Swallowing is induced using electrical stimulation applied via surface electrodes

Abstract

A system and method for inducing a swallowing reflex in a human subject. A stimulation signal is generated that, when applied to the skin overlying the thyroid cartilage region of the neck, induces a full swallowing reflex. The stimulation signal is delivered to the skin overlying at least the thyroid cartilage region of the neck via surface electrodes to induce a full swallowing reflex in the human subject.

Description

[0001] Related Applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 594,109, filed on December 4, 2017, entitled “Eliciting Swallowing Using Electrical Stimulation Applied Through Surface Electrodes,” the entire contents of which are incorporated herein by reference. Technical Field

[0003] The present invention relates to methods and systems for inducing swallowing, and more particularly, to methods and systems for inducing swallowing using electrical stimulation applied via surface electrodes. Background Art

[0004] Swallowing is a vital and complex process involving many muscles. Dysphagia can be caused by stroke, neurodegenerative disease, brain tumors, breathing disorders, etc., resulting in insufficient control of the muscles needed to swallow. In severe cases, aspiration pneumonia may result. Dysphagia is often caused by poor control of certain muscles in the upper respiratory system. Many muscles in this system are also involved in speech and voice.

[0005] Figure 1A Various structures of the neck and oral cavity involved in swallowing are shown. Swallowing disorders are generally a human problem because having highly developed speech abilities is directly related to the much lower position of the larynx (which is lower in humans than in many animals), which in turn increases the dangers associated with swallowing. The larynx is located in the neck and is involved in breathing, manipulation of the voice, and protecting the trachea from aspiration of food and water via the esophagus. Complete closure of the larynx and its timing are critical to ensuring safe swallowing because the larynx controls whether food enters the trachea or the esophagus. If the larynx fails to close, food or liquid may enter the airway harmfully. In some animals, the larynx is not a highly developed natural speech apparatus, and the higher position of the larynx even allows these animals to drink and breathe at the same time - which is impossible for humans.

[0006] In humans, at least twelve muscles are involved in the swallowing process. Figure 1Bis a front view of the human neck showing the various muscles and associated structures in their natural positions. It is particularly important to control their movement correctly, as failure to do so can have serious consequences. However, because the swallowing process varies from person to person, it is not clear which muscle may be dominant, or even whether coordinated contraction of all twelve muscles or more is required for proper swallowing. For example, different individuals selectively use the geniohyoid, mylohyoid, and digastric muscles, for example, with some individuals using all three muscles at the start of a swallow, while others use different pairs. In addition, the temporal association of submental muscle contraction varies between individuals.

[0007] Electrical stimulation has been successfully used to control weakened muscles / nerves (e.g., aging or degenerated nerves / muscles), to re-innervate nerves (including synkinetic re-innervation), and / or to provide electrical signals to nerves to compensate for hearing defects (e.g., cochlear implant stimulation provides hearing for the deaf) or to overrule erroneously induced neural signals.

[0008] Although various stimulation systems and methods have been proposed to control the upper respiratory muscles for swallowing, none of them address the problem of lifting the larynx for proper swallowing. For example, Freed et al. describe non-invasive methods and devices that continuously stimulate the skin surface to help patients initiate swallowing (see, e.g., U.S. Pat. Nos. 5,725,564, 6,104,958, and 5,891,185). In addition, there are systems that induce glottal closure by appropriate electrical stimulation (see, e.g., Bidus et al., Laryngoscope, 110: 1943-1949, 2000; Ludlow et al., Journal of Artificial Organs, 23: 463-465, 1999; and Ludlow et al., Muscle and Nerve, 23: 44-57, 2000). U.S. Patent Application No. 2007 / 0123950, Ludlow et al. (hereinafter referred to as Ludlow '950), discloses a method and system for co-producing muscle movement during speech, swallowing or phonation by electrically stimulating at least two different muscles using implanted electrodes to move the hyoid bone and / or part of the upper airway and / or vocal tract. Ludlow '950 found that neuromuscular stimulation of only two of the muscles produced a significant portion of the normal desired movement of the hyoid bone. In addition, Ludlow disclosed that the muscles involved in swallowing remain in their normal given positions in the human body. All of the above cited documents are incorporated herein by reference in their entirety.

[0009] Using conventional techniques to induce swallowing with surface electrodes remains problematic because pain thresholds are often exceeded or unwanted responses are activated. Some methods include inserting a catheter through the nose into the pharynx / esophagus and applying electrical stimulation pulses to electrodes located on the catheter. This is painful and unpleasant for the patient and is not a long-term solution.

[0010] Another method of inducing swallowing using surface electrodes is to apply short (eg, 0.2 ms) regular rectangular pulses. Although surface electrical stimulation has received increasing attention as an adjunctive swallowing treatment for dysphagia in recent years (see, for example, Freed ML et al., Electrical stimulation for swallowing disorders caused by stroke, Respir Care, 2001, 46(5):466-74 [PubMed]; Leelamanit V, Limsakul C, Geater A, Synchronized electrical stimulation in treating pharyngeal dysphagia, Laryngoscope, 2002, 112(12):2204-10 [PubMed]; Park CL, O'Neill PA, Martin DF, A pilot exploratory study of oral electrical stimulation on swallow function following stroke: an innovative technique, Dysphagia, 1997, 12(3):161-6 [PubMed]; and Power M et al., Changes in pharyngeal corticobulbar excitability and swallowing behavior after oral stimulation, Am J Surg Surg Surg., 2003, 112(12):2204-10 [PubMed]; Physiol Gastrointest Liver Physiol, 2004, 286(1):G45-50 [PubMed], the contents of which are hereby incorporated by reference in their entirety), but prior to the study by Christy L. Ludlow, Ianessa Humbert, Keith Saxon, Christopher Poletto, Barbara Sonies and Lisa Crujido, Effects of Surface Electrical Stimulation Both at Rest and During Swallowing in Chronic Pharyngeal Dysphagia, Dysphagia, January 2007, 22(1):1-10 (the contents of which are hereby incorporated by reference in their entirety), little was known about the effects of transcutaneous stimulation on the physiology of swallowing.It is hypothesized that electrical stimulation may aid swallowing by promoting hyo-laryngeal elevation (see, e.g., Freed et al., Electrical stimulation for swallowing disorders caused by stroke; and Leelamanit et al.) or by increasing sensory input to the central nervous system, thereby enhancing the urge to swallow (see, e.g., Park et al. and Power et al.).

[0011] As described in Ludlow et al., Effects of Surface Electrical Stimulation Both at Rest and During Swallowing in Chronic Pharyngeal Dysphagia, electrical stimulation at low current levels applied to the skin excites superficial sensory nerve endings that provide sensory feedback to the central nervous system. As the amplitude increases, the electric field depolarizes nerve endings in the muscles below the surface of the skin (see Loeb GE, Gans C. Electromyography for Experimentists, The University of Chicago, Chicago: 1986, the contents of which are incorporated herein by reference in their entirety) and the electric field spreads (its density decreases) to produce muscle contraction. Therefore, when the electrode is placed in the submental area of ​​the neck, the current density is greatest at the surface of the skin, and the current density through the platysma muscle below the skin and subcutaneous fat decreases with depth (see Sobotta J, Sobotta Atlas of Human Anatomy, in: Staubes and J, eds., Head, Neck, Upper limbs, skin, 11th edition, Vol. 1, Urban & Schwarzenberg; Baltimore-Munich: 1990, the contents of which are incorporated herein by reference in their entirety). If the current amplitude is increased, deeper muscles are mobilized, although less efficiently. Such muscles may include the anterior belly of the digastric muscle, which can lower the mandible or pull the hyoid bone upward depending on whether the mouth is closed. Even deeper are the mylohyoid and geniohyoid muscles, which pull the hyoid bone upward and toward the mandible, respectively. However, because these muscles are deeper, they are less likely to be activated by surface stimulation.

[0012] Similarly, when electrodes are placed on the skin overlying the thyroid cartilage of the neck, the current will be greatest at the skin, with less intensity in the underlying platysma and even less intensity in the underlying sternohyoid and omohyoid muscles (see Sobatta), which pull the hyoid bone downward and backward toward the sternum. The field strength decreases further when it reaches the deeper thyrohyoid muscle, which holds the larynx and hyoid together, and the sternothyroid, which lowers the larynx toward the sternum. Given that the sternohyoid muscle is larger and overlies the thyrohyoid and sternothyroid muscles, high-level surface electrical stimulation of the neck is likely to pull the hyoid bone downward due to stimulation of the sternohyoid or underlying sternothyroid muscles, but is unlikely to raise the larynx toward the hyoid bone as occurs during normal swallowing.

[0013] In Ludlow et al., Effects of Surface Electrical Stimulation Both at Rest andDuring Swallowing in Chronic Pharyngeal Dysphagia, according to Therapy is suggested to use paired electrodes in the submental and laryngeal regions simultaneously (see Wijting Y, Freed ML, VitalStim Therapy Training Manual, Chattanooga Group, Hixson, TN: 2003, the entire contents of which are incorporated herein by reference), with the goal of producing simultaneous contraction of the mylohyoid muscle in the submental region (to elevate the hyoid bone) and the thyrohyoid muscle in the neck (to elevate the larynx to the hyoid bone). Figure 2As shown, two sets of electrodes are used, with the upper set placed horizontally in the submental area above the mylohyoid region above the hyoid bone. However, because these muscles are located deep beneath the anterior belly of the digastric muscle and the sternohyoid and omohyoid muscles, Ludlow et al., Effects of Surface Electrical Stimulation Both at Rest and During Swallowing in Chronic Pharyngeal Dysphagia, hypothesized that simultaneous transcutaneous stimulation using two pairs of electrodes at rest would result in: 1) descent of the hyoid bone in the neck (due to the action of the sternohyoid muscle); 2) posterior movement of the hyoid bone (due to omohyoid activity); and 3) descent of the larynx (if the current activates the sternohyoid or sternothyroid muscles). Furthermore, in severe chronic dysphagia: 4) when the same array is used at low stimulation levels just above sensory threshold (enough to produce sensation, but not activate muscles), the patient's swallowing may improve due to sensory facilitation; whereas 5) when the same array is used at higher levels required for motor stimulation, hyoid descent may interfere with swallowing, leading to increased penetration and aspiration.

[0014] The results of Ludlow et al., Effects of Surface Electrical Stimulation Both at Rest and During Swallowing in Chronic Pharyngeal Dysphagia do suggest that when surface stimulation is applied to the neck at rest, the stimulation is too weak or not deep enough to stimulate the axons innervating the muscles that elevate the hyoid bone and larynx, respectively (e.g., mylohyoid and thyrohyoid muscles). No changes in the position of the larynx were observed with surface stimulation at rest. Patients who had reduced aspiration and penetration during swallowing after stimulation had greater depression of the hyoid during resting stimulation. When the hyoid is depressed by stimulation, Ludlow et al., Effects of Surface Electrical Stimulation Both at Rest and During Swallowing in Chronic Pharyngeal Dysphagia speculate that patients may develop greater resistance to hyoid-larynx elevation during swallowing. Perhaps when stimulation was turned on to the maximum extent, patients who felt that the hyoid was pulled down more put in greater effort to elevate the hyoid-larynx complex during swallowing in an attempt to overcome the effects of the stimulation. It is also possible that those patients with greater residual strength in the hyoid-laryngeal muscles will not only experience greater hyoid descent upon stimulation, but will also have greater residual strength that can be mobilized to elevate the hyoid-larynx to counteract the stimulation-induced descent during swallowing.

[0015] As theorized by Ludlow et al., Effects of Surface Electrical Stimulation Both at Rest and During Swallowing in Chronic Pharyngeal Dysphagia, simultaneous stimulation may result in hyoid descent because the more superficial and larger sternohyoid and sternothyroid muscles overcome any effects that may be caused by stimulation of the mylohyoid in the submental region or the thyrohyoid beneath the sternohyoid in the pharyngeal region. Some have proposed using submental stimulation alone to activate the anterior belly of the digastric and mylohyoid muscles to pull the hyoid upward. However, raising the hyoid without simultaneously stimulating the thyrohyoid muscle to elevate the larynx will lower the larynx, causing further vestibular opening and increasing the risk of aspiration. As previously shown with intramuscular stimulation, the hyoid bone and laryngeal meridian are elevated together only when the mylohyoid and thyrohyoid muscles are stimulated simultaneously without contraction of the sternohyoid muscle (see Burnett TA et al., Laryngeal elevation achieved by neuromuscular stimulation at rest, J Appl Physiol., 2003; 94(1): 128-34, the entire contents of which are incorporated herein by reference). This is problematic when using surface stimulation because the larger sternohyoid muscle overlies the thyrohyoid muscle and pulls the hyoid bone downward. Summary of the invention

[0016] According to an embodiment of the present invention, a method of inducing a swallowing reflex in a human subject is provided. The method includes generating a stimulation signal that, when applied to the skin covering the thyroid cartilage region of the neck, induces a complete swallowing reflex. The stimulation signal is transmitted to the skin covering at least the thyroid cartilage region of the neck via surface electrodes to induce a complete swallowing reflex in the human subject.

[0017] According to a related embodiment of the present invention, the stimulation signal may include a bipolar stimulation pulse having a first pulse phase with a duration of at least 100 ms. Generating the stimulation signal may include increasing the amplitude of the first pulse phase of the bipolar stimulation pulse over time. The first pulse phase of the bipolar stimulation signal may be one of the following: gradual rise, exponential rise, linear rise, curve rise, continuous rise or discontinuous rise, and combinations thereof. The surface electrode may include a first surface electrode and a second surface electrode of a bipolar configuration, and the method further includes positioning the first surface electrode and the second surface electrode on the skin on the left and right sides of the laryngeal prominence, respectively, covering the thyroid cartilage area of ​​the neck.

[0018] According to other related embodiments of the present invention, the swallowing initiation signal includes a monopolar stimulation pulse. The monopolar stimulation pulse may be a triangular pulse having a rising edge with a duration of at least 100 ms. The surface electrodes may include a first surface electrode and a second surface electrode (respectively located on the skin on the left and right sides of the Adam's apple, covering the thyroid cartilage area of ​​the neck) and a third surface electrode and a fourth surface electrode (placed on the left and right shoulder blades of the human subject).

[0019] According to yet another embodiment of the invention, a complete swallowing reflex may include at least partially raising the larynx. The method may include providing a trigger signal that triggers the generation and delivery of a stimulation signal. The trigger signal may include one of: an activation switch, a manual switch, a motion sensor, an inertial mass sensor, an electromyogram of the submental muscle, or measuring bioimpedance of the neck, and combinations thereof. The swallowing reflex may be induced in human subjects who do have denervated laryngeal muscles and in subjects who do not have denervated laryngeal muscles.

[0020] According to another embodiment of the present invention, a system for inducing a complete swallowing reflex in a human subject is provided. The system includes a plurality of surface electrodes configured to cover at least one area of ​​the thyroid cartilage of the neck. A controller is configured to generate a stimulation signal that induces a complete swallowing reflex in the human subject, and the controller is configured to provide the stimulation signal to the plurality of surface electrodes after receiving a trigger signal.

[0021] According to a related embodiment of the present invention, the controller may be configured to generate a bipolar stimulation pulse having a first pulse phase with a duration of at least 100 ms. The first phase of the bipolar stimulation pulse may have an amplitude that increases over time. The first pulse phase of the bipolar stimulation signal may be one of the following: a gradual rise, an exponential rise, a linear rise, a curve rise, a continuous rise or a discontinuous rise, and a combination thereof. The surface electrode may include a first surface electrode and a second surface electrode of a bipolar structure, the first surface electrode and the second surface electrode being respectively located on the skin on the left and right sides of the Adam's apple, covering the thyroid cartilage area of ​​the neck.

[0022] According to other related embodiments of the present invention, the controller may be configured to generate a monopolar stimulation pulse. The monopolar stimulation pulse may be a triangular pulse including a rising edge with a duration of at least 100 ms. The surface electrodes may include a first surface electrode and a second surface electrode (located on the skin on the left and right sides of the Adam's apple, respectively, covering the thyroid cartilage area of ​​the neck) and a third surface electrode and a fourth surface electrode (placed on the left and right shoulder blades of the human subject).

[0023] According to yet another embodiment of the invention, the complete swallowing reflex may include at least partially raising the larynx. The system may include a trigger mechanism configured to provide a trigger signal. The trigger mechanism may include one of: a manual switch activated by a human subject, a motion sensor, an inertial mass sensor, a sensor for electromyography of the submental muscle, or a sensor for measuring bioimpedance of the neck, and combinations thereof. The swallowing reflex may be induced in human subjects who do have denervated laryngeal muscles and in subjects who do not have denervated laryngeal muscles.

[0024] According to another embodiment of the present invention, a method for inducing a swallowing reflex in a human subject is provided. The method includes: generating a stimulation signal that, when applied to the thyroid cartilage region of the neck, induces a complete swallowing reflex; and transmitting the stimulation signal to the thyroid cartilage region of the neck through an implanted electrode to induce a complete swallowing reflex in the human subject.

[0025] According to a related embodiment of the present invention, the stimulation signal may include a bipolar stimulation pulse having a first pulse phase with a duration of at least 100 ms. Generating the stimulation signal may include increasing the amplitude of the first pulse phase of the bipolar stimulation pulse over time. The first pulse phase of the bipolar stimulation signal may be one of the following: gradually rising, exponentially rising, linearly rising, curved rising, continuously rising or discontinuously rising, and combinations thereof. The implanted electrode may include a first electrode and a second electrode of a bipolar configuration.

[0026] According to other related embodiments of the present invention, the swallowing initiation signal comprises a monopolar stimulation pulse. The monopolar stimulation pulse may be a triangular pulse having a rising edge with a duration of at least 100 ms.

[0027] According to yet another embodiment of the invention, the complete swallowing reflex may include at least partially raising the larynx. The method may include providing a trigger signal that triggers the generation and delivery of a stimulation signal. The trigger signal may include one of: an activation switch, a manual switch, a motion sensor, an inertial mass sensor, an electromyogram of the submental muscle, or measuring bioimpedance of the neck, and combinations thereof. The swallowing reflex may be induced in human subjects who do have denervated laryngeal muscles and in subjects who do not have denervated laryngeal muscles.

[0028] According to another embodiment of the present invention, a system for inducing a complete swallowing reflex in a human subject is provided. The system includes a plurality of electrodes configured to be implanted at least adjacent to the thyroid cartilage of the neck. A controller is configured to generate a stimulation signal that induces a complete swallowing reflex in the human subject, and the controller is configured to provide the stimulation signal to the plurality of electrodes after receiving a trigger signal.

[0029] According to a related embodiment of the present invention, the controller may be configured to generate a bipolar stimulation pulse having a first pulse phase with a duration of at least 100 ms. The first phase of the bipolar stimulation pulse may have an amplitude that increases over time. The first pulse phase of the bipolar stimulation signal may be one of the following: gradually rising, exponentially rising, linearly rising, curved rising, continuously rising or discontinuously rising, and combinations thereof. The electrode may include a first electrode and a second electrode of a bipolar configuration.

[0030] According to other related embodiments of the present invention, the controller may be configured to generate a monopolar stimulation pulse. The monopolar stimulation pulse may be a triangular pulse including a rising edge with a duration of at least 100 ms.

[0031] According to yet another embodiment of the invention, the complete swallowing reflex may include at least partially raising the larynx. The system may include a trigger mechanism configured to provide a trigger signal. The trigger mechanism may include one of: a manual switch activated by a human subject, a motion sensor, an inertial mass sensor, a sensor for electromyography of the submental muscle, or a sensor for measuring bioimpedance of the neck, and combinations thereof. The swallowing reflex may be induced in human subjects who do have denervated laryngeal muscles and in subjects who do not have denervated laryngeal muscles. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] The foregoing features of the embodiments will be more readily understood by referring to the following detailed description with reference to the accompanying drawings, in which:

[0033] Figure 1A The various structures of the neck and mouth involved in swallowing are shown;

[0034] Figure 1B is a front view of the human neck showing the various muscles and associated structures in their natural position;

[0035] Figure 2 A prior art electrode configuration for treating dysphagia is shown;

[0036] Figure 3 A system for inducing a complete swallowing reflex according to an embodiment of the present invention is shown;

[0037] Figure 4 shows a bipolar electrode configuration of an embodiment of the present invention;

[0038] Figure 5 shows a monopolar electrode configuration of an embodiment of the present invention;

[0039] Figure 6The rheobase and chronaxi points defined on the intensity-duration curve for stimulating excitable tissue are shown;

[0040] Figure 7 Strength-duration curves for normally innervated and denervated muscles are shown;

[0041] Figure 8 Different accommodation indices of human muscle groups are shown;

[0042] Fig. 9 shows the grade of muscle denervation based on electromuscular testing and EMG; and

[0043] Fig.10 The principle of selectively stimulating denervated muscles using a long exponentially increasing current pattern is shown. DETAILED DESCRIPTION

[0044] In an exemplary embodiment, a system and method for eliciting a complete swallowing reflex in a human subject is provided. More specifically, exemplary embodiments of the invention are based on the surprising and completely unexpected discovery that a long, slowly rising stimulation pulse induces a complete swallowing reflex in a human subject. Such stimulation pulses are typically only used in people with muscle denervation. The details are described below. Such a swallowing reflex can be induced in human subjects who do have denervated laryngeal muscles and in subjects who do not have denervated laryngeal muscles.

[0045] Figure 3 A system 300 for inducing a complete swallow reflex is shown in accordance with an embodiment of the present invention. The complete swallow reflex activates not only a single muscle in the deep neck region, but also includes activation of a complete swallowing cycle that includes coordinated contraction of, for example, twelve or more pairs of muscles and / or activation of one or more participating muscles of the afferent leg of the swallowing circuit in an appropriately timed and peristaltic manner. The complete swallow reflex advantageously includes elevation of the larynx.

[0046] The complex pharyngeal phase of swallowing begins with the triggering of the swallowing reflex and ends with the opening of the upper esophageal sphincter, which takes 0.7 to 1 second. This phase cannot be controlled voluntarily. During this phase, the pharyngeal space expands to allow the passage of the bolus, pressure builds up to facilitate bolus transport, and the airway closes to prevent aspiration. The rapid piston-like movement of the tongue supports the passage of the bolus into the hypopharynx. The peristaltic movement of the pharyngeal wall supports the piston function of the tongue. Depending on the volume of the bolus, the hyoid bone and larynx move upward due to the contraction of the suprahyoid muscles. This movement results in: expansion of the hypopharyngeal space, positioning of the larynx below the root of the tongue to prevent aspiration, improvement of the tilt of the epiglottis, and opening of the pharyngeal-esophageal segment. To prevent aspiration, the closure of the larynx is carried out in three stages: closure of the vocal folds, vertical approach of the adducted arytenoids to the base of the epiglottis, and tilting of the epiglottis to cover the laryngeal vestibule. The combined pressure of the bolus from above, the downward muscular action of the aryepiglottic muscles and the pressure due to the backward movement of the tongue and the elevation of the larynx make it possible to close the epiglottis. The forward-upward movement of the hyoid bone and the larynx makes it possible to open the upper esophageal sphincter. As soon as the bolus reaches the upper esophageal sphincter, the pharyngeal phase ends. Thereafter, the pharyngeal-esophageal elements, tongue, hyoid bone and larynx return to their starting positions. The palatopharyngeal and laryngeal closures open and the pharyngeal-esophageal elements close.

[0047] The esophageal phase begins with closure of the pharyngeal-esophageal segment and lasts 8 to 20 seconds. Bolus transit is facilitated by the swallowing reflex and secondarily by the primary peristaltic wave induced by local stretch stimulation.

[0048] Sensory involvement in swallowing is described in: Pommerenke WT, A study of the sensory areas Eliciting the swallowing reflex, American Journal of Physiology 1927, 84(1):36–41; Jean A, Control of the central swallowing program by inputs from theperipheral receptors, A review.J Auton.Nerv Syst.1984, 10:225–233[PubMed]; Jafari S et al., Sensory regulation of swallowing and airway protection: a role for the internal superior laryngeal nerve in humans, J Physiol.2003, 550(Pt 1):287–304; and Hamdy S et al., Modulation of human swallowing behavior by thermal and chemical stimulation in health and after brain injury, Neurogastroenterol Motil. 2003, 15(1):69–77 [PubMed]. The entire contents of each of the above references are incorporated herein by reference in their entirety.

[0049] Return to reference Figure 3 , the system 300 may include, but is not limited to, a plurality of surface electrodes 305, the surface electrodes 305 being configured to cover at least the thyroid cartilage of the neck. The controller 301 is configured to generate a stimulation signal to induce a complete swallowing reflex in a human subject. The controller 301 is also configured to provide the stimulation signal to the plurality of surface electrodes 305 upon receiving a trigger signal. The controller 301 may include, but is not limited to, circuits and / or processors, which may be pre-programmed or configured to be loaded with an appropriate software program to generate and provide the stimulation signal.

[0050] In various embodiments, the electrode stimulation arrangement can be a bipolar electrode configuration. Figure 4 As shown, electrodes 401 may be placed on the left and right sides of the Adam's apple, i.e., they are placed on the skin covering the thyroid cartilage of the neck. In an alternative embodiment, the electrode stimulation arrangement may be a monopolar electrode configuration. According to one embodiment of the present invention, for example, Figure 5 As shown, two electrodes (similar to a bipolar setup) 501 may be placed above the larynx (ie they are placed on the skin overlying the thyroid cartilage of the neck) and two indifferent electrodes 503 (eg large self-adhesive electrodes 13 cm x 8 cm) are placed on the shoulder blades.

[0051] Conventional stimulation systems and methods use electrodes placed on the skin overlying the thyroid cartilage of the neck to stimulate muscle and / or nerve tissue with bipolar pulses of typical duration of 0.05ms to 50ms, thereby stimulating the underlying platysma and the underlying sternohyoid and omohyoid muscles (see Sobotta). This in turn pulls the hyoid bone downward and backward toward the sternum and sternothyroid muscle, thus lowering the larynx toward the sternum, which may pull the hyoid bone downward due to stimulation of the sternohyoid muscle or the underlying sternothyroid muscle, but is unlikely to raise the larynx toward the hyoid bone as occurs during normal swallowing. In some cases, this stimulation can also cause pain.

[0052] To avoid the shortcomings of these conventional systems and methods, embodiments of the present invention can exploit the principle of accommodation by using very long phase durations (e.g., greater than 100 ms) in combination with slowly rising phase shapes (pulses, similar to those used in various treatments of denervated muscle tissue). Accommodation is the ability of a muscle to not respond to slowly increasing electrical pulses. Accommodation describes the response of an excitatory membrane to a slowly depolarizing current without generating an action potential.

[0053] To describe adaptation, the terms "base intensity" and "duration" are first explained with the aid of the intensity-duration curve. The intensity-duration curve is a graphical representation of the relationship between the intensity of the electrical stimulus and the length of time that must elapse to cause a minimal contraction (see, e.g., Rodríguez-Fernández, L., Rebollo-Roldán, J., Jiménez-Rejano, J.J. and Güeita-Rodríguez, J. (2016), Strength-duration curves of the common fibularnerve show hypoexcitability in people with functional ankle instability, PMand R, pp. 536-544, the contents of which are incorporated herein by reference in their entirety). In functional electrical stimulation, strength-duration curves are often used to determine the characteristics of the stimulation electrodes and to determine the most effective choice of stimulation parameters for an appropriate safety margin.

[0054] Figure 6 Base intensity points and timing points defined on the intensity-duration curve for stimulating excitable tissue are shown. Usually around the 1 ms mark on the intensity-duration curve, the curve flattens out at the base intensity, which is the point where the gradual increase in pulse duration is no longer associated with the gradual decrease in voltage. In other words, for longer stimulus durations, the minimum voltage required to get the nerve to threshold will be the base intensity. If two nerves have the same base intensity, then the timing (stimulation duration corresponding to twice the base intensity) can indicate their relative excitability. The smaller the timing, the more excitable the nerve.

[0055] Figure 7 Strength-duration curves for normally innervated and denervated muscles are shown, as described in Schuhfried, O., Kollmann, C., and Paternostro-Sluga, T. (2005), Excitability of chronic hemiparetic muscles: determination of chronaxie values ​​and strength-duration curves and its implication in functional electrical stimulation, Transactions on Neural Systems and Rehabilitation Engineering: A Publication of the IEEE Engineering in Medicine and Biology Society, 13(1), 105–9, the contents of which are incorporated herein by reference in their entirety. The average normal duration for innervated muscles is 0.4 ms (see Schuhfried et al.). Values ​​exceeding 1 ms are considered evidence of muscle denervation. A rightward shift and the presence of a kink in the strength-duration curve are associated with muscle denervation. The intensity-duration curve was determined by successively decreasing the width of monophasic rectangular pulses (500ms, 300ms, 200ms, 100ms, 70ms, 50ms, 30ms, 20ms, 10ms, 5ms, 2ms, 1ms, 0.5ms, 0.2ms, 0.1ms, 0.05ms).

[0056] The timing of sensory nerves in the human arm is 0.35 ms to 1.17 ms. The timing of denervated skeletal muscle in humans is 9.5 ms to 30 ms -> this value decreases again during reinnervation (see Geddes, LA (2004), Accuracy Limitations of Chronaxie Values, IEEET Bio-Med Eng, 51(1), 176, the contents of which are incorporated herein by reference in their entirety).

[0057] The accommodation index is the ratio of the threshold amperage of a slowly rising pulse to the threshold amperage of a suddenly rising rectangular pulse. Accommodation describes the response of an excitatory membrane to a slowly depolarizing current without generating an action potential. In nerve fibers, the current rises slowly to at most twice the base strength, inactivating the sodium conductance before the depolarization reaches the threshold, so no action potential is generated. This is called a high accommodation rate. In muscle fibers, the sodium conductance is hardly inactivated by a slowly rising current, so an action potential is generated even when the slowly rising current is less than twice the base strength. This is called a low accommodation rate. The difference between the high accommodation rate of normal nerve fibers and the low accommodation rate of normal muscle fibers is the physiological basis of the accommodation index. Denervated muscle fibers have the same or even lower adaptation rate than normal muscle fibers (see Schuhfried O, Vacariu G, Paternostro-Sluga T: Reliability of chronaxie and accommodation index in the diagnosis of muscle denervation, Phys. Medicin Rehabil. Kurortmedizin 2005, 15: 174-178, the contents of which are incorporated herein by reference in their entirety).

[0058] Fitness index of healthy people:

[0059] As stated by Schuhfried et al., Figure 8 Different fitness indices are shown for human muscle groups: deltoid, extensor digitorum communis, hypothenar, tibialis anterior, peroneus longus, and gastrocnemius. The fitness index for healthy muscles should be ≥ 2 by applying rectangular and triangular pulses of 500ms duration.

[0060] Adaptability index for patients with neurogenic lesions:

[0061] Paternostro-Sluga, T., Schuhfried, O., Vacariu, G., Lang, T., & Fialka-Moser, V. (2002). Chronaxie and accommodation index in the diagnosis of muscle denervation. American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists, 81 (4), 253-60, http: / / doi.org / 10.1055 / s-2004-834713 studied the adaptability of human muscle groups, which divided 17 different muscles into three types: muscles of the upper limbs (excluding the intrinsic muscles of the hand), intrinsic muscles of the hand, and muscles of the lower limbs. The adaptability index was determined by dividing the ampere threshold of 500ms duration by the base strength value. As described by Paternostro-Sluga et al., Fig. 9 The grades of muscle denervation according to electromuscular testing and EMG are shown. A fitness index (shown below) < 2 indicates neurogenic damage.

[0062] Adaptability index for patients with muscle denervation:

[0063] Cummings, JP (1985: The Journal of Orthopaedic and Sports Physical Therapy, 7 (1), 11-5. Retrieved from http: / / www.ncbi.nlm.nih.gov / pubmed / 18802291), the contents of which are incorporated herein by reference in their entirety, selective electrical stimulation of denervated muscles in the form of exponentially increasing current. As described by Cummings, Fig.10 The principle of selective stimulation of denervated muscle using a long exponentially increasing current pattern is shown. Intensity-duration curves for normally innervated muscle, denervated muscle, and intact sensory nerves are shown. Denervated muscle can be selectively stimulated without mobilizing normally innervated muscle or sensory axons (shaded areas). Follow the method described by Thom H. Electrotherapy of paralysis; basic principles and application. [Internet]. Zeitschrift für und ihre Grenzgebiete 1953, 84:104-23 (the contents of which are incorporated herein by reference in their entirety), Cummins et al. showed that completely paralyzed muscles with advanced denervation atrophy responded best to slowly rising pulses lasting 150 ms to 600 ms, such as Fig.10 Shown as the shaded area in .

[0064] Therefore, by using very long phase durations (>100ms) and slowly rising pulse phase shapes, one would expect to: 1. avoid stimulating the underlying innervated muscles by increasing the threshold for motor neuron depolarization, and 2. selectively activate deep muscles that show signs of atrophy or denervation by increasing the depolarization threshold of excitatory neural membranes, and therefore exhibit membranes that are excitatory to this slow depolarizing current, thereby avoiding stimulating the underlying nerves.

[0065] However, as described above, in exemplary embodiments of the present invention, these very slowly rising, very long pulse phases surprisingly, reliably, and selectively elicited a complete swallowing reflex in human subjects, not only activating a single muscle in the deep cervical region, but initiating the entire swallowing cycle, which requires all twelve or more pairs of muscles to contract in a coordinated manner with proper timing and peristaltic motion.

[0066] More specifically, according to various embodiments of the present invention, bipolar pulses are used that have a first pulse phase of very long duration (e.g., but not limited to >100ms) and a slowly rising shape of this pulse phase, causing a complete swallowing reflex. In addition, the use of these bipolar pulses increases the threshold for depolarization of the excitatory membrane and reduces the depolarizing current, thereby advantageously inhibiting / avoiding the generation of action potentials in motor neurons and muscles innervated by the motor neurons. At the same time, the generation of action potentials in mucosal pain fibers is also inhibited / avoided, thereby avoiding reaching the pain threshold.

[0067] In various embodiments of the present invention, the amplitude of the first pulse phase of the bipolar stimulation pulse increases over time. For example, the first pulse phase of the bipolar stimulation signal may gradually increase so that its amplitude does not decrease over time. In other embodiments, the first pulse phase of the bipolar stimulation signal may increase exponentially, linearly, curvedly, continuously, and / or discontinuously.

[0068] In various embodiments of the present invention, as described above, a monopolar electrode configuration may be used, and a monopolar stimulation pulse may be generated / delivered to induce a complete swallowing reflex. The monopolar stimulation pulse may be, but is not limited to, a triangular pulse. The monopolar stimulation pulse (e.g., a triangular pulse) may have a rising edge with a duration greater than 100ms. In a monopolar electrode configuration, the anode and cathode pulses may depolarize different neural (muscle) structures. The electric field generated (e.g., using a triangular pulse) may advantageously depolarize the vocal cord muscles more selectively. In various tests conducted on healthy subjects, a comparison between cathode and anodal stimulation polarities (referring to laryngeal electrodes) showed that the activation threshold for cathode stimulation was lower. The activation threshold for anodal stimulation polarity was about twice as high. Both pulse polarities induced a swallowing reflex.

[0069] According to an exemplary embodiment of the present invention, the system described herein may include implantable electrodes to replace the surface electrodes described herein so far. The implantable electrodes may be placed subcutaneously and attached to, for example, the thyroid cartilage. The implantable controller may be configured to generate a stimulation signal that induces a complete swallowing reflex in a human subject, and may be configured to provide the stimulation signal to the plurality of implantable electrodes upon receiving a trigger signal.

[0070] According to an exemplary embodiment of the invention, the system described herein can be used as a rehabilitation system or a therapeutic system. The main purpose of rehabilitation is to restore the disturbed function through, for example, sensory stimulation of the swallowing reflex or the teaching of special swallowing techniques. A necessary condition for success is sufficient cortical potential after the injury and existing connections from the cortex to the muscles. If this connection is lost or the muscles cannot be adequately controlled, the swallowing process cannot be restored. The patient then relies on eating through a feeding tube and a tracheal cannula.

[0071] In these cases, electrical stimulation of the extrinsic laryngeal muscles as a therapeutic approach, by activating the swallowing reflex, can be used to enhance the swallowing process. The stimulation may have to be applied in time. The stimulation may be triggered by the patient himself via a switch (e.g., a manual switch), or by using a sensor as a trigger - for example, but not limited to, electromyography (EMG) of the submental muscle or measuring bioimpedance (BI) of the neck (see, e.g., www.mpi-magdeburg.mpg.de / bioimpedance , the contents of which are incorporated herein by reference in their entirety). Aspiration detection may be performed via electrodes on the thyroid cartilage at the level of the vocal cords. A trigger signal generated by a switch or various sensors may be provided to a controller to initiate the generation and delivery of a stimulation signal that induces a complete swallowing response.

[0072] According to other embodiments of the invention, the system can be used as an auxiliary training for the patient, enhancing the exercise by stimulating swallowing, which is triggered by the patient himself through a manual switch or through the use of a sensor as described above.

[0073] Embodiments of the present invention may be implemented in whole or in part in any conventional computer programming language. For example, preferred embodiments may be implemented in a procedural programming language (e.g., "C") or an object-oriented programming language (e.g., "C++", Python). Alternative embodiments of the present invention may be implemented as pre-programmed hardware elements, other related components, or as a combination of hardware and software components.

[0074] Embodiments may be implemented in whole or in part as a computer program product for use with a computer system. Such implementation may include a series of computer instructions that are fixed on a tangible medium (e.g., a computer-readable medium, such as a floppy disk, CD-ROM, ROM, or fixed disk) or transmitted to a computer system via a modem or other interface device (e.g., a communication adapter connected to a network via a medium). The medium may be a tangible medium (e.g., an optical communication line or an analog communication line) or a medium implemented with a wireless technology (e.g., microwave, infrared, or other transmission technology). The series of computer instructions embody all or part of the functions previously described herein for the system. Those skilled in the art will appreciate that such computer instructions may be written in many programming languages ​​for use in many computer architectures or operating systems. In addition, such instructions may be stored in any storage device (e.g., semiconductor, magnetic, optical, or other storage device) and may be transmitted using any communication technology (e.g., optical, infrared, microwave, or other transmission technology). It is contemplated that such a computer program product may be distributed as a removable medium with accompanying printed or electronic documentation (e.g., compressed package software), pre-installed on a computer system (e.g., on a system ROM or fixed disk), or may be distributed from a server or electronic bulletin board over a network (e.g., the Internet or the World Wide Web). Of course, some embodiments of the present invention may be implemented as a combination of both software (e.g., a computer program product) and hardware. Other embodiments of the present invention are implemented as either entirely hardware or entirely software (e.g., a computer program product).

[0075] Although various exemplary embodiments of the invention have been disclosed, it will be apparent to those skilled in the art that various changes and modifications can be made which will achieve certain advantages of the invention without departing from the true scope of the invention.

Claims

1. A system for inducing a complete swallowing reflex in a human subject, the system comprising: a plurality of surface electrodes, the plurality of surface electrodes being configured to cover at least the thyroid cartilage of a human neck; as well as A controller configured to generate a stimulation signal that induces a complete swallowing reflex in a human subject, wherein the complete swallowing reflex includes raising the larynx, and the stimulation signal includes one of the following: a bipolar stimulation pulse with a first pulse phase duration of at least 100 ms, a monopolar stimulation pulse comprising a rising edge of at least 100 ms duration; and After receiving the trigger signal, a stimulation signal is provided to the plurality of surface electrodes.

2. The system according to claim 1, wherein: The first phase of the bipolar stimulation pulse has an amplitude that increases over time.

3. The system according to claim 2, wherein: The first pulse phase of the bipolar stimulation signal is one of the following: gradual rise, exponential rise, linear rise, curve rise, continuous rise or discontinuous rise, and combinations thereof.

4. The system according to claim 1, wherein: The stimulation signal includes a bipolar stimulation pulse, and the surface electrode includes a first surface electrode and a second surface electrode of a bipolar structure, wherein the first surface electrode and the second surface electrode are respectively located on the skin on the left and right sides of the Adam's apple, covering the thyroid cartilage area of ​​the neck.

5. The system according to claim 1, wherein: The monopolar stimulation pulse is a triangular pulse including a rising edge with a duration of at least 100 ms.

6. The system according to claim 1, wherein: The surface electrode comprises: a first surface electrode and a second surface electrode, the first surface electrode and the second surface electrode being respectively located on the skin on the left and right sides of the Adam's apple, covering the thyroid cartilage area of ​​the neck; and A third surface electrode and a fourth surface electrode are placed on a left shoulder blade and a right shoulder blade of a human subject.

7. The system according to claim 1, wherein: The complete swallowing reflex includes at least partially raising the larynx.

8. The system of claim 1, further comprising a trigger mechanism configured to provide a trigger signal.

9. The system according to claim 8, wherein: The trigger mechanism includes one of: a manual switch activated by a human subject, a motion sensor, an inertial mass sensor, a sensor for electromyography of the submental muscle, or a sensor for measuring bioimpedance of the neck, and combinations thereof.

10. A system for inducing a complete swallowing reflex in a human subject, the system comprising: a plurality of electrodes configured to be implanted adjacent at least the thyroid cartilage of the neck; as well as A controller configured to generate a stimulation signal that induces a complete swallowing reflex in a human subject, wherein the complete swallowing reflex includes raising the larynx, and the stimulation signal includes one of the following: bipolar stimulation pulses with a first pulse phase duration of at least 100 ms, a monopolar stimulation pulse comprising a rising edge of at least 100 ms duration; and After receiving the trigger signal, a stimulation signal is provided to the plurality of electrodes.

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