A transcranial physical stimulation device

Abstract

The present application provides a transcranial physical stimulation device, which includes at least a phototherapy unit and an AC transcranial electrical stimulation unit. The phototherapy unit is configured to irradiate transcranial near-infrared light to at least the frontal lobe, temporal lobe, and parietal lobe of the subject's head. The AC transcranial electrical stimulation unit includes a first scalp electrode pair and a second scalp electrode pair. The first scalp electrode pair forms a first electric field and acts on a target deep part. The second scalp electrode pair forms a second electric field and acts on the target deep part. The first electric field and the second electric field are AC oscillating electric fields applied simultaneously, with a frequency of more than 1000 Hz and a frequency difference of 10 Hz-80 Hz. The device is easy to operate and can provide comprehensive, gentle, and comfortable transcranial physical therapy for multiple brain areas involved in AD. It can also coordinate transcranial alternating current (tACS) to provide targeted and precise treatment of deep parts of the brain such as the hippocampus.

Description

Technical Field

[0001] The present application relates to a transcranial physical stimulation device for treating brain diseases, and in particular to a transcranial physical stimulation device. Background Art

[0002] With the aging of the population, the widespread prevalence of Alzheimer's disease (AD) in people over 65 is becoming a common challenge for society and families. The pathogenesis of AD is not fully understood, but the generally recognized main pathological features include extracellular neuritic plaques formed by the deposition of beta-amyloid protein and intracellular neurofibrillary tangles (NFTs) formed by the aggregation of hyperphosphorylated tau protein, with the degeneration and disappearance of a large number of neurons.

[0003] Among various AD treatment methods, tACS (transcranial alternating current stimulation) has recently become a safer non-invasive brain stimulation technology. It applies 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 brain's endogenous oscillations, such as the abnormal gamma oscillations in AD patients, and inducing the restoration of functional connectivity between brain regions.

[0004] The pathogenesis of AD is still unclear, and the lesions involve a wide range of brain areas, including the prefrontal lobe, temporal lobe, hippocampus, etc. After all, tACS is a form of electrical stimulation, and AD patients generally have a low acceptance of tACS in a wide range of brain areas. Arranging more electrodes on the heads of AD patients will increase the pressure on AD patients, and AD patients often suffer from mental and behavioral symptoms such as depression and anxiety, resulting in poor treatment compliance. The hair on the patient's head also makes it difficult to arrange more electrodes. If a conductive gel similar to an EEG electrode is used, it will increase the discomfort and resistance of AD patients. The tACS dose for a certain brain area is likely to act on an area that is not expected to be affected by the tACS dose. Doctors will worry about whether the specific electric field distribution of tACS in the skull can meet the actual needs of AD patients. Summary of the Invention

[0005] This application is based on the above-mentioned technical problems existing in the prior art. This application aims to provide a transcranial physical stimulation device for treating diseases related to deep brain regions, including Alzheimer's disease, which is easy to operate and can provide comprehensive, gentle and comfortable transcranial physical therapy to multiple brain regions involved in AD. It can also coordinate with transcranial alternating current (tACS) to provide targeted and precise treatment of deep brain regions such as the hippocampus.

[0006] According to the first scheme of the present application, a transcranial physical stimulation device is provided. The transcranial physical stimulation device includes at least a phototherapy unit and an AC transcranial electrical stimulation unit, and the phototherapy unit is configured to irradiate transcranial near-infrared light to at least the frontal lobe, temporal lobe and parietal lobe of the subject's head. The AC transcranial electrical stimulation unit includes a first scalp electrode pair and a second scalp electrode pair, the first scalp electrode pair includes a first electrode and a second electrode, the first electrode is arranged on the scalp near the first side temporal lobe, and the second electrode is arranged on the scalp more anterior to the first electrode, so that a first electric field is formed between the first electrode and the second electrode and acts on the target deep part. The second scalp electrode pair includes a third electrode and a fourth electrode, the third electrode is arranged on the scalp near the other side temporal lobe, and the fourth electrode is arranged on the scalp more anterior to the third electrode, so that a second electric field is formed between the third electrode and the fourth electrode and acts on the target deep part, the first electric field and the second electric field are AC oscillating electric fields applied simultaneously, with a frequency above 1000 Hz and a frequency difference of 10 Hz-80 Hz.

[0007] According to a second embodiment of the present application, a transcranial physical stimulation device is provided. The phototherapy unit further includes a head cap, wherein a plurality of near-infrared light source assemblies are disposed inside the head cap, wherein the plurality of near-infrared light source assemblies are configured to emit pulsed light toward the treatment subject, wherein the pulsed light has a wavelength of 620 nm to 1080 nm, and wherein the radiation range of the pulsed light from each near-infrared light source assembly includes at least a portion of the hippocampus and overlaps at the hippocampus to form a second overlapping region.

[0008] Compared to the prior art, the beneficial effects of the embodiments of the present application are that the phototherapy unit can work in conjunction with the AC transcranial electrical stimulation unit to irradiate a wide range of brain regions with mild near-infrared light. This gentle and comfortable irradiation reduces the psychological stress on the irradiated subject. Furthermore, by conveniently attaching scalp electrodes in a few locations, AC transcranial electrical stimulation can be targeted and enhanced to target deep areas such as the hippocampus. The electrodes are placed in areas with less hair, allowing for easy adaptation based on the location of the target deep area. This not only provides comprehensive treatment for diffuse superficial lesions, but also provides targeted and enhanced stimulation for concentrated, deep target areas. Furthermore, widespread transcranial near-infrared light irradiation of diffuse superficial lesions can widely reduce or even eliminate these lesions. For example, in Alzheimer's disease, this can reduce inflammatory mediators and Aβ plaque deposition. Furthermore, the exogenous oscillation-neural entrainment mechanism can be used to focus on the target deep areas, providing comprehensive treatment from the perspective of both the therapeutic mechanism and the lesions at different stages of the disease. Furthermore, the subject experiences greater comfort and less psychological stress during treatment.

[0009] 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

[0010] In the drawings, which are not necessarily drawn to scale, the same reference numerals may describe similar components 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, serve to illustrate the disclosed embodiments. Such embodiments are illustrative and exemplary and are not intended to be exhaustive or exclusive embodiments of the present method, apparatus, system, or non-transitory computer-readable medium having instructions for implementing the method.

[0011] FIG1( a ) shows a schematic left side view of a transcranial physical stimulation device for treating diseases related to a target deep part of the brain according to an embodiment of the present application;

[0012] FIG1( b ) shows a schematic right side view of a transcranial physical stimulation device for treating diseases related to a target deep part of the brain according to an embodiment of the present application;

[0013] FIG2( a ) shows a first example of an electrode configuration of a transcranial physical stimulation device according to an embodiment of the present application;

[0014] FIG2( b ) shows a second example of an electrode configuration of a transcranial physical stimulation device according to an embodiment of the present application;

[0015] FIG2( c ) shows a third example of an electrode configuration of a transcranial physical stimulation device according to an embodiment of the present application;

[0016] FIG2( d ) shows a fourth example of an electrode configuration of a transcranial physical stimulation device according to an embodiment of the present application;

[0017] Figure 3 A diagram showing a superimposed envelope of a first electric field and a second electric field applied simultaneously according to an embodiment of the present application; and

[0018] Figure 4 A diagram showing the radiation range of the light therapy part of the transcranial physical stimulation device relative to the hippocampus according to an embodiment of the present application. DETAILED DESCRIPTION

[0019] 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 embodiments. The embodiments of the present application are further described in detail below in conjunction with the accompanying drawings and specific embodiments, but are not intended to limit the present application.

[0020] The words "first", "second" and similar terms 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 terms 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 steps in the execution order can be combined, decomposed, or swapped, as long as the logical relationship of the execution content is not affected.

[0021] All terms (including technical 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 as such 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.

[0022] Figures 1(a) and 1(b) respectively show a schematic left side view and a schematic right side view of a transcranial physical stimulation device for treating diseases related to target deep areas of the brain according to an embodiment of the present application. As used herein, the term "for treating diseases related to deep areas of the brain" is intended to mean that the disease is related to deep areas of the brain, such as at least one of the basal ganglia, thalamus, amygdala, hippocampus, and neural nuclei. For example, AD is closely associated with the hippocampus. For another example, anxiety and post-traumatic stress disorder (PTSD) are both associated with the amygdala. For another example, post-stroke cognitive impairment (PSCI) and thalamic dementia are associated with the thalamus. The so-called transcranial physical stimulation device is intended to mean that the applied physical stimulation, such as light, electricity, or magnetism, still has a physical stimulation amount after being attenuated by the skull, and can act on the brain tissue below the skull, at least on the cortex. Brain tissues from shallow to deep include the cerebral cortex, white matter, basal ganglia, thalamus, hypothalamus, etc. For example, the hippocampus is located in the temporal lobe of the brain, close to the medial temporal lobe, and is part of the limbic system. It is located in the deep structures of the brain, but not as deep as the basal ganglia, thalamus, or brainstem. The hippocampus is often considered anatomically to be a subcortical structure.

[0023] As shown in Figures 1(a) and 1(b), the transcranial physical stimulation device includes at least a phototherapy unit 101 and an alternating current transcranial electrical stimulation (tACS) unit 102. Please note that for the sake of simplicity in the diagram, only the head cap of the phototherapy unit 101 and the scalp electrode sheet of the alternating current transcranial electrical stimulation unit 102 are shown, and structures such as the cables and the host device to which the cables are connected are not shown. For example, the phototherapy unit 101 may include an array of LED light panels distributed in the head cap to emit transcranial near-infrared light to multiple parts of the subject's head, and these LED light panels can be powered externally via cables to light up the LED lamp beads to emit transcranial near-infrared light. For another example, the phototherapy unit 101 may include an array of optical fiber bundles introduced into the head cap, and the optical fiber bundles can transmit near-infrared light from an external light source (such as but not limited to a near-infrared light excitation generator) via an optical cable.

[0024] The phototherapy unit 101 is configured to irradiate transcranial near-infrared light to at least the frontal, temporal, and parietal lobes of the subject's head. For diseases related to targeted deep brain regions, before clinical symptoms appear or during disease progression, lesions are not limited to the targeted deep brain regions but frequently occur in more superficial regions of the frontal, temporal, and parietal lobes.

[0025] Let’s take Alzheimer’s disease as an example.

[0026] Alzheimer's disease is a brain disease associated with the hippocampus, a region deep within the brain. Widespread deposition of Aβ plaques in the cerebral cortex and the formation of neurofibrillary tangles caused by tau protein pathology in the cortex are prominent pathological hallmarks of Alzheimer's disease. The accumulation of Aβ plaques triggers a chain reaction that leads to the misfolding and assembly of tau protein within cells, which in turn spreads to wider neural circuits and the cortex, ultimately leading to neurological failure and cognitive decline. Years before clinical symptoms of Alzheimer's disease appear, Aβ plaques accumulate in the medial prefrontal and parietal regions of the neocortex. Tau protein also accumulates in the medial temporal lobe of the neocortex and gradually spreads to the hippocampus and limbic cortex. The progression of Aβ plaque deposition and tau protein aggregation also reflects, to some extent, the course of Alzheimer's disease.

[0027] Furthermore, neuroinflammation also plays a significant role in the development of Alzheimer's disease. Neuroinflammation refers to the activation of the brain's immune response, involving immune cells such as microglia and astrocytes. In healthy conditions, neuroinflammation plays a beneficial role in maintaining brain homeostasis and defending against infection or injury. However, in patients with Alzheimer's disease, this inflammatory response becomes chronic and dysregulated, even before symptoms appear, leading to harmful consequences such as neuronal damage. Neuroinflammation is closely associated with the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles caused by hyperphosphorylated tau protein. Microglia and astrocytes are resident immune cells in the brain and play a key role in regulating neuroinflammation in Alzheimer's disease. Following the accumulation of Aβ plaques, microglia and astrocytes undergo a shift from an M1 / A1 phenotype to an M2 / A2 phenotype, thereby losing their protective function and promoting the production of proinflammatory cytokines, exacerbating neuroinflammation. In addition, the phagocytic function of microglia is impaired, resulting in reduced clearance of Aβ plaques and further neurotoxicity. These two types of glial cells are widely distributed in the brain, from the cortex to deep structures such as the hippocampus. This leads to the diffuse distribution of inflammatory mediators during the course of Alzheimer's disease, occurring in the frontal, temporal, and parietal lobes of the cortex before symptoms appear.

[0028] For brain diseases with diffuse, multi-focal distributions, such as Alzheimer's disease, by irradiating at least the frontal, temporal, and parietal lobes of a subject's head with an appropriate dose of transcranial near-infrared light, a comprehensive, gentle, and comfortable treatment can be provided for diffuse lesions more superficial than those deep within the target area. Specifically, irradiating the frontal, temporal, and parietal lobes of a subject with an appropriate dose of transcranial near-infrared light can significantly reduce the accumulated volume and number of Aβ plaques in the cerebral cortex and hippocampus, lower inflammation levels, upregulate corresponding stress response proteins in the brain, reduce protein aggregation and neuronal apoptosis, and enhance the phagocytic activity of cells such as microglia on accumulated Aβ plaques, thereby alleviating the progression of Alzheimer's disease.

[0029] The scalp electrode pads of the AC transcranial electrical stimulation unit 102 are paired, including a first scalp electrode pair and a second scalp electrode pair. The first scalp electrode pair includes a first electrode e1 and a second electrode e2. The first electrode e1 is placed on the scalp near the first temporal lobe, and the second electrode e2 is placed on the scalp more anterior to the first electrode. This creates a first electric field E1 between the first and second electrodes, which acts on the target deep area. The second scalp electrode pair includes a third electrode e4 and a fourth electrode e3. The third electrode e4 is placed on the scalp near the other temporal lobe, and the fourth electrode e3 is placed on the scalp more anterior to the third electrode e4. This creates a second electric field E2 between the third and fourth electrodes e3, which acts on the target deep area. The first and second electric fields E1 and E2 are simultaneously applied AC oscillating electric fields with a frequency above 1000 Hz and a frequency difference of 10 Hz to 80 Hz.

[0030] Such electrodes are placed near or further forward on the temporal lobe, such as near the temporal hairline, behind the ears, on the forehead, etc., where there is less hair and it is easy to expose (for example, shaving a portion of the hairline does not greatly affect the appearance). For example, as shown in Figures 1(a) and 1(b), it is easier to attach and remove, and it is also more convenient and comfortable to wipe off when using conductive gel. In addition, because the electrode sheets are placed in areas with less hair, they can also be easily adapted according to the location of the target deep part. For example, the electrode configurations shown in Figures 2(a), 2(b), 2(c), and 2(d) can provide precise targeted intensive treatment of different target deep parts, which will be described in detail below.

[0031] The electrode arrangement of Figures 1(a) and 1(b) is used as an example for explanation. Figure 2(a) shows this electrode arrangement in a head MRI image. Electrode e1 and electrode e2 are a pair, and electrode e3 and electrode e4 are a pair. As shown in Figure 2(a), electrode e1 is arranged around the left ear, and electrode e2 is arranged on the right forehead near the temporal lobe; electrode e3 is arranged around the left ear, separated from electrode e1 on both sides of the upper edge of the helix, and electrode e4 is arranged on the right occipital near the temporal lobe. The hair around the ear is also sparse, and the hair around the frontal lobe near the temporal lobe and the hair around the occipital lobe near the temporal lobe are relatively sparse, making it easy to attach electrodes and clean them. For the hippocampus, in some embodiments, the two electrode patches around the ear can be arranged basically symmetrically on both sides of the upper edge of the helix, with a spacing of 4-6 cm, which just corresponds to the front and back of the hippocampus.

[0032] The paired electrode sheets e1-e2 can be connected to a corresponding current source I1 of an alternating sinusoidal waveform to generate an oscillating first electric field in the brain between the pair of electrode sheets, denoted as E1, and the paired electrode sheets e3-e4 can be connected to a corresponding current source I2 of an alternating sinusoidal waveform to generate an oscillating second electric field in the brain between the pair of electrode sheets, denoted as E2. The first electric field E1 and the second electric field E2 can be superimposed at the elongated target deep part on the left - the hippocampus, and the superimposed area is shown as the white circle in Figure 2(a). A sinusoidal current source is used as an example here, but it should be noted that the waveform of the current is not limited to this and may also include other waveforms such as square waves.

[0033] The first electric field E1 and the second electric field E1 are simultaneously applied AC oscillating electric fields with a frequency above 1000 Hz and a frequency difference of 10 Hz to 80 Hz. This creates a beat frequency phenomenon, which occurs when two sinusoidal or periodic signals with similar but different frequencies are superimposed. When the frequency difference between the two signals is small, a low-frequency oscillation envelope can be observed, with a frequency equal to the difference between the two original signal frequencies.

[0034] The first electric field E1 and the second electric field E2 are two sine wave signals with very close frequencies, such as f1 and f2, respectively, with f2>f1. Both frequencies are greater than 1000Hz, or even several thousand Hz. The frequency difference Δf=f2-f1 is a few Hz to tens of Hz. These two signals E1 and E2 are superimposed in the overlapping area. The frequency difference is small enough relative to the frequency. After superposition, a low-frequency oscillating electric field E is obtained. The envelope curve obtained after superposition is as follows Figure 3 The frequency of the low-frequency oscillation is Δf, and the frequency of the low-frequency oscillation can be changed by adjusting the frequency difference.

[0035] Although two high-frequency oscillating electric fields with a frequency of more than 1000Hz are applied, the cells in the area where the two electric fields do not overlap will not be activated, and the neurons will not respond to it. Because neurons only respond to low-frequency signals <100Hz and are not affected by high-frequency signals >1KHz, this allows the high-frequency electric field signal to reach the deep part of the target without causing any impact on the neurons in the superficial areas such as the cortex and sub-cortex along the way. In the deep part of the target, the low-frequency oscillating electric field signal obtained by superimposing two high-frequency electric field signals with a frequency difference Δf has a frequency range that effectively acts on neurons, regulates the endogenous oscillations of the brain, forms neural entrainment, and thus regulates neural activity and induces the recovery of functional connections between brain regions.

[0036] High-frequency electric field signals can introduce sufficient energy, but this energy has no effect on cells and neurons along the pathway of a single high-frequency electric field signal, and is not wasted on or stimulated in undesirable superficial areas. Instead, two high-frequency electric field signals with a frequency difference of Δf form a low-frequency oscillating electric field in the overlapping region, a frequency difference to which cells and neurons are sensitive. This allows sufficient energy to be efficiently focused and targeted to the target deep within the overlapping region, such as the hippocampus, ensuring a precise targeted dose.

[0037] Unlike relying solely on near-infrared radiation to reach deep target areas such as the hippocampus, the phototherapy unit 101 of the present application can work in conjunction with the AC transcranial electrical stimulation unit 102 to irradiate a wide range of brain areas using near-infrared light with mild energy. The irradiation is gentle and comfortable, and the psychological pressure on the irradiated subject is relatively small. By conveniently attaching scalp electrodes in a few locations, AC transcranial electrical targeted intensive stimulation can be performed on deep target areas such as the hippocampus. In this way, not only is the diffuse shallow lesion tissue treated thoroughly, but also the concentrated and deep target deep areas are targeted for intensive stimulation. Furthermore, the extensive irradiation of diffuse shallow lesion tissue with transcranial near-infrared light can widely reduce or even eliminate diffuse shallow lesions. For example, for Alzheimer's disease, it can reduce inflammatory mediators, reduce the deposition of Aβ plaques, and focus on the target deep areas with the mechanism of exogenous oscillation-neural entrainment. The present application uses a rich therapeutic mechanism to carry out comprehensive treatment for lesions of different disease courses, and the subject feels more comfortable and has less psychological pressure during the treatment process.

[0038] Please note that Figure 2(a) is only an example of an electrode arrangement, which is particularly suitable for treating Alzheimer's disease and performing transcranial alternating current focused targeted stimulation of the hippocampus. Figure 2(a)-Figure 2(d) As shown, each cerebral hemisphere has a hippocampus, which is C-shaped and elongated and located between the thalamus and medial temporal lobe on the corresponding side. Returning to Figure 2(a), during the course of Alzheimer's disease, the lesions in the hippocampus are often asymmetrical. Using the electrode arrangement shown, the two electrodes e1 and e3 around the ear can be staggered to determine which hippocampus is to be stimulated. These two electrodes can be used as positive electrodes, placing the positive electrode closer to the hippocampus to be stimulated. This reduces electric field diffusion, increasing the electric field strength and current intensity acting on the hippocampus.

[0039] Not only that, for the hippocampus that is slender on each side, the hippocampus can also be subjected to partial focused stimulation. The main extension direction of the hippocampus is called the longitudinal direction, and a single hippocampus can be divided into several longitudinal target parts, such as the longitudinal front, the longitudinal middle, the longitudinal back, etc. For example, among electrodes e1 and e3, the former corresponds to the longitudinal front and the latter corresponds to the longitudinal middle. If the longitudinal front is stimulated, the stimulation current amplitude of electrode e3 can be made larger than the stimulation current amplitude of electrode e1, that is, the stimulation current of the electrode corresponding to the longitudinal target part is made smaller than the stimulation current of the electrode corresponding to other parts of the hippocampus. Thus, the focal area of transcranial electrical stimulation can be guided to the longitudinal front, thereby achieving precise targeted intensive treatment of the deep target parts, and even the positioning of the target area can be flexibly adjusted.

[0040] In some embodiments, the current of the first scalp electrode pair 102 and the second scalp electrode pair 102 is adjustable within a range of 0-10 mA. Specifically, by adjusting the relative current magnitudes of the first scalp electrode pair 102 and the second scalp electrode pair 102, the location of the targeted area can be flexibly adjusted. For example, in the electrode arrangement shown in Figures 1(a) and 1(b), by adjusting the relative current magnitudes of the first scalp electrode pair 102 and the second scalp electrode pair 102, the targeted area can even be flexibly adjusted to traverse various longitudinal divisions of the hippocampus on the side where electrodes e1 and e3 are located.

[0041] The arrangement of the electrodes for the hippocampus is not limited to this, and other arrangements can also be used.

[0042] As shown in Figure 2(b), the two positive electrodes e1 and e3 can be placed near the ear on the side where the hippocampus is to be stimulated, and the corresponding two negative electrodes e2 and e4 can be placed near the ear on the opposite side. It can be seen that e2, the second electrode, is in front of e1, the first electrode, and e3, the fourth electrode, is in front of e4, the third electrode, and the third electrode e4 is on the opposite side of the first electrode e1. In this way, the high-frequency first electric field E1 and the second electric field E2 intersect in a cross-shaped manner, and the intersection is the overlapping area, which forms a low-frequency oscillating electric field E. If a part of the hippocampus is to be stimulated, the high-frequency first electric field E1 and the second electric field E2 can be cross-overlapped at the stimulated part. This method can form a targeted area that extends more in the longitudinal direction of the hippocampus but is more restricted in the transverse direction perpendicular to the longitudinal direction.

[0043] As shown in Figure 2(c), a positive electrode e3 (serving as the fourth electrode) and a negative electrode e1 (serving as the first electrode) can also be placed near the ear on the side where the hippocampus is to be stimulated. The positive electrode e2 (serving as the second electrode) corresponding to the negative electrode e1 can be an electrode on the forehead, spanning the left and right sides of the forehead, to form a first electric field that enters from the forehead and exits from the ear. The negative electrode e4 (serving as the third electrode) corresponding to the positive electrode e3 can be placed near the forehead in the temporal lobe on the other side. It can be seen that the third electrode e4 is opposite to the first electrode e1 and behind the fourth electrode e3. Thus, a second electric field with an electric field direction opposite to the first electric field is formed. This method can form a targeted area that is tilted relative to the hippocampus.

[0044] As mentioned above, in addition to the hippocampus, the deep part of the brain may include at least one of the basal ganglia, thalamus, amygdala, and nerve nucleus. Taking the thalamus as an example, as shown in Figure 2(d), the two positive electrodes e2 and e3 in Figure 2(a) (serving as the second electrode and the fourth electrode, respectively) can be changed to the same electrode and arranged on the left and right sides of the forehead across the forehead, and the two negative electrodes e1 and e4 (serving as the first electrode and the third electrode, respectively) are arranged at the mastoid process behind the ears on both sides. It can be seen that the second electrode and the fourth electrode e2 / e3 are in front of the first electrode e1 and the third electrode e4, and the third electrode e4 is on the opposite side of the first electrode e1. In this way, the overlapping area of the first electric field and the second electric field formed can be located in the thalamus to achieve targeted and precise treatment of the thalamus.

[0045] In some embodiments, the light therapy unit 101 is at a first frequency f1 ’ Irradiate transcranial near-infrared light, the first frequency f1 ’ The frequency difference Δf between the first electric field and the second electric field is less than the first threshold. In this way, the first frequency f1 of the near-infrared light can be ’ As close as possible to the frequency Δf of the synthetic low-frequency electric field E. For example, when the frequency difference Δf between the first electric field and the second electric field is 40 Hz, the first frequency f1 ’ The frequency of light therapy and transcranial alternating current stimulation can be synchronized or nearly synchronized, which can significantly enhance neural entrainment and strengthen the therapeutic effect.

[0046] For example, the first frequency f1 ’ The frequency difference Δf between the two electric fields can be the same frequency among 10Hz, 20-40Hz and 75-80Hz. The same frequency can significantly improve the matching and strengthening of oscillations, enhance the neural entrainment effect, and enhance the therapeutic effect.

[0047] In particular, the 40Hz frequency of photoelectric combined stimulation can synergistically improve the condition of Alzheimer's patients from multiple aspects: promoting the exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF) in Alzheimer's patients, playing a positive role in p-Tau protein deposition, accelerating the lymphatic clearance of amyloid protein, inducing endogenous EEG oscillations through external current to produce entrainment, stimulating and improving gamma oscillations, and specifically regulating the neural network in the damaged area. It improves the neural oscillations and brain functional connections in the damaged area, promotes brain function improvement, enhances the patient's cognitive ability, and delays the course of the disease.

[0048] In some embodiments, each electrode is a flexible transparent electrode that can be attached to a curved scalp surface, such as the forehead, the mastoid processes on both sides, and near the helix of the ear. This allows the transcranial light radiation from the phototherapy area to be effectively delivered to the frontal and temporal lobes. It should be noted that the locations where the scalp electrodes are attached in this application, such as the temporal and frontal lobes, are important areas for near-infrared light irradiation. By using the transmission and close contact of the flexible transparent electrodes, the attenuation of near-infrared light along the optical path of the electrodes and the electrode-scalp connection area can be reduced, thereby ensuring the desired irradiation dose distribution in important areas.

[0049] Various flexible transparent electrodes can be used, such as but not limited to flexible nano-metal mesh transparent electrodes, silver nanowire embedded silk protein electrodes, nanofiber-based flexible transparent electrodes, etc. The flexible transparent electrode can be 2cm 2 -4cm 2 The shape of the flexible transparent electrode can be a rounded rectangle or a circle, and can be different according to the exposed area of the scalp to be adhered. For example, the flexible transparent electrode on the forehead can adopt a larger area, and the flexible transparent electrode at the mastoid can adopt a smaller area, so as to ensure sufficient adhesion while ensuring the amount of stimulation current and avoiding folding or detachment of the electrode as much as possible.

[0050] In some embodiments, each electrode is adhered to the scalp via a conductive transparent gel that maintains a 70%-90% transmittance for near-infrared light between 620nm and 1080nm. For example, a conductive transparent gel can be used that adheres securely and painlessly. Specifically, a conductive transparent gel can be used that is triggered by body temperature and automatically and painlessly removed when the body temperature drops.

[0051] This conductive transparent gel can be prepared based on the polyphenol-protein complexation strategy. For example, it is as follows. First, a polyphenol prepolymer (PGA) rich in phenolic and quinone groups is formed; secondly, the multiple interactions of the polyphenol groups are utilized in the gelation process of double-bonded gelatin (GelMA) to break the hydrogen bonding between the GelMA molecular chains, adjust the entanglement density of the GelMA chain to make it body temperature responsive, and achieve stability under body temperature conditions and enhance the fluidity of the molecular chains. When the hydrogel comes into contact with human skin, the body temperature triggers a phase change, achieving efficient and rapid adhesion, and maintaining stability for a long time. After a simple cooling of the hydrogel surface, hydrogen bonds are regenerated between the GelMA molecular chains in the network, the adhesion force is reduced, and damage-free peeling is achieved. Furthermore, the introduction of PGA adjusts the cross-linking mode of the GelMA network, giving the PGA-GelMA hydrogel mechanical flexibility and high ductility that match the skin tissue, avoiding damage caused by pulling the hydrogel when it is peeled off the skin surface. In addition, the PGA-GelMA hydrogel also exhibits excellent anti-inflammatory, antioxidant, and anti-allergic biological activities, which can effectively avoid skin irritation or allergies caused by traditional skin adhesives during long-term contact with the skin.

[0052] Another example is a highly transparent, self-adhesive, and thermally responsive conductive hydrogel based on dopamine-triggered gelation. Dopamine acts as an initiator, triggering monomer polymerization to form a polymer backbone. It also acts as a non-covalent crosslinker, dynamically regulating the hydrogel's crosslinked network through intermolecular forces. The dopamine content is as high as 50%, and the hydrogel maintains a 70%-90% transmittance to near-infrared light.

[0053] Now returning to FIG. 1 (a) and FIG. 1 (b), the phototherapy unit 101 further comprises a head cap, the inner side of which is provided with a plurality of near-infrared light source assemblies (such as Figure 4 As shown in 401 in the figure, the multiple near-infrared light source assemblies 401 are configured to emit pulsed light to the treatment object, the wavelength of the pulsed light is 620nm-1080nm, and the radiation range of the pulsed light of each near-infrared light source assembly 401 includes at least part of the hippocampus, and the near-infrared light is with sufficiently large power to act deep under the dura mater and on the hippocampus, and overlap at the hippocampus to form a second overlapping area.

[0054] In some embodiments, the second overlapping area of the pulsed light of each near-infrared light source assembly 401 can be combined and radiated with the action area of the first electric field or the second electric field (such as Figure 2(a)-Figure 2(d)) at least partially overlap. This is particularly applicable to situations where the lesions of brain diseases develop into deep parts of the target. Taking Alzheimer's disease as an example, early Aβ plaques accumulate in the medial prefrontal and parietal regions of the neocortex, and Tau protein also begins to accumulate in the middle temporal lobe of the endocortex, and then gradually spreads to the hippocampus, showing significant deposition in the hippocampus. In this way, the targeted focusing of focused light therapy and transcranial alternating current stimulation is carried out in coordination with the hippocampus. The former can reduce plaque deposition and inflammation in the hippocampus, and the latter rhythmically regulates the endogenous oscillations of the brain, forming neural entrainment to achieve neural regulation; further, the focused irradiation of pulsed light in all directions, coordinated with the targeted enhancement of transcranial alternating current stimulation, can ensure sufficient photoelectric synergistic dose in the hippocampus, and can especially enhance the therapeutic effect for the middle and late stages of Alzheimer's disease.

[0055] 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., solutions that intersect various embodiments), adaptations, or changes. The elements in the claims are to be interpreted broadly based on the language employed in the claims and are not limited to the examples described in this specification or during the prosecution of this application, which examples are to be interpreted as non-exclusive. Therefore, this specification and examples are intended to be considered as examples only, with the true scope and spirit being indicated by the following claims and the full scope of their equivalents.

[0056] The above description is intended to be illustrative and not restrictive. For example, the above examples (or one or more of their solutions) can be used in combination with each other. For example, those 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 can be grouped together to simplify the 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 specific disclosed embodiment. Thus, the claims are incorporated into the specific embodiments as examples or embodiments, wherein each claim is independently a separate embodiment, and it is considered that these embodiments can be combined with each other in various combinations or arrangements. The scope of this application should be determined with reference to the appended claims and the full scope of equivalents to which these claims are entitled.

[0057] The above embodiments are merely exemplary embodiments of the present application and are not intended to limit the scope of the present application. The scope of protection 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 scope of protection of the present application, and such modifications or equivalent substitutions shall also be deemed to fall within the scope of protection of the present application.

Claims

1. A transcranial physical stimulation device, characterized in that: The transcranial physical stimulation device includes at least a phototherapy unit and an AC transcranial electrical stimulation unit that act in concert, wherein the phototherapy unit is configured to irradiate transcranial near-infrared light to at least the frontal lobe, temporal lobe, and parietal lobe of the subject's head, and the phototherapy unit further includes a head cap having a plurality of near-infrared light source assemblies disposed inside the head cap, wherein the plurality of near-infrared light source assemblies are configured to emit transcranial near-infrared light with a wavelength of 620 nm to 1080 nm to the subject; The AC transcranial electrical stimulation unit includes a first scalp electrode pair and a second scalp electrode pair, wherein the first scalp electrode pair includes a first electrode and a second electrode, wherein the first electrode is arranged on the scalp near the first lateral temporal lobe, and the second electrode is arranged on the scalp more anterior to the first electrode, so that a first electric field is formed between the first electrode and the second electrode and acts on a target deep part; The second scalp electrode pair includes a third electrode and a fourth electrode, the third electrode is arranged on the scalp near the other temporal lobe, and the fourth electrode is arranged on the scalp more anterior to the third electrode, so that a second electric field is formed between the third electrode and the fourth electrode and acts on the deep target area, and the first electric field and the second electric field are AC oscillating electric fields applied simultaneously, with a frequency above 1000 Hz and a frequency difference of 10 Hz-80 Hz.

2. The transcranial physical stimulation device according to claim 1, characterized in that The phototherapy unit irradiates transcranial near-infrared light at a first frequency, and the difference between the first frequency and the frequencies of the first electric field and the second electric field is less than a first threshold.

3. The transcranial physical stimulation device according to claim 1, characterized in that The second electrode and the fourth electrode are the same electrode and are arranged on the forehead across the left and right sides of the forehead. The first electrode and the third electrode are arranged at the mastoid processes behind the ears on both sides.

4. The transcranial physical stimulation device according to claim 1, characterized in that One of the first electrode and the second electrode is arranged around the ear on one side, and the other is arranged on the forehead or occipital region of the other side adjacent to the temporal lobe; one of the third electrode and the fourth electrode is arranged around the ear on the same side, and the other is arranged on the forehead or occipital region of the other side adjacent to the temporal lobe.

5. The transcranial physical stimulation device according to claim 4, characterized in that The transcranial physical stimulation device is used to treat diseases in a target deep part of the brain, wherein the diseases in the target deep part include Alzheimer's disease, and the target deep part includes the hippocampus on the first side. The periauricular electrode is located at the periauricular part of the first side and serves as an anode.

6. The transcranial physical stimulation device according to claim 5, characterized in that The target deep part includes the longitudinal target part of the hippocampus, and the stimulation current of the electrodes around the ear corresponding to the longitudinal target part is smaller than the stimulation current of the electrodes corresponding to other parts of the hippocampus.

7. The transcranial physical stimulation device according to claim 3, characterized in that The target deep site includes the thalamus.

8. The transcranial physical stimulation device according to any one of claims 1 to 6, characterized in that: The current of the first scalp electrode pair and the second scalp electrode pair is adjustable in the range of 0-10 mA.

9. The transcranial physical stimulation device according to any one of claims 1 to 4, characterized in that: The target deep part includes at least one of the basal ganglia, hippocampus, thalamus, amygdala, and nerve nucleus.

10. The transcranial physical stimulation device according to claim 2, characterized in that The frequency difference between the first electric field and the second electric field is 40 Hz, and the first frequency is also 40 Hz.

11. The transcranial physical stimulation device according to any one of claims 1 to 7, characterized in that: Each electrode is a flexible transparent electrode.

12. The transcranial physical stimulation device according to claim 11, characterized in that Each electrode is adhered to the scalp via a conductive transparent gel, which maintains a light transmittance of 70% to 90% for near-infrared light of 620 nm to 1080 nm.

13. The transcranial physical stimulation device according to any one of claims 1 to 7, characterized in that: The multiple near-infrared light source assemblies are configured to emit pulsed light to the treatment subject, and the radiation range of the pulsed light of each near-infrared light source assembly includes at least a portion of the hippocampus and overlaps at the hippocampus to form a second overlapping area.

14. The transcranial physical stimulation device according to claim 13, characterized in that The second overlapping region at least partially overlaps with an active region of the first electric field or the second electric field.

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