Medical devices and methods for stimulating neurons of a patient to suppress their pathological synchronous activity

Abstract

The present invention relates to a medical device (10) for stimulating neurons in a patient to inhibit pathological synchronous activity of neurons. The device (10) includes a non-invasive stimulation unit (12) configured to simultaneously apply at least one auditory stimulus and at least one non-auditory stimulus to the patient's body, each of the at least one auditory stimulus and at least one non-auditory stimulus being configured to inhibit pathological synchronous activity when applied to the patient's body.

Description

Technical Field

[0001] This invention relates to a medical device and a corresponding method for stimulating a patient's neurons to inhibit pathological synchronous activity of the neurons. Background Technology

[0002] Some brain disorders, such as Parkinson's disease, are characterized by abnormally strong synchronous activity of neurons, that is, intensely synchronized neuronal firing or cluster firing. Besides Parkinson's disease, this can also apply to, for example, essential tremor, dystonia, post-stroke dysfunction, epilepsy, depression, migraine, tension headache, obsessive-compulsive disorder, irritable bowel syndrome, chronic pain syndrome, pelvic pain, borderline dissociative personality disorder, and post-traumatic stress disorder.

[0003] Pharmacological treatment of Parkinson's disease using methods such as L-DOPA may have limited efficacy and can cause significant long-term side effects. High-frequency deep brain stimulation (DBS) is the standard of care for patients with advanced, medically refractory Parkinson's disease. However, DBS requires surgery associated with significant risks. For example, implantation of deep electrodes in specific target areas of the brain can lead to bleeding. Furthermore, standard continuous high-frequency DBS can cause side effects.

[0004] Furthermore, non-invasive vibratory tactile stimulation therapy is known to counteract Parkinson's symptoms and can be applied to the patient's head area. Vibratory tactile stimulation is applied to the outer surface of the patient's head to generate a vibratory tactile stimulus designed to affect the pathological activity of the patient's neuronal clusters, particularly in the brain or spinal cord. This technique is known as co-reset stimulation, which allows for the counteraction of abnormal synchronization of neuronal clusters through desynchronization. Typically, to generate vibratory tactile stimulation, a vibratory tactile stimulation element is employed and actuated and secured to the patient's head.

[0005] Typically, when a vibratory tactile stimulation element is actuated, auditory stimulation is also perceived by the patient in addition to the vibratory tactile stimulation. This is caused by the sound waves generated when the stimulation element is actuated, which are conducted to the patient's inner ear through air and bone conduction. However, these auditory stimuli constitute an undesirable side effect, which often makes patients feel annoyed and uncomfortable, thus reducing compliance. This is particularly relevant when treatment is used frequently, such as for extended periods of time each day over weeks or months. Summary of the Invention

[0006] Starting with existing technologies, the aim is to provide an improved non-invasive medical device and corresponding method that can effectively suppress pathological synchronous activity of a patient's neuronal clusters.

[0007] This objective is achieved by the medical device and method according to the independent claim. Preferred embodiments are set forth in this specification, the accompanying drawings, and the dependent claims.

[0008] Therefore, a medical device is provided for stimulating neurons in a patient to inhibit pathological synchronous activity of the neurons. The medical device includes a non-invasive stimulation unit configured to simultaneously apply at least one auditory stimulus and at least one non-auditory stimulus to the patient's body, each of the at least one auditory stimulus and at least one non-auditory stimulus being configured to inhibit pathological synchronous activity when applied to the patient's body.

[0009] Furthermore, a medical method is provided for stimulating a patient's neurons to inhibit pathological synchronous activity of the neurons. This medical method includes the step of simultaneously and non-invasively applying at least one auditory stimulus and at least one non-auditory stimulus to the patient's body, each of the at least one auditory stimulus and at least one non-auditory stimulus being configured to inhibit pathological synchronous activity.

[0010] The proposed method refers to the method features corresponding to those defined in conjunction with the medical device. Therefore, the technical features defined in this disclosure in conjunction with the medical device can also be applied to and incorporated into the proposed method, and vice versa. Attached Figure Description

[0011] This disclosure will be more readily understood by referring to the following detailed description, when considered in conjunction with the accompanying drawings, in which:

[0012] Figure 1 This is a schematic diagram of a medical device used to stimulate a patient's neurons to inhibit pathological synchronous activity;

[0013] Figure 2 schematically shown Figure 1 The medical device depicted is used to provide stimulation to a patient's forehead;

[0014] Figure 3 schematically shown Figure 1 The medical device depicted in the image is used for another purpose: to provide stimulation to the patient's occipital bone.

[0015] Figure 4 The diagram schematically illustrates a sequence of actuation cycles according to a first configuration, wherein a non-invasive stimulating element of a medical device is actuated according to the sequence of actuation cycles to inhibit pathological synchronous activity; and

[0016] Figure 5 Another sequence of actuation cycles according to the second configuration is illustrated schematically. Detailed Implementation

[0017] The invention will now be described in more detail with reference to the accompanying drawings. In the drawings, the same elements are indicated by the same reference numerals, and repeated descriptions may be omitted to avoid redundancy.

[0018] Figure 1 A medical device 10 configured to stimulate a patient’s neurons to inhibit pathological synchronous activity of the neurons is illustrated schematically.

[0019] Device 10 is intended for the treatment of migraines, headaches, depression, obsessive-compulsive disorder, borderline personality disorder, and Parkinson's disease, but is not limited to these applications. Rather, the proposed medical device 10 can also be used to treat other neurological or psychiatric disorders, such as essential tremor, dystonia, epilepsy, tremor caused by multiple sclerosis and other pathological tremors, movement disorders, cerebellar disorders, Tourette syndrome, post-stroke dysfunction, spasms, tinnitus, sleep disorders, schizophrenia, irritable bowel syndrome, addiction disorders, personality disorders, attention deficit disorder, attention deficit hyperactivity disorder, gaming addiction, neurosis, eating disorders, burnout syndrome, fibromyalgia, migraines, cluster headaches, neuralgia, ataxia, tic disorders, or hypertension, etc.

[0020] The aforementioned diseases may be caused by disruptions in the bioelectrical communication of groups of neurons interconnected in specific circuits. Therefore, neuronal clusters generate continuous pathological neuronal activity and potentially associated pathological connections (network structures). In this respect, a large number of neurons form synchronized action potentials. This means that the neurons of interest fire excessively synchronously or in clusters. Additionally, pathological neuronal clusters exhibit oscillating neuronal activity, meaning that neurons fire rhythmically or in clusters. In the case of neurological or psychiatric diseases, the average frequency of the pathological rhythmic activity of the neuronal group of interest can range from approximately 1 Hz to 30 Hz, however, it can also be outside this range. In contrast, neurons in healthy individuals fire or in clusters in a different manner, for example, in an unrelated manner.

[0021] In other words, each of the aforementioned diseases is characterized by at least one cluster of neurons in the patient's brain or spinal cord exhibiting pathologically synchronized neuronal activity. To inhibit such pathologically synchronized activity, the medical device 10 is configured to stimulate the affected neuronal clusters to cause them to fire asynchronously or in clusters in an unrelated manner. Such a therapeutic technique is also known as coordinated repositioning stimulation.

[0022] In order to act on a patient's body and thus provide stimulation to the patient's neurons, device 10 includes a non-invasive stimulation unit 12 configured to provide various stimuli to the patient's body. In the context of this disclosure, the term "non-invasive" means that medical device 10, i.e., stimulation unit 12, achieves the desired therapeutic effect using a non-invasive process. In other words, the proposed medical device 10 does not require the implantation of components into the patient's body in connection with an interventional procedure.

[0023] The stimulation unit 12 is designed and configured to simultaneously apply at least one auditory stimulus and at least one non-auditory stimulus to a patient's body, each of the at least one auditory stimulus and the at least one non-auditory stimulus being configured to inhibit pathological synchronous activity when applied to the patient's body. More specifically, the stimulation unit 12 is designed to be capable of simultaneously generating multiple different auditory and non-auditory stimuli. For this purpose, the stimulation unit 12 includes a plurality of stimulation elements 14a to 14d, particularly at least two stimulation elements, which are configured to generate auditory and non-auditory stimuli to be applied to the patient's body. (The last sentence appears to be incomplete and possibly refers to a different context.) Figure 1 The medical device 10 shown includes at least four stimulating elements 14a to 14d, but is not limited to this number. It should be noted that satisfactory therapeutic effects can also be achieved using a medical device 10 having fewer or more than four stimulating elements 14. Therefore, according to another configuration, the stimulation unit 12 may include, for example, at least two, particularly between three and eight, or more, such as ten or twenty stimulating elements 14. In one configuration, the stimulation unit 12 may include three or five stimulating elements.

[0024] To correctly operate the different stimulation elements 14a to 14d, the stimulation unit 12 also includes a control unit 16, which is configured to selectively actuate the stimulation elements 14a to 14d. In this way, the individual stimulation elements 14a to 14d can be actuated independently of each other. Furthermore, the control unit 16 is configured to actuate the stimulation elements 14a to 14d in a varied manner to produce different stimuli, i.e., different stimuli in terms of stimulation duration, vibration frequency, vibration amplitude, etc. The control unit 16 is connected to each of the stimulation elements 14a to 14d via connecting lines, and control signals are guided through the connecting lines for actuating the stimulation elements 14a to 14d.

[0025] If possible Figure 1The stimulation unit 12 is embedded or included in a band or strap 18, which is configured to be releasably and adjustablely fastened to the patient's body, for example, by means of a Velcro fastener. Specifically, the band 18 is designed such that, with the band 18 fastened to the patient's body, the stimulation elements 14a to 14d are positioned at different locations on the patient's body, i.e., spaced apart from each other. For example, a medical device 10 can be provided such that, with the medical device 10 fastened, a plurality of stimulation elements 14a to 14d are arranged in at least one array to position the stimulation elements 14a to 14d respectively to predetermined areas on the patient's body surface to achieve the desired therapeutic effect.

[0026] Figure 2 One embodiment of a medical device 10 is depicted, which is provided in the form of a headband configured to be fastened to a patient's forehead. In this configuration, the medical device 10 is intended for the treatment of migraines, headaches, depression, obsessive-compulsive disorder, borderline personality disorder, and / or other mental disorders. (As can be seen from...) Figure 2 In this configuration, the medical device 10 includes four stimulating elements 14 arranged in a linear array. These stimulating elements 14 are positioned in the area of ​​the cutaneous segment of the trigeminal nerve in the patient's forehead with the medical device 10 secured thereto to stimulate the ophthalmic nerve or trigeminal nerve, particularly the ophthalmic nerve. Figure 2 In this context, "Trig.1" refers to the first branch of the trigeminal nerve. In this manner, with the medical device 10 secured, the stimulation unit 12 is configured to provide auditory stimulation to the patient's inner ear and non-auditory stimulation to the patient's skin in the region of the first branch of the trigeminal nerve, Trig.1. Figure 2 The diagram also shows the second branch Trig.2 and the third branch Trig.3 of the trigeminal nerve, as well as the C2 to C4 dermatomes. In other configurations, the illustrated medical device 10 may include an array of two stimulating elements 14, for example, each of the array of stimulating elements 14 may include four stimulating elements 14 arranged in a row.

[0027] Figure 3 Another embodiment of the medical device 10 is depicted, which is provided in the form of a headband configured to be fastened to the occipital bone of a patient. In this configuration, the medical device 10 is intended for treating dysphagia (swallowing problems) and / or drooling (excessive salivation), such as dysphagia (swallowing problems) and / or drooling (excessive salivation) caused by Parkinson's disease. (The last sentence appears to be incomplete and possibly refers to a different embodiment.) Figure 3 In this configuration, the medical device 10 includes eight stimulating elements 14 arranged in two arrays, each array including four stimulating elements 14 arranged in a row. Figure 3As depicted, in the secured state of the medical device 10, which is fastened to the patient's occipital bone, the stimulation element 14 is arranged to stimulate the C2 and C3 dermatomes. In this way, in the secured state of the medical device 10, the stimulation unit 12 is configured to provide auditory stimulation to the patient's inner ear and non-auditory stimulation to the skin in the areas of the patient's C2 and C3 dermatomes. Figure 3 The image also shows dermatomes C4 to C6.

[0028] In other embodiments, the medical device 10 may be combined with Figure 2 and Figure 3 The headband form of the above-described embodiments is provided. Therefore, in this configuration, the medical device 10 is configured to stimulate the patient's forehead and occipital bone, and may include at least two or four stimulating elements for stimulating the patient's forehead and at least two or four stimulating elements for stimulating the patient's occipital bone.

[0029] The characteristics of the stimulation unit 12 in each of the above embodiments of the medical device 10 that is associated with the present invention are further described below, particularly in view of its structural configuration and operational characteristics.

[0030] As described above, the stimulation unit 12 includes a plurality of stimulation elements 14a to 14d configured to generate auditory and non-auditory stimuli. Generally, the terms "stimulus" or "stimuli" refer to excitations that can be sensed by the patient's body—that is, by corresponding receptors in, for example, the patient's eyes, ears, and / or skin, depending on the form of the stimulus—directed from, for example, the patient's eyes, ears, and / or skin to the patient's nervous system, thereby actuating neurons in the patient's brain or spinal cord. In the context of this disclosure, a distinction is made between the two forms of stimulation, namely, auditory and non-auditory stimuli.

[0031] Generally, the term "auditory stimulus" refers to an excitation sensed by receptors located in a patient's ear, particularly the inner ear. These excitations are typically delivered to the inner ear as sound waves via air and bone conduction. Therefore, in the context of this disclosure, the term "non-auditory stimulus" refers to any stimulus that does not constitute an auditory stimulus. For example, a non-auditory stimulus can refer to any of the mechanical stimuli, particularly tactile or vibratory stimuli, light stimuli, electrical stimuli, and thermal stimuli. These stimuli may be sensed by corresponding receptors, such as those in the patient's skin or eyes.

[0032] As described above, the stimulation unit 12 is configured and designed to simultaneously apply at least one auditory stimulus and at least one non-auditory stimulus to the patient's body, wherein each of the at least one auditory stimulus and the non-auditory stimulus is configured to inhibit pathological synchronous activity when applied to the patient's body. In other words, each of the auditory and non-auditory stimuli is configured to perform a coordinated repositioning stimulus. In one mode of operation of the medical device 10, the non-auditory stimulus may be configured to inhibit pathological synchronous activity when applied to the patient's body, while the auditory stimulus may not be configured to inhibit pathological synchronous activity when applied to the patient's body.

[0033] More specifically, the stimulation unit 12 is provided such that at least one auditory stimulus is configured to inhibit pathological synchronous activity of a first neuronal subcluster when applied to the patient's body. Furthermore, the stimulation unit 12 is provided such that at least one non-auditory stimulus is configured to inhibit pathological synchronous activity of a second neuronal subcluster that is different from or demarcated from the first neuronal subcluster when applied to the patient's body.

[0034] In order to inhibit neuronal clusters affected by pathological synchronous activity, each of the auditory and non-auditory stimuli is provided to at least partially actuate the affected neuronal clusters when sensed by corresponding receptors in the patient's body and directed to their nervous system. For this purpose, the form and characteristics of the generated stimuli and the intended location within the patient's body are respectively configured, as described in more detail below.

[0035] In the illustrated configuration, to provide non-auditory stimulation, the stimulation unit 12 is configured to generate tactile or vibratory stimulation, also known as vibratory-tactile stimulation, to be applied to corresponding receptors in the patient's skin, particularly in the patient's head region. Typically, human skin includes different types of mechanoreceptor afferent units capable of sensing tactile or vibratory stimuli. The distribution and density of these different types of mechanoreceptors typically vary depending on their location on human skin.

[0036] To selectively stimulate the patient's desired mechanosensory afferent unit, the stimulation unit 12 includes a plurality of vibratory tactile stimulation elements 14a to 14d configured to generate non-auditory stimuli in the form of vibratory tactile stimulation. Specifically, each of the vibratory tactile stimulation elements 14a to 14d is configured to act oscillatingly or periodically on the surface of the patient's body to apply non-auditory stimulation to the patient's body. Thus, the non-auditory stimulation to be applied to the patient's body constitutes a periodic or oscillatory stimulus, i.e., its amplitude or intensity changes periodically over time.

[0037] More specifically, according to one configuration, the vibratory tactile stimulation elements 14a to 14d include a rod or any other component configured to act mechanically on a patient's skin. For this purpose, the stimulation elements 14a to 14d include an electromechanical actuator for converting electrical energy into movement of the rod. For example, the electromechanical actuator may be an equal current motor, a voice coil, a transformer made of an electroactive polymer that changes its shape when an electric current is applied, or a piezoelectric transducer. To provide electrical energy to the electromechanical actuator, the stimulation unit 12 may include or be connected to an energy source, particularly an energy source provided in the form of a battery.

[0038] To this end, in order to provide auditory stimulation, the stimulation unit 12 also includes a corresponding auditory stimulation element 14, which is configured to generate auditory stimulation to be applied to the patient's inner ear. Specifically, the auditory stimulation element 14 is configured to generate sound waves that are delivered to the patient's inner ear via air and / or bone conduction to apply auditory stimulation.

[0039] Typically, the auditory stimulation element 14 can be provided in the form of any suitable component capable of selectively generating sound waves. Therefore, the auditory stimulation element 14 can be provided in the form of a loudspeaker, which can be provided separately from the band 18. In the illustrated configuration, the auditory stimulation element 14 is composed of vibratory tactile stimulation elements 14a to 14d. In other words, each of the stimulation elements 14a to 14d is configured to generate both auditory and non-auditory stimuli. Therefore, the stimulation unit 12 is configured to simultaneously generate auditory and non-auditory stimuli when the corresponding stimulation elements 14a to 14d are oscillatingly or periodically actuated. In other words, the stimulation unit 12 is configured to generate auditory stimuli while generating non-auditory stimuli. Thus, each of the stimulation elements 14a to 14d is configured to provide, upon actuation, a set of stimuli consisting of non-auditory stimuli and associated auditory stimuli. Therefore, each auditory stimulus is associated with a non-auditory stimulus, wherein stimulation unit 12—that is, each of stimulation elements 14a to 14d—is configured to generate a non-auditory stimulus and an associated auditory stimulus.

[0040] Specifically, the stimulation unit 12 is provided such that each of the plurality of stimulation elements 14a to 14d is actuated at an actuation frequency v within the range of human hearing, i.e., between 20 Hz and 20 kHz. For example, stimulation element 14 is actuated at an actuation frequency v within the range of 20 Hz to 250 Hz. Alternatively or additionally, stimulation elements 14a to 14d may be actuated in a frequency range associated with low-frequency tones, i.e., between 200 Hz and 600 Hz or between 330 Hz and 600 Hz, which may be perceived as relaxing and pleasant by the patient. Specifically, stimulation elements 14a to 14d are configured such that they can be selectively and variedly actuated at different actuation frequencies within the indicated frequency range.

[0041] In the following text, refer to Figure 4 The operation of the medical device 10, specifically its stimulation unit 12, is specified in more detail. During operation, the control unit 16 is configured to selectively and intermittently actuate different stimulation elements 14a to 14d. Specifically, the control unit 16 is configured to perform sequential actuation cycles T. A1-Ai Sequence C actuates stimuli 14a to 14d, where the character "i" refers to the total number of actuation cycles within sequence C. Figure 4 The continuous actuation cycle T is shown. A1-Ai The sequence C, whose formation illustrates the control sequence or control mode of actuation of the corresponding actuating elements 14a to 14d over time. Specifically, in Figure 4 In the middle, by means of the actuation period T A The dashed areas within indicate the actuation of the corresponding stimulation elements 14a to 14d.

[0042] Sequence C consists of i time-shifted, non-overlapping actuation periods T. A1-Ai During this period, at least one of the stimulating elements 14a to 14d is actuated to produce auditory stimulus S. A Non-auditory vibrational tactile stimulation S V Both. To distinguish the auditory stimuli S to be generated by the corresponding stimuli 14a to 14d. A Non-auditory stimulus S V The different patterns in the dashed area, that is, regarding their orientation and line thickness, were chosen by... Figure 4 As indicated by the legend in the diagram. Actuation period T A1-Ai The duration corresponds to the corresponding stimulus S generated by stimulating elements 14a to 14d. A S V The length of the actuation cycle. For example, the actuation cycle can have a duration between 25ms and 3s, especially 100ms or 125ms.

[0043] In the sequential actuation cycle TA1-Ai Between these, there is an interval period T. R1-Ri During this period, the patient's body is not subjected to stimulation generated by stimulation unit 12. Interval period T R1-Ri The length of the interval period T can vary or remain constant during sequence C. R The length can be 0s, allowing two sequential actuation cycles to follow each other directly. In alternative configurations, the actuation cycles within a sequence can at least partially overlap.

[0044] During the actuation period T A During this period, the control unit 16 can be configured to actuate only one of the stimulation elements 14a to 14d or to actuate more than one of the stimulation elements 14a to 14d simultaneously. In one configuration, the control unit 16 is configured to actuate for each actuation cycle T A The variation is determined in the corresponding actuation period T A The number n of stimulation elements 14a to 14d to be simultaneously actuated during the period. In this context, the term "variably" means that the value of the number n varies differently, specifically non-periodicly, over the sequence C. Specifically, the parameter n is an integer greater than 1. If n equals 1, this means that during the corresponding actuation period T... A During this period, only one of the stimulation elements 14a to 14d is actuated. If n is greater than 1, this means more than one, i.e., n stimulation elements 14a to 14d are actuated in the corresponding actuation period T. A It was activated simultaneously during the period.

[0045] Regarding the control unit 16, it is used to vary the determination of the corresponding actuation cycle T. A The number n of different stimulation elements 14a to 14d to be simultaneously activated during the period, and the number used to determine the actuation period T. A and the corresponding interval period T R The specific process and implementation method for determining the length are explicitly referenced in the published international application WO 2019 / 243634 A1. Specifically, the control unit 16 can employ methods for varying the determination of the length in the corresponding actuation cycle T. A The number n of different stimuli 14a to 14d to be simultaneously actuated, and the method used to determine the actuation period T. A and the corresponding interval period T R The length is determined by at least one of the following algorithmic methods: deterministic, random, chaotic, and (pseudo) random.

[0046] If possible Figure 4 The stimulation elements 14a to 14d obtained in the process are at a predetermined frequency v. 1-4 When actuated, auditory stimulus S is generated simultaneously. A and vibrational tactile stimulation S VThe stimulation unit 12, i.e., its control unit 16, is configured to operate at different actuation frequencies v. 1-4 Different stimulation elements 14a to 14d are operated. In other words, in the illustrated configuration, the actuation frequency of the corresponding stimulation elements 14a to 14d is different among the different stimulation elements 14a to 14d.

[0047] During sequence C, at a substantially constant and identical actuation frequency v 1-4 Each stimulation element 14a to 14d is actuated. Specifically, when actuated by the control unit 16, the first stimulation element 14a operates at a first actuation frequency v1, the second stimulation element 14 operates at a second actuation frequency v2, the third stimulation element 14c operates at a third actuation frequency v3, and the fourth stimulation element 14d operates at a fourth actuation frequency v4.

[0048] More specifically, the stimulation unit 12 is configured to actuate the stimulation elements 14a to 14d, particularly to simultaneously actuate them at an actuation frequency v. 1-4 It is adjusted to a musical scale. In other words, the stimulation unit 12 can be set with a predetermined set of actuation frequencies v that can actuate individual stimulation elements 14a to 14d. 1-4 Among them, the actuation frequency v 1-4 That is, the various components of the aforementioned set of actuating frequencies constitute, in particular, at least a portion of a musical scale. In this way, the effectiveness of treatment and patient acceptability can be improved.

[0049] To further improve the effectiveness of treatment and / or patient acceptability, the actuation frequency is adjusted to the consonant frequency of a musical scale.

[0050] In another development, the stimulation unit 12 can be configured such that the actuation frequency v 1-4 This means that the individual components of the set of actuation frequencies are tuned to a pentatonic scale. In this way, a particularly acceptable, smooth, and / or relaxing sequence of auditory stimuli can be provided. Furthermore, the pentatonic frequencies can provide the advantageous effect of being smoothly combined.

[0051] Specifically, the stimulation unit 12 may be configured with a set of different actuation frequencies v that constitute at least a portion of a pentatonic scale. 1-5 Starting from the first actuation frequency v1, other frequencies to be included in the set of actuation frequencies can be determined or calculated based on at least one of the following equations (1) to (4):

[0052] v2 = v1 * 9 / 8, (1)

[0053] v3 = v1 * 5 / 4, (2)

[0054] v4 = v1 * 3 / 2, and (3)

[0055] v5 = v1 * 5 / 3, (4)

[0056] Specifically, v1 can have a value of, for example, 200 Hz or 220 Hz, or any other value in the range of 200 Hz to 600 Hz. Therefore, v1 can be the frequency of piano keys or any other musical instrument.

[0057] In the context of the proposed medical device 10, it has been found that the above-mentioned advantageous effects can also be achieved by using the octave scale of the various components included in a set of actuation frequencies. Therefore, alternatively or additionally, other actuation frequencies to be included in a set of actuation frequencies can be calculated based on at least one of the following equations:

[0058] v6=2 k *v1, (5)

[0059] v7=2 k *v2, (6)

[0060] v8=2 k *v3, (7)

[0061] v9=2 k *v4, and (8)

[0062] v 10 =2 k *v5, (9)

[0063] Where k is a natural number equal to or greater than 1, such as 1, 2, 3 or 4.

[0064] Furthermore, the stimulation unit 12 can be configured to adjust the vibration amplitude of each of the different stimulation elements 14a to 14d. Specifically, the stimulation unit 12 can be configured to adjust the vibration amplitude of each of the different stimulation elements 14a to 14d according to the patient's auditory stimulation S. A Or non-auditory stimulus S V The vibration amplitude of each of the different stimulation elements 14a to 14d is adjusted according to the patient's perception. For this purpose, the stimulation unit 12 can be configured to adjust the vibration amplitude of each of the different stimulation elements 14a to 14d according to the patient's instructions regarding auditory stimulation S. A Non-auditory stimulus S V The amplitude of vibration of each of the different stimulus elements 14a to 14d is adjusted by at least one of the corresponding proprioceptive perception, corresponding loudness perception, or any other parameter.

[0065] As explained above, in Figure 4 In the configuration depicted, the stimulation unit 12 is configured such that the actuation frequency of each of the stimulation elements 14a to 14d is such that during operation (i.e., during the actuation period T)A The sequence (C) remains constant or unchanged during the period.

[0066] In another development, the stimulation unit 12 can be configured to actuate at least one stimulation element 14a to 14d at different stimulation frequencies v. In other words, the stimulation unit 12 can be configured such that the actuation frequency of at least one stimulation element 14a to 14d varies over time. For example, the stimulation unit 12 can be configured such that the actuation frequency of at least one stimulation element 14a to 14d varies over the actuation period T. A The frequency of actuation varies during the actuation period T. Alternatively or additionally, the stimulation unit 12 may be configured such that the actuation frequency of at least one stimulation element 14a to 14d varies during the actuation period T. A It remains constant during the period, but between sequences C, i.e., within the sequential actuation period T. A The frequency varies between these intervals. This means, for example, that the first stimulating element 14a can vary during the first actuation cycle T. A1 It operates at the first actuation frequency v1 during the period and can operate in another actuation cycle T. A At different actuation frequencies, such as the second, third, or fourth actuation frequency v 2-4 Or operate at any other actuation frequency. Specifically, the actuation frequency of the corresponding stimulation elements 14a to 14d can be changed such that they are sequentially increased or decreased, particularly by being sequentially adjusted to include an increasing or decreasing frequency within a set of predefined actuation frequencies.

[0067] In one configuration, the stimulation unit 12 can be configured such that each stimulation element 14a to 14d is variedly selected at the corresponding actuation period T. A During this period, the stimulation elements 14a to 14d are to be actuated at which actuation frequency, included in a predetermined set of actuation frequencies. Specifically, for this purpose, the control unit 12 can be configured to randomly and / or deterministically and / or randomly determine, in combination and / or determine at the corresponding actuation cycle T for each stimulation element 14a to 14d. A During this period, the stimulation elements 14a to 14d are to be actuated at which actuation frequency is included in a predetermined set of actuation frequencies. For this purpose, in such a configuration, the control unit 16 can be configured to ensure that during the actuation cycle T... A Within each of the elements, stimulation elements 14a to 14d operate at different actuation frequencies.

[0068] Figure 5 Operation of a medical device 10 according to another configuration is illustrated. In this configuration, the medical device 10 includes: a set of first actuating elements 20a to 20d configured to generate auditory stimulation S for inhibiting pathological synchronous activity of neurons. A; and a set of second actuating elements 22a to 22d, configured to generate non-auditory vibratory tactile stimuli S for inhibiting pathological synchronous activity of neurons. A The first stimulation elements 20a to 20d and the second stimulation elements 22a to 22d constitute independent components of the stimulation unit 12. The first stimulation elements 20a to 20d may be provided as a single component, for example, in the form of a speaker configured to generate multiple auditory stimuli simultaneously.

[0069] In this configuration, the control unit 16 is configured to be controlled by... Figure 5 The first operating mode shown in sequence C1 and the one by Figure 5 The second operating mode is operated on the stimulation unit 12 as shown in sequence C3.

[0070] Specifically, in the first operating mode, the control unit 16 is configured to operate the stimulation unit 12, causing the auditory stimulus S to... A The generation of the stimulus is paired with or associated with the generation of the non-auditory stimulus. Therefore, the control unit 16 is configured to control the first actuating elements 20a to 20d and the second actuating elements 22a to 22d, such that the non-auditory stimulus S... V The auditory stimulus S associated with it A Simultaneously or together, each of the first stimulating elements 20a to 20d is associated with one of the second stimulating elements 22a to 22d in such a way that the first stimulating elements 20a to 20d and their associated second stimulating elements 22a to 22d generate a non-auditory stimulus S. V and its associated auditory stimulus S A A corresponding set of stimuli. From Figure 5 As can be seen from the diagram, in the configuration shown, the following pairs of first and second stimulating elements are simultaneously actuated and are therefore correlated with each other: 20a-22a; 20b-22b; 20c-22c; and 20d-22d.

[0071] The first stimulating elements 20a to 20d are actuated at an actuation frequency v', which depends on the actuation frequency v of their associated second stimulating elements 22a to 22d. Specifically, each of the first stimulating elements 20a to 20d can be actuated at an actuation frequency v' that is equal to or constitutes a harmonic of the actuation frequency v of its associated second stimulating elements 22a to 22d. Therefore, the actuation frequency v' of each of the first stimulating elements 20a to 20d can be 1 / m or m / 1 of the actuation frequency v of its associated second stimulating elements 22a to 22d, where m is a natural number greater than 1. Furthermore, the frequency v” of the sound waves generated by the corresponding first stimulating elements 20a to 20d and transmitted to the patient's inner ear can be 1 / m or m / 1 of the actuation frequency v of the associated second stimulating elements 22a to 22d. Alternatively or additionally, the actuation frequency v' of each first stimulating element 20a to 20d and / or the frequency v” of the sound waves generated by the corresponding first stimulating elements 20a to 20d and the actuation frequency v of the associated second stimulating elements 22a to 22d can be adjusted to a pentatonic scale. In other words, the actuation frequency v' and / or the frequency v” and the actuation frequency v of the associated second stimulating elements 22a to 22d can constitute part of a pentatonic scale. Therefore, the actuation frequency v' and / or the frequency v” can be related to the actuation frequency v of the associated second stimulating elements 22a to 22d, or can be calculated based on at least one of the following equations (10) to (14):

[0072] v ′ / ″ =v*2 l (10)

[0073]

[0074]

[0075]

[0076]

[0077] Where v ′ / ″ It refers to the actuation frequency v' of each first stimulation element 20a to 20d and / or the frequency v” of the sound wave generated by the corresponding first stimulation element 20a to 20d; where v refers to the actuation frequency of the associated second stimulation element 22a to 22d; and l refers to a natural number equal to or greater than 0.

[0078] Therefore, in the second operating mode of the stimulation unit 12, the control unit 16 is configured to operate the first stimulation elements 20a to 20d and the second stimulation elements 22a to 22d, so that the auditory stimulation S A With non-auditory stimulus S V The generation is unrelated to the generation. From Figure 5As can be seen, in the second operating mode, i.e., within the second sequence C2, the patient did not experience non-auditory stimulation S. V .

[0079] In the second operating mode, the control unit 16 is configured to vary the actuation cycle T. A The number n of the first stimulating elements 20a to 20d to be simultaneously actuated during the period, and the selection varies during the actuation cycle T. A During this period, it is determined which of the first stimulation elements 20a to 20d should be actuated. To this end, the control unit 16 can be configured to randomly and / or deterministically and / or a combination of random and deterministic determination at the corresponding actuation cycle T. A The number n of the first stimulation elements 20a to 20d to be simultaneously actuated during the period. Furthermore, the control unit 16 can be configured to randomly and / or deterministically and / or randomly determined combinations of selection during the corresponding actuation cycle T. A During this period, which of the first stimulatory elements 20a to 20d should be activated?

[0080] By operating the stimulation unit 12 in the first operating mode, the principles of conditioned and / or associative learning can be used to effectively downregulate the weights of abnormal synapses. More specifically, by combining auditory stimuli with non-auditory stimuli, conditioned or associative learning can be provided in a specific, natural manner, thereby increasing patient acceptability of treatment.

[0081] In the proposed medical device 10 according to any of the above configurations, all actuation frequencies, i.e., the different stimulation elements 14; 20a to 20d, 22a to 22d thereunder, are operated in a manner, in particular, such that they are adjusted to a predefined pentatonic scale and are related to each other. For this purpose, a fundamental actuation frequency v0 of one of the stimulation elements, in particular one of the second stimulation elements 22a to 22d, can be determined or provided, based on which all other actuation frequencies of the remaining stimulation elements are adjusted. For this purpose, other actuation frequencies v can be related to the fundamental actuation frequency v0 based on at least one of the following equations (15) to (19):

[0082] v = v0 * 2 l (15)

[0083]

[0084]

[0085]

[0086]

[0087] Where 1 refers to a natural number equal to or greater than 0. Furthermore, note that the actuation frequencies of the stimulation elements 14; 22a to 22d configured to generate auditory stimuli can refer to, in particular, equal to, the frequency of the sound waves generated by the stimulation element and transmitted to the patient's inner ear.

[0088] It will be apparent to those skilled in the art that these embodiments and items merely depict examples of a variety of possibilities. Therefore, the embodiments shown herein should not be construed as limiting these features and configurations. Any possible combination and configuration of the features can be selected according to the scope of the invention.

[0089] This is especially true regarding the following optional features, which can be combined with some or all of the previously mentioned implementations, items and / or features in any technically feasible combination.

[0090] A medical device is provided for stimulating neurons in a patient to inhibit pathological synchronous activity of the neurons. The medical device includes a non-invasive stimulation unit configured to simultaneously apply at least one auditory stimulus and at least one non-auditory stimulus to the patient's body, each of the at least one auditory stimulus and at least one non-auditory stimulus being configured to inhibit pathological synchronous activity when applied to the patient's body.

[0091] As mentioned above, the abnormally strong neuronal synchronization that induces several brain diseases, including Parkinson's disease, may be caused by abnormally upregulated synaptic connections. Downregulating synaptic weights is particularly advantageous in order to counteract this abnormal neuronal synchronization process in a long-term, sustained manner.

[0092] It has been found that effective downregulation of abnormal synaptic weights can be achieved by mutually activating neuronal clusters with stimuli of different compositions (i.e., in terms of location and form). Therefore, by providing a medical device configured to simultaneously administer at least one auditory stimulus and at least one non-auditory stimulus for the purpose of inhibiting pathological synchronicity, the proposed device can effectively inhibit the pathological synchronicity of neurons, i.e., by desynchronizing the pathological synchronicity of neurons.

[0093] Specifically, the medical device can be configured to be fastened to the patient's head, wherein, in the fastened state of the medical device, the stimulation unit can be configured to provide auditory stimulation to the patient's ears and non-auditory stimulation to the patient's skin in the forehead region, particularly the first branch of the trigeminal nerve. Alternatively or additionally, the stimulation unit can be configured to provide non-auditory stimulation to the patient's skin in the occipital region, particularly to the C2 or C3 dermatomes.

[0094] In another development, a stimulation unit may be provided such that auditory stimulation is configured to, when applied to a patient's body, inhibit pathological synchronous activity of a first neuronal cluster, particularly in at least one of the patient's brain or spinal cord. Alternatively or additionally, non-auditory stimulation may be configured to, when applied to a patient's body, inhibit pathological synchronous activity of a second neuronal cluster, particularly in at least one of the patient's brain or spinal cord, which is distinct from or separated from the first neuronal cluster.

[0095] Specifically, at least one non-auditory stimulus is a mechanical stimulus, particularly a vibratory tactile stimulus.

[0096] In another development, each of at least one auditory stimulus can be associated with a non-auditory stimulus. Furthermore, the stimulus unit can be configured to simultaneously generate a non-auditory stimulus and its associated auditory stimulus.

[0097] The stimulation unit may include at least one vibratory tactile stimulation element configured to act oscillatingly or periodically on the surface of the patient's body to apply non-auditory stimulation to the patient's body.

[0098] In another development, the stimulation unit can be configured to simultaneously generate auditory and non-auditory stimuli when the vibratory tactile stimulation element is oscillatingly or periodically actuated. Alternatively, the stimulation unit may include at least one auditory stimulation element for generating auditory stimuli. The auditory stimulation element may be disposed separately from the vibratory stimulation element. Furthermore, the stimulation unit can be configured to simultaneously actuate the vibratory tactile stimulation element and the auditory stimulation element to generate both non-auditory and auditory stimuli simultaneously.

[0099] Vibratory tactile stimulators and auditory stimulators can be actuated in the range of 20 Hz to 20 kHz, especially at actuation frequencies in the range of 20 Hz to 250 Hz or 200 Hz to 600 Hz.

[0100] The stimulation unit may include at least two vibratory tactile stimulation elements or any other stimulation elements for generating non-auditory and / or auditory stimuli. Each of the at least two stimulation elements may be configured to generate one of at least two non-auditory stimuli, and wherein the stimulation unit is configured to operate the at least two stimulation elements at different actuation or vibration frequencies. In another development, the actuation or vibration frequency actuating the stimulation elements may be tuned to a musical scale, particularly a pentatonic scale.

[0101] Furthermore, the stimulation unit can be configured with a set of different actuation frequencies. This set of actuation frequencies may include actuation frequencies under which at least one stimulation element can be actuated, specifically predefined actuation frequencies. In other words, the stimulation element can be configured to be actuated at actuation frequencies included in this set of actuation frequencies. Therefore, it is possible to prevent the stimulation element from being operated at actuation frequencies not included in this set of actuation frequencies.

[0102] The set of actuation frequencies may include a first actuation frequency and at least one additional actuation frequency determined based on or related to the first actuation frequency. In this way, when determining the first actuation frequency, at least one additional actuation frequency may also be determined.

[0103] Specifically, at least one of the different actuation frequencies in the set can be related to the first actuation frequency, or can be determined based on the first actuation frequency according to at least one of the following equations (20) to (28):

[0104]

[0105]

[0106]

[0107]

[0108] v6 = v1 * 2 k , (twenty four)

[0109]

[0110]

[0111]

[0112]

[0113] Where v1 refers to the first actuation frequency; v2 to v 10 Each of these refers to at least one other actuation frequency; and k is a natural number equal to or greater than 1.

[0114] In another development, the stimulation unit may include: at least one first stimulation element configured to apply at least one auditory stimulus; and at least one second stimulation element configured to apply at least one non-auditory stimulus, wherein each first stimulation element is associated with one of the at least one second stimulation element in such a way that the first stimulation element and the associated second stimulation element are actuable to simultaneously generate auditory and non-auditory stimuli.

[0115] Alternatively or additionally, the stimulation unit may include a control unit for controlling the operation of the stimulation unit, particularly its stimulating elements. Specifically, the control unit may be configured to operate the stimulation unit in a first operating mode and a second operating mode, in which the generation of auditory stimuli is associated with or paired with the generation of non-auditory stimuli, and in the second operating mode, the generation of auditory stimuli is independent of the generation of non-auditory stimuli.

[0116] Furthermore, a medical method is provided for stimulating neurons in a patient to inhibit pathological synchronous activity of the neurons. The method includes the step of simultaneously and non-invasively applying at least one auditory stimulus and at least one non-auditory stimulus to the patient's body, each of the at least one auditory stimulus and at least one non-auditory stimulus being configured to inhibit pathological synchronous activity.

[0117] List of reference numerals

[0118] 10 Medical Equipment

[0119] 12 stimulation units

[0120] 14 Stimulating elements

[0121] 16 Control Unit

[0122] 18 belts

[0123] 20 Stimulating elements used to generate auditory stimuli

[0124] 22 Stimulating elements used to generate non-auditory stimuli

[0125] C Actuation Cycle Sequence

[0126] S A auditory stimulation

[0127] S V Non-auditory stimulation

[0128] T A Actuation cycle

[0129] T R Interval period

[0130] v Actuation frequency

Claims

1. A medical device for stimulating neurons in a patient to inhibit pathological synchronous activity of said neurons, said medical device comprising a non-invasive stimulation unit configured to simultaneously apply at least one auditory stimulus and at least one non-auditory stimulus to the patient's body, each of said at least one auditory stimulus and said at least one non-auditory stimulus being configured to inhibit said pathological synchronous activity when applied to the patient's body. in, The stimulation unit includes a vibratory tactile stimulation element configured to oscillate or periodically act on the surface of the patient's body to simultaneously apply the non-auditory stimulation and the auditory stimulation to the patient's body. The stimulation unit is configured to simultaneously generate the auditory stimulus and the non-auditory stimulus when the vibratory tactile stimulation element is oscillatingly or periodically actuated. When applied to the patient's body, the auditory stimulus is configured to inhibit pathological synchronous activity of a first neuronal cluster, and the non-auditory stimulus is configured to inhibit pathological synchronous activity of a second neuronal cluster, which is different from or separated from the first neuronal cluster.

2. The medical device according to claim 1, wherein, The auditory stimulus is configured to inhibit pathological synchronous activity of the first neuronal cluster in at least one of the patient's brain or spinal cord, and the non-auditory stimulus is configured to inhibit pathological synchronous activity of the second neuronal cluster in at least one of the patient's brain or spinal cord.

3. The medical device of claim 1, wherein the medical device is configured to be fastened to the patient's head, wherein, With the medical device secured to the patient's head, the stimulation unit is configured to provide auditory stimulation to the patient's ears and non-auditory stimulation to the patient's skin in the forehead region or to the patient's skin in the occipital region.

4. The medical device according to claim 3, wherein, The stimulation unit is configured to provide the non-auditory stimulation to the first branch of the trigeminal nerve or to the C2 or C3 dermatome.

5. The medical device according to any one of claims 1 to 4, wherein, The at least one non-auditory stimulus is a vibratory tactile stimulus.

6. The medical device according to any one of claims 1 to 4, wherein, Each of the at least one auditory stimulus is associated with a non-auditory stimulus, and wherein the stimulus unit is configured to simultaneously generate a non-auditory stimulus and its associated auditory stimulus.

7. The medical device according to any one of claims 1 to 4, wherein, The vibratory tactile stimulation element is actuated at an actuation frequency in the range of 20 Hz to 20 kHz.

8. The medical device according to claim 7, wherein, The vibratory tactile stimulation element is actuated at an actuation frequency ranging from 20 Hz to 250 Hz or from 200 Hz to 600 Hz.

9. The medical device according to any one of claims 1 to 4, wherein, The stimulation unit includes at least two vibratory tactile stimulation elements, each of which is configured to generate one of at least two non-auditory stimuli, and wherein the stimulation unit is configured to operate the at least two stimulation elements at different actuation frequencies.

10. The medical device according to claim 9, wherein, The actuation frequency for actuating the stimulating element is adjusted to a musical scale.

11. The medical device according to claim 10, wherein, The actuation frequency for actuating the stimulating element is adjusted to a pentatonic scale.

12. The medical device according to any one of claims 1 to 4, wherein, The stimulation unit is configured with a set of different actuation frequencies including a frequency that actuates the at least one stimulation element, wherein the set of different actuation frequencies includes a first actuation frequency and at least one additional actuation frequency, the at least one additional actuation frequency being determined based on or related to the first actuation frequency.

13. The medical device according to claim 12, wherein, The at least one additional actuation frequency in the set of different actuation frequencies is related to the first actuation frequency according to at least one of the following equations: as well as Wherein, v1 refers to the first actuation frequency; v2 to v 10 Each of these refers to the at least one additional actuation frequency; and k refers to a natural number equal to or greater than 2.

14. The medical device according to any one of claims 1 to 4, wherein, The stimulation unit includes: at least one first stimulation element configured to apply the auditory stimulus; and at least one second stimulation element configured to apply the non-auditory stimulus, wherein each first stimulation element is associated with one of the at least one second stimulation element in such a way that the first stimulation element and the associated second stimulation element are actuated to simultaneously generate the auditory stimulus and the non-auditory stimulus.

15. The medical device according to any one of claims 1 to 4, wherein, The control unit of the stimulation unit is configured to operate in the following operating modes: - A first operating mode, in which the generation of the auditory stimulus is associated with the generation of the non-auditory stimulus, and - Second operating mode, in which the generation of the auditory stimulus is independent of the generation of the non-auditory stimulus.

Images