Apparatus and method for controlling tremor

Abstract

The present disclosure relates to devices and methods for controlling tremor. A peripheral nerve stimulator can be used to stimulate a peripheral nerve to treat essential tremor, Parkinsonian tremor, and other forms of tremor. The peripheral nerve stimulator can be a non-invasive surface stimulator or an implantable stimulator. The stimulation can be electrical, mechanical, or chemical. An open loop system with feedback or a closed loop system can be used to deliver the stimulation.

Description

[0001] This application is a divisional application of the invention patent application with application number "201480005343.5", application date "January 21, 2014", and invention title "Device and method for controlling tremors".

[0002] Cross-references to related applications

[0003] This application claims priority to U.S. Provisional Application No. 61 / 754,945, filed January 21, 2013; U.S. Provisional Application No. 61 / 786,549, filed March 15, 2013; U.S. Provisional Application No. 61 / 815,919, filed April 25, 2013; U.S. Provisional Application No. 61 / 822,215, filed May 10, 2013; and U.S. Provisional Application No. 61 / 857,248, filed July 23, 2013, each of which is incorporated herein by reference in its entirety.

[0004] Merging by reference

[0005] All publications and patent applications mentioned in this specification are incorporated herein by reference to the same extent as each individual publication or patent application is specifically and individually indicated to be incorporated by reference. Technical Field

[0006] The embodiments of the present invention generally relate to systems, devices, and methods for treating tremors, and more specifically to systems, devices, and methods for treating tremors by stimulating peripheral nerves. Background Technology

[0007] Essential tremor (ET) is the most common movement disorder, affecting an estimated 10 million people in the United States, with the number increasing due to the aging population. The prevalence of ET increases with age, from 6.3% in the population aged 65 and older to over 20% in the population aged 95 and older. ET is characterized by involuntary oscillatory movements, typically between 4 and 12 Hz. It can produce oscillations in the voice as well as unwanted movements of the head and limbs. Tremors in the hands and forearms are particularly common and problematic, making it difficult to write, type, eat, and drink. Unlike Parkinson's tremor, which exists at rest, essential tremor is postural and motor, meaning that the tremor is either induced by relative gravity holding the limb still or during movement.

[0008] Disability associated with tremor tremor is variable and ranges from distress when tasks such as writing and self-sufficiency become impossible due to uncontrolled movements of the hands and arms to an inability to live independently. Despite the high incidence and high rate of disability among many patients with tremor tremor, there are not enough treatment options available to address the problem.

[0009] Medications used to treat tremor (e.g., propranolol and primidone) have been found to effectively reduce tremor amplitude by only 50% in just 60% of patients. These medications have potentially serious side effects that are intolerable to many patients with ET. An alternative treatment is deep brain stimulation (DBS), which involves surgically implanting a stimulator into the brain. This can effectively reduce tremor amplitude by 90%, but it is a highly invasive surgical procedure with significant risks that many ET patients cannot tolerate. Therefore, there is a strong need for alternative treatments to reduce tremor without the side effects of medication and the risks of brain surgery for patients with ET.

[0010] Tremor is also a significant issue for patients with orthostatic tremor, multiple sclerosis, and Parkinson's disease. A variety of neurological disorders can cause tremor, including those related to stroke, alcoholism, alcohol withdrawal, peripheral neuropathy, Wilson's disease, Creutzfeldt-Jakob disease, Gurgbach syndrome, and Fragile X syndrome, as well as tremor from brain tumors, hypoglycemia, hyperthyroidism, hypoparathyroidism, insulinoma, normal aging, and traumatic brain injury. Stuttering or stammering can also be a form of tremor. In these cases, the underlying cause of the tremor may differ from ET; however, for some of these cases, treatment options are limited, and alternative therapies are necessary.

[0011] ET is thought to be caused by abnormalities in the circuit dynamics associated with motor generation and control. Previous work has shown that these circuit dynamics can be temporarily altered by cooling, local analgesics, and vibration. Previous reports on electrical stimulation using transcutaneous electrical nerve stimulation (TENS) have not improved tremor (Munhoz 2003). Therefore, in our clinical study, we were surprised to find that the circuit dynamics associated with ET could be altered by peripheral nerve simulation, resulting in a substantial reduction in tremor in patients with ET.

[0012] This invention is a novel peripheral stimulation device that sends signals along sensory nerves to the central nervous system to modify aberrant network dynamics. Over time, this stimulation normalizes natural firing in the aberrant network and reduces tremor. While deep brain stimulation (DBS) directly stimulates the brain, our peripheral stimulation influences aberrant brain circuit dynamics by sending signals along sensory nerves connecting the periphery to the brain. This approach is non-invasive and is expected to avoid the surgical risks of DBS and associated problems such as cognitive, expressive, and spatial memory dysarthria, ataxia, or gait disturbances. Peripheral nerve stimulation can effectively treat tremor by dephasing, covering, or blocking aberrant brain circuit dynamics. Covering, blocking, or training the brain to ignore aberrant brain circuit dynamics follows the assumptions about the mechanisms of conventional DBS.

[0013] Perhaps the technique most closely related to our approach is transcutaneous electrical nerve stimulation (TENS). High-frequency TENS (50 to 250 Hz) is commonly used to treat pain, where the hypothesis is that stimulation of large, myelinated peripheral proprioceptive fibers (A-β) blocks the entry of pain signals. Although inconsistent clinical results achieved with TENS for pain control have led to much skepticism about its use in treating pain, it is well documented that surface electrical stimulation stimulates A-β neurons. A-β neurons transmit proprioceptive sensory information to the same brain circuits that are abnormal in diseases including ET and Parkinson's disease. Without being limited by any of the proposed mechanisms of action, this leads us to propose that nerve stimulation can be used to stimulate A-β neurons and thereby improve tremor. This proposal is particularly surprising because previous studies by Munhoz et al. did not find any significant improvement in any tremor parameters tested after the application of TENS. See Munhoz et al., “Acute Effect of Transcutaneous Electrical Nerve Stimulation on Tremor,” Movement Disorders, 18(2), 191-194 (2003). Summary of the Invention

[0014] This invention relates to systems, devices, and methods for treating tremor, and more particularly to systems, devices, and methods for treating tremor by stimulating peripheral nerves.

[0015] In some embodiments, a method for reducing tremor in a patient is provided. The method includes: placing a first peripheral nerve effector at a first location relative to a first peripheral nerve; delivering a first stimulus to the first peripheral nerve via the first peripheral nerve effector; and reducing the tremor amplitude by modifying the patient's neural network dynamics.

[0016] In some embodiments, the placement step includes placing a first peripheral nerve effector on the patient's skin and the first stimulation being an electrical stimulation applied to the skin surface.

[0017] In some embodiments, the first stimulus has an amplitude from about 0.1 mA to 10 mA and a frequency from about 10 Hz to 5000 Hz. In some embodiments, the first stimulus has an amplitude less than about 15 mA, 14 mA, 13 mA, 12 mA, 11 mA, 10 mA, 9 mA, 8 mA, 7 mA, 6 mA, 5 mA, 4 mA, 3 mA, 2 mA, or 1 mA.

[0018] In some embodiments, the placement step includes implanting a first peripheral nerve effector into the patient and the first stimulation being electrical stimulation.

[0019] In some embodiments, the implantation step includes injecting a first peripheral nerve effector into the patient. In some embodiments, the first stimulus has an amplitude of less than about 3 mA and a frequency from about 10 Hz to 5000 Hz. In some embodiments, the first stimulus has an amplitude of less than about 5 mA, 4 mA, 3 mA, 2 mA, or 1 mA.

[0020] In some embodiments, the peripheral nerve effector includes a power source.

[0021] In some embodiments, the method further includes: wirelessly powering a first peripheral nerve effector via an externally located power source.

[0022] In some embodiments, the first stimulus is a vibratory tactile stimulus.

[0023] In some embodiments, the first stimulus is chemical.

[0024] In some embodiments, the method further includes: using a measurement unit to sense the movement of the patient's limbs to generate motion data; and determining tremor information from the motion data.

[0025] In some embodiments, the delivery step includes: delivering a first stimulus based on tremor information.

[0026] In some embodiments, tremor information includes the maximum deviation of the patient’s limbs from a resting position.

[0027] In some embodiments, tremor information includes resting positions for the patient's limbs.

[0028] In some embodiments, the tremor information includes tremor frequency, phase, and amplitude.

[0029] In some embodiments, the step of delivering the first stimulus includes: delivering a plurality of stimulus bursts with a variable time delay between the stimulus bursts.

[0030] In some embodiments, the method further includes: placing a second peripheral nerve effector at a second position relative to a second peripheral nerve; and delivering a second stimulus to the second peripheral nerve via the second peripheral nerve effector.

[0031] In some embodiments, the method further includes: determining the period of the patient's tremor, wherein the step of delivering the second stimulus includes: offsetting the delivery of the second stimulus from the delivery of the first stimulus by a predetermined fraction or multiple of the tremor period.

[0032] In some embodiments, the method further includes: dephase the synchronization of neural networks in the patient's brain.

[0033] In some embodiments, the first position and the second position are located on adjacent fingers.

[0034] In some embodiments, the first peripheral nerve and the second peripheral nerve are adjacent nerves.

[0035] In some embodiments, the first peripheral nerve is the median nerve and the second peripheral nerve is the ulnar nerve or the radial nerve.

[0036] In some embodiments, the first peripheral nerve and the second peripheral nerve are adjacent to each other in a specific area of ​​the body.

[0037] In some embodiments, the first stimulus has an amplitude below the sensory threshold.

[0038] In some embodiments, the first stimulus is greater than 15 Hz.

[0039] In some embodiments, the first peripheral nerve carries proprioceptive information from the patient's limbs.

[0040] In some embodiments, the method further includes: determining the duration of the effect of the first stimulus on reducing tremor amplitude; and delivering a second stimulus before the duration of effect expires.

[0041] In some embodiments, the step of determining the duration of efficacy includes analyzing multiple applications of stimulation applied over a predetermined time period.

[0042] In some embodiments, the step of determining the duration of efficacy further includes: determining an activity profile for the patient.

[0043] In some embodiments, the step of determining the duration of effectiveness further includes: determining a profile of the tremor.

[0044] In some embodiments, the activity profile includes data on caffeine and alcohol consumption.

[0045] In some embodiments, the method further includes placing a conduction pathway enhancer on a first peripheral nerve.

[0046] In some embodiments, the conduction pathway enhancer is a conduction tattoo.

[0047] In some embodiments, the conduction pathway enhancer includes one or more conduction strips.

[0048] In some embodiments, the first position is selected from the group consisting of the wrist, forearm, carpal tunnel, fingers, and upper arm.

[0049] In some embodiments, a system for treating tremor in a patient is provided. The device may include a decision unit; and an interface unit adapted to deliver electrical stimulation to a peripheral nerve, the interface unit including a first peripheral nerve effector in communication with the decision unit, the first peripheral nerve effector including at least one electrode; wherein the decision unit includes a processor and a memory storing instructions that, when executed by the processor, cause the decision unit to: deliver a first electrical stimulation to the first peripheral nerve via the first peripheral nerve effector, the electrical stimulation being configured by a controller to reduce tremor in the patient's limbs by modifying the patient's neural network dynamics.

[0050] In some embodiments, the first electrical stimulation has an amplitude of less than about 10 mA and a frequency from about 10 Hz to 5000 Hz. In some embodiments, the amplitude is less than about 15 mA, 14 mA, 13 mA, 12 mA, 11 mA, 10 mA, 9 mA, 8 mA, 7 mA, 6 mA, 5 mA, 4 mA, 3 mA, 2 mA, or 1 mA.

[0051] In some embodiments, the interface unit further includes a second peripheral nerve effector that communicates with the decision unit. The second peripheral nerve effector includes at least one electrode, wherein the memory stores instructions that, when executed by the processor, also cause the decision unit to deliver a second electrical stimulus to a second peripheral nerve in the patient's limbs via the second peripheral nerve effector.

[0052] In some embodiments, when executed by the processor, the instruction causes the decision unit to: deliver a second electrical stimulus that is temporally offset from the first electrical stimulus by a predetermined fraction or multiple of the tremor cycle.

[0053] In some embodiments, a first peripheral nerve effector is adapted to be placed on a first finger and a second peripheral nerve effector is adapted to be placed on a second finger.

[0054] In some embodiments, the first peripheral nerve effector includes a plurality of electrodes arranged in a linear array. In some embodiments, the plurality of electrodes are spaced apart by about 1 mm to 100 mm.

[0055] In some embodiments, the first peripheral nerve effector includes a plurality of electrodes arranged in a two-dimensional array.

[0056] In some embodiments, the memory stores instructions that, when executed by the processor, also cause the decision unit to select a subset of multiple electrodes based on the location of the first peripheral nerve effector on the patient's limbs, wherein the selection of a subset of multiple electrodes occurs each time the first peripheral nerve effector is located or relocated on the limbs.

[0057] In some embodiments, a plurality of electrodes are spaced apart by about 1 mm to 100 mm along a first axis and by about 1 mm to 100 mm along a second axis perpendicular to the first axis. In some embodiments, some of the electrodes are adjacent to each other to form a strip. In some embodiments, the spacing may be less than about 100 mm, 90 mm, 80 mm, 70 mm, 60 mm, 50 mm, 40 mm, 30 mm, 20 mm, 10 mm, 5 mm, 4 mm, 3 mm, 2 mm, or 1 mm.

[0058] In some embodiments, the system further includes a measurement unit, wherein the memory stores instructions that, when executed by a processor, also cause a decision unit to: use the measurement unit to measure the movement of the patient's limbs to generate motion data; and analyze the motion data to determine the tremor frequency and amplitude.

[0059] In some embodiments, the analysis of motion data includes frequency analysis of the spectral power of the motion data.

[0060] In some embodiments, frequency analysis is limited to the range of approximately 4 Hz to 12 Hz. In some embodiments, frequency analysis is limited to a desired frequency range approximately equal to one or more flutters of interest.

[0061] In some embodiments, the analysis of motion data is performed over a predetermined duration of the motion data.

[0062] In some embodiments, the decision unit is also adapted to determine tremor phase information based on motion data and to deliver a first electrical stimulus based on the tremor phase information.

[0063] In some embodiments, the tremor phase information includes peak tremor deviation, and the decision unit is further adapted to deliver a first electrical stimulus at a time corresponding to the peak tremor deviation.

[0064] In some embodiments, the memory stores instructions that, when executed by the processor, also cause the decision unit to: deliver a first electrical stimulus as a plurality of electrical stimulation bursts having a variable time delay between the electrical stimulation bursts.

[0065] In some embodiments, the memory stores instructions that, when executed by the processor, also cause the decision unit to set parameters of the first electrical stimulation based on the determined tremor frequency.

[0066] In some embodiments, the memory stores instructions that, when executed by the processor, also cause the decision unit to set parameters for the first electrical stimulation based on the determined tremor amplitude.

[0067] In some embodiments, the memory stores instructions that, when executed by the processor, also cause the decision unit to: compare the determined tremor amplitude with a predetermined threshold; and wherein, when the determined tremor amplitude exceeds the predetermined threshold, a first electrical stimulus is delivered.

[0068] In some embodiments, the electrodes are adapted to deliver a first electrical stimulation through the patient's skin.

[0069] In some embodiments, the electrodes are adapted to be implanted and deliver electrical stimulation. In some embodiments, the decision unit includes a user interface adapted to receive input from a user to adjust parameters of the first electrical stimulation.

[0070] In some embodiments, the memory also stores a library of one or more predetermined stimulation protocols.

[0071] In some embodiments, the interface unit is integrated with the decision unit.

[0072] In some embodiments, the interface unit and the decision unit are separate from each other and have separate housings.

[0073] In some embodiments, the decision unit is configured to wirelessly provide power to the interface unit or communicate with the interface unit.

[0074] In some embodiments, the system further includes a measurement unit located within the decision unit.

[0075] In some embodiments, the system further includes a measurement unit located in the interface unit.

[0076] In some embodiments, the decision-making unit is a computing device selected from the group consisting of smartphones, tablets, and laptops.

[0077] In some embodiments, the system further includes a server that communicates with a computing device and is configured to receive motion data from the computing device along with a history of electrical stimulation delivered to the patient.

[0078] In some embodiments, the server is programmed to add the received motion data and the history of electrical stimulation delivered to the patient to a database storing data from multiple patients.

[0079] In some embodiments, the server is programmed to: compare received motion data and the history of electrical stimulation delivered to the patient with data stored in a database; determine a modified electrical stimulation protocol based on the comparison results of the received motion data and the history of electrical stimulation delivered to the patient with the data stored in the database; and transmit the modified electrical stimulation protocol to a computing device.

[0080] In some embodiments, the electronic device is flexible and disposed on a flexible substrate, which may be a sleeve, pad, strip, or other housing.

[0081] In some embodiments, a system for monitoring tremors in the limbs of a patient is provided. The system may include an interface unit having an inertial motion unit for capturing motion data, a power supply, and a wireless transmitter and receiver, the interface unit being adapted to be worn on the patient's limbs; and a processing unit communicating with the interface unit, the processing unit being configured to receive motion data from the interface unit, wherein the processing unit is programmed to determine a tremor signature and profile over a predetermined time period based on analysis of the motion data.

[0082] In some embodiments, the processing unit is a mobile phone.

[0083] In some embodiments, the system further includes a server that communicates with a mobile phone and is configured to receive motion data from the mobile phone.

[0084] In some embodiments, the processing unit is further programmed to compare the tremor amplitude with a predetermined threshold.

[0085] In some embodiments, the processing unit is further programmed to generate an alarm when the tremor amplitude exceeds a predetermined threshold.

[0086] In some embodiments, the predetermined threshold may be adjusted by the patient.

[0087] In some embodiments, the processing unit is programmed to prompt the patient to enter activity data, which includes a description of the activity and the time when the activity occurred.

[0088] In some embodiments, the processing unit is programmed to correlate activity data with determined tremor frequency and amplitude.

[0089] In some embodiments, activity data includes caffeine or alcohol consumption.

[0090] In some embodiments, activity data includes drug consumption.

[0091] We have invented a peripheral nerve stimulation device and method that effectively reduces tremor without the side effects of medication and the risks of brain surgery. Our method is safe and, in some embodiments, non-invasive, and effectively reduces tremor. In some embodiments, the device works by altering the neural circuit dynamics associated with essential tremor, Parkinson's tremor, and other tremors. The device is simple to use, comfortable, and adjustable for optimal treatment for each patient. Attached Figure Description

[0092] The novel features of the invention are particularly set forth in the appended claims. The features and advantages of the invention can be better understood by referring to the following detailed description and accompanying drawings of illustrative embodiments in which the principles of the invention are employed, wherein:

[0093] Figure 1 The illustration shows an example of delivering stimulation to the median nerve to reduce tremor.

[0094] Figure 2 The illustration shows the therapeutic effects of peripheral nerve stimulation in (A) mild, (B) moderate, and (C) severe ET patients. It presents the results of a clinical study in which stimulation with a frequency of 150 Hz, a duration of 300 μs, and an on-time of 40 minutes reduced tremor amplitude in patients with essential tremor. Immediately after stimulation was turned off, a tremor reduction was observed as shown in a spiral pattern when comparing ET patients.

[0095] Figure 3 The A-3C diagram is from... Figure 2 Wrist flexion-extension calculated from gyroscopic data of subject B. 3A shows the tremor before treatment; Figure 3 B shows a reduction in tremor immediately following treatment; Figure 3 C shows that the reduction in tremor was maintained for 20 minutes after treatment.

[0096] Figure 4 The illustration shows an example of ineffective treatment in a patient with moderate ET.

[0097] Figure 5 The diagram shows various locations on the patient that can be used to locate the tremor-altering system.

[0098] Figure 6 The diagram shows the main nerves that control the hand and their distal branches.

[0099] Figure 7 A-7D is a block diagram illustrating various embodiments of a flutter alteration system.

[0100] Figure 8 Figure A illustrates an embodiment of an electrode pair used to stimulate nerves in different fingers, wherein both electrodes are located on the fingers. Figure 8 Figure B illustrates alternative devices for stimulating nerves in different fingers, with the second electrode located on the wrist. Figure 8 Figure C illustrates an example of placing electrodes on the wrist to target different underlying nerves. Figure 8 Figure D illustrates various stimulation sites.

[0101] Figure 9 A is a diagram illustrating an embodiment of a stimulation scheme for a brain region receiving sensory input from two fingers during de-phase. Figure 9 B is a diagram illustrating an embodiment of a stimulation scheme for a brain region receiving sensory input from the four fingers during de-phase.

[0102] Figure 10 The A-10C diagram illustrates an example of how hand placement can determine the optimal stimulation cycle and timing.

[0103] Figure 11 The illustration shows an example of a variable stimulus whose frequency changes over time.

[0104] Figure 12 The accompanying drawings illustrate an example where the stimulator is chemical and two neuromodulatory chemicals can be mixed to provide a customized chemical stimulus.

[0105] Figure 13 Various forms of user controls are shown.

[0106] Figure 14 A-14L illustrates various non-invasive or invasive embodiments of the tremor alteration system. Figure 14 E is a diagram illustrating an embodiment in which the stimulator is mechanical. Figure 14 The figure H illustrates a form factor embodiment of a wristwatch device. Figure 14 I diagram Figure 14 The back of the device shown in Figure H displays electrodes for the user interface. Figure 14 The illustration shows an embodiment of a disposable electrode interface that snaps onto the watch-shaped element of the device housing. Figure 14 The K diagram illustrates an embodiment that allows a disposable electrode interface to be snapped into a self-aligning snap-fit ​​feature in a device housing with a wristwatch shape factor. Figure 14 L is a diagram illustrating an embodiment of a device in which the effector is electrical, in which electrodes may be placed along the spine.

[0107] Figure 15 The A-15C diagram illustrates various embodiments of the electrode array.

[0108] Figure 16 A-16D illustrates various embodiments of conductive ink tattoos.

[0109] Figure 17 This is a diagram illustrating an embodiment of positioning an accelerometer on the hand or wrist to measure a patient's activity and tremor.

[0110] Figure 18 The illustration shows an example of spectral analysis of gyroscopic motion data from a patient whose tremor was concentrated at 6.5 Hz.

[0111] Figure 19 The diagram illustrates the correlation between postural tremor and action tremor.

[0112] Figure 20 The illustration shows an embodiment capable of recording and transmitting data such as tremor characteristics and stimulation history to a data portal device, such as a smartphone, which transmits the data to a cloud-based server.

[0113] Figure 21 This is a flowchart illustrating the monitoring, integration, analysis, and display of data used to notify users or improve stimuli.

[0114] Figure 22 This is a flowchart illustrating the feedback logic.

[0115] Figure 23 The accompanying drawing illustrates an embodiment in which the stimulator is an electrode implanted at least partially subcutaneously.

[0116] Figure 24 The A-24D illustrations depict various embodiments of implantable and skin-surface devices that allow for wireless power supply and control.

[0117] Figure 25 The A-25F diagram illustrates various geometries for electrodes used in implantable electrical stimulation.

[0118] Figure 26 Figure A-26B illustrates two preferred embodiments of a control module for interacting with the device. The control system for the tremor device utilizes feedback to modify the stimulus. It is a closed loop in which the stimulus is adjusted based on measurements of activity and tremor. Detailed Implementation

[0119] Definition of terminology

[0120] As used herein, the terms “stimulus” and “stimulator” generally refer to the delivery of signals, stimuli, or impulses to neural tissue in a targeted area. The effect of such stimulation on neuronal activity is called “modulation”; however, for simplicity, the terms “stimulus” and “modulation,” and their variations, are sometimes used interchangeably herein. The effect of delivering signals to neural tissue can be stimulatory or inhibitory and can amplify acute and / or long-term changes in neuronal activity. For example, the effect of “stimulating” or “modulating” neural tissue can include one or more of the following: (a) depolarizing neurons to fire action potentials, (b) hyperpolarizing neurons to inhibit action potentials, (c) depleting neuronal ion reserves to inhibit firing action potentials, (d) altering proprioceptive input, (e) influencing muscle contraction, (f) influencing changes in neurotransmitter release or uptake, or (g) inhibiting firing. “Proprioception” refers to a person’s sense of the relative position of their own body parts or the effort made to move their body parts. Proprioception may also be referred to as somatosensory, kinesthetic, or tactile. "Proprioceptors" are receptors that provide proprioceptive information to the nervous system and include extensor receptors in muscles, joints, ligaments, and tendons, as well as receptors for pressure, temperature, light, and sound. "Effectors" are mechanisms by which devices modulate target nerves. For example, an "effector" can be an electrical stimulus to a nerve or a mechanical stimulus to a proprioceptor.

[0121] "Electrostimulation" refers to the application of electrical signals to the soft tissues and nerves of a targeted area. "Vibrational-tactile stimulation" refers to the stimulation of proprioceptors, such as by applying biomechanical loads to the soft tissues and nerves of a targeted area. "Thermal stimulation" refers to induced cooling or heating of a targeted area. "Chemical stimulation" refers to the delivery of chemical agents, drugs, or pharmaceutical preparations that can stimulate neuronal activity in nerves or nerve tissues exposed to these agents. This includes local anesthetics that affect the release or uptake of neurotransmitters in neurons, electroexcitable cells that process and transmit information via electrical and chemical signals. "Cloud" refers to computer networks that communicate using real-time protocols such as the Internet to analyze, display, and interact data across distributed devices.

[0122] Clinical research

[0123] We evaluated methods for using peripheral nerve stimulation to alter the circuit dynamics associated with ET in clinical studies. For example... Figure 1As shown, a device 100 delivering transcutaneous electrical nerve stimulation (TENS) using a surface electrode 102 located on the palmar side of the wrist stimulates the median nerve 104 for 40 minutes with a square wave of 150 Hz pulse width and 300 microseconds. In this embodiment, a lead 106 is used to connect the device 100 to the electrode 102. Surprisingly, tremor was reduced, as previous work reported that peripheral nerve stimulation using TENS did not improve tremor (Munhoz 2003 cited above).

[0124] Electrical stimulation effectively reduced tremor in subjects with tremor severity ranging from mild to severe. Action tremor was assessed using widely used measurements of action tremor: the Archimedes spiral drawing task of the Fahn-Tolosa Marin test. Postural tremor was assessed by measuring the angular velocity of a gyroscope worn on the back of the hand.

[0125] exist Figure 2 Three patients, designated as subjects A, B, and C, are shown in the spiral diagrams drawn before and after stimulation, depicting subjects with mild, moderate, and severe postural tremor (ET). Postural tremor was reduced by 70%, 78%, and 92% in subjects with mild, moderate, and severe tremor, respectively. Postural tremor was also reduced with electrical stimulation, and this effect lasted for up to 45 minutes after treatment. Figure 3 A-3C shows that, for example, from... Figure 2 The effect of wrist flexion-extension was determined using gyroscopic data from subject B, as a representative example. A 15-minute treatment reduced the tremor amplitude from 0.9° ( Figure 3 A) Reduced to 0.2° ( Figure 3 B). The reduction in tremor amplitude was maintained through 40 minutes of treatment. Measurements taken 20 minutes after treatment showed a continued reduction in tremor amplitude, which remained at 0.2°. Figure 3 C). The reduction in tremor is variable among subjects. (e.g.) Figure 4 As shown, some subjects did not respond to the treatment.

[0126] Optimal treatment outcomes are achieved by reducing tremors in subjects with end-stage renal syndrome (ET) through the application of electrical stimulation. This stimulation can reduce tremors during treatment, immediately following treatment, and for up to twenty minutes after treatment. For long-term use and to allow patients with ET to integrate treatment into their lives, it is important that the system be easy to use and effective over the long term. The innovations and devices described below achieve this goal.

[0127] Equipment location

[0128] The device stimulates sensory nerves to modify the dynamics of the aberrant network. Over time, the stimulation normalizes the neural discharges in the aberrant network and reduces tremor. Preferably, the stimulated nerve is one carrying sensory proprioceptive information from the tremor-affected limb. This nerve can be directly modulated, such as by electrical stimulation at any location along or adjacent to the nerve carrying the proprioceptive information. Alternatively, the target nerve can be indirectly modulated, such as by stimulating the proprioceptors of the target nerve. Figure 5 Access points to nerves carrying proprioceptive information from the limbs, vocal cords, or larynx are shown. These access points may include, but are not limited to, the fingers (510), hand (520), wrist (530), forearm (540), elbow (550), upper arm (560), shoulder (570), spine (580) or neck (590), foot, ankle, calf, knee, or thigh. Nerves influencing proprioception may include, for example, the hand, arm, and spinal region, or along the median nerve, ulnar nerve, radial nerve, or other nerves within muscles or joints. These regions targeting nerves may include the brachial plexus, median nerve, radial nerve, ulnar nerve, dermal nerve, or articular space nerves. These regions may also target muscular tissue including shoulder muscles, arm muscles, and forearm, hand, or finger muscles. By way of non-limiting example, shoulder muscles may include the deltoid, teres major, and supraspinatus muscles. Arm muscles may include the coracobrachialis and triceps brachii. The forearm muscles can include the extensor carpi radialis longus, abductor pollicis longus, extensor carpi ulnaris, and flexor carpi ulnaris.

[0129] In a preferred location, the device interfaces with the dermal surface of the user's trembling upper limb and applies neuromodulation signals to a group of nerve bundles selected from the brachial plexus, median nerve, radial nerve, and ulnar nerve, or excitable structures in the muscle tissue of the upper limb on the skin or within the joint.

[0130] Proprioceptors can be found in, for example, muscles, tendons, joints, skin, and the inner ear. Criteria limiting candidate nerves for direct modulation include the location of the tremor to be reduced, the proximity of the nerve to the skin surface, the density of proprioceptive fibers, and the distance from easily excitable pain receptors or muscles. The median nerve, targeting the wrist, and the ulnar nerve, targeting the elbow, rank highly by these criteria. Criteria limiting candidate locations for indirect proprioceptive modulation include the density and type of proprioceptors. Pacinian corpora provide information about touch; muscle spindles provide information about changes in muscle length by triggering action potentials in the afferent nerves of the muscle spindles when mechanogated ion channels open due to muscle stretching; and Golgi tendon organs provide information about muscle tension. These structures can also be stimulated to alter circuit dynamics and reduce tremors.

[0131] The device targets synapses on specific neurons in abnormal brain circuits. These synapses can be direct or occur via multiple relay synapses. Figure 6 A representative set of nerves that transmit proprioceptive information to the olivary-cerebellar network, which is anomalous in ET, is shown. These nerves include (620) the median nerve and (630) the (610) distal branch and main branch of the ulnar nerve, and (650) the (640) distal branch and main branch of the radial nerve. In a preferred embodiment, the device targets the nerves from which proprioceptive information from the hand, wrist, and forearm is input.

[0132] In another embodiment, any combination of components described herein can be used to influence nerves associated with vocal tremor, including but not limited to branches of the vagus nerve such as the superior laryngeal nerve or the recurrent laryngeal nerve.

[0133] Equipment components: Various embodiments

[0134] Figure 7 A-7D is a conceptual diagram illustrating some embodiments of a tremor alteration system 700. System 700 includes a housing 720, one or more effectors 730, one or more controls 740 electrically communicating with the effectors 730, and one or more power supplies 750. In some embodiments, housing 720 may include an interface 760. This interface facilitates coupling of the effector to a patient. For example, the interface may provide a physical, electrical, chemical, thermal, or magnetic connection between the device and the patient's nerves. In some embodiments, housing 720 may also include a sensor 780 for detecting tremors, a memory 770, a display 790, and a processor 797. In this embodiment, the device may include a processor 797 coupled to an effector capable of performing calculations and controls on other components. The device may also include a digital library stored on the processor 797 or memory 770, which may contain pre-loaded modulation protocols. The device may include a control module 740 communicating with the processor 797 and usable by a user to control stimulation parameters. This control allows the user to adjust the operation of the device. For example, the control may be configured to turn the device on, off, or adjust parameters of the effector, such as intensity. The device may include a sensor 780 connected to a processor 797, which can detect and transmit predefined parameter information. The device may also include a data storage unit 770 connected to the sensor 780 and the processor 797; and a power supply 750 may be connected to the processor.

[0135] The device may further include a display or indicator 790 that communicates with the user and reports the device's status. The indicator is preferably a light-emitting diode (LED) or some visual indicator, but may alternatively be an audio indicator. This information may include battery power or stimulus status.

[0136] The device may be without effector 730. It can be a diagnostic, non-therapeutic device. In a preferred embodiment, interface unit 704 may be worn on the tremor limb to track tremors that change over time. Providing feedback to the user of the device allows them to be aware of their tremors and enables monitoring over time. This biofeedback can also help some individuals reduce their tremors, even without therapeutic stimulation. Alternatively, the device may not have sensor 780. It can be a therapeutic, non-diagnostic device.

[0137] To make the device compact and simple, many of these components can be housed in separate units. Processing, control, and possibly sensing can be performed remotely in the decision unit 702, thereby enabling the interface unit 704 to provide therapeutic contact with the patient for a variety of applications. Figure 7 The B-7D is compact, simple, and flexible. The decision unit 702 can be a new device designed for this application, or it can be integrated into existing technologies such as smartphones. This will allow the system to achieve robust handheld form factor while reducing cost and size.

[0138] exist Figure 7 In the preferred embodiment shown in B, the interface unit 704 is an implant; the effector 730 provides electrical stimulation of the nerve; and the command set and power are wirelessly transmitted from an external device. Optionally, the implanted interface unit 704 may be powered by an on-board battery. Optionally, the implanted interface unit 704 may include a sensor 780 for directly detecting tremors or neuromuscular activity detected by electroencephalography (ENG) or electromyography (EMG).

[0139] exist Figure 7 In the preferred embodiment shown in C, the interface unit 704 is worn on the surface of the body; the effector 730 provides electrical stimulation of deep nerves or vibratory tactile stimulation of nearby proprioceptors. The sensor 780 may include a motion sensor, which includes an accelerometer, a gyroscope, and a magnetometer.

[0140] exist Figure 7In the preferred embodiment shown in D, one or more sensor units 780 that sense motion, temperature, etc., can be worn at different locations on the body. The effector 730 and decision unit 702 are separate entities worn on the body at different locations from the sensor 780. This is useful if the nerve stimulation occurs at a location where tremors cannot be measured easily or accurately. For example, a stimulation device 700 placed on the underside of the wrist to reduce hand tremors is very effective. However, it can be demonstrated that measuring hand tremors from the wrist using an accelerometer or gyroscope is difficult; sensor units placed separately on the palm or back of the hand in a glove, or worn as a ring on one of the fingers, show greater sensitivity to hand tremors because they are located outside the wrist joint.

[0141] Effector: General Effectors can be used to modulate neural tissue in the upper limb region targeted by stimulation. For example, an effector can modify neuronal signaling in a nerve and / or modify the flow or content of proprioceptive information. Effectors can be delivered percutaneously or subcutaneously. One or more effectors can be used to influence nerves. In some embodiments, the effector can excite the nerve. In other embodiments, the effector can inhibit the nerve. In some embodiments, the system can be used to stimulate the nerve during some portions of treatment and inhibit the nerve during other portions of treatment.

[0142] Effector: Electrical stimulation

[0143] In some embodiments, the effector may be an electrical stimulator. An electrical effector may include electrodes, electrode pairs, electrode arrays, or any device capable of delivering electrical stimulation to a desired location. The electrical stimulation may be percutaneous or subcutaneous. For example, percutaneous electrical stimulation can be achieved using electrodes placed on the skin surface, while subcutaneous electrical stimulation can be achieved using implanted electrodes located near nerves.

[0144] Stimulation parameters can be automatically adjusted or controlled by the user. Stimulation parameters may include on / off, duration, intensity, pulse rate, pulse width, waveform, and pulse ramp on and off. In a preferred embodiment, the pulse rate may be approximately 50 Hz to 5000 Hz, and preferably approximately 50 Hz to 300 Hz, or 150 Hz. The preferred pulse width range may be from 50 μs to 500 μs (microseconds), and preferably approximately 300 μs. The intensity of the electrical stimulation may vary from 0 mA to 500 mA, and preferably the current may be approximately 1 mA to 6 mA. These preferred settings are derived from the aforementioned clinical studies, which provide valuable reductions in tremors maintained for a given time period. We note that electrical stimulation can be adjusted in different patients using different stimulation methods; therefore, these preferred settings are non-limiting examples. Increments in intensity adjustment may be from 0.1 mA to 1.0 mA. In a preferred embodiment, stimulation may last from approximately 10 minutes to 1 hour.

[0145] In a preferred embodiment, the electrodes may contact the user's skin surface at one or more nerves, including the median nerve, radial nerve, and ulnar nerve. The electrodes may be configured with electrode pairs, one electrode proximally (near the elbow) and the other distally (near the hand). The electrodes may communicate with the opposing electrode. The electrode pairs may have polarity with either positive or negative charges through which current flows.

[0146] The effector may include two electrodes, each having either positive or negative polarity, or the electrode array may include multiple electrode pairs, each of which is programmed independently or non-independently relative to other electrode pairs. As an example, the program may allow cyclic stimulation of different nerves, such as the ulnar nerve, then the median nerve, then the radial nerve, or any combination thereof, at different times.

[0147] Electrical stimulation can be designed to suppress tremors by interfering with proprioceptive input, inducing compensatory muscle contractions, or a combination of both. Electrodes can be replaced by any equivalent material capable of conducting electrical signals via a stimulator that interfaces with the dermal surface of the upper limb. Electrodes can be attached to control unit 740, which can apply electrical stimulation to soft tissues and nerves in the area where the electrodes are placed and in the surrounding area. In another variation of the embodiment, a combination of several electrodes can be placed in the targeted area.

[0148] A function generator, connected to and controlled by a processor, serves to adjust the electrical stimulation parameters. The function generator is preferably an arbitrary waveform generator that uses direct digital synthesis technology to generate any waveform that can be described by an amplitude table. Parameters are selected from, but are not limited to, frequency, intensity, pulse width, or pulse duration and total duration. Preferably, the output has a power limit set by the maximum output voltage. In a preferred embodiment, a digitally stored protocol is cycled through various stimulation parameters to prevent the patient from adapting to the environment. Variations in electrical stimulation are implemented by the function generator.

[0149] Optimized stimulus: de-phase

[0150] In a preferred embodiment, the stimulation is designed to dephase synchronicity in the brain. The concept of dephased anomalous circuits follows recent work showing that neural retraining reduces the tendency of networks to fall into anomalous rhythms. Interestingly, movement disorders are often associated with anomalous periodic synchronous discharges in brain circuits. In Parkinson's disease, this circuit is located in the basal ganglia. In ET, it is the olivary-cerebellar circuit. As supported by numerous studies showing tremors observed in the muscles of the hand and forearm synchronized with pathological rhythmic discharges in the brain, these anomalous oscillations are thought to drive tremors. Recent DBS studies have shown that low-voltage phase-shift bursts on adjacent electrode pairs (called coordinated resets) can reduce synchronicity in anomalous brain networks and have shown that this reduces Parkinsonian tremors. The application of coordinated reset theory to treat tinnitus supports the concept of using synaptic stimulation to retrain neural networks.

[0151] The device disclosed herein offers several advantages over high-frequency TENS stimulation, including the use of lower power (leading to extended battery life, less discomfort from motor recalls and contractions, and less discomfort from sensory stimulation), less inhibition of active discharges in adjacent nerves (through depletion or other mechanisms), and a more sustained effect, allowing the device to be used only intermittently to train or maintain neural circuit dynamics. The device stimulates neural ensembles by targeting specific neural subgroups to reduce synchronization of the group. This can be achieved, for example, by stimulating different fingers on the hand. Figure 8A is a diagram illustrating a preferred embodiment of the device, wherein a pair of (810) anode and (820) cathode electrodes on each finger are used to stimulate branches of proprioceptive nerves (median, radial, and ulnar nerves) in each finger. The arrangement of the anode (distal) and cathode (proximal) is designed to induce neural impulses traveling toward the brain. Due to the somatic specificity of the brain, the unique stimulation pattern on each finger will send a unique signal to a specific subgroup of neurons in the brain, where signals from different adjacent or nearby body parts synapse at nearby locations in the brain. In an alternative embodiment, the anode and cathode positions may be reversed to inhibit the pathway of sensory impulses to the brain (reverse collision). Figure 8 B illustrates an alternative arrangement in which only a single electrode (830) is located on the finger and a second electrode (840) is located on the wrist. It should be understood by those skilled in the art that the finger merely represents one possible set of targets, and different locations can similarly represent the target-adjacent neuron subpopulations used. Figure 8 In the alternative embodiment shown in C, the electrodes are positioned at different locations on the wrist to target (850) the median nerve, (860) the ulnar nerve, and (870) the radial nerve. It will be understood by those skilled in the art that the input can also be located at other locations or directed to branches of nerves in abnormal brain circuits. This location can be on the same or opposite side of the limb experiencing the tremor. The location can be on the surface of the skin, through the skin, or implanted. Figure 8 The diagram shows various stimulation sites that can be subjected to a predetermined fraction or multiple of a delayed or offset tremor period T (e.g., as shown in Figure 9).

[0152] The device uses stimulation schemes designed to de-phase, cover, or blur anomalous networks. Figure 9 A is a conceptual diagram illustrating a sample stimulation scheme for a brain region that receives sensory input from two sites during dephasing. For example, the two sites could be... Figure 8 Two fingers from A to 8D are shown. After site 1, the stimulus at site 2 is delayed by T / 2, where T is the natural tremor period. For example, if the tremor is 8 Hz, the period is 125 ms and the stimulus at site 2 will be delayed by 62.5 ms. The stimulus is designed to reset the phase of the neuron, which can be implemented using high-frequency stimulation (greater than 100 Hz) or DC pulses. Figure 9B is a conceptual diagram illustrating a sample stimulation scheme for a brain region receiving sensory input from four sites during dephasing, where subsequent sites are delayed by T / 4. In another embodiment, the stimulation at different locations is parameter-variable, except for timing such as frequency or pulse width, or combinations thereof. These variations are similarly designed to retrain the brain through dephasing, overlaying, or blurring of anomalous network dynamics. In yet another embodiment, stimulation may occur at a single location, but the parameters vary over time. For example, it may vary in frequency every few seconds or be turned on and off. In yet another embodiment, the stimulation is constant and at a single location. In a preferred embodiment of these embodiments, the location is near the median nerve at the wrist.

[0153] Optimized stimulation: Subsensory Stimulations with intensity below the sensory threshold will avoid discomfort (tingling, numbness, pain) that can be associated with peripheral nerve stimulation. Because precise electrode placement, size, and surface contact have a significant impact on the stimulation level and the anatomy receiving the stimulation, the sensory threshold may need to be calibrated for each patient and even for each session. This calibration can be performed by the user manually setting the stimulation parameters or otherwise indicating their sensory threshold. Another possible mechanism for the device is to automatically sweep through a range of stimulation parameters and have the patient select the set of parameter values ​​that are most comfortable. For the patient, another possible mechanism is to select from a previously selected set of parameter values ​​that provide effective and comfortable stimulation. In some embodiments, the electrode pads may include a local analgesic such as lidocaine to reduce discomfort caused by stimulation, thereby increasing the patient's tolerable sensory threshold. In some embodiments, the local analgesic may be delivered using a controlled release formation to provide pain relief for the duration the electrode pads are to be worn, which may last for days, weeks, or months. Such an approach can provide greater comfort or better therapeutic outcomes due to the reduction of tremor in some patients caused by greater stimulation intensity and / or synergistic effects with the local analgesic.

[0154] Optimized stimulation: high frequency

[0155] Optionally or additionally, the stimulation waveform can be of very high frequency, typically kHz and above, so that the stimulation is not perceived by the user, or is perceived very little. Very high-frequency stimulation is thought to cause conduction blockade. However, prior to blockade, there is an initial response, including strong depolarization of the nerve. To effectively implement very high-frequency stimulation without causing discomfort to the patient, it is preferable to eliminate this initial response. This can be done by cooling the nerve during the initial stimulation. Motor nerves are typically stimulated by stimuli of approximately 15 Hz and below, while sensory nerves are typically stimulated by stimuli of approximately 50 Hz and above. In some embodiments, it may be desirable to specifically stimulate motor neurons above a 15 Hz threshold to avoid inducing muscle contraction.

[0156] Optimized stimulus: triggered

[0157] Optionally or additionally, triggering stimulation of the tremor phase can improve efficacy. The goal of this stimulation is to disrupt the rhythmic entrainment of the motor unit. More effective treatment may allow for lower levels of stimulation to achieve similar therapeutic benefits with less discomfort. Idiopathic tremor is essentially a feedback problem in a resonant circuit. Timing out-of-phase stimulation from the tremor can reduce tremor by altering circuit dynamics, such as by shifting the gain in the feedback loop.

[0158] like Figure 10 As shown in B, high-frequency stimulus bursts can be timed to occur when the wrist is in its maximum flexion or extension (…). Figure 10 In example (A) Figure 10 In C), the burst has been shifted to a random phase. The position of the hand ( Figure 10 A) can determine the optimal stimulation cycle and timing, such as ( Figure 10 B) Stimulate the off-resonance or ( ) with the maximum tremor deviation. Figure 10 C) Use variable time delay bursts to avoid resonance with tremors.

[0159] Optionally or additionally, the stimuli can be disordered or variable. The goal of disordered, random, or variable stimuli is to prevent habituation and reduce resonance in the circuit. This can be achieved, for example, by varying the stimulus frequency over time and / or by superimposing higher and lower frequency components (e.g., ...). Figure 11 This can be achieved as shown in the diagram.

[0160] Optionally or additionally, the stimulus can be a high-frequency alternating current. Because these are transmitted along the axon and can modulate loop dynamics, this has been shown to block action potentials.

[0161] In some embodiments, the stimulation parameters described above can be cycled in a predetermined order to determine the optimal stimulation parameters. In some embodiments, the effectiveness of the stimulation parameters can be monitored over time to determine whether a particular set of stimulation parameters is losing effectiveness. In some embodiments, when the effectiveness of a particular set of stimulation parameters has decreased by a predetermined amount, the stimulation parameters can be changed or cycled in a predetermined order. For example, if the stimulation is being triggered to the phase of a tremor, the stimulation can be delivered with a random or variable time delay, or if the stimulation is using a set amplitude and / or frequency, the stimulation can be changed to a disordered, random, or variable form to prevent or disrupt "habituation." In some embodiments, random or variable types of stimulation parameters can be used according to a predetermined routine, such as a predetermined number of hours per day, or a predetermined number of days per week, or some other predetermined interval including the time of day.

[0162] Effector: Vibratory tactile stimulation

[0163] The effector can be a proprioceptor that is mechanically stimulated, including vibratory tactile or tactile sensation. This mechanical stimulation can include force, vibration, and / or motion. The effector evokes action potentials in the target nerve by stimulating Golgi tendon organs (GTOs) or Pacinian corpora. Mechanical effectors can include, for example, small electric motors; piezoelectric elements; one or more vibratory tactile units consisting of a mass and an effector that moves the mass to apply a vibratory stimulus to the body; an eccentric mass mounted on a shaft to generate a vibratory stimulus when the shaft rotates; or an ultrasonic motor, but optionally a magnetorheological fluid (MRF) effector or an electroactive polymer (EAP) effector.

[0164] The optimal vibrational stimulation frequency is 250 Hz, corresponding to the optimal sensitivity of the Pacinian corpuscle (also known as the lamellar corpuscle). The Pacinian corpuscle is a nerve ending in the skin that senses touch and vibration. Deformation of the corpuscle opens pressure-sensitive sodium ion channels to induce action potentials. Alternatively, vibrations can be less than 50 Hz to stimulate Meissner corpuscles (also known as tactile corpuscles) in the light-touch-sensitive fingers.

[0165] This mechanical stimulator can reduce tremor through several methods. One method is to transmit ambiguous or modified proprioceptive signals to the brain that drive the proprioceptive signals transmitted from the tremoring muscles. Another method is impedance control. Nodal impedance can alter co-contracting muscles through transcutaneous nerve stimulation, affecting muscle stiffness and thus muscle contraction. Yet another method is to generate compensatory muscle contractions in contrast to tremorous contractions through nerve stimulation. Preferably, the stimulator is securely attached to the dermal surface, for example, using elastic or Velcro bands.

[0166] Effectors: chemical, thermal, and other

[0167] The examples in this article have primarily described stimulation such as electrical or vibratory tactile stimulation. However, alternatively, stimulation can be achieved using other effectors that can provide significant benefits in terms of patient comfort, portability, safety, or cost.

[0168] In another variation of the embodiments, the effector may be a neuromodulatory chemical that raises or lowers the neuronal firing threshold. The chemicals used in this invention may be, but are not limited to, local anesthetics of the "caine" family. These "caine" family anesthetics may include, but are not limited to, benzocaine, bupivacaine, butacaine, carbisocaine, chloroprocaine, ciprocaine, decabivacaine, eticaine, heptacaine, levobupivacaine, lidocaine, lidocaine hydrochloride, mabivocaine, misucaine, prilocaine, procaine, propancaine, ropivacaine, and tetracaine. Other chemical families may include those of the menthol family, or α-hydroxysansinol derived from Sichuan pepper, or capsaicin, all of which are known to affect peripheral sensory nerves.

[0169] Figure 12 A chemical stimulator is shown that can deliver chemical stimulation percutaneously via a patch or via microinjection. Preferably, the pre-loaded protocol can be a predetermined composition of one or more chemical substances. In this invention, the local anesthetic may be known for other indications, and the recommended dose for simulation has been tested and approved for the treatment of other indications. For example, the local anesthetic lidocaine may be administered at 2 to 10% by weight. Optionally, lidocaine may be administered in combination with other anesthetics. Figure 12 As shown, two neuromodulatory chemicals are mixed to provide a customized composition. The chemostimulator can be administered as a composition comprising 2.5% by weight lidocaine and 2.5% by weight prilocaine. Alternatively, the chemostimulator can be administered as a composition comprising 0.1 to 5% by weight lidocaine and 0.1 to 5% by weight prilocaine.

[0170] The chemical stimulant can be α-hydroxysanshool derived from Sichuan pepper seeds. This α-hydroxysanshool can be contained in an excipient or carrier. The excipient can include a gel, cream, oil, or other liquid. If the delivery method is a percutaneous patch, the chemical agent is preferably formulated as a cream or gel. The user can access the control module 740 (… Figure 7 Choose a composition. If the delivery method is microinjection, the formulation may preferably be a solution.

[0171] In some embodiments, the effector may be a temperature effector 732 that induces cooling or heating. Figure 7 This effector can modulate neuronal firing by directly cooling the nerve or indirectly by cooling adjacent muscles, skin, or other parts of the arm. Temperature effectors can include, for example, piezoelectric elements (e.g., Peltier cooling tiles), circulating fluids, compressed expandable gases, cooled or heated solid materials, or evaporative materials. An example of a cooling effector may be as disclosed in U.S. Publication No. 2010 / 0107657, which is incorporated herein by reference. Heating or cooling can be applied as a patch that can be attached (such as an armband) to the dermal surface or as an implant.

[0172] In embodiments with a thermal stimulator, preferably, the pre-loaded protocol may be a predetermined stimulation temperature and associated stimulation duration. Preferably, the pre-loaded protocol may require a thermal cooling duration of 15 minutes and a cooling temperature in the range of 15 to 25°C. The stimulation duration may be pre-programmed (but not limited to) approximately 5 to 30 minutes. The maximum stimulation length should be well tolerated by the user without causing any muscle or nerve damage. In embodiments where the stimulator is a thermal stimulator, a temperature sensor may serve to detect the effective cooling temperature. The effective cooling or heating temperature may be the temperature felt by the user, but it does not necessarily have to be the same as the applied temperature. If the temperature sensor determines that the effective temperature reaches a threshold (which can range from 5°C to greater or less than the applied temperature for a particular protocol), then the processor 797 (from...) Figure 7 The protocol can be modified to cool or heat more than initially programmed to compensate for the difference between effective cooling and expected cooling.

[0173] Alternatively, the present invention may apply other effectors including acoustic (using ultrasonic stimulation to stimulate sensory nerves at the fingertips), vibratory, tactile, luminescent (e.g., light exposed to optogenetically modified nerves), magnetic (e.g., by rapidly switching RF fields), or combinations of these mechanisms.

[0174] Shape factor: Common wearable stimulators

[0175] Reference Figure 14 AE, Figure 7The system 700 can be non-invasive, fully implantable, or partially implantable. For example, a non-invasive embodiment may include a non-invasive shell such as a sheath 1400, a patch 1410, or a glove. In such a non-invasive embodiment, the shell's interface communicates with an external part of the patient. In some embodiments, one or more components of the system components may be implanted 1420. For example, at least a portion of the effector and / or shell interface may be implanted in the patient at a contact point, while the power source is outside the patient's body.

[0176] A non-invasive system shell can help keep the interface and / or effector very close to the patient. The shell can cover a long arm or can be a narrow band. The shell can cover at least a portion of the circumference of any part of the limb, or the shell can cover the entire circumference of any part of the limb. The function of the shell can be to maintain the position of the external device relative to the implant. The purpose of maintaining this position can include achieving good power delivery, reliable communication, or other purposes.

[0177] The shell can be made of any material suitable for achieving the desired performance. For example, the shell material can be a flexible and / or stretchable material, a polymer, or a fabric. The shell can include fasteners such as Velcro, ties, buckles, and / or knots to secure the device to the patient. The shell can include multiple layers and / or pockets configured to hold various components of the system as disclosed herein.

[0178] The system can be positioned by the patient, with or without the assistance of a caregiver. In some embodiments, the system may have assistive mechanisms for positioning it on the arm, such as pressure-responsive snaps and / or self-aligning magnets. In some embodiments, such as sleeve 1400, the system may slide onto (similar to a sports sleeve) the end of the limb or wrap around the arm or self-wrap (similar to a snap strap) around the arm.

[0179] In some embodiments, the outer shell may take the form of a patch 1410. For example, the outer shell patch 1410 may be fastened to the patient's skin using a removable or biodegradable adhesive. The patch may be worn at different times, including but not limited to patches worn only during the stimulation phase and patches left in place for days, weeks, or months. The patch may also be attached mechanically, chemically, or electrically. Such embodiments include, but are not limited to, staples, strings, or magnets for securing the patch in the desired location.

[0180] In some embodiments, the non-invasive system may include an interface that communicates with a patient, but in which the housing is not attached to the patient. For example, the system may be an external device for patient interaction. For instance, the housing may be an open or closed tubular structure where the patient can place a limb. Figure 14As illustrated in D, another example includes an external device such as a wrist pad or support pad 1430 or support structure on which a patient can place at least a portion of a limb.

[0181] In one embodiment, the housing 1450 may have a design for wearing on a user's wrist or arm, such as... Figure 14 The configuration of the wristwatch shown in HK. The housing 1450 may include an interface 1452 that is detachable from, partially detachable from, or attached to the housing and can interact with the user. This interface 1452 can be attached to the housing 1450 and can be discarded after a period of use. The electrodes 1454 of the interface can be arranged in a strip and can be arranged in an anode / cathode pair. Other electrode configurations as described herein may also be used. This period of time may be after a single use, or after multiple uses over a cycle of minutes, hours, days, weeks, or months. The interface itself may be an entire part of the wristband, a part of the wristband, or attached to the wristband. The wristband itself may be part of the interface or part of the housing, or both. In one example, a wristband with or without an interface can fasten around the wrist by including a slightly curved, elastic material that wraps into a circle around the wrist when it moves. In another example, there is a temperature-sensitive material with shape memory (such as a nickel-titanium alloy), so that when the device comes into contact with the skin, the wristband with or without an interface can change shape to wrap around the patient's wrist. In another example, the wristband, with or without an interface, has one or more metal wires inside or outside the wristband that maintain a new shape as it moves to allow the user to place the device on their wrist and apply force to shape the wristband into the user's unique anatomy. In yet another example, the wristband, with or without an interface, partially or completely wraps around the wrist. This wrapping can be on the same axis or can be a spiral wrap.

[0182] Disposable or non-disposable interfaces can be attached to the housing in many different ways, including but not limited to snap-on features that may or may not include self-aligning features, Velcro, press-fit, magnets, temperature, and adhesives. The connection can be in one or more dimensions or axes. As an example, Figure 14 J and Figure 14K illustrates a possible embodiment with a self-aligning segment, which can be a magnet that can connect the interface to the body in three dimensions. The circular shape of the alignment segment allows alignment in a first dimension within a plane. The rod-shaped portion of the alignment segment, which may deviate from the circular feature of the alignment segment, can align the interface on the appropriate axis. The overall shape of the alignment segment can align the interface in the final dimension, which is depth in this particular example of the embodiment. The housing may have matching features of the shape to which the connection can be attached. It is possible that the connection features can be inverted, and the alignment segment can be placed on the housing, while the matching features of the shape are placed on the interface. These connections of the alignment segment may have or not have magnets on one, two, or none of the housing or interface components.

[0183] Alternatively, the external device can be an object that is not worn on the body. For example, it can have the shape of a mobile phone and the patient carries the device in their pocket, bag, hand, or in other ways, such as transporting and supporting a cellular phone on a table. It can be designed to be placed on a furniture surface where the patient wants their tremor to be controlled, such as at a dining table, in the kitchen, or in their locker room.

[0184] like Figure 14 As shown in Figure L, another preferred embodiment of the invention may include a stimulation device 1460 having one or more electrodes applied along the spine. This stimulation device can be used to stimulate the release of neurotransmitters and reduce tremors by neurally modulating nerves located along the spine. Stimulation can affect the release and uptake of neurotransmitters, thereby affecting the nerves innervating the tremor area. Preferably, the electrodes are placed on the dermal surface at the cervical vertebrae, preferably C1 to C8, but most preferably between C5 and C8. Preferably, these electrodes are patch electrodes. Preferably, the operating unit can be attached to the user, and for ease of connection, the leads connecting the electrodes to the operating unit are preferably magnetized. The operating unit can be connected to and controlled by a processor. Because the electrodes are preferably placed along the spine (user's back), a separable and portable control module allows for easier user operation.

[0185] In one embodiment, electrodes can be placed on either side of the spine surrounding the C2 to C8 region of the neck and shoulder. The electrodes can be placed approximately 100 cm to 1 cm from the spine and spaced 200 cm to 5 cm apart. Stimulation parameters can include a phase duration of 500 μs to 30 μs, preferably 300 μs to 60 μs (microseconds). The pulse rate can range from 10 Hz to 5000 Hz, and preferably from 50 Hz to 200 Hz or 150 Hz. The cycle time can be continuous or range from 5 seconds to 1 hour. A preferred cycle time is approximately 5 seconds to 20 seconds or 10 seconds. The duration of electrical stimulation can range from 5 minutes to 24 hours per day. A preferred range can include 30 minutes to 60 minutes, repeated approximately 10 times per day, or a preferred range can be approximately 40 minutes to 1 hour per day, repeated once per week to once per day. The amplitude (which can be used interchangeably with the intensity) can range from 0.1 mA to 200 mA, and preferably from 1 mA to 10 mA. The user can use the device for a period of time ranging from one day to one month, or preferably from two to four days, before it becomes effective on the user's vibration.

[0186] Shape factor: for electrical stimulation

[0187] Traditional TENS devices are often difficult to position, bulky, and uncomfortable. The innovations described below are solutions that make them easy and quick to apply, allow for the adjustment of the simulator to control ET, and enable patients to use them separately and comfortably.

[0188] With traditional TENS devices, it is difficult to properly determine the size and location of the sticker electrode for optimal targeting of the desired nerve. Smaller electrodes increase the current density at the target nerve, but with a small pad, they are likely to miss the nerve, and the higher current density from a smaller electrode can cause discomfort. Larger pads are easier to position, but require more power and are more likely to unintentionally stimulate adjacent tissue. The following innovation addresses these challenges and achieves consistent, effective, comfortable, and safe stimulation.

[0189] Instead of using only a single electrode as the cathode and a single electrode as the anode, such as Figure 15As shown in A-15C, the device may comprise an electrode array 1500. While the electrodes are shown individually on the patient's skin for clarity, in practice, the electrode array may be integrated into a sleeve, flexible pad, or substrate, or other shape factor, as described herein. An appropriate combination of electrodes can be selected each time the device is repositioned or not based on a detected stimulation need. Stimulation may be performed using a single electrode as both anode and cathode, or a combination of electrodes may be used to shape a simulated field. Electrode selection may be automatic based on feedback from sensors within the device (see below). Alternatively, electrode selection may be performed manually by the user. For example, the user may cycle through electrode combinations until they find a combination that provides optimal tremor reduction or achieves the same tingling sensation in the first (index) and second fingers as occurs with median nerve sensory stimulation. Figure 15 Figure A illustrates a two-dimensional discrete electrode array 1500. Optionally, some of the electrodes can be combined into linear rows so that the two-dimensional array is formed by multiple rows of electrodes. Figure 15 Figure B shows a linear electrode array 1500 that can be worn as a band, patch, pad, sleeve, etc., as shown in the figure. Figure 15 The diagram in Figure C can be used to hold the housing 1502 of the electrode array 1500.

[0190] Optionally, electrical stimulation from poorly positioned electrodes can be redirected to the target nerve by modifying the conduction pathway between the electrode and the target nerve. For example, as... Figure 16 As illustrated in A-16D, a conduction pathway enhancer 1600, which may be made of conductive material, can be placed on, embedded in, implanted, or a combination thereof on a patient's skin to enhance the conduction of electrical stimulation from electrode 1602 to target nerve 1604. This conduction pathway enhancer can be placed on and / or across a nerve. For example, in one embodiment, a tattoo with conductive ink can direct off-target stimulation toward the median nerve. Tattoos that are more conductive than adjacent structures (i.e., blood vessels, nerves) will provide a path of least resistance and redirect the current. To place or locate the conductive tattoo, the target nerve is first clearly identified. The conductive tattoo is then placed on the target nerve. Figure 16 As shown in A-16D, conductive tattoos may include multiple conductive strips passing through a nerve. In some embodiments, the strips may be parallel to each other and pass laterally through the nerve. In other embodiments, the strips may be formed into a star-shaped or mesh pattern with a center located on the nerve. In other embodiments, the strips may also be placed on the nerve and parallel to the nerve (not shown).

[0191] For user adoption, wearable devices should be discrete and comfortable. Figure 14In the preferred embodiments shown in B and 14F, for example, the effector is electrical, and the skin patch has a single or multiple electrode electronics printed in a predetermined pattern onto a flexible substrate to create a bandage-like "second skin." For optimal comfort and surface adhesion, mechanical characteristics such as elasticity and stiffness should be matched to the skin. Circuits and wiring for surface electrical stimulation can be printed or etched into a flexible material to make the device conform to the body or tissue within the body. For example, it can be copper printed on a flexible substrate such as plastic.

[0192] exist Figure 14 In another embodiment shown in G, the device may be located on a body surface but includes percutaneous penetrating elements 1470 to improve effects on nerves. These elements may be microneedles for improving stimulation and / or drug delivery. In some embodiments, the percutaneous penetrating elements may be formed as an array of microelectrodes placed on the skin surface and penetrating the skin. The microelectrode array can function as similar to microneedles and can improve signal transmission from the electrodes to nerves and improve skin permeability to improve local drug delivery.

[0193] Sensors: Types of sensors

[0194] Devices or systems may include sensors. Sensors used to monitor tremor may include combinations of single-axis or multi-axis accelerometers, gyroscopes, inclinometers (to measure and correct for changes in the gravitational field caused by slow changes in device orientation), magnetometers; fiber optic goniometers, optical or electromagnetic tracking; electromyography (EMG) to detect electrical discharges in tremor muscles; electroneurography (ENG) signals; cortical recordings performed using techniques such as electroencephalography (EEG) or direct neural recordings on implants very close to the nerves. Figure 17 The diagram shows a representative location of the motion sensor on the hand (1710) or wrist (1720). Other tracking locations may include fingers or other body parts.

[0195] Data from these tremor sensors are used to measure current and historical tremor characteristics in patients, such as amplitude, frequency, and phase. These sensors can also be used to determine activities, such as to distinguish between involuntary movements (e.g., tremor) and voluntary movements (e.g., drinking, writing) or the presence or absence of tremor relative to other detected activities, such as the time of day or the sleep / wake cycle.

[0196] The device may also include sensors that provide performance and usage data, including when the device is worn (e.g., from a temperature sensor), the device's location (e.g., from GPS), battery level, or video recording. In another embodiment, the sensor is a temperature sensor that measures the temperature of a cooled limb. In another embodiment, the sensor includes video recording. In yet another embodiment, sensors from existing hardware such as smartphones are used. For example, tremor can be measured using an accelerometer on a smartphone or by having the patient participate in a tremor-inducing writing task by analyzing lines traced on a smartphone screen.

[0197] Sensors: Algorithms for extracting vibrations

[0198] The algorithm will be used to extract information about tremors from the data stream provided by sensors. Tremors may not be identified based on their time-domain signal, frequency-domain signal, amplitude, or discharge pattern (e.g., bursts, spikes). For example, in Figure 18 In the study, frequency analysis of the spectral power of the gyroscope motion data showed that the tremor was centered at approximately 6.5 Hz (see the maximum power in the curve below).

[0199] Motion data can be taken as each raw sensor channel or by fusing raw signals from multiple sensors. As an example, multi-axis accelerometer data can be combined into a single numerical value for analysis. The algorithm will extract motion data in the range of 4 to 12 Hz to remove movements not attributable to tremor. This can be done by using any combination of notch filters, low-pass filters, weighted frequency Fourier linear combiners, or wavelet filters. Since each patient has a dominant tremor frequency, this range can be narrowed based on specific knowledge of the patient's tremor or tremor history. For example, for a patient with a 6 Hz tremor, the analysis algorithm may extract motion data only in the range of 5 to 7 Hz. Optionally, if the patient is known to have a tremor with a maximum wrist flexion and extension of 5°, the analysis algorithm determines that the measured 45° wrist flexion movement is likely due to intentional total movement rather than tremor. Optionally, the algorithm will sample motion data by identifying time periods to likely correspond to posture maintenance or fine motor tasks.

[0200] Once the appropriate motion data is extracted, the algorithm will analyze the key characteristics of the tremor, including amplitude, center frequency, frequency spread, amplitude, phase, and spectral power.

[0201] Sensor fusion technology can also be used to analyze different aspects of tremor. For example, multi-axis accelerometers and gyroscopes attached to the back of the hand can be combined to reduce noise and drift and determine the hand's accurate orientation in space. If a second pair of multi-axis accelerometers and gyroscopes are also used on the wrist, the joint angle and position of the wrist can be determined during tremor. This can isolate what stimulation affects which nerves cause damping in the different muscle groups that control tremor.

[0202] Patients with ET have two parts of their tremor. Action tremor is present during intentional movement and has a major impact on quality of life because it affects people's ability to perform daily tasks such as drinking, eating, writing, and dressing. Postural tremor is present during periods of resistance to gravity and maintaining a stationary position. While less impactful on quality of life, it can be embarrassing. Postural tremor usually presents earlier in the course of the disease and is thought to drive action tremor. Both parts typically range from 4 to 12 Hz, with older patients experiencing the lower frequency tremor.

[0203] Detecting postural and action tremors is more challenging than detecting resting tremors. Resting tremors are present in other movement disorders, including Parkinson's disease, and can be easily identified by analyzing only the presence of tremors in the limbs at rest. Extracting action tremors from movement data is challenging because it requires separating movement caused by tremors from movement caused by tasks.

[0204] Because accelerometer / gyroscope data during a motion task is involved in motion disruptions during the task, identifying postural tremor may be easier than identifying action tremor. It is believed that postural tremor can drive action tremor because people often develop postural tremor earlier in life than action tremor and their frequencies are approximately equal. In our clinical studies, we found that, as... Figure 19 As shown, the correlation between postural tremor and action tremor supports the theory of using postural tremor data to analyze or treat action tremor.

[0205] Sensors: Data storage and use

[0206] like Figure 20 As shown, the stimulation device 2000 may include hardware, software, and firmware to record and transmit data such as tremor characteristics, stimulation history, performance, and the use and / or control of the device to a data portal device 2002 (such as a smartphone, cellular phone, tablet computer, laptop computer, desktop computer, or other electronic device using a wireless communication protocol such as Bluetooth).

[0207] Data recorded by devices used by ET patients can be stored on smartphones, which then transmit the data to a cloud-based database / server 2004. Alternatively, the devices used by ET patients can directly transmit data to the cloud-based database / server 2004, enabling numerous activities including tremor tracking, stimulation optimization, sharing with caregivers and physicians, and community building. This data can inform controllers, providing real-time feedback to patients, caregivers, and / or clinicians, or it can be stored to provide historical data to patients, caregivers, and clinicians. Data stored in the cloud 2004 can be viewed by multiple users 2008 on multiple platforms 2006. Furthermore, data in the cloud 2004 can be merged and analyzed by computing devices 2010.

[0208] Tremors are typically monitored every few months, or perhaps annually, when patients visit their physicians. This monitoring is usually highly subjective. Moreover, the severity of tremors can be significantly influenced by many factors, including sleep patterns, emotional state, prior physical activity, caffeine intake, food, medication, and more.

[0209] This infrequent and inaccurate monitoring limits the ability of patients, their caregivers, and physicians to understand the severity and development of a patient's tremor, as well as the effectiveness of various treatments and behaviors. These factors can interact with the effects of stimulation provided by the device, and these interactions are difficult to detect. These interactions can be identified to optimize treatment and help patients better understand how their behaviors affect their tremor.

[0210] exist Figure 21 In one embodiment shown in A, 2100 tremors are monitored using sensors, which may be an IMU, electrodes, or any other sensors previously discussed. This monitoring may be continuous or over discrete time periods. Data from these sensors is 2110 analyzed to identify changes in tremor characteristics (amplitude, frequency, etc.) over time. The results are recorded and 2120 displayed to the user. This 2110 analysis and / or 2120 display may be performed on the stimulation device itself or by transmitting the raw or analyzed data to a secondary device such as a smartphone or computer.

[0211] In another embodiment, behavioral data can also be collected to allow the analysis to examine the relationship between tremor history and user behavior. Behavioral data may include caffeine, alcohol, medication consumption, and anxiety levels. The system can then alert the patient to the interaction between behavior and tremor.

[0212] In another embodiment where the device is therapeutic (i.e., if it has an effector), 2102 stimulation history can be collected so that the analysis can examine the relationship between stimulation history and tremor characteristics.

[0213] Figure 21 The embodiment shown in B adds 2140 uploading to the cloud. The order of 2140 uploading and 2110 analysis can be reversed so that analysis is performed on-board (not shown) before uploading. Using the cloud enables the results to be displayed to user 2120 on various networked devices, including smartphones, tablets, laptops, and desktop computers; or to other users such as physicians or caregivers 2150; or for pooled analysis across multiple patients 2160.

[0214] Figure 21 C illustrates some potential uses of the merged data, including connecting patients 2170 to similar patients or 2180 improving stimulation algorithms based on characteristics such as their tremor features, region, age, and gender.

[0215] Figure 21 D shows Figure 21 The data monitoring and analysis shown in AC are used to adjust stimulation parameters in a closed loop. In this way, the algorithm detects interactions between variables to optimize treatment.

[0216] The device can incorporate closed-loop control of stimulation to adaptively respond to detected tremor or activity levels. This device enables optimal tremor reduction through tremor sensing via activity sensors, data logging of stimulation parameters, and systematic tuning. Figure 26 A diagram illustrates the control of the basic components of such a detection and response system. The (2650) target defines the intended profile. For example, in an ET patient, the profile may be free of tremor, and in a PD patient, the profile may be free of tremor or rigidity. The (2670) error between the (2650) target and the (2660) detection is fed to the (2680) controller, which modifies the (2690) output. The (2680) controller may include a processor and memory. In addition to errors and measurements, the (2680) controller algorithm may also input the history of measurements, stimuli, and activities into its algorithm. The output (2690) modifies the stimulus. If the effector is electrical, this may include modifying the waveform, frequency, phase, position, and / or amplitude of the stimulus. In a preferred embodiment ( Figure 15In this device, the small electrode array is included, and the output modifies which electrodes are used as the anode and cathode. The effects of these modifications are then detected by a measuring device (2660), and the process is repeated. The detection and / or output modification by (2690) can occur continuously in real time, with a periodic delay between predetermined number of times (e.g., per hour or per day), or in response to signals generated by the user (such as a predefined motion sequence or button press). Optionally, the controller can prompt the patient to manually modify the stimulation parameters. This closed loop can be used for automatic self-calibration.

[0217] Figure 26 Figure B shows a control diagram of the basic components of the detection and response system, which is similar to... Figure 26 As shown in Figure A, but now with components located both internally and externally.

[0218] Control can also consider other behavioral patterns, more similar to the feedforward controller 2640. For example, a typical pattern during mealtimes might cause the effector to discharge more actively at specific times to reduce tremors used for those activities. Similarly, people can indicate in their schedules whether they want to increase therapy during certain time periods based on their daily activities, such as whether they are giving a speech or have other anxiety-inducing events. This type of information can also be obtained by the control unit and understood over time. Figure 20 and Figure 21 As shown, data such as sleep, food intake (especially alcohol and caffeine consumption), exercise history, mood (especially anxiety levels), and medication use are collected through other mobile technologies and applications that can be integrated into cloud-based patient databases, such as Azumio, Jawbone, and Fitbit. Users can be prompted to enter such data (e.g., taking a picture of a meal to determine food intake using an imaging processing application). The database will combine discrete events (e.g., the time and amount of caffeine intake) and time-series data (e.g., tremor measurements). Algorithms will examine the relationship between patient behavior, stimuli, and tremor. These will optimize stimuli and alert the patient to behaviors that affect tremor. This will allow for individually optimized tremor treatment and feedback into the system.

[0219] In some embodiments, a user may be prompted to perform a specific task at a predetermined time via a device or cellular phone. This task may be tailored to the type of tremor affecting the patient, such as maintaining an arm in a specific posture for ET or keeping the arm in a static position for Parkinson's disease. During this time, sensors may record the tremor. In some embodiments, the patient may be additionally or optionally instructed to consume caffeine or the time elapsed since their last caffeine consumption may be recorded. This data can be used to determine how caffeine affects the tremor, the efficacy of the treatment protocol, and the duration of the effect of stimulation parameters. In some embodiments, the patient may be prompted at a predetermined time after stimulation (such as 10, 20, 30, and / or 60 minutes after stimulation). This time may be adjusted based on the duration of a measured reduction in tremor after stimulation.

[0220] The device will have onboard data logs and can transmit this information to external data portal devices such as smartphones or internet-enabled charging and sync stations. This transmission can be wireless or direct. External devices have greater storage capacity and allow transmission to databases in the cloud. The external device can analyze the onboard data and present the information on a screen or using indicators such as light-emitting diode (LED) lights, or the data can be displayed on the device itself.

[0221] Data in the cloud will be viewable on multiple platforms, including smartphones, tablets, and computers. This data can be viewed by multiple people, including the user, their physician, caregiver, or family member. This will provide a more comprehensive picture of the patient's tremor and allow for optimized treatment. In some embodiments, users viewing the data can also add comments and annotations, which may be tagged with the identifier of the user who made the comment or annotation, and the time the comment or annotation was made. In some embodiments, the ability to create annotations may be limited to healthcare providers such as the patient's physician and the patient.

[0222] In some embodiments, access to the data is restricted to healthcare providers and patients. Access is restricted by requiring users to establish a secure username and password to access the data. In some embodiments, patients may also grant access to the data to other people such as family and friends.

[0223] Algorithms used for optimization:

[0224] Our data indicate that stimulation with the TENS device is highly effective in some patients, somewhat effective in others, and ineffective in still others. However, optimizing simulation parameters (simulation intensity, frequency, waveform, duty cycle, phase adjustment, etc.) enables the device to minimize tremor while ensuring maximum comfort for each patient, and allows the device to adjust over time to respond to loop dynamics, device positioning, patient status, and more. Figure 22 The decision-making algorithm / controller used for the device is shown.

[0225] In one embodiment, the optimization algorithm is initiated by initializing one or more parameters 2200, which may include stimulus amplitude, desired frequency, on-time duration, off-time duration, and desired stimulus effect delay time. Next, the sensor detects 2202 and records jitter characteristics, including jitter amplitude, frequency, phase, and other characteristics described herein. The detected jitter characteristics 2202 are compared with the desired target jitter characteristics 2204, which may be absent or reduced. The comparison step 2206 may determine the error or difference between the detected jitter characteristics and the target jitter characteristics, and determine whether jitter or reduced jitter exists 2208, or in other words, whether the detected jitter meets or exceeds the target condition. If no jitter is detected, or more generally, if the predetermined target jitter condition is not exceeded, the algorithm loops back to the detection step 2202. If a jitter is detected, or more generally, if the predetermined target jitter condition is exceeded, the stimulus may be turned on 2210. Once the stimulation has exceeded the set on-time duration 2212, the stimulation is turned off 2214, and the algorithm continues back to the detection step 2202. While the stimulation is on, the device can upload the recorded data 2218 to the cloud or other devices for further processing. Once the stimulation has been turned off 2214, the algorithm can monitor the off-time duration 2216, and can continue uploading data 2218 once the off-time has expired. Optionally, data can be uploaded even before the off-time has expired. User-reported events 2220, including caffeine or alcohol intake, feelings of anxiety, and other events that can affect tremor, can also be entered into the system and sent to the cloud. This data can be processed by a controller 2222 that can use various algorithms, including machine learning algorithms, to optimize the stimulation parameters. Once the parameters are optimized, new stimulation parameters are set 2224. Reports 2226 can also be sent to the patient that can highlight or correlate various behaviors identified in the user-reported events with the measured tremor.

[0226] In one embodiment, the stimulation algorithm is designed to optimize the timing of therapeutic “on”. This optimization algorithm can find the optimal solution for the output, including but not limited to minimizing tremor throughout the day to control tremor during a specific task, at a specific time of day, in a specific location, or simply by optimizing the minimization of tremor throughout the day. The algorithm can self-calibrate to adjust stimulation parameters, including but not limited to frequency, amplitude, pulse width, electrode selection for cathodes and anodes, and / or the timing of turning stimulation on and off. The algorithm can respond to user input or can be fully pre-programmed. The algorithm can be a learning algorithm to tailor stimulation over time to adjust in real-time to the patient’s tremor or patient-defined needs. Stimulation can be triggered to turn on or off in response to inputs including but not limited to user input (e.g., turning the device on or off), timing since previous use, time of day, tremor detection (e.g., via accelerometer), electrical recording, or input based on the previously described algorithm or other inputs. As an example, a user can use voice activation to turn off the device to utilize a therapeutic window (i.e., the time of tremor reduction after stimulation is turned off) to provide the stability required for intentional movement over a time interval. In another example, the user bites down or uses tongue muscles detected by an external device placed inside or outside the mouth, which signals to shut off the stimulation and allows the user to stabilize their arm so that intentional movements can be performed in a stable state. In some embodiments, the system and algorithm may detect the type of tremor based on analysis of tremor parameters and measured patient activity, such as distinguishing between postural and action tremors. In some embodiments, stimulation parameters may be determined in part based on the type of tremor detected.

[0227] In some embodiments, the system may be controlled by event triggering. Event triggering may include defined motion, temperature, sound activation, GPS location, or data received by sensors, or any combination thereof. For example, the device may be turned on or off during intentional motion, such as before tremor has begun or ended. In another example, the device may be turned on or off when a specified temperature is reached. The system may act to achieve a desired tremor suppression profile. For example, controls may activate the device during a desired tremor suppression period; continue the action after use of the device before the desired tremor suppression period; and / or respond to tremor detection.

[0228] Optimization based on community data

[0229] Currently, little is known about the temporal course of tremor. While creating a database of individual patients improves our ability to reduce tremor in those patients, combining individual patient data into a database that includes records from many patients allows for the application of more powerful statistical methods to identify optimal stimulation parameters. In some embodiments, data from patients with the same type of tremor can be combined. In some embodiments, tremor data from each patient can include searchable and categorizable metadata, which allows data to be categorized, searched, and / or reorganized on demand within the database. Metadata can include tremor type (tremor amplitude, tremor frequency, tremor duration, etc.), name, age, ethnicity, sex, location, time, food and beverage consumption (especially caffeine and alcohol), activity history (exercise, sleep, etc.), medications, past treatments, and current treatments.

[0230] Compared to Figure 20 and Figure 21 The system described above can be adapted to data from many patients entering the database, and the algorithm can operate on large datasets.

[0231] Community building

[0232] Individuals with ET feel isolated by the disability associated with their tremors. Therefore, they are highly motivated to meet with other people with ET. There are active and growing support groups that organize meetings and enable patients with ET to talk about their issues and discuss possible solutions. Attending these meetings can be challenging because some patients with ET have difficulty driving. Furthermore, individuals in a particular physical location participating in a support group may have different symptoms from each other, and they may lack the ability to identify other patients who are most similar to them.

[0233] Algorithms can help individuals find members of ET communities with similar profiles. For example, algorithms can characterize patients based on their age, tremor severity, tremor features, treatment success, type of treatment, type of medication, location (based on address or GPS), and other characteristics. This will help them communicate with each other and share information from central community websites tailored for specific patients or caregivers with ET. For example, the system can identify patients within a geographic location or other patients within a predetermined distance of a specific patient. Patients can choose to connect to online ET communities and make their location searchable on the system. For patients, the system can identify existing ET community support groups within a predetermined distance.

[0234] Other processors, libraries, and data storage:

[0235] like Figure 7As shown in A-7D, for example, processor 797 can be used to manipulate data, perform calculations, and control other components of the tremor reduction device. Preferably, it can be a microprocessor with peripheral devices or a microcontroller. For example, the processor can receive input from the user via control module 740 and can control the execution of stimuli such as those selected by the user. In another embodiment, processor 797 can execute predefined stimulation protocols selected by the user. These stimulation protocols can be found in a digital library 798 of stimulation protocols, which can be loaded into processor 797 or stored in external memory, such as EEPROM, SD card, etc. Processor 797 can also receive information from sensor 780 and process that information on-board and adjust the stimulation accordingly. The selection of processor is determined by the degree of signal processing required and the number and type of peripheral devices to be controlled. For example, communication with peripheral devices can be performed via any known standard such as USB, UART, SPI, I2C / TWI. The processor can also communicate wirelessly with other device components using Bluetooth, Wi-Fi, etc. The processor can be an on-board device, or tremor data can be transmitted via a wireless link between the processing unit and the stimulation unit.

[0236] In embodiments with electrical stimulator 730, the pre-loaded protocol 798 may be electrical stimulation or a sequence of electrical stimulation. Electrical stimulation or electrical signal refers to electrical pulses or patterns of electrical pulses. Electrical stimulation may include electrical stimulation parameters such as pulse frequency, amplitude, phase, pulse width, or duration. These parameters may be predefined or controlled by the user.

[0237] The data storage unit 770 can be used to store operational statistics and usage statistics of the device, preferably in NAND flash memory. NAND flash memory is a non-volatile data storage device that does not require power to maintain the stored information and can be electrically erased and rewritten. In some cases, it is advantageous that this memory, in the form of a micro SD card, is removable.

[0238] power supply :

[0239] like Figure 7As shown in A-7D, for example, the effector can be electrically coupled to one or more power sources. Power source 750 serves to supply power to the device. Power source 750 can be connected to processor 797 and provide power for processor operation. Preferably, the power source is rechargeable and removable, as this allows the device to be reused. Preferably, the power source is a battery. Several different combinations of chemicals are typically used, including lead-acid, nickel-cadmium (NiCd), nickel metal hydride (NiMH), lithium-ion (Li-ion), and lithium-ion polymer (Li-ion polymer). Preferably, the method of recharging the battery relies on a wall socket or other electrical outlet, solar energy, radio frequency, and electrochemical methods. An alternative power source is a supercapacitor. Supercapacitors can be classified into three different families: double-layer capacitors, pseudo-capacitors, and hybrid capacitors. Preferably, the supercapacitor can be made of nanoporous materials including activated carbon, graphene, carbon nanotubes, carbide-derived carbon, carbon aerogel, solid activated carbon, tunable nanoporous carbon, and mineral-based carbon. Supercapacitors offer the advantages of faster charging than batteries and tolerance to multiple charge-discharge cycles. Optionally, batteries and supercapacitors can be used in combination because their tolerance to a large number of charge-discharge cycles makes them well-suited for parallel operation with batteries and can improve battery performance in terms of power density. Optionally, the power source can harness energy from the body. In some embodiments, the power source can be harnessed by physical movement, heat, and / or sound. Optionally, the power source can include a plug to an external power source such as a commonly used appliance.

[0240] In one embodiment, a special charging station or dongle can be used to recharge the device. The advantage of a special charging station is that it can also facilitate uploading data from the device to a network via Wi-Fi or another communication protocol.

[0241] Implants:

[0242] In some embodiments, at least a portion of the system is implantable. The implanted stimulator can provide better control and comfort than surface stimulation because it is positioned closer to the nerve and avoids stimulating the cutaneous afferent nerves.

[0243] Methods of controlling hand tremors by stimulating peripheral nerves introduce specific requirements for the appropriate implanted stimulator. First, the implant should be small to minimize the invasiveness of the procedure used to position it and to ensure proper implantation. Second, since stimulation can respond to detected tremors or user input, the implant should be able to receive communication from external devices. Third, the device should allow for variability in positioning external devices.

[0244] Any number of the system components disclosed herein can be implanted. In some embodiments, the housing, interface, effector, and power supply are implanted, and the controller is external to the patient. In such embodiments, the controller may, for example, communicate wirelessly with the effector. In other embodiments, the power supply is external to the patient.

[0245] The device can be implanted subcutaneously, partially, or percutaneously (through the skin), and may be on the surface of the skin or not in contact with the body. It can be a component of these devices, such as a surface component that communicates with or provides power to the implanted part. If implanted, the device can be implanted in or around nerves, muscles, bones, ligaments, or other tissues.

[0246] In one embodiment, the implant is positioned in or near the carpal tunnel to affect nerves passing through it. In another embodiment, the implant is located on or near the median nerve between the biceps brachii muscles of the upper arm. In yet another embodiment, the implant is located on or near the median, radial, or ulnar nerves in the forearm or wrist. In yet another embodiment, the implant is located on or near the brachial plexus to affect proprioceptive nerves passing from the arm into the central nervous system.

[0247] The implanted portion can be placed or delivered intravascularly to affect nerves in an area within the implant's effective range. In one example, the device is placed in or through the subclavian artery or vein to affect the nerves of the brachial plexus.

[0248] like Figure 23 As shown, a preferred embodiment of a controllable device for reducing essential tremor for a user includes an electrode 2310 made of biocompatible material, at least partially implanted subcutaneously to stimulate targeted nerves; an external operating unit 2320, which includes a user control interface and is connected to the implanted electrode 2310 via leads. The device may also include other components, including a processor 797 that may perform calculations and control other components; a processor-controlled function generator; a digital library 799 containing a pre-loaded modulation protocol stored on the processor or memory; a sensor 780 connected to or communicating with the processor 797 to detect predefined parameters and transmit that parameter information to the processor; a data storage unit 770 connected to the sensor and the processor; and a power supply 750.

[0249] In this embodiment, the implanted electrode 2310 can be used to provide direct electrical stimulation to the targeted nerve. Since the electrode is at least partially implanted in the body and will remain there for an extended period (preferably several years), it can be made of a material with suitable electrical properties and biocompatibility. Preferably, the material of the electrode 2310 is selected from the group consisting of silicone, PTFE, parylene, polyimide, polyesterimide, platinum, ceramic, and gold, or natural materials such as collagen or hyaluronic acid. The electrode 2310 can have varying shapes and sizes, but it is important that it contacts the nerve of interest. Electrode shapes include planar shanks, simple uniform microwires, and probes that taper from a wider base to a tip. The electrode can have a proximal end and a distal end. The distal end can contact the nerve and can be adapted to deliver nerve stimulation pulses to the selected nerve. The proximal end of the lead can be adapted to connect to an external operating unit operated by the processor 797.

[0250] In a variation of the embodiment, there may be multiple leads connected to different nerve bundles. In another variation, such as Figure 24 As shown in A-24D, the implant can communicate wirelessly. The implant 2400, which may be a microelectrode or microstimulator, can be approached for nerve insertion using needle insertion. The needle 2402 can be inserted into the patient near or close to the target nerve 2404, and then the implant can be withdrawn from the needle. The implant 2400 can communicate with, transmit and receive data with, and be powered by an external device 2406, such as the decision unit described herein.

[0251] In one embodiment, the interface can be an implanted nerve cuff. The cuff can completely or partially surround the nerve. The cuff can be attached to the nerve by means of a shut-off butterfly electrode. In another embodiment, the interface can be a nerve abutment. The abutment can be very close to the nerve or can be placed along the nerve. The cuff can serve to provide good contact or very close proximity between the device and the nerve. In another embodiment, the interface can be anchored to the nerve or a sheath surrounding the nerve. For example, the device can be wrapped around the nerve or nerve sheath, can be attached to, clamped to, secured to using small barbs, or chemically fused to the nerve or nerve sheath. Cuffs, coils, abutments, or anchors all serve to provide good contact or very close proximity between the device and the nerve. Some of these embodiments are... Figure 25 It was depicted in A-25F.

[0252] For example, Figure 25The A-25C illustration may be an embodiment of a coil electrode interface with a multi-coil electrode or a single-coil electrode as shown. In some embodiments, the coil electrode 2500 may be made of a shape memory material such as a nickel-titanium alloy and may have a relaxed straight configuration before insertion and implantation, as well as a coiled configuration after exposure to body temperature. Figure 25 D and Figure 25 Figure E illustrates an embodiment of a butterfly-shaped cuff electrode 2510 that may at least partially surround a nerve. As in other embodiments, the interface may include one or more electrodes and may be made of shape memory material to be configured as an opening during delivery and as a closed configuration surrounding the nerve after implantation. Figure 25 Figure F illustrates an embodiment with an interface having a linear electrode array 2520 capable of contacting and placing along a nerve.

[0253] Methods of implanting an implant can involve local or general anesthesia. The implant can be delivered through one or more perforations in the skin, such as needles or sutures, or it can be an open incision made in the skin to access the target area, or it can combine both methods. In one embodiment, the device can be implanted by passing all or part of the device through tissue surrounding nerves and / or around tissue such as blood vessels or tendons.

[0254] In one embodiment, the implant may include two electrodes positioned along a vascular pathway. This pathway may be along the palmar arch, and the electrodes may be located in the brachial and axillary arteries. A fluid column between the electrodes may carry electricity and stimulate adjacent nerves. The electrodes may be internal to the vascular pathway (such as a stent) or external to the vascular pathway, similar to a vascular wrap. In one embodiment, the device may be an implant capable of bidirectional communication with an external device. Embodiments may include memory. The external “listener” device may also be a power source. The implant may transmit information such as its power reserves or usage history to the “listener.” In another embodiment, the device is an implant capable of sensing activity on a nerve or adjacent nerves and reporting this information to the listener.

[0255] In another embodiment, one or more devices used to place the device may be guided by ultrasound. Ultrasound can be used to measure the proximity of blood vessels, nerves, or other tissues, or to characterize the type and location of adjacent tissues.

[0256] In another embodiment, the electrode for stimulation can be injected as a liquid. In another embodiment, the electrode can be flexible and delivered into a viscous medium (such as hyaluronic acid). In another embodiment, the electrode can be made of a nickel-titanium alloy that takes its shape at 37°C. This would allow the electrode to be injected or inserted into a needle in a configuration such as an elongated arrangement, and then take its form when heated to body temperature. Some of these examples are in... Figure 25 Described in the text.

[0257] The implant may include necessary components for one-way or two-way communication between the implant, external power transmission, communication systems, and / or electronics storing programmable stimulation parameters. The device may include a wireless micromodule that receives command and power signals from an external antenna via radio frequency inductive coupling. If the effector is electrical, the incoming communication channel may include information such as stimulation frequency, delay, pulse width, and on / off interval.

[0258] Percutaneous charging or power supply reduces implant size by eliminating the need for large power sources (such as batteries) and eliminates the need for repeated surgeries to replace the entire power source. External components can be used to wirelessly power internal components, such as through radio frequency (RF) power transmission. For example, the external device can transmit RF power that the internal component receives using a resonant coil. This power can be transmitted at various wavelengths, including but not limited to the RF and microwave spectrum, ranging from 3 kHz to 300 GHz. Optionally, the internal device can contain a battery. The external device can be worn or carried on the body, or it can be in the surrounding environment, such as on a nearby table or wall. It can be portable or stationary. The device can contain capacitive energy storage module electrodes that, when discharged, stimulate the device. If the power supply itself drives the stimulation profile, the electronics can be significantly simplified. The capacitor allows alternating current to pass through while blocking direct current. When the capacitor reaches its dielectric breakdown, it discharges and releases a stimulation pulse.

[0259] The implant can also directly sense tremors, such as using electroencephalography (ENG) or electromyography (EMG) signals, or an accelerometer, or a combination thereof. In this case, the implant can include multiple electrodes, since microelectrodes and macroelectrodes are preferred for sensing and stimulation, respectively. The device can also include an outgoing communication channel for transmitting the detected events.

[0260] Various embodiments of the vibration alteration device and methods of using it have been disclosed above. These various embodiments can be used alone or in combination, and various variations of individual features of the embodiments can be made without departing from the scope of the invention. For example, the order of the various method steps may be changed in some instances, and / or one or more optional features may be added to or removed from the described device. Therefore, the above description of the embodiments should not be construed as unduly limiting the scope of the invention as set forth in the claims.

[0261] Certain features described herein in the context of separate embodiments may also be implemented in combination in a single embodiment. Conversely, various features described in the context of a single embodiment may also be implemented separately or in any suitable sub-combination in multiple embodiments. Moreover, although features are described above as functioning in certain combinations and even initially claimed in this way, in some cases one or more features of a claimed combination may be removed from that combination, and the claimed combination may be for sub-combinations or variations thereof.

Claims

1. A system for treating tremor, comprising: A first device, which is a transcutaneous device for treating tremors in a user, comprising: Control unit; A first peripheral nerve effector is configured to be positioned such that a first afferent nerve pathway is modulated by either electrical or vibrational stimulation. A second peripheral nerve effector is configured to be positioned such that a second afferent nerve pathway is modulated by either electrical or vibrational stimulation. At least one sensor is configured to measure the movement of the user's limbs to characterize one or more features of the tremor, the one or more features of the tremor being selected from a group consisting of tremor frequency and tremor period; and The control unit includes a processor and a memory for storing instructions that, when executed by the processor, cause the first device to: The first peripheral nerve effector delivers either electrical or vibrational stimulation to the first afferent nerve; and The second peripheral nerve effector delivers either electrical or vibrational stimulation to the second afferent nerve. The delivery of the electrical stimulation and the vibration stimulation reduces the tremors in the user's limbs; and The computing system is configured as follows: Receive data including one or more vibration characteristics from the first device; Based on the application of learning algorithms to comprehensive data, optimized stimulation parameters are determined for additional electrical or vibration stimulation. This comprehensive data includes (i) received data or (ii) received data plus community data related to other users obtained from other wearable devices. The optimized stimulation parameters are transmitted to the first device.

2. The system of claim 1, wherein the second peripheral nerve effector is configured to be positioned to modulate the second afferent nerve pathway by vibration stimulation, and wherein the second peripheral nerve effector comprises one or more mechanical effectors.

3. The system of claim 1, wherein the second peripheral nerve effector is configured to be positioned to modulate the second afferent nerve pathway by vibrational stimulation, and wherein the second peripheral nerve effector comprises one or more piezoelectric elements.

4. The system of claim 1, wherein the second peripheral nerve effector is configured to be positioned to modulate the second afferent nerve pathway by vibration stimulation, and wherein the second peripheral nerve effector comprises one or more vibration tactile units.

5. The system of claim 1, wherein the second peripheral nerve effector is configured to be positioned to modulate the second afferent nerve pathway by vibration stimulation, and wherein the second peripheral nerve effector comprises an ultrasonic motor.

6. The system of claim 1, wherein the first peripheral nerve effector is located on a first portion along the circumference of the band, and the second peripheral nerve effector is located on a second portion along the circumference of the band.

7. The system of claim 6, wherein the strap is configured to be wearable on the user's wrist or arm.

8. The system of claim 1, wherein the characterization of the one or more features of the tremor includes frequency analysis of the spectral power of the measured motion.

9. The system of claim 8, wherein the frequency analysis is limited to between 4 Hz and 12 Hz.

10. A system for treating tremor, comprising: A first device, which is a transcutaneous device for treating tremors in a user, comprising: Control unit; A first peripheral nerve effector includes (i) at least one stimulating electrode configured to be positioned such that a first afferent nerve pathway is modulated by electrical stimulation; or (ii) at least one mechanical effector configured to be positioned such that the first afferent nerve pathway is modulated by vibrational stimulation. A second peripheral nerve effector includes: (i) one or more stimulating electrodes configured to be positioned such that a second afferent nerve pathway is modulated by electrical stimulation; or (ii) one or more mechanical effectors configured to be positioned such that a second afferent nerve pathway is modulated by vibrational stimulation. At least one sensor is configured to measure the movement of the user's limbs to characterize one or more features of the tremor; and The control unit includes a processor and a memory for storing instructions that, when executed by the processor, cause the first device to: Depending on whether the first peripheral nerve effector includes at least one stimulating electrode or at least one mechanical effector, one of which is delivered electrical stimulation to the first afferent nerve via the first peripheral nerve effector; and Depending on whether the second peripheral nerve effector includes one or more stimulating electrodes or one or more mechanical effectors, vibrational stimulation is delivered to the second afferent nerve via the second peripheral nerve effector. The delivery of the electrical stimulation and the vibration stimulation reduces the tremors in the user's limbs; and The computing system is configured as Receive data including one or more vibration characteristics from the first device; Based on the application of learning algorithms to comprehensive data, optimized stimulation parameters are determined for additional electrical or vibration stimulation. This comprehensive data includes (i) received data or (ii) received data plus community data related to other users obtained from other wearable devices. The optimized stimulation parameters are transmitted to the first device.

11. A system for treating tremor, comprising: A first device, which is a transcutaneous device for treating tremors in a user, comprising: Control unit; A first peripheral nerve effector includes at least one stimulating electrode or piezoelectric element, the at least one stimulating electrode or piezoelectric element being configured to be positioned such that a first afferent nerve pathway is modulated by one of electrical stimulation or vibrational stimulation. A second peripheral nerve effector includes at least one stimulating electrode or piezoelectric element, the at least one stimulating electrode or piezoelectric element being configured to be positioned such that a second afferent nerve pathway is modulated by one of electrical stimulation or vibrational stimulation. At least one sensor is configured to measure the movement of the user's limbs to characterize one or more features of the tremor, the one or more features of the tremor being selected from a group consisting of tremor frequency and tremor period; and The control unit includes a processor and a memory for storing instructions that, when executed by the processor, cause the first device to: Depending on whether the first peripheral nerve effector includes at least one stimulating electrode or piezoelectric element, one of electrical stimulation or vibration stimulation is delivered to the first afferent nerve via the first peripheral nerve effector; and Depending on whether the second peripheral nerve effector includes at least one stimulating electrode or piezoelectric element, it delivers either electrical stimulation or vibrational stimulation to the second afferent nerve via the second peripheral nerve effector; and The computing system is configured as follows: Receive data including one or more vibration characteristics from the first device; Based on the application of learning algorithms to comprehensive data, optimized stimulation parameters are determined for additional electrical or vibration stimulation. This comprehensive data includes (i) received data or (ii) received data plus community data related to other users obtained from other wearable devices. The optimized stimulation parameters are transmitted to the first device.

12. The system according to any one of claims 1-3, 10-11, wherein the delivery of the vibration stimulus transmits proprioceptive signals to the brain.

13. The system according to any one of claims 1-3, 10-11, wherein the memory further comprises instructions that, when executed by the processor, also cause the control unit to: The motion data generated by measuring the user's limbs; Based on the analysis of the motion data, the tremor frequency or tremor period is determined; and One or more parameters of the electrical stimulation or the vibration stimulation are set based on the tremor frequency or the tremor period.

14. The system according to any one of claims 1-3, 10-11, wherein the electrical stimulation comprises a frequency between 50 Hz and 300 Hz.

15. The system according to any one of claims 1-3, 10-11, wherein the vibration stimulation comprises a frequency of 250 Hz.

16. The system according to any one of claims 1-3, 10-11, wherein the electrical stimulation comprises a frequency below 50 Hz.

17. The system according to any one of claims 1-3, 10-11, wherein the first afferent nerve is one of the radial nerve, median nerve, and ulnar nerve.

18. The system according to any one of claims 1-3, 10-11, wherein the first afferent nerve is one of the radial nerve, median nerve, and ulnar nerve.

19. The system according to any one of claims 1-3, 10-11, wherein the electrical stimulation comprises sudden stimulation.

20. The system of claim 19, wherein the burst stimulus comprises a plurality of bursts of said stimuli having a variable time delay between bursts of the stimuli.

21. The system according to any one of claims 1-3, 10-11, wherein the first peripheral nerve effector comprises a plurality of electrodes arranged in an array.

22. A system for treating tremor, comprising: A first device, which is a transcutaneous device for treating tremors in a user, comprising: Control unit; A first peripheral nerve effector is configured to be positioned to modulate a first afferent nerve pathway by either electrical stimulation or ultrasound stimulation. A second peripheral nerve effector is configured to be positioned to modulate a second afferent nerve pathway; At least one sensor is configured to measure the movement of the user's limbs to characterize one or more features of the tremor; and The control unit includes a processor and a memory for storing instructions that, when executed by the processor, cause the first device to: The first peripheral nerve effector delivers either electrical stimulation or ultrasound stimulation to the first afferent nerve; and The second peripheral nerve effector delivers either electrical or ultrasonic stimulation to the second afferent nerve. The delivery of the electrical stimulation and / or the ultrasound stimulation reduces the tremors in the user's limbs; and The computing system is configured as follows: Receive data including one or more vibration characteristics from the first device; Based on the application of learning algorithms to comprehensive data, optimized stimulation parameters are determined for additional electrical or ultrasonic stimulation. This comprehensive data includes (i) received data or (ii) received data plus community data related to other users obtained from other wearable devices. The optimized stimulation parameters are transmitted to the first device.

23. The system of claim 22, wherein the second peripheral nerve effector is configured as one or more acoustic effectors.

24. The system of claim 22, wherein the first peripheral nerve and the second peripheral nerve are adjacent nerves.

25. The system of claim 22, wherein the first peripheral nerve and the second peripheral nerve are adjacent in a specific area of ​​the body.

26. The system of claim 22, wherein the electrical stimulation has an amplitude below the sensory threshold.

27. The system of claim 22, wherein the first peripheral nerve carries proprioceptive information from the user's limbs.

28. The system of claim 22 further includes a user interface adapted to receive input from a user to adjust parameters of the electrical stimulation or the ultrasound stimulation.

29. The system of claim 22, wherein the delivery of the ultrasound stimulation transmits proprioceptive signals to the brain.

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