Patent Grant
10646708
All publications and patent applications mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.
Described herein are methods and apparatuses for noninvasive neuromodulation of a subject at the subject's neck. This neuromodulation may be for therapeutic use (including to treat a disorder) and/or to induce relaxation, calm, mental clarity, and associated mental and physical states. These methods and devices in particular include a neck-worn apparatus which need only contact the user in a single location at the back of the users neck while coupled (e.g., magnetically) to controller and/or power source.
Noninvasive neuromodulation technologies that affect neuronal activity can modulate the pattern of neural activity and cause altered behavior, cognitive states, perception, and motor output without requiring an invasive procedure. For example, transcranial/transdermal electric stimulation (hereinafter “TES”) through scalp electrodes has been used to affect brain function in humans in the form of transcranial alternating current stimulation (hereinafter “tACS”), transcranial direct current stimulation (hereinafter “tDCS”), cranial electrotherapy stimulation (hereinafter “CES”), and transcranial random noise stimulation (hereinafter “tRNS”). Systems and methods for TES have been disclosed (see for example, Capel U.S. Pat. No. 4,646,744; Haimovich et al. U.S. Pat. No. 5,540,736; Besio et al. U.S. Pat. No. 8,190,248; Hagedorn and Thompson U.S. Pat. No. 8,239,030; Bikson et al. U.S. Patent Publication 2011/0144716; and Lebedev et al. U.S. Patent Publication 2009/0177243). tDCS systems with numerous electrodes and a high level of configurability have been disclosed (see for example Bikson et al. U.S. Patent Publications 2012/0209346, 2012/0265261, and 2012/0245653), as have portable TES systems for auto-stimulation (Brocke U.S. Pat. No. 8,554,324). Other portable systems include U.S. patent application Ser. No. 14/639,015, titled “TRANSDERMAL ELECTRICAL STIMULATION DEVICES FOR MODIFYING OR INDUCING COGNITIVE STATE”, filed Mar. 4, 2015, which is a continuation of U.S. patent application Ser. No. 14/320,461, titled “TRANSDERMAL ELECTRICAL STIMULATION DEVICES FOR MODIFYING OR INDUCING COGNITIVE STATE,” filed on Jun. 30, 2014, now U.S. Pat. No. 9,002,458, and U.S. patent application Ser. No. 14/091,121, titled “WEARABLE TRANSDERMAL ELECTRICAL STIMULATION DEVICES AND METHODS OF USING THEM”, filed on Nov. 26, 2013.
Typically, TES has been used therapeutically in various clinical applications, including treatment of pain, depression, epilepsy, and tinnitus. In at least some cases of TES therapeutic use, more data concerning the efficacy of TES in treatment is needed. Despite the research to date on TES neuromodulation, existing systems and methods for TES are lacking in at least some cases regarding the design and use of effective TES waveforms. Available systems are limited regarding the design and delivery of TES waveforms. Moreover, available systems do not permit the user to modulate a predetermined/preconfigured electrical stimulation protocol.
For example, U.S. Pat. No. 8,554,324 to Brocke discloses a mobile system for TES auto-stimulation by a user. Brocke further describes an embodiment wherein a wired or wireless remote control is used to control an electrical stimulation generator, as well as the use of smartphones, cellular telephones, or PDAs as a remote control. However, the systems and methods described by Brocke are lacking in at least some instances for defining, acquiring, and/or delivering effective TES waveforms to a user.
Unfortunately, the majority of the devices, including wearable devices, described to date must be positioned on one more likely two body locations, often including the face and head, which can be uncomfortable and visually unappealing to many consumers. Further, the stimulator electronics interfaces for such devices may be cumbersome, and the small size may limit the power and battery life. Even so-called self-contained devices may project from the body (including the face) making them uncomfortable, and may be easily disrupted.
In addition, the stimulation parameters (e.g., waveforms described to date have proven to be difficult to generalize across users; stimulation parameters that are effective for one set of users may be ineffective and/or uncomfortable (particularly when applied to the head and face) for other users.
Finally, most electrodes for TES (and TENS, transcutaneous electrical nerve stimulation) systems require single-use electrodes applied to the skin (or scalp) by an adhesive. Such electrodes may be reused for a limited number of uses, however they are difficult or impossible to clean, and may dry out, interfering with their ability to reliable make electrical contact with the skin.
It would be beneficial to provide apparatuses for effective neuromodulation of a wide number of users that may be worn discretely and comfortably. In particular, such apparatuses (e.g., systems and devices) may also be easily operated and attached to the user, without disrupting the user's hair, skin, glasses, etc. It would also be beneficial to provide electrodes, and in particular electrodes for TES apparatuses, that may be re-used, cleaned and/or rewetted. Described herein are methods and apparatuses that may address these needs.
In general, described herein are methods and apparatuses for the application of transdermal electrical stimulation (TES) in to provide a therapeutic effect, including to modulate a user's cognitive (e.g., mental) state, such as to induce a state of calm or relaxation. The apparatuses described herein may include a neck-applied electrode pad (also referred to herein as an electrode patch) that may automatically couple with a neck-worn TMS controller. The electrode patch may be worn (e.g., adhesively coupled) to the skin of a neck to make electrical contact with the midline of the back of user's neck. The electrode pad may include two or more electrodes for contacting the user's skin. A neck-worn controller (TES stimulator) may be configured as a cord, band, wire, torque (torc), necklace, loop, strap, or the like, and may be rigid or semi-rigid. The neck-worn controller may automatically self-couple (e.g., via a magnetic force coupler) to the electrode pad, and may be worn around the subject's neck, e.g., completely or partially around the subject's collar and/or shoulders. The controller (TES stimulator) may controllably apply one or more waveforms to the electrodes of the electrode pad to deliver TES. The waveforms applied are adapted to induce or enhance a cognitive state such as relaxation and/or calm.
Any of these TES apparatuses (devices and systems) described herein may include one or more re-usable electrodes, including cleanable (or self-cleaning), re-wettable (or self-re-wetting) electrodes. For example, a re-wettable electrode may include a “dry” electrode that is automatically wetted before use by applying a conductive material (conductive liquid, such as an aqueous solution, salt solution, conductive gel, etc.) by a vapor. In particular, an electrode may be integrated with a vaporizer (e.g., piezoelectric vaporizer, thermal vaporizer, etc.) that can saturate the electrode's skin-contacting region. The electrode's skin-contacting region may be a porous material (e.g., sponge, etc.). In some variations the apparatus may include a reservoir of the conducive material in contact with the vaporizer that may be used to automatically wet the skin-contacting region. In some variations the apparatus may configured to detect the wetness of the skin-contacting material and regulate the activity of the vaporizer based on feedback from the detected wetness (e.g., the detected resistance or conductivity of the skin-contacting region or the electrical contact with a skin surface). Any of the reusable (e.g., automatically re-wettable and/or self-cleaning) electrodes described herein may be used in whole or in part as part of a skin-contacting electrode, including as part of a physiological monitoring system (e.g., electrocardiogram, electroencephalogram, electromyogram, etc.). In particular, these devices may be part of a TES apparatus, as mentioned.
For example, described herein are neck-worn controller devices for applying transdermal electrical stimulation (TES) to the back of a subject's neck to modify a user's cognitive state and induce a relaxed state. These devices may include: a rigid or semi-rigid torc body configured to be worn around the user's neck; an electrode-coupling region at a middle region of torc body, wherein the electrode-coupling region comprises: a pair of electrode supports arranged adjacent to each other and separated by between 5 mm and 60 mm apart, and a skin-contacting electrode on each of the electrode supports configured to be secured against the user's neck when the torc body is placed around the users neck; and wherein the torc body encloses a control circuitry, a power source and a wireless communication circuitry. In any of the apparatuses described herein an electrode support may be an electrical contact (or may include an electrical contact) connecting a skin-contacting electrode to the control circuitry of the apparatus.
For example, a neck-worn controller device for applying transdermal electrical stimulation (TES) to the back of a subject's neck to modify a user's cognitive state and induce a relaxed state, may include: a rigid or semi-rigid torc body configured to be worn around the user's neck, the torc body extending in a U-shape from a first end to a second end; an electrode-coupling region near middle region of torc body between the first and second ends, wherein the electrode-coupling region comprises: a pair of electrode supports arranged adjacent to each other and separated by between 5 mm and 60 mm apart in a line that is at an angle (e.g., between 90° or perpendicular and 15 degrees) to an axis of the U-shaped torque body, and a skin-contacting reusable and rewettable electrode on each of the electrode supports configured to be secured against the user's neck when the torc body is placed around the users neck; and wherein the torc body encloses a control circuitry, a power source and a wireless communication circuitry.
In general, the spacing between the electrodes (or electrical contacts) connecting to the electrodes (as well as the relative arrangement of the electrodes on the user's neck) in order to evoke a relaxed state may be important, and is typically between 5 mm and 80 mm apart (e.g., 5 mm and 70 mm, 5 mm and 60 mm, 5 mm and 50 mm, 5 mm and 40 mm, 5 mm and 30 mm, 5 mm and 20 mm, 10 mm and 70 mm, 10 mm and 60 mm, 10 mm and 50 mm, 10 mm and 40 mm, etc.). This spacing may be edge-to-edge (nearest edge to nearest edge) or center-to-center between the two electrode contacts and/or electrodes.
Any of these apparatuses may include a control (e.g., on/off, rest, start/stop, rewet, etc.) on the torc body; the control may be electrically connected to the control circuitry and may be any appropriate control, including but not limited to a button, dial, touchpad, slider, etc.
As mentioned, the skin-contacting electrode on each of the electrode supports may comprise a re-wettable electrode, including self-re-wetting electrodes and/or automatically re-wetting electrodes, self-cleaning electrodes, or the like. For example, the skin-contacting electrode on each of the electrode supports may include a mist generator (e.g., vaporizer), and may be coupled to a fluid reservoir on the torc body. The mist generator may be configured to wet one or both of the skin-contacting electrodes. For example a mist generator comprises a piezo driver configured to generate a mist. In some variations the mist generator may be a piezo that is configured to be driven by the same circuitry driving the electrical stimulation (e.g., TES), e.g., at a frequency between 100 KHz to 2 MHz (or greater).
The body (torc body) may be partial rigid, including having one or more rigid portions connected by a flexible region or regions. The torc body may be flexible. The torc body may be any appropriate shape, including U-shaped or C-shaped. The torc body may include a charging port for charging a battery within the torc body. The torc body may be an elongate body that generally extends from a first end to a second end, and fits over the user's neck while holding the electrodes to the back of the user's neck. The torc body may include a hinge on the torc body. The electrode-coupling region may be rigid. The control circuitry, the power source and the wireless communication circuitry may be located at an end of the elongate body. The control circuitry and wireless communication circuitry may be located at a first end region of the elongate body and the power source may be located at a second end region of the elongate body.
As will be described in more detail below, any of the skin-contacting electrodes described herein may be fixed to the neck-worn TES apparatus or may be removably coupled to the neck-worn TES apparatus (e.g., to the electrode supports). For example, the electrodes may be removable and replaceable. The electrode-coupling region may comprise a pair of magnetic attachments. Alternatively or additionally, the skin-contacting electrodes may self-adhere to the TES apparatus allowing for electrical and physical connection via an adhesive, mechanical (e.g., hook-and-loop fasteners, artificial setae, etc.), etc.
Any of the neck-worn TES apparatuses described herein may include one or more speakers and/or an audio connector (jack) for coupling to a speaker or headphones.
In general, any of the neck-worn TES apparatuses may include control circuitry for driving TES through the electrodes and/or regulating the apparatus (including the wetting of the electrodes in some variations). For example, the control circuitry may be configured to deliver electrical energy between the pair of electrodes (or electrical contacts), wherein the electrical energy comprises a carrier wave having a frequency that is greater than 250 Hz that is amplitude modulated at a frequency that is ten percent or less the frequency of the carrier wave, further wherein the amplitude modulation is varied at least once every 40 seconds.
Any of the apparatuses and method described herein may be used (and may be further configured for use) to apply neuromodulation to a user's neck. This neuromodulation may be for therapeutic effect and/or to enhance relaxation. For example, any of these neuromodulators may be used to modulate parasympathetic and/or sympathetic drive; such as to improve parasympathetic drive and inhibit sympathetic drive.
Any of these methods and apparatuses may be used to treat an immune disorder. In particular, any of these apparatuses may be used to treat psoriasis.
Alternatively or additionally, these apparatuses and methods may be used to lower stress. Stress may be monitored (and in some variations used as feedback, including visual or audio feedback, such as displaying an indicator of the user's stress level (blood pressure, heart rate, skin conductance, etc.) and/or providing controlling feedback (increasing or decreasing stimulation, modulating a stimulation parameter, etc.). Thus, an indicator of stress (or mood) may be used as a control input for controlling/adjusting stimulation including turning on/off, adjusting a parameter of electrical stimulation (frequency, current, duty cycle, peak amplitude, rise time, duration, etc.). Alternatively or additionally, any of the apparatuses and methods described herein may be used to elevate mood. Thus, in general, any of the apparatuses and methods described herein may be useful to reduce stress, reduce anxiety, improve sleep, and/or improve mood.
For example, any of the apparatuses and methods described herein may be used to improve sleep (e.g., one or more of: sleep quality, sleep onset, sleep duration, sleep depth/stage, etc.). An indicator of sleep (e.g., sleep stage/sleep level) may be used as a control input for controlling/adjusting stimulation including turning on/off, adjusting a parameter of electrical stimulation (frequency, current, duty cycle, peak amplitude, rise time, duration, etc.).
The methods described herein may be used to apply neurostimulation to one or more nerves (e.g., nerve bundles) though the skin of the subject's neck at two nearby (e.g., adjacent) locations near the cervical spinal region, such as beneath the hairline but above the C7 cervical region. The two locations may be separated by between about 0.5 and 2.5 inches apart from each other. A single electrode pad may be used to make contact with both sites.
The TES waveforms used to apply energy herein may include a carrier frequency that is between 250 Hz and 50 kHz, and may typically an amplitude between about 1-40 mA (e.g., peak amplitude of between 10 mA and 35 mA, between 10 mA and 30 mA, etc.). The carrier waves may be asymmetric and/or biphasic. Significantly, the applied TES waveforms are modulated by an amplitude modulation envelope that comprises a lower frequency that is at least 10× lower than the frequency of the carrier wave (e.g., a modulation envelope between 10-1 kHz, e.g., between 10-900 Hz, between 10-850 Hz, between 10-800 Hz, etc., and a carrier wave of greater than 2250 Hz, e.g., greater than 300 Hz, 350 Hz, 400 Hz, 450 Hz, 500 Hz, 550 Hz, 600 Hz, 650 Hz, 700 Hz, 750 Hz, 800 Hz, 850 Hz, 900 Hz, 950 Hz, 1 kHz, 2 kHz, 3 kHz, 4 kHz, 5 kHz, 6 kHz, etc., and particularly greater than 5 kHz). The applied waveform may be varied every 5 to 60 seconds, typically by varying the amplitude modulation, alternatively, the waveform may be held for longer durations (e.g., 1 minute to 5 minutes, 1 minute to 10 minutes, 1 minute to 20 minutes, 1 minute to 30 minutes, 1 minute to 40 minutes, etc.). For example, the shape of the amplitude modulation envelope may be changed (e.g., from a sinusoidal envelope to a rectangular envelope, a saw tooth envelope, a triangular envelope, a stair-case envelope, etc.), and the frequency of the amplitude modulation may change separately or at the same time. In some variations the shape of the amplitude modulation envelope is changed by adjusting one or more of: 1) the symmetry ratio (meaning the wave form in time may be non-symmetrical in the time axis; the ratio is an estimate of how non-symmetrical it is), or 2) the flat ratio (meaning the portion(s) of the waveform that remains unchanged in amplitude over as a portion of the wave period), etc. In any of the method and apparatuses (configured to perform these methods) described herein, the waveforms duration may be controlled by the subject; thus subject may continue to apply the waveform until an effect is achieved. For example, a waveform may be applied in a loop that is repeated until terminated by the subject.
In some variations, the rise time of the waveform(s) applied may be controlled to minimize discomfort. For example, the rise-time of a basic pulse waveform applied may be between 1 and 20 microsecond. The rise-time of the pulse may affect both comfort and efficacy; based on preliminary data, it may be beneficial to vary the rise time between 1-20 μs, including varying the rise time continuously between 1 and 20 μs, or picking a rise time that is between 1 and 20 μs and using this, and/or allowing the device and/or use to adjust the rise time (e.g., between 1-20 μs) during application of the waveforms.
As mentioned, the apparatuses described herein include neck-worn controller devices for applying transdermal electrical stimulation (TES) to the back of a subject's neck to modify a user's cognitive state and induce a relaxed state. For example, described herein are neck-worn (also referred to herein as “neck wearable”) that may be comfortably worn around the user's neck and may include: an elongate body configured to be worn at least partially around the user's neck; an electrode-coupling region on the elongate body, the electrode-coupling region comprising: a pair of electrical contacts, and at least one self-connecting (e.g., magnetic, adhesive, etc.) attachment configured to automatically couple the electrical contacts with a complimentary electrical contact on an electrode pad worn on the user's neck when the magnetic attachment is placed adjacent to the electrode pad; and wherein the elongate body encloses a control circuitry, a power source such as a battery, a high voltage source of power for neural stimulation greater than 20 volts, and a wireless communication circuitry.
Any of the neck-worn controller devices may include one or more controls on the body of the device. For example, a neck-worn controller may include a switch, dial, button, slider, etc. The controller may control one or more of (and/or multiple controls may control): power (e.g., on/off/standby), intensity of the TES being applied, communication with a remote (e.g., wireless) controller, playing of the TES (e.g., TES start/pause/stop), selection of a TES waveform, etc.
Any of the neck-worn controller devices described herein may include one or more output such as a display (e.g., LCD, LED, etc.) or other visual output (LED), a tactile output (haptic, e.g., vibrational output, etc.).
The elongate body may be stiff, flexible, or semi-stiff, and may include both stiff and flexible regions (e.g., stiff regions connected by flexible regions). For example, the elongate body may be flexible so that it generally retains its shape but can be “opened” (e.g., when the device is U- or C-shaped) to fit over a user's neck. In general, the elongate body may be U-shaped or C-shaped. In some variations the elongate body include a hinge or hinges that may be used to open the elongate body for placing it on/taking it off of the user's neck.
Any of the apparatuses described herein may include a charging port on the elongate body (e.g., micro USB port). Alternatively or additionally any of these apparatuses may include a non-contact charger (e.g., inductive charging, etc.) or the like.
As mentioned, in general, any of the neck-worn controller devices described herein may include an electrode-coupling region that may be used to secure the neck-worn controller to the user via a connection to an electrode pad that can be separately worn on the user's neck. For example, an electrode-coupling region may be located in a middle region of the elongate body. The electrode-coupling region may generally be rigid or stiff so that it does not shift during wearing or dislodge the coupling attachments (e.g., attachment between the electrical contact and a connector on an electrode pad. Either the connector on the electrode pad or the electrical contact on the neck-worn controller, or both, may include a magnet and/or a magnetic material (that may be attracted to a magnet, such as steel, etc.). This may allow self-connection between the two. The magnetic material, when included, may be any appropriate magnetic material, including “static” magnetic material (e.g., ferrous or magnetic material) and/or electromagnetic materials.
In some variations the electrode-coupling region is at an end of the elongate body.
In general, any of the apparatuses described herein may include a self-connecting or self-engaging connector drawing together the electrode pad and the neck-worn apparatus so that an electrical and/or mechanical connection is made between the two. Although the primary self-engaging connectors described herein are magnetic connectors, any appropriate connector may be used, including adhesive, and/or mechanical self-attaching couplings. However in some variations the electrode-coupling region may comprise a pair of magnetic attachments.
The electrical contact may be integrally formed with the magnetic attachment. For example, the electrical contact may be made through a magnetic (including ferrous) material. In some variations the connector and/or the electrical contacts may be made of an electrically conductive material forming the electrical pathway surround by or adjacent to a magnetic connector (e.g., the electrical contact may be adjacent to or surrounded by the magnetic attachment). One or more self-connecting connectors (magnets) may be included.
In any of these variations, the power source and the wireless communication circuitry are located at an end of the elongate body. For example, the control circuitry and wireless communication circuitry may be located at a first end region of the elongate body and the power source may be located at a second end region of the elongate body. In general, when the neck-worn controller device is configured to be worn around both sides of a user's neck (e.g., is U-shaped), then the two ends (arms) of the U-shaped body may be balanced in shape, size and/or weight.
The electrical contacts may be further adapted to connect to a properly oriented and configured electrode pad to achieve the desired relaxation effect by transdermal electrical stimulation of the neck (e.g., and in some variations just at the neck). In particular, the pair of electrical contacts may be separated by between 1.2 inches and 0.7 inches along the length of the elongate body. This separation may allow them to properly and automatically engage (e.g., self-engage) with the electrode pads described herein for TES of the neck to induce relaxation.
Any of the neck-worn devices described herein may be configured to include one or more speakers (e.g., headphones, etc.). In some variations the apparatuses described herein may be configured to include one or more ear-based electrodes.
In general, the control circuitry may be configured to deliver electrical energy (e.g., TES) between the pair of electrical contacts in order to evoke relaxation in a user by applying TES at the midline of the user's neck between the C1 and T2 region (e.g., C3 and T1, C3 and T2, etc.). For example the control circuitry may be configured to deliver electrical energy comprising a carrier wave having a frequency that is greater than 250 Hz that is amplitude modulated at a frequency that is ten percent or less the frequency of the carrier wave, further wherein the amplitude modulation is varied at least once every 60 seconds (e.g., once every: 50 sec, 45 sec, 40 sec, 35 sec, 30 sec, etc.).
In any of the apparatuses (e.g., systems) described herein, software, firmware, or hardware may be separate from the neck-worn device and may wirelessly connect with the device to regulate, control, select, and/or modify the TES waveforms applied by the apparatus. For example, a user electronics device (e.g., a handheld user electronics device such as a smartphone, wearable electronics, etc.) may wirelessly communicate with the neck-worn controller to transmit or deliver the TES waveform and/or to modify the TES waveform (e.g., increase/decrease intensity, etc.) and/or start/stop/pause operation of the TES waveform delivery.
A neck-worn controller device for applying transdermal electrical stimulation (TES) to the back of a subject's neck may include: an elongate body configured to be worn around the user's neck; a rigid electrode-coupling region on the elongate body, the electrode-coupling region comprising: a pair of electrical contacts adjacent to each other, and at least one magnetic attachment configured to automatically couple the electrical contacts with a complimentary electrical contact on an electrode pad worn on the user's neck when the magnetic attachment is placed adjacent to the electrode pad; and control circuitry, a power source and a wireless communication circuitry.
Also described herein are systems for applying transdermal electrical stimulation (TES) to the back of a subject's neck to modify a user's cognitive state and induce a relaxed state, that include an electrode pad to be worn on the back of the neck and a neck-worn controller (and in some variations control software that operates on a controller of a user electronic device and wirelessly communicates with the neck-worn controller).
For example, a system for applying transdermal electrical stimulation (TES) to the back of a subject's neck may include: an adhesive electrode pad comprising a first electrode and second electrode on a first side, and a first connector electrically connected to the first electrode and a second connector electrically connected to the second electrode, wherein the first and second connectors are on a second side opposite from the first side; and a neck-worn controller device, the neck-worn controller comprising: an elongate body configured to be worn on a user's neck, an electrode-coupling region on the elongate body having at least one magnetic attachment configured to automatically couple the first connector on the electrode pad to the a first electrical contact on the neck-worn controller device when the magnetic attachment is placed adjacent to the electrode pad, and a control circuitry, a power source and wireless communication circuitry.
The first electrode and the second electrode may be arranged in a line that on the first side that is at angle (e.g. between 90° or perpendicular and 15 degrees, e.g. between 30 degrees and 60 degrees, etc.) to a line connecting the first connector and the second connector electrically connected on the second side.
The adhesive electrode pad(s) may be configured to be worn on the back of a subject's neck so that the first electrode and the second electrode are arranged along a midline of the back of the user's neck. In any of the apparatuses and methods described herein, the pads may be adhered to the neck-worn body before it is placed around the user's neck. Thus, the device may be used to place the pads onto the skin for the user.
In some variations, the applicants have found that it is particularly advantageous when applying TES energy to the back of the user's neck to induce relaxation, to have one of the electrodes (e.g., the second electrode) be larger than the other electrode. For example, a surface area of one of the electrodes may be greater than 1.25 times the surface are of the other electrode (e.g., greater than 1.4×, greater than 1.5×, greater than 1.6×, greater than 1.7×, greater than 1.8×, greater than 1.9×, greater than 2×, etc.).
In general, the neck-worn controller used as part of any of the systems described herein may be any of the neck-worn controllers described above.
For example, a system for applying transdermal electrical stimulation (TES) to the back of a subject's neck may include: an adhesive electrode pad comprising a first electrode and second electrode arranged in a vertical line on a first side, and a first connector electrically connected to the first electrode and a second connector electrically connected to the second electrode, wherein the first and second connectors are arranged in a horizontal line perpendicular to the vertical line on a second side that is opposite from the first side; and a neck-worn controller device, the neck-worn controller comprising: an elongate body configured to be worn on a user's neck, an electrode-coupling region on the elongate body having a magnetic attachment configured to automatically electrically and mechanically couple a pair of electrical contacts on the electrode-coupling region with the first and second connectors on the electrode pad when the magnetic attachment is within less than 1 inch from the electrode pad, a control circuitry, a power source, and a wireless communication circuitry.
Also described herein are methods of applying transdermal electrical stimulation (TES) to the back of a user's neck, e.g., for a therapeutic purpose, including to modulate that parasympathetic and/or sympathetic systems, e.g., to treat an immune (e.g., autoimmune) disorder, e.g., to treat psoriasis, and/or to modify a user's cognitive state and induce a relaxed state. In general such a method may include: attaching a first electrode and second electrode to a back of the user's neck between the user's hairline and the user's C7 cervical region; applying electrical energy between the first electrode and the second electrode to deliver TES; and inducing, in the user. In some variation, this may apply therapy (e.g., for 2 minute or more, for 5 minutes or more, for 7 minutes or more, for 10 minutes or more, etc.). As mentioned, this may treat the immune disorder, may treat psoriasis and/or may induce a relaxed mental by the application of TES.
Attaching may comprise adhesively attaching an electrode pad comprising the first and second electrode to the back of a user's neck so that the first and second electrodes are arranged along the midline of the user's neck.
Any of these methods may also include placing a neck-worn controller around the neck of the user and allowing the neck-worn controller to self-engage (including magnetically, mechanically, chemically (e.g., adhesively), etc.) with the electrode pad to form an electrical contact between the neck-worn controller and the first electrode and second electrode.
Applying electrical energy may comprise applying TES by delivering electrical energy between the first electrode and the second electrode, wherein the electrical energy comprises a carrier wave having a frequency that is greater than 250 Hz that is amplitude modulated at a frequency that is ten percent or less the frequency of the carrier wave, further wherein the amplitude modulation is varied at least once every 60 seconds (e.g., once every 55 sec, once every 50 sec, once every 45 sec, once every 40 sec., once every 35 seconds, once every 30 seconds, etc.).
In general, the amplitude modulation may be varied in any appropriate manner, including by varying the shape of an envelope of the amplitude modulation. For example, the envelope shape may be changed between two or more of: a square wave, a step-function, a saw tooth, a triangular shape, a sinusoid, etc. The amplitude modulation may be varied by varying one or both of a symmetry ratio and a flat ratio of the amplitude modulation.
Applying TES to induce relaxation may include applying electrical energy for any appropriate length of time (e.g., for 2 min or greater, 5 minutes or greater, 10 minutes or greater, 15 minutes or greater, etc.).
In general, applying may comprise delivering TES to a nerve fiber, nerve or nerve bundle extending through the user's neck, including spinal nerve, cranial nerves, etc.
For example, a method of applying transdermal electrical stimulation (TES) to the back of a user's neck may include: attaching a first electrode and second electrode to a midline of a back of the user's neck between the user's hairline and the user's C7 cervical region, wherein the first and second electrode form part of an electrode pad; placing a neck-worn controller over at least one of the user's shoulders and allowing the neck-worn controller to magnetically self-engage with the electrode pad to form an electrical contact between the neck-worn controller and the first electrode and second electrode; applying TES by delivering electrical energy between the first electrode and the second electrode, wherein the electrical energy comprises a carrier wave having a frequency that is greater than 250 Hz that is amplitude modulated at a frequency that is ten percent or less the frequency of the carrier wave, further wherein the amplitude modulation is varied at least once every 60 (e.g., 55 sec, 50 sec, 45 sec, 40 sec, 35 sec, 30 sec, etc.); and inducing, in the user, a relaxed mental by the application of TES.
In general, any of the methods and apparatuses described herein for self-engaging or attaching the electrode and the device may be configured to mechanically (e.g., loop-and-hook, artificial setae, etc.), chemically (e.g., adhesive), magnetically, or otherwise (including combinations of these) attach. Alternatively, in some variations the apparatuses and methods described herein are configured with the electrode affixed or attached (including integrally attached) to the rest of the apparatus including the electrical contact (or electrical support).
The novel features of the invention are set forth with particularity in the claims that follow. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:
In general, described herein are apparatuses and methods for applying transdermal electrical stimulation (TES) to the back of a subject's neck. In particular, described herein are electrode patches and neck-worn controllers that are adapted to deliver TES to a specific and particularly effective region of a patient's neck (and in some variations only this region) at or near the midline of the back of the neck between/over the C1 and C7 regions of the spine, beneath the hairline. Stimulation with the apparatuses and parameters described herein outside of this region, and with other parameters than those descried herein, are less effective or may be ineffective, and in some variations may induce contrary effects.
These apparatuses and methods may be useful for applying therapy, and in particular for modulating the parasympathetic and/or parasympathetic systems. These methods and apparatuses may also be useful for applying therapy for treating an immune (e.g., autoimmune) disorder. In particular, these methods and apparatus may be useful to treating psoriasis. In some variations, these methods and apparatuses may be useful for inducing a cognitive effect on the wearer, including, e.g., to modify a user's cognitive state and induce a relaxed state.
A generic system for applying transdermal electrical stimulation (TES) to the back of a subject's neck (e.g., for therapeutic purposes, including, but not limited to modify a user's cognitive state and induce a relaxed state) is illustrated in
As shown in
For example, the neck-worn controller shown in
As mentioned, the electrode coupling region is configured to automatically connect (in a proper orientation) and secure to the connector on an electrode patch worn on a user. In some variations the electrode coupling region may include one or more magnets (electromagnets, permanent magnetics such as neodymium iron boron (NdFeB), samarium cobalt (SmCo), alnico, and ceramic or ferrite magnets, etc.). Alternatively or additionally, the attachment may be a mechanical attachment such as a snap, etc. that forms the electrical connection. The attachment may be a hybrid electrical and mechanical attachment, such as an electrically conductive hook-and-latch (e.g., “conductive VELCRO”) material. The self-connecting attachment may be integrated with or separate from the electrical connection. Alternatively or additionally, the attachment and/or connection may be physical and self-adhesive by employing conductive and adhesive materials to the patches like a hydrogel, hydrocolloid and the like.
Similarly,
In general, the apparatus is configured so that the electrode patch is applied beneath the user's hairline, in the cervical region of the back of the neck (e.g., down to approximately C7 spinal region). This midline location and spinal level may help the TES applied as described herein in correctly activating and/or inhibiting nerves under the electrode patch and may improve parasympathetic drive and inhibit sympathetic drive at this cervical region. The electrode pair is generally placed behind the neck, so that the top electrode is close to the hairline around the center (midline) of the spine. The second electrode is about an inch (e.g., between 0.6 and 1.3 inches, 0.7 and 1.2 inches, 0.8 and 1.2 inches, etc.) below the first electrode. The two electrodes may be connected to the connectors. In some variations the connectors are iron, steel, or other material that may be magnetically attracted and held. These connectors may be snaps that can make an electrical and/or mechanical connection. In some examples they may be placed on the left and right sides of the neck.
As illustrated in the example shown in
In operation, as shown in
As shown in
Any of the variations described herein could also include an output (e.g., LED) showing status of the device as it operates, and/or the operational state of the device. In some variations the apparatus includes speakers (e.g., ear buds that may be worn in the ears) and may also be configured to play music or other audio content. For example, in any of the apparatuses and methods described herein, the neck-worn controller may include a radio, music player, and/or may wireless communicate with a music or other source of audio (CD player, digital music player, radio, etc. including a phone). The audio content (music, ambient noise, etc.) may be synchronized or otherwise coordinated with the applied TES waveforms. In some variations the music (tempo, changes/transitions in tempo, etc.) could trigger or modulate the TES waveform parameters (including one or more of the parameters of AM as described in
Any of these variations may also or additionally include a charging or other input/output port, such as a microUSB port. Alternatively or additionally the devices may include an inductive charging circuit or any other appropriate charging apparatus.
The exemplary neck-worn connector shown in
Signal Modulation
As described above, any of the devices described herein are configured to apply transdermal electrical stimulation to achieve neuromodulation (e.g., through the back of the neck). Both the TES application location at the midline of the back of the user's neck and the waveforms applied (“TES waveforms”) have been optimized to for treatment on the back of the neck, including to evoke a therapeutic effect. In some variations these waveforms have been optimized to induce a relaxed mental state.
For example,
In the example of
Amplitude modulation typically applies an envelope (e.g., bursting) at a lower frequency that modulates the peak amplitude of the carrier wave forming the waveform. Transitions in the TES waveforms may include changes in frequency, amplitude, duty cycle, etc., as shown in
An example of the compound waveform (ensemble waveform) for use with any of the methods and apparatuses descried herein is shown in the table in
Thus, by creating transitions in the flat ratio, symmetry ratio and DC offset in the amplitude modulation, the apparatus may greatly enhance the efficacy of the TMS waveform applied in evoking a relaxed cognitive state. For example, during the application of a TMS waveform, the amplitude modulation maybe transitioned (e.g., every 1-30 seconds) from a square shape to a saw tooth to a trapezoid shape; the carrier wave may have an amplitude from between 1-30 mA, a frequency of between 250 Hz and 50 kHz, be biphasic (and in some variations asymmetric), similar to what is shown in
In general, a TES carrier waveform such as shown in
In some variations, amplitude modulation below 100 Hz may be particularly effective, including amplitude modulation at frequencies as low as 10 Hz (e.g., between 10 Hz and 100 Hz); this AM frequency when used to modulate a carrier wave as described herein in regions other than the midline of the back of the neck is not typically effective to induce relaxation. For example, amplitude modulation frequency as low as or lower than 100 Hz when applied to the neck and temple region are not effective, often causing pain and disturbing flashes of light.
Also described herein are TMS waveforms in which the polarity of the electrodes (anode and cathode) may be switched during the TMS application by the neck-worn controller.
Although the apparatuses and methods described herein are primarily for use in inducing relaxation (calm) by applying particular subsets of TES to just the region in the back of the user's neck, these methods and apparatuses may be modified for use with additional electrodes on other body regions, including the temple; interestingly, the inventors have found that a feeling of euphoria may be induced when stimulating with some of the waveforms described herein when applied between an electrode on the midline of the neck (between the C1-C7 region) and an electrode on the forehead.
The neck-worn TES apparatus may also include one or more indicator lights 2409, such as LEDS that may indicate operation of the device. The ends of the neck-worn device(s) (e.g., first end 2413 and second end 2415) may hold some of the electronics (e.g., controller, battery, antenna, etc.). Any of these devices may also include one or more speakers, headset (e.g., earbuds, etc.) or the like, and may include a tuner (e.g., for connecting to commercial radio or wireless radio to play audio content) and/or memory (e.g. for playing stored audio files, including digital audio content).
As will be described below in reference to
The example device shown in
As mentioned, any of the apparatuses described herein may include electrodes (e.g., electrode patches) that couple to the body of the neck-wearable apparatus (neckband, torc, etc.). In some variations the electrode(s) may form part of a cartridge or package that that may include one or more gel pads that connect via adhesion or mechanical contact to couple to the apparatus; these electrodes may be replaced by the user. In practice, this may mean that the apparatus, including electrodes, may be assembled before placing the device on the neck. Alternatively, as mentioned above, the electrodes may be applied to the neck, then coupled (e.g., magnetically) to the neck-wearable body of the apparatus.
One example of a cartridge or electrode assembly that may be coupled to the apparatus may include a double-sided, conductive gel pad with a flood print of silver on carbon PVC film between gel. This film may help buffer the DC reduction and oxidation reactions, as well as help disperse the current. The electrode formed in this manner may then be coupled to the apparatus through an electrical connector in any appropriate manner. In some variations, a gel pad may adhere to one or more conductive contacts on the device made of an inert conductor like carbon, gold or stainless steel contacts. Gel pads may have a backing material to improve handling; and may include a blank space through which contact between the apparatus conductive contact and a gel body is feasible. In some variations the backing material can match the size/shape of the conductive contact to key where the gel body should be placed on the device. The gel body portion of an electrode patch can also be configured as part of a more durable cartridge that needs less frequent replacement. A gel body may or may not be adhesive. If the gel is not adhesive, a secondary material or structure (e.g., bias) may provide or maintain the contact with the users skin. In any of these variations a reusable electrode pad, that may be removed from the body and reapplied later, may include multiple sacrificial adhesive layers. For example, a secondary material may be a single layer or a plurality of layers, whereby removing one exposes fresh layers of underlying materials.
In any of the variations described herein, the device contacts (e.g., electrodes) may be configured to move independent of each other. For example, and upper electrode (or electrode patch) may be adhered to the user; as the user moves their head, the upper electrode may travels with the head differently from the lower electrode, which is attached to a separate part of the head. Alternatively or additionally, the material geometry and/or durometer may allow the electrode patch to differentially contact and expand over its width and length, allowing the different electrodes to move independent of each other and with the users' movements.
Reusable Electrodes
Any of the neck-worn TES apparatuses described herein may include reusable electrodes that are configured to be automatically cleaned (e.g., when inserting into a holder or cartridge, as described herein) and/or self-re-wetting electrodes.
In general, it may be desirable for any of the apparatuses described herein to be “dry” electrodes. A dry electrode becomes conductive when moistened, e.g., with droplets of saline solution. Dry electrodes may be easier to store and use, and may be used without leaving adhesive residue on the skin. As mentioned, any of the apparatuses described herein may be configured for use with dry (also referred to herein as “self re-wetting” or simply “self-wetting”) electrodes. In particular, described herein are electrodes and apparatuses including such electrodes that may be wetted (automatically or manually) using a vaporizer (mister or source of mist). It may be particularly advantageous to include a source of mist that is based on vibration (e.g., sonic/ultrasonic vibration) using a piezo. For example, as described herein, the TES waveforms found to be effective to invoke the neuromodulator effects desired may a range of frequencies that are also effective for vibrating a piezoelectric transducer to produce a mist.
For example, a piezoelectric ceramic discs operating at the frequency between 100 KHz to 2 MHz is known to create droplets when the piezo disc is immersed in a fluid. In any of the apparatuses described herein, a piezoelectric vaporizer may be included to apply mist (e.g., of saline or other conductive fluid) onto the electrode surface/skin interface (which may be a sponge or the like) either continuously or discretely (in intervals) to maintain the conductive connection between the dry electrode and the subject's skin. The moisture (vapor) applied may be regulated by feedback based on the electrical contact determined between the subject's skin and the electrode and/or one or more other sensors. A piezo driver may require a voltage between 20 Volt to 100 Volt to create the mist.
Any of the apparatuses described herein may include a controller (local controller) for controlling the application of electrical energy to the electrodes. The same controller, or a separate controller, may be used to control the vaporizer in applying vapor to the electrode(s). For example, any of the apparatuses may include a switching power supply that uses a frequency of oscillation between 100 KHz to 2 MHz. To apply vapor to the electrodes, the high frequency from the power supply may be rectified to create DC for waveforms (e.g., ensemble waveforms, TES waveforms) applied to evoke the cognitive effect(s). Power may also be taken from the power supply before rectification, and the voltage applied to a piezo driver (e.g., disc) at a corresponding resonance frequency, causing the disc to vibrate and generate droplets of vapor that may be delivered as conductive material onto the dry electrode. Thus, in some variations the oscillating power source (also referred to as a switching power source) driving the TES waveforms may be adapted for use with the vaporizer, to provide power for the atomizer without additional circuitry or increasing size of the apparatus.
The piezo driver (e.g., disc) can be embedded into the dry electrode, or submersed in a small reservoir built into the apparatus (including the elongate body/torc body of the neck-worn apparatus). For example, in some cases the apparatus may include an ultrasound mist generator having a matrix of laser drilled holes on the center of the piezo (e.g., ceramic disc) that are less than 2 cm in diameter (e.g., between about 0.5 mm and 2 cm, between about 0.5 mm and 1 cm, between about 0.5 mm and 8 mm, between about 0.5 mm and 7 mm, between about 0.5 mm and 5 mm, between about 0.5 mm and 3 mm, between about 0.5 mm and 2 mm, between about 0.5 mm and 1 mm, etc.); the piezo may be thin (e.g., between 0.5 mm and 5 mm thick, between 0.5 mm and 4 mm, between about 0.5 mm and 3 mm, between about 0.5 mm and 2 mm, etc.). In operation, fluid may be wicked from the bottom side of the piezo through the holes, and then may be atomized by the ultrasound vibration on the “air side” of the piezo.
In some example of self-rewetting electrodes as described herein, an embed ultrasound transducer may be posited behind a gel (or sponge) contacting the electrode (forming the skin-contacting surface of the electrode). The skin-contacting surface may be in a dry state during storage. When a gel is used, the gel may be a matrix that absorbs fluid (e.g., saline) when the mist is applied, but may dry out completely or near completely after vapor is no longer applied.
As previously mentioned, although the examples provided here may include such self-wetting electrodes as part of TES apparatus as described herein, in general such self-rewetting electrodes may be incorporated into any apparatus that uses a skin-contacting electrode, including wearable electronics in general (for either or both sensing and stimulation).
In implanting the self-rewetting electrode a fluid reservoir including an electrically conductive fluid (e.g., saline) may be included in the apparatus (including as part of a cartridge or refillable (e.g., by user). The reservoir may be included as part of the wearable (e.g., the elongate body, such as the electrode-coupling region, etc.). The vaporizer (the piezo material) may be on the apparatus, including in contact with the electrode, and particularly the skin-contacting surface of the electrode and/or it may be separate and positioned to direct the stream of vapor on the users skin and/or directly onto the skin-contacting surface. In some variations the vaporizer is behind, beside, surrounding or surrounded by the electrode.
Alternatively or additionally, a re-wettable and/or cleanable electrode may include a storage compartment the holds, rewets and/or cleans the electrodes between uses. For example,
As shown in
In some variations, the apparatus may be used with a stand. For example, the rewetting cartridge may be configured as a stand; alternatively, the stand may be used to clean and store the electrodes and protect the electrode surfaces when not in use. In some variations the stand may include refilling (e.g., of conductive fluid) and/or recharging (e.g., of battery) between uses.
For example,
Neck Placement
In any of the apparatuses described herein, as shown and described above, the apparatuses may be positioned so that the electrode(s) contact the user (e.g., subject) behind the neck. Both electrodes may be positioned behind the neck.
In some variations the lower electrode may be positioned on the skin over the upper thoracic region of the spine; the upper electrode may also be positioned over the upper thoracic region or in the lower cervical region. For example.
In general, in any of the methods and apparatuses described herein, it may be beneficial for the electrodes to be arranged so that the first electrode is above the second electrode when worn on the body along the subject's anterior-to-posterior (e.g. foot-to-head) longitudinal midline at the back of the neck/upper back. The separation between the first and second electrodes may also be important. For example, the separation may be between 0.7 inches and 2 inches, preferably between 0.8 inches and 1.4 inches. The minimum distance may be between 0.7 and 1.2 inches (e.g., approximately 1 inch), from the nearest edge to the nearest edge. The maximum distance may be between 1.7 inches and 2.2 inches (e.g., 2 inches) from nearest edge to nearest edge. For example, as shown in
In addition, maintaining the electrodes in this region of the neck (or neck and back), so that the pair of electrodes are positioned on the skin over the lower cervical/upper thoracic region is surprisingly more comfortable and effective than placement in other regions, particularly other neck and/or head regions. In this configuration at least one of the electrodes (e.g., the lower electrode) may be highly stable, even while the subject moves his or her neck and head, preventing discomfort and avoiding dislodging the apparatus
The anode and cathode electrodes may be arranged in any orientation (e.g., vertically relative to the long axis of the user's body, horizontally, etc.). In some variations it may be beneficial for the electrodes to be arranged vertically relative to the long-axis of the user's body (e.g., from the head to the feet). For example, the electrodes may be arranged with the electrodes vertically aligned, one on top of the other. Surprisingly, in some configurations parallel vertical strips covering the area do not seem to work as well. One preferred placement may be to place the anode at the base of the neck (e.g., versus just below the hairline) and the cathode downward from there, correspondingly to the top of the back. This arrangement may provide optimal effect (e.g., cognitive effect, while minimizing discomfort).
In
The apparatus of
Adapter Electrode Pads
Although many of the apparatuses and methods described herein are configured so that the controller (or stimulator or controller/stimulator) apparatus for applying transdermal electrical stimulation (TES) to the back of a subject's neck to modify a user's cognitive state (e.g., to induce a relaxed state) includes a wearable torc body that extends around the subject's neck, these techniques may be configured so that the controller apparatus is a small, lightweight and wearable apparatus that does not extend around the neck. For example, any of the TES stimulator apparatuses described in the following patent applications (herein incorporated by reference in their entirety) may be adapted for use in neck (and particularly C3-T2 neck/back) only stimulation: US-2014-0148872; US-2015-0088224; US-2016-0008632; US-2015-0005840; US-2015-0005841; US-2015-0174403; US-2015-0238762; US-2016-0317809; US-2015-0035877; US-2015-0335876; US-2016-0346545; US-2015-0335875; US-2015-0335888; US-2015-0328461; US-2015-0328467; US-2016-0346530; and US-2017-0076414. The apparatuses described therein typically include a wearable portion that couples to an electrode (often referred to as a cantilever electrode) and generally connect between the subject's forehead and a location on the back of the subject's neck or behind the ear. Thus, these TES controller devices are configured to couple with an electrode pad on the temple region of the subject's head, and may be adapted to have a body shape that is well suited for this location. Described herein are electrode pads (referred to as adapter electrode pads) that are configured to apply the TES to the C3-T2 neck/back region of the skin which have surprisingly been found to be both comfortable and effective, even as compared to the application at the head and neck.
For example,
Any of the wearable TES controller devices described herein, including the wearable example shown in
In
The electrode pad shown in
In any of these patches it is surprisingly advantageous, particularly so that the TES controller may fit onto the neck to allow neck bending and head motion, to arrange the first electrode and the second electrode in a first line that is parallel to a longest axis of the electrode pad, and arrange the first male snap connector (or whatever type of connector is used) and the second male snap connector (ow whatever type of connector is used) in a second line that is at an angle of between 25 and 65 degrees relative to the first line (e.g., between 15 and 60 degrees, between 30 and 60 degrees, approximately 45 degrees, etc.). This angled arrangement has surprisingly proven to be particularly helpful in allowing the vertical arrangement of the electrodes on the body (back/neck) while permitting the TES controller/simulator to be worn without impeding movement or irritating the subject (also referred to throughout as the “user”).
In any of these variations, the electrode pad may be adhesively held to the skin. For example, the first side may comprise an adhesive. As mentioned, the flat substrate may have a two-lobed (e.g., bi-lobed) shape. The first electrode and the first and second male snap connectors may be on a first lobe of the flat substrate and wherein the second electrode may be on a second lobe of the flat substrate, as shown in
In this example, the electrode pad is formed from a flexible substrate onto which each electrode is formed by adding layers, as illustrated schematically in
For example, as shown in
The electrode pad may include text or writing that provides instructions for applying and/or removing the electrode pad, as shown in
The design of the electrode pads shown in
Treatment of Immune Disorders
The methods and apparatuses described herein may be used for treating disorders including immune disorders. In particular, these methods and apparatuses may be use for treating an autoimmune disorder, including (but not limited to) psoriasis. See, e.g.,
Although the disorders, such as psoriasis, described herein are typically inflammatory medical disorders, other inflammatory and/or other skin disorders may be treated using any of the apparatuses and methods described herein. For example, other inflammatory (and/or autoimmune) disorders that may be treated include: rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, Sjogren's syndrome, Graves' or Hashimoto's thyroiditis, asthma and/or lupus. Other skin-specific disorders that may be treated include, but are not limited to: Pruritus (Itch), Hyper-hidrosis (excessive sweating), facial erythema (facial flush), atopic dermatitis, eczema, prurigo nodularis, lichen planus, chronic urticarial, alopecia areata, rosacea and/or vitiligo. Other medical disorders may include migraines. Although the examples described herein focus primarily on psoriasis, the methods and apparatuses described herein may be used to treat any of the disorders discussed above.
The transdermal neuromodulation approaches described herein (e.g., the application of TES) may target peripheral nerves and utilize these pathways to influence brain function; by delivering pulsed electrical currents to specific nerve pathways, biochemical and biometric data has shown a significant suppression of basal sympathetic tone and lower stress. Surprisingly this method has also resulted in a reduction in the severity (e.g., reduction in plaque/maculopapules number and/or size) of psoriasis maculopapules/plaques. As stated above, psoriasis patients are believed to have an upregulated sympathetic response which is directly correlated to the severity of their condition. Without being bound by a particular theory, the methods described herein for transdermal neuromodulation may lower sympathetic tone in individuals with psoriasis thereby improving their condition. The lack of side effects using the transdermal neuromodulation described herein makes it particularly advantageous as compared to current methods of treatment of psoriasis.
The TES applicator may be applied by the patient herself, and in some variations the patient may manually adjust one or more of the TES waveform parameters to enhance comfort. The attachment sites for the electrodes may be on the neck/upper back; one electrode location may be on the subject's neck (over the C1-C7 region) and a second electrode location may be below the neck (upper back, e.g., over the C4-T2 region); or two electrodes may be on the subject's skin below the neck (e.g., within the C5-T2 region, etc.).
For example, a method of non-invasively treating psoriasis (e.g.,
The wearable TES applicator may be attached by any appropriate method, including adhesively attaching, attaching using a strap, attaching via a garment such as a hat, band, etc., attaching via a bandage or wrap, or the like. As mentioned, the first electrode may be attached to the subject's head, e.g., to the subject's temple region, forehead region, etc. The first electrode may be on or attached directly to the body of the wearable TES applicator. The second electrode may also be attached to the subject's neck; for example, the second electrode may be attached to the subject's neck above the subject's vertebra prominens.
Any of these methods may allow the subject (who may also be referred to as the user) to select a set of parameters for the electrical stimulation to be applied. Any individual or combination of parameters may be modulated/set by the user, and this modulation may be performed before and/or during the application of the stimulation. For example, a subject may modify one or more parameters such as: stimulation duration, frequency, peak amplitude, duty cycle, capacitive discharge on or off, and DC offset. The adjustment may be made within a fixed/predetermined range of values (e.g., for frequency, the subject may adjust the frequency between a minimum value, such as 250 Hz, and a maximum value, such as 40 kHz, or any sub-range therebetween). The TES applicator may be worn (and energy applied) while the subject is awake and/or while the subject sleeps.
In general, the TES ensemble waveforms may be monophasic or biphasic (or both during different periods); in particular TES ensemble waveforms may include biphasic electrical stimulation. This biphasic electrical stimulation may be asymmetric with respect to positive and negative going phases. Psoriasis-treating TES waveforms may also have a duty cycle (e.g., time on relative to time off) of between 10% and 90%, e.g., a duty cycle of between 30% and 60%. The peak amplitude of the applied current may also be controlled. In general, the peak amplitude may be greater than 3 mA (greater than 4 mA, greater than 5 mA, greater than 6 mA, greater than 7 mA, greater than 8 mA, etc. or between about 3 mA and about 30 mA, between 3 mA and 20 mA, between 5 mA and 30 mA, between 5 mA and 20 mA, etc.).
As mentioned above, any of the stimulation parameters (e.g., peak current amplitude, frequency, DC offset, percent duty cycle, capacitive discharge, etc.) may be changed during the ensemble waveform, so that sub-periods of different parameters may be consecutively applied. The frequency may be between 250 Hz and 50 kHz (e.g., a minimum of: 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1500, 2000, 3000, 4000, 5000, etc. Hz and a maximum of 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1500, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, 10000, 12000, 15000, 20000, 25000, 30000, 35000, 40000, 50000 Hz, where the minimum is always less than the maximum).
As mentioned, any appropriate stimulation duration may be used. For example, the step of continuing application of the electrical stimulation for a stimulation duration may include continuing for a stimulation duration of at least five minutes.
Any of the TES ensemble waveforms described herein may be modulated by amplitude modulation, using an appropriate AM carrier frequency. For example, applying the TES waveform(s) may comprise applying electrical stimulation having amplitude modulation, and the amplitude modulation may generally have a frequency of less than 250 Hz (e.g., between 0.01 Hz and 250 Hz, 1 Hz and 250 Hz, 5 Hz and 200 Hz, 10 Hz and 200 Hz, etc.).
In some variations, applying the TES psoriasis-treating ensemble waveform may include applying electrical stimulation having a burst mode. A bursting mode may include periods where the applied TES stimulation is quiescent (“off”). Note that although the majority of the examples described herein include the use of ensemble waveforms in which one or more (though often just one) stimulation parameter changes during different, predefined component waveforms that are sequentially applied as the ensemble waveform, in some variations only a single component waveform is applied. Similarly, a component waveform may vary continuously or discretely (by steps) for one or more component waveforms.
For example, described herein are methods of non-invasively treating psoriasis that may include: placing a first electrode and second electrode of a wearable transdermal electrical stimulation (TES) applicator on a subject's body; activating the wearable TES applicator to deliver a biphasic electrical stimulation between the first and second electrodes having a duty cycle of greater than 10 percent, a frequency of 250 Hz or greater, and an intensity of 3 mA or greater, wherein the biphasic electrical stimulation is asymmetric with respect to positive and negative going phases; and reducing repeating the placing and activating steps to reduce psoriasis.
Any of the methods of applying TES for treating psoriasis described herein may be used in conjunction with, and may surprisingly enhance, pharmaceutical treatments of psoriasis. In particular, when a subject is co-treated with both a pharmaceutical treatment (e.g., a biologic such as AMEVIVE, ENBREL, HUMIRA, AND REMICADE and RAPTIVA), the effect of the biological may be accelerated. In addition, lower doses may be effectively used.
In some variations, the methods described herein may be configured to apply a dosage of TES that is predetermined and/or optimized for treating psoriasis; the patient may be prevented from adjusting the dosage.
In any of these methods, the first step may be identifying a subject suffering from psoriasis. Psoriasis may be diagnosed by any method known in the art, including by identifying maculopapules/plaques on the patient's skin. The therapy may be provided at regular (e.g., daily, multiple times daily, every other day) until an appropriate response is seen, including a reduction in maculopapule/plaque size and/or frequency (e.g., a 5% or greater reduction, a 10% or greater reduction, a 15% or greater reduction, a 20% or greater reduction, a 25% or greater reduction, etc.).
For example, a method of non-invasively applying TES to treat psoriasis may include: placing a first electrode of a wearable transdermal electrical stimulation (TES) applicator on the subject's skin on the subject's temple region and a second electrode on a back of the subject's neck above a vertebra prominens; treating psoriasis by activating the wearable TES applicator to deliver a biphasic electrical stimulation having a duty cycle of greater than 10 percent, a frequency of 250 Hz or greater, and an intensity of 3 mA or greater, wherein the biphasic electrical stimulation is asymmetric with respect to positive and negative going phases; and treating psoriasis by applying the biphasic electrical stimulation between the first and the second electrodes for 10 seconds or longer.
A method of treating psoriasis in a subject in need thereof may include: placing a first electrode of a wearable transdermal electrical stimulation (TES) applicator on the skin of a subject having psoriasis at the subject's temple region and a second electrode on a back of the subject's neck above a vertebra prominens; activating the wearable TES applicator to deliver a biphasic electrical stimulation having a duty cycle of greater than 10 percent, a frequency of 250 Hz or greater, and an intensity of 3 mA or greater, wherein the biphasic electrical stimulation is asymmetric with respect to positive and negative going phases; and treating the subject's psoriasis by applying the biphasic electrical stimulation between the first and second electrodes for 5 minutes or longer.
Any of the method components described above may be incorporated into any of these exemplary methods as well. For example, attaching the TES applicator and/or electrodes may refer to adhesively attaching, mechanically attaching or the like. In general, the TES applicator may be applied directly to the body (e.g., coupling the body to the skin or clothing of the patient directly) or indirectly, e.g., attaching to the body only by coupling with another member (e.g., electrode) that is already attached or attachable to the body. The attachment location may be independent of the location of one or more maculopapules and/or plaques on the subject's skin.
In any of the methods described herein, the user may be allowed and/or required to select the waveform ensemble from a list of possible waveform ensembles, which may be labeled to indicate name, content, efficacy, and/or the like. Alternatively or additionally, the user may be prevented from selecting or altering the waveform(s). In some variations, the subject may be permitted or allowed (e.g., using a wearable electronic and/or handheld electronic apparatus) to select and/or modify one or more parameters for the electrical stimulation to be applied, wherein the parameters may include one or more of: stimulation duration, frequency, peak amplitude, and duty cycle.
The electrodes and TES applicator may be worn while the subject sleeps, or prior to sleeping.
Any of the methods described herein may be automatically or semi-automatically controlled, and may include processing of feedback from any of the sensors to regulate the application of TES, including modifying one or more TES waveform parameter based on the sensed values.
In any of these variations, the apparatus may be specifically adapted for comfort, convenience or utility when used with a subject's suffering from psoriasis. For example, in apparatuses in which there is a visible psoriatic plaque.
Although the stimulation parameters may be adjusted or modified by the subject wearing the apparatus, any of these method may include modifying, by a party that is not the subject, a stimulation parameter of the wearable TES device, wherein the stimulation parameter includes one or more of: stimulation duration, frequency, peak amplitude, duty cycle, capacitive discharge, DC offset, etc. For example, the physician may adjust any of these parameters.
Any of these methods may also include automatically stopping, starting or modulating the wearable TES applicator per a physician-provided prescription.
In operation, the wearable TES applicator may automatically or manually triggered to deliver the biphasic electrical stimulation. The apparatus may also be configured to transmit a notification (directly or via a user computing device) that reminds the subject to wear the TES applicator, for example, transmitting a notification that reminds the subject to wear the TES applicator based on input from a location sensor in the TES applicator or wirelessly connected to the TES applicator.
The methods described herein may also include providing a metric to the subject showing compliance with the treatment protocol (e.g., regular use for the prescribed time). The methods may include a metric showing improvement based on user-reported and/or quantified (e.g., plaque/maculopapule count and/or size) metrics.
In addition, any of the methods described herein may also include concurrently delivering a calming sensory stimulus when activating the wearable TES applicator, such as concurrently delivering a calming sensory stimulus when activating the wearable TES applicator, wherein the calming sensory stimulus is one or more of auditory stimulus, olfactory stimulus, thermal stimulus, and mechanical stimulus.
Also described herein are wearable transdermal electrical stimulation (TES) applicators for treating psoriasis. These apparatuses may be configured to perform any of the methods described herein. In general, these apparatuses may include: a body; a first electrode; a second electrode (the apparatuses may be part of a separate but attachable, e.g., disposable, electrode assembly that couples to the body); and a TES control module at least partially within the body. The TES control module may include a processor, a timer and a waveform generator, and the TES control module may be adapted to deliver an electrical (e.g., biphasic, asymmetric) stimulation signal for a stimulation duration (e.g., 10 seconds or longer) between the first and second electrodes. The electrical stimulation which may be a TES ensemble waveform, may have a duty cycle of greater than 10 percent, a frequency of 250 Hz or greater, and an intensity of 3 mA or greater, wherein the biphasic transdermal electrical stimulation is asymmetric with respect to positive and negative going phases. The wearable TES applicator may generally be lightweight (e.g., may weigh less than 50 grams, etc.). Any of the TES applicators described herein may include at least one sensor coupled to the body for monitoring the subject (e.g., the subject's sympathetic and/or parasympathetic tone or state).
Any of these apparatuses may include a psoriasis medicament on the treatment pad for jointly treating with a psoriasis medicine.
Any appropriate TES waveform(s) may be used, particularly those that enhance a relative reduction in sympathetic tone, compared to parasympathetic tone. For example, the duty cycle may be between 10% and 90%. The transdermal electrical stimulation may have a frequency greater than 250 Hz, 500 Hz, 750 Hz, 5 kHz, etc. For example, the frequency may be between 250 Hz to 50 kHz. The transdermal electrical stimulation may comprise amplitude modulation, as discussed above, having a frequency of less than 250 Hz. The transdermal electrical stimulation may include a burst mode, such as a burst mode having a frequency of bursting that is less than 250 Hz.
The TES waveform(s) may be pre-programmed. The apparatus may include at least one sensor that measures the subject's autonomic function, wherein the measurement of autonomic function may measure one or more of: galvanic skin resistance, heart rate, heart rate variability, or breathing rate. The feedback from the at least one sensor may be used to adjust the stimulation parameters. Ideally, the treatment may be performed to induce a sustained (e.g., greater than 5 minutes, greater than 10 minutes, greater than 15 minutes, greater than 20 minutes, greater than 25 minutes, greater than 30 minute, etc.) upregulated sympathetic response. Based on the sensor detection, the apparatus may increase any of the one or more stimulation parameters, such as: the current, the frequency, the duration, etc., until the subject is experiencing a robust suppression of basal sympathetic tone, and therefore a reduction in stress.
Any of these devices may include a visual indicator (e.g., light, screen, etc., including LED(s), displays, etc.) that is configured to be turned down or turned off when the wearable TES system is activated.
When a feature or element is herein referred to as being “on” another feature or element, it can be directly on the other feature or element or intervening features and/or elements may also be present. 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 present. It will also be understood that, when a feature or element is referred to as being “connected”, “attached” or “coupled” to another feature or element, it can be directly connected, attached or coupled to the other feature or element or intervening features or elements may be present. 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 present. Although described or shown with respect to one embodiment, the features and elements so described or shown can apply to other embodiments. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed “adjacent” another feature may have portions that overlap or underlie the adjacent feature.
Terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. For example, as used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, steps, operations, elements, and/or components, but do not preclude 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 “/”.
Spatially relative terms, such as “under”, “below”, “lower”, “over”, “upper” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated 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 depicted in the figures. For example, if a device in the figures is inverted, elements described as “under” or “beneath” other elements or features would then be oriented “over” the other elements or features. Thus, the exemplary term “under” can encompass both an orientation of over and under. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Similarly, the terms “upwardly”, “downwardly”, “vertical”, “horizontal” and the like are used herein for the purpose of explanation only unless specifically indicated otherwise.
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 feature/element. Thus, a first feature/element discussed below could be termed a second feature/element, and similarly, a second feature/element discussed below could be termed a first feature/element without departing from the teachings of the present invention.
Throughout this specification and the claims which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” and “comprising” means various components can be co-jointly employed in the methods and articles (e.g., compositions and apparatuses including device and methods). For example, the term “comprising” will be understood to imply the inclusion of any stated elements or steps but not the exclusion of any other elements or steps. In general, any of the apparatuses and methods described herein should be understood to be inclusive, but all or a sub-set of the components and/or steps may alternatively be exclusive, and may be expressed as “consisting of” or alternatively “consisting essentially of” the various components, steps, sub-components or sub-steps.
As used herein in the specification and claims, including as used in the examples and unless otherwise expressly specified, all numbers may be read as if prefaced by the word “about” or “approximately,” even if the term does not expressly appear. The phrase “about” or “approximately” may be used when describing magnitude and/or position to indicate that the value and/or position described is within a reasonable expected range of values and/or positions. For example, a numeric value may have a value that is +/−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 values given herein should also be understood to include about or approximately that value, unless the context indicates otherwise. For example, if the value “10” is disclosed, then “about 10” is also disclosed. Any numerical range recited herein is intended to include all sub-ranges subsumed therein. It is also understood that when a value is disclosed that “less than or equal to” the value, “greater than or equal to the value” and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value “X” is disclosed the “less than or equal to X” as well as “greater than or equal to X” (e.g., where X is a numerical value) is also disclosed. It is also understood that the throughout the application, data is provided in a number of different formats, and that this data, represents endpoints and starting points, and ranges for any combination of the data points. For example, if a particular data point “10” and a particular data point “15” are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.
Although various illustrative embodiments are described above, any of a number of changes may be made to various embodiments without departing from the scope of the invention as described by the claims. For example, the order in which 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 altogether. Optional features of various device and system embodiments may be included in some embodiments and not in others. Therefore, the foregoing description is provided primarily for exemplary purposes and should not be interpreted to limit the scope of the invention as it is set forth in the claims.
The examples and illustrations included herein show, by way of illustration and not of limitation, specific embodiments in which the subject matter may be practiced. As mentioned, other embodiments may be utilized and derived there from, such that structural and logical substitutions and changes may be made without departing from the scope of this disclosure. Such embodiments of the inventive subject matter may be referred to herein individually or collectively by the term “invention” merely for convenience and without intending to voluntarily limit the scope of this application to any single invention or inventive concept, if more than one is, in fact, disclosed. Thus, although specific embodiments have been illustrated and described herein, any arrangement calculated to achieve the same purpose may be substituted for the specific embodiments shown. This disclosure is intended to cover any and all adaptations or variations of various embodiments. Combinations of the above embodiments, and other embodiments not specifically described herein, will be apparent to those of skill in the art upon reviewing the above description.
This patent application claims priority as a continuation-in-part of U.S. patent application Ser. No. 15/601,394 (filed on May 22, 2017), now U.S. Pat. No. 9,956,405, which claimed priority to: U.S. Provisional Patent Application No. 62/339,737, filed on May 20, 2016; U.S. Provisional Patent Application No. 62/383,239, filed Sep. 2, 2016; and U.S. Provisional Patent Application No. 62/431,365, filed Dec. 7, 2016. Each of these applications is herein incorporated by reference in its entirety. This patent application also claims priority as a continuation-in-part to PCT application PCT/US2017/033809, filed on May 22, 2017 (titled “TRANSDERMAL ELECTRICAL STIMULATION AT THE NECK TO INDUCE NEUROMODULATION”), which also claims priority to U.S. Provisional Patent Applications No. 62/339,737, filed on May 20, 2016; U.S. Provisional Patent Application No. 62/383,239, filed Sep. 2, 2016; and U.S. Provisional Patent Application No. 62/431,365, filed Dec. 7, 2016. Each of these applications is herein incorporated by reference in its entirety. This patent application also claims priority to U.S. Provisional Patent Application No. 62/509,603, filed on May 22, 2017; U.S. Provisional Patent Application No. 62/522,054, filed on Jun. 19, 2017; U.S. Provisional Patent Application No. 62/522,629, filed on Jun. 20, 2017; and U.S. Provisional Patent Application No. 62/598,462, filed on Dec. 13, 2017. Each of these applications is herein incorporated by reference in its entirety.
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| 20180272118 A1 | Sep 2018 | US |
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| Parent | 15601394 | May 2017 | US |
| Child | 15967576 | US | |
| Parent | PCT/US2017/033809 | May 2017 | US |
| Child | 15601394 | US |
