Vibration stimulation device, vibration stimulator, and treatment method

Abstract

This vibration stimulation device for treating a neuropsychiatric disorder in an animal such as a human comprises a vibration unit for applying vibration stimulation at a vibration frequency of 100-300 Hz to the neck of the animal.

Description

Vibration stimulation device, vibration stimulation instrument, and treatment method REFERENCE TO RELATED APPLICATIONS

[0001] This application benefits from the priority of an earlier Japanese application, Patent Application No. 2024-82629 (filing date: May 21, 2024), the entire disclosure of which is incorporated herein by reference.

[0002] The present disclosure relates to vibration stimulation devices, vibration stimulation instruments, and treatment methods.

[0003] With the increasing complexity and aging of society due to modernization, neuropsychiatric disorders such as depression, bipolar disorder, and schizophrenia are on the rise, placing a heavy burden on both patients and society. According to the World Health Organization, the number of people suffering from depression worldwide is estimated to be over 320 million, many of whom are not receiving appropriate treatment. Symptoms of depression include, for example, depressed mood, anhedonia, guilt, attention deficit, psychomotor retardation, suicidal tendencies, or any combination thereof.

[0004] Medication therapy using antidepressants is a common treatment for depression, but for treatment-resistant depression for which antidepressants are ineffective, non-drug treatments such as transcranial magnetic stimulation (TMS) and modified electroconvulsive therapy (EST) are available. While these treatments have the advantage of being non-invasive, the remission rate remains at a maximum of around 50%. Furthermore, because these treatments directly deliver electrical stimulation to the brain, they also pose a greater physical and mental burden to patients than medication. Therefore, there has been a demand for non-invasive treatment methods that do not directly stimulate the brain.

[0005] In this regard, Non-Patent Document 1 reports that whole-body vibration stimulation improves depressive-like behavior in animals. Specifically, a depression model animal, in which depressive-like behavior was induced in a healthy animal (rat) by continuously applying restraint stress, was placed on a device with a 30 Hz floor vibration, and vibration stimulation was continuously applied to the whole body. Non-Patent Document 1 reports that the depression model animal, to which vibration stimulation from floor vibration was continuously applied to the whole body, showed a decrease in immobility time in a forced swimming test (i.e., depressive-like behavior was improved).

[0006] Neurochemistry International Volume 142, Guangcong Peng et al., “Whole body vibration training improves depression-like behaviors in a rat chronic restraint stress model”, 2021

[0007] However, the model animals used in Non-Patent Document 1 were healthy animals in which stress was applied to induce depressive-like symptoms. Therefore, the reported improvement in depressive-like behavior was not due to vibration stimulation, and it cannot be denied that the depressive-like symptoms may have spontaneously improved simply as a result of the long-term vibration stimulation period. Furthermore, when considering applying floor vibration to humans, it is expected that the vibration device would be relatively large and expensive. Furthermore, the above report states that it takes about eight weeks of vibration stimulation before improvement in depressive-like behavior is observed, so there is a need for technology that can expect improvement effects in a shorter period of time.

[0008] Therefore, an object of the present disclosure is to provide a technology that can treat neuropsychiatric disorders with a higher remission rate non-invasively and without directly stimulating the brain.

[0009] The present inventors discovered that neuropsychiatric disorders can be treated by applying vibration stimuli of a specific vibration frequency to the neck of an animal, and have completed the present invention.

[0010] That is, a first aspect of the present disclosure is a vibration stimulation device for treating neuropsychiatric disorders in animals, including humans, comprising a vibration unit that applies vibration stimulation to the neck of the animal at a vibration frequency of 100 Hz to 300 Hz.

[0011] A second aspect of the present disclosure is a method for treating a neuropsychiatric disorder in an animal, including a human, comprising applying a vibration stimulus of 100 Hz to 300 Hz to the neck of the animal.

[0012] The disclosed aspects may also be realized by a program executed by a computer, i.e., the disclosed aspects can be specified as a program for causing a computer to execute control of the vibration unit in the above-described aspects, or a computer-readable recording medium on which the program is recorded.

[0013] The technology disclosed herein makes it possible to treat neuropsychiatric disorders with a higher remission rate, non-invasively and without directly stimulating the brain.

[0014] 1 is an overall view showing an example of the basic configuration of a vibration stimulation device according to an embodiment. FIG. 2 is a graph showing a vibration detection threshold. FIG. 3 is a plan view of a wearable vibration stimulation device including a vibration stimulation device according to an embodiment. FIG. 4 is a diagram showing a state in which the wearable vibration stimulation device according to an embodiment is in use. FIG. 5 is a diagram showing a state in which a chair-type vibration stimulation device including a vibration stimulation device according to an embodiment is in use. FIG. 6 is a diagram showing a state in which the vibration stimulation device according to an embodiment is viewed along the axial direction of the vibration motor. FIG. 7 is a diagram showing a state in which the vibration stimulation device according to an embodiment is attached to a depression model animal. FIG. 8 is a graph showing the results of Experiment 1. FIG. 9 is a graph showing the results of Experiment 2. FIG. 10 is a diagram for explaining an outline of Experiment 3. FIG. 11 is a diagram for explaining an outline of Experiment 3. FIG. 12 is a diagram for explaining an outline of Experiment 3. FIG. 13 is a graph showing an example of the measurement results of one cycle of potential using a microelectrode. FIG. 14 is a graph showing an example of overlapping potentials for 100 cycles. FIG. 15 is a graph showing an example of the time at which an action potential (spike) occurred in 100 cycles of vibration stimulation. FIG. 16 is a histogram of the total number of spikes in the healthy group. FIG. 17 is a histogram of the total number of spikes in the control group 3. FIG. 18 is a histogram of the total number of spikes in the intervention group 3.

[0015] The following describes a vibration stimulation device, a vibration stimulation instrument, and a treatment method for treating neuropsychiatric disorders in animals as embodiments of the present disclosure. However, the configurations of the following embodiments are merely examples, and the present disclosure is not limited to the configurations of the embodiments.

[0016] In this specification, a numerical range expressed by "to" means a range that includes the numerical values ​​written before and after "to" as the lower and upper limits, for example, "A to B" means A or more and B or less.

[0017] [Neuropsychiatric disorders] The vibration stimulation device, vibration stimulation instrument, and treatment method according to the embodiments are effective for treating neuropsychiatric disorders, particularly stress-induced neuropsychiatric disorders. In this specification, "neuropsychiatric disorders" refer to disorders that are caused by abnormalities in the central nervous system and primarily affect the mind. Furthermore, "neuropsychiatric disorders caused by stress" refer to neuropsychiatric disorders that are thought to be caused in part by psychological or physical stress, including, but not limited to, depression, depressive states, bipolar disorder, anxiety disorders, and schizophrenia.

[0018] As used herein, "treatment" includes treatment to cure or alleviate the symptoms of the target disease and / or slow or stop its progression, as well as treatment to prevent and / or slow the onset of the target disease. Furthermore, as used herein, "treatment" is not limited to complete treatment, but may be treatment to the extent that a potential therapeutic effect is exerted.

[0019] In addition, in this specification, "medical use" means intended for use by medical professionals such as doctors and nurses. Hereinafter, embodiments will be described in the context of medical use, but aspects of the present disclosure are not limited to medical use. For example, aspects of the present disclosure may be health devices for personal health purposes.

[0020] [Animal] The subject of application of the technology according to the embodiment (hereinafter simply referred to as "subject") may be an animal, and may be an animal including or excluding humans. The animal is not particularly limited, but is preferably a mammal or a bird, more preferably a mammal, and even more preferably a human. Specific examples of animals include humans, mice, rats, guinea pigs, hamsters, cows, goats, sheep, pigs, monkeys, dogs, cats, chickens, etc., and preferably include industrial animals such as cows, pigs, and chickens, pet animals such as dogs and cats, and humans. In certain embodiments, the subject animal is a human, which may also be referred to as a "patient."

[0021] [Device Configuration] Fig. 1 is an overall view showing an example of the basic configuration of a vibration stimulation device according to an embodiment. As shown in Fig. 1, a vibration stimulation device 10 includes a vibration unit 1 and a power supply unit 2. Reference symbol A1 in Fig. 1 indicates the direction in which the motor shaft of a vibration motor 11 included in the vibration unit 1 extends (hereinafter referred to as the axial direction).

[0022] The vibration unit 1 vibrates to apply a vibration stimulus to the neck of the target animal. The vibration unit 1 has a vibration motor 11 and a case 12.

[0023] The vibration motor 11 generates vibrations when power is supplied from the power supply unit 2. The vibration motor 11 is configured as a cylindrical, so-called eccentric motor, with a weight attached to the motor shaft with the center of gravity shifted. When power is supplied to the vibration motor 11 and the motor shaft rotates, the weight rotates eccentrically, generating vibrations. The shape of the vibration motor 11 is not limited to a cylindrical shape, and may be a disk shape.

[0024] The vibration motor 11 is an example of a "vibration source" (vibration generating unit) according to the present disclosure. However, the vibration source according to the present disclosure is not limited to a vibration motor (eccentric motor), and various vibration actuators can be used. For example, in addition to a vibration motor, a linear resonant actuator, a piezoelectric actuator, or the like can be used as the vibration source. Furthermore, in this embodiment, the vibration motor 11 only operates to start and stop, but the vibration frequency and vibration speed (vibration amplitude) may also be variable under the control of, for example, a computer, a microcontroller, or the like.

[0025] The case 12 is formed in a cylindrical shape and houses the vibration motor 11. The space between the vibration motor 11 and the case 12 is filled with a curable resin such as epoxy resin, thereby fixing the vibration motor 11 to the case 12. This unites the vibration motor 11 and the case 12, causing the entire vibration unit 1 to vibrate. However, the method for fixing the vibration motor 11 to the case 12 is not limited to this, and they may also be fixed by a mechanical method such as fitting.

[0026] Vibration unit 1 can vibrate at a vibration frequency of 100 Hz to 300 Hz, more preferably 100 Hz to 250 Hz, more preferably 150 Hz to 200 Hz, more preferably 160 Hz to 200 Hz, and more preferably 175 Hz to 185 Hz by operation of vibration motor 11. Note that case 12 is not an essential component of vibration unit 1, and vibration unit 1 may be configured with vibration motor 11 alone.

[0027] The power supply unit 2 supplies power to the vibration motor 11 for vibrating the vibration unit 1. The power supply unit 2 includes a battery box 21 attached to the case 12 of the vibration unit 1, and a battery 22 housed in the battery box 21 and serving as the power source for the vibration motor 11. In this embodiment, a size AA battery is used as the battery 22, for example. However, the size of the battery 22 is not limited to this, and may be a size AA battery or a size AAA battery. Furthermore, the battery 22 may be a primary battery, a secondary battery, or the like, and is not particularly limited.

[0028] The case 12 and the battery box 21 are fixed together with a curable resin such as epoxy resin. The vibration motor 11 and the battery 22 are electrically connected together via the battery box 21 and lead wires (not shown). The vibration stimulation device 10 may also include a switch for turning on and off the power supply from the power supply unit 2 to the vibration motor 11.

[0029] The power source for the vibration motor 11 is not limited to the battery 22. For example, power may be supplied to the vibration motor 11 from an external power source.

[0030] The vibration stimulation device 10 can apply a vibration stimulus of 100 Hz to the subject's neck by vibrating the vibration unit 1 at a vibration frequency within the above range while the vibration unit 1 is in direct or indirect contact with the subject's neck. The vibration frequency applied to the subject's neck is more preferably 100 Hz to 250 Hz, even more preferably 150 Hz to 200 Hz, even more preferably 160 Hz to 200 Hz, and even more preferably 175 Hz to 185 Hz. Here, the part of the neck to which the vibration stimulus is applied may be any of the anterior, lateral, or posterior neck, but it is preferable to apply the vibration stimulus to the posterior neck.

[0031] The vibration stimulation device 10 may also include a control unit that controls the operation of the vibration motor 11 (vibration unit 1). The control unit may be configured as a computer, and may have, for example, a hardware configuration including a CPU, a storage device, an input device, and an output device, all connected to each other by a bus. The hardware configuration of the control unit may be omitted, replaced, or added as appropriate. The control unit may apply a vibration stimulus of 100 Hz to 300 Hz to the subject's neck by operating the vibration motor 11. For example, the control unit may define a cycle as application of continuous vibration stimulus for at least 30 minutes, and may execute multiple cycles continuously or intermittently. Furthermore, application of vibration stimulus by the vibration stimulation device 10 may be realized by the CPU executing a program loaded in a storage device. In other words, the program may cause a computer to operate the vibration motor 11 to apply a vibration stimulus of 100 Hz to 300 Hz to the subject's neck. In this case, for example, the program may cause the computer to execute multiple cycles continuously or intermittently, with application of continuous vibration stimulus for at least 30 minutes. This program can be recorded on a recording medium that can be read by a computer, etc. Then, by having a computer, etc. read and execute the program from this recording medium, the function can be provided. Note that a "recording medium that can be read by a computer, etc." refers to a recording medium that stores information such as data and programs through electrical, magnetic, optical, mechanical, or chemical action and can be read by a computer, etc.

[0032] The control unit may, for example, based on a program, control at least one of the vibration frequency and the vibration speed of the vibration motor 11. When controlling the vibration frequency, the control unit may control the vibration frequency within a range including at least a portion of 100 Hz to 300 Hz, more preferably 100 Hz to 250 Hz, more preferably 150 Hz to 200 Hz, more preferably 160 Hz to 200 Hz, and even more preferably 175 Hz to 185 Hz.

[0033] FIG. 2 shows a graph of vibration detection thresholds. The graph of vibration detection thresholds shown in FIG. 2 has been reported as a guide to human vibration sensation. In the graph, the horizontal axis represents vibration frequency, and the vertical axis represents amplitude threshold. The graph in FIG. 2 is an example of an investigation into whether humans can detect (perceive) vibration, i.e., tactile sensitivity. The amplitude threshold is the vibration amplitude value below which humans cannot detect vibration. As shown in FIG. 2, the amplitude threshold is relatively low in the range of 100 Hz to 300 Hz, even lower in the range of 100 Hz to 250 Hz, and lowest in the range of 160 Hz to 200 Hz. In other words, it is believed that vibration stimuli with vibration frequencies in the above range are easily perceived by animals.

[0034] The vibration stimulation device 10 according to this embodiment can improve depressive-like behavior by applying vibration stimulation with a vibration frequency in the range of 100 Hz to 300 Hz to the neck of a subject. As described above, vibration stimulation in this range is easily perceived, allowing depressive-like behavior to improve in a relatively short period of time. Furthermore, in the above range, where the vibration threshold is low, the vibration amplitude required to perceive the vibration stimulation is small, so the power required to drive the vibration motor 11, which serves as the vibration source, can be kept low. Therefore, the vibration stimulation device 10 can efficiently stimulate the sensations in the neck with low power consumption. As a result, depressive-like behavior can be efficiently improved, and depression can ultimately be treated.

[0035] Furthermore, use of the vibration stimulation device 10 according to this embodiment is expected to be effective in treating psychoneurological disorders other than depression, such as stress-induced psychoneurological disorders such as schizophrenia.

[0036] The vibration stimulation device 10 can treat neuropsychiatric disorders in a non-invasive manner without directly stimulating the brain, resulting in a higher remission rate. Furthermore, because the vibration stimulation device 10 applies vibration stimulation to the neck, it can be provided at a smaller size and lower cost than devices that apply vibration stimulation to the entire body.

[0037] The application of vibration stimulation may be performed at least once every 10 days (number of days) over a 24-26 day period, with one cycle consisting of continuous application of vibration stimulation for at least 30 minutes. It is preferable to wait at least one day between one cycle of application of vibration stimulation and the start of the next cycle of application of vibration stimulation. It is particularly preferable to provide an interval of about one to five days. In other words, it is preferable to apply vibration stimulation with a rest period of at least one day rather than applying vibration stimulation continuously within two days. This is expected to enable more effective treatment of neuropsychiatric disorders. One cycle may also be 30 minutes or less.

[0038] [Application Example] An application example of the vibration stimulation device 10 according to the present embodiment will be described. Fig. 3 is a plan view of a wearable vibration stimulation device 100A including the vibration stimulation device 10 according to the embodiment. Fig. 4 is a diagram showing the wearable vibration stimulation device 100A according to the embodiment in use. As shown in Fig. 3, the vibration stimulation device 100A includes the vibration stimulation device 10 and an attachment device 20 that enables the vibration stimulation device 10 to be attached and detached to the neck of a subject (mainly a human). The vibration stimulation device 100A shown in Figs. 3 and 4 is configured to be applied to humans, but the animals that the vibration stimulation device 100A is intended for use with are not limited to humans.

[0039] The attachment device 20 has a holding part 201 that holds the vibration stimulation device 10 and a pair of strap-like parts 202, 202 for attaching the attachment device 20 to the patient's neck. The holding part 201 is a bag that can store the vibration stimulation device 10. The pair of strap-like parts 202, 202 are straps that extend in opposite directions from the holding part 201. Each of the pair of strap-like parts 202, 202 is provided with an engaging member 203 that can engage the pair of strap-like parts 202, 202 with each other. The engaging member 203 can be any type of fastener, such as a hook-and-loop fastener, a hook-and-loop fastener, or a snap-fit ​​fastener.

[0040] As shown in FIG. 4 , the vibration stimulation device 10 is attached to the subject's neck by placing the holding unit 201 housing the vibration stimulation device 10 against the subject's neck (specifically, the back of the neck), wrapping the pair of straps 202 around the subject's neck, and engaging the engaging member 203. This places the vibration motor 11 in contact with the subject's neck via the holding unit 201. By operating the vibration motor 11 of the vibration stimulation device 10 in this state, vibration stimulation is applied to the subject's neck. By fixing the vibration stimulation device 10 to the subject's neck with the attachment 20, a vibration transmission path from the vibration motor 11 to the subject's neck can be formed and maintained. As a result, vibrations can be reliably transmitted to the subject's neck, allowing vibration stimulation to be applied efficiently to the neck. The vibration stimulation device 10 can be removed from the subject's neck by releasing the engagement with the engaging member 203.

[0041] The attachment 20 further includes an elastic member 204. The elastic member 204 is formed of an elastic material, such as a rubber string, and is provided along the pair of band-like portions 202, 202 so as to straddle the vibration stimulation device 10, as shown in FIG. 3 . Both ends of the elastic member 204 are fixed to each of the pair of band-like portions 202, 202. In this example, two elastic members 204, 204 are provided, but the number of elastic members 204 is not limited to this and may be one, three, or more. As shown in FIG. 4 , when the vibration stimulation device 100A is in use, the elastic member 204 is disposed on the opposite side of the neck across the vibration stimulation device 10 in a stretched (tensioned) state so as to straddle the vibration stimulation device 10. The restoring force (elastic force) of the elastic member 204 urges the vibration stimulation device 10 toward the neck, pressing the vibrating unit 1 against the neck. This allows vibrations to be more reliably transmitted to the patient's neck.

[0042] Next, another application example of the vibration stimulation device 10 according to this embodiment will be described. Fig. 5 is a diagram showing a state in which a chair-type vibration stimulation device 100B equipped with the vibration stimulation device 10 according to this embodiment is in use. The vibration stimulation device 100B shown in Fig. 5 is configured for use by humans.

[0043] As shown in FIG. 5 , the vibration stimulation device 100B includes the vibration stimulation device 10 and a chair body 30 on which a patient (human) can sit. The chair body 30 includes a seat portion 301 that supports the patient's buttocks, a backrest portion 302 that supports the patient's torso, a head support portion 303 that supports the patient's head, and a leg support portion 305 that supports the patient's legs, allowing the patient to sit on the chair body 30. The chair body 30 also includes a neck-facing region 304 between the backrest portion 302 and the head support portion 303 that faces the neck of a patient seated on the chair body 30. In the vibration stimulation device 100B according to this embodiment, the vibration stimulation device 10 is disposed in the neck-facing region 304. In the embodiment shown in FIG. 5 , the vibration stimulation device 10 is disposed on the surface of the neck-facing region 304, but it may also be disposed inside the neck-facing region 304. The vibration stimulation device 10 may, for example, be incorporated into a cushion (not shown) that constitutes the chair body 30. By arranging the vibration stimulation device 10 in the neck-facing region 304, when the patient is seated on the chair body 30, the vibration motor 11 of the vibration stimulation device 10 is arranged facing the patient's neck (specifically, the posterior neck), and the vibration motor 11 comes into direct or indirect contact with the patient's neck. This forms and maintains a vibration transmission path from the vibration motor 11 to the patient's neck, making it possible to apply vibration stimulation to the patient's neck.

[0044] The vibration stimulation device 100B may also have the functions of a general massage chair. Specifically, the vibration stimulation device 100B may include a massage mechanism for massaging various parts of the patient's body in at least one of the seat portion 301, backrest portion 302, head support portion 303, and leg support portion 305. The massage mechanism may massage various parts of the patient's body by repeating general massage actions such as kneading, tapping, and vibration stimulation. The vibration stimulation device 100B may also include a control unit for controlling the vibration stimulation device 10 and the massage mechanism. The control unit may independently perform vibration stimulation by the vibration stimulation device 10 and massage by the massage mechanism, or may perform these operations simultaneously or consecutively, in accordance with the patient's operation or a program.

[0045] The present invention will be explained in more detail below with reference to examples, but the present invention is not limited to the following examples as long as it does not deviate from the gist of the invention.

[0046] Fig. 6 is a diagram showing the vibration stimulation device 100C according to the embodiment as viewed along the axial direction of the vibration motor 11. Fig. 7 is a diagram showing the vibration stimulation device 100C according to the embodiment attached to a rat, which is an example of a depression model animal. The vibration stimulation device 100C according to the embodiment includes a vibration stimulation device 10C and an attachment 20C, and is capable of applying vibration stimulation to the neck of the depression model animal.

[0047] The vibration stimulation device 10C according to the embodiment was configured similarly to the vibration stimulation device 10 shown in FIG. 1 . The case 12 in the embodiment was a cylindrical case (outer diameter: 14.5 mm, inner diameter: 12.5 mm). The vibration motor 11 in the embodiment was a vibration motor (Microrotor, SSI JAPAN) rated at 1.5 V. The vibration motor 11 was housed in the case 12, and the gap between the vibration motor 11 and the case 12 was filled with epoxy resin (Bond Quick 5, Konishi) to secure them together. The battery 22 was a AAA alkaline battery, and the battery box 21 was a battery box for AAA batteries (external dimensions: 13 mm x 14 mm x 35 mm) (Battery Box, ELPA). The case 12 and battery box 21 were fixed with epoxy resin, and the vibration motor 11 and battery box 21 were wired together. When the battery 22 is attached to the battery box 21, the vibration motor 11 is activated and vibration begins.

[0048] The attachment 20C allows the vibration stimulation device 10C to be attached and detached to the neck of the depression model animal. As shown in Figure 6, the attachment 20C includes an animal jacket 3, a hook-and-loop fastener strip 4, a suture 5, and an elastic member 6.

[0049] The animal jacket 3 is placed over the chest of the depression model animal and wrapped around the back. The animal jacket 3 is separated around the neck at a location corresponding to the posterior neck. Loop-shaped hook-and-loop fasteners 31 are provided on the inner surface of both ends of the animal jacket 3. Furthermore, hooks 32 are provided on both ends, folded back to the outside of the animal jacket 3. A rat jacket (Rat Jacket, Bio Research Center) was used as the animal jacket 3.

[0050] The hook-and-loop fastener strip 4 connects both ends of the animal jacket 3 and abuts against the posterior neck of the depression model animal. A hook-and-loop fastener measuring 45 mm in length (in the neck direction) and 25 mm in width was used for the hook-and-loop fastener strip 4. The hook-and-loop fastener strip 4 is placed inside the animal jacket 3 and connects to the hook-and-loop fastener 31 of the animal jacket 3, thereby connecting both ends of the neck of the animal jacket 3 together.

[0051] The suture thread 5 secures the vibration stimulation device 10C to the hook-and-loop fastener strip 4. The vibration stimulation device 10C is positioned so that the vibration unit 1 is sandwiched between the hook-and-loop fastener strip 4 and the power supply unit 2, and the suture thread 5 is passed through the battery box 21 and both ends are sewn to the hook-and-loop fastener strip 4, thereby securing the vibration stimulation device 10C to the hook-and-loop fastener strip 4.

[0052] The elastic member 6 is stretched (in a tensioned state) and is hung over hooks 32 at both ends of the animal jacket 3, straddling the vibration stimulation device 10C. Rubber bands (O-Band #7, Kyowa) are used for the elastic member 6. When the vibration stimulation device 100C is worn around the neck, the elastic member 6 is located on the opposite side of the neck, sandwiching the vibration stimulation device 10C between them. Its restoring force (elastic force) biases the vibration stimulation device 10C toward the neck, pressing the vibrating unit 1 against the neck. This allows vibrations to be transmitted to the neck more reliably.

[0053] The specifications of the vibration stimulation device 100C according to the embodiment are as follows: Weight of the vibration stimulation device (excluding battery): 9.0 g Weight of AA battery: 9.1 g Weight of attachment: 4.0 g Total weight of the vibration stimulation device: 22.1 g Vibration frequency of the vibration stimulation device: 150 Hz to 200 Hz (average 180 Hz) Vibration speed of the vibration stimulation device: 2.5 mm / s to 3.1 mm / s

[0054] <Evaluation of Vibration Stimulation> The effect of improving depressive-like behavior when vibration stimulation was applied to the neck of a depression model animal using the vibration stimulation device 100C according to the above-described embodiment was evaluated.

[0055] [Depression Model Animal] As an example of an animal, WKY (Wistar Kyoto) rats were used as a depression model animal. WKY rats are congenitally vulnerable to environmental and social stress and are known as a hypothetical animal model of treatment-resistant depression. WKY rats, 10-11 weeks old, were obtained from Jackson Laboratory Japan.

[0056] [Application of Vibration Stimulation] As shown in Figure 7, the vibration stimulation device 100C according to the embodiment was attached to the neck of a test rat, and the vibration motor 11 was operated to chronically apply vibration stimulation to the rat's neck. The vibration stimulation was administered from the 24th to 26th days, with one cycle consisting of 30 minutes of continuous vibration stimulation. Ten cycles of vibration stimulation were administered during the stimulation period. Specifically, during the stimulation period from the 24th to 26th days, 10 randomly selected days (excluding weekends (Saturday and Sunday)) were used as test days, and one cycle of vibration stimulation was administered on each test day. The vibration motor 11 vibrated at a vibration frequency of 150 Hz to 200 Hz and a vibration speed of 2.5 mm / s to 3.1 mm / s.

[0057] Typically, when animals are fitted with a device for an experiment, they often feel pain or discomfort and resist attempts to remove the device. However, during vibration stimulation using the vibration stimulation device 100C, the test rats did not show any signs of pain or discomfort, nor did they resist attempts to remove the device, and no abnormal behavior was observed. Rather, the rats appeared relaxed. This suggests that the neck vibration stimulation of the present invention is acceptable to animals and has a relaxing effect on animals, including humans. Furthermore, all test rats were observed to search for the vibration stimulation device 100C for approximately three minutes after the end of the vibration stimulation. This suggests that the relaxing effect of neck vibration stimulation may have led to a preference for the vibration stimulation device 100C. Furthermore, a vibration stimulation device equivalent to the vibration stimulation device 100A was created using a vibration motor with a drive voltage of DC 3V, a vibration frequency of 185Hz to 195Hz, and a vibration speed of 17m / s to 18m / s. When this device was worn around the neck of a test subject and vibration stimulation was applied, it was confirmed that a relaxation effect was obtained. This suggests that vibration stimulation to the neck according to the present invention can also be expected to have a relaxation effect on humans.

[0058] Experiment 1: Novelty-Suppressed Feeding Test (NSFT) A novelty-suppressed feeding test (NSFT) was conducted on rats exposed to vibration stimulation (intervention group 1) and rats not exposed to vibration stimulation (control group 1). The rats were fasted for 24 hours, and the latency to eating was measured and compared to evaluate depressive symptoms. N = 11 rats were included in each group. For rats in intervention group 1, another cycle of vibration stimulation was administered 7 to 11 days after the last vibration stimulation session, followed by the NSFT. For the NSFT, a novel cage (cleaned plastic cage, base: 21 cm x 38 cm, height: 19.7 cm) different from the cage the rats were previously housed in was prepared and placed in a novel environment (specifically, a room the test rats had never been in before). Food (solid pellets approximately 14 mm in diameter and 20 mm in length) (Oriental Yeast Co., Ltd.) was placed in the center of the cage. After fasting for 24 hours, the rats were placed in a novelty cage and the time from when the rat was placed until it first bitten the food in the cage was measured as the "latency to eat." The length of time it took to eat during the NSFT is an indicator of the rat's depressive symptoms. The stronger the tendency toward depression, the longer the latency to eat.

[0059] [Results of Experiment 1] As the results of Experiment 1, the group means and standard errors of the time until eating are shown in Table 1. Table 1 also shows the P values ​​of the t-test in comparison with Control Group 1. FIG. 8 is a graph showing the results of Experiment 1. The bar graph in FIG. 8 shows the group means of the time until eating, and the error bars show the standard errors. As shown in Table 1 and FIG. 8, the results showed that the time until eating was shorter in Intervention Group 1 with a clear significant difference compared to Control Group 1. Specifically, the time until eating (mean) was approximately 303 seconds in Control Group 1, while it was approximately 95 seconds in Intervention Group 1, indicating an improvement in depressive-like behavior due to the application of vibration stimulation.

[0060] Experiment 2: Forced Swimming Test (FST) Rats exposed to vibration stimulation (Intervention Group 2) and rats not exposed to vibration stimulation (Control Group 2) were subjected to a forced swimming test (FST). Depression symptoms were assessed by measuring and comparing the distance traveled. Six rats were included in each group. Rats in Intervention Group 2 were randomly selected from among the rats in Intervention Group 1 of Experiment 1. Rats in Control Group 2 were randomly selected from among the rats in Control Group 1 of Experiment 1. Rats in Intervention Group 2 underwent another cycle of vibration stimulation 4 to 14 days after the NSFT, and then underwent the FST the following day. For the FST, a black (opaque) plastic tank (bottom: 26 cm x 37 cm, height: 42 cm) was prepared. Water (25°C) was then placed in the tank to a depth of 300 mm, and the test rats were allowed to swim individually for 5 minutes. The swimming was videotaped from directly above using a personal computer with a digital camera ("E10-VL" manufactured by Mouse Computer Co., Ltd.). After the test, the rats were quickly removed from the water and wiped clean with a paper towel. The video images were used for behavioral analysis. In the behavioral analysis, the video images were binarized every second to obtain a contour image of the rat. The geometric center of gravity of this contour image was determined, and the distance traveled by the center of gravity per second was calculated. The cumulative distance traveled by the center of gravity during the test period (5 minutes) was calculated as the rat's "movement amount." The amount of movement during the FST is an index of the rat's depressive symptoms. Stronger depression tends to result in smaller movement amounts.

[0061] [Results of Experiment 2] Table 2 shows the group means and standard errors of the movement amounts as results of Experiment 2. Table 2 also shows the P values ​​of the t-tests in comparison with Control Group 2. FIG. 9 is a graph showing the results of Experiment 2. The bar graph in FIG. 9 shows the group means, and the error bars show the standard errors. As shown in Table 2 and FIG. 9, the results showed that the movement amount of Intervention Group 2 was significantly greater than that of Control Group 2. Specifically, the movement amount (mean) was approximately 4967 mm in Control Group 2, while it was approximately 6819 mm in Intervention Group 2, indicating an improvement in depressive-like behavior due to the application of vibration stimulation. Visual observation showed that the rats in Intervention Group 2 moved more than the rats in Control Group 2, and they were more likely to exhibit behaviors such as climbing the walls of the tank.

[0062] [Experiment 3: Evaluation of neural activity in the prefrontal cortex] Experiment 3 was conducted under anesthesia to evaluate neural activity in the prefrontal cortex of rats in response to acute vibration stimulation. Experiment 3 was conducted on rats with a depression model that had been chronically stimulated to the neck with the vibration stimulation device 100C (intervention group 3), rats that had not been chronically stimulated to the neck with the vibration stimulation device 100C (control group 3), and healthy rats that were not depression models (healthy group). Wistar rats (normal) were used for the healthy group. For the healthy group, no chronic vibration stimulation was applied to the neck with the vibration stimulation device 100C. Each group contained one rat.

[0063] 10 and 11 are diagrams for explaining the outline of Experiment 3. In Experiment 3, neural activity was evaluated by measuring action potentials generated by neurons in the prefrontal cortex when vibration stimuli were repeatedly applied to the neck of a test rat under urethane anesthesia. Specifically, as shown in FIG. 10, a vibration stimulation pendulum was applied to the neck of the test rat, and vibration was applied at a vibration frequency of 180 Hz, a vibration velocity of 2.0 mm / s to 3.0 mm / s, and an acceleration of 0.36 mm / s. ２ ~0.54 mm / s ２ Vibration stimulation was applied to the rats. This vibration stimulation was switched between an active state (ON) and a stopped state (OFF) every two seconds. As shown in Figure 11, one cycle of vibration stimulation was defined as a four-second cycle including one active state and one stopped state of the vibration stimulation, and the vibration stimulation was repeated 100 times. Furthermore, as shown in Figure 10, a microelectrode was inserted into the brain tissue of the test rats, and action potentials were measured during the 100 cycles of vibration stimulation.

[0064] Figure 12 is a graph showing an example of the potential measurement results for one cycle using a microelectrode. Figure 13 is a graph showing an example of the potentials for 100 cycles superimposed. Figure 14 is a graph showing an example of the time when action potentials (spikes) occurred during 100 cycles of vibration stimulation. As shown in Figure 12, potential peaks below a predetermined threshold were recorded as action potentials (spikes). The number of spikes every 10 ms in each cycle was then tallied. The number of spikes every 10 ms for 100 cycles was summed to create histograms of the total number of spikes, as shown in Figures 15 to 17. In other words, the histograms shown in Figures 15 to 17 represent the frequency of neural activity during one cycle of vibration stimulation.

[0065] [Results of Experiment 3] Figure 15 is a histogram of the total number of spikes in the healthy group. Figure 16 is a histogram of the total number of spikes in control group 3. Figure 17 is a histogram of the total number of spikes in intervention group 3. In the histograms shown in Figures 15 to 17, the horizontal axis represents time, and the vertical axis represents the number of spikes (more specifically, the total value of 100 cycles of the number of spikes every 10 ms). Furthermore, the period from -2000 ms to 0 ms is the period during which vibration stimulation was stopped, and the period from 0 ms to 2000 ms is the period during which vibration stimulation was applied.

[0066] In the histograms shown in Figures 15 to 17, at points (times) where the number of spikes was higher than at other points (i.e., where the number of action potentials was higher), neurons generated action potentials more frequently per unit time, which suggests that the prefrontal cortex responded to the vibration stimulus. Table 3 shows the number of points where neural activity was recorded during the period when the vibration stimulus was applied, the number of points where the prefrontal cortex responded, and the percentage of points where the prefrontal cortex responded. The points where neural activity was recorded were identified based on the number of action potentials (spike counts). Noise caused by vibration was excluded from the identification of neural activity.

[0067] As shown in Figure 15 and Table 3, in the healthy group, approximately 70% of recording sites exhibited a prefrontal cortex response during the period when vibration stimulation was applied, and this was particularly common between 0 ms and 500 ms after the start of vibration. On the other hand, in control group 3, which had not previously been subjected to chronic vibration stimulation to the neck, no prefrontal cortex response to vibration stimulation was observed at any recording site. In contrast, in intervention group 3, which had previously been subjected to chronic vibration stimulation to the neck, approximately 40% of recording sites exhibited a prefrontal cortex response within 500 ms after the start of vibration.

[0068] In the human brain, the prefrontal cortex is responsible for advanced cognitive functions such as decision-making and problem-solving, and is known to be associated with depression. From this perspective, unlike the control group 3, intervention group 3 showed a high prefrontal cortex response similar to the healthy control group, demonstrating a similar tendency. This suggests that chronic neck vibration stimulation can improve depressive symptoms. However, the technology disclosed herein is not bound by the above theory.

[0069] [Summary] The results of Experiments 1 to 3 above demonstrate that the use of the technology disclosed herein can improve depressive-like behavior and depressive symptoms in a relatively short period of time (approximately 3 weeks). This demonstrates that the present invention is effective in treating depression. The depression model animals used in the above experiments are animals that congenitally exhibit depressive-like behavior and are unlikely to recover spontaneously. Therefore, the results of the above experiments are considered to demonstrate the effectiveness of the present invention with high reliability.

[0070] <Others> Although the embodiments and examples of the technology according to the present disclosure have been described above, the above-described embodiments and examples can be combined as much as possible.

[0071] The present invention can be applied to neuropsychiatric disorders in humans. The present invention can also be applied to neuropsychiatric disorders in non-human animals. Non-human animals may also exhibit abnormal behavior due to stress. For example, industrial animals such as cows, pigs, and chickens are prone to problems such as reduced meat quality, aggressive behavior toward other animals, and reduced egg production due to abnormal behavior. Applying the technology disclosed herein to industrial animals can be expected to improve abnormal behavior caused by stress. Pet animals such as dogs and cats may also exhibit abnormal or depressive-like behavior when continuously exposed to environmental or social stress. Applying the technology disclosed herein to pet animals can be expected to improve abnormal or depressive behavior. Furthermore, because the technology disclosed herein treats neuropsychiatric disorders by applying vibration stimulation to the animal's neck, it is easier to miniaturize the device compared to applying vibration stimulation to the entire body, making it applicable to a wider variety of animals.

[0072] According to the present invention, there is provided a method for treating neuropsychiatric disorders in animals, including humans, which comprises applying a vibration stimulus of 100 Hz to 300 Hz to the neck of the animal. The method of treatment of the present invention can be carried out in accordance with the description of the vibration stimulation device and vibration stimulation instrument of the present invention.

[0073] 1: Vibration unit 11: Vibration motor (an example of a vibration source) 2: Power supply unit 3: Animal jacket 4: Hook-and-loop fastener 5: Suture thread 6: Rubber band 10, 10C: Vibration stimulation device 20, 20C: Mounting fixture 100A, 100B, 100C: Vibration stimulation instrument

Claims

1. A vibration stimulation device for treating neuropsychiatric disorders in animals, including humans, comprising a vibration unit that applies vibration stimulation to the neck of the animal at a vibration frequency of 100 Hz to 300 Hz.

2. The vibration stimulation device according to claim 1, wherein the vibration frequency of the vibration stimulation is 100 Hz to 250 Hz.

3. The vibration stimulation device according to claim 1, wherein the vibration frequency of the vibration stimulation is 150 Hz to 200 Hz.

4. The vibration stimulation device according to claim 1, wherein the vibration frequency of the vibration stimulation is 160 Hz to 200 Hz.

5. A vibration stimulation device according to any one of claims 1 to 4, wherein the vibration speed of the vibration stimulation is 2.5 mm / s to 3.1 mm / s.

6. The vibration stimulation device according to any one of claims 1 to 4, wherein the vibration unit has a vibration motor as a vibration source.

7. A vibration stimulation device comprising: a vibration stimulation device according to any one of claims 1 to 4; and an attachment that enables the vibration stimulation device to be attached to and detached from the neck.

8. A vibration stimulation device comprising: a vibration stimulation device according to any one of claims 1 to 4; and a chair body on which a person can sit, the chair body having a seat portion that supports the buttocks of the person and a backrest portion that supports the torso of the person, the vibration stimulation device being positioned in an area of ​​the chair body that faces the neck of the person.

9. A method for treating a neuropsychiatric disorder in an animal, including a human, comprising applying a vibration stimulus of 100 Hz to 300 Hz to the neck of the animal.

10. The method of treatment according to claim 9, wherein one cycle comprises continuous application of the vibration stimulus for at least 30 minutes, and at least one cycle is performed on at least 10 days out of 24 to 26 days.

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