JP2008516696A - Medical device for detection, prevention and / or treatment of neurological disorders and method related to the medical device - Google Patents

Medical device for detection, prevention and / or treatment of neurological disorders and method related to the medical device Download PDF

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JP2008516696A
JP2008516696A JP2007536997A JP2007536997A JP2008516696A JP 2008516696 A JP2008516696 A JP 2008516696A JP 2007536997 A JP2007536997 A JP 2007536997A JP 2007536997 A JP2007536997 A JP 2007536997A JP 2008516696 A JP2008516696 A JP 2008516696A
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stimulation
electrode
medical device
electrical
neurological
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ラビッシュ ヴィー. パットワードハン、
モハメッド ファシウディン、
ウォルター ジー. ベジオ、
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ボード オブ スーパーバイザーズ オブ ルイジアナ ステート ユニバーシティ アンド アグリカルチュアル アンド メカニカル カレッジ オフィス オブ ザ バイス チャンセラー フォー アカデミック
ルイジアナ テック ユニバーシティ ファウンデーション
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Application filed by ボード オブ スーパーバイザーズ オブ ルイジアナ ステート ユニバーシティ アンド アグリカルチュアル アンド メカニカル カレッジ オフィス オブ ザ バイス チャンセラー フォー アカデミック, ルイジアナ テック ユニバーシティ ファウンデーション filed Critical ボード オブ スーパーバイザーズ オブ ルイジアナ ステート ユニバーシティ アンド アグリカルチュアル アンド メカニカル カレッジ オフィス オブ ザ バイス チャンセラー フォー アカデミック
Priority to PCT/US2005/037246 priority patent/WO2006044793A2/en
Publication of JP2008516696A publication Critical patent/JP2008516696A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/04Measuring bioelectric signals of the body or parts thereof
    • A61B5/0476Electroencephalography
    • A61B5/0478Electrodes specially adapted therefor
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/40Detecting, measuring or recording for evaluating the nervous system
    • A61B5/4076Diagnosing or monitoring particular conditions of the nervous system
    • A61B5/4094Diagnosing or monitoring seizure diseases, e.g. epilepsy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014External stimulators, e.g. with patch electrodes
    • A61N1/36025External stimulators, e.g. with patch electrodes for treating a mental or cerebral condition
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/04Measuring bioelectric signals of the body or parts thereof
    • A61B5/0476Electroencephalography
    • A61B5/0482Electroencephalography using biofeedback
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/05Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radiowaves
    • A61B5/053Measuring electrical impedance or conductance of a portion of the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/72Signal processing specially adapted for physiological signals or for diagnostic purposes
    • A61B5/7271Specific aspects of physiological measurement analysis
    • A61B5/7275Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014External stimulators, e.g. with patch electrodes
    • A61N1/36017External stimulators, e.g. with patch electrodes with leads or electrodes penetrating the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36082Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease

Abstract

  Disclosed are devices and methods for detecting, preventing, and / or treating neurological disorders. These devices and methods utilize electrical stimulation and have unique concentric ring electrode components. The disclosed method includes placing a plurality of electrodes on the scalp of a mammal, monitoring the electrical pattern of the mammalian brain to confirm the onset of a neurological phenomenon, and a brain exhibiting the neurological phenomenon. Identifying the location of the electrical pattern and applying percutaneous or transcranial electrical stimulation to the location of the neurological phenomenon to beneficially alter the electrical pattern of the brain. Disclosed methods include epilepsy, Parkinson's disease, Huntington's disease, Alzheimer's disease, depression, bipolar disorder, phobia, schizophrenia, multiple personality disorder, migraine or headache, shaking, attention deficit hyperactivity disorder, eating disorder Can be useful in the detection, prevention, and / or treatment of various indications, such as substance abuse and anxiety. The disclosed method can also be used with other peripheral stimulation techniques.

Description

  The present invention relates generally to medical devices, and more particularly to medical devices and methods related to the medical devices for the detection, prevention, and / or treatment of neurological disorders.

[Cross-reference of related applications]
This application is a non-provisional claiming the benefit and priority of provisional application No. 10/9677891 filed on October 18, 2004, and continuation-in-part application filed on October 17, 2005. Application, both provisional and partially continuation applications, are incorporated herein by reference.

  Epilepsy is one of several neurological disorders that can be severely debilitating and / or dangerous. Epilepsy is characterized by the occurrence of seizures, particularly sudden dysfunction, loss of consciousness, abnormal motor phenomena, mental or sensory disturbances. It is believed that between 2 and 4 million Americans will suffer from various forms of epilepsy. Studies have shown that the prevalence of epilepsy can be even higher globally, especially in countries that are economically behind, with the global number of epilepsy patients estimated at 100 million It has been suggested that

  While conventional treatment modalities for epilepsy are reasonably effective, these treatment modalities have several significant drawbacks. One technique for suppressing epilepsy involves the use of dopaminergic or anticholinergic agents. In order to control epilepsy using this technique, it is necessary to repeat dosage adjustments to balance efficacy and side effects. A number of drugs, including lorazopan, diazapan, sodium valproate, phenobarbital / primidone, ethosuximide, gabapentin, phenytoin and carbamazepine, are approved and available for the treatment of epilepsy. Unfortunately, these drugs usually have serious side effects, especially toxicity. In addition, in most cases it is crucial to maintain accurate therapeutic serum levels to avoid catastrophic seizures (when doses are too low) or toxic effects (when doses are too high). is there. The need for training a patient is high, especially when the combination therapy results in unpleasant side effects that the patient would want to avoid. In addition, many patients with epilepsy respond well to medication, but a significant number (at least 20% to 30%) do not. For those patients, surgery is now the most established and most viable alternative treatment strategy.

  Common surgical procedures performed for medically difficult to treat epilepsy include cerebral hemispherectomy, cortical resection, lobectomy and partial lobectomy, and less radical resection of the lesion There are surgical resections, such as cutting, stereotaxic destruction. Surgery is not always completely successful and is generally at risk of complications. In addition, surgery can damage language-related (ie, functionally important) areas of the brain and result in long-term impairment of various cognitive and other neurological functions. Surgical treatment is contraindicated for a number of reasons in a significant number of patients. In addition, many epilepsy patients who have undergone surgery are still not released from epilepsy after surgery.

  Another conventional technique for suppressing epilepsy is tissue destruction. Tissue destruction is usually performed by stereotactic neurosurgical procedures, including pallidal bulb destruction, thalamic destruction, hypothalamic destruction, and other destruction. These approaches are only moderately effective.

  Tissue disruption not only has an inherent surgical risk, but also has a number of fundamental limitations. One obvious limitation is the irreversibility of tissue removal or destruction. Therefore, excessive or accidental removal of tissue is fatal.

  Electrical stimulation is an emerging method for treating epilepsy. However, currently approved and available electrical stimulation devices are those that apply continuous electrical stimulation to the neural tissue surrounding or in the vicinity of the implanted electrode, and can be detected. In short, these electrical stimulators do not respond to the associated neurological condition. An example of an electrical stimulator is Cyberonics, Inc. There is a Neurobernetic Process (NCP). The device's vagus nerve stimulator (VNS), for example, applies a continuous electrical signal to the patient's vagus nerve. VNS has been found to reduce seizures by about 50% in about 50% of patients examined. However, in order to provide substantial clinical benefit, it is necessary to further reduce the incidence of seizures. VNS can change the electrical pattern of seizures, and can eventually suppress seizures by lengthening the time between seizures. However, one study suggests that quality of life depends on the frequency of seizures and not necessarily on the time between seizures. Therefore, the ultimate goal of anti-epileptic therapy should not merely promote seizure reduction by changing seizure patterns or increasing the time between seizures, but actually stop seizures. Should be allowed to.

  Electrical stimulation has also been used to treat other neurological disorders. For example, the commercially available product, Medtronic, Inc.'s Activa Deep Brain Stimulator is primarily intended for the treatment of Parkinson's disease and is a chest-embedded continuous deep brain stimulator. . This device has electrodes embedded within a given neurological region and provides continuous electrical pulses to selected deep brain structures. Chronic high frequency intracranial electrical stimulation is usually used to suppress cellular activity with the aim of functionally mimicking the effects of tissue destruction. Short-term electrical stimulation of nerve tissue, as well as electrical recording and impedance measurement of nerve tissue, are widely used for the identification of brain structures such as target localization during neurosurgery for the treatment of various neurological disorders. This is the method used.

  There has been no consistent success in continuously stimulating deep brain structures for the treatment of epilepsy. In order to effectively stop seizures, it is believed that stimulation should be performed near the epileptic lesion. Lesions are often in the neocortex, and continuous stimulation in the neocortex can cause serious neurological deficits with clinical symptoms including aphasia, sensory disturbances, or involuntary movements. Alternatively, generalized seizure lesions can move, thus necessitating the insertion of an electrode where the lesion moves. This, like other normal treatment modalities, offers some benefit to patients with epilepsy, but its effect is often limited.

  Therefore, auto-responsive epilepsy treatment based on the detection of impending seizures has also been the subject of research. Neuropath, Inc. Is currently developing and clinically testing an implantable responsive neurostimulator. Again, there are risks associated with implantable systems. If symptoms develop when the epileptic focus is moving or there is no clear focus, it is almost impossible to place the electrode at all the locations where the seizure focus will be. A compromise must be made to minimize the number of electrodes to embed and still maximize effectiveness. Another major concern is that such devices cannot be implanted quickly enough during sudden attacks with drug resistance.

  Trigeminal stimulation is a possible method for desynchronizing seizure activity. Advanced Bionics, Inc. The company is currently developing an implantable device for treating epilepsy that applies electrical stimulation to the trigeminal nerve. Like the vagus nerve, the trigeminal nerve does not protrude into all areas of the brain and cannot stop all seizures. This method also has the same concerns as in an implantable device similar to the device described above.

  There is only one case report in the literature regarding the use of electrical shock therapy (ECT) in medically refractory seizures in human patients (Griesemer et al., Neurology; 1997 49 (5): 1389-92). In some cases, one patient experienced “change in seizure pattern with pause at high intensity” and another patient experienced “decreased frequency of spontaneous seizures”. Surprisingly, there are no further studies investigating this methodology in animal models or in human clinical systems. Electric shock therapy (ECT) is performed using a normal EEG electrode, which does not allow the stimulation to be focused on a specific volume of biological tissue. To perform ECT, strong muscle relaxants as well as sedatives are often used. Therefore, patients must be closely monitored.

  It has been proposed that the efficiency of seizure suppression is improved if electrical stimulation can be applied at or near the beginning of the lesion, ie, epileptiform activity. The detection of seizure lesions usually required very expensive and non-portable image processing equipment such as a functional magnetic resonance (fMRI) system. Even with such an elaborate system, real-time analysis of seizure activity still cannot be achieved. Another means for identifying the location of the stroke lesion is to drill a hole in the skull, insert an electrode, record and analyze the electrical activity from the brain, and identify the location of the lesion. The latter technique affects very healthy tissue, requires a neurosurgeon, and can lead to complications. Similar techniques are applicable for the treatment of Parkinson's disease and other neurological disorders. Another problem that none of these techniques can overcome is that the lesion can move to various other locations. Other image processing systems, such as fMRI and positron emission tomography (PET), rely on changes in blood flow, which changes in blood flow can take several minutes to occur and therefore change rapidly. It is impossible to capture an image of brain activity. In any case, it is difficult to map moving seizure lesions with electrodes inserted into the brain, and tracking the moving lesions requires many electrodes and many holes in the skull. .

  The use of electroencephalogram (EEG) is another approach to treating epilepsy. EEG is a method of recording brain electrical activity from the surface of the scalp without affecting healthy tissue. EEG can have a very good time resolution of less than 1.0 ms per sample. Also, EEG can make the system mobile and does not become particularly expensive. However, the type of electrode used has limitations in EEG, such as the difficulty of locating the source in the brain due to the smoothing effect of the skull and other body tissues.

  There are various ways to disclose mechanisms for locating biological electrical activity. All of these methods involve post-processing data acquired from either discs or bipolar electrodes. Post-processing includes either repeatedly comparing the simulated potential with the measured potential, or using a bank of software filters. A solution for locating the source by these methods is not to be real-time, and it is often necessary to use MRI / CT data. In one example, a magnetoencephalogram (MEG) is used to locate the source in the brain (see, eg, US Pat. No. 6,697,660). MEG has a high temporal resolution similar to EEG, but is very costly, immobile, and requires a dedicated room to use.

  In other examples, multiple spatial filters have been used to locate electrical sources from EEG signals in the brain (see, eg, US Pat. No. 5,263,488). This technique requires post-processing and uses normal EEG electrodes, which limits resolution.

  In other examples of locating electrical sources in the brain using EEG, MRI, other methods of imaging the head determine scalp, skull, cerebrospinal fluid, and brain shape and thickness (See, for example, US Pat. No. 5,331,970). Once this information is obtained, a computer model is then created and a mathematical blur correction algorithm is applied to estimate the location of the source on the cortical surface of the brain. This method requires a great deal of pre-processing time to determine where the source originates and cannot be used in real time.

  Similar techniques have been utilized to image cardiac electrical activity (see, eg, US Pat. No. 6,856,830). The method includes recording an ECG of the body surface, acquiring an MRI or CT image of the patient's torso, and inputting both elements into the heart-torso model. The next step of the method involves post-processing, where the body surface potential is calculated for a source in the heart and compared to the measured body surface potential. This procedure must be iteratively repeated until the two elements are within a given preset error range. Therefore, this procedure cannot be performed in real time. Furthermore, since a clear position of the source is not specified and recording is performed with a normal ECG electrode, distortion of the image due to the spherical source is clarified.

  In other examples, normal EEG recording techniques and / or MEG are used to limit where brain electrical activity may occur (see, eg, US Patent Application No. 2003093004). This approach is limited by the following facts. That fact is the fact that in order for this type of system to solve the reverse localization from the surface potential, the position of the activity must be known before the technique is performed. Furthermore, this technique has the disadvantage that the head is a volume conductor, resulting in a blur effect.

  In other examples, electrical impedance plethysmography (EIP) has been proposed for locating electrical sources within biological tissues (see, eg, US Patent Application No. 2003038095). In EIP, impedance characteristic tests made over a period of time are utilized to locate changes in body tissue. Electrical stimulation is injected into the tissue and the return signal is measured to determine the impedance. Sources below the surface interact with the injected signal, so the conductivity map is developed and a model is built to iteratively locate sources within the tissue based on these conductivities Is done. This type of device still relies on a typical EEG electrode, which receives a spherical signal and distorts the location process.

  Current approaches to treatment include currently available and under development systems, such as drugs, surgery and implantable systems, but such current approaches have various complex issues that can There is a need for a system that detects, treats, and prevents epilepsy without affecting healthy tissue in disorders, particularly epilepsy.

  Currently, electric shock therapy is used to treat various disorders such as depression. However, other treatment methods such as ECT and drug treatment and implantable systems currently used to treat various neurological disorders have a variety of complex issues, and satisfactory standardization of use and treatment can be met by the problems. Limited.

  In view of the above, there is a need for medical devices that can detect, prevent, and / or treat neurological disorders and that minimally affect healthy tissue. Preferably, such devices involve electrical stimulation because this approach shows great potential to achieve the desired result. It would also be desirable to have a method of detecting, preventing and / or treating that is safe, effective, short in duration, and with minimal or minimal impact on healthy tissue.

  Accordingly, it is an object of the present invention to provide a medical device for the detection, prevention and / or treatment of neurological disorders that can produce the desired results in a safe and consistent manner.

  Another object of the present invention is to provide an electrical stimulator utilizing a unique electrode system that distinguishes between various sources of electricity within the body's volumetric conductor by directly measuring brain electrical activity, Furthermore, it is to provide a medical device such as a feedback device.

  Another object of the present invention is to provide such a medical device that can improve the location of the source.

  Another object of the present invention is to provide a method for the detection, prevention and / or treatment of neurological disorders.

  Yet another object of the present invention is to provide a method for detecting, preventing and / or treating seizures by application of electrical stimulation.

  It is a further object of the present invention to provide a method that is safe, effective, minimally affecting healthy tissue, and shortening the treatment period.

  The present invention relates to a medical device for the detection, prevention and / or treatment of neurological disorders based on electrical stimulation. In one embodiment of the present invention, such a device comprises a unique electrode system that can be used to measure various electrical sources within the body volume conductor by directly measuring brain electrical activity. Can be distinguished. The electrode preferably comprises at least one outer conductive element and one central conductive element, which surrounds the central conductive element and thereby forms a concentric configuration. This concentric ring electrode has a very high spherical signal attenuation, thereby improving the localization process. The conductive elements of the electrodes can be arranged in rings, squares, rectangles, ovals, or polygonal concentric geometric configurations having any number of sides. The electrode is fabricated from a metal, a non-metallic conductive material, or a combination thereof, the metal or non-metallic conductive material being biocompatible or provided with a conductive biocompatible coating.

  In one embodiment of the present invention, a bioelectric nerve device includes a control module, one or more electrodes, and a power source. The control module includes a stimulation subsystem, a communication subsystem, and a central processing unit (CPU). The clock may be attached to the outside of the CPU or may be incorporated in the CPU. The electrode arbiter includes a directing logic controller and one or more electronic switches. The detection subsystem includes one or more amplifiers, one or more analog-to-digital (A / D) converters, and a digital signal processor (DSP). The impedance subsystem includes one or more impedance signal generators and an impedance controller. The stimulation subsystem includes one or more stimulation signal generators, a stimulation controller, and a high voltage power source.

  In one embodiment of the invention, the wires from the electrodes are connected to the electrode arbiter, detection subsystem and stimulation subsystem. The electric wire transmits a signal such as an electroencephalogram (EEG) signal from the electrode to the electrode mediator. Electrodes attached to a part of the patient are stimulated by the stimulation subsystem via an electrode mediator, whereby the electrodes are energized. The electrodes can preferably be attached to the patient's scalp by placing them above or below the scalp, or by placing them anywhere between the scalp and the brain, or anywhere in the brain. This attachment promotes brain stimulation.

  The invention also relates to a method for the detection, prevention and / or treatment of neurological disorders.

  In one embodiment, the method includes placing at least one two-element electrode on a portion of the mammal and monitoring the electrical signal pattern of the mammalian brain to detect the presence or onset of a neurological phenomenon. Including confirming, confirming the position of the brain electrical pattern exhibiting neurological phenomena before applying electrical stimulation, and applying electrical stimulation to beneficially change the electrical pattern of the brain .

  In one embodiment of the present invention, brain electrical signals directly locate at least two specific volumes of tissue with at least nine electrodes arranged in a specific configuration. In other embodiments, this direct localization is achieved by a tripolar or more concentric electrode configuration.

  The methods of the present invention include the application of electrical stimulation percutaneously, transcranial or in combination. The electrical stimulation can be applied in the form of a continuous current, a pulse current, a continuous voltage of a specific pulse pattern, a pulse voltage, or any combination thereof. Suitable electrical stimulation frequencies for use herein are in the range of about 0.1 Hz to about 2500 Hz, and suitable pulse widths for use herein are in the range of about 10 μs to about 10 seconds. Yes, suitable stimulation durations for use herein range from about 15 seconds to about 30 minutes. The method of the present invention provides a voltage in the range of about 500 mV to about 2 kV, preferably about 30 volts to about 100 volts, and a current amplitude in the range of about 0.01 mA to about 1000 mA, preferably about 5.0 mA to about 50 mA. Including applying.

  The method of the present invention also relates to the use of a bioelectric neural device to deliver electrical stimulation via concentric electrodes, along with other peripheral stimulation techniques such as drugs.

  The bioelectric neurological device and methods associated with the device of the present invention can minimize the impact on healthy tissue and preferably prevent the healthy tissue from being affected.

  The above summary of the present invention is not intended to describe each illustrated embodiment or every implementation of the present invention. These embodiments are specifically illustrated by the following figures and detailed description.

  While the invention is readily amenable to various modifications and alternative forms, the details thereof are shown by way of example in the drawings and will be described in detail. However, it is to be understood that the intention is not to limit the invention to the specific embodiments. On the contrary, the intent is to include all modifications, equivalents, and alternatives falling within the spirit and scope of the invention as defined by the appended claims.

  The present invention relates to a medical device for detecting, preventing and / or treating a neurological disorder based on electrical stimulation. The invention also relates to methods for detecting, preventing and / or treating neurological disorders utilizing such devices.

[1. Definition)
The term “bioelectric neural device” as used herein refers to a medical device for the detection, prevention, and / or treatment of neurological disorders through electrical stimulation.

  The term “concentric” as used herein refers to an electrode element in which a larger element surrounds a smaller element. In a preferred embodiment, a conductive element configured as a ring with a continuously increasing radius surrounds the central conductive disk.

  In other embodiments, the conductive elements surrounding the central electrode element may be square, rectangular, elliptical, or polygonal with any number of sides.

  The term “electric source” as used herein generally refers to a neuron or nerve that produces an electrical signal in the brain. However, since it may be preferable to locate an artificial electricity source, such as deep brain stimulation therapy, such an artificial electricity source can also be contemplated herein.

  The term “electrode” as used herein refers to a conductor through which current passes as it enters and exits an electrolytic cell or other medium.

  The term “Laplacian” is derived from the second derivative of the potential and is named after its French inventor, Pierre Laplace (1749-1827), and is used herein. Sometimes refers to the second-order spatial differentiation of the sensed potential measured by the concentric ring electrodes. Laplacian increases the spatial frequency. When used to perform stimulation, these concentric ring electrodes similarly concentrate the electric field in the tissue more clearly than typical electrodes.

  The term “neurological disorder” as used herein refers to disorders, diseases, and / or due to or resulting from neurological, psychiatric, psychological, and / or cerebrovascular symptoms or origins. Or refers to syndrome. Neurological disorders include epilepsy or other general or partial seizure disorders, Parkinson's disease, Huntington's disease, Alzheimer's disease, Pick's disease, Parkinsonism, rigidity, half-sided ballism, chorea athetosis, dystonia, inequity, slow movement, Hyperactivity, depression, bipolar disorder, anxiety, phobia, schizophrenia, multiple personality disorder, substance abuse, attention deficit / hyperactivity disorder, eating disorder, abnormal control of aggression or sexual behavior, headache Or include, but are not limited to, chronic headache, migraine, shaking, post-concussion syndrome, stress-related disease, or any combination thereof.

  The term “neurological phenomenon” as used herein refers to abnormal neural activity such as seizures, migraine, depression.

  The term “stimulus” as used herein refers to one or more electrical signals applied to the scalp, brain tissue or the vicinity of brain tissue, or the skin surface such as the face or neck.

  The term “N” as used herein refers to an indefinite or overlapping occurrence of an item, eg 1 to N.

  The term “sensitivity” as used herein refers to signals detected by an electrode from an electrical source directly below the center of the electrode and detected by the electrode from an electrical source that is not directly below the center of the electrode. The ratio to the measured signal.

  It should be understood that the singular forms “a” and “the”, when used in the specification and the appended claims, refer to the plural unless the context clearly dictates otherwise. Contains.

[2. (Bioelectric nerve device)
An embodiment of a medical device of the present invention, ie, a bioelectric neurological device 100, is shown in FIG. 1, which includes a control module 110, one or more electrodes 120, and a power source. The bioelectric neurological device 100 may further include an external device for observing a signal, a device control unit, and an electric wire. Depending on the application, the medical device of the present invention may have different functions and / or configurations. For example, for the detection, prevention, and / or treatment of seizures such as epileptic seizures, the device may be an oncogenic stimulator or fibrillator, and for the treatment of depression, the device may be depressed. It may be a stimulator for medical use, and the same applies to other uses. The function of the triggering fibrillator includes detecting specific electrical activity due to or resulting from a neurological disorder such as epilepsy. Depressive stimulator functions include detecting specific electrical signals due to or resulting from depression. Regardless of the intended application, this device includes a unique concentric electrode design that directly detects the depth of the electrical source, locates the source at the body surface, and provides high resolution. It can be used for the detection of electrical signals. Thus, the bioelectric neural device has the ability to locate the source of the generated electrical activity. In addition, the device is able to target areas with more limited area and deliver more uniform stimuli and improve neuropathy more quickly than is possible with normal electrodes. The bioelectric neurological device can also compare the states before and after applying the stimulus to determine whether a further dose of stimulation is required. If it is determined that more stimuli are needed, the device can apply additional stimuli, and if it determines that no more stimuli are needed, the device will continue to analyze the electrical signal and need further treatment. It is determined whether or not.

  The control module 110 of the bioelectric neurological device includes an electrode arbiter 111, a detection subsystem 112, an impedance subsystem 113, a memory subsystem 114, a stimulation subsystem 115, a communication subsystem 116, and a central processing unit ( CPU) 117. The clock 117a may be attached to the outside of the CPU 117, or may be incorporated in the CPU 117. An embodiment of the electrode arbiter 111 is shown in FIG. 2, and includes an orientation logic controller 111a and one or more electronic switches 111b. The detection subsystem 112, one embodiment of which is shown in FIG. 3, includes one or more amplifiers 112a, one or more analog-to-digital (A / D) converters 112b, and a digital signal processor ( DSP) 112c. An embodiment of the impedance subsystem 113 is shown in FIG. 6 and includes one or more impedance signal generators 113a and an impedance controller 113b. The stimulation subsystem 115, one embodiment of which is shown in FIG. 7, comprises one or more stimulation signal generators 115a, a stimulation controller 115b, and a high voltage power supply 115c.

  The analog-to-digital converter 112b, digital signal processor 112c, digital memory 114, central processing unit 117, which may be a microcomputer, and amplifier 112a components used in the apparatus of the present invention are known in the art. It may be any component that is commercially available, or any component that is commercially available. The technique for wiring and programming these components may be any technique as is known in the art. Alternatively, the apparatus of the present invention may utilize custom built very large scale integrated circuits (VLSI) or hybrid circuits with these components or any combination of the functions of these components.

  In one embodiment of the invention, the wires from electrode 120 are connected to electrode arbiter 111 and to detection subsystem 112 and stimulation subsystem 115 as shown in FIG. The electric wire transmits a signal such as an electroencephalogram (EEG) signal from the electrode 120 to the electrode arbiter 111. The electrode 120 attached to the patient's scalp is stimulated by the stimulation subsystem 115 through the electrode arbiter 111, whereby the electrode 120 injects current into the patient. The electrode 120 can be attached to the scalp by placing it above or below the scalp, or it can be attached anywhere between the scalp and the brain, or anywhere in the brain. This attachment promotes brain stimulation. In another embodiment, a separate set of electrodes 120 and associated wires are utilized in each subsystem. In such a configuration, it may not be necessary to include the electrode arbiter 111.

  The bioelectric neurological device 100 of the present invention can minimize the impact on healthy tissue and preferably does not affect the healthy tissue. This can be advantageous for a variety of reasons. For example, the device can be used without having to perform a surgical procedure to implant the device. Thus, the device can act on a person very quickly in an emergency situation. Studies show that better treatment results can be achieved if treatment is given earlier to reduce seizures. In addition, no surgical procedure is required to replace the electrodes. The electrodes can be easily replaced as needed. Also, existing electrodes can be replaced without surgery if a new electrode design is determined to be more effective. Also, the position of the electrodes can be changed without resorting to surgery. Only reconfiguration of the electrode attachment mechanism is required to accomplish this task, and the reconfiguration can be performed by a technician rather than a neurosurgical team. In addition, the battery can be replaced without the need for surgery. This task can be performed by anyone other than the neurosurgical team, such as a technician. These and other advantages make the use of bioelectric neurological devices very cost effective. One specific cost effective property of this device is that it can only be used for one person's treatment in the case of one implantable device, whereas one device can be used for treatment of multiple people. It can be used for. This is particularly important from a medical point of view because it can address the needs of multiple people rather than just one when using the device in an emergency situation.

[2.1 Detection Subsystem]
The detection subsystem 112 of the bioelectric neural device 100, such as a triggering fibrillator, serves to detect neurological phenomena. The detection subsystem 112 automatically detects neurological phenomena. In one embodiment of the invention, the detection subsystem 112 receives a signal, such as an EEG signal (referenced to the system ground), from the brain or other source, as shown in FIG. 3, and processes the signal. Identify neurological phenomena such as epileptic seizures or precursors of epileptic seizures. Central processing unit (CPU) 117 and memory subsystem 114 function to control and coordinate all functions of the firing fibrillator. CPU 117 transmits programming parameters and instructions to detection subsystem 112 through the interconnect. The detection subsystem 112 transmits a signal to the CPU 117 that confirms the detection of the neurological phenomenon. The detection subsystem 112 can also transmit EEG and other related data to the memory subsystem 114 for storage. Currently available memory techniques are suitable for EEG storage. For example, EEG storage for a 42-electrode system using 16 bits per sample (2 bytes) at a sampling rate of 500 samples per second (greater than 5 times the sampling frequency of up to 100 hertz (Hz)) is 1 A data storage device of 2,520,000 bytes per minute is required. Generally, flash memory is available as a 256 megabyte device capable of storing about 100 minutes of data.

  The detection subsystem 112 includes one or more amplifiers 112a, one or more analog-to-digital (A / D) converters 112b, and a digital signal processor (DSP) 112c. The amplifier 112a may include additional signal processing circuitry such as a bandpass filter. The bandpass filter operates as a prefilter that can remove the frequency components of the signal from the outside, or the signal frequency components that can interfere with the components of the higher detection subsystem 112. Usually, bandpass filters limit the transmission of low and high frequencies. The bandpass filter needed to be attached to the scalp surface without affecting healthy tissue should not use the same frequency parameters used in devices that affect healthy tissue. On the scalp surface, contact between the skin and the electrode can produce an artificial result that the frequency is lower than the frequency from the implanted electrode. In addition, movement of the subject may result in an artificial result that the frequency is lower than the frequency seen when using electrodes that affect healthy tissue. For external devices that do not affect healthy tissue, it may be advantageous to set the cutoff frequency (cut-off) of the high-pass filter higher than the frequency for systems that affect healthy tissue. Usually, there are not many signals exceeding 40 Hz present in the electroencephalogram activity. If the low pass filter is set for 40 Hz, a 60 Hz or 50 Hz notch filter may not be necessary.

  These components are preferably modular and may have a separate structure (architecture), but may be incorporated into a dedicated integrated circuit due to space, power or cost issues. The dedicated integrated circuit may be a single mixed type, or may be a dual type including one circuit for analog processing and one circuit for digital conversion and processing. The detection subsystem 112 may exist as a stand-alone unit and may be integrated with the electrodes, amplifier 112a, stimulation subsystem 115, or other components of the stimulation device.

  The components of the detection subsystem 112 can be placed in or on the subject's body. For example, the detection subsystem 112 and other triggering fibrillator components can be placed subcutaneously in the subject so that the triggering fibrillator is completely independent within the subject's body.

  Usually, the electrical activity (recorded by electroencephalogram) generated in the subject's brain where no neurological phenomenon exists is normal, and is generally a constant signal that hardly changes in magnitude. During neurological phenomena such as seizures, electrical activity has a synchronous additive effect, resulting in an EEG that is higher or lower than normal EEG.

  In one embodiment, the firing fibrillator detection subsystem 112 uses the signal filtered by the bandpass filter to identify the pattern of brain activity that characterizes the neurological phenomenon. Such a detection subsystem 112 can identify seizures using any of a number of algorithms. Such an algorithm can be adapted to identify components of the signal, including, but not limited to, signal magnitude, signal main frequency component, and time frequency analysis.

  When a neurological phenomenon such as a seizure is detected by the detection subsystem 112, the CPU 117 transmits an electrical signal to any one or more of the electrodes 120 through the electrode arbiter 111 and the wire, Commands can be directed to the stimulation subsystem 115. It is anticipated that transmission of appropriate electrical signals to specific locations in, on or near the brain can stop the normal progression of epileptic seizures. Also, in order to prevent the stimulation signal from being erroneously interpreted as a neurological phenomenon by the detection subsystem 112 or damaging the detection subsystem 112, the stimulation subsystem 115 may Immediately before, it may be necessary to temporarily disable the detection subsystem 112 through the electrode arbiter 111.

  In other embodiments of the present invention, the detection subsystem 112 sends signals to the stimulation subsystem 115 (to the CPU and then) during periods when the signal meets the requirements of a given neurological phenomenon, and the neurology No signal is sent to the stimulation subsystem 115 when the brain activity associated with the target phenomenon has ceased. That is, the stimulus signal is sent only when a neurological phenomenon is present, and the stimulus signal is not sent when the EEG signal is below a threshold or does not meet a known pattern of neurological phenomena. . Side effects can be prevented by sending a signal to the stimulation subsystem 115 only during periods when a neurological phenomenon is present. Moreover, by doing so, possible damage or harm to the tissue can be minimized or eliminated.

The detection subsystem 112 can directly detect sources at different depths to facilitate source localization, and this feature is essential for unique electrode designs. Sources of different depths are detected based on analysis of concentric disc guidance fields and ring bipolar guidance. In such a system, the sensitivity decreases rapidly at 1 / r 4 for dipoles outside the outer radius of the ring (ring), and the sensitivity to radial dipole localization is The maximum value is reached in the gap. A triode electrode system having a disc and two concentric rings around the disc can be considered as two bipolar electrode systems, ie the disc and the smaller ring form one bipolar system. The disc and the larger ring form a second bipolar system. If a source of electricity is found outside the area between the disc and the smaller ring, but inside the area enclosed by the larger ring, as in point “a” in FIG. The signal detected by the bipolar system of the disc and the smaller ring decays abruptly at 1 / r 4 while the signal detected by the bipolar system of the disc and the larger ring does not attenuate. The potential measured at the larger electrode is greater than the potential at the smaller electrode. If the source is within the radius of the smaller electrode, the potential measured by the smaller electrode will be greater than the potential measured by the larger electrode. Thus, each disk and ring bipolar system spatially selects sources that are within the radius of those systems. In addition, the addition of a larger ring further expands the area where the electricity source can be located by the electrode system.

The source need not be on the plane of the electrode. The same concept applies to depth detection. In this way, a specific depth range can be determined. Consider a source below the plane of the electrode, as shown at point “b” in FIG. The distance from the source to the center of the disc is outside the radius of the smaller ring bipolar electrode (IR) and inside the radius of the larger ring bipolar electrode (OR). Thus, the signal detected by the disk and the bipolar electrode of the smaller ring abruptly attenuates at 1 / r 4 , but the signal detected by the outer larger ring is not attenuated. The potential of the outer ring is greater than the difference potential between the disc and the middle ring. On the other hand, when the dipole is within the radius of the middle ring, the difference potential between the disc and the middle ring is greater than the difference potential of the outer ring.

  Limiting the location of the source directly to a specific volume of tissue, or directly limiting the location of the source to another medium is achieved by the unique concentric electrode configuration provided by the device of the present invention. It can also be achieved by a specific configuration with ordinary electrodes. This unique feature is achieved significantly better with concentric electrodes than with normal electrodes, because concentric electrodes can distinguish spherical sources much more than normal electrodes. . This spherically decaying feature limits noise that occurs beyond the distance outside the concentric electrodes. The hardware, i.e. electrodes and circuit components, provides the electrode difference signal from the electrode 120 controlled by the detection subsystem 112 to the digital signal processor 112c. These difference pairs combine increasing electrode sizes. First, the difference between the potential of the disc and the innermost ring is obtained in a bipolar arrangement [disc-ring (1)], and then the disc and the same ring are shorted together as shown in FIG. Then, the difference between the potential of the next largest ring and the shorted pair is measured as [1/2 (disk + ring (1)) − ring (2)]. The average potential of the shorted electrode element is always used. This pseudo-bipolar difference method can be applied to any number of concentric elements. The pseudo-bipolar difference method can be implemented using electronic circuitry, or it can also be implemented by taking a differential input between the electrode element and the reference electrode and digitally linking the difference signal with a software algorithm. it can.

[2.2 Impedance subsystem]
The stimulation impedance subsystem 113 of the present invention is used to examine the impedance between the skin and the electrodes. In general, signals are transmitted more effectively when the impedance is low. In one embodiment of the present invention, the impedance subsystem 113 is used to inspect and confirm that the skin and electrode are in contact and maintained as shown in FIG. If the contact between the skin and the electrode becomes too strong, the signal degrades in both directions, i.e. from the detection side to the stimulation side. Impedance subsystem 113 generates a signal of known magnitude and frequency and teaches electrode arbiter 111 that a particular electrode 120 needs to be tested for skin-to-electrode impedance. The impedance controller 113b determines which electrodes are to be tested and incorporates them during the stimulation waveform or at the beginning of the stimulation waveform sequence. The arbiter 111 routes the impedance test signal to a specific electrode 120 and routes the return path of the signal to the detection subsystem 112. The magnitude of the received signal is then compared to the magnitude of the transmitted signal, and the real part of the impedance between the skin and the electrode can be determined based on Ohm's law. At low frequencies suitable for use herein, such as from about 1 Hz to about 500 Hz, preferably from about 100 Hz to about 200 Hz, the impedance between the skin and the electrode is primarily a real resistance component. The stimulation subsystem 115 can also generate a signal for use in impedance detection, however, this creates a complex problem because the specification of the stimulation signal generator is not suitable for impedance detection applications. May occur. For example, the stimulus subsystem 115 typically applies stimuli in the milliamp range, while the impedance test circuit requires a current in the microamp range. Further, the stimulation subsystem 115 may generate a less complex stimulation waveform as compared to the impedance subsystem 113.

  Implantable systems currently in use may decrease in efficiency over time due to the electrode impedance increasing as a result of the electrode being encased in fibers. In one embodiment of the invention, constant current stimulation is used. When the impedance changes, the magnitude of the stimulation current is still the same and the efficiency is the same.

[2.3 Electrode Arbiter]
The stimulation electrode arbiter 111 of the present invention is a multiplexing mechanism. Stimulation electrode arbiter 111 is used to make or break connections between electrodes and subsystems such as stimulation subsystems. In one embodiment of the present invention, the electrode arbiter 111 can direct signals to and from a particular electrode 120 as shown in FIG. If separate electrodes are used for recording and stimulation, an arbiter is not necessary. Each electrode 120 can be connected to three subsystems: detection, impedance and stimulation. The orientation logic of electrode arbiter 111 receives commands from each of these subsystems and determines which electrode 120 is connected to which subsystem. For example, when the stimulation subsystem 115 attempts to apply a stimulus to a particular electrode that has been determined to be over an area that is causing a neurological phenomenon, the stimulation subsystem 115 may apply the stimulation subsystem to that particular electrode. Command the electrode arbiter 111 to connect 115. The arbiter 111 informs the detection subsystem 111 that the electrode 120 is about to be stimulated and is not connected to the detection subsystem 112. The other electrode 120 may still be connected to the detection subsystem 112 while the stimulus is ongoing in order to evaluate the effect of the stimulus on the neurological phenomenon. The electrode switch is utilized by the electrode arbiter 111 for quick and consistent activation and deactivation, and to prevent switch bounce. This electrical mechanism allows for a series of connections that map the various interconnections of the electrodes 120.

[2.4 Stimulation subsystem]
The stimulation subsystem 115 of the present invention can be started manually or automatically. Stimulation parameters may be entered manually or programmatically, and resident stimulation parameters may be used automatically.

  In one embodiment of the present invention, FIG. 7 shows stimulation subsystem 115 including interconnections with other subsystems. The stimulation subsystem 115 is used to stimulate the scalp, brain, or other biological tissue in response to detecting a neurological phenomenon. A preferred embodiment of the stimulation subsystem 115 comprises a stimulation controller and N stimulation signal generators, which are connected to the electrodes 120 via the electrode mediator 111 through wires. The phenomenon detection signal from the CPU 117 is received by the stimulus controller, which first sends a signal to the electrode arbiter 111 via the interconnection to link a specific electrode 120 from the detection subsystem 112. Disconnect. And it is prepared for the artificial result by stimulation to occur during stimulation. The stimulus controller then provides a stimulus command signal to the stimulus signal generator for a specific preprogrammed time period. Stimulation command signals may occur simultaneously and may have a relative delay with respect to each other. These delays can be downloaded by downloading instructions and parameters from the CPU 117. It may be desirable to adjust the delay so that the stimulus signals from the stimulus signal generator reach the lesion of the neurological phenomenon in the brain simultaneously and in phase. In doing so, the performance of the stimulation subsystem 115 in breaking the neurological phenomenon can be improved. Alternatively, experience has shown that out-of-phase when a particular signal reaches the lesion of a neurological phenomenon can be particularly effective in stopping the neurological phenomenon.

  The stimulus command signal can be used to control the amplitude, waveform, frequency, phase, and duration of the output signal of the stimulus signal generator, or any combination thereof. Different stimulation parameters can be applied to different electrodes 120, thereby allowing an interference pattern to be generated. The stimulus controller can also include multiple patterns of stimuli that are pre-programmed to automatically execute when triggered by the CPU 117 after a neurological phenomenon has been detected. ing. The CPU 117 can also be used to instruct stimulation parameters. Such a preset stimulation pattern may include a plurality of stimulation sequences, which may be other combinations of stimulation parameters used over various frequencies, magnitudes and / or specific lengths of time. You may have.

  A typical stimulus signal generated by the stimulus signal generator 115a is biphasic (ie, has equal energy positive and negative with respect to earth) with a typical frequency in the range of about 10 Hz to about 250 Hz. Although a frequency in the range of about 0.1 Hz to about 2500 Hz may be effective. It is also contemplated that a pure DC voltage may be used, although less desirable. When using frequencies above 30 Hz, a stimulation signal generator can be capacitively coupled to the electrode 120 to block the DC voltage. The typical width of a biphasic pulse is preferably between about 50 microseconds and about 500 microseconds, although pulse widths of about 10 microseconds to 10 seconds may be effective for certain patients. . The pulse widths of the positive and negative phases may be different in duration and / or magnitude. Typically, the voltage is applied in the range of about 30 volts to about 100 volts, and the current amplitude is applied in the range of about 5.0 milliamps (mA) to about 50 mA. However, when the impedance between the skin and the electrode is high, for example, 40,000 ohms or more, it may be necessary to use a size exceeding 2000V. Also, the current can be effective and safe without exceeding or exceeding this typical range. The stimulus is applied for a duration of about 15 seconds to 30 minutes, preferably about 30 seconds to about 5 minutes.

  Two-phase voltage (current) generation circuits are well known in the art of circuit design and need not be illustrated here. Similarly, programming code that provides various command parameters to the stimulus signal generator by the stimulus controller is easily accomplished using well-known programming techniques.

  If the waveform parameter adjusted by the stimulation controller's control law is the magnitude of the stimulation voltage, the design will not benefit from the independent impedance variation when controlling the stimulation current. Alternatively, adjustment of the stimulation pulse width may be desired. In certain circuit implementations, the available resolution or number of bits for specifying the magnitude of the pulse width may be greater than the resolution or number of bits for specifying the pulse voltage or current. In such cases, it may be desirable to modulate the pulse width if it is desired to control the magnitude of the stimulus more finely than is done with control of the pulse current or pulse voltage. Whether to select pulse voltage, pulse current, or pulse width adjustment as a managed pulse amplitude parameter is determined by the stimulus controller, which uses communication through the operator interface. Can be set. In other embodiments, the modulation of the pulse frequency and the number of pulses per burst are managed. Other such features may be managed in addition to or in place of the features described above.

  In one embodiment, a charge balanced biphasic waveform is preferably generated. The net charge contained in a given pulse is determined by the time integration of the stimulation current over the duration of the pulse. In a two-phase configuration, a pair of pulses of opposite polarity are generated, and the amplitude and pulse width of the pulse current are selected such that the magnitude of the charge amplitude is equal and the polarity is opposite. In some cases, it may be desirable for a pulse with a pair of biphasic pulses to have different amplitudes, in which case the pulse pair introduces a net charge of zero into the biological tissue, The pulse width is selected so that the charges are equal and opposite.

  The pulse pair waveform parameters are calculated to deliver a net zero charge, but in practice, due to noise and accuracy limitations and non-linearities in the digital-to-analog conversion and amplification stages, the resulting charge of the pulse pair There may be slight imbalances. Over time, this can result in a substantial accumulated net charge being delivered to the biological tissue. Capacitors that block direct current (DC) are used to eliminate the possibility of net charges being delivered to the neural tissue. This technique is well known in the art. In a preferred embodiment, a DC blocking capacitor is included in series with the stimulator output path.

  It is also expected that applying a stimulus from multiple sets of electrodes will produce a superposition effect where the intensity is weighted at the location where the stimulus is concentrated. This is beneficial because it reduces the stimulation intensity required for each set of electrodes and reduces the risk of damaging the tissue. Decreasing intensity also reduces the chance of stimulating areas of the brain that do not affect seizures.

  The feedback control signal for the detector / stimulator combination is preferably, but not limited to, an EEG signal and / or EMG and EOG. Stimulation is applied while a neurological phenomenon is being detected. This is basically proportional control. Where there are indications of stability and performance requirements, other components such as integrators and / or differentiators can be added to the control to form a proportional integral derivative (PID) controller.

  The power supply supplies power to each component of the apparatus. Such power sources typically utilize a primary (rechargeable) storage battery with an associated DC / DC converter to obtain the necessary voltage required by the bioelectric neurological device.

[2.5 Communication subsystem]
The communication subsystem 116 of the present invention can be used to allow external communication with a bioelectric neural device. In one embodiment of the present invention, the bioelectric neural device comprises a component based on a wireless telemeter, which component stores a stored EEG signal, detection parameter, or other parameter, computer, data storage It can be used for wireless transmission or downloading to a device, or an analytical component or device. New detection algorithms can also be downloaded to the detection subsystem 112 by radio telemeter or any other method.

  In one embodiment, data stored in the memory of the device is retrieved by the surgeon via a wireless communication link when the data communication subsystem is connected to the central processing system 117. Alternatively, an external data interface can be directly connected to an external surgeon or operator's workstation using a serial or USB connection in RS-232 format. Alternatively, the serial connection may be connected to the surgeon's workstation from the patient's home, emergency vehicle, or remote location via a modem and telephone line. Software within the computer component of the surgeon's workstation allows the surgeon to include EEG information before, during and after the neurological event, and the spike frequency of the patient's EEG, etc. The history of detected phenomena can be read, including specific information regarding the detection of neurological phenomena. The workstation also allows a surgeon or operator to specify or change programmable parameters of the bioelectric neurological device. High frequency transceiver circuits and antennas for this purpose are widely used in medical device data communications.

[2.6 Real-time clock subsystem]
The real-time clock 117a is externally attached to the CPU 117 or incorporated in the CPU 117, and is used to time and synchronize various parts of the bioelectric neurological device and is detected by the device. Used to enable the device to provide an accurate date and time corresponding to each neurological phenomenon recorded in memory. In one embodiment of the present invention, the CPU 117 transmits data to the clock 117a in order to set the correct date and time in the real time clock 117a.

[2.7 Concentric electrodes]
The electrode 120 for use herein is a surface electrode or a buried electrode, each type probably having different physical and material properties. Electrode 120 is sufficiently soft and flexible to adapt to the tissue it is in contact with, and may be flexible, rigid, and any deformation therebetween. Good. The conductive electrode 120 can be fabricated from various metals such as gold, platinum, iridium, non-metals such as conductive polymer materials, or any combination thereof, which are biocompatible or conductive. Biocompatible coating. Each electrode 120 has a multipolar configuration and comprises at least two conductive elements, although embodiments of electrodes having three elements, three poles are primarily disclosed herein. One or more conductive elements surround a central conductive element, such as a disc, in a concentric configuration. The width of the conductive element can vary such that increasing the width has an adverse effect on the spatial resolution. The conductive elements are configured such that a gap is formed between the conductive elements. The gap between the electrodes is preferably equal to the width of the conductive element to ensure the best approximation to Laplacian. This gap can be adjusted to provide a specific spatial filter, such as exponential filtering.

  Many unique features of the bioelectric neurological device provide various advantages to the medical device of the present invention. In one embodiment, the bioelectric neurological device performs an automatic determination of treatment dose. This dose is determined by the number of stimulating electrodes, the polarity of the electrodes, the electrode configuration, the stimulation frequency, the waveform of the stimulation parameters, the temporal transition of the stimulation size, the stimulation operating period, and the reference stimulation size. Including intermittent stimulation magnitude and timing, and other stimulation parameters. This automation feature provides additional benefits to the bioelectric neurological device.

  In one embodiment, the bioelectric neurological device provides the clinician with a signal processed sensory feedback signal to help the clinician manually select the size and pattern for optimal treatment. Sensory feedback provided to the clinician via the interface between the clinician and the patient includes the location of the seizure focus, seizure interval, tremor estimates, EEG signals, and other signals. It is not limited to.

  In one embodiment, the unique concentric electrodes of the bioelectric neurological device allow enhanced local electrical signal acquisition while rapidly attenuating electrical signals from more distant sources.

  In one embodiment, the unique concentric electrodes of the bioelectric neural device directly measure the depth and surface location of electrical activity without using other imaging modalities such as CT, PET, MRJ. This is particularly useful for locating abnormal neurological sources. Once the sources are located, they are targeted for focused electrical stimulation.

  In one embodiment, the concentric electrodes of the bioelectric neural device are used for stimulation. The same benefits gained by enhancing the detection of local electrical signals are also effective when applying electrical stimulation due to reciprocity. Stimulation can be focused on a specific volume of biological tissue (or other medium) using concentric electrodes.

  In one embodiment, the bioelectric neurological device is used to apply electrical stimulation simultaneously from a plurality of concentric electrodes, where the electrical stimulation originates from different sites and is directed to a specific location, and the stimulation intensity is Summed when routes intersect. Thus, the stimulation intensity from the individual electrodes can be reduced, thereby increasing the safety factor.

  Although the present disclosure describes medical devices having concentric ring electrodes, other electrode shapes such as rectangles, ellipses, or polygons such as triangles or pentagons may be utilized. However, the proximity of such electrodes to the Laplacian is reduced. In some possible situations, it may be advantageous to utilize a non-circular electrode shape to perform spatial filtering of the signal prior to electronic capture, such as exponential or elliptical filtering.

[3. Method for detection, prevention, and / or treatment of neuropathy]
A method for detecting, preventing and / or treating a neurological disorder using the bioelectric nerve device of the present invention will be described below. The flowchart of FIG. 8 shows the condition decision path used to implement these methods. The basic means for performing include a system located on the subject, as shown in FIG. In one embodiment, the neurological phenomenon is detected by the surgeon and confirmed by the detection subsystem 112.

  In other embodiments, the detection subsystem 112 automatically detects neurological phenomena. When a neurological phenomenon is detected, such as during epilepsy, the location of the origin of the neurological phenomenon is determined relative to a phenomenon having a specific origin. An electrical or other stimulus or some combination is then applied to treat the neurological phenomenon. The signal is accessed again to determine whether the neurological phenomenon is suppressed, and if not, the stimulus is reapplied. Each neurological phenomenon has specific characteristics that allow the detection subsystem to detect various neurological disorders, diseases, or syndromes using the same basic hardware and different detection algorithms and pattern matching databases. Distinguish. To prevent a neurological phenomenon, stimulation can be applied prior to the neurological phenomenon that is expected to occur, or at intermittent intervals as needed. Details thereof will be described below.

[3.1 Detection of neurological phenomena]
Past efforts to detect seizures by electrical stimulation and treat them accordingly have dealt with analysis of EEG and cortical electroencephalogram (ECoG) waveforms. In general, the EEG signal represents the overall neural activity potential that can be detected via electrodes attached to the patient's scalp. An ECoG signal, which is a deep brain counterpart corresponding to an EEG signal, can be detected via electrodes embedded above or below the dura mater and usually in the patient's brain. Unless the context clearly dictates otherwise, the term “EEG” is used generically herein to refer to both EEG and ECoG signals.

In order to improve the efficiency of seizure suppression, the focus of seizure activity is located before applying electrical stimulation. The unique method and apparatus of the present invention can directly measure the depth Z and X, Y position of the electricity source. This localization is used to locate the electrical activity origin of the neuropathy. The method of using the EEG signal for localization is very unique. The bioelectric neural device preferably detects the depth of the electrical source using a pseudo-bipolar method, as described in “Detection Subsystem”. Alternatively, the concentric electrodes are configured in a five-point or nine-point format for deeper depth detection. Moreover, a normal electrode can also be arrange | positioned so that a concentric electrode may be imitated for the purpose of depth detection. Considering the configuration shown in FIG. 10, where v 0 and v 1 to v 8 are potentials measured by ordinary disk electrodes respectively arranged at these positions, the potential difference of the five-point method P 5 is given by:

A modification of the 5-point method, ie the 9-point method, is used to calculate the potential difference P 9 according to the following equation:

  The 9-point method has an attenuation effect similar to the 5-point method. However, since 9 electrodes occupy a wider surface than 5 electrodes, the attenuation effect tends to begin at a greater distance from the source. This somewhat slower effect of the 9-point method can be seen from the comparison shown in FIG. As can be seen from the fact that the slope of the 5-point method is steeper than the slope of the 9-point method, the slopes of potentials in the 5-point method and the 9-point method are different. This difference in response in the five-point and nine-point methods for source position variation can be used to quantize the dipole source depth. Since disc electrodes are not effective in overall signal rejection, concentric electrodes are used in the apparatus and method of the present invention and the depth of the electrical source is directly measured.

  When the depth of the electricity generation source is measured with concentric electrodes having a plurality of dimensions, the X and Y positions are determined. When equation (8) is solved, the position of the dipole P (X, Y) is obtained. Here, it is assumed that the depth dz is known or measured by some method such as pseudo-bipolar difference method. The potential measured by the electrode is then used to locate the electrical source within the multiconducting medium. We speculate that a greater potential is observed on the electrode closer to the source than the far electrode.

The Laplacian potential at the center of the electrode can be approximated by equation (4) for a bipolar concentric ring electrode.

In the above equation, V disc1 is potential on the disc electrode, V Oring1 is potential on the outer ring, r o is the radius of the outer ring, LP1 is calculated using bipolar electrodes Laplacian potential. It has already been shown by the inventor that the tripolar concentric Laplacian potential is approximated by equation (5).

In the above equation, V disc1 is potential on the disc electrode, V mring1 is potential on the intermediate ring, V oring1 is potential on the outer ring, r o is a radius of the outer ring , LPN1 is the calculated Laplacian potential for the triode electrode.

The potential on the electrode is given by equation (6). Let R be the distance of the dipole from the center of the sphere. Referring to FIG. 12, R ≦ R 4 , and the line connecting the dipole and the electrode disk P 1 at the position P passes through the inner sphere (in the direction of PP 1 ) at the position P 4 . It intersects the other two balls in position P 3 and P 2. The potential on the surface electrode due to the dipole at position P is then given by:

Where V PE1 is the potential on the electrode and PP 4 is the distance between positions P and P 4 . Similarly, P 4 P 3 , P 3 P 2 , P 2 E 1 are the distances between these points, and dz 4 is the difference between the z coordinates of P and P 4 . Similarly, dz 3 is the difference between P 4 and P 3, dz 2 is the difference between P 3 and P 2, dz 1 is the difference between P 2 and P 1 .

The Laplacian potentials for the dipole and tripolar electrode configurations are calculated by Equations (4) and (5) and expressed as exp in Equation (8), and the analytical Laplacian of the surface potential is given by Equation (7 ) And is represented by cal in equation (8).

In the above equation, LPN 1 cal is the calculated Laplacian potential, and V PE1 is the potential on the disk given by equation (6). The position is specified using equation (8).

Where

Is the position located by (I + 1) iterations, and the matrix AT is the transpose of the matrix A given by

Of course, the above description is for the potential calculated in the computer model. In an actual system, the potential on the electrode is automatically measured and used to directly solve the X and Y positions in equation (8), and to solve the depth Z directly using pseudo-dipole or other methods. Used for.

  Other methods for locating the depth of the electricity source include a transfer function. As is generally known, the potential measured away from the surface or source depends on the dipole moment of the electricity source and the position of the electricity source in the volume conductor. It is also known that the potential measured at the surface and the potential measured in the volume conductor are further dependent on the size and shape of the electrode.

  There are many equations that relate the surface potential to the dimensions and shape of the electrode or to a position in a plane parallel to the surface. However, there is no analytical formula describing the three-dimensional position of the electricity generation source and the shape and dimensions of the electrode system at the same time.

As applicable to the present invention, an analytical equation that gives the potential measured by a disk electrode on the surface of the volume conductor by means of a radial dipole inside the volume conductor is defined as follows: The

Where Φ is the potential measured at the surface, q is the dipole charge, (xp, yp, d) is the dipole position, σ is the conductivity of the volume conductor material. Yes, r is the radius of the disc.

  By developing this equation, the potential measured by the fact that the ring is concentric with the disc electrode can be easily determined. Thus, this formula for the disc and the rings coupled together gives depth, but this is not possible with any other formula disclosed in the prior art.

  As shown in FIGS. 1 and 3, the detection subsystem has built-in functionality and the ability to receive new algorithms for detecting neurological disorders. There are generally many types of algorithms disclosed for this purpose, and these algorithms can be utilized in this detection subsystem. Since concentric electrodes have been shown to have significant advantages in signal detection compared to regular electrodes, the use of concentric electrodes with these detection algorithms should improve the efficiency of the algorithm.

[A. Detection and localization of epilepsy activity
The first task of suppressing epileptic seizures is to know that epileptic seizures are occurring. The occurrence of an epileptic seizure is determined by a bioelectric neurological device, such as a triggering fibrillator, or some means placed outside. While it is preferred to check for a seizure when it occurs, more preferred is to check the seizure prior to the occurrence of the seizure. An algorithm can be used to identify pre-seizure activity. A prominent feature of brain activity associated with seizures is that signals with large changes in voltage values (ie spikes) appear in the EEG signal transition. Such spikes can be caused by excessive synchronization of brain activity and quantitatively exceed voltage measurements due to brain activity that is normal and unrelated to seizures. Therefore, in general, the presence of a seizure can be confirmed by the appearance of a voltage spike in the transition of the EEG signal.

  In one embodiment, the seizure detection subsystem of the fibrillator compares the input EEG signal processed by the bandpass filter to a pre-set level with a predetermined threshold or seizures or epilepsy. The presence of seizures is detected by comparison with other patterns of brain activity associated with the condition. The seizure detection subsystem analyzes the input data using standard circuitry and / or software and performs a comparison between the input data and the seizure detection algorithm.

  The seizure detection algorithm can be adapted to “learn” the distinct characteristics of a subject's brain activity before, during, and even after an epileptic seizure. In this way, the seizure detection algorithm can store one or more parameters, which are monitored during the epileptic seizure of the subject. Subsequently, when the seizure is suppressed, the seizure detection algorithm incorporates data into the algorithm itself. Preferably, when a subsequent seizure occurs or is predicted to occur, the seizure detection algorithm recognizes the onset of the seizure based on the measured data and addresses the seizure early. The seizure detection algorithm is preferably adapted to evolve over time in a manner that makes it more effective for seizure recognition and prevention and / or suppression.

  The operator can preset the seizure detection algorithm. This seizure detection algorithm can be set manually via the operator's communication interface either before or after the final setting of the triggering fibrillator. Suitable seizure detection algorithms will be apparent to those skilled in the art in view of the present disclosure. Appropriate seizure detection algorithms can be modified and adapted as needed, which can help the detection subsystem improve over time and thereby constantly improve the efficiency of seizure detection. Then, the improvement in efficiency can also apply electrical stimulation more efficiently. Over a longer period of time, this results in a reduced seizure frequency and improved quality of life for those suffering. The seizure detection algorithm is preferably adapted to evolve over time in a manner that makes the algorithm more effective for seizure recognition and prevention and / or improvement.

[B. (Pain detection and localization)
It should be understood that a number of methods can be used to determine sites where it may be necessary to place electrodes for the purpose of suppressing pain such as headaches. Since the location of pain due to headaches varies from patient to patient, the exact location where the electrodes are placed must be determined on an individual basis. Electrode stimulation is preferably performed at diagnosis to identify the optimal stimulation site or sites that maximize pain relief. The bioelectric neurological device can be controlled by an operator as needed for self-administration doses, whether it be a surgeon, a treatment specialist, or a patient. Also good.

  The hardware and methods described above for epilepsy activity detection and localization are generally similar to the hardware and methods used for pain detection and localization. There are certain specific electroencephalogram patterns for different types of pain. An empirical database can be built for those suffering from the symptoms, and the data can be used to determine by comparison whether the patient's brain waves match any of the symptoms in the database. . If a match is found, appropriate treatment can be applied to relieve pain. Stimulation in a specific area can be used to facilitate the localization and diagnosis of a specific type of pain arising from a specific location.

  The method of the present invention can be used to treat pain that can be caused by a variety of conditions, including migraine with aura, migraine without aura, menstrual migraine, sub-migraine. Migraine, including type, atypical migraine, complex migraine, hemiplegic migraine, metamorphic migraine, and chronic daily headache, recurrent paroxysmal tension headache, chronic tension headache, Drug abuse headache, recurrent paroxysmal cluster headache, chronic cluster headache, subtype of cluster headache, chronic paroxysmal unilateral headache, persistent unilateral headache, posttraumatic headache, post-lumbar puncture headache, and cerebrospinal fluid Headache due to pressure drop, neuralgia due to chronic migraine, cervical headache, posttraumatic neck pain, postherpetic neuralgia involving the head or face, pain due to spinal injury following osteoporosis, and joint pain in the spine Headaches associated with cerebrovascular disease and stroke, and vascular disorders Headache due to arteriovenous malformation), joint pain in the spine, reflex sympathetic dystrophy, neck pain, glossodynia, carotid tenderness, cricoid pain, ear pain due to middle ear injury, stomach pain, Sciatica, maxillary neuralgia, sore throat, cervical muscle pain, trigeminal neuralgia (sometimes called painful tics), temporomandibular disorders, atypical facial pain, ciliary neuralgia, Trigeminal neuralgia (also called Raeder syndrome), musculoskeletal neck pain, pyramidal neuralgia, Eagle syndrome, idiopathic intracranial hypertension, orofacial pain, head, neck, and shoulder muscles Fascial pain syndrome, paratrigemic paralysis, neuralgia of the wing and palate ganglion (also referred to as subfacial half-headache, lower facial neuralgia syndrome, Thrader neuralgia, Sladder syndrome), carotid tenderness, Vidian neuralgia, and burning pain Although there are, but are not limited to.

[C. Detection and localization of other neurological disorders)
The hardware and methods described above for detection and localization of epilepsy activity are generally similar to the hardware and methods used for detection and localization of other neurological disorders. For certain movement disorders, it may be appropriate to incorporate means of detecting tremors that can detect EEG signatures or other signs related to movement disorders using various types of algorithms. For other types of neuropathy, there is evidence that specific electroencephalogram patterns can be clear. An empirical database can be constructed for those suffering from the symptoms, and the data is used to determine by comparison whether the patient's brain waves match any of the symptoms of neuropathy in the database be able to. If a match is found, appropriate treatment can be applied to alleviate the neuropathy. Stimulation at a specific area can be used to block pain from a specific area, thereby facilitating the localization and diagnosis of a specific type of neurological disorder arising from a specific position.

  The methods of the present invention can be used to detect and locate various neurological disorders, including Parkinson's disease, Huntington's disease, Parkinsonism, stiffness, hemi-barism, chorea athetosis, immobility Other movement disorders such as dysphagia, slow movement, hyperactivity, dystonia, cerebral palsy, essential tremor, hemifacial spasm, epilepsy, or neurological disorders such as general or partial seizure disorders, Alzheimer's disease, and Pick's disease Mental disorders such as depression, bipolar disorder, anxiety, phobias, schizophrenia, multiple personality disorders, and substance abuse, attention deficit / hyperactivity disorder, aggressive control abnormalities, or sexual behavioral abnormalities Mental disorders and other neurological conditions such as those associated with headache, shaking, post-concussion syndrome, stress, migraine, chronic headache, and atherosclerosis, cerebral aneurysm, stroke, brain And cerebrovascular diseases such as blood, although there are a any combination thereof, but is not limited to.

[3.2 Treatment and prevention of neurological disorders]
The bioelectric neural device of the present invention can be used to treat and / or prevent neurological disorders. This device applies a stimulus to a patient alone or with sensory input to elicit a therapeutic response. Sensory inputs are physical representations such as vibration, other electrical signals not directed to brain tissue (eg, somatic sensory stimulation by scalp twitching or sensation in the scalp or other parts of the body), flash, acoustic pulses May be included. For example, other types of stimuli by drug delivery may be provided from the detection subsystem on demand.

  The stimulation parameter generation algorithm resident in the stimulation controller 115b determines which electrodes must be supplied with electrical stimulation to reach the source when stimulation is required. The stimulation parameter generation algorithm instructs the electrode arbiter 111 to accomplish this task.

[A. Treatment and prevention of epilepsy
Preliminary studies by the inventors have shown that electrical stimulation can be used to suppress seizure activity in the brain. This idea can be easily changed to create an internal seizure arrester. Alternatively, both external and internal components can be used.

  The biological nerve device of the present invention, for example, a working fibrillator, is used for treatment and / or prevention of epilepsy. In its most basic variation, the firing fibrillator provides neural stimulation in the first mode, which is a non-responsive (ie, programmed) stimulation that regulates neural activity. However, this results in neuronal desynchronization in the brain, resulting in a decrease in neuropathy. Although non-responsive and responsive stimuli can be delivered from the same electrode, they may also be delivered from separate electrodes connected to the same triggering fibrillator. The position of the stimulation electrode is preferably such that the stimulation can target a lesion of neuropathy. However, this need not be the case.

  Non-responsive stimuli are typically delivered at a rate in the range of about 10 Hz to about 250 Hz and are made up of low intensity, short duration pulses. The pulse may be a square pulse, and may have other forms such as an exponential shape, a sine wave shape, a triangular shape, or a trapezoidal shape. The pulses can be voltage controlled or preferably current controlled. In general, the pulse is biphasic to achieve charge balance, but waveforms with a net DC component may also have utility when used with appropriate electrodes. In order to reduce the likelihood that the stimulus will promote epilepsy, a high frequency stimulus having a primary frequency in the range of about 10 Hz to about 250 Hz (ie, an inter-pulse interval of about 100 milliseconds to about 4 milliseconds) is applied for about 15 seconds From about 30 minutes or longer, and can be delivered from the same electrode as a responsive stimulus or from a different electrode as needed. Stimulation can be delivered periodically, as needed, or as required by the patient.

  The electrode 120 of the bioelectric neural device is preferably controllable to generate an output stimulus signal that can vary in voltage, frequency, pulse width, current, and intensity. Furthermore, the electrode 120 is preferably controlled so that the controller can generate both positive and negative current from the electrode, stop the current from the electrode, or change the direction of the current from the electrode. Is possible. The electrode 120 preferably has variable output capability, such as a complex exponential waveform, and linear output capability. The signal generator is typically expected to be used to control the electrode 120, but it should be understood that any signal may be used to allow the operator to adjust the electrode as described herein. A device or combination of devices may be used.

  Application of stimuli from the electrode 120 and adjustment of electrode parameters as described herein are preferably performed under the direction and guidance of the surgeon. However, the operator may be a technician or a patient, and the operator can activate the electrode 120 to stimulate the desired area. Although it is possible to configure the electrode 120 and the controller of the electrode 120 so that the patient can change the parameters of the electrode stimulation without the surgeon's instructions, it is not suitable for incorrect application of the methods disclosed herein. Such a configuration is not recommended because the patient may not have sufficient knowledge to avoid the associated risks.

  In one embodiment, electrode 120 is connected to a power source (such as a battery or a pulse generator) that provides an energy source for electrical stimulation. The electrode 120 may be monopolar or multipolar. However, it is preferred to use multipolar electrodes. Monopolar stimulation typically uses one pole and one reference electrode and requires a relatively large amount of current. In bipolar stimulation, adjacent electrodes are used in a state where current flows from the negative electrode (cathode) to the positive electrode (anode), and depolarization of nerve tissue occurs at a current level lower than that of monopolar stimulation. However, multipolar stimulation has multiple anodes and cathodes, so in practice one electrode can be the anode for another electrode and still the cathode for the positive electrode. Very complex electrolysis can be established in a biological tissue with a multipolar electrode configuration, which can benefit in desynchronizing epileptiform activity.

  In one embodiment, the electrode 120 is controlled to generate an electronic current for applying a stimulus. Preferably, the current comprises relatively high frequency pulses and can have a low frequency amplitude or frequency modulation. The exact parameters for electrode electrical stimulation can vary from patient to patient. However, based on known data regarding stimuli performed on the brain, suitable parameters for use herein are as follows: The frequency is in the range of about 0.1 Hz to about 2500 Hz, preferably in the range of about 10 Hz to about 250 Hz, and the pulse width is in the range of about 10 microseconds to about 10 seconds, preferably about 50 microseconds to about 250 microseconds. The voltage amplitude is in the range of about 500 mV to about 2 K volts, preferably in the range of about 30 volts to about 100 volts, and the current amplitude is in the range of about 0.01 mA to about 1 ampere (A). Preferably in the range of about 5.0 mA to about 50 mA. Shorter pulse widths are preferred due to safety concerns. In other embodiments, a high frequency burst of current is generated overlying the underlying low frequency continuous stimulus. Preferably, the electrodes are associated with a programmable controller that can be utilized to generate continuous, planned, or intermittent responsive stimuli. In other embodiments, the programmable controller is utilized to gradually increase the stimulus to a desired maximum level. Alternatively, the programmable controller is utilized to immediately generate the desired maximum level of stimulation or to perform any number of intermediate steps to reach the maximum level.

  In one embodiment of the present invention, the bioelectric neurological device 100 is used to prevent neurological phenomena. The method includes detecting and analyzing electrical activity in the brain to detect epileptiform activity or to detect such impending activity. A responsive stimulus can be initiated if epileptiform activity is present or imminent. The results of analyzing epileptiform activity can also be used to modify the parameters of non-responsive stimuli to improve the suppression of seizures or other undesirable neurological phenomena. Responsive stimulation is initiated when analysis of EEG or other signals indicates that a neurological phenomenon, such as epileptiform activity, is imminent or present. When the onset of a seizure is detected and an electrical stimulus is applied, the seizure is avoided. By definition, if all seizures are avoided, epilepsy is prevented.

  In other embodiments, the stimulus is applied intermittently or for a pre-set period to prevent epilepsy. Electrical stimulation can be applied as needed by the epileptic patient to prevent epileptic activity. When an epileptic patient feels a precursor, the patient can initiate electrical stimulation to avoid a seizure. The VNS system allows the patient to manually initiate stimulation as needed. Sustained effects of using electrical stimuli for seizures have been reported, suggesting that long-term benefits can be obtained using stimuli for short periods, such as using stimuli before going to bed. ing.

  In other embodiments, responsive stimulus parameters (eg, number of electrodes used, form of stimulus signal, number of pulses or cycles of stimulus signal, amplitude of stimulus signal, interval or frequency between pulses, duration of stimulus signal Time etc.) will be changed. The parameter change may be based on a pre-programmed sequence or may be based on some characteristic of detected abnormal neural activity. In addition, the response parameters of the response formula are determined between the various onsets of spontaneous abnormal neural activity, so that the stimulus itself predisposes the brain to the development of epilepsy (kindling). Be changed. Analysis of the brain's electrical activity can continue by analyzing the unstimulated electrodes while the stimulus is being applied to determine if the stimulus has the desired effect.

[B. Treatment and prevention of other neurological disorders
The bioelectric neural device of the present invention, such as a nerve stimulator, is used for the treatment and / or prevention of other neurological disorders. In one embodiment of the invention, the neurostimulator changes the stimulation intensity. The stimulus may be activated, inhibitory, or a combination of active and inhibitory, and the disorder is neurological or psychiatric.

  In the basic mode of operation, the neurostimulator 100 is used to apply a non-responsive stimulus, similar to that for epilepsy. Stimulation may be applied at a predetermined time interval as a preventive measure, or may be applied in response to detection of a neuropathy phenomenon. In the case of certain neurological diseases such as Parkinson's disease, the stimulus is applied to interrupt the neural activity that causes the development of the disease. For stimulation of the deep brain, bilateral stimulation of the thalamus or pallidum is usually targeted. Preferred stimulation parameters for use herein are a pulse in the range of about 100 Hz to about 200 Hz and a pulse width in the range of about 50 μsec to about 100 μsec for most of the time from start to stop. All of these stimulation techniques can be performed without affecting healthy tissue.

  Both non-responsive and responsive modes can be beneficial in preventing neuropathy. Electrical stimulation such as electric shock therapy is known to cause neurogenesis, so applying non-responsive neural stimulation even at preset intervals or occasionally causes it to act as a preventive maintenance mechanism for the patient's nervous system be able to.

[C. (Pain treatment and prevention)
The pathophysiology causing the discussed pain is often not completely clear. For example, in the case of migraine, a number of neurological and vascular events have been identified that occur before migraine pain occurs. Studies have shown that primary neuronal processes cause changes in the dural blood vessels, which induce aseptic inflammation that leads to trigeminal nucleus activation and the development of head pain. Specifically, activation of the central part of migraine in the brainstem and cortical depression following the onset of perivascular inflammation suppresses the patient's cortical nerve activity. In addition, dilation and contraction of the blood vessels in the head may occur. Because the main structures sensitive to pain in the brain are thick blood vessels, sinuses, and meninges, perivascular inflammation is thought to be the main cause of headaches often felt by migraine patients It has been.

  Thick cerebral blood vessels, cerebral puffy vasculature, thick sinus and surrounding dura mater appear after the nerve fiber plexus (mostly unmyelinated) that emerges from the trigeminal ganglion and the nerve roots on the upper cervical dorsal It is innervated by a skull cavity tumor. The nerve fiber plexus is the outer cylinder that wraps around the dural sinus and blood vessels. The nerve fiber plexus contains numerous inflammatory mediators. When the trigeminal ganglion is stimulated, inflammatory mediators are released, resulting in aseptic neurogenic inflammation of the perivascular space.

  The bioelectric neural device of the present invention is surgically implanted on or near the scalp with one or more electrodes, or on, in or near the brain for the treatment of a number of medical conditions Using electrodes, or any combination thereof, electrical stimulation of the adjacent dura or cerebral sickle of the sinus and superior sagittal sinus and blood, sinus, sigmoid, lateral sinus, It can be used to locate the junction of a straight sinus, a sagittal sinus, or a combination thereof.

  In one embodiment of the present invention, the bioelectric neurological device 100 is used to cut off neurogenic inflammation by stimulating nerve fibers that innervate the dural sinus. This uses the electrode 120 to apply electrical stimulation to one or more dural sinuses and / or the surrounding dura and cerebral sickle to cancel signals that pass through nerve fibers and stimulate neurogenic inflammation. Achieved by sending to It stimulates neurons that function to suppress signals, stimulates neurons that activate other neurons that function to suppress signals, stimulates neurons to directly suppress neurons, and neurogenic inflammation. May be caused by stimulation of stimulable neurons, or stimulation of a combination of the above. Such stimulation can also function to interrupt the process by which inflammatory mediators such as vasoactive peptides are released from afferent nerve fibers. The electrode need not be in direct contact with the nerve fiber, only the stimulation current needs to contact the nerve fiber.

  In one embodiment, the method of treatment provides pain relief even with neurogenic inflammation by blocking pain signals transmitted via nerve fibers. When a nerve becomes sensitive due to neurogenic inflammation, the nerve functions as a transducer, changing a chemical pain signal into an electrical pain signal. The nerve then sends the generated electrical pain signal back to the trigeminal ganglion and then to the brain stem and brain pain center, so that the patient perceives pain. Electrical stimulation applied by electrode 120 to one or more dural sinuses and / or surrounding dura mater and cerebral sickle affects the conversion of chemical pain signals into electrical pain signals. And the conversion can be adjusted, and further the transmission of electrical pain signals can be suppressed or prevented.

  The methods of the present invention also relate to using a bioelectric device to deliver electrical stimulation through concentric electrodes, along with other peripheral stimulation techniques such as drugs and / or speech.

  Although the above description of the invention has been presented with respect to human subjects (patients), it is understood that the invention is also applicable to the treatment of other mammals.

  As mentioned above, the present invention is applicable to devices for detecting, preventing and / or treating neurological disorders, and methods related to the devices. The present invention should not be limited to the specific embodiments described above, but rather should be understood to include all aspects of the present invention as explicitly set forth in the appended claims. It is. Various modifications, equivalent processes, as well as numerous structures to which the present invention can be applied will be readily apparent to those of skill in the art to which the present invention is directed upon review of the present specification. . The claims are intended to cover such modifications and devices.

  The invention will be more fully understood in view of the following detailed description of various embodiments of the invention in conjunction with the accompanying drawings.

FIG. 1 is a diagram schematically showing a control module of a bioelectric nerve device according to an embodiment of the present invention. FIG. 2 is a diagram schematically showing an electrode arbiter of the bioelectric nerve device according to the embodiment of the present invention and a connection between the electrode arbiter and other components. FIG. 3 is a diagram schematically showing the detection subsystem of the bioelectric neurological device according to the embodiment of the present invention and the connection between the detection subsystem and other components. FIG. 4 is a diagram schematically illustrating a configuration of a tripolar concentric electrode for directly detecting volumes at two depths according to an embodiment of the present invention. FIG. 5 is a diagram schematically showing a configuration of a tripolar concentric electrode for performing the pseudo-bipolar difference method according to the embodiment of the present invention. FIG. 6 is a diagram schematically showing the impedance subsystem of the bioelectric neurological device according to the embodiment of the present invention and the connection between the impedance subsystem and other components. FIG. 7 is a diagram schematically showing the stimulation subsystem of the bioelectric neurological device according to the embodiment of the present invention and the connection between the stimulation subsystem and other components. FIG. 8 is a flowchart illustrating a method for detecting, locating, and / or treating a neurological disorder according to an embodiment of the present invention. FIG. 9 is a diagram schematically showing the head of a subject on which the tripolar concentric electrodes according to the embodiment of the present invention are arranged. FIG. 10 is a diagram schematically showing the arrangement of nine electrodes arranged in an array for use in 5-point and 9-point calculations according to an embodiment of the present invention. FIG. 11 is a diagram schematically showing the difference between the electrical signals measured by the 5-point method and the 9-point method according to the embodiment of the present invention with respect to the variation in the lateral position of the dipole. FIG. 12 is a diagram showing a two-dimensional representation of the “four concentric sphere” head model according to the embodiment of the present invention.

Claims (31)

  1.   A medical device, comprising a control module, one or more electrodes, and a power source, the control module comprising an electrode arbiter, a detection subsystem, an impedance subsystem, a memory subsystem, and a stimulation subsystem. A medical device comprising a system, a communication subsystem, and a central processing unit, wherein the one or more electrodes include a multipolar configuration.
  2.   The medical device according to claim 1, wherein the detection subsystem comprises one or more amplifiers, one or more analog-to-digital converters, and a digital signal processor.
  3.   The medical device according to claim 1, wherein the impedance subsystem comprises one or more impedance signal generators and an impedance controller.
  4.   The medical device according to claim 1, wherein the stimulation subsystem comprises one or more stimulation signal generators, a stimulation controller, and a high voltage power source.
  5.   The medical device according to claim 1, wherein the one or more electrodes comprise at least one outer conductive element and a central conductive element, the at least one outer conductive element being the central conductive element. The medical device that surrounds the element.
  6.   6. The medical device according to claim 5, wherein the conductive elements are arranged in a ring, square, rectangular, elliptical, or polygonal concentric geometric configuration having any number of sides.
  7.   6. The medical device according to claim 5, wherein the conductive elements are arranged to form a gap between the conductive elements, the gap being equal to the width of the at least one outer conductive element.
  8.   The medical device according to claim 5, wherein the conductive elements are arranged to form a gap between the conductive elements, the gap being narrower than a width of the at least one outer conductive element; Or a medical device equal to the width of said at least one outer conductive element.
  9.   6. The medical device according to claim 5, wherein the one or more electrodes are surface or implantable.
  10.   6. The medical device according to claim 5, wherein the one or more electrodes are fabricated from a metal, a non-metallic conductive material, or a combination thereof, wherein the metal or the non-metallic conductive material is biocompatible. A medical device having a biocompatible coating that is conductive or conductive.
  11.   5. The medical device according to claim 4, wherein the one or more stimulation signal generators provide an electrical signal having a monophasic, biphasic, or polyphasic waveform.
  12.   5. The medical device of claim 4, wherein the one or more stimulation signal generators have a frequency in the range of about 0.1 Hz to about 2500 Hz and a pulse width in the range of about 10 μs to about 10 seconds. A medical device providing an electrical signal having a duration of about 15 seconds to about 30 minutes.
  13.   5. The medical device of claim 4, wherein the one or more stimulation signal generators supply a voltage in the range of about 500 mV to about 2 kV, or a current in the range of about 0.01 mA to about 1000 mA. apparatus.
  14.   The medical device according to claim 1, wherein the device is used for the detection, prevention, treatment of neurological disorders, or any combination thereof.
  15.   15. The medical device according to claim 14, wherein the neurological disorder is epilepsy or other seizure disorder, Parkinson's disease, Huntington's disease, Alzheimer's disease, Pick's disease, Parkinsonism, rigidity, hemi-ballistic, chorea, dystonia Ataxia, slow movement, hyperactivity, other movement disorders, depression, bipolar disorder, anxiety, phobia, schizophrenia, multiple personality disorder, substance abuse, attention deficit hyperactivity disorder, eating disorder, A medical device that is an aggressive or abnormal sexual behavior disorder, headache or chronic headache, migraine, shaking, post-concussion syndrome, stress-related disease, or any combination thereof.
  16. A medical method,
    a. Placing at least one electrode from two or more elements on a portion of a mammal;
    b. Monitoring the pattern of electrical signals in the mammalian brain to confirm the presence or onset of a neurological phenomenon;
    c. Applying electrical stimulation to beneficially alter the electrical pattern of the brain, wherein the stimulation is applied transcutaneously, transcranial, or a combination thereof;
    d. A medical method performed for the detection, prevention or treatment of a neurological disorder, or any combination thereof.
  17.   17. The medical method according to claim 16, further comprising the step of confirming a position of the brain electrical pattern exhibiting a neurological phenomenon before applying the electrical stimulation.
  18.   17. The medical method according to claim 16, wherein the electrode by the at least two elements is placed on or under the scalp, or surgically implanted on, in or near the brain. Or a medical method that is any combination thereof.
  19.   17. The medical method according to claim 16, wherein the electrical stimulation is applied in the form of a continuous current, a pulse current, a specific pulse pattern, a pulse voltage, or any combination thereof.
  20.   17. The medical method of claim 16, wherein the electrical stimulation is performed at a frequency in the range of about 0.1 Hz to about 2500 Hz, with a pulse width in the range of about 10 μs to about 10 seconds, for about 15 seconds to about 30 minutes. Medical method applied over the duration of.
  21.   17. The medical method of claim 16, wherein the electrical stimulation lasts for about 30 seconds to about 5 minutes at a frequency in the range of about 10 Hz to about 250 Hz, with a pulse width in the range of about 50 microseconds to about 250 microseconds. A medical method applied over time.
  22.   17. The medical method of claim 16, wherein the one or more stimulation signal generators supply a voltage in the range of about 500 mV to about 2 kV, or a current in the range of about 0.01 mA to about 1000 mA. .
  23.   17. The medical method of claim 16, wherein the one or more stimulation signal generators supply a voltage in the range of about 30V to about 100V, or a current in the range of about 5mA to about 75mA.
  24.   17. The medical method according to claim 16, wherein the neurological disorder is epilepsy or other seizure disorder, Parkinson's disease, Huntington's disease, Alzheimer's disease, Pick's disease, Parkinsonism, rigidity, hemi-ballistic, choreoathetosis, dystonia Ataxia, slow movement, hyperactivity, other movement disorders, depression, bipolar disorder, anxiety, phobia, schizophrenia, multiple personality disorder, substance abuse, attention deficit hyperactivity disorder, eating disorder, A medical method that is an aggressive or abnormal sexual behavioral control, headache or chronic headache, migraine, shaking, post-concussion syndrome, a stress-related disorder, or any combination thereof.
  25.   18. The medical method of claim 17, wherein the electrical signal directly locates at least two specific volumes of tissue through at least nine electrodes arranged in a specific configuration.
  26.   18. The medical method of claim 17, wherein the electrical signal directly locates at least two specific volumes of tissue through a tripolar or more concentric electrode configuration.
  27.   18. The medical method of claim 17, wherein the electrical signal directly locates at least two specific volumes of tissue through at least nine single-element electrodes arranged in a specific configuration.
  28.   17. The medical method of claim 16, further comprising an electrode with at least three elements, wherein the brain electrical signal is an electrical signal between the first two elements of the electrode and the second two elements of the electrode. Medical methods that are monitored by detecting potentials.
  29.   29. The medical method according to claim 28, wherein the electrical potential is further utilized to detect the position of the brain electrical signal within a volume of the mammalian body.
  30.   17. The medical method of claim 16, further comprising an electrode with at least three elements, and applying a stimulus by generating a voltage between at least two elements of the electrode.
  31.   31. The medical method of claim 30, wherein the stimulation is directed to a specific location within a volume of the mammal's body using at least two electrodes.
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