Eliciting Swallowing using Electrical Stimulation Applied via Surface Electrodes

Abstract

A system and method of eliciting a swallowing reflex in a human subject. Stimulation signals are generated for eliciting a full swallowing reflex when applied to skin overlying a region of thyroid cartilage in the neck. The stimulation signals delivered via surface electrodes to the skin overlying at least the region of thyroid cartilage in the neck to elicit the full swallowing reflex in the human subject.

Claims

1. A method of eliciting a swallowing reflex in a human subject, the method comprising: generating stimulation signals for eliciting a full swallowing reflex when applied to a region of thyroid cartilage in the neck of the human subject, the full swallowing reflex including raising the larynx, the stimulation signals including a bipolar stimulation pulse having a first pulse phase duration of at least 100 ms; and delivering the stimulation signals via electrodes to the region of thyroid cartilage in the neck to elicit the full swallowing reflex in the human subject.

2. The method according to claim 1, wherein generating the stimulation signals includes increasing a magnitude of the first pulse phase of the bipolar stimulation pulse over time.

3. The method according to claim 1, wherein the electrodes include a first electrode and a second electrode in a bipolar configuration, the method further comprising positioning the first electrode and the second electrode to the left and right of the laryngeal prominence, respectively.

4. The method according to claim 1, wherein the stimulation signals are deliverd via surface electrodes to skin overlying a region of thyroid cartilage in the neck of the human subject.

5. The method according to claim 1, wherein the stimulation signals are delivered via electrodes implanted subcutaneously proximate the thyroid cartilage.

6. The method according to claim 1, wherein the electrodes include: a first electrode and a second electrode for positioning to the left and right of the laryngeal prominence, and a third surface electrode and a fourth surface electrode for placing proximate left and right shoulder blades of the human subject.

7. The method according to claim 1, further comprising providing a trigger signal that triggers the generating and delivering of the stimulation signal.

8. The method according to claim 1, wherein the human subject does not suffer from denervated laryngeal muscles.

9. A method of eliciting a swallowing reflex in a human subject, the method comprising: generating stimulation signals for eliciting a full swallowing reflex when applied to a region of thyroid cartilage in the neck of the human subject, the full swallowing reflex including raising the larynx, the stimulation signals including a unipolar stimulation pulse that increases in magnitude for a duration of at least 100 ms; and delivering the stimulation signals via electrodes to the region of thyroid cartilage in the neck to elicit the full swallowing reflex in the human subject, wherein the human subject does not suffer from denervated laryngeal.

10. The method according to claim 9, wherein the unipolar stimulation pulse is a triangular pulse having a rising edge with a duration of at least 100 ms.

11. The method according to claim 9, wherein the stimulation signals are delivered via surface electrodes to skin overlying a region of thyroid cartilage in the neck of the human subj ect.

12. The method according to claim 9, wherein the stimulation signals are delivered via electrodes implanted subcutaneously proximate the thyroid cartilage.

13. The method according to claim 9, further comprising providing a trigger signal that triggers the generating and delivering of the stimulation signal.

14. A system for eliciting a full swallowing reflex in a human subject, the system comprising: a plurality of electrodes configured to be placed proximate a region of thyroid cartilage in the neck; and a controller configured to generate a stimulation signal for eliciting the full swallowing reflex in the human subject, the full swallowing reflex including raising the larynx, the stimulation signal including a bipolar stimulation pulse having a first pulse phase duration of at least 100 ms, the controller configured to provide the stimulation signal to the plurality of electrodes upon receipt of a trigger signal.

15. The system according to claim 14, wherein the first phase of the bipolar stimulation pulse has an increasing magnitude over time.

16. The system according to claim 14, wherein the electrodes include a first electrode and a second electrode in a bipolar configuration, the first electrode and the second electrode for positioning to the left and right of the laryngeal prominence, respectively.

17. The system according to claim 14, further comprising a trigger mechanism configured to provide the trigger signal.

18. The system according to claim 14, wherein the human subject does not suffer from denervated laryngeal muscles.

19. The system according to claim 14, wherein the plurality of electrodes are configured to be implanted subcutaneously proximate the thyroid cartilage.

20. The system according to claim 14, wherein the the plurality of electrodes are surface electrodes configured to be applied to skin overlying a region of thyroid cartilage in the neck of the human subject.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

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

[0033] FIG. 1A shows various structures of the neck and mouth that are involved in swallowing;

[0034] FIG. 1B is an anterior view of a human's neck showing various muscles and associated structures in their natural positions;

[0035] FIG. 2 shows a prior art electrode configuration using to treat dysphagia;

[0036] FIG. 3 shows a system for eliciting a full swallowing reflex, in accordance with an embodiment of the invention;

[0037] FIG. 4 shows a bipolar electrode configuration, in accordance with an embodiment of the invention;

[0038] FIG. 5 shows a unipolar electrode configuration, in accordance with an embodiment of the invention;

[0039] FIG. 6 shows rheobase and chronaxie points defined on a strength-duration curve for stimulus of an excitable tissue;

[0040] FIG. 7 shows a strength—duration curve of a normally innervated muscle and a denervated muscle;

[0041] FIG. 8 shows different accommodation indices in human muscle groups;

[0042] FIG. 9 shows grading of muscle denervation according to electrical muscle testing and EMG; and

[0043] FIG. 10 shows the principle of selective stimulation of denervated muscle utilizing a long exponentially progressive current form.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS

[0044] In illustrative embodiments, a system and method of eliciting a full swallowing reflex in a human subject is provided. More particularly, illustrative embodiments of the invention are based on the surprising and completely unexpected finding that long, slowly rising stimulation pulses elicit a full swallowing reflex in human subjects. Such stimulation pulses are usually only used for persons with denervated muscles. Details hereto are described below. This swallowing reflex may be elicited in human subjects who do suffer from denervated laryngeal muscles and in subjects who do not suffer from denervated laryngeal muscles.

[0045] FIG. 3 shows a system 300 for eliciting a full swallowing reflex, in accordance with an embodiment of the invention. The full swallowing reflex not only activates single muscles in the deep neck region only, but includes activating full swallowing cycles which include coordinated contraction of, for example, twelve or more muscle pairs with appropriate timing and peristaltic manner and/or activation of one or more players of the afferent leg of the swallowing circuit. The full swallowing reflex advantageously includes raising 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 and takes 0.7 to 1 second. It is not voluntarily controllable. During this phase the pharyngeal space expands for bolus passage, pressure is built up to promote bolus transportation, and the airways are closed to protect against aspiration. Rapid piston-like movements of the tongue support passage of the bolus into the hypopharynx. Peristaltic movements of the pharyngeal wall support the piston function of the tongue. Depending on the bolus volume, hyoid bone and the larynx move upwardly due to contraction of the suprahyoid muscles. This motion results in an expansion of space in the hypopharynx, positioning of the larynx under the root of the tongue to prevent aspiration, improved epiglottic tilting, and opening of the pharyngo-esophageal segment. To protect against aspiration, closure of the larynx proceeds in 3 stages: closure of the vocal folds, vertical approach of the adducted arytenoids to the base of the epiglottis, and epiglottic tilting to cover the laryngeal vestibule. Closure of the epiglottis is made possible by the bolus pressure from above, the downward muscular action of the aryepiglottic muscles, and the combined pressure as a result of the backward movement of the tongue and the laryngeal elevation. Opening of the upper esophageal sphincter is made possible by the anterior-superior movement of hyoid bone and larynx. The pharyngeal phase ends as soon as the bolus has reached the upper esophageal sphincter. Thereafter, the pharyngo-esophageal element, the tongue, hyoid and larynx return to their original positions. Velopharyngeal and laryngeal closures open up, and the pharyngo-esophageal element is closed.

[0047] The esophageal phase begins with the closure of the pharyngo-esophageal segment and lasts for 8 to 20 s. Bolus transportation proceeds by means of primary peristaltic waves induced by the swallowing reflex and, secondarily, by local stretch stimuli.

[0048] Sensory involvement in the swallowing is described in: Pommerenke W T. 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 the peripheral receptors. A review. J Auton.Nery 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 behaviour by thermal and chemical stimulation in health and after brain injury. Neurogastroenterol Motil. 2003; 15(1):69-77. [PubMed]. Each of the above-described references is hereby incorporated herein by reference in its entirety.

[0049] Referring back to FIG. 3, the system 300 may include, without limitation, a plurality of surface electrodes 305 configured to overlay at least thyroid cartilage in the neck. A controller 301 is configured to generate a stimulation signal for eliciting the full swallowing reflex in the human subject. The controller 301 is further configured to provide the stimulation signal to the plurality of surface electrodes 305 upon receipt of a trigger signal. The controller 301 may include, without limitation, a circuit and/or a processor that 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 set-up may be a bipolar electrode configuration. Illustratively, as shown in FIG. 4, the electrodes 401 may be placed left and right of laryngeal prominence, i.e., they are placed on the skin overlying the thyroid cartilage in the neck. In alternative embodiments, the electrode stimulation set-up may be unipolar electrode configuration. Illustratively, as shown in FIG. 5, two electrodes (similar to the bipolar set-up) 501 may be placed above the larynx, i.e. on the skin overlying the thyroid cartilage in the neck, and two indifferent electrodes 503 on the shoulder blades (for, example, large self-adhesive electrodes with 13×8 cm), in accordance with an embodiment of the invention.

[0051] With conventional stimulation systems and methodologies, stimulation of muscle and/or nervous tissue with bipolar pulses of typically 0.05 to 50 ms duration using electrodes placed on the skin overlying the thyroid cartilage in the neck caused stimulation of the underlying platysma muscle and the underlying sternohyoid and omohyoid muscles (see Sobotta). This in turn pulled the hyoid downward and backward towards the sternum and the sternothyroid muscle, which lowers the larynx towards the sternum, which could pull the hyoid downward due to stimulation of either the sternohyoid or the underlying sternothyroid, but would be much less likely to raise the larynx toward the hyoid bone as occurs in normal swallowing. In some circumstance such stimulation may also cause pain.

[0052] In order to avoid the drawbacks of these conventional systems and methodologies, embodiments of the invention may take advantage of the accommodation principle by using very long phase duration (for example, greater than 100 ms) combined with slowly rising phase shapes (pulses similar to those used in various treatments of denervated muscle tissue). Accommodation is the muscle capacity not to respond to slowly incrementing electrical pulses. Accommodation describes the response of excitable membranes to slow depolarizing currents without the generation of action potential.

[0053] In order to describe accommodation, first the terms rheobase and chronaxie are explained with the help of strength-duration curves. Strength-duration curves are graphic representations of the relationship between the intensity of an electric stimulus and the length of time it must flow to elicit a minimal contraction (See, for example, Rodríguez-Fernández, Á. L., Rebollo-Roldán, J., Jiménez-Rejano, J. J., & Güeita-Rodríguez, J. (2016). Strength-duration curves of the common fibular nerve show hypoexcitability in people with functional ankle instability. PM and R, pp. 536-544, which is hereby incorporated herein by reference in its entirety) In functional electrical stimulation, the strength-duration curve is often useful in determining characteristics of a stimulation electrode and determining the most efficient selection of stimulation parameters for an appropriate safety margin.

[0054] FIG. 6 shows rheobase and chronaxie points defined on a strength-duration curve for stimulus of an excitable tissue. Usually around the 1 ms mark on the strength-duration curve, the curve flattens out at the Rheobase, this is the point where a progressive increase in pulse duration is no longer associated with a progressive decrease in voltage. In other words, for longer stimulus durations, the minimal voltage required to bring the nerve to threshold will be the Rheobase. Given that two nerves have the same Rheobase, the chronaxie (the stimulus duration corresponding to twice the rheobase) can give an indication of their relative excitabilities. The smaller the Chronaxie the more excitable the nerve is.

[0055] FIG. 7 shows a strength—duration curve of a normally innervated muscle and a denervated muscle, as depicted in Schuhfried, O., Kollmann, C., & Paternostro-Sluga, T. (2005). Excitability of chronic hemiparetic muscles: determination of chronaxie values and strength-duration curves and its implication in functional electrical stimulation. IEEE Transactions on Neural Systems and Rehabilitation Engineering : A Publication of the IEEE Engineering in Medicine and Biology Society, 13(1), 105-9), which is hereby incorporated herein by reference in its entirety. The average normal chronaxie value of an innervated muscle is 0.4 ms (see Schuhfried et al.). Chronaxie values above 1 ms are considered as evidence of muscle denervation. The shift to the right and the appearance of kinks in the strength-duration curves is associated with muscle denervation. The strength—duration curve was determined by successively decreasing the widths of monophasic rectangular impulses (500, 300, 200, 100, 70, 50, 30, 20, 10, 5, 2, 1, 0.5, 0.2, 0.1, 0.05 ms).

[0056] The Chronaxie values for human arm sensory nerves range from 0.35 to 1.17 ms. Chronaxie Values for human denervated skeletal muscles ranges from 9.5 to 30 ms->this value drops again during reinnervation (see Geddes, L. A. (2004). Accuracy Limitations of Chronaxie Values. IEEE T Bio-Med Eng, 51(1), 176, which is hereby incorporated by reference herein in its entirety).

[0057] The accommodation index is the ratio of threshold amperage of a slowly rising impulse to the threshold amperage of a suddenly rising rectangular impulse. Accommodation describes the response of excitable membranes to slow depolarizing currents without generation of an action potential. In nerve fibers, a slowly rising current up to double rheobase intensity inactivates sodium conductance before the depolarization reaches the threshold, and therefore, no action potential is generated. This is named a high accommodation rate. In muscle fibers, sodium conductance is much less inactivated by slowly rising currents, and therefore, an action potential is generated also with slowly rising currents of less than twice the rheobase intensity. This is named 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 physiologic basis of the accommodation index. Denervated muscle fibers have the same or even a lower accommodation rate than normal muscle fibers (See Schuhfried 0, Vacariu G, Paternostro-Sluga T: Reliability of chronaxie and accommodation index in the diagnosis of muscle denervation. Phys. Medizin Rehabil. Kurortmedizin 2005, 15:174-178,which is hereby incorporated herein by reference in its entirety).

[0058] Accomodation Index for Healthy Persons:

[0059] As described in Schuhfried et al., FIG. 8 shows different accommodation indices in human muscle groups consisting of the deltoid muscle, extensor digitorum communis muscle, the hypothenar muscle, the thibialis anterior muscle, the peroneus longus muscle and gastrochemius muscle. By applying rectangular and triangular impulses of 500 ms duration the accommodation index should be ≥2 in a healthy muscle.

[0060] Accomodation Index for Persons with Neurogenic Lesion:

[0061] Paternostro-Sluga, T., Schuhfried, 0., 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/1.1055/s-2004-834713 examined accommodation in human muscle group of 17 different muscles divided into three types: muscles of the upper extremity without the intrinsic muscles of the hand, intrinsic muscles of the hand, and muscles of the lower extremity and determined the accommodation index by dividing the threshold amperage of 500 ms duration by the rheobase values. As described in Paternostro-Sluga et al., FIG. 9 shows grading of muscle denervation according to electrical muscle testing and EMG. Accommodation indices (shown below) <2 indicated a neurogenic lesion.

[0062] Accomodation Index for Persons with Denervated Muscles:

[0063] Cummings, J. P. (1985: The Journal of Orthopaedic and Sports Physical Therapy, 7(1), 11-5. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/18802291), which is hereby incorporated herein by reference in its entirety, utilized selective electrical stimulation of denervated muscle with exponentially progressive current forms. FIG. 10 shows the principle of selective stimulation of denervated muscle utilizing a long exponentially progressive current form, as described in Cummings. The strength duration curves for normally innervated muscle, denervated muscle, and intact sensory nerves are illustrated. Selective stimulation of the denervated muscle without recruitment of either normally innervated muscle or the sensory axons is possible (shaded area). Following guidelines according to Thom H. Electrotherapy of paralysis; basic principles and application. [Internet]. Zeitschrift für Orthopädie and ihre Grenzgebiete 1953, 84:104-23., which is hereby incorporated herein by reference in its entirety, Cummins et al. showed that completely paralyzed muscle with advanced denervation atrophy will respond best to slowly rising impulses of 150 to 600 ms duration like shown in the shaded area in FIG. 10.

[0064] Thus, by using very long phase duration (>100 ms) and slow rising pulse phase shapes, one expected to: 1. avoid stimulation of the underlying innervated muscles by increasing the thresholds for depolarization of motoneurons; and 2. avoid stimulation of the underlying nerves by increasing the thresholds for depolarization of excitable nerve membranes to slow depolarizing currents via surface electrodes, thereby selectively activating deep muscles showing signs of atrophy or denervation and accordingly showing excitable membranes to such slow depolarizing currents.

[0065] However, as described above, in illustrative embodiments of the invention these very slow rising, very long pulse phases surprisingly, reliably and selectively elicited full swallowing reflexes in human subjects. Not only were single muscles in the deep neck region activated, but full swallowing cycles were elicited that required coordinated contraction of all twelve or more muscle pairs with appropriate timing and peristaltic manner.

[0066] More specifically, in accordance with various embodiments of the invention, using bipolar pulses having a very long first pulse phase duration , such as, without limitation, >100 ms, and having a slow rising shape of this pulse phase, a full swallowing reflex is elicited. Additionally, use of these bipolar pulses increased the thresholds for depolarization of excitable membranes and reduced depolarizing currents, thereby advantageously suppressing/avoiding the generation of action potentials in the motoneurons and their innervated muscles. At the same time, the generation of action potentials in the mucosal pain fibers are also suppressed/avoided, thereby avoiding reaching the pain threshold.

[0067] In various embodiments of the invention, the magnitude of the first pulse phase of the bipolar stimulation pulse is increasing over time. For example, the first pulse phase of the bipolar stimulation signal may be progressively rising, such that it does not decrease in magnitude over time. In further embodiments, the first pulse phase of the bipolar stimulation signal may be exponentially rising, linearly rising, curvilinearly rising, continuously rising and/or discontinuously rising.

[0068] In various embodiments of the invention, a unipolor electrode configuration may be used, as described above, and unipolar stimulation pulses may be generated/delivered to elicit the full swallowing reflex. The unipolar stimulation pulse may be, without limitation, a triangular pulse. The unipolar stimulation pulse, such as the triangular pulse, may have a rising edge with a duration of greater 100 ms. In a unipolar electrode configuration, the anodic and cathodic pulse may depolarize different nervous (muscular) structures. The generated electrical field (e.g., using a triangular pulse) may advantageously depolarize the vocalis muscle more selectively. In various tests on healthy subjects, comparison between cathodic and anodic stimulation polarity (referring to the laryngeal electrodes) showed a lower activation threshold for the cathodic stimulation. The activation threshold was approximately two-fold higher for the anodic stimulation polarity. The swallowing reflex was elicited with both pulse polarities.

[0069] In accordance with illustrative embodiments of the invention, the system described herein may include implantable electrodes instead of surface electrodes as described herein so far. The implantable electrodes may be placed subcutaneous and attached e.g. to thyroid cartilage. An implantable controller may be configured to generate a stimulation signal for eliciting the full swallowing reflex in the human subject and configured to provide the stimulation signal to the plurality of implantable electrodes upon receipt of a trigger signal.

[0070] In accordance with illustrative embodiments of the invention, the system described herein may be used either as a rehabilitation or as a treatment system. The primary objective of rehabilitation is the restoration of disturbed functions by, for example, sensory stimulation of the swallowing reflex or teaching of special swallowing techniques. Necessary conditions for success are sufficient cortical potential after the injury and an existing connection from the cortex to the muscles. If this connection is lost or if the muscles cannot be sufficiently controlled, a rehabilitation of the swallowing process is not possible. Then, the patient is dependent on a diet via a feeding tube and a tracheal cannula.

[0071] In these cases, electrical stimulation of the external laryngeal muscles via activation of the swallowing reflex as a therapeutic approach may be used to enhance the swallowing process. Stimulation may have to be applied in a timely manner. Stimulation may be triggered either by the patient himself via a switch, such as a hand switch, or by using sensors as a trigger—for example, but not limiting, the electromyography (EMG) of the submental muscles or to measure bioimpedances (BI) at the neck (see, for example, www.mpi-magdebum.mpg.de/bioimpedance, which is hereby incorporated by reference in its entirety). Aspiration detection may be acquired via electrodes on the thyroid cartilage at the level of the vocal cords. The trigger signal generated by the switch or various sensors may be provided to the controller to initiate the generation and delivery of the stimulation signals that elicit the full swallowing response.

[0072] In accordance with further embodiments of the invention, the system may be used as assisting training of the patient via enhancing the exercises by stimulated swallowing—triggered, as described above, either by the patient himself via a hand-switch or by using sensors as trigger.

[0073] Embodiments of the 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 invention may be implemented as pre-programmed hardware elements, other related components, or as a combination of hardware and software components.

[0074] Embodiments can 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 fixed either on a tangible medium, such as a computer readable medium (e.g., a diskette, CD-ROM, ROM, or fixed disk) or transmittable to a computer system, via a modem or other interface device, such as a communications adapter connected to a network over a medium. The medium may be either a tangible medium (e.g., optical or analog communications lines) or a medium implemented with wireless techniques (e.g., microwave, infrared or other transmission techniques). The series of computer instructions embodies all or part of the functionality previously described herein with respect to the system. Those skilled in the art should appreciate that such computer instructions can be written in a number of programming languages for use with many computer architectures or operating systems. Furthermore, such instructions may be stored in any memory device, such as semiconductor, magnetic, optical or other memory devices, and may be transmitted using any communications technology, such as optical, infrared, microwave, or other transmission technologies. It is expected that such a computer program product may be distributed as a removable medium with accompanying printed or electronic documentation (e.g., shrink wrapped software), preloaded with a computer system (e.g., on system ROM or fixed disk), or distributed from a server or electronic bulletin board over the network (e.g., the Internet or World Wide Web). Of course, some embodiments of the invention may be implemented as a combination of both software (e.g., a computer program product) and hardware. Still other embodiments of the invention are implemented as entirely hardware, or entirely software (e.g., a computer program product).

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