A neuromodulatory device and system for performing transcranial alternating current stimulation on the hippocampus

Abstract

The present application provides a neuroregulatory device and system for performing transcranial alternating current stimulation on the hippocampus. The neuroregulatory device is used to stimulate the hippocampus on the first side to treat related brain diseases, including a first electrode sheet arranged at the scalp corresponding to the temporal lobe on the first side, and at least a group of second electrode sheets arranged at the scalp corresponding to the temporal lobe on the second side, one of the first electrode sheet and the group of second electrode sheets is grounded and used as a cathode, and the other of the first electrode sheet and the group of second electrode sheets is connected to an alternating current source and used as an anode, so that the alternating current flows into the first electrode sheet, or flows from the first electrode sheet to a group of second electrode sheets. In this way, the stimulation intensity of the hippocampus on the first side can be increased, and the treatment effect of related brain diseases can be improved.

Description

Technical Field

[0001] The present application relates to the technical field of transcranial electrical stimulation, and in particular to a neuromodulatory device and system for performing transcranial alternating current electrical stimulation on the hippocampus. Background Art

[0002] Neurodegenerative diseases such as Alzheimer's disease cause neural damage, which can lead to impaired brain function and affect the quality of life of patients. The pathological characteristics of Alzheimer's disease include the deposition of amyloid-β (Aβ) plaques and phosphorylated tau neurofibrillary tangles, which lead to nerve cell damage and death, thereby affecting cognitive function. Aβ plaques usually begin to form in the hippocampus and neocortex regions of the brain in the early stages of the disease, while the deposition of Tau protein begins in the middle temporal lobe of the inner cortex and may then gradually spread to the hippocampus and other brain regions, leading to memory loss and cognitive decline.

[0003] Currently, non-invasive treatment methods such as electrical stimulation can usually be used to stimulate the brain through the cranium to promote neuronal activity and activate potential neural repair mechanisms, thereby improving the neurological function of patients with neurodegenerative diseases. Transcranial alternating current stimulation (also known as tACS) can apply low-intensity alternating current of a specific frequency to the target area of ​​the brain through electrodes installed on the surface of the scalp, thereby regulating the endogenous oscillations of the brain and inducing the recovery of functional connections between brain regions. In recent years, researchers have used gamma-frequency tACS to induce the synchronization of gamma oscillations in target brain areas, namely neural oscillation "entrainment", which can regulate neural activity, improve inherent endogenous gamma neural oscillations within and between brain regions, and promote brain function recovery, and is used to treat various brain diseases including Alzheimer's disease.

[0004] However, existing transcranial electrical stimulation-related treatment programs are usually of low intensity to avoid causing discomfort or pain to patients. However, low-intensity stimulation currents, such as 1 mA, will spread to other undesired parts of the brain after transcranial attenuation and cannot target the hippocampus deep in the brain. The final stimulation intensity acting on the hippocampus is significantly insufficient, and the treatment effect is not ideal. In particular, when the course of Alzheimer's disease develops to the middle and late stages, the progression is more rapid, and the hippocampus undergoes significant atrophy and lesions. Current transcranial electrical stimulation-related treatment programs have a poor inhibitory effect on this. Summary of the invention

[0005] This application is proposed to solve the above technical problems in the prior art. This application aims to provide a neuromodulatory device and system for performing transcranial alternating current stimulation on the hippocampus, which can target the hippocampus for electrical stimulation, reduce the current attenuation multiple at the hippocampus, and significantly enhance the stimulation intensity of the hippocampus, thereby improving the treatment effect of related brain diseases, especially Alzheimer's disease.

[0006] According to the first scheme of the present application, a neuroregulatory device for performing transcranial alternating current stimulation on the hippocampus is provided, and the neuroregulatory device is used to stimulate the hippocampus on the first side to treat related brain diseases. The neuroregulatory device includes a first electrode sheet arranged at the scalp corresponding to the first temporal lobe, and at least a group of second electrode sheets arranged at the scalp corresponding to the second temporal lobe. One of the first electrode sheet and the group of second electrode sheets is grounded and used as a cathode, and the first electrode sheet and the other of the group of second electrode sheets are connected to an alternating current source and used as an anode, so that the alternating current flows into the first electrode sheet, or flows from the first electrode sheet to the group of second electrode sheets.

[0007] According to the second scheme of the present application, a multimodal neuroregulatory system is provided, which includes one or more of a light therapy device, a sound stimulation therapy device, a transcranial magnetic stimulation therapy device, and a neuroregulatory device for performing transcranial alternating current stimulation of the hippocampus according to the various embodiments of the present application.

[0008] Compared with the prior art, the beneficial effects of the embodiments of the present application are:

[0009] The neuroregulatory device provided in the embodiment of the present application includes a first electrode sheet arranged at the scalp corresponding to the first temporal lobe, and a group of second electrode sheets arranged at least at the scalp corresponding to the second temporal lobe, and one of the first electrode sheet and the group of second electrode sheets is grounded, and the other is connected to an alternating current source. In this way, on the one hand, targeted stimulation of the hippocampus can be achieved, and on the other hand, the alternating current can be crossed at one temporal lobe, which can reduce the attenuation of the alternating current at the hippocampus compared to the scheme in which the alternating current does not cross, and improve the electric field strength at one hippocampus, so that the stimulation intensity of the hippocampus on one side can be significantly enhanced, and the electric field of the transcranial alternating current stimulation acting on the hippocampus in the wide frequency band of alpha waves, beta waves and gamma waves can produce analgesic and euphoric effects on the stimulated object through the cortical area, so that the stimulated object can comfortably tolerate the higher stimulation intensity of the hippocampus on one side. By increasing the intensity of targeted stimulation of the hippocampus, the removal effect of Tau protein and Aβ plaques in and near the hippocampus can be improved and optimized, memory and cognitive function can be improved, and the therapeutic effect of related brain diseases can be effectively improved.

[0010] The above description is only an overview of the technical solution of the present application. In order to more clearly understand the technical means of the present application, it can be implemented in accordance with the contents of the specification. In order to make the above description and other purposes, features and advantages of the present application more obvious and easy to understand, the specific implementation methods of the present application are listed below. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] In the drawings, which are not necessarily drawn to scale, the same reference numerals may describe similar parts in different views. Similar reference numerals with letter suffixes or different letter suffixes may represent different examples of similar components. The accompanying drawings generally illustrate various embodiments by way of example and not by way of limitation, and together with the description and claims, are used to illustrate the disclosed embodiments. Such embodiments are illustrative and exemplary and are not intended to be exclusive embodiments of the present apparatus, system, or

[0012] Figure 1 A schematic diagram showing an arrangement of an electrode patch on the scalp outside the brain region according to an embodiment of the present application.

[0013] Figure 2 Another schematic diagram showing the arrangement of the electrode patch on the scalp outside the brain region according to an embodiment of the present application.

[0014] Figure 3 Another schematic diagram showing the arrangement of the electrode patch on the scalp outside the brain region according to an embodiment of the present application.

[0015] Figure 4 A schematic diagram showing that a first electrode sheet disposed at a scalp corresponding to the right temporal lobe is grounded, and a second electrode sheet disposed at a scalp corresponding to the left temporal lobe is connected to an alternating current source according to an embodiment of the present application.

[0016] 5( a ) shows a schematic diagram of a first electrode sheet disposed at the scalp corresponding to the right temporal lobe being grounded, and second electrode sheets disposed at the scalp corresponding to the left temporal lobe and the scalp corresponding to the frontal lobe being connected to an alternating current source according to an embodiment of the present application.

[0017] 5( b ) shows a schematic diagram of a first electrode sheet disposed at the scalp corresponding to the right temporal lobe connected to an alternating current source, and second electrodes disposed at the scalp corresponding to the left temporal lobe and the scalp corresponding to the frontal lobe are grounded according to an embodiment of the present application.

[0018] Figure 6 A schematic diagram showing that a first electrode sheet disposed at the scalp corresponding to the right temporal lobe is grounded, and second electrode sheets disposed at the scalp corresponding to the left temporal lobe and the scalp corresponding to the parietal lobe are connected to an alternating current source according to an embodiment of the present application.

[0019] Figure 7 A schematic diagram showing that a first electrode sheet disposed at the scalp corresponding to the right temporal lobe is grounded, and second electrode sheets disposed at the scalp corresponding to the left temporal lobe and the scalp corresponding to the occipital lobe are connected to an alternating current source according to an embodiment of the present application.

[0020] Figure 8A schematic diagram showing that a first electrode sheet disposed at the scalp corresponding to the right temporal lobe is grounded, and second electrode sheets disposed at the scalp corresponding to the left temporal lobe, the occipital lobe, and the frontal lobe, respectively, are connected to an alternating current source according to an embodiment of the present application.

[0021] Fig. 9 A schematic diagram showing two electrode sheets respectively arranged near the left ear and the right ear according to an embodiment of the present application is shown. DETAILED DESCRIPTION

[0022] In order to enable those skilled in the art to better understand the technical solution of the present application, the present application is described in detail below in conjunction with the accompanying drawings and specific implementation examples. The embodiments of the present application are further described in detail below in conjunction with the accompanying drawings and specific implementation examples, but are not intended to limit the present application.

[0023] The words "first", "second" and similar words used in this application do not indicate any order, quantity or importance, but are only used to distinguish. The words "include" or "comprises" and similar words used in this application mean that the elements before the word include the elements listed after the word, and do not exclude the possibility of covering other elements. In this application, the arrows shown in the figures of each step are only examples of the execution order, not limitations. The technical solution of this application is not limited to the execution order described in the embodiments. The various steps in the execution order can be combined, decomposed, or the order can be changed, as long as the logical relationship of the execution content is not affected.

[0024] All terms (including technical terms or scientific terms) used in this application have the same meaning as those understood by ordinary technicians in the field to which this application belongs, unless otherwise specifically defined. It should also be understood that terms defined in general dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant technology, and should not be interpreted in an idealized or extremely formal sense, unless explicitly defined here. Techniques and equipment known to ordinary technicians in the relevant field may not be discussed in detail, but where appropriate, the techniques and equipment should be considered as part of the specification.

[0025] In an embodiment of the present application, a neuroregulatory device for performing transcranial alternating current stimulation on the hippocampus is provided, and the neuroregulatory device is used to stimulate the hippocampus on the first side to treat related brain diseases including Alzheimer's disease. Related brain diseases can include all brain diseases involving lesions of the hippocampus and its surrounding areas (such as the temporal lobe), except Alzheimer's disease, including but not limited to: depression, Parkinson's disease, schizophrenia, anxiety, dementia, bipolar disorder, autism, etc. Please note that the so-called "treatment" of "related brain diseases" is intended to indicate the course of the "related brain diseases" to various degrees, and the course of the disease includes but is not limited to: the related brain diseases have not been diagnosed but are in an early pathological state and according to medical knowledge, they will develop into confirmed related brain diseases with a certain probability. For example, MCI (mild cognitive impairment) is a pathological stage in the early stage of many AD patients, so suppressing MCI to various degrees is also considered to be used to treat the related brain disease-Alzheimer's disease.

[0026] like Figure 1 , Figure 2 , Figure 3 and Figure 4 As shown, the nerve regulation device includes a first electrode sheet 101 disposed at the scalp corresponding to the first temporal lobe, and at least a group of second electrode sheets (such as Figure 4 The second electrode sheet 1021 at the scalp corresponding to the left temporal lobe shown). An example is shown in which the right side is used as the first side and the left side is used as the second side, but it should be noted that the present application is not limited to this, and the left side may also be used as the first side and the right side as the second side. Please note that the so-called scalp corresponding to the temporal lobe, frontal lobe, parietal lobe and other lobes in the neocortex in the present application is intended to indicate that the current field applied at the scalp can act on at least part of the temporal lobe, frontal lobe or parietal lobe through the skull. Specifically, an electrode sheet is attached to a single small area of ​​the scalp above the ear to apply an alternating current field. As long as the alternating current stimulation can act on a part of the temporal lobe through the skull, it is regarded as the scalp corresponding to the temporal lobe. Taking the scalp corresponding to the temporal lobe as an example, this place can fall outside the space where the temporal lobe is located after being vertically mapped to the cortex through the skull. The alternating electric field applied there will have a certain field diffusion through the skull, and after diffusion, it can act on at least part of the temporal lobe, so this place can be considered as the scalp corresponding to the temporal lobe. For example, the first electrode sheet 101 and a group of second electrode sheets can be attached to the scalp where the hair is sparse, such as around the ears and temples, and can act on the temporal lobe through the cranium, to facilitate the attachment and removal operations and optimize the contact between the electrode sheets and the scalp.

[0027] The first electrode sheet 101 disposed at the scalp corresponding to the first temporal lobe and a group of second electrode sheets disposed at the scalp corresponding to the second temporal lobe can adopt various structures to facilitate attachment to the scalp around the ear. Specifically, Figure 1A method of setting the first electrode sheet 101 at the scalp corresponding to the first temporal lobe is shown. A series of small electrodes can be set around the ear to form a semi-circular arrangement of the first electrode sheet 101, so that the first electrode sheet 101 can fit the scalp. The first electrode sheet 101 set at the scalp corresponding to the first temporal lobe can also be as follows Figure 2 As shown, the first electrode sheet 101 is semi-circular and fits the scalp above the ear. In addition, the first electrode sheet 101 arranged at the scalp corresponding to the first temporal lobe can also be as shown in FIG. Figure 3 As shown, the first electrode sheet 101 is annular and fits around the ear. The method of setting a group of second electrode sheets at the scalp corresponding to the second temporal lobe is the same as the method of setting the first electrode sheet 101 at the scalp corresponding to the first temporal lobe, which will not be described here.

[0028] Setting the electrode sheet in a semi-circular or ring shape can not only adapt to the structural characteristics of the ear and improve the fit of the electrode sheet on the scalp around the ear, but also improve the correspondence with the position of the hippocampus, which is conducive to the targeted positioning and precise stimulation of the hippocampus. Specifically, the hippocampus is located between the thalamus and the medial temporal lobe of the brain, and bends and extends in the front-to-back direction of the head on both sides of the brain to form the shape of a hippocampus. By setting the electrode sheet in a semi-circular or ring shape extending in the front-to-back direction of the head, the applied electric field can act on multiple positions in the extension direction of the hippocampus on the target side, thereby optimizing the structured targeted and precise stimulation of the hippocampus on the target side.

[0029] In this embodiment, the first electrode sheet 101 and one of the group of second electrode sheets are grounded and used as cathodes, and the first electrode sheet 101 and the other of the group of second electrode sheets are connected to an alternating current source and used as anodes, so that the alternating current flows into the first electrode sheet 101, or flows from the first electrode sheet 101 to the group of second electrode sheets. By grounding the electrode sheet serving as the cathode, the diffusion shunt of the current flowing out of the current source to the brain area other than the grounding point can be reduced, the guidance and concentration of the electric field in the brain area between the anode flowing out of the current source and the cathode at the grounding point are optimized, the electric field strength of the hippocampus area near the anode and the cathode is increased, and the current attenuation of the hippocampus area near the anode and the cathode is reduced. This is also verified by simulation below, and will not be repeated here.

[0030] When a group of second electrode sheets are only arranged at the scalp corresponding to the left temporal lobe, and the first electrode sheet 101 is arranged at the scalp corresponding to the right temporal lobe, as Figure 4 As shown, the first electrode sheet 101 disposed at the scalp corresponding to the right temporal lobe is grounded as a cathode, and the second electrode sheet 1021 disposed at the scalp corresponding to the left temporal lobe is connected to an alternating current source as an anode. In the figure, the position where the arrow flows out is the electrode sheet connected to the current source, and the position where the arrow points to is the grounded electrode sheet. Figure 4 In the embodiment, when the first electrode sheet 101 is set to be grounded, current flows out from the current source and flows into the first electrode sheet 101. The current flows through the hippocampus on the right side, and compared with the case where the first electrode sheet 101 on the right side is not grounded, the electric field strength at the hippocampus on the right side is increased, thereby increasing the stimulation intensity of the hippocampus.

[0031] In some other embodiments, the group of second electrode sheets is not only arranged at the scalp corresponding to the second temporal lobe, but also arranged at at least one of the scalp corresponding to the frontal lobe, the occipital lobe, and the parietal lobe. Specifically, as shown in FIG5 (a), a group of second electrode sheets includes a second electrode sheet 1021 arranged at the scalp corresponding to the left temporal lobe and a second electrode sheet 1022 arranged at the scalp corresponding to the frontal lobe. Among them, the second electrode sheet 1021 arranged at the scalp corresponding to the left temporal lobe and the second electrode sheet 1022 arranged at the scalp corresponding to the frontal lobe are used to distinguish between different brain regions. The first electrode sheet 101 is arranged at the scalp corresponding to the right temporal lobe and is grounded, and the second electrode sheet 1021 arranged at the scalp corresponding to the left temporal lobe and the second electrode sheet 1022 arranged at the scalp corresponding to the frontal lobe are connected to an AC current source. In this case, the current flowing out of the current sources of the second electrode sheet 1021 at the scalp corresponding to the left temporal lobe and the second electrode sheet 1022 at the scalp corresponding to the frontal lobe are combined and flow into the first electrode sheet 101. There is an AC current crossing at the first electrode sheet 101, which can reduce the current attenuation at the hippocampus, increase the current density at the hippocampus, and improve the intensity of electrical stimulation at the hippocampus.

[0032] In a specific embodiment, a four-layer ball head model is used to simulate and verify the experimental scheme and the comparative scheme shown in Figure 5 (a). In the comparative scheme, the second electrode sheet arranged at the scalp corresponding to the frontal lobe is connected to the AC current source, and the second electrode sheet arranged at the scalp corresponding to the left temporal lobe and the first electrode sheet arranged at the scalp corresponding to the right temporal lobe are both grounded, that is, there is no AC current crossing for the first electrode sheet at the scalp corresponding to the right temporal lobe.

[0033] The four-layer ball head model includes scalp, skull, CSF and brain tissue. The transcranial alternating current stimulation parameters are set to sine wave, with a current of 15mA and a frequency of 40Hz. The simulation results show that for the comparison scheme without AC current crossing, the current density at the left hippocampus is 0.135×10 -3 mA / mm 2 The current density in the right hippocampus was 0.135×10 -3 mA / mm 2 , and the current attenuation in the left and right hippocampus is as high as 1300 times; for the experimental scheme in Figure 5 (a), there is an AC current crossover, and the current density in the left hippocampus is 0.294×10-3 mA / mm 2 The current density in the right hippocampus was 0.43×10 -3 mA / mm 2 , and the current attenuation factor in the left hippocampus decreased to 500 times, and the current attenuation factor in the right hippocampus decreased to 400 times.

[0034] Therefore, based on the simulation results, it can be concluded that the current density attenuation degree at the hippocampus in the experimental scheme illustrated in FIG5 (a) is greatly reduced, and the electrical stimulation intensity of the hippocampus can be increased compared with the comparative scheme without AC current crossing. Please note that the so-called current crossing at a certain place is intended to indicate that other currents flow to the grounded place, or flow out from the place to other grounded places. In the second case, in some embodiments, as shown in FIG5 (b), the first electrode sheet 101 is set at the scalp corresponding to the right temporal lobe and connected to the AC current source, as the anode; the second electrode sheet 1021 set at the scalp corresponding to the left temporal lobe and the second electrode sheet 1022 set at the scalp corresponding to the frontal lobe are grounded and serve as the cathode. Compared with FIG5 (a), FIG5 (b) only swaps the anode and the cathode, and both of them ground the cathode. In the case of FIG5 (b), the current flowing out of the current source of the first electrode sheet 101 at the scalp corresponding to the right temporal lobe flows to the second electrode sheet 1021 set at the scalp corresponding to the left temporal lobe and the second electrode sheet 1022 at the scalp corresponding to the frontal lobe, respectively. In this way, when the current flows from the first electrode sheet 101 to the second electrode sheets, that is, the situation in Figure 5 (b), the current intensity flowing through the hippocampus is greater than the situation in which the current flows into the grounded first electrode sheet 101, that is, the situation in Figure 5 (a), which is beneficial to further reduce the current attenuation in the hippocampus and increase the electric field strength in the hippocampus.

[0035] In order to verify the conclusion of this embodiment, the four-layer spherical head model is further used to simulate and verify the experimental scheme of AC current crossing at the anode shown in FIG. 5 ( b ), and other simulation configurations are as described above.

[0036] Furthermore, the simulation results show that for the experimental scheme shown in Figure 5(b), the current density at the left hippocampus and the right hippocampus are 0.314×10 -3 mA / mm 2 , 0.447×10 -3 mA / mm 2. Therefore, based on the simulation verification results, the current intensity of the current flowing out from the first electrode sheet 101 and flowing through the downstream hippocampus, as shown in FIG5 (b), is greater than the current intensity of the current flowing into the first electrode sheet 101 and acting on the upstream hippocampus (as shown in FIG5 (a)), and although the first electrode sheet 101 is set at the scalp corresponding to the right temporal lobe, such as the mastoid behind the right ear, it is used as the anode for the alternating current crossing, which can increase the current density for both the right and left hippocampus, and increase the tACS current stimulation intensity. The current density at the right hippocampus is more than 40% higher than that at the left hippocampus. In other words, in order to strengthen the tACS stimulation intensity of the target side hippocampus, an electrode where the alternating current crosses can be set at the scalp corresponding to the target side temporal lobe. Furthermore, the electrode can be set as the anode and the other cathode can be grounded to further increase the current density caused by the alternating current crossing and thus enhance the electrical stimulation effect.

[0037] Taking the first electrode sheet 101 being disposed at the scalp corresponding to the right temporal lobe as an example, the group of second electrode sheets can also be arranged at various positions.

[0038] In some embodiments, Figure 6 As shown, a set of second electrode sheets may also include a second electrode sheet 1021 disposed at the scalp corresponding to the left temporal lobe and a second electrode sheet 1023 disposed at the scalp corresponding to the parietal lobe. Figure 7 As shown, a set of second electrode sheets may also include a second electrode sheet 1021 disposed at the scalp corresponding to the left temporal lobe and a second electrode sheet 1024 disposed at the scalp corresponding to the occipital lobe. Figure 8 As shown, a set of second electrode sheets may also include a second electrode sheet 1021 disposed at the scalp corresponding to the left temporal lobe, a second electrode sheet 1024 disposed at the scalp corresponding to the occipital lobe, and a second electrode sheet 1022 disposed at the scalp corresponding to the frontal lobe. This is only used as an example and does not constitute a limitation on the specific solution. Please note that Figure 6-Figure 8 The various electrode settings in the embodiment are described by taking the first electrode sheet 101 being grounded as a cathode to aggregate and receive current from each second electrode sheet as an example, but the present application is not limited to this. Each second electrode sheet may also be grounded as a cathode and the first electrode sheet 101 may be used as a common anode to feed current to each second electrode sheet, which will not be elaborated here.

[0039] In some other embodiments of the present application, the neuroregulatory device is further configured to provide a first stimulation level and a second stimulation level higher than the first stimulation level to the hippocampus on the first side, and when the first stimulation level is to be provided to the hippocampus on the first side, the group of second electrode sheets is only arranged at the scalp corresponding to the second temporal lobe; when the second stimulation level is to be provided to the hippocampus on the first side, the group of second electrode sheets is arranged at the scalp corresponding to the second temporal lobe and at the scalp corresponding to the frontal lobe. Specifically, second electrode sheets are arranged at both the scalp corresponding to the left temporal lobe and the scalp corresponding to the frontal lobe (as shown in FIG. 5 (a)), compared with the second electrode sheet 1021 only at the scalp corresponding to the left temporal lobe (as shown in FIG. 5 (b)). Figure 4 The stimulation intensity for the hippocampus was higher.

[0040] This is also confirmed by the simulation results. Figure 4 The experimental scheme shown in Figure 5 (a) is simulated and verified, and other simulation configurations are as described above. Figure 4 In the experimental scheme shown in FIG. 5 (a), the first electrode sheet 101 provided at the scalp corresponding to the right temporal lobe is grounded, and the second electrode sheet 1021 provided at the scalp corresponding to the left temporal lobe is connected to a current source. In the experimental scheme shown in FIG. 5 (a), the first electrode sheet 101 provided at the scalp corresponding to the right temporal lobe is grounded, and the second electrode sheet 1021 provided at the scalp corresponding to the left temporal lobe and the second electrode sheet 1022 provided at the scalp corresponding to the frontal lobe are connected to an AC current source.

[0041] The simulation results show that for Figure 4 The experimental scheme shown, the current density in the left hippocampus was 0.23×10 - 3 mA / mm 2 The current density in the right hippocampus was 0.23×10 -3 mA / mm 2 , the attenuation factor in the left and right hippocampus is 600 times; while for the experimental scheme shown in Figure 5(a), the current density in the left hippocampus is 0.43×10 -3 mA / mm 2 The current density in the right hippocampus was 0.294×10 -3 mA / mm 2 , the attenuation multiples at the left and right hippocampi are 400 and 500. It can be seen that the second electrode sheet 1021 at the scalp corresponding to the left temporal lobe and the second electrode sheet 1022 at the scalp corresponding to the frontal lobe significantly reduce the current attenuation at the hippocampus, and the stimulation level of the hippocampus is higher than that of the second electrode sheet 1021 only at the scalp corresponding to the left temporal lobe.

[0042] In addition, when providing the second stimulation level to the hippocampus on the first side, the group of second electrode sheets can also be arranged at the scalp corresponding to the second temporal lobe and the scalp corresponding to the parietal lobe, or at the scalp corresponding to the second temporal lobe and the scalp corresponding to the occipital lobe. That is to say, the second electrode sheet is arranged at the scalp corresponding to the second temporal lobe and the scalp corresponding to the parietal lobe, or at the scalp corresponding to the second temporal lobe and the scalp corresponding to the occipital lobe, and the stimulation level for the hippocampus is higher than that of only arranging the second electrode sheet at the scalp corresponding to the second temporal lobe. Due to the sparse hair at the extracerebral scalp corresponding to the frontal lobe, it is easier to stick the electrode sheet at the scalp corresponding to the frontal lobe than to stick the electrode sheet at the scalp corresponding to the parietal lobe and the occipital lobe. Therefore, preferably, when providing the second stimulation level to the hippocampus on the first side, the group of second electrode sheets is arranged at the scalp corresponding to the second temporal lobe and the scalp corresponding to the frontal lobe, so that the second electrode sheet can be attached to the scalp and not fall off easily, and high-intensity stimulation of the hippocampus area can be achieved.

[0043] In some other embodiments of the present application, the neuroregulatory device is further configured to provide a third stimulation level higher than the second stimulation level to the hippocampus on the first side, and when the third stimulation level is to be provided to the hippocampus on the first side, the set of second electrode sheets is arranged at least one of the scalp corresponding to the temporal lobe of the second side, the scalp corresponding to the frontal lobe, the scalp corresponding to the parietal lobe, and the scalp corresponding to the occipital lobe. Specifically, the four-layer ball head model is continued to be used to simulate and verify experimental schemes A, B, and C, and other simulation configurations are as described above.

[0044] exist Figure 8 In the experimental scheme A shown, the first electrode sheet 101 set at the scalp corresponding to the right temporal lobe is grounded, and the second electrode sheet 1021 at the scalp corresponding to the left temporal lobe, the second electrode sheet 1024 at the scalp corresponding to the occipital lobe and the second electrode sheet 1022 at the scalp corresponding to the frontal lobe are connected to the current source respectively; in the experimental scheme B (not shown in the figure), the first electrode sheet set at the scalp corresponding to the right temporal lobe is grounded, and the second electrode sheets set at the scalp corresponding to the left temporal lobe, the scalp corresponding to the parietal lobe and the scalp corresponding to the frontal lobe are connected to the current source respectively; in the experimental scheme C (not shown in the figure), the first electrode sheet set at the scalp corresponding to the right temporal lobe is grounded, and the second electrode sheets set at the scalp corresponding to the left temporal lobe, the scalp corresponding to the parietal lobe, the scalp corresponding to the frontal lobe and the scalp corresponding to the occipital lobe are connected to the current source respectively.

[0045] The simulation results show that for experimental scheme A, the current density in the left hippocampus is 0.587×10 -3 mA / mm 2 The current density in the right hippocampus was 0.339×10 -3 mA / mm 2, the attenuation times in the left and right hippocampus were 300 and 500 times respectively; for experimental scheme B, the current density in the left hippocampus was 0.587×10 -3 mA / mm 2 The current density in the right hippocampus was 0.339×10 -3 mA / mm 2 , the attenuation times in the left and right hippocampus were 300 and 500 times, respectively; for experimental scheme C, the current density in the left hippocampus was 0.757×10 -3 mA / mm 2 The current density in the right hippocampus was 0.407×10 -3 mA / mm 2 , the attenuation multiples at the left and right hippocampi are 250 and 450 times respectively. From the simulation results, when the second electrode sheet has been set at the scalp corresponding to the left temporal lobe and the scalp corresponding to the frontal lobe and connected to the current source, the attenuation multiple of the current at the hippocampus is reduced, and the current density at the left and right hippocampi is significantly increased.

[0046] It should be noted that since the simulation was performed using a four-layer spherical head model, the parameters of the spherical head model in the same layer were the same, so the results of experimental schemes A and B were the same, but the skull thickness of each brain region of the real head was different, so the simulation results might be slightly different.

[0047] That is to say, on the basis of setting the first electrode sheet 101 at the scalp corresponding to the temporal lobe on one side and grounding it, setting the second electrode sheet at the scalp corresponding to the temporal lobe on the other side and at the scalp corresponding to the frontal lobe and connecting it to an AC current source, setting the second electrode sheet at the scalp corresponding to either the parietal lobe or the occipital lobe and connecting it to an AC current source, the third stimulation level to the hippocampus is higher than the second stimulation level, so that the attenuation multiple of the current at the hippocampus is further reduced, and the stimulation intensity to the hippocampus is greater. Moreover, when the second electrode sheet is set at the scalp corresponding to the parietal lobe and the scalp corresponding to the occipital lobe and connected to the AC current source, the attenuation multiple of the current at the hippocampus is smaller, and the stimulation intensity to the hippocampus is further increased.

[0048] Therefore, by configuring each second electrode sheet in a group of second electrode sheets, three different stimulation levels of stimulation intensity can be provided to the hippocampus, so as to be suitable for patients with different stages of brain-related diseases and requiring different stimulation intensity levels. For example, for patients in the middle stage of the disease and requiring a higher stimulation intensity level, a second electrode sheet can be provided at least one of the scalp corresponding to the second temporal lobe, the scalp corresponding to the frontal lobe, the scalp corresponding to the parietal lobe, and the scalp corresponding to the occipital lobe to provide the hippocampus with a third stimulation level of electrical stimulation intensity, thereby helping to improve the treatment effect of brain-related diseases.

[0049] In some embodiments, the stimulation intensity to the hippocampus region can also be further adjusted by adjusting the frequency of the alternating current. In some embodiments of the present application, the frequency of the alternating current is 10Hz, 40Hz or 70-80Hz. For example, the frequency of the alternating current can be 10Hz, which is conducive to enhancing the neuroplasticity of the hippocampus, enhancing prominent activities, promoting information transfer between neurons, and improving the stimulation level to the hippocampus.

[0050] When the frequency of the alternating current is 40Hz, stimulation at a frequency of 40Hz can especially promote the exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF) in patients with Alzheimer's disease, play a positive role in p-Tau protein deposition, accelerate the lymphatic clearance of amyloid protein, stimulate and improve gamma oscillations, enhance the cognitive ability of patients with Alzheimer's disease, and delay the course of Alzheimer's disease. The gamma oscillations of patients with Alzheimer's disease are impaired. By inducing endogenous EEG oscillations through external current to produce entrainment, the neural network in the damaged area can be specifically regulated. Transcranial alternating current stimulation in the same frequency band as the abnormal gamma oscillations of Alzheimer's patients can improve the neural oscillations and brain functional connections in the damaged area and promote brain function improvement. Transcranial alternating current stimulation at 40Hz can significantly improve patients' memory, regulate neural oscillations, increase the perfusion of key brain areas, regulate the level of cholinergic transmission, and also has a significant effect on emotional regulation.

[0051] Also as a frequency range in the gamma band, transcranial alternating current stimulation at 75-80Hz can significantly increase the release of beta-endorphin in the brain of Alzheimer's patients. Even with longer treatment time or greater current stimulation intensity, for example, the total stimulation current for Alzheimer's disease reaches 5mA, or even 10mA, or even 15mA, 16mA, 17mA, 18mA, 19mA or even 20mA, Alzheimer's patients do not feel obvious pain.

[0052] In some embodiments, a first electrode sheet is set at the scalp corresponding to the right temporal lobe and grounded using a four-layer ball head model, and a second electrode sheet is set at the scalp corresponding to the left temporal lobe and connected to an AC current source, and the AC current source is simulated and verified with an AC current of 40 Hz and an AC current of 75 Hz respectively. The simulation verification results show that when the frequency of the AC current is changed from 40 Hz to 75 Hz, the current attenuation multiple in the hippocampus is reduced from 600 times to 310 times, indicating that the electrical stimulation intensity of the hippocampus is increased. The inventor modified the frequency of the AC current from 75 Hz to 70 Hz, 70.5 Hz, 71 Hz, 71.5 Hz, 72 Hz, 72.5 Hz, 73 Hz, 73.5 Hz, 74 Hz, 74.5 Hz, 75 Hz, 75.5 Hz, 76 Hz, 76.5 Hz, 77 Hz, 78 Hz, 78.5 Hz, 79 Hz, 79.5 Hz and 80 Hz, and then simulated and verified it. The simulation verification results show that compared with 40Hz, the current attenuation multiples of tACS in the hippocampus at these frequencies are all reduced, but the deviation of the current attenuation multiples of tACS in the hippocampus at each frequency of 70Hz-80Hz is not large. The inventor modified the frequency of the alternating current from 40Hz to 25Hz, 25.5Hz, 26Hz, 26.5Hz, 27Hz, 27.5Hz, 28Hz, 28.5Hz, 29Hz, 29.5Hz and 30Hz, and conducted simulation verification. The simulation verification results show that compared with 40Hz, the current attenuation multiples of tACS in the hippocampus at these frequencies are all increased, but the current attenuation multiples of tACS in the hippocampus at each frequency of 25Hz-30Hz also follow the higher the frequency, the lower the current attenuation multiple, but the attenuation deviation is not large.

[0053] That is, the neuroregulatory device is further configured to provide a first current attenuation level and a second current attenuation level lower than the first current attenuation level to the hippocampus on the first side, and when the first current attenuation level is to be provided to the hippocampus on the first side, the frequency of the alternating current is a first frequency in 25-85 Hz, and when the second current attenuation level is to be provided to the hippocampus on the first side, the frequency of the alternating current is a second frequency in 25-85 Hz that is higher than the first frequency. In some embodiments, the first frequency can be set in the range of 25-40 Hz (or 25-30 Hz), and the second frequency can be set in the range of 70-80 Hz. By further increasing the frequency of the alternating current, it is beneficial to further enhance the stimulation intensity of the hippocampus.

[0054] When the frequency of the alternating current is 25-85Hz, it is beneficial to improve gamma oscillations. tACS stimulation in this frequency range can also increase the release of beta-endorphin in the brains of Alzheimer's patients.

[0055] In some other embodiments of the present application, the amplitude of the alternating current can be adjusted within the range of 0 to 15 mA. Specifically, the currently known maximum adjustment of the amplitude of the alternating current is only 5 mA. However, the neuromodulator provided in the embodiment of the present application can achieve an amplitude of the alternating current of up to 15 mA by setting the first electrode sheet and a group of second electrode sheets. For example, when the frequency of the alternating current was set at 70 Hz, 70.5 Hz, 71 Hz, 71.5 Hz, 72 Hz, 72.5 Hz, 73 Hz, 73.5 Hz, 74 Hz, 74.5 Hz, 75 Hz, 75.5 Hz, 76 Hz, 76.5 Hz, 77 Hz, 78 Hz, 78.5 Hz, 79 Hz, 79.5 Hz and 80 Hz, a 5-10 minute tACS test was performed on a single voluntary participant with an amplitude of approximately 10 mA, and the beta-endorphin concentration in the cerebrospinal fluid (CSF) sample was tested using an ELISA (enzyme-linked immunosorbent assay) kit. The results showed that the beta-endorphin in the cerebrospinal fluid of the subjects increased. At this time, when the amplitude of the alternating current was briefly adjusted to a maximum of 15 mA, the subjects did not feel obvious pain, which can further increase the stimulation intensity of the hippocampus and improve the therapeutic effect on brain-related diseases.

[0056] In some other embodiments of the present application, the neuromodulatory device is used to synergistically stimulate the hippocampus on the first side and the hippocampus on the second side, such as Fig. 9 As shown, there are two first electrode sheets arranged at the scalp corresponding to the first side temporal lobe, one in front of the ear on the first side, and the other behind the ear on the first side; there are also two second electrode sheets arranged at the scalp corresponding to the second side temporal lobe, one in front of the ear on the second side, and the other behind the ear on the second side. Fig. 9 In the figure, the electrode sheet indicated by the dotted line is located behind the ear, and the electrode sheet indicated by the solid line is located in front of the ear.

[0057] Among them, the first electrode sheet 9012 in front of the ear on the first side is connected to the alternating current source, the first electrode sheet 9011 behind the ear on the first side is grounded, the second electrode sheet 9022 in front of the ear on the second side is connected to the alternating current source, and the second electrode sheet 9021 behind the ear on the second side is grounded, thereby forming a first current field from the first electrode sheet 9012 in front of the ear on the first side to the second electrode sheet 9021 behind the ear on the second side, and a second current field from the second electrode sheet 9022 in front of the ear on the second side to the first electrode sheet 9011 behind the ear on the first side. In this way, by increasing the number of electrode sheets at the scalp corresponding to the temporal lobe, it is beneficial to form two crossed electric fields at the hippocampus, thereby further reducing the attenuation of the current at the hippocampus and increasing the stimulation intensity of the hippocampus.

[0058] In some embodiments of the present application, a multimodal neuroregulatory system is provided, and the multimodal neuroregulatory system includes one or more of a light therapy device, a sound stimulation therapy device, a transcranial magnetic stimulation therapy device, and a neuroregulatory device for performing transcranial alternating current stimulation on the hippocampus according to various embodiments of the present application. For example, the multimodal neuroregulatory system includes a neuroregulatory device for performing transcranial alternating current stimulation on the hippocampus, and also includes a light therapy device, so as to realize the combination of transcranial alternating current stimulation and light stimulation, thereby more comprehensively regulating the neural activity of the brain, further strengthening the stimulation effect, and improving the effect of treating brain-related diseases.

[0059] This application describes various operations or functions that may be implemented as software codes or instructions or defined as software codes or instructions. Such content may be source code or differential code ("incremental" or "patch" code) that can be directly executed ("object" or "executable" form). Software codes or instructions may be stored in a computer-readable storage medium, and when executed, may cause a machine to perform the described functions or operations, and include any mechanism for storing information in a form accessible to a machine (e.g., a computing device, an electronic system, etc.), such as recordable or non-recordable media (e.g., read-only memory (ROM), random access memory (RAM), magnetic disk storage media, optical storage media, flash memory devices, etc.).

[0060] The exemplary methods described in this application may be implemented at least in part by a machine or computer. In some embodiments, a computer-readable storage medium stores computer program instructions, which, when executed by a processor, cause the processor to perform the steps of performing transcranial alternating current stimulation of the hippocampus by the neuromodulatory device of each embodiment of the present application.

[0061] The implementation of such a method may include software code, such as microcode, assembly language code, high-level language code, etc. Various software programming techniques may be used to create various programs or program modules. For example, a program portion or program module may be designed with or by means of Java, Python, C, C++, assembly language, or any known programming language. One or more of such software portions or modules may be integrated into a computer system and / or a computer-readable medium. Such software code may include computer-readable instructions for executing various methods. The software code may form a part of a computer program product or a computer program module. In addition, in an example, the software code may be tangibly stored on one or more volatile, non-temporary or non-volatile tangible computer-readable media, such as during execution or at other times. Examples of these tangible computer-readable media may include, but are not limited to, hard disks, removable disks, removable optical disks (such as optical disks and digital video disks), cassettes, memory cards or memory sticks, random access memories (RAMs), read-only memories (ROMs), etc.

[0062] In addition, although exemplary embodiments have been described herein, the scope includes any and all embodiments based on the present application with equivalent elements, modifications, omissions, combinations (e.g., various embodiments intersecting schemes), adaptations or changes. The elements in the claims are to be interpreted broadly based on the language adopted in the claims, and are not limited to the examples described in this specification or during the practice of this application, and the examples are to be interpreted as non-exclusive. Therefore, this specification and examples are intended to be considered as examples only, and the true scope and spirit are indicated by the following claims and the full scope of their equivalents.

[0063] The above description is intended to be illustrative rather than restrictive. For example, the above examples (or one or more schemes thereof) may be used in combination with each other. For example, a person of ordinary skill in the art may use other embodiments when reading the above description. In addition, in the above-mentioned specific embodiments, various features may be grouped together to simplify the present application. This should not be interpreted as an intention that a disclosed feature that is not required to be protected is necessary for any claim. On the contrary, the subject matter of the present application may be less than all the features of a particular disclosed embodiment. Thus, the claims are incorporated herein as examples or embodiments in the specific embodiments, wherein each claim is independently a separate embodiment, and it is considered that these embodiments may be combined with each other in various combinations or arrangements. The scope of the present application should be determined with reference to the attached claims and the full scope of equivalent forms granted by these claims.

[0064] The above embodiments are only exemplary embodiments of the present application and are not intended to limit the present application. The protection scope of the present application is defined by the claims. Those skilled in the art may make various modifications or equivalent substitutions to the present application within the essence and protection scope of the present application, and such modifications or equivalent substitutions shall also be deemed to fall within the protection scope of the present application.

Claims

1. A neuromodulatory device for performing transcranial alternating current stimulation on the hippocampus, characterized in that: The neuromodulator is used to stimulate the hippocampus on the first side to treat related brain diseases, and comprises a first electrode sheet arranged at the scalp corresponding to the temporal lobe on the first side, and a group of second electrode sheets, wherein at least one of the second electrode sheets is arranged at the scalp corresponding to the temporal lobe on the second side, The first electrode sheet is grounded and used as a cathode, and the second electrode sheet is connected to an AC current source and used as an anode, so that the AC current flows into the first electrode sheet; or the second electrode sheet is grounded and used as a cathode, and the first electrode sheet is connected to an AC current source and used as an anode, so that the AC current flows from the first electrode sheet to the second electrode sheet, so as to reduce the attenuation of the AC current in the hippocampus and increase the electric field strength in the hippocampus on one side.

2. The neural regulation device according to claim 1, characterized in that: The second electrode sheet is not only arranged at the scalp corresponding to the second temporal lobe, but also arranged at the scalp corresponding to at least one of the frontal lobe, the occipital lobe and the parietal lobe.

3. The neuromodulator according to claim 1 or 2, characterized in that: The neuromodulation device is further configured to provide a first stimulation level and a second stimulation level higher than the first stimulation level to the hippocampus on the first side, When the first stimulation level is to be provided to the hippocampus on the first side, the second electrode sheet is only arranged at the scalp corresponding to the temporal lobe on the second side; When the second stimulation level is to be provided to the hippocampus on the first side, the second electrode patch is arranged on the scalp corresponding to the temporal lobe and the frontal lobe on the second side.

4. The neural regulation device according to claim 3, characterized in that: The neuroregulatory device is further configured to provide a third stimulation level higher than the second stimulation level to the hippocampus on the first side. When the third stimulation level is to be provided to the hippocampus on the first side, the second electrode patch is arranged on the scalp corresponding to the temporal lobe of the second side, the scalp corresponding to the frontal lobe, and at least one of the parietal lobe and occipital lobe.

5. The neural regulation device according to claim 1 or 2, characterized in that: The frequency of the alternating current is 10 Hz, 40 Hz or 70-80 Hz.

6. The neuromodulator according to claim 1 or 2, characterized in that: The neuromodulation device is further configured to provide a first current decay level and a second current decay level lower than the first current decay level to the hippocampus on the first side, When the first current attenuation level is to be provided to the hippocampus on the first side, the frequency of the alternating current is a first frequency in the range of 25-85 Hz, When a second current attenuation level is to be provided to the hippocampus on the first side, the frequency of the alternating current is a second frequency higher than the first frequency and within a range of 25-85 Hz.

7. The neuromodulator according to claim 1 or 2, characterized in that: The amplitude of the alternating current can be adjusted within the range of 0 to 15 mA.

8. The neuromodulator according to claim 1 or 2, characterized in that: The neuromodulator is used to stimulate the hippocampus on the first side and the hippocampus on the second side in a coordinated manner. There are two first electrode sheets arranged at the scalp corresponding to the first side temporal lobe, one in front of the ear on the first side, and the other behind the ear on the first side; There are also two second electrode sheets arranged at the scalp corresponding to the second side temporal lobe, one in front of the ear on the second side, and the other behind the ear on the second side; Among them, the first electrode sheet in front of the ear on the first side is connected to the AC current source, the first electrode sheet behind the ear on the first side is grounded, the second electrode sheet in front of the ear on the second side is connected to the AC current source, and the second electrode sheet behind the ear on the second side is grounded, thereby forming a first current field from the first electrode sheet in front of the ear on the first side to the second electrode sheet behind the ear on the second side, and a second current field from the second electrode sheet in front of the ear on the second side to the first electrode sheet behind the ear on the first side.

9. The neuromodulator according to claim 1 or 2, characterized in that: The first electrode sheet arranged at the scalp corresponding to the first temporal lobe and the second electrode sheet arranged at the scalp corresponding to the second temporal lobe are semi-annular or annular in shape so as to be attached to the scalp around the ear.

10. A multimodal neural regulation system, characterized in that: The multimodal neuroregulatory system includes one or more of a light therapy device, a sound stimulation therapy device, a transcranial magnetic stimulation therapy device, and a neuroregulatory device for performing transcranial alternating current stimulation of the hippocampus according to any one of claims 1-9.

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