Electrical and Magnetic Nerve Stimulation

Abstract

Provides electrical and magnetic nerve stimulation. [Solution] Neuromodulation is achieved by administering modulated pulsed electrical or magnetic stimulation to a patient in need thereof. Neuromodulation inhibits or enhances neuron-synaptic or muscle-synaptic transmission between neurons and muscle fibers. The modulated pulsed electrical or magnetic stimulation is varied based on the mean and standard deviation of one or more of biological variables. The biological variables include heart rate variability, EEG variability, EMG variability, and motion frequency measured in the spinal cord. The invention further comprises a device for delivering modulated electrical or magnetic pulses to the patient. Magnetic stimulation is provided by stimulation with an electromagnet or solid magnet.

Description

[Technical field]

[0001] The present invention relates to non-invasive neuromodulation using electrical and magnetic stimulation. Electrical and magnetic stimulation can suppress neuron-synaptic or neuron-muscle junction transmission. Electrical and magnetic stimulation can also enhance neuron-synaptic and neuron-muscle junction transmission. The present invention also relates to devices for delivering modulated electrical and magnetic pulses according to the present invention. [Background technology]

[0002] Neuromodulation is a medical process that acts directly on nerves to enhance or inhibit neural activity. Historically, neuromodulation has been achieved by delivering small amounts of electrical stimulation or drugs directly to the target area to affect activity in secondary area(s) associated with the target area. Neuromodulation can be applied to virtually every part of the body and can treat a wide variety of diseases and conditions, including but not limited to acute and chronic nerve and muscle pain, headaches, tremors, Parkinson's disease, spinal cord injuries, migraines, epilepsy, and urinary incontinence. Current magnetic field therapy employs single frequency stimulation. DISCLOSURE OF THEINVENTION

[0003] Briefly, in accordance with the present invention, neuromodulation is achieved by providing electrical or magnetic stimulation to a patient using modulated magnetic or electric pulses. Magnetic stimulation includes electromagnetic stimulation and solid magnet stimulation. Preferably, the magnetic pulses are random in the form of noise patterns, such as white noise, pink noise, purple noise, blue noise, brown noise, and red noise. Current therapies can inhibit or enhance neuronal synaptic transmission or neuronal muscular junction (NMJ) transmission. The present invention can be applied to treat a variety of indications and conditions, including but not limited to pain and various psychiatric disorders, including but not limited to post-traumatic stress disorder (PTSD), stroke, Alzheimer's Disease, autism, addiction, depression, sleep disorders, performance deficiencies, and similar conditions.

[0004] In one embodiment, the method of treatment includes first measuring a patient's biometric characteristics and generating a biometric data set. The biometric data set is compared to a normative database to determine whether the patient requires neuromodulation. The biometric data set is analyzed to identify distribution probability characteristics of one or more variables, and the mean and standard deviation of pulse period values ​​are derived. Then, the patient is subjected to magnetic stimulation, which includes modulated pulses based on the mean and standard deviation of one or more biovariables. The biovariables include, but are not limited to, heart rate variability, electroencephalogram variability, electromyogram variability, and movement variability frequency measured in the spinal cord. Depending on the modulated electromagnetic pulse employed, the neuromodulation can inhibit or enhance neural transmission between neurons or neuromuscular junctions.

[0005] Of particular interest in implementing the present invention is that both acute and chronic pain are controlled by administering random electromagnetic pulse stimulation limited to the high frequency band with a preferred noise pattern, and personalized transcranial magnetic stimulation is controlled by random TTL pulse trains normalized by a Gaussian distribution with individualized electroencephalogram mean period and its standard deviation, which is determined by the psychiatric or other neurological disorder of the patient being treated.

[0006] Medical conditions that may be treated in accordance with the present invention include rheumatoid arthritis, osteoporosis, fibromyalgia, spondylosis, cervical herniation, and muscle spasms, cramps, aches and pains caused by spondylosis, pain and stenosis of the neck, shoulders and arms, muscle or ligament sprains, herniated or ruptured disks, arthritis, osteoporosis, sciatica, amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), epileptic seizures, or back pain caused by Benign Fasciculation Syndrome, muscle wasting, upper motor neuron disease, stroke, multiple sclerosis (MS), arthritis, myositis, and polio, paralysis, tingling or pain, peripheral neuritis caused by autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, Guillain-Barré syndrome, and the like. syndrome), diabetes, injuries, vitamin B deficiency, and infectious diseases, including but not limited to shingles, Lyme disease, Severe Acute Respiratory Syndrome (SARS), SARS-CoV-2, long COVID, loss of smell and taste, and the AIDS virus. [Brief description of the drawings]

[0007] [Figure 1] FIG. 1 is an explanatory diagram showing a magnetic stimulation device according to an embodiment of the present invention. [Diagram 2] FIG. 1 is an explanatory diagram showing a magnetic stimulation device according to an embodiment of the present invention. [Diagram 3]FIG. 1 is an explanatory diagram showing a battery-powered electrical stimulation device according to one embodiment of the present invention. [Figure 4] 1 is a graph showing the color of noise according to an embodiment of the present invention. [Diagram 5] 1 is an explanatory diagram showing a rotary permanent magnet device according to an embodiment of the present invention; DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] All references herein to magnetic stimulation are equally applicable to electrical stimulation and vice versa. Magnetic stimulation includes electromagnetic stimulation and solid state (permanent) magnet stimulation.

[0009] In this embodiment, personalized neuro-muscular measurements for a patient are used with personalized electromagnetic or electrical stimulation methods.

[0010] Chronic nerve and muscle pain is often accompanied by local compensatory muscle spasms. Pain relief treatment must consider muscle relaxation. The present invention uses random electromagnetic stimulation to block signals at the neuromuscular junction (NMJ). The NMJ is the chemical synapse between motor neurons and muscle fibers. It allows motor neurons to transmit signals to muscle fibers, causing muscle contraction.

[0011] When an action potential reaches the presynaptic terminal of a motor neuron, synaptic transmission at the NMJ is initiated, and the motor neuron activates voltage-gated calcium channels, allowing calcium ions to enter the neuron. The calcium ions bind to sensor proteins in synaptic vesicles, triggering fusion of the vesicles with the cell membrane, and neurotransmitters are released from the motor neuron into the synaptic cleft. In vertebrates, motor neurons release acetylcholine (ACh), which binds to nicotinic acetylcholine receptors (nAChRs) on the muscle fiber cell membrane.

[0012] At the postsynaptic side, the muscle membrane generates a series of electrical activity called end-plate potentials (EPPs). When the presynaptic nerve terminal produces a large amount of ACh to trigger EPPs until a certain threshold is reached, an action potential is generated in the muscle fiber, causing it to contract. Effectively blocking the nerve impulse from reaching the NMJ, reducing neurotransmitter release or inhibiting EPPs, reducing muscle contraction or relaxing the muscle during twitching. In the absence of action potentials, ACh cysts spontaneously leak into the NMJ and cause a very small depolarization in the postsynaptic membrane. Such a small response is called a miniature end-plate potential (MEPP). MEPPs occur spontaneously and have a random period of about 50 ms. The frequency of muscle activity associated with MEPPs measured by electromyography (EMG) varies between 20 Hz and 150 Hz (periods of 50 ms and 6 ms), reaching a peak value at about 70 Hz (period of 14 ms).

[0013] Random magnetic noise in the EMG frequency range applied to the NMJ is used to prevent EPPs from reaching the threshold of muscle contraction, relaxing the spasm and reducing the associated pain. Animal studies have shown that the diaphragm muscle contracts when external stimulation is applied to the connected nerve, and the contractile force of the diaphragm muscle increases with increasing nerve stimulation frequency, decreasing rapidly above 40 Hz. High frequency random stimulation has been used to relax muscle spasms and reduce associated pain.

[0014] In another embodiment, personalized transcutaneous magnetic stimulation is controlled by a random TTL pulse train that is limited to an individualized EMG frequency bandwidth (or periodic range between pulse-to-pulse) and employs the following scheme: 1. Record and store one or more digital EMG channels for offline analysis. 2. The raw data is band pass filtered between 20 Hz and 150 Hz to extract the dominant EMG signal at the wave's rest position. 3. Plot the wave at the zero-crossings of each complete cycle and calculate the time values ​​of the wave between each adjacent zero-crossing point. 4. The range of pulse-to-pulse time values ​​obtained from the above calculations is then used to generate a TTL pulse train with a white noise pattern within the limits of the EMG periodic variation.

[0015] In another embodiment, the present invention is used to enhance neural synaptic transmission in the central nervous system. In a preferred embodiment, repetitive transcranial magnetic stimulation (rTMS) is administered to patients to treat the psychiatric and physical conditions described hereinabove. To treat these patients, random magnetic noise in the EEG frequency band of 0.1-15 Hz is employed. Preferably, the magnetic stimulation pattern described above is white noise.

[0016] The personalized transcranial magnetic stimulation is controlled by a random TTL pulse sequence normalized by a Gaussian distribution, and the Gaussian distribution has an individualized EEG mean period and its standard deviation, using the following method. a. Record and store one or more digital EEG channels for offline analysis. b. The raw data is band-pass filtered between 4 Hz and 15 Hz to extract the dominant EMG signal at the wave's rest position. c. Plot the wave at the zero crossing points of each complete cycle and calculate the time values ​​of the wave between each adjacent zero crossing point. d. Calculate the mean and standard deviation of the aforementioned time values ​​for each recording channel over the entire recording period. e. Perform a Box-Muller transformation based on the individualized mean EEG period and standard deviation to generate independent standard normally distributed numbers for each TTL column.

[0017] <Noise Color> Besides Gaussian noise for EEG based stimulation methods, we also have the following types (colors) of noise, each type of noise being adapted to a specific electrical activity curve, e.g. mEPP or MEG.

[0018] Noise is classified based on its spectral density, which is directly proportional to the inverse of frequency (f) raised to the power of beta (β), and the power spectral density (W / Hz) is proportional to the power (W) or intensity (W / m 2 ) changes with frequency (Hz). JPEG0007654800000001.jpg10150

[0019] White Noise: One defining characteristic of such noise is that it has a flat power spectral density, meaning that it has equal power at every frequency. For white noise, β = 0. Pink noise is a signal whose power spectral density is inversely proportional to frequency, with β = 1. Brown Noise: If β = 2, the noise is brown noise. Compared to pink noise, brown noise loses power as frequency increases, and the rate at which it does so is much faster than pink noise. Blue Noise is a signal whose power spectral density increases proportionally to frequency, and β = -1. Purple Noise: When β = -2, the noise is purple / violet. Purple Noise has more energy in the high frequencies.

[0020] <Noise color discrimination> Data acquired in biometric measurements → Fourier transform → power → optical spectrum → curve fitting → noise color classification.

[0021] The generation of the TTL series random sequence is a reverse process, scaling the frequency (1 / period) of the random pulses based on the color of noise identified in the individualized biometric data. Figure 4 shows the simulated power spectral density as a function of frequency for each color of noise: purple (top), blue, white, pink, and brown / red (bottom).

[0022] The present examples illustrate the practice of the invention and should not be construed as limiting its scope.

[0023] Example 1: Treating the pain of shingles Shingles is a painful rash caused by a viral infection. It is most commonly described as linear blisters along the cranial or spinal nerve distribution. Symptoms usually include pain, burning, numbness or tingling, rash, blisters, and itching. All of these symptoms are related to the infected nerve. Hibernating herpes viruses tend to lie dormant in the body and reactivate in the ganglion. The pulse trains described in this patent application deliver electromagnetic stimulation treatment to the ipsilateral side of the ganglion (e.g., the spinal ganglion or trigeminal ganglion of the affected nerve) to effectively relieve the symptoms. The patient received white noise treatment on the ipsilateral side of the lesion every day (Monday through Friday), for 2 minutes each time, and reported a 60% or greater reduction in pain severity after the first treatment and a 90% reduction in pain severity after the third daily treatment. Ten hours after the first treatment, the red blisters at the site of the shingles skin lesions reduced by more than 50%.

[0024] Example 2: Treatment for quadriplegia caused by a traffic accident A 24-year-old male suffered a traumatic brain injury in a traffic accident nine (9) months prior to treatment. His injury included bleeding from the right hemisphere of the brain, resulting in quadriplegia. The patient developed uncontrollable stiffness and spasms in his left arm and leg. His Babinski sign was positive. Repetitive transcranial electromagnetic stimulation was administered to the patient's left cortex for 10 minutes continuously, with low frequency random pulses (<5Hz - white noise) stimulating for 10 seconds every 30 seconds. Four minutes after the first treatment, the patient's entire arm, including his leg and hand, relaxed. This was the first time the patient had been able to move both hands in the nine months since the traffic accident.

[0025] Example 3: Treatment of cerebral palsy A 4-year-old boy with cerebral palsy and incapacitated lower limbs was treated with electromagnetic stimulation (EMS) of low-frequency random pulses (<5Hz - white noise) for 6 seconds every 60 seconds, delivered continuously for 30 minutes to the cortical areas on both sides of the patient (5 days per week). After the 40th treatment, the patient achieved 80% muscle tone and was able to walk with assistance using some object (i.e., other person's hand, stable handrail, etc.) for support.

[0026] Example 4: Treatment of shoulder movement restriction A 40-year-old male patient had limited movement in his right shoulder. He could only raise his right arm approximately 30 degrees. The patient received electromagnetic stimulation of the affected scapula with high frequency random pulses (30-150Hz - white noise) for 3 minutes in alternating 10 second cycles (10 seconds stimulation / 10 seconds recovery / 10 seconds stimulation). After the 3 minute treatment course of magnetic stimulation was completed, the patient was immediately able to raise his right arm past the top of his head.

[0027] Example 5: Treatment of cervical movement restriction One 43-year-old female patient had limited cervical movement. She could only rotate her neck about 20 degrees to either side. The patient received electromagnetic stimulation of the posterior neck with high frequency random pulses (30-150Hz - white noise) in this restricted area (posterior neck) for 3 minutes in alternating 10 second cycles (10 seconds stimulation / 10 seconds recovery / 10 seconds stimulation). After the 3-minute course of electromagnetic stimulation was completed, the patient quickly recovered to full cervical movement.

[0028] Example 6: Treating stroke patients A 52-year-old male stroke patient had a stroke one year before receiving this electromagnetic stimulation treatment. Due to the stroke, the patient was unable to move his left arm and left leg. Electromagnetic stimulation was administered to the motor cortex on the right side of the brain for 30 minutes continuously with low-frequency random pulses (<5Hz - white noise) stimulating for 6 seconds every 60 seconds. After the initial treatment, the patient was able to move his left leg and left arm.

[0029] Example 7: Handling a scuba diving accident (bending) An experienced 41 year old male scuba diver dived below 150ft below the surface of the ocean but surfaced too quickly resulting in paralysis from the waist down for 7.5 years. Repetitive transcranial electromagnetic stimulation was administered to the patient's bilateral cortical areas for 30 minutes continuously (5 days per week) with low frequency random pulses (<5Hz - white noise) for 6 seconds every 60 seconds. Within 2 weeks of starting treatment the diver regained feeling in his legs and toes. By the end of the 5th week the diver was able to stand up.

[0030] Another feature of the present invention is equipment or hardware for delivering electromagnetic stimulation to a patient. This includes magnetic stimulators and electrical stimulators.

[0031] The magnetic stimulation device includes a magnetic field generator, a power source arranged to trigger the magnetic field generator to generate magnetic field pulses, and a digital program for guiding the magnetic field generator to generate modulation pulses according to the present invention, which may be based on a previously identified noise pattern or the mean and standard deviation of one or more biometric variables normalized by a Gaussian distribution, or a selected frequency bandwidth.

[0032] FIG. 1 is an explanatory diagram of a magnetic stimulation device according to an embodiment of the present invention. The device includes a control module 12 including a coil 11 and a power supply (not shown). In general, the control module controls a TTL pulse, and an electric wire is extended to the coil 11. When the power supply (not shown) is turned on, a magnetic field is generated by the current flowing through the wound electric wire. A software or hardware program 13 guides the modulated pulse generated by the device according to the present invention, which includes the low frequency and high frequency ranges mentioned above. When performing magnetic stimulation therapy on a patient, the magnetic coil member that is already attached is positioned at the part of the body to be treated or is brought close to the part of the body to be treated. The muscle fiber 14 and the neuron 15 in the figure are used to illustrate the muscle synaptic transmission between the neuron of the peripheral tissue and the muscle fiber.

[0033] The electrical stimulation device includes two or more electrode pads for adhering to the skin, a power source for generating current in the electrodes as described above, and a digital program for guiding the generation of the electrical stimulation of the modulated pulse of the present invention as described above. The modulated pulse may be based on the mean and standard deviation of one or more biometric variables normalized by a previously identified noise pattern or Gaussian distribution. In a preferred embodiment of the electrical stimulation device, the power source of the electrical stimulation device is a battery, and includes a transcutaneous electrical nerve stimulation (TENS unit) device for home use without a doctor's prescription, providing ease of use for medical treatment. When administering electrical stimulation treatment to a patient, the electrode pads are positioned contiguous to the painful area of ​​the body or adjacent to the painful area of ​​the body to be treated.

[0034] 2 is a schematic diagram of a magnetic stimulation device 20 according to one embodiment of the present invention, comprising a power source 21 and a pair of electrode pads 22, 23. The electrode pads 22, 23 are connected to a control module 24 via wires 25, 26. The control module is connected to ground 27. A digital or computer program in the control module 24 guides the generation of modulated pulsed electrical stimulation in accordance with the present invention, the modulated pulses including the low and high frequency ranges discussed above. When administering electrical stimulation treatment to a patient, the electrodes are positioned contiguous to the painful area of ​​the body or adjacent to the painful area of ​​the body being treated.

[0035] 3 is a schematic diagram of a battery powered electrical stimulation device according to one embodiment of the present invention, comprising a battery powered electrical pulse generator 31 and a pair of electrode pads 32, 33 connected to a control module 31 via electrical wires 32, 33. The control module is grounded 36. A digital or computer program in the control module guides the generation of modulated pulsed electrical stimulation in accordance with the present invention, the modulated pulses including the low frequency and high frequency ranges discussed above. When administering electrical stimulation treatment to a patient, the electrodes are positioned contiguous or adjacent to the painful area of ​​the body to be treated.

[0036] FIG. 5 is an explanatory diagram of a rotary permanent magnet device according to an embodiment of the present invention, which includes a permanent magnet 51 and a power supply 52. ​​When the power supply is energized, it drives the power supply to rotate the permanent magnet and generate a magnetic field. A software or hardware program 53 guides the modulated rotation speed generated by the device according to the present invention, including the low frequency and high frequency ranges mentioned above. When performing magnetic stimulation therapy on a patient, a covered permanent magnet member (not shown) is positioned at or close to the part of the body to be treated. Muscle fibers 54 and neurons 55 in the figure are used to illustrate muscle synaptic transmission between neurons and muscle fibers in peripheral tissues.

[0037] The above-mentioned embodiment is for the purpose of facilitating understanding of the present invention, and is not intended to limit the present invention. The present invention can be modified or improved without departing from the spirit of the present invention, and it goes without saying that the present invention includes equivalents thereof. [Explanation of symbols]

[0038] 21 Power supply 22 Electrode pads 23 Electrode Pads 24 Control Module 25 Electric wire 26 Electric wire 27 Earth Wire 31 Control Module 32 Electrode Pads 33 Electrode Pads 32 Electric wire 33 Electric wire 36 Earth wire 51 Permanent Magnets 52 Power supply 53 Software or hardware programs 54 Muscle Fibers 55 Neurons

Claims

1. an output unit for transmitting the magnetic or electrical stimulation to the subject; a power source electrically connected to the output unit for maintaining the magnetic or electrical stimulation; and a program for generating a modulated pulse based on a setting operation for the output unit, The setting operation includes: filtering, with a band-pass filter of 4 to 15 Hz or 20 to 150 Hz, an electroencephalogram (EEG), surface electromyogram (EMG), or spinal cord electrical signal of the subject as a biological data set for identifying characteristics of a probability density distribution of one or more biological variables from the subject, and analyzing zero crossing points of waves of the signal that are dominant in the power spectral density; deriving the modulated pulse such that the time interval between adjacent pulses is equal to the time interval between adjacent zero crossing points in the wave; A random TTL pulse train normalized with a noise pattern is generated as the magnetic stimulus or the electrical stimulus to the subject based on the modulated pulse. A stimulation device characterized by:

2. 2. The stimulation device of claim 1, wherein the noise pattern is one selected from the group consisting of white noise, pink noise, purple noise, blue noise, brown noise, and red noise.

3. 2. The stimulation device according to claim 1, wherein the modulated pulses have a frequency range of 30 to 150 Hz and a pulse interval of 33.3 ms to 6.7 ms.

4. 2. The stimulation device according to claim 1, wherein the modulated pulses have a frequency range of 0.1 to 15 Hz and a pulse interval of 10,000 ms to 66.7 ms.

5. 2. The stimulation device of claim 1, wherein the stimulation device is a magnetic stimulation device, the output unit is a magnetic field generator, the power supply is used to strengthen the magnetic field generator and generate magnetic field pulses, and the program is a digital program that generates the modulated pulses generated by the magnetic field generator.

6. 2. The stimulation device of claim 1, wherein the stimulation device is an electrical stimulation device, the output unit is at least two or more electrode pads, the power source is used to generate a current in the electrode pads, and the program is a digital program for generating modulated pulses of the electrical stimulation.

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