WO2023023707A1

WO2023023707A1 - A closed loop control in-ear wearable electroceutical

Info

Publication number: WO2023023707A1
Application number: PCT/AU2022/050927
Authority: WO
Inventors: Wade McFarlane
Original assignee: Mcfarlane Wade
Priority date: 2021-08-21
Filing date: 2022-08-19
Publication date: 2023-03-02

Abstract

A closed loop control in-ear wearable electroceutical is designed for transcutaneous electrostimulation of the auricular branch of the Vagus nerve for optimising the stimulation of the autonomic nervous system for non-pharmacological therapeutic treatment of neurological conditions and/or disease. The system has an optimising controller which is configured for controlling an electrode controller according to an electrostimulation control parameter using closed-loop control whereby the optimising controller measures sensor signals for optimising the electrostimulation control parameter to maximise autonomic nervous system response.

Description

A closed loop control in-ear wearable electroceutical

Field of the Invention

[0001 ] This invention relates generally to electroceuticals and, more particularly, to a closed loop control in-ear wearable electroceutical for transcutaneous electrostimulation of the auricular branch of the Vagus nerve for stimulation of the autonomic nervous system for therapeutic treatment.

Background of the Invention

[0002] Mental health is a global issue with significant social and financial impact. In 2016, 2866 suicides were reported in Australia. In a 2019 Australian Productivity report, mental health was estimated to cost up to $181 billion annually.

[0003] Treatment options for anxiety and depression are mainly limited to pharmacological and psychological therapies, and alternative treatments are urgently required to help manage this growing health crisis.

[0004] The present invention seeks to provide way to overcome or substantially ameliorate at least some of the deficiencies of the prior art, or to at least provide an alternative.

[0005] It is to be understood that, if any prior art information is referred to herein, such reference does not constitute an admission that the information forms part of the common general knowledge in the art, in Australia or any other country.

Summary of the Disclosure

[0006] There is provided herein closed loop control in-ear wearable electroceutical for transcutaneous electrostimulation of the auricular branch of the Vagus nerve for optimising the stimulation of the autonomic nervous system for non-pharmacological therapeutic treatment of neurological conditions and/or disease.

[0007] According to one aspect, there is provided a system comprising an in-ear wearable electroceutical having neurostimulation electrodes for transcutaneous electrostimulation of the auricular branch of the Vagus nerve.

[0008] The system has an electrode controller controlling the electrodes and a heart rate sensor. [0009] An optimising controller interfaces the electrode controller and the heart rate sensor.

[0010] The optimising controller is configured for controlling the electrode controller according to an electrostimulation control parameter using closed-loop control whereby the optimising controller measures heart rate from signals received from the heart rate sensor. The optimising controller may also measure heart rate variability from the signals received from the heart rate sensor.

[001 1 ] The optimising controller optimises the electrostimulation control parameter by varying the electrostimulation control parameter to detect an autonomic nervous system response wherein the heart rate decreases and the heart rate variability increases.

[0012] Electroceutical stimulation of the Vagus nerve in this particular closed-loop control manner to decrease heartrate and increase heart rate variability was found to be able to maximise autonomic nervous system response in a way that more effectively treats a range of neurological conditions and disease.

[0013] Furthermore, in embodiments, the optimising controller may optimise the autonomic nervous system response in a patient specific manner by adjusting the electrostimulation control parameter and measuring patient specific autonomic nervous system responses.

[0014] For example, the optimising controller may optimise the autonomic nervous system response for one patient using a square wave and whereas the optimising controller optimises the autonomic nervous system response for another patient using a sinusoidal waveform.

[0015] In embodiments, the optimising controller could even optimise for patient specific physiological variations in the auricular branch of the Vagus nerve by controlling active electrode patterns to apply voltage between subsets of electrodes to vary transdermal current flow path across the canal to thereby more effectively target patient specific physiology of the Vagus nerve. [0016] For scalar electrostimulation control parameters, such as voltage/current amplitude, frequency and the like, the optimising controller may apply minima or maxima seeking closed-loop control.

[0017] Patient specific optimised control parameters may be stored in memory by the system for subsequent retrieval an application for each patient.

[0018] The electroceutical may comprise a flexible in-ear component having the neurostimulation electrodes thereon which preferably target the auricular branch of the Vagus nerve from the cymba concha region of the ear. This area of the ear is relatively devoid of motor nerves, allowing for application of greater current which would otherwise cause muscular spasms at other parts of the body.

[0019] The present electroceutical is a non-invasive device which may be conveniently utilised once or twice a day for approximately 20 minutes a day [0020] Other aspects of the invention are also disclosed.

Brief Description of the Drawings

[0021 ] Notwithstanding any other forms which may fall within the scope of the present invention, preferred embodiments of the disclosure will now be described, by way of example only, with reference to the accompanying drawings in which:

[0022] Figure 1 shows a system for stimulating the autonomic nervous system comprising an in-ear wearable electroceutical and an electronic device;

[0023] Figure 2 shows closed-loop control implemented by the system of Figure 1 ;

[0024] Figure 3 shows a medial side perspective view of an exemplary physical embodiment of the electroceutical in accordance with an embodiment;

[0025] Figure 4 shows a lateral side perspective view of the exemplary physical embodiment of the electroceutical of Figure 3;

[0026] Figures 5 - 7 show the manner of insertion of the electroceutical in accordance with a further embodiment; and

[0027] Figures 8 - 10 show the electroceutical in accordance with a further embodiment;

[0028] Figures 11 - 13 the electroceutical in accordance with a yet further embodiment; and [0029] Figure 14 shows a specific type of closed-loop control for optimising the autonomic nervous system response.

Description of Embodiments

[0030] Figure 1 shows a system 100 for stimulating the autonomic nervous system to induce a parasympathetic response.

[0031 ] The system 100 comprises an in-ear wearable electroceutical 101 for wearing in the ear 1 14. In embodiments, system 100 further comprise an electronic device 102 in operable communication with the electroceutical 101.

[0032] The electroceutical 101 and the device 102 may comprise a microprocessor 106 for processing digital data. In operable communication with the processor 106 via a system bus 109 is a memory device 105. The memory device 105 is configured for storing digital data 103 including computer program code instructions which may be logically divided into a plurality of controllers 104.

[0033] In use, the microprocessor 106 is configured for fetching these computer program code instructions and associated data 103 for interpretation and execution of the implementation of the functionality described herein.

[0034] The electroceutical 101 and the device 102 may comprise a data interface 107 for communication across a communication link 108. Preferably, the communication link 108 is a wireless data communication link 108 such as a short-range Bluetooth wireless data communication link.

[0035] The electroceutical 101 comprises an I/O interface 1 13 for driving a plurality of neurostimulation electrodes 1 10. The electroceutical 101 may comprise a rechargeable battery power supply (not shown).

[0036] The electroceutical 101 further comprises a heart rate sensor 1 1 1 . In embodiments, the heart rate sensor 1 1 1 is a photoplethysmography sensor or an EDA (Electrodermal activity) sensor so that the electroceutical itself may house the heart rate sensor 1 1 1 as shown in Figures 3 or 13 for example.

[0037] In embodiments, electronic device 102 may comprises an image sensor 1 15 configured for obtaining images of an eye 1 12 of the user during use. The electronic device 102 may further comprise a digital display 132 for the display of digital information thereon.

[0038] In embodiments, the electronic device 102 may take the form of a mobile communication device and wherein the controllers 104 thereof are downloaded as part of a software application for installation and execution thereon.

[0039] Figures 3 and 4 show an exemplary physical embodiment of the electroceutical 101.

[0040] The electroceutical 101 may comprise an inner in-ear flexible component 127 for in-ear insertion and an outer rigid electronic housing 133. The flexible component 127 may comprise silicon.

[0041 ] The flexible component 127 may comprise an ear canal insertion portion 128 and an outer ear wing 129 which contacts the cymba concha region of the ear. As is shown, the outer ear wing 129 may be shaped for engaging within the folds of the cymba concha region of the ear, thereby acting in opposition to the ear canal insertion portion 128 and thereby holding the electroceutical 101 to the ear 1 14.

[0042] The outer ear wing 129 may be open at the interior thereof and may comprise a plurality of the electrodes 1 10 at a periphery thereof.

[0043] The heart rate sensor 1 1 1 may locate on the inner surface of the rigid electronic housing 133. Furthermore, recharging contacts 131 may be exposed via the rigid electronic housing 133 for periodically recharging the internal rechargeable battery thereof.

[0044] The electroceutical 101 may further comprise a pushbutton user interface 130 thereon for controlling various operational aspects thereof.

[0045] The system 100 may comprise one electroceutical 101 for insertion in one ear 1 14, such as the left ear for example.

[0046] Figures 5 - 10 illustrate a further exemplary embodiment of the electroceutical 101 wherein the electroceutical 101 comprises a shelf 135 that rotates in under the anti-tragus 135 of the ear shown in Figure 5 to lock the electroceutical 101 in place and to ensure good electrical contact between the electrodes 1 10 and the skin of the ear. [0047] Specifically, the ear canal insertion portion 128 may be inserted between the tragus 134 and the anti-tragus 135 to the ear canal in the manner shown in Figure 6 whereafter the electroceutical 101 is rotated so that the shelf 135 pivots about the ear canal insertion portion 128 to slide under the anti-tragus 135 to hold the electroceutical 101 in place. When engaged in the manner shown in Figure 7, the shelf 136 may lie beneath both the tragus 134 and the anti-tragus 135.

[0048] As is further shown in Figures 9 and 10, the neurostimulation electrodes 1 10 may be spring-bound (i.e., so as to be biased to extend from the shelf 135 but which can be depressed therein under pressure) and mushroom-headed to enhance the electrical contact with the ear.

[0049] The shelf 135 may be metallic in the electrodes 1 10 may be insulated therefrom so that the shelf 135 can act as a ground electrode.

[0050] Figure 10 shows the electroceutical 101 having the pushbutton user interface 130 which, in the embodiment shown, comprises plus and minus pushbuttons which may be used to increase or decrease stimulus and/or cycle through programs.

[0051 ] With reference to Figure 10, an exterior surface of the electroceutical 101 may comprise a main power pushbutton 136.

[0052] Figures 1 1 and 12 show a further over-the-ear embodiment of the electroceutical 101 having an in-ear housing 140 and a behind-the-ear housing 141 joined by a bridge 142 which goes over the ear.

[0053] The in-ear housing 140 may house the microprocessor 106, I/O interface, electrodes 1 10 and the like whereas the behind the ear housing may house a rechargeable battery and a larger rechargeable battery as compared to the embodiments given in Figures 3 - 10. The behind-the-ear housing 141 may have a charge state indicator 143 representing the charge state of the rechargeable battery by a gauge of a series of LEDs.

[0054] As shown in Figure 12, the electrodes 1 10 may similarly be spring bound although may comprise a flatter head as compared to the mushroom heads shown in Figures 9 and 10 for increased electrical contact. Furthermore, the electrodes 1 10 of the embodiment of Figure 12 generally surround the base of the canal insertion portion 128. In the embodiment shown, the electroceutical comprises three electrodes.

[0055] Figure 2 shows a closed-loop control system 1 16 implemented by the controllers 104 of the system 100.

[0056] In embodiments, the sensor controller 1 19 interfaces the image sensor 1 15 via an image processor 1 18 to determine pupil size 123. During use, the user may hold the electronic device 102 such that the image sensor thereof 1 15 is able to capture images of one or both eyes 1 12 of the user.

[0057] The image processor 1 18 may employ colour, intensity level and shape image processing analysis and/or recognition techniques to estimate the size of the pupil of the eye 1 12. The image processor 1 18 may measure the size of the pupil with relative reference to the size of the surrounding iris thereby accounting for variations in the distance of the electronic device 102 from the eye 1 12.

[0058] The sensor controller 1 19 further interfaces the heart rate sensor 1 1 1 to determine at least one of heart rate 125 and heart rate variability 124, and preferably both.

[0059] The control system 1 16 comprises an optimising controller 1 17 interfacing the sensor controller 1 19 and an electrode controller 121 to control at least one electrostimulation control parameter applied by the electrodes 1 10 to optimise a parasympathetic autonomic nervous system response.

[0060] The electrode controller 121 may employ tri-phasic charge balancing to optimise neural activation. Occasional, or in alternative embodiments, the electrode controller 121 may use bi-phasic charge balancing.

[0061 ] Specifically, the optimising controller 1 17 may control the electrode controller 1 12 to stimulate the autonomic nervous system 120 to decrease the heart rate 125. Furthermore, the optimising controller 1 17 may control the electrode controller 1 12 to stimulate the autonomic nervous system 120 to increase heart rate variability 124. In a preferred embodiment, the optimising controller 1 17 controls the electric controller 1 12 in a way to decrease the heart rate 125 and increase heart rate variability 124. [0062] The optimising controller 1 17 may optimise (i.e. maximise) the autonomic nervous system response by optimising the at least one electrostimulation control parameter by varying the electrostimulation control parameter, measuring the sensed bio parameters 122 and storing the at least one electrostimulation control parameter when the associated sensed bio parameters 122 are optimal.

[0063] Figure 13 shows exemplary closed-loop control 144 by the system 100 in accordance with a preferred embodiment wherein the optimising controller 1 15 optimises the electrostimulation control parameter in a particular way to optimise an autonomic nervous system which decreases heart rate and an increases heart rate variability.

[0064] At step 145, the optimising controller 1 17 controls the electrode controller 121 according to at least one electrostimulation control parameter.

[0065] At step 146, the optimising controller 1 17 varies the control parameter.

[0066] The electrostimulation control parameter may comprise a plurality of discrete control parameter options and wherein the optimising controller 1 17 cycles between options during closed-loop control. Furthermore, the electrostimulation control parameter may comprise a scalar discrete control parameter and wherein the optimising controller 1 17 varies the control parameter using maxima or minima seeking closed-loop control. In a preferred embodiment, the optimising controller 1 17 is configured to optimise more than one electrostimulation control parameter, and, further preferably, simultaneously.

[0067] The optimising controller 1 17 may vary the control parameter at periodic intervals. In embodiments, the optimising controller 1 17 varies the optimising controller 1 17 during a configuration period until the optimising parameter is sufficiently optimised, including specifically for a patient in embodiments.

[0068] The electrostimulation control parameter may be used to control voltage and/or or current applied between the electrodes 1 10. For example, with reference to the embodiment shown in Figure 12, electrode 1 10A may be a positive voltage electrode and electrode 1 10C may be a ground electrode. As such, the optimising controller 1 17 may control the electrode controller 121 to vary the voltage and/or current applied between the electrodes 1 10A and 1 10C.

[0069] In embodiments, the optimising controller 1 17 may vary polarity. For example, the optimising controller 1 17 may control the electrode controller 121 to switch the voltage applied between the electrodes 1 10 wherein electrode 1 10C becomes the positive voltage electrode and electrode 1 10A becomes the ground electrode. In embodiments, the optimising controller 1 17 may control the electric controller 1 21 so that the three electrodes apply different voltages comprising a positive voltage, ground and negative voltage.

[0070] In embodiments, the electrostimulation control parameter may comprise differing patterns of operation and nonoperation of subsets of electrodes. For example, the optimising controller 1 17 may vary an active electrode pattern by controlling subsets of the electrodes 1 10. For example, with reference to the embodiment shown in Figure 12, the optimising controller 1 17 may control the electric controller 121 so that electrode 1 10B is a positive voltage electrode and electrode 1 10C is a ground electrode so that transdermal current flows therebetween, such as directly across the base of the canal insertion portion 128.

[0071 ] However, the optimising controller 1 17 may vary the control parameter by disconnecting electrode 1 10B and switching in electrode 1 10A so that transdermal current flows via a different path across the ear canal from electrode 1 10A to electrode 1 10C

[0072] The electrostimulation control parameter may comprise a type of electrostimulation waveform applied by the electrodes 1 10. For example, the type of waveform applied between the electrodes 1 10 may be varied by the optimising controller 1 17 from a sinusoidal waveform to a square waveform. Furthermore, the optimising controller may vary the pulse width duty cycle of a square waveform. Other waveform shapes are envisaged, including burst waveforms.

[0073] Furthermore, the optimising controller 1 17 may vary the frequency of the waveform, such as by switching from a 5 kHz to 10 kHz waveform. [0074] As the optimising controller 1 17 adjusts the at least one electrostimulation control parameter, the optimising controller 1 17 records the sensed bio parameters 122 and records stimulation parameters which optimise the sensed bio parameters 122 at step 149. The optimised stimulation parameters may be stored by the system 100 within one or both of the memory devices 105 for subsequent application.

[0075] For example, the system 100 may store in memory 105 first optimised electrostimulation control parameter optimised for a first patient and a second optimised electrostimulation control parameter optimised for a second patient. The patient may then be selected via the a user interface 130 wherein the system 100 retrieves either the first or second optimised electrostimulation control parameter accordingly for control of the electrode controller.

[0076] According to the embodiment shown in Figure 14, at step 147, the optimising controller 1 17 interfaces the heart rate sensor 1 1 1 to determine whether there is a decrease in heart rate. For example, after varying the electrostimulation control parameter, the optimising controller 1 17 may average a measured heart rate over a one-minute period. If heart rate decreases, the optimising controller 1 17 may store the optimised control parameter.

[0077] Similarly, at step 148, the optimising controller 1 17 interfaces the heart rate sensor 100 to determine whether there is an increase in heart rate variability. Heart rate variability may be measured by the optimising controller 1 17 as the percentage variation in timing between a series of heartbeats.

[0078] In some embodiments as alluded to above, the control parameter is selected from a set of discrete options and wherein the optimising controller 1 17 cycles through the discrete options.

[0079] For example, the optimising controller may cycle through sinusoidal, triangular, burst and square waveforms when varying the waveform applied by the electrodes, recording the variation to the sensed bio parameters 122 for each.

[0080] For example, if a square waveform shows a decrease in heart rate and an increase in heart rate variability, the optimising controller 1 17 may store the square waveform control parameter option for subsequent application. If the variation adversely affects one of the bio parameters, such as wherein heart rate decreases but heart rate variability also decreases, the system 100 may be programmed to favour one of these bio parameters.

[0081 ] Optimising of the control parameter may allow for patient specific optimisation. For example, the autonomic nervous system of one patient may respond more favourably to a square waveform as opposed to another patient which responds more favourably to a sinusoidal waveform.

[0082] Other types of discrete value electrode stimulator control parameter options may include electrode pattern wherein, as alluded to above, the optimising controller 117 may either apply a control parameter option wherein voltage/current is applied between electrodes 1 10B and 1 10C or another control parameter option wherein voltage/current is applied between electrodes 1 10A and 1 10C.

[0083] In embodiments, for scalar electrostimulation control parameters, the optimising controller 117 may control the direction of variation (i.e., up or down) depending on the sensed bio parameters 122. In other words, the optimising controller 117 may use gradient ascent maxima or gradient descent minima seeking closed-loop control.

[0084] For example, if, when increasing a 50% pulse width duty cycle to 60%, the optimising controller 117 detects a decrease in heart rate, the optimising controller 117 may continue to increase the duty cycle through successive iterations until such time that there is detected an increase in heart rate.

[0085] If, on the other hand, the increasing duty cycle stimulates an increase in heart rate, the optimising controller 1 17 may subsequently decrease the duty cycle (i.e. reverse the direction of variation).

[0086] Other types of scalar electrostimulation control parameters may comprise voltage and/or current applied between electrodes 110 and frequency applied between the electrodes.

[0087] In embodiments, the optimising controller 117 may control the electrode controller 112 to stimulate the autonomic nervous system 120 to decrease pupil size 123 (i.e., pupil constriction). [0088] In embodiments, the system 100 may be preprogramed to treat various conditions wherein the system 100 is configured with optimum bio parameters for each type of neurological condition and wherein the optimising controller 1 17 is configured to optimise at least one electrostimulation control parameter to optimise the sensed bio parameters 122 according to the optimum bio parameters for each type of neurological condition.

[0089] These various conditions may include obesity, sleep disorders, Rheumatoid Arthritis, headaches or migraines, pain, Alzheimer’s disease, tinnitus, diabetes, memory loss, stroke, heart failure, endotoxemia and drug dependency substitution.

[0090] The foregoing description, for purposes of explanation, used specific nomenclature to provide a thorough understanding of the invention. However, it will be apparent to one skilled in the art that specific details are not required in order to practise the invention. Thus, the foregoing descriptions of specific embodiments of the invention are presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the invention to the precise forms disclosed as obviously many modifications and variations are possible in view of the above teachings. The embodiments were chosen and described in order to best explain the principles of the invention and its practical applications, thereby enabling others skilled in the art to best utilize the invention and various embodiments with various modifications as are suited to the particular use contemplated. It is intended that the following claims and their equivalents define the scope of the invention .

Claims

1. A system comprising: an in-ear wearable electroceutical having neurostimulation electrodes for transcutaneous electrostimulation of the auricular branch of the Vagus nerve; an electrode controller controlling the electrodes; a heart rate sensor; an optimising controller interfacing the electrode controller and the heart rate sensor, wherein the: optimising controller is configured for: controlling the electrode controller according to an electrostimulation control parameter using closed-loop control whereby the optimising controller: measures heart rate from signals received from the heart rate sensor measures heart rate variability from the signals received from the heart rate sensor; and optimises the electrostimulation control parameter by varying the electrostimulation control parameter to detect an autonomic nervous system response wherein: the heart rate decreases; and the heart rate variability increases.

2. The system as claimed in claim 1 , wherein the heart rate sensor is a photoplethysmography sensor and wherein the heart rate sensor is housed by the electroceutical.

3. The system as claimed in claim 1 , wherein the heart rate sensor is an EDA (Electrodermal activity) sensor and wherein the heart rate sensor is housed by the electroceutical.

4. The system as claimed in claim 1 , further comprising: an image sensor; an image processor configured to determine pupil size using image data captured by the image sensor and wherein the optimising controller is further configured for optimising the electrostimulation control parameter by varying the electrostimulation control parameter to detect a pupil constriction autonomic nervous system response.

5. The system as claimed in claim 4, wherein the image processor employs at least one of colour, intensity and shape detection to determine the size of the pupil.

6. The system as claimed in claim 4, wherein the image processor determines the size of the pupil with reference to a size of an iris surrounding the pupil.

7. The system as claimed in claim 1 , wherein the electrostimulation control parameter comprises a plurality of discrete control parameter options and wherein the optimising controller cycles between options during closed-loop control.

8. The system as claimed in claim 7, wherein the discrete control parameter options comprises a shape waveform option.

9. The system as claimed in claim 7, wherein the discrete control parameter options comprise an electrode voltage polarity option.

10. The system as claimed in claim 7, wherein the electrodes comprise more than two electrodes and wherein the discrete control parameter options comprise: a first option which controls voltage applied between a first subset pair of the electrodes; and a second option which controls voltage applied between a second subset pair of the electrodes, to thereby vary a transdermal current path between the electrodes.

1 1 . The system as claimed in claim 1 , wherein the electrostimulation control parameter comprises a scalar discrete control parameter and wherein the optimising controller varies the control parameter using maxima or minima seeking closed-loop control.

12. The system as claimed in claim 1 1 , wherein the scalar discrete control parameter comprises voltage magnitude applied between the electrode pairs.

13. The system as claimed in claim 1 , wherein the electroceutical comprises an inear component having a wing having the electrode pairs thereon which contact the cymba concha region of the ear.

14. The system as claimed in claim 13, wherein the in-ear component further comprises an ear canal insertion portion.

15. The system as claimed in claim 1 , wherein the optimising controller is configured with optimum bio parameters for a plurality of types of conditions and wherein the optimising controller is configured to optimise at least one electrostimulation control parameter to optimise the sensed bio parameters according to the optimum bio parameters for each type of condition.

16. The system as claimed in claim 1 , wherein the electroceutical comprises a shelf configured to rotate in under the anti-tragus of the ear in use.

17. The system as claimed in claim 16, wherein the electroceutical comprises an in-ear component comprises an ear canal insertion portion and wherein the ear canal insertion portion extends from the shelf so that, when the electroceutical is rotated, the shelf pivots about the ear canal insertion portion so that the shelf can slide in under the anti-tragus.

18. The system as claimed in claim 16, wherein the shelf is metallic.

19. The system as claimed in claim 18, wherein the electrodes are insulated from the shelf.

20. The system as claimed in claim 19, wherein the shelf is a ground electrode for the simulation electrodes.

21 . The system as claimed in claim 1 , wherein the neurostimulation electrodes are spring bound between extended and retracted positions.

22. The system as claimed in claim 1 , wherein the system stores in memory first optimised electrostimulation control parameter optimised for a first patient and a second optimised electrostimulation control parameter optimised for a second patient and wherein the system comprises a user interface for the selection of a patient and wherein the system retrieves either the first or second optimised electrostimulation control parameter accordingly for control of the electrode controller.

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