WO2019088366A1 - Procédé d'extinction de mémoire de peur et dispositif d'extinction de mémoire de peur utilisant une neuromodulation et une image cérébrale d'utilisateur - Google Patents

Procédé d'extinction de mémoire de peur et dispositif d'extinction de mémoire de peur utilisant une neuromodulation et une image cérébrale d'utilisateur Download PDF

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WO2019088366A1
WO2019088366A1 PCT/KR2018/001144 KR2018001144W WO2019088366A1 WO 2019088366 A1 WO2019088366 A1 WO 2019088366A1 KR 2018001144 W KR2018001144 W KR 2018001144W WO 2019088366 A1 WO2019088366 A1 WO 2019088366A1
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brain
connectivity
region
deep
user
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Korean (ko)
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김정윤
윤수정
마지영
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이화여자대학교 산학협력단
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014—External stimulators, e.g. with patch electrodes
    • A61N1/36025—External stimulators, e.g. with patch electrodes for treating a mental or cerebral condition
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0033—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room
    • A61B5/004—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room adapted for image acquisition of a particular organ or body part
    • A61B5/0042—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room adapted for image acquisition of a particular organ or body part for the brain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves 
    • A61B5/055—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves  involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/40—Detecting, measuring or recording for evaluating the nervous system
    • A61B5/4058—Detecting, measuring or recording for evaluating the nervous system for evaluating the central nervous system
    • A61B5/4064—Evaluating the brain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0408—Use-related aspects
    • A61N1/0456—Specially adapted for transcutaneous electrical nerve stimulation [TENS]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0472—Structure-related aspects
    • A61N1/0492—Patch electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014—External stimulators, e.g. with patch electrodes
    • A61N1/36025—External stimulators, e.g. with patch electrodes for treating a mental or cerebral condition
    • A61N1/36028—External stimulators, e.g. with patch electrodes for treating a mental or cerebral condition for aversion therapy

Definitions

  • the present invention relates to a neural control technique and a method of erasing a fear memory using a user's brain image. More specifically, the present invention relates to a method of erasing a fear memory imprinted on a brain through a user's experience using neural control and a user's brain image And a method of erasing the fear memory.
  • Post Traumatic Stress Disorder is a syndrome of mental or physical symptoms that can occur after a person experiences a shocking event.
  • This post-traumatic stress disorder is a traumatic event that can be frequently experienced directly or indirectly in modern society. Even after experiencing a traumatic event, the traumatic event recurs repeatedly, resulting in continuous psychological distress, impaired emotional regulation and cognitive ability It is reported that patients with posttraumatic stress disorder have abnormal structures or functions of the brain regions involved in fear response and fear memory.
  • posttraumatic stress disorder is caused by an abnormal phenomenon in the brain tissue responsible for fear memory because the trauma event learned by the object which did not cause fear is imprinted on the user's brain.
  • CBT Cognitive behavioral therapy
  • drug treatment have been proposed as methods for treating such post-traumatic stress disorder.
  • Drug therapy works by eliminating the imbalance of neurotransmitters in the body of drugs by injecting drugs to reduce the anxiety and airport of the person experiencing trauma.
  • a drug treatment takes a certain period of time before the human body adapts to the drug in the early stage of taking it, and side effects are caused by taking the drug.
  • the longer the drug is taken for a person the greater the frequency of dependence on the drug and the greater the dosage due to tolerance.
  • the drug since the drug has different components depending on the symptoms appearing in the person due to the trauma event, the medication may interfere with the daily life due to the concentration and the dysfunction due to the high dose and the large dose.
  • post-traumatic stress disorder is known to be a disease of the brain, whereas ordinary drug therapy has a drawback in that it is not a brain-specific treatment because it affects not only the brain but also other body organs.
  • Cognitive behavior therapy also called stress inoculation training, is a method of changing beliefs, attitudes, thoughts, and techniques to behavior by positively altering the person experiencing trauma events, Prevent emotional reactions and mental disorders to trauma events.
  • these cognitive behavioral treatments need to grasp the thoughts and behaviors of the traumatic events that they feel, and must themselves be aware of the effects on other people from their thought and actions. Therefore, if the problem is identified and clarification and cognition are not achieved, this treatment method may recognize the trauma event more greatly.
  • neuromodulation technique has the effect of restoring the function of patients suffering from depression or stroke by directly or indirectly activating or inhibiting specific brain regions through long-term strengthening and long-term inhibition of the cranial nervous system by using neuromodulation technique.
  • This neuromodulation technique is different from brain deep stimulation which directly stimulates the deep part of the brain through brain surgery. In the usual way, it transmits electric or magnetic stimulus to the head in a non-invasive manner Is known as a treatment method.
  • deep brain stimulation which stimulates the deep brain area to the present, the area of the brain that can be directly stimulated through neuromodulation is usually limited to the cortical area.
  • the brain is different in the location and size of the brain, depending on the human being, and there is a difference in the state of the nerve connection.
  • a more careful selection should be made about the area of the brain to be stimulated.
  • the position of the brain is discretely accurately detected and stimulated abnormally by the traumatic event, and it is involved in the onset of the post-traumatic stress disorder A more accurate method of controlling the deep region of the brain is needed.
  • the present invention can provide a fear memory erasing method that indirectly adjusts the abnormal fear response of the brain by applying neural control to a specific part of the brain deep part in order to erase the fear memory imprinted on the brain by the user's experience .
  • the present invention combines multimodal brain magnetic resonance imaging to apply the amygdala, hippocampus, It is possible to provide a fear memory erasing method that directly or indirectly stimulates the user.
  • the present invention can provide a fear memory erasing method that efficiently erases the fear memory through activation and suppression of the deep brain region by directly or indirectly stimulating the amygdala and hippocampus, which control the fear memory.
  • a method of erasing a fear memory comprising: acquiring a brain image of a user to identify a region of interest of the brain stem related to fear memory imprinted on the brain by a user's experience; Determining the strength of the neuromodulation using the connectivity information about the cortex-subcortical region, which may be differently formed according to the aspect of the user's fear memory, according to the position and the connectivity information to which the patch or the electrode is attached to the user; And erasing the brain memory imprinted horror memory by stimulating a region of interest in the deep brain region via a patch or electrode attached to the determined location.
  • the step of acquiring the user's brain image includes the steps of 1) T1-weighted image reflecting the relaxation time between the deep part of the brain, 2) diffusion tensor image (DTI : Diffusion Tensor Imaging) and 3) resting state functional magnetic resonance imaging (rsfMRI) for the deep brain area.
  • DTI diffusion tensor image
  • rsfMRI resting state functional magnetic resonance imaging
  • the step of determining a position may determine a position using a user's cortical area map based on a T1 weighted image.
  • the cortical area map may be a map indicating the precise location of the cortical area having a high structural linkability and functional connectivity with the region of interest of the brain deep part and the degree of connectivity between the subcortical structure and the cortex of the deep brain part.
  • the structural connectivity according to an exemplary embodiment may be determined by analyzing the diffusion tensor image and analyzing the localization of the cortex having connectivity with the subcortical structure of the brain deep part and the nerve bundle connecting the sub- And intensity information, which is expressed in terms of the number and density.
  • the functional connectivity according to one embodiment is analyzed by analyzing the functional magnetic resonance imaging of the resting state, and localization of the cerebral cortex area correlated with the activity of the subcortical structure of the brain deep part, And intensity information indicating a correlation index of activity between cortical structures.
  • the step of erasing the brain memory imprinted in the brain stimulates the brain cortex area based on the area information of the structural connectivity, the intensity information and the area information of the functional connectivity and the intensity information,
  • the degree of activation can be indirectly controlled to clear fear memory.
  • a fear memory erasure apparatus comprising a processor, the processor being adapted to acquire the user's brain image to identify a region of interest in the brain stem associated with fear memory imprinted in the brain by the user's experience And determines the position to which the patch or electrode is attached to the user by using the connectivity information about the cortex-cortical region differently formed according to the pattern of fear memory imprinted on the user, The degree of the liquor can be quantified and the fear region imprinted on the brain can be erased by stimulating the region of interest of the brain deep region through the patch or electrode attached to the determined position.
  • the method of erasing the fear memory is performed by applying a neuromodulation technique to a specific region of the brain cortex region to erase the brain memory imprinted by the user's experience, which can be indirectly controlled by the abnormalities and activities of the subcortical region of the brain.
  • the fear memory-erasing method in applying non-invasive neuromodulation, combines multiple brain magnetic resonance images to generate brain regions responsible for storage and erasure of fear memory, Can stimulate.
  • the fear memory cancellation method can efficiently erase the fear memory through activation and suppression of the deep brain region by indirectly stimulating the amygdala and hippocampus, which are responsible for fear memory.
  • FIG. 1 is a block diagram illustrating an entire configuration using a fear memory erase device to erase the fear memory imprinted on a user's brain according to an embodiment.
  • FIGS. 2A and 2B are views for explaining an operation of determining a position to attach a patch or electrode according to an embodiment.
  • FIGS. 3A and 3B illustrate structural and functional connectivity between the amygdala and the cerebral cortical area according to one embodiment.
  • FIGS. 4A to 4D are views for explaining an operation of stimulating a region of interest of the brain stem non-invasively according to an embodiment.
  • FIGS. 5A and 5B are diagrams for explaining an operation of indirectly suppressing the degree of activation of an area of interest of a brain stem according to an embodiment.
  • FIG. 6 is a flowchart illustrating a fear memory erasing method according to an embodiment.
  • FIG. 1 is a block diagram illustrating an entire configuration using a fear memory erase device to erase the fear memory imprinted on a user's brain according to an embodiment.
  • the Foucauld memory erasure device 104 can use the neural control technique to stimulate the brain cortex area that manages the fear memory, thereby controlling the fear memory due to stimulation.
  • neuromodulation is a method of regulating the brain's nervous system by using dichotomous DC stimulation, transthoracic magnetic stimulation, etc. This is a long term potentiation (LTP) and long term depression (LTD) of the nervous system, To activate or inhibit a specific brain region directly or indirectly.
  • LTP long term potentiation
  • LTD long term depression
  • the present invention can use the neuromodulation technique to control the function of the brain region associated with the elimination of fear memory.
  • the brain regions responsible for the formation and maintenance of the horror memory include the amygdala 101 and the hippocampus 102.
  • the amygdala (101) is a brain stem that collectively manages emotional information as a collection of neuronal nuclei inside the temporal lobe, and can process information related to motivation, memory, attention, learning, and emotion.
  • the amygdala 101 processes emotions associated with fear, and can thus be critically involved in fear control, fear learning, and fear memory formation. And, the amygdala 101 can transmit fear-related information to other parts of the brain based on the learned fear memory, thereby causing a challenge or avoidance reaction to fear.
  • fear memory is a memory imprinted on the brain due to a situation that is not normally threatening, or fearful learning of the object, emotions due to fear memory detect danger in terms of self-defense, and actively avoiding actions Lt; / RTI >
  • fear memory imprinted on the brain for avoidance behavior for life support can be expressed as a mental symptom of the user due to sudden recognition in everyday life rather than fear.
  • the user may experience anxiety, autism, discouragement, somnolence, post-traumatic stress disorder, fear, schizophrenia, and the like due to sudden external stimuli It can cause mental symptoms.
  • fear memory plays a major role in the subcortex brain region including the amygdala and hippocampus, and the cortex region including the prefrontal and parietal lobes forms and sustains fear memory in the cortical brain region And the like.
  • the stage and intensity of fear memory can be determined by how effectively the cortical area can control the action of the sub-cortical area.
  • the cortical areas including the amygdala and the hippocampus and the cortical areas with strong structural-functional connectivity may be different depending on the timing and intensity of fear memory, and individual differences.
  • the connectivity of the cerebral cortex area around the cortex and the prefrontal cortex including the amygdala may be strong.
  • the connectivity of cortical areas including the amygdala and cortex areas around the prefrontal cortex may be very weak.
  • the brain cortex area having connectivity with the cortical-brain area may be slightly different depending on the individual.
  • the present invention extracts a brain cortex region having connectivity to the cortical brain region including the amygdala and the hippocampus and adjusts the intensity of the non-stimulation neural control depending on the degree of connectivity, Can be provided.
  • the cerebral cortex including the prefrontal lobe, may play a role in inhibiting or regulating the formation and maintenance of panic memory in the subcortical brain region including the hippocampus and the amygdala. Therefore, when the function of the cortical area is activated, it can restrain or normalize the abnormal activation of the hippocampus and the amygdala through the structural and functional connectivity between the hippocampus and the amygdala. At this time, there are individual differences in the structural connectivity and functional connectivity between the cerebral cortex area, hippocampus and amygdala, and the functions of the brain cortex area also vary from person to person.
  • a neuromodulation technique for targeting an accurate brain cortical area having structural connectivity and functional connectivity between hippocampus and amygdala as described above is applied using the fear memory erasure device 102 .
  • the phantom memory cancellation device 102 can stimulate the amygdala closely related to mental symptoms due to fear memory through neuromodulation.
  • neural control is a noninvasive neuromodulation method, and it can not directly stimulate the amygdala located in the deep part of the brain.
  • the fear memory erasing apparatus 104 proposed in the present invention stimulates a brain cortical region having direct connection with an amygdala located at the deep part of the brain, and as a result, the activity of the amygdala can be controlled.
  • Multiple brain magnetic resonance imaging can be used.
  • the multimodal brain magnetic resonance imaging may be a brain image obtained by photographing a deep part of the brain for intensively examining a specific region for eliminating the fear memory, that is, the amygdala and the hippocampus.
  • the multiple brain magnetic resonance imaging may include T1-weighted images, DTI (Diffusion Tensor Imaging), and resting state functional magnetic resonance imaging (rsfMRI).
  • the T1-weighted image may be a reflection of the relaxation time between the deep part of the brain
  • the diffusion tensor image may be a visualized image of the nerve root of the brain
  • the functional magnetic resonance image of the resting state may indicate the resting functional connection state It may be a displayed image.
  • the fear memory erasure device 104 may analyze the user's brain image (multi-brain magnetic resonance image) to determine the location 103 to which the user will attach the patch or electrode to the head surface.
  • the fear memory erasing device 104 acquires and analyzes the brain image to confirm the connectivity between the brain area and the cortical area of the brain deep part related to the fear memory imprinted on the brain by the user's experience, Based on this information, the optimal location of the brain cortex that can be activated or inhibited can be selected and the location 103 about the precise cortical area to which the patch or electrode is attached to the user can be determined.
  • the area of interest in the deep brain tissue may correspond to the amygdala 101 or the hippocampus 102, which is located in the deep brain region and controls fear memory. Details will be described with reference to FIGS. 2A and 2B.
  • the pole position determination through the fear cancellation device 104 has the following steps. It is possible to acquire multiple brain magnetic resonance imaging data of each individual to which the stimulation apparatus is to be applied considering the differences among individuals. At this time, the present invention can select the cerebral cortex area having the highest connectivity with the amygdala and hippocampus of the deep part of the brain in the order of high correlation index through structural connectivity and functional connectivity analysis based on brain image data. In other words, the present invention can prioritize the brain cortical areas that are simultaneously established in structural connectivity and functional connectivity.
  • T1-weighted images with good spatial resolution are required to accurately determine the location of the cortical area having characteristics for each user.
  • the present invention can register a deep brain tissue stimulated cortical area map specific to each user by registering with a T1 weighted image having a high spatial resolution (or a good spatial resolution). That is, the fear memory erasure device 104 optimizes the connectivity information in the diffusion tensor image, the resting state functional magnetic resonance image, and the information analysis of the T1 weighted image, A cortical area map optimized for the user can be generated.
  • the cortical area map generated through this process includes a stimulus position, a brain map showing the state of the neural connection and the reaction state such as the tissue position and size of the different brain according to the user, and a map capable of grasping the user's brain activity Can be utilized.
  • the cortical area map can indicate the precise location of the structural link or functional link with the region of interest in the deep brain region. Details will be described with reference to FIGS. 3A and 3B.
  • each area of the brain cortex is involved in the entire human cognitive domain, such as subjective cognition and memory.
  • the connectivity of the deep brain region with other areas of the brain is different, and the specific psychological function or physical function can be controlled through this difference.
  • the precise location of the brain cortex and the connectivity between the brain regions may vary depending on the individual user, and this should be considered particularly important to select non-invasive brain stimulation locations.
  • the present invention can determine a position 103 that can stimulate a region of interest (anisotropy) of the deep brain of the brain using a cortical area map showing the features of the brain deep part that varies depending on the user.
  • the fear memory erasing device 104 can indirectly stimulate the region of interest of the deep brain region through a patch or electrode attached to the determined location to erase the brain memory imprinted fear memory.
  • the fear memory-erasing device 104 can effectively erase the horror memory by activating and suppressing the deep brain area, such as an amygdala, via a patch or electrode.
  • the degree of the stimulus transmitted through the electrodes of the attached patches can be determined according to the degree of structural connectivity and functional connectivity.
  • the present invention constitutes a standard group for each age, sex, and race, and standardizes the structural connectivity and functional connectivity of the amygdala, hippocampus, and cerebral cortex areas and then ranks them as a percentage, The strength information of each connectivity can be determined.
  • the present invention can be used as an additional factor in determining the degree of stimulation for neural control by indexing the determined strength of each of the structural connectivity and functional connectivity.
  • the present invention measures the structural connectivity and functional connectivity of the amygdala, hippocampus and cortical area of a subject in their twenties, female, and Asian, and converts each measured intensity to a percentage value in a standard population have. Thereafter, the present invention is applied to the upper 80th percentile based on the converted percentage value, and if the connectivity is weaker than that of the normal, the intensity of the neural control technique, i.e., the stimulus level, can be increased by 8% within the permitted range.
  • FIGS. 2A and 2B are views for explaining an operation of determining a position to attach a patch or electrode according to an embodiment.
  • the fear memory erasing device proposed in the present invention analyzes a brain image of a user and can determine a position to attach a patch or an electrode to a user.
  • FIG. 2A is a schematic diagram of a brain obtained in order to confirm the precise position of a region of interest in the deep brain related to fear memory imprinted on the brain by the user's experience through the diffusion tensor imaging, the functional magnetic resonance imaging analysis in the resting state,
  • the figure corresponds to the T1-weighted image in the image.
  • T1-weighted images can be images in which the radio-frequency radiation emitted to the body resonates the hydrogen nuclei in the body region and images the difference in signals from each resonant tissue.
  • T1-weighted images are the images reflecting the relaxation time between the deep brain areas, showing the highest signal in adipose tissue, and low signal intensity in the order of white matter, gray matter, cerebrospinal fluid, and skull.
  • T1-weighted images do not provide direct information on functional connectivity and structural connectivity, they provide a high spatial resolution (less than 1 mm) for the region of interest in the brain cortex extracted through diffusion-tensor imaging and functional magnetic resonance imaging . In addition, it is possible to select the location of non-invasive neural stimulation precisely.
  • the FELM can determine the precise location of the electrode or patch outside the skull using a map of the cortical area that shows connectivity between the deep brain structure of the user and the brain cortex.
  • the cortical area map may be a map showing the degree of connectivity of the subcortical structure and cortex of the deep brain area with the location of the cortical area with high structural connectivity and functional connectivity with the area of interest in the deep brain area.
  • the fear memory erase device can determine the exact position of the electrode or patch based on the cortical area map.
  • the fear memory erasing device determines a location to attach a patch or electrode to a user to erase the fear memory to minimize psychological or physical pain due to the event repeatedly recalled .
  • the user's brain can detect a 'danger signal', and transmit an 'alert signal' to the brain, the nervous system, or the entire body of the danger.
  • alert signals are managed in the amygdala of the brain, and the behavior of the user can be expressed to an emotional and instinctive level depending on whether the amygdala is activated or not.
  • the amygdala inhibits all activities of the brain and activates only the instinctive, impulsive areas of fear memory, so that the user may experience panic, anxiety, The same behavior can occur.
  • the amygdala can maximize the excitement state of the user by suppressing activation of the upper level brain stem such as the frontal lobe coordinating thought and emotion.
  • the activation frequency of the amygdala becomes low and the excited state of the user can be reduced. This can minimize the emotional / instinctual behavior and induce the user's rational / conscious behavior as the frontal lobe controls the user's thoughts, emotions and behaviors.
  • the fear memory cancellation apparatus can cancel the user's fear memory by controlling the abnormal activity through the action of the frontal lobe and other cortical regions.
  • the position and intensity of the cortical area including these amygdala and frontal lobes are different for each user. Due to these differences, the degree of expression of fear memory may vary from person to person.
  • the fear memory erasure device activates the brain cortex area including the frontal lobe in consideration of the specificity of the connectivity between the different regions of the brain cortex and the brain central region The user can determine where to attach the patch or electrode.
  • FIGS. 3A and 3B illustrate structural and functional connectivity between the amygdala and the cerebral cortical area according to one embodiment.
  • the fear memory erase device can analyze the user's brain image and determine the location where the patch or electrode is to be attached to the user in the neural control technique.
  • Brain imaging may include emphasized imaging, diffusion tensor imaging, and functional magnetic resonance imaging in the resting state.
  • Selection of the location to which the patch or electrode is to be attached i.e., the area of interest of the brain to which the stimulus is applied, can be selected based on structural connectivity and functional connectivity information with the brain stem such as amygdala / hippocampus.
  • the following methods can be used to select brain stimulation areas based on structural connectivity.
  • the present invention calculates the number of neural tracts between each cortical area for the amygdala / hippocampus through analysis of the diffusion tensor image obtained from each user, Can be sequentially selected.
  • the present invention is a method for acquiring structural connectivity information, which calculates the fractional anisotropy reflecting the degree of connection of the nerve bundle between the amygdala / hippocampus and each cortical region, thereby obtaining the brain cortex area having the highest nerve bundle fractional anisotropy Can be selected sequentially.
  • the present invention is based on the information of the brain cortex area selected through the two methods described above, by adding an indicator of ease of brain stimulation to the information of the brain cortex area (an index according to the degree to which a stimulation patch can be easily attached) , And brain stimulation regions based on structural connectivity. That is, the present invention can confirm the structural connectivity including 'area information' and 'intensity information' described below by analyzing the diffusion tensor image.
  • the area information forming the structural connectivity is defined as the area of the cortex having connectivity with the subcortical structure of the brain, and the intensity information includes the number and density of the nerve bundles connecting the subcortical structure of the deep brain and each cortical area . ≪ / RTI >
  • the intensity information of structural connectivity can be determined differently depending on the number and density of nerve bundles. That is, the high number and density of nerve bundles connecting the brain cortical region may mean that stimulation to the region of interest in the deep brain region is easy even with low stimulation. Conversely, a low number and density of nerve bundles connecting the cerebral cortex can mean that stimulation to the area of interest in the deep brain area is not easy even with low stimuli. Accordingly, the present invention can set the intensity according to the connectivity of the nerve bundle between the region of interest and the brain cortex, that is, the degree of stimulation.
  • a method for selecting a brain stimulation region based on functional connectivity may be as follows.
  • the selection of the brain stimulation region according to the functional connectivity can be selected through the functional magnetic resonance imaging analysis in the resting state.
  • the present invention can measure the resting activity of the amygdala / hippocampus and measure the resting activity of each cortical area.
  • the present invention can sequentially select a brain cortex area having an activity that appears as the highest correlation index with the resting activity of the amygdala / hippocampus. Further, the present invention is based on the information of the selected brain cortex area, thereby adding a convenience index of the brain stimulation to the brain cortex area (an index according to the degree to which a stimulation patch can be easily attached) Area can be selected.
  • the present invention can confirm the functional connectivity including 'area information' and 'intensity information' described below by analyzing the functional magnetic resonance image in the resting state.
  • Functional connectivity domain information can be defined as the area of the brain cortex with high activity correlated with the activity of subcortical structures in the deep brain. That is, when the activity of the cortical structure is increased to a similar degree to that of the cortical structures including the prefrontal cortex, parietal lobe and temporal lobe, that is, when the correlation index between the activities is high, the two structures (cortical structures and cortex Structure) can be judged to be high. Conversely, the activity of the cortical structures is high. If the activity of the cortical structures is low, the functional connectivity of the two structures is low.
  • the strength information of the functional connectivity can be defined as the correlation index between the activities of the two structures by repeatedly measuring the activity of the two structures.
  • the brain memory area can be selected as the final brain cortex stimulus area at the same time as the brain memory area selected by the structural connectivity and the functional connectivity criterion.
  • the phoresis memory erasure device can construct a personalized cortical area map using a T1 weighted image represented by a high spatial resolution.
  • the cortical area map shows the connectivity between the deep brain area and the brain cortex area, and can show structural and functional connectivity between the brain's area of interest and the brain cortex area.
  • FIG. 3A can be a diffusion tensor image of acquired brain images to identify a region of interest in the brain.
  • Diffusion tensor imaging can be a visualization of the neural pathways of the deep brain.
  • the diffusion tensor image is a measure of the structural connectivity of the cranial nerve by measuring the connection direction of the nerve bundle by applying a magnetic stimulus to the human body, which may be not only the degree of compression of the median nerve but also the image of the nerve damage information.
  • the FEM can analyze the diffusion tensor image to confirm the structural connectivity between the brain region of interest and the brain cortex region.
  • the structural connectivity may be the neural arrangement of the brain, such as the number, density, etc. of nerve bundles connecting the amygdala and each cortical area.
  • diffusion-tensor imaging is a water-based imaging technique that traces the fiber pathway that connects different regions of the brain to form the whole brain structural connexion or network foundation foundation.
  • the present invention can connect the areas related to cognitive skills through the diffusion tensor image to enable individual identification of the brain cortical region with high structural connectivity to the neural arrangement of the entire brain.
  • the 3B may be a functional magnetic resonance image in a resting state among brain images acquired to identify a region of interest in the brain.
  • the functional magnetic resonance imaging in the resting state can be an image showing the activation pattern of the deep brain part of the resting period.
  • the FEM can analyze the functional magnetic resonance imaging in the resting state to confirm the functional connectivity between the brain area of interest and the brain cortex area.
  • the functional connectivity can be represented as a cortical area activated at the same time when the amygdala is activated, or a cortical area deactivated simultaneously when the amygdala is activated.
  • Fear memory erasing device can indicate activation or inactivation of the brain cortex area depending on activation of the region of interest in the deep brain region as a function between the region of interest and the region of the brain cortex in accordance with functional magnetic resonance imaging in the resting state. That is, according to the present invention, the functional cognitive image of the cognitive state can be used to identify individual brain cortical regions with high functional connectivity to the region of interest.
  • FIGS. 4A to 4D are views for explaining an operation of stimulating a region of interest of the brain stem non-invasively according to an embodiment.
  • a fear memory cancellation device includes a brain image, which is a multiple brain magnetic resonance image including a structural connectivity (DTI) and a functional connectivity (rsfMRI) through emphasis, diffusion tensor imaging and resting state functional magnetic resonance imaging You can shoot.
  • DTI structural connectivity
  • rsfMRI functional connectivity
  • the Foucault erasure apparatus analyzes a user's brain image to determine a position where a patch or an electrode is to be attached to the user.
  • the fear memory cancellation device can determine the precise location where the stimulus is to be applied by using the cortical area map showing the connectivity between the deep brain part and the brain cortex area of the user.
  • the FER can identify the cortical area of interest 402 of the brain stem 401, which can best stimulate a pair of amygdas located respectively on the left and right sides of the brain.
  • the fear memory erasing device can determine a position for stimulating the area of interest 402 of the brain stem 401 through neural control based on the deep part of the brain where the pair of amygdala is located.
  • the fear memory cancellation device suppresses the cortical area having a high structural and functional connectivity with the area of interest 402 of the deep brain part 401 through noninvasive neural control, It is possible to indirectly control overactivity for the region of interest 402.
  • non-invasive neuromodulation has a limitation in directly stimulating the structure of the brain deep part. It is possible to control the overactivity of the amygdala around the region.
  • the fear memory erasing device proposed in the present invention can also be used for controlling a neural network in accordance with the direction of functional connectivity with the region of interest 402 of the brain stem 401 in order to control overactivity of the region of interest 402 of the brain stem 401 Adjustments can be applied differently.
  • the present invention can be used to inhibit the cortical area, which is also activated when the area of interest 402 of the brain stem 401 is activated, Can be indirectly inhibited by overactivity of the cortical area 401 of the brain stem 401 by simultaneously activating the cortical area that is inactivated at the same time.
  • the fear memory erasing device can accurately determine the attachment position of the patch or the electrode by utilizing the area information of the structural connectivity and the functional connectivity.
  • the present invention can control the degree of non-invasive neural control applied to the cerebral cortex area using the intensity information measured in each of the structural connectivity and the functional connectivity.
  • the present invention can precisely stimulate a brain cortex region having high structural connectivity and functional connectivity corresponding to a region of interest in the deep brain region, and indirectly adjust the degree of activation of a region of interest in the deep brain region to cancel fear memory have.
  • FIGS. 5A and 5B are diagrams for explaining an operation of indirectly suppressing the degree of activation of an area of interest of a brain stem according to an embodiment.
  • the fear memory erasing device can activate the amygdala 501 as the user experiences a fear memory imprinted in the brain.
  • the activated amygdala 501 can inhibit high-level cognitive activity of the brain and activate an instinctive, impulsive response to fear memory.
  • the fear memory erasing device can indirectly stimulate an amygdala 501 having an activated state through a patch or an electrode attached to the brain to control the amygdala 501, which is a region of interest of the brain, using neural control.
  • the patch or electrode is attached to the scalp surface where the user's frontal lobe is located, and the fear memory erasing device stimulates or activates the frontal lobe of the user through a patch or electrode attached to the scalp surface,
  • the controller 502 can deactivate the switch.
  • FIG. 6 is a flowchart illustrating a fear memory erasing method according to an embodiment.
  • the fear memory erase device can acquire the brain image of the user.
  • the fear memory erasing device can acquire the user's brain image to identify the region of interest of the brain deep part related to the fear memory imprinted on the brain by the user's experience.
  • the brain image is an image that can detect the activation of the deep brain due to the cognitive activity of the user and may be a multiple brain image.
  • the brain image may be a multi-brain magnetic resonance image, including a highlighted image, a diffusion tensor image, and a functional magnetic resonance image in a resting state.
  • the fog memory erasure device uses the connectivity information on the cortex-subcortical region that is differently formed according to the pattern of fear memory imprinted on the user's brain,
  • the intensity of neuromodulation can be determined.
  • the Fourier memory cancellation apparatus can determine a location based on a highlight image using a cortical area map indicating connectivity between the brain deep part and the brain cortex area of the user.
  • the emphasized image may be a T1-weighted image reflecting the relaxation time between the deep portions of the brain.
  • the cortical area map may be a map showing the degree of connectivity of the subcortical structure and cortex of the deep brain area with the location of the cortical area with high structural connectivity and functional connectivity with the area of interest in the deep brain area.
  • structural connectivity
  • the diffusion tensor image was analyzed to determine the localization of the cortex having connectivity with the subcortical structure of the brain and the intensity information represented by the number and density of the nerve bundles connecting the subcutaneous structures of the deep brain and each brain cortex intensity).
  • the functional connectivity is analyzed by the functional magnetic resonance imaging of the resting state.
  • the localization of the cerebral cortex which correlates with the activity of the subcortical structure of the brain, and the activity between the subcortical and cortical structures And intensity information indicating the correlation index.
  • Fear memory erasure device uses a cortical area map based on structural connectivity and functional connectivity between the deep brain region and the brain cortex to locate a patch or electrode that can stimulate a region of interest in the deep brain of the user, You can decide. That is, the present invention can determine the position for stimulating the amygdala through a non-invasive method, rather than an invasive method that directly stimulates the amygdala to manage the user's fear memory.
  • the present invention utilizes the actual brain image of the user, thereby accurately grasping the position of the deep brain part expected to cause individual mental disorder.
  • the Foucault erasure apparatus can erase the fear memory imprinted on the brain by stimulating a region of interest of the deep brain region through a patch or electrode attached to the determined position.
  • the fear memory erasing device can non-invasively stimulate the region of interest of the brain deep region through the attached patch or electrode, and indirectly suppress the degree of activation of the region of interest of the brain deep region to erase the fear memory . That is, by stimulating the brain cortex area based on the area information of the structural connectivity, the intensity information, and the area information and the strength information of the functional connectivity, the activation degree of the deep region of the brain is indirectly suppressed to erase the fear memory .
  • the fear memory erase device can apply the neural control differently according to the state of the user.
  • the FER can stimulate areas of interest in the deep brain tissue such that the brain cortical area is activated or deactivated depending on the direction of functional connectivity between the cortical area of interest and the cortical area. Accordingly, the fear memory erasing device can selectively transmit the stimulus in response to a mental disorder generated by the user.
  • Implementations of the various techniques described herein may be implemented in digital electronic circuitry, or in computer hardware, firmware, software, or combinations thereof. Implementations may be implemented in a computer program product, such as an information carrier, e.g., a machine readable storage device, such as a computer readable storage medium, for example, for processing by a data processing apparatus, May be embodied as a computer program recorded on a device (computer readable medium).
  • a computer program such as the computer program (s) described above, may be written in any form of programming language, including compiled or interpreted languages, and may be stored as a stand-alone program or in a module, component, subroutine, As other units suitable for use in the present invention.
  • a computer program may be deployed to be processed on one computer or multiple computers at one site or distributed across multiple sites and interconnected by a communications network.
  • processors suitable for processing a computer program include, by way of example, both general purpose and special purpose microprocessors, and any one or more processors of any kind of digital computer.
  • a processor will receive instructions and data from a read-only memory or a random access memory or both.
  • the elements of a computer may include at least one processor for executing instructions and one or more memory devices for storing instructions and data.
  • a computer may include one or more mass storage devices for storing data, such as magnetic, magneto-optical disks, or optical disks, or may receive data from them, transmit data to them, .
  • Information carriers suitable for embodying computer program instructions and data include, for example, semiconductor memory devices, for example, magnetic media such as hard disks, floppy disks and magnetic tape, compact disk read only memory A magneto-optical medium such as a floppy disk, an optical disk such as a DVD (Digital Video Disk), a ROM (Read Only Memory), a RAM , Random Access Memory), a flash memory, an EPROM (Erasable Programmable ROM), an EEPROM (Electrically Erasable Programmable ROM), and the like.
  • the processor and memory may be supplemented or included by special purpose logic circuitry.
  • the computer-readable medium can be any available media that can be accessed by a computer, and can include both computer storage media and transmission media.

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Abstract

La présente invention concerne un procédé d'extinction de mémoire de peur et un dispositif d'extinction de mémoire de peur utilisant une neuromodulation et une image cérébrale d'utilisateur. Le procédé d'extinction de mémoire de peur analyse une image cérébrale d'un utilisateur pour identifier une région d'intérêt dans le cerveau profond qui est associée à une mémoire de peur imprimée dans le cerveau par l'expérience de l'utilisateur, et stimule la région d'intérêt dans le cerveau profond au moyen d'une électrode, ce qui permet d'éteindre une mémoire de peur imprimée dans le cerveau.
PCT/KR2018/001144 2017-11-02 2018-01-26 Procédé d'extinction de mémoire de peur et dispositif d'extinction de mémoire de peur utilisant une neuromodulation et une image cérébrale d'utilisateur WO2019088366A1 (fr)

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KR1020170145476A KR102090369B1 (ko) 2017-11-02 2017-11-02 신경 조절술 및 사용자의 뇌 영상을 이용한 공포 기억 소거 장치
KR10-2017-0145476 2017-11-02

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090054800A1 (en) * 2005-07-22 2009-02-26 Centre National De La Recherche Scientifique-Cnrs- Method and Device for Representing A Dynamic Functional Image of the Brain, By Locating and Discriminating Intracerebral Neuroelectric Generators and Uses Thereof
US20130096363A1 (en) * 2010-04-02 2013-04-18 M. Bret Schneider Neuromodulation of deep-brain targets by transcranial magnetic stimulation enhanced by transcranial direct current stimulation
US20150119689A1 (en) * 2012-05-16 2015-04-30 Beth Israel Deaconess Medical Center, Inc. Identifying individual target sites for transcranial magnetic stimulation applications
US20150157858A1 (en) * 2013-12-08 2015-06-11 Case Western Reserve University Activation Map Based Individualized Planning For Deep Brain Stimulation
US20150223721A1 (en) * 2004-03-11 2015-08-13 Dirk De Ridder Electrical stimulation system and method for stimulating tissue in the brain to treat a neurological condition

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20150223721A1 (en) * 2004-03-11 2015-08-13 Dirk De Ridder Electrical stimulation system and method for stimulating tissue in the brain to treat a neurological condition
US20090054800A1 (en) * 2005-07-22 2009-02-26 Centre National De La Recherche Scientifique-Cnrs- Method and Device for Representing A Dynamic Functional Image of the Brain, By Locating and Discriminating Intracerebral Neuroelectric Generators and Uses Thereof
US20130096363A1 (en) * 2010-04-02 2013-04-18 M. Bret Schneider Neuromodulation of deep-brain targets by transcranial magnetic stimulation enhanced by transcranial direct current stimulation
US20150119689A1 (en) * 2012-05-16 2015-04-30 Beth Israel Deaconess Medical Center, Inc. Identifying individual target sites for transcranial magnetic stimulation applications
US20150157858A1 (en) * 2013-12-08 2015-06-11 Case Western Reserve University Activation Map Based Individualized Planning For Deep Brain Stimulation

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