Forgetfulness treatment device

Abstract

To provide a therapy device for reducing a symptom of forgetfulness and brain fog of MCI.SOLUTION: A therapy device comprises: a PBM therapy instrument 10 for blinking at a repeating frequency of almost 40 Hz, a light source with a wavelength of 650-1000 nm which is called "a window of a living body" and which transmits a living body tissue, and radiating the wavelength to an affected part of MCI at light energy density of 10 mW / cm2 or less; and a perception therapy instrument 20 for guiding a brain wave of almost 40 Hz by SSVEP and ASSR, in which, a phase control unit 150 is used for controlling a phase difference of stimulations generated on a plurality of therapy instruments thereby securing safety.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention aims to provide a device for non-invasively and safely treating MCI in the technical field of 40Hz Therapy for the prevention, alleviation, and treatment of dementia.

Background Art

[0002] The development strategies for therapeutic drugs in Alzheimer's disease (AD) are broadly classified into three types: disease modification therapy that suppresses the progression of pathological changes, symptomatic therapy that improves symptoms, and neuro-regeneration therapy that repairs damaged nerve cells and promotes regeneration (Non-Patent Document 1). However, even to this day, traditional pharmaceuticals using biochemical substances have not realized a treatment method that is safe, effective, and sufficiently low-cost for patients.

[0003] Dementia in the elderly, which has been said to have "no fundamental therapeutic drugs" until now, has recently seen progress in elucidating the mechanism of the disorder by adding perspectives from electrical, information, and system engineering, and the number of successful examples of clinical trials applying digital medicine has also begun to increase. In particular, it is known that if appropriate treatment measures can be taken at the stage of mild cognitive impairment (MCI, Mild Cognitive Impairment), which does not interfere with daily life before the onset of dementia, the therapeutic effect will be extremely improved.

[0004] Hereinafter, for the purpose of applying the treatment method using digital medicine for AD, whose effectiveness has been confirmed to date, to the treatment of mild cognitive impairment (MCI, Mild Cognitive Impairment) as a prodromal symptom of dementia, the background art of digital medicine will be listed from a system engineering perspective.

[0005] (1). From the perspective of systems and control The human body can only function normally as long as the brain, the entire nervous system, and the complex control systems distributed throughout the body like a chemical plant are functioning properly. In particular, since the human body is not a manufactured product based on a blueprint designed by humankind, the only way to improve repair methods is through trial and error, experimenting and analyzing the existing object (the human body). This is nothing less than the perspective of reverse engineering based on the field of cybernetics.

[0006] (2) System theory for identifying the location of failure in neurological diseases in the cerebrum Non-patent document 2 is a paper that proposes the integrated triple network model as a powerful paradigm linking large-scale brain networks with psychopathology. Advances in methodology in this field are driving new thinking about brain connectivity disorders such as autism, schizophrenia, and dementia. This theory integrates the brain into three large-scale networks and describes cognitive and other functional impairments that occur like connectivity problems in communication systems. The three large-scale networks are the default mode network (DMN), which governs past memories and circular thinking related to the future and oneself and others; the central executive network (CEN), which attempts to solve problems linearly while referencing perceptions (including emotions) in the here and now; and the salience network (SN), which switches between operating only the DMN and CEN in response to changes in the situation.

[0007] (3) Connectivity and cognitive function of different brain regions Non-patent document 3 is an important study that showed that when stimulating different brain regions, adjusting the phase angle of the stimulus (same relative opposite phase) can improve or, conversely, induce cognitive impairment. There is a cross-frequency coupling called "phase-amplitude coupling (PAC)" between theta wave frequencies (4-8 Hz) and gamma wave frequencies (above 25 Hz) between the prefrontal cortex and the temporal region, and in elderly individuals with working memory defects, the theta-gamma PAC in the temporal region and theta phase synchronization between the prefrontal cortex and the temporal region are impaired. The study also presents experimental results in which working memory impairment was rapidly induced in young adult subjects using transcranial alternate current stimulation (tACS), which was designed to desync cortical interactions between the frontotemporal regions. This phenomenon suggests that the setting of the phase difference when applying multiple phase-synchronized stimuli to multiple locations in the brain may lead to differences in therapeutic effects (and side effects), and therefore requires careful attention.

[0008] (4) "Sensory Therapy Device 20" as a type of 40Hz therapy In 2016, Non-Patent Document 4 revealed a mechanism by which 40Hz stimulation of brain nerves enhances 40Hz brain waves, leading to the phagocytosis and reduction of amyloid-beta and tau proteins, which are causative substances of Alzheimer's disease (AD), by microglia, an immune cell. This research established the basis (Patent Document 1) for "40Hz therapy" as a digital medicine that functions as a disease modification therapy to suppress the progression of pathological changes in Alzheimer's disease. This groundbreaking "40Hz therapy" is being actively applied to various applications, including not only a sensory therapy device 20 that uses the phenomena of SSVEP and ASSR to induce brainwaves of approximately 40Hz with visual and auditory stimuli using light and sound, but also a PBM therapy device 10 that utilizes photobiomodulation (PBM) by irradiating near-infrared light of approximately 40Hz through the nasal cavity, and magnetic stimulation therapy (TMS, rTMS) that applies stimulation of approximately 40Hz to the head.

[0009] (5) Sensory therapy device 20 using a light-emitting element 170 According to reports of a 2021 Phase 2 clinical trial of a sensory therapy device 20 using a light-emitting device 170 (Non-Patent Literature 5, Non-Patent Literature 6), electroencephalography (EEG) was induced using a 2-foot square LED light-emitting panel placed 5 feet away from subjects as the light-emitting device 170, which focused subjects on 40Hz light and sound without observing their surroundings. The results showed a statistically significant therapeutic effect on "associative memory of faces and names" related to the default mode network (DMN). However, therapeutic effects related to the central executive network (CEN) and the spleness network (SN) were not reported.

[0010] The report also states that because subjects experienced drowsiness during the trial, a monitor screen designed to entertain the subjects was placed in the center of a 2-foot square LED light panel to prevent them from falling asleep. Furthermore, it is noted that the subjects' sleep quality improved during the trial, and this had a favorable effect on the treatment of dementia.

[0011] (6) Sensory therapy device using an LCD element 20 Between 2019 and 2020, patent applications were filed almost simultaneously in Japan and the United States for a therapeutic device for 40Hz therapy (Patent Document 2 in the United States, Patent Document 3 in Japan) that uses liquid crystal (LCD) elements to flash ambient light at approximately 40Hz to provide visual stimulation through light. Conventional therapeutic devices that require patients to gaze at a light-emitting element 170 (Patent Document 1) have problems such as the inability to use non-pharmacological therapies such as exercise therapy and cognitive therapy in conjunction with 40Hz therapy because patients cannot freely observe their surroundings. To solve these problems, this invention improves the system by allowing subjects to freely observe their surroundings through sunglasses (hereinafter abbreviated as LCD sunglasses 180) that incorporate an LCD element that flashes at approximately 40Hz into the lens portion.

[0012] To stimulate the auditory system of these LCD sunglasses 180 with a phase-synchronized sound of approximately 40 Hz, audio equipment such as earphones, headphones, or speakers are used as therapeutic devices. This is similar to the method described in Patent Document 1, etc. Furthermore, the sensory therapy device 20, which uses LCD sunglasses 180, also enhances 40Hz brain waves through 40Hz stimulation of the cranial nerves, thus possessing the same mechanism of action as 40Hz therapy as a disease-modifying therapy that suppresses the progression of pathological changes in Alzheimer's disease.

[0013] In the following, whether the light-emitting device 170 or the LCD sunglasses 180 are used as therapeutic devices for visual stimulation using light, they will both be collectively referred to as "perceptual therapy devices 20".

[0014] <Note 1: Notation of 40Hz or approximately 40Hz> Even when using the notation "40Hz" to describe the frequency to which 40Hz therapy is applied, the numerical value of the repetition frequency of the stimulus used for treatment does not necessarily have to be exactly 40.0Hz. It is acceptable to apply frequencies around 40Hz within the range in which the mechanism of action of disease-modifying therapy that suppresses the progression of pathological changes in Alzheimer's disease, as described in Patent Document 1 and Non-Patent Document 4, functions. If one wishes to explicitly express this meaning, the notation "approximately 40Hz" may be used instead of "40Hz," but in substance, they mean the same thing.

[0015] <Note 2: The expression "flashing" or "blinking"> The terms "flashing" and "blinking" appear in the text of this invention. "Flashing" is mainly used in the context of operating a light source in two stages (on / off) using a square wave, as described in Patent Document 1, while "blinking" tends to be used in the context of brightening / dimening a light beam in multiple stages using a waveform other than a square wave (e.g., a sine wave), as described in Patent Document 3. However, from the perspective of activating the mechanism of action of 40Hz therapy, both terms have substantially the same meaning in this invention.

[0016] (7) SSVEP and ASSR Regardless of whether the source of the 40Hz light is a light emitter 170 or LCD sunglasses 180, the technique of inducing brain waves with light and sound stimuli is called SSVEP (Steady State Visual Evoked Potential) and ASSR (Auditory Steady State Response). SSVEP is detected by electrodes on an electroencephalograph (EEG) placed in the occipital lobe, while ASSR is detected by electrodes on the forehead and parietal lobe (Non-Patent Literature 7). In other words, the sensory therapy device 20 forcibly generates 40Hz brainwaves in two different areas of the brain corresponding to light and sound. Therefore, the appropriateness of setting the phase difference between the two types of stimuli, light and sound, may affect the therapeutic effect (or side effects) of 40Hz therapy. This point requires careful attention.

[0017] (8) Photobiomodulation (PBM) therapy Photobiomodulation is a technique that utilizes the phenomenon in which light assists energy production processes such as mitochondria in cells, positively influencing cellular metabolism and resulting in clinical benefits such as cell regeneration, faster wound healing, pain reduction, and improved function.

[0018] A key characteristic of photobiomodulation is that if the energy density of the irradiated light is too high, cells are damaged; if the energy density is moderate, cell activity is suppressed; and if the energy density is weak but sufficient, cells regenerate. In other words, significantly different effects occur at each of the three levels of light energy density, and the appropriate light energy density for each type of cell varies considerably.

[0019] Patent Document 4 describes an existing PBM therapy device 10, which irradiates light from above the scalp through the skull to the cerebral cortex, and further irradiates light from inside the nasal cavity through the skull below the cerebrum to the back of the frontal lobe. This device utilizes photobiomodulation technology to provide neuro-regeneration therapy, repairing and promoting the regeneration of nerve cells damaged in dementia. Furthermore, it can be used in combination with 40Hz therapy, which involves flashing light stimuli at approximately 40Hz when irradiating near-infrared light, making it a promising treatment method that also serves as disease-modifying therapy.

[0020] Non-patent document 8 from 2015 proposes irradiating the substantia nigra (substantia compacta), located deeper than the hippocampus, with near-infrared laser light (wavelength 808 nm) from the oral cavity or ventricles for the purpose of treating Parkinson's disease with photobiomodulation. This paper describes how the light transmittance of different human tissues, which forms the basis for the amount of energy to be irradiated, was calculated by taking anatomical samples of dead human tissue and using computer simulations to determine the path of light rays with low energy absorption. It proposes both an invasive method of implanting a light source in the ventricles of a monkey's brain and a method of installing a laser light source in the oral cavity, in which case it is described that a high-output light source should be water-cooled and the light should be irradiated to the target area using an endoscope.

[0021] Furthermore, experiments with mice indicated that an energy density of 1-15 mW / cm² is required to reach the substantia nigra pars compacta, and by working backward from the light transmittance results of simulations, it was found that the light energy that should be irradiated from the oral cavity towards the substantia nigra pars compacta is 1 watt per square centimeter (i.e., 1000 mW / cm²).

[0022] Although this document presents the idea of ​​"directly irradiating the hippocampus from the oral cavity," it should be noted that irradiating such a powerful laser beam from the oral cavity towards the brain of a living human patient is dangerous and therefore this idea lacks practical applicability as a treatment for living human subjects. That is, this document does not show that "the idea of directly irradiating the hippocampus from the oral cavity is practical", but it can also be read as "To directly irradiate the hippocampus from the oral cavity, light energy of a dangerous intensity of 1 watt per square centimeter is required, and the method of irradiating the hippocampus from the oral cavity is dangerous and should be avoided." Incidentally, Patent Document 4 in 2020 employs light irradiation from the nasal cavity and does not employ direct irradiation from the oral cavity to the hippocampus.

[0023] On the other hand, the inventor of the PBM therapy device 10 (Patent Document 5) in 2021 actually irradiated near-infrared light with a light energy density comparable to that of PBM that irradiates the cerebral cortex through the skull from above the scalp, passing through the sphenoid bone (skull bone under the brain) from the oral cavity and aiming at the hippocampus deep in the brain using a highly directional LED element. In this experiment, as a result of irradiating inside the oral cavity of a patient (the inventor himself / herself was the subject) for about 20 minutes, for the symptoms of amnestic MCI (forgetfulness), extremely remarkable improvement of the symptoms was immediately observed after the light irradiation. However, in a subsequent MRI examination, very slight white shadows were found in the cells around the irradiation target site. Although the causal relationship was unclear, the inventor pointed out that it is an important issue in the future to find the level of energy density that can be irradiated while ensuring safety, and then interrupted the continuation of the experiment.

[0024] (9). Brain regions where MCI lesions are observed According to Non-Patent Document 9, MCI includes "amnestic MCI (aMCI: amnestic MCI)" with memory disorders such as forgetfulness and "non-amnestic MCI" without forgetfulness symptoms. Among 917 MCI patients, 848 were amnestic MCI. Furthermore, the affected parts of MCI are mainly in the left and right tonsils and the hippocampus, and also spread to the left temporal pole, thalamus, and left and right prefrontal gyri. Among them, in amnestic MCI, reduction of gray and white matter and decline of cognitive function in the tonsils, hippocampus, and thalamus were revealed. Also, the limbic thalamus is said to be strongly involved in AD. In short, it is introduced that the main lesions of MCI are in the left and right temporal regions and deep in the brain, and also spread to other regions.

[0025] (10) Appropriate light energy density in PBM According to Non-Patent Literature 10, it is known that the energy density of light to be irradiated with PBM yields contradictory results depending on the wavelength of light, pulse mode, and treatment duration, with some researchers recommending less than 100 mW / cm2, or even five times that amount. In particular, different trends are observed depending on whether the target cells have a large or small number of mitochondria. It is also stated that "study cases where the effect is less pronounced in cells with high mitochondrial activity seem to be more often due to overdose than underdose." In short, this literature lists examples where the appropriate light energy density for each target tissue cell varies by orders of magnitude, from 1800 mW / cm² to less than 1 mW / cm². In other words, "you can't know the appropriate light energy density to achieve the desired effect unless you actually irradiate each target cell with light energy and conduct experiments." <Note> In this invention, the term "energy density" is used to refer to the physical quantity described in terms of "power per unit area (cm2) (mW)" of the light flux 40 emitted from the treatment device, that is, in units of "mW / cm2". While the correct terminology, in terms of proper use of physical terminology, should be "power density of luminous flux," to prevent the description in the specification from becoming even more difficult to understand, we have deliberately standardized the expression using a simpler, more intuitive term (light energy density 140). [Prior art documents] [Patent Documents]

[0026] [Patent Document 1] Special Publication No. 2019-502429 [Patent Document 2] US-A1-2020 / 0108270 publication [Patent Document 3] Japanese Patent Publication No. 2022-002674 [Patent Document 4] Special Publication No. 2020-534042 [Patent Document 5] Japanese Patent Publication No. 2021-100727 [Non-patent literature]

[0027] [Non-Patent Document 1] Nemoto, "Future Anti-Dementia Drugs and Fundamental Dementia Treatments Awaiting Future Development," MEDICINAL, 2012 / 5 Vol.2, No.5, 120~ [Non-Patent Document 2] Vinod Menon., “Large-scale brain networks and psychopathology: a unifying triple network model”, Trends Cogn Sci. 2011 Oct;15(10):483-506 [Non-Patent Document 3] Robert MG Reinhart et al., “Working memory revived in older adults by synchronizing rhythmic brain circuits”, Nature Neuroscience volume 22, pages820-827 (2019) [Non-Patent Document 4] Hannah F Iaccarino, Li-Huei Tsai et al., “Gamma frequency entrainment attenuates amyloid load and modifies microglia”, Nature . 2016 Dec 7;540(7632):230-235. [Non-Patent Document 5] Diane Chan et al., “40Hz sensory stimulation induces gamma entrainment and affects brain structure, sleep and cognition in patients with Alzheimer's dementia,” MedRxiv, Posted March 03, 2021. [Non-Patent Document 6] Diane Chan et al., “4Gamma Frequency Sensory Stimulation in Probable Mild Alzheimer's Dementia Patients: Results of a Preliminary Clinical Trial,” MedRxiv, Posted May 17, 2021. [Non-Patent Document 7] Rafal Kus et al., “Integrated trimodal SSEP experimental setup for visual, auditory and tactile stimulation”, J Neural Eng. 2017 Dec;14(6) [Non-Patent Document 8] A Pitzschke et al., “Red and NIR light dosimetry in the human deep brain”, Phys Med Biol. 2015 Apr 7;60(7):2921-37. [Non-Patent Document 9] Thomas Nickl-Jockschat et al., “Neuroanatomic changes and their association with cognitive decline in mild cognitive impairment: a meta-analysis,” Brain Struct Funct. 2012 Jan;217(1):115-25 [Non-Patent Document 10] Randa Zein et al., “Review of light parameters and photobiomodulation efficacy: dive into complexity”, J Biomed Opt. 2018 Dec;23(12):1-17 [Overview of the Initiative] [Problems that the invention aims to solve]

[0028] There are two problems that this invention aims to solve.

[0029] (1) The first challenge (insufficient therapeutic effect with conventional methods) The main lesions in MCI are primarily located in the left and right temporal lobes and deep brain regions, and it is important to target these two areas with therapeutic effects. Furthermore, the quality of the coordination of cognitive functions in various parts of the brain (i.e., functional connectivity) can be estimated by using electroencephalography (EEG) coherence (phase synchronization) as an indicator.

[0030] According to the clinical trial report for the conventional "Sensory Therapy Device 20 using a Luminescent Body 170," it was reported that 40Hz electroencephalogram (EEG) coherence increased in many EEG electrodes placed on the scalp, but detailed information was not made public. Furthermore, whether or not there was an increase in coherence in the deep brain was also not disclosed. Furthermore, evaluation tests conducted after the clinical trial to assess the improvement in the subjects' cognitive abilities revealed that many evaluation items showed less therapeutic effect than initially expected. This suggests that there may be brain regions where the therapeutic effect of conventional sensory therapy devices 20 is insufficient.

[0031] The inventor also conducted a follow-up experiment using the conventional "perceptual therapy device 20 using LCD sunglasses 180," but found that in MCI patients, increased coherence was observed in only about 50% to 70% of the EEG electrodes covering the entire scalp, mainly the frontal, parietal, and occipital regions. Instability in the increase of coherence was particularly noticeable in the left and right temporal regions. The inventor does not have the means to verify coherence in the deep brain, so it remains unknown.

[0032] In short, while coherence increases relatively steadily in the frontal, parietal, and occipital lobes, where stimulation of approximately 40 Hz can be applied using the conventional sensory therapy device 20, there is no conclusive evidence that coherence increases steadily in the temporal lobe and deep brain regions, where stimulation of approximately 40 Hz cannot be applied. In other words, since stimulation of approximately 40 Hz is not applied to the left and right temporal lobes and the deep brain, "the conventional sensory therapy device 20 alone may be insufficient in treating MCI."

[0033] (2) Second challenge (ensuring safety when using stimuli in combination) If conventional sensory therapy devices 20 lack sufficient stimulation at approximately 40 Hz, it might seem that the problem could be easily solved by simply supplementing the stimulation with PBM therapy devices 10, which utilize photobiomodulation technology, by irradiating with light energy at approximately 40 Hz.

[0034] However, when different stimuli are applied to multiple internal brain regions, it is known that cognitive impairment can be improved if the phase difference between the stimuli is appropriately set, and cognitive impairment can be induced if the phase difference value is inappropriate (Non-Patent Literature 3). Therefore, it is necessary to pay attention to properly managing the phase difference between multiple stimuli.

[0035] In the inventor's own experience, while experimenting with the sensory therapy device 20, when the phase difference between two phase-synchronized stimuli—light and sound—was set to +90 degrees, he was struck by an unusually intense drowsiness and a slight headache, to the point of feeling his life was in danger. It is a fact that the setting of the phase difference in phase synchronization across multiple stimuli can have a significant impact on the therapeutic effect (or side effects).

[0036] In other words, when sensory therapy device 20 and PBM therapy device 10 are used in combination (i.e., simultaneously) to apply multiple types of stimuli and forcibly generate brain waves in different parts of the brain, phenomena such as interference, cancellation, or synchronization problems may occur in many parts of the brain, potentially affecting inter-functional connectivity and cognitive function within the brain. Therefore, when using multiple types of stimuli in combination, it is dangerous if sufficient attention is not paid to managing the phase difference in the waveform of the stimuli that are repeated at approximately 40 Hz and generated by the sensory therapy device 20 or the PBM therapy device 10.

[0037] Furthermore, if multiple treatment devices, such as the sensory therapy device 20 and the PBM therapy device 10, are used simultaneously without phase synchronization, a dangerous situation arises where, due to slight frequency errors in each of the multiple stimuli repeated at a frequency of around 40 Hz, the phase difference between the multiple stimuli continues to fluctuate uncontrollably between 0 degrees and ±180 degrees over time. [Means for solving the problem]

[0038] (1) Solution to the first problem (insufficient therapeutic effect in conventional methods) To address the issue that "conventional sensory therapy devices 20 alone may not be sufficient to treat MCI," an additional PBM therapy device 10 that provides new stimulation to the deep brain and the left and right temporal lobes can be added. These multiple stimulation methods can then be combined and phase-synchronized at a common frequency of approximately 40 Hz to reinforce brain stimulation.

[0039] For deep brain regions, as described in Patent Document 5, light irradiation should be directed from the oral cavity to the hippocampus via the shortest possible route. Therefore, the top priority is to first determine an appropriate upper limit for light energy density. Furthermore, the goal is to create a PBM therapy device 10 that can stimulate the hippocampus, the left and right amygdala and thalamus, as well as the posterior side of the temporal lobe (i.e., the deep brain side) at approximately 40 Hz.

[0040] Furthermore, for the left and right temporal regions, by improving the conventional BM therapy device 10, which stimulates the scalp with light energy from above, so that it can be used in combination with the sensory therapy device 20 and the PBM therapy device 10 that stimulates the deep brain, it is possible to supplement the approximately 40Hz stimulation that is lacking in the left and right temporal regions.

[0041] In this invention, in order to determine the appropriate light energy density for the BM therapy device 10, the inventor conducted experiments using himself as the subject to find the numerical value that yields therapeutic effects. Furthermore, a simple therapeutic device was realized that can be used by MCI patients on their own without any disruption to their daily lives. The specific details of this device will be explained in detail in Example 1 below. Furthermore, we have also realized a treatment device with a simple configuration for illuminating the left and right temporal lobes and the deep brain. The "back side of the temporal lobe (deep brain side) and the deep brain" will be explained in detail in Example 2, and the "front side of the temporal lobe (scalp side)" will be explained in Example 3.

[0042] (2) Solution to the second problem (Ensuring safety when using stimuli in combination) As already mentioned, the brain regions stimulated by the conventional sensory therapy device 20 and the PBM therapy device 10 of the present invention are different. Furthermore, when combining and using multiple therapy devices, a safety measure is needed that allows the phase difference between the multiple stimuli to be set to an appropriate value.

[0043] Therefore, in order to safely manage the phase difference of stimuli between each brain region, a phase control device 150 is provided that comprehensively controls the phase difference of each stimulus. Furthermore, both the conventional sensory therapy device 20 and the PBM therapy device 10 of the present invention are equipped with an external excitation function 100 that allows the phase difference of multiple types of stimuli to be controlled by an external synchronization signal 130. Details of this phase control device 150 will be described in detail in Example 4. [Effects of the Invention]

[0044] Even with the conventional combination of LCD sunglasses 180 and headphones 164, which are used as sensory therapy devices 20, mild "brain fog" symptoms could be alleviated within an hour. However, the therapeutic effect was weak on "memory loss" symptoms where the MCI affected the deeper parts of the brain.

[0045] When using the PBM therapy device 10 disclosed in Examples 1, 2, and 3 of the present invention, mild "memory loss" symptoms that could not be improved with the prior art can be alleviated within one hour.

[0046] In Example 4, by using the sensory therapy device 20 and the PBM therapy device 10 in combination, it became possible to reduce the symptoms of mild memory loss and brain fog that were occurring simultaneously within one hour.

[0047] In severe cases of MCI where symptoms of "severe memory loss" and "severe brain fog" are present simultaneously, the above-mentioned treatment within one hour may not alleviate the symptoms.

[0048] In such cases, it is advisable to apply the therapeutic device of the present invention in a continuous treatment method based on the usage and dosage determined by clinical trials conducted by a medical institution, for example, by continuing treatment for one hour each day for three months. Alternatively, treatment should be carried out under the guidance of a physician, including combination therapy with exercise therapy or cognitive therapy, or with appropriate medications if available.

[0049] In other words, this invention makes it possible to treat MCI (Mild Cognitive Impairment) by using appropriate treatment devices, either alone or in combination, depending on the severity of the condition, from mild to severe, or the symptoms of memory loss or brain fog. [Brief explanation of the drawing]

[0050] [Figure 1] EEG generation site using sensory therapy device 20 and affected area of ​​MCI [Figure 2] 20 Examples of Sensory Therapy Devices Using Light and Sound Stimuli at Approximately 40Hz [Figure 3] (Example 1) LED lance with a 40Hz light source that irradiates in one direction inside the oral cavity [Figure 4] (Example 2) LED mouthpiece with a 40Hz light source that irradiates in multiple directions within the oral cavity [Figure 5] (Example 3) LED pad that provides light stimulation to the temporal region from the scalp side. [Figure 6] (Example 4) General explanation of phase synchronization [Figure 7] (Example 4) Phase control device that manages multiple stimulus sources [Figure 8] Supplementary explanation for Examples 2 and 4 [Figure 9] (Example 4) Modified form of phase control device [Figure 10] (Example 4) Self-excited actions and other-excited actions, etc. [Modes for carrying out the invention]

[0051] (1) Effects of sensory therapy device 20 around the affected area of ​​MCI Figure 1 shows the electroencephalogram (EEG) generation sites using the sensory therapy device 20 and the affected areas of MCI. In the diagram, (L) represents the occipital region where stimulation with 40Hz light generates 40Hz brain waves, and (S) represents a broad area from the forehead to the parietal region where stimulation with 40Hz sound generates 40Hz brain waves. Furthermore, among the major affected areas of MCI, the deep brain regions of the hippocampus, amygdala, and thalamus are shown in (A), while the temporal region, including the temporal pole, is shown in black in (B).

[0052] Furthermore, MCI (Mild Cognitive Impairment) can occur in areas other than (A) and (B) due to sequelae of cerebral infarction, etc., and some patients experience only brain fog symptoms without memory problems caused by damage or atrophy of the hippocampus or other areas. In such cases, stimulating a wide area from the frontal to the occipital lobe with the sensory therapy device 20 may improve symptoms of mild brain fog.

[0053] According to reports of Phase 2 clinical trials on devices for treating AD (Non-Patent Literature 5, Non-Patent Literature 6), 40Hz light and sound stimulation resulted in an "increase in amplitude" of 40Hz brain waves not only in the frontal and parietal (S) and occipital (L) regions, but also in electroencephalogram (EEG) electrodes on the scalp in the temporal region and EEG electrodes implanted deep within the brain. As a result, it is stated that the mechanism by which 40Hz brain waves cause immune cells (microglia) to phagocytose the substances that cause Alzheimer's disease (amyloid-beta and tau protein) extends throughout the entire brain. In a follow-up experiment conducted by the inventor using LCD sunglasses 180 and earphones, an "increase in amplitude" of 40Hz brain waves was confirmed at all EEG electrodes placed across the scalp, indicating that it functions as a "disease-modifying therapy" that prevents Alzheimer's disease through a similar mechanism of action.

[0054] On the other hand, from the perspective of improving cognitive impairment caused by decreased interfunctional connectivity in the brain's large-scale networks, it is important that the 40Hz brainwaves not only "increase in amplitude" but also "increase in coherence" in response to phase-synchronized 40Hz light and sound stimuli. Therapies that increase coherence and eliminate cognitive impairment symptoms caused by connectivity failures in large networks function as "symptomatic therapy" to improve the symptoms of MCI.

[0055] However, according to the Phase 2 clinical trial reports (Non-Patent Documents 5 and 6), detailed data on inter-electrode coherence of EEG signals measured in the scalp were not released, and only the fact that coherence increased was stated. Furthermore, data on coherence in the deep brain has not been released.

[0056] The inventor of this invention conducted a follow-up experiment using himself as a subject, employing a research-grade multi-channel digital electroencephalograph, OpenBCI®, and phase-locked 40Hz light and sound stimuli. As a result, increased coherence was observed in approximately 50% to 70% of all electrode combinations.

[0057] Specifically, for EEG electrodes placed in the frontal, parietal, and occipital regions, surrounded by points (S) and (L) where brain waves induced by light and sound stimuli are generated, increased coherence was observed between almost all electrodes. However, in the left and right temporal regions, the increase was only about 50%, and furthermore, the observed areas were constantly fluctuating and unstable. The inventor does not have a means to measure brain waves in the deep brain, but the deep brain is similar to the left and right temporal lobes in that it is not surrounded by brain regions such as (S) and (L) that generate brain waves, and therefore the increase in coherence in the deep brain is likely to be unstable.

[0058] To briefly summarize the above explanation, the following problem becomes apparent: "Analysis of the electroencephalogram (EEG) data from the sensory therapy device 20 reveals that the coherence increase of 40Hz EEGs for treating MCI may be insufficient in the deep brain and temporal lobe."

[0059] (2) MCI symptoms that can be eliminated with 40Hz light and sound stimulation, and MCI symptoms that cannot be eliminated. The inventor developed LCD sunglasses 180 (Patent Document 3) with the aim of alleviating brain fog caused by sequelae of a cerebral infarction suffered in 2018. Using this sensory therapy device 20, he succeeded in non-invasively eliminating mild brain fog symptoms of "non-amnesic MCI" within 30 minutes. However, after mild memory loss symptoms, which are associated with the hippocampus and can be classified as "amnesic MCI," began to appear, I was troubled because I couldn't get rid of the memory loss symptoms.

[0060] Therefore, by 2021, a PBM therapy device 10 was developed that irradiates the hippocampus with near-infrared light that flashes at approximately 40 Hz, and it was successful in eliminating mild "memory loss" symptoms within 30 minutes (Patent Document 5). However, there were concerns that an excessively strong light beam 40 could damage brain cells, and there were challenges such as the need to determine a safe irradiation dose (light energy density 140) and the need to improve the device's completeness as a therapeutic tool. Please note that in the following, "near-infrared light in the wavelength range known as the biological window 3 (650-1000 nm) that penetrates biological tissue" is simply referred to as "near-infrared" or "near-infrared light." This does not represent the general technical term "near-infrared (wavelengths 800 nm-1200 nm, or 700 nm-2500 nm)."

[0061] This invention presents (1) an example of an improved safety of a PBM therapy device 10 that emits near-infrared light flashing at approximately 40 Hz, (2) an improved PBM therapy device 10 that enhances ease of use when irradiating not only the hippocampus but also the amygdala, thalamus, and temporal pole, which are affected areas of MCI, and (3) a therapeutic device for performing treatment by combining the PBM therapy device 10 with a sensory therapy device 20.

[0062] Below, we will first briefly describe the conventional technology and application examples of the sensory therapy device 20 that can alleviate mild brain fog symptoms, and then provide a detailed explanation using examples related to the present invention.

[0063] (3) Sensory therapy device 20 Figure 2 shows an example of a sensory therapy device 20 that uses phase-synchronized light and sound at approximately 40 Hz, which is effective in alleviating mild brain fog symptoms.

[0064] Figure 2(a) is a prior art diagram schematically depicting the investigational device described in the Phase 2 clinical trial report (Non-Patent Literature 5, Non-Patent Literature 6). The investigational device consists of a square LED panel 172 with sides of 2 feet (approximately 61 cm) and a speaker 166 placed 5 feet (approximately 152 cm) away from the subject, supplying the subject with flashing lights and clicking sounds at 40 Hz.

[0065] Figure 2(b) shows an application example in which a bright white LED bulb 174 is blinked at approximately 40Hz, and while continuously viewing the light transmitted through light-diffusing glasses 176 fitted with a white, semi-transparent optical scattering plate as a lens, an auditory stimulus is added by listening to a click sound phase-synchronized with the light stimulus through headphones 164. Previously, a treatment method was used that involved simply placing a dim, small LED light bulb (174) in the corner of a room and flashing it at approximately 40Hz. However, this method had problems because the light stimulation was insufficient, resulting in an inadequate increase in the amplitude of the induced approximately 40Hz brainwaves and only a slight increase in coherence. As a countermeasure, in the example shown in Figure 2(b), in order to induce strong brain waves by having as many cone cells as possible in the retina participate in electroencephalography (ESVEP), it is desirable that the white light stimulus entering the eye covers the entire field of vision, and that the brightness of the light entering the eye is 600 Lux or higher, so that the cone cells that perceive bright primary colors of light can function sufficiently. For bedridden patients, it is best to place an extremely bright LED bulb 174 that flashes at approximately 40Hz as close to the face as possible. Furthermore, in order to efficiently generate 40Hz brain waves, it is desirable to use white light to evenly stimulate the three types of cone cells in the retina corresponding to the three primary colors of light. Therefore, a white light source is used so that the entire field of vision is covered with white light, and treatment is performed while wearing white light-diffusing glasses 176. It is important to keep your eyes open and watch the flashing white light to ensure a stable treatment effect. Closing your eyes and watching the red light passing through the blood vessels in your eyelids, or falling asleep during treatment, will reduce the effectiveness of the treatment.

[0066] Figure 2(c) also shows an application example. This treatment involves sitting with the sun at the back of a large, south-facing wall of white tiles or plaster in front of the LCD sunglasses 180, which flash at approximately 40 Hz, in a bright outdoor setting during the daytime. When the illuminance just before the light enters the LCD sunglasses 180 in this state is measured, it ranges from 4000 Lux to tens of thousands of Lux in the vicinity of Tokyo, Japan. The auditory stimulus is a click sound of approximately 40 Hz, phase-synchronized with the LCD sunglasses 180, which is heard through earphones 168.

[0067] Figure 2(d) also shows prior art (Patent Document 3), illustrating an example of using LCD sunglasses 180 in combination with outdoor exercise therapy. Note that looking directly at sunlight constricts the pupils, weakening the light stimulus flashing at approximately 40 Hz and making it less likely to reach the brain. Therefore, it is best to avoid looking directly at the sun by keeping your back to it or wearing a hat with a brim. Looking at dark objects also weakens the light stimulus, so try to look at bright objects as much as possible, and shift your gaze so that you can clearly perceive the flashing (flickering) of light. This will enhance the effect of eliminating brain fog. Furthermore, for traffic safety purposes such as outdoor walks, we recommend using bone conduction earphones 162 so that you can also hear surrounding sounds.

[0068] As explained above using Figure 2, in conventional technology or application examples, the perceptual therapy device 20 consists of a visual stimulation device 800 and an auditory stimulation device 810. The visual stimulator 800 is a light-emitting element 170 such as an LED panel 172 or LED bulb 74 that emits light at a repetition frequency of approximately 40 Hz, or LCD sunglasses 180 that control the transmittance of the lens portion at approximately 40 Hz. The auditory stimulator 810 includes at least one of the following: an earphone 168, headphones 164, or a speaker 166, which includes a bone conduction earphone 162 as a sound-emitting element 160 that emits sound at a repeating frequency of approximately 40 Hz. In other words, assuming listening with both ears, the sound-producing element 160 can be stereo or mono, and the speaker-166 can be one unit or more. [Examples]

[0069] In this first example, we introduce a digital medical device used for symptomatic treatment of MCI, which emits near-infrared light in the wavelength range known as the "biological window 3" (650-1000 nm), which penetrates biological tissue, in a repeating waveform of approximately 40 Hz, and irradiates it from the oral cavity towards the MCI affected area, such as the hippocampus, stimulating it at approximately 40 Hz. The treatment device described in Example 1 is called "LED Lance 200," and an image of the invention is shown in Figure 3.

[0070] (1) Invention In this Example 1, we will explain in detail the technical concept and design of the following two inventions, focusing on the two main inventive features. Although Example 1 includes numerous inventive features that further define specific details, to avoid complexity in the explanation, we will focus on and explain only the following two inventive features.

[0071] <Inventive Feature A of Example 1> The main inventions related to the LED Lance 200 are as follows: In a digital medicine treatment device used for symptomatic treatment of MCI, An LED lance 200, which serves as a PBM therapy device 10, flashes a light source in the wavelength range called the biological window 3, which penetrates biological tissue, with a repeating waveform of approximately 40 Hz, and irradiates the affected area of ​​MCI from inside the oral cavity with a light energy density of 140, which is a predetermined value of 5 or less.

[0072] The LED lance 200 is composed of an LED light source 30, a gripping portion 80, and an LED driving device 50. The LED light source 30 is configured to include a semiconductor chip 65 of an LED element 60 that irradiates a light beam 40 having an output wavelength (or peak wavelength) in the wavelength range of 650 to 1000 nm of the biological window 3, and an optical system 70 that adjusts the half-angle of power of the directivity of the light beam 40. The gripping portion 80 is a rod-shaped member that, while holding the LED lance 200 in the hand, inserts the LED light source 30, which is disposed at the tip of the LED lance 200, into the inside of the oral cavity and then manipulates the position and irradiation direction of the LED light source 30. The LED driving device 50 is a device that supplies a driving current to the LED element 60 and irradiates the LED light source 30 with a light energy density of 140 of 10 mW / cm2 or less, which is a predetermined value 5.

[0073] The LED driver device 50 also comprises a 40Hz signal source 210, an LED driver circuit 220, an output adjustment means 230, and an output monitoring means 240. The 40Hz signal source 210 outputs a command value 250 of the approximately 40Hz time-series waveform of the luminous flux 40 emitted by the LED light source 30 of the LED lance 200. The LED driving circuit 220 receives the command value 250 output by the 40Hz signal source 210 and supplies a driving current to the LED light source 30. The output adjustment means 230 continuously and / or discontinuously adjusts the light energy density 140 of the light flux 40 irradiated from the LED light source 30. The output monitoring means 240 indirectly or directly measures and displays the light energy density 140 irradiated by the LED lance 200. A treatment device for MCI treatment that utilizes 40Hz therapy, characterized by its unique features.

[0074] <Inventive Features B of Example 1> Furthermore, the functions of externally excited, self-excited, and switching for the 40Hz signal source can be summarized as follows: The command value 250 emitted by the 40Hz signal source 210 is, The LEDs are generated by the external excitation operation 100 or the self-excitation operation 105, which are controlled by the self-excitation and external excitation switching means 260 provided in the LED driver device 50. When generating by the externally excited operation 100, the signal source built into the 40Hz signal source 210 is synchronized in phase with the synchronization signal 130 input from the outside to generate the command value 250. When generated by the self-excited operation 105, the command value 250 is generated independently by a signal source incorporated inside the 40Hz signal source 210. Characterized by, A therapeutic device for MCI treatment using 40Hz therapy, as described in Invention A of Example 1.

[0075] (2) Problems with Example 1 In Patent Document 5, the inventor used himself as a subject and irradiated his hippocampus with near-infrared light. As a result, the "memory loss" symptom of MCI was resolved, confirming the effectiveness of this treatment method. However, a subsequent MRI examination revealed tiny white shadows in brain cells around the hippocampus, so the experiment was discontinued, although the causal relationship was unclear. In Example 1, the challenge is to realize a treatment device that ensures safety by setting the irradiation dose, i.e., the light energy density of 140, directed towards the affected area of ​​MCI within an appropriate range. Furthermore, to compensate for the increase in coherence caused by the sensory therapy device 20, another challenge is to apply phase-synchronized stimulation of approximately 40 Hz to the affected area of ​​MCI in conjunction with the sensory therapy device 20.

[0076] (3).Solution The solution becomes clear when we consider the positioning of this treatment device as a PBM therapy device 10 that applies photobiomodulation (PBM) technology. In other words, we utilize the characteristics of PBM technology, where if the irradiated light energy density 140 is too high, cells are damaged; if it is moderate, cell activity is suppressed; and if it is weak but sufficient, cells regenerate. Although this invention utilizes a weak light energy density of 140, it still forcibly stimulates brain cells with flashing light at approximately 40 Hz, and can therefore be used as supplementary stimulation to compensate for the coherence increase provided by the sensory therapy device 20. To achieve this, a synchronization signal 130 for use in conjunction with the sensory therapy device 20 should be input to the LED lance 200 and operated by external excitation 100.

[0077] Therefore, compared to the experiment in Patent Document 5, we decided to drastically reduce the light energy density 140 and apply the weakest possible light energy density 140 within a range that is sufficient to adequately alleviate the symptoms of "forgetfulness" for treatment purposes. However, it is important to note that the appropriate light energy density of 140 for PBM irradiation varies depending on the type of cells in the target tissue, and that there are individual differences in the effective value of light energy density 140.

[0078] Therefore, the design philosophy for this PBM therapy device 10 was to "ensure safety from various perspectives while enabling each individual patient to explore their own optimal settings (or settings to improve their symptoms at that time)."

[0079] (4) Criteria for selecting light energy density The upper limit for the light energy density of 140 must be set within a safe range that does not cause harm to the human body. According to Non-Patent Document 10, some researchers recommend high-density power of less than 100 mW / cm2 or five times that amount as experimental conditions for PBM. However, on the other hand, some researchers believe that low-density power of less than 1 mW / cm2 is sufficiently useful in terms of pharmacological effects. Even if seemingly useful numerical values ​​are written in the literature, the actual effective values ​​that are useful vary greatly depending on the type of cells or tissues being irradiated, the expected effect, and the irradiation conditions. Therefore, simply copying the light energy density values ​​listed in the literature is completely useless.

[0080] Therefore, I abandoned relying on literature information and instead became a test subject myself, experimenting at various light energy densities of 140, and obtained the following results.

[0081] <Result 1> When I shone a light beam of 40, which flashes at approximately 40Hz and has a high light energy density of 140 (measured at a distance of 1cm from the tip of the highly directional LED element itself, with an instantaneous maximum value exceeding approximately 100mW / cm2), into my mouth for about 20 minutes, the events of just moments ago flashed before my eyes like a kaleidoscope. Subsequently, a white shadow was discovered in the MRI images, and the experiment was suspended due to concerns about potential risks.

[0082] <Result 2> An optical lens that significantly widens the directionality was attached to an LED element, and a light beam of 40, flashing at approximately 40Hz with a light energy density of 140 (measured at a distance of 1cm from the tip) was shone into the oral cavity for about 20 minutes. Then, by chance, when I went to a parking lot, I was able to remember the license plate of a parked car just by glancing at it. The image disappeared from my memory after 3 days, but I recalled it many times during that time, so after 3 days I was able to recall the contents of the license plate as text. Since then, I have not experienced any particular health problems.

[0083] The experimental results in these two cases were, in the inventor's opinion, at a level that could be described as "exceptionally strong memory," and he judged that it was "an excessive dose" of hippocampal stimulation for the purpose of treating MCI. Therefore, going forward, as the upper limit for the light energy density of 140 that can be safely used in a "treatment device that irradiates a light flux of 40 from the oral cavity towards the hippocampus while flashing at approximately 40 Hz," we have decided to apply a value of 10 mW / cm2 (10 milliwatts per square centimeter) as the instantaneous maximum value when measuring the light flux of 40 at a distance of 1 cm from the tip of the optical system 70 attached to the LED element.

[0084] Therefore, we further reduced the light energy density to 140 and continued the experiment with the premise that it could be used as a symptomatic treatment to temporarily improve symptoms of forgetfulness. <Result 3> The inventor himself experimented to find a light energy density of 140 that could restore his memory from a state of "forgetfulness" to his "original memory" in about 30 minutes. However, the light energy density at a distance of 1 cm from the tip of the LED's optical lens varied from several mW / cm² to less than 1 mW / cm², depending on his physical condition and the degree of his "forgetfulness" on any given day. It seems there is no single optimal value. Therefore, as a treatment device, it is necessary to design it so that the output can be adjusted through trial and error, with a maximum value of 10 mW / cm², so that even weak light of 1 mW / cm² or less can be used for treatment.

[0085] Therefore, the light energy density 140 of all PBM therapy devices 10 of the present invention is set to an upper limit of 10 mW / cm2, with a predetermined value of 5, and is intended to be used in a range smaller than this. Furthermore, in order to further reduce the light energy density 140, an output adjustment means 230 is provided for adjusting the driving current of the LED light source 30 using the LED driving device 50. Furthermore, this predetermined value of 5 was applied in common to all embodiments of the present invention, and sufficient effects were obtained.

[0086] (5) Design policy for Example 1 Therefore, the design principles for the treatment device in Example 1 are as follows: 1) This treatment device is designed to be used by MCI patients themselves, who can hold it in their hands and use it through trial and error. 2) The irradiable light energy density will be variable, with only an upper limit set to avoid damaging brain cells. 3) The light energy density irradiated will be made as weak as possible within the range effective for resolving memory loss in MCI, thereby creating a PBM treatment device that also aims to regenerate damaged brain cells. 4) If the means for limiting the upper limit of the light energy density of the treatment device malfunctions, the device shall be equipped with a fail-safe function that immediately disables irradiation for safety purposes. 5) To prevent errors in setting the light energy density of the treatment device, a function will be provided that allows the patient to monitor the output themselves.

[0087] (6) Description of the Figure in Example 1 Figure 3 illustrates the LED lance 200 with a 40Hz light source for irradiation in the oral cavity, as described in Example 1. The treatment device "LED lance 200" described in Example 1 is a device that can be used by the MCI patient themselves by holding the rod-shaped gripping part 80 in their hand and experimenting with it. Therefore, the patient can feel the improvement in their subjective symptoms, such as the amygdala, thalamus, or temporal pole adjacent to the hippocampus, which is the affected area of ​​MCI, and irradiate the effective area with weak near-infrared light.

[0088] Figures 3(a) and 3(b) show the location of the hippocampus. The light beam 40 emitted by the LED light source 30 penetrates the biological tissues within the brain, including the skull on the lower side of the brain (such as the sphenoid bone), and illuminates the hippocampus and other areas.

[0089] Figure 3(c) shows the LED lance 200 being inserted into the oral cavity to irradiate the hippocampus. The device includes a gripping part 80, which is a rod-shaped member, that allows the user to hold the LED lance 200 in their hand, insert the LED light source 30 located at the tip of the LED lance 200 into the oral cavity, and then manipulate the position and irradiation direction of the LED light source 30. Since MCI patients themselves do not know the exact location of the hippocampus, it is best to get a general idea of ​​its location by following the instructions of the treating physician. Note that the luminous beam 40 emitted by the LED Lance 200 is wide, so even if the central optical axis of the LED Lance 200 does not hit the hippocampus precisely, it is sufficient to include the hippocampus within the spread luminous beam 40.

[0090] Figure 3(d) shows the configuration of the LED lance 200. The rear end of the LED lance 200 is connected to the LED driver 50 via an electric wire. The LED light source 30 described above consists of a semiconductor chip 65 of an LED element 60 that irradiates a luminous beam 40 having an output wavelength (or peak wavelength) in the wavelength range of 650 to 1000 nm of the biological window 3, and an optical system 70 that adjusts the half-angle of power of the directivity of the luminous beam 40. By arranging multiple LED light sources 30 on the tip or near the tip of the gripping portion 80 and irradiating multiple luminous beams 40, the directivity of the overall luminous beam 40, which is composed of multiple luminous beams 40 irradiated by the LED lance 200, can be broadened. Furthermore, by bending the tip of the LED lance 200 and providing LED light sources 30 on its side, it is possible to irradiate in multiple directions simultaneously.

[0091] Furthermore, since the directivity of the light emission from the semiconductor chip 65 and the LED element 60 enclosed in a transparent resin case are diverse, the design of the optical system 70 for adjusting the half-angle of power of the light beam 40 should be such that the hippocampus is included within the spread light beam 40, while considering a predetermined value of 5 as the upper limit of the light energy density 140 and a practical drive current that prevents the LED light source 30 from overheating. Of course, if the design conditions can be met solely by the lens shape at the tip of the transparent resin case of the LED element 60, then this optical system 70 can be used as is.

[0092] The LED driver unit 50 is equipped with an output adjustment knob 230, which serves as an output adjustment means 230 for the patient to adjust the output themselves, and an ammeter 240, which serves as an output monitoring means 240 for the patient to monitor the output themselves. The maximum drive current of the LED light source 30 that emits near-infrared light is set to an upper limit by a control circuit built into the LED driver unit 50.

[0093] Figure 3(e) is a diagram illustrating the configuration of the control system of the LED driver device 50. The LED driver 50 also comprises a 40Hz signal source 210, an LED driver circuit 220, an output adjustment means 230, an output monitoring means 240, and a power supply such as a battery. The 40Hz signal source 210 outputs a command voltage using a control microcomputer as the command value 250 of the approximately 40Hz time-series waveform of the luminous flux 40 emitted by the LED light source 30 of the LED lance 200, which is an arbitrary waveform with a repetition period of 40Hz (for example, a sine wave, a square wave with a selectable duty cycle, a triangular wave, a step-like waveform, or a waveform specified by storing the output every 1 millisecond in memory).

[0094] The LED driver circuit 220 receives the command value 250 output by the 40Hz signal source 210 and supplies a drive current to the LED light source 30. The output adjustment means 230 can continuously and / or discontinuously adjust the light energy density 140 of the luminous flux 40 emitted from the LED light source 30 by changing the amplification factor of the LED drive circuit 220 with a variable resistor or switch to set the drive current supplied to the LED element 60 of the LED light source 30. Alternatively, although not shown in the figure, waveform parameters such as the amplitude and average value of the command value can be specified using a potentiometer or the like on the 40Hz signal source 210 side. Of course, the parameters of the control microcomputer program can also be adjusted. The output monitoring means 240 indirectly or directly measures and displays the light energy density 140 irradiated by the LED lance 200. In Figure 4(e), an ammeter is used to indirectly measure the relative increase or decrease of the light energy density 140. The measurement is performed in this manner. Alternatively, although not shown in the diagram, the luminous flux 40 of the LED light source 30 can be divided and detected by a light sensor, and the measurement and display can be performed directly.

[0095] If an inappropriately large current flows to the LED element 60 of the LED light source 30 due to an electronic circuit failure such as a short circuit in the feedback resistor circuit, and an excessively high light energy density 140 light flux 40 is irradiated, there is a risk of damaging brain cells. Therefore, for fail-safe purposes, as shown in Figure 3(e), a highly sensitive fuse, such as 20mA or 30mA, is installed in series with the main circuit through which the LED drive current flows. Although not shown in the diagram, multiple high-sensitivity fuses may be connected in series to reduce the probability of non-blown fuses causing accidents, or a drive circuit for a buzzer or similar device may be provided to emit a warning sound to indicate that treatment should be interrupted when a fuse blows.

[0096] Incidentally, since Patent Document 5 discloses a configuration method in which LED elements and laser light sources are housed in a separate enclosure and optical energy is transmitted to the LED lance 200 via optical fiber, as well as various shapes and structures of the LED lance 200, those skilled in the art should be able to easily modify the design based on the present invention.

[0097] Furthermore, the command value 250 emitted by the 40Hz signal source 210 is, The LEDs are generated by an external excitation operation 100 or an external excitation operation 105 via a self-excitation / external excitation switching means 260 provided in the LED driver device 50. When generated by external excitation operation 100, the signal source built into the 40Hz signal source 210 is synchronized in phase with the synchronization signal 130 input from an external source to generate the command value 250. When generated by self-excited operation 105, the command value 250 is independently generated by a signal source built inside the 40Hz signal source 210.

[0098] In other words, the LED driver 50 can be equipped with a switch to select between externally excited operation 100 and self-excited operation 105. When the LED lance 200 is used alone, the 40Hz signal source 210 is switched to self-excited operation 105, and the built-in signal source spontaneously outputs a signal as a command value 250 with a repetition period of approximately 40Hz. Alternatively, when using the LED Lance 200 in combination with other treatment devices, the system is switched to externally excited operation 100, a synchronization signal 130 of approximately 40 Hz is acquired, and the signal is output by resetting the phase of the signal as a command value 250 at each repetition period so that it matches the phase of the synchronization signal 130 of approximately 40 Hz from an external source.

[0099] Incidentally, the means 260 for switching between self-excitement and external excitation may be a manual changeover switch. Alternatively, an automatic changeover switch may be used so that it operates in external excitation mode 100 when it detects that a synchronization signal 130 has been input from an external source, and operates in self-excitement mode 105 when no synchronization signal 130 has been input from an external source. Of course, if the design is to be modified to be a dedicated machine for self-excited operation 105 or externally excited operation 100, then the design only needs to be modified to have the function of self-excited operation 105 or externally excited operation 100, and the means 260 for switching between self-excited and externally excited operation is unnecessary.

[0100] Figure 3(f) shows a simple circuit example of the LED driver device 50 shown in Figure 3(e). The 40Hz signal source 210 uses a control microcomputer to output a command voltage of the aforementioned arbitrary waveform from its analog output AO. In this figure, in order to prevent harmonic components of 80Hz and 120Hz from being mixed into the waveform of the light beam 40 that blinks at a fundamental frequency of 40Hz generated by the LED light source 30, the command voltage waveform is a sine wave with a lower limit of 0V, an upper limit of 3V, and an average value of 1.5V.

[0101] The LED driver 50 uses a full-swing operational amplifier OP1 to drive the LED driver transistor TR1, corresponding to the power supply voltage of +5V. A feedback resistor circuit consisting of R5, R6, R7, SW1 and VR1 is provided on the emitter side of TR1, and the voltage drop caused by the current passing through the LED element 60 of the LED light source 30 is used as a voltage feedback signal to operate the differential amplifier circuit of the operational amplifier OP1. For example, if the total resistance of the feedback resistor circuit is 300Ω, the waveform of the current output from the LED driver circuit will be a sine wave with a lower limit of 0mA, an upper limit of 10mA, and an average value of 5mA. The ammeter displays the approximate average value of the current flowing through the LED light source 30, so it will show approximately 5mA.

[0102] The output adjustment means 230 continuously and / or discontinuously adjusts the light energy density 140 of the luminous flux 40 irradiated from the LED light source 30. This feedback resistor circuit is also used as an output adjustment means 230. For example, a professional staff member at a pharmacy or other facility that sells medical devices according to a doctor's prescription can switch the upper limit of the current supplied to the LED elements 60 of the LED light source 30 discontinuously by switching the switch SW1 built into the LED driver unit 50 ON and OFF, thereby switching the current range. Alternatively, the patient receiving treatment can continuously adjust the drive current supplied to the LED elements 60 of the LED light source 30 by adjusting the variable resistor VR1 which is linked to the output adjustment knob.

[0103] The output monitoring means 240 indirectly or directly measures and displays the light energy density 140 irradiated by the LED lance 200. The ammeter display is an output monitoring means 240 that indirectly monitors the light energy density 140 irradiated during treatment, for the purpose of comparing it with the patient's own past experience of symptom improvement. Therefore, as long as the reproducibility of the display is maintained relatively, the accuracy of the absolute value of the display is not a major issue. The ammeter display is used by the MCI patient to decide whether to increase or decrease the light energy density 140 according to their symptoms, and by the patient or caregiver to check whether a light energy density 140 significantly different from the normal value is being mistakenly used during treatment. If sufficient reliability can be ensured, a digital display ammeter or an ammeter with a data recording function may be used. Alternatively, it goes without saying that the system could be equipped with a semiconductor illuminometer (i.e., a photodiode) that divides the luminous flux 40 output by the LED lance 200 and directly measures its intensity, thereby measuring and monitoring the light energy density 140.

[0104] Non-patent document 8 proposes combining an intraoral laser light source with an endoscope. Applying this idea, for example, if a near-infrared LED (wavelength 850nm) used for communications is used in an LED lance 200 to irradiate light at approximately 40Hz, the image can be observed using an inexpensive imaging semiconductor for an infrared camera sensitive to a wavelength of 850nm. Therefore, by also equipping the tip of the LED lance 200 with a small infrared camera, intermittent images can be taken during light irradiation, and the patient can observe the image of the area being irradiated with light during treatment using a monitor image. This allows the light to be directed in the direction instructed by the doctor with high reproducibility, thereby improving the effectiveness of the treatment.

[0105] Furthermore, as a method for switching the 40Hz signal source 210 to self-excited operation 105 and outputting a signal with a repetition frequency of approximately 40Hz using the built-in signal source, for example, an arbitrary waveform stored in memory can be generated by the control microcomputer in accordance with the elapsed time, as referred to in Patent Document 3. Alternatively, the command voltage to be output may be defined using a time function such as a sine wave function according to the elapsed time counted in microseconds by the OS of the control microcomputer. The method of externally excited operation 100 can also be described as follows: for example, 3D active glasses for viewing stereoscopic televisions flash the lenses of the left and right LCD elements alternately in synchronization with a phase synchronization signal emitted from the television. In addition, a command voltage can be output by resetting a stored signal waveform or a function-defined signal waveform in accordance with a synchronization signal pulse input from an external source. In any case, the circuit design of the self-excited operation 105 and externally excited operation 100 of the 40Hz signal source 210, and the switching means 260 between self-excitement and external excitement, can be easily realized by a person skilled in the art through modifications to existing technology.

[0106] (7) Points to note regarding Example 1 There are three important points to keep in mind when MCI patients use the LED Lance 200 treatment device.

[0107] [Note 1] Treatment devices using photobiomodulation (PBM) technology have the characteristic of being able to regenerate and repair cells even at a weak level if the light energy density of 140 is sufficient. On the other hand, when the LED Lance 200 is irradiated at a high light energy density of 140, memory temporarily and rapidly improves, which may cause a certain kind of "intense feeling of pleasure." Therefore, if you forget the original purpose of improving the "memory loss" symptoms of MCI patients and greedily administer an excessive amount of light energy density 140 in an attempt to "strengthen their memory," it can reduce cell regeneration and, although there are individual differences, may even damage cells. Therefore, you shouldn't try to greedily increase the light energy density to 140 in an attempt to enhance your memory.

[0108] [Note 2] Machines are prone to malfunction. If a problem occurs, such as the optical system 70 that spreads the light at the tip of the LED lance 200 becoming detached, and the directivity of the LED element 60 becomes sharper, the light energy density 140 in the optical axis direction will increase sharply, posing a risk of damaging brain cells. To avoid this risk, it is desirable to use an LED light source 30 that, although within the wavelength range of the biological window, has optical spectral characteristics that allow the human eye to perceive at least a slight red color (for example, red light with a wavelength of 850 nm or less, within the biological window range). This way, immediately before performing a treatment, the presence or absence of a malfunction in the optical system 70 can be checked by tilting the LED lance 200 significantly to 30 degrees or more in a dark place and confirming that the semiconductor chip 65 of the LED element 60 glows slightly red. If the light emission of the LED light source 30 can be seen normally regardless of the direction in which it is tilted significantly, there is a high probability that there are no major defects in the optical characteristics.

[0109] [Note 3] Even if the optical system is functioning correctly, saliva or other liquids can adhere to it, potentially altering its optical properties. As a precaution, if significant water droplets or other liquids adhere to the surface of the optical system during treatment while it is in the mouth, we recommend wiping them off occasionally.

[0110] (8) Effects of Example 1 By using the LED Lance 200, a treatment device for MCI according to the present invention, patients with amnesic MCI who suffer from memory loss symptoms can operate the treatment device according to their own subjective symptoms to temporarily improve their memory loss symptoms as a symptom-improving therapy.

[0111] Furthermore, the light beam 40 emitted by the treatment device LED Lance 200 flashes (or blinks, which is synonymous with this term) at approximately 40 Hz, and therefore, through the mechanism of action described in Patent Document 1 and Non-Patent Document 4, it has the effect of preventing or delaying the risk of MCI progressing to Alzheimer's disease.

[0112] Furthermore, because the light beam 40 emitted by the LED Lance 200 treatment device is weak, it also has the effect of regenerating cells in the already damaged MCI area through the mechanism of photobiomodulation.

[0113] Furthermore, since photobiomodulation provides approximately 40Hz stimulation to the brain cells in the affected area of ​​MCI, if the phase difference is properly managed when used in conjunction with the sensory therapy device 20, it is possible to simultaneously treat brain fog and memory loss symptoms of MCI. (See Example 4 for details) [Examples]

[0114] In this second example, we introduce a digital medical device used for symptomatic treatment of MCI, which emits near-infrared light in the wavelength range known as the "biological window 3" (650-1000 nm) that penetrates biological tissue, flashing in a repeating waveform of approximately 40 Hz, and irradiating the affected area of ​​MCI, such as the hippocampus, from the oral cavity to stimulate it at approximately 40 Hz. The treatment device described in Example 2 is called the LED mouthpiece 400, and an image of the invention is shown in Figure 4.

[0115] (1) Invention In this second example, we will explain in detail the technical concept and design of the following four inventive features, focusing on the technical aspects of each feature. Although Example 2 also contains numerous inventive features that define even more detailed aspects, to avoid the complexity of the explanation, only the following inventive features will be extracted and explained in detail.

[0116] <Inventive Feature A of Example 2> The main inventions related to the LED mouthpiece 400 are as follows: In a digital medicine treatment device used for symptomatic treatment of MCI, An LED mouthpiece 400, which serves as a PBM therapy device 10, flashes a light source in a wavelength range called the biological window 3 that penetrates biological tissue with a repeating waveform of approximately 40 Hz, and irradiates the affected area of ​​MCI from inside the oral cavity with a light energy density of 140, which is a predetermined value of 5 or less.

[0117] The LED mouthpiece 400 is composed of an LED light source 30, a mouthpiece portion 410, and an LED driver 50. The LED light source 30 is configured to include a semiconductor chip 65 of an LED element 60 that irradiates a light beam 40 having an output wavelength (or peak wavelength) in the wavelength range of 650 to 1000 nm of the biological window 3, and an optical system 70 that adjusts the half-angle of power of the directivity of the light beam 40. The mouthpiece portion 410 includes a mouthpiece 460 that is fitted into the upper or lower jaw dentition and fixed inside the oral cavity while maintaining the reproducibility of its position and orientation in the mouthpiece coordinate system 420, three or more insertion points 450 for contrast-enhancing members that define a coordinate transformation matrix 440 between two orthogonal coordinate systems, the mouthpiece coordinate system 420 and the skull coordinate system 430, and a connecting member 470 that arranges the LED light source 30 on the mouthpiece 460 while maintaining the reproducibility of its installation position and irradiation direction. The LED driving device 50 is a device that supplies a driving current to the LED element 60 and irradiates the LED light source 30 with a light energy density of 140 of 10 mW / cm2 or less, which is a predetermined value 5.

[0118] The LED driver device 50 also comprises a 40Hz signal source 210, an LED driver circuit 220, an output adjustment means 230, and an output monitoring means 240. The 40Hz signal source 210 outputs a command value 250 of the approximately 40Hz time-series waveform of the luminous flux 40 emitted by the LED light source 30 of the LED mouthpiece 400. The LED driving circuit 220 receives the command value 250 output by the 40Hz signal source 210 and supplies a driving current to the LED light source 30. The output adjustment means 230 continuously and / or discontinuously adjusts the light energy density 140 of the light flux 40 irradiated from the LED light source 30. The output monitoring means 240 indirectly or directly measures and displays the light energy density 140 irradiated by the LED mouthpiece 400. A treatment device for MCI treatment that utilizes 40Hz therapy, characterized by its unique features.

[0119] <Inventive Feature B of Example 2> The mouthpiece section 410, which is fixed to the upper jaw, is characterized by its LED circuit board section 480. The mouthpiece portion 410, which is fixed to the upper jaw, further comprises an LED circuit board portion 480. The LED substrate 480 is connected to the connecting member 470 and has the LED light source 30 arranged on it, and maintains the position and direction of the LED light source 30 so that the irradiation target point 490 is included in the luminous flux 40. Characterized by, A therapeutic device for MCI treatment using 40Hz therapy, as described in Invention A of Example 2.

[0120] <Inventive Feature C of Example 2> A key feature of the mouthpiece portion 410, which is fixed to the lower jaw, is that the LED light source 30 is directly attached to the connecting member 470. The LED light source 30 is connected to the connecting member 470 and positioned and positioned so that the irradiation target point 490 is included in the luminous flux 40, maintaining the position and irradiation direction of the LED light source 30. Characterized by, A therapeutic device for MCI treatment using 40Hz therapy, as described in Invention A of Example 2.

[0121] <Inventive Feature D of Example 2> Furthermore, the functions of externally excited, self-excited, and switching for the 40Hz signal source can be summarized as follows: The command value 250 emitted by the 40Hz signal source 210 is, The LEDs are generated by the external excitation operation 100 or the self-excitation operation 105, which are controlled by the self-excitation and external excitation switching means 260 provided in the LED driver device 50. When generating by the externally excited operation 100, the signal source built into the 40Hz signal source 210 is synchronized in phase with the synchronization signal 130 input from the outside to generate the command value 250. When generated by the self-excited operation 105, the command value 250 is generated independently by a signal source incorporated inside the 40Hz signal source 210. Characterized by, A therapeutic device for MCI treatment using 40Hz therapy, as described in Invention A of Example 2.

[0122] (2) Problems with Example 2 In the aforementioned Example 1, we introduced the LED Lance 200, a treatment device intended for use by patients with mild amnesic MCI who are able to operate the treatment device themselves. However, as the symptoms of MCI progress, it becomes difficult for patients to judge the appropriate light energy density of 140 and manipulate the treatment device to direct it towards the affected area. Furthermore, the MCI lesions to be treated spread from deep within the brain to the temporal region, making treatment difficult with the LED Lance 200, which can only emit a beam of light spread in a single direction.

[0123] (3).Solution Therefore, to treat patients with advanced amnesic MCI symptoms, the problem is solved by simultaneously irradiating multiple affected areas with multiple light beams 40. Specifically, the problem is solved by using an LED mouthpiece 400, a treatment device that incorporates multiple LED light sources 30 into a mouthpiece fixed to the upper or lower jaw teeth of the patient.

[0124] Furthermore, considering that the device will be used by patients whose judgment is impaired due to MCI (Mild Cognitive Impairment), the technological concept is designed so that a prescription is provided to the patient after examination and consultation at a medical institution, and the patient or caregiver purchases a custom-made product (or a standard product with adjusted control parameters, etc.) from a specialist in digital pharmaceuticals based on the specifications such as device dimensions and control parameters. Therefore, since the means for adjusting the light energy density 140 is necessary for a professional to set the parameters according to the prescription, an output adjustment means 230 for adjusting the light energy density 140 is also provided, similar to Example 1.

[0125] Similar to Example 1, accident prevention measures include a fail-safe design that uses a high-sensitivity fuse to cut off excessive output in the event of a treatment device malfunction, a means of indirectly monitoring the output by measuring the drive current to check for abnormalities in the irradiation conditions, or a means of directly monitoring the output by measuring a portion of the irradiated light.

[0126] (4) Detailed description of Example 2 Figure 4 illustrates an LED mouthpiece 400 equipped with multiple LED light sources 30 that emit a light beam 40 that flashes at approximately 40 Hz in multiple directions within the oral cavity. Figure 4(a) illustrates the definition of coordinates and the method for measuring parameters for coordinate transformation, which are used to calculate the coordinate transformation matrix 440 between the three-dimensional coordinate system of the mouthpiece and the three-dimensional coordinate system of the skull, for the purpose of irradiating multiple affected areas of MCI with a light beam 40 from inside the oral cavity, with the target irradiation points 490.

[0127] The mouthpiece portion 410 used for patient examinations can be sealed with contrast agents (lead for X-ray imaging, iodine solution for CT, gadolinium or iron preparations for MRI, etc.) at its rightmost point Pr, frontal center point Pc, and leftmost point Pl. After imaging of the skeleton and various parts of the brain, it is also possible to use the device without the contrast agent sealed inside. Alternatively, a mouthpiece 410 containing contrast agent may be used during measurement, and a mouthpiece 410 of the same dimensions but without contrast agent may be used during treatment after measurement. The three points mentioned above—the rightmost point Pr, the frontal center point Pc, and the leftmost point Pl—are referred to as the 450 points where the contrast agent can be inserted.

[0128] This contrast-enhanced material insertion point 450 is a representative point for measuring coordinates using X-ray, CT, or MRI in order to calculate a coordinate transformation matrix 440 for the coordinate transformation between the three-dimensional coordinate system of the mouthpiece and the three-dimensional coordinate system of the skull. Once the measurements are complete, there is a concern that leakage of the contrast agent during the long treatment period could cause health problems. Therefore, to improve safety, it is desirable to fix the mouthpiece 410 to the patient's teeth and perform the patient's examination. Once the coordinate measurements of the skull and various parts of the brain are completed and the coordinate transformation matrix 440 for coordinate transformation applicable to that patient is determined, it is desirable to use a mouthpiece 410 of the same dimensions but without the contrast agent for subsequent treatment of the patient.

[0129] The mouthpiece coordinate system 420 defines the x-axis from the left endpoint pl to the right endpoint pr, draws a perpendicular from the front center point pc to the x-axis, and defines the intersection point of these perpendiculars as the origin p0 of the mouthpiece coordinate system 420. The y-axis is defined from the origin p0 to the front center point pc. Finally, the z-axis is defined passing through the origin p0 and pointing upward perpendicular to the x and y axes. Therefore, the mouthpiece coordinate system 420 is a right-handed 3D Cartesian coordinate system. By defining the mouthpiece coordinate system 420 in this way, the three contrast-enhancing member insertion points 450 uniquely define the origin p0 of the mouthpiece coordinate system 420, the xy-plane, and the direction of the z-axis pointing upward orthogonal to the xy-plane.

[0130] Therefore, if we let a be the length from the origin p0 to the rightmost point pr, and b be the length from the origin p0 to the front center point pc, then the coordinates of each point in the mouthpiece coordinate system 420 are: origin p0=[0,0,0], rightmost point pr=[a,0,0], front center point pc=[0,b,0]. Incidentally, if we let c be the distance from the origin p0 to the left endpoint pl, then the left endpoint pl = [-c, 0, 0].

[0131] Next, the cranial coordinate system 430 defines the X-axis from the left to the right auditory canal of the subject's skull, and a perpendicular is drawn from the anterior fontanelle of the subject's skull to the X-axis. The intersection of these two perpendiculars is defined as the origin of the cranial coordinate system 430, and the Z-axis is defined from this origin towards the anterior fontanelle of the skull. Finally, the Y-axis is defined forward, passing through the origin of the cranial coordinate system 430 and perpendicular to the X and Z axes. Therefore, the cranial coordinate system 430 is also a right-handed three-dimensional Cartesian coordinate system. By using the cranial coordinate system 430 defined in this way, and measuring the three coordinates of the contrast-enhanced material insertion point 450 after imaging from multiple directions using an X-ray device, CT, or MRI, the amount of translation from the origin p0 of the mouthpiece coordinate system 420 to the origin of the cranial coordinate system 430, and the amount of rotational movement along the x, y, and z axes are uniquely defined.

[0132] The coordinate value P0 in the skull coordinate system 430 for the origin p0=[0,0,0] in the mouthpiece coordinate system 420 can be determined from the above definition of the origin p0 in the mouthpiece coordinate system 420 using the coordinate points of the left endpoint PL, right endpoint PR, and frontal center point PC measured by an X-ray device. If the coordinate value P0 corresponding to the origin p0 of the mouthpiece coordinate system 420 in the skull coordinate system 430, measured by an X-ray device, is P0=[Vx,Vy,Vz], then the translation matrix between the mouthpiece coordinate system 420 and the skull coordinate system 430 can be calculated from this value. Furthermore, by performing a similar translation on the coordinate values ​​of the rightmost point PR and the frontal center point PC measured in the skull coordinate system 430, the rotational translation matrices around the origins of both the mouthpiece coordinate system 420 and the skull coordinate system 430 can be uniquely calculated.

[0133] Therefore, by fitting a mouthpiece portion 410 containing contrast agent into three contrast agent insertion points 450 into the dental arch in the oral cavity, and measuring the coordinate values ​​of the three contrast agent insertion points 450 (i.e., the leftmost point pl, the rightmost point pr, and the frontal center point pc) in the cranial coordinate system 430 using an X-ray device, the translation matrix and rotation matrix between the two coordinate systems are uniquely defined. Furthermore, both the mouthpiece coordinate system 420 and the skull coordinate system 430 are right-handed systems, and since the units of length in both systems are SI units of physical quantities, the length scaling ratio is 1:1. Also, there is no geometric shear relationship in the linear transformation between the mouthpiece coordinate system 420 and the skull coordinate system 430.

[0134] Therefore, by utilizing known affine transformations in two three-dimensional Cartesian coordinate systems, a coordinate transformation matrix 440 and its inverse can be defined for the mouthpiece coordinate system 420 and the skull coordinate system 430. Then, by superimposing the coordinate position and irradiation direction of the LED light source 30 measured in the mouthpiece coordinate system 420 with the coordinates of the MCI affected area measured in the skull coordinate system 430 using CT or MRI, the LED light source 30 and the MCI affected area can be displayed on the same three-dimensional Cartesian coordinate system. In other words, by drawing a diagram using design tools such as 3D CAD, it is possible to design the position and direction of the LED light source 30 on the mouthpiece coordinate system 420 in order to direct the LED light source 30 towards the coordinates of the MCI affected area, such as the hippocampus. To calculate and define the coordinate transformation matrix 440, a minimum of three points are required as the contrast-enhanced material insertion points 450: the leftmost point pl, the rightmost point pr, and the frontal center point pc, as explained in the definition of the mouthpiece coordinate system 420. However, to improve measurement accuracy, the number of contrast-enhanced material insertion points 450 may be increased to three or more.

[0135] <Mouthpiece worn on the upper jaw> Figure 4(b) is a schematic diagram of the prototype LED substrate 480, and is an example of designing the position and irradiation direction of the LED light source 30 on the mouthpiece coordinate system 420 in order to irradiate the LED light source 30 toward the coordinates of the affected area of ​​MCI. The LED substrate 480, which is a component of the mouthpiece 410 that is fixed to the upper jaw, is connected to the connecting member 470 of the mouthpiece 460 and has an LED light source 30 installed on it. Its position and the direction of the illumination of the optical axis are directed in an appropriate direction so that the irradiation target point 490 such as the hippocampus is included in the luminous beam 40, and it is fixed in place to maintain that position and direction. In Figure 4(b), eight surface-mount LED elements are arranged as LED light sources 30 so that eight optical axes are generated in different directions. The number of luminous fluxes 40, that is, the number of mounted LED elements, can be other than the eight exemplified in the figure. However, the light energy density 140 of the luminous fluxes 40 must be used in a range less than 10 mW / cm2, which is a predetermined value of 5.

[0136] Figure 4(c) is a schematic diagram of the prototype mouthpiece 410. In this diagram, the mouthpiece 410 is fitted to the upper teeth, and the LED substrate 480 is mounted between two connecting members 470 located on the left and right sides of the inside of the mouthpiece 460, so that the eight optical axes of the LED light source 30 extend diagonally upward from the upper mouthpiece 410. The driving current for the LED light source 30 is supplied via wires from an LED driver device 50 (not shown).

[0137] The shape of the LED substrate 480 and the mounting position and optical axis direction of the surface-mount LED elements as the LED light source 30 were determined so that the orientation of these eight optical axes and the spread of the luminous beam 40 include the location of the MCI affected area, such as the hippocampus, as described in the mouthpiece coordinate system 420. Because the luminous beam 40 is designed to spread widely, even if the center of the optical axis does not hit the exact center of the MCI affected area, it is sufficient to ensure that the MCI affected area is properly included within the spread of the luminous beam 40. Furthermore, in the stage of industrial use, if the LED substrate 480 is created with a precise shape using a 3D printer or similar to match the shape of the upper part of the patient's oral cavity, discomfort in the patient's mouth can be reduced.

[0138] Furthermore, during the prototype stage, experiments were conducted by wrapping the LED substrate section 480 and the surface-mount LED elements as the LED light source 30 in food wrap to prevent leakage due to saliva in the mouth. For industrial use, it is essential to cover the device with a nearly transparent waterproof cover that efficiently transmits near-infrared light.

[0139] The above describes a mouthpiece 410 that is fitted onto the upper teeth, but a mouthpiece 410 that is fitted onto the lower teeth is also feasible. In other words, the LED mouthpiece 400 is composed of an LED light source 30, a mouthpiece section 410, and an LED driver 50. The LED light source 30 is composed of a semiconductor chip 65 of an LED element 60 that irradiates a light beam 40 having an output wavelength (or peak wavelength) in the range of 650 to 1000 nm, which is the biological window 3, and an optical system 70 that adjusts the half-angle of power of the directivity of the light beam 40. The mouthpiece portion 410 includes a mouthpiece 460 that is fitted into the upper or lower jaw dentition and fixed inside the oral cavity while maintaining the reproducibility of its position and orientation in the mouthpiece coordinate system 420, three or more insertion points 450 for contrast-enhancing members that define a coordinate transformation matrix 440 between two orthogonal coordinate systems, the mouthpiece coordinate system 420 and the skull coordinate system 430, and a connecting member 470 that arranges the LED light source 30 on the mouthpiece 460 while maintaining the reproducibility of its installation position and irradiation direction. The LED driver device 50 is a device that supplies a drive current to the LED element 60 and irradiates the LED light source 30 with a light energy density of 140, which is a predetermined value of 5, of 10 mW / cm2 or less.

[0140] Figure 4(d) shows the external dimensions of a surface-mount LED element (model number OSI3120641E, wavelength 850nm, standard test current 20mA) used as the LED element 60 for the prototype LED light source 30. It includes a semiconductor chip 65 that irradiates with an output wavelength (or peak wavelength) corresponding to the near-infrared wavelength region, which is referred to as the "biological window 3" in this invention. The half-angle of maximum power (FWHM) of this LED element 60 is wide at 35 degrees. In the prototype LED light source 30, in order to further reduce the light energy density of 140, a (handmade) optical lens was attached to the light-emitting end of the LED element 60 to further widen the FWHM to over 40 degrees. For industrial use, a dedicated lens or an LED with a dedicated lens should be used.

[0141] For reference, here's how to process a handmade lens. A protective film of uniform thickness is applied to a flat surface such as a hand mirror, and a jig is made to temporarily fix a surface-mount LED element upright. Next, UV-curing transparent adhesive BONDIC (trademark registered) is poured between the protective film and the LED element and cured with ultraviolet light. Due to the effect of surface tension, a transparent prototype lens optical system 70 with a base shape as shown in the diagram is created. Furthermore, when peeling the prototype LED light source 30 from the mirror surface, the optical system 70 made with a handmade lens tends to detach from the LED element 60. Therefore, if grooves are cut laterally along the contour lines of the hemispherical head of the LED element 60 using a diamond cutter before applying the adhesive, the adhesive strength is improved, and the optical system 70 becomes less likely to detach from the LED element 60.

[0142] Figure 4(e) shows the configuration of the LED driver unit 50. The LED driver device 50 also comprises a 40Hz signal source 210, an LED driver circuit 220, an output adjustment means 230, and an output monitoring means 240. The 40Hz signal source 210 outputs a command value 250 of the approximately 40Hz time-series waveform of the luminous flux 40 emitted by the LED light source 30 of the LED mouthpiece 400. The LED drive circuit 220 receives the command value 250 output by the 40Hz signal source 210 and supplies drive current to the LED light source 30. The output adjustment means 230 continuously and / or discontinuously adjusts the light energy density 140 of the luminous flux 40 irradiated from the LED light source 30. The output monitoring means 240 indirectly or directly measures and displays the light energy density 140 irradiated by the LED mouthpiece 400.

[0143] In other words, the basic design concept of the LED driver device 50 is the same as in Example 1, with a 40Hz signal source 210 and an LED driver circuit 220 connected to an ammeter, a high-sensitivity fuse, and an LED light source 30, and driving power supplied from a power supply. In this example, eight LED light sources 30 are connected in series and driven with the same driving current value. The power supply voltage was set to 15V to accommodate the voltage drop across the LEDs.

[0144] The function of the ammeter is the same as that of the output monitoring means 240 in Example 1, and is an indirect means of monitoring the light energy density 140 to confirm whether the same amount of drive current as in the past is being supplied normally during treatment. Of course, a photodiode or the like that divides the light beam emitted by the LED and directly monitors the light energy density 140, and the output of the light may be displayed and monitored.

[0145] In Figure 4, all LED light sources 30 incorporated into the LED mouthpiece 400 are controlled by a single LED driver 50. However, by redesigning the device and providing one LED driver 50 for every few LED light sources 30, or for each individual LED light source 30, it is possible to redesign the device so that multiple luminous beams 40 each emit luminous beams 40 with a light energy density of 140, tailored to the characteristics of the cells in the affected area of ​​MCI being irradiated.

[0146] <Switching between self-motivated and externally motivated actions> The command voltage, which is the command value 250 emitted by the 40Hz signal source 210, is generated by an externally excited operation 100 or a self-excited operation 105 using a self-excitement / external excitation switching means 260 provided in the LED driver device 50. When generated by externally excited operation 100, the signal source built into the 40Hz signal source 210 is synchronized in phase with an externally input synchronization signal 130 to generate the command value 250. When generated by self-excited operation 105, the signal source built into the 40Hz signal source 210 generates the command value 250 independently.

[0147] In other words, the 40Hz signal source 210 can be equipped with a manual switch on the LED driver 50 to switch between externally excited operation 100, which generates a command voltage phase-synchronized with an external synchronization signal 130, and self-excited operation 105, which generates a command voltage independently or independently by an internal signal source, similar to the first embodiment. Alternatively, the externally excited operation 100 and self-excited operation 105 may be automatically switched depending on the presence or absence of the external synchronization signal 130, or switching may not be necessary if a dedicated product for either externally excited operation 100 or self-excited operation 105 is designed.

[0148] Figure 4(f) shows an example circuit of the LED driver 50. The design concept is the same as in Example 1, where the 40Hz signal source 210, which can be switched between self-excited and externally excited, outputs a sinusoidal waveform with an amplitude of 0 to 3V as a command voltage, and the LED driver circuit 220 provides voltage feedback of the LED driver current through a feedback resistor circuit. Similar to Example 1, a feedback resistor circuit consisting of R5, R6, R7, SW1, and VR1 is provided in the LED driving circuit 220, and the current supplied to the LED light source 30 is adjusted by continuously changing the resistance value with VR1 and discontinuously changing it with SW1.

[0149] In Example 2, to allow a professional to set the drive current based on a doctor's prescription, the SW1 for adjusting the feedback resistor and the VR1 for adjusting the variable resistor are operated by the professional after opening the housing of the LED driver device. However, if the doctor decides to allow the patient to make adjustments, then, as in Example 1, the prescription should specify a product designed to allow adjustment of the variable resistor VR1 using an output adjustment knob mounted on the housing. For a detailed explanation of other operations, please also refer to the descriptions of Figures 3(e) and 3(f) in Example 1.

[0150] <Mouthpiece worn on the lower jaw> In this invention, a mouthpiece fitted to the lower jaw teeth is also designed based on the present invention, with the aim of irradiating a small luminous beam 40 with a light energy density of 140 for photobiomodulation. This is achieved by incorporating an optical system 70 into the LED light source 30 (or by integrating it as a resin lens into the LED element 60), increasing the half-angle to widen the luminous beam 40, and further limiting the current to use an energy density of 140 at a predetermined value of 5, which is 10 mW / cm2 or less. To avoid hindering tongue movement in the mouth as much as possible, the mouthpiece portion 410 fixed to the lower jaw has an extremely simple structure. An LED light source 30 that emits a wide beam of light 40 within the oral cavity is directly attached to a connecting member 470. The position and direction of the LED light source 30 are held by the mouthpiece fixed to the lower jaw so that the irradiation target points 490, such as the hippocampus, are included within the beam of light 40.

[0151] Figure 8(a) illustrates how to use the mouthpiece 410, which is fitted onto the lower jaw teeth. The wire supplying the driving current to the LED light source 30 is routed from the left side of the lip to prevent it from being bitten off by the teeth. The method of routing the wire can be modified as needed to improve usability.

[0152] In the mandibular type mouthpiece 460 shown in Figure 8(b), the optical system 70 is incorporated into the LED light source 30 (or integrated as a lens at the tip of the transparent resin case of the LED element 60), and the LED light source 30 is directly attached to the connecting member 470 of the mouthpiece 460 (i.e., without the LED circuit board 480) and fixed in place. The dental grooves of the mandibular type mouthpiece 460 face downwards, so the mandibular teeth are fitted into the dental grooves to secure the mouthpiece 460. In addition, since the dental grooves of the upper jaw type mouthpiece 460 face upward, the mouthpiece 460 is fixed by fitting the upper jaw teeth into the dental grooves. However, similar to the lower jaw type mouthpiece 460, the LED light source 30 may also be directly attached to the connecting member 470 of the mouthpiece 460 in the upper jaw type, and the light beam 40 may be directed to illuminate the affected area of ​​MCI.

[0153] In the conventional mandibular type mouthpiece described in Patent Document 5, the technology was based on the idea of ​​irradiating light with a narrow, highly directional beam of light 40 to precisely target only the hippocampus with a high light energy density of 140. On the other hand, the present invention adopts a design concept that "based on photobiomodulation technology, the LED driving current is limited to a low value, and a weak light beam 40, which is further widened by a lens system, is irradiated to include the surrounding cells of the hippocampus, and all cells in the irradiated area are regenerated indiscriminately if damaged." Therefore, the irradiation is carried out without avoiding the exposure of unintended cells around the hippocampus to weak light. To achieve this, the position and orientation for fixing the LED light source 30 to the connecting member 470 of the mouthpiece 460 are designed using 3D CAD or similar software from the coordinate system shown in Figure 4(a).

[0154] Figure 8(b) shows an example where the lower right LED light source 30 illuminates the upper left hippocampus, and the lower left LED light source 30 illuminates the upper right hippocampus. By "crossing the light beams 40 in the oral cavity" in this way, a relatively long distance can be secured from the LED light source 30 to the irradiation target point 490, and the light beam 40 of the LED light source 30 with a large half-angle of maximum power can be easily spread, so that a wide area of ​​the deep brain can be irradiated with a small number of LED elements. Incidentally, Figure 8(b) shows an example where two LED light sources 30 are provided, but the design may be modified to attach two or more LED light sources 30 to the mouthpiece 460 to irradiate an even wider area deep within the brain.

[0155] In the prototype, the LED light source 30 was protected with transparent food wrap to prevent saliva and other substances from entering and short-circuiting the electronic circuit. However, when manufacturing the mouthpiece 460 as an actual product for industrial application, it is desirable to design it so that the LED light source 30 and the wire outlet are waterproofed and sealed within a transparent resin material that transmits near-infrared light.

[0156] (5) Effects of Example 2 By using the LED mouthpiece 400, a treatment device for MCI according to the present invention, multiple light axes can be irradiated to treat multiple affected areas simultaneously. Therefore, therapeutic effects can be achieved without delay even in patients with advanced MCI, and memory loss symptoms can be treated as a symptom-improving therapy.

[0157] Furthermore, since the light beam 40 emitted by the treatment device LED mouthpiece 400 flashes at approximately 40 Hz, it has the effect of preventing or delaying the risk of the disease progressing to Alzheimer's disease through the mechanism of action described in Patent Document 1.

[0158] Furthermore, because the light beam 40 emitted by the treatment device LED mouthpiece 400 is weak, it also has the effect of regenerating cells in the already damaged MCI area through the mechanism of photobiomodulation.

[0159] Furthermore, since photobiomodulation provides approximately 40Hz stimulation to the brain cells in the affected area of ​​MCI, if the phase difference is properly managed when used in conjunction with the sensory therapy device 20, it is possible to simultaneously treat brain fog and memory loss symptoms of MCI. (See Example 4 for details) [Examples]

[0160] This third example introduces a digital medical device used for symptomatic treatment of MCI, which emits near-infrared light in the wavelength range known as the "biological window 3" (650-1000 nm) that penetrates biological tissue, flashing in a repeating waveform of approximately 40 Hz. This light is irradiated from above the scalp towards the affected area of ​​MCI in the temporal region, stimulating it at approximately 40 Hz as it penetrates the skull. The treatment device described in Example 3 is called the LED Pad 600, and an image of the invention is shown in Figure 5.

[0161] (1) Invention In this third example, we will explain in detail the technical concept and design of the following four inventive features, focusing on the technical aspects of each feature. Although Example 3 also contains numerous inventive features that define even more detailed matters, to avoid the complexity of the explanation, only the following inventive features will be extracted and explained in detail.

[0162] <Inventive Feature A of Example 3> The main inventions related to the LED pad 600 are as follows: In a digital medicine treatment device used for symptomatic treatment of MCI, An LED pad 600, which serves as a PBM therapy device 10, flashes a light source in a wavelength range called the biological window 3, which penetrates biological tissue, with a repeating waveform of approximately 40 Hz, and irradiates the affected area of ​​MCI from above the scalp with a predetermined light energy density of 140 or less.

[0163] The LED pad 600 is composed of an LED light source 30, an LED pad body 610, and an LED driver 50. The LED light source 30 is configured to include a semiconductor chip 65 of an LED element 60 that irradiates a light beam 40 having an output wavelength (or peak wavelength) in the wavelength range of 650 to 1000 nm of the biological window 3, and an optical system 70 that adjusts the half-angle of power of the directivity of the light beam 40. The LED pad body 610 is configured to include a head fixing member 620 that fixes the LED pad body 610 to the head, a connecting member 625 that determines the emission position and direction of the luminous flux 40 emitted from the LED light source 30, and a transmissive plate 630 from which the luminous flux 40 is emitted from the LED pad body 610, and further comprises an internal structure that is either a matrix system 640 in which the LED light sources 30 are arranged vertically and horizontally, or a backlight system 650 in which the LED light sources 30 are incorporated as the light source of the backlight 660. The LED driving device 50 is a device that supplies a driving current to the LED element 60 and irradiates the LED light source 30 with a light energy density of 140 of 10 mW / cm2 or less, which is a predetermined value 5.

[0164] The LED driver device 50 also comprises a 40Hz signal source 210, an LED driver circuit 220, an output adjustment means 230, and an output monitoring means 240. The 40Hz signal source 210 outputs a command value 250 of the approximately 40Hz time-series waveform of the luminous flux 40 emitted by the LED light source 30 of the LED pad 600. The LED driving circuit 220 receives the command value 250 output by the 40Hz signal source 210 and supplies a driving current to the LED light source 30. The output adjustment means 230 continuously and / or discontinuously adjusts the light energy density 140 of the light flux 40 irradiated from the LED light source 30. The output monitoring means 240 indirectly or directly measures and displays the light energy density 140 irradiated by the LED pad 600. A treatment device for MCI treatment that utilizes 40Hz therapy, characterized by its unique features.

[0165] <Inventive Features B of Example 3> The invention relating to the internal structure of the matrix system 640 of the LED pad body 610 is as follows: The internal structure of the matrix system 640 is such that a transmissive plate 630 that transmits the luminous flux 40 is disposed on the top surface of the LED pad body 610, and LED light sources 30 that irradiate the luminous flux 40 toward the transmissive plate 630 are arranged vertically and horizontally on the bottom surface of the LED pad body 610. Characterized by, A therapeutic device for MCI treatment using 40Hz therapy, as described in Invention A of Example 3.

[0166] <Inventive Feature C of Example 3> The invention relating to the internal structure of the backlight system 650 of the LED pad body 610 is as follows: The internal structure of the backlight system 650 includes a transmissive plate 630 that transmits the luminous flux 40 through the top surface of the LED pad body 610, and a backlight 660 consisting of an LED light source 30 that directs the luminous flux 40 toward the transmissive plate 630, a reflector 662, and a light guide plate 664 and / or a diffuser plate 666 on the bottom surface of the LED pad body 610. Characterized by, A therapeutic device for MCI treatment using 40Hz therapy, as described in Invention A of Example 3.

[0167] <Inventive Feature D of Example 3> Furthermore, the functions of externally excited, self-excited, and switching for the 40Hz signal source can be summarized as follows: The command value 250 emitted by the 40Hz signal source 210 is, The LEDs are generated by the external excitation operation 100 or the self-excitation operation 105, which are controlled by the self-excitation and external excitation switching means 260 provided in the LED driver device 50. When generating by the externally excited operation 100, the signal source built into the 40Hz signal source 210 is synchronized in phase with the synchronization signal 130 input from the outside to generate the command value 250. When generated by the self-excited operation 105, the command value 250 is generated independently by a signal source incorporated inside the 40Hz signal source 210. Characterized by, A therapeutic device for MCI treatment using 40Hz therapy, as described in Invention A of Example 3.

[0168] (2) Problems with Example 3 Example 3 has two problems. <Irradiation from deep within the brain alone is insufficient to improve severe memory loss.> As described in Examples 1 and 2, the symptom of "mild memory loss" where the lesion of MCI is located only in the deep part of the brain was improved. However, in cases of "severe memory loss" where the lesion has spread to the side of the temporal lobe closer to the cortex (for example, the temporal pole), simply irradiating the deep brain with weak near-infrared light based on photobiomodulation technology is insufficient, as the light is absorbed by the biological tissue along the transmission path and does not penetrate from the deep brain to the lesion closer to the cortex.

[0169] <40Hz light and sound alone are insufficient to improve "severe brain fog"> To improve mild brain fog symptoms, stimulating the brain with phase-synchronized 40Hz light and sound using conventional technology increases the amplitude of the 40Hz component of brainwaves not only in the frontal, parietal, and occipital regions but also in the temporal region. As a result, mild brain fog symptoms were improved. However, improving the symptoms of severe brain fog that develops as MCI progresses requires an increase in "coherence" that is phase-synchronized with 40Hz light and sound stimuli. However, the increase in coherence is unstable in the left and right temporal lobes, and 40Hz light and sound cannot deliver 40Hz stimulation to the temporal lobes.

[0170] (3) Solution of Example 3 <Phase synchronization with irradiation from deep within the brain> To alleviate severe memory loss symptoms, if irradiation from the deep brain side as in Examples 1 and 2 above does not reach the cortex, then phase-synchronized light energy at 40 Hz can be irradiated from the cortical side of the temporal lobe as well.

[0171] <Phase-synchronize with 40Hz light and sound> To alleviate the symptoms of severe brain fog, it is necessary to enhance and stabilize temporal lobe coherence using conventional 40Hz light and sound stimulation. To achieve this, the temporal lobe should be stimulated by irradiating it with phase-synchronized light energy at 40Hz from the cortical side, thereby synchronizing the temporal lobe with the light.

[0172] <Irradiate the temporal region with light energy> In conclusion, to improve severe memory problems, it is sufficient to irradiate the temporal region with 40Hz light energy in phase synchronization with the light energy irradiation from the deep brain side as described in Examples 1 and 2. Furthermore, to improve severe brain fog symptoms, it is possible to irradiate the temporal region with 40Hz light energy in phase synchronization with conventional light or sound stimulation techniques. In either case, if the light energy being irradiated is too strong, it will damage brain cells and have the opposite effect. Therefore, it is best to set an upper limit and limit the light energy density being irradiated, and then adjust it accordingly.

[0173] (4) Design policy for Example 3 Therefore, the design principles for the treatment device in Example 3 were as follows: 1) This treatment device is designed to be secured to the head using a headband (or a head restraint member 620 such as a hat, helmet, glasses, goggles, or specialized device). 2) The irradiable light energy density will be variable, with only an upper limit set to avoid damaging brain cells. 3) The light energy density irradiated will be kept as low as possible within the range effective in alleviating MCI symptoms (memory loss and brain fog), making it a PBM treatment device intended to regenerate damaged brain cells. 4) Equipped with a fail-safe function that immediately disables irradiation if the means for limiting the upper limit of the light energy density of the treatment device malfunctions. 5) To prevent errors in setting the light energy density of the treatment device, a function will be provided that allows the patient to monitor the output themselves.

[0174] (5) Detailed description of Example 3 Figure 5 is a diagram illustrating in detail the LED pad 600 that provides light stimulation to the temporal region from the scalp side in Example 3. The LED pad 600 is a digital medicine treatment device used for symptomatic treatment of MCI, and is a PBM therapy device 10 that flashes a light source in the range of wavelengths called the biological window 3, which penetrates biological tissue, with a repeating waveform of approximately 40 Hz, and irradiates the affected area of ​​MCI from above the scalp with a light energy density of 140, which is a predetermined value of 5 or less.

[0175] Figure 5(a) shows the location of the left and right temporal (P) cortices as treatment targets for the LED pad 600 in Example 3. The right-hand diagram in Figure 5(a) is a cross-sectional view of the brain from the front, with (A) and (B) representing the deep brain areas affected by the PBM therapy device 10, which treats memory loss symptoms. The left diagram in Figure 5(a) is a cross-sectional view of the brain from the side, showing the point (L) where brain waves are generated by 40Hz light stimulation using the sensory therapy device 20, and the point (S) where brain waves are generated by sound stimulation.

[0176] Figure 5(b) shows how to use the LED pad 600, illustrating a method of fixing the LED pad body 610 to the left and right sides of the head using a headband as a head fixing member 620. Various connection methods can be designed for connecting the LED pad body 610 to the headband, including connecting members 625 such as resin buckles or Velcro (registered trademark). For example, a hat, helmet, or dedicated fastener can be used as the head fixing member 620, but the connecting member 625 that determines the emission position and direction of the luminous flux 40 emitted from the LED light source 30 by connecting the LED pad body 610 to these can also be a button, hook, or snap used to secure fixing bands. The LED pad 600 consists of an LED pad body 610, an LED light source 30 disposed within it, and an LED driver 50 that supplies LED driving current to the LED pad body 610. The LED pad body 610 and the LED driver 50 are connected by a multi-core cable or similar electrical wire.

[0177] Each LED light source 30, as in Examples 1 and 2, is composed of a semiconductor chip 65 of an LED element 60 that irradiates a luminous beam 40 having an output wavelength (or peak wavelength) in the range of 650 to 1000 nm of the biological window 3, and an optical system 70 that adjusts the half-angle of power of the luminous beam 40's directivity. If sufficient directivity of the luminous beam 40 is obtained by the lens shape of the transparent resin formed on the output portion of the LED element 60, there is no need to add a new optical system.

[0178] It is also possible to design the LED light source 30 to incorporate the LED element 60 (or laser light source) into the LED driver unit 50, and in that case, it goes without saying that the design can replace some or all of the wires with optical fibers.

[0179] <Matrix Method> The upper diagram in Figure 5(c) shows a front view of an example of a matrix system 640 in which 16 LED light sources 30 are arranged vertically and horizontally in a 4x4 grid inside the LED pad body 610. The arrangement of the LED light sources 30 does not necessarily have to be a grid pattern; any arrangement that is two-dimensional in the vertical and horizontal directions, such as a staggered arrangement or a hexagonal plane, can be applied as long as it does not become too dense and impair the heat dissipation characteristics of the LED elements 60 of the LED light sources 30.

[0180] The lower part of Figure 5(c) is a side view of the LED pad body 610, showing the arrangement of the LED light source 30 and the transmissive plate 630. The internal structure of the matrix system 640 is such that a transmissive plate 630 that transmits the luminous flux 40 is placed on the top surface of the LED pad body 610, and LED light sources 30 that irradiate the luminous flux 40 toward the transmissive plate 630 are arranged vertically and horizontally on the bottom surface of the LED pad body 610. As illustrated, the light emitted from the LED light source 30 needs a sufficient distance to spread and pass through the transmissive plate 630, so the LED pad body 610 in this matrix type tends to be thicker. Furthermore, because the luminous flux 40 overlaps, the light energy density 140 is higher in the center of the LED pad body 610. In other words, a peak in light energy density 140 occurs in the center. Although not shown in the diagram, a light sensor for directly monitoring the brightness of the emitted light may also be provided inside the LED pad body 610. The transmissive plate 630 may be colorless and transparent, or it may be white and semi-transparent to diffuse the light flux 40.

[0181] <Backlight System> The upper part of Figure 5(d) is a front view showing the structure of the backlight 660 using near-infrared LEDs. By thinning the directionality of the luminous flux 40 emitted from the optical system 70 included in the LED light source 30 of the backlight system 650 so that most of the emitted luminous flux 40 passes through the light guide plate 664 from the side of the thin backlight 660, is reflected by the reflector plate 662, and then passes through the light guide plate 664 and / or diffuser plate 666 towards the front.

[0182] In other words, the backlight 660 has a structure similar to the LED backlights incorporated into PC LCD monitors, with LED elements 60 arranged in a straight line at the bottom of the backlight 660 as the LED light source 30. This diagram shows an example where a light leakage section is provided on the side of the backlight 660. By doing so, the light leaking from the side can be detected by a light sensor, and the light energy density 140 of the emitted light can be directly monitored by the light sensor.

[0183] The lower part of Figure 5(d) is a side view of the LED pad body 610 of the backlight system 650. Near-infrared light irradiated from below by the LED light source 30 is reflected perpendicular to the screen of the backlight 660 by a white or mirrored reflector 662, and the entire screen is made to emit near-infrared wavelength light uniformly using a light guide plate and a diffuser plate. In other words, the internal structure of the backlight system 650 consists of a transmissive plate 630 that transmits the luminous flux 40 through the top surface of the LED pad body 610, and on the bottom surface of the LED pad body 610, an LED light source 30 that directs the luminous flux 40 toward the transmissive plate 630, a reflector 662, and a light guide plate 664 and / or a diffuser plate 666. The backlight type 650 has the characteristic of being able to emit light with a nearly uniform light energy density of 140 in the rightward direction as shown in Figure 5(d). In addition, the LED pad body 610 of the backlight type 650 tends to be thinner compared to the matrix type 640. The transmissive plate 630 may be colorless and transparent, or it may be white and semi-transparent to diffuse the light flux 40.

[0184] Incidentally, when replacing the white LEDs incorporated in the backlight of an LCD panel (hereinafter referred to as "commercial monitor") such as a commercially available small game console or ultra-small notebook PC with the near-infrared LED light source 30, it is desirable to also modify the optical system 70 of the LED light source 30 to reduce its directivity. After that, the energizing current of the LED light source 30 is controlled to blink at about 40 Hz. The liquid crystal display layer in Fig. 5(d) incorporated in the commercial monitor may be removed. Alternatively, as shown in Fig. 5(d), without removing the liquid crystal display layer incorporated in the commercial monitor, the entire liquid crystal display layer may be blinked at about 40 Hz to irradiate a light stimulus.

[0185] Note that the transmissive plate 630 on the emission surface of the backlight 660 is covered with an "LCD element that controls the drive voltage to simultaneously blink the entire surface corresponding to the lens of the sunglasses" similar to the LCD sunglasses 180. A constant current is passed through the LED light source 30 to make the entire light-emitting surface of the backlight 660 emit light with a uniform light energy density 140. Then, the LCD element is driven with a drive voltage having a time-series waveform that repeats at 40 Hz, and the design can be changed so that the irradiated light beam 40 blinks at 40 Hz.

[0186] Regarding the transmissive plate 630 on the emission surface of the matrix method 640 in Fig. 5(c) as well, the design can be changed so that the LED light source 30 emits light evenly, the transmissive plate 630 is composed of an LCD element similar to the LCD sunglasses 180, and it blinks at 40 Hz. Thus, various design changes can be made based on the technical idea of the present invention.

[0187] Fig. 5(e) is a diagram showing the configuration of the LED driving device 50. The LED driving device 50 is a device that supplies a driving current to the LED element 60 to irradiate the light beam 40 from the LED light source 30 with a light energy density 140 of 10 mW / cm2 or less as a predetermined value 5.

[0188] In Fig. 5(e), an example is shown in which eight surface-mounted LED elements 60 connected in series and a resistor R are grouped together, and two such groups are connected in parallel, with the resistor R used to balance the current to form an LED group. The symbols of the individual LEDs constituting the LED group in this Fig. 5(e) correspond to the LED light sources 30, and each is provided with an optical system 70. Note that the number of LED light sources 30 constituting the LED group can be designed and changed according to device specifications such as LED element characteristics and the dimensions and shapes of the LED pads 600. In the LED group, based on the same design concept as in the first and second embodiments, a high-sensitivity fuse (e.g., 20 mA, etc.) and an ammeter are connected in series, and current is supplied from the LED driving device 50.

[0189] The LED driving device 50 also includes a 40 Hz signal source 210, an LED driving circuit 220, an output adjustment means 230, and an output monitoring means 240. The 40 Hz signal source 210 outputs a command voltage with an arbitrary waveform having a repetition frequency of approximately 40 Hz, such as a sine wave, a rectangular wave, etc., as a command value 250 of the time-series waveform of approximately 40 Hz of the light beam 40 emitted by the LED light source 30 of the LED pad 600. The LED driving circuit 220 inputs the command value 250 output by the 40 Hz signal source 210 and supplies a driving current to the LED light source 30. The output adjustment means 230 continuously adjusts the LED driving current using, for example, a variable resistor, based on the light energy density 140 of the light beam 40 irradiated from the LED light source 30. Note that discontinuous adjustment may also be performed using a switch or the like. The output monitoring means 240 indirectly measures the light energy density 140 irradiated by the LED pad 600 by displaying the LED driving current on an ammeter, or directly measures and displays the light beam 40 irradiated by the LED light source 30 using, for example, the optical sensor in Fig. 5(d).

[0190] Figure 5(f) shows a specific circuit example of the LED driver device 50. As already explained in Examples 1 and 2, the command value 250 is set to a command voltage that repeats at 40Hz with an arbitrary waveform output by the 40Hz signal source 210, and the LED driver circuit 220, which receives the command voltage, supplies drive current to the LED group. In the figure, a sine wave waveform with a maximum value of 3V, a minimum value of 0V, and an average value of 1.5V is used as the command voltage for the LED driver circuit 220, and the current flowing through the feedback resistor circuit consisting of R5, R6, R7, SW1, and VR1 is used to supply drive current to the LED group.

[0191] In this case, if the total resistance of the feedback resistor circuit is adjusted to, for example, 300 ohms, the current flowing through the LED group will be controlled to a maximum of 10mA, a minimum of 0mA, and an average of 5mA. Based on the arrangement of the LED light sources 30 of the LED pad 600 and the design of the optical system 70, the total resistance value of this feedback resistor circuit is set so that the upper limit of the light energy density 140 irradiated by the LED pad 600 is 10 mW / cm2 or less, which is a predetermined value of 5. In other words, the light energy density 140 can be adjusted to a predetermined value of 5 or less by adjusting SW1, VR1 or R5, R4, R3 that make up the feedback resistor circuit. Of course, the design may also be modified to adjust the amplitude or average value of the command voltage output by the 40 Hz signal source 210 using variable resistors or switches.

[0192] <Regarding 40Hz phase-locked signals> The LED Pad 600 can be used independently to treat only the cerebral cortex of a specific brain region by irradiating it. For example, the LED Pad 600 can be used independently to stimulate any part of the scalp other than the temporal region (e.g., the forehead, parietal region, or occipital region) with near-infrared light at approximately 40 Hz for the purpose of preventing Alzheimer's disease.

[0193] In Figures 5(e) and 5(f), a pulse-like synchronization signal 130 is input to the 40Hz signal source 210 from an external source in order to phase-synchronize the frequency of the LED drive current supplied to the LED light source 30, which is approximately 40Hz, with an external signal. This is intended to phase-synchronize the stimulation from the near-infrared light irradiation of the LED pad 600 when used in combination with PBM therapy devices 10, such as the LED lance 200 in Example 1 or the LED mouthpiece 400 in Example 2, which generate near-infrared light at approximately 40 Hz, for the purpose of improving symptoms of forgetfulness. Alternatively, when used in conjunction with a conventional sensory therapy device 20 that uses light and sound stimuli at approximately 40 Hz to improve symptoms of brain fog, this LED pad 600 can also be used to phase-synchronize the stimulation from near-infrared light irradiation.

[0194] In other words, the command value 250 emitted by the 40Hz signal source 210 is generated by either external excitation operation 100 or self-excitation operation 105 using a self-excitation / external excitation switching means 260 provided in the LED driver device 50. When generated by external excitation operation 100, the signal source built into the 40Hz signal source 210 is synchronized in phase with an externally input synchronization signal 130 to generate the command value 250. When generated by self-excitation operation 105, the signal source built into the 40Hz signal source 210 generates the command value 250 independently. When the LED pad 600 is used alone, it can be used to treat only the cerebral cortex of a specific brain region by irradiating it from the scalp. When designed specifically for this standalone use, neither the externally input synchronization signal 130 nor the self-excitement / external excitation switching means 260 is required, and the 40Hz signal source 210 can output a 40Hz command signal in self-excitement operation 105 without external synchronization for the 40Hz synchronization signal, similar to Examples 1 and 2.

[0195] (6) Effects of Example 3 <When used alone> The LED Pad 600 can deliver approximately 40Hz stimulation to the cerebral cortex from the scalp side using photobiomodulation technology. Therefore, it is expected to not only reduce Alzheimer's disease-causing substances such as amyloid-beta with approximately 40Hz stimulation, but also to heal damaged brain cells with weak light. Therefore, the LED pad 600 can be used alone to irradiate any part of the scalp other than the temporal region for the purpose of preventing Alzheimer's disease.

[0196] <When used in combination with other medical devices> As shown in Example 4 below, the LED pad 600 can be used in conjunction with the approximately 40Hz deep brain stimulation described in Examples 1 and 2, in phase synchronization, to provide stimulation from the scalp side of the temporal region. Therefore, it can improve the symptoms of severe amnesic MCI memory loss that could not be cured by the approximately 40Hz deep brain stimulation described in Examples 1 and 2 alone.

[0197] Furthermore, as shown in Example 4 below, if the weak light energy density of 140 light stimulation from the LED pad 600 is phase-synchronized and used in combination with the conventional light and sound perceptual therapy device 20 of approximately 40 Hz while irradiating the temporal region, the coherence of the temporal region will steadily increase, thus improving even severe brain fog symptoms that could not be cured with the conventional light and sound perceptual therapy device 20 of approximately 40 Hz alone. [Examples]

[0198] This fourth example describes a digital medicine treatment device used for symptomatic treatment of MCI, which combines a PBM (Physiological Body Mechanism) therapy device 10 that flashes a light source in the wavelength range called the biological window 3, which penetrates biological tissue, with a repeating waveform of approximately 40 Hz, and irradiates a light beam 40 with a light energy density of 140 or less, directed towards the MCI affected area, with a sensory therapy device 20 that induces brain waves of approximately 40 Hz using visual stimulation with light and auditory stimulation with sound, utilizing the phenomena of SSVEP and ASSR. The treatment device described in Example 4 is called the phase control device 150. A general explanation of the phase of the treatment device is shown in Figure 6, and an image of the invention is shown in Figure 7, part of Figure 8, Figure 9, and Figure 10.

[0199] (1) Invention In this Example 4, we will explain in detail the following seven inventive features, including variations, to clarify the technical concept and design of these features. Although Example 4 includes numerous inventive features that define even more detailed aspects, to avoid complexity in the explanation, we will focus on and explain only the following seven inventive features.

[0200] <Inventive Feature A of Example 4> The main inventions relating to the phase control device 150 are as follows: In a digital medicine treatment device used for symptomatic treatment of MCI, A PBM therapy device 10 irradiates the MCI area with a light beam 40 at a predetermined value of 5 or less, by flashing a light source in a wavelength range called the biological window 3, which penetrates biological tissue, with a repeating waveform of approximately 40 Hz, and a light energy density of 140. A sensory therapy device 20 induces an electroencephalogram (EEG) of approximately 40 Hz using visual stimulation with light and auditory stimulation with sound, utilizing the phenomena of SSVEP and ASSR. The PBM therapy device 10 and the sensory therapy device 20 are equipped with a phase control device 150 that phase-synchronizes the phase angles 110 of two or more types of stimuli and outputs a synchronization signal 130 that sets and controls the phase difference 120 of the phase angles 110 of the multiple types of stimuli. Characterized by, A treatment device for MCI treatment using 40Hz therapy.

[0201] <Inventive Features B of Example 4> The PBM therapy device 10 in Example 4 is characterized by its ability to perform externally stimulated movements 100. The PBM therapy device 10 includes an LED light source 30 and an LED driver 50. The LED light source 30 is configured to include a semiconductor chip 65 of an LED element 60 that irradiates a light beam 40 having an output wavelength (or peak wavelength) in the wavelength range of 650 to 1000 nm of the biological window 3, and an optical system 70 that adjusts the half-angle of power of the directivity of the light beam 40. The LED driver 50 supplies a drive current to the LED element 60 and irradiates the LED light source 30 with a light energy density of 140, which is 10 mW / cm2 or less, as a predetermined value 5. At the same time, perform an external excitation operation 100 that supplies a drive current to the LED element 60 in a repetitive waveform of approximately 40 Hz while being phase-locked to the synchronization signal 130 input from the outside. Characterized by The therapeutic device for 40 Hz therapy for MCI treatment described in Invention Item A of Example 4

[0202] <ID= <Invention Item C of Example 4> Among the sensory therapy devices 20 in Example 4, in particular, it is characterized by performing an external excitation operation 100 for one synchronization signal 130. The sensory therapy device 20 comprises a visual stimulation device 800, an auditory stimulation device 810, and a visual-auditory phase control device 820. The visual stimulation device 800 is a light emitter 170 that emits light at a repetitive frequency of approximately 40 Hz, or LCD sunglasses 180 that control the transmittance of the lens portion at 40 Hz. The auditory stimulation device 810 includes at least one or more of an earphone 168 including a bone conduction earphone 162 as a sound emitter 160 that emits sound at a repetitive frequency of approximately 40 Hz, a headset 164, and a speaker 166. The visual-auditory phase control device 820 performs the external excitation operation 100 that sets the phase difference 120 between the visual stimulation device 800 and the auditory stimulation device 810 at a repetitive frequency of approximately 40 Hz while being phase-locked to the "single" synchronization signal 130 input from the outside to control the phase of the stimulation by light and sound. Characterized by The therapeutic device for 40 Hz therapy for MCI treatment described in Invention Item A of Example 4

[0203] <Invention Item D of Example 4> Among the sensory therapy devices 20 in Example 4, in particular, it is characterized by performing an external excitation operation 100 for two synchronization signals 130 of light and sound. The sensory therapy device 20 comprises a visual stimulation device 800, an auditory stimulation device 810, and a visual-auditory phase control device 820. The visual stimulator 800 is a light-emitting element 170 that emits light at a repetition frequency of approximately 40 Hz, or LCD sunglasses 180 that control the transmittance of the lens portion at approximately 40 Hz, The auditory stimulator 810 includes at least one of the following: an earphone 168, headphones 164, or speaker 166, which includes a bone conduction earphone 162 as a sound-emitting element 160 that emits sound at a repeating frequency of approximately 40 Hz. The audiovisual phase control device 820 performs the external excitation operation 100, which controls the phase of light and sound stimuli in the visual stimulant 800 and the auditory stimulant 810 at a repetition frequency of approximately 40 Hz, in phase synchronization with the synchronization signals 130, which are "separate for visual and auditory input from an external source." Characterized by, A therapeutic device for MCI treatment using 40Hz therapy, as described in Invention A of Example 4.

[0204] <Inventive Feature E of Example 4> In Example 4, the sensory therapy device 20 is particularly characterized by performing self-excited movements 105 and outputting a reference synchronization signal 830. "The aforementioned sensory therapy device 20 consists of a visual stimulator 800, an auditory stimulator 810, and an audiovisual phase control device 820." The visual stimulator 800 is a light-emitting element 170 that emits light at a repetition frequency of approximately 40 Hz, or LCD sunglasses 180 that control the transmittance of the lens portion at approximately 40 Hz, The auditory stimulator 810 includes at least one of the following: an earphone 168, headphones 164, or speaker 166, which includes a bone conduction earphone 162 as a sound-emitting element 160 that emits sound at a repeating frequency of approximately 40 Hz. The audiovisual phase control device 820 controls the phase of light and sound stimuli by setting the phase difference 120 between the visual stimuli device 800 and the auditory stimuli device 810 at a repetition frequency of approximately 40 Hz in phase synchronization with "a single reference synchronization signal 830 generated inside the sensory therapy device 20", The self-excited operation 105 is performed to output the aforementioned reference synchronization signal 830 to the outside. Characterized by, A therapeutic device for MCI treatment using 40Hz therapy, as described in Invention A of Example 4.

[0205] <Inventive Feature F of Example 4> In Example 4, the phase control device 150 is particularly characterized by outputting a synchronization signal 130 to both the PBM therapy device 10 and the sensory therapy device 20. The phase control device 150 phase-synchronizes the phase angles 110 of two or more types of stimuli from among the PBM therapy device 10 and the sensory therapy device 20 that perform the externally excited operation 100, and outputs the synchronization signal 130 that sets and controls the phase difference 120 of the phase angles 110 of the multiple types of stimuli. Characterized by, A therapeutic device for MCI treatment using 40Hz therapy, as described in Inventions A to D of Example 4.

[0206] <Inventive Features G of Example 4> In Example 4, the phase control device 150 is particularly characterized by receiving a reference synchronization signal 830 from the sensory therapy device 20 and outputting a synchronization signal 130 to the PBM therapy device 10. The phase control device 150 receives the reference synchronization signal 830 output by the sensory therapy device 20 that performs the self-excitation operation 105, and phase-synchronizes the PBM therapy device 10 that performs the externally excitation operation 100, and outputs the synchronization signal 130 that sets and controls the phase difference 120 of the PBM therapy device 10. Characterized by, Therapeutic device for MCI treatment using 40Hz therapy, as described in Inventions A, B, and E of Example 4.

[0207] (2) Problems with Example 4 Mild MCI has two main symptoms: forgetfulness and brain fog. Mild forgetfulness was improved with PBM therapy device 10, which irradiates the deep MCI area of ​​the brain with weak near-infrared light that flashes at approximately 40 Hz. Mild brain fog was improved with sensory therapy device 20, which applies SSVEP and ASSR through sensory stimulation with light and sound at approximately 40 Hz to enhance the amplitude and coherence of brain waves at approximately 40 Hz throughout the brain.

[0208] However, as MCI progresses and the condition worsens to the point where the affected area spreads to both the deep brain and the cortex, neither of the two treatment methods mentioned above can provide sufficient treatment. Furthermore, indiscriminately combining these treatment methods poses a risk of cognitive impairment and clouding due to harmful phase difference disruption caused by simultaneous stimulation of multiple brain regions.

[0209] (3) Solution of Example 4 The problem lies in the fact that "simultaneous stimulation of multiple parts of the brain" can cause "harmful phase differences," so the solution is nothing less than "properly managing the phase differences in multiple simultaneous stimuli." In other words, the present invention provides a therapeutic device that intentionally and appropriately manages the phase difference of multiple types of stimuli using the PBM therapy device 10 and the sensory therapy device 20.

[0210] On the other hand, the phase synchronization described in Non-Patent Documents 5 and 6 of the conventional method merely presents the mathematically obvious fact that "the phase difference between the waveforms of a phase-synchronized 40Hz light square wave and a sound square wave pulse (also called a click sound) is between 0 and ±180." In other words, conventional methods neither disclose nor suggest the technical concept of "actively and intentionally setting and maintaining a phase difference value" or "aiming for a specific effect (or avoiding side effects) with that value."

[0211] Therefore, the technical concept of this invention is to actively and intentionally set and maintain a phase difference value for the PBM therapy device 10 and the sensory therapy device 20, while aiming for effects such as safety specific to that value (or avoiding side effects).

[0212] (4) General explanation of phase lock Figure 6 illustrates the definitions of phase angle and phase difference in the present invention using an example, where two waveforms with the same frequency are phase-synchronized. Incidentally, as already explained, the notation 40Hz in this invention is merely a simplified expression intended to include frequencies near 40Hz within the range in which the mechanism of action of 40Hz therapy described in Patent Document 1 and Non-Patent Document 4 is established. Therefore, the expressions "approximately 40Hz" and "40Hz" represent the same thing in this invention.

[0213] Figure 6(a) illustrates the definition of a phase difference of 0 degrees in this invention, using phase-synchronized waveforms of light and sound stimuli at approximately 40 Hz. Here, as an example of a light stimulus waveform with a frequency of "approximately 40 Hz," to be precise, if a frequency of 41.67 Hz is applied, one period is 24.0 milliseconds. The illustrated light stimulus waveform depicts a square wave with a duty cycle of 50%. Furthermore, the waveform of the sound stimulus also has a repetition frequency of "approximately 40 Hz," which is phase-synchronized with the light. More precisely, it is the same frequency as light, 41.67 Hz. In this figure, it depicts a click sound with a square wave shape, a pulse width of 1.0 millisecond, and a duty cycle of 4.17%. Thus, if the horizontal axis of the diagram explaining phase synchronization is described in terms of elapsed time (milliseconds), the explanation using the notation "approximately 40 Hz (or 40 Hz)" in this invention may not be limited to 41.67 Hz but could also apply to other frequencies. As a result, the numerical values ​​on the horizontal axis of the graph would change, making the explanatory text and diagrams complicated. Therefore, in the following explanation and diagrams regarding phase synchronization at a frequency of approximately 40 Hz, the horizontal axis will represent the phase angle (degrees) or phase difference (degrees) with values ​​ranging from -180 degrees to +180 degrees.

[0214] In this invention, as shown in Figure 6(a), the moment when the rectangular wave of the light stimulus rises from a "dark state with a logical value of 0" to a "bright state with a logical value of 1" is defined as a phase angle of 0 degrees. Furthermore, it is defined that "if the two rectangular waves of light and sound rise from a logical value of 0 (a state where the light is dim and there is no sound) to a logical value of 1 (a state where the light is bright and there is sound) at the same time, using the phase of light as a reference, then the phase difference is 0 degrees." Therefore, it is mathematically obvious that the phase difference between the two rectangular waves of light and sound lies between 0 degrees and ±180 degrees.

[0215] Figure 6(b) illustrates the relationship between the phase difference of a square wave of light and a click sound, when the phase difference of the sound stimulus is set to -90 degrees relative to the phase of the light stimulus. In other words, if the phase difference is -90 degrees, the sound stimulus occurs at a position that is temporally earlier than the light stimulus.

[0216] Figure 6(c) is a diagram that defines the phase angle in a sine wave representing the fundamental frequency component of a square wave waveform. In this invention, "the moment when the rectangular wave of the light stimulus rises from a logical value of 0 to a logical value of 1 is defined as a phase angle of 0 degrees." Therefore, for a sine wave, which is the fundamental frequency component of a rectangular wave with a duty cycle of 50%, if we define the moment when it intersects with the average value of the sine wave and increases as a phase angle of 0 degrees, the timing for defining a phase angle of 0 degrees matches.

[0217] Figure 6(d) illustrates the relationship between the phase difference of a sinusoidal light wave and a click sound, when the phase difference of the sound stimulus is set to -90 degrees relative to the phase angle of the light wave. In other words, if the phase difference is -90 degrees, the sound stimulus occurs at a position that is temporally earlier than the light stimulus.

[0218] <Selection of Phase Contrast (Safety and Side Effects)> Non-patent document 3 of the prior art describes how disrupting the phase difference of stimuli applied to different locations in the brain resulted in a decrease in the cognitive level of subjects. Similarly, in a series of experiments conducted by the inventor, setting the phase difference to +90 degrees (i.e., sound lagging +90 degrees behind light) caused intense drowsiness and a slight headache in the subject (the inventor himself). In other words, from the standpoint of ensuring safety, it is desirable to set the phase difference to 0. In experiments conducted by the inventor himself as a subject, whether the light waveform was a square wave or a sine wave, a phase difference of 0 degrees with the click sound showed a significant therapeutic effect in eliminating the brain fog symptoms of MCI. Conversely, from the perspective of avoiding side effects, increasing the phase difference to near +90 degrees in the positive direction (i.e., delaying the phase of the sound) may cause temporary cognitive impairment such as drowsiness or headaches, although this may vary from person to person. Therefore, it is best to avoid making the phase difference too large.

[0219] Incidentally, for example, if you were to generate a stimulus sound that repeats precisely at 40.0 Hz using a speaker, and you placed a large, bright light source that flashes precisely at 40.0 Hz and a high-volume, high-quality speaker about 2 meters away from the subject, and generated a sound stimulus from the speaker that was phase-synchronized with the light stimulus with a phase difference of 0 degrees, the speed of sound at a room temperature of 20°C would be approximately 344 m / s. This means that the wavelength of a precise 40.0 Hz sound is approximately 8.6 m, and if the sound is heard from a distance of about 2 m, the phase delay of the sound will exceed 80 degrees and approach 90 degrees. In this case, although there may be individual differences, there is a higher possibility of side effects such as drowsiness and headaches, which is undesirable from the perspective of avoiding side effects. If the distance from the speaker to the subject cannot be shortened due to circumstances such as those at a treatment facility, safety can be improved by setting a negative phase difference in the sound stimulus so that the phase difference between the sound and light at the moment they reach the subject is close to 0 degrees.

[0220] Similarly, we do not recommend the treatment method in which a large speaker 166 is placed in the corner of a large room and multiple patients wear LCD sunglasses 180 to treat MCI. This is because the phase difference between light and sound varies depending on the patient's position (more precisely, their distance from the speaker), resulting in uneven treatment effects. Moreover, depending on the distance from the speaker, patients may experience intense drowsiness or slight headaches. Please be extremely careful.

[0221] When using wired earphones 168 or headphones 164 as auditory stimulation devices 810, the phase delay of sound during air propagation is negligibly small. Therefore, in the case of treatment using the sensory therapy device 20, when treating a large number of patients at once in a large room using a common large screen or individual LCD sunglasses 180 as the visual stimulation device 800, it is recommended to use wired earphones 168 or headphones 164, including bone conduction earphones 162 as sound-emitting elements 160 that emit sound at a repeating frequency of approximately 40 Hz, as the auditory stimulation device 810.

[0222] Conversely, the specifications of the sound-producing element 160, which functions as a wireless auditory stimulator 810, vary from product to product. In the case of products with a significant phase delay between audio signal input and sound output, caution is advised, as this may result in uneven or unexpected therapeutic effects, and subjects may experience intense drowsiness or slight headaches.

[0223] Thus, even when using conventional technology to apply two types of stimuli to different parts of the brain using light and sound at approximately 40 Hz, the phase difference between each stimulus must be explicitly managed to ensure quality control of the therapeutic effect and eliminate risks. Furthermore, when applying multiple types of stimuli using the PBM therapy device 10 and the sensory therapy device 20 in combination, as in this Example 4, a means of explicitly setting and managing the phase difference between each stimulus is essential, as will be explained below.

[0224] (5) Description of Example 4 Figure 7(a) is a conceptual diagram illustrating the treatment of severe MCI accompanied by memory loss and brain fog, using simultaneously an LCD sunglasses 180 as a visual stimulator 800 for light stimulation, earphones 168 as an auditory stimulator 810 for sound stimulation, LED pads 600 that stimulate the left and right temporal lobes with near-infrared light, and an LED lance 200 that stimulates the deep brain with near-infrared light. This diagram omits the wires between each stimulator and the control device that supplies the drive current (or drive voltage). However, in actual treatment, numerous wires surround the face, so care must be taken to prevent accidents caused by wires becoming entangled around the neck or other parts of the body, especially in MCI patients who are in poor health.

[0225] Figure 7(b) shows an example of using a helmet for treatment to prevent medical accidents caused by numerous electrical wires around the face, by integrating the electrical wires and treatment devices such as the LED Pad 600 into the helmet. In the example shown, an LED Mouthpiece 400 is fixed to the helmet like a mask instead of an LED Lance 200. If the LCD sunglasses 180 and headphones 164 are integrated as part of the helmet, they will be easier to handle as therapeutic devices. It is sufficient to include at least one of the following: earphones 168 including bone conduction earphones 162 as sound-producing bodies 160 that allow sound stimuli to be heard in both ears, headphones 164, or speakers 166. When designing this helmet, it is possible to implement various new designs and ideas, such as making the fixing position of the LED pad 600 variable, making the LCD sunglasses 180 fixed or flip-up, and improving the routing of electrical wiring inside the helmet. In addition, the visual stimulator 800 may use a light-emitting element 170 that emits light at a repetition frequency of approximately 40 Hz instead of the LCD sunglasses 180.

[0226] Figure 7(c) shows an example of comprehensively adjusting the phase angles of multiple therapeutic devices. When using the PBM therapy devices 10 of Example 1, Example 2, and Example 3 individually, the control device of the therapeutic device is used in self-excited operation 105 to generate a frequency of 40 Hz. However, in the example shown in this figure, an example is shown in which the LED driver device 50 and sensory therapy device 20 of each PBM therapy device 10 are used in externally excited operation 100, in which a synchronization signal 130 is input from an external source to synchronize their phases.

[0227] Furthermore, Figure 7(c) shows a phase control device 150 that supplies a synchronization signal 130 to each of the multiple treatment devices. In this figure, the phase control device 150 outputs the synchronization signal 130 to the sensory therapy device 20 with channel Ch-C as the reference phase. In this invention, the entire system is designed by "defining the light stimulus as a phase reference" in the sensory therapy device 20, and the phase of the light stimulus in the sensory therapy device 20 is externally synchronized using the phase signal Ch-C of this reference. Specifically, an audiovisual phase control device 820 is incorporated into the sensory therapy device 20, which is phase-synchronized with a single synchronization signal 130 input from the phase control device 150 and performs an externally excited action 100 to control the phase of light and sound stimuli by setting a phase difference 120 between the visual stimuli device 800 and the auditory stimuli device 810 with a repetition frequency of approximately 40 Hz. In this case, the phase control device 150 is assumed to operate in self-excited mode 105. Furthermore, if the entire system is redesigned by "defining the sound stimulus as the phase reference," then each device in Embodiment 4 should be redesigned to perform an externally excited operation 100 that synchronizes the phase of the sound with the synchronization signal 130 from the phase control device 150 and sets and controls the phase difference 120 between the light and sound stimuli.

[0228] To summarize the above explanation, the sensory therapy device 20 consists of a visual stimulator 800, an auditory stimulator 810, and an audiovisual phase control device 820, and the visual stimulator 800 is a light-emitting body 170 that emits light at a repetition frequency of approximately 40 Hz, or LCD sunglasses 180 that control the transmittance of the lens portion at approximately 40 Hz, The auditory stimulator 810 includes at least one of the following: an earphone 168, headphones 164, or speaker 166, which includes a bone conduction earphone 162 as a sound-emitting element 160 that emits sound at a repeating frequency of approximately 40 Hz. The audiovisual phase control device 820 performs an externally excited operation 100 that controls the phase of light and sound stimuli by setting the phase difference 120 between the visual stimuli device 800 and the auditory stimuli device 810 at a repetition frequency of approximately 40 Hz in phase synchronization with a single synchronization signal 130 input from an external source.

[0229] In Figure 7(c), the slider knob of the variable resistor on the control panel of the phase control device 150 is operated to explicitly set a phase difference of, for example, ±40 degrees relative to channel Ch-C, which serves as the phase reference, for the synchronization signals 130 of approximately 40 Hz to be output to channel Ch-A (for the LED pad 600 located on the scalp of the right temporal region), channel Ch-B (for the LED pad 600 located on the scalp of the left temporal region), and channel Ch-D (for the LED lance 200 or LED mouthpiece 400). The upper and lower limits of this phase difference can also be changed to values ​​other than ±40 degrees. In clinical treatment, it is generally safest to set all slider knobs to a phase difference of 0 degrees. However, based on individual patient differences and the physician's judgment regarding medical objectives such as sleep improvement, the phase difference of each channel can be explicitly set.

[0230] Figure 7(d) provides a brief explanation using an example where a control microcomputer is used as the phase control device 150. To set the phase difference for each channel, the slider knob of a variable resistor is adjusted to generate the input voltage for each analog input channel, and this input voltage is converted to the target value of the set phase difference. Then, the digital output (DO-1 to DO-4) of the control microcomputer outputs a synchronization signal 130 with the phase difference for each channel.

[0231] Here, we will specifically explain the synchronization signal 130 for each channel. Although this invention is explained based on a repetition frequency of approximately 40 Hz, for the purpose of making the explanation clear and concise, in this example, channel Ch-C, which serves as the phase reference, will output a pulse signal as the synchronization signal 130 at a timing of a phase angle of 0 degrees every 25 milliseconds, which corresponds to one period of a precise 40.0 Hz. In Figure 7(d), the slider knob for channel Ch-A is set to a phase difference of 0 degrees, so the digital output DO-1 outputs a pulse signal as synchronization signal 130 at the same phase difference of 0 degrees as the reference channel Ch-C. Since the slider knob for channel Ch-B is set to a phase difference of -20 degrees, the digital output DO-2 outputs the synchronization signal 130 at a timing with a phase difference of -20 degrees compared to the reference channel Ch-C. In other words, using the control microcomputer, the pulse signal as the synchronization signal 130 is output approximately 1.4 milliseconds earlier than the reference phase angle of 0 degrees (25 milliseconds × 20 degrees / 360 degrees), while managing the timing with the 25-millisecond period exemplified above. Since the slider knob for channel Ch-D is set to a phase difference of +20 degrees, the digital output DO-4 outputs a pulse signal as synchronization signal 130 at a timing with a phase difference of +20 degrees compared to the reference channel Ch-C. In other words, the pulse signal as synchronization signal 130 is output approximately 1.4 milliseconds later than the reference (25 milliseconds × 20 degrees / 360 degrees).

[0232] <Externally Excited Action of Sensory Therapy Device 20 with Single Input> Figure 8(c) illustrates the configuration of the sensory therapy device 20 described in Figures 7(c) and 7(d). The sensory therapy device 20 consists of a visual stimulator 800, an auditory stimulator 810, and an audiovisual phase control device 820. The audiovisual phase control device 820 has a function to perform an externally excited operation 100 that controls the phase of light and sound stimuli by setting the phase difference 120 between the visual stimuli device 800 and the auditory stimuli device 810 at a repetition frequency of approximately 40 Hz, in phase synchronization with a single synchronization signal 130 input from an external source. In this invention, since the visual stimulus by light is used as the reference phase, the audiovisual phase control device 820 outputs a synchronization signal for generating a light stimulus to the visual stimulus device 800 (for example, a 40Hz light emitter 170 or LCD sunglasses 180) with a phase difference of 0 degrees from the synchronization signal 130 input to the audiovisual phase control device 820. Furthermore, the audiovisual phase control device 820 has a function to set a phase difference 120 using a variable resistor VR or the like, and adds a phase difference 120 to the synchronization signal 130 input from an external source to output a synchronization signal for generating sound stimuli to the auditory stimulator 810.

[0233] <Variation 1: Other-excited operation of sensory therapy device 20 with multiple inputs> Figures 8(d) and 9(a) show modified examples in which the phases of visual stimuli by light and auditory stimuli by sound are specified by the phase control device 150. A synchronization signal 130 is pulsed out from channel Ch-C based on the phase of the light stimulus, and the phase difference of the sound stimulus is set using the slider knob C2 of the phase control device 150, and a synchronization signal 130 is pulsed out from channel Ch-C2. These two synchronization signals 130 are supplied to the sensory therapy device 20. Figure 8(d) is a diagram illustrating the audiovisual phase control device 820 included in the perceptual therapy device 20 of Figure 9(a), and has the function of performing the externally excited operation 100 which controls the phase of light and sound stimuli in the visual stimuli device 800 and the auditory stimuli device 810 at a repetition frequency of approximately 40 Hz, in phase synchronization with the separate synchronization signals 130 for visual and auditory input from the outside. As shown in Figure 8(d), if the visual stimulator 800 and the auditory stimulator 810 are equipped with a function to perform external excitation 100, the function of the audiovisual phase control device 820 in this modified example is simply to pass two synchronization signals 130. In other words, the audiovisual phase control device 820 receives two synchronization signals: one for the visual stimulus caused by light input to the visual stimulator 800, and another for the auditory stimulus caused by sound input to the auditory stimulator 810. It then synchronizes the phase of these two signals with the individual synchronization signals 130 for visual and auditory stimuli, respectively, to perform external excitation 100.

[0234] Therefore, the configuration of this modified example 1 can be described in detail as follows. The perceptual therapy device 20 consists of a visual stimulator 800, an auditory stimulator 810, and an audiovisual phase control device 820. The visual stimulator 800 is a light-emitting element 170 that emits light at a repetition frequency of approximately 40 Hz, or LCD sunglasses 180 that control the transmittance of the lens portion at approximately 40 Hz. The auditory stimulator 810 includes at least one of the following: an earphone 168, headphones 164, or speaker 166, which includes a bone conduction earphone 162 as a sound-emitting element 160 that emits sound at a repeating frequency of approximately 40 Hz. The audiovisual phase control device 820 performs an externally excited operation 100 that controls the phase of light and sound stimuli in the visual stimuli device 800 and the auditory stimuli device 810 at a repetition frequency of approximately 40 Hz, in phase synchronization with the separate synchronization signals 130 for visual and auditory input from an external source. Furthermore, the configuration of the phase control device 150 in this modified example 1 can be described in detail as follows. "The phase control device 150 phase-synchronizes the phase angles 110 of two or more types of stimuli from among the PBM therapy device 10 and the sensory therapy device 20 that perform the externally excited action 100, and outputs a synchronization signal 130 that sets and controls the phase difference 120 of the phase angles 110 of the multiple types of stimuli." In this case, the phase control device 150 is assumed to operate in self-excited mode 105.

[0235] <Modification 2: Self-excited movements of sensory therapy device 20> Figure 9(b) shows a modified example in which the phase control device 150 is controlled by external excitation 100 based on the phase of visual stimulation by light in the perceptual therapy device 20. As shown in Figure 10(a), the audiovisual phase control device 820 of the sensory therapy device 20 outputs a pulsed reference synchronization signal 830 synchronized with the phase of the light stimulus, which is input to the phase control device 150 as a phase reference. Subsequently, a synchronization signal 130 is supplied to the PBM therapy device 10 based on the phase difference 120 set by the slider of the phase control device 150. In other words, "The phase control device 150 receives a reference synchronization signal 830 output by the sensory therapy device 20 that performs the self-excited movement 105, phase-synchronizes the PBM therapy device 10 that performs the externally excited movement 100, and outputs a synchronization signal 130 that sets and controls the phase difference 120 of the PBM therapy device 10."

[0236] Furthermore, the phase difference 120 between light and sound stimuli in the sensory therapy device 20 shown in Figure 9(b) is set internally within the sensory therapy device 20. That is, the sensory therapy device 20 consists of a visual stimulator 800, an auditory stimulator 810, and an audiovisual phase control device 820. The visual stimulator 800 is a light-emitting body 170 that emits light at a repetition frequency of approximately 40 Hz, or LCD sunglasses 180 that control the transmittance of the lens portion at approximately 40 Hz. The auditory stimulator 810 includes at least one of the following: an earphone 168 including a bone conduction earphone 162 as a sound-emitting body 160 that emits sound at a repetition frequency of approximately 40 Hz, headphones 164, or a speaker 166. The audiovisual phase control device 820 controls the phase of light and sound stimuli by setting the phase difference 120 between the visual stimuli device 800 and the auditory stimuli device 810 at a repetition frequency of approximately 40 Hz in phase synchronization with a single reference synchronization signal 830 generated inside the perceptual therapy device 20, and also performs a self-excited operation 105 that outputs the reference synchronization signal 830 to the outside.

[0237] In this invention, a repeating waveform of approximately 40 Hz is used. However, as an example for the sake of simplicity, the phase control device 150 is designed to manage time at an exact 40.0 Hz, which is merely one example of a nearby frequency included in approximately 40 Hz. Then, by phase-synchronizing with the exact 40.0 Hz quasi-synchronous signal 830 and considering this as the reference phase, synchronization signals 130 with phase differences applied to Ch-A, Ch-B, and Ch-D in Figure 9(b) can be output to the PBM therapy device 10. Incidentally, in Modification 2, when the sensory therapy device 20 is made to perform self-excited movements 105, a reference synchronization signal 830 synchronized with the phase of the light stimulus is pulsed and input to the phase control device 150 as a phase reference, based on the phase of the light stimulus to the visual system. However, it is also possible to redesign the device so that the reference synchronization signal 830 is pulsed and based on the "phase of the sound stimulus".

[0238] In Example 4, we introduced a phase control device 150 as a therapeutic device that sets and controls the phase difference 120 of multiple stimuli when using the PBM therapy device 10 and the sensory therapy device 20 in combination. However, it is possible to modify the design based on the technical concept of the present invention. For example, an embodiment was shown in which a phase difference of 120 is set using a slider resistor with a phase control device 150, but it can also be set as a control parameter in the program or specified via external communication. Furthermore, while the above example shows how to change the phase difference of 120, it is also possible to fix all phase differences of 120 to, for example, 0 degrees. Furthermore, although we have described a design example in which the PBM therapy device 10, the sensory therapy device 20, and the phase control device 150 are housed in separate enclosures, it is also possible to modify the design to combine them into a single enclosure.

[0239] Furthermore, in addition to the method of using the standalone PBM therapy device 10 and sensory therapy device 20 in combination simultaneously as shown in Figure 7(a), or the method of using the helmet as shown in Figure 7(b), it is also possible to combine them with known therapeutic devices based on the operating principles of magnetic stimulation therapy devices (TMS, tTMS, etc.) or electrical stimulation therapy devices, which apply electromagnetic coils to the scalp to provide electromagnetic stimulation to specific areas of the cerebral cortex. In that case, an electromagnetic therapy control device for controlling the phase of stimuli emitted by an electromagnetic therapy device can be designed to be externally synchronized by external excitation operation 100, and the electromagnetic stimuli applied using the phase control device 150 of the present invention can be controlled by channel-specific synchronization signals 130 with a phase difference 120 so as to be phase-synchronized with the phase angles 110 of multiple types of stimuli from other light or sound sensory therapy devices 20 or PBM therapy devices 10 using photobiomodulation technology. This can be easily added to the design based on the technical concept of the present invention.

[0240] Finally, the method for switching between self-excited operation 105 and externally excited operation 100 will be explained using a simple reset method as an example. In the upper diagram of Figure 10(b), device A is assumed to operate self-excited at, for example, 39.8 Hz if there is no input of a synchronization signal. That is, device A generates an output pulse with a period of approximately 25.13 milliseconds, corresponding to a frequency of 39.8 Hz. In this example, a pulse is output, but any waveform with a repetition period of 39.8 Hz, such as a square wave or sine wave, would be acceptable.

[0241] In the lower part of Figure 10(b), a device B is added that generates a synchronization signal 130 of exactly 40.0 Hz and performs self-excitation operation 105, and this synchronization signal 130 is input to device A. Then, by resetting device A every 25.00 milliseconds with a synchronization signal 130 of exactly 40.0 Hz, device A, which was operating on its own with a period of 25.13 seconds, will start operating on its own by generating output pulses with a period of 25.00 seconds in synchronization with the synchronization signal 130 of exactly 40.0 Hz from device B.

[0242] The operation of this device A can be designed in various ways for different applications, such as synchronizing a bistable multivibrator with an external pulse if it is a hardware circuit, or resetting a repeating waveform stored in internal memory with an external pulse if it is a control microcomputer.

[0243] Incidentally, in the case of the fourth embodiment, the phase control device 150 is self-excited 105 in the examples of Figure 7(c) and Figure 9(a), and is externally excited 100 in synchronization with the reference synchronization signal 830 in the example of Figure 9(b).

[0244] Summary of the overall inventive features of this invention This invention relates to a treatment device for MCI (Mild Cognitive Impairment). Following a description of a conventional sensory therapy device 20 for treating "brain fog," the invention of a PBM (Physical-Based Medication) therapy device 10 for treating "memory loss" is explained with specific examples. Furthermore, a phase control device 150 that treats "severe MCI" by using the PBM therapy device 10 and the sensory therapy device 20 in combination is also described. In other words, each treatment device and the phase control device 150 in this invention constitute a unified technological concept from the perspective of being devices for treating the symptoms of MCI.

[0245] In the following, we will list 15 inventive features in accordance with the technical concept of the present invention and explain them in correspondence with the content illustrated in each embodiment. In this invention, the term "energy density" is used to refer to the physical quantity described in terms of "power per unit area (cm2) (mW)" of the light flux 40 emitted from the treatment device, that is, in units of "mW / cm2". While the correct terminology, in terms of proper use of physical terminology, should be "power density of luminous flux," to prevent the explanatory text in the specification from becoming even more difficult to understand, we have deliberately standardized the expression using a simpler, more intuitive term (light energy density 140).

[0246] <Invention Item 1> Invention 1 relates to a new type of PBM therapy device 10 for treating "memory loss," and is a technology that combines known 40Hz therapy and photobiomodulation technology by irradiating weak light energy that flashes with a repeating waveform of approximately 40Hz from the oral cavity towards the MCI affected area located in the deep brain such as the hippocampus. In this invention, we discovered that under the condition of "irradiating the hippocampus and other deep brain regions from the oral cavity for the purpose of treating memory loss," a light energy density of 10 mW / cm2 or less is sufficient to achieve a sufficient effect. Based on this discovery, paragraphs 0079 to 0085 describe in detail how the device was enhanced as a highly useful MCI treatment instrument for industrial use by incorporating output adjustment and output monitoring means to ensure safety for the treatment of MCI patients. Invention 1 is as follows:

[0247] "A PBM therapy device 10 is a treatment device for MCI that applies photobiomodulation (PBM) in the oral cavity, The PBM therapy device 10 is composed of an LED light source 30, an LED light source holder 35, and an LED driver 50. The LED light source 30 is composed of an LED element 60 having an output wavelength in the range of 650 to 1000 nm, known as the biological window 3 that penetrates biological tissue, and an optical system 70 for adjusting the directionality. The LED light source holding part 35 is a member that holds the LED light source 30 in the oral cavity and determines its position and irradiation direction. The LED driver device 50 is a control device that supplies a drive current to the LED element 60 and irradiates it with a light energy density of 140 at a predetermined value of 5 or less, causing the light flux 40 to blink in a repeating waveform of approximately 40 Hz. The LED driver device 50 also comprises a 40Hz signal source 210, an LED driver circuit 220, an output adjustment means 230, and an output monitoring means 240. The 40Hz signal source 210 outputs a command value 250 of a time-series waveform of approximately 40Hz. The LED driving circuit 220 receives the command value 250 and supplies a driving current to the LED light source 30. The output adjustment means 230 adjusts the light energy density 140 continuously and / or discontinuously. The output monitoring means 240 measures and displays the light energy density 140 indirectly or directly. Furthermore, the predetermined value 5 for irradiation in the oral cavity is 10 mW / cm2. A treatment device for MCI treatment that utilizes 40Hz therapy, characterized by the following features.

[0248] Invention 1 is a PBM therapy device 10 as a treatment device for mild coagulation (MCI) that applies photobiomodulation (PBM) in the oral cavity, and is a rewritten version of the common parts of the LED lance 200 in Example 1 and the LED mouthpiece 400 in Example 2. In other words, to organize the common parts, a new concept called the LED light source holding part 35 was created, and in the LED lance 200, the term "gripping part 80" was replaced with "mouthpiece part 410" in the LED mouthpiece 400, and these are defined in detail from Invention Item 2 onward. Other minor expressions were rephrased in an easy-to-read manner based on the wording described in Invention Item A of Example 1 and Invention Item A of Example 2, with reference to the explanatory text regarding Figure 3 of Example 1 and the explanatory text regarding Figure 4 of Example 2. If the wording is ambiguous, it can be reverted to a more precise description of the invention for each embodiment.

[0249] Furthermore, the approximately 40Hz time-series waveform at command value 250 refers to, as described in paragraph 0093, "an arbitrary waveform with a repetition period of 40Hz (for example, a sine wave, a square wave with a selectable duty cycle, a triangular wave, a step-like waveform, or a waveform specified by storing the output every 1 millisecond in memory)." Furthermore, the reason for using output wavelengths in the 650-1000nm range, known as the biological window 3, which allows light to penetrate biological tissues, is that it is desirable for light stimulation to reach areas such as the hippocampus inside the brain from the oral cavity without light energy being absorbed as much as possible by biological tissues such as bone, muscle, nerves, blood vessels, and blood. Furthermore, the output adjustment means 230 and the output monitoring means 240 are not "items that can be easily thought of and added." When imitations of this invention appear on the market, they will probably try to circumvent this patent by omitting the output adjustment means 230 and the output monitoring means 240. However, an imitation that omits the output monitoring means 240 would be a defective product that leaves MCI patients feeling uneasy because it lacks a means to avoid accidents where they could suffer brain damage due to excessive light output during treatment. Also, an imitation that omits the output adjustment means 230 would deprive patients of the freedom to independently choose the intensity of their treatment. In other words, these two functions, while seemingly easy to conceive, are actually essential elements of a "reliable product specification" that respects patient safety and free will as a treatment device for MCI.

[0250] <Invention Item 2> Invention Item 2 is a description of the gripping portion 80, which is referred to as the LED light source holding portion 35, a common element in Invention Item 1, within the description of the LED lance 200 of Invention Item A of Example 1. While the gripping portion 80 is described in detail in the caption of Figure 3, paragraph 0090 states that not only is the gripping portion 80 rod-shaped, but also that "by arranging multiple LED light sources 30 on the tip or near the tip of the gripping portion 80 and irradiating multiple luminous beams 40, the directivity of the overall luminous beam 40 composed of multiple luminous beams 40 irradiated by the LED lance 200 can be broadened. Furthermore, by bending the tip of the LED lance 200 and providing LED light sources 30 on its side, it is possible to irradiate in multiple directions simultaneously." This is incorporated into Invention Item 2 below. Furthermore, in the LED lance 200, when multiple LED light sources 30 are used, there may be areas where multiple luminous beams 40 overlap. Whether there is one or multiple LED light sources 30, it is important for safety to manage the upper limit of the light energy density 140 so that it is 5 or less at a distance of 1 cm from the tip of any optical system 70 of the LED light sources 30.

[0251] In Invention 1, the PBM therapy device 10 is an LED lance 200, The LED light source holding portion 35 is a gripping portion 80 that includes a rod-shaped member for manipulating the position and irradiation direction of the LED light source 30, which is disposed at the tip and / or the side of the tip, within the oral cavity. A therapeutic device for treating MCI using 40Hz therapy, as described in Invention 1, characterized by the above.

[0252] <Invention Item 3> Invention Item 3 is a description of the mouthpiece portion 410, which is referred to as the LED light source holding portion 35 in the description of the LED mouthpiece 400 in Invention Item A of Example 2. A detailed explanation is provided in the description of Figure 3 of Example 2. Invention Item 3 is as follows:

[0253] In Invention 1, the PBM therapy device 10 is an LED mouthpiece 400, The LED light source holding unit 35 is a mouthpiece unit 410 comprising a mouthpiece 460 that is fitted into the upper or lower jaw dentition to maintain reproducibility of position and irradiation direction in the mouthpiece coordinate system 420 and fixed in the oral cavity, three or more insertion points 450 for contrast-enhancing members that define a coordinate transformation matrix 440 of two orthogonal coordinate systems, the mouthpiece coordinate system 420 and the skull coordinate system 430, and a connecting member 470 that is disposed on the mouthpiece 460 to maintain reproducibility of position and irradiation direction for the LED light source 30. A therapeutic device for treating MCI using 40Hz therapy, as described in Invention 1, characterized by the above.

[0254] Furthermore, the example of "directly attaching" the LED light source 30 to the connecting member 470 is described in the section relating to Invention C and Figures 8(a) and 8(b) of Example 2 for the mouthpiece portion 410 fixed to the lower jaw, and in paragraph 0152 for the mouthpiece portion 410 fixed to the upper jaw. This "direct attachment example" is included in Invention 3 above, whether for the upper or lower jaw. Furthermore, since the LED mouthpiece 400 uses multiple LED light sources 30, there may be areas where multiple light beams 40 overlap. For safety reasons, it is important to manage the upper limit of the light energy density 140 so that it is 5 or less at a distance of 1 cm from the tip of any optical system 70 of the LED light source 30.

[0255] <Invention Item 4> Invention Item 4 relates to the LED substrate section 480 described in Invention Item B of Example 2, and is described in detail in the caption of Figure 4. Note that Invention Item B of Example 2 and the caption of Figure 4(c) in paragraph 0136 also include explanations of the connection relationship between the connecting member 470 and the LED substrate section 480, so if there are any points of "unclear descriptions," they can be corrected. Invention Item 4 is as follows:

[0256] In the mouthpiece portion 410 that is fitted into the upper jaw teeth as described in Invention Item 3, The device further includes an LED substrate section 480 that maintains the position and irradiation direction within the oral cavity for arranging the LED light source 30 so that the irradiation target point 490 is included in the luminous flux 40. A therapeutic device for treating MCI using 40Hz therapy, as described in Invention Item 3, characterized by the above.

[0257] <Invention Item 5> Invention Item 5 relates to a phase control device 150 that treats MCI (Mild Cognitive Impairment) that has progressed and worsened by simultaneously stimulating (or using in combination with) the PBM (Physiological Body Mechanics) therapy device 10 and the sensory therapy device 20, which represent the technical concept of the present invention. The content described in Invention Item 5 mainly corresponds to Invention Item A of Example 4. To improve readability, the word order and other expressions have been changed, and the statement that "the predetermined value 5 is 10 mW / cm2," as explained in paragraph 0085, has been included here as well to clarify the text. Further detailed explanations are provided in the sections corresponding to Figures 6 to 10. Invention Item 5 is as follows:

[0258] A PBM therapy device 10 stimulates the MCI area by flashing a light source in the wavelength range called the biological window 3, which penetrates biological tissue, with a repeating waveform of approximately 40 Hz, and irradiating the MCI area with a light beam 40 at a predetermined light energy density of 5 or less, 140. A sensory therapy device 20 induces brain waves of approximately 40 Hz using visual stimulation with light and auditory stimulation with sound, utilizing the phenomena of SSVEP and ASSR. The MCI treatment device is equipped with a phase control device 150 that controls the phase of these multiple types of stimuli when used in combination. The predetermined value 5 is 10 mW / cm2. The phase control device 150 synchronizes the phase angles 110 of multiple types of stimuli generated by the PBM therapy device 10 and the sensory therapy device 20, and outputs a synchronization signal 130 that sets and controls the phase difference 120 of the phase angles 110 of the multiple types of stimuli. A treatment device for MCI treatment that utilizes 40Hz therapy, characterized by the following features.

[0259] <Invention Item 6> Invention Item 6 largely overlaps with Invention Item 1. However, while Invention Item 1 mainly describes the case where the PBM therapy device 10 is operated independently, Invention Item 6 describes the PBM therapy device 10 which performs external excitation operation 100 by a synchronization signal 130 from the phase control device 150. This point is described in Invention Item B of Example 1, Invention Item D of Example 2, Invention Item D of Example 3, and Invention Item F of Example 4, and is explained in detail in the description of each example. Incidentally, the PBM therapy device 10 of the present invention performs externally excited operation 100 when operated by a synchronization signal 130 from a phase control device 150, and performs self-excited operation 105 when used alone without a synchronization signal 130 from a phase control device 150. Invention item 6 is as follows:

[0260] In invention item 5, The PBM therapy device 10 is composed of an LED light source 30, an LED light source holder 35, and an LED driver 50. The LED light source 30 is configured to include an LED element 60 having an output wavelength in the range of 650 to 1000 nm, called the biological window 3, which penetrates biological tissue, and an optical system 70 for adjusting the directionality. The LED light source holding part 35 is a member that holds the LED light source 30 inside the mouth or on the scalp and determines its position and emission direction. The LED driver device 50 is a control device that supplies a drive current to the LED element 60 and irradiates the luminous flux 40 with a repeating waveform of approximately 40 Hz at a light energy density of 140, which is less than or equal to a predetermined value of 5. The LED driver device 50 also comprises a 40Hz signal source 210, an LED driver circuit 220, an output adjustment means 230, and an output monitoring means 240. The 40Hz signal source 210 outputs a command value 250 of a time-series waveform of approximately 40Hz. The LED driving circuit 220 receives the command value 250 and supplies a driving current to the LED light source 30. The output adjustment means 230 adjusts the light energy density 140 continuously and / or discontinuously. The output monitoring means 240 measures and displays the light energy density 140 indirectly or directly. Along with, The 40Hz signal source 210 performs external excitation operation 100 based on the synchronization signal 130 from the phase control device 150. A therapeutic device for treating MCI using 40Hz therapy, as described in Invention Item 5, characterized by the above.

[0261] Furthermore, while the area to which the PBM therapy device 10 is irradiated was limited to the oral cavity in Invention 1, in Invention 6 it is either the oral cavity or the scalp. The phrase "in the oral cavity or on the scalp" indicates that the types of PBM therapy devices 10 include the LED lance 200 in Example 1, the LED mouthpiece 400 in Example 2, and the LED pad 600 in Example 3. Therefore, multiple types of PBM therapy devices 10 may be used simultaneously in the oral cavity and on the scalp. In other words, the PBM therapy devices 10 in the oral cavity and on the scalp can be used simultaneously with the phase control device 150. This is evident from Figures 7 and 9 and their captions.

[0262] <Invention Item 7> Invention Item 7 clarifies that the LED lance 200 can be used as the PBM therapy device 10. For details of the LED lance 200, please refer to the description in Invention Item 2. Invention Item 7 is as follows:

[0263] In invention item 6, the PBM therapy device 10 is an LED lance 200, The LED light source holding portion 35 is a gripping portion 80 that includes a rod-shaped member for manipulating the position and irradiation direction of the LED light source 30, which is disposed at the tip and / or the side of the tip, within the oral cavity. A therapeutic device for treating MCI using 40Hz therapy, as described in Invention Item 6, characterized by the above.

[0264] <Invention Item 8> Invention Item 8 clarifies that the LED mouthpiece 400 can be used as the PBM therapy device 10. For details of the LED mouthpiece 400, please refer to the description in Invention Item 3. Invention Item 8 is as follows:

[0265] In invention item 6, the PBM therapy device 10 is an LED mouthpiece 400, The LED light source holding unit 35 is a mouthpiece unit 410 comprising a mouthpiece 460 that is fitted into the upper or lower jaw dentition to maintain reproducibility of position and irradiation direction in the mouthpiece coordinate system 420 and fixed in the oral cavity, three or more insertion points 450 for contrast-enhancing members that define a coordinate transformation matrix 440 of two orthogonal coordinate systems, the mouthpiece coordinate system 420 and the skull coordinate system 430, and a connecting member 470 that is disposed on the mouthpiece 460 to maintain reproducibility of position and irradiation direction for the LED light source 30. A therapeutic device for treating MCI using 40Hz therapy, as described in Invention Item 6, characterized by the above.

[0266] <Invention Item 9> Invention Item 9 states that the PBM therapy device 10 is the LED substrate portion 480 of the LED mouthpiece 400, and for details, please refer to the description in Invention Item 4. Invention Item 9 is as follows.

[0267] In the mouthpiece portion 410 that is fitted into the upper jaw teeth as described in Invention Item 8, The device further includes an LED substrate section 480 that maintains the position and irradiation direction within the oral cavity for arranging the LED light source 30 so that the irradiation target point 490 is included in the luminous flux 40. A therapeutic device for treating MCI using 40Hz therapy, as described in Invention Item 8, characterized by the above.

[0268] <Invention Item 10> Invention item 10 demonstrates that the LED pad 600 can be used as a PBM therapy device 10. This invention relates to a matrix system 640 that uses multiple LED light sources 30 to broaden the luminous flux 40 in order to enhance the therapeutic effect when used in combination with an LED lance 200, LED mouthpiece 400, or sensory therapy device 20 that irradiates deep brain tissue. It mainly corresponds to invention item B of Example 3, and further details are described in the explanatory text related to Figure 5. Furthermore, as shown in Figure 5(c), in the matrix system 640, there are many areas where the luminous flux 40 overlaps after passing through the transmissive plate 630. In the case of the matrix system 640, because the LED pad body 610 has thickness, it is important for safety to manage the upper limit of the light energy density 140 so that it is 5 or less at a predetermined value immediately after passing through the transmissive plate 630, rather than at a distance of 1 cm from the tip of the optical system 70 of the LED light source 30. Invention item 10 is as follows:

[0269] In invention item 6, the PBM therapy device 10 is an LED pad 600, The LED light source holding unit 35 is an LED pad body 610 of a matrix type 640, which has an internal structure in which the LED light sources 30 are arranged vertically and horizontally on the bottom surface and a translucent plate 630 is arranged on the top surface to irradiate the light flux 40. A therapeutic device for treating MCI using 40Hz therapy, as described in Invention Item 6, characterized by the above.

[0270] <Invention Item 11> Invention 11 demonstrates that a backlit LED pad 600 can be applied as a PBM therapy device 10. The backlit LED pad 600 has a luminous flux of 40 and a nearly uniform light energy density of 140. This mainly corresponds to Invention C of Example 3, and further details are described in the explanatory text related to Figure 5. In the case of the LED pad 600 of the backlight system 650, as shown in Figure 5(d), the luminous flux 40 after passing through the transmissive plate 630 is illuminated almost uniformly without overlapping, however, from a quality control perspective, some unevenness or inconsistency may remain. In the case of the backlight system 650 as well, it is important for safety to control the upper limit of the light energy density 140 so that it is 5 or less at the position immediately after passing through the transmissive plate 630, rather than at a distance of 1 cm from the tip of the optical system 70 of the LED light source 30. Invention item 11 is as follows:

[0271] In invention item 6, the PBM therapy device 10 is the LED pad 600, The LED light source holding unit 35 is the LED pad body 610 of a backlight system 650, which has an internal structure in which a backlight 660 consisting of the LED light source 30, a reflector 662, and a light guide plate 664 and / or a diffuser plate 666 is disposed on the bottom surface, and the light beam 40 is irradiated by the transmissive plate 630 disposed on the top surface. A therapeutic device for treating MCI using 40Hz therapy, as described in Invention Item 6, characterized by the above.

[0272] <Invention Item 12> Invention item 12 indicates that the perceptual therapy device 20 includes a visual stimulation device 800 and an auditory stimulation device 810 that perform externally stimulated actions 100, and an audiovisual phase control device 820 that outputs a synchronization signal 130 to these two. The content of Invention 12 corresponds to the common parts of Inventions C, D, and E of Example 4, and the explanatory text related to Figures 7 to 10. Invention 12 is as follows:

[0273] In invention item 5, The aforementioned sensory therapy device 20 consists of a visual stimulator 800, an auditory stimulator 810, and an audiovisual phase control device 820. The visual stimulator 800 is a light-emitting element 170 that emits light at a repetition frequency of approximately 40 Hz, or LCD sunglasses 180 that control the transmittance of the lens portion at a repetition frequency of approximately 40 Hz. The auditory stimulator 810 includes at least one of the following: an earphone 168, headphones 164, or speaker 166, which includes a bone conduction earphone 162 as a sound-emitting element 160 that emits sound at a repeating frequency of approximately 40 Hz. The audiovisual phase control device 820 outputs a synchronization signal 130 that controls the phases of the visual stimulus (light) and the auditory stimulus (sound) by setting the phase difference 120 between the visual stimulus device 800 and the auditory stimulus device 810. Along with, The visual stimulator 800 and the auditory stimulator 810 perform the externally excited operation 100 based on the synchronization signal 130 from the audiovisual phase control device 820. A therapeutic device for treating MCI using 40Hz therapy, as described in Invention Item 5, characterized by the above.

[0274] <Invention Item 13> Invention item 13 describes a type of sensory therapy device 20 that "performs an externally excited action 100 by inputting a single synchronization signal 130." The content of Invention Item 13 is related to Invention Item C and Invention Item F of Example 4, but the parts that overlap with Invention Item 12 have been omitted and it has been expressed as simply as possible. For details, please refer to the captions for Figures 7 and 8 of Example 4. Invention item 13 is as follows:

[0275] In invention item 12, The audiovisual phase control device 820 receives one of the synchronization signals 130 from the phase control device 150 and performs the external excitation operation 100. A therapeutic device for treating MCI using 40Hz therapy, as described in Invention Item 12, characterized by the above.

[0276] <Invention Item 14> Invention item 14 describes a type of sensory therapy device 20 that "performs an externally excited action 100 by inputting two synchronization signals 130." The content of Invention Item 14 is related to Invention Item D and Invention Item F of Example 4, but the parts that overlap with Invention Item 12 have been omitted and expressed as simply as possible. For details, please refer to the captions in Example 4, particularly those for Figures 8 and 9. Invention item 14 is as follows:

[0277] In invention item 12, The audiovisual phase control device 820 receives the two synchronization signals 130 from the phase control device 150 and outputs them as synchronization signals 130 to the visual stimuli device 800 and the auditory stimuli device 810 to control the phase of the visual stimuli of light and the auditory stimuli of sound. A therapeutic device for treating MCI using 40Hz therapy, as described in Invention Item 12, characterized by the above.

[0278] <Invention Item 15> Invention item 15 describes a type of sensory therapy device 20 that "outputs a reference synchronization signal 830 and performs a self-excited operation 105". The content of Invention Item 15 is related to Invention Item F and Invention Item G of Example 4, but the parts that overlap with Invention Item 12 have been omitted and expressed as simply as possible. For details, please refer to the explanatory text for Figures 9 and 10 in Example 4. Invention item 15 is as follows:

[0279] In claim 12, The audiovisual phase control device 820 performs a self-excited operation 105 that outputs a reference synchronization signal 830 to the phase control device 150. The phase control device 150 receives the reference synchronization signal 830, performs the external excitation operation 100, sets the phase difference 120 of the PBM therapy device 10, and outputs the synchronization signal 130. A therapeutic device for MCI treatment using 40Hz therapy, as described in claim 12, characterized by the above.

[0280] ≪Remarks≫ One of the features of the MCI treatment device of the present invention is the low light energy emitted from the oral cavity. Conventional technologies required a light energy density of 1000 mW / cm² (Non-Patent Literature 8) for the purpose of irradiating the substantia nigra pars compacta (located behind the hippocampus) from the oral cavity in order to treat Parkinson's disease. On the other hand, in the present invention, for the purpose of treating "memory loss" in MCI, it was discovered that when irradiating the hippocampus from the oral cavity with flashing at a repetition frequency of approximately 40 Hz, the light energy density can be 1 mW / cm2 or less (described in paragraphs 0079 to 0085), with an upper limit of 10 mW / cm2. Furthermore, the safety of the treatment was enhanced by providing an output adjustment means 230 and an output monitoring means 240 to prevent treatment errors. In any case, since sufficient effects can be obtained with an energy density of 1 mW / cm2 or less than the upper limit of 10 mW / cm2, this treatment device can be safely used with an unusually low power energy for those skilled in the art, when used to stimulate the hippocampus with light energy from the oral cavity for the purpose of treating "memory loss" in MCI. [Industrial applicability]

[0281] The 40Hz therapy employed in this invention is a disease-modifying therapy based on a known mechanism of action: stimulating the affected area of ​​MCI (Mild Cognitive Impairment) at 40Hz, thereby causing microglia, which are immune cells in the brain, to phagocytose amyloid-beta and tau proteins, which are causative substances of Alzheimer's disease. This therapy has the effect of preventing Alzheimer's disease at the MCI stage.

[0282] Therefore, in this invention, the function of "disease-modifying therapy" is enhanced compared to conventional technology, treating symptoms of "brain fog" with perceptual stimulation using light and sound at approximately 40 Hz (perceptual therapy device 20) and treating symptoms of "memory loss" with stimulation at approximately 40 Hz combined with weak light from photobiomodulation (PBM therapy device 10).

[0283] Furthermore, the present invention can also act as a "nerve repair and regeneration therapy" that regenerates damaged cells in the deep brain and temporal lobe, which are affected areas of MCI, by irradiating them with weak light, which is a basic function of photobiomodulation.

[0284] Thus, the present invention is a therapeutic device that combines photobiomodulation technology with 40Hz sensory stimulation, which has a proven track record as a conventional technology, thereby enhancing the functions of "disease modification therapy" and "symptom improvement therapy" while newly adding the function of "nerve repair and regeneration therapy." Therefore, this invention is expected to be industrially applicable and contribute to not only the manufacture and sale of medical devices, but also to various medical services and elderly care businesses.

[0285] The LED lance 200 in Figure 3, the LED mouthpiece 400 in Figure 4, the LED pad 600 in Figure 5, and the helmet and phase control device 150 in Figure 7 for integrating multiple treatment devices for safe MCI treatment, as specifically disclosed in each embodiment of the present invention, can be industrially utilized by those skilled in the art within the scope of design modifications, based on the technical concept and the disclosures of the embodiments of the present invention.

[0286] If further research and development are conducted to improve the usage and treatment techniques in clinical applications, this invention may inspire the invention and design of new improved products, and could contribute to industrial applications as one of the fundamental technologies for related industries.

[0287] This invention is a therapeutic device used for electromagnetic treatment of neurological diseases as a form of so-called digital medicine. However, if this invention is used in conjunction with other technologies to explore new ideas for "developing new drugs in conventional medicine to enhance the effectiveness of preventing and treating dementia," it could also contribute to industrial applications through the digital strategies of the existing pharmaceutical industry. [Explanation of Symbols]

[0288] number 3. The window of life 5. Predetermined value 10 PBM therapy equipment 20 Sensory Therapy Devices 30 LED light sources 35 LED light source holder 40 luminous flux 50 LED Drivers 60 LED elements 65 Semiconductor Chips 70 Optical system 80 Gripping part 90 Mouthpiece 100 Separately excited operation 105 Self-excited movements 110 Phase angles of multiple types of stimuli 120 phase difference 130 Synchronization signal 140 Light energy density 150 Phase control device 160 phonetic elements 162 Bone conduction earphones 164 headphones 166 speakers 168 earphones 170 Luminous elements 172 LED panels 174 LED light bulbs 176 Light-diffusing glasses 180 LCD Sunglasses 200 LED Lance 210 40Hz signal source 220 LED driver circuit 230 Output adjustment means 240 Output monitoring means 250 Command value 260 Means of switching between self-encouragement and external encouragement 400 LED Mouthpieces 410 Mouthpiece section 420 Mouthpiece Coordinate System 430 Cranial Coordinate System 440 Coordinate Transformation Matrix 450 points where contrast-enhanced material can be inserted 460 Mouthpiece 470 Connecting member 480 LED board section 490 Irradiation Target Locations 600 LED Pad 610 LED Pad Unit 620 Head fixing member 625 Connecting member 630 Transparent plate 640 matrix system 650 Backlight System 660 Backlight 662 Reflector 664 Light guide plate 666 Diffuser 800 Visual Stimulation Devices 810 Auditory Stimulation Devices 820 Audiovisual Phase Control Device 830 Reference synchronization signal

Claims

1. A therapeutic device for treating symptoms of forgetfulness, comprising: One or more first light sources having a wavelength range of 650 to 1000 nm that transmits through biological tissue are provided in the oral cavity and are made to blink, A weak light beam with an instantaneous maximum value of 100 mW / cm2 or less is irradiated to the deep brain such as the hippocampus and / or the left and right temporal regions through biological tissues in the brain, including the skull (sphenoid bone, etc.) below the brain. A treatment device for forgetfulness characterized by:

2. The light output generated by each of the first light sources provided in the oral cavity is 10 mW / cm2 or less as an instantaneous maximum value measured at a position 1 cm away from the first light source.

2. The forgetfulness treatment device according to claim 1.

3. The first light source provided in the oral cavity is made to blink with an arbitrary waveform (e.g., a sine wave, a rectangular wave with a selectable duty ratio, a triangular wave, a stepped waveform, or a waveform specified by storing an output every millisecond in a memory, etc.).

3. The forgetfulness treatment device according to claim 1, wherein the forgetfulness treatment device is a device for treating forgetfulness.

4. The first light source provided in the oral cavity is an LED element that emits light in the oral cavity, or an LED element or a laser light source provided outside the oral cavity that emits light through an optical fiber.

4. The forgetfulness treatment device according to claim 1, wherein the forgetfulness treatment device is a device for treating forgetfulness.

5. The light output of the first light source provided in the oral cavity can be monitored by an output display means.

5. The forgetfulness treatment device according to claim 1, wherein the forgetfulness treatment device is a device for treating forgetfulness.

6. The first light source is installed in the oral cavity, and the position and direction of irradiation in the oral cavity are adjusted or fixed by attaching it to the "tip of a rod-shaped treatment instrument equipped with a grip" or to a "mouthpiece." 6. The forgetfulness treatment device according to claim 1,

7. In addition to the first light source provided in the oral cavity, a second light source is provided which is fixed to the scalp side of the head using a headband, a hat, a helmet, glasses, goggles or a dedicated device; The second light source is composed of an LED element or a laser light source emitting light in a wavelength range of 650 to 1000 nm, Furthermore, the first light source and the second light source are blinked in phase synchronization.

7. The forgetfulness treatment device according to claim 1, wherein the forgetfulness treatment device is a device for treating forgetfulness.

8. In addition to the first light source and the second light source, a third light source that "provides a visual stimulus by flashing light" and a stimulus sound source that "provides an auditory stimulus by repeating a stimulus sound" are provided, The first light source, the second light source, the third light source, and the stimulus sound source are further provided with a phase control device capable of setting a phase difference between the phases of the first light source, the second light source, the third light source, and the stimulus sound source blinking or repeating in phase synchronization with each other.

8. The forgetfulness treatment device according to claim 7.

9. The third light source is a light source that blinks in phase with the first light source, and is an "illuminant that emits light, such as an LED panel or an LED bulb" or "LCD sunglasses that control the transmittance of the lens portion." 9. The forgetfulness treatment device according to claim 8.

10. The stimulation sound source is a sound source that repeats a stimulation sound in phase synchronization with the first light source, and is a sound source such as a bone conduction earphone, an earphone, a headphone, or a speaker.

9. The forgetfulness treatment device according to claim 8.

11. the phase in which the first light source blinks; the phase in which the second light source blinks; The phase of the stimulus sound source is repeated as follows: The third light source is provided with a phase control device capable of individually adjusting the phase difference based on the phase at which the third light source blinks.

9. The forgetfulness treatment device according to claim 8.

12. the phase in which the first light source blinks; A phase control device capable of changing a phase difference between the phase at which the second light source blinks and the phase at which the second light source blinks.

9. The forgetfulness treatment device according to claim 7 or 8.

13. the phase in which the first light source blinks; A phase control device capable of changing a phase difference between the phase at which the third light source blinks and the phase at which the third light source blinks.

9. The forgetfulness treatment device according to claim 8.

14. the phase in which the first light source blinks; A phase control device capable of changing a phase difference between the phase of the stimulus sound source and the phase that the stimulus sound source repeats 9. The forgetfulness treatment device according to claim 8.

15. The first light source is provided in the oral cavity, and the object is to treat amnesic MCI accompanied by symptoms of forgetfulness.

15. The forgetfulness treatment device according to claim 1, wherein the forgetfulness treatment device is a device for treating forgetfulness.

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