Neuromodulation system and method using feedback optimized electric field generation

Abstract

A neuromodulation system and method using feedback-optimized electric field generation for stimulating a patient's target tissue to treat neurological and non-neurological conditions generally includes an implantable electrode, an implantable sensor, an implantable or external electrical signal generator, and an implantable or external controller. The controller controls the electrical signal generator to generate an electrical noise stimulation signal delivered to the target tissue via the electrode, the electrical noise stimulation signal generating an optimized electric field with a maximized voltage at a low current density. The sensor generates temperature and impedance data about the target tissue, and the controller automatically responds to values ​​of the sensor data indicative of potential damage to the target tissue by reducing the strength of the electric field.

Description

[Technical field]

[0001] background Field Example embodiments relate generally to neuromodulation systems and methods using feedback-optimized electric field generation to modulate activity or stimulate neural tissue, non-neural tissue, or combinations thereof, as a therapeutic treatment for pain and other neurological and non-neurological conditions. [Background technology]

[0002] Related Technology Any discussion of related art throughout this specification shall in no way be taken as an admission that such related art is widely known in the art or forms part of common general knowledge.

[0003] Many techniques and methods have been used to treat neurological and non-neurological conditions, such as pain, incontinence, depression, obesity, headaches, and other conditions. Both destructive and non-destructive methods have been used to treat pain. Various destructive methods have been used to treat chronic pain symptoms, including radiofrequency (RF) ablation, cryoablation, chemical ablation (phenol, Botox®), sonographic ablation, and mechanical transection. However, destructive methods cause destruction of portions of the nerve in the treatment area, which can lead to immediate loss of functionality (e.g., movement, sensation, and proprioception) and long-term atrophy, neuropathy, and worsening pain. Therefore, destructive methods are usually a treatment of last resort and should be used sparingly.

[0004] A variety of non-destructive methods have also been used to treat pain, including the use of prescription painkillers (opioids), local anesthetic injections, local cocktails composed of steroids and other anti-inflammatory agents, continuous infusions of local anesthetics, and electrical stimulation. Each method has its own set of challenges that can compromise the effectiveness and / or usefulness of the treatment.

[0005] For example, non-destructive methods using drugs, usually including opioids, may expose the patient to the risk of undesirable side effects such as constipation, nausea, emesis, and intestinal blockage, and may even ultimately lead to poisoning and death. Non-destructive methods using injections of local anesthetics and / or cocktails usually have a short duration of effectiveness, lasting only a few hours, and may become ineffective over time. For this reason, such methods usually require ongoing, routine maintenance. Continuous injections of anesthetics generally require the patient to be hooked up to an external device for long-term treatment, often for several days. For this reason, routine maintenance of the device is burdensome for the patient, reminding them that they are in pain, and is often undesirable. The use of local anesthetics and long-lasting local anesthetics (e.g., Exparel®) may also cause neurotoxic, vascular toxic, and allergic reactions. Furthermore, these drugs cannot be quickly reversed, titrated, or selected according to the type of neural activity they block (e.g., pain versus movement).

[0006] Electrical stimulation techniques have been used to relieve both acute (e.g., after surgery) and chronic types of pain. Unlike pharmaceutical interventions, electrical stimulation techniques are reversible, non-addictive, and can be selected depending on the stimulation paradigm and treatment site. Electrical stimulation can be delivered to various parts of the central nervous system, including sensory receptors in the brain, the spinal cord, the skin, and various peripheral nerves, as well as the peripheral nervous system. Furthermore, electrical stimulators can be configured to provide treatment in a transcutaneous, percutaneous, and / or implantable manner.

[0007] Two electrical stimulation paradigms have been primarily used to treat pain, both of which use electrical signals with periodic waveforms. Traditional stimulation uses relatively low frequency (e.g., <1500Hz) electrical signals to generate paresthesia, which can partially drown out pain with a tingling or numbing sensation. Subsensory paresthesia stimulation, such as that used in Nevro Corp.'s HF10® technology, uses relatively high frequency (e.g., in the 10KHz range) electrical signals to at least partially block the propagation of nerve signals to the brain. See, for example, WO 2009 / 061813 A1.

[0008] Unlike local anesthetics, none of these electrical stimulation types completely eliminates pain sensation. Conventional stimulation merely attenuates pain sensation while simultaneously inducing electroparesthesia (i.e., buzzing, tingling, or vibration sensations) overlying the receptive field of the stimulated nerve. Subsensory paresthesia stimulation does not induce electroparesthesia, but is still effective in attenuating pain sensation. Furthermore, despite the promise of electrical stimulation, its therapeutic effectiveness may decrease after several years of use. This phenomenon is known as neural tolerance and is the primary reason why implanted stimulators are removed from patients. Still further, the use of relatively low frequency, periodic electrical stimulation signals, e.g., less than about 100 KHz, provides a relatively short-term therapeutic effect. Thus, although the therapeutic effect of electrical stimulation using such signals is usually felt within minutes to hours after the start of stimulation, the therapeutic effect tends to last only for a relatively short period of time, e.g., several hours after treatment is stopped. Because the therapeutic effects tend to be temporary, continuous and / or frequent stimulation sessions are generally required to extend the duration over which the therapeutic effect is felt, which in turn typically requires ongoing maintenance of the device (e.g., daily battery charging), which can be cumbersome and inconvenient.

[0009] Electrical stimulation has also been used to treat other neurological and non-neurological conditions, such as incontinence, obesity, etc. For example, electrical stimulation signals have been applied to nerves, such as the sacral and posterior tibial nerves, and muscles, such as the pelvic muscles, associated with the bladder and urination as a treatment for incontinence. Electrical stimulation of the intestinal tract has been used as a treatment for gastrointestinal motility disorders and obesity. Electrical stimulation signals have also been applied to the nerves and muscles of the stomach to suppress or reduce hunger and / or regulate gastric motor function as a treatment for obesity, and to help control chronic nausea and vomiting associated with gastroparesis resulting from diabetes.

[0010] Recently, WO 2018 / 136354 A1 ("the '354 application") has disclosed stimulating or modulating neural tissue, non-neural tissue, or a combination thereof, with electrical signals exhibiting statistically random waveforms, i.e., noise, to treat pain and certain other nervous system disorders. According to the '354 application, the electrical noise signal can be adjusted, thereby improving patient outcomes over traditional periodic electrical signals. The '354 application discloses adjusting or modulating the electrical noise signal by delivering a noise signal to the patient and then adjusting or modulating the signal based on feedback provided by the patient about what the patient is feeling. However, if the patient cannot provide accurate and timely feedback, the noise signal cannot be adjusted accurately or appropriately, resulting in less than optimal therapeutic effects and, in some cases, even harmful. As a result, the patient may even suffer discomfort or tissue damage.

[0011] As described in the '354 application, the use of adjustable statistically random electrical noise signals to modulate or stimulate neural tissue, non-neural tissue, or a combination of both can improve therapeutic outcomes compared to the use of traditional periodic electrical signals. However, the inventors have discovered that improved and more durable therapeutic outcomes can be achieved by optimizing and maximizing the electric field generated in the target tissue. Optimizing and maximizing the electric field in the target tissue produces long-term plastic functional changes in the tissue. This results in shorter and less frequent treatments, resulting in therapeutic results that last for a relatively long period of time without the need to continuously or repeatedly apply electrical signals to the target tissue at short intervals. At the same time, the electric field must be optimized and maximized in a manner that does not cause discomfort to the patient or risk damage to the target tissue. Furthermore, the optimized and maximized electric field must be rapidly and automatically controlled in response to changes in physical parameters associated with the target tissue so as not to cause discomfort to the patient or damage to the tissue. Summary of the Invention [Problem to be solved by the invention]

[0012] Thus, there is a need for a neuromodulation system and method that addresses the various deficiencies and shortcomings of conventional therapeutic devices and methods. More specifically, there is a need for a system and method that uses an electrical noise signal to modulate or stimulate a target neural tissue, non-neural tissue, or a combination thereof to effectively treat neurological and non-neurological conditions, including, but not limited to, acute and chronic pain types, Parkinson's disease, stroke, depression, bowl / bladder incontinence, obesity (reduced appetite induction), and the like. There is a need for a system and method that is non-destructive to the tissue being treated, preserves all other neural functions of the tissue, such as touch, movement, proprioception, and the like, and provides effective therapeutic results without inducing tolerance. There is a need for a system and method that allows for less frequent application, shorter treatment times, and produces effective therapeutic results over a relatively long period of time, thus also reducing the need for device maintenance, e.g., battery recharging. There is a need for a system and method that optimizes and maximizes the electric field generated in the target tissue to achieve the aforementioned therapeutic effects while rapidly and automatically controlling the electric field in response to changes in physical parameters associated with the tissue, so as not to cause patient discomfort or tissue damage. [Means for solving the problem]

[0013] overview Exemplary embodiments are directed to neuromodulation systems and methods using feedback optimized electric field generation to provide therapeutic effects on target tissues of a patient. The target tissues can be nervous system tissues, non-nervous system tissues, or a combination of both. The target tissues can be tissues within or adjacent to tissues of the patient's central nervous system, peripheral nervous system, or autonomic nervous system, including the brain, spinal cord, dorsal root ganglia, sympathetic chain ganglia, cranial nerves, parasympathetic nerves, and peripheral nerves, among others. The target tissues can be nervous system tissues associated with other organs, including the stomach, bladder, and intestines, or non-nervous system tissues. The therapeutic effects include long-term functional changes in the plasticity of the target tissues to reduce or eliminate pathophysiological diseases or syndromes. The therapeutic effects can treat multiple nervous system and non-nervous system conditions, including chronic and acute pain, autonomic disorders, sensory disorders, motor disorders, movement disorders, and cognitive disorders, obesity, psychotic conditions, seizure disorders, and incontinence, among others.

[0014] Neuromodulation systems and methods using feedback-optimized electric field generation generally include an implantable electrode, an implantable sensor, an electrical signal generator coupled to the implantable electrode, and a controller coupled to the implantable sensor and the electrical signal generator.

[0015] The electrical signal generator may be external or implantable within the patient's body and is adapted to generate an electrical noise stimulation signal for stimulating or modulating a target tissue of the patient, including nervous system tissue, non-nervous system tissue, or a combination of both.

[0016] The implantable electrode can include one electrode or multiple electrodes and can be implanted in or near the target tissue. The electrode receives and delivers an electrical noise stimulation signal to the target tissue to generate an electric field in the target tissue.

[0017] The implantable sensor may include a single sensor or multiple sensors. The one or more sensors may be incorporated into one or more electrodes or may be separately implantable in or near the target tissue. The one or more sensors generate data indicative of a physical parameter associated with the target tissue. In one embodiment, the sensor includes a temperature sensor and the physical parameter of the target tissue includes temperature. In another embodiment, the sensor includes an impedance sensor and the physical parameter of the target tissue includes impedance.

[0018] The controller, which may be external or implantable within the patient's body, is configured to receive the sensor data and, in response, automatically control the electrical signal generator to generate an electrical noise stimulation signal in a manner that optimizes and maximizes the electric field to produce an optimal therapeutic effect, but prevents the electric field from becoming the sensor data indicative of a value of a physical parameter of the target tissue associated with possible damage to the target tissue.

[0019] Generally, the controller is configured to control the electrical signal generator to optimize and maximize the electric field by generating and applying an electrical noise stimulation signal that maximizes the voltage component of the electric field while maintaining the current density and flow rate levels to the target tissue, so that the sensor data does not indicate values ​​of the physical parameters of the target tissue that are associated with possible damage to the target tissue. In one embodiment, the electrical noise stimulation signal can have a peak voltage level in the range of about 5V to about 200V, and the current flow rate can be maintained in the range of about 10mA to about 300mA or less. The electrical noise stimulation signal can have a frequency spectrum in the range of about 50Hz, more preferably about 100Hz to about 750KHz.

[0020] In one aspect, the electrical signal generator is adapted to generate the electrical noise stimulation signal in a frequency band having a center frequency corresponding to a peak value of the impedance, and the controller is configured to control the electrical signal generator to optimize and maximize the electric field by adjusting the center frequency. In one aspect, the electrical signal generator is adapted to generate the electrical noise stimulation signal in a plurality of selectable frequency bands corresponding to a plurality of peak values ​​of the impedance, and the controller is configured to control the electrical signal generator to optimize and maximize the electric field by selecting one of the frequency bands. In one aspect, the system includes a plurality of selectable combinations of implantable electrodes, and the electrical signal generator is adapted to generate the electrical noise stimulation signal to be received by a selected combination of the implantable electrodes, and the controller is configured to control the electrical signal generator to optimize and maximize the electric field by selecting a combination of the implantable electrodes that will receive the electrical noise stimulation signal.

[0021] The controller is configured to automatically take steps to reduce the strength of the electric field in response to data from the sensor indicating a value of a physical parameter associated with possible damage to the target tissue. In one embodiment, the step of reducing the strength of the electric field includes a step of reducing a current density and a flow rate to the target tissue. In one embodiment, the value of the physical parameter associated with possible damage to the target tissue can be a particular high temperature value, e.g., 42°C, or a temperature range. In another embodiment, the value of the physical parameter associated with possible damage to the target tissue can be a particular low impedance value or impedance range.

[0022] The detailed description of some of the embodiments of the neuromodulation system and method with feedback optimized electric field generation has been outlined in this rather broad outline so that the detailed description of some of the embodiments of the neuromodulation system and method with feedback optimized electric field generation may be better understood and their contribution to the art may be better appreciated. There are additional embodiments of the neuromodulation system and method with feedback optimized electric field generation described below and forming the subject matter of the claims appended hereto. In this regard, before describing in detail at least one embodiment of the neuromodulation system and method with feedback optimized electric field generation, it should be understood that the application of the neuromodulation system and method with feedback optimized electric field generation is not limited to the details of construction or the arrangement of components set forth in the following description or illustrated in the drawings. The neuromodulation system and method with feedback optimized electric field generation are capable of other embodiments and can be practiced and carried out in various ways. Similarly, it should be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting.

[0023] BRIEF DESCRIPTION OF THE DRAWINGS Exemplary embodiments of neuromodulation systems and methods using feedback-optimized electric field generation will become more fully understood from the detailed description set forth herein below and the accompanying drawings, in which like elements are represented by like reference characters, which are provided by way of example only and are therefore not limiting of the exemplary embodiments described herein. [Brief description of the drawings]

[0024] [Figure 1] FIG. 1 is a schematic diagram of a neuromodulation system and method using feedback-optimized electric field generation associated with electrical noise stimulation of target neural tissue associated with the central nervous system, and more specifically, target neural tissue in the brain, according to an exemplary embodiment. [Diagram 2] 1. FIG. 2 is an enlarged view of the portion of FIG. 1 contained within the dashed line. [Diagram 3]FIG. 1 is a schematic diagram of a neuromodulation system and method using feedback-optimized electric field generation associated with electrical noise stimulation of target neural tissue associated with the central nervous system, and more specifically, target neural tissue in the brain, according to another exemplary embodiment. [Figure 4] FIG. 1 is a schematic diagram of a neuromodulation system and method using feedback-optimized electric field generation associated with electrical noise stimulation of target neural tissue associated with the central nervous system, and more specifically, of target neural tissue in the spinal cord, according to an exemplary embodiment. [Diagram 5] 4. FIG. 5 is an enlarged view of the portion of FIG. 4 included within the dashed line. [Figure 6] FIG. 1 is a schematic diagram of a neuromodulation system and method using feedback-optimized electric field generation associated with electrical noise stimulation of target neural tissue associated with the peripheral nervous system, and more specifically, of a peripheral nerve target neural tissue, according to an exemplary embodiment. [Figure 7] FIG. 1 is a schematic diagram of a neuromodulation system and method using feedback-optimized electric field generation associated with electrical noise stimulation of targeted non-neural tissue associated with the gastrointestinal tract, and more specifically, targeted non-neural tissue of the stomach, according to an illustrative embodiment. [Figure 8] 8 is an enlarged view of the portion of FIG. 7 contained within the dashed line. [Figure 9] FIG. 1 is a schematic diagram of a neuromodulation system and method using feedback-optimized electric field generation associated with electrical noise stimulation of target neural tissue associated with the peripheral nervous system, and more specifically, of a sacral nerve target neural tissue, according to an exemplary embodiment. [Figure 10] FIG. 1 is a block diagram illustrating the interconnections and communication between the main components of a neuromodulation system and method with feedback-optimized electric field generation, according to an illustrative embodiment. [Figure 11] FIG. 1 is a block diagram illustrating the interconnections and communications between the main components of an implantable internal controller and a noise generator of a neuromodulation system and method using feedback-optimized electric field generation, according to an illustrative embodiment. [Figure 12]FIG. 1 is a block diagram illustrating the interconnections and communications between an implantable internal controller and an external controller of a neuromodulation system and method with feedback-optimized electric field generation according to an exemplary embodiment associated with an external telecommunications network. [Figure 13] 1 is a graph illustrating the amplitude versus time of an electrical noise stimulation signal of an implantable internal controller and noise generator of a neuromodulation system and method with feedback-optimized electric field generation, according to an illustrative embodiment. [Figure 14] 1 is a graph illustrating the power spectrum versus frequency of the electrical noise stimulation signal of the implantable internal controller and noise generator of a neuromodulation system and method with feedback-optimized electric field generation, according to an illustrative embodiment. [Figure 15A] 1 is a graph illustrating an impedance amplitude spectrum versus frequency in response to application of an electrical noise stimulation signal of an implantable internal controller and noise generator of a neuromodulation system and method with feedback optimized electric field generation, according to an illustrative embodiment. [Figure 15B] 13 is a graph illustrating another impedance amplitude spectrum versus frequency in response to application of an electrical noise stimulation signal of an implantable internal controller and noise generator of a neuromodulation system and method with feedback optimized electric field generation, in accordance with an illustrative embodiment. [Figure 15C] 13 is a graph illustrating yet another impedance amplitude spectrum versus frequency in response to application of an electrical noise stimulation signal of an implantable internal controller and noise generator of a neuromodulation system and method with feedback optimized electric field generation, in accordance with an illustrative embodiment. [Figure 16] 1 is a graph illustrating impedance amplitude versus time in response to application of an electrical noise stimulation signal of an implantable internal controller and noise generator of a neuromodulation system and method with feedback-optimized electric field generation, according to an illustrative embodiment. [Figure 17]1 is a graph illustrating temperature versus time in response to application of an electrical noise stimulation signal of an implantable internal controller and noise generator of a neuromodulation system and method with feedback optimized electric field generation, according to an illustrative embodiment. [Figure 18A] FIG. 1 is a partial perspective schematic diagram illustrating electrode selection of a multi-electrode lead for applying an electrical noise stimulation signal of an implantable internal controller and noise generator to tissue of a neuromodulation system and method with feedback-optimized electric field generation, according to an illustrative embodiment. [Figure 18B] FIG. 13 is a partial perspective schematic diagram illustrating alternative electrode selections of a multi-electrode lead for applying an electrical noise stimulation signal of an implantable internal controller and noise generator to tissue of a neuromodulation system and method with feedback-optimized electric field generation, according to an illustrative embodiment. [Figure 18C] FIG. 13 is a partial perspective schematic diagram illustrating yet another selection of electrodes of a multi-electrode lead for applying an electrical noise stimulation signal of an implantable internal controller and noise generator to tissue of a neuromodulation system and method with feedback-optimized electric field generation, according to an illustrative embodiment. [Figure 18D] FIG. 13 is a partial perspective view illustrating yet another selection of electrodes of a multi-electrode lead for applying an electrical noise stimulation signal of an implantable internal controller and noise generator to tissue of a neuromodulation system and method with feedback-optimized electric field generation, according to an illustrative embodiment. [Figure 19A] FIG. 1 is a partial perspective view illustrating electrode selection of a pair of percutaneous leads for applying an electrical noise stimulation signal of an implantable internal controller and noise generator to tissue of a neuromodulation system and method using feedback-optimized electric field generation, according to an exemplary embodiment. [Figure 19B]FIG. 13 is a partial perspective view illustrating another selection of electrodes of a pair of percutaneous leads for applying an electrical noise stimulation signal of an implantable internal controller and noise generator to tissue of a neuromodulation system and method using feedback-optimized electric field generation, according to an illustrative embodiment. [Figure 19C] FIG. 13 is a partial perspective view illustrating electrode selection of a single percutaneous lead for applying an implantable internal controller and noise generator electrical noise stimulation signal to tissue of a neuromodulation system and method with feedback-optimized electric field generation, according to an exemplary embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0025] Detailed Description A. Overview An exemplary embodiment of a neuromodulation system and method 10 using feedback optimized electric field generation (herein referred to as neuromodulation system 10) provides effective and durable therapeutic results by delivering an electrical noise stimulation signal to a target tissue 12 of a patient 14 in a manner that optimizes and maximizes the electric field within the target tissue 12 while preventing damage to the target tissue 12 and discomfort to the patient 14. By optimizing and maximizing the electric field in the target tissue 12, the system can produce long-term plastic functional changes in the target tissue 12 with a relatively short period of treatment. This treatment produces relatively long-lasting, effective therapeutic results.

[0026] Exemplary embodiments of the neuromodulation system 10 optimize and maximize the electric field in a manner that maximizes the voltage component of the electric field while maintaining relatively low levels of current density and flow rate within the target tissue 12, thereby helping to prevent potential damage to the target tissue 12 and discomfort to the patient due to thermal effects. Exemplary embodiments of the neuromodulation system 10 also rapidly and automatically respond to sensed values ​​of physical parameters associated with the target tissue 12, such as temperature and impedance, that are indicative of potential damage to the target tissue 12, and control the electric field to reduce its strength, including reducing the current density and flow rate, thereby preventing damage to the target tissue 12 and discomfort to the patient 14.

[0027] The exemplary neuromodulation system 10 generally includes one or more implantable electrodes 30, one or more implantable sensors S1, S2, an electrical signal generator 40, and a controller 50. The electrical signal generator 40 and the controller 50 are preferably enclosed within an implantable housing 16 adapted for implantation within the body of a patient 14.

[0028] The electrodes 30 and sensors S1, S2 are implantable in, on, or around a target tissue 12 of a patient 14 to be treated. An electrical signal generator 40 is coupled to the implantable electrodes 30, and a controller 50 is coupled to the implantable sensors S1, S2 and the electrical signal generator 40. The controller 50 is adapted and configured to control the electrical signal generator 40 to generate and deliver an electrical noise stimulation signal via the electrodes 30 to the target tissue 12 of the patient 14. The electrical noise stimulation signal generates an optimized and maximized electric field in the target tissue 12 by maximizing the voltage component while maintaining the current density and flow rate at relatively low values. This optimization and maximization of the electric field results in long-term plastic functional changes in the target tissue 12 without damaging the target tissue 12 or causing discomfort to the patient 14 due to thermal effects.

[0029] The sensors S1, S2 are adapted to generate sensor data including values ​​of physical parameters of the target tissue 12, such as temperature and impedance, when an electrical noise stimulation signal is applied to the target tissue 12. The controller 50 is adapted and configured to receive and use the sensor data to optimize and maximize the electric field for treatment. The controller 50 is also adapted and configured to control the electric signal generator 40 by controlling the electric field in the target tissue 12 to reduce the field strength, including current density and flow rate, in rapid and automatic response to values ​​of the sensor data indicative of possible damage to the target tissue 12.

[0030] A number of techniques have been disclosed for controlling the electric field to optimize and maximize the strength of the electric field and to reduce the strength of the electric field. One technique involves limiting the duration of administration of the electric noise stimulation signal. Another technique involves generating and delivering the electric noise stimulation signal in a relatively narrow frequency band whose center frequency corresponds to a peak impedance value and varying or adjusting this center frequency. Another technique involves generating and delivering the electric noise stimulation signal in a number of relatively narrow frequency bands whose center frequencies correspond to a number of different peak impedance values ​​and selecting the frequency band in which the peak impedance is at a desired value. Another technique involves delivering the electric noise stimulation signal by selecting among various electrodes 30 or combinations of electrodes 30 with different spacing and orientations with respect to the target tissue 12 and therefore different corresponding impedance values.

[0031] B. System Overview 1-10 generally illustrate an exemplary neuromodulation system 10 that generates and delivers an electrical noise stimulation signal to a target tissue 12 of a patient 14 in a manner that optimizes and maximizes the electric field within the target tissue 12, thereby producing long-term plastic functional changes in the target tissue 12, thereby providing effective and durable therapeutic results to the patient 14, and that automatically responds to feedback from sensors, S1, S2 to control the electric field and help prevent patient discomfort and possible tissue damage.

[0032] Generally, the exemplary neuromodulation system 10 includes one or more implantable electrodes 30, one or more implantable sensors S1, S2, an electrical signal generator 40 electrically coupled to the implantable electrodes 30, and a controller 50 electrically coupled to the implantable sensors S1, S2 and the electrical signal generator 40. The electrical signal generator 40 and the controller 50 may also be implantable and may be enclosed in a suitable housing 16 that is implantable within the body of the patient 14. Suitable electrical leads 18 may electrically couple the electrical signal generator 40 and the electrodes 30. The implantable housing 16 may include a lead connection port 19 for that purpose. Alternatively, as shown in FIG. 6, the electrical signal generator 40 may be external to the patient 14 and the electrical signal generator 40 and the electrodes 30 may be coupled wirelessly, for example, electromagnetically via an antenna, inductively via an induction coil, or by any other suitable wireless arrangement.

[0033] 10, the neuromodulation system 10 may also include an internal power source 52 that provides power to the controller 50 and the electrical signal generator 40, a separate external controller 60, a user interface 62, and an external power source 64. If used, the external controller 60 may be directly coupled to the controller 50 or may be coupled wirelessly within the implantable housing 16 by a percutaneous electrical lead 65 or in any suitable manner, including those described above.

[0034] A lead 18 having one or more electrodes 30 may be implanted in or near the target tissue 12 of the patient 14 to be treated. In some applications, the electrodes 30 may also be placed on or just under the patient's skin at or near the target tissue 12. The sensors S1 and S2 may also be implanted in or near the target tissue 12 and may be located coincident with or near the electrodes 30.

[0035] As shown in Figures 1-3, in an exemplary embodiment of the neuromodulation system 10, the target tissue 12 may include neural tissue of the central nervous system of the patient 14 in, on, or around the patient's brain 22. For example, in deep brain stimulation, which may be used to treat certain neurological conditions, the electrodes 30 are embedded relatively deeply into the brain tissue. The electrodes 30 may be located near the tip of a relatively stiff insulated wire 31 extending from the tip of the lead 18, as shown in Figure 2, or in a segmented portion 32 near the tip of the lead 18, as shown in Figure 3, or a combination of both. Exemplary embodiments of the neuromodulation system 10 may be used to stimulate neural tissue in, on, and around the brain 22 to treat various neurological conditions and diseases. Various nervous system conditions and diseases include, but are not limited to, chronic pain, acute pain, autonomic neuropathy, sensory disorders, movement disorders including tremors, tics, Tourette's syndrome, and cognitive disorders including Parkinson's disease, Alzheimer's disease and dementia, psychiatric disorders including depression, anxiety, schizophrenia, seizure disorders including epilepsy, narcolepsy, incontinence, and Meniere's disease.

[0036] In an exemplary embodiment of the neuromodulation system 10, the target tissue 12 can include neural and non-neural tissue of the central nervous system of the patient 14 on and around the patient's spinal cord 24, including, but not limited to, neural and non-neural tissue in or around the spinal column, dorsal root, dorsal root ganglion, and ventral root. For example, as shown in Figures 4-5, one or more leads 18 having electrodes 30 near their tips can be inserted into the epidural space between the spinal skeleton and the spinal cord and advanced until one or more of the electrodes 30 are positioned on or adjacent to the target neural and / or non-neural tissue in, on, or adjacent to the spinal cord.

[0037] One or more electrodes 30 may be positioned laterally relative to the spinal cord in various locations including, for example, the dorsal (rear) region, the dorsal region, the lateral region, and the ventral (anterior) region, and may be positioned at various levels of the spine, for example, S5-S1, L5-L1, T12-T1, and C8-C1, depending on the condition being treated. Exemplary embodiments of the neuromodulation system 10 may be used to stimulate neural tissue in, on, and around the spinal cord at various levels of the spine to treat various diseases and syndromes. For example, one or more leads 18 with one or more electrodes 30 may be positioned in the epidural space on or adjacent to target neural tissue in, on, or around the spinal cord. That is, For the treatment of spinal and lumbar pain, the thoracic vertebrae between T7 and T12 are used. To provide treatment for chronic low back and leg pain, the thoracic spine is located between T10 and T11. For the treatment of neck pain, the area between C2 and T1 of the cervical vertebrae is For the treatment of stable or unstable angina, the area between C2 and T8 of the spine, For the treatment of abdominal pain, the area between C2 and T8 of the spine, For the treatment of diseases of the peripheral arteries of the lower limbs, the area between T10 and L5 of the spine, For the treatment of upper extremity ischemia, between cervical spine C2 and T1. One or more leads 18 with one or more electrodes 30 may also be positioned in or near the dorsal root ganglion to treat chronic or acute pain.

[0038] Other conditions that may be treated depending on the particular target tissue stimulated, as well as the spinal location and spinal level of the electrode 30, include, but are not limited to, acute pain, lumbar post-operative pain syndrome, complex regional pain syndrome, peripheral vascular disease and chronic limb ischemia, angina pain, diabetic pain, abdominal / visceral pain syndrome, brachial plexus neuritis, phantom limb pain, intractable pain due to spinal cord injury, mediastinal pain, Raynaud's syndrome, cervical neuritis, post-herpetic neuralgia, dizziness, tinnitus, hearing loss, and inflammatory pain such as arthritis, irritable bowel pain, osteoarthritis pain, and fibromyalgia.

[0039] In an exemplary embodiment of the neuromodulation system 10, the target tissue 12 may include neural and non-neural tissue of the peripheral nervous system of the patient 14, including tissue of the autonomic and somatic nervous systems. The target tissue 12 of the autonomic nervous system may include the sympathetic nervous system, e.g., the sympathetic chain ganglion and sympathetic tissue, and the parasympathetic nervous system, e.g., the parasympathetic tissue. The target tissue 12 of the somatic nervous system may include, for example, the cranial nerves and the sacral nerve. The target tissue 12 may also include neural and non-neural tissue of the major peripheral nerves, including the tibial, sacral, and sciatic nerves, as well as neural and non-neural tissue of any other peripheral nerves.

[0040] Depending on the placement of the electrodes 30 relative to target neural and non-neural tissue of the sympathetic chain ganglia at various levels of the spine, exemplary embodiments of the neuromodulation system 10 can provide treatment for a variety of conditions. For example, one or more electrodes 30 can be positioned on or adjacent to target neural tissue of the autonomic sympathetic chain at the anterior of the lumbar spine at level L1 to stimulate or modulate nerves of the celiac plexus connecting to the pancreas, gallbladder, intestines, liver, and stomach as a treatment for pain, at level L3 to stimulate or modulate lumbar nerves connecting to the legs and feet as a treatment for pain, or at level L5 to stimulate or modulate the hypogastric nerves connecting to the uterus, prostate, bladder, rectum, and perineum as a treatment for incontinence and sexual dysfunction.

[0041] As a further example, one or more leads 18 having one or more electrodes 30 may be Into the sacral plexus or foramen to treat urinary or fecal incontinence; Near or around the lumbar sympathetic plexus to treat chronic or acute pain in the extremities To treat chronic or acute pain in the abdomen, near or around the celiac sympathetic plexus, Near or around the hypogastric sympathetic plexus to treat chronic or acute pain in the pelvic region Near or around the stellate ganglion to treat pain in the upper extremities near or around the vagus nerve to treat seizure disorders, obesity, pain, or autonomic disorders; They can be positioned near or around peripheral nerves to treat acute pain, chronic pain, fecal or urinary incontinence, seizure disorders, movement disorders, obesity, spasticity, and to regulate other unpleasant neurological conditions.

[0042] The electrodes 30 may also be positioned on or adjacent to other target neural and non-neural tissues of the peripheral, autonomic, and somatic nervous systems associated with, among others, the eyes, lacrimal glands, salivary glands, sweat glands, hair follicles, blood vessels of the head, neck, and arms, the heart and lungs, stomach, duodenum, pancreas, liver, kidneys, colon, rectum, bladder, and external genitalia, as well as blood vessels of the lower limbs and perineum. Thus, exemplary embodiments of the neuromodulation system 10 may provide treatment for a variety of diseases and syndromes, including, but not limited to, complex regional pain syndrome, peripheral vascular disease and chronic limb ischemia, angina pain, diabetic pain, abdominal / visceral pain syndrome, phantom limb pain, Raynaud's syndrome, hypertension, hypotension, headaches and migraines, and inflammatory pain such as arthritis, irritable bowel pain, osteoarthritis pain, fibromyalgia, etc. As a further example, one or more leads 18 having one or more electrodes 30 can be positioned near or around somatic tissue, muscle, connective tissue, or non-neural tissue, and / or near or around visceral tissue or organs and non-neural tissue to treat acute pain, chronic pain, fecal or urinary incontinence, seizure disorders, movement disorders, obesity, spasticity, and to regulate other unpleasant neurological conditions.

[0043] In one exemplary embodiment shown in FIG. 6, the electrode 30 may be implanted on or adjacent to the target tissue 12, which includes a major peripheral nerve, such as the tibial nerve 25, that runs down the leg 26 of the patient 16. Depending on the application and the patient's anatomy, the electrode 30 may also be positioned on the skin adjacent to the target tissue 12, or just under the skin. The electrode 30 may include a single electrode or may include multiple electrodes 30. One or more electrodes 30 may be positioned adjacent the tibial nerve 25 at a desired location along its length. One or more electrodes 30 may be partially or completely wrapped around a segment of the tibial nerve 25. The electrical signal generator 40 may be external to the patient 14 and may be electrically coupled to the electrode 30 wirelessly, for example, electromagnetically via an antenna, inductively via an inductive coil, or via any other suitable wireless arrangement. Alternatively, the electrical signal generator 40 may be electrically coupled to the electrode 30 by a percutaneous or transcutaneous lead 18. Also alternatively, the electrical signal generator 40 may be implanted within the patient 14 along with the electrode 30. Using this arrangement, an exemplary embodiment of the neuromodulation system 10 may stimulate targeted neural and non-neural tissues of the tibial nerve 25 to provide treatment for one or more diseases and syndromes, including, but not limited to, acute pain, lumbar post-operative pain syndromes, complex regional pain syndromes, peripheral vascular disease and chronic limb ischemia, angina pain, diabetic pain, abdominal / visceral pain syndromes, brachial plexus neuritis, phantom limb pain, intractable pain due to spinal cord injury, mediastinal pain, Raynaud's syndrome, headaches and migraines, cervical neuritis, post-herpetic neuralgia, dizziness, tinnitus, hearing loss, and inflammatory pain such as arthritis, irritable bowel pain, osteoarthritis pain, and fibromyalgia.

[0044] In one exemplary embodiment of the neuromodulation system 10, the target tissue 12 may include neural and non-neural tissue of various organs of the patient 14. In one exemplary embodiment shown in FIGS. 7-8, the target tissue 12 includes neural and non-neural tissue of the stomach 27 of the patient 14. In this exemplary embodiment, the electrodes 30 of the neuromodulation system 10 may be implanted in or adjacent to the neural and non-neural tissue of the stomach 27, for example, in or adjacent to the tissue of the stomach wall of the stomach 27. Using this arrangement, the exemplary embodiment of the neuromodulation system 10 may stimulate the neural, e.g., parasympathetic, and non-neural, muscle tissue of the stomach 27. Thus, the exemplary embodiment of the neuromodulation system 10 may provide treatment for obesity by suppressing or reducing hunger in the patient 14 and / or regulating gastric motor function in the patient 14, and / or provide treatment to help the patient 14 control, among other symptoms, chronic nausea and vomiting associated with gastroparesis resulting from diabetes.

[0045] In one exemplary embodiment of the neuromodulation system 10 shown in FIG. 9, the target tissue 12 may include neural and non-neural tissue associated with the bladder 28 of the patient 14, such as the neural and non-neural tissue of the sacral nerves 29 associated with the bladder 28. The leads 18 and electrodes 30 of the neuromodulation system 10 may be percutaneously inserted into the patient 14 and extended across or adjacent the sacral foramina in the spine of the patient 14 until the electrodes 30 are positioned on or adjacent the appropriate sacral nerve 29. Using this arrangement, the exemplary embodiment of the neuromodulation system 10 may provide treatment to the patient 14 for overactive bladder symptoms, incontinence symptoms, and other symptoms by stimulating the neural and non-neural tissue of the sacral nerves 29 associated with the muscles and organs, such as the bladder 28, sphincters, and pelvic floor muscles involved in bladder control.

[0046] In each of the exemplary embodiments of the neuromodulation system 10 described above, the electrical signal generator 40 generates an electrical noise stimulation signal that is delivered by the electrodes 30 to the target tissue 12 of the patient 14 in a manner that optimizes and maximizes the electric field in the target tissue 12. This is effective to provide a durable therapeutic result to the patient 14 by producing long-term plastic functional changes in the target tissue 12. One or more sensors S1 and S2 may be implanted in or near the target tissue 12 of the patient 14, or may be located in line with or near the electrodes 30. As described in more detail below, the sensors S1 and S2 generate data indicative of physical parameters associated with the target tissue 12. In an exemplary embodiment, the data may include data indicative of the temperature or impedance of the target tissue 12, or some other data indicative of the physical condition of the target tissue 12. As also described in more detail below, the sensor data is received by the controller 50 and used to optimize and maximize the electric field for therapy. The controller 50 is also configured to respond to the sensor data by controlling the electrical signal generator 40 to control and reduce the strength of the electric field as necessary to quickly and automatically take action to help prevent possible tissue damage and patient discomfort without the need for any direct input or feedback from the patient.

[0047] C. Implantable Electrodes The electrodes 30 of the exemplary embodiment of the neuromodulation system 10 may be implantable within the patient 14 in, on, or around the target tissue 12 to be treated. Depending on the application and the anatomy of the patient 14, the electrodes 30 may also be placed on or under the skin of the patient 14. The electrodes 30 may be electrically coupled to the electrical signal generator 40 by a suitable lead or leads 18. Alternatively, the electrodes 30 may be wirelessly electrically coupled to the electrical signal generator 40 electromagnetically via a suitable antenna, inductively via a suitable inductive coil, or by any other suitable wireless arrangement.

[0048] The electrodes 30 receive an electrical noise stimulation signal generated by an electrical signal generator 40 as described in further detail below. The electrodes 30 generate an electric field for application to the target tissue 12, which may include neural tissue, non-neural tissue, or a combination thereof, as described.

[0049] Exemplary embodiments may include a single electrode 30 or multiple electrodes 30. The electrode 30 may include one or more conductive contacts that are integral with the lead 18 and electrically connected to one or more conductive wires of the lead 18. The multiple electrodes 30 may be arranged in a variety of configurations, for example, as shown in Figures 18A-18D and 19A-19C. In many cases, the electrode 30 will be carried by and located near the tip of the percutaneous lead 18, as shown in Figures 1-2 and 19A-19C. In other cases, the electrode 30 may be incorporated into a laminotomy or paddle lead 18, as shown in Figures 18A-18D.

[0050] Depending at least in part on the nature and location of the target tissue, the condition being treated, and the treatment being provided, the shape, size, and placement of the electrodes 30, as well as the spacing between the electrodes 30, can be selected to generate one or more electric fields in and around the target tissue 12 having desired characteristics. The electrodes 30 can generate one or more electric fields alternately, sequentially, or simultaneously in and around the target tissue 12. In addition, and as further described below, a particular electrode 30 and / or one or more pairs of electrodes 30, or other combinations of electrodes, can be selected to optimize and maximize the strength or intensity of the electric field in the target tissue 12 to provide optimal therapeutic results and / or to control the strength of the electric field in the target tissue 12 to prevent discomfort to the patient 14 and damage to the target tissue 12. For example, particular electrodes 30, or pairs or other combinations of electrodes 30, can be selected with different distances and / or different orientations, e.g., angles, relative to the target tissue 12, which can affect the impedance to current flow between the electrodes, the direction of current flow to the target tissue 12, the current density within the target tissue 12, and the strength and direction of the electric field within the target tissue 12. Also, for example, two or more electrodes 12 on the same or separate leads can be selected and bundled or used together as a single electrode with a larger surface area to increase the current density. For example, referring to FIG. 19A, electrodes 30c, 30g can be selected together to include a common cathode with electrode 30e as the anode, and referring to FIG. 19B, electrodes 30a, 30c can be selected together to include a common cathode with electrode 30g as the anode. Different electrodes 30 can also have different sizes and shapes, including surface areas, which can affect the current density and flow, as well as the strength of the electric field within the target tissue 12.

[0051] Furthermore, one or more electrodes 30 can be configured to function as monopolar, bipolar, or multipolar electrodes 30. For example, a pair of electrodes 30 can be configured to function in a bipolar manner, with one of the electrodes 30 acting as an anode and the other acting as a cathode, as shown, for example, in Figures 18A-18D and 19A-19b. In a particularly preferred bipolar arrangement, one electrode 30 of the bipolar electrode pair is located in, on, or adjacent to the target tissue 12 to generate an electric field in, on, and around the target tissue 12, and the other electrode 30 is located in or on a non-excitable tissue, such as fat, fascia, or myelin tissue. Alternatively, each electrode 30 of the bipolar electrode pair can be located in tissue, including non-excitable tissue, adjacent to the target tissue 12 to generate an electric field in, through, and around the target tissue 12. Preferably, regardless of the location of the electrode 30, the generated electric field is optimized and maximized by applying an electrical noise stimulation signal to the electrode 30 having a relatively high peak voltage, for example, in the range of about 5 V to about 200 V, while maintaining an acceptable relatively low current flow rate within the target tissue 12, for example, a current flow rate of about 10 mA to about 300 mA or less.

[0052] Alternatively, multiple electrodes 30 can function in a multipolar fashion, with some electrodes 30 acting as anodes and others as cathodes, or vice versa. The various electrodes 30 functioning in a bipolar or multipolar fashion can be carried on the same lead 18, as shown in Figures 18A-18D and 19C, or on separate leads 18, as shown in Figures 19A and 19B, or a combination of both. Still further, one or more electrodes 30 can function as one or more monopolar cathodes located in, on, or around the target tissue 12, and another electrode 30 is positioned a significant distance from the target tissue 12 such that most or all of the electric field is dissipated within the tissue of the patient 14. Alternatively, the implantable housing 16 can function as an anode in a monopolar configuration.

[0053] D. Implantable Sensors The one or more implantable sensors S1, S2 of the exemplary embodiment of the neuromodulation system 10 are implantable within the body of the patient 14, preferably within or near the target tissue 12. The sensors S1, S2 may be located in line with or near the electrodes 30. The sensors S1, S2 may each comprise a separate physical unit. Alternatively, one or more of the sensors S1, S2 may be integrated together and / or integral with one or more of the leads 18 or electrodes 30.

[0054] The sensors S1, S2 are preferably electrically coupled and in communication with the controller 50 via leads, which may include the leads 18 or may be separate from the leads 18. Alternatively, one or more of the sensors S1, S2 may be electrically coupled and in communication with the controller 50 wirelessly, for example using RF signal transmission. The sensors S1, S2 may be coupled and in communication with the controller 50 via a sensor interface 56, which is shown in FIG. 11 and described in more detail below.

[0055] The sensors S1, S2 are preferably adapted to generate sensor data indicative of one or more physical parameters associated with the target tissue 12. The sensor data may be generated and communicated to the controller 50 synchronously or asynchronously, and continuously or at regular or irregular time intervals. The sensors S1, S2 may actively communicate the sensor data to the controller 50, or the controller 50 may initiate communication with the sensors S1, S2 to retrieve the sensor data, for example, by polling the sensors S1, S2.

[0056] In an exemplary embodiment of the neuromodulation system 10, the sensors S1, S2 preferably include one or more of a temperature sensor and an impedance sensor. The temperature sensor may include a thermistor, a solid-state temperature sensor, or any other type of temperature sensor suitable for use not inconsistent with the purposes described herein. The impedance sensor may include a miniature impedance sensor, or an electrical conductivity sensor. The impedance sensor may include a semiconductor-based sensor, such as an integrated circuit, or any other type of impedance sensor or electrical conductivity sensor suitable for use not inconsistent with the purposes described herein.

[0057] The reason that the sensors S1, S2 preferably include temperature and / or impedance sensors, and more preferably at least one of each type, is because the temperature and impedance of the target tissue 12 of the patient 14 are physical parameters of the target tissue 12 that exhibit specific values, the range of values ​​of which clearly indicate the onset of possible damage and / or injury to the target tissue 12 and, potentially, the occurrence of discomfort to the patient 14. For example, one skilled in the art will recognize that the type of target tissue 12 of interest associated with the exemplary embodiment of the neuromodulation system 10 begins to suffer damage due to ablation at a temperature of about 42° C. Furthermore, as the target tissue 12 begins to suffer damage due to ablation, the impedance value of the tissue tends to decrease rapidly.

[0058] The temperature of the target tissue 12 varies in response to the level of current density and flow in the target tissue 12 induced by the application of an electric field to the target tissue 12 by the electrodes 30. Thus, values ​​and ranges of temperature and impedance parameters provided by the sensor data that are indicative of possible damage to the target tissue 12 will similarly indicate that the current density and flow induced by the electric field are too high. At the same time, relatively low temperatures and relatively large impedance values ​​and ranges indicate that the current density and flow are not at levels that will potentially cause damage to the target tissue 12.

[0059] Accordingly, the exemplary embodiments of the neuromodulation system 10 can use the temperature and impedance values ​​of the target tissue 12 provided by the sensor data to optimize and maximize the strength of the electric field to provide optimal therapeutic results without damaging the target tissue 12 or causing discomfort to the patient 14. The exemplary embodiments of the neuromodulation system 10 can also take immediate and automatic action in response to temperature and impedance values ​​indicative of possible damage to the target tissue 12 or discomfort to the patient 14 to control the electric field strength, including current density and flow rate, to be reduced, if necessary, to prevent such damage or discomfort, even without direct feedback from the patient 14. The sensors S1, S2 and controller 50, described further below, therefore comprise an automatic closed-loop feedback system.

[0060] E. Electrical signal generator The electrical signal generator 40 of the exemplary embodiment of the neuromodulation system 10 may be implantable within the patient 14, for example, within an implantable housing 16 as shown in Figures 1-5 and 7-11. Alternatively, the electrical signal generator 40 may be external to the patient 14, as shown in Figure 6.

[0061] The electrical signal generator 40 may comprise a separate physical unit or may be integrated with the controller 50 and / or one or more other electrical or electronic components described below in connection with the electrical signal generator 40 and the controller 50. The electrical signal generator 40 may also be integrated with an external controller 60, which is described in more detail below.

[0062] The electrical signal generator 40 may be electrically coupled to and in communication with the electrode 30 via one or more electrical leads 18, as shown in Figures 1-5 and 7-10. Alternatively, the electrical signal generator 40 may be wirelessly electrically coupled to the electrode 30, as shown in Figure 6. The electrical signal generator 40 may be wirelessly coupled to the electrode 30 electromagnetically via a suitable antenna, inductively via a suitable inductive coil, or by any other suitable wireless arrangement. The electrical signal generator 40 may be electrically coupled to the electrode 30 via an electrode interface 54, as shown in Figure 11 and described in more detail below.

[0063] The electrical signal generator 40 may also be electrically coupled to and in communication with the controller 50. The electrical signal generator 40 may be electrically coupled to the controller 50 via a wired connection or wirelessly.

[0064] The electrical signal generator 40 is adapted to generate an electrical noise stimulation signal for delivery through the electrodes 30 to the target tissue 12 of the patient 14 to generate an electric field in the target tissue 12 to stimulate or modulate the target tissue 12, thereby producing a therapeutic result as described herein. More specifically, the electrical signal generator 40 is adapted under the control of, and responsive to, the controller 50 to generate the electrical noise stimulation signal to optimize and maximize the electric field in the target tissue 12 to produce an optimal therapeutic effect without the data from the sensors S1, S2 indicating values ​​of physical parameters, such as temperature or impedance, associated with possible damage to the target tissue 12, as discussed above.

[0065] The electrical signal generator 40 is preferably adapted and configurable to generate an electrical noise stimulation signal having characteristics determined by parameters and commands received by the electrical signal generator 40, for example, in real time from the controller 50 or an operator, and / or by parameters and commands contained in an embedded or external program or storage device. For example, in response to and under the control of the controller 50, the electrical signal generator 40 may be adapted and configured to start and stop generating the electrical noise stimulation signal such that an exemplary embodiment of the neuromodulation system 10 can apply dosages of the electrical noise stimulation signal to the target tissue 12 for selected durations and at selected time intervals.

[0066] Also responsive to and under the control of the controller 50, the electrical signal generator 40 is preferably adapted and configurable to selectively generate an electrical noise signal having one or more selected peak voltage values ​​at frequencies within a selected frequency spectrum or at one or more selected bands of frequencies within the selected frequency spectrum, each of the selected bands having a selected bandwidth and center frequency. The electrical signal generator 40 is also preferably configurable to selectively generate an electrical noise signal having one or more selected peak voltage levels at one or more selected frequencies within the selected frequency spectrum and / or within one or more selected frequency bands within that spectrum. The particular characteristics of the electrical noise stimulation signal that the electrical signal generator 40 is actually controlled to generate will depend on a variety of factors, including the nature and location of the target tissue, the nature and severity of the condition being treated, and the like. For ease of understanding, references herein to the "peak voltage level" of the electrical noise stimulation signal refer to a unipolar peak value of the electrical noise stimulation signal, i.e., a positive peak value or a negative peak value, and not a peak-to-peak value that is approximately twice the peak value.

[0067] More specifically, the electrical signal generator 40 is preferably adapted to generate the electrical noise stimulus signal using one or more forms of synthesis, alone or in combination, including subtractive synthesis, additive synthesis, component modeling synthesis, wavetable synthesis, linear arithmetic synthesis, phase distortion synthesis, frequency modulation synthesis, and sample-based synthesis. Furthermore, the electrical signal generator 40 is preferably adapted to generate the electrical noise stimulus signal to include at least one of the noise forms, including Gaussian noise, white noise, pink noise, Brownian noise, red noise, and gray noise.

[0068] Also, more specifically, the electrical signal generator 40 is preferably adapted and configurable to selectively generate an electrical noise stimulation signal having a peak voltage value in the range of about 5 V to about 200 V and over a spectrum of frequencies ranging from about 50 Hz, and more preferably from about 100 Hz to about 750 KHz. It will be appreciated that within these ranges, the peak voltage value and frequency selected for use will depend, among other considerations, on the nature and location of the tissue being stimulated or modulated and the nature and severity of the condition being treated.

[0069] Alternatively, other forms of noise stimulation signals may be substituted for the electrical noise stimulation signals described above, and other generators of such noise stimulation signals may be substituted for the electrical signal generator 40 to similarly stimulate the target tissue 12, provide the same or similar treatment for the same condition, and achieve the same or comparable therapeutic effect. For example, a magnetic noise stimulation signal, an electromagnetic noise stimulation signal, or a mechanically induced noise stimulation signal, such as an ultrasonic noise stimulation signal, may be substituted for the electrical noise stimulation signal, and a magnetic noise generator, an electromagnetic noise generator, or an ultrasonic noise generator may be substituted for the electrical signal generator 40.

[0070] F. Controller The controller 50 of the exemplary embodiment of the neuromodulation system 10 may be implantable within the patient 14, for example, in an implantable housing 16, as shown in Figures 1-5 and 7-11. The controller 50 may include a separate physical unit or may be integrated with the electrical signal generator 40 and / or with one or more other electrical or electronic components described in connection with the electrical signal generator 40 and the controller 50.

[0071] The controller 50 may include a general-purpose microprocessor or a dedicated processor such as a microcontroller. The microprocessor may be a single chip processor or may be implemented with multiple components. The controller 50 may also include a computer readable memory for storing an operating system, program code or instructions, as well as data and parameters for controlling the operation of the controller 50. The memory may include random access memory (RAM), read only memory (ROM), and / or other volatile and / or non-volatile memory types. The program code, data, etc. may also reside on a removable storage medium, e.g., CD-ROM, PC card, USB drive, and may be loaded or installed as needed. Using instructions retrieved from the memory, the microprocessor may control the receipt and manipulation of input data from components of the neuromodulation system 10, such as the sensors S1, S2, and the output and communication of data, parameters, instructions, or commands to other components, such as the electrical signal generator 40.

[0072] The controller 50 may be coupled to and control the electrode interface 54. The electrode interface may be enclosed within the implantable housing 16 along with the controller 50. The electrode interface 54 may comprise a separate component or may be integrated with the controller 50. The electrode interface 54 is preferably located between the output of the electrical signal generator 40 and the electrodes 30. The electrode interface 54 is adapted to receive as an input an electrical noise stimulation signal from the electrical signal generator 40 and selectively connect as an output the electrical noise stimulation signal to one or more selected electrodes 30 via one or more leads 18. The electrode interface 54 may include, for example, a MUX or similar controllable selector for selectively connecting an input, e.g., the electrical noise stimulation signal, to one or more selected outputs, e.g., the electrodes 30, via the leads 18.

[0073] The controller 50 may be coupled to the sensors S1, S2 and may communicate with and receive sensor data from the sensors through a sensor interface 56, which may be enclosed within the embeddable housing 16 along with the controller 50. The sensor interface 56 may include separate components or may be integrated with the controller 50. The sensor interface 56 is preferably adapted to receive sensor data from the sensors S1, S2 and, if necessary, pre-process it for use by the controller 50. To that end, the sensor interface 56 may include one or more data buffers, filters, and any other components necessary or desirable for receiving, cleaning, formatting, etc., the sensor data for use by the controller 50.

[0074] The controller 50 may be coupled to a communication interface 58, which may be enclosed within the implantable housing 16 along with the controller 50. The communication interface 58 may comprise a separate component or may be integrated with the controller 50. The communication interface 58 is preferably adapted to enable the controller 50 to communicate with other components of the exemplary embodiment of the neuromodulation system 10, such as the external controller 60 and user interface 62 shown in FIG. 10, and / or with other devices, such as remote devices of a telecommunications network 80 shown in FIG. 12 and described below. The communication interface 58 preferably includes wired and / or wireless connections, interfaces, and protocols necessary to implement and support such communications. Suitable connections, interfaces, and protocols may include, for example, Ethernet, Wi-fi, USB, Bluetooth, as well as various other network, internet, and cellular connections, interfaces, and protocols identified below in connection with the telecommunications network 80.

[0075] The controller 50 is preferably adapted and configurable to automatically control the electrical signal generator 40 to generate and deliver the electrical noise stimulation signal to the target tissue 12 in a manner that optimizes and maximizes the electric field in the target tissue 12 by maximizing the voltage component of the electric field while limiting the current density and flow rate in the target tissue 12 to a level low enough so as not to create a thermal effect in the target tissue 12 that may cause damage to the target tissue 12 and discomfort to the patient 14. In this manner, the controller 50 can automatically control the electrical signal generator 40 to generate and deliver an electrical noise stimulation signal that optimizes and maximizes the electric field in the target tissue 12 to produce an optimal therapeutic effect, although the sensor data from the sensors S1, S2 does not indicate the value of a physical parameter of the target tissue 12, such as temperature or impedance, that is associated with possible damage to the target tissue 12.

[0076] The inventors have discovered that by optimizing and maximizing the electric fields generated in the neural, e.g., spinal cord or nerve tissue, and non-nerve, e.g., muscle or myelin, target tissues 12 in this manner (high voltage - low current density and flow rate), it is possible to deliver a larger dose (i.e., higher voltage levels for a longer period of time) of electrical noise stimulation signal to the target tissue 12 without causing overheating and damage to the target tissue 12. The inventors have further discovered that this, in turn, produces long-term plastic functional changes in the target tissue 12, resulting in a more complete inhibition of the nerve or blocking of its function, which may last for a relatively long period of time (days to weeks). As a result, relatively short, infrequent treatments can provide effective therapeutic results essentially continuously, without the need for very frequent or substantially continuous application of electrical modulation signals and the associated substantially continuous maintenance of the device. The inventors have also found that the target tissue 12 is less likely to "tolerate" the anatomical changes caused by repeated administration, a phenomenon that plagues conventional spinal cord stimulation (SCS) systems.

[0077] In order to optimize and maximize the electric field to have the described voltage and current characteristics, the controller 50 is preferably adapted and configurable to determine peak impedance values ​​for the flow of electrical current in the target tissue 12 at one or more frequencies within a selected portion or within the full spectrum of frequencies of the electrical noise stimulation signal that the electrical signal generator 40 is intended to potentially deliver to the target tissue 12 for treatment. Once the peak impedance values ​​and corresponding frequencies are determined, the controller 50 can control the electrical signal generator 40 to selectively generate and deliver to the target tissue 12 an electrical noise stimulation signal in one or more selected relatively narrow frequency bands having center frequencies corresponding to the peak impedance values. The controller 50 can also be configurable to control the electrical signal generator 40 to adjust characteristics of the noise signal within the selected bands, such as, for example, the peak voltage value of the signal, the center frequency of the band, and the bandwidth. In this manner, exemplary embodiments of the neuromodulation system 10 can optimize and maximize the electric field generated within the target tissue 12 by generating and delivering an electrical noise stimulation signal whose peak voltage value is selected to maximize the voltage component of the electric field, while maintaining current density and flow rate at relatively low levels to prevent overheating and damage to the target tissue 12.

[0078] The controller 50 may be configured to determine the resulting impedance peak value and corresponding frequency in any suitable manner. Several suitable exemplary approaches are described below. In each approach, the electrode 30 is first inserted into the patient 14 in a conventional manner and positioned as desired in relation to the target tissue 12 as described herein.

[0079] According to one approach, the controller 50 is preferably configurable to control the electrical signal generator 40 to generate and deliver to the target tissue 12 via the electrodes 30 an electrical noise stimulation signal having a selected peak voltage level and a selected frequency spectrum that includes the full range of frequencies of the electrical noise stimulation signal that the electrical signal generator 40 is intended to potentially deliver to the target tissue 12 for treatment.

[0080] For example, as shown in Figure 13, the electrical noise stimulus signal 70 may have a selected peak-to-peak voltage of approximately 300 V, with selected peak values ​​of approximately +150 V and -150 V. Note that for ease of illustration, Figure 13 does not show the entire electrical noise stimulus signal 70, but only the portion of the signal that approximates the peak values. As shown in Figure 14, the power spectrum 72 of the electrical noise stimulus signal 70 is substantially constant over the entire frequency bandwidth.

[0081] As described herein, the frequency spectrum of the electrical noise stimulation signal 70 may be selected based on a variety of considerations, including, but not limited to, the nature of the tissue being stimulated or modulated, the nature and severity of the condition or disease being treated, the location and orientation of the electrodes 30 relative to the target tissue, and others. As previously mentioned, a suitable bandwidth may include about 50 Hz, and more preferably, from about 100 Hz to about 750 KHz.

[0082] The controller 50 can be further configured to control the electrical signal generator 40 to generate and deliver to the target tissue 12 via the electrodes 30 an electrical noise stimulation signal that includes a band of frequencies within a selected frequency spectrum having a center frequency and a relatively narrow bandwidth. Both the center frequency and the bandwidth are selectable and can be adjusted or changed by the controller 50. The bandwidth can be selected based on the degree of resolution desired to determine impedance peak values ​​and the corresponding frequencies at which they occur. For example, the bandwidth could be selected to be in the range of about 100 Hz to about 1 KHz. Alternatively, the controller 50 can be configured to generate and deliver a non-noise electrical stimulation signal, i.e., a periodic signal, that includes a single selectable frequency.

[0083] The controller 50 can be further configured to control the electrical signal generator 40 to continuously generate and deliver electrical noise stimulation signals having the same relatively narrow bandwidth but with multiple different center frequencies spanning a selected portion or entire spectrum of frequencies that the electrical signal generator is intended to potentially deliver to the target tissue 12 for treatment. The controller 50 can be configured to control the electrical signal generator 40 to continuously sweep or scan the center frequency across the entire frequency spectrum, or a selected portion or portions of the entire spectrum, or alternatively, to adjust the center frequency in one or more fixed increments or steps. For example, the controller 50 can be configured to control the electrical signal generator 40 to continuously or discretely scan or sweep the center frequency from the lowest frequency to the highest frequency across the entire spectrum, or a selected portion or portions of the entire spectrum. Alternatively, the controller 50 may be configurable to control the electrical signal generator to continuously or discretely scan a non-noise electrical stimulation signal, i.e., a periodic signal, including a single selectable frequency, across the entire spectrum, or a selected portion or portions of the entire spectrum.

[0084] The controller 50 can be configured to receive and monitor sensor data from the sensors S1, S2 while the electrical noise stimulation signal is delivered to the target tissue 12 via the electrodes 30. The controller 50 can be configured to determine from the sensor data an impedance to current flow in the target tissue 12 at each center frequency, or a subset of center frequencies, of the narrowband electrical noise stimulation signal. Accordingly, the impedance values ​​can be substantially continuous or a series of discrete values. FIGS. 15A-15C show several examples of impedance (Z) 74 versus frequency, demonstrating how the magnitude of impedance (Z) 74 can change as the center frequency of the narrowband electrical noise stimulation signal is scanned or swept substantially continuously across a selected frequency spectrum. The double-headed arrows in each diagram indicate that the diagram shows only a portion of the impedance (Z) 74 values ​​for the corresponding portion of the frequencies scanned or swept in either direction.

[0085] The controller 50 can be configured to determine from the impedance (Z) sensor data those peaks or peaks at which the maximum magnitude and maximum frequency occurs. The controller 50 also determines the center frequency (f c ), and the lower and upper frequency limits (f 1 , f 2 ) can be preferably configured to determine the center frequency (f c ) will generally correspond to the center frequency of the narrow frequency band of electrical noise stimulus signal that caused the peak, but may vary for various reasons. Similarly, the lower and upper frequencies (f 1 , f 2The upper and lower frequencies (f) of each peak will generally correspond to the lower and upper frequencies of the narrow frequency band of the electrical noise stimulus signal that produces the peaks, but may vary. The band of frequencies corresponding to the peaks, like the band of frequencies of the electrical noise stimulus signal that produced the peaks, will comprise a relatively small subset of the total frequencies of the selected frequency spectrum. 1 , f 2 ) can be determined in a number of ways, including, for example, treating the shape of the peak as a band-pass filtered signal and applying conventional calculations to determine the attenuation or cutoff frequency of the filter.

[0086] Different impedance peaks having different magnitudes may occur at different frequencies within the entire spectrum or within the range of frequencies scanned or swept. For example, FIG. 15A shows a first peak in impedance (Z) 74 having a first magnitude and a corresponding center frequency (f c ), and FIG. 15B shows a second peak in impedance (Z) 74 having a second value of magnitude and a different center frequency (f) at a corresponding second frequency value. c ), and FIG. 15C shows a third peak in impedance (Z) 74 having a magnitude of a third value and a corresponding center frequency (f c) is shown. The controller 50 is preferably configurable to distinguish or filter the detected impedance peaks and reserve for use only their center frequencies and relatively narrow frequency bands corresponding to peaks with sufficient magnitude of impedance in providing therapy to effectively optimize and maximize electric fields having desired characteristics of voltage and current as described herein. For example, impedances in the range of about 200 ohms to about 10,000 ohms may be appropriate for use depending on a variety of factors including the selected value of the peak voltage of the applied electrical noise stimulation signal, the target tissue, the nature and severity of the condition being treated, the configuration and location of the electrodes relative to the target tissue, and other factors. It will be appreciated that for ease of understanding, the aforementioned ranges of impedance values ​​(Z) are intended to include the contributions of the impedance of the target tissue, tissue interfaces, lead wires, and electrodes.

[0087] According to another approach to determining the impedance peak value and the corresponding frequency and frequency band at which the impedance peak value occurs, the controller 50 is preferably configurable to control the electrical signal generator 40 to generate and deliver, via the electrodes 30, to the target tissue 12, an electrical noise stimulation signal having a selected peak voltage level and a selected frequency spectrum that includes the full range of frequencies that the electrical signal generator 40 is intended to potentially deliver to the target tissue 12 for treatment, as shown in Figures 13-14. The electrical noise stimulation signal can have the same parameters as those of the approach described above.

[0088] The controller 50 can be configured to receive and monitor sensor data from the sensors S1, S2 while the electrical noise stimulation signal is applied to the target tissue 12 via the electrodes 30. The controller 50 can be preferably configured to determine from the sensor data an impedance to current flow in the target tissue 12 at one or more frequencies and frequency bands within a selected frequency spectrum. For example, the controller 50 can be configured to apply a band pass filter to the impedance sensor data to determine an impedance magnitude to an electrical noise stimulation signal that includes one or more narrow frequency bands. The band pass filter can have a selected pass band and a discrete or continuously variable center frequency. The band pass filter can be applied to the impedance sensor data in real time, or the sensor data can be stored for processing by the filter. The filter can generate a set of substantially continuous impedance values ​​related to frequency, similar to those shown in Figures 15A-15C, or a set of discrete values ​​at discrete values ​​of frequency. The controller 50 can be configured to process the filtered impedance sensor data in a manner similar to that described above to determine impedance peaks, impedance magnitudes at the peaks, and the corresponding frequencies and frequency bands at which they occur for use in optimizing and maximizing the electric field to provide therapy.

[0089] It should be noted that all of the above mentioned techniques are examples, and that the impedance peaks and the magnitude of the peaks, as well as the frequencies and frequency bands at which they occur, can be determined in other ways without departing from the broad concepts present in the exemplary embodiments of the neuromodulation system 10 described herein. It should further be noted that regardless of the technique used, it is preferred that the controller 50 monitors the sensor data from the sensors S1, S2 while the technique is being performed. In that way, if the sensor data corresponding to a physical parameter of the target tissue 12, such as impedance or temperature, exhibits a value indicative of possible damage to the target tissue 12, such as excessive heating, the controller 50 can quickly and automatically respond and take action by controlling the electrical signal generator 40 to control the strength of the electric field (which may include reducing the current density and flow rate) to prevent damage to the target tissue 12 and discomfort to the patient 14. To this end, the sensors S1, S2 and the controller 50 include an automatic closed-loop feedback control system that does not require any direct feedback from the patient 14. Additionally, to further reduce the risk of damage to the target tissue 12 or discomfort to the patient 14 while determining the impedance peaks and peak magnitudes, the controller 50 can control the electrical signal generator 40 to generate and deliver an electrical noise stimulation signal having a peak voltage value that is less than a peak voltage value that can be used to optimize and maximize the electric field for the actual treatment.

[0090] Several exemplary techniques for controlling the strength of the electric field are described in further detail below. The same techniques are equally applicable when the electrical noise stimulus signal is applied to the target tissue 12 prior to treatment to determine impedance peaks, and when the electrical noise stimulus signal is applied to the target tissue 12 to provide treatment. Furthermore, the same techniques are applicable to control the electric field to optimize and maximize the strength of the electric field by maximizing the voltage component while limiting the current density and flow rate to provide optimal treatment to the target tissue 12, and to reduce the strength of the electric field, including reducing the current density and flow rate, to prevent damage to the target tissue 12 and discomfort to the patient 14.

[0091] 18A-18D and 19A-19C, in connection with determining the impedance peaks and peak values ​​and the frequencies at which they occur, it is also noted that the controller 50 is preferably configurable to control the electrode interface 54, as described above, to select a number of different combinations of electrodes 30 to deliver electrical noise or non-noise electrical stimulation signals to the target tissue 12. As previously described, the location, orientation, and distance of the electrodes 30 relative to the target tissue 12 can have a substantial effect on the impedance to current flow and the strength of the electric field within the target tissue 12 in response to a particular electrical noise stimulation signal.

[0092] The controller 50 may be configured to perform any of the techniques described above multiple times using multiple different combinations of electrodes 30 to determine the impedance peaks and peak values ​​and corresponding frequencies for each of multiple combinations of electrodes 30. For example, for the paddle-type leads 18 and electrodes 30 shown in Figures 18A-18D, the controller 50 may be configured to determine the peaks and peak values ​​and corresponding frequencies using one, some or all of the selected electrode combinations 30a-30d, 30A-30e, 30a-30f, 30c-30d, 30c-30e, 30c-30f, 30b-30d, 30b-30e, 30b-30f, 30a-30b, 30a-30c, or other selected combinations in a unipolar, bipolar, or multipolar configuration. Similarly, for percutaneous leads 18 and electrodes 30 such as those shown in FIGS. 19A-19C, the controller 50 can be configured to determine the peaks, peak values, and corresponding frequencies using one, some, or all of selected electrode combinations 30a-30d, 30a-30f, 30b-30e, 30g-30e, 30c-30f, 30a-30g, 30c-30g, 30c / 30g-30e, 30a-30c, 30a-30g, 30a / 30c-30g, 30b-30g, or other selected combinations in a unipolar, bipolar, or multipolar configuration.

[0093] Additionally, the selected combination of electrodes 30 may be on different leads 18, as shown in Figures 19A-19B, or on the same lead 18, as shown in Figures 18A-18D and 19C. The selected combination of electrodes 30 may include a combination of one or more electrodes 30 located in, on, or adjacent to the target tissue 12, as shown in Figures 18A-18C and 19A-19B, and one or more electrodes 30 located at a distance from the target tissue 12, in non-neural tissue, such as myelin or fascia, for example. The selected combination of electrodes 30 may include a combination of all of the electrodes 30 located in, on, or adjacent to the target tissue 12, as shown in Figures 18D and 19C.

[0094] When continuing to use the exemplary embodiment of the neuromodulation system 10 to provide therapy, the controller 50 can be configured to use information regarding the impedance peaks and peak values ​​and the corresponding frequencies at which they occur for each of a plurality of selected electrode 30 combinations to select a particular combination of electrodes 30 to deliver an electrical noise stimulation signal to the target tissue 12 that optimizes and maximizes the electric field within the target tissue 12 having the desired voltage and current characteristics described herein to produce an optimal therapeutic outcome. This can be done either under operator control or automatically by the controller 50.

[0095] To provide therapy to the patient 14, the controller 50 can be configured in a number of ways to control the electrical signal generator 40 to optimize and maximize the electric field in the target tissue 12 having the desired voltage and current characteristics to provide optimal therapeutic results without sensor data indicative of possible damage to the target tissue 12. In one exemplary approach, the controller 50 can be configured to control the electrical signal generator 40 to limit the administration of the electrical noise stimulation signal, and therefore the electric field, to the target tissue 12 by limiting the duration that the electrical signal generator 40 delivers an electrical noise stimulation signal having a peak voltage value within the preferred range described herein to the target tissue 12. This, in turn, gradually limits the current density and flow rate and limits heating of the target tissue 12 to produce optimal therapeutic effects without sensor data indicative of the value of a physical parameter, e.g., temperature or impedance, associated with possible damage to the target tissue 12 or discomfort to the patient 14. For example, the inventors have found that in some cases, electrical stimulation signals having peak voltage values ​​within a suitable range can be delivered to the target tissue 12 to generate optimized and maximized electric fields in as little as four minutes of administration, effectively reducing pain for up to a week or more without causing any damage to the target tissue 12 or discomfort to the patient 14.

[0096] In another exemplary approach, the controller 50 can be configured to optimize and maximize the electric field in the target tissue 12 by controlling the electrical signal generator 40 to generate and deliver to the target tissue 12 one of a plurality of narrow frequency bands that have been previously determined to correspond to a peak value of the impedance of the target tissue 12. Additionally, the controller 50 can be configured to control the electrical signal generator 40 to adjust the center frequency of the frequency band upward or downward to further control and adjust the electric field, and monitor sensor data to determine the effect of the adjustments on the impedance, voltage, current density and flow rate, and temperature of the target tissue 12 to optimize and maximize the electric field in the target tissue 12.

[0097] In another exemplary approach, the controller 50 can be configured to optimize and maximize the electric field in the target tissue 12 by selecting a first frequency band corresponding to a first peak value of the impedance of the target tissue 12 from a plurality of frequency bands previously determined to correspond to peak values ​​of the impedance of the target tissue 12. The controller 50 can be further configured to control the electrical signal generator 40 to generate and deliver an electrical noise stimulation signal to the target tissue 12 in the selected first frequency band. The controller 50 can be further configured to monitor the sensor data, make a determination regarding a characteristic of the electric field generated in the target tissue 12 by the electrical noise stimulation signal in the first frequency band, select a second frequency band corresponding to a second peak value of the impedance of the target tissue 12, and control the electrical signal generator 40 to generate and deliver an electrical noise stimulation signal to the target tissue 12 in the selected second frequency band. The controller 50 can be configured to continue selecting additional frequency bands corresponding to the previously determined impedance peak values ​​and control the electrical signal generator 40 to generate and deliver an electrical noise stimulation signal in each selected band until the most optimized electric field possible, e.g., the highest voltage component with an acceptably low current density and flow rate, is generated within the target tissue 12.

[0098] In another exemplary approach, the controller 50 may be configured to control the electrode interface 54 to select a first electrode 30 or combination of electrodes 30 from the plurality of electrodes 30 and possible combinations of the plurality of electrodes 30, as described above. The controller 50 may be further configured to control the electrical signal generator 40 to generate and deliver an electrical noise stimulation signal to the target tissue 12 via the first selected electrode 30 or combination of electrodes 30 to generate an electric field in the target tissue 12. The controller 50 may be further configured to monitor the sensor data, make a determination regarding a characteristic of the electric field generated in the target tissue 12 using the first selected electrode 30 or combination of electrodes 30, select a second electrode 30 or combination of electrodes 30, and control the electrical signal generator 40 to generate and deliver an electrical noise stimulation signal to the target tissue 12 using the second electrode 30 or combination of electrodes 30. The controller 50 can be configured to continue selecting additional electrodes 30 or combinations of electrodes 30 to deliver the electrical noise stimulation signal to the target tissue 12 until the most optimized electric field possible, e.g., the highest voltage component with an acceptably low current density and flow rate, is generated within the target tissue 12.

[0099] It will be appreciated that any one or more of the above techniques, as well as other techniques, may be used alone or in combination, and that the controller 50 may also be configured to control the electrical signal generator 40 to vary or adjust the peak voltage value of the electrical noise stimulus signal in combination with any one or more of the above techniques or other techniques.

[0100] From the foregoing description of exemplary techniques for optimizing and maximizing the electric field, it will also be appreciated that the controller 50 is adapted and configured to automatically optimize and maximize the electric field in response to sensor data, even in the absence of direct feedback from the patient 14. Additionally, and if desired, an operator or user of the exemplary embodiment of the neuromodulation system 10 can further adjust the optimized electric field based on subjective input regarding the sensations of the patient 14 in response to application of the automatically optimized electric field to the target tissue 12 in order to optimize the subjective sensations felt by the patient 14 and the subjective therapeutic experience of the patient. For example, the operator or user can have the patient 14 being treated compare and describe the sensations the patient 14 subjectively feels when the center frequency of the selected frequency band is adjusted, when different frequency bands are selected, and / or when different combinations of electrodes 30 are selected. The operator or user can then provide corresponding input to the controller 50 to control the electrical signal generator 40 to adjust parameters of the electrical noise stimulation signal and / or to adjust the selection of electrodes 30 in order to adjust the electric field generated in the target tissue 12 and optimize the subjective sensations felt by the patient and the therapeutic experience of the patient.

[0101] Further, with regard to optimizing and maximizing the electric field, the controller 50 is preferably configured to control the electrical signal generator 40 to generate an electrical noise stimulation signal having peak voltage values ​​ranging from about 5V to about 200V across a frequency spectrum of about 50Hz, and more preferably from about 100Hz to about 750KHz. Within each range, the peak voltage values ​​and frequency values ​​selected for treatment will depend, among other considerations, on the nature and location of the tissue being stimulated or modulated and the nature and severity of the condition being treated.

[0102] Still further, within the aforementioned voltage and frequency ranges, the controller 50 is also preferably configured to control the electrical signal generator 40 to generate and deliver an electrical noise stimulation signal to generate an optimized and maximized electric field within the target tissue 12 having a strength value in the range of about 1,000 V / m to about 500,000 V / m, with a current flow rate in the range of about 10 mA to about 300 mA or less.

[0103] As mentioned above, the controller 50 is preferably configured to monitor the sensor data generated by both sensors S1, S2 while the electrical noise stimulation signal is being delivered to the target tissue 12 to determine impedance peaks and peak values ​​and stimulate or modulate the target tissue 12 to provide therapy. The controller 50 is preferably configured to rapidly and automatically respond to sensor data indicative of physical parameters, such as impedance and / or temperature values ​​associated with potential damage to the target tissue 12, to rapidly and automatically take steps to control and reduce the strength of the electric field and / or reduce current density and flow rate to prevent damage to the target tissue 12 and discomfort to the patient 14, as previously mentioned. To this end, as previously mentioned, the sensors S1, S2 and the controller 50 include an automatic closed loop feedback system in which no direct feedback from the patient 14 is required.

[0104] For example, as shown in Figures 16-17, while an electrical noise stimulus signal is applied to the target tissue 12 at a selected frequency band, the value of the monitored impedance (Z) 76 derived from the sensor data generated by one or more of the sensors S1, S2 may be expected to remain relatively stable. Similarly, the value of the monitored temperature 78 of the target tissue 12 derived from the sensor data generated by one or more of the sensors S1, S2 may be expected to remain relatively stable and possibly increase with increasing dosage, e.g., increasing duration of the electrical noise stimulus signal, or increasing peak voltage value. However, if or when the value of the monitored temperature 78, as shown by the horizontal dashed line in Figure 17, rises to a predetermined level or value indicative of possible damage to the target tissue 12, the temperature action point 79 has been reached. Similarly, if or when the value of the monitored impedance 76, as shown by the horizontal dashed line in Figure 16, decreases to a predetermined level or value indicative of possible damage to the target tissue 12, the impedance action point 77 has been reached. The controller 50 can be configured to determine when an action point has been reached and to immediately and automatically take action as described herein.

[0105] The predetermined level or value of temperature corresponding to temperature action point 79 can be a predetermined relative or absolute value, such as 42° C., or a range of temperature, or another derived temperature parameter, such as an average, mean, or slope. Similarly, the predetermined level or value of impedance corresponding to impedance action point 77 can be a predetermined absolute or relative value, such as a 50% decrease, or a range of absolute or relative impedance values, or another derived impedance parameter, such as an average, mean, or slope.

[0106] Typically, a relatively rapid increase in temperature value and a relatively rapid decrease in impedance value corresponding to time can be expected to both be indicative of possible damage to the target tissue 12, but this is not always the case. Accordingly, the controller 50 may be configured to monitor and use the sensor data values ​​of either physical parameter, but preferably both, in determining whether and when to take action.

[0107] With regard to actions that the controller 50 may take to control the strength of the electric field or the current density and flow rate to prevent damage to the target tissue 12 and discomfort to the patient 14, it will be appreciated that any one or more, or combination of, the above-described actions for controlling the electric field to optimize and maximize the electric field may also be used to control the electric field to reduce its strength, including reducing the current density and flow rate in the target tissue 12. Thus, such techniques, e.g., any one or more, or combination of adjusting the center frequency, selecting a different frequency band, and selecting different electrodes, may include one or more actions taken by the controller 50 in response to sensor data indicative of physical parameters, e.g., temperature and impedance values, associated with possible damage to the target tissue 12.

[0108] G. User Interface As shown in FIG. 10, an exemplary embodiment of the neuromodulation system 10 may, but need not, include a user interface 62 external to the patient 14. If included, the user interface 62 may include a conventional computer or computer system and / or one or more peripherals, such as a conventional display, a keyboard, a keypad, and a pointing device, such as a mouse. As shown in FIG. 12, the user interface 62 may also include a mobile device 84, such as a tablet computer. The user interface is adapted and configured to allow a user or operator to interact with the controller 50 either directly, or indirectly via an external controller 60, described below. The user interface 62 may include a separate unit or component, or may be integrated in whole or in part with the external controller 60.

[0109] The user interface 62 may be used to communicate with the controller 50 and the external controller 60 to allow power to be increased or decreased to the exemplary embodiment of the neuromodulation system 10, to perform system setup, to input start / stop commands for generating the electrical noise stimulation signal, to make adjustments to the parameters and characteristics of the electrical noise stimulation signal for either future or real-time use, and to otherwise allow a user or operator to control the exemplary embodiment of the neuromodulation system 10. The user interface 62 may also be adapted and configured to receive and display various items of information to allow a user or operator to monitor the status, operation, and functionality of the exemplary embodiment of the neuromodulation system 10 and to intervene if necessary. Such information may include, for example, sensor data, such as temperature and impedance values, the identity of the selected electrodes, and various characteristics of the electrical noise stimulation signal, such as voltage levels, current intensity levels, field strength, center frequency, and frequency bandwidth. Such information may also include treatment information, including the selected administration time and time remaining. Information may also include information regarding the status of the system, such as the remaining charge level of the battery, including the internal power source 52, which will be described further below, the internal temperature of the implantable housing 16, and the like.

[0110] H. External Controller As shown in Figure 10, an exemplary embodiment of the neuromodulation system 10 may, but need not, include an external controller 60 that is external to the patient 14. If included, the external controller 60 may include a conventional computer or computer system, or may also include a mobile device 84, such as a tablet computer, as shown in Figure 12. The external controller 60 may include a separate unit or component, or may be integrated in whole or in part with the user interface 62.

[0111] The external controller 62 may be electrically coupled to and adapted and configured to communicate with the controller 50 via leads 65 or wirelessly. The wireless communication may be by any suitable wireless arrangement, including electromagnetically via RF transmission with a suitable antenna, inductively via a suitable inductive coil arrangement, or by any other suitable wireless arrangement. Similarly, the external controller 60 may also be adapted and configured to couple to and communicate with a remote device via an electrical communication network 80 as shown in FIG. 12.

[0112] The external controller 60 may be adapted and configured to incorporate some or all of the functionality and operability of the controller 50 described herein, such that in some embodiments there may be no implantable controller 50. Alternatively, the external controller 60 may be adapted and configured in combination with a user interface 62 to allow a user or operator to externally control some or all of the functionality and operation of the controller 50, including, for example, generation and control of the electrical noise stimulation signal, selection of electrodes 30 and application of the electrical noise stimulation signal to the target tissue 12, and monitoring of sensor data generated by the sensors S1, S2.

[0113] The external controller 60 may also be adapted and configured to control, in whole or in part, the use of an external power source 64, shown in FIG. 10 and described further below, to remotely provide power to components within the implantable housing 16 shown in FIG. 11. The external controller 60 may be adapted and configured to control the use of the external power source 64 to, for example, provide a source of power for the internal power source 52, if the internal power source includes a transformer or voltage converter, and to provide power to recharge the internal power source 52, if the internal power source includes a rechargeable battery. In embodiments without an internal power source 52, the external controller 60 may be adapted and configured to control the use of the external power source 64 to directly provide power to other components of the implantable housing 16, including the electrical signal generator 40, to generate the electrical noise stimulus signal. Additionally, in embodiments in which the electrical signal generator 40 is external to the patient 14, the external controller 60 may be adapted and configured to control the use of the external power source 64 to directly provide power to the external electrical signal generator 40.

[0114] I. Power supply The internal power source 52 may be enclosed within the implantable housing 16 and may be implantable within the patient 14. The internal power source 52 may be electrically coupled to and provide power for operation to the electrical signal generator 40, the controller 50, and other components enclosed within the implantable housing 16, including the electrode interface 54, the sensor interface 56, and, to the extent necessary, the communication interface 58.

[0115] The internal power source 52 may include an internal power source, such as a transformer, voltage converter, or the like, that is powered by an external power source, such as the external power source 64 shown in Figure 11 and described below. In that case, the internal power source 52 may be coupled to and receive power from the external power source via a wired connection or wirelessly, for example, via a suitable induction coil arrangement.

[0116] However, the internal power supply 52 would preferably include a self-contained power source, such as a suitable battery or batteries. Moreover, the battery or batteries would preferably be of a rechargeable type. Suitable batteries may include lithium ion, lithium air, lithium / iodine, and lithium / manganese oxide type batteries, which are commercially available from a number of sources. The battery or batteries would preferably be rechargeable, either via a wired connection to an external power source, such as external power supply 64, or wirelessly, for example, via a suitable induction coil arrangement.

[0117] The external power source 64 is preferably located external to the patient 14 and adapted to provide power to the external controller 60 and the user interface 62 to operate. The external power source 64 is also preferably adapted to serve as an external power source to the internal power source 52 as described above. In embodiments without an internal power source 52, the external power source 64 would also preferably be adapted to directly provide power to other components of the implantable housing 16, including the electrical signal generator 40, to generate the electrical noise stimulus signal. Additionally, in embodiments where the electrical signal generator 40 is external to the patient 14, the external controller 60 would preferably be adapted to directly provide power to the external electrical signal generator 40. The external power source 64 may include any suitable power source, including, but not limited to, one or more connections to an external power grid, a generator, or one or more batteries.

[0118] J. Exemplary Telecommunications Network 12, the exemplary embodiment of the neuromodulation system 10 may be utilized over or in connection with any telecommunications network 80 capable of transmitting data, including voice data and other types of electronic data. For example, the controller 50 and the external controller 60 of the exemplary embodiment of the neuromodulation system 10 may connect to and communicate with remote devices using the telecommunications network 80. Examples of telecommunications networks 80 suitable for the exemplary embodiment of the neuromodulation system 10 include, but are not limited to, a global computer network (e.g., the Internet), a wireless network, a cellular network, a satellite communication network, a cable communication network (via a cable modem), a microwave communication network, a peer-to-peer network, a local area network (LAN), a wide area network (WAN), a campus area network (CAN), a metropolitan area network (MAN), and a home area network (HAN). The communication interface 58 and external controller 60 of the exemplary embodiment of the neuromodulation system 10 may include a suitable modem or other interface and may implement a suitable protocol to allow the exemplary embodiment of the neuromodulation system 10 to communicate with remote devices over a telecommunications network 80. The exemplary embodiment of the neuromodulation system 10 may communicate over a single telecommunications network 80 or multiple telecommunications networks 80 simultaneously. Different electronic devices may use a variety of protocols for communication, such as, but not limited to, HTTP, SMTP, FTP, and WAP (Wireless Application Protocol). The exemplary embodiment of the neuromodulation system 10 may be used in conjunction with a variety of wireless networks, such as, but not limited to, 3G, 4G, LTE, CDPD, CDMA, GSM, PDC, PHS, TDMA, FLEX, REFLEX, IDEN, TETRA, DECT, DATATAC, and MOBITEX.Exemplary embodiments of the neuromodulation system 10 may also be utilized using online services and internet service providers.

[0119] The Internet is an exemplary telecommunications network in which exemplary embodiments of the neuromodulation system 10 operate or are connected. The Internet is made up of a global computer network with multiple computer systems around the world in communication with each other. Through the Internet, the computer systems can transmit various types of data between each other. Communication between the computer systems may be accomplished through a variety of methods, including, but not limited to, wireless, Ethernet, cable, direct connection, telephone line, and satellite.

[0120] K. Central Communication Unit The exemplary embodiment of the neuromodulation system 10 may be in communication with a central communication unit 82. The central communication unit 82 may comprise any central communication site where communication is preferably established. The central communication unit 82 may comprise a server computer, a cloud-based computer, a virtual computer, a personal computer capable of receiving and transmitting data over an IP network and / or a telecommunication network, or other computer system. As will be appreciated, a modem or other communication device may be required between each central communication unit 82 and the corresponding telecommunication network 80. The central communication unit 82 may comprise any electronic system capable of receiving and transmitting information (e.g., voice data, computer data, etc.).

[0121] L. Mobile Devices The exemplary embodiment of the neuromodulation system 10 may be configured in part by or in communication with a mobile device 84. For example, all or a portion of the external controller 60 shown in FIG. 10 and described above may be configured by the mobile device 84. The mobile device 84 may be configured by any type of computer for implementing various aspects of the exemplary embodiment of the neuromodulation system 10. For example, the mobile device 84 may be a personal computer (e.g., an APPLE®-based computer, an IBM-based computer, or compatibles) or a tablet computer (e.g., an IPAD®). The mobile device 84 may also be configured by various other electronic devices capable of transmitting and receiving electronic data, including, but not limited to, a smart phone, a mobile telephone, a telephone, a personal digital assistant (PDA), a mobile electronic device, a portable wireless device, a two-way radio, a smart phone, a communicator, a video viewing device, a television device, a television receiver, a cable television receiver, a pager, a communication device, and a digital satellite receiver.

[0122] The mobile device 84 may be comprised of any conventional computer. A conventional computer preferably includes a display screen (or monitor), a printer, a hard disk drive, a network interface, and a keyboard. A conventional computer also includes a microprocessor, a memory bus, a random access memory (RAM), a read-only memory (ROM), a peripheral bus, and a keyboard controller. The microprocessor is a general-purpose digital processor that controls the operation of the computer. The microprocessor may be a single chip processor or may be implemented with multiple components. Using instructions retrieved from the memory, the microprocessor controls the receipt and manipulation of input data, and the output and display of data on an output device. The memory bus is utilized by the microprocessor to access the RAM and ROM. The RAM is used by the microprocessor as a general-purpose storage area and as a scratch pad memory, and can also be used to store input data and processed data. The ROM can be used to store instructions or program code followed by the microprocessor as well as other data. The peripheral bus is used to access the input, output, and storage devices used by the computer. These devices may include a display screen, a printer device, a hard disk drive, and / or a network interface. The display screen includes an output device that displays images of data provided by the microprocessor via the peripheral bus or by other components of the computer. The keyboard controller is used to receive input from the keyboard and send decoded symbols for each key pressed to the microprocessor via the bus. The keyboard is used by a user to enter commands and other instructions to the computer system. Other types of user input devices can also be used in conjunction with exemplary embodiments of the neuromodulation system 10.For example, a pointing device such as a computer mouse, trackball, stylus, or tablet for manipulating a pointer on the screen of a computer system. All or part of the user interface 62 of the exemplary embodiment of the neuromodulation system 10 shown in FIG. 10 and described above may be constituted in whole or in part by a display screen, a keyboard, and / or other input devices as mentioned above. A printer device, when operating as a printer, provides an image on a sheet of paper or similar surface. A hard disk drive may be utilized to store various types of data. A microprocessor operates with an operating system to execute computer code and generate and use data. Computer code and data may reside on RAM, ROM, or a hard disk drive. Computer code and data may also reside on removable program media and be loaded or installed on the computer system as needed. Removable program media include, for example, CD-ROMs, PC cards, USB drives, floppy disks, and magnetic tapes. A network interface circuit is utilized to receive and transmit data over a network connected to other computer systems. An interface card or similar device and appropriate software implemented by a microprocessor can be utilized to connect the computer system to an existing network and transmit data according to standard protocols.

[0123] M. Operation of the Preferred Embodiment In one example of the use of an exemplary embodiment of the neuromodulation system 10, one or more leads 18 having electrodes 30 may be inserted into the patient 14 in a conventional manner and positioned in, on, and around the target tissue 12 at desired locations to provide therapy as described herein. Similarly, the sensors S1, S2 are implanted in the patient 14 either coincident with or proximate to the electrodes 30 in, on, or around the target tissue 12. The one or more leads 18 extending from the electrodes 30 and the sensors S1, S2 may be connected to an electrical signal generator 40, a controller 50, an external controller 60, and / or an external user interface 62. Typically, but not necessarily, the electrical signal generator 40 will be external to the patient 14 while the exemplary embodiment of the neuromodulation system 10 is configured for permanent implantation in the patient 14 or when the system is configured to provide only temporary therapy. Once configured, the implantable electrical signal generator 40 will typically be permanently implanted within the patient 14 within the implantable housing 16 .

[0124] A user or operator may use the user interface 62 and the controller 50 or external controller 60, as described herein, to select an electrode 30 or combination of electrodes 30, cause the electrical signal generator 40 to selectively generate and deliver an electrical noise stimulation signal to the target tissue 12, and monitor sensor data generated by the sensors S1, S2. The controller 50 or external controller 60, as described herein, controls the electrical signal generator 40 to scan or sweep the center frequency of a relatively narrow band electrical noise stimulation signal over the entire bandwidth or a portion of the bandwidth of possible frequencies for such a signal, and determine multiple peak values ​​of impedance present at multiple different center frequencies. This process is repeated for multiple different selected electrodes 30 and / or combinations of electrodes 30, as desired.

[0125] If necessary or desired, one or more of the electrodes 30 and sensors S1, S2 can be repositioned to achieve better impedance peak values, for example, to provide better contact, to change the distance and / or orientation of the electrodes 30 and / or sensors S1, S2 relative to the target tissue 12, to better position the electrodes 30 within certain neural and / or non-neural tissues of the target tissue 12, etc. The process of determining impedance peak values ​​versus frequency can then be repeated. One or more of the electrodes 30 and sensors S1, S2 can be repositioned, and the process of determining impedance peak values ​​can be repeated as many times as necessary to obtain one or more sets of impedance peak values ​​or multiple impedance peak values ​​sufficient for use in providing treatment.

[0126] The user or operator then uses the user interface 62 and the controller 50 or external controller 60 to generate and deliver an electrical noise stimulation signal to the target tissue 12 of the patient 14 to stimulate or modulate the target tissue 12 and provide treatment for one or more conditions, including one or more of the conditions identified herein. The electrical noise stimulation signal is generated and delivered to the target tissue 12 in the manner described herein to optimize and maximize the electric field within the target tissue 12 by maximizing the voltage while maintaining an acceptably low level of current density to provide optimal therapeutic results while also preventing overheating and damage to the target tissue 12 and discomfort to the patient 14.

[0127] Once the desired therapeutic result has been achieved, the leads 18 can be connected to the lead connection ports 19 of the implantable housing 16 to electrically couple the electrodes 30 and sensors S1, S2 to the implantable controller 50 and implantable electrical signal generator 40 within the implantable housing 16. The implantable housing 16 is then permanently implanted within the patient's body in a conventional manner.

[0128] Thereafter, the patient 14, or a user, or an operator of an exemplary embodiment of the neuromodulation system 10, using the external controller 60, if included, or another remote device, can periodically communicate with the implantable controller 50 and manually initiate therapy administration, if desired. The therapy administration can have preset parameters for the electrical noise stimulation signal, such as a preset duration and / or peak voltage level. Alternatively, the duration and some or all of the parameters of the electrical noise stimulation signal can be manually selected by the patient 14, or a user or operator. Also alternatively, the implantable controller 50 can be configured to automatically initiate therapy administration based on a predetermined schedule, with a predetermined duration and preset parameters of the electrical noise stimulation signal.

[0129] All headings are for convenience only and are not intended to have a limiting effect. 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 this invention belongs. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety to the extent permitted by applicable law and regulations.

[0130] Any data structures and code described in this detailed description are typically stored on a computer-readable storage medium, which can be any device or medium that can store code and / or data for use by a computer system. This includes, but is not limited to, magnetic and optical storage devices such as disk drives, magnetic tape, CDs (compact discs), DVDs (digital video discs), and computer instruction signals embodied in a transmission medium (with or without a carrier wave upon which the signal is modulated). For example, a transmission medium may include a telecommunications network such as the Internet.

[0131] At least one embodiment of the neuromodulation system and method with feedback-optimized electric field generation has been described above with reference to block diagrams and / or flow diagrams of systems, methods, devices, and / or computer program products according to exemplary embodiments of the present invention. It will be understood that one or more blocks of the block diagrams and flow diagrams, and combinations of blocks in the block diagrams and flow diagrams, respectively, can be implemented by computer-executable program instructions. Similarly, some blocks of the block diagrams and flow diagrams do not necessarily have to be executed in the order presented, or even necessarily, according to some embodiments of the present invention. These computer-executable program instructions may be loaded onto a general-purpose computer, a special-purpose computer, a processor, or other programmable data processing device to create a particular machine, such that the instructions executing on the computer, processor, or other programmable data processing device create means for implementing one or more functions specified in one or more blocks of the flow diagrams. These computer program instructions may also be stored in a computer readable memory such that the instructions stored in the computer readable memory can direct a computer or other programmable data processing apparatus to function in a particular manner to produce a product including instruction means that implement one or more functions specified in one or more blocks of the flow diagram. As an example, embodiments of the present invention may provide a computer program product including a computer usable medium having computer readable program code or program instructions embodied therein, the computer readable program code adapted to be executed to implement one or more functions specified in one or more blocks of the flow diagram.Computer program instructions may also be loaded onto a computer or other programmable data processing apparatus to cause a sequence of operational elements or steps to be executed on the computer or other programmable apparatus to generate a computer-implemented process, such that the instructions executing on the computer or other programmable apparatus provide elements or steps for implementing the functions specified in one or more blocks of the flow diagrams. Thus, the blocks of the block diagrams and / or flow diagrams embody combinations of means for performing the specified functions, combinations of elements or steps for performing the specified functions, and program instruction means for implementing the specified functions. It will also be understood that each block of the block diagrams and / or flow diagrams, and combinations of blocks in the block diagrams and / or flow diagrams, may be implemented by a dedicated, hardware-based computer system that executes the specified functions, elements or steps, or a combination of dedicated hardware and computer instructions.

[0132] The present invention may be embodied in other specific forms without departing from the spirit or essential attributes of the invention, and therefore, the present embodiments should be considered in all respects as illustrative and not restrictive. Many modifications and other embodiments of the neuromodulation system and method using feedback optimized electric field generation will come to mind to one skilled in the art having the benefit of the teachings related to the present invention and presented in the foregoing description and the associated drawings. Moreover, features illustrated or described as part of one embodiment can be used with another embodiment to yield still further embodiments. It is therefore to be understood that the invention is not limited to the particular embodiments disclosed, and that modifications and other embodiments are intended to be included within the scope of the appended claims. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the neuromodulation system and method using feedback optimized electric field generation, suitable methods and materials have been described above. Thus, the neuromodulation system and method using feedback optimized electric field generation are not intended to be limited to the embodiments shown, but are intended to be accorded the widest scope consistent with the principles and features disclosed herein.

Claims

1. 1. A system for providing therapy to a patient, comprising: an electrical signal generator adapted to generate an electrical noise stimulus signal; an implantable electrical lead having a plurality of electrodes and in communication with the electrical signal generator, the implantable electrical lead adapted to receive the electrical noise stimulation signal and generate, by the plurality of electrodes, an electric field for application to a target tissue of the patient, the target tissue including neural tissue, non-neural tissue, or a combination thereof; an implantable sensor adapted to be implanted within or near the target tissue, the implantable sensor configured to generate sensor data indicative of a value of a physical parameter associated with the target tissue in response to application of the electric field to the target tissue; a controller in communication with the electrical signal generator and the implantable sensor, receiving data from the sensor; In response to the sensor data, generating said electrical noise stimulation signal to optimize said electric field to produce a therapeutic effect without said value indicative of possible damage to said target tissue by said electrical noise stimulation signal; and and automatically controlling the electrical signal generator to select from a plurality of combinations of the plurality of electrodes to deliver the electrical noise stimulation signal. the electrical noise stimulus signal is comprised of a statistically random waveform; The system, wherein the controller is configured to control the electrical signal generator to optimize the electric field by generating and applying the electrical noise stimulation signal to maximize the voltage of the electric field while maintaining current density and flow rate levels to the target tissue.

2. The system of claim 1 , wherein the electrical noise stimulus signal has a frequency spectrum ranging from about 100 Hz to about 750 KHz.

3. The system of claim 1 , wherein the implantable sensor comprises an impedance sensor, and the physical parameter of the target tissue comprises impedance.

4. 2. The system of claim 1, wherein the controller is configured to respond to data from the sensor indicating that the value of the physical parameter is related to potential damage to the target tissue by automatically reducing the strength of the electric field.

5. 2. The system of claim 1, wherein the controller is configured to receive input by the patient regarding a patient's sensation in response to application of the electric field to the target tissue and configured to control the electrical signal generator in response to adjusting the electric field.

6. the electrical signal generator is adapted to generate the electrical noise stimulus signal in a frequency band having a center frequency; the physical parameter of the target tissue comprises impedance; 2. The system of claim 1, wherein the controller is configured to control the electrical signal generator to optimize the electric field by adjusting the center frequency to a value corresponding to a peak value of the impedance.

7. The system of claim 1 , wherein the target tissue comprises the nerve tissue.

8. 1. A system for providing therapy to a patient, comprising: an electrical signal generator adapted to generate an electrical noise stimulus signal; an implantable electrical lead having a plurality of electrodes and adapted to be implanted in or near a target tissue of the patient, the implantable electrical lead adapted to receive the electrical noise stimulus signal from the electrical signal generator and generate, by the plurality of electrodes, an electric field for application to the target tissue of the patient, the electric field comprising neural tissue; an implantable sensor adapted to be implanted in or near the target tissue of the patient, the implantable sensor being configured to generate sensor data indicative of a value of a physical parameter associated with the target tissue in response to application of the electric field to the target tissue, the implantable sensor including a temperature sensor or an impedance sensor; a controller in communication with the electrical signal generator and the implantable sensor, receiving data from the sensor; In response to the sensor data, generating the electrical noise stimulation signal to maximize the voltage of the electric field to produce a therapeutic effect without the value being indicative of possible damage to the target tissue due to the electrical noise stimulation signal; and and automatically controlling the electrical signal generator to select from a plurality of combinations of the plurality of electrodes to deliver the electrical noise stimulation signal; the electrical noise stimulus signal is comprised of a statistically random waveform; The system, wherein the controller is configured to control the electrical signal generator to optimize the electric field by generating and applying the electrical noise stimulation signal to maximize the voltage of the electric field while maintaining current density and flow rate levels to the target tissue.

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