AU2021106979A4 - A neuromodulatory device with a therapy delivery system for detecting and treating anxiety disorder. - Google Patents

Abstract

: A neuromodulatory device with a therapy delivery system for detecting and treating anxiety disorder. This invention describes a neuromodulatory device, systems and methods, and more particularly to devices, systems, and methods for treating anxiety and anxiety associated disorders. It includes a sensing component, a delivery component, and a controller. The device can detect at least one physiological parameter associated with the anxiety disorder. The controller can automatically coordinate the operation of the sensing and delivery components. The controller delivers an electrical signal to the delivery component to modulate activity at the autonomic nervous tissue target or a spinal nervous tissue target and effectively treat the anxiety or anxiety-associated disorder and autism. SIGNATURE: Dr. Abhinandan Ravsaheb Patil Mr. Gaurav Ghewade Dr. Kritika Rastogi Shreedhan Asgekar Sheet 5 of 8 APPLICANT Dr. Abhinandan Ravsaheb Patil Mr. Gaurav Ghewade Dr. Kritika Rastogi Shreedhan Asgekar FIG:5 SIGNATURE: Dr. Abhinandan Ravsaheb Patil Mr. Gaurav Ghewade Dr. Kritika Rastogi Shreedhan Asgekar

Description

Sheet 5 of 8

APPLICANT Dr. Abhinandan Ravsaheb Patil Mr. Gaurav Ghewade Dr. Kritika Rastogi Shreedhan Asgekar

FIG:5

SIGNATURE: Dr. Abhinandan Ravsaheb Patil

Mr. Gaurav Ghewade

Dr. Kritika Rastogi

Shreedhan Asgekar

TITLE A neuromodulatory device with a therapy delivery system for detecting and treating anxiety disorder.

FIELD OF INVENTION

0001] This invention relates to the field of pharmaceuticals and medical sciences more particularly neuromodulatory devices, systems and methods, for treating anxiety and anxiety associated disorders. 0002] Here the device is programmed to deliver an electrical signal to the delivery component to modulate activity at the autonomic nervous tissue target or a spinal nervous tissue target and effectively treat the anxiety or anxiety-associated disorder. It has a sensing component configured to detect at least one physiological parameter associated with the anxiety or anxiety-associated disorder

PRIOR ART AND PROBLEM TO BE SOLVED

0003] Anxiety and depression are major psychiatric disorders of significant clinical and socioeconomic significance. Clinical depression often presents alongside anxiety disorders, and vice-versa. In the general population, these disorders affect daily performance and correlate with impulse control, financial behaviours, substance abuse and organization. Anxiety is an unpleasant state that involves a complex combination of emotions that include fear, apprehension, and worry. It is often accompanied by physical sensations, such as heart palpitations, nausea, chest pain, shortness of breath, or tension headache. "Anxiety disorder" is a blanket term covering several different forms of abnormal, pathological anxiety, fears, phobias and nervous conditions that may come on suddenly (acute anxiety) and/or gradually over several years (chronic), and may impair or prevent the pursuing of normal daily routines. Anxiety disorders are often debilitating chronic conditions, which can be present from an early age or begin suddenly after a triggering event. They are prone to flare up at times of high stress.

[0004] Anxiety is often described as having cognitive, somatic, emotional, and behavioural components. The cognitive component entails the expectation of a diffuse and uncertain danger. Somatically, the body prepares the organism to deal with the threat (known as an emergency reaction) in the following ways: blood pressure and heart rate are increased; sweating is increased; blood flow to the major muscle groups is increased, and immune and digestive system functions are inhibited. Externally, somatic signs of anxiety may include pale skin, sweating, trembling, and pupillary dilation. Emotionally, anxiety causes a sense of dread or panic and physically causes nausea and chills. Behaviorally, both voluntary and involuntary behaviours may arise directed at escaping or avoiding the source of anxiety. These behaviours are frequent and often maladaptive, being most extreme in anxiety disorders. However, anxiety is not always pathological or maladaptive - it is a common emotion along with fear, anger, sadness, and happiness, and it has a very important function concerning survival. Conventional treatments for anxiety include behavioural therapy, lifestyle changes and/or pharmaceutical therapy (medications). Most drugs used to treat these disorders are known to have negative side effects that may limit their use, or cause habituation and dependence. 00051 To resolve the above-stated problem here is a closed-loop therapy system for treating anxiety or anxiety-associated disorder in a subject. The therapy delivery system can include a sensing component, a delivery component, and a controller. The sensing component can be configured to detect at least one physiological parameter associated with the anxiety disorder. The delivery component can be configured for implantation on or about an autonomic nervous tissue target or a spinal nervous tissue target. The controller can be configured to automatically coordinate the operation of the sensing and delivery components. The controller can also be configured to deliver an electrical signal to the delivery component to modulate activity at the autonomic nervous tissue target or a spinal nervous tissue target and effectively treat the anxiety or anxiety-associated disorder.

THE OBJECTIVES OF THE INVENTION:

[00061 There is a wide range of neurological and psychological disorders for which treatment may be provided by various means. For many disorders, the administration of pharmaceutical agents is the most common treatment modality. In cases in which the symptoms of the disorder are resistant to pharmacological treatment or for which no pharmacological treatment exists, other modalities may be used. 00071 It has already been proposed where the use of a sensor in combination with a signal generator (neurostimulator) to treat an anxiety disorder is described. In this embodiment, the sensor generates a signal related to a condition resulting from the anxiety disorder. Control means responsive to the sensor signal regulate the signal generator so that the neurological disorder is treated. One of the types of sensor signals is cortical potentials recorded above the neurons controlling specific aspects of behaviour associated with the neurological disorder; in this case, the sensor would take the form of an implanted depth electrode. In this system, the sensor is an integral component of the stimulating device. There is no teaching or suggestion in the, proposed technique, however, of the method of obtaining or computing a sensor signal relating to the anxiety disorder or treatment efficacy. 0008] The principal objective of the invention is a closed-loop therapy system for treating anxiety or anxiety-associated disorder in a subject. The therapy delivery system can include a sensing component, a delivery component, and a controller. The sensing component can be configured to detect at least one physiological parameter associated with the anxiety or anxiety-associated disorder. The delivery component can be configured for implantation on or about an autonomic nervous tissue target or a spinal nervous tissue target. The controller can be configured to automatically coordinate the operation of the sensing and delivery components. The controller can also be configured to deliver an electrical signal to the delivery component to modulate activity at the autonomic nervous tissue target or a spinal nervous tissue target and effectively treat the anxiety or anxiety-associated disorder.

[00091 Another objective of the invention is the use of the same method of a closed-loop therapy delivery system for treating autism in a subject. The therapy delivery system can comprise a sensing component, a delivery component, and a controller. The sensing component can be configured to detect at least one physiological parameter associated with autism. The delivery component can be configured for implantation on or about an autonomic nervous tissue target. The controller can be configured to automatically coordinate the operation of the sensing and delivery components. The controller can be configured to deliver an electrical signal to the delivery component to modulate the activity of the autonomic nervous tissue target and effectively treat autism. 00101 The further objective of the invention is to use the same method for treating anxiety or anxiety-associated disorder in a subject. One step of the method can include placing a therapy delivery device into electrical communication with an autonomic nervous tissue target or a spinal nervous tissue target. Next, the therapy delivery device can be activated to deliver an electrical signal to the autonomic nervous tissue target or a spinal nervous tissue target to effectively treat the anxiety or anxiety associated disorder in the subject.

SUMMARY OF THE INVENTION

0011] Anxiety disorders are among the most common psychiatric illnesses. In their more severe forms, such disorders can leave the patient dysfunctional. In addition to the subjective feelings of anxiety and panic, physiologi- cal changes such as tachycardia, palpitations, sweating and trembling are reported. Secondary insomnia is commonly observed in patients with anxiety, with complaints of difficulty in getting to sleep and of frequent waking from sleep. Symptoms of anxiety often accompany withdrawal from sedatives or may arise from the use of stimulants such as amphetamines 00121 This invention provides a closed-loop therapy system for treating anxiety or anxiety associated disorder in a subject. The therapy delivery system can include a sensing component, a delivery component, and a controller. The sensing component can be configured to detect at least one physiological parameter associated with the anxiety or anxiety-associated disorder. The delivery component can be configured for implantation on or about an autonomic nervous tissue target or a spinal nervous tissue target. The controller can be configured to automatically coordinate the operation of the sensing and delivery components. The controller can also be configured to deliver an electrical signal to the delivery component to modulate activity at the autonomic nervous tissue target or a spinal nervous tissue target and effectively treat the anxiety or anxiety-associated disorder. The controller can be configured to deliver an electrical signal to the delivery component to modulate the activity of the autonomic nervous tissue target and effectively treat autism.

DETAILED DESCRIPTION OF THE INVENTION

0013] While the present invention is described herein by way of example, using various embodiments and illustrative drawings, those skilled in the art will recognize that the invention is neither intended to be limited to the embodiment of drawing or drawings described nor designed to represent the scale of the various components. Further, some components that may form a part of the invention may not be illustrated with specific figures, for ease of illustration, and such omissions do not limit the embodiment outlined in any way. The drawings and detailed description of it are not intended to restrict the invention to the form disclosed, but on the contrary, the invention covers all modifications, equivalents, and alternatives falling within the spirit and scope of the present invention as defined by the appended claims. The headings are used for organizational purposes only and are not meant to limit the scope of the description or the claims. As used throughout this specification, the worn "may" be used in a permissive sense (i.e., meaning having the potential to), rather than the mandatory sense (i.e., meaning, must). 0014] Further, the words "an" or "a" mean "at least one" and the word "plurality" means one or more unless otherwise mentioned. Furthermore, the terminology and phraseology used herein is solely used for descriptive purposes and should not be construed as limiting in scope. Language such as "including," "comprising," "having," "containing," or "involving," and variations thereof, is intended to be broad and encompass the subject matter listed thereafter, equivalents and any additional subject matter not recited, and is not supposed to exclude any other additives, components, integers or steps. Likewise, the term "comprising" is considered synonymous with the terms "including" or "containing" for applicable legal purposes. Any discussion of documents acts, materials, devices, articles and the like are included in the specification solely to provide a context for the present invention.

[0015] In this disclosure, whenever an element or a group of elements is preceded with the transitional phrase "comprising", it is also understood that it contemplates the same element or group of elements with transitional phrases "consisting essentially of, "consisting", "selected from the group comprising", "including", or "is" preceding the recitation of the element or group of elements and vice versa.

00161 Before explaining at least one embodiment of the invention in detail, it is to be understood that the present invention is not limited in its application to the details outlined in the following description or exemplified by the examples. The invention is capable of other embodiments or of being practised or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein is for description and should not be regarded as limiting. 00171 Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Besides, the descriptions, materials, methods, and examples are illustrative only and not intended to be limiting. Methods and materials similar or equivalent to those described herein are used in the practice or testing of the present invention. 00181 The present disclosure includes various therapy delivery devices (not shown) and related systems configured to treat anxiety or anxiety-associated disorder in a subject. In some instances, therapy delivery devices that may be used to practice the present disclosure may be positioned directly on or in an autonomic nervous tissue target or spinal nervous tissue target. In other instances, therapy delivery devices that may be used to practice the present disclosure can be positioned below the skin of a subject, but not directly on or in an autonomic nervous tissue target or spinal nervous tissue target. In further instances, therapy delivery devices that may be used to practice the present disclosure can comprise external devices, e.g., positioned in a lumen adjacent to an autonomic nervous tissue target or spinal nervous tissue target. In still further instances, therapy delivery devices used to practice the present disclosure can comprise an external device, e.g., positioned on the skin of a subject adjacent to an autonomic nervous tissue target or spinal nervous tissue target. Therapy delivery devices can be temporarily or permanently implanted within, on, or otherwise associated with a subject suffering from, afflicted by, or suspected of having an anxiety or anxiety-associated disorder.

[00191 Therapy delivery devices of the present disclosure can be configured to deliver various types of therapy signals to an autonomic nervous tissue target or spinal nervous tissue target. For example, therapy delivery devices of the present disclosure can be configured to deliver only electrical energy, only magnetic energy, only pharmacological or biological agent, or a combination thereof. In one example, therapy delivery devices of the present disclosure can comprise at least one electrode and an integral or remote power source, which is in electrical communication with one or more electrodes and configured to produce one or more electrical signals (or pulses). In another example, therapy delivery devices can include a pharmacological or biological agent reservoir, a pump, and a fluid dispensing mechanism. Non limiting examples of pharmacological and biological agents can include chemical compounds, drugs (e.g., prazosin, clonidine), nucleic acids, polypeptides, stem cells, toxins (e.g., botulinum), as well as various energy forms, such as ultrasound, radiofrequency (continuous or pulsed), magnetic waves, cryotherapy, and the like. In yet another example, therapy delivery devices can be configured to deliver magnetic nerve stimulation with desired field facility and depth of penetration. 0020] In some instances, therapy delivery devices can comprise a stimulator (or inhibitor), such as an electrode, a controller or programmer, and one or more connectors (e.g., leads) for connecting the stimulating (or inhibiting) device to the controller. In one example, which is described in further detail below, the present disclosure can include a closed-loop therapy delivery system 10 (FIG. 2) for treating anxiety or anxiety-associated disorder. As shown in FIG. 2, the therapy delivery system 10 can include a sensing component 12, a delivery component 14, a controller 16, and a power source 18. Each of the sensing components 12, delivery component 14, controller 16, and power source 18 can be in electrical communication with one another (e.g., via a physical connection, such as a lead, or a wireless link). In some instances, each of the sensing and delivery components 12 and 14 can comprise an electrode. In other instances, the delivery component 14 can comprise a coil configured to deliver magnetic stimulation. In further describing representative electrodes, which are described in the singular, it will be apparent that more than one electrode may be used as part of a therapy delivery device. Accordingly, the description of a representative electrode suitable for use in the therapy delivery devices of the present disclosure applies to other electrodes that may be employed.

[00211 An electrode can be controllable to provide output signals that may be varied in voltage, frequency, pulse-width, current and intensity. The electrode can also provide both positive and negative current flow from the electrode and/or is capable of stopping current flow from the electrode and/or changing the direction of current flow from the electrode. In some instances, therapy delivery devices can include an electrode that is controllable, i.e., in regards to producing positive and negative current flow from the electrode, stopping current flow from the electrode, changing the direction of current flow from the electrode, and the like. In other instances, the electrode has the capacity for variable output, linear output and short pulse-width, as well as paired pulses and various waveforms (e.g., sine wave, square wave, and the like). 0022] The power source 18 can comprise a battery or generator, such as a pulse generator that is operatively connected to an electrode via the controller 16. The power source 18 can be configured to generate an electrical signal or signals. In one example, power source 18 can include a battery that is rechargeable by inductive coupling. The power source 18 may be positioned in any suitable location, such as adjacent to the electrode (e.g., implanted adjacent to the electrode), or a remote site in or on the subject's body or away from the subject's body in a remote location. An electrode may be connected to the remotely positioned power source 18 using wires, which may be implanted at a site remote from the electrode(s) or positioned outside the subject's body. In one example, an implantable power source 18 analogous to a cardiac pacemaker may be used. 0023] Controller 16 can be configured to control the pulse waveform, the signal pulse width, the signal pulse frequency, the signal pulse phase, the signal pulse polarity, the signal pulse amplitude, the signal pulse intensity, the signal pulse duration, and combinations thereof of an electrical signal. In other instances, controller 16 can be configured to control the delivery of magnetic energy or stimulation to the delivery component 14. Controller 16 may be used to convey a variety of currents and voltages to one or more electrodes and thereby modulate the activity of a target sympathetic nervous tissue. Controller 16 may be used to control numerous electrodes independently or in various combinations as needed to provide stimulation or inhibition of nerve activity. In some instances, an electrode may be employed that includes its power source, e.g., which is capable of obtaining sufficient power for operation from surrounding tissues in the subject's body, or which may be powered by bringing a power source 18 external to the subject's body into contact with the subject's skin, or which may include an integral power source.

[00241 The electrical signal (or signals) delivered by the controller 16 to the delivery component 14 may be constant, varying and/or modulated concerning the current, voltage, pulse-width, cycle, frequency, amplitude, and so forth. For example, a current may range from about 0.001 to about 1000 microampere (mA) and, more specifically, from about 0.1 to about 100 mA and even more specifically between about 0.1 mA to about 25 mA. Similarly, the voltage may range from about 0.1 millivolts to about 25 volts, or about 0.5 to about 4000 Hz, with a pulse-width of about 5 microseconds to about 5000 microseconds and more specifically about 10 to about 1000 microseconds. In certain instances, the frequency can be between about 5 Hz and about 25,000 Hz. In one example, the electrical signal can be oscillatory. The type of stimulation may vary and involve different waveforms known to the skilled artisan. For example, the stimulation may be based on the H waveform found in nerve signals (i.e., Hoffinan Reflex). In another example, different forms of interferential stimulation may be used. 00251 To increase nerve activity in a portion of the ANS, for example, voltage or intensity may range from about 1 millivolt to about 1 volt or more, e.g., 0.1 to about 50 mA or volts (e.g., from about 0.2 volts to about 20 volts), and the frequency may range from about 1 Hz to about 10,000 Hz, e.g., about 1 Hz to about 1000 Hz (e.g., from about 2 Hz to about 100 Hz). In some instances, pure DC and/or AC voltages may be employed. The pulse-width may range from about 1 microsecond to about 10,000 microseconds or more, e.g., from about 10 microseconds to about 2000 microseconds (e.g., from about 15 microseconds to about 1000 microseconds). The electrical signal may be applied for at least about 1 millisecond or more, e.g., about 1 second (e.g., about several seconds). In some instances, stimulation may be applied for as long as about 1 minute or more, e.g., about several minutes or more (e.g., about 30 minutes or more).

[00261 To decrease activity in a portion of the ANS, for example, voltage or intensity may range from about 1 millivolt to about 1 volt or more, e.g., 0.1 to about 50 mA or volts (e.g., from about 0.2s volt to about 20 volts), and the frequency may range from about 1 Hz to about 2500 Hz, e.g., about 50 Hz to about 2500 Hz. In one example, an electrical signal can have a frequency range of about 10,000 Hz or greater (e.g., high frequency stimulation) to effectively block nerve conduction. In certain instances, the frequency can be between about 10,000 Hz and 25,000 Hz. In some instances, pure DC and/or AC voltages may be employed. The pulse-width may range from about 1 microsecond to about 10,000 microseconds or more, e.g., from about 10 microseconds to about 2000 microseconds (e.g., from about 15 microseconds to about 1000 microseconds). The electrical signal may be applied for at least about 1 millisecond or more, e.g., about 1 second (e.g., about several seconds). In some instances, the electrical energy may be applied for as long as about 1 minute or more, e.g., about several minutes or more (e.g., about 30 minutes or more may be used). 00271 In some instances, controller 16 can be configured to deliver an electrical signal to the delivery component 14 so that the activity of an autonomic nervous tissue target or spinal nervous tissue target is continuously and substantially blocked. Prior art methods for delivering electrical signals to sympathetic nervous tissue (e.g., the stellate ganglion) include the application of pulsed radiofrequency (PRF) to reduce sympathetic activity. PRF is characterized by the delivery of high-intensity current in pulses; during each cycle, an active phase is followed by a silent phase. Although PRF increases the temperature of the target tissue, the silent phase allows heat to dissipate so that neurodestructive temperatures are not reached. PRF does not provide a continuous reduction or blockade of nerve activity, however, since current is not applied during the silent phase. Advantageously, one example of the present disclosure includes continuous application of an electrical signal that substantially blocks or reduces autonomic nerve activity (e.g., sympathetic activity) without an increase in temperature of the target nerve tissue. As described in more detail below, application of such an electrical signal can be performed by the closed-loop system 10 of the present disclosure to effectively normalize or regulate intrinsic autonomic activity (e.g., sympathetic activity) or tone in a subject diagnosed with, or suspected of having, an anxiety or anxiety-associated disorder.

[00281 The electrode may be mono-polar, bipolar or multi-polar. To minimize the risk of an immune response triggered by the subject against the therapy delivery device, and also to minimize damage thereto (e.g., corrosion from other biological fluids, etc.), the electrode (and any wires and optional housing materials) can be made of inert materials, such as silicon, metal, plastic and the like. In one example, a therapy delivery device can include a multi-polar electrode having about four exposed contacts (e.g., cylindrical contacts).

[00291 As discussed above, controller 16 (or a programmer) may be associated with a therapy delivery device. Controller 16 can include, for example, one or more microprocessors under the control of a suitable software program. Other components of a controller 16, such as an analogue-to-digital converter, etc., will be apparent to those of skill in the art. In some instances, controller 16 can be configured to record and store data indicative of the intrinsic autonomic tone or activity in the subject. Therefore, controller 16 can be configured to apply one or more electrical signals to the delivery component 14 when the intrinsic autonomic tone or activity of a subject increases or decreases above a certain threshold value (or range of values). 00301 Therapy delivery devices can be pre-programmed with desired stimulation parameters. Stimulation parameters can be controllable so that an electrical signal may be remotely modulated to desired settings without removal of the electrode from its target position. The remote control may be performed, e.g., using conventional telemetry with an implanted power source 18, an implanted radiofrequency receiver coupled to an external transmitter, and the like. In some instances, some or all parameters of the electrode may be controllable by the subject, e.g., without supervision by a physician. In other instances, some or all parameters of the electrode may be automatically controllable by a controller 16. 00311 In one example, the therapy delivery device can be configured for percutaneous placement or implantation. In this instance, the therapy delivery device can comprise one or more implantable electrodes shaped or configured, for example, as a wire, a rod, a filament, a ribbon, a cord, a tube, a formed wire, a flat strip, or a combination thereof. In one example, one or more of the electrodes can comprise a laminotomy electrode array. Laminotomy electrodes, for example, generally have a flat paddle configuration and typically possess a plurality of electrodes (e.g., 2, 3, 4 or more) arranged on the paddle. The arrangement of electrodes on the paddle may be in rows and columns, staggered, spaced, circular, or any other arrangement that will position the electrodes for optimal delivery of electrical energy. The one or more implantable electrodes may be controlled individually, in series, in parallel, or in any other manner desired. Once implanted, the implantable electrode(s) may be held in position using any method known to the skilled artisan, such as stitches, epoxy, tape, glue, sutures, or a combination thereof.

[00321 In another example, the therapy delivery device can be configured for intravascular or intraluminal placement or implantation. In some instances, a therapy delivery device configured for intravascular or intraluminal placement or implantation can be configured identically or similarly as the expandable electrode disclosed in U.S.

patent application Ser. No. 11/641,331 to Greenberg et al. (hereinafter, "the '331 application"). In one example, the therapy delivery device can be configured for intravascular or intraluminal placement or implantation at an implantation site that is adjacent or directly adjacent, an autonomic nervous tissue target or spinal nervous tissue target. 00331 In yet another example, the therapy delivery device can be configured for transcutaneous neuromodulation. In some instances, transcutaneous neuromodulation can include positioning a delivery component (e.g., an electrode or magnetic coil) on a skin surface so that a therapy signal (e.g., an electrical signal or magnetic field) can be delivered to an autonomic nervous tissue target or spinal nervous tissue target. Transcutaneous neuromodulation can additionally include partially transcutaneous methods (e.g., using a fine, needle-like electrode to pierce the epidermis). In other instances, a surface electrode (or electrodes) or magnetic coil can be placed into electrical contact with an autonomic nervous tissue target or spinal nervous tissue target associated with anxiety or anxiety-associated disorder. Non-limiting examples of transcutaneous neuromodulation devices that may be used for treating anxiety or anxiety-associated disorder are discussed below. 00341 In one example, an electrical signal used for transcutaneous neuromodulation may be constant, varying and/or modulated concerning the current, voltage, pulse-width, cycle, frequency, amplitude, and so forth (e.g., the current may be between about 1 to 100 microampere), about 10 V (average), about 1 to about 1000 Hz or more, with a pulse-width of about 250 to about 500 microseconds.

[00351 In another example, the present disclosure can include a therapy delivery device or system configured for transcutaneous neuromodulation using magnetic stimulation. A magnetic stimulation device or system can generally include a pulse generator (e.g., a high current pulse generator) and a stimulating coil capable of producing magnetic pulses with desired field strengths. Other components of a magnetic stimulation device can include transformers, capacitors, microprocessors, safety interlocks, electronic switches, and the like. In operation, the discharge current flowing through the stimulating coil can generate the desired magnetic field or lines of force. As the lines of force cut through tissue (e.g., neural tissue), a current is generated in that tissue. If the induced current is of sufficient amplitude and duration such that the cell membrane is depolarized, nervous tissue will be stimulated in the same manner as conventional electrical stimulation. It is therefore worth noting that a magnetic field is simply how an electrical current is generated within the nervous tissue and that it is the electrical current, and not the magnetic field, which causes the depolarization of the cell membrane and thus stimulation of the target nerve tissue. Thus, in some instances, advantages of magnetic over electrical stimulation can include: reduced or sometimes no pain; access to nervous tissue covered by poorly conductive structures; and stimulation of nervous tissues lying deeper in the body without requiring invasive techniques or very high energy pulses. 00361 Therapy delivery devices can be part of an open- or closed-loop system. In an open loop system, for example, a physician or subject may, at any time, manually or by the use of pumps, motorized elements, etc., adjust treatment parameters, such as pulse amplitude, pulse width, pulse frequency, duty cycle, dosage amount, type of pharmacological or biological agent, etc. Alternatively, in a closed-loop system 10 (as discussed above), treatment or stimulation parameters, as described herein, of electrical signals may be automatically adjusted in response to a sensed physiological parameter or a related symptom or sign indicative of the extent and/or presence of an anxiety or anxiety-associated disorder. In a closed-loop feedback system 10, a sensing component 12 can comprise a sensor (not shown in detail) that senses a physiological parameter associated with anxiety or anxiety-associated disorder can be utilized. More detailed descriptions of sensors that may be employed in closed-loop systems, as well as other examples of sensors and feedback control techniques. One or more sensing components 12 can be implanted on or in any tissue or organ of a subject. For example, a sensing component 12 can be implanted in or on a component of the ANS, such as nerves, ganglia, afferents or efferents, or the spinal cord. Alternatively or additionally, a sensing component 12 can be implanted on or in a body organ and/or an anatomical connection thereof.

[00371 The present method includes the steps of providing a therapy delivery device; placing the therapy delivery device into electrical communication with an autonomic nervous tissue target or spinal nervous tissue target associated with the anxiety or anxiety-associated disorder; and activating the therapy delivery device to deliver a therapy signal (e.g., an electrical signal or magnetic field) to the autonomic nervous tissue target or spinal nervous tissue target to effectively treat the anxiety or anxiety associated disorder. Subjects treatable by the present disclosure can, in some instances, be diagnosed with (or suspected of having) an anxiety or anxiety associated disorder as well as one or more related or unrelated medical conditions. Non-limiting examples of medical conditions that can be co-treated by the methods of the present disclosure can include substance abuse, sleep deprivation or sleep disorders, psychiatric disturbances or diseases, impulse control disorders, cardiovascular disease, metabolic disorders (e.g., diabetes), and major depressive episodes. 00381 In some instances, the step of placing a therapy delivery device into electrical communication with an autonomic nervous tissue target or spinal nervous tissue target can entail different surgical and/or medical techniques depending, for example, upon the target tissue. In some instances, a therapy delivery device can be surgically placed into electrical communication with an autonomic nervous tissue target or spinal nervous tissue target via a percutaneous or endoscopic route. In other instances, a therapy delivery device can be placed into electrical communication with an autonomic nervous tissue target or spinal nervous tissue target via an intravascular or intraluminal route. In further instances, a therapy delivery device can be placed into electrical communication with an autonomic nervous tissue target or spinal nervous tissue target via a transcutaneous approach. 0039] Examples of autonomic nervous tissue targets into which a therapy delivery device may be placed into electrical communication can include but are not limited to, any tissues of the SNS or the PNS. In some instances, autonomic nervous tissue targets into which a therapy delivery device may be placed into electrical communication can include a sympathetic chain ganglion, an efferent of a sympathetic chain ganglion, or an afferent of a sympathetic chain ganglion. In other instances, the sympathetic chain ganglion can be a cervical sympathetic ganglion, a thoracic sympathetic ganglion, or a stellate ganglion. Examples of cervical sympathetic ganglia can include an upper cervical sympathetic ganglion, a middle cervical sympathetic ganglion, or a lower cervical sympathetic ganglion. Examples of thoracic sympathetic ganglia can include a TI sympathetic ganglia, a T2 sympathetic ganglia, a T3 sympathetic ganglia, a T4 sympathetic ganglia, a T6 sympathetic ganglia, or a T7 sympathetic ganglia.

[00401 After placing the therapy delivery device, the therapy delivery device can be activated to deliver a therapy signal (e.g., an electrical signal or magnetic field) to the autonomic nervous tissue target or spinal nervous tissue target. In some instances, delivery of a therapy signal to the autonomic nervous tissue target or spinal nervous tissue target can prevent a sign and/or symptom associated with anxiety or anxiety associated disorder from either increasing or decreasing (as compared to a control or baseline). In other instances, delivery of a therapy signal to the autonomic nervous tissue target or spinal nervous tissue target can cause a sign and/or symptom associated with anxiety or anxiety-associated disorder to decrease (as compared to a control or baseline). The therapy delivery device can be activated at the onset of an episode (e.g., the onset of a sign and/or symptom) associated with anxiety or anxiety associated disorder or the therapy delivery device can be activated continuously or intermittently to reduce or eliminate the frequency of such episode(s). 0041] Delivery of the electrical signal to the autonomic nervous tissue target or spinal nervous tissue target can affect central motor output, nerve conduction, neurotransmitter release, synaptic transmission, and/or receptor activation at the target tissue(s). For example, the ANS may be electrically modulated to alter, shift, or change sympathetic and/or parasympathetic activity from a first state to a second state, where the second state is characterized by a decrease in sympathetic and/or parasympathetic activity relative to the first state. As discussed above, delivery of an electrical signal to the autonomic nervous tissue target or spinal nervous tissue target can, in some instances, substantially block the activity of the autonomic nervous tissue target or spinal nervous tissue target. In other instances, delivery of an electrical signal to the autonomic nervous tissue target or spinal nervous tissue target can achieve a complete nerve conduction block of autonomic nervous tissue target or spinal nervous tissue target for the desired period. In other instances, delivery of an electrical signal to the autonomic nervous tissue target or spinal nervous tissue target can achieve a partial block of the autonomic nervous tissue target or spinal nervous tissue target for some time sufficient to decrease sympathetic and/or parasympathetic nerve activity. The degree to which sympathetic and/or parasympathetic activity is decreased or increased can be titrated by one skilled in the art depending, for example, upon the nature and severity of the anxiety or anxiety-associated disorder in the subject.

[00421 In another aspect, the present disclosure can include a method 20 (FIG. 4) for treating an anxiety disorder or an anxiety-associated disorder in a subject, such as autism. One step of method 20 can include providing a therapy delivery device (Step 22). Alternatively, Step 22 can include providing a closed-loop therapy delivery system. Examples of suitable therapy delivery devices (and systems) are described above and further illustrated below. At Step 24, the therapy delivery device (or system) can be placed into electrical communication with an autonomic nervous tissue target or spinal nervous tissue target associated with the anxiety disorder or the anxiety-associated disorder (e.g., autism). In some instances, the therapy delivery device can be placed in direct electrical contact with the autonomic nervous tissue target or spinal nervous tissue target. "Direct electrical contact" can mean that the therapy delivery device (or system) is placed on or in the autonomic nervous tissue target or spinal nervous tissue target. In other instances, "direct electrical contact" can mean that the therapy delivery device (or system) is located adjacent or directly adjacent (but not in physical contact with) the autonomic nervous tissue target or spinal nervous tissue target such that delivery of a therapy signal (e.g., an electrical signal or a magnetic field) can modulate a function, activity, and/or characteristic of the autonomic nervous tissue target or spinal nervous tissue target. 00431 After placing the therapy delivery device (or system) into direct electrical communication with the autonomic nervous tissue target or spinal nervous tissue target, the therapy delivery device (or system) can be activated to deliver the therapy signal to the autonomic nervous tissue target or spinal nervous tissue target (Step 26). The therapy signal can be delivered in an amount and for a time sufficient to effectively treat the anxiety disorder or the anxiety-associated disorder (e.g., autism). In one example, electrical energy can be delivered to the stellate ganglion by an electrode or electrode array that is placed directly on or in the stellate ganglion. In some instances, an anxiety or anxiety-associated disorder may be caused by hyper sympathetic activity, which may lead to increased adrenal gland function. In such instances, it may be desirable to deliver continuous blocking stimulation to the stellate ganglion to decrease sympathetic activity in the subject and thereby cause adrenal output to decrease (e.g., to a normal level).

[00441 One example of method 20 is illustrated in FIG. 5. At Step 22, method 20 can include providing a closed-loop therapy system 10 as described above. The closed loop therapy system 10 can be configured for percutaneous implantation in the subject. As shown in FIG. 5, system 10 can be implanted in the subject so that the delivery component 14 and the sensing component 12 are in direct electrical contact with the stellate ganglion and the middle cervical ganglion, respectively. Additionally, system 10 can be implanted so that controller 16 and the power source 18 are secured at the same or different subcutaneous locations. 00451 Once system 10 is implanted (Step 24), the sensing component 12 can detect electrical activity in the middle cervical ganglion, which may be indicative of intrinsic sympathetic tone in the subject. The detected level(s) of electrical activity can then be relayed to controller 16, which determines if the detected level(s) is/are within a normal or abnormal range or level. Where the detected level(s) is/are within an abnormal range (e.g., at an elevated level as compared to a control or baseline), controller 16 can cause the power source 18 to deliver an electrical signal to the delivery component 14. The electrical signal is then delivered to the stellate ganglion to substantially block activity therein (Step 26). While the electrical signal(s) is/are being delivered to the stellate ganglion, the sensing component 12 can continue to detect the level of electrical activity within the middle cervical ganglion (Step 28). When the level of electrical activity in the middle cervical ganglion is equal, or about equal to, a normal or baseline level, the controller 16 can cease delivery of the electrical signal(s) to the delivery component 14. Stimulation or treatment parameters, as described herein, can be adjusted based on the detected electrical activity. By continuously or intermittently monitoring the intrinsic sympathetic tone or activity of the subject, the closed-loop therapy delivery system 10 can automatically decrease or normalize hyper sympathetic activity and thus effectively treat an anxiety disorder or an anxiety-associated disorder (e.g., autism).

[00461 Another aspect of the present disclosure can include transvascular or transluminal delivery of electrical energy to an autonomic nervous tissue target or spinal nervous tissue target associated with an anxiety disorder or an anxiety-associated disorder (e.g., autism). Thus, in some instances, method 20 can include providing a therapy delivery device (or system) configured for transvascular or transluminal insertion and placement within the subject. For instance, a therapy delivery device configured for intravascular or intraluminal placement in a subject can include an expandable electrode as disclosed in the '331 application. The therapy delivery device can be inserted into a vessel or lumen of the subject. Non-limiting examples of vessels and lumens into which the therapy delivery device can be inserted include arteries, veins, an oesophagus, a trachea, a vagina, a rectum, or any other bodily orifice. The therapy delivery device can be surgically inserted into the vessel or lumen via a percutaneous, transvascular, laparoscopic, or open surgical procedure. 00471 After inserting the therapy delivery device into the vessel or lumen, the therapy delivery device can be advanced (if needed) to an intraluminal target site so that the therapy delivery device is in electrical communication with the autonomic nervous tissue target or spinal nervous tissue target. In some instances, advancement of the therapy delivery device can be done under image guidance (e.g., fluoroscopy, CT, MRI, etc.). Intraluminal target sites can include intravascular or intraluminal locations at which the therapy delivery device can be positioned. For example, an intraluminal target site can include a portion of a vessel wall that is innervated by (or in electrical communication with) the autonomic nervous tissue target or spinal nervous tissue target. Examples of intraluminal target sites can include, without limitation, vascular or luminal sites innervated by and/or in electrical communication with any nervous tissue(s) of the SNS or PNS, such as neurons, axons, fibres, tracts, nerves, plexus, afferent plexus fibres, efferent plexus fibres, ganglion, pre-ganglionic fibres, post-ganglionic fibres, cervical sympathetic ganglia/ganglion, thoracic sympathetic ganglia/ganglion, afferents thereof, efferents thereof, a sympathetic chain ganglion, a thoracic sympathetic chain ganglion, an upper cervical chain ganglion, a lower cervical ganglion, and inferior cervical ganglion, and a stellate ganglion.

100481 After placing the therapy delivery device, a therapy signal (e.g., an electrical signal or a magnetic field) can be delivered to the autonomic nervous tissue target or spinal nervous tissue target. The therapy signal can be delivered in an amount and for a time sufficient to effectively treat the anxiety disorder or the anxiety-associated disorder (e.g., autism).

[00491 In another aspect, method 20 can include providing a therapy delivery device (or system) configured for placement on the skin of the mammal. Examples of therapy delivery devices configured for transcutaneous delivery of one or more therapy signals are disclosed above and described in more detail below. In some instances, a therapy delivery device (or system) can be positioned about the subject, without penetrating the skin of the subject, so that the therapy delivery device is in electrical communication with an autonomic nervous tissue target or spinal nervous tissue target associated with an anxiety disorder or an anxiety-associated disorder (e.g., autism). Non-limiting examples of an autonomic nervous tissue target or spinal nervous tissue target into which the therapy delivery device can be placed into electrical communication are described above. After placing the therapy delivery device (or system), a therapy signal can be delivered to the autonomic nervous tissue target or spinal nervous tissue target. The therapy signal can be delivered in an amount and for a time sufficient to effectively treat the anxiety disorder or anxiety associated disorder (e.g., autism). 00501 In one example, a transcutaneous neuromodulation device can comprise a wearable accessory item, such as a necklace or collar 30 (FIG. 6). As shown in FIG. 6, a necklace or collar 30 can be configured to include at least one electrode 32 for delivering a therapy signal to a particular region of a subject's neck (e.g., an anterior or posterior region thereof) depending upon the desired neuromodulatory effect. The necklace or collar 30 can additionally include an integral power source 34 (e.g., a rechargeable battery). It will be appreciated that the electrode(s) 32 can alternatively be powered by a wireless power source (not shown). The necklace or collar 30 can be configured to obtain a pre-selected position about a subject's neck by, for example, using a positioning guide (not shown), weighting the necklace or collar, etc. Alternatively, the subject can manually adjust the necklace or collar 30 as needed to optimize the delivery of the therapy signal from the electrode(s) 32 to an autonomic nervous tissue target or spinal nervous tissue target. 100511 In another example, a transcutaneous neuromodulation device can comprise a pillow 40 (FIGS. 7A-B). In some instances, pillow 40 (FIG. 7A) can be configured as a collar for use in a reclined or upright position, such as on an aeroplane, in a car, on a couch. Pillow 40 can include at least one electrode 42 configured to deliver a therapy signal to an autonomic nervous tissue target or spinal nervous tissue target (e.g., in a subject's head or neck). As shown in FIG. 7A, the pillow 40 includes two oppositely disposed of electrodes 42. The pillow 40 can also include a power source (not shown), which may be integrally connected with the pillow or located remotely (i.e., wirelessly) therefrom. In other instances, pillow 40 (FIG. 7B) can comprise a traditional pillow for use when a subject is sleeping or lying in bed. As shown in FIG. 7B, the pillow 40 can include two oppositely disposed of electrodes 42 configured to deliver a therapy signal to a target nerve when the subject neck or head is straddled between the electrodes. The pillow 40 can further include a power source 44 that is in direct electrical communication with the electrodes 42; however, it will be appreciated that the power source can be located remotely (i.e., wirelessly) from the pillow. 00521 It will be appreciated that the transcutaneous neuromodulation devices illustrated in FIGS. 6 and 7A-B are illustrative only and that such devices can include any wearable item, accessory, article of clothing, or any object, device, or apparatus that a subject can use and, during use, comes into close or direct contact with a portion of the subject's body (e.g., the subject's neck). Examples of such transcutaneous neuromodulation devices can include vests, sleeves, shirts, socks, shoes, underwear, belts, scarves, wrist bands, gloves, earpieces, band-aids, turtle neck, pendants, buttons, earrings, stickers, patches, bio-films, skin tattoos (e.g., using neuro-paint), chairs, computers, beds, headrests (e.g., of a chair or car seat), cell phones, and the like. 00531 Another example of method 20 is illustrated in FIG. 8. At Step 22, method 20 can include providing a closed-loop therapy system 10 as described above. The closed loop therapy system 10 can be configured for percutaneous (e.g., subcutaneous) implantation in the subject. As shown in FIG. 8, system 10 can be implanted in the subject so that the delivery component 14 and the sensing component 12 are in direct electrical contact with a spinal cord segment at the level of C8 and a spinal cord segment at the level of C6, respectively. Additionally, system 10 can be implanted so that controller 16 and the power source 18 are secured at the same or different subcutaneous locations.

[00541 Once system 10 is implanted (Step 24), the sensing component 12 can detect electrical activity in the C6 spinal cord segment, which may be indicative of intrinsic sympathetic tone in the subject. The detected level(s) of electrical activity can then be relayed to controller 16, which determines if the detected level(s) is/are within a normal or abnormal range or level. Where the detected level(s) is/are within an abnormal range (e.g., at an elevated level as compared to a control or baseline), controller 16 can cause the power source 18 to deliver an electrical signal to the delivery component 14. The electrical signal is then delivered to the spinal cord segment at the level of C8 to substantially block activity therein (Step 26). While the electrical signal(s) is/are being delivered to the spinal cord segment at the level of

C8, sensing component 12 can continue to detect the level of electrical activity within the spinal cord segment at the level of C6 (Step 28). When the level of electrical activity in the spinal cord segment at the level of C6 is equal, or about equal to, a normal or baseline level, the controller 16 can cease delivery of the electrical signal(s) to the delivery component 14. Treatment or stimulation parameters, as described herein, can be adjusted based on the detected electrical activity. By continuously or intermittently monitoring the intrinsic sympathetic tone or activity of the subject, the closed-loop therapy delivery system 10 can automatically decrease or normalize hyper sympathetic activity and thus effectively treat anxiety or an anxiety-associated disorder (e.g., autism). 00551 While there has been illustrated and described embodiments of the present invention, those of ordinary skill in the art, to be understood that various changes may be made to these embodiments without departing from the principles and spirit of the present invention, modifications, substitutions and modifications, the scope of the invention being indicated by the appended claims and their equivalents.

FIGURE DESCRIPTION

00561 The accompanying drawings, which are incorporated in and constitute a part of this disclosure, illustrate an exemplary embodiment and, together with the description, explain the disclosed embodiment. In the figures, the left and rightmost digit(s) of a reference number identify the figure in which the reference number first appears. The same numbers are used throughout the figures to reference features and components. Some embodiments of the system and methods of an embodiment of the present subject matter are now described, by way of example only, and concerning the accompanying figures, in which:

[00571 FIG. 1 is a schematic illustration showing the cervical and upper thoracic portions of the sympathetic nerve chain and the spinal cord;

[00581 FIG. 2 is a schematic illustration of a human spinal cord and associated vertebrae;

0059] FIG. 3 is a schematic illustration showing a closed-loop therapy delivery system for treating anxiety or anxiety-associated disorder configured according to one aspect of the present disclosure;

0060] FIG. 4 is a process flow diagram illustrating a method for treating anxiety or anxiety-associated disorder according to another aspect of the present disclosure; 0061] FIG. 5 is a schematic illustration showing the closed-loop therapy delivery system of FIG. 3 implanted in a subject;

0062] FIG. 6 is a schematic illustration showing a transcutaneous neuromodulatory device constructed following another aspect of the present disclosure;

0063] FIGS. 7A-B are schematic illustrations showing alternative transcutaneous neuromodulatory devices constructed following other aspects of the present disclosure; and

0064] FIG. 8 is a schematic illustration showing the closed-loop therapy delivery system in FIG. 3 implanted in a human subject.

Claims (4)

CLAIMS: I/We claim that:

1. A closed-loop therapy deliver/system for treating an anxiety or anxiety-associated disorder in a subject, the therapy delivery system comprising: a sensing component configured to detect at least one physiological parameter associated with the anxiety or anxiety-associated disorder; a delivery component configured for implantation on or about an autonomic nervous tissue target or a spinal nervous tissue target: and a controller configured to automatically coordinate operation of the sensing and delivery components; wherein the controller is programmed to deliver an electrical signal to the delivery component to modulate activity at the autonomic nervous tissue target or a spinal nervous tissue target and effectively treat the anxiety or anxiety-associated disorder.

2. The closed loop therapy as claimed in claim - 1, the controller is programmed to deliver an electrical signal that substantially blocks activity at the autonomic nervous tissue target or a spinal nervous tissue target. two electrodes for acquiring electrophysiological signals from a body suffering from a neurological disorder which is one or more of depression, major depressive disorder, obsessive compulsive disorder, dementia, mood disorders and anxiety disorders, wherein one of said at least two electrodes for acquiring electrophysiological signals from the body is positioned at electrode position

3. The closed loop therapy as claimed in claim - 1, acquires electrophysiological signals from a body suffering from a neurological disorder which is one or more of depression, major depressive disorder, obsessive compulsive disorder, dementia, mood disorders and anxiety disorders, said signals being acquired through electrodes placed on the body, wherein one of said at least two electrodes for acquiring electrophysiological signals from the body is positioned at electrode position

4. The closed loop therapy as claimed in claim - 1, calculates at least one feature relating to the efficacy of said treatment without referencing said at least one feature to a normative data set, said at least one feature being a measure of a self-reported mood or anxiety score; with varying treatment parameters in order to maximize the calculated treatment efficacy. Signatory:

SIGNATURE: Dr. Abhinandan Ravsaheb Patil

Mr. Gaurav Ghewade

Dr. Kritika Rastogi

Shreedhan Asgekar

Sheet 1 of 8

APPLICANT 24 Aug 2021

Dr. Abhinandan Ravsaheb Patil Mr. Gaurav Ghewade Dr. Kritika Rastogi Shreedhan Asgekar 2021106979

FIG : 1

SIGNATURE: Dr. Abhinandan Ravsaheb Patil

Mr. Gaurav Ghewade

Dr. Kritika Rastogi

Shreedhan Asgekar

Sheet 2 of 8

APPLICANT 24 Aug 2021

Dr. Abhinandan Ravsaheb Patil Mr. Gaurav Ghewade Dr. Kritika Rastogi Shreedhan Asgekar 2021106979

FIG : 2

SIGNATURE: Dr. Abhinandan Ravsaheb Patil

Mr. Gaurav Ghewade

Dr. Kritika Rastogi

Shreedhan Asgekar

Sheet 3 of 8

APPLICANT 24 Aug 2021

Dr. Abhinandan Ravsaheb Patil Mr. Gaurav Ghewade Dr. Kritika Rastogi Shreedhan Asgekar 2021106979

FIG : 3

SIGNATURE: Dr. Abhinandan Ravsaheb Patil

Mr. Gaurav Ghewade

Dr. Kritika Rastogi

Shreedhan Asgekar

Sheet 4 of 8

APPLICANT 24 Aug 2021

Dr. Abhinandan Ravsaheb Patil Mr. Gaurav Ghewade Dr. Kritika Rastogi Shreedhan Asgekar 2021106979

FIG : 4

SIGNATURE: Dr. Abhinandan Ravsaheb Patil

Mr. Gaurav Ghewade

Dr. Kritika Rastogi

Shreedhan Asgekar

Sheet 5 of 8

APPLICANT 24 Aug 2021

Dr. Abhinandan Ravsaheb Patil Mr. Gaurav Ghewade Dr. Kritika Rastogi Shreedhan Asgekar 2021106979

FIG : 5

SIGNATURE: Dr. Abhinandan Ravsaheb Patil

Mr. Gaurav Ghewade

Dr. Kritika Rastogi

Shreedhan Asgekar

Sheet 6 of 8

APPLICANT 24 Aug 2021

Dr. Abhinandan Ravsaheb Patil Mr. Gaurav Ghewade Dr. Kritika Rastogi Shreedhan Asgekar 2021106979

FIG : 6

SIGNATURE: Dr. Abhinandan Ravsaheb Patil

Mr. Gaurav Ghewade

Dr. Kritika Rastogi

Shreedhan Asgekar

Sheet 7 of 8

APPLICANT 24 Aug 2021

Dr. Abhinandan Ravsaheb Patil Mr. Gaurav Ghewade Dr. Kritika Rastogi Shreedhan Asgekar 2021106979

FIG : 7 – A

FIG : 7 – B

SIGNATURE: Dr. Abhinandan Ravsaheb Patil

Mr. Gaurav Ghewade

Dr. Kritika Rastogi

Shreedhan Asgekar

Sheet 8 of 8

APPLICANT 24 Aug 2021

Dr. Abhinandan Ravsaheb Patil Mr. Gaurav Ghewade Dr. Kritika Rastogi Shreedhan Asgekar 2021106979

FIG : 8

SIGNATURE: Dr. Abhinandan Ravsaheb Patil

Mr. Gaurav Ghewade

Dr. Kritika Rastogi

Shreedhan Asgekar