.

Description

SYSTEMS AND METHODS FOR EVALUATING EFFICACY OF TREATMENT FOR IMPROVEMENT OF SLEEP DISORDERED BREATHING

CROSS-REFERENCE TO RELATED APPLICATION(S)

[0001] The present technology claims the benefit of priority to U.S. Provisional Patent Application No. 63/520,764, filed August 21, 2023, titled SYSTEMS AND METHODS FOR EVALUATING EFFICACY OF TREATMENT FOR IMPROVEMENT OF SLEEP DISORDERED BREATHING, which is incorporated by reference herein in its entirety.

TECHNICAL FIELD

10002] The present technology relates to systems and methods of evaluating efficacy of treatment for improvement of sleep disordered breathing.

BACKGROUND

[0003] Sleep disordered breathing (SDB), such as upper airway sleep disorders (UASDs), is a condition that occurs that diminishes sleep time and sleep quality, resulting in patients exhibiting symptoms that include daytime sleepiness, tiredness, and lack of concentration. Obstructive sleep apnea (OSA), the most common type of SDB, affects one in five adults in the United States. One in 15 adults has moderate to severe OSA and requires treatment. Untreated OSA results in reduced quality of life measures and increased risk of disease, including hypertension, stroke, heart disease, and others.

[0004] OSA is characterized by the complete obstruction of the airway, causing breathing to cease completely (apnea) or partially (hypopnea). During sleep, the tongue muscles relax. In this relaxed state, the tongue may lack sufficient muscle tone to prevent the tongue from changing its normal tonic shape and position. When the base of the tongue and/or soft tissue of the upper airway collapse, the upper airway channel is blocked, causing an apnea event. Blockage of the upper airway prevents air from flowing into the lungs, thereby decreasing the patient’s blood oxygen level, which in turn increases blood pressure and heart dilation. This causes a reflexive forced opening of the upper airway channel until normal patency is regained, followed by normal respiration until the next apneic event. These reflexive forced openings briefly arouse the patient from sleep. I0005J Current treatment options range from drug intervention, non-invasive approaches, to more invasive surgical procedures. In many of these instances, patient acceptance and therapy compliance are well below desired levels, rendering the current solutions ineffective as a long-term solution. Continuous positive airway pressure (CPAP), for example, is a standard treatment for OSA. While CPAP is non-invasive and highly effective, it is not well tolerated by all patients and has several side effects. Patient compliance and/or tolerance for CPAP is often reported to be between 40% and 60%. Surgical treatment options for OSA, such as anterior tongue muscle repositioning, orthognathic bimaxillary advancement, uvula-palatalpharyngoplasty, and tracheostomy are available too. However, these procedures tend to be highly invasive, irreversible, and have poor and/or inconsistent efficacy. Even the more effective surgical procedures are undesirable because they usually require multiple invasive and irreversible operations, they may alter a patient's appearance (e.g., maxillomandibular advancement), and/or they may be socially stigmatic (e.g., tracheostomy) and have extensive morbidity.

SUMMARY

[0006J The subject technology is illustrated, for example, according to various aspects described below, including with reference to FIGS. 1-7. Various examples of aspects of the subject technology are described as numbered Examples (1, 2, 3, etc.) for convenience. These are provided as examples and do not limit the subject technology.

[0007] Example 1. A method of treating sleep disordered breathing with a neuromodulation system at least partially implanted in a patient having an airway compromised by an obstruction, wherein the method comprises: delivering stimulation energy to a target nerve in the patient using an electrode of the neuromodulation system, wherein the target nerve is associated with patency of the airway; receiving sensor data from a sensor arrangement of the neuromodulation system, wherein the sensor data is indicative of airflow in the airway proximal to the obstruction; and assessing efficacy of the stimulation energy based at least in part on the received sensor data.

[0008| Example 2. The method of example 1, wherein the sensor data characterizes vibrations indicative of airflow in the airway proximal to the obstruction. f 0009 J Example 3. The method of example 1 or 2, wherein the sensor data characterizes vibrations of oral tissue of the patient.

[0010] Example 4. The method of any one of examples 1-3 wherein the sensor data characterizes vibrations of air in an oral region of the patient.

[0011] Example 5. The method of any one of examples 1-4, wherein the sensor data characterizes vibrations of air in a nasal region of the patient.

[0012] Example 6. The method of any one of examples 1-5, wherein the sensor data characterizes air pressure in the airway proximal to the obstruction.

[0013] Example 7. The method of any one of examples 1-6, wherein the sensor data characterizes pressure in a Eustachian tube of the patient.

[0014] Example 8. The method of any one of examples 1-7, wherein the sensor data characterizes pressure in a tear duct of the patient.

[0015] Example 9. The method of any one of examples 1-8, wherein the sensor data characterizes pressure in an oral region of the patient.

[0016] Example 10. The method of any one of examples 1-9, wherein the sensor data characterizes pressure in a nasal region of the patient.

[0017] Example 11. The method of any one of examples 1-10, wherein the sensor data comprises at least one of oral temperature or nasal temperature.

[0018] Example 12. The method of any one of examples 1-11, wherein the sensor data comprises impedance of a region of tissue proximate the patient’s airway.

[0019] Example 13. The method of any one of examples 1-12, wherein the sensor data is indicative of airflow through a trachea of the patient.

[0020] Example 14. The method of any one of examples 1-13, wherein the sensor data is indicative of snoring.

[0021] Example 15. The method of any one of examples 1-14, wherein the sensor data is indicative of at least one of tongue motion or chest motion.

[0022] Example 16. The method of any one of examples 1-15, wherein the sensor data comprises content of breath from the patient. [0023] Example 17. The method of any one of examples 1-16, wherein assessing efficacy comprises assessing efficacy of the stimulation energy substantially in real-time during a treatment session.

[0024] Example 18. The method of example 17, wherein assessing efficacy comprises assessing efficacy of the stimulation energy on a breath-by-breath basis.

[0025J Example 19. The method of any one of examples 1-18, further comprising updating one or more stimulation parameters of the stimulation energy based on the assessed efficacy of the stimulation energy.

[0026] Example 20. The method of example 19, wherein the one or more stimulation parameters comprise at least one of amplitude, frequency, pulse width, duty cycle, pulse width, or polarity.

[0027] Example 21. The method of example 19 or 20, wherein updating one or more stimulation parameters comprises updating one or more stimulation parameters of the stimulation energy substantially in real-time during a treatment session.

[0028] Example 22. The method of any one of examples 19-21, updating one or more stimulation parameters comprises updating one or more stimulation parameters of the stimulation energy on a breath-by-breath basis.

[0029] Example 23. The method of any one of examples 19-22, further comprising delivering stimulation energy in accordance with the updated one or more stimulation parameters.

[0030] Example 24. The method of any one of examples 1-23, wherein the electrode is on a neuromodulation lead is configured to be implanted in a sublingual region of the patient.

[0031 ] Example 25. The method of example 24, wherein the neuromodulation lead is configured to be implanted between a geniohyoid muscle and a genioglossus muscle of the patient.

[0032] Example 26. The method of any one of examples 1-25, wherein the target nerve is a hypoglossal nerve.

[0033] Example 27. A neuromodulation system for the treatment of sleep disordered breathing in a patient having an airway compromised by an obstruction, wherein the system is configured to be at least partially implanted in the patient, wherein the system comprises: an electrode configured to be implanted in the patient and deliver stimulation energy to a target nerve in the patient associated with patency of the airway; a sensor arrangement configured to provide sensor data indicative of airflow in the airway proximal to the obstruction; one or more processors; and a memory operably coupled to the one or more processors and storing instructions that, when executed by the processor, cause the system to: deliver stimulation energy to the target nerve via the electrode; receive sensor data from the sensor; and assess efficacy of the delivered stimulation energy for based at least in part on the received sensor data.

[0034] Example 28. The system of example 27, wherein the sensor data characterizes vibrations indicative of airflow in the airway proximal to the obstruction.

[0035] Example 29. The system of example 27 or 28, wherein the sensor data characterizes vibrations of oral tissue of the patient.

[0036] Example 30. The system of any one of examples 27-29, wherein the sensor data characterizes vibrations of air in an oral region of the patient.

[0037] Example 31. The system of any one of examples 27-30, wherein the sensor data characterizes vibrations of air in a nasal region of the patient.

[0038] Example 32. The system of any one of examples 27-31, wherein the sensor data characterizes air pressure in the airway proximal to the obstruction.

[0039] Example 33. The system of any one of examples 27-32, wherein the sensor data characterizes pressure in a Eustachian tube of the patient.

[0040] Example 34. The system of any one of examples 27-33, wherein the sensor data characterizes pressure in a tear duct of the patient.

[0041] Example 35. The system of any one of examples 27-34, wherein the sensor data characterizes pressure in an oral region of the patient.

[0042] Example 36. The system of any one of examples 27-35, wherein the sensor data characterizes pressure in a nasal region of the patient.

[0043] Example 37. The system of any one of examples 27-36, wherein the sensor data comprises at least one of oral temperature or nasal temperature. |0O441 Example 38. The system of any one of examples 27-37, wherein the sensor data comprises impedance of a region of tissue proximate the patient’s airway.

[0045] Example 39. The system of any one of examples 27-38, wherein the sensor data is indicative of airflow through a trachea of the patient.

[0046] Example 40. The system of any one of examples 27-39, wherein the sensor data is indicative of snoring.

[0047] Example 41. The system of any one of examples 27-40, wherein the sensor data is indicative of at least one of tongue motion or chest motion.

[0048] Example 42. The system of any one of examples 27-41, wherein the sensor data comprises content of breath from the patient.

[0049] Example 43. The system of any one of examples 27-42, wherein at least a portion of the sensor arrangement is configured to be implanted in the patient.

[0050] Example 44. The system of any one of examples 27-43, wherein at least a portion of the sensor arrangement is configured to be implanted in a sublingual region of the patient.

[0051] Example 45. The system of any one of examples 27-44, wherein at least a portion of the sensor arrangement is configured to be implanted adjacent to a dorsal surface of a genioglossus muscle of the patient.

[0052] Example 46. The system of any one of examples 27-45, further comprising an oral insert comprising at least a portion of the sensor arrangement and configured to be positioned in an oral region of the patient.

[0053] Example 47. The system of example 46, wherein the oral insert comprises at least one of a mouthguard, a retainer, a tooth attachment, a palate attachment, or a dental implant.

[0054] Example 48. The system of any one of examples 27-47, further comprising a wearable device comprising at least a portion of the sensor arrangement and configured to be positioned over a nasal region of the patient.

[0055] Example 49. The system of any one of examples 27-48, further comprising a wearable device comprising at least a portion of the sensor arrangement and configured to be positioned under a chin or around a neck of the patient. |0O56 J Example 50. The system of any one of examples 27-49, further comprising a wearable device comprising at least a portion of the sensor arrangement and configured to be positioned around a torso of the patient.

[0057] Example 51. The system of any one of examples 27-50, further comprising a wearable device comprising at least a portion of the sensor arrangement and configured to be worn in or on the ear of the patient.

[0058] Example 52. The system of any one of examples 27-51, wherein the sensor arrangement comprises an accelerometer.

[0059] Example 53. The system of any one of examples 27-52, wherein the sensor arrangement comprises a pressure sensor.

[0060] Example 54. The system of any one of examples 27-53, wherein the memory stores instructions that cause the system to assess efficacy of the stimulation energy substantially in real-time during a treatment session.

[0061] Example 55. The system of example 54, wherein the memory stores instructions that cause the system to assess efficacy of the stimulation energy on a breath-by-breath basis.

[0062] Example 56. The system of any one of examples 27-55, wherein the memory stores instructions that cause the system to update one or more stimulation parameters of the stimulation energy based on the assessed efficacy of the stimulation energy.

[0063] Example 57. The system of example 56, wherein the one or more stimulation parameters comprise at least one of amplitude, frequency, pulse width, duty cycle, pulse width, or polarity.

[0064] Example 58. The system of example 56 or 57, wherein the memory stores instructions that cause the system to update one or more stimulation parameters of the stimulation energy substantially in real-time during a treatment session.

(0065] Example 59. The system of any one of examples 56-58, wherein the memory stores instructions that cause the system to update one or more stimulation parameters of the stimulation energy on a breath-by-breath basis.

[0066] Example 60. The system of any one of examples 56-59, wherein the memory stores instructions that cause the system to deliver stimulation energy in accordance with the updated one or more stimulation parameters. [0067] Example 61. The system of any one of examples 27-60, further comprising a neuromodulation lead comprising the electrode, wherein the neuromodulation lead is configured to be implanted in a sublingual region of the patient.

[0068] Example 62. The system of example 61, wherein the neuromodulation lead is configured to be implanted between a geniohyoid muscle and a genioglossus muscle of the patient. f 0069 J Example 63. The system of any one of examples 27-62, wherein the target nerve is a hypoglossal nerve.

BRIEF DESCRIPTION OF THE DRAWINGS

[0070] Many aspects of the present disclosure can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale. Instead, emphasis is placed on illustrating clearly the principles of the present disclosure.

[0071 ] FIG. 1 A is a fragmentary midline sagittal view of an upper airway of a human patient.

[0072] FIG. IB is an illustration of the musculature and hypoglossal innervation of the human tongue.

[0073] FIG. 1C is a schematic superior view of a distal arborization of right and left hypoglossal nerves of a human patient. The hypoglossal nerves of FIG. 1C are shown as extending anteriorly from the bottom of the page to the top of the page (e.g., from the hyoid bone to the anterior mandible).

[0074] FIG. 2A is a schematic illustration of a neuromodulation system configured in accordance with several embodiments of the present technology.

[0075] FIG. 2B is a perspective view of a neuromodulation device configured in accordance with several embodiments of the present technology.

[0076] FIGS. 2C and 2D are top and side views, respectively, of the neuromodulation device of FIG. 2B.

[0077] FIGS. 3A-3F are various views of the neuromodulation device shown in FIGS. 2B-2D implanted in a human patient in accordance with several embodiments of the present technology. [0078] FIG. 4 is an illustrative schematic of a method for evaluating and improving efficacy of treatment for improvement of sleep disordered breathing, in accordance with several embodiments of the present technology.

[0079] FIGS. 5A-5H are illustrative schematics of example sensor carriers with sensors, in accordance with several embodiments of the present technology.

[0080J FIG. 6 is a perspective view of a neuromodulation device configured in accordance with several embodiments of the present technology.

[0081] FIG. 7 is an illustrative schematic of a method for evaluating and improving efficacy of treatment for improvement of sleep disordered breathing, in accordance with several embodiments of the present technology.

DETAILED DESCRIPTION

[0082] The present disclosure relates to devices, systems, and methods for wirelessly powering implantable medical devices. For example, an external system of the present technology can comprise a control unit coupled to an external device comprising a carrier carrying an antenna configured to conduct electrical current such that the antenna generates an electromagnetic field. When the implantable device is positioned within the electromagnetic field generated by the antenna, current can be induced in an antenna of the implantable device that can be used to power one or more electronic components carried by the implantable device. In some embodiments, the external devices and systems disclosed herein are used to power a neuromodulation system, which can be used to provide a variety of electrical therapies, including neuromodulation therapies such as nerve and/or muscle stimulation. Stimulation can induce excitatory or inhibitory neural or muscular activity. Such therapies can be used at various suitable sites within a patient's anatomy. According to some embodiments, the neuromodulation systems of the present technology are configured to treat sleep disordered breathing (SDB), including obstructive sleep apnea (OSA) and/or mixed sleep apnea, via neuromodulation of the hypoglossal nerve (HGN).

[0083] For the purpose of contextualizing the structure and operation of the neuromodulation systems and devices disclosed herein, some of the relevant anatomy and physiology are first described below. The headings provided herein are for convenience only and do not interpret the scope or meaning of the claimed present technology. Embodiments under any one heading may be used in conjunction with embodiments under any other heading. I. Anatomy and Physiology

[0084] As previously mentioned, respiration in patients with SDB is frustrated due to obstruction, narrowing, and/or collapse of the upper airway during sleep. As shown in FIG. 1 A, the upper airway comprises the nasal cavity, the oral cavity, the pharynx, and the larynx. Patency of the upper airway and resistance to airflow in the upper airway are controlled by a complex network of muscles under both voluntary and involuntary neuromuscular control. For example, the muscles of the tongue, the suprahyoid muscles (e.g., the geniohyoid, mylohyoid, stylohyoid, hyoglossus, and the anterior belly of the digastric muscle), and the muscles comprising the soft palate (e.g., palatal muscles) open, widen, and/or stabilize the upper airway during inspiration to counteract the negative airway pressure responsible for drawing air into the airway and the lungs.

[0085] With reference to FIG. IB, the tongue comprises both intrinsic and extrinsic lingual muscles. Generally, activation of the intrinsic muscles changes the shape of the tongue while activation of the extrinsic muscles tends to move the position of the whole tongue. The extrinsic muscles originate at a bony attachment and insert within the tongue. They comprise the genioglossus muscle, the styloglossus muscle, the hyoglossus muscle, and the palatoglossus muscle. The intrinsic muscles both originate and insert within the tongue, and comprise the superior longitudinalis, the inferior longitudinalis, the transversal! s, and the verticalis. In a patient who is awake, the brain supplies neural drive to these muscles through the HGN to maintain tongue shape and position, preventing the tongue from blocking the airway.

[0086] The lingual muscles are also functionally categorized as either retrusor or protrusor muscles and both intrinsic and extrinsic muscles fall into these categories. The retrusor muscles include the intrinsic superior and inferior longitudinalis muscles and the extrinsic hyoglossus and styloglossus muscles. The protrusor muscles include the intrinsic verticalis and transversalis muscles and the extrinsic genioglossus muscle. Contraction of the styloglossus muscle causes elevation of the tongue while depression of the tongue is the result of downward movements of hyoglossus and genioglossus muscles. Also labeled in FIG. IB is the geniohyoid muscle, which is a suprahyoid muscle (not a tongue muscle) but still an important protrusor and pharyngeal dilator, and thus contributes to maintaining upper airway patency. It is believed that effective treatment of OSA requires stimulation of the protrusor muscles with minimal or no activation of the retrusor muscles. Thus, for neuromodulation therapy to be effective it is considered beneficial to localize stimulation to the protrusor muscles while avoiding activation of the retrusor muscles. I0087J The largest of the tongue muscles, the genioglossus, comprises two morphological and functional compartments according to fiber distribution, action, and nerve supply. The first, the oblique compartment (GGo), comprises vertical fibers that, when contracted, depress the tongue without substantially affecting pharyngeal patency. The second, the horizontal compartment (GGh), contains longitudinal fibers that, when activated, protrude the posterior part of the tongue and enlarge the pharyngeal opening. The GGo contains Type II muscle fibers that are quickly fatigued, whereas the GGh contains Type I muscle fibers that are slower to fatigue. Accordingly, it can be advantageous to stimulate the GGh with little or no stimulation of the GGo to effectively protrude the tongue while preventing or limiting fatigue of the tongue.

I0088J The suprahyoid muscles, which comprise the mylohyoid, the geniohyoid, the stylohyoid, and the digastric (only a portion of which is shown in FIG. IB), extend between the mandible and the hyoid bone to form the floor of the mouth. The geniohyoid is situated inferior to the genioglossus muscle of the tongue and the mylohyoid is situated inferior to the geniohyoid. Contraction of the geniohyoid and tone of the sternohyoid (an infrahyoid muscle, not shown) cooperate to pull the hyoid bone anteriorly to open and/or widen the pharyngeal lumen and stabilize the anterior wall of the hypopharyngeal region. In contrast to the genioglossus and geniohyoid, which are considered tongue protrusors, the hyoglossus and styloglossus are considered tongue retrusors. Activation of the hyoglossus and styloglossus tends to retract the tongue posteriorly, which reduces the size of the pharyngeal opening, increases airway resistance, and frustrates respiration.

|0089] As previously mentioned, all of the extrinsic and intrinsic muscles of the tongue are innervated by the HGN, with the exception of the palatoglossus, which is innervated by the vagal nerve. There are two hypoglossal nerves in the body, one on the right side of the head and one on the left side. Each hypoglossal nerve originates at a hypoglossal nucleus in the medulla oblongata of the brainstem, exits the cranium via the hypoglossal canal, and passes inferiorly through the retrostyloid space (a portion of the lateral pharyngeal space) to the occipital artery. The hypoglossal nerve then curves and courses anteriorly to the muscles of the tongue, passing between the anterior edge of the hyoglossus muscle and the posterior edge of the mylohyoid muscle into the sublingual area where it splits into a distal arborization.

[0090] FIG. 1C is a schematic superior view of the distal arborization of the right and left hypoglossal nerves. Referring to FIGS. IB and 1C together, the HGN comprises (1) portions of the distal arborization that innervate the styloglossus and the hyoglossus (tongue retrusor muscles) and (2) portions of the distal arborization that innervate the intrinsic muscles of the tongue, the genioglossus, and the geniohyoid (tongue protrusor muscles). Additionally, the portions of the distal arborization that innervate the tongue retrusor muscles tend to be located posterior of the portions of the distal arborization that innervate the tongue protrusor muscles.

[0091] A reduction in activity of the muscles responsible for airway maintenance can result in an increase in airway resistance and a myriad of downstream effects on a patient’s respiration and health. Activity of the genioglossus muscle, for example, can decrease during sleep which, whether alone or in combination with other factors (e.g., airway length, airway diameter, soft tissue volume, premature wakening, etc.), can result in substantial airway resistance and/or airway collapse leading to sleep disordered breathing, such as OSA. It is believed that in order for neuromodulation therapy to be effective, it may be beneficial to largely confine stimulation of the HGN to the portions of the distal arborization that innervate protrusor muscles while avoiding or limiting stimulation of the portions of the distal arborization that activate the retrusor muscles.

II. Neuromodulation Systems

[0092] Various embodiments of the present technology are directed to devices, systems, and methods for modulating neurological activity and/or control of one or more nerves associated with one or more muscles involved in airway maintenance. Such neuromodulation can increase activity in targeted muscles, for example the genioglossus and geniohyoid, to reduce a patient’s airway resistance and improve the patient’s respiration. Moreover, targeted modulation of specific portions of the distal arborization of the hypoglossal nerve can increase activity in tongue protrusor muscles without substantially increasing activity in tongue retrusor muscles to provide a highly efficacious treatment. Additionally or alternatively, targeted modulation of specific portions of the distal arborization of the hypoglossal nerve that innervate the GGh but not portions of the distal arborization of the hypoglossal nerve that innervate the GGo can be used to effectively protrude the tongue while preventing or limiting fatigue of the tongue.

[0093] FIG. 2 A shows a neuromodulation system 10 for treating SDB configured in accordance with the present technology. The system 10 can include an implantable neuromodulation device 100 and an external system 15 configured to wirelessly couple to the neuromodulation device 100. The neuromodulation device 100 can include a lead 102 having a plurality of conductive elements 114 and an electronics package 108 having a first antenna 116 and an electronics component 118. The neuromodulation device 100 is configured to be implanted at a treatment site comprising submental and sublingual regions of a patient's head, as detailed below with reference to FIGS. 3A-3F. Furthermore, the system 10 can include a sensor carrier 120 with a sensor 122 configured to obtain and provide sensor data indicative of airflow in an airway of the patient. Various example embodiments of the sensor carrier 120 and sensor 122, and the analysis of various kinds of sensor data provided by the sensor 122, are described in further detail below.

|0094] In use, the electronics package 108 or one or more elements thereof can be configured provide a stimulation energy to the conductive elements 114 that has a pulse width, amplitude, duration, frequency, duty cycle, and/or polarity such that the conductive elements 114 apply an electric field at the treatment site that modulates the hypoglossal nerve. The stimulation energy can be delivered according to a periodic waveform including, for example, a charge-balanced square wave comprising alternating anodic and cathodic pulses.

[0095] One or more pulses of the stimulation energy can have a pulse width between about 10 ps and about 1000 ps, between about 50 ps and about 950 ps, between about 100 ps and about 900 ps, between about 150 ps and about 800 ps, between about 200 ps and about 850 ps, between about 250 ps and about 800 ps, between about 300 ps and about 750 ps, between about 350 ps and about 700 ps, between about 400 ps and about 650 ps, between about 450 ps and about 600 ps, between about 500 ps and about 550 ps, about 50 ps, about 100 ps, about 150 ps, about 200 ps, about 250 ps, about 300 ps, about 350 ps, about 400 ps, about 450 ps, about 500 ps, about 550 ps, about 600 ps, about 650 ps, about 700 ps, about 750 ps, about 800 ps, about 850 ps, about 900 ps, about 950 ps, and/or about 1000 ps. In some embodiments, one or more pulses of the stimulation energy has a pulse width of between about 50 ps and about 450 ps.

[0096] One or more pulses of the stimulation energy can have an amplitude sufficient to cause an increase in phasic activity of a desired muscle. For example, one or more pulses of the stimulation energy can have a current-controlled amplitude between about 0.1 mA and about 5 mA. In some embodiments, the stimulation energy has an amplitude of about 0.3 mA, about 0.4 mA, about 0.5 mA, about 0.6 mA, about 0.7 mA, about 0.8 mA, about 0.9 mA, about 1 mA, about 1.5 mA, about 2 mA, about 2.5 mA, about 3 mA, about 3.5 mA, about 4 mA, about 4.5 mA, and/or about 5 mA. Additionally or alternatively, an amplitude of one or more pulses of the stimulation energy can be voltage-controlled. An amplitude of one or more pulses of the stimulation energy can be based at least in part on a size and/or configuration of the conductive elements 114, a location of the conductive elements 114 in the patient, etc.

[0097] A frequency of the pulses of the stimulation energy can be between about 10 Hz and about 50 Hz, between about 20 Hz and about 40 Hz, about 10 Hz, about 15 Hz, about 20 Hz, about 25 Hz, about 30 Hz, about 35 Hz, about 40 Hz, about 45 Hz, and/or about 50 Hz. In some embodiments, the frequency can be based on a desired effect of the stimulation energy on one or more muscles or nerves. For example, lower frequencies may induce a muscular twitch whereas higher frequencies may include complete contraction of a muscle.

[0098] The external system 15 can comprise an external device 11 and a control unit 30 communicatively coupled to the external device 11. In some embodiments, the external device 11 is configured to be positioned proximate a patient’s head while they sleep. The external device 11 can comprise a carrier 9 integrated with a second antenna 12. While the control unit 30 is shown separate from the external device 11 in FIG. 2A, in some embodiments the control unit 30 can be integrated with and/or comprise a portion of the external device 11. The second antenna 12 can be configured for multiple purposes. For example, the second antenna 12 can be configured to power the neuromodulation device 100 through electromagnetic induction. Electrical current can be induced in the first antenna 116 when it is positioned above the second antenna 12 of the external device 11, in an electromagnetic field produced by second antenna 12. The first and second antennas 116, 12 can also be configured transmit data to and/or receive data from one another via one or more wireless communication techniques (e.g., Bluetooth, WiFi, USB, etc.) to facilitate communication between the neuromodulation device 100 and the external system 15. This communication can, for example, include programming, e.g., uploading software/firmware revisions to the neuromodulation device 100, changing/adjusting stimulation settings and/or parameters, and/or adjusting parameters of control algorithms.

[0099] The control unit 30 of the external system 15 can include a processor and/or a memory that stores instructions (e.g., in the form of software, code or program instructions executable by the processor or controller) for causing the external device to generate an electromagnetic field according to certain parameters provided by the instructions. The external system 15 or one or more portions thereof, such as the control unit 30, can include and/or be configured to be coupled to a power source such as a direct current (DC) power supply, an alternating current (AC) power supply, and/or a power supply switchable between DC and AC. The processor can be used to control various parameters of the energy output by the power source, such as intensity, amplitude, duration, frequency, duty cycle, and polarity. Instead of or in addition to a processor, the external system can include drive circuitry. In such embodiments, the external system 15 or one or more portions thereof (e.g., control unit 30), can include hardwired circuit elements to provide the desired waveform delivery rather than a software-based generator. The drive circuitry can include, for example, analog circuit elements (e.g., resistors, diodes, switches, etc.) that are configured to cause the power source to supply energy to the second antenna 12 to produce an electromagnetic field according to the desired parameters. In some embodiments, the neuromodulation device 100 can be configured for communication with the external system via inductive coupling.

[0100] The system 10 can also include a user interface 40 in the form of a patient device 70 and/or a physician device 75. The user interface(s) 40 can be configured to transmit and/or receive data with the external system 15, the second antenna 12, the control unit 30, the neuromodulation device 100, and/or the remote computing device(s) 80 via wired and/or wireless communication techniques (e.g., Bluetooth, WiFi, USB, etc.). In the example configuration of FIG. 2A, both the patient device 70 and physician device 75 are smartphones. The type of device could, however, vary. One or both of the patient device 70 and physician device 75 can have an application or “app” installed thereon that is user specific, e.g., a patient app or a physician app, respectively. The patient app can allow the patient to execute certain commands necessary for controlling operation of neuromodulation device 100, such as, for example, start/stop therapy, increase/decrease stimulation power or intensity, and/or select a stimulation program. In addition to the controls afforded the patient, the physician app can allow the physician to modify stimulation settings, such as pulse settings (patterns, duration, waveforms, etc.), stimulation frequency, amplitude settings, and electrode configurations, closed-loop and open loop control settings and tuning parameters for the embedded software that controls therapy delivery during use.

[0101] The patient and/or physician devices 70, 75 can be configured to communicate with the other components of the system 10 via a network 50. The network 50 can be or include one or more communications networks, such as any of the following: a wired network, a wireless network, a metropolitan area network (MAN), a local area network (LAN), a wide area network (WAN), a virtual local area network (VLAN), an internet, an extranet, an intranet, and/or any other suitable type of network or combinations thereof. The patient and/or physician devices 70, 75 can be configured to communicate with one or more remote computing devices 80 via the network 50 to enable the transfer of data between the devices 70, 75 and the remote computing device(s) 80. Additionally, the external system 15 can be configured to communicate with the other components of the system 10 via the network 50. This can also enable the transfer of data between the external system 15 and remote computing device(s) 80.

[0102] The external system 15 can receive the programming, software/firmware, and settings/parameters through any of the communication paths described above, e.g., from the user interface(s) 40 directly (wired or wirelessly) and/or through the network 50. The communication paths can also be used to download data from the neuromodulation device 100, such as measured data regarding completed stimulation therapy sessions, to the external system 15. The external system 15 can transmit the downloaded data to the user interface 40, which can send/upload the data to the remote computing device(s) 80 via the network 50.

In addition to facilitating local control of the system 10, e.g., the external system 15 and the neuromodulation device 100, the various communication paths shown in FIG. 2A can also enable:

(0104] Distributing from the remoting computing device(s) 80 software/firmware updates for the patient device 70, physician device 75, external system 15, and/or neuromodulation device 100.

[0105] Downloading from the remote computing device(s) 80 therapy settings/parameters to be implemented by the patient device 70, physician device 75, external system 15, and/or neuromodulation device 100.

(0106] Facilitating therapy setting/parameter adjustments/algorithm adjustments by a remotely located physician.

[0.107] Uploading data recorded during therapy sessions.

[0108] Maintaining coherency in the settings/parameters by distributing changes and adjustments throughout the system components.

[0109] The therapeutic approach implemented with the system 10 can involve implanting only the neuromodulation device 100 and leaving the external system 15 as an external component to be used only during the application of therapy. To facilitate this, the neuromodulation device 100 can be configured to be powered by the external system 15 through electromagnetic induction. In use, the second antenna 12, operated by control unit 30, can be positioned external to the patient in the vicinity of the neuromodulation device 100 such that the second antenna 12 is close to the first antenna 116 of the neuromodulation device 100. In some embodiments, the second antenna 12 is carried by a flexible carrier 9 that is configured to be positioned on or sufficiently near the sleeping surface while the patient sleeps to maintain the position of the first antenna 116 within the target volume of the electromagnetic field generated by the second antenna 12. Through this approach, the system 10 can deliver therapy to improve SDB (such as OSA), for example, by stimulating the HGN through a shorter, less invasive procedure. The elimination of an on-board, implanted power source in favor of an inductive power scheme can eliminate the need for batteries and the associated battery changes over the patient's life.

[0110] In some embodiments, the system 10 can include one or more sensors, which may be implanted and/or external. For example, the system 10 can include one or more sensors carried by (and implanted with) the neuromodulation device 100. Such sensors can be disposed at any location along the lead 102 and/or electronics package 108. In some embodiments, one, some, or all of the conductive elements 114 can be used for both sensing and stimulation. Use of a single structure or element as the sensor and the stimulating electrode reduces the invasive nature of the surgical procedure associated with implanting the system, while also reducing the number of foreign bodies introduced into a patient. In certain embodiments, at least one of the conductive elements 114 is dedicated to sensing only.

[0111] In addition to or instead of inclusion of one or more sensors on the neuromodulation device 100, the system 10 can include one or more sensors separate from the neuromodulation device 100. In some embodiments, one or more of such sensors are wired to the neuromodulation device 100 but implanted at a different location than the neuromodulation device 100. In some embodiments, the system 10 includes one or more sensors that are configured to be wirelessly coupled to the neuromodulation device 100 and/or an external computing device (e.g., control unit 30, user interface 40, etc.). Such sensors can be implanted at the same or different location as the neuromodulation device 100, or may be disposed on the patient’s skin.

[0112] The one or more sensors can be configured to record and/or detect physiological data (e.g., data originating from the patient's body) over time including changes therein. The physiological data can be used to select certain stimulation parameters and/or adjust one or more stimulation parameters during therapy. Physiological data can include an electromyography (EMG) signal, temperature, movement, body position, electroencephalography (EEG), air flow, audio data, heart rate, pulse oximetry, and/or combinations thereof. In some embodiments, the physiological data can be used to detect and/or anticipate other physiological parameters. For example, the one or more sensors can be configured to sense an EMG signal which can be used to detect and/or anticipate physiological events such as phasic contraction of anterior lingual musculature (such as phasic genioglossus muscle contraction) and measure physiological data such as underlying tonic activity of anterior lingual musculature (such as tonic activity of the genioglossus muscle). Phasic contraction of the genioglossus muscle can be indicative of inspiration, particularly the phasic activity that is layered within the underlying tonic tone of the genioglossus muscle. Changes in physiological data include changes in one or more parameters of a measured signal (e.g., frequency, amplitude, spike rate, etc.), start and end of phasic contraction of anterior lingual musculature (such as phasic genioglossus muscle contraction), changes in underlying tonic activity of anterior lingual musculature (such as changes in tonic activity of the genioglossus muscle), and combinations thereof. In particular, changes in phasic activity of the genioglossus muscle can indicate a respiration or inspiration change and can be used to trigger stimulation. Such physiological data and changes therein can be identified in signals recorded from sensors during different phases of respiration including inspiration. As such, the one or more sensors can include EMG sensors. The one or more sensors can also include, for example, wireless or tethered sensors that measure body temperature, movement (e.g., an accelerometer), breath sounds (e.g., audio sensors), heart rate, pulse oximetry, etc.

[0113] In operation, the physiological data provided by the one or more sensors enables closed-loop operation of the neuromodulation device 100. For example, the sensed EMG responses from the genioglossus muscle can enable closed-loop operation of the neuromodulation device 100 while eliminating the need for a chest lead to sense respiration. Operating in closed-loop, the neuromodulation device 100 can maintain stimulation synchronized with respiration, for example, while preserving the ability to detect and account for momentary obstruction. The neuromodulation device 100 can also detect and respond to snoring, for example.

10114] The system 10 can be configured to provide open-loop control and/or closed- loop stimulation to configure parameters for stimulation. In other words, with respect to closed- loop stimulation, the system 10 can be configured to track the patient's respiration (such as each breath of the patient) and stimulation can be applied during or prior to onset of inspiration, for example. However, with respect to open-loop stimulation, stimulation can be applied without tracking specific physiological data, such as respiration or inspiration. However, even under such an “open loop” scenario, the system 10 can still adjust stimulation and record data, to act on such information. For example, one way the system 10 can act upon such information is that the system 10 can configure parameters for stimulation to apply stimulation in an open loop fashion but can monitor the patient's respiration to know when to revert to applying stimulation on a breath to breath, closed-loop fashion such that the system 10 is always working in a closed-loop algorithm to assess data. Treatment parameters of the system may be automatically adjusted in response to the physiological data. The physiological data can be stored over time and examined to change the treatment parameters; for example, the treatment data can be examined in real time to make a real time change to the treatment parameters. In some embodiments, the treatment parameters can be learned from the physiological data stored over time and used to adjust the therapy in real time. This learning can be patient-specific and/or across multiple patients.

[0115] Operating in real-time, the neuromodulation device 100 can record data (e.g., via one or more sensors) related to the stimulation session including, for example, stimulation settings, EMG responses, respiration, sleep state including different stages of REM and non- REM sleep, etc. For example, changes in phasic and tonic EMG activity of the genioglossus muscle during inspiration can serve as a trigger for stimulation or changes in stimulation can be made based on changes in phasic and tonic EMG activity of the genioglossus muscle during inspiration or during different sleep states. This recorded data can be uploaded to the user interface 40 and to the remote computing device(s) 80. Also, the patient can be queried to use the interface 40 to log data regarding their perceived quality of sleep, which can also be uploaded to the remote computing device(s) 80. Offline, the remote computing device(s) 80 can execute a software application to evaluate the recorded data to determine whether settings and control parameters can be adjusted to further optimize the stimulation therapy. The software application can, for example, include artificial intelligence (Al) models that learn from recorded therapy sessions how certain adjustments affect the therapeutic outcome for the patient. In this manner, through Al learning, the model can provide patient-specific optimized therapy.

[0116] In some embodiments, the system 10 can additionally or alternatively include one or more sensors providing sensor data that can be used for assessing efficacy of treatment (e.g., efficacy of stimulation energy delivered by the neuromodulation device 100). For example, the system 10 can include a sensor carrier 120 with at least one sensor 122 for providing sensor data. As shown in FIG. 2A, the sensor carrier 120 can be operably coupled (e.g., communicatively coupled) to one or more other components of the neuromodulation system 10, such as the neuromodulation device 100, the external device 11, the control unit 30, the patient device 70, the physician device 75, and/or remote computing device(s) 80. For example, the sensor 122 can be operably coupled to the control unit 30, the patient device 70, the physician device 75, and/or the remote computing device(s) 80 via the network 50. In some embodiments, the sensor carrier 120 (or the one or more sensors 122 themselves) can be included in the neuromodulation device 100. For example, the one or more sensors 122 can be part of the electronics package 108. In some embodiments, the sensor carrier 120 can be implanted in the patient or worn by the patient as a wearable. Additional examples of the sensor carrier 120 and sensor 122 are described in further detail below.

III. Neuromodulation Devices

|0117] FIGS. 2B-2D illustrate various views of an example configuration of the neuromodulation device 100. While specific features of the neuromodulation device 100 are discussed with reference to FIGS. 2B-2D, other configurations of the neuromodulation device 100 are possible. Example configurations of neuromodulation devices 100 within the scope of the present technology include the neuromodulation devices found in U.S. Patent Application No.18/475,818, filed September 27, 2023, U.S. Provisional Patent Application No. 63/573,726, filed April 3, 2024, U.S. Patent Application No. 16/865,541, filed May 4, 2020, U.S. Patent Application No. 16/866,488, filed May 4, 2020, U.S. Patent Application No. 16/866,523, filed May 4, 2020, and U.S. Patent Application No. 16/865,668, filed May 4, 2020, each of which is incorporated herein by reference. As previously mentioned, the device 100 can be configured to be implanted at a treatment site within submental and sublingual regions of the patient’s head and deliver electrical energy at the treatment site to stimulate the HGN and/or one or more tongue protrusor muscles (e.g., the genioglossus, the geniohyoid, etc.). The device 100 can include an electronics package 108 and a lead 102 coupled to and extending away from the electronics package 108. The lead 102 can comprise a lead body 104 having a plurality of conductive elements 114 and an extension portion 106 extending between the lead body 104 and the electronics package 108. The extension portion 106 can have a proximal end portion 106a coupled to the electronics package 108 via a first connector 110 and a distal end portion 106b coupled to the lead body 104 via a second connector 112.

[0118] The electronics package 108 can be configured to supply electrical current to the conductive elements 114 (e.g., to stimulate) and/or receive electrical energy from the conductive elements 114 (e.g., to sense physiological data). The extension portion 106 of the lead 102 can mechanically and/or electrically couple the electronics package 108 to the lead body 104. The extension portion 106 can comprise a polymeric material such as, but not limited to, a thermoplastic elastomer, a thermoplastic polyurethane, a silicone, or other suitable materials. The extension portion 106 can be sufficiently flexible such that it can bend so as to position the lead body 104 on top of, but spaced apart from, the electronics package 108. As discussed in greater detail below with reference to FIGS. 3A-3F, the neuromodulation device 100 is configured to be implanted within both a submental region and a sublingual region such that the electronics package 108 and lead body 104 are vertically stacked with one or more muscle and/or other tissue layers positioned therebetween. The flexibility of the extension portion 106 enables such a configuration.

[0119J In some embodiments, the extension portion 106 comprises a sidewall defining a lumen extending through the extension portion 106. The conductive elements 114 can be electrically coupled to the first antenna 116 and/or the electronics component 118 via one or more electrical connections extending through the lumen of the extension portion 106. For example, the proximal end portions of the electrical connections can be routed through the first connector 110 to the electronics component 118 on the electronics package 108. The electrical connections may comprise, for example, one or more wires, cables, traces, vias, and others extending through the extension portion 106 and lead body 104. The electrical connections can comprise a conductive material such as silver, copper, etc., and each electrical connection can be insulated along all or a portion of its length. In some embodiments, the device 100 includes a separate electrical connection for each conductive element 114. For example, in those embodiments in which the device 100 comprises eight conductive elements 114 (and other embodiments), the device 100 can comprise eight electrical connections, each extending through the lumen of the extension portion 106 from a proximal end at the electronics component 118 to a distal end at one of the conductive elements 114.

|0120| In some embodiments, the electronics component 118 comprise an applicationspecific integrated circuit (ASIC), a discrete electronic component, and/or an electrical connector. In these and other embodiments, the electronics component 118 can comprise, for example, processing and memory components (e.g., microcomputers, microprocessors, computers-on-a-chip, etc.), charge storage and/or delivery components (e.g., batteries, capacitors, electrical conductors) for receiving, accumulating, and/or delivering electrical energy, switching components (e.g., solid state, pulse-width modulation, etc.) for selection and/or control of the conductive elements 114. In some embodiments, the electronics component 118 comprise a data communications unit for communicating with an external device (such as external system 15) via a communication standard such as, but not limited to, near-field communication (NFC), infrared wireless, Bluetooth, ZigBee, Wi-Fi, inductive coupling, capacitive coupling, or any other suitable wireless communication standard. In some examples, the electronics component 118 include one or more processors having one or more computing components configured to control energy delivery via the conductive elements 114 and/or process energy and/or data received by the conductive elements 114 according to instructions stored in the memory. The memory may be a tangible, non-transitory computer- readable medium configured to store instructions executable by the one or more processors. For instance, the memory may be data storage that can be loaded with one or more of the software components executable by the one or more processors to achieve certain functions. In some examples, the functions may involve causing the conductive elements 114 to obtain data characterizing activity of a patient’s muscles. In another example, the functions may involve processing data to determine one or more parameters of the data (e.g., a change in muscle activity, etc.). According to various embodiments, the electronics component 118 can comprise a wireless charging unit for providing power to other electronics component 118 of the device 100 and/or recharging a battery of the device 100 (if included).

[0121] The electronics package 108 can also be configured to wirelessly receive energy from a power source to power the neuromodulation device 100. In some embodiments, the electronics package 108 comprises a first antenna 116 configured to wirelessly communicate with the external system 15. As shown in FIG. 2B, in some embodiments the electronics component 118 can be disposed in an opening at a central portion of the first antenna 116. In other embodiments, the electronics component 118 and antenna 116 may have other configurations and arrangements.

[0122] The second antenna 12 can be configured to emit an electromagnetic field to induce an electrical current in the first antenna 116, which can then be supplied to the electronics component 118 and/or conductive elements 114. In some embodiments, the first antenna 116 comprises a coil or multiple coils. For example, the first antenna 116 can comprise one or more coils disposed on a flexible substrate. The substrate can comprise a single substrate or multiple substrates secured to one another via adhesive materials. For instance, in some embodiments the substrate comprises multiple layers of a heat resistant polymer (such as polyimide) with adhesive material between adjacent layers. Whether comprising a single layer or multiple layers, the substrate can have one or more vias extending partially or completely through a thickness of the substrate, and one or more electrical connectors can extend through the vias to electrically couple certain electronic components of the electronics package 108, such as the first antenna 116 and/or the previously discussed electronics component 118.

[0123] In some embodiments, the first antenna 116 comprises multiple coils. For example, the first antenna 116 can comprise a first coil at a first side of the substrate and a second coil at a second side of the substrate. This configuration can be susceptible to power losses due to substrate losses and parasitic capacitance between the multiple coils and between the individual coil turns. Substrate losses occur due to eddy currents in the substrate due to the non-zero resistance of the substrate material. Parasitic capacitance occurs when these adjacent components are at different voltages, creating an electric field that results in a stored charge. All circuit elements possess this internal capacitance, which can cause their behavior to depart from that of “ideal” circuit elements.

[0124] Advantageously, in some embodiments the first antenna 116 comprises a two- layer, pancake style coil configuration in which the top and bottom coils are configured in parallel. As a result, the coils can generate an equal or substantially equal induced voltage potential when subjected to an electromagnetic field. This can help to equalize the voltage of the coils during use, and has been shown to significantly reduce the parasitic capacitance of the first antenna 116. In this parallel coil configuration, the top and bottom coils are shorted together within each turn. This design has been found to retain the benefit of lower series resistance in a two-coil design while, at the same time, greatly reducing the parasitic capacitance and producing a high maximum power output. Additional details regarding the two-coil configuration can be found in U.S. Application No. 16/866,523, filed May 4, 2020, which is incorporated by reference herein in its entirety.

[0125] The first antenna 116 (or one or more portions thereof) can be flexible such that the first antenna 116 is able to conform at least partially to the patient’s anatomy once implanted. In some embodiments, the first antenna 116 comprises an outer coating configured to encase and/or support the first antenna 116. The coating can comprise a biocompatible material such as, but not limited to, epoxy, urethane, silicone, or other biocompatible polymers. In some embodiments, the coating comprises multiple layers of distinct materials.

[0126] With continued reference to FIGS. 2B-2D, the lead body 104 can comprise a substrate carrying one or more conductive elements 114 configured to deliver and/or receive electrical energy. In some embodiments, the lead body 104 (or one or more portions thereof) comprises flexible tubing with a sidewall defining a lumen. The lead body 104 can comprise a polymeric material such as, but not limited to, a thermoplastic elastomer, a thermoplastic polyurethane, a silicone, or other suitable materials. The lead body 104 can comprise the same material as the extension portion 106 or a different material. The lead body 104 can comprise the same material as the extension portion 106 but with a different durometer. In some embodiments, the lead body 104 has a lower durometer than the extension portion 106, which can enhance patient comfort.

[01271 As shown in FIGS. 2B-2D, the lead body 104 has a branched shape comprising a first arm 122 and a second arm 124. To facilitate this configuration, for example, the second connector 112 can be bifurcated and/or branching. The first arm 122 and the second arm 124 can each extend distally and laterally from the second connector 112 and/or the distal end portion 106b of the extension portion 106. The first arm 122 can comprise a proximal portion 122a, a distal portion 122b, and an intermediate portion 122c extending between the proximal portion 112a and the distal portion 122b. Similarly, the second arm 124 can comprise a proximal portion 124a, a distal portion 124b, and an intermediate portion 124c extending between the proximal portion 124a and the distal portion 124b. In some embodiments, the first arm 122 can comprise a cantilevered, free distal end 123 and/or the second arm 124 can comprise a cantilevered, free distal end 125. The first arm 122 and/or the second arm 124 can include one or more fixation elements 130, for example the fixation elements 130 shown at the distal end portions 122b, 124b of the first and second arms 122, 124 in FIGS. 2B-2D. The fixation elements 130 can be configured to securely, and optionally releasably, engage patient tissue to prevent or limit movement of the lead body 104 relative to the tissue.

[0128] While being flexible, the lead 102 and/or one or more portions thereof (e.g., the lead body 104, the extension portion 106, etc.) can also be configured to maintain a desired shape. This feature can, for example, be facilitated by electrical conductors that electrically connect the conductive elements 114 carried by the lead body 104 to the electronics package 108, by an additional internal shape-maintaining (e.g., a metal, a shape memory alloy, etc.) support structure (not shown), by shape setting the substrate comprising the lead 102, etc. In any case, one or more portions of the lead 102 can have a physical property (e.g., ductility, elasticity, etc.) that enable the lead 102 to be manipulated into a desired shape or maintain a preset shape. Additionally or alternatively, the lead 102 and/or one or more portions thereof (e.g., the lead body 104, the extension portion 106, etc.) can be sufficiently flexible to at least partially conform to a patient’s anatomy once implanted and/or to enhance patient comfort. I0129J The conductive elements 114 can be carried by the sidewall of the lead body 104. For example, the conductive elements 114 can be positioned on an outer surface of the sidewall and/or within a recessed portion of the sidewall. In some embodiments, one or more of the conductive elements 114 is positioned on an outer surface of the sidewall and extends at least partially around a circumference of the sidewall. The lumen of the lead body 104 can carry one or more electrical conductors that extend through the lumen of the lead body 104 and the lumen of the extension portion 106 from the conductive elements 114 to the electronics package 108. The sidewall can define one or more apertures through which an electrical connector can extend.

[0130] Each of the conductive elements 114 may comprise an electrode, an exposed portion of a conductive material, a printed conductive material, and other suitable forms. In some embodiments, one or more of the conductive elements 114 comprises a ring electrode. The conductive elements 114 can be crimped, welded, adhered to, or positioned over an outer surface and/or recessed portion of the lead body 104. Additionally or alternatively, each of the conductive elements 114 can be welded, soldered, crimped, or otherwise electrically coupled to a corresponding electrical connector. In some embodiments, one or more of the conductive elements 114 comprises a flexible conductive material disposed on the lead body 104 via printing, thin film deposition, or other suitable techniques. Each one of the conductive elements 114 can comprise any suitable conductive material including, but not limited to, platinum, iridium, silver, gold, nickel, titanium, copper, combinations thereof, and/or others. For example, one or more of the conductive elements 114 can be a ring electrode comprising a platinum iridium alloy. In some embodiments, one or more of the conductive elements 114 comprises a coating configured to improve biocompatibility, conductivity, corrosion resistance, surface roughness, durability, or other parameter(s) of the conductive element 114. As but one example, one or more of the conductive elements 114 can comprise a coating of titanium and nitride.

10131] In some embodiments, one or more conductive elements 114 has a length of about 1 mm. Additionally or alternatively, one or more conductive elements 114 can have a length of about 0.25 mm, about 0.5 mm, about 0.75 mm, about 1.25 mm, about 1.5 mm, about 1.75 mm, about 2 mm, about 2.25 mm, about 2.5 mm, about 2.75 mm, about 3 mm, about 3.25 mm, about 3.5 mm, about 3.75 mm, about 4 mm, about 4.25 mm, about 4.5 mm, about 4.75 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9 mm, about 10 mm, more than 10 mm, or less than 0.25 mm. In any case, adjacent conductive elements 114 carried by one of the first or second arms 122, 124 can be spaced apart along a length of the arm by about 0.25 mm, about 0.5 mm, about 0.75 mm, about 1 mm, about 1.25 mm, about 1.5 mm, about 1.75 mm, about 2 mm, about 2.25 mm, about 2.5 mm, about 2.75 mm, about 3 mm, about 3.25 mm, about 3.5 mm, about 3.75 mm, about 4 mm, about 4.25 mm, about 4.5 mm, about 4.75 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9 mm, about 10 mm, more than 10 mm, or less than 0.25 mm. The conductive elements 114 can have the same length or different lengths.

101321 While the device 100 shown in FIGS. 2B-2D includes eight conductive elements 114 (four conductive elements 114 carried by the first arm 122 and four conductive elements 114 carried by the second arm 124), other numbers and configurations of conductive elements 114 are within the scope of the present technology. For example, the first arm 122 can carry the same number of conductive elements 114 as the second arm 124, or the first arm 122 can carry a different number of conductive elements 114 as the second arm 124. The first arm 122 and/or the second arm 124 can carry one conductive element 114, two conductive elements 114, three conductive elements 114, four conductive elements 114, five conductive elements 114, six conductive elements 114, seven conductive elements 114, eight conductive elements 114, nine conductive elements 114, ten conductive elements 114, or more than ten conductive elements 114. In some embodiments, one of the first arm 122 or the second arm 124 does not carry any conductive elements 114.

[0133] The conductive elements 114 can be configured for stimulation and/or sensing. Stimulating conductive elements 114 can be configured to deliver energy to an anatomical structure, such as, for example, a nerve or muscle. In some embodiments, the conductive elements 114 are configured to deliver energy to a hypoglossal nerve of a patient to increase the activity of the patient’s tongue protrusor muscles. Sensing conductive elements 114 can be used obtain data characterizing a physiological activity of a patient (e.g., muscle activity, temperature, etc.). In some embodiments, the sensing conductive elements 114 are configured to detect electrical energy produced by a muscle of a patient to obtain EMG data characterizing an activity of the muscle. In some embodiments, the sensing conductive elements are configured to measure impedance across the conductive elements. As but one example, in some embodiments the conductive elements 114 are configured to deliver energy to a hypoglossal nerve of a patient to increase activity of the genioglossus and/or geniohyoid muscles, and obtain EMG data characterizing activity of the genioglossus muscle and/or the geniohyoid muscle of the patient. Still, the conductive elements 114 can be configured to deliver energy to and/or measure physiological electrical signals from other patient tissues.

[0134] The function that each of the conductive elements 114 is configured to perform (e.g., delivering energy to patient tissue, receiving energy from patient tissue, etc.) can be controlled by a processor of the electronics component 118 of the electronics package 108. In some embodiments, one or more of the conductive elements 114 is configured for only one of delivering energy to patient tissue or receiving energy from patient tissue. In various embodiments, one or more of the conductive elements 114 is configured for both delivering energy to patient tissue and receiving energy from patient tissue. In some embodiments, the functionality of a conductive element 114 can be based, at least in part, on an intended positioning of the device 100 within a patient and/or the position of the conductive element 114 on the lead body 104. One, some, or all of the conductive elements 114 can be positioned relative to patient tissue, such as nerves and/or muscles, so that it may be desirable for the conductive element(s) 114 to be able to both deliver energy to the patient tissue and receive energy from the patient tissue. Additionally or alternatively, some conductive elements 114 can have an intended position relative to specific patient tissues so that only delivery of stimulation energy is desired while other conductive elements 114 can have an intended position relative to specific patient tissues so that only receipt of sensing energy is desired. Advantageously, the configurations of the conductive elements 114 can be configured in software settings (which can be facilitated by electronics component 118 of the electronics package 108) so that the configurations of the conductive elements 114 are easily modifiable.

[0135] Whether configured for stimulating and/or sensing, each of the conductive elements 114 can be configured and used independently of the other conductive elements 114. Because of this, all or some of conductive elements 114, whichever is determined to be most effective for a particular implementation, can be utilized during the application of stimulation therapy. For example, one conductive element 114 of the first arm 122 can be used as a cathode while one conductive element 114 of the second arm 124 is used as an anode (or vice versa), two or more conductive elements 114 of the first arm 122 can be used (one as the cathode and one as the anode) without use of any conductive elements 114 of the second arm 124 (or vice versa), multiple pairs of conductive elements 114 of the first and second arms 122, 124 can be used, or any other suitable combination. The conductive element(s) 114 used for sensing and/or stimulation can be selected based on desired data to be collected and/or desired modulation of neural or muscle activity. For example, specific pairs of the conductive elements 114 can be used for creating an electric field tailored to stimulation of certain regions of the muscle and/or HGN that causes favorable changes in tongue position and/or pharyngeal dilation. Additionally or alternatively, conductive element(s) 114 that are positioned in contact with muscle tissue when the device 100 is implanted may be more favorable to use for EMG sensing than conductive element(s) 114 that are not positioned in contact with muscle tissue.

{0136] The lead body 104 can have a shape configured to facilitate delivery of electrical energy to a specific treatment location within a patient and/or detection of electrical energy from a sensing location within the patient. The conductive elements 114 carried by the first arm 122 can be configured to deliver electrical stimulation energy to one hypoglossal nerve (e.g., the right or the left hypoglossal nerve) of a patient and the conductive elements 114 carried by the second arm 124 can be configured to deliver electrical stimulation energy to the other hypoglossal nerve (e.g., the other of the right or the left hypoglossal nerve) of the patient.

[0137] Without being bound by theory, it is believed that increased activity of the tongue protrusor muscles during sleep reduces upper airway resistance and improves respiration. Thus, devices of the present technology are configured to deliver stimulation energy to motor nerves that control the tongue protrusors. In some embodiments, the device 100 is configured to deliver stimulation energy to the hypoglossal nerve to cause protrusion of the tongue. Additionally or alternatively, the device 100 can be configured to receive sensing energy produced by activity of one or more muscles of a patient (such as the genioglossus muscle), which can be used for closed-loop delivery of stimulation energy, evaluation of patient respiration, etc.

[0138] The device can be configured to be implanted at an anatomical region of a patient that is bound anteriorly and laterally by the patient's mandible, superiorly by the superior surface of the tongue, and inferiorly by the patient's platysma. Such an anatomical region can include, for example, a submental region and a sublingual region. The sublingual region can be bound superiorly by the oral floor mucosa and inferiorly by the mylohyoid and includes the plane between the genioglossus muscle and the geniohyoid muscle. The submental region can be bound superiorly by the mylohyoid and inferiorly by the platysma muscle. FIGS. 3A-3F depict various views of the device 100 implanted within a patient. As shown in FIGS. 3A-3F, the neuromodulation device 100 is configured to be positioned such that the electronics package 108 is disposed on or near the inferior surface of the mylohyoid in a submental region while the lead body 104 is positioned between the geniohyoid and genioglossus in a sublingual region with the arms 122, 124 disposed along the left and right hypoglossal nerves. The arms 122, 124 can be positioned such that the conductive elements 114 are disposed near the distal arborization of the hypoglossal nerves that innervate the genioglossus. In particular, the conductive elements 114 can be positioned proximate the portions of the distal arborization that innervate the horizontal fibers of the genioglossus while limiting and/or avoiding stimulation of the portions of the distal arborization of the hypoglossal nerve that activate retrusor muscles. When implanted, the extension portion 106 of the lead 102 can extend in an anterior direction away from the electronics package 108 (towards the mandible), then bend superiorly and extend through the geniohyoid muscle until bending back posteriorly and extending within a tissue plane between the geniohyoid and genioglossus muscles. In some embodiments, the extension portion 106 straddles the right and left geniohyoid muscles.

(0139] The electronics package 108 can be sufficiently flexible so that, once implanted, the electronics package 108 at least partially conforms to the curvature of the mylohyoid. Additionally or alternatively, the electronics package 108 can have a shape reflecting the curvature of the mylohyoid. In some embodiments, the electronics package 108 can comprise fixation elements (similar to fixation elements 130 or otherwise) that are configured to engage the mylohyoid (or other surrounding tissue) and prevent or limit motion of the electronics package 108 once implanted.

[0140] The lead body 104 can be configured to be positioned between the genioglossus and geniohyoid muscles of a patient so that the conductive elements 114 are positioned proximate the hypoglossal nerve. Although not shown in FIGS. 3A-3F, the hypoglossal nerve is located between the genioglossus and fascia and/or fat located between the genioglossus and the geniohyoid. In some embodiments, the lead body 104 is configured to be positioned at or just inferior to the fat between the hypoglossal nerve and the geniohyoid and thus is not positioned in direct contact with the hypoglossal nerve. In any case, once the device 100 is implanted, the lead body 104 can extend posteriorly away from the distal end portion 106b of the extension portion 106. The lead body 104 can then branch laterally such that the first arm 122 of the lead body 104 is positioned proximate one of the patient’s hypoglossal nerves and the second arm 124 is positioned proximate the contralateral hypoglossal nerve. The fixation elements 130 can engage patient tissue (e.g., the fat underlying the hypoglossal nerves, etc.) to prevent or limit motion of the first and second arms 122, 124 relative to the patient tissue. 01411 As best shown in FIG. 3C, the arms 122, 124 of the lead body 104 can bend out of the plane of the extension portion 106, in addition to extending laterally away from the extension portion 106, such that the arms 122, 124 outline a somewhat concave shape. Advantageously, this concave shape can accommodate the convex inferior surface of the genioglossus and still keep the arms 122, 124 positioned near the distal arborization of the hypoglossal nerve.

[0142] In some embodiments, conductive elements 114 are selected for use that selectively activate the protrusor muscles of a patient. In these and other embodiments, the specific positioning of the first and second arms 122, 124 relative to specific branches of the hypoglossal nerves need not be identified prior to stimulation of desired portions of the nerve and/or muscle. For example, in embodiments in which the lead body 104 includes more than two conductive elements 114, the combination of conductive elements 114 that is used for treating a patient can be selected based on physiological responses to test stimulations. For example, stimulation energy can be delivered to the hypoglossal nerve(s) via multiple combinations of conductive elements 114 and a physiological response (e.g., EMG data, tongue position, pharyngeal opening size, etc.) and/or a functional outcome (e.g., Fatigue Severity Scale, Epworth Sleepiness Scale, etc.) can be evaluated for each combination. Based on the evaluation(s), the conductive elements 114 that are selected to deliver stimulation energy can be conductive elements 114 that are associated with favorable responses/outcomes.

IV. Treatment Efficacy Assessment

[0143] As described above, in some embodiments, the system 10 can include one or more sensors providing sensor data that can be used for assessing efficacy of treatment (e.g., efficacy of stimulation energy delivered by the neuromodulation device 100). For example, such sensor data can be used to assess the ability of the stimulation from the neuromodulation device 100 to achieve airflow in a patient’s airway that is compromised by an obstruction (e.g., to assess the airway’s response to the stimulation, where the response is ideally to maintain proper airflow in the airway from breath to breath). For example, the system 10 can include a sensor carrier 120 with at least one sensor 122 in a sensor arrangement for providing sensor data.

[0144] In some embodiments, the sensor 122 can obtain sensor data that is indicative of airflow in an airway of a patient in which the neuromodulation device 100 has delivered stimulation energy to a target nerve for treating sleep disordered breathing. For example, in some embodiments, the sensor 122 can obtain sensor data that indicative of airflow at one or more regions of a patient’s airway that are proximal to an obstruction of the airway (e.g., blockage, narrowing, collapse, and/or other obstruction of the upper airway), such as during sleep. For example, in instances where base of the tongue and/or soft tissue of the upper airway collapse to cause an obstruction in the upper airway channel of a patient, the sensor 122 can be configured to detect one or more parameters indicative of airflow in an oral and/or nasal region of the patient. The sensor data from the sensor 122 can be analyzed to assess the efficacy of stimulation energy that has been delivered to a target nerve for purposes of treating sleep disordered breathing (e.g., assessing improvement in respiration such as by measuring amount of airflow in the airway proximal to the obstruction). As described herein, the amount of airflow proximal to an obstruction of an airway (e.g., intake of air before airflow reaches the obstruction) can be used as a measure of efficacy of stimulation energy or treatment of sleep disordered breathing. Such measurement of airflow entering the patient’s airway before the obstruction can provide a more accurate indication of efficacy, compared to measurement of airflow in other regions of the airway in which the volume of the airway may be greater (e.g., volume of airflow in lungs). For example, since the region of the airway proximal to the obstruction is typically constricted and has a narrower path for inhalation and exhalation, airflow is faster in this narrower region compared to wider regions of the airway. Measurements of airflow proximal to the obstruction are advantageous for assessing stimulation efficacy at least in part because the magnitude of any airflow changes is more apparent in narrower regions, compared to wider airway regions in which airflow is slower. Furthermore, airflow and/or other characteristics proximal to the obstruction can be separately indicative of total or partial obstruction of the airway, as total obstruction will cause airflow to cease, and partial obstruction will cause airflow to be reduced while noise and/or vibrations (e.g., snoring) will increase.

|0145] In some embodiments, one or more parameters of the stimulation energy can also be adjusted based at least in part on the sensor data with the goal of improving the efficacy of delivered stimulation energy for the treatment of sleep disordered breathing.

[0146] In some embodiments, as further described herein, the sensor data can be assessed to measure airflow in the airway on a breath-to-breath basis to assess efficacy of the stimulation energy. Furthermore, in some embodiments, one or more stimulation parameters of the stimulation energy to be delivered to the patient can be updated on a breath-to-breath basis as well, thereby allowing for a timely and/or more precise modulation of the stimulation energy for improving respiration in the patient. Additionally or alternatively, one or more stimulation parameters of the stimulation energy can be updated periodically based on sensor data for a given period of time, as further described below.

[0147] FIG. 4 illustrates various aspects of a method 400 of treating sleep disordered breathing with a neuromodulation system. The neuromodulation system can be at least partially implanted in a patient having an airway compromised by an obstruction. As shown in FIG. 4, the method 400 includes delivering stimulation energy to a target nerve associated with patency of an airway of the patient 410, receiving sensor data indicative of airflow in the airway 420, and assessing efficacy of the stimulation energy based at least in part on the received sensor data 430. In some embodiments, the method 400 can further include updating one or more stimulation parameters of the stimulation energy 440, based at least in part on the assessed efficacy of the stimulation energy.

[0148] In some embodiments, delivering stimulation energy to a target nerve associated with patency of an airway of the patient 410 includes modulating neurological activity and/or control of one or more nerves associated with one or more muscles involved in airway maintenance. Such neuromodulation can increase activity in targeted muscles, for example the genioglossus and geniohyoid, to reduce the patient’s airway resistance and improve the patient’s respiration. For example, delivering stimulation energy can include delivering stimulation energy to a hypoglossal nerve of a patient to increase the activity of the patient’s tongue protrusor muscles, to thereby help improve patency of the patient’s airway.

[0149] In some embodiments, stimulation energy can be delivered via one or more stimulation electrodes of a neuromodulation device similar to neuromodulation device 100 (e.g., with respect to FIGS. 2B-2D) and operated as described herein. The neuromodulation device can be part of a neuromodulation system including one or more components of neuromodulation system 10 (e.g., with respect to FIG. 2 A) and operated as described herein. As previously mentioned, the neuromodulation device 100 can be configured to be implanted at a treatment site within submental and sublingual regions of the patient’s head and deliver electrical energy at the treatment site to stimulate the HGN and/or one or more tongue protrusor muscles (e.g., the genioglossus, the geniohyoid, etc.).

[0150] Receiving sensor data indicative of airflow in the airway 420 functions to obtain information that is a direct measurement of airflow in the airway or can be correlated to a measurement of airflow in the airway, for purposes of assessing efficacy of stimulation energy. The airflow measurement can include, for example, a binary indication of presence or absence of airflow, and/or an indication of speed and/or direction of airflow. Additionally or alternatively, the received sensor data can be used to characterize a different metric of patient status (e.g., blood oxygen) that may be useful for patient monitoring purposes, and/or the like.

1. Sensor arrangements

[0151J The sensor data can be obtained using a sensor arrangement including one or more sensors in one or more various configurations. Generally, at least a portion of the sensor arrangement can be located on a sensor carrier 120. In some embodiments, the sensor carrier 120 can be a peripheral device worn by the patient to position at least a portion of the sensor arrangement on or in the patient’s body. For example, FIGS. 5A-5C are schematic illustrations of various example embodiments of sensor carriers that can be removably worn within an oral cavity (e.g., over dentition). For example, FIG. 5 A illustrates a sensor carrier 120a including a mouthguard or other suitable tooth-receiving tray that can be worn over upper or lower dentition of the patient, FIG. 5B illustrates a sensor carrier 120b including a retainer that can be worn over dentition to position a sensor 122b adjacent an upper or lower palate, and FIG. 5C illustrates a sensor carrier 120c including a tooth cap or other dental covering with at least one sensor 122c. In these examples, sensors 122a, 122b, and/or 122c can be positioned via the sensor carrier so as to be exposed to air in the patient’s mouth adjacent to potential airflow for enabling the sensors to measure one or more properties indicative of airflow (e.g., oral air vibration, oral pressure, oral temperature, CO2 content in breathed air, etc., as further described herein).

[0152] In some embodiments, the sensor carrier 120 can be worn on other body parts of the patient. For example, FIG. 5D illustrates a sensor carrier 120d including an ear insert (e.g., hearing aid-style device) with at least one sensor 122d to measure one or more properties indictive of airflow, such as pressure in a Eustachian tube of the patient, as further described herein. As another example, FIG. 5E illustrates a sensor carrier 120e including a nasal strip configured to be worn over the bridge of the patient’s nose, with a sensor 122e positioned to measure a property of nasal tissue and/or nasal air (e.g., nasal tissue vibration, nasal air vibration, nasal pressure, nasal temperature, CO2 content in breathed air, etc., as further described herein). Other examples of sensor carriers include nasal devices such as a nasal cannula, an implant on the nasal septum, a nasal piercing, and/or the like can include one or more sensors similar to sensor 122e. I0153J As another example, FIG. 5F illustrates an example sensor carrier 120f including a chin strap configured to position a sensor 122f underneath the chin of the patient and/or adjacent the trachea of the patient. The sensor 122f can, for example, be positioned to measure oral air vibration and/or airflow through the trachea, as further described herein. FIG. 5G illustrates an example sensor carrier 120g including a collar configured to position a sensor 122g adjacent the trachea of the patient and/or underneath the chin of the patient. The sensor 122g can, for example, be positioned to measure neck vibration, airflow through the trachea, etc., as further described herein. Other neck-based peripheral devices or garments, such as a necklace, choker, collar and/or other portion of a shirt, or any combination thereof can similarly include one or more sensors similar to sensors 122f and 122g.

I0154J FIG. 5H illustrates an example sensor carrier 120h including a chest strap or band configured to position a sensor 122h. The chest strap can, for example, position a sensor 122h over the trachea for detecting airflow through the trachea and/or a sensor 122h for measuring chest motion, as further described herein.

[0155] Additionally or alternatively, in some embodiments the system can include a sensor carrier that is configured to be implanted in the body of a patient. For example, the sensor carrier 120 can be coupled to or integrated in a portion of the neuromodulation device 100 described herein, such as the electronics package 108 or the lead 102, such that the sensor(s) in the sensor carrier 120 are configured to measure one or more properties of the environment surrounding the implanted neuromodulation device 100 (e.g., musculature). As another example, the sensor carrier 120 can be implanted in a suitable region proximate an oral or nasal cavity, or other portion of the airway of the patient (e.g., dental implant, nasal septum implant, submandibular gland implant, etc.). As another example, the sensor carrier 120 can be configured to be implanted in a suitable region proximate a tear duct (e.g., punctal plug) for measuring one or more properties of the tear duct, such as tear duct pressure.

[0156] Furthermore, in some embodiments the system can additionally or alternatively include a sensor carrier that is placed in an environment near the patient, such as on an external device 11 (e.g., mat), another bed surface (e.g., mattress, mattress topper, pillow, blanket, sheet, etc.), bedside surface (e.g., nightstand, headboard, bed frame, etc.), and/or elsewhere in the room (e.g., dresser, wall, floor, etc.).

2. Sensor data fOl 571 The method can include obtaining one or more various suitable types of sensor data that can be indicative of airflow in the patient’s airway, using one or more suitable sensor arrangements such as those described herein. Suitable kinds of sensor data can include, for example, vibration, pressure, temperature, impedance, patent motion, breath composition, and/or the like.

10158) For example, in some embodiments, the sensor data can be indicative of vibration of oral tissue (e.g., tissue in the mouth or other regions of the oral cavity). Such oral tissue vibrational data can be correlated to airflow, and can be obtained with one or more sensors that are wearable or implanted in the patient. For example, FIG. 6 illustrates an example implantable neuromodulation device 100 (similar to neuromodulation device 100 described above with respect to FIGS. 2B-3E) including a lead body 104 coupled to an electronics package 108 by an extension portion 106. The extension portion 106 has a first end coupled to the electronics package 108 and a second end that includes or is coupled to a bifurcation leading to arms 122 and 124 of the lead body 104. In some embodiments, one or more sensors 622 can located at or near the bifurcation and communicatively coupled via wires 624 passing within or along the extension portion 106 to the electronics package 108 for communicating sensor data. Additionally or alternatively, one or more sensors can be arranged on the electronics package 108 (e.g., part of electronics component 118), and/or be implanted in the patient at a target location (e.g., in a housing, such as a pill-shaped sensor carrier). In some embodiments, the sensors for detecting oral tissue vibrations can include an accelerometer, an ultrasonic sensor, a Doppler measurement of reflected sound, any combination thereof, and/or any suitable vibrational sensor. When the neuromodulation device 100 is implanted in a patient (e.g., as described with respect to FIGS. 3A-3E), the sensors can be configured to detect oral tissue vibration via detection of vibration of one or more anterior lingual muscles (e.g., genioglossus muscle) that experience a muscle response to airflow. Additionally or alternatively, an accelerometer or other vibrational sensor can be directly clamped onto a dorsal surface of the genioglossus muscle or other anterior lingual muscle(s) to detect tissue vibration. Vibrational sensor data from sensor(s) in the neuromodulation device 100 can be analyzed by one or more processors in the electronics package 108, and/or can be communicated (e.g., via Bluetooth or other suitable wireless communication techniques) to an external device for analysis.

[0159] As another example, the sensor data can be indicative of vibration of air in an upper airway region, such as the oral cavity. Airflow within the oral cavity can cause vibration of the air passing within the oral cavity. Accordingly, oral air vibrational data can be correlated to airflow. Such oral air vibrational data can be obtained with one or more sensors that are wearable or implanted in the patient. For example, an oral insert similar to sensor carriers shown in FIGS. 5A-5C (e.g., mouthguard, retainer, tooth cap, etc.) can include one or more sensors for measuring oral air vibration. Additionally or alternatively, an oral insert can include a chip or housing carrying an oral air vibration sensor that can be attached by tape, gum, etc. to the upper palate of the patient. In some embodiments, the oral insert sensor carrier, when worn, is configured to position the air vibration sensor such that the sensor has a sensing side or surface facing the oral cavity (e.g., is exposed to airflow in the oral cavity). As another example, oral air vibrational data can be obtained using one or more sensors housed in a wearable device, such as a chin strap (FIG. 5F) configured to position the one or more sensors underneath the patient’s chin, in contact with tissue whose vibrations can be correlated to airflow. In some embodiments, the sensors for detecting oral air vibrations can include an accelerometer, a pressure sensor, and/or other flow sensor.

(0160 J Similarly, as another example, the sensor data can be indicative of vibration of air in the nasal region (e.g., nasal cavity or nasal passageways, as nasal air vibrational data can be correlated to airflow. Such nasal air vibrational data can be obtained with one or more sensors that are wearable or implanted in the patient. For example, a nasal covering (e.g., nasal strip as shown in FIG. 5E), a nasal insert (e.g., nasal cannula) or nasal implant (e.g., nasal septum implant, nasal piercing, etc.) can include one or more sensors for measuring nasal air vibration. Similar to that described above for oral air vibrations, the sensors for detecting nasal air vibrations can include an accelerometer, a pressure sensor, and/or other flow sensor.

[0161] Similarly, sensor data can be indicative of vibrations of tissue and/or air in a throat region, such as the neck or trachea. For example, similar to oral tissue vibration and nasal or oral air vibrations, vibration of neck tissue and/or air in the trachea may be correlated to airflow. Such vibration data can be obtained with one or more sensors that are wearable or implanted. For example, neck tissue vibration can be measured by a sensor in a sensor carrier worn around the neck (e.g., collar as shown in FIG. 5G, necklace, choker, shirt collar, etc.). As another example, tracheal air vibration can be measured by a sensor in a sensor carrier worn around the chest (e.g., chest band as shown in FIG. 5H) or neck (e.g., collar as shown in FIG. 5G, necklace, choker, shirt collar, etc.).

[0162] In some embodiments, the sensor data can additionally or alternatively characterize air pressure that can be correlated to airflow in the airway. For example, the sensor data can be indicative of pressure in the Eustachian tube of the patient, as air pressure in the Eustachian tube generally decreases during inspiration and generally increases during expiration. In other words, a negative change in Eustachian tube pressure can indicate inhalation of air through the patient’s airway, while a positive change in Eustachian tube pressure can indicate exhalation of air through the patient’s airway. Accordingly, in some embodiments, the magnitude and/or rate of pressure change can be analyzed to obtain an indication of the amount of actual airflow in the patient’s airway. For example, absence of change in pressure in the Eustachian tube can indicate lack of airflow in the airway such as due to presence of an obstruction in the airway. In some embodiments, Eustachian tube pressure can be measured using a pressure sensor in a hearing-aid style sensor carrier such as that shown in FIG. 5D, with a pressure sensor positioned proximate the Eustachian tube (e.g., in the ear canal). In some embodiments, Eustachian tube pressure sensors can be calibrated to the specific patient (e.g., to enable analysis of absolute numbers of Eustachian tube pressure). Additionally or alternatively, relative changes (e.g., percent change) in Eustachian tube pressure data can be analyzed to assess airflow and/or presence of an obstruction.

|0163] Sensor data can additionally or alternatively be indicative of air pressure in one or more upper airway regions such as the oral cavity and/or nasal region (e.g., nasal cavity or nasal passageways). Airflow in an airway generally results in lower air pressure in the airway according to Bernoulli’s principle. As such, in some embodiments, oral and/or nasal pressure can be used to determine phases of inspiration and/or expiration. Furthermore, the magnitude and/or rate of pressure change can be analyzed to obtain an indication of the amount of actual airflow in the patient’s airway. For example, absence of change in pressure in the oral cavity, and/or the nasal regions can indicate lack of airflow in the airway such as due to presence of an obstruction in the airway. In some embodiments, an oral insert similar to sensor carriers shown in FIGS. 5A-5C (e.g., mouthguard, retainer, tooth cap, etc.) can include one or more sensors for measuring oral pressure. Additionally or alternatively, an oral insert can include a chip or housing carrying an oral air pressure sensor that can be attached by tape, gum, etc. to the upper palate of the patient. In some embodiments, the oral insert sensor carrier, when worn, is configured to position the pressure sensor such that the sensor has a sensing side or surface facing the oral cavity (e.g., is exposed to airflow in the oral cavity). A nasal covering (e.g., nasal strip as shown in FIG. 5E), a nasal insert (e.g., nasal cannula), or nasal implant (e.g., nasal septum implant, nasal piercing, etc.) can include one or more sensors for measuring nasal pressure. In some embodiments, pressure can be measured using a pressure sensor such as a bladder pressure sensor and/or any suitable vibrational sensor. In some embodiments, oral and/or nasal pressure sensors can be calibrated to the specific patient (e.g., to enable analysis of absolute numbers of oral and/or nasal pressure). Additionally or alternatively, relative changes (e.g., percent change) in oral and/or nasal pressure data can be analyzed to assess airflow and/or presence of an obstruction in the airway.

10164) In some embodiments, sensor data can additionally or alternatively be indicative of pressure in a tear duct. As tear ducts drain into the nasal cavity, air pressure in a tear duct of the patient may be indicative of airflow in an airway. For example, similar to that described above with respect to air pressure in the nasal region, airflow in an airway generally results in lower air pressure in the airway according to Bernoulli’s principle. As such, in some embodiments, tear duct pressure can be used to determine phases of inspiration and/or expiration. Furthermore, the magnitude and/or rate of pressure change can be analyzed to obtain an indication of the amount of actual airflow in the patient’s airway. For example, absence of change in pressure in the tear duct can indicate lack of airflow in the airway such as due to presence of an obstruction in the airway. In some embodiments, one or more pressure sensors can be arranged in a comer of an eye of the patient, to measure tear duct pressure. For example, a sensor carrier can include a punctal plug (e.g., silicone plug) that is configured to be placed in an inferior tear duct (and/or superior tear duct) of the patient. The punctal plug can include one or more pressure sensors configured to measure pressure in the tear duct in which the punctal plug is placed. In some embodiments, the punctal plug pressure sensor(s) can be calibrated to the specific patient (e.g., to enable analysis of absolute numbers of tear duct pressure). Additionally or alternatively, relative changes (e.g., percent change) in tear duct pressure data can be analyzed to assess airflow and/or presence of an obstruction in the airway.

[0165] In some embodiments, sensor data can additionally or alternatively include temperature (e.g., oral temperature, nasal temperature) measured at a location in or adjacent to the patient’s airway. Temperature in an oral cavity and/or nasal cavity generally decreases during inspiration and generally increases during expiration. In other words, a negative change in oral cavity or nasal cavity temperature can indicate inhalation of air through the patient’s airway, while a positive change in oral cavity or nasal cavity temperature can indicate exhalation of air through the patient’s airway. Furthermore, similar to pressure, the magnitude and/or rate of temperature change can be analyzed to obtain an indication of the amount of actual airflow in the patient’s airway. For example, absence of change in temperature in the oral cavity and/or the nasal cavity can indicate lack of airflow in the airway such as due to presence of an obstruction in the airway. In some embodiments, temperature can be measured using a thermistor and/or other suitable temperature sensor. For example, an oral insert similar to sensor carriers shown in FIGS. 5A-5C (e.g., mouthguard, retainer, tooth cap, etc.) can include one or more sensors for measuring oral temperature. Additionally or alternatively, an oral insert can include a chip or housing carrying an oral temperature sensor that can be attached by tape, gum, etc. to the upper palate of the patient. In some embodiments, the oral insert sensor carrier, when worn, is configured to position the pressure sensor such that the sensor has a sensing side or surface facing the oral cavity (e.g., is exposed to airflow in the oral cavity). Furthermore, a nasal insert (e.g., nasal cannula), or nasal implant (e.g., nasal septum implant, nasal piercing, etc.) can include one or more sensors for measuring nasal temperature. In some embodiments, an external nasal wearable (e.g., nasal strip) can include one or more sensors that are configured to measure nasal temperature in a nasal cavity (e.g., one or more temperature sensors on an arm or other member extending from the nasal wearable into the nasal cavity such as into the nostrils). Additionally or alternatively, an external nasal wearable (e.g., nasal strip) can include one or more sensors that are configured to measure an external nasal temperature that can be correlated to an internal temperature of the nasal cavity, such as an external nasal temperature of a region proximate a nasal bridge of the patient.

[0166] In some embodiments, sensor data can additionally or alternatively include impedance of a region of tissue proximate the patient’s airway. For example, the sensor data can include impedance measured between a first electrode placed in soft tissue behind the oropharyngeal space and a second electrode placed in another implant location (e.g., electrodes of an implanted neurostimulation device 10). In example embodiments in which at least one of the impedance electrodes is located on an implanted neurostimulation device 10, the lead (including the extension portion 106) can be tunneled around the pharynx to the musculature behind the oropharyngeal space. Generally, a change of impedance between such electrodes can indicate presence of an obstruction caused by contact of the patient’s tongue with the pharynx. For example, a positive change in impedance can indicate less obstruction in the airway (more volume behind the oropharyngeal space for airflow), while a negative change in impedance can indicate more obstruction in the airway (less volume behind the oropharyngeal space for airflow).

|0.167| Additionally or alternatively, in some embodiments sensor data can include sound, which can be correlated to airflow in an airway. For example, airflow through the trachea can, in some embodiments, be measured using an acoustic sensor implanted in the patient (e.g., on an implanted neurostimulation device 10). As another example, airflow through the trachea can be measured using an acoustic sensor located in a wearable device worn at a target location (e.g., on the neck, back, chest, etc.) of the patient, such as in a collar (e.g., as shown in FIG. 5G), chest band (e.g., as shown in FIG. 5H), a necklace, choker, shirt collar, etc. As another example, airflow through the trachea can be measured using an acoustic sensor located near the patient (e.g., in an external device 11 such as a mat, or on another bed surface or bedside location). As another example, airflow through the nasal region (e.g., nasal cavity or nasal passageways) can be measured using an acoustic sensor located in a sensor carrier in the form of a nasal insert (e.g., nasal cannula), nasal implant (e.g., nasal septum implant, nasal piercing, etc.) or other nasal attachment (e.g., nasal strip). Sound can be measured, for example, with a microphone or any other suitable acoustic sensor (e.g., ultrasonic sensor).

[0168] Furthermore, in some embodiments, sensor data can additionally or alternatively include data associated with snoring, which can be correlated to airflow in an airway. For example, more snoring can, in some embodiments, be correlated to less airflow and greater obstruction of the airway. In some embodiments, snoring can be identified using a microphone or other suitable acoustic sensor located in a wearable device worn over a suitable bony surface of the patient (e.g., mandible, clavicle, zygomatic bone, etc.). For example, a sensor carrier such as a chin strap (e.g., as shown in FIG. 5F), face mask, collar, choker, etc. can be worn and configured to position an acoustic sensor over a target location. In some embodiments, snoring can additionally or alternatively be identified using an acoustic sensor located near the patient (e.g., in an external device 11 such as a mat, or on another bed surface or bedside location). Furthermore, in some embodiments, snoring can be additionally or alternatively identified using motion or vibration of the patient’ s nostrils and/or other soft tissue proximate to the airway, which may be correlated to snoring. For example, motion or vibration of the patient’s nostrils can be measured using a sensor carrier in the form of a nasal insert (e.g., nasal cannula), or nasal implant (e.g., nasal septum implant, nasal piercing, etc.) that includes one or more sensors (e.g., accelerometer).

[0169] In some embodiments, sensor data can additionally or alternatively include a measurement of patient motion. For example, tongue motion can be indicative of respiratory effort that may indicate the possibility of airflow. Tongue motion can be measured, for example, using EMG sensors configured to obtain EMG signals of the genioglossus muscle. As another example, chest motion can be indicative of respiratory effort that may indicate the possibility of airflow, as in some instances greater amplitude of detected chest motion (e.g., rising and falling chest) can be correlated to respiratory effort (and the possibility of greater airflow). Furthermore, in some embodiments, chest motion data can be combined with other sensor data (e.g., vibration, pressure, temperature, etc. as described herein) to help identify and exclude instances in which chest motion occurs due to solely respiratory effort without airflow. In some embodiments, chest motion can be measured using one or more sensors (e.g., force sensor, strain sensor, pressure sensor, accelerometer, piezoelectric device, etc.) on a wearable chest strap or other device worn around the patient’s chest. Chest motion can additionally or alternatively be measured using one or more non-contact sensors (e.g., a millimeter wave sensor) that is mounted in the environment surrounding the patient, such as bedside, on a bed surface, elsewhere in the room, etc. In some embodiments, chest motion can additionally or alternatively be measured using one or more implantable sensors, such as implantable bioimpedance sensors that measure change impedance across a chest wall of the patient (e.g., transthoracic impedance), etc. In some embodiments, sensor data measuring patient motion can be analyzed in combination with one or more other sensor data types to determine airflow and/or efficacy of a treatment for sleep disordered breathing, as further described herein (e.g., with respect to FIG. 7).

[0170] Additionally or alternatively, in some embodiments sensor data can include breath content (e.g., gas composition of air exhaled by the patient), as breath content may be indicative of gas exchange that occurs with a non-obstructed airway path (e.g., in some instances, an approximately 4% breath composition exchange between carbon dioxide (CO2) and oxygen (O2) typically occurs in normal respiration). For example, carbon dioxide (CO2) content in exhaled air can be indicative of airflow, in that a positive change in CO2 content can generally be correlated to greater airflow. As another example, oxygen (O2) content in exhaled air can be indicative of airflow, in that a negative change in O2 content in exhaled breath can generally be correlated to greater airflow. Carbon dioxide and/or oxygen content in breath can be measured, for example, using a CO2 and/or O2 sensor located near or proximate the patient (e.g., on an external device 11 such as a mat, another bed surface, or bedside to the patient). As another example, carbon dioxide and/or oxygen content in breath can additionally or alternatively be measured with an oral insert similar to sensor carriers shown in FIGS. 5A-5C (e.g., mouthguard, retainer, tooth cap, etc.) including one or more CO2 and/or O2 sensors. Additionally or alternatively, an oral insert can include a chip or housing carrying a CO2 sensor and/or O2 sensor that can be attached by tape, gum, etc. to the upper palate of the patient. |0171] In some embodiments, the method can additionally or alternatively include obtaining sensor data including blood gas content. For example, in some embodiments the sensor data can include blood oxygen content (e.g., SpCh) of the patient. Blood oxygen level of a patient may provide information indicative of treatment efficacy. Blood oxygen level measured over a period of time (e.g., multiple hours) can, for example, be analyzed to help assess whether the patient is experiencing a decreasing number of apneas, whether the patient is experiencing a change of apneas to hypopneas or change of hypopneas to apneas, or number of apneas before they change to hypopneas, etc. For example, an increasing level of oxygen in blood over time can be indicative of decreasing number of apneas, while a decreasing level of oxygen in blood over time can be indicative of presence and possibly increasing number of apneas. In some embodiments, blood oxygen content can be used to provide an index of longterm treatment outcome for a patient undergoing the treatment for sleep disordered breathing. Additionally or alternatively, in some embodiments, blood oxygen content can be analyzed to determine an oxygen desaturation index (ODI) (e.g., average number of desaturation episodes per hour) that may provide information indicative of treatment efficacy.

|0172] In some embodiments, blood oxygen content can be measured using one or more blood oxygen sensors on a wearable or implantable device, such as one or more sensors configured to produce a photoplethysmogram (PPG). As an example, the system can include a sensor carrier 120 include a pulse oximeter device (e.g., including infrared and red light sources and one or more light sensors for measuring reflected light). The sensor carrier 120 can, for example, include a clip configured to be worn on the patient’s finger or attached to another suitable appendage of the patient, or another suitable sensor carrier otherwise configured to contact a surface of the patient’s skin to detect blood oxygen of the patient. Additionally or alternatively, blood oxygen content can be measured using a implantable blood sensor, such as a luminometric O2 optrode optical arrangement, on a chip that is implantable in the body of the patient and configured to directly sample blood.

|0173] As another example, in some embodiments the sensor data can include blood carbon dioxide (CO2) content. Carbon dioxide content in the bloodstream may provide information indicative of treatment efficacy. Blood carbon dioxide level measured over a period of time (e.g., multiple hours) can, for example, be analyzed to help assess whether the patient is experiencing an increasing number of apneas, whether the patient is experiencing a change of apneas to hypopneas or change of hypopneas to apneas, or number of hypopneas before they change to apneas, etc. For example, an increasing level of carbon dioxide in blood (e.g., hypercapnia) over time can be indicative of an increasing number of apneas, while a decreasing level of carbon dioxide in blood over time can be indicative of absence and possibly decreasing number of apneas. IN some embodiments, blood carbon dioxide content can be used to provide an index of long-term treatment outcome for a patient undergoing the treatment for sleep disordered breathing. In some embodiments, blood carbon dioxide content can be measured by measuring acidity of blood (e.g., with one or more pH sensors).

[0174] In some embodiments, the sensor data can be communicated from the sensor(s) 122 to one or more components of neuromodulation system 10 such as the neuromodulation device 100, the external device 11 (e.g., mat), and/or other suitable component such as via the network 50 (e.g., control unit 30, remote computing device(s) 80, patient device 70, physician device 75, etc.). The sensor data can be communicated in a wired or wireless manner (e.g., Bluetooth). In some embodiments, the sensor data can be communicated substantially in realtime or intermittently such as once every 1-5 seconds, once every 10 seconds, once every 30 seconds, one per minute, once per hour, once per two hours, once per three hours, once per night, once per two nights, once per week, once per two weeks, once per month, etc. Furthermore, in some embodiments, the sensor data can be communicated to one system component at one frequency (e.g., every minute or less) to allow for a more immediately responsive adjustment of stimulation parameters as appropriate, and additionally communicated to another system component at a second frequency (e.g., every night, every other night, every week, etc.) for long-term analysis. For example, the sensor data can be communicated to the implanted neuromodulation device 100, external device 11, and/or control unit 30 at a first frequency and communicated to the remote computing device(s) 80, patient device 70, physician device 75 at a second frequency lower than the first frequency.

[0175] The received sensor data can undergo one or more signal processing techniques, such as to reduce noise and/or isolate a desired sensor signal from the sensor data. For example, patient snoring may result in a complex sensor signal when measuring tissue and/or air vibration (e.g., oral, nasal, etc.), as snoring can cause measurable vibration in anterior lingual muscles and in the airway. Snoring can also be particularly prevalent among patients with certain kinds of sleep disordered breathing such as hypopneas. For example, in some instances, a vibrational sensor signal associated with snoring may be detected alongside a vibrational sensor signal associated with airflow, and the airflow-related vibrational sensor signal may have a lower amplitude than the snoring-related vibrational sensor signal. Furthermore, a snoring-related vibrational sensor signal may generally have a lower frequency than an airflow- related vibrational sensor signal, since normal airflow generally results in minute variations of movement relative to snoring.

[0176] Accordingly, in some embodiments, the received sensor data can be processed to help isolate a signal indicative of a respiratory event (e.g., inspiration/expiration), through suitable signal processing techniques such as noise removal and feature extraction(s). For example, suitable signal processing techniques can remove portions of a sensor signal that are characterized by an amplitude above a certain threshold and suspected of being associated with snoring. Additionally or alternatively, a suitable high-pass filter can be applied in an analog and/or digital manner to a sensor signal in order to remove portions of a sensor signal that are characterized by a frequency below a certain threshold and suspected of being associated with snoring and/or other noise. In some embodiments, such thresholds can be set in programming based at least in part on known or average patient snoring metrics. Additionally or alternatively, such thresholds can be dynamic. For example, filtering thresholds can be modified based at least in part on other patient metrics (e.g., breathing rate as measured by one or more other sensors). Additionally or alternatively, signal processing techniques can remove errors in the signal acquisition process (e.g., by adjusting the sampling rate), remove common electromagnetic signal interference, remove artifacts of motion during sleep, and/or help extract specific features from the signal relevant to identifying respiratory events.

[0177] Assessing efficacy of stimulation energy 430 functions to transform the sensor data measurements into an indication of how well the delivered stimulation energy has performed in reducing obstruction in the patient’s airway or otherwise improving patency of the patient’s airway.

[0178] In some embodiments, sensor data can be transformed into respiration events (e.g. inhalation, exhalation) that can be used to identify the efficacy of the stimulation treatment. For example, respiration events can be used to calculate an Effectiveness of Treatment Apnea-Hypopnea Index (ET-AHI) score for a treatment session. This score can be calculated (e.g., calculated automatically) by one or more processors in the neuromodulation system 10, such as after every treatment session. The score can be stored in system 80. Historical data analysis of AHI score comparison before and after a treatment session and/or between multiple treatment sessions can be used to determine the overall efficacy of the treatment. fOl 791 In some embodiments, the relative change in one or more parameters of sensor data can be correlated to quantified airflow information (e.g., magnitude and/or direction of airflow). For example, the relative change in magnitude and/or frequency in vibrational data (e.g., oral air or tissue vibration, nasal air or tissue vibration) can be correlated to at least a magnitude of airflow. As another example, the relative change in pressure data (e.g., Eustachian tube pressure, oral pressure, nasal pressure, etc.) can be correlated to a magnitude and/or direction of airflow. Other aspects of sensor data as described herein can similar be correlated to one or more airflow characteristics.

[0180] Additionally or alternatively, in some embodiments, the absolute value of one or more parameters of sensor data can be correlated to quantified airflow information (e.g., magnitude and/or direction of airflow). For example, a numerical value of a sensor measurement can be correlated to one or more characteristics of airflow based at least in part on a lookup table or a single- or multi-variable function, where the lookup table or function can be generated based at least in part on empirical data. Furthermore, in some embodiments, both the absolute value and the relative change in one or more parameters of sensor data can used in suitable correlations to determine airflow information. For example, airflow information can be determined based at least in part on a function incorporating both absolute values and relative change. As another example, airflow information can be determined based at least in part by averaging the separate results obtained by separately correlating absolute values to airflow and relative change to airflow. As another example, airflow information can be determined based at least in part by taking the lesser or greater of the separate results obtained by separately correlating absolute values to airflow and relative change to airflow.

[0181] The correlation between sensor data and airflow information can be based at least in part on empirical data. In some embodiments, the empirical data used to correlate sensor data to airflow information can be based at least in part on personalized data from the patient themselves. For example, sensor data can obtained during a period when the patient is known to have normal airflow without airway obstruction, and can subsequently be used as a baseline reference (e.g., average of sensor data over one night with normal airflow, over three nights with normal airflow, etc.). Sensor data obtained during treatment of sleep ordered breathing can be compared to the baseline reference, and any deviation from the baseline reference that is larger than a certain predetermined threshold can provide insight into airflow characteristics (e.g., presence or absence of an obstruction, degree of obstruction, etc.). Additionally or alternatively, in some embodiments, empirical data used to correlate sensor data to airflow information can be based at least in part on sensor data associated with a patient population relevant or sufficiently similar to the patient being treated.

[0182] Various types of sensor measurements can be individually or in combination correlated to airflow. For example, a single sensor data type can be correlated to airflow information as described above. In other words, in some embodiments, the number of sensor data types to number of quantified airflow results is 1 : 1.

[0183] In some embodiments, multiple types of sensor measurements can be combined when correlating to a single airflow result. In other words, in some embodiments, the number of sensor data types to number of quantified airflow results is n:l, where n is greater than 1. Such a correlation can, for example, be based on a multi-variate function or multi-variate lookup table, as described above.

[0184] Furthermore, in some embodiments, a correlation can be performed separately for each of multiple sensor data types, and a single airflow result from the multiple correlations can be taken as representative of airflow. For example, the lowest value, the greatest value, or a median value from the multiple airflow results (as determined from correlating measurements of different sensor data types) can be taken as representative of airflow. As another example, a ratio of multiple airflow results can be used in a second-level analysis to determine certain airflow information. In a specific example correlating nasal airflow to oral airflow, a second- level analysis to quantify airflow in an airway can be based at least in part on the ratio of (i) a first airflow result determined by correlating nasal air vibration, nasal tissue vibration, and/or nasal pressure and (ii) a second airflow result determined by correlating oral air vibration, oral tissue vibration, and/or oral pressure). Other kinds of sensor data types can similarly be analyzed in a multi-level analytical process.

[0185] Additionally or alternatively, the correlation between sensor data and airflow information can be based at least in part on a rule-based algorithm and/or a trained machine learning algorithm (e.g., deep learning algorithm such as a convolutional neural network). The trained algorithm can receive one or more sensor measurements (e.g., measurements of one or more sensor data types), and can generate output data characterizing airflow. The algorithm can be trained, for example, on sensor measurements obtained from a patient while the patient is sleeping under observation, where a clinician characterizes the quality of airflow in the patient’s airway (e.g., characterizing episodes of apnea, hypopnea, etc.). Any suitable rulebased algorithm(s), machine learning algorithm(s), or combination thereof can be used to perform such a correlation between sensor data and airflow information. Examples of machine learning algorithms that may be used include: regression algorithms (e.g., ordinary least squares regression, linear regression, logistic regression, stepwise regression, multivariate adaptive regression splines, locally estimated scatterplot smoothing), instance-based algorithms (e.g., k-nearest neighbor, learning vector quantization, self-organizing map, locally weighted learning), regularization algorithms (e.g., ridge regression, least absolute shrinkage and selection operator, elastic net, least-angle regression), decision tree algorithms (e.g., Iterative Dichotomiser 3 (ID3), C4.5, C5.0, classification and regression trees, chi-squared automatic interaction detection, decision stump, M5), Bayesian algorithms (e.g., naive Bayes, Gaussian naive Bayes, multinomial naive Bayes, averaged one-dependence estimators, Bayesian belief networks, Bayesian networks, hidden Markov models, conditional random fields), clustering algorithms (e.g., k-means, single-linkage clustering, k-medians, expectation maximization, hierarchical clustering, fuzzy clustering, density-based spatial clustering of applications with noise (DBSCAN), ordering points to identify cluster structure (OPTICS), non negative matrix factorization (NMF), latent Dirichlet allocation (LDA), Gaussian mixture model (GMM)), association rule learning algorithms (e.g., apriori algorithm, equivalent class transformation (Eclat) algorithm, frequent pattern (FP) growth), artificial neural network algorithms (e.g., perceptrons, neural networks, back-propagation, Hopfield networks, autoencoders, Boltzmann machines, restricted Boltzmann machines, spiking neural nets, radial basis function networks), deep learning algorithms (e.g., deep Boltzmann machines, deep belief networks, convolutional neural networks, stacked auto-encoders), dimensionality reduction algorithms (e.g., principle component analysis (PCA), independent component analysis (ICA), principle component regression (PCR), partial least squares regression (PLSR), Sammon mapping, multidimensional scaling, projection pursuit, linear discriminant analysis, mixture discriminant analysis, quadratic discriminant analysis, flexible discriminant analysis), ensemble algorithms (e.g., boosting, bootstrapped aggregation, AdaBoost, blending, gradient boosting machines, gradient boosted regression trees, random forest), or suitable combinations thereof. The machine learning algorithms described herein can be trained using any suitable technique, including supervised learning, unsupervised learning, semi -supervised learning, reinforcement learning, or suitable combinations thereof.

[0186] In some embodiments, the quantified airflow information determined based on any of the above-described analysis can be transformed to a qualitative assessment of efficacy of stimulation energy or treatment of sleep disordered breathing. For example, the airflow information can be bucketed into one of multiple categories based on predetermined thresholds (e.g., low efficacy, medium efficacy, high efficacy). However, in some embodiments, the airflow information can be normalized into a predefined range and indexed to an efficacy score (e.g., between 1 and 5, between 1 and 10, between 1 and 100, etc.).

[0187] Once an assessment of efficacy is obtained, one or more parameters of stimulation energy delivered to the patient can be modified. Updating stimulation parameters 440 functions to improve the efficacy of treatment, as appropriate in view of the efficacy determined to be achieved by current stimulation parameters. In other words, updating stimulation parameters can provide a manner of “self-calibration” to optimize or improve the treatment efficacy, such as in a closed-loop manner. In some embodiments, updating stimulation parameters can include identifying one or more stimulation parameters for modification. For example, one or more of the following can be identified for modification: one or more pulse settings (patterns, duration, waveforms, etc.), stimulation frequency, one or more amplitude settings, electrode configurations of the neuromodulation device 100, or any combination thereof. Additionally or alternatively, in some embodiments, updating stimulation parameters can include modifying a level or other quantification of one or more stimulation parameters. For example, updating stimulation parameters can include modifying one or more pulse settings (patterns, duration, waveforms, etc.), stimulation frequency, one or more amplitude settings, electrode configurations of the neuromodulation device 100, or any combination thereof. For example, stimulation intensity (e.g., amplitude) can be increased if assessed efficacy of treatment is below a target level of efficacy.

|0188] In some embodiments, one or more stimulation parameters for modification can be identified based at least in part on short-term sensor data. For example, in some embodiments the short-term sensor data (e.g., obtained as described herein) can be inputted into a trained machine learning algorithm configured to output one or more stimulation parameters suitable for modification. Such a machine learning algorithm (e.g., neural network, or other suitable machine learning algorithm) can be trained, for example, using training data that includes training sensor data (e.g., sensor data obtained as described herein) from example patients and efficacy outcome data following modification of one or more stimulation parameters for such example patients.

[0189] In some embodiments, one or more stimulation parameters can be updated in substantially real-time (e.g., on a breath-by-breath basis) or at a high frequency (e.g., every 5 seconds, every 10 seconds, etc.) based on short-term sensor data and assessment of the sensor data as described above. For example, if after a first adjustment of stimulation parameters the airflow in the patient’s airway is still below a desirable level (e.g., for one, two, three, four, five, or other suitable number of test breaths after the first adjustment has been implemented), a second adjustment of stimulation parameters can be performed to further pursue improved airflow in the patient’s airway. This process can be repeated as appropriate until a suitable amount of airflow or treatment efficacy is determined.

[0190] In some embodiments, a first period of time can function as a calibration session in which sensor data is obtained and analyzed to enable generation of updated stimulation parameters, then subsequent periods of time can utilize the updated stimulation parameters unless additional modification to stimulation parameters is determined to be appropriate based on subsequent sensor data. Calibration sessions can be performed repeatedly as appropriate. For example, if a patient reports experiencing worse sleep after stimulation parameters have been updated, one or more follow-up calibration sessions can be run to generate additional updated stimulation parameters in an effort to continually pursue effective treatment of sleep disordered breathing in the patient.

[0191 ] Additionally or alternatively, identification of stimulation parameters for modification and/or the modification of one or more stimulation parameters can be stored and suggested to an operator (physician, patient, etc.) after a period of time, such as a single night of sleep. Suggested stimulation parameter types for modification and/or modifications of stimulation parameters can be presented to an operator via physician device 75 and/or patient device 70, such as displayed or otherwise communicated through a user interface 40. The user interface 40 can be configured to allow the operator confirm and/or manually adjust any such suggested modifications of stimulation energy.

[0192] FIG. 7 illustrates various aspects of an example method 700 of treating sleep disordered breathing with a neuromodulation system, where the method 700 involves analyzing the relationship between different sensor data types. The method 700 can be similar to method 400 described herein except as described below. For example, like the method 400, the method 700 can be a method of treating sleep disordered breathing with a neuromodulation at least partially implanted in a patient having an airway compromised by an obstruction. As shown in FIG. 7, the method 700 includes delivering stimulation energy to a target nerve associated with patency of an airway of the patient 710 (similar to the delivering process 410 of method 400), receiving various sensor data, and assessing efficacy of the stimulation energy based at least in part on the received sensor data 730 (similar to the assessing process 430 of method 400). In some embodiments, the method 700 can further include updating one or more stimulation parameters of the stimulation energy 740, based at least in part on the assessed efficacy of the stimulation energy (similar to the updating process 440 of method 400).

[0193] However, in receiving sensor data, the method 700 can include receiving first sensor data indicative of respiratory effort by the patient 720, and receiving second sensor data indicative of oxygenation in the patient 722. In some embodiments, the first sensor data indicative of respiratory effort comprises sensor data indicative of patient motion (e.g., tongue motion, chest motion, etc. which can be obtained as described elsewhere herein). Furthermore, in some embodiments, the second sensor data indicative of oxygenation in the patient can include blood oxygen level (e.g., SpCh), blood carbon dioxide level, carbon dioxide content in exhaled breath, and/or oxygen content in exhaled breath (e.g., any of which can be obtained as described elsewhere herein). In various examples, oxygenation can be measured more directly by measuring oxygen content in blood or breath, or more indirectly by measuring carbon dioxide content in blood or breath (which may be reflective of the amount of gas exchange occurring in the patient’s lungs).

|0194] During a typical respiration cycle, heart rate increases during inspiration to accelerate or increase gas exchange in the patient’s lungs. Assuming an unobstructed airway and otherwise normal respiratory mechanics in a patient, this accelerated or increased gas exchange may lead to an increase in oxygenation in the patient that is measurable some time after the inspiratory effort. As such, an increase in oxygenation levels in a patient after the inspiratory effort can be indicative of an unobstructed airway. Accordingly, for a patient being treated for sleep disordered breathing (e.g., with a neuromodulation system such as that described herein), efficacy of the treatment can be determined based at least in part on collective sensor data that indicates an increase in oxygenation levels in a patient after inspiratory effort. In some embodiments, increase in oxygenation level can include an increase in blood oxygen level, decrease in blood carbon dioxide level, decrease in oxygen level in breath, and/or increase in carbon dioxide level in breath, for example.

[0195] In some embodiments, assessing efficacy of the stimulation energy based at least in part on the received first and second sensor data 730 can include analyzing the time delay between the indicated inspiratory effort event and the increase in oxygenation level, and/or analyzing the amount of change in oxygenation level itself in the patient, both of which can be indicative of airflow in the patient’s airway. In other words, an analysis of a change in the oxygenation level and/or time delay between inspiratory effort and change in the oxygenation level can provide information indicative of airflow in the airway. For example, in some embodiments, the efficacy of the treatment can be based at least in part on increased oxygenation in a patient as measured a predetermined time after an indication of inspiratory effort (e.g., an increase in oxygenation level measured at least a predetermined threshold amount of time after the indication of inspiratory effort, or within a predetermined time window duration after the indication of inspiratory effort). Additionally or alternatively, the efficacy of the treatment can be based at least in part on a predetermined threshold change (e.g., increase) in oxygenation level in the patient as measured after an indication of inspiratory effort.

[0196] In operation, the methods described herein can be performed at any suitable frequency with respect to treatment sessions. For example, assessment of treatment efficacy can be performed every night the patient receives the neuromodulation treatment for sleep disordered breathing. As another example, assessment of treatment efficacy can be performed on a periodic or other intermittent basis (e.g., every other day, every week, every month, every two months, every six months, every weekend day, every weekday, etc.), according to a suitable self-diagnostic or calibration schedule that may be regular or irregular. Additionally or alternatively, assessment of treatment efficacy can be performed in response to an instruction by an operator (e.g., physician or patient), such as in response to a menu selection or button push on the patient device 70, the physician device 75, a peripheral wearable device including the sensor carrier 120, the external device 11 (e.g., mat), and/or any suitable user input feature on a component of the neuromodulation system 10.

[0197] In some embodiments, the method can involve the patient wearing a peripheral wearable device such as those described herein. Accordingly, in these embodiments, the method can include alerting or instructing the patient to don the peripheral wearable device prior to sleep, so as to facilitate the gathering of sensor data for assessing treatment efficacy. Such an alert or instruction can, for example, be communicated to the patient through the patient device 70 in a visual and/or auditory manner.

Conclusion

[0198] Although many of the embodiments are described above with respect to systems, devices, and methods for evaluating efficacy of treatment of improvement of sleep disordered breathing, the technology is applicable to other applications and/or other approaches. Moreover, other embodiments in addition to those described herein are within the scope of the technology. Additionally, several other embodiments of the technology can have different configurations, components, or procedures than those described herein. A person of ordinary skill in the art, therefore, will accordingly understand that the technology can have other embodiments with additional elements, or the technology can have other embodiments without several of the features shown and described above with reference to the Figures.

[0199] The descriptions of embodiments of the technology are not intended to be exhaustive or to limit the technology to the precise form disclosed above. Where the context permits, singular or plural terms may also include the plural or singular term, respectively. Although specific embodiments of, and examples for, the technology are described above for illustrative purposes, various equivalent modifications are possible within the scope of the technology, as those skilled in the relevant art will recognize. For example, while steps are presented in a given order, alternative embodiments may perform steps in a different order. The various embodiments described herein may also be combined to provide further embodiments.

[0200] As used herein, the terms “generally,” “substantially,” “about,” and similar terms are used as terms of approximation and not as terms of degree, and are intended to account for the inherent variations in measured or calculated values that would be recognized by those of ordinary skill in the art.

10201] Moreover, unless the word “or” is expressly limited to mean only a single item exclusive from the other items in reference to a list of two or more items, then the use of “or” in such a list is to be interpreted as including (a) any single item in the list, (b) all of the items in the list, or (c) any combination of the items in the list. Additionally, the term "comprising" is used throughout to mean including at least the recited feature(s) such that any greater number of the same feature and/or additional types of other features are not precluded. It will also be appreciated that specific embodiments have been described herein for purposes of illustration, but that various modifications may be made without deviating from the technology. Further, while advantages associated with certain embodiments of the technology have been described in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the technology. Accordingly, the disclosure and associated technology can encompass other embodiments not expressly shown or described herein.

Claims

CLAIMS I/We claim:

1. A method of treating sleep disordered breathing with a neuromodulation system at least partially implanted in a patient having an airway compromised by an obstruction, wherein the method comprises: delivering stimulation energy to a target nerve in the patient using an electrode of the neuromodulation system, wherein the target nerve is associated with patency of the airway; receiving sensor data from a sensor arrangement of the neuromodulation system, wherein the sensor data is indicative of airflow in the airway proximal to the obstruction; and assessing efficacy of the stimulation energy based at least in part on the received sensor data.

2. The method of claim 1, wherein the sensor data characterizes vibrations indicative of airflow in the airway proximal to the obstruction.

3. The method of claim 1 or 2, wherein the sensor data characterizes vibrations of oral tissue of the patient.

4. The method of any one of claims 1-3, wherein the sensor data characterizes vibrations of air in an oral region of the patient.

5. The method of any one of claims 1-4, wherein the sensor data characterizes vibrations of air in a nasal region of the patient.

6. The method of any one of claims 1-5, wherein the sensor data characterizes air pressure in the airway proximal to the obstruction.

7. The method of any one of claims 1-6, wherein the sensor data characterizes pressure in a Eustachian tube of the patient.

8. The method of any one of claims 1-7, wherein the sensor data characterizes pressure in a tear duct of the patient.

9. The method of any one of claims 1-8, wherein the sensor data characterizes pressure in an oral region of the patient.

10. The method of any one of claims 1-9, wherein the sensor data characterizes pressure in a nasal region of the patient.

11. The method of any one of claims 1-10, wherein the sensor data comprises at least one of oral temperature or nasal temperature.

12. The method of any one of claims 1-11, wherein the sensor data comprises impedance of a region of tissue proximate the patient’s airway.

13. The method of any one of claims 1-12, wherein the sensor data is indicative of airflow through a trachea of the patient.

14. The method of any one of claims 1-13, wherein the sensor data is indicative of snoring.

15. The method of any one of claims 1-14, wherein the sensor data is indicative of at least one of tongue motion or chest motion.

16. The method of any one of claims 1-15, wherein the sensor data comprises content of breath from the patient.

17. The method of any one of claims 1-16, wherein assessing efficacy comprises assessing efficacy of the stimulation energy substantially in real-time during a treatment session.

18. The method of claim 17, wherein assessing efficacy comprises assessing efficacy of the stimulation energy on a breath-by-breath basis.

19. The method of any one of claims 1-18, further comprising updating one or more stimulation parameters of the stimulation energy based on the assessed efficacy of the stimulation energy.

20. The method of claim 19, wherein the one or more stimulation parameters comprise at least one of amplitude, frequency, pulse width, duty cycle, pulse width, or polarity.

21. The method of claim 19 or 20, wherein updating one or more stimulation parameters comprises updating one or more stimulation parameters of the stimulation energy substantially in real-time during a treatment session.

22. The method of any one of claims 19-21, updating one or more stimulation parameters comprises updating one or more stimulation parameters of the stimulation energy on a breath- by-breath basis.

23. The method of any one of claims 19-22, further comprising delivering stimulation energy in accordance with the updated one or more stimulation parameters.

24. The method of any one of claims 1-23, wherein the electrode is on a neuromodulation lead is configured to be implanted in a sublingual region of the patient.

25. The method of claim 24, wherein the neuromodulation lead is configured to be implanted between a geniohyoid muscle and a genioglossus muscle of the patient.

26. The method of any one of claims 1-25, wherein the target nerve is a hypoglossal nerve.

27. A neuromodulation system for the treatment of sleep disordered breathing in a patient having an airway compromised by an obstruction, wherein the system is configured to be at least partially implanted in the patient, wherein the system comprises: an electrode configured to be implanted in the patient and deliver stimulation energy to a target nerve in the patient associated with patency of the airway; a sensor arrangement configured to provide sensor data indicative of airflow in the airway proximal to the obstruction; one or more processors; and a memory operably coupled to the one or more processors and storing instructions that, when executed by the processor, cause the system to: deliver stimulation energy to the target nerve via the electrode; receive sensor data from the sensor; and assess efficacy of the delivered stimulation energy for based at least in part on the received sensor data.

28. The system of claim 27, wherein the sensor data characterizes vibrations indicative of airflow in the airway proximal to the obstruction.

29. The system of claim 27 or 28, wherein the sensor data characterizes vibrations of oral tissue of the patient.

30. The system of any one of claims 27-29, wherein the sensor data characterizes vibrations of air in an oral region of the patient.

31. The system of any one of claims 27-30, wherein the sensor data characterizes vibrations of air in a nasal region of the patient.

32. The system of any one of claims 27-31, wherein the sensor data characterizes air pressure in the airway proximal to the obstruction.

33. The system of any one of claims 27-32, wherein the sensor data characterizes pressure in a Eustachian tube of the patient.

34. The system of any one of claims 27-33, wherein the sensor data characterizes pressure in a tear duct of the patient.

35. The system of any one of claims 27-34, wherein the sensor data characterizes pressure in an oral region of the patient.

36. The system of any one of claims 27-35, wherein the sensor data characterizes pressure in a nasal region of the patient.

37. The system of any one of claims 27-36, wherein the sensor data comprises at least one of oral temperature or nasal temperature.

38. The system of any one of claims 27-37, wherein the sensor data comprises impedance of a region of tissue proximate the patient’s airway.

39. The system of any one of claims 27-38, wherein the sensor data is indicative of airflow through a trachea of the patient.

40. The system of any one of claims 27-39, wherein the sensor data is indicative of snoring.

41. The system of any one of claims 27-40, wherein the sensor data is indicative of at least one of tongue motion or chest motion.

42. The system of any one of claims 27-41, wherein the sensor data comprises content of breath from the patient.

43. The system of any one of claims 27-42, wherein at least a portion of the sensor arrangement is configured to be implanted in the patient.

44. The system of any one of claims 27-43, wherein at least a portion of the sensor arrangement is configured to be implanted in a sublingual region of the patient.

45. The system of any one of claims 27-44, wherein at least a portion of the sensor arrangement is configured to be implanted adjacent to a dorsal surface of a genioglossus muscle of the patient.

46. The system of any one of claims 27-45, further comprising an oral insert comprising at least a portion of the sensor arrangement and configured to be positioned in an oral region of the patient.

47. The system of claim 46, wherein the oral insert comprises at least one of a mouthguard, a retainer, a tooth attachment, a palate attachment, or a dental implant.

48. The system of any one of claims 27-47, further comprising a wearable device comprising at least a portion of the sensor arrangement and configured to be positioned over a nasal region of the patient.

49. The system of any one of claims 27-48, further comprising a wearable device comprising at least a portion of the sensor arrangement and configured to be positioned under a chin or around a neck of the patient.

50. The system of any one of claims 27-49, further comprising a wearable device comprising at least a portion of the sensor arrangement and configured to be positioned around a torso of the patient.

51. The system of any one of claims 27-50, further comprising a wearable device comprising at least a portion of the sensor arrangement and configured to be worn in or on the ear of the patient.

52. The system of any one of claims 27-51, wherein the sensor arrangement comprises an accelerometer.

53. The system of any one of claims 27-52, wherein the sensor arrangement comprises a pressure sensor.

54. The system of any one of claims 27-53, wherein the memory stores instructions that cause the system to assess efficacy of the stimulation energy substantially in real-time during a treatment session.

55. The system of claim 54, wherein the memory stores instructions that cause the system to assess efficacy of the stimulation energy on a breath-by-breath basis.

56. The system of any one of claims 27-55, wherein the memory stores instructions that cause the system to update one or more stimulation parameters of the stimulation energy based on the assessed efficacy of the stimulation energy.

57. The system of claim 56, wherein the one or more stimulation parameters comprise at least one of amplitude, frequency, pulse width, duty cycle, pulse width, or polarity.

58. The system of claim 56 or 57, wherein the memory stores instructions that cause the system to update one or more stimulation parameters of the stimulation energy substantially in real-time during a treatment session.

59. The system of any one of claims 56-58, wherein the memory stores instructions that cause the system to update one or more stimulation parameters of the stimulation energy on a breath-by-breath basis.

60. The system of any one of claims 56-59, wherein the memory stores instructions that cause the system to deliver stimulation energy in accordance with the updated one or more stimulation parameters.

61. The system of any one of claims 27-60, further comprising a neuromodulation lead comprising the electrode, wherein the neuromodulation lead is configured to be implanted in a sublingual region of the patient.

62. The system of claim 61, wherein the neuromodulation lead is configured to be implanted between a geniohyoid muscle and a genioglossus muscle of the patient.

63. The system of any one of claims 27-62, wherein the target nerve is a hypoglossal nerve.