Wearable Neurostimulation System

Abstract

A band is provided for securing a wearable neurostimulation device worn by a user to stimulate one or more peripheral nerves of the user. The band can include a frame having an engagement structure. The band can have an outer side and an inner side. When the band is worn by a user, the user can see the outer side and the inner side faces the user's skin. The neurostimulation device can have an upper side, a lower side, and an outer wall disposed therebetween. The outer wall can be sized and shaped to be secured within the engagement structure when the neurostimulation device is inserted into the engagement structure from the inside of the band while preventing the neurostimulation device from passing completely through the engagement structure.

Description

[Technical field]

[0001] (Reference to Related Application) This application claims the benefit of U.S. Provisional Patent Applications Nos. 63 / 262,331, 63 / 367,577, 63 / 203,895, and 63 / 264,498, filed on October 8, 2021, July 1, 2022, August 3, 2021, and November 23, 2021, respectively, the entire disclosures of each of which are incorporated herein by reference in their entirety.

[0002] Some embodiments of the present invention relate generally to systems, devices, methods, and methods of manufacture for neuromodulating (e.g., stimulating) nerves, and more specifically to a wearable device including a band for releasably securing a stimulation device to a user's limb or other body part for electrically stimulating peripheral nerves to treat various diseases and disorders. [Background technology]

[0003] A wide variety of modalities can be utilized to neuromodulate peripheral nerves. For example, the applicant's own research has demonstrated that electrical energy can be delivered transcutaneously via electrodes on the skin surface using a neurostimulation system to stimulate peripheral nerves, such as, but not limited to, the median, radial, and / or ulnar nerves of the upper limbs, the tibial, saphenous, and / or peroneal nerves of the lower limbs, or the auricular vagus nerve, auricular temporal nerve, trigeminal nerve, or cranial nerve on the head or ear. Some conditions, such as tremors, can be treated by some form of transcutaneous, transdermal, or other implanted form of peripheral nerve stimulation. Summary of the Invention

[0004] A wearable system for neuromodulation of nerves in a compact ergonomic form factor is necessary to increase efficacy, compliance, and / or comfort with the use of the device. The device can be attached to a band that is wrapped around the patient's wrist. The band is worn throughout the day, including during daily activities. The device is not permanently attached to the band to provide the patient the ability to replace or swap out bands while maintaining the same device. This feature allows the patient to replace or upgrade bands without incurring the cost of purchasing a new device. This feature further allows the patient to switch devices between bands designed for different purposes and / or activities. The characteristics of each band (e.g., material, weight, size, color, etc.) can be optimized or selected depending on the purpose or activity. The patient can simply remove their device from their current band and engage the same device on another band optimized for the upcoming activity.

[0005] In some embodiments, because the device and band are used during daily activities and are not permanently attached to one another, the engagement between the band and the device needs to be secure, but also ergonomic, allowing the patient to easily remove the device from the band without resorting to hand tools (e.g., screwdrivers, wrenches, pliers.) Simple attachment structures such as snaps may not provide the desired level of fixation between the device and band.

[0006] Some embodiments of the system disclosed herein include a band made of one or more soft materials (e.g., silicone, fabric). In contrast, the device can be a hard or rigid material to house the electronics. In this way, the soft goods (e.g., band) are separated from the electronics of the device. Another advantage of the soft goods being separable from the device is that it allows the user to personalize the size, feel, and / or aesthetics of the band without having to replace the device.

[0007] Another advantage of some of the systems disclosed herein is the use of an overmolded silicone band. In some embodiments, the band is formed by molding silicone over the electrodes. The overmolding process allows for tight control of the surface variations between the band and the electrodes. For example, the degree to which the electrodes protrude or recess relative to the strap portion of the band can be optimized. This optimization can result in improved patient comfort, improved band durability, and / or improved protection from contact with liquids.

[0008] Another advantage of some of the systems disclosed herein is that they allow the user to easily replace devices and bands. The user can remove a less expensive device from a less expensive band. For example, in some embodiments, the user only needs to apply a nominal force to the top surface of the device to release the device from the band. Due to the flexibility of the band, it is also easier to separate the device from the band. The shape of the band adjusts and fits to the shape of the device preventing tight pinch points from forming when the device engages the band. Without tight pinch points, the level of force required from the user to separate the band from the device is consistent over time.

[0009] The interchangeable feature allows the user to change bands depending on the anticipated situations in which the user expects to use the band and / or the desired comfort level when wearing the band. The interchangeable feature also allows the user to change bands depending on the desired electrode configuration. For example, the user can select a band with a desired number of electrodes and / or the location of the electrodes on the band. Different arrangements of the electrodes on the band can target different nerves and / or anatomical structures of the user. For example, some bands can have electrodes that not only target different nerves, but also target specific properties of the nerves. These features can include, for example, variations in the size, depth, and / or location on the body of the nerve. In some embodiments, the device includes, consists of, or consists essentially of 3, 6, 9, or 12 electrodes or 1-2 electrodes.

[0010] Another advantage of some of the systems disclosed herein is that the device can select a subset of multiple electrodes for a stimulation session. The subset of electrodes can be selected depending on the desired characteristics of a particular treatment session and / or the power efficiency of the electrodes. For example, the subset of electrodes can be selected and / or changed depending on the real-time battery level of the device. In some embodiments, machine learning is used.

[0011] Another advantage is that the system preserves battery life. For example, in some embodiments, the electrodes that complete the electrical circuit are placed in close proximity to each other (e.g., reducing electrical resistance through the user), allowing low current (e.g., 2 mA) to effectively neuromodulate the user's target nerves and / or anatomical structures while preserving battery life.

[0012] In some embodiments, magnets are used alone or in combination with other engagement structures to attach or lock the device to the band, and can be used in combination with other structures (e.g., hooks, tongues, lips, slots, keyways, etc.) to secure the device to the band. Magnets can be used in combination with a snap-fit ​​engagement between the band and the device.

[0013] Another advantage is that the system is efficient and can be provided at a lower cost. For example, the band can be provided as a disposable device for use by a user for a trial period. Once the trial period has expired, the user can discard the band. The more expensive device can be reused for another user during the trial period.

[0014] In some embodiments, either the devices or methods are used to treat depression (including but not limited to postpartum depression, depression associated with neurological disorders, major depression, seasonal affective disorder, depressive disorders, etc.), inflammation (e.g., neuroinflammation), Lyme disease, stroke, neurological disorders (such as Parkinson's disease and Alzheimer's disease), and gastrointestinal issues (including Parkinson's disease issues).

[0015] In some embodiments, one or more of bradykinesia, dyskinesia, gait dysfunction, dystonia and / or rigidity are treated with the devices and methods described herein (e.g., in association with Parkinson's disease or in association with other disorders). Motor rehabilitation is treated in some embodiments (e.g., to restore or improve movement and movement) in subjects suffering from acute or chronic events, including, for example, cardiac events (atrial fibrillation, hypertension, stroke, etc.), inflammation, neuroinflammation, etc. In one embodiment, epilepsy is treated. Treatment of movement disorders herein also includes treatment of involuntary and / or repetitive movements, such as, for example, tics, twitches, etc. (including, but not limited to, Tourette's syndrome, tic disorders). In some embodiments, rhythmic and / or non-rhythmic involuntary movements can be controlled. Involuntary vocalizations and other vocalizations can also be treated. Motor rehabilitation can include, for example, limb movement rehabilitation. In some embodiments, provided herein is the treatment of restless legs syndrome, periodic limb movement disorder, repetitive limb movements, and abnormal sensations. The devices described herein can be placed on the wrist or leg (or both) to treat, for example, leg disorders. For example, one or more nerves can be treated, including peroneal, saphenous, tibial, femoral, and sural. In some embodiments, two, three, or more nerves are treated. In some embodiments, the median nerve is modulated (e.g., stimulated) along with one, two, or more other nerves. The band or other device may be placed on the wrist and leg, only on the wrist or leg, or in two or more locations on one or both limbs. A single device, two or more devices physically coupled and / or communicating with each other may be used. The stimulation may be automated, user controllable, or both.

[0016] In some embodiments, disorders and symptoms caused or exacerbated by microbial infection (e.g., bacteria, viruses, fungi, and parasites) are treated. Symptoms include, but are not limited to, sympathetic / parasympathetic imbalance, autonomic dysfunction, inflammation (e.g., neuroinflammation), inflammation, movement and balance dysfunction, pain, and other neurological conditions. Disorders include, but are not limited to, tetanus, meningitis, Lyme disease, urinary tract infection, mononucleosis, chronic fatigue syndrome, autoimmune disorders, and the like. In some embodiments, autoimmune disorders and / or pain unrelated to microbial infection are treated, including, for example, inflammation (e.g., neuroinflammation), headache, back pain, joint pain and stiffness, muscle pain and tension, and the like.

[0017] In some embodiments, a wearable system for modulating one or more peripheral nerves of a user is provided. The system can, for example, include, consist of, or consist essentially of a band having a frame with an engagement structure. The band can have an exterior and an interior, the exterior being visible to the user and the user's inwardly facing skin being visible when the band is worn on the user. The system can further include a neurostimulation device having an upper surface, a lower surface, and an outer wall disposed therebetween. The outer wall can be sized and shaped to be secured against the engagement structure when the neurostimulation device is inserted into the frame from the interior side of the band while preventing the neurostimulation device from passing completely through the frame.

[0018] In some embodiments, the engagement structure is an abutment surface and the neurostimulator device includes a contact surface shaped and sized to contact the abutment surface when the neurostimulator device is secured to the band.

[0019] In some embodiments, the engagement structure is an opening. In some embodiments, at least a portion of the outer wall is curved between the upper surface and the lower surface. In some embodiments, at least a portion of the outer wall is flat between the upper surface and the lower surface. In some embodiments, the outer wall has a step shape, the step including a riser and a tread, the circumference of the riser being less than the inner circumference of the opening. In some embodiments, only a portion of the outer wall has a circumference greater than the inner circumference of the opening.

[0020] In some embodiments, a portion of the outer wall has a conical shape. In some embodiments, a portion of the outer wall has a stepped shape. In some embodiments, the band includes a mechanical connection and an electrical connection with the frame. In some embodiments, the band includes a first strap portion connected to a second strap portion, the first strap portion being made from silicone and the second strap portion being made from fabric. In some embodiments, the band is flexible.

[0021] In some embodiments, the band further includes an electrode system having an inner side and an outer side, the inner side including at least one electrode for each nerve to be modulated. In some embodiments, the outer side includes one or more electrodes. In some embodiments, the one or more electrodes disposed on the outer side are configured as sensors for measuring physiological data. For example, the electrodes disposed on the outer side can be used as sensors that contact selected locations on the user's body. In some embodiments, the band is configured to be fastened around the limb that presses the at least one electrode firmly against the user's skin. In some embodiments, the electrode system includes one or more electrical traces extending between the frame and the at least one electrode.

[0022] In some embodiments, a wearable system for modulating one or more peripheral nerves of a user is provided. The system can, for example, include, consist of, or consist essentially of a band having an exterior and an interior. When the band is worn by a user, the user can see the exterior. The interior can face the user's skin when the band is worn by the user. The system can further include a frame coupled to the band, having an opening, and a neurostimulation device having a screen on an upper surface. The neurostimulation device can be sized and shaped such that when the neurostimulation device is inserted into the frame from the interior of the band, only a portion of the neurostimulation device fits within the opening. The screen is viewable within the opening from the exterior of the band.

[0023] In some embodiments, the band further includes an electrode system having an inner side and an outer side, the inner side including at least one electrode for each nerve to be modulated. In some embodiments, the at least one electrode includes at least a first electrode and a second electrode, the first electrode configured to stimulate the user's median nerve and the second electrode configured to stimulate the user's radial nerve or ulnar nerve. In some embodiments, the at least one electrode includes a return or ground electrode configured to be electrically coupled to the user. In some embodiments, the band includes a first strap portion coupled to a second strap portion, the first strap portion being manufactured from silicone and the second strap portion being manufactured from fabric.

[0024] In some embodiments, a wearable system for modulating one or more peripheral nerves of a user is provided. The system can, for example, include, consist of, or consist essentially of a neurostimulator device having a lower surface, an upper surface, and a screen. The screen can be disposed on the upper surface. At least a portion of the lower surface can contact the user's limb when the system is worn by the user. The system can further include a band configured to capture the neurostimulator device relative to the limb such that a portion of the lower surface contacts the limb and the screen is visible to the user.

[0025] In some embodiments, at least a portion of the neurostimulator device is disposed between a surface of the band and the limb, the surface contacting the neurostimulator device. In some embodiments, at least a portion of the neurostimulator device forms a press-fit with the band. In some embodiments, the band includes a frame sized and shaped to engage with the neurostimulator device. In some embodiments, the neurostimulator device includes an outer wall configured to engage with the frame. In some embodiments, the outer wall forms a step in a direction from the lower surface to the upper surface, the step including a riser and a tread, the tread being disposed between the frame and the limb to prevent the neurostimulator device from passing completely through the frame when the neurostimulation is being captured by the band. In some embodiments, the outer wall has a tapered conical shape in a direction from the lower surface to the upper surface, the tapered conical shape preventing the neurostimulator device from passing completely through the frame when the neurostimulation is being captured by the band. In some embodiments, the band further includes an electrode system having an inner side and an outer side, the inner side including at least one electrode for each nerve to be modulated.

[0026] In some embodiments, a wearable system for modulating one or more peripheral nerves of a user is provided. The system can, for example, consist of or consist essentially of a band having an outer side and an inner side, the outer side being visible by the user when the band is worn by the user, and including the skin facing the inner side of the user when the band is worn by the user. The system can further include a frame coupled to the band, the frame having an abutment surface and an opening, and a neurostimulation device having a contact surface. The neurostimulation device can be insertable into the opening from the inside of the band such that the contact surface abuts the abutment surface of the frame, preventing the neurostimulation device from passing completely through the opening and exiting the opening on the outside of the band.

[0027] In some embodiments, a band is provided for releasably securing a neurostimulator device to a limb of a user. The neurostimulator device can be configured to generate a signal for modulating one or more peripheral nerves of the user. The band can include, consist of, or consist essentially of, for example, a strap having an outer side and an inner side that is visible to the user and the user's inner-facing skin when the band is secured to the limb, and a frame coupled to the strap and having an opening. The opening can be sized and shaped relative to the neurostimulator device to secure the neurostimulator device relative to the frame while preventing the entire neurostimulator device from passing through the opening when the neurostimulator device is inserted into the opening from the inner side of the strap.

[0028] In some embodiments, a method of releasably securing a neurostimulation device to a band is provided. The band can have a frame with an opening. The opening can be sized and shaped relative to the neurostimulation device to secure the neurostimulation device relative to the frame while preventing the entire neurostimulation device from passing through the opening. The neurostimulation device can be configured to generate a signal to modulate one or more peripheral nerves of a user. The method can include inserting the neurostimulation device into the opening in a direction to secure the neurostimulation device and removing the neurostimulation device from the opening in the direction.

[0029] In some embodiments, a method of releasably securing a neurostimulation device to a band is provided. The band can, for example, include, consist of, or consist essentially of an outer side and an inner side with the outer side visible to the user when the band is secured to the user's limb and the skin facing the user's inner side. The method can include inserting at least a portion of the neurostimulation device into an opening in a frame of the band from the inner side of the band and abutting a contact surface of the neurostimulation device against an abutment surface of the frame, such that the neurostimulation device is secured by the band while the entire neurostimulation device continues through the opening and is prevented from exiting the outer opening of the band.

[0030] In some embodiments, a band is provided for releasably securing a neurostimulator device to a limb of a user, the neurostimulator device being capable of generating a signal for modulating one or more peripheral nerves of the user, and including means for inserting at least a portion of the neurostimulator device into an opening in a frame of the band from an interior side of the band, and means for abutting the neurostimulator device against the frame such that the neurostimulator device is secured by the band while the entire neurostimulator device continues through the opening and is prevented from exiting the exterior opening of the band.

[0031] In some embodiments, a band configured to secure a neurostimulation system to a user's wrist is provided. The band can, for example, include, consist of, or consist essentially of an outer surface and an inner surface, the inner surface being configured to contact the user's wrist. The band can include a first portion adjacent to a first end along the length of the band. The first portion can be configured to releasably engage the neurostimulation system. The first portion can include connections and apertures on either side of the first portion. A second portion along the length of the band can include an electrode system having at least one electrode on the inner surface of the band for each nerve to be stimulated. A third portion along the length of the band can be configured to pass through an aperture in the first portion and fold back onto itself. A fourth portion along the length of the band adjacent to the third portion can include an attachment mechanism for securing the fourth portion to an outer surface of the band.

[0032] In some embodiments, a wrist-wearable system configured to removably secure a controller is provided. The system can, for example, include, consist of, or consist essentially of an inner side and an outer side, the inner side being configured to contact a user's wrist. The wrist-wearable system can include a frame including an engagement structure configured to receive a controller from the inner side of the system to engage and secure the controller, and a strap extending from a first portion of the frame, an end of the strap not secured to the frame.

[0033] In some embodiments, a wearable system for transcutaneously delivering an electrical signal to one or more nerves of a user is provided. The system can have a durable component and a replaceable component including at least one electrode. The replaceable component can be configured to maintain the durable component and the at least one electrode in contact with the user's skin by applying a force to the durable component in a direction toward the skin.

[0034] In some embodiments, the at least one electrode contacts the user's skin at a location different than where the durable component contacts the patient's skin. In some embodiments, the at least one electrode includes a first electrode and a second electrode, the first electrode configured to stimulate the user's median nerve and the second electrode configured to stimulate the user's radial nerve or ulnar nerve. In some embodiments, the at least one electrode includes a return or ground electrode configured to be electrically coupled to the user. In some embodiments, the durable component can withstand more use than the replaceable component. In some embodiments, the durable component has a longer useful life than the replaceable component. In some embodiments, the direction is perpendicular to the user's skin.

[0035] In some embodiments, the replaceable component includes a band configured to encircle a user's limb. In some embodiments, the replaceable component includes a frame, the frame contacting the durable component when the replaceable component maintains the durable component in contact with the user's skin. In some embodiments, the frame includes a receptacle, the receptacle sized and shaped to receive at least a portion of the durable component. In some embodiments, the durable component includes a screen. In some embodiments, the screen is visible to the user when the durable component is in contact with the user's skin.

[0036] In some embodiments, the system further includes an electrical coupling between the replaceable component and the durable component, the electrical coupling being inaccessible when the replaceable component maintains contact between the durable component and the user's skin. In some embodiments, the electrical coupling includes an electrical interconnect. In some embodiments, the electrical interconnect is spring loaded. In some embodiments, the electrical interconnect moves from the retracted position to the extended position when the durable component is removed from the replaceable component.

[0037] In some embodiments, the system includes a mechanical coupling between the replaceable component and the durable component. In some embodiments, the mechanical coupling includes an engagement structure. In some embodiments, the mechanical coupling includes an abutment surface. In some embodiments, the mechanical coupling includes a contact surface. In some embodiments, the mechanical coupling includes an opening. In some embodiments, the mechanical coupling is configured to prevent removal of the durable component from the disposable component in the absence of force.

[0038] In some embodiments, the magnitude of force applied by the user to detach the durable component from the disposable component is less than the magnitude of force applied by the disposable component to maintain the durable component in contact with the user's skin. In some embodiments, the direction of the force that detaches the durable component from the disposable component is parallel to the direction of the force that keeps the durable component in contact with the user's skin. In some embodiments, the disposable component includes a first strap portion coupled to a second strap portion, the first strap portion fabricated from silicone and the second strap portion fabricated from fabric.

[0039] In some embodiments, the disposable component is flexible. In some embodiments, the disposable component includes an electrode system having an inner side and an outer side, the inner side including at least one electrode. In some embodiments, the disposable component is configured to be fastened around a limb of a user. In some embodiments, the fastened disposable component presses the at least one electrode firmly against the skin of the user.

[0040] In some embodiments, the electrode system includes one or more electrical traces. In some embodiments, the one or more electrical traces are in electrical contact with at least one electrode. In some embodiments, the one or more electrical traces are in electrical contact with the durable component, at least when the replaceable component maintains the durable component in contact with the user's skin. In some embodiments, at least a portion of the durable component forms a press fit with the disposable component. In some embodiments, the durable component is a nerve stimulation device. In some embodiments, the electrical signal delivered to one or more nerves of the user blocks the nerve signal. In some embodiments, the electrical signal delivered to one or more nerves of the user stimulates the nerve signal.

[0041] In some embodiments, a wearable system for transcutaneously delivering an electrical signal to one or more nerves of a user is provided. The system has a first component including at least one electrical interconnect. The system has a second component including at least one electrical interconnect arranged to contact the at least one electrical interconnect of the first component when the second component selectively engages with the first component. The second component can be configured to maintain the first component in contact with the skin of the user when worn by the user.

[0042] In some embodiments, the second component includes at least one electrode. In some embodiments, the at least one electrode contacts the user's skin at a location different than where the first component contacts the patient's skin. In some embodiments, the at least one electrode includes a first electrode and a second electrode, the first electrode configured to stimulate the user's median nerve and the second electrode configured to stimulate the user's radial nerve or ulnar nerve. In some embodiments, the at least one electrode includes a return or ground electrode configured to be electrically coupled to the user. In some embodiments, the first component can withstand more use than the second component. In some embodiments, the first component has a longer useful life than the useful life of the replaceable component. In some embodiments, the direction is perpendicular to the user's skin. In some embodiments, the second component includes a band configured to encircle the user's limb.

[0043] In some embodiments, the second component includes a frame, the frame contacting the first component when the second component leaves the first component in contact with the user's skin. In some embodiments, the frame includes a receptacle, the receptacle sized and shaped to receive at least a portion of the first component. In some embodiments, the first component includes a screen. In some embodiments, the screen is visible to the user when the first component is in contact with the user's skin. In some embodiments, the at least one electrical interconnect is spring loaded. In some embodiments, the at least one electrical interconnect moves from a retracted position to an extended position when the first component is removed from the second component.

[0044] In some embodiments, the system includes a mechanical coupling between the second component and the first component. In some embodiments, the mechanical coupling includes an engagement structure. In some embodiments, the mechanical coupling includes an abutment surface. In some embodiments, the mechanical coupling includes a contact surface. In some embodiments, the mechanical coupling includes an opening. In some embodiments, the second component is configured to apply a force to the first component in a direction toward the skin when worn by a user. In some embodiments, the mechanical coupling is configured to prevent removal of the first component from the second component in the absence of force. In some embodiments, a magnitude of force applied by a user to detach the first component from the second component is less than a magnitude of force applied by the second component to maintain the first component in contact with the user's skin.

[0045] In some embodiments, the direction of the force that detaches the first component from the second component is parallel to the direction of the force that maintains the first component in contact with the user's skin. In some embodiments, the second component includes a first strap portion coupled to a second strap portion, the first strap portion being manufactured from silicone and the second strap portion being manufactured from fabric. In some embodiments, the second component is flexible. In some embodiments, the second component includes an electrode system having an inner side and an outer side, the inner side including at least one electrode. In some embodiments, the second component is configured to be clamped around the limb of the user. In some embodiments, the clamped second component presses the at least one electrode firmly against the user's skin.

[0046] In some embodiments, the electrode system includes one or more electrical traces. In some embodiments, the one or more electrical traces are in electrical contact with at least one electrode. In some embodiments, the one or more electrical traces are in electrical contact with the first component when at least the second component maintains the first component in contact with the user's skin. In some embodiments, at least one electrical interconnect of the first component and at least one electrical interconnect of the second component are inaccessible when the second component selectively engages with the first component.

[0047] In some embodiments, at least a portion of the first component forms an indentation with the second component. In some embodiments, the first component is a neurostimulation device. In some embodiments, the electrical signal delivered to one or more nerves of the user blocks the nerve signal. In some embodiments, the electrical signal delivered to one or more nerves of the user stimulates the nerve signal.

[0048] In some embodiments, the electrical signal delivered to the one or more nerves of the user changes the burst frequency after a pre-specified period of time. In some embodiments, the electrical signal delivered to the one or more nerves of the user changes the burst frequency after a pre-specified number of bursts. In some embodiments, the electrical signal delivered to the one or more nerves of the user changes the pulse frequency after a pre-specified period of time. In some embodiments, the electrical signal delivered to the one or more nerves of the user changes the pulse frequency after a predetermined number of bursts.

[0049] In some embodiments, a system for providing a treatment recommendation to a user is provided. In some embodiments, the system includes one or more hardware processors configured to receive kinematic data and / or patient satisfaction of an evaluation period, display a tremor improvement score based at least in part on the kinematic data and / or patient satisfaction of the evaluation period, and / or provide a plurality of waveform patterns for selection by a user.

[0050] In some embodiments, a method is provided for providing a treatment recommendation to a user. In some embodiments, the method includes receiving kinematic data and / or patient satisfaction for an evaluation period, displaying a tremor improvement score based at least in part on the kinematic data and / or patient satisfaction for the evaluation period, and / or providing a plurality of waveform patterns for selection by a user. [Brief description of the drawings]

[0051] The following drawings are for illustrative purposes only and depict non-limiting embodiments. In some embodiments, features of different drawings can be combined.

[0052] [Figure 1] FIG. 1 illustrates a system including a device and a band worn by a user, the device being removably coupled to the band to provide transcutaneous peripheral nerve stimulation to the user.

[0053] [Diagram 2] FIG. 2 shows another photograph of the system of FIG. 1 taken from the side of the system.

[0054] [Diagram 3] FIG. 2 is a perspective view of the system of FIG. 1 showing the electrode system inside the band.

[0055] [Figure 4]FIG. 13 is a perspective side view of the system with the device aligned with the opening in the frame prior to inserting the device into the opening to secure the device to the band.

[0056] [Diagram 5] FIG. 5 is a perspective view of the device of FIG.

[0057] [Figure 6] FIG. 5 is a perspective view of the band of FIG. 4.

[0058] [Figure 7] This is a similar view to FIG. [Figure 8] This is a similar view to FIG. [Figure 9] This is a similar view to FIG. [Figure 10] This is a similar view to FIG.

[0059] [Figure 11] This is a similar view to FIG. [Figure 12] This is a similar view to FIG. [Figure 13] This is a similar view to FIG. [Figure 14] This is a similar view to FIG.

[0060] [Figure 15] This is a similar view to FIG. [Figure 16] This is a similar view to FIG. [Figure 17] This is a similar view to FIG. [Figure 18] This is a similar view to FIG.

[0061] [Figure 19] FIG. 2 is a perspective view of a system similar to that of FIG. 1, showing the electrode system inside the band.

[0062] [Figure 20] FIG. 20 is a top view of the system of FIG. 19.

[0063] [Figure 21] FIG. 20 is a side view of the system of FIG. 19.

[0064] [Figure 22] FIG. 20 is a bottom perspective view of the system of FIG. 19.

[0065] [Diagram 23] FIG. 13 is a top perspective view of the system with the device aligned with the opening in the frame prior to inserting the device into the opening to secure the device to the band.

[0066] [Figure 23A] FIG. 24 is a partial view of the frame of FIG. 23 showing one or more electrical contacts on the frame.

[0067] [Figure 24] FIG. 13 is a bottom perspective view of the system with the band removed.

[0068] [Diagram 25] FIG. 25 illustrates the system of FIG. 24.

[0069] [Figure 26] FIG. 13 is another bottom perspective view of the system with the band removed.

[0070] [Figure 27] FIG. 27 illustrates the system of FIG. 26.

[0071] [Figure 28] FIG. 7 is a right-front perspective view of a system similar to those of FIGS. 1 to 6.

[0072] [Figure 29] FIG. 29 is a left rear perspective view of the system of FIG. 28.

[0073] [Diagram 30] FIG. 29 is a rear view of the system of FIG. 28.

[0074] [Diagram 31] FIG. 29 is a front view of the system of FIG. 28.

[0075] [Diagram 32] FIG. 29 is a right side view of the system of FIG. 28.

[0076] [Diagram 33] FIG. 29 is a left side view of the system of FIG. 28.

[0077] [Diagram 34] FIG. 29 is a top view of the system of FIG. 28.

[0078] [Diagram 35] FIG. 29 is a bottom view of the system of FIG. 28.

[0079] [Diagram 36] FIG. 29 is an anterior-posterior perspective view of the device of FIG. 28.

[0080] [Figure 37] FIG. 29 is a left rear perspective view of the device of FIG. 28.

[0081] [Figure 38] FIG. 29 is a rear view of the device of FIG. 28.

[0082] [Figure 39] FIG. 29 is a front view of the device of FIG. 28.

[0083] [Diagram 40] FIG. 29 is a right side view of the device of FIG. 28.

[0084] [Diagram 41] FIG. 29 is a left side view of the device of FIG. 28.

[0085] [Diagram 42] FIG. 29 is a top view of the device of FIG. 28.

[0086] [Diagram 43] FIG. 29 is a bottom view of the device of FIG. 28.

[0087] [Diagram 44] FIG. 29 is a right front perspective view of the band of FIG. 28.

[0088] [Diagram 45] FIG. 29 is a left rear perspective view of the band of FIG. 28.

[0089] [Diagram 46] FIG. 29 is a rear view of the band of FIG. 28.

[0090] [Figure 47] FIG. 29 is a front view of the band of FIG. 28.

[0091] [Figure 48] FIG. 29 is a right side view of the band of FIG. 28.

[0092] [Figure 49] FIG. 29 is a left side view of the band of FIG. 28.

[0093] [Figure 50] FIG. 29 is a top view of the band of FIG. 28.

[0094] [Figure 51] FIG. 29 is a bottom view of the band of FIG. 28.

[0095] [Figure 52A] FIG. 1 illustrates an example block diagram of a neuromodulation (e.g., neurostimulation) device disclosed herein.

[0096] [Figure 52B] FIG. 2 is a block diagram of one embodiment of a user interface device that can be implemented with the hardware components described herein.

[0097] [Diagram 53]FIG. 1 is a block diagram of an embodiment of a device and system for providing peripheral nerve stimulation, sensing biological or kinematic measures, and / or receiving user satisfaction data that is used to customize or modify the delivery of electrical stimulation.

[0098] [Figure 54A] FIG. 13 illustrates an example of how a stimulation parameter (e.g., burst frequency) varies between two or more predetermined values ​​as stimulation alternates across two nerves (e.g., the median nerve and the radial or ulnar nerve). [Figure 54B] FIG. 13 illustrates an example of how a stimulation parameter (e.g., pulse frequency) varies between two or more predetermined values ​​as stimulation alternates across two nerves (e.g., the median nerve and the radial or ulnar nerve). [Fig. 54C1] FIG. 13 illustrates an example of how a stimulation parameter (pulse phase) varies between two or more predetermined values ​​as stimulation alternates across two nerves (e.g., the median nerve and the radial or ulnar nerve). [Fig. 54C2] FIG. 13 illustrates an example of how stimulation parameters (e.g., burst frequency, pulse frequency, and pulse phase) vary between two or more predetermined values ​​as stimulation alternates across two nerves (e.g., the median nerve and the radial or ulnar nerve).

[0099] [Fig. 54D1] FIG. 13 illustrates an example of how a stimulation parameter (e.g., pulse frequency) varies between two or more values ​​based on a physiological parameter (e.g., tremor frequency) as stimulation alternates across two nerves (e.g., the median nerve and the radial or ulnar nerve). [Fig. 54D2] FIG. 13 illustrates an example of how a stimulation parameter (e.g., pulse frequency) varies between two or more values ​​based on a physiological parameter (e.g., tremor frequency) as stimulation alternates across two nerves (e.g., the median nerve and the radial or ulnar nerve). [Figure 54E] FIG. 13 illustrates an example of how a stimulation parameter (e.g., pulse frequency) varies between two or more values ​​based on a physiological parameter (e.g., respiratory rate) when stimulation is alternated across two nerves (e.g., the median nerve and the radial or ulnar nerve). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0100] Disclosed herein is a system including a band for securing a device configured to provide neuromodulation (e.g., neurostimulation). The device may be configured to be coupled to a surface of a user's skin for transcutaneous stimulation using the band. The system may include any combination of features disclosed in any of the figures. Thus, the system may have any number of different configurations. Thus, although each figure illustrates a particular combination of features, the features are not limited to being incorporated as part of the illustrated combination. In this manner, any feature disclosed in any of the figures may be used with any other feature disclosed in any of the figures. For ease of explanation, a particular combination of features has been selected to be shown in any given figure. However, the selected combination of features is not intended to limit the present disclosure. Thus, any of the features illustrated in Figures 1-54E may be combined in any manner.

[0101] The bands provided herein may be configured to secure the device to a user. The devices provided herein may be configured to stimulate peripheral nerves of the user when secured by the band. The neuromodulation (e.g., neurostimulation) device may be configured to transmit one or more neuromodulation (e.g., neurostimulation) signals across the skin of the user. In many embodiments, the device is a wearable device configured to be worn by a user. The user may be a human, another mammal, or other animal user. The system may also include signal processing systems and methods for enhancing diagnostic and treatment protocols associated therewith.

[0102] In some embodiments, the device is configured to be wearable on the user's upper extremities (e.g., the user's wrist, forearm, arm, and / or finger). In some embodiments, the device is configured to be wearable on the user's lower extremities (e.g., ankle, calf, knee, thigh, foot, and / or toes). In some embodiments, the device is configured to be wearable on the head or neck (e.g., forehead, ear, neck, nose, and / or tongue). In some embodiments, one or more bands are provided that partially or completely encircle the limb (wrist, ankle, arm, leg, etc.). In some embodiments, an ear device is also provided that can be used with or without the limb band. In one embodiment, an ear device and a wrist band are provided for synergistic treatment.

[0103] In some embodiments, the device is configured to be wearable or in close proximity to the ear of a user, including, for example, but not limited to, auricular neuromodulation (e.g., neurostimulation) of the auricular branch of the vagus nerve. In some embodiments, the vagus nerve, the trigeminal nerve, and / or the greater auricular nerve are neuromodulated. In some embodiments, only the vagus nerve is neuromodulated. In some embodiments, the vagus nerve and one, two, or more other nerves are neuromodulated (e.g., the trigeminal nerve, the greater auricular nerve, a nerve in the auricular branch, the auricular branch of the vagus nerve, the facial nerve, the auricular temporal nerve, etc.). In some embodiments, the vagus nerve is not stimulated, and instead, for example, another nerve is stimulated (e.g., the trigeminal nerve, the greater auricular nerve, the facial nerve, the auricular temporal nerve, another nerve in the auricular branch, etc.). Auricular (e.g., ear) devices can include earpieces or earbud-type devices for one or more portions of the ear, such as the ear canal or outer ear. In some embodiments, the device may include a housing or enclosure (e.g., miniaturized) attached to a portion of the user (e.g., secured behind the ear, wrapped around the ear, secured in the ear, secured over the ear, in a headband secured around the user's head, around the user's neck, and / or around the user's arm). One to six or more electrodes may be located on an earpiece or earbud type device, or a device connected to an earpiece / earbud type device. In some embodiments, only a portion of the device fits behind the ear, and one to six or more electrodes of the device are located adjacent (e.g., adjacent to, within, or in contact with) a target area of ​​the ear (e.g., the concha, the tragus, etc.). In some embodiments, a right, left, or two earpieces are provided. In some embodiments, one or more of the vagus nerve, auriculotemporal nerve, trigeminal nerve, or cranial nerve may be treated. In certain embodiments of the present disclosure, the device stimulates the vagus nerve via contact with the concha of the user's ear. The device may be unilateral or bilateral, including a single device or multiple devices connected by wire or wirelessly.

[0104] In some embodiments, attenuation or blocking of nerve impulses and / or neurotransmitters is provided. In some embodiments, nerve impulses and / or neurotransmitters are enhanced. In some embodiments, transcutaneous neuromodulation is provided, although subcutaneous and transcutaneous components may also be used. In some embodiments, the device includes 3-6 or more (e.g., 3, 4, 5, 6) electrodes and is partially implantable or completely transcutaneous. In some embodiments, the electrodes themselves are used as sensing elements (e.g., to measure neural activity (e.g., evoked compound action potentials), to detect electrodermal activity, or cardiac activity, or EEG) and may be placed on or near the subject's wrist, or on or near different parts of the subject's body (e.g., ear, finger, part of arm, etc.). In some embodiments, the sensing electrodes are placed on the outside of the band 36.

[0105] In some embodiments, modulation of blood vessels (either dilation or constriction) is provided using the devices and methods described herein (e.g., by neurostimulation). Such treatment may then reduce inflammation (including, but not limited to, inflammation following microbial infection). The devices and methods described herein, in some embodiments, increase, decrease or otherwise balance vasodilation and vasoconstriction via neuromodulation. For example, a reduction in vasodilation is provided in some embodiments to treat or prevent migraines or other conditions that are exacerbated by vasodilation. In other embodiments, vasoconstriction is reduced, for example, in conditions where dilation is beneficial (e.g., conditions involving high blood pressure and pain). In one embodiment, the reduction in inflammation treats tinnitus. In some embodiments, modulation of blood vessels (either dilation or constriction) is used to treat tinnitus. Tinnitus can be treated according to some embodiments with modulation (e.g., stimulation) of the vagus nerve alone or in combination with one, two or more other nerves (including, for example, the trigeminal nerve, the great auricular nerve, the nerve of the auricular branch, the auricular branch of the vagus nerve, the facial nerve, the auriculotemporal nerve, etc.). In one embodiment, a nerve other than the vagus nerve is modulated to treat tinnitus. In some embodiments, the cranial / auditory nerve can be modulated to treat tinnitus and / or auricular inflammation. Ear devices may in some embodiments be used in conjunction with devices placed on the limb (e.g., an ear device in conjunction with a wrist device).

[0106] Any of the neuromodulation devices discussed herein can be utilized to modulate (e.g., stimulate) the median, radial, ulnar, sural, femoral, peroneal, saphenous, tibial and / or other nerves or meridians accessible to the subject's limbs, either alone or in combination with one or more other nerves (e.g., the vagus nerve) of the subject, for example, via a separate neuromodulation device. In some embodiments, provided herein is treatment of restless legs syndrome, periodic limb movement disorder, repetitive limb movements and abnormal sensations. The devices described herein can be placed, for example, on the wrist or leg (or both) to treat limb disorders. In some embodiments, vagus nerve stimulation is used to treat restless legs syndrome, periodic limb movement disorder, repetitive limb movements and / or abnormal limb sensations. The vagus nerve can be stimulated alone or in addition to one or more of the sural nerve, femoral nerve, peroneal nerve, saphenous nerve, and tibial nerve. Alternatively, one or more of the sural nerve, femoral nerve, peroneal nerve, saphenous nerve, and tibial nerve are stimulated without stimulating the vagus nerve.

[0107] In some embodiments, transcutaneous neuromodulation at the arm and / or wrist (e.g., median and / or radial or ulnar nerve stimulation) can advantageously inhibit sympathetic excitation-related blood pressure rise and pre-motor sympathetic firing in the rostral ventrolateral medulla (rVLM). For example, neuromodulation of the median nerve and / or radial or ulnar nerve can provide a more convergent input to cardiovascular pre-motor sympathetic neurons in the rVLM. In some embodiments, the median nerve is modulated (e.g., stimulated) along with one, two or more other nerves in the same device or separate devices. For example, the median nerve and one or both of the radial and ulnar nerves are modulated within the same device. Optionally, separate devices for modulating (e.g., stimulating) in or around the ear or leg are also provided to provide a synergistic effect, which in one embodiment may be controlled by a common controller. In some embodiments, the device may also be configured to deliver one, two or more of magnetic, vibrational, mechanical, thermal, ultrasonic, or other forms of modulation (e.g., stimulation) instead of or in addition to electrical stimulation. Different types of modulation may be provided on the same device or on different devices. For example, a wrist device may provide electrical and vibrational stimulation, or, for example, a wrist device may provide electrical stimulation and a leg device provides vibrational stimulation.

[0108] Also, in some embodiments, vagus nerve stimulation can modulate the trigeminal nucleus to suppress inflammation. Thus, in some embodiments, the vagus nerve is stimulated to reduce inflammation via the trigeminal pathway. In other embodiments, the trigeminal nerve is directly stimulated instead of or in addition to the vagus nerve. In some embodiments, transcutaneous nerve stimulation projects to the nucleus tractus solitarius (NTS) and spinal trigeminal nucleus (Sp5) regions to modulate the excitability of the trigeminal sensory complex and its connectivity with higher brain structures. The trigeminal sensory nucleus can be involved in neurogenic inflammation during migraine (e.g., characterized by vasodilation). In some embodiments, nerve stimulation modulates the trigeminal sensory pathway to improve migraine pathophysiology and reduce headache frequency and severity. For example, increased activation of the raphe nucleus and locus coeruleus can inhibit nociceptive processing in the sensory trigeminal nucleus. Human skin is well innervated by autonomic nerves, and neuromodulation (e.g., stimulation) of nerves or meridian points as disclosed herein may potentially aid in the treatment of migraine or other headache conditions. For example, transcutaneous neurostimulation of peripheral or distal limb afferent nerves, including but not limited to the median nerve, is connected by neural circuits to the arcuate nucleus of the hypothalamus. In some embodiments, the devices and methods described herein increase, decrease, or balance vasodilation and vasoconstriction via neuromodulation (e.g., the vagus nerve, trigeminal nerve, and / or other nerves around the ear). For example, to treat or prevent migraine or other conditions exacerbated by vasodilation, some embodiments provide for decreased vasodilation. In other embodiments, vasoconstriction is decreased, for example, in conditions where dilation is beneficial (e.g., hypertension and painful conditions). In some embodiments, modulation of blood vessels (either dilation or constriction) is used to treat tinnitus. In one embodiment, the devices and methods described herein reduce inflammation (including but not limited to inflammation following microbial infection), and reduced inflammation treats tinnitus.

[0109] When using non-invasive or wearable neuromodulation devices, systems with compact ergonomic form factors are necessary to enhance efficacy, compliance, and / or comfort. In some embodiments, neuromodulation systems and methods are provided that enhance or inhibit nerve impulses and / or neurotransmission, and / or modulate the excitability of nerves, neurons, neural circuits, and / or other neuroanatomical structures that affect the activation of nerves and / or neurons. For example, neuromodulation (e.g., neurostimulation) can include one or more of the following effects on neural tissue: depolarizing neurons so that they fire action potentials, hyperpolarizing neurons to inhibit action potentials, depleting neuronal ion stores to inhibit firing action potentials, making changes in proprioceptive input, affecting muscle contraction, affecting changes in neurotransmitter release or uptake, and / or inhibiting firing.

[0110] Stimulation of peripheral nerves may provide therapeutic benefits across a variety of diseases, including, but not limited to, movement disorders (including, but not limited to, essential tremor, Parkinson's tremor, orthostatic tremor, and multiple sclerosis), urinary system disorders, gastrointestinal disorders, cardiac diseases, inflammatory diseases (e.g., neuroinflammation), mood disorders (including, but not limited to, depression, bipolar disorder, dysthymia, and anxiety disorders), pain syndromes (including, but not limited to, migraine and other headaches, trigeminal neuralgia, fibromyalgia, complex regional pain syndrome), Lyme disease, stroke, among others. Inflammatory bowel disease (such as Crohn's disease, colitis, and functional dyspepsia), rheumatoid arthritis, multiple sclerosis, psoriatic arthritis, psoriasis, chronic fatigue syndrome, and other inflammatory diseases are treated in some embodiments. In one embodiment, cardiac conditions (such as atrial fibrillation, high blood pressure, stroke, etc.) are treated. In one embodiment, epilepsy is treated. In some embodiments, inflammatory skin conditions and immune dysfunction are also treated. In some embodiments, provided herein is the treatment of restless legs syndrome, periodic limb movement disorder, repetitive limb movements and abnormal limb sensation. The treatment of movement disorders herein also includes the treatment of involuntary and / or repetitive movements, such as, for example, tics, twitches, etc. (including, but not limited to, Tourette's syndrome, tic disorders). In some embodiments, rhythmic and / or non-rhythmic involuntary movements can be controlled. Involuntary vocalizations and other vocalizations can also be treated. The devices described herein can be placed, for example, on the wrist or leg (or both) to treat limb disorders. In some embodiments, vagus nerve stimulation is used to treat restless legs syndrome, periodic limb movement disorder, repetitive limb movements and / or abnormal limb sensation. With respect to the leg, the device can be placed, for example, on the thigh, calf, ankle, or other suitable location to treat the target nerve.

[0111] In some embodiments, the device may include the ability to track user motion data for the purpose of measuring one, two, or more tremor frequencies of the patient. A patient may have a single tremor frequency, or possibly multiple discrete tremor frequencies that appear when performing different tasks. Once tremor frequencies are observed, they can be used as one of many seminal input parameters for personalized neuromodulation therapy.

[0112] The treatment can be delivered, for example, percutaneously via one, two, or more nerves (e.g., the median nerve and the radial or ulnar nerve, and / or other nerves disclosed elsewhere herein) to reduce or improve the patient's condition, including but not limited to the patient's tremor load. In some embodiments, the treatment modulates the afferent nerve but not the efferent nerve. In some embodiments, the treatment preferentially modulates the afferent nerve. In some embodiments, the treatment does not include functional electrical stimulation.

[0113] Although percutaneous delivery is used in many embodiments, in some embodiments, at least a portion of the device may be implanted subcutaneously or percutaneously. In one embodiment, a first electrode stimulates the median nerve, a second electrode stimulates the radial or ulnar nerve, and a third electrode stimulates the ulnar nerve. In one embodiment, two or more electrodes stimulate the same nerve (e.g., at different frequencies or other parameters). In one embodiment, one, two or all of the median, radial and ulnar nerves are stimulated. In some embodiments, the median nerve is modulated (e.g., stimulated) along with one, two or more other nerves in the same device or separate devices. For example, the median nerve and one or both of the radial and ulnar nerves are modulated in the same device. Optionally, a separate device for modulating (e.g., stimulating) in or around the ear or leg is also provided to provide a synergistic effect, and in one embodiment may be controlled by a common controller. In some embodiments, the stimulation electrodes themselves are used as sensing elements (e.g., to measure neural activity (e.g., evoked compound action potentials), to detect electrodermal activity, or cardiac activity, or EEG) and may be placed on or near the subject's wrist, or on or near a different part of the subject's body (e.g., an ear, a finger, part of an arm, etc.).

[0114] In some embodiments, one or more of bradykinesia, dyskinesia, gait dysfunction, dystonia and / or rigidity are treated. These can be treated in conjunction with Parkinson's disease or in conjunction with other disorders. In some embodiments, motor rehabilitation is treated (e.g., to restore or improve movement and movement) in subjects suffering from acute or chronic events, including, for example, cardiac events (atrial fibrillation, hypertension, stroke, etc.), inflammation, neuroinflammation, etc. In one embodiment, epilepsy is treated.

[0115] In some embodiments, the wearable systems and methods disclosed herein can be advantageously used to identify whether a treatment is effective in significantly reducing or preventing a medical condition, including but not limited to tremor severity. Although tremor is treated in some embodiments, the devices described herein are used to treat conditions other than tremor.

[0116] Wearable sensors can advantageously monitor, characterize, and assist in the clinical management of hand tremors as well as other medical conditions, including those disclosed elsewhere herein. Clinical assessment of a medical condition, e.g., tremor severity, can be correlated with simultaneous measurement of wrist motion using an inertial measurement unit (IMU). For example, tremor features extracted from an IMU at the wrist can provide distinctive information about the tremor phenotype that can be leveraged for diagnosis, prognosis, and / or to improve treatment outcomes. Kinematic measures can be correlated with tremor severity, and machine learning algorithms, e.g., incorporated in the neuromodulation systems and methods disclosed herein, can predict tremor severity.

[0117] In other non-tremor embodiments, physiological data including heart rate, blood glucose, blood pressure, respiratory rate, temperature, blood volume, sound pressure, photoplethysmography, electroencephalogram, electrocardiogram, blood oxygen saturation, and / or skin conductance, as well as patient data from third party devices, may be collected and / or aggregated to improve the diagnosis, prognosis, and / or treatment outcome of disorders such as migraine headaches, depression, and / or Lyme disease. For example, physiological data including respiratory rate and heart rate, along with data related to sleep patterns and activity levels, may be collected and / or aggregated to improve the diagnosis, prognosis, and / or treatment outcome of depression.

[0118] In some embodiments, neuromodulation, such as neurostimulation, used herein is used to replace pharmaceutical drugs, thus reducing undesirable drug side effects. In other embodiments, neuromodulation, such as neurostimulation, is used together with pharmaceutical drugs (e.g., synergistically) to, for example, reduce the dose or duration of drug therapy, thereby reducing undesirable side effects. Undesirable drug side effects include, for example, addiction, tolerance, dependence, GI problems, nausea, confusion, dyskinesia, loss of appetite, etc.

[0119] FIG. 1 is a photograph of the system 30 including the band 32 and the device 34 worn by a user. FIG. 2 is another photograph of the system 30 of FIG. 1 taken from the side of the system 30. The band 32 may be configured to be worn by a user around their arm, wrist finger, leg, ankle, knee, waist, etc. In some embodiments, the band 32 includes an electrode system 42 for distributing an electrical stimulation signal generated by the device 34 to the user's skin. FIG. 3 is a perspective view of the system 30 of FIG. 1 showing the electrode system 42 on the inner side 78 of the band 32.

[0120] The device 34 is removably coupled to the band 32 to provide transcutaneous peripheral nerve stimulation to the user. In some embodiments, the band 32 is configured to be mechanically and electrically coupled to the device 34. In many embodiments, the device 34 is a wearable cuff or earpiece. The band 32 can partially or completely encircle the wrist, finger, arm, leg, ankle, or head. Although a patch may be used, in many embodiments, a patch is not used.

[0121] In some embodiments, the band 32 includes a strap 36. In some embodiments, the strap 36 secures and fastens the band 32, including the electrode system 42, to a user. In some embodiments, the band 32 is configured with a clasp or buckle that secures and fastens the band 32 to the user's wrist.

[0122] In some embodiments, the strap 36 includes a first portion 38 and / or a second portion 40. In some embodiments, the first portion 38 and the second portion 40 are made from the same material. In some embodiments, the first portion 38 and the second portion 40 are made from different materials. The materials may include silicone, urethane, thermoplastic elastomer (TPE), fabric, or any other material. For example, in some embodiments, the first portion 38 is made from silicone and the second portion 40 is made from fabric. The first portion 38 and / or the second portion 40 may be any color, including white, and may have any finish, including matte. In some embodiments, the first portion 38 and / or the second portion 40 are flexible.

[0123] The band 32 can include a frame 44. The frame 44 can be sized and shaped to engage with the device 34. In some embodiments, the frame 44 is manufactured by molding. In some embodiments, the frame 44 is manufactured from plastic. In some embodiments, the plastic can be any plastic, such as polycarbonate (PC) and acrylonitrile butadiene styrene (ABS). In some embodiments, the frame 44 includes any other material. The frame 44 can be any color, including white, and can have any finish, including matte. In some embodiments, the frame 44 and the first portion 38 are manufactured as a unitary structure.

[0124] The device 34 may include one or more displays or screens 46 (e.g., digital displays, LEDs, etc.) for displaying information to a user, such as on a top surface 58 of the device 34 ( FIG. 4 ). The screen 46 may also be touch-sensitive to receive input from the user. In some embodiments, the screen 46 comprises acrylonitrile butadiene styrene (ABS) or any other material. The screen 46 may be any color, including light gray, and may have any finish, including gloss.

[0125] The device 34 may include one or more audio signal generators. In certain embodiments, the device 34 has a communication module 210 (FIG. 53) for transmitting data to other devices or remote servers via standard wired or wireless communication protocols. The communication module 210 may include one or more antennas for wireless communication over one or more communication networks. For example, the device 34 may provide a wireless connection to a cloud for uploading and / or downloading data. In some embodiments, the device 34 connects to a hub, base station, or other interim device via a wired or wireless network to share data. Examples of communication networks include, but are not limited to, a local area network (LAN), a wide area network (WAN), a cellular telecommunications network, and a global network (e.g., the Internet), other network types, and any combination thereof. In some embodiments, the wireless communication includes, among others, Wi-Fi, Bluetooth, short-range wireless communication, and infrared communication for connecting with a hub or other interim device to share data. In some embodiments, the base station is configured to upload and / or download data with the cloud via a wired or wireless communication network.

[0126] In some embodiments, the device 34 includes a Bluetooth module, a Wi-Fi module, and / or a cellular module along with associated antennas. For example, in some embodiments, the device 34 includes a cellular module, a Bluetooth module, and their associated antennas. For example, in some embodiments, the antennas associated with the Bluetooth module and the cellular module are located on the same surface within the device 34. For example, in some embodiments, the antenna for the cellular module spans a first portion of the interior surface of the device 34, and the Bluetooth module is located on a second portion of the interior surface. In some embodiments, the first portion substantially surrounds the second portion. In certain embodiments, the cellular module communicates with the Internet via a mobile carrier's network. Depending on the location and carrier, various standards such as GPRS, GSM, LTE, MIMO, and CDMA may be applied.

[0127] The device 34 may also include a haptic motor that provides feedback or notification to the wearer via vibration. The device 34 may include one or more interface features, such as, for example, pressable or solid-state buttons 48, by which a user can interface with the device 34.

[0128] In some embodiments, the depressible or solid-state button 48 comprises a tactile electrical switch (e.g., a conductive dome). In some embodiments, an outer edge portion of the conductive dome contacts a first electrical contact underlying the dome when the dome is in the electrically closed configuration. In some embodiments, an inner portion of the conductive dome contacts a second electrical contact underlying the conductive dome when the conductive dome is in the electrically closed configuration. In some embodiments, the conductive dome is snap-reconfigurable from an electrically open configuration to an electrically closed configuration. For example, in some embodiments, the snap response occurs in response to a force applied by the tip of a finger.

[0129] 4 is a perspective side view of system 30 with device 34 aligned with opening 50 in frame 44 prior to insertion of device 34 into opening 50 in direction 82 to secure device 34 to band 32. In some embodiments, frame 44 is configured to mechanically and / or electrically interface with device 34.

[0130] In some embodiments, the frame 44 includes an abutment surface 52. In some embodiments, the abutment surface 52 is disposed on a surface of the frame 44. In some embodiments, one or more electrical contacts 90 (FIG. 45) are disposed on the abutment surface 52. In some embodiments, the abutment surface 52 is shaped and sized to contact a contact surface 56 of the device 34 when the device 34 is secured to the band 32. At least a portion of the contact surface 55 can be disposed near the bottom, the top, or anywhere between the bottom and the top of the device 34. In the illustrated embodiment, the contact surface 55 is disposed between the bottom and the top of the device 34. In some embodiments, the contact surface 55 is disposed near the bottom of the device 34. In some embodiments, the one or more electrical contacts 90 are shaped and sized to contact one or more electrical contacts 86 of the device 34 (FIGS. 36 and 42) when the device 34 is secured to the band 32. In some embodiments, each of the one or more electrical contacts 86, 90 includes four contacts. In other embodiments, the one or more electrical contacts 86, 90 each include more or less than four contacts.

[0131] In some embodiments, the band 32 can have an outer side 80 and an inner side 78. In certain embodiments, the outer side 80 is viewable by a user and the inner side 78 faces the user's skin when the band 32 is worn by a user. In some embodiments, the device 34 is insertable into the opening 50 from the inner side 78 of the band 32 in a direction 82 such that the contact surface 56 abuts the abutment surface 52 of the frame 44, preventing the device 34 from passing completely through the opening 50 and exiting the opening 50 on the outer side 80 of the band 32.

[0132] In some embodiments, the device 34 can have an upper surface 58 and a lower surface 60 (FIG. 5). In some embodiments, the device 34 includes an outer wall 54 disposed between the upper surface 58 and the lower surface 60. In some embodiments, the outer wall 54 engages with the frame 44. In some embodiments, the outer wall 54 includes one or more engagement structures 88 (FIGS. 40 and 41). In some embodiments, the one or more engagement structures 88 of the device 34 are disposed to engage with one or more engagement structures 92 of the band 32 (FIGS. 44 and 45). In some embodiments, the one or more engagement structures 88 of the device 34 are formed as protrusions that engage with one or more engagement structures 92 of the band that are formed as recesses. In some embodiments, the one or more engagement structures 88 of the device 34 are formed as recesses that engage with one or more engagement structures 92 of the band that are formed as protrusions. In some embodiments, at least a portion of the lower surface 60 contacts the limb of a user when the system 30 is worn by the user.

[0133] In some embodiments, the band 32 captures the device 34 against the limb such that a portion of the lower surface 60 contacts the limb and the screen 46 is visible to the user. In some embodiments, at least a portion of the device 34 is disposed between a surface of the band 32 and the limb. In some embodiments, at least a portion of the device 34 forms a press fit with the band 32.

[0134] In some embodiments, the outer wall 54 is sized and shaped to secure within the opening 50 when the device 34 is inserted into the opening 50 in direction 82. In some embodiments, the device 34 is inserted from the inside 78 of the band 32. In some embodiments, the opening 50 is sized and shaped to prevent the device 34 from passing completely through the opening 50. In some embodiments, the engagement between one or more engagement structures 88 of the device 34 and one or more engagement structures 92 of the band 32 prevents inadvertent removal of the device 34 from the band 32.

[0135] The outer wall 54 can have any size or shape. In some embodiments, a portion of the outer wall 54 has a circumference that is greater than the inner circumference of the opening 50. In some embodiments, a portion of the outer wall 54 has a conical shape. For example, in some embodiments, the outer wall 54 has a conical shape that tapers in a direction from the lower surface 60 to the upper surface 58. In some embodiments, the tapered conical shape prevents the device 34 from passing completely through the frame 44 when the device 34 is captured by the band 32.

[0136] In some embodiments, the outer wall 54 has a step shape. For example, the steps can include a riser 64 and a tread 62. In some embodiments, the circumference of the riser 64 is smaller than the inner circumference of the opening 50. In some embodiments, the circumference of the riser 64 is not significantly larger than the inner circumference of the opening 50. For example, in some embodiments, the circumference of the riser 64 is slightly larger than the inner circumference of the opening 50, thereby forming a press-fit (e.g., interference fit) engagement between the riser 64 and the opening 50. In some embodiments, the device 34 is sized and shaped such that only a portion of the device 34 fits within the opening 50 when the device 34 is inserted into the frame 44 from the inner side 78 of the strap 36. In some embodiments, the screen 46 is viewable within the opening 50 from the outer side 80 of the strap 36.

[0137] In some embodiments, the electrical interface of the device 34 (e.g., one or more electrical contacts 86) couples to the frame 44 through the opening 50. In some embodiments, the electrical interface of the device 34 includes one or more electrical contacts 86 (FIGS. 36 and 42). In some embodiments, the one or more electrical contacts 86 extend upwardly or outwardly from a surface of the device 34. The opening 50 may substantially coincide with a portion of the surface of the device 34 that includes the one or more electrical contacts 86. For example, the one or more electrical contacts 86 of the device 34 may be disposed on the contact surface 56, while the one or more electrical contacts 90 of the band 32 (FIG. 45) may be disposed on the frame 44 and positioned to contact the one or more electrical contacts 86.

[0138] In some embodiments, the device 34 and frame 44 may include corresponding keying features that ensure that the device 34 and band 32 are coupled in the proper orientation.

[0139] In some embodiments, the opening 50 is sized and shaped to form a receptacle that surrounds at least a portion of the outer wall 54 of the device 34. The shape of the opening 50 can match the shape of the device 34. In some embodiments, the opening 50 has an elliptical shape. Of course, the opening 50 need not have an elliptical shape, but can have any other shape, including the shapes shown in Figures 7-51. In some embodiments, the opening 50 has a shape that is symmetrical across the longitudinal and transverse axes of the band 32.

[0140] In some embodiments, the thickness or width of the frame 44 varies. For example, in some embodiments, the thickness decreases in the area between the connection 68 and the aperture 70 (FIG. 6). The change in thickness can reduce any bending force applied by the user to remove the device 34 from the frame 44. In some embodiments, the user first holds the frame 44 at the connection 68 and the aperture 70, and then presses the screen 46 of the device 34 to pop the device 34 out of the opening 50 in a direction toward the inside 78. In this manner, the frame 44 can assume a slightly curved or bent shape, such as a U-shape. In some embodiments, when the device 34 is secured within the opening 50, the frame 44 has a generally planar shape. In some embodiments, the frame 44 has a slightly bent shape even when the device 34 is secured within the opening 50.

[0141] The size and shape of the connection 68 and aperture 70 can be configured to provide one or more suitable contact surfaces for a user to manipulate the connection 68 and aperture 70 when removing the device 34 from the frame 44. A user can advantageously use one or more of their fingers to pull back the connection 68 and aperture 70 while pushing the device 34 forward to remove the device 34 from the opening 50. The connection 68 and aperture 70 can allow the user to apply a slight bending moment to the device 34. In some embodiments, the connection 68 is adjacent to the opening 50. In some embodiments, the aperture 70 is adjacent to the opening 50.

[0142] In some embodiments in which the opening 50 has a non-circular shape that matches the shape of the outer wall 54, the shape requires the user to mount the device 34 in one or more specific orientations. The keying mechanism can ensure, for example, that one or more electrical contacts 86 of the device 34 are properly connected to one or more electrical contacts 90 of the frame 44 and are not inverted. The keying mechanism can be particularly advantageous in embodiments in which the electrical contacts form a symmetrical arrangement. The keying mechanism can ensure that the proper stimulation signal is electrically coupled to the proper electrode of the electrode system 42 and correspondingly the proper nerve, and can prevent the device 34 from being worn on the wrong hand (e.g., right or left hand).

[0143] In addition to the engagement features described below, the shape of the opening 50 can further prevent relative rotation of the device 34 when secured to the band 32. In this manner, the device 34 can be configured (e.g., shaped and sized) to be received in the opening 50 in the frame 44. For example, the opening 50 can have any suitable shape, including those described elsewhere herein, and a general height that matches the height of the outer wall 54 of the device 34. Thus, the opening 50 can be circular, elliptical, oval / stadium shaped, or any other suitable shape.

[0144] The opening 50 can form a reversibly removable interference or snap fit with the device 34. In some embodiments, the opening 50 can include an abutment surface 52 and / or a recess, and the device 34 can include a protrusion. For example, the protrusion can be disposed on the outer wall 54 and positioned to engage the abutment surface 52 and / or the recess. Locating the electrical contacts of the electrical interface on a surface of the frame 44 hidden by the device 34 can advantageously protect the electrical contacts from damage.

[0145] In some embodiments, the frame 44 may include all electrical contacts with the device 34. For example, the frame 44 may include embedded conductors or wires that extend from the openings 50 (e.g., from one or more electrical contacts 90) in the first portion 38 of the strap 36 to the electrode system 42 for one or more electrical contacts 86 (e.g., ground and stimulation) from the device 34 to electrically contact the electrodes 74 of the electrode system 42. The one or more electrical contacts 86 from the device 34 may be snap connections that form a snap fit (e.g., annular snap fit) with a corresponding one or more contacts or holes 90 on the frame 44.

[0146] In some embodiments, the one or more electrical contacts 86, 90 further include an optional return or ground contact for dispersing the stimulation current from the body by returning to the stimulation source. In some embodiments, the one or more electrical contacts 86, 90 may also provide a mechanical connection between the band 32 and the device 34. In some embodiments, the one or more electrical contacts 86, 90 are metallic conductive snap fasteners for providing the mechanical connection. In some embodiments, the frame 44 may include recessed electrical contacts 90 and the device 34 may include protruding electrical contacts 86. In some embodiments, the frame 44 may include protruding electrical contacts 90 and the device 34 may include recessed electrical contacts 86.

[0147] In some embodiments, the first portion 38 of the strap includes the electrode system 42 and is mechanically coupled to the frame 44. For example, in some embodiments, the proximal end of the electrode system 42 engages the frame 44 via a connection 68. The strap 36 can be attached to the frame 44 by any suitable means, such as an adhesive, an overmolding, or a permanent or removable mechanical fastener.

[0148] FIG. 5 is a perspective view of the device 34 of FIG. 4. In some embodiments, the device 34 can have an upper surface 58 and an opposing lower surface 60. In some embodiments, the lower surface 60 is the bottom surface of the device 34. Only the upper surface 58 of the device 34 is shown in FIG. 5. In some embodiments, the outer wall 54 extends from the upper surface 58 to the lower surface 60 and defines the height of the device 34. In some embodiments, at least a portion of the outer wall 54 is curved between the upper surface 58 and the lower surface 60. In some embodiments, at least a portion of the outer wall 54 is flat between the upper surface 58 and the lower surface 60.

[0149] The upper surface 58 and the lower surface 60 may have substantially the same shape. In some embodiments, the upper surface 58 and the lower surface 60 have different shapes. For example, the upper surface 58 and / or the lower surface 60 may be substantially rectangular, substantially oval, or an intermediate shape between rectangular and oval. In other embodiments, the shape may be circular, triangular, polygonal, etc. Of course, the device 34 need not have one of the enumerated shapes, but can have any other shape, including the shapes shown in Figures 7-51.

[0150] The device 34 can be configured to enclose or house electronic circuitry for generating and providing neural stimulation signals to be applied to a user (FIGS. 52A, 52B, 53). The circuitry may be housed in the device 34 such that the device 34 is portable. The circuitry may include a pulse generator 201 for generating electrical stimulation pulses and a controller 200 for controlling the delivery of the electrical pulses. The device 34 may also include a power source, such as a battery 214. The device 34 may also include one or more processors and memory 209. Further possible combinations of electronic circuits for generating and providing neural stimulation signals are described, for example, in U.S. Pat. No. 9,452,287 to Rosenbluth et al., U.S. Pat. No. 9,802,041 to Wong et al., WO 2016 / 201366 to Wong et al., WO 2017 / 132067 to Wong et al., WO 2017 / 023864 to Hamner et al., WO 2017 / 053847 to Hamner et al., WO 2018 / 009680 to Wong et al., WO 2018 / 039458 to Rosenbluth et al., WO 2018 / 023864 to Hamner et al., WO 2017 / 023864 to Hamner et al., WO 2017 / 053847 to Hamner et al., WO 2018 / 009680 to Wong et al., WO 2018 / 023864 to Hamner ... No. 2018 / 187241 by Hamner et al., No. 2019 / 213433 by Liberatore et al., No. 2020 / 006048 by Rosenbluth et al., No. 2020 / 069219 by Ross et al., No. 2020 / 086726 by Hamner et al., No. 2020 / 185601 by Hamner et al., No. 2021 / 0252278 by Hamner et al., and No. 2021 / 236815 by Kent et al., each of which is incorporated by reference in its entirety herein.

[0151] The inner, medial, or skin side of the strap 36 can include an electrode system 42. The electrode system 42 can include electrodes or electrical contacts 74 configured to stimulate the user. In some embodiments, the electrodes or electrical contacts 74 are removable from the strap 36, either individually or as a subset (e.g., the electrode system 42). For example, in some embodiments, one or more of the electrodes or electrical contacts 74 are part of a removable / replaceable member from the strap 36.

[0152] The electrical contacts of the device 34 can deliver or transfer the electrical signal to the electrode system 42. The electrical contacts may be disposed on the outer wall 54 of the device 34. The electrical contacts may include one electrical stimulation contact for each electrode 74 applied to the user. The electrical contacts may include at least one electrical stimulation contact for each nerve to be stimulated. For example, the electrical contacts may include electrical stimulation contacts configured to deliver signals to the median nerve, the radial nerve, the ulnar nerve, or any combination thereof. In some embodiments, the stimulation may alternate between each nerve such that the nerves are not stimulated simultaneously. In some embodiments, all nerves are stimulated simultaneously. In some embodiments, the stimulation is delivered to the various nerves in one of a number of burst patterns. For example, the burst patterns may include variations in stimulation parameters including, for example, on / off, duration, intensity, pulse rate, pulse width, waveform shape, and ramps of pulses on and off. In one embodiment, the pulse rate may be about 1 to about 5000 Hz, about 1 Hz to about 500 Hz, about 5 Hz to about 50 Hz, about 50 Hz to about 300 Hz, or about 150 Hz, and overlapping ranges therein. In some embodiments, the pulse rate may be 1 kHz to 20 kHz. In some embodiments, the pulse width may be in the range of 50 to 500 μs (microseconds), such as about 50 to 150, 150 to 300, 300 to 500, 100, 200, 300, 400 μs, and overlapping ranges therein. Some embodiments use high frequency stimulation (e.g., at or near the wrist or ear) of 5 to 75 kHz (e.g., 10 to 40 kHz, 15 to 60 kHz, etc.) and pulse widths of 1 to 20, 10 to 50, 10 to 40 μs, although some embodiments use frequencies below 5 kHz. The intensity of the electrical stimulation may vary from 0 mA to 500 mA (e.g., 1 mA, 2 mA, 3 mA, 4 mA, 5 mA, 6 mA, 7 mA, 8 mA, etc.), and the current may be about 1 to 11, 1 to 20, 5 to 50, 10 to 100 mA (e.g., 1 mA, 2 mA, 3 mA, 4 mA, 5 mA, 6 mA, 7 mA, 8 mA, etc.), and overlapping ranges therein. The electrical stimulation can be adjusted with different electrical stimulation methods in different patients.In some embodiments, the user can adjust the current between a minimum and a maximum value. For example, in some embodiments, the user can adjust the current in increments of 0.1-12 mA, e.g., a minimum of 0.5 mA to a maximum of 8 mA (e.g., in increments of 0.1, 0.5, 1.0 mA). The intensity adjustment increments may be, e.g., 0.1 mA to 1.0 mA, e.g., 0.1-0.5, 0.5-0.75, 5-1 mA, and overlapping ranges therein. In some embodiments, the stimulation may last for about 10 minutes to 1 hour, such as about 10, 20, 30, 40, 50, or 60 minutes, or a range including any two of the above values. In some embodiments, the stimulation may be provided for 30, 40, 50, 60, 80, 90, 120, 150 minutes to 4 times per day. In some embodiments, stimulation is administered for 2-15 minutes every hour (e.g., 3, 5, 7, 10 minutes) (or at another interval) for a total of 40-240 minutes (e.g., 60, 80, 90, 120, 150 minutes) over a 12- or 24-hour period. Different administration schedules and / or different stimulation parameters may reduce tolerance or habituation and / or increase patient comfort / compliance. In one embodiment, the beneficial effects of stimulation are provided during off periods, e.g., the patient's tremor or other symptoms / signs are reduced due to the previous stimulation resulting in a long-term effect on the nerve. Thus, the patient may be able to reduce the length, duration, etc. of treatment over time. In some embodiments, parameters (e.g., frequency, amplitude, etc.) of the stimulation signals delivered to various nerves vary between nerves. Burst patterns include, but are not limited to, theta burst stimulation.

[0153] Although several neurostimulation devices are described herein, in some embodiments, the nerve is non-invasively modulated to achieve neural inhibition. Neural inhibition can occur in a variety of ways, including but not limited to, hyperpolarizing the neuron to inhibit action potentials and / or depleting the neuron's ionic stores to inhibit firing action potentials. This can occur in some embodiments, for example, via anodal or cathodal stimulation, high frequency stimulation (e.g., in some cases greater than about 1 kHz), or continuous or intermediate burst stimulation (e.g., theta burst stimulation). In some embodiments, the wearable device has at least one implantable portion that can be temporary or more chronic. In many embodiments, the device is fully wearable and non-implantable.

[0154] In some embodiments, the multiple electrical stimuli may be delivered offset in time from one another by a predetermined fraction of a multiple of the period of a measured rhythmic biosignal, such as hand tremor, such as, for example, about ¼, ½, or ¾ of the period of the measured signal. Additional possible stimulation parameters are described, for example, in U.S. Pat. No. 9,452,287 to Rosenbluth et al., U.S. Pat. No. 9,802,041 to Wong et al., WO 2016 / 201366 to Wong et al., WO 2017 / 132067 to Wong et al., WO 2017 / 023864 to Hamner et al., WO 2017 / 053847 to Hamner et al., WO 2018 / 009680 to Wong et al., WO 2018 / 039458 to Rosenbluth et al., WO 2018 / 023865 to Hamner et al., WO 2018 / 023866 to Hamner et al., WO 2018 / 023865 ... No. 2018 / 187241, WO 2019 / 213433 by Liberatore et al., WO 2020 / 006048 by Rosenbluth et al., WO 2020 / 069219 by Ross et al., WO 2020 / 086726 by Hamner et al., WO 2020 / 185601 by Hamner et al., WO 2021 / 0252278 by Hamner et al., and WO 2021 / 236815 by Kent et al., each of which is incorporated by reference in its entirety.

[0155] In some embodiments, in addition to the engagement between the openings 50 of the frame 44 and the device 34, the frame 44 may include one or more engagement structures 88, 92 for releasably securing the device 34 to the band 32. Any suitable coupling mechanism may be used. For example, in some embodiments, the frame 44 includes one or more hooks and / or one or more magnets. In some embodiments, the one or more hooks may be configured to mechanically interlock with a ridge or lip of the device 34 to secure the device 34 to the band 32. The surface of the device 34 may include an aperture for the one or more hooks to enter into the device 34 and secure to the ridge or lip. Of course, in some embodiments, the coupling mechanism may include a single structure.

[0156] In some embodiments, the magnet(s) may include a magnet or ferromagnetic material that is attracted to the magnet. When the magnets are close enough to be magnetically attracted to one another, the magnetic attraction or force facilitates holding the device 34 and the band 32 together and / or aligned. This engagement may provide a physical and audible confirmation to the user that installation of the device 34 is complete. In some embodiments, an audible sound is heard when the device 34 is engaged with the band 32. In some embodiments, the magnet(s) facilitate rough alignment of the opening 50 with the outer wall 54 of the device 34.

[0157] Other reversible connection mechanisms for connecting the device 34 to the band 32 may also be utilized, including, but not limited to, threads, rotating / rotating connection elements, elastomers, etc. Non-limiting examples of such other structures include mechanical structures such as one or more holes or recesses configured to accept protrusions, pins, Velcro® (e.g., hook-and-loop fasteners), adhesives, or any combination of the above.

[0158] The device 34 may also include one, two, three, or more sensors 112 (FIG. 52A), which may include any number of combinations of, for example, an inertial measurement unit (IMU), single or multi-axis accelerometer, gyroscope, inclinometer (to measure and compensate for changes in the gravitational field resulting from slow changes in the device's orientation), magnetometer, fiber optic electrogoniometer, optical tracking, or electromagnetic tracking, electromyography (EMG) to detect tremor muscle firing, electroneurography (ENG) signals, cortical recordings by techniques such as electroencephalography (EEG) or direct neurography at implants in close proximity to the nerves, e.g., heart rate or HRV sensors, galvanic skin response sensors (GSR), thermocouples, photoplethysmography sensors (PPG), temperature sensors (e.g., for body / skin temperature or ambient temperature), and / or other physiological sensors. In some embodiments, one or more sensors 112 may be used to measure responses to a treatment as well as to calibrate the treatment.

[0159] The device 34 can be used in some embodiments to treat depression (including but not limited to postpartum depression, depression associated with neurological disorders, major depression, seasonal affective disorder, depressive disorders, etc.), inflammation, Lyme disease, stroke, neurological disorders (such as Parkinson's disease and Alzheimer's disease), and gastrointestinal problems (including Parkinson's disease problems). The devices described herein can also be used for the treatment of inflammatory bowel disease (such as Crohn's disease, colitis, and functional dyspepsia), rheumatoid arthritis, multiple sclerosis, psoriatic arthritis, osteoarthritis, psoriasis, and other inflammatory diseases. The devices described herein can be used in some embodiments to treat inflammatory skin conditions. The neuromodulation devices, e.g., neurostimulation devices, described herein can be used to treat chronic fatigue syndrome. The devices described herein can be used to treat chronic inflammatory conditions and erythema. According to some embodiments, bradykinesia, dyskinesia, and rigidity can also be treated. In some embodiments, rehabilitation as a result of a particular event is treated, e.g., rehabilitation from a stroke or other cardiovascular event. In some embodiments, treatment of involuntary and / or repetitive movements is provided, including but not limited to tics, twitches, and the like (including, e.g., Tourette's syndrome, tic disorders). In some embodiments, rhythmic and non-rhythmic involuntary movements can be controlled. Involuntary vocalizations and other vocalizations can also be treated. Systems and methods for reducing habituation and / or tolerance to stimulation in disorders and conditions identified herein are provided in some embodiments, for example, by introducing variability in stimulation parameters as described herein.

[0160] In some embodiments, the device 34 described herein can be used to treat cardiac conditions (such as atrial fibrillation, high blood pressure, and stroke) and immune dysfunction. In one embodiment, epilepsy is treated. The device described herein can be used to stimulate the autonomic nervous system. The device described herein can be used to balance the sympathetic / parasympathetic nervous system. Dysfunction or imbalance of the autonomic nervous system is believed to be a potential underlying mechanism for various chronic diseases. Autonomic dysfunction can develop when the nerves of the ANS are damaged or degraded, or in the absence of a known nerve pathology. This condition is called autonomic neuropathy or autonomic neuropathy. Autonomic dysfunction can range from mild to life threatening and can affect parts of the ANS or the entire ANS. Sometimes the condition causing the problem is temporary and reversible. Others are chronic or long-term and may continue to worsen over time. Examples of chronic diseases associated with autonomic dysfunction include, but are not limited to, diabetes, Parkinson's disease, tremors, cardiac arrhythmias including atrial fibrillation, hypertension, overactive bladder, urinary incontinence, fecal incontinence, inflammatory bowel disease, rheumatoid arthritis, migraine headaches, depression, social phobia, addition, and anxiety.

[0161] In some embodiments, disorders and symptoms caused or exacerbated by microbial infections (e.g., bacteria, viruses, fungi, and parasites) are treated. Symptoms include, but are not limited to, sympathetic / parasympathetic imbalance, autonomic dysfunction, inflammation (including but not limited to neuroinflammation and other inflammation), movement and balance dysfunction, pain, and other neurological conditions. Disorders include, but are not limited to, tetanus, meningitis, Lyme disease, urinary tract infections, mononucleosis, chronic fatigue syndrome, autoimmune disorders, and the like. In some embodiments, autoimmune disorders and / or pain unrelated to microbial infections are treated, including, for example, inflammation (e.g., neuroinflammation, etc.), headaches, back pain, joint pain and stiffness, muscle pain and tension, and the like. Other disorders (e.g., high blood pressure, dexterity, and cardiac arrhythmias) may also be treated using the embodiments described herein. In some embodiments, Tourette's and other involuntary or unwanted tics or movements are treated.

[0162] FIG. 6 is a perspective view of the band 32 of FIG. 4. FIGS. 7-10 are views similar to FIGS. 3-6, respectively. FIGS. 11-14 are views similar to FIGS. 3-6, respectively. FIGS. 15-18 are views similar to FIGS. 3-6, respectively. The band 32 can include a strap 36 and a frame 44. In some embodiments, the strap 36 extends from both sides of the frame 44 to selectively form a closed shape. In some embodiments, the strap 36 can have an adjustable length sufficient to accommodate any size user. In some embodiments, the strap 36 can be sized for various sizes of users (e.g., small, medium, large, pediatric, adult, etc.). The width of the strap 36 can be less than the width of the frame 44 and / or the corresponding width of the opening 50.

[0163] The length (longer dimension) of the frame 44 may be oriented substantially perpendicular to the length of the strap 36 and may be configured to align the length of the frame 44 with the length of the user's arm, leg, or other body appendage. Aligning the length of the frame 44 with the length of a body part can facilitate easier movement of a body part, such as the hand and wrist, while the device 34 is being worn, and is generally less protruding and unwieldy, and therefore less likely to get caught on or inadvertently come into contact with something in the user's environment. Of course, the frame 44 need not have one of the shapes illustrated, but can have any other shape, including the shapes shown in Figures 7-51.

[0164] In some embodiments, the straps 36 may be substantially centrally located along the length of the frame 44 and / or opening 50. In some embodiments, the straps 36 may be offset toward or near one side of the length of the frame 44 and / or opening 50. Offsetting the straps 36 may allow the straps 36 to be worn, for example, around a user's wrist and allow the frame 44 to extend upward or proximally toward the shoulder or toward the hand rather than distally from the wrist, which may advantageously enable or facilitate wrist movement (e.g., a greater range of motion).

[0165] In some embodiments where the strap 36 includes multiple portions, the band 32 may include a connection 72 between the first portion 38 and the second portion 40. In some embodiments, the connection 72 includes overmolding the first portion 38 onto the second portion 40. For example, in some embodiments where the first portion 38 is made from silicone and the second portion 40 is made from fabric, the silicone strap portion 38 may be overmolded onto the fabric strap portion 40. In some embodiments, the connection 72 provides a secure, permanent connection between the first portion 38 and the second portion 40. In some embodiments, the connection 72 is an aperture (e.g., a D-loop).

[0166] In some embodiments, the frame 44 may include a connection 68 configured to couple to a first end of the strap 36. In some embodiments, the connection 68 provides a secure, permanent connection between the frame 44 and the first portion 38 of the strap 36.

[0167] The frame 44, in some embodiments, may also include an aperture 70 (e.g., a D-loop) configured to couple to a second end of the strap 36. In some embodiments, the aperture 70 is configured to receive the strap 36 to allow a user to adjust the length of the strap 36. The effective length of the strap 36 may be adjusted by pulling the strap 36 further through the aperture 70. In some embodiments, the frame 44 and the first portion 38 of the strap 36 are manufactured as a unitary structure.

[0168] Complementary portions of hook-and-loop fasteners 76 (e.g., Velcro®) can be attached to straps 36 to enable straps 36 to form closed loops of adjustable length for securing band 32 to a user, for example around the user's arm, wrist, or leg. In some embodiments, complementary hook-and-loop fasteners 76 are disposed on first portion 38 and second portion 40 of straps 36. In some implementations, band 32 may be manufactured by attaching portions of hook-and-loop fasteners 76 to straps 36 after straps 36 are received through apertures 70.

[0169] In some embodiments, at least a portion of the strap 36 can include a width that is less than the maximum width of the electrode system 42. The narrow portion can be configured to be received through the aperture 70. In some embodiments, one of the complementary portions of the hook-and-loop fastener 76 is attached to a proximal portion of the strap 36 (e.g., adjacent the connection portion 68) and the other portion of the hook-and-loop fastener 76 is attached to a distal portion (e.g., at a free end of the strap 36). In some embodiments, the complementary hook-and-loop fasteners 76 can be attached to the same side of the strap 36. For example, the hook-and-loop fasteners 76 can be attached to an outer surface of the strap 36. The free end of the strap 36 can be wrapped around itself to join the complementary hook-and-loop fasteners 76 to one another. The relative positioning of the complementary hook-and-loop fasteners 76 can be used to tighten or adjust the loop on the user's body.

[0170] The electrode system 42 can have any number of electrodes 74 disposed between the distal and proximal ends of the electrode system 42 for contacting the skin of the user. In some embodiments, the device includes 3-6 or more (e.g., 3, 4, 5, 6) electrodes and is partially implantable or completely transcutaneous. In some embodiments, 2-12 electrodes can be provided (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more). In some embodiments, 3-12 or more electrodes 74 are used (e.g., 3, 6, 9 or 12). In one embodiment, none of the electrodes 74 are in contact with the area causing discomfort. The electrodes can be transcutaneous or microneedle electrodes in other embodiments, or only transcutaneous (e.g., in some embodiments, not transcutaneous, microneedle, or implanted electrodes). In many embodiments, the transcutaneous device is a wearable band or earpiece. The band can partially or completely encircle the wrist, finger, arm, leg, ankle, or head. A patch may be used, but in many embodiments no patch is used. Some embodiments provide a wrist-worn device or an ear-worn device, or both.

[0171] The electrodes 74 may be transcutaneous or microneedle electrodes in other embodiments, or may be only transcutaneous (e.g., in some embodiments, not transcutaneous, microneedle, or implanted electrodes). In many embodiments, the transcutaneous device is a wearable band or earpiece. The band 32 may partially or completely encircle the wrist, finger, arm, leg, ankle, or head. A patch may be used, but in many embodiments, a patch is not used.

[0172] In some embodiments, the electrode system 42 has a generally rectangular shape and includes six electrodes 74. In other embodiments, the electrodes 74 have a circular shape or any other shape. Varying the electrode shape can also control excitation in certain areas and make the stimulation more comfortable. Square or partially rounded shapes can also be provided. While six electrodes are shown, in some embodiments, 3-12 (e.g., 3, 9, 12, etc.) electrodes may be provided. In one embodiment, mechanical (e.g., vibration) stimulation can be provided before, after, or during electrical stimulation for diagnostic and / or therapeutic purposes. Such stimulation can be provided via one or more mechanical / vibration elements or bands configured to vibrate at a steady or varying frequency (e.g., approximately 5-50 Hz, 4-60 Hz, 50-100 Hz, 50-300 Hz, 100-450 Hz and overlapping ranges therein). Similarly, the electrical stimulation parameters disclosed herein can vary or be stable within a given time frame (seconds, minutes, hours, etc.). One or more frequencies (e.g., two, three, or more electrical and / or mechanical / vibration stimulation) can be used on the same nerve, overlapping nerves, or different nerves. In one embodiment, varying frequency or other parameters reduces tolerance or habituation and / or improves patient comfort / compliance.

[0173] In some embodiments having six electrodes 74, the six electrodes 74 may be arranged in two sets of three electrodes 74 spaced along the length of the first portion 38 of the band 32. Of course, the electrode system 42 is not limited to the shape or number of electrodes 74 shown. In some implementations, the electrode system 42 of the band 32 may be manufactured as a single flat, flexible piece of material. Manufacturing the portion as a single piece of material (e.g., the first portion 38) may simplify the manufacturing process.

[0174] As described elsewhere herein, in some embodiments, there may be one or more electrodes 74 for each electrical contact 90. The electrodes 74 may be electrically connected to complementary electrical contacts 90 on the frame 44 using one or more electronic traces 94 when the device 34 is secured to the frame 44. In some embodiments, the one or more electronic traces 94 are embedded within the strap 36 (see FIG. 2). In some embodiments, the one or more electronic traces 94 are embedded within the first portion 38 of the strap 36. In some embodiments, a subset of the electrodes 74 electrically connects to a subset of the one or more traces 94. The electrical contacts 90 may include stimulation contacts and / or ground contacts. In some embodiments, the electrodes 74 may be spatially positioned in the same manner as the electrical contacts 90. In some embodiments, the electrodes 74 may be positioned differently. For example, the electrodes 74 may be positioned such that the electrodes 74 are at least partially positioned axially and / or circumferentially around a body part (e.g., the wrist). In some embodiments, the electrodes 74 may be configured to be approximately aligned with the axons of the target nerve to be stimulated.

[0175] In some embodiments, the electrode system 42 uses three or more electrodes 74 to apply the stimulation signal to the patient. For example, in some embodiments, at least one electrode 74 is redundant with another electrode (e.g., two or more redundant common electrodes and / or two or more redundant stimulation electrodes). In this way, even if the electrical contact between one of the two electrodes 74 and the patient's skin is of insufficient increased resistance, the electrical contact between the redundant electrode 74 and the patient's skin can complete an electrical circuit with a normal or expected level of resistance.

[0176] In some embodiments, the two or more common electrodes 74 and / or the two or more stimulation electrodes 74 are spaced circumferentially around the band 32 so that even if the band 32 rotates slightly on the wrist and an electrode 74 loses contact with the patient's skin, the redundant electrode 74 still makes contact with the patient's skin to compete with the normal or expected level of resistance for the circuit. In this way, the desired stimulation signal (e.g., frequency, phase, timing, amplitude, and / or offset) is applied to the patient even as the band 32 rotates on the patient's wrist. The band 32 is less sensitive to changes in electrical contact between the electrodes 74 and the patient's skin caused by changes in the angular orientation of the band 32 on the wrist.

[0177] In some embodiments, components of the electrode system 42 can be integrated into the band 32. The advantage of this configuration, where the electrical contacts are on the device 34, is that no electronics are required in the band 32.

[0178] The one or more electrodes 74 are configured to contact the user's skin. In some embodiments, the inner layer of the electrodes 74 is formed by overmolding the one or more electrodes 74 with a conductive material (e.g., silicone). In this manner, a surface of the inner layer exposes the one or more electrodes 74.

[0179] In some embodiments, the system 30 includes one or more electrical connectors 84 (FIG. 38). In the illustrated embodiment, the one or more electrical connectors 84 are positioned so as to be accessible for charging the system 30. In some embodiments, the one or more electrical connectors 84 are positioned on the device 34. In some embodiments, the one or more electrical connectors 84 connect the system 30 to a complementary electrical connector on a base station (not shown). The base station can be configured to stream motion sensor and usage data and charge the neurostimulation device 34 periodically, for example daily. In some embodiments, the base station can connect to the cloud or the Internet via any wired or wireless connection protocol and can be configured to upload and / or download data in the cloud. In some embodiments, the base station and the neurostimulation device 34 share data when the neurostimulation device 34 is being charged by the base station. In some embodiments, the base station and the neurostimulation device 34 transmit and receive data wirelessly. In some embodiments, the controller 200 can consistently update the neurostimulation device 34 to provide a more tailored therapy experience to the user. The base station is used in some embodiments for both charging and synchronizing data.

[0180] In some embodiments, the user can review their tremor improvement scores (e.g., kinematic data and / or patient satisfaction ratings) via a user portal during and / or after an evaluation period (e.g., one or more treatment sessions). The user can select a waveform pattern for future treatment sessions based on the tremor improvement score via the user portal. In some embodiments, the waveforms can be selected based on which waveform maximizes the tremor improvement score and / or other criteria (e.g., patient satisfaction), thereby providing a treatment recommendation. In some embodiments, the base station downloads the selected waveforms from the cloud and then forwards them to the neurostimulator device 34 for future treatment sessions.

[0181] In some embodiments, the wearable system 30 delivers electrical signals transcutaneously to one or more nerves of the user. In some embodiments, the device 34 is configured as a durable component 34. In some embodiments, the band 32 is configured as a replaceable component 32. In some embodiments, the replaceable component 32 at least partially surrounds the limb of the user. In some embodiments, the replaceable component 32 includes a frame 44. In some embodiments, the frame 44 contacts the durable component 34 when the replaceable component 32 maintains the durable component 34 in contact with the skin of the user. In some embodiments, the frame 44 includes a receptacle. In some embodiments, the receptacle is sized and shaped to receive at least a portion of the durable component 34.

[0182] In some embodiments, the durable component 34 can withstand more usage than the replaceable component 32. In some embodiments, the durable component 34 has a longer useful life than the replaceable component 32. In some embodiments, the useful life of the replaceable component 32 may be, in some cases, 30-210 days, such as about 30-50, 50-70, 70-90, 90-110, 110-130, 130-150, 150-170, 170-190, 190-210, such as 40, 60, 80, 100, 120, 140, 160, 180, 200, and overlapping ranges therein. In some embodiments, the durable component 34 stops operating at the end of the replaceable component 32's useful life. In some embodiments, the durable component 34 provides a warning to the user a predetermined amount before the end of the replaceable component 32's useful life to replace the replaceable component 32. In some embodiments, durable component 34 provides one or more warnings to the user 20 days, 15 days, 10 days, 5 days, and / or 1 day prior to the end of the useful life of replaceable component 32. In some embodiments, the warning is displayed on screen or display 46.

[0183] In some embodiments, the useful life of the replaceable component 32 is predetermined. In some embodiments, the useful life is dynamically determined based on one or more characteristics. In some embodiments, the one or more characteristics may include, for example, efficacy of treatment, changes in impedance over time between the electrodes and the user's skin, wear and tear on the electrodes, accumulation of material on the electrode surface, cumulative stimulation time, geographic location, characteristics of the user, cumulative intensity of stimulation, and / or age of the replaceable component 32. In some embodiments, automatic shutoff is implemented after 90 days of use of the replaceable component or if the system detects a malfunction, with an optional warning provided prior to said shutoff.

[0184] In some embodiments, durable component 34 includes at least one electrode 74. In some embodiments, replaceable component 32 is configured to maintain durable component 34 and at least one electrode 74 in contact with the user's skin by applying a force to durable component 34 in a direction toward the skin. In some embodiments, the direction of the force is perpendicular to the user's skin.

[0185] In some embodiments, durable component 34 includes a screen 46. In some embodiments, screen 46 is visible to the user when durable component 34 is in contact with the user's skin.

[0186] In some embodiments, the at least one electrode 74 contacts the user's skin at a location different than where the durable component 34 contacts the patient's skin. In some embodiments, the at least one electrode 74 includes a first electrode 74 and a second electrode 74. In some embodiments, the first electrode 74 is configured to stimulate the user's median nerve and the second electrode 74 is configured to stimulate the user's radial nerve or ulnar nerve. In some embodiments, at least one electrode 74 includes a return or ground electrode 74 configured to be electrically coupled to the user.

[0187] In some embodiments, the system 30 includes electrical contacts or couplings 86, 90 for conducting electrical signals between the replaceable component 32 and the durable component 34. In some embodiments, the electrical contacts or couplings 86, 90 include electrical interconnects. In some embodiments, the electrical interconnects are spring loaded. In some embodiments, the electrical interconnects move from a retracted position to an extended position when the durable component 34 is removed from the replaceable component 32.

[0188] In some embodiments, the system 30 includes one or more engagement structures or mechanical couplings 88, 92 to prevent the replaceable component 32 from separating from the durable component 34 in the absence of force. In some embodiments, the mechanical couplings 88, 92 include abutment surfaces. In some embodiments, the mechanical couplings 88, 92 include contact surfaces. In some embodiments, the mechanical couplings 88, 92 include openings 50. In some embodiments, at least a portion of the durable component 34 forms a press fit with the disposable component 32. In some embodiments, the amount of force applied by the user to remove the durable component 34 from the disposable component 32 is less than the amount of force applied by the disposable component 32 to maintain the durable component 34 in contact with the user's skin. In some embodiments, the direction of the force that removes the durable component 34 from the disposable component 32 is parallel to the direction of the force that maintains the durable component 34 in contact with the user's skin.

[0189] In some embodiments, the disposable component 32 includes a first portion 38 coupled to a second portion 40. In some embodiments, the first portion 38 is made from silicone and the second portion 40 is made from fabric. In some embodiments, the disposable component 32 is flexible.

[0190] In some embodiments, the disposable component 32 includes an electrode system 42. In some embodiments, the electrode system 42 includes an inner side and an outer side. In some embodiments, the inner side includes at least one electrode 74. In some embodiments, the outer side can include at least one electrode 74. For example, the electrode 74 located on the outer side can be used as a sensor that contacts a selected location on the user's body. In some embodiments, the disposable component 32 is configured to be fastened around a user's limb. In some embodiments, fastening the disposable component 32 presses the at least one electrode 74 firmly against the user's skin. In some embodiments, the electrode system 42 includes one or more electrical traces 94. In some embodiments, the one or more electrical traces 94 are in electrical contact with the at least one electrode 74. In some embodiments, the one or more electrical traces 94 are in electrical contact with the durable component 34 at least when the replaceable component 32 maintains the durable component 34 in contact with the user's skin.

[0191] In some embodiments, the durability component 34 is a nerve stimulation device. In some embodiments, the electrical signal delivered to one or more nerves of the user blocks the nerve signal. In some embodiments, the electrical signal delivered to one or more nerves of the user stimulates the nerve signal.

[0192] FIG. 19 is a perspective view of a system 30 similar to that of FIG. 1, showing the electrode system 42 on the inner side 78 of the band 32. A device 34 is removably coupled to the band 32 to provide transcutaneous peripheral nerve stimulation to the user. In some embodiments, the band 32 is configured to be mechanically and electrically coupled to the device 34. In many embodiments, the device 34 is a wearable cuff or earpiece. The band 32 can partially or completely encircle the wrist, finger, arm, leg, ankle, or head. Although a patch may be used, in many embodiments, a patch is not used.

[0193] In some embodiments, the band 32 includes a strap 36. In some embodiments, the strap 36 secures and fastens the band 32, including the electrode system 42, to a user. In some embodiments, the band 32 is configured with a clasp or buckle that secures and fastens the band 32 to the user's wrist. The band 32 can include a frame 44. The frame 44 can be sized and shaped to engage with the device 34.

[0194] FIG. 20 is a top view of the system 30 of FIG. 19. FIG. 21 is a side view of the system 30 of FIG. 19. In some embodiments, the frame 44 is configured to mechanically and / or electrically interface with the device 34. In some embodiments, the frame 44 includes an abutment surface 52. In some embodiments, the abutment surface 52 is disposed on a surface of the frame 44. In some embodiments, one or more electrical contacts 90 are disposed on the abutment surface 52. In some embodiments, the abutment surface 52 is shaped and sized to contact a contact surface 56 of the device 34 when the device 34 is secured to the band 32. In some embodiments, the one or more electrical contacts 90 are shaped and sized to contact one or more electrical contacts 86 of the device 34 when the device 34 is secured to the band 32. In some embodiments, the one or more electrical contacts 86, 90 each include four contacts. In other embodiments, the one or more electrical contacts 86, 90 each include more or less than four contacts.

[0195] FIG. 22 is a bottom perspective view of the system of FIG. 19. FIG. 23 is a top perspective view of the system 30 with the device 34 aligned with the opening 50 of the frame 44 prior to inserting the device 34 into the opening 50 in a direction 82 to secure the device 34 to the band 32. FIG. 23A is a partial view of the frame 44 of FIG. 23, showing one or more electrical contacts 90. The band 32 can include a strap 36 and a frame 44. In some embodiments, the strap 36 extends from both sides of the frame 44 to selectively form a closed shape. In some embodiments, the strap 36 can have an adjustable length sufficient to accommodate any size user. In some embodiments, the strap 36 can be sized for various sizes of users (e.g., small, medium, large, pediatric, adult, etc.). The width of the strap 36 can be less than the width of the frame 44 and / or the corresponding width of the opening 50.

[0196] System 30 may include any combination of features disclosed in any of the figures. For example, FIG. 24 is a bottom perspective view of system 30 with band 32 removed. FIG. 25 includes a view of system 30 of FIG. 24. FIG. 26 is another bottom perspective view of system 30 with band 32 removed. FIG. 27 includes a view of system 30 of FIG. 26. FIG. 28 is a front right perspective view of system 30 similar to FIGS. 1-6. FIG. 29 is a left rear perspective view of system 30 of FIG. 28. FIG. 30 is a rear view of system 30 of FIG. 28. FIG. 31 is a front view of system 30 of FIG. 28. FIG. 32 is a right side view of system 30 of FIG. 28. FIG. 33 is a left side view of system 30 of FIG. 28. FIG. 34 is a top view of system 30 of FIG. 28. FIG. 35 is a bottom view of system 30 of FIG. 28.

[0197] Figure 36 is a front-to-back perspective view of the device 34 of Figure 28. Figure 37 is a left rear perspective view of the device 34 of Figure 28. Figure 38 is a rear view of the device 34 of Figure 28. Figure 39 is a front view of the device 34 of Figure 28. Figure 40 is a right side view of the device 34 of Figure 28. Figure 41 is a left side view of the device 34 of Figure 28. Figure 42 is a top view of the device 34 of Figure 28. Figure 43 is a bottom view of the device 34 of Figure 28.

[0198] FIG. 44 is a right front perspective view of the band 32 of FIG. 28. FIG. 45 is a left rear perspective view of the band 32 of FIG. 28. FIG. 46 is a rear view of the band 32 of FIG. 28. FIG. 47 is a front view of the band 32 of FIG. 28. FIG. 48 is a right side view of the band 32 of FIG. 28. FIG. 49 is a left side view of the band 32 of FIG. 28. FIG. 50 is a top view of the band 32 of FIG. 28. FIG. 51 is a bottom view of the band 32 of FIG. 28. Thus, the system 30 can have any number of different configurations. Thus, although each figure shows a particular combination of features, the features are not limited to being incorporated as part of the combinations shown. In this manner, any feature disclosed in any of the figures can be used with any other feature disclosed in any of the figures. Thus, any of the features shown in FIGS. 1-54E can be combined in any manner.

[0199] FIG. 52A illustrates a block diagram of an exemplary neuromodulation (e.g., neurostimulation) device 34. The device 34 includes multiple hardware components capable of or programmed to provide therapy across the user's skin. As illustrated in FIG. 52A, some of these hardware components may be optional, as indicated by the dashed blocks. In some cases, the device 34 may include only the hardware components necessary for stimulation therapy. The hardware components are described in more detail herein.

[0200] The device 34 may further include stimulation circuitry 104 for generating a signal that is applied via the electrodes 74. In certain embodiments, the signal may vary in, for example, frequency, phase, timing, amplitude, on / off cycle, or offset. The device 34 may also include power electronics 106 for powering the hardware components. For example, the power electronics 106 may include a battery.

[0201] The signals may vary in frequency, phase, timing, amplitude, or offset. The device 34 may also include power electronics 106 for powering the hardware components. For example, the power electronics 106 may include a battery.

[0202] The device 34 may include one or more hardware processors 108. The hardware processor 108 may include a microcontroller, a digital signal processor, an application specific integrated circuit (ASIC), a field programmable gate array (FPGA) or other programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein. In one embodiment, all of the processing described herein is performed by the hardware processor 108. The memory 110 may store patient-specific data and rules, as described below.

[0203] In some embodiments, the tremor signal can be calculated based on input from one or more of the sensors 112. The tremor signal is a representation of the tremor activity generated in the brain and motor nerves that cause tremor muscle activation resulting in tremor in the hands, head, neck, legs, feet, and vocal cords.

[0204] In some embodiments, the sensor (e.g., IMU) 112 may include one or more of a gyroscope, an accelerometer, and a magnetometer. The sensor 112 may be attached to or integrated with the neuromodulation (e.g., neurostimulation) device 34. In one embodiment, the sensor 112 is a commercially available component. In addition to its usual meaning, the sensor 112 may also include specific components as described below. For example, the sensor 112 may include one more sensor capable of collecting motion data. In one embodiment, the sensor 112 includes an accelerometer. In some embodiments, the sensor 112 may include multiple accelerometers for determining motion in multiple axes. Furthermore, the sensor 112 may also include one or more gyroscopes and / or magnetometers in additional embodiments. Since the sensor 112 may be integrated with the neurostimulation device 34, the sensor 112 may generate data therefrom in response to motion, movement, or vibrations sensed by the device 34. Additionally, when a device 34 with an integrated sensor 112 is worn by a user, the sensor 112 can enable detection of voluntary and / or involuntary movements of the user.

[0205] The one or more sensors 112 may include audio sensors, including but not limited to microphones, audio transducers, or accelerometers, configured to measure biological processes such as respiration, speech, or repetitive movements. In some embodiments, the sensors sense parameters used to optimize the neurostimulation and facilitate the introduction of variability in the stimulation parameters to reduce tolerance and / or habituation to the neurostimulation. As an example, electroencephalogram signals, brain activity, and / or neural activity may be used in this manner. In one embodiment, variability in one or more parameters may be configured / introduced to generate natural or desired characteristics of brain or neural activity over a period of time for the treatment of motor, inflammatory, neurological, and psychiatric disorders.

[0206] The device 34 can optionally include user interface components such as a feedback generator 114 and a screen or display 46. The display 46 can provide instructions or information to the user regarding calibration or treatment. The display 46 can also provide alerts, such as, for example, an indication of response to treatment. Alerts may also be provided using the feedback generator 114, which can provide haptic feedback to the user when stimulation begins or ends, for reminder alerts, to alert the user of troubleshooting conditions, to perform tremor elicitation activities to measure tremor motion, among others. Thus, the user interface components such as the feedback generator 114 and the display 46 can provide audio, visual, and haptic feedback to the user. In certain embodiments, the feedback generator 114 and / or the display 46 are configured to allow the user to provide satisfaction data to the device 34.

[0207] Additionally, the device 34 may include communications hardware 118 for wireless or wired communications between the device 34 and external systems, such as the user interface device 150 described below. The communications hardware 118 may include an antenna, as described above. The communications hardware 118 may also include an Ethernet or data bus interface for wired communications.

[0208] Although the illustrated diagram shows several components of the device 34, some of these components are optional and not required for all embodiments of the device 34. In some embodiments, the system may include diagnostic devices or components that do not include neuromodulation functionality. The diagnostic device may be a companion wearable device wirelessly connected via a connected cloud server and may include sensors such as, for example, cardiac activity, skin conductance, and / or motion sensors as described elsewhere herein.

[0209] In some embodiments, the device 34 can also be configured to deliver one, two, or more of magnetic, vibrational, mechanical, thermal, ultrasonic, or other forms of stimulation instead of, or in addition to, electrical stimulation. Such stimulation may be delivered via one, two, or more effectors in contact with or in proximity to the patient's skin surface. However, in some embodiments, the device is configured to deliver only electrical stimulation and not one or more of magnetic, vibrational, mechanical, thermal, ultrasonic, or other forms of stimulation.

[0210] FIG. 52B illustrates communication between the neurostimulator device 34 and the user interface device 150 via the communication link 130. The communication link 130 may be wired or wireless. The neuromodulation (e.g., neurostimulation) device 34 may communicate with and receive instructions from the user interface device 150. The user interface device 150 may include a computing device. In some embodiments, the user interface device 150 is a mobile computing device, such as a mobile phone, a smart watch, a tablet, or a wearable computer. The user interface device 150 may also include a server computing system separate from the neurostimulator device. In certain embodiments, the user interface device 150 may include a hardware processor 152, a memory 154, a display 156, and power electronics 158. In some embodiments, the user interface device 150 may also include one or more sensors 160, such as the sensors described elsewhere herein. Additionally, in some cases, the user interface device 150 may generate an alert in response to a problem with the device or a response to a treatment. The alert may be received from the neurostimulator device 34 via the communication hardware 162.

[0211] In additional embodiments, data obtained from one or more sensors 112 is processed by a combination of hardware processor 108 and hardware processor 152. In further embodiments, data collected from one or more sensors 112 is transmitted to user interface device 150 with little or no processing by hardware processor 108. In some embodiments, user interface device 150 may include a remote server that processes the data and sends a signal back to device 34 (e.g., via the cloud).

[0212] The device stimulation burst frequency can be calibrated to a side-stance task, "wing beat" or forward-stance task, for a predetermined time, e.g., 5-30 seconds (e.g., 20 seconds) for each subject. Other non-limiting examples of device parameters can be as disclosed elsewhere herein.

[0213] In some embodiments, stimulation may be applied to two or more nerves in alternating intervals defined by the tremor frequency (also called burst frequency). In some embodiments, the burst frequency is equal to the measured pathological tremor oscillation calculated from the measured movement, muscle activity, or brain activity.

[0214] Various embodiments of the devices and / or systems discussed herein can stimulate nerves in the user's outer ear, including, but not limited to, the auricular branch of the vagus nerve, the greater auricular nerve, the auriculotemporal nerve, and / or the lesser occipital nerve, among others. In one embodiment, the system can include a neuromodulation device on the wrist or other location on the arm to target a nerve (e.g., the median nerve) of the subject, and a neuromodulation device in the ear (such as any of the auricular devices described herein) to target the vagus nerve. In some implementations, each neuromodulation device in the system can communicate with each other via a wired or wireless connection. Multiple neuromodulation devices can provide synchronous stimulation to multiple nerves. Stimulation may be, for example, burst, offset, or alternating between multiple nerves. Vagus nerve modulation can be achieved with the devices described herein according to some embodiments. In some embodiments, the devices described herein are used to stimulate the autonomic nervous system. In some embodiments, the devices described herein are used to balance the sympathetic / parasympathetic nervous system.

[0215] Variability in stimulation parameters, including but not limited to jitter or dither-like variability, can enhance the symptomatic and / or long-term reduction in tremor severity brought about by the application of alternating stimulation between two or more peripheral nerves. This approach can overcome the challenges of variability observed in people with hand tremors between intrapersonal tremor episodes, or between people in brain responses to peripheral nerve stimulation. Thus, some embodiments include systems and methods for reducing habituation and / or tolerance to stimulation, for example, by introducing variability into stimulation parameters.

[0216] Adding variation in burst frequency may account for natural variation in pathological tremor frequency. For example, in some cases, pathological tremor frequency may vary over time, for example, within an individual subject, between tasks by more than 2 Hz, and up to 32% for the same task. Calibrating the burst frequency to the tremor frequency may improve the therapeutic effect. However, as described above, it may be difficult to target a specific tremor frequency due to natural variation. In some cases, it may not be appropriate to continuously track changing tremor characteristics using the sensors described herein. This may consume too many computational resources and may also drain the battery. Thus, the inventors have recognized that instead of focusing on a specific value or attempting to match the pathological characteristics precisely, adding variation in stimulation parameters such as burst frequency may enhance therapeutic benefit in treating a condition. Pathological characteristics may vary depending on the pathological condition. For example, for the treatment of tremor, tremor characteristics may include tremor frequency, power, phase, amplitude, etc. For example, for the treatment of migraines, a burst frequency of 3 Hz with a pulse frequency of 150 Hz may override thalamocortical arrhythmias in an individual. For example, for the treatment of stroke, a burst frequency of 1 Hz with a pulse frequency of 10 Hz may reduce neuronal inhibition in the motor cortex that would otherwise inhibit motor activity in an individual. In some cases, the characteristics may include physiological parameters such as heart rate, respiratory rate and / or content (respiratory rate, respiratory phase, capnogram, oximetry, spirometry), heart rate variability, blood pressure, etc. The characteristics may also correspond to sympathetic and / or parasympathetic activity. Additionally, the characteristics may correspond to neural oscillations. In some instances, neural oscillations may be observed in the alpha, beta, delta, theta, and gamma frequency bands. In some embodiments, an EEG sensor is not required to probe these oscillations and provide a therapeutic effect based on the stimulation.

[0217] In some instances, the variability increases the probability of matching with the changing pathological characteristics over time and across tasks during a portion of a treatment session. In some embodiments, one or more stimulation parameters are continuously changed over the course of the stimulation. Furthermore, in some cases, measuring the tremor characteristics with one or more sensors is not necessary to provide a therapeutic effect. In addition to tremor, the introduction of variability to treat conditions other than tremor is also provided (e.g., other movement disorders, migraines, stroke, other neurological disorders, etc.).

[0218] In further embodiments, the stimulation parameters are agnostic to any particular individual and may vary within commonly known therapeutic ranges during the course of stimulation. Adding variation in pulse frequency may account for individual differences in brain response to peripheral nerve stimulation. For example, evoked responses in the ventral thalamus nucleus by median nerve stimulation were maximal in some subjects at a pulse frequency of 50 Hz and maximal in others at 100 Hz. By varying the pulse frequency across a range of these values, the brain response is maximized during a portion of the treatment session for all individuals, which may enhance therapeutic benefit. Varying pulse frequency during deep brain stimulation (DBS) therapy improved motor score outcomes, gait speed, and freezing of gait episodes in Parkinson's disease patients compared to fixed frequency DBS. Finally, varying pulse frequency may result in natural stimulation-induced sensations.

[0219] Adding variations in pulse intensity, current amplitude, voltage amplitude, or pulse width is expected to alter the degree of neural recruitment in the target nerve, with higher intensities and amplitudes, or longer pulse widths, increasing the degree of recruitment. These variations in neural recruitment may alter the degree of activation of downstream neural subpopulations in the brain, which may potentially enhance therapeutic benefit by reducing the likelihood of neural adaptation or habituation to the stimulation. Furthermore, varying pulse intensity or pulse width may create a more natural stimulation-induced sensation than fixed stimulation. In some embodiments, systems and methods are provided that reduce habituation and / or tolerance to stimulation by introducing variability in stimulation parameters, for example, as described herein. In some embodiments, adaptation and / or tolerance to neural stimulation that occurs in the treatment of movement disorders, inflammatory disorders, neurological disorders, and psychiatric disorders is treated.

[0220] Adding on / off periods to the stimulation waveform can enhance the therapeutic effect by increasing the desired desynchronizing effect in downstream neuronal subpopulations in the brain.

[0221] Additionally, without being limited by theory, variability in any of the above parameters can enhance the desired neuronal desynchronization effect that enhances therapeutic benefit (e.g., lower tremor or symptom severity following application of stimulation).

[0222] Variability can be applied to one or more of the following parameters for stimulating a nerve, including, but not limited to, burst or AC frequency, pulse frequency, pulse width, pulse interval, intensity, current amplitude, voltage amplitude, duration of stimulation, on / off period, or amplitude envelope period. Variation can be applied across multiple stimulation parameters for stimulating a nerve, including, but not limited to, simultaneous variation, braided variation, timescale variation, and adaptive learning. In certain embodiments, adaptive learning is used in combination with the listed variations and other variations to improve the outcome of neural stimulation therapy.

[0223] In some embodiments, the neuromodulation, e.g., neurostimulation device 34 can apply transcutaneous stimulation to a patient with tremor who is a candidate for implanted deep brain stimulation or thalamotomy. The tremor characteristics and other sensor measurements of tremor severity are used to evaluate the response over a pre-specified period of use, which may be one or three months, or 5, 7, 14, 30, 60, or 90 days or more or less. For example, the response to transcutaneous stimulation, evaluated by the algorithms described herein using the sensor measurements from the device, can advantageously provide input to a predictive model that provides an assessment of the likelihood that the patient will respond to implanted deep brain stimulation or other implanted or non-implanted treatments.

[0224] In some embodiments, when the tremor induction task is being performed, the neuromodulation, e.g., neurostimulation device 34 or a secondary device with a sensor can collect motion data or data from other sensors. The patient can be directly instructed to perform the task, e.g., via a display or audio on the device. In some embodiments, the features of the tremor induction task are stored in the device and used to automatically activate the sensor to measure and store data in memory during the relevant tremor task. The time for measuring and storing data can be, for example, 10, 20, 30, 60, 90, 120 seconds, or 1, 2, 3, 5, 10, 15, 20, 30 minutes, or 1, 2, 3, 4, 5, 6, 7, 8 hours or more or less, or a range incorporating any two of the aforementioned values. Based on a training set of data from a cohort of previous wearers with tremor or another condition, the feature extraction engine can detect features that correlate with the response to stimulation, so that the patient or physician can be presented with a quantitative and / or qualitative likelihood of the patient responding or not responding to the treatment. This data can optionally be measured prior to prescribing neuromodulation, e.g., neurostimulation, or during a trial period.

[0225] In another embodiment, the features can be correlated with the type of tremor measured, such as rest tremor (associated with Parkinson's disease), postural tremor, action tremor, intention tremor, rhythmic tremor (e.g., single dominant frequency) or mixed tremor (e.g., multiple frequencies). The type of tremor most likely to be detected can be presented to the patient or physician as a diagnostic or informational evaluation prior to stimulation or to assess the appropriateness of prescribing neuromodulation, e.g., stimulation therapy. In another embodiment, various stimulation modes can be applied based on the determined tremor type, and different modes can include changes in stimulation parameters such as frequency, pulse width, amplitude, burst frequency, duration of stimulation, or time of day that stimulation is applied. In one embodiment of the smartphone, tablet, or other device 150, the task of inducing tremor can be included in an application that asks the patient to take a self-photograph, whereby the patient performs a task with both posture and intention actions.

[0226] In some embodiments, the neuromodulation, e.g., neurostimulation device 34 or secondary device with sensors can collect motion data or data from other sensors and measure the data over a longer period of time, e.g., 1, 2, 3, 4, 5, 10, 20, 30 weeks, 1, 2, 3, 6, 9, 12 months, or 1, 2, 3, 5, 10 years or more or less, or a range incorporating any two of the aforementioned values, to determine features or biomarkers associated with the development of a tremor disorder, such as essential tremor, Parkinson's disease, dystonia, multiple sclerosis, etc. Biomarkers may include specific changes in one or more features of the data over time, or one or more features exceeding a predetermined threshold. In some embodiments, the features of the tremor induction tasks are stored in the device and are used to automatically activate the sensors when those tremor induction tasks are being performed, and measure and store data during the relevant time in memory.

[0227] In some embodiments, the neuromodulation device 34 may include the ability to track user motion data for the purpose of measuring one, two, or more tremor frequencies of the patient. The patient may have a single tremor frequency, or possibly multiple discrete tremor frequencies that appear when performing different tasks. Once the tremor frequencies are observed, they may be used as one of many seminal input parameters into a customized neuromodulation therapy. The treatment may be delivered, for example, percutaneously via one, two, or more nerves (e.g., the median nerve and the radial or ulnar nerve, and / or other nerves disclosed elsewhere herein) to reduce or improve the patient's condition, including but not limited to the patient's tremor burden. In some embodiments, the treatment modulates the afferent nerves but not the efferent nerves. In some embodiments, the treatment preferentially modulates the afferent nerves. In some embodiments, the treatment does not include functional electrical stimulation. The tremor frequency may be used to calibrate the patient's neuromodulation therapy, and in some embodiments is used as a calibration frequency to set one or more parameters of the neuromodulation therapy, such as the burst envelope duration. In some embodiments, the calibration frequency can be, for example, about 4 Hz to about 12 Hz, about 3 Hz to about 6 Hz, or about 3 Hz, 4 Hz, 5 Hz, 6 Hz, 7 Hz, 8 Hz, 9 Hz, 10 Hz, 11 Hz, or 12 Hz, or a range including any two of the aforementioned values. In some embodiments, the calibration process to match the tremor frequency (or otherwise be personalized or tailored to the user) includes one or more sessions. For example, in some embodiments, the calibration process includes 1 to 5 sessions lasting 10 to 120 seconds, such as three 20-second sessions. After calibration, the therapy (e.g., neurostimulation) is adjusted or personalized to the user. Specific examples for controlling the neurostimulation device 34 are described in more detail below.

[0228] 53 shows a block diagram of another embodiment of a system 30 for providing peripheral nerve stimulation. In certain embodiments, the device and system senses biological, kinematic, and / or user satisfaction data. In certain embodiments, the system 30 uses biological, kinematic, and / or user satisfaction data to customize or modify the delivery of electrical stimulation.

[0229] In some embodiments, the system 30 includes a pulse generator 201. In certain embodiments, the pulse generator 201 delivers electrical stimulation to the nerves via one or more skin interfaces 203. In certain embodiments, the one or more skin interfaces 203 may be electrodes 74 as described elsewhere herein. In certain embodiments, the one or more skin interfaces 203 are located adjacent to one or more target peripheral nerves. The controller 200 receives one or more signals generated by the one or more sensors 112 to control the timing and parameters of the stimulation. In certain embodiments, the controller 200 uses instructions stored in the memory 209 to coordinate the reception of the signals from the one or more sensors 112. In certain embodiments, the controller 200 uses the received signals to control the stimulation delivered by the pulse generator 201. The memory 209 in the system 216 can store signal data from the sensors 112.

[0230] In certain embodiments, the system 30 has a communication module 210 for transmitting data to other devices or remote servers via standard wired or wireless communication protocols. In certain embodiments, the system 30 is powered by a battery 214. In certain embodiments, the system 30 has a user interface 46. In certain embodiments, the user interface 46 allows a user to receive feedback from the system 30. In certain embodiments, the user interface 46 allows a user to provide input to the system 30, for example, via one or more buttons. In certain embodiments, a user provides satisfaction data via the user interface 46. For example, a user can provide input to the user interface 46 in the form of a Patient Session Impression of Improvement (PSII) score and / or a patient satisfaction scope. In certain embodiments, the user interface 46 allows a user to receive instructions, feedback, and control aspects of the delivered stimulation, such as the intensity of the stimulation. In certain embodiments, a user manually enters a Patient Session Impression of Improvement (PSII) score to indicate one or more of 1) improvement, 2) no change, or 3) poor patient satisfaction for a treatment or calibration session. This information is then used, in one embodiment, to adjust therapy (eg, neurostimulation) parameters.

[0231] In certain embodiments, the controller 200 can receive the kinematic data and / or the satisfaction data to determine a method for varying a plurality of stimulation parameters based on the adaptive learning disclosed herein. In certain embodiments, the controller 200 causes the device 34 to adjust one or more parameters of the first electrical stimulus based at least in part on the kinematic data and / or the satisfaction data.

[0232] In some embodiments, the controller 200 of the wearable system 30 uses a therapy algorithm. For example, in certain embodiments, a user selects from a number of different types of therapy waveforms. The controller 200 can use predictive capabilities to determine the best of a number of waveforms for a particular patient (e.g., Transcutaneous Afferent Patterned Stimulation (e.g., CALA TAPS™), Burst Frequency Jitter (BFV), and Pulse Frequency Jitter (PFV)). For example, in some embodiments, the controller 200 can use machine learning to predict improved efficacy and / or patient satisfaction for two, three, or more waveforms. The controller 200 can use the predicted improvement in efficacy and / or patient satisfaction to recommend improved therapy. The improved therapy can include identifying the best or desired waveform for a particular patient. In some embodiments, the improved waveform can be retrieved from a base station while the neurostimulator device 200 is charging.

[0233] 54A-C2 show examples of how stimulation parameters (e.g., burst frequency, pulse frequency, and pulse phase) vary between two or more predetermined values ​​as stimulation alternates across two nerves (e.g., the median and radial nerves). The plots show the pattern of current delivered by device 34 over time.

[0234] FIG. 54A illustrates an embodiment of the device 34 that delivers patterned stimulation to the median nerve 1202 and the radial nerve 1204, where the burst frequency is changed after a pre-specified period or a pre-specified number of bursts. As shown in FIG. 54A, the burst frequency is initially a burst frequency A with a period of 1 / f1 1206. Thereafter, the burst frequency is changed to a burst frequency B with a different period of 1 / f2 1208. FIG. 54A is merely illustrative and is not intended to limit the variation in burst frequency to the values ​​illustrated or the number of different burst frequencies. Additionally, while FIG. 54A illustrates the variation occurring across multiple nerves (e.g., the median and radial nerves), the disclosure is not so limited. The disclosed variations may be applied to only a single nerve.

[0235] In some embodiments, the burst frequency variation is centered around a window (or range including any two of the aforementioned values) of about, at least about, or about 0.1, 0.2, 0.25, 0.3, 0.4, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, or 6 Hz or more or less, or any combination thereof, around a calibration frequency measured from a tremor-inducing task such as postural maintenance. In certain embodiments, if the measured tremor frequency is at the lower edge of the partial tremor frequency range (e.g., 3-12 Hz window), the burst frequency variation window does not go below 3 Hz. In certain embodiments, if the measured tremor frequency is at the higher edge of the partial tremor frequency range (e.g., 3-12 Hz window), the burst frequency variation window does not go above 12 Hz. In another embodiment, the burst frequency variation is applied within the full tremor frequency range or partial tremor frequency range, e.g., between 3-12 Hz for essential tremor. This alternative embodiment may have the advantage of not requiring the user to perform a tremor induction task for calibration. In yet another embodiment, the range of values ​​for burst frequency variation is set based on the minimum and maximum tremor frequencies measured from multiple tremor induction task measurements. In some embodiments, burst frequency variation can avoid precise alignment to pathological vibration frequencies over time and enhance therapeutic response compared to a constant burst frequency. In some embodiments, the rate of change of the burst frequency parameter can be between 0.001 Hz / s (i.e., the slowest rate of change of burst frequency is an increment of 0.1 Hz every 100 seconds) and 100 Hz / s (i.e., the fastest rate of change of burst frequency is an increment of 8 Hz burst frequency, changed every tremor cycle, rounded up).

[0236] FIG. 54B illustrates an embodiment of the device 34 that delivers patterned stimulation to the median nerve 1202 and the radial nerve 1204, where the pulse frequency is changed after a pre-specified period or a pre-specified number of bursts. As shown in FIG. 54B, the pulse frequency is initially a pulse frequency A having a period of 1 / F1 1210. Thereafter, the pulse frequency is changed to a pulse frequency B having a different period of 1 / F2 1212. FIG. 54B is merely illustrative and is not intended to limit the variation in pulse frequency to the values ​​or number of pulse frequencies shown. Additionally, while FIG. 54B illustrates the variation occurring across multiple nerves (e.g., the median nerve and the radial nerve), the disclosure is not so limited. The disclosed variations may be applied to only a single nerve.

[0237] In some embodiments, the pulse frequency of the electrical stimulation applied to a peripheral nerve or neuron can control the frequency at which the stimulated nerve or neuron generates an action potential. In some cases, if the stimulation pulse width and amplitude are high enough, peripheral nerve fibers can be activated to generate an action potential with each stimulation pulse at a pulse frequency of less than about 1,000 Hz. In some cases, stimulation of the median nerve at pulse frequencies of 5, 50, 100, 150, and 200 Hz can evoke responses in the VIM thalamus as measured with microelectrodes implanted during surgery. Furthermore, the pulse frequency that produces the maximum amplitude evoked response in the VIM thalamus can vary between subjects. In some embodiments, the pulse frequency can vary from 5 to 200, 5 to 150, 5 to 100, 5 to 50, 50 to 200, 50 to 150, 50 to 100, 100 to 200, 100 to 150, or 150 to 200 Hz (or a range inclusive of any two of the aforementioned values) to enhance the therapeutic response compared to a constant pulse frequency. The change in pulse frequency can be implemented by directly changing the timing of the pulse delivery or by maintaining the alternating stimulation amplitude with fixed timing for each pulse to change the effective pulse frequency. For example, setting a lower stimulation amplitude that is below the threshold for neuronal or neural recruitment for every one of two pulses can decrease the effective pulse frequency by 1 / 2. In some embodiments, the rate of change of the pulse frequency parameter can be between 0.001 and 10,000 Hz / s. In some embodiments, varying pulse frequencies can generate activity in the brain that modulates pathological cortical dynamics associated with hand tremors. An additional benefit of varying pulse frequencies is that this type of stimulation can induce more natural paresthesia similar to tapping, pressure, touch, and / or vibration sensations experienced during daily life.

[0238] In one embodiment, the pulse frequency may be about 1 to about 5000 Hz, about 1 Hz to about 500 Hz, about 5 Hz to about 50 Hz, about 50 Hz to about 300 Hz, or about 150 Hz, or any other range including any two of the foregoing values. In some embodiments, the pulse frequency may be 1 kHz to 20 kHz.

[0239] 54C1-54C2 show an embodiment of device 34 that delivers biphasic patterned stimulation to median nerve 1202 and radial nerve 1204, where the leading pulse phase changes or alternates (e.g., one or more pulses or bursts of a cathodic first phase of current flowing from electrode 1 to electrode 2 followed by one or more pulses or bursts of an anodic first phase of current flowing from electrode 2 to electrode 1 or vice versa) after (1) a prespecified period (FIG. 54C1), (b) a prespecified number of bursts (FIG. 54C2), or (c) a prespecified number of pulses (FIG. 54C2). In this manner, at least some of the delivered stimulation pulses have different leading first phases as opposed to all of the stimulation pulses having a constant cathodic first phase pattern or a constant anodic first phase pattern (e.g., FIG. 54A).

[0240] As shown in Fig. 54C1, the leading pulse phase is pulse phase A1214 (e.g., current flows first during a pulse from electrode 1 to electrode 2) during each pulse of a pre-specified period or number of bursts. In the illustrated embodiment of Fig. 54C1, leading pulse phase A1214 is maintained for a series of three bursts, each burst including three pulses. Thereafter, the leading pulse phase alternates to pulse phase B1216 (e.g., current flows first during a pulse from electrode 2 to electrode 1).

[0241] In the illustrated embodiment of FIG. 54C1, the leading pulse phase B1216 is maintained for a series of three bursts, each burst including three pulses. FIG. 54C1 is merely illustrative and is not intended to limit the variation of leading pulse phase to the illustrated number of bursts or pulses. Additionally, while FIG. 54C1 shows variation occurring across multiple nerves (e.g., the median and radial nerves), the disclosure is not so limited. The disclosed variations may be applied to only a single nerve.

[0242] As shown in FIG. 54C2, the leading pulse phase is pulse phase A 1214 of one pulse (e.g., current flows first during a pulse from electrode 1 to electrode 2). Thereafter, the leading pulse phase alternates with pulse phase B 1216 during a second pulse (e.g., current flows first during a pulse from electrode 2 to electrode 1). This alternating pattern can be repeated continuously for an interval. FIG. 54C2 is merely illustrative and is not intended to limit the variation of pulse phases to the illustrated number of pulses or intervals for alternating between leading pulse phases. For example, the leading phase of a first pulse can be repeated for two or more pulses before alternating with leading pulse phase B 1216. Additionally, the leading phase of a second pulse can be repeated for two or more pulses before alternating back to the leading phase of the first pulse. Additionally, although FIG. 54C2 illustrates changes occurring across a single nerve, the disclosure is not so limited. The disclosed variations can be applied to multiple nerves (eg, the median nerve and the radial or ulnar nerve).

[0243] In some embodiments, prolonged transcutaneous stimulation sessions using a constant pattern of leading cathodic or anodic first phases can cause electrochemical changes at the electrode-skin interface, even though each pulse is intended to balance the charge by passing current in one direction and then reversing the current during the pulse (e.g., biphasic). Thus, electrochemical changes can occur during biphasic operation, causing discomfort and adverse biological effects (e.g., skin irritation) due to the movement of charged molecules in the skin caused by the flow of current across the skin. Such adverse biological effects can be mitigated by alternating the leading phases of at least some of the pulses in a stimulation session, as shown in Figures 54C1 and 54C2.

[0244] FIG. 54D1 illustrates an embodiment of a device 34 that uses dynamic tremor frequency matching. In some embodiments, the device 34 dynamically changes the burst frequency of patterned stimulation to the median nerve 1202 and / or radial nerve 1204 based at least in part on the change in tremor frequency. In some embodiments, the frequency of stimulation to the median nerve 1202 and radial nerve 1204 dynamically tracks the real-time measured change in tremor frequency. As shown in FIG. 54D2, in some embodiments, the frequency of stimulation to a first nerve (e.g., median nerve 1202) tracks a first phase of the tremor (e.g., hand moving in a downward direction 1224) and stimulation to a second nerve (e.g., radial nerve 1204) tracks a different phase of the tremor (e.g., hand moving in an upward direction 1222).

[0245] In some embodiments, the tremor frequency can be, for example, about 4Hz to about 12Hz, about 3Hz to about 6Hz, or about 3Hz, 4Hz, 5Hz, 6Hz, 7Hz, 8Hz, 9Hz, 10Hz, 11Hz, or 12Hz, or a range including any two of the aforementioned values. In some cases, the pathological tremor frequency can vary for an individual patient, for example, by more than 2Hz between tasks and up to 32% over time on the same task. In some embodiments, phase-locking burst frequency versus tremor frequency can improve therapeutic efficacy.

[0246] As shown in FIG. 54D1, the burst frequency of the midline and radial stimulation can first match tremor frequency A with a period of 1 / tremor 1218. The tremor frequency can then change to tremor frequency B. The burst frequency can change to tremor frequency B with a different period of 1 / tremor 1220 to continue to match the tremor frequency.

[0247] As shown in FIG. 54D2, in some embodiments, the timing of median nerve stimulation and radial nerve stimulation can be determined based on the measured real-time phase of the patient's tremor. For example, median nerve stimulation can be delivered while the tremor is between phase 0 and 180 degrees (e.g., hand moving in a downward direction 324), while radial nerve stimulation can be delivered when the tremor is between phase 180 and 360 degrees (e.g., hand moving in an upward direction 1222). In other embodiments, radial nerve stimulation can be delivered while the tremor is between phase 0 and 180 degrees (e.g., hand moving in a downward direction 1224), while median nerve stimulation can be delivered when the tremor is between phase 180 and 360 degrees (e.g., hand moving in an upward direction 1222).

[0248] In some embodiments, the duration of the different phases is asymmetric. For example, in some embodiments, the duration of the first phase (e.g., hand moving in a downward direction 1224) is not the same as the duration of the second phase (e.g., hand moving in an upward direction 1222). In some embodiments, the device 34 delivers asymmetric stimulation to a first nerve and a second nerve based at least in part on the asymmetric phases of the tremor. FIG. 54D1 and FIG. 54D2 are merely illustrative and are not intended to limit the associated timing variations between the neural stimulation and the real-time phase of the patient's tremor. Additionally, although FIG. 54D1 and FIG. 54D2 show variations that occur across multiple nerves (e.g., the median nerve and the radial nerve), the disclosure is not so limited. The disclosed variations can be applied to only a single nerve.

[0249] In some embodiments, one or more sensors 112 of the device 34 track the patient's motion data for the purpose of measuring the patient's tremor frequency and / or tremor phase in real time. When a tremor frequency is observed, the device 34 can use the frequency as a semantic input parameter. The one or more sensors 112 (e.g., an inertial measurement unit (IMU), accelerometer, gyroscope, etc.) measure the patient's limb motion to allow the device 34 to generate motion data, determine the tremor frequency from the motion data, and set the burst frequency to match or closely match (e.g., phase-lock) the measured motion. For example, in some embodiments, an accelerometer configured as the sensor 112 passively measures the tremor during a treatment session. In some embodiments, the device 34 uses the one or more sensors 112 to continuously track changing tremor characteristics. In some embodiments, the one or more hardware processors 108, 152 analyze the phase and trigger median nerve stimulation 1202 or radial nerve stimulation 1204 accordingly.

[0250] In some embodiments, the phase cutoffs (e.g., 0 degrees and 180 degrees) for switching between median nerve stimulation 1202 and radial nerve stimulation 1204 can be individualized for the patient, as shown in FIG. 54D2. For example, multiple different phase cutoffs and ranges can be used for a series of stimulation sessions (e.g., 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330, and 360 degrees, or a range including any two of the aforementioned values). The device 34 can use the phase cutoff that provides the best tremor reduction. As described above, the phase cutoffs can be symmetrical or asymmetrical depending on, for example, the measured phase of the tremor.

[0251] In some embodiments, the burst frequency of the dynamic tremor frequency alignment is centered around a window of about, at least about, or about 0.1, 0.2, 0.25, 0.3, 0.4, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, or 6 Hz or more or less than 6 Hz (or a range including any two of the aforementioned values) around the measured tremor frequency, or any combination thereof. In certain embodiments, the burst frequency variation dynamically matches the pathological vibration frequency over time. In some embodiments, the rate of change of the measured tremor frequency can be 0.001 Hz / s (i.e., the slowest rate of change of burst frequency is an increment of 0.1 Hz every 100 seconds) to 100 Hz / s (i.e., the fastest rate of change of burst frequency is an increment of 8 Hz burst frequency change every tremor cycle, rounded up).

[0252] FIG. 54E illustrates an embodiment of the device 34 that delivers patterned stimulation to a first nerve (e.g., median nerve 1202) and a second nerve (e.g., radial nerve 1204) based at least in part on the patient's respiratory cycle (e.g., respiratory gating). As shown in FIG. 54E, in some embodiments, the timing of the median nerve stimulation and radial nerve stimulation can be determined based on the measured real-time phase of the respiratory cycle. Delivering stimulation during a first portion of the respiratory cycle and then interrupting stimulation during a second portion of the respiratory cycle (or vice versa) can enhance the autonomic modulation effect. In some embodiments, a first target nerve can be modulated during the inspiratory phase of the respiratory cycle and then no stimulation is applied to the first target nerve during the expiratory phase of the respiratory cycle. In this manner, the device 34 can be configured to synchronize / gate stimulation to one or more specific phases of the respiratory cycle.

[0253] In some embodiments, stimulation of the median nerve 1202 and the radial nerve 1204 tracks the measured changes in the respiratory cycle. As shown in FIG. 54E, in some embodiments, stimulation of the first and second nerves (e.g., median nerve 1202 and radial nerve 1204) occurs during a first portion of the respiratory cycle (e.g., exhalation 1226) and is interrupted during a second portion of the respiratory cycle (e.g., inspiration 1228). In some embodiments, the cycle can be repeated by re-stimulating the first and second nerves during the next exhalation and interrupting stimulation during the subsequent inspiration. Although the first portion (stimulation on) and second portion (stimulation off) are shown as corresponding to the expiratory and inhalation phases of the respiratory cycle, the disclosure is not so limited. The first and second portions can correspond to any portion of the respiratory cycle. In some embodiments, the device 34 can analyze the voltage or other signal from the sensor 112 in real time and can detect different features of the patient's respiratory cycle. The features detected by the sensor 112 may include, for example, peaks, troughs, and slopes that reach, exceed, or are below a predetermined value. Additionally, in some embodiments, the respiratory cycle may be divided into three or more portions (e.g., peaks, troughs, slopes, etc.) based on the data received by the sensor 112, with each portion corresponding to an on or off stimulation.

[0254] In some embodiments, the sensor 112 is carried by a respiratory detection device (e.g., a respiratory belt) worn by the patient. In some embodiments, the respiratory detection device may further include a communication module, which may be cellular, Bluetooth, etc., for communicating with the device 34. In some embodiments, the timing of the stimulation may depend on an algorithm used to trigger the stimulation from one or more of the measured bio-signals (e.g., respiratory cycle) received from the sensor 112. For example, in certain embodiments, the stimulation is triggered at least in part based on the burst being of fixed duration, a percentage of one or more measured bio-signals (e.g., respiratory cycle), terminating at a detected phase of a periodic bio-signal (e.g., respiratory cycle), or some other algorithm implemented in the device 34. For example, in some embodiments, device 34 triggers stimulation when the inhalation and / or exhalation phase of the respiratory cycle is detected and continues for at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% of the average measured respiratory interval or range including any two of the above-mentioned values.

[0255] In some embodiments, the device 34 can identify specific points on the respiratory signal that may be more receptive to stimulation. In some embodiments, the stimulation is synchronized to respiratory activity, but the stimulation is not necessarily configured to affect or substantially affect respiratory function (e.g., one or more of respiratory rate, tidal volume, or minute ventilation). For example, in some embodiments, dual peripheral nerve stimulation (e.g., median nerve stimulation 1202 and radial nerve stimulation 1204) can be synchronized to two different phases of the respiratory cycle to treat a patient without affecting or substantially affecting the patient's respiratory function and / or without affecting or substantially affecting the patient's heart rate or rhythm.

[0256] In some embodiments, stimulation can be synchronized to early expiration, late expiration, early inspiration, and / or late inspiration. Stimulation can also be synchronized to the first, second, third, fourth, fifth, sixth, seventh, eighth, ninth, and / or tenth decile in time of the inspiration and / or expiration cycle, including, for example, any range and / or combination of the aforementioned values. In some embodiments, stimulation can be synchronized continuously to a target phase(s) of each respiratory cycle, every other respiratory cycle, every third respiratory cycle, on during a predetermined or calculated target phase(s) of the respiratory cycle, and off during the same or different predetermined or calculated target phase(s) of the respiratory cycle, or other patterns depending on the desired clinical outcome. In some embodiments, stimulation can include a first stimulation mode during a first portion of the respiratory cycle, e.g., expiration, and a second, different stimulation mode during a second portion of the respiratory cycle, e.g., another portion of expiration and / or inspiration.

[0257] In some embodiments, the durations of different phases of the respiratory cycle are asymmetric. For example, in some embodiments, the duration of a first phase (e.g., expiration 1226) is not the same as the duration of a second phase (e.g., inspiration 1228). In some embodiments, the device 34 delivers asymmetric stimulation to the first and second nerves based at least in part on the asymmetric phases of the respiratory cycle. FIG. 54E is merely illustrative and is not intended to limit the associated timing variations between neural stimulation and real-time phases of the patient's respiratory cycle. Additionally, although FIG. 54E illustrates variations that occur across multiple nerves (e.g., the median and radial nerves), the disclosure is not so limited. The disclosed variations may be applied to only a single nerve.

[0258] In some embodiments, one or more sensors 112 of the device 34 track patient motion data for the purpose of measuring the real-time phase of the patient's respiratory cycle. When a respiratory cycle is observed, the device 34 can use the frequency as a semantic input parameter. The one or more sensors 112 measure the patient's respiratory rate and / or content (respiratory rate, respiratory phase, capnogram, oximetry, spirometry) in order for the device 34 to generate respiratory data, determine the phase of the respiratory cycle from the respiratory data, and turn stimulation on or off based at least in part on the measured respiration. For example, in some embodiments, the respiration detection device passively measures respiration during a therapy session. In some embodiments, the device 34 uses the respiration detection device to continuously track changing respiratory characteristics. In some embodiments, the one or more hardware processors 108, 152 analyze the respiratory cycle and trigger median nerve stimulation 1202 or radial nerve stimulation 1204 accordingly.

[0259] When a feature or element is referred to herein as being "on" another feature or element, it can be directly on the other feature or element, or there may be intervening features and / or elements. In contrast, when a feature or element is referred to as being "directly on" another feature or element, there are no intervening features or elements. When a feature or element is referred to as being "connected," "attached," or "coupled" to another feature or element, it will also be understood that it can be directly connected, attached, or coupled to the other feature or element, or there may be intervening features or elements. In contrast, when a feature or element is referred to as being "directly connected," "directly attached," or "directly coupled" to another feature or element, there are no intervening features or elements. Although described or illustrated with respect to one embodiment, the features and elements so described or illustrated may be applicable to other embodiments. It will also be understood by one skilled in the art that a reference to a structure or feature located "adjacent" to another feature may have portions that overlap or underlie the adjacent feature.

[0260] The terms used herein are for the purpose of describing particular embodiments only and are not intended to limit the present invention. For example, as used herein, the singular forms "a", "an" and "the" are intended to include the plural unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and / or "comprising" as used herein specify the presence of the stated features, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups thereof. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items and may be abbreviated as " / ".

[0261] Spatially relative terms such as "under," "below," "lower," "over," "upper," and the like may be used herein for ease of description to describe the relationship of one element or feature to another element or feature as shown in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation shown in the figures. For example, if the device in the figures is inverted, an element described as being "below" or "directly below" another element or feature would be oriented "above" the other element or feature. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Similarly, terms such as "upwardly," "downwardly," "vertical," "horizontal," and the like are used herein for descriptive purposes only, unless otherwise noted.

[0262] Although the terms "first" and "second" may be used herein to describe various features / elements (including steps), these features / elements should not be limited by these terms unless the context indicates otherwise. These terms may be used to distinguish one feature / element from another. Thus, a first feature / element described below can be referred to as a second feature / element, and similarly, a second feature / element described below can be referred to as a first feature / element without departing from the teachings of the present invention.

[0263] Throughout this specification and the claims that follow, unless the context requires otherwise, the word "comprise" and variations such as "comprises" and "comprising" mean that various components may be used jointly in methods and articles (e.g., devices and compositions and devices that include methods). For example, the term "comprising" is understood to mean the inclusion of any described element or step, but not the exclusion of any other element or step. However, some embodiments can consist of or consist essentially of any number of the described elements or steps disclosed herein.

[0264] As used in this specification and claims, including as used in the examples, unless expressly specified otherwise, all numbers can be read as if they were preceded by the word "about" or "approximately", even if the term does not appear explicitly. The phrase "about" or "approximately" can be used when describing a magnitude and / or location to indicate that the stated value and / or location is within a reasonable expected range of values ​​and / or locations. For example, a numerical value can have values ​​of + / -0.1% of the stated value (or range of values), + / -1% of the stated value (or range of values), + / -2% of the stated value (or range of values), + / -5% of the stated value (or range of values), + / -10% of the stated value (or range of values), etc. Any numerical value set forth herein should also be understood to include approximately that value unless the context indicates otherwise. For example, if the value "10" is disclosed, then "about 10" is also disclosed. Any numerical ranges recited herein are intended to include all subranges subsumed therein. As would be well understood by one of ordinary skill in the art, when a value is disclosed, it is also understood that "less than or equal to" that value, "greater than or equal to" that value, and possible ranges between the values ​​are also disclosed. For example, when a value "X" is disclosed, "less than or equal to" and "greater than or equal to X" (e.g., where X is a number) are also disclosed. It is also understood that throughout this application, data is provided in several different formats, and this data represents endpoints and starting points, as well as ranges for any combination of data points. For example, when a specific data point "10" and a specific data point "15" are disclosed, it is understood that greater than, greater than, less than, less than, less than, and equal to 10 and 15, as well as between 10 and 15, are considered to be disclosed. It is also understood that each unit between two specific units is also disclosed. For example, when 10 and 15 are disclosed, 11, 12, 13, and 14 are also disclosed.

[0265] Although various exemplary embodiments have been described above, any of a number of modifications may be made to the various embodiments without departing from the scope of the invention as described by the claims. For example, the order in which the various described method steps are performed may often be changed in alternative embodiments, and in other alternative embodiments, one or more method steps may be skipped entirely. Any feature of the various device and system embodiments may be included in some embodiments and not in other embodiments. Thus, the foregoing description should not be construed as limiting the scope of the invention as described in the claims.

[0266] The examples and illustrations contained herein show, by way of illustration and not limitation, specific embodiments in which the subject matter may be practiced. As noted above, other embodiments may be utilized and derived therefrom, such that structural and logical substitutions and changes may be made without departing from the scope of the present disclosure. Such embodiments of the subject matter of the present invention may be individually or collectively referred to herein by the term "invention" when more than one is actually disclosed, merely for convenience, and without any intention of spontaneously limiting the scope of the present application to any single invention or inventive concept. Thus, although specific embodiments have been illustrated and described herein, any configuration calculated to achieve the same purpose may be substituted for the specific embodiment illustrated. The present disclosure is intended to cover any and all adaptations or modifications of the various embodiments. Combinations of the above embodiments, and other embodiments not specifically described herein, will be apparent to one of skill in the art upon reviewing the above description. The methods disclosed herein include specific actions performed by a physician, but they may also include, explicitly or implicitly, any third-party instruction of those actions. For example, an act such as "transcutaneously stimulating a peripheral afferent nerve" includes "instructing stimulation of the peripheral afferent nerve."

Claims

1. 1. A wearable system having a detachable neurostimulation device for enhancing mechanical fixation, the detachable neurostimulation device configured to modulate one or more peripheral nerves of a user, the system comprising: a band having an outer side and an inner side, the outer side being visible to the user and the inner side facing the user's skin when the band is worn by the user; an electrode system supported by the band and having an inner side and an outer side, the inner side including at least one electrode for each of the one or more peripheral nerves to be modulated; a frame mechanically and electrically coupled to the band, the frame further comprising an engagement structure and one or more electrical contacts; one or more electrical traces extending between the frame and the at least one electrode; a removable neurostimulation device having an upper surface, a lower surface, and an outer wall disposed therebetween, the outer wall including one or more electrical contacts, the outer wall being sized and shaped to be mechanically secured within the engagement structure of the frame; Including, the one or more electrical contacts of the neurostimulation device are configured to electrically interface with the one or more electrical contacts of the frame when the outer wall is mechanically secured within the engagement structure of the frame; when the removable neurostimulation device is inserted into the frame from the inside of the band, the engagement structure prevents the removable neurostimulation device from passing completely through the frame; A wearable system, wherein the removable neurostimulation device is configured to modulate one or more peripheral nerves of a user.

2. 2. The system of claim 1, wherein the engagement structure is an abutment surface, the removable neurostimulation device includes a contact surface shaped and sized to contact the abutment surface when the neurostimulation device is secured to the band, and the band is interchangeable with alternative bands.

3. The system of claim 1 , wherein the engagement structure is an opening.

4. 4. The system of claim 3, wherein the removable neurostimulation device further includes a screen, the screen being viewable inside the opening from outside the band when the removable neurostimulation device is inserted into the frame.

5. The system of claim 3 , wherein the outer wall has a stepped shape, the stepped shape including a riser and a tread, the riser having a circumference smaller than the inner circumference of the opening.

6. The system of claim 5 , wherein the tread prevents the removable neurostimulation device from passing completely through the frame when the removable neurostimulation device is captured by the band.

7. The system of claim 1 , wherein the at least one electrode includes a return or ground electrode configured to be electrically coupled to the user.

8. 7. The system of claim 1, wherein the at least one electrode includes at least a first electrode and a second electrode, the first electrode configured to stimulate the median nerve of the user and the second electrode configured to stimulate the radial nerve or the ulnar nerve of the user.

9. The system of claim 1 , wherein at least a portion of the outer wall is curved between the upper surface and the lower surface.

10. The system of claim 1 , wherein at least a portion of the outer wall is flat between the upper surface and the lower surface.

11. 7. The system of claim 1, wherein the band is configured to be fastened around a limb and press the at least one electrode firmly against the skin of the user.

12. 7. The wearable system of claim 1, wherein the electrical signals supplied to the one or more peripheral nerves of the user change burst frequency after a pre-specified period of time.

13. 7. The wearable system of claim 1, wherein the electrical signals supplied to the one or more peripheral nerves of the user change burst frequency after a pre-specified number of bursts.

14. 7. The wearable system of claim 1, wherein the electrical signals supplied to the one or more peripheral nerves of the user change pulse frequency after a pre-specified period of time.

15. 7. The wearable system of claim 1, wherein the electrical signal supplied to the one or more peripheral nerves of the user changes pulse frequency after a pre-specified number of bursts.

16. 1. A wearable system for modulating one or more peripheral nerves of a user, comprising: a band having a frame with an engaging structure, the band having an outer side and an inner side, the outer side being visible to the user when the band is worn by the user and the inner side facing the user's skin; A wearable system comprising: a neurostimulation device having an upper surface, a lower surface, and an outer wall disposed therebetween, the outer wall being sized and shaped to be secured to the engagement structure while preventing the neurostimulation device from passing completely through the frame when the neurostimulation device is inserted into the frame from inside the band.

17. 17. The system of claim 16, wherein at least a portion of the neurostimulator device is positioned between a surface of the band and the limb, the surface contacting the neurostimulator device.

18. The system of claim 16 , wherein at least a portion of the neurostimulation device forms a press fit with the band.

19. 19. The system of claim 16, wherein the band includes a frame sized and shaped to engage the neurostimulation device.

20. The system of claim 19 , wherein the neurostimulation device includes an outer wall configured to engage the frame.

21. 21. The system of claim 20, wherein the outer wall forms a step in a direction from the lower surface to the upper surface, the step including a riser and a tread, the tread being positioned between the frame and the limb to prevent the neurostimulation device from passing completely through the frame when the neurostimulation is captured by the band.

22. 21. The system of claim 20, wherein the outer wall has a tapered conical shape in a direction from the lower surface to the upper surface, the tapered conical shape preventing the neurostimulation device from passing completely through the frame when the neurostimulation is captured by the band.

23. 19. The system of any one of claims 16 to 18, wherein the band further comprises an electrode system having an inner and an outer side, the inner side comprising at least one electrode for each nerve to be modulated.

24. 1. A wearable system for modulating one or more peripheral nerves of a user, comprising: a band having an outer side and an inner side, the outer side being visible to the user when the band is worn by the user, and the inner side facing the user's skin when the band is worn by the user; a frame coupled to the band and having an abutment surface and an opening; A wearable system comprising: a neurostimulation device having a contact surface, the neurostimulation device being insertable into the opening from inside the band so that the contact surface abuts the abutment surface of the frame, and preventing the neurostimulation device from passing completely through the opening and exiting the opening to the outside of the band.

25. 25. The system of claim 24, wherein the neurostimulation device further includes a screen, the screen being viewable from outside the band and inside the opening when the contact surface abuts the abutment surface.

26. 26. The system of claim 24 or 25, wherein the band further comprises an electrode system having an inner side and an outer side, the inner side comprising at least one electrode for each nerve to be modulated.

27. 1. A band for releasably securing a neurostimulation device to a limb of a user, the neurostimulation device configured to generate signals for modulating one or more peripheral nerves of the user, the band comprising: a strap having an outer side and an inner side, the outer side being visible to the user and the inner side facing the user's skin when the band is secured to the limb; a frame coupled to the strap and having an opening sized and shaped relative to the neurostimulation device so as to secure the neurostimulation device relative to the frame while preventing the entire neurostimulation device from passing through the opening when the neurostimulation device is inserted into the opening from the inside of the strap.

28. 28. The band of claim 27, wherein the size and shape of the opening relative to the neurostimulation device allows a screen on the neurostimulation device to be viewed inside the opening from outside the strap when the neurostimulation device is secured by the frame.

29. 29. The band of claim 27 or 28, further comprising an electrode system having an inner side and an outer side, the inner side including at least one electrode for each nerve to be modulated.

30. 1. A wrist-wearable system configured to removably secure a controller, the system having an inner side and an outer side, the inner side configured to contact a user's wrist, the wrist-wearable system comprising: a frame including an engagement structure configured to receive the controller from the interior of the system and engage and secure the controller; a strap extending from a first portion of the frame, the end of the strap not being fixed to the frame; and A wrist wearable system including:

31. 31. The wrist wearable system of claim 30, wherein the engagement structure is an abutment surface, and the controller includes a contact surface shaped and sized to contact the abutment surface when the controller is secured to the frame.

32. The wrist wearable system of claim 30 , wherein the engagement structure is an opening.

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