Pulse generation and stimulation engine system

Abstract

To provide an internal or external pulse generation and / or stimulation engine system for facilitating interruption, modification, and / or attenuation of a biological signal through a nervous tissue including processing of a biological tissue, a cardiac tissue, or the other potential sensitive tissue within a nervous system tissue.SOLUTION: This specification discloses a system that may include a neuromodulation device configured to operate in a plurality of electrical modulation modes by using a single architecture, and discloses a method.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] Incorporation by Reference of Priority Application This application claims the nonprovisional benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 62 / 939,666, filed November 24, 2019, and U.S. Provisional Application No. 62 / 965,772, filed January 24, 2020, which are incorporated by reference in their entireties. Any and all applications for which a foreign or domestic priority claim is identified in the Application Data Sheet filed with this application are hereby incorporated by reference under 37 CFR §1.57.

[0002] The present application relates in some embodiments to facilitating the blocking, modulation, or attenuation of biological signals through nervous tissue, including the treatment of biological tissue within nervous system tissue, cardiac tissue, or other voltage-sensitive tissue. [Background technology]

[0003] The gate control theory of pain, developed in the 1960s, led to the emergence of stimulation-based pain management therapies, which selectively stimulate non-nociceptive (non-pain transmitting) fibers in the spinal cord to inhibit pain stimuli from reaching the brain, thereby reducing pain input (see Mendell, Constructing and Deconstructing the Gate Theory of Pain, Pain, February 2014; 155(2):210-216). Current stimulation systems for spinal cord stimulation (SCS), which act to indirectly reduce pain based on this gate control theory, have typically utilized stimulation signals in the <100 Hz frequency range, and more recently in the kHz frequency range. Stimulation of the dorsal root ganglion (DRG) in a similar frequency range has also been used to reduce segmental pain through the same mechanism.

[0004] However, techniques based on this premise have drawbacks because pain transmission inhibition is not complete and side effects such as paresthesia can be unpleasant for patients. Therefore, it is desirable to have a system and method for treating pain that more effectively blocks or attenuates the transmission of pain signals through pain fibers or reduces the excitability of neurons that process pain signals, rather than indirectly reducing pain signals through the activation of non-nociceptive fibers via the gate theory, and avoids undesirable side effects. Furthermore, blocking or attenuating nerve tissue or nerve activity has been implicated not only in affecting pain, but also in the management of movement disorders, psychiatric disorders, cardiovascular health, and conditions such as diabetes. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] U.S. Patent No. 10,071,241 [Patent Document 2] U.S. Patent No. 9,008,800 [Patent Document 3] U.S. Patent Application Publication No. 2018 / 0280691 [Non-patent literature]

[0006] [Non-Patent Document 1] Mendell, Constructing and Deconstructing the Gate Theory of Pain, Pain, February 2014 155(2):210-216 [Non-patent document 2] Nahin, Estimates of Pain Prevalence and Severity in Adults: United States, 2012, The Journal of Pain, August 2015 16(8):769-780 [Non-patent document 3] Borsook, A Future Without Chronic Pain: Neuroscience and Clinical Research, Cerebrum, June 2012. [Non-patent document 4] Tjepkema-Cloostermans et al., Effect of Burst Stimulation Evaluated in Patients Familiar With Spinal Cord Stimulation, Neuromodulation, July 2016 19(5):492-497 [Non-patent document 5] Bhadra and Kilgore, Direct Current Electrical Conduction Block of Peripheral Nerve, IEEE Transactions on Neural Systems and Rehabilitation Engineering, September 2004, 12(3):313-324 Summary of the Invention [Means for solving the problem]

[0007] Various systems, devices, and methods are disclosed herein. In some variations, a neuromodulation device can operate in multiple electrical modulation modes using a single architecture. The neuromodulation device can include a power source. The neuromodulation device can include a control unit. The neuromodulation device can include a bipolar current generator connectable to at least one working electrode. The neuromodulation device can include a stimulation circuit, the stimulation circuit can include at least one blocking capacitor capable of blocking direct current, at least one indifferent electrode switch electrically communicating with at least one indifferent electrode, and / or at least one blocking capacitor switch electrically communicating to bypass the at least one blocking capacitor. The device can include a first stimulation mode in which the current generator can supply alternating current to at least one working electrode, and / or a second stimulation mode in which the current generator can supply direct current to at least one working electrode, with both return electrodes being absorbed through the indifferent electrode. In a first stimulation mode, the control unit can configure another current generator through the second working electrode, and can cause at least one indifferent electrode switch to disable electrical communication between the current generator and the at least one indifferent electrode, with the at least one blocking capacitor functioning to block direct current. In a second stimulation mode, the two current generators are configured to allow an offset current of 0 μA to 1,000 μA or more through the indifferent electrode switch to the indifferent electrode, and the control unit can cause at least two blocking capacitor switches to disable electrical communication between the current generator and the at least one blocking capacitor, thereby bypassing the at least two blocking capacitors.

[0008] In some variations, the direct current may include extremely low frequency current.

[0009] In some variations, the extremely low frequency current may be less than about 5 Hz.

[0010] In some variations, the extremely low frequency current may be less than about 2 Hz.

[0011] In some variations, the extremely low frequency current may be less than about 1 Hz.

[0012] In some variations, the alternating current may be a high frequency alternating current.

[0013] In some variations, the high frequency alternating current may be at least about 1 kHz.

[0014] In some variations, the alternating current may be between about 5 Hz and about 1 kHz.

[0015] In some variations, the power source may include a battery.

[0016] In some variations, the control unit may include a first control unit and a second control unit capable of executing independent algorithms.

[0017] In some variations, the device may measure the offset current when the device is in the second stimulation mode.

[0018] In some variations, the device is capable of measuring the cyclic Vpp of at least one working electrode.

[0019] In some variations, the device may include a virtual ground that may be operably connected to the indifferent electrode, in which case the virtual ground may be set to any level to minimize power consumption.

[0020] In some variations, the device may include one or more mitigation mechanisms selected from the group consisting of: (a) a control system configured to measure bias current from an indifferent electrode and suspend or modify operation if the bias current deviates outside of preset parameters; (b) a control system configured to measure electrode voltages between any pair of working electrodes, between the working and reference electrodes, and between the working and indifferent electrodes; (c) a control system configured to resolve electrode monitoring in relation to waveform transitions; and (d) a control system configured to receive data regarding the total or components of the electrode voltages that are subjected to statistical analysis based on electrode characteristics.

[0021] In some variations, the device may include all of the following mitigation mechanisms: (a) a control system configured to measure bias current from the indifferent electrode and suspend or modify operation if the bias current deviates outside of preset parameters; (b) a control system configured to measure electrode voltages between any pair of working electrodes, between the working and reference electrodes, and between the working and indifferent electrodes; (c) a control system configured to resolve electrode monitoring in relation to waveform transitions; and (d) a control system configured to receive data regarding the total or components of the electrode voltages that undergo statistical analysis based on electrode characteristics.

[0022] In some variations, a method for delivering electrical neuromodulation to electrically excitable tissue of a patient using a neuromodulation therapy device is disclosed. The method can include applying an alternating current to at least one active electrode in electrical communication with the electrically excitable tissue. Applying the alternating current can include utilizing at least one blocking capacitor of the neuromodulation therapy device to block direct current and preventing electrical communication between the neuromodulation therapy device and at least one indifferent electrode.

[0023] In some variations, the method can include interrupting the supply of alternating current and / or supplying direct current to at least one working electrode and supplying an offset current to at least one indifferent electrode, wherein supplying the direct current includes bypassing at least one blocking capacitor of the neuromodulation therapy device.

[0024] In some variations, the method can include interrupting the supply of direct current to the at least one working electrode and / or resuming the supply of alternating current to the at least one working electrode. Resuming the supply of alternating current can include utilizing at least one blocking capacitor of the neuromodulation therapy device to block the direct current. The method can include interrupting electrical communication between the neuromodulation therapy device and the at least one indifferent electrode.

[0025] In some variations, the direct current may include extremely low frequency current.

[0026] In some variations, the extremely low frequency current may be less than about 5 Hz.

[0027] In some variations, the extremely low frequency current may be less than about 2 Hz.

[0028] In some variations, the extremely low frequency current may be less than about 1 Hz.

[0029] In some variations, the alternating current may be a high frequency alternating current.

[0030] In some variations, the high frequency alternating current may be at least about 1 kHz.

[0031] In some variations, the alternating current may be between about 10 Hz and about 1 kHz.

[0032] In some variations, the method may include measuring the offset current using a neuromodulation device.

[0033] In some variations, the method may include measuring the periodic Vpp of at least one working electrode.

[0034] In some variations, disclosed herein are methods for delivering electrical neuromodulation to electrically excitable tissue of a patient utilizing a neuromodulation therapy device. The method can include supplying direct current to at least one working electrode and supplying an offset current to at least one indifferent electrode, where supplying the direct current can include bypassing at least one blocking capacitor of the neuromodulation therapy device.

[0035] In some variations, the method can include interrupting the supply of direct current to at least one working electrode and the supply of an offset current to at least one indifferent electrode. The method can include supplying alternating current to at least one working electrode in electrical communication with the electrically excitable tissue. Supplying the alternating current can include utilizing at least one blocking capacitor of the neuromodulation therapy device to block the direct current and interrupting electrical communication between the neuromodulation therapy device and the at least one indifferent electrode.

[0036] In some variations, the method can include discontinuing the supply of alternating current. The method can include resuming the supply of direct current to the at least one working electrode and the supply of an offset current to the at least one indifferent electrode, where resuming the supply of direct current can include bypassing at least one blocking capacitor of the neuromodulation therapy device.

[0037] In some variations, the direct current may include extremely low frequency current.

[0038] In some variations, the extremely low frequency current may be less than about 5 Hz.

[0039] In some variations, the extremely low frequency current may be less than about 2 Hz.

[0040] In some variations, the extremely low frequency current may be less than about 1 Hz.

[0041] In some variations, the alternating current may be a high frequency alternating current.

[0042] In some variations, the high frequency alternating current may be at least about 1 kHz.

[0043] In some variations, the alternating current may be between about 10 Hz and about 1 kHz.

[0044] In some variations, the method may include measuring the offset current using a neuromodulation device.

[0045] In some variations, the method may include measuring the periodic Vpp of at least one working electrode.

[0046] In some variations, disclosed herein are neuromodulation devices configured to operate in multiple electrical modulation modes using a single architecture. The device can include a power source. The device can include a control unit. The device can include a current generator connectable to at least one working electrode. The device can include a stimulation circuit, the stimulation circuit including at least one blocking capacitor capable of blocking direct current, at least one indifferent electrode switch capable of electrical communication with at least one indifferent electrode, and at least one blocking capacitor switch in electrical communication to bypass the at least one blocking capacitor.

[0047] In some variations, the device can include a first stimulation mode in which the current generator can supply an alternating current to at least one working electrode.

[0048] In some variations, the device can include a second stimulation mode in which the current generator can supply direct current to at least one working electrode, and both return electrodes are absorbed through an indifferent electrode.

[0049] In some variations, in the first stimulation mode, the control unit configures another current generator through the second working electrode, causes the at least one indifferent electrode switch to disable electrical communication between the current generator and the at least one indifferent electrode, and the at least one blocking capacitor can function to block direct current.

[0050] In some variations, in the second stimulation mode, the two current generators are configured such that an offset current of 0 μA to 100 μA or more is configured to pass through the indifferent electrode switch to the indifferent electrode, and the control unit causes the at least two blocking capacitor switches to disable electrical communication between the current generators and at least one blocking capacitor, thereby bypassing the at least two blocking capacitors. [Brief explanation of the drawings]

[0051] [Figure 1] 1 is a schematic diagram of an application specific integrated circuit (ASIC). [Figure 2] 1 is a schematic diagram of an ASIC that takes a DC and AC discrete approach. [Figure 3] FIG. 1 is a schematic diagram of an ASIC adapted to supply DC. [Figure 4] FIG. 1 is a schematic diagram of an ASIC adapted to supply DC using a current source. [Figure 5] FIG. 1 is a schematic diagram of a system using a current source. [Figure 5B] FIG. 1 is a schematic diagram of a system using a current source. [Figure 6] FIG. 1 is a schematic diagram of a fail-safe hybrid system. [Figure 7] 1 is a table of exemplary mechanisms and mitigations. [Figure 8] 1 is a graph of lost capacity and voltage protection. [Figure 9A] 1 is a graph of reference electrode disconnection. [Figure 9B] 10 is a graph relating to bias removal. [Figure 10] 1 is a graph showing the relationship between stimulus onset and time in seconds. [Figure 11] FIG. 1 is a schematic diagram of HW and FW fail-safes. DETAILED DESCRIPTION OF THE INVENTION

[0052] The present application relates, in some embodiments, to internal and external pulse generation and / or stimulation engine systems for facilitating the blocking, modulation, and / or attenuation of biological signals through neural tissue, including the treatment of biological tissue within nervous system tissue (including, but not limited to, neurons and glial cells), cardiac tissue, or other voltage-sensitive tissue. In some embodiments, the anodic or cathodic phase, or both the anodic and cathodic phases, of a waveform delivered to a patient can have a therapeutic effect on electrically excitable tissue, such as neural tissue.

[0053] In some embodiments, the pulse generation and / or stimulation engine system comprises any one or more of the features described in this disclosure.

[0054] In some embodiments, the pulse generation and / or stimulation engine method includes any one or more of the features described in this disclosure.

[0055] Conventional stimulation systems may utilize capacitors to ensure or facilitate fail-safe operation because capacitors are highly reliable and low cost.

[0056] Some systems cannot use capacitors because they are fully integrated on silicon, the output frequency is too low, the capacitors are too large, or some systems must pass direct current (DC). Some system embodiments can operate by providing a low-frequency AC (LF-AC) waveform along with a low-level DC bias to keep the electrode operating range within a potential window. This safety mechanism essentially ensures that both components remain within specification and that the resulting electrode voltage remains within a specified range, as assessed, for example, by at least two independent check mechanisms. For conventional high-frequency AC, a capacitor can be switched in to protect against DC, and protection from switch failure can be obtained by ensuring that substantially no DC passes through the can, which is the only single fault path through which DC can pass.

[0057] In some embodiments, alternatives to capacitors to enhance patient safety and / or the use of capacitors in combination to provide protection and in some cases just to achieve higher frequencies are disclosed herein.

[0058] Without being limited by theory, propagation of an action potential in electrically excitable tissue, such as nervous tissue, results in a refractory period for sodium channels on the order of milliseconds, typically between about 1 ms and about 20 ms, or between about 2 ms and about 5 ms for a combination of absolute and relative refractory periods; therefore, extremely low frequency AC current waveforms whose half-periods are significantly greater than this refractory period (e.g., greater than about 1 ms, 1.5 ms, 2 ms, 2.5 ms, 3 ms, 10 ms, 30 ms, 50 ms, 100 ms, 300 ms, 500 ms, 1000 ms, 2000 ms, 5000 ms, 6000 ms, or more) and which have sufficiently small differential rates (e.g., rise and fall times) so as not to elicit action potentials may also be used to produce tissue blockage or damping, which is sensed by electrically excitable tissue as a direct current stimulus. Thus, direct current (DC), as defined herein, includes low-frequency AC current waveforms that are perceived as direct current and functionally direct current from the perspective of the tissue whose action potentials or neural processing are being modulated. The frequency can be, for example, less than about 10 Hz, 9 Hz, 8 Hz, 7 Hz, 6 Hz, 5 Hz, 4 Hz, 3 Hz, 2 Hz, 1 Hz, 0.5 Hz, 0.1 Hz, 0.05 Hz, 0.01 Hz, 0.005 Hz, 0.0001 Hz, or a range including any two of the foregoing values, so long as the direction of current flow is constant for at least the entire refractory period of the target tissue or for at least two, or at least five, or at least ten times the refractory-causing membrane channel time constant (e.g., fast sodium channel inactivation gate time constant).

[0059] In some embodiments, the systems and methods can incorporate a variety of waveform frequencies, including high frequencies, e.g., about 1.2-50 kHz or higher, conventional frequencies, e.g., about 20-1.2 kHz, low frequencies, e.g., about 1-20 Hz, and very low frequencies, e.g., less than about 1 Hz. As noted elsewhere herein, direct current, as defined herein, includes low-frequency AC current waveforms that are perceived as, and functionally are, direct current from the perspective of the tissue whose action potentials are being modulated.

[0060] Chronic pain poses a significant burden to individuals and society as a whole. In the United States alone, it is estimated that nearly 50 million adults suffer from significant chronic or severe pain (see Nahin, Estimates of Pain Prevalence and Severity in Adults: United States, 2012; The Journal of Pain, August 2015, 16(8):769-780). Globally, chronic pain is estimated to affect more than 1.5 billion people (Borsook, A Future Without Chronic Pain: Neuroscience and Clinical Research, Cerebrum, June 2012). While surgical techniques are sometimes applied to eliminate specific pain sources, often due to nerve impingement, the exact cause of pain is often unclear and cannot be reliably addressed through surgical procedures. Pain management can instead be addressed by overpowering the central nervous system with stimulation signals that disrupt the registration of pain input (the gate control theory of pain). Typically, this stimulation, in the case of spinal cord stimulation (SCS), is performed using metal electrodes and alternating current (AC) stimulation to generate these additional stimulation signals that interfere with pain sensation. However, one major drawback is the presence of paresthesia, a tingling sensation, within the innervated area downstream from the stimulated nerve. To address this paresthesia, which patients may find unpleasant, approaches have emerged that differ from traditional tonic SCS (approximately 30–120 Hz) stimulation, including high-frequency stimulation (approximately 10 kHz) and burst stimulation (e.g., five pulses at 500 Hz delivered 40 times per second) (Tjepkema-Cloostermans et al., Effect of Burst Stimulation Evaluated in Patients Familiar With Spinal Cord Stimulation, Neuromodulation, July 2016, 19(5):492–497).

[0061] An alternative approach to managing pain signal transmission to the central nervous system is to prevent the conduction of pain signals from peripheral sources by directly blocking or attenuating the pain signal, as opposed to masking the pain signal by generating alternative neural inputs to eliminate or inhibit its transmission, as in traditional SCS and gating theories. One means of doing this is by applying direct current (DC) to the nerve to prevent the generation and transmission of action potentials (APs). This avoids paresthesia because the nerve is not stimulated as with conventional stimulation. The mechanism leading to AP blockade has been attributed to a depolarization or hyperpolarization block, which inactivates sodium channels necessary for action potential events under the electrode site (see Bhadra and Kilgore, Direct Current Electrical Conduction Block of Peripheral Nerve, IEEE Transactions on Neural Systems and Rehabilitation Engineering, September 2004, 12(3):313-324). Wide dynamic range (WDR) neurons have been implicated in integrating pain signals and as a causative source of pain in patients, and application of direct current (DC) can be well positioned to reduce this activity and affect the associated inhibitory and excitatory neurons that drive WDR activity.

[0062] It has long been known that unmitigated use of direct current is dangerous to neural tissue due to the production of toxic species at the electrode-nerve interface. Therefore, systems and methods that facilitate the safe delivery of direct current therapy are highly desirable. In some embodiments, the systems and methods can be configured to treat nociceptive pain. In some embodiments, systems and methods for treating pain and other medical conditions can involve selective blocking of antero-lateral column tissue within the spinal cord. Additionally, some embodiments relate to systems and methods for treating pain via the aforementioned systems and methods, particularly through selective blocking of dorsal root tissue and / or dorsal root ganglia. Furthermore, in some embodiments, systems and methods for treating pain, particularly through blocking or attenuating one or more peripheral nerves, are disclosed herein.

[0063] In some embodiments, the systems and methods can safely block or attenuate pain signals within the spinal column (including modulating pain processing) by delivering extremely low frequency stimulation into the epidural space for up to two weeks or longer, achieving clinically measurable pain reduction in patients with chronic low back pain who are candidates for spinal cord stimulation (SCS).

[0064] Targeted nerve blockade can be used to manage pain from specific dermatometastatic zones and pain within localized body areas. Several local targets can be addressed that are involved in alleviating pain signal transduction. For example, the spinothalamic tract and dorsal root ganglion, both of which are more centrally located, can be targeted to manage low back pain, sciatica, and complex regional pain syndrome (CPRS), among other pain considerations.

[0065] In some embodiments, the electrodes may include contacts comprising high charge capacity materials. The electrode contacts may, in some cases, be about 1 mm 2 Approximately 10 mm from2 Between, or about 1 mm 2 , 2mm 2 , 3mm 2 , 4mm 2 , 5mm 2 , 6mm 2 , 7mm 2 , 8mm 2 , 9mm 2 , 10mm 2 , 20mm 2 , 50mm 2 , 100mm 2The electrode contacts can have a geometric surface area of ​​0.01 μC or a range inclusive of any two of the foregoing values. The electrode contacts themselves can be fabricated from a high charge capacity material, such as those described in U.S. Patent No. 10,071,241 to Bhadra et al., which is incorporated herein by reference in its entirety. Alternatively, the electrode contacts can comprise a base at least partially or entirely coated with a high charge capacity material. In some embodiments, the high charge capacity material can have a Q value of at least about 25, 50, 100, 200, 300, 400, 500, 1,000, 2,500, 5,000, 10,000, 50,000, 100,000, 500,000 μC, or more, or a range inclusive of any two of the foregoing values. The Q value of an electrode contact can refer to the total amount of charge that can be delivered through the electrode contact before the electrode contact begins to undergo irreversible chemical reactions at a rate that cannot be removed through the body's nominal transport mechanisms. These chemical reactions include, but are not limited to, the evolution of oxygen or hydrogen, or the dissolution of the electrode material. Non-limiting examples of high charge capacity materials are platinum black, iridium oxide, titanium nitride, tantalum, silver chloride, poly(ethylenedioxythiophene), and suitable combinations thereof. In some embodiments, the electrode can comprise a fractal coating or a high surface area format. The high charge capacity material can be configured monolithically or as a coating on a base substrate. Non-limiting examples of substrates for coatings include stainless steels such as 304 and 316LVM, nickel-cobalt-chromium alloys such as MP35N®, platinum and platinum-iridium, titanium, and nickel-titanium alloys such as Nitinol. In some embodiments, the electrode can comprise tantalum coated with titanium nitride. Tantalum, as a non-limiting example, can be a particularly advantageous material because it has excellent radiopacity, thereby enabling improved implantation, verification, and / or removal of implantable neuromodulation devices. In some embodiments, the electrodes may include one or more of titanium nitride, tantalum, and MP35N.To create more surface area for the electrochemical reaction to occur, conventional electrodes may be fabricated from high surface area to volume structures, such as roughened, textured, or patterned surfaces, reticulated foam structures, porous sintered bead structures, or nano- or micro-patterned structures to expose additional material surface area. In some embodiments, the electrode may be a SINE (separated-interface nerve electrode) or EICCC (electron to ion current conversion cell) electrode, in which the electrode is immersed in an electrolyte solution, the electrolyte solution contacts the ion-conducting material using an ion-conducting material-electrolyte solution interface, and the ion-conducting material is in electrical contact with cardiac tissue or an area adjacent to cardiac tissue, as described, for example, in U.S. Pat. No. 9,008,800 to Ackermann et al. and U.S. Patent Application Publication No. 2018 / 0280691 to Ackermann et al., which are incorporated by reference in their entireties.

[0066] Disclosed herein, in some embodiments, are systems and methods for safely and effectively stimulating neural tissue, advantageously utilizing a variety of waveforms ranging from DC to high frequencies. While DC stimulation is potentially very useful, it has not been commercially utilized for neuromodulation due to the lack of available neurostimulation systems capable of safely delivering DC for extended periods of time. Available commercial systems prevent DC delivery and utilize charge-balancing mechanisms to limit irreversible electrochemical reactions. These systems may block the DC component using a capacitor, i.e., a blocking capacitor, or include mechanisms to remove charge accumulation at the end of a stimulation cycle. While typical capacitors are highly reliable, they limit charge to less than approximately 1 millicoulomb (mC) per phase, preventing the use of very low-frequency signals with large charge magnitudes beyond this charge capacity. Another widely used technique utilizes actively balanced current sources, but these current sources require redundancy to be fault-tolerant, typically do not intentionally control electrode voltage, which is important for some electrode technologies, and have not been shown to be advantageous for long-term, high-charge delivery. Active systems, along with coatings, can increase charge densities to approximately 2 mC / cm in devices such as retinal implants. 2 Although many techniques have been used to increase the charge per phase required for DC, these densities are still insufficient to allow the use of waveforms with very high charge per phase, or very low frequency waveforms with sufficient current amplitude.

[0067] Some embodiments involve high surface area electrode coatings and bias currents, e.g., DC bias, to maintain the electrode voltage within an optimal range for the particular electrode material for long-term operational durability. This approach reduces the charge per phase to, e.g., about 50 μC / cm used in conventional systems without damaging the electrode or electrically excitable tissue. 2 to about or at least about 5,000 μC / cm 2 , 25,000μC / cm 2 , 50,000μC / cm 2The net bias current, e.g., DC bias, can be increased to, and in some cases even beyond, 1000 μC. Systems and methods configured to allow an intentional net bias current, e.g., DC bias, such as through a control system, can, in some cases, advantageously maintain the integrity of high charge capacity electrodes (by preventing or inhibiting corrosion, e.g., oxidation, or other damage to the electrode) and minimize or prevent undesired reactions and the generation of species such as OH − , H + , or oxygen free radicals that can lead to tissue damage. In some embodiments, the charge per anodic and / or cathodic phase is about 3,000 μC, 3,500 μC, 4,000 μC, 4,500 μC, 5,000 μC, 5,500 μC, 6,000 μC, or more or less, such as between about 4,000 μC and about 5,000 μC per phase, and ranges including any two of the foregoing values.

[0068] In some embodiments, the systems and methods for delivering current through implanted electrodes do not include a capacitor, such as a blocking capacitor, hi some embodiments, the systems and methods for delivering current through implanted electrodes do not include a resistor.

[0069] In some embodiments, the bias current is the current resulting from the sum of currents simultaneously supplied to electrode contacts or working electrodes proximate the target excitable or voltage-sensitive tissue. In some embodiments, the bias current is equal in magnitude and opposite in polarity to the sum of currents simultaneously supplied to the electrode contacts or working electrodes. In some embodiments, the currents simultaneously supplied to the electrode contacts or working electrodes can be adjusted to modulate the bias current.

[0070] In some embodiments, conventional AC systems, which may include AC-only systems, utilize capacitors on each / all outputs, e.g., electrodes, to prevent the delivery of DC to the tissue. Conventional AC systems typically do not include bypass switches that can bypass the capacitors, which may be required for the delivery of DC waveforms (including, e.g., very low frequencies, as discussed above).

[0071] In some embodiments, disclosed herein are neuromodulation devices configured to operate in multiple electrical modulation modes using a single architecture. The device may include, for example, a power source, a control unit, and / or one or more current generators (e.g., unipolar and / or bipolar) configured to be connected to at least one, two, three, four, or more working electrodes.

[0072] In some embodiments, the device can include a stimulation circuit including at least one, two, or more blocking capacitors configured to block direct current, at least one, two, or more indifferent electrode switches configured in electrical communication with at least one, two, or more indifferent electrodes, and at least one, two, or more blocking capacitor switches in electrical communication to bypass the at least one, two, or more blocking capacitors.

[0073] The device can include a first stimulation mode in which the current generator is configured to supply alternating current to at least one working electrode, and a second stimulation mode in which the current generator is configured to supply direct current to at least one working electrode, with both return electrodes being absorbed through an indifferent electrode.

[0074] In some embodiments, in the first stimulation mode, the control unit configures another current generator through the second working electrode, causes at least one indifferent electrode switch to disable electrical communication between the current generator and the at least one indifferent electrode, and at least one blocking capacitor functions to block direct current.

[0075] In some embodiments, in the second stimulation mode, the two current generators are configured to direct an offset current, e.g., from 0 μA to 1,000 μA or more, through the indifferent electrode switch to the indifferent electrode, and the control unit causes the at least two blocking capacitor switches to disable electrical communication between the current generators and at least one blocking capacitor, thereby bypassing the at least two blocking capacitors.

[0076] In some embodiments, the device can be configured so that very low frequency, conventional frequency, or high frequency alternating current can be supplied from the current generator to any number of working electrodes, while an anodic or cathodic bias current is supplied to any number of working electrodes with a blocking capacitor switch configured to bypass the blocking capacitor, which can be advantageous, for example, for electrode life.

[0077] In some embodiments, application specific integrated circuits (ASICs) including some embodiments herein are configured for low-power, highly versatile AC stimulation. Some embodiments can add DC, but may not necessarily be optimal for DC because the resolution of DACs (digital-to-analog converters) is relatively low, thereby limiting DC bias / offset selectivity (DC offset can be as low as 1 μA, for example, while simultaneously providing stimulation currents as high as 25 mA, for example, on the same channel), and because the power when running in DC mode is relatively high, as the current can be on continuously (100% duty cycle) or substantially continuously, whereas a conventional AC stimulation pulse can be on for 250 μS every 25 mS (1% duty cycle).

[0078] In some embodiments, referring to FIG. 1 , an application specific integrated circuit (ASIC) based DC and AC approach can include a bypass switch that bypasses each output blocking capacitor, such that a current, e.g., DC, can be supplied when the bypass switch is closed and a charge-balanced AC can be supplied when the bypass switch is open. This can be applied to each channel, e.g., channel 1 and channel 16. Thus, if the bypass switch fails and a short circuit in the switch (or other cause) causes current to flow due to an imbalance in the current sources and into the tissue, a “sense” safety mechanism (the “sense” circuit shown in FIG. 1 ) can be used to detect the excessive current flowing through the system and back through the indifferent electrode, and the IPG, for example, can then stop stimulation and / or take other safety precautions.

[0079] In some embodiments, referring to FIG. 2 , the DC and AC discrete approaches can be implemented using fewer components. For example, the blocking capacitors and bypass switches can be reduced to a single set between the current source and a multiplexer (mux), which directs current to several channels, e.g., one of 16 channels. In some embodiments, two or more sets are used. In some embodiments, more or fewer than 16 channels can be used and / or current can be directed to one or more channels. A second current source and mux can also be used to sink or source current for bipolar operation. Not including a capacitor and switch per mux output (electrode) can advantageously simplify this discrete approach, which may reduce cost, manufacturing complexity, etc. When the discrete approach described above and shown in FIGS. 3-4 is not implemented, a capacitor and switch per channel may be required (e.g., for a 16-channel system, 16 pairs of capacitors and switches may be required). As explained with reference to FIG. 2, the "sense" safety mechanism and IE can also be used in DC and AC discrete approaches.

[0080] Figure 3 shows a schematic of one embodiment of an ASIC adapted to provide both DC and AC. The DAC can directly control the current generators (source and sink), and an external capacitor bypass switch is included in the system to support DC. The bypass switch, e.g., a silicon bypass switch, is in contact with the body and can shut down if DC current is detected through the indifferent electrode (IE) / can to ensure safety.

[0081] Alternatively, both AC and DC systems can be implemented using discrete systems that share common components. Some embodiments include a single bipolar channel that can be configured across any pair of electrodes in the system, such as 16 electrodes in some cases. The AC system can be configured to include only a single current sink, which in some embodiments can be configured to be fast enough to generate pulses of approximately 10 μS, requiring a slew rate of approximately 10 V / μS. This current source can first pass through a cross-point switch to alternate polarity across a set of capacitors, which are then routed to a multi-channel multiplexer, such as a 1-to-16 channel multiplexer. A single set of capacitors can be used rather than a capacitor on each electrode because safety can still be verified by detecting DC current through the IE / CAN.

[0082] For example, the AC discrete architecture embodiments described above can be extended to handle DC by adding a current source, such as that shown schematically in FIG. 4. To conserve power, this current source can be very slow, requiring, for example, about 5, 4, 3, 2, or 1 V / mS, or less than about 5, 4, 3, 2, or 1 V / mS, rather than the larger amounts required by current sinks, such as 10 V / μS or more. In addition, switches can be added to bypass capacitors that may not be required in DC configurations. DC generally requires higher current resolution than AC so that bias / offset currents can be accurately set. Thus, in some embodiments, the DAC resolution for both the current source and current sink should be less than about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 μA, or in some cases less than about 5 μA.

[0083] Regarding current sinks and current sources, in some cases, discrete current sinks can be implemented simply and inexpensively. Current sources can in some cases be more complex and require circuits similar to those shown in Figures 5A-5B. Current sinks implement AC and generally need to be highly efficient, while current sources generally only handle low-speed DC and can operate at much slower speeds, advantageously reducing power significantly.

[0084] As described herein, some stimulation systems utilize capacitors to ensure near fail-safe operation because they are passive, low-cost, and generally reliable components. However, some systems cannot use capacitors (or at least it is less desirable to use capacitors) because they are fully integrated on silicon, the output frequency may be too low, the system may be able to pass DC, and / or the capacitors may be too large.

[0085] Figure 5B is a schematic diagram of a bipolar current generator that can be dynamically reconfigured to generate AC or DC stimulation. DACs A and B provide the stimulation amplitude. For slow DC stimulation, DACs A and B are updated slowly (e.g., 100 Hz or less) with bias applied to each current. For AC, DACs A and B are updated with activation and recovery current values, and S1 is switched to generate fast AC activation and recovery pulses. A discharge switch is available to create other AC modes, such as passive recharge.

[0086] FIG. 6 shows a schematic block diagram of a fail-safe hybrid system. The system can have a first control unit, e.g., a main microcontroller unit (MCU), configured to implement a charge management algorithm through a current generator and IE voltage output. The system can also include a second MCU, e.g., a watchdog MCU, also referred to herein as a monitoring MCU, which can have an independent charge management algorithm that can monitor the main MCU and shut down the system if there is a discrepancy. The main and watchdog MCUs can be configured to monitor the electrodes and the system in a variety of ways, including, for example, any number of: (1) monitoring electrode voltage to protect against electrode degradation and failure and electronic failure; (2) monitoring IE current to protect against device failure in AC or DC mode; and / or (3) voltage waveform morphology analysis to protect against device failure. During AC mode, a blocking capacitor can be switched inline. The main and watchdog MCUs can cross-check each other for proper orientation. The system may include a third MCU, e.g., a supervisor watchdog MCU, that can prevent the device from being reset. In external, non-implanted variations, only the clinician may be allowed to change the battery to avoid stim cycling termination when the electrodes are loaded with charge.

[0087] FIG. 7 shows a table with non-limiting potential failure mechanisms listed in each row and mitigation mechanisms in each column. Checkmarks indicate which mitigation measures protect against which failures, according to some embodiments. When a failure occurs, stimulation is stopped immediately (instant off) or at the end of the stimulation cycle when it is beneficial to end at charge balance. For example, bias current monitor out of range protects against surface electrode (IE) disconnection, current source error, coupling capacitor error, or measurement signal chain error, which would result in instant off stimulation. Cyclic VPP out of range (e.g., 10 cycles or other number of cycles) is the primary mechanism that protects against long-term electrode degradation, which would result in stimulation terminating at the completion of the stimulation cycle. Waveform morphology violations (e.g., 10 cycles or other number of cycles) protect against electrode disconnection, current source failure, or measurement error, which would result in stimulation terminating at the completion of the stimulation cycle. MCU / WD voltage monitoring protects against stimulation or other power supply issues, immediately terminating stimulation and potentially turning off power. Hardware watchdog protection guards against firmware / MCU failures that result in a total reset and immediate termination of the stimulation cycle. Offline impedance check is a proactive check to rule out faulty electrodes and insufficient electrode capacitance. MCU / WD crosscheck ensures that both MCUs are operating properly, resulting in a total reset and immediate termination of the stimulation cycle. Independent charge management algorithms (two different algorithms with independent code bases) guard against firmware bugs and unexpected algorithmic defects that result in a total reset and immediate termination of the stimulation cycle.

[0088] In some embodiments, the device can include a virtual ground configured to be operably connected to the indifferent electrode, in which case the virtual ground can be set to any level to minimize power consumption.

[0089] In some embodiments, the current drawn from the output multiplexer is measured to detect any faults in active silicon components that are directly coupled to the body, particularly to prevent unintended DC current flow due to component failure caused by ESD discharge damage.

[0090] In some embodiments, the device includes any number of mitigation mechanisms: (a) indifferent electrode current monitoring suspends operation if the bias current deviates from preset minimum and maximum ranges. The currents used can be processed to remove noise using statistical processes; (b) electrode voltage monitoring from each working electrode to the indifferent electrode, each working electrode to the reference electrode, or between pairs of working electrodes; (c) electrode monitoring can be resolved instantaneously or statistically over a preset time period, e.g., from 1 μs to 1 hour, or longer or shorter, or synchronized to waveform transitions, and statistics can include mean, median, variance, minimum, and / or maximum; and (d) electrode monitoring can examine the electrode voltage as a whole or separate it into components using a filter mechanism or by subtracting components based on what is known about the electrode, e.g., what is being measured or the electrode specifications. As an example, the filtered voltage minus stimulation current * measured access resistance described above can be less than a specified value.

[0091] Figure 8 shows a graph of lost capacity that may be related to voltage protection. Cyclic VPP: VPP-2*RA*I, which can help ensure that the peak voltage over the stimulation cycle stays within specified limits to ensure the electrodes have sufficient capacity over time. The electrode waveform shape (sawtooth) can help ensure that the electrode voltage waveform is as expected for a specified current, which can help ensure the system is operating properly.

[0092] Figures 9A and 9B relate to bias current monitoring. Figure 9A shows a graph of reference electrode removal. Figure 9B shows a graph of bias current removal. Bias current monitoring can protect against a variety of faults, including IE failure (open circuit or Hi-Z), WE failure (open circuit or Hi-Z), WE current source failure (high level or low level), IE voltage source failure (no current causing current source failure), and / or capacitor bypass switch failure (current leakage or fail open). In DC-only modulation mode, the monitor can check that the bias is within the correct range (e.g., 25-75 μA). In AC-only modulation mode, the monitor can check that the DC current is below a predetermined value, such as ≦100 nA (e.g., electronic circuit failure or complex capacitor failure).

[0093] FIG. 10 relates to reducing (e.g., minimizing) irrecoverable charge. FIG. 10 shows the relationship between stimulation onset and time in seconds. Injecting a bias current can place the electrode within an operating voltage range that can allow for increased charge and / or maximized electrode life, etc. The operating condition of the electrode can be determined, which can include determining that the electrode is in good operating condition. For example, a determination that the electrode is in good operating condition can be made by (1) determining (e.g., ensuring) that the peak of a referenced voltage waveform is below a calculated or empirically calculated voltage, and / or (2) taking the cycle voltage as an indicator of irreversible charge and / or determining (e.g., ensuring) that it is below a certain threshold.

[0094] Figure 11 shows an example block diagram for HW and FW failsafes. Charge management algorithm - main MCU controls the ASIC (or discrete current generator). MCU / WD voltage / current monitoring - watchdog MCU ensures HW and FW are operational so that independent ADCs and algorithms in main and watchdog can be kept alive. MCU / WD crosscheck - main and watchdog MCUs check each other to ensure HW and FW are operational. MCU / WD ASIC reset - either main or watchdog MCU can reset the ASIC when a problem is detected.

[0095] AC neurostimulation systems can rely primarily on series capacitors to isolate the active circuitry from the body. In conjunction with an internal discharge resistor / switch, the capacitor not only protects against circuit failure but also provides a charge-balanced waveform. High-capacity electrode systems utilizing unbalanced-charge biphasic waveforms operating at very low frequencies utilize DC stimulation and cannot easily utilize capacitors, and therefore must implement alternative safety mechanisms.

[0096] DC works by providing an imbalanced charge ultra-low frequency imbalanced waveform that allows the electrodes to operate within their protected voltage region where long-term electrode capacitance is optimized and preserved. This safety mechanism ensures that the resulting electrode voltage remains within a specified range as assessed by at least two independent mechanisms, even in the event of one or more system failures, any detected failures can result in stimulation being shut down and the stimulation engine being powered down.

[0097] To better understand mitigation strategies, the electrode can be modeled by a simple Randles cell: series access resistance (Ra) and capacitance (Cdl) and polarization resistor (Rp or Rct). The polarization resistor is ignored in this treatment because it is approximately >10× larger than Ra. The total voltage across the electrode (Vt) is equal to Ra * I + cyclic Vpp, where cyclic Vpp is the peak-to-peak voltage across the capacitive component (Cdl) of the electrode. Given this relationship, Va (from Ra × I) and cyclic Vpp can be separated on each stimulation cycle using real-time measurements of Vt and Ra can be calculated.

[0098] To ensure tissue safety, it can be important to operate electrodes within their electrode capacity. Driving electrodes outside of their capacity can ultimately reduce electrode capacity, promoting reactions that can affect tissue health and potentially causing irreversible electrochemical reactions. The cyclic Vpp is a key measure of electrode health and is inversely proportional to the electrode's capacity. It is expected that the cyclic Vpp will be fairly constant once the electrode achieves steady-state operation. If changes to the electrode occur over its lifetime, they can be detected via the cyclic Vpp, and stimulation can be adjusted to ensure operation within the electrode capacity, or the stimulating electrode can be replaced as needed.

[0099] The stimulus engine may include several mitigation mechanisms, which may be categorized into firmware-based charge management algorithm (CMA) components, which are firmware-based mitigation mechanisms and hardware mitigation mechanisms, summarized in the table shown in FIG. 7.

[0100] Because the firmware has a 100% long-term failure probability, the CMA component can be implemented independently on multiple independent MCUs, such as the main and safety MCUs. Two independent firmware images running two independent algorithms running on two independent processors can result in a very low failure probability over a finite time window. If a failure is detected within one second and both systems independently have an average failure rate of one failure per day, the probability of failure over a 10-year lifetime is (1 / 86,4002) x 10y x 365d / y = 1 / 31,104,000.

[0101] The foregoing description and examples have been set forth to illustrate the present disclosure in accordance with various embodiments and are not intended to be unduly limiting. The headings provided herein are for organizational purposes only and should not be used to limit the embodiments. Each of the disclosed aspects and examples of the present disclosure may be considered individually or in combination with other aspects, examples, and variations of the present disclosure. In addition, unless otherwise specified, none of the steps of the methods of the present disclosure are limited to any particular order of performance. References cited herein are incorporated by reference in their entirety.

[0102] While the methods and devices described herein may be susceptible to various modifications and alternative forms, specific examples of which have been shown in the drawings and are described in detail herein, it is to be understood, however, that the disclosed embodiments are intended to cover modifications, equivalents, and alternatives that are within the spirit and scope of the various embodiments described herein and the appended claims.

[0103] Depending on the embodiment, one or more acts, events, or functions of any of the algorithms, methods, or processes described herein may be performed in a different order, or may be added, merged, or omitted entirely (e.g., not all described acts or events may be required to execute an algorithm). In some examples, acts or events may be performed simultaneously rather than sequentially, for example, through multithreading, interrupt processing, or multiple processors or processor cores, or on other parallel architectures.

[0104] The use of sequential or chronological language such as "then," "next," "after," "then," and the like, unless specifically stated otherwise or understood otherwise in the context of use, is generally intended to facilitate the flow of the text and is not intended to limit the order in which actions are performed.

[0105] The various illustrative logic blocks, modules, processes, methods, and algorithms described in connection with the embodiments disclosed herein may be implemented as electronic hardware, as computer software, or as a combination of both. To clearly illustrate this interchangeability of hardware and software, various illustrative components, blocks, modules, operations, and steps have been described above generally in terms of their functionality. Whether such functionality is implemented as hardware or software depends on the particular application and design constraints imposed on the overall system. The described functionality may be implemented in various ways for each particular application, and such implementation decisions should not be interpreted as causing a departure from the scope of the present disclosure.

[0106] The various illustrative logic blocks and modules described in connection with the embodiments disclosed herein may be implemented or performed by a machine, such as a general-purpose processor, a digital signal processor (DSP), an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA) or other programmable logic device, discrete gate or transistor logic circuitry, discrete hardware components, or any combination thereof, designed to perform the functions described herein. A general-purpose processor may be a microprocessor, but in the alternative, the processor may be a controller, microcontroller, or state machine, combinations thereof, or the like. A processor may also be implemented as a combination of computing devices, such as a combination of a DSP and a microprocessor, multiple microprocessors, one or more microprocessors and a DSP core, or any other such configuration.

[0107] The blocks, operations, or steps of a method, process, or algorithm described in connection with the embodiments disclosed herein may be embodied directly in hardware, as a software module executed by a processor, or as a combination of the two. The software module may reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, a hard disk, a removable disk, an optical disk (e.g., a CD-ROM or DVD), or any other form of volatile or non-volatile computer-readable storage medium known in the art. The storage medium may be coupled to the processor such that the processor can read information from, and write information to, the storage medium. In the alternative, the storage medium may be integral to the processor. The processor and the storage medium may reside in an ASIC. The ASIC may reside in a user terminal. In the alternative, the processor and the storage medium may reside as discrete components in a user terminal.

[0108] Conditional language used herein, such as "can," "might," "may," "for example," among others, is generally intended to convey that some examples include certain features, elements, and / or conditions, and other examples do not, unless specifically stated otherwise or understood otherwise in the context of use. Thus, such conditional language is generally not intended to imply that features, elements, blocks, and / or conditions are in any way required by one or more examples, or that one or more examples necessarily include logic for determining whether those features, elements, and / or conditions are included in or will be implemented in any particular embodiment, with or without authorial input or direction.

[0109] While the methods disclosed herein may include some actions performed by a practitioner, the methods may also include, explicitly or implicitly, any third-party instruction of those actions. For example, an action such as "positioning an electrode" includes "instructing to position the electrode."

[0110] Ranges disclosed herein encompass any and all overlaps, subranges, and combinations thereof. Phrases such as "up to," "at least," "greater than," "less than," and "between" are inclusive of the recited number. Numbers preceded by words such as "about" or "approximately" are inclusive of the recited number and should be interpreted as precisely as reasonably possible given the circumstances (e.g., ±5%, ±10%, ±15%, etc.). For example, "about 1 hour" includes "1 hour." Phrases preceded by words such as "substantially" are inclusive of the recited phrase and should be interpreted as broadly as reasonably possible given the circumstances (e.g., as broadly as reasonably possible given the circumstances). For example, "substantially vertical" includes "vertical." Unless otherwise specified, all measurements are at standard conditions, including temperature and pressure. The phrase "at least one of" is intended to require at least one item from the subsequent list, rather than requiring one type from each item in the subsequent list. For example, "at least one of A, B, and C" can include A, B, C, A and B, A and C, B and C, or A, B, and C.

Claims

1. 1. A neuromodulation device configured to operate in multiple electrical modulation modes using a single architecture, comprising: Power supply and a control unit; a bipolar current generator configured to be connected to at least one working electrode; a stimulation circuit comprising at least one blocking capacitor configured to block direct current, at least one indifferent electrode switch configured to be in electrical communication with the at least one indifferent electrode, and at least one blocking capacitor switch in electrical communication to bypass the at least one blocking capacitor; Equipped with The device includes a first stimulation mode, in which the current generator is configured to supply an alternating current to the at least one working electrode, and a second stimulation mode, in which the current generator is configured to supply a direct current to the at least one working electrode, and both return electrodes are absorbed through the indifferent electrode; In the first stimulation mode, the control unit configures another current generator through a second working electrode, causes the at least one indifferent electrode switch to disable electrical communication between the current generator and the at least one indifferent electrode, and at least one blocking capacitor functions to block direct current; the two current generators are configured such that, in the second stimulation mode, an offset current is configured to pass through the indifferent electrode switch to the indifferent electrode, and the control unit causes at least two blocking capacitor switches to disable electrical communication between the current generators and the at least one blocking capacitor, thereby bypassing the at least two blocking capacitors. Neuromodulation devices.

2. The neuromodulation device of claim 1 , wherein the direct current comprises an extremely low frequency current.

3. 3. The neuromodulation device of claim 2, wherein the extremely low frequency current is less than about 5 Hz.

4. 3. The neuromodulation device of claim 2, wherein the extremely low frequency current is less than about 2 Hz.

5. 3. The neuromodulation device of claim 2, wherein the extremely low frequency current is less than about 1 Hz.

6. The neuromodulation device of claim 1 , wherein the alternating current is a high-frequency alternating current.

7. 7. The neuromodulation device of claim 6, wherein the high frequency alternating current is at least about 1 kHz.

8. 2. The neuromodulation device of claim 1, wherein the alternating current is between about 5 Hz and about 1 kHz.

9. The neuromodulation device of claim 1 , wherein the power source comprises a battery.

10. 10. The neuromodulation device of claim 1, wherein the control unit comprises a first control unit and a second control unit configured to execute independent algorithms.

11. The neuromodulation device of claim 1 , configured to measure the offset current when the device is in the second stimulation mode.

12. The neuromodulation device of claim 1 configured to measure the periodic Vpp of the at least one working electrode.

13. 10. The neuromodulation device of claim 1, further comprising a virtual ground configured to be operably connected to the indifferent electrode, wherein the virtual ground can be set to any level to minimize power consumption.

14. (a) a control system configured to measure a bias current from an indifferent electrode and to suspend or modify operation if said bias current deviates outside preset parameters; (b) a control system configured to measure electrode voltages between any pair of working electrodes, between the working electrode and a reference electrode, and between the working electrode and an indifferent electrode; (c) a control system configured to resolve the electrode monitoring in relation to waveform transitions; and (d) a control system configured to receive data relating to the total or components of the electrode voltage that are subjected to statistical analysis based on the electrode characteristics.

10. The neuromodulation device of claim 1, comprising one or more of the mitigation mechanisms selected from the group consisting of:

15. The neuromodulation device of claim 14 comprising all of the mitigation mechanisms.

16. 1. A method of delivering electrical neuromodulation to electrically excitable tissue of a patient utilizing a neuromodulation therapy device, comprising: applying an alternating current to at least one working electrode in electrical communication with the electrically excitable tissue. Including, and wherein the step of supplying alternating current includes the steps of: utilizing at least one blocking capacitor of the neuromodulation therapy device to block direct current; and preventing electrical communication between the neuromodulation therapy device and at least one indifferent electrode. method.

17. interrupting the supply of alternating current; applying a direct current to the at least one working electrode; and applying an offset current to the at least one indifferent electrode. further comprising and wherein supplying direct current comprises bypassing the at least one blocking capacitor of the neuromodulation therapy device.

17. The method of claim 16.

18. 18. The method of claim 16 or 17, further comprising the steps of: interrupting the supply of direct current to the at least one working electrode; and resuming the supply of alternating current to the at least one working electrode, wherein resuming the supply of alternating current comprises utilizing the at least one blocking capacitor of the neuromodulation therapy device to block the direct current; and preventing electrical communication between the neuromodulation therapy device and at least one indifferent electrode.

19. 18. The method of claim 16 or 17, wherein the direct current comprises an extremely low frequency current.

20. 20. The method of claim 19, wherein the extremely low frequency current is less than about 5 Hz.

21. 20. The method of claim 19, wherein the extremely low frequency current is less than about 2 Hz.

22. 20. The method of claim 19, wherein the extremely low frequency current is less than about 1 Hz.

23. The method of claim 16, wherein the alternating current is a high frequency alternating current.

24. 24. The method of claim 23, wherein the high frequency alternating current is at least about 1 kHz.

25. 17. The method of claim 16, wherein the alternating current is between about 10 Hz and about 1 kHz.

26. 18. The method of claim 17, further comprising measuring the offset current using the neuromodulation device.

27. 17. The method of claim 16, further comprising measuring the periodic Vpp of the at least one working electrode.

28. 1. A method of delivering electrical neuromodulation to electrically excitable tissue of a patient utilizing a neuromodulation therapy device, comprising: applying a direct current to at least one working electrode and an offset current to at least one indifferent electrode; Including, and wherein supplying direct current comprises bypassing at least one blocking capacitor of the neuromodulation therapy device. method.

29. interrupting the supply of the direct current to the at least one working electrode and the supply of the offset current to the at least one indifferent electrode; applying an alternating current to the at least one working electrode in electrical communication with the electrically excitable tissue; further comprising and wherein the step of supplying alternating current includes the steps of: utilizing at least one blocking capacitor of the neuromodulation therapy device to block direct current; and preventing electrical communication between the neuromodulation therapy device and at least one indifferent electrode.

29. The method of claim 28.

30. interrupting the supply of alternating current; resuming the supply of direct current to the at least one working electrode and the supply of the offset current to the at least one indifferent electrode; further comprising and wherein resuming the supply of direct current comprises bypassing the at least one blocking capacitor of the neuromodulation therapy device.

30. The method of claim 29.

31. 30. The method of claim 28, wherein the direct current comprises extremely low frequency current.

32. 32. The method of claim 31, wherein the extremely low frequency current is less than about 5 Hz.

33. 32. The method of claim 31, wherein the extremely low frequency current is less than about 2 Hz.

34. 32. The method of claim 31, wherein the extremely low frequency current is less than about 1 Hz.

35. 30. The method of claim 29, wherein the alternating current is a high frequency alternating current.

36. 36. The method of claim 35, wherein the high frequency alternating current is at least about 1 kHz.

37. 30. The method of claim 29, wherein the alternating current is between about 10 Hz and about 1 kHz.

38. 30. The method of claim 28, further comprising measuring the offset current using the neuromodulation device.

39. 30. The method of claim 28, further comprising measuring the periodic Vpp of the at least one working electrode.

40. 1. A neuromodulation device configured to operate in multiple electrical modulation modes using a single architecture, comprising: Power supply and a control unit; a current generator configured to be connected to the at least one working electrode; a stimulation circuit comprising at least one blocking capacitor configured to block direct current, at least one indifferent electrode switch configured to be in electrical communication with at least one indifferent electrode, and at least one blocking capacitor switch in electrical communication to bypass the at least one blocking capacitor; A device comprising:

41. 41. The device of claim 40, comprising a first stimulation mode in which the current generator is configured to supply an alternating current to the at least one working electrode.

42. 42. The device of claim 41, further comprising a second stimulation mode in which the current generator is configured to supply direct current to the at least one working electrode and both return electrodes are absorbed through the indifferent electrode.

43. 43. The device of claim 41 or 42, wherein in the first stimulation mode, the control unit configures another current generator through a second working electrode, causes the at least one indifferent electrode switch to disable electrical communication between the current generator and the at least one indifferent electrode, and at least one blocking capacitor functions to block direct current.

44. 44. The device of any one of claims 41 to 43, wherein in the second stimulation mode, the two current generators are configured to pass an offset current of from 0 μA to 100 μA or more through the indifferent electrode switch to the indifferent electrode, and the control unit causes at least two blocking capacitor switches to disable electrical communication between the current generators and the at least one blocking capacitor, thereby bypassing the at least two blocking capacitors.

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