AURICULAR NEUROSTIMULATION DEVICE AND SYSTEM

Abstract

The present invention relates to an auricular neurostimulation device wearable by a user and configured to stimulate the Auricular Branch of Vagus Nerve (ABVN) on the user’s ear: the device comprises at least two electrodes designed to be located in the cymba and in the cavity of the cavum conchae respectively; the electrodes stimulate the nerve ramifications of the cymba and the cavum conchae, respectively, when an electrical voltage difference is applied between them. The invention further refers to an auricular neurostimulation system comprising an auricular neurostimulation device as described and a charging case where the device can charge an internal battery and where the device discharges into this case the data captured by the photoplethysmographic or biosensor during stimulation and sends them to a dedicated platform in the cloud. The invention also refers to a method of operation of an auricular neurostimulation system as described.

Claims

1. An auricular neurostimulation device wearable by a user and configured to stimulate the Auricular Branch of Vagus Nerve (ABVN) on the user’s ear, wherein: the device comprises at least two electrodes designed to be located in the cymba and in the cavity of the cavum conchae respectively; the electrodes electrically stimulate the nerve ramifications of the cymba and the cavum conchae respectively; characterized in that: the device is configured as a wireless earbud comprising an earmold and a miniaturized faceplate wherein, the electrodes are arranged the earmold which is customized to the user’s ear anatomy such that the cymba electrode is a large-surface electrode covering almost the whole cymba surface area of the user’s; a photoplethysmographic or biosensor with a miniaturized configuration is arranged inside the earmold; and the miniaturized faceplate incorporates inside it all the elements of an electronic circuit built on a Printed Circuit Board (PCB) that combines rigid elements with flexible elements, either in an ITE (In The Ear) configuration or in an BTE (Behind The Ear) configuration.

2. The auricular neurostimulation device according to claim 1 wherein the electrodes are made of graphene, biocompatible metals, nontoxic metals, conductive biocompatible inks for 3D printing or flexible conductive biocompatible polymers, and wherein the earmold is made of a biocompatible material and preferably thermoelastic so that it improves the fit with the user’s ear as the earmold acquires body temperature.

3. The auricular neurostimulation device according to claim 1, wherein the photoplethysmographiic or biosensor measures the environment temperature and the user’s temperature and to estimate the amount of hemoglobin and oxyhemoglobin circulating through the most superficial capillary vessels of the ear of the patient or user, the measurements made by the photoplethysmographic or biosensor are used to calculate the heart rate, the heart rate variability (HRV) and the oxygen saturation and to detect the breathing phase (exhalation or inhalation) of the user or patient; and wherein the measurements made by the photoplethysmographic or biosensor are used to determine which electrical charge is the most suitable for the user at any given time.

4. The auricular neurostimulation device according to claim 1, wherein the electronic circuit comprises the following elements: a central circuitthat controls all the functioning of the device; a voltage amplifier that raises the voltage supplied by a battery; a charger circuitthat takes advantage ofelectric current generated in a coilthat receives the magnetic field created by a further coil located in a charging case and a battery that is rechargeable with the current generated in the coil.

5. The auricular neurostimulation deviceaccording to claim 4 wherein the electronic circuitis configured to: generate stimulation patterns with variable duration, intensity, frequency of bursts and pulses, number of pulses per burst, pulse widths, and pulse delays, among others; generate stimulation patterns synchronized with the exhalation of the user; control an electrical charge applied in each stimulation and daily-accumulated charge; exchange data with external devices through wireless connections; exchange data with the charging case; and wireless charging of a batteryby electromagnetic induction with the charging case.

6. The auricular neurostimulation deviceaccording to claim 3 wherein the stimulation done by the electrodes is synchronized with the exhalation-breathing phase of the user.

7. The auricular neurostimulation deviceaccording to claim 5 wherein the electronic circuit implements a plurality of stimulation protocols, where the intensity of electric current, pulse width and repetition frequency ofpulses is variable; and wherein the stimulation protocols are based on a waveform of rectangular, biphasic, symmetric and with a delay between a negative and positive pulse.

8. The auricular neurostimulation deviceaccording to claim 7 wherein the stimulation protocols include any of the following types: a BEAT type protocol, consisting of continuous application of bursts of pulses; a BFS (Breathing Focused on Stimulation) type protocol combining stimulation moments with standstill moments, so the user breathes in during the standstill moments and breathes out during the stimulation; and an EVANS (Exhalation Vagus Auricular Nerve Stimulation) type protocol stimulating only duringexhalation of the user.

9. The auricular neurostimulation deviceaccording to claim 1 wherein an electrical charge quantity applied to electrodesis personalized for the user, according to the therapeutic dose needed.

10. The auricular neurostimulation device according to claim 1 wherein an electrical voltage difference applied to electrodes adjusted in real time to an impedance of a contact of the electrodes withskin, in order to ensure thatintensity of stimulation is as established.

11. The auricular neurostimulation device according to claim 1 wherein the auricular neurostimulation device is stored in a charging case device when not used in order to charge a battery wirelessly by electromagnetic induction and where the device discharges into the charging casethe data captured by the photoplethysmographic or biosensor during stimulation for transmission to a dedicated platform in the cloud.

12. The auricular neurostimulation system comprising an auricular neurostimulation device according to claim 1wherein the neurostimulation device is configurable via a smartphone application.

13. A method of configuration of an auricular neurostimulation device according to claim 12 comprising the following steps creation, via the smartphone application, by the user of a user account using the application for the smartphone or the web entering a series of personal data; assignment, via the smartphone application, of an initial electrical charge value to apply in each stimulation session and a maximum daily electrical charge, depending on the user’s profile and on the basis of statistical studies; detection of the user into the application; connection to the auricular neurostimulation device to match a serial number of the auricular neurostimulation device to the user account, so the device is associated to the user; application prompting the user to set his/her ‘perception and pain thresholds; based on both thresholds, establishment of a range in which the stimulation intensity must be placed, so that the stimulation is effective but also comfortable; detection of a selection of a stimulation protocol by the user; and configure the auricular neurostimulation device in accordance with the range of stimulation intensity and the stimulation protocol.

14. A method of configuration of an auricular neurostimulation device according to claim 1 comprising the following steps after a stimulation session: reception, from the auricular neurostimulation device and at a charging case or a smartphone application, session data including readings stored by the pilotoplethysmographic or biosensor transmission of the data from the stimulation session to a cloud platform for storage thereat reception of a result of an algorithm that analyses data stored at the cloud platform to determine an optimizeddose of electrical charge required by the user enablement of the user to modify the optimized dose of electrical charge; and reception of a notification recommending stimulation sessions that prevent stress peaks based on an analysis of the data stored at the cloud platform obtained from other devices associated with the user that continuously monitorcardiac activity of the user.

15. A method of operation of an auricular neurostimulation device according to claim 1 comprising the following steps during automatic activation of the auricular neurostimulation device when it is removed from the charging case; automatic check of the correct positioning inside the ear by a proximity detector of the photoplethysmographic or biosensor; automatic start of stimulation of the auricular neurostimulation device according to defined stimulation conditions; automatic monitoring of the amount of electrical charge entered in the user’s ear by the auricular neurostimulation device; automatic stop of the stimulation by the auricular neurostimulation device when a defined stimulation condition indicating an assigned electrical charge value is reached or when a maximum daily electrical charge is reached and during stimulation, storage by the photoplethysmographic or biosensorof temperature, hemoglobin and oxyhemoglobin readings of the user.

16. The method of operation of an auricular neurostimulation system according to claim 15 wherein the stimulation conditions of the stimulation are used to enhance physical and cognitive performance.

17. The method of operation of an auricular neurostimulation system according to claim 16 wherein the performance enhancement is any of improvement of learning processes, improvement of attention and concentration skills, improvement of divergent thinking, enhancement of response selection processes, enhancement of motor learning, optimization of athlete’s adaptation to training loads, enhancement of muscle growth as well as weight control.

18. (canceled)

19. The method of operation of an auricular neurostimulation system according to claim 15 wherein the stimulation conditions of the therapeutic stimulation are used to treat at least one of epilepsy, chronic stress, pre-diabetes, obesity, depression, chronic tinnitus, migraine, rehabilitation after ischemic stroke, alleviation of chronic inflammation, muscle regeneration and growth, ventricular arrhythmias, respiratory symptoms associated to COVID-19 as well as to boost associative memory to help patients with Alzheimer’s disease and other dementia types.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0080] Further features, advantages and objects of the present invention will become apparent for a skilled person when reading the following detailed description of non-limiting embodiments of the present invention, when taken in conjunction with the appended drawings, in which:

[0081] FIG. 1: Detailed view of the different ear areas that may be stimulated in a human person.

[0082] FIG. 2: Perspective view of the auricular neurostimulation device according to a first preferred embodiment of the present invention, showing its main components.

[0083] FIG. 3: Lateral perspective view of the auricular neurostimulation device according to a first preferred embodiment of the present invention, as represented in FIG. 2.

[0084] FIG. 4: Perspective view of the auricular neurostimulation device according to a first preferred embodiment of the present invention, as represented in FIG. 2, shown in the position where it will be placed in the ear of the patient.

[0085] FIG. 5: Perspective view of the auricular neurostimulation device according to a first preferred embodiment of the present invention, as represented in FIG. 2, from its bottom position.

[0086] FIG. 6: Scheme with the components of the connected auricular neurostimulation system of the invention.

[0087] FIG. 7: Perspective view of the auricular neurostimulation device of the invention in an alternative mode of implementation to that in FIG. 2, with the electronics located Behind The Ear (BTE).

[0088] FIG. 8A:Graph showing the stimulation pattern of the auricular neurostimulation device of the present invention.

[0089] FIG. 8B:Graph showing the stimulation pattern of the auricular neurostimulation device of the present invention, synchronized with the patient’s exhalation.

[0090] FIG. 9A: A first exemplary layout of a Printed Circuit Board (PCB) of the auricular neurostimulation device of the invention, where discontinuous lines represent the flexible parts and the continuous lines the rigid parts.

[0091] FIG. 9B: A second exemplary layout of a Printed Circuit Board (PCB).

[0092] FIG. 10: Graph showing the Vagus sensory evoked potential (VSEP) induced by auricular stimulation applied comparing the auricular neurostimulation device of the present invention with a prior art stimulation device.

[0093] FIG. 11: Landmarks and lengths to characterize the surface of the cymba.

DETAILED DESCRIPTION OF THE EXEMPLARV EMBODIMENTS

[0094] The object of the invention is a connected auricular neurostimulation device 1, wearable by a patient that optimizes the stimulation of the ABVN present in the cymba and cavum conchae, as it can be seen in FIG. 1.

[0095] The auricular neurostimulation device 1 of the invention comprises the following components, as represented in FIG. 2, according to a first preferred embodiment where the device 1 is arranged in the patient’s ear: [0096] An electrode 2 that occupies the entire section of the cymba (the only ear zone with 100% ABVN). In a preferred embodiment, this electrode is configured as a working electrode on which a cathodic stimulation is applied in order to maximize the activation of the ABVN. [0097] An electrode 3 placed in the cavum conchae (ear zone with 45% ABVN). In a preferred embodiment, this electrode serves as a reference for applying the electrical voltage difference generated by cathodic stimulation. [0098] The electrodes are typically manufactured using graphene, biocompatible metals such as titanium, nickel titanium (nitinol), platinum, platinum-iridium, non-toxic metals as gold, conductive biocompatible inks for 3D printing or flexible conductive biocompatible polymers that adapt to the anatomy of the stimulation zone, therefore providing good comfort and perfect adaptation to the patient’s ear. [0099] Earmold 4: This part is used as a support for the cymba and cavum conchae electrodes 2, 3 respectively in order to ensure that the positioning of these electrodes 2, 3 is adequate to maximize cymba and cavum conchae stimulation. The advantage of this earmold 4 in the device 1 of the invention is that it is custom made to the user’s anatomy, so it can be personalized and shaped to optimally fit each patient’s or user’s anatomy. The earmold material is biocompatible and preferably thermoelastic so that it improves the fit with the user’s ear as the earmold acquires body temperature. [0100] Photoplethysmographic or biosensor 5: This sensor serves to measure the environment temperature and the user’s temperature and to estimate the amount of hemoglobin and oxyhemoglobin circulating through the most superficial capillary vessels of the ear of the patient or user, once the device 1 has been arranged on him or her. These data can be used to calculate the heart rate, the heart rate variability (HRV) and the oxygen saturation, among other biomedical variables and to detect the breathing phase (exhalation or inhalation) of the user or patient.

[0101] This photoplethysmographic or biosensor 5 is able to detect a very low heart rate of the user: in case this is detected, the device 1 is configured to automatically stop the stimulation.

[0102] In addition, the measurements made by the sensor make it possible to know how much electrical charge needs to be applied to each user at any given time to achieve vagal activation. This allows personalizing the stimulation treatments reaching efficiency levels much higher than other existing devices known in the art.

[0103] Moreover, the photoplethysmographic or biosensor 5 is also able to detect the breathing phase (exhalation or inhalation) of the patient or user wearing it with the aim to automatically synchronize the stimulation of the device 1 only with the user’s exhalation with the goal to obtain a more efficient activation of the vagus nerve. [0104] Electronic circuit 6: The auricular neurostimulation device 1 is equipped with an electronic circuit 6 allowing it to develop the following functionalities, as indicated below. [0105] Generation of stimulation patterns with variable duration, intensity, frequency of bursts and pulses, number of pulses per burst, pulse widths, and pulse delays, amongst others, by applying electrical voltage differences between electrodes 2 and 3. [0106] Generation of stimulation patterns synchronized with the exhalation of the user. [0107] Control of electrical charge applied in each stimulation and daily-accumulated charge. [0108] Exchange of data with external devices through wireless connections. [0109] Data exchange with a charging case. [0110] Wireless charging of the battery 10 by electromagnetic induction with a charging case. [0111] Faceplate 12: The auricular neurostimulation device 1 is equipped with a faceplate 12 that protects the electronic circuit 6 and makes it easy for the user to pick the device up for its placement and removal in the user’s ear and in the charging case 13.

[0112] Moreover, an external charging case 13 and the connection of an internal application for smartphone 14 of the device 1 to an external cloud 15 configure a complete auricular neurostimulation system according to the invention, as shown in FIG. 6. [0113] Charging case 13: The auricular neurostimulation device 1 is stored when not used in a case 13 that charges its battery 10 wirelessly by electromagnetic induction. The device 1 discharges into this case 13 the data captured by the photoplethysmographic or biosensor 5 during stimulation when in use and sends them to a dedicated platform in the external cloud 15. [0114] Application for smartphone: The auricular neurostimulation device 1 has a smartphone application 14 that allows the patient or user to interact with the neurostimulation device 1, for example configuring certain stimulation parameters. The app 14 exchanges data with the dedicated platform in the cloud 15 to where the data captured by the photoplethysmographic or biosensor 5 during stimulation are sent. [0115] Stimulation protocols: The auricular neurostimulation device 1 implements a plurality of charge-controlled stimulation protocols. Preferably, these stimulation protocols are cathodic stimulation protocols. The charge is injected by applying an electrical voltage difference in the cymba electrode 2 with respect to the cavum electrode 3 that varies in real time depending on the impedance of the electrode-skin contact. The electrical voltage difference applied is a rectangular, biphasic, symmetrical wave with a delay between the first pulse and the second pulse (see FIG. 8A). The first pulse of the waveform, or stimulating pulse, is used to elicit the desired physiological effect such as initiation of an action potential in the nerve endings, and the second pulse, or reversal pulse, is used to reverse electrochemical processes occurring during the stimulating pulse. The stimulation pulse is negative (cathodic stimulation) as it achieves faster depolarization of nerve endings than a positive pulse (anodic stimulation). It is estimated that the depolarization that occurs with anodic stimulation is roughly one-seventh to one-third that of the depolarization with cathodic stimulation (Daniel R. Merrill et al. 2004). Thus, cathodic stimulation requires less current to bring a nerve ending to threshold. The addition of a delay between the stimulation and reversal pulses also contributes to the reduction of the threshold to achieve the action potential of the nerve endings. However, the delay should not be too long to prevent the products of the Faradaic reactions caused by the stimulation pulse from accumulating to levels that could cause tissue damage. Delay values between 0 and 150 .Math.s are considered appropriate.

[0116] Stimulation protocols include pulse bursts as these improve the effectiveness of stimulation. The action potentials triggered at the sensory auricular vagus endings in response to continuous stimuli are less likely to influence systemic regulation or brain activity, rather than a rhythmic sequence of these impulses. This is because gradual natural sensory information is coded as the gradual temporal density of non-gradual impulses, likewise, coded as the instantaneous frequency of impulses. On the other hand, the brain with its very large number of neurons and its sophisticated processing is not likely to respond reasonably to a single or a few impulses but to a train of impulses. Stimulation protocols may include between 1 and 10 bursts per second.

[0117] The intensity of the electric current, the width of the pulses and their frequency are also variable in the stimulation protocols. The stimulation intensity can vary between 0 and 5 mA as it has been proven experimentally that in this range is sufficient to produce an effective stimulation of nerve endings in a way that is comfortable for the user. The pulse width usually determines the type of fibers to be excited. That is, short pulses recruit easily excitable thick fibers only while elongated pulses recruit both thick and thin fibers. The ABVN is composed mainly of fibres Aβ, Aδ and C (Safi et al., 2016). The Aβ have diameters between 5 and 12 .Math.m and are associated with sensitive functions. The Aδ has diameters between 3 and 6 .Math.m and transmits localized pain, temperature and touch. Those of type C have diameters between 0,4 and 1,2 .Math.m and transmit diffuse pain and temperature. In stimulation, it is desirable to activate Aβ and not Aδ or C, so the stimulation pulse must be short. It has been proven that values between 50 and 250 .Math.s can be appropriate. Another important parameter in stimulation is the frequency or number of pulses per second, since depending on its value, one type of fiber or another is activated. The range of frequency variation in the stimulation protocols is between 1 and 30 Hz.

[0118] The different stimulation protocols can be conceptually grouped into three modalities: [0119] Protocols BEAT in which the patient’s breathing is not taken into account. [0120] Protocols BFS that establish guidelines for the user to accommodate his breathing rhythm. [0121] Protocols EVANS in which the device automatically detects the user’s inspiration and exhalation and stimulates only during exhalation.

[0122] BEAT type protocols apply pulse burst with variable parameters within the above ranges (see FIG. 8A). The BSF and EVANS protocols also apply pulse bursts with variable parameters but only during user expiration (See FIG. 8B). In the BSF the user adapts his exhalation to the moments of stimulation and in the EVANS the device detects the exhalation and synchronizes the stimulation with it.

[0123] The auricular neurostimulation device 1 of the invention is configured to detect when the user is exhaling thanks to the photoplethysmographic or biosensor 5. The duration of the stimulation sessions depends on the electrical charge (dosis) assigned to the session and the stimulation intensity selected by the user. Initially, each user is assigned an electrical charge depending on his/her profile, but based on the analysis of the data captured by the biosensor 5, the electrical charge to be applied can be customized. The stimulator keeps track of the applied electrical charge by stopping the stimulation when the set electric charge of the session has been reached. It is also possible to assign a maximum daily dose that the device will control not to be exceeded.

[0124] The auricular neurostimulation device 1 of the invention has been described according to a preferred embodiment, as represented in FIGS. 2-5: according to this embodiment, the electronic of the device 1 is placed in the conchae of the user’s ear (ITE or In The Ear). However, a different possible embodiment of the device 1 of the invention would be to configure the device to be placed behind the ear (BTE) of the user, as represented in FIG. 7. The components of the device are the same as in the preferred configuration (that represented in FIGS. 2-5) but having a different configuration allowing the device to be placed behind the ear of the user. This way, the electronic components of the device are arranged behind the user’s ear and are not visible from outside. Moreover, the user is very comfortable with this BTE configuration.

[0125] The electronic circuit 6 in the device of the invention is built on a Printed Circuit Board (PCB) that combines rigid parts with flexible parts, as shown in FIGS. 9A and 9B, each figure showing a different exemplary layout. The parts can be stacked to form an assembly that can be inserted into the faceplate 12, both in the ITE (In The Ear) configuration of FIGS. 2-5 and in the BTE (Behind The Ear) configuration of FIG. 7. The electronic circuit 6 comprises the following elements: [0126] A central circuit 7 that controls all the functioning of the device, including the communication with the smartphone and the charger case, the generation of the stimulation patterns and the adjustment of the electrical voltage difference applied to the electrodes 2 and 3, according to the skin-electrode contact impedance. [0127] A voltage amplifier 8 that raises the voltage supplied by the battery to the level necessary to apply the electrical voltage difference to electrodes 2 and 3 required at any given time. [0128] A charger circuit 9 that takes advantage of the electric current generated in the coil 11. [0129] A battery 10 that is rechargeable with the current generated in coil 11. [0130] A coil 11 that receives the magnetic field created by a coil located in the charger case and generates electric current to recharge the battery.

[0131] FIG. 10 shows the Vagus sensory evoked potential (VSEP) induced by auricular stimulation applied a) in the lobe where there are no vagal nerve endings b) according to the electrode arrangement of the object of the present invention with two large electrodes, one in cymba as working electrode and one in cavum as counter electrode c) according to the electrode arrangement of Cerbomed’s stimulator (corresponds with prior art device disclosed in EP3100764) with two small electrodes in cymba. Vagus sensory evoked potential (VSEP) via electrical ABVN stimulation and to measure it with EEG electrodes on the scalp as a far field potential has been demonstrated to be another way to evaluate the vagus nerve response (Fallgatter AJ et al, 2003,Lewine JD. et al., 2019). The graphs have been obtained by measuring neuronal electrical activity between points C3-F3 of the international 10-20 EEG measurement system. Neuronal activity is produced by the postsynaptic potentials generated in the nucleus of the solitary tract (NTS) in response to auricular electrical stimulation (See FIG. 1B). The graphs shown have been obtained by averaging the neuronal response (vagal sensory evoked potential-VSEP) after the application of at least 50 electrical stimulation pulses. The amplitude of the VSEP is representative of the effectiveness of the stimulation. The results obtained in the measurement of 26 volunteers indicate that the stimulation performed as indicated in the present invention generates a vagal evoked potential with an amplitude 2.9 times greater than that generated by the stimulation of Cerbomed (prior art).

[0132] The auricular neurostimulation device 1 of the invention presents as explained below, several advantages with respect to other neurostimulation devices known in the state of the art, in particular relating to safety, effectiveness, comfort, usability and personalization:

[0133] Safety. The photoplethysmographic or biosensor 5 included in stimulator 1 makes it possible to anticipate a very low heart rate and stop the stimulation to prevent risky situations. On the other hand, circuit 6 keeps track of the daily electric charge introduced to the user, preventing it from exceeding a limit. It also adjusts in real time the electrical voltage difference applied to electrodes 2 and 3 according to the impedance of the contact of the electrodes with the skin, preventing the applied current from rising to dangerous limits if the impedance drops quickly, due to effects such as electroporation.

[0134] Effectiveness. The study carried out with vagus sensory evoked potentials concludes that stimulation with one electrode covering the whole cymba (electrode 2) and another in cavum (electrode 3) obtains a neuronal response associated with vagal activation 3.9 times greater than stimulation with two electrodes placed in the cymba. One reason for this is that with two electrodes in the cymba (100% vagal fibres) the whole surface of the cymba is not well used as there must be a minimum separation between them.

[0135] The surface of the cymba, as in general the anatomy of the whole ear, is very variable. In an anthropometric study carried out with 326 volunteers (Wonsup Lee, et al, 2018), the length was measured between superior cavum conchae and anterior cymba (SC-AC) and between the posterior conchae and anterior cymba (PC-AC) (see FIG. 11).

[0136] The result was as follows:

TABLE-US-00001 Length Age group 20 s (n=133) 30 s (n=73) 40 s (n=55) 50 s (n=57) Superior cavum conchae to anterior cymba (SC-AC) 6.3 ± 1.5 mm 6.3 ± 1.7 mm 6.4 ± 1.3 mm 6.6 ± 1.4 mm Posterior conchae to anterior cymba (PC-AC) 16.3 ± 2.0 mm 15.8 ± 1.9 mm 15.4 ± 1.6 mm 14.9 ± 1.7 mm

[0137] In terms of gender differences, the average length of SC-AC and PC-AC is greater for men than for women, 18% in the first case and 7% in the second.

[0138] The auricular neurostimulator device 1 of this invention is designed to maximize the stimulation in the cymba. When in this report the term ‘large-surface electrode covering almost the whole cymba surface’ is used, it refers to an electrode 2 which occupies more than 75% of the cymba surface. Therefore, taking into account the human anthropometric standards and the figures indicated in the table above, electrode 2 has a surface between 25 mm.sup.2 and 45 mm.sup.2, depending on variables such as the age, sex and size, etc. of the user.

[0139] The electrode 3 is placed in the cavum conchae where 45% are vagal endings that are also stimulated.

[0140] Both electrode 2 and electrode 3 are placed on an earmold 4 customized to the anatomy of the user in order to ensure the best possible quality of contact between the electrodes and the area to be stimulated.

[0141] On the other hand, according to Merrill, et al, 2005, cathodic stimulation (the stimulation pulse is negative) is 3 to 7 times more effective than anodic stimulation and the addition of a delay between the stimulation pulse and the reversal pulse reduces tissue damage and improves the effectiveness of the stimulation.

[0142] The auricular neurostimulator device 1 of this invention implements a cathodic stimulation pattern on electrode 2 (cymba) and a delay between the stimulation pulse and the reversal pulse (see image 8A).

[0143] In addition, the device 1 can execute BSF or EVAN protocols, in which stimulation is synchronized with the user’s exhalation, thus enhancing parasympathetic activation. During exhalation, the activation of arterial baroreceptors leads to the excitation of second-order neurons of the Nucleus Tractus Solitarii (NTS) that in turn increases premotor cardiovagal neuron firing rate. In addition, during inhalation, NTS receives inhibitory inputs from ventral respiratory nuclei in the medulla, reducing vagal outflow to the heart that could lead to respiratory sinus arrhythmia (RSA). As the dorsal medullary vagal system operates in tune with respiration, gating vagal afferent stimulation to the exhalation phase of respiration optimizes ABVN stimulation and its effects on cardiac vagal modulation.

[0144] Comfort. Transcutaneous electrical stimulation generates a throbbing sensation when the current density (amount of electrical current per unit area) is too high. The way to avoid this unpleasant sensation is to apply the electric current evenly over a large contact surface. To achieve this, device 1 of the invention uses large surface electrodes which are also placed in earmold 4 whose geometry is customized for each user. In this way, the contact zone between the electrodes and the stimulation zones is wide and of good quality so that the current can flow without concentrating excessively at any point.

[0145] Usability. The majority of auricular neurostimulators known in the state of the art consist of a large generator to which an accessory that applies an electrical voltage difference to some parts of the ear is connected by means of a cable. The volume and weight of the set limits its portability and consequently its availability for use. The auricular neurostimulation device 1 of the present invention, however, has been developed as a small, lightweight device that is comfortable to wear. Moreover, being configured as a wireless earbud or auricular, the user recognizes it as a familiar product so the adoption of use is very simple. In this regard, it is also important to highlight the technical characteristic that the miniaturized faceplate (12) incorporates inside it all the elements of an electronic circuit (6) built on a Printed Circuit Board (PCB) able to connect wirelessly with other devices or systems.

[0146] Personalization. The auricular neurostimulation device 1 of the invention includes two types of customizations: anatomical and therapeutic, as they will be explained in what follows. [0147] Anatomical customization consists of customizing the shape that is in contact with the user’s ear. To achieve this, a sample is taken from the user’s ear and then scanned. Another option is to scan the user’s ear directly in 3D. The 3D geometry generated by both options is used to create a custom earmold 4 to which the faceplate 12 is added with the electronic circuit 6, and the stimulating device 1 is manufactured. [0148] Therapeutic personalization consists of personalizing the electrical charge (dosis) introduced by the stimulation and the possibility of stimulating it in a synchronized manner together with the user’s breathing (EVANS/BFS protocols).

[0149] In addition, if the user integrates data from devices for continuous monitoring of cardiac activity such as watches, bracelets or rings, among others, the analysis of these data allows, for example, to know the pattern of evolution of stress of a user and define personalized stimulation treatments to prevent high peaks.

[0150] The auricular neurostimulation device 1 of the invention is a connected device, the connection of it being made through two pathways. On the one hand, it can connect wirelessly (e.g. via Bluetooth) to an application for a smartphone, which in turn is connected to a software in the cloud. On the other hand, the charging case 13 is connected to the software in the cloud, in order to be able to transmit the stimulator usage data, including those captured by the photoplethysmographic or biosensor 5.

[0151] In a broader way, as described earlier, the invention further relates to an auricular neurostimulation system comprising an auricular neurostimulation device 1 as described, an external charging case 13, and the connection of an internal application in the device to a cloud software for its correct connection and parametrization.

[0152] The method of operation of the auricular neurostimulation system according to the present invention comprises several steps, which are now described in detail.

[0153] Before stimulation. [0154] 1. The user creates an account on the system using the application for the smartphone or the web. For the registration, the user is asked for a series of personal data. [0155] 2. The system assigns an initial electrical charge value (therapeutic dose or reference value for non-therapeutic uses) to apply in each stimulation session and a maximum daily electrical charge, depending on the user’s profile. The initial values of the stimulation electric charge and the maximum daily electric charge are assigned on the basis of statistical studies. However, as the stimulator is used, the analysis of the data captured by photopletismographic or biosensor 5 allows these values to be customized. [0156] 3. Once the registration is complete, the user logs into the application and connects to device 1 to match its serial number to the user account, so device 1 is associated with the user. [0157] 4. The application asks the user to set his/her ‘perception and pain thresholds’ (this can be changed at a later stage). The pain threshold indicates that Aβ type fibres have been stimulated and Aδ and C type fibres are beginning to be stimulated. With the value of both thresholds, the application establishes the range in which the stimulation intensity must be placed, so that the stimulation is effective but also comfortable. The user can now choose the stimulation intensity that is most comfortable within the range set by the app. This value of intensity can be modified whenever the user wishes, but always within the range established by the app. [0158] 5. The user selects a stimulation protocol from those available (BEAT, BFS or EVANS types). The app sends the data of the protocol selected to device 1. From here on, the stimulator can operate autonomously without the need to be connected to the smartphone. This will only be necessary if the user wants to change the stimulation protocol or the intensity of stimulation.

[0159] Stimulation. [0160] 1. When the user takes the device 1 out of the charging case 13, the device detects it thanks to a magnetic switch connecting it to the case 13, so it is then activated. It also detects when it is in the ear thanks to the proximity detector of the photoplethysmographic or biosensor 5. If the stimulator is well placed in the user’s ear and therefore the impedance of contact of the electrodes with the stimulation zones is good, device 1 starts to stimulate automatically according to defined stimulation conditions. The stimulation can have therapeutic or non-therapeutic purposes. [0161] 2. The device 1 keeps track of the electrical charge it is inserting in the user’s ear. When it reaches the assigned value (therapeutic dose or reference value for non-therapeutic uses), it stops automatically. It also stops when it has reached the maximum daily limit or when the user removes the device (it is detected by the proximity detector of the photoplethysmographic sensor 5). [0162] 3. During stimulation, the photoplethysmographic or biosensor 5 stores temperature, hemoglobin and oxyhemoglobin readings of the user.

[0163] After stimulation. [0164] 1. Once the stimulation is completed, the device 1 downloads the session data (day and time, stimulation time, stimulation parameters and biosensor data) into the charging case 13 or the smartphone application 14 and prepares for the next session. The battery 10 of the device 1 is also recharged wirelessly in the case 13. [0165] 2. The charging case 13 or the smartphone application 14 sends the data from each stimulation session to the cloud, so the information can be properly analyzed. [0166] 3. The platform in the cloud stores the data of the sessions sent to it. [0167] 4. An algorithm analyses all the data to optimize the dose of electrical charge required by each user. If it is decided to change it, the platform sends the new values to the application so that the next stimulation is done with these newly modified values. [0168] 5. If the user has data available on the cloud platform obtained from devices for continuous monitoring of cardiac activity such as watches, bracelets or rings, among others, a further algorithm can send to the app a notification recommending stimulation sessions that prevent stress peaks.

[0169] Although the present invention has been described with reference to preferred embodiments thereof, many modifications and alterations may be made by a person having ordinary skill in the art without departing from the scope of this invention, which is defined by the appended claims.