WO2023067532A1

WO2023067532A1 - Measuring electrode-tissue impedance during active current stimulation

Info

Publication number: WO2023067532A1
Application number: PCT/IB2022/060076
Authority: WO
Inventors: Omid Shoaei; Foad BEHESHTI; Saeed Mohseni; Elaheh ANSARI
Original assignee: Omid Shoaei
Priority date: 2021-10-20
Filing date: 2022-10-20
Publication date: 2023-04-27

Abstract

A method for measuring an electrode-tissue impedance during active current stimulation of a tissue of a subject's body. The method includes placing a first electrode on the tissue, placing a second electrode on a region of the subject's body, applying a biphasic current stimulation to the tissue, measuring a current-stimulus-response voltage signal of the tissue during the biphasic current stimulation, and calculating the electrode-tissue impedance based on the current-stimulus-response voltage signal. Applying the biphasic current stimulation to the tissue includes passing a stimulation current between the first electrode and the second electrode inside the tissue in a first direction for a first time period, stopping a passage of the stimulation current inside the tissue for a second time period, and passing the stimulation current between the first electrode and the second electrode inside the tissue in a second direction for a third time period.

Description

MEASURING ELECTRODE-TISSUE IMPEDANCE DURING ACTIVE CURRENT

STIMULATION

TECHNICAL FIELD

[0001] The present disclosure generally relates to electronic circuits, and particularly, to medical stimulators.

BACKGROUND ART

[0002] Electrical stimulation is an effective approach for controlling syndromes of diseases. This approach is practical for cardiac, auditory, visual, muscular, and deep brain stimulators. These medical stimulators are designed to apply electrical stimulation to different tissue areas of a patient’s body. A typical stimulator device consists of three major circuitries including control, stimulation, and impedance measurement along with a number of electrodes. The electrodes deliver electrical stimulation to tissue areas that are in contact with the electrodes.

[0003] In general, electrical stimulators are able to measure an impedance between electrodes to monitor an electrode-tissue impedance and the contact quality of the electrodes. However, conventional stimulators devices may perform impedance measurement before a regular active stimulation [US Patents no. 8,239,036 B2, 8,788,056 B2, 9,802,045 B2, and 10,952,627 B2], As a result, not only impedance measurement precision may decrease but also patients may experience pain and discomfort as a result of applying irregular stimulation pulses for impedance measurement.

[0004] There is, therefore, a need for a method for electrode-tissue impedance measurement during active stimulation of tissues. There is also a need for an electronic circuit that may facilitate measurement of electrode-tissue impedance during electrical stimulation of tissues.

SUMMARY OF THE DISCLOSURE

[0005] This summary is intended to provide an overview of the subject matter of the present disclosure, and is not intended to identify essential elements or key elements of the subject matter, nor is it intended to be used to determine the scope of the claimed implementations. The proper scope of the present disclosure may be ascertained from the claims set forth below in view of the detailed description below and the drawings. [0006] In one general aspect, the present disclosure describes an exemplary method for measuring an electrode-tissue impedance during active current stimulation of a tissue of a subject’s body. An exemplary method may include placing a first electrode on the tissue, placing a second electrode on a region of the subject’s body, applying a biphasic current stimulation to the tissue, measuring a current-stimulus-response voltage signal of the tissue during the biphasic current stimulation, and calculating the electrode-tissue impedance based on the biphasic current stimulation and the current-stimulus-response voltage signal. An exemplary current stimulation circuitry may be utilized for applying the biphasic current stimulation to the tissue. An exemplary voltage measurement circuitry may be utilized for measuring the current-stimulus-response voltage signal.

[0007] In an exemplary embodiment, applying the biphasic current stimulation to the tissue may include passing a stimulation current between the first electrode and the second electrode inside the tissue in a first direction for a first time period, stopping a passage of the stimulation current inside the tissue for a second time period, and passing the stimulation current between the first electrode and the second electrode inside the tissue in a second direction for a third time period after the second time period. An exemplary second time period may start at an end of the first time period. An exemplary second direction may be opposite to the first direction.

[0008] In an exemplary embodiment, placing the first electrode and placing the second electrode may include placing an electrode array on the tissue. In an exemplary embodiment, placing the second electrode may include placing an electrode of a size of at least one order of magnitude larger than a size of the first electrode on the region.

[0009] In an exemplary embodiment, passing the stimulation current in the first direction may include selecting the first electrode from a plurality of electrodes, coupling the first electrode to a power source of the current stimulation circuitry by closing a first switch of the current stimulation circuitry at a beginning of the first time period, selecting the second electrode from the plurality of electrodes, and coupling the second electrode to a current source of the current stimulation circuitry by closing a second switch of the current stimulation circuitry at the beginning of the first time period. An exemplary first switch may be connected between the first electrode and the power source. An exemplary second switch may be connected between the second electrode and the current source. An exemplary first demultiplexer of the current stimulation circuitry may be utilized for selecting the first electrode. An exemplary control logic circuitry may be utilized for closing the first switch and the second switch. An exemplary second demultiplexer of the current stimulation circuitry may be utilized for selecting the second electrode.

[0010] In an exemplary embodiment, stopping the passage of the stimulation current may include decoupling the second electrode from the current source by opening the second switch at the end of the first time period and decoupling the first electrode from the power source by opening the first switch at an end of the second time period. An exemplary control logic circuitry may be utilized for opening the first switch and the second switch.

[0011] In an exemplary embodiment, passing the stimulation current in the second direction may include coupling the first electrode to the current source by closing a third switch of the current stimulation circuitry at a beginning of the third time period and coupling the second electrode to the power source by closing a fourth switch of the current stimulation circuitry at the beginning of the third time period. An exemplary third switch may be connected between the first electrode and the current source. An exemplary fourth switch may be connected between the second electrode and the power source. An exemplary control logic circuitry may be utilized for closing the third switch and the fourth switch.

[0012] In an exemplary embodiment, closing the first switch may include applying a first control signal to the first switch by the control logic circuitry. In an exemplary embodiment, closing the second switch may include applying a second control signal to the second switch by the control logic circuitry. In an exemplary embodiment, closing the third switch and closing the fourth switch may include applying a third control signal to each of the third switch and the fourth switch by the control logic circuitry.

[0013] In an exemplary embodiment, measuring the current-stimulus-response voltage signal may include obtaining a first attenuated voltage of the first electrode and a second attenuated voltage of the second electrode by equally attenuating voltages of the plurality of electrodes. In an exemplary embodiment, equally attenuating the voltages may include passing a respective voltage of each of the plurality of electrodes through a respective resistive attenuator of a front end circuitry of the voltage measurement circuitry. In an exemplary embodiment, measuring the current-stimulus-response voltage signal may further include selecting the first attenuated voltage from a plurality of attenuated voltages of the plurality of electrodes, selecting the second attenuated voltage from the plurality of attenuated voltages, obtaining an amplitude- altered voltage signal by differentially amplifying a voltage difference between the first attenuated voltage and the second attenuated voltage, and obtaining the current-stimulus- response voltage signal by digitizing the amplitude-altered voltage signal. An exemplary first multiplexer of the front end circuitry may be utilized for selecting the first attenuated voltage. An exemplary second multiplexer of the front end circuitry may be utilized for selecting the second attenuated voltage. An exemplary programmable-gain difference amplifier (PGDA) of the voltage measurement circuitry may be utilized for amplifying the voltage difference. An exemplary analog-to-digital converter (ADC) of the voltage measurement circuitry may be utilized for digitizing the amplitude-altered voltage signal.

[0014] Other exemplary systems, methods, features and advantages of the implementations will be, or will become, apparent to one of ordinary skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, methods, features and advantages be included within this description and this summary, be within the scope of the implementations, and be protected by the claims herein.

BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The drawing figures depict one or more implementations in accord with the present teachings, by way of example only, not by way of limitation. In the figures, like reference numerals refer to the same or similar elements.

[0016] FIG. 1A shows a flowchart of a method for measuring an electrode-tissue impedance during active current stimulation of a tissue of a subject’s body, consistent with one or more exemplary embodiments of the present disclosure.

[0017] FIG. IB shows a flowchart for applying a biphasic current stimulation to a tissue, consistent with one or more exemplary embodiments of the present disclosure.

[0018] FIG. 1C shows a flowchart for passing a stimulation current in a first direction, consistent with one or more exemplary embodiments of the present disclosure.

[0019] FIG. ID shows a flowchart for stopping a passage of a stimulation current, consistent with one or more exemplary embodiments of the present disclosure.

[0020] FIG. IE shows a flowchart for passing a stimulation current in a second direction, consistent with one or more exemplary embodiments of the present disclosure.

[0021] FIG. IF shows a flowchart for measuring a current-stimulus-response voltage signal, consistent with one or more exemplary embodiments of the present disclosure. [0022] FIG. 2A shows a schematic of a circuit for measuring an electrode-tissue impedance during active current stimulation of a tissue of a subject’s body, consistent with one or more exemplary embodiments of the present disclosure.

[0023] FIG. 2B shows a schematic of a current stimulation circuitry, consistent with one or more exemplary embodiments of the present disclosure.

[0024] FIG. 2C shows a schematic of a front end circuitry of a voltage measurement circuitry, consistent with one or more exemplary embodiments of the present disclosure.

[0025] FIG. 2D shows a schematic of a first implementation of a reference electrode, consistent with one or more exemplary embodiments of the present disclosure.

[0026] FIG. 2E shows a schematic of a second implementation of a reference electrode, consistent with one or more exemplary embodiments of the present disclosure.

[0027] FIG. 3A shows a diagram of stimulation control signals, consistent with one or more exemplary embodiments of the present disclosure.

[0028] FIG. 3B shows a diagram of voltage signals, consistent with one or more exemplary embodiments of the present disclosure.

[0029] FIG. 4 shows a schematic of an electrode-tissue-electrode impedance model, consistent with one or more exemplary embodiments of the present disclosure.

[0030] FIG. 5 shows a high-level functional block diagram of a computer system, consistent with one or more exemplary embodiments of the present disclosure.

DESCRIPTION OF EMBODIMENTS

[0031] In the following detailed description, numerous specific details are set forth by way of examples in order to provide a thorough understanding of the relevant teachings. However, it should be apparent that the present teachings may be practiced without such details. In other instances, well known methods, procedures, components, and/or circuitry have been described at a relatively high-level, without detail, in order to avoid unnecessarily obscuring aspects of the present teachings.

[0032] The following detailed description is presented to enable a person skilled in the art to make and use the methods and devices disclosed in exemplary embodiments of the present disclosure. For purposes of explanation, specific nomenclature is set forth to provide a thorough understanding of the present disclosure. However, it will be apparent to one skilled in the art that these specific details are not required to practice the disclosed exemplary embodiments. Descriptions of specific exemplary embodiments are provided only as representative examples. Various modifications to the exemplary implementations will be readily apparent to one skilled in the art, and the general principles defined herein may be applied to other implementations and applications without departing from the scope of the present disclosure. The present disclosure is not intended to be limited to the implementations shown, but is to be accorded the widest possible scope consistent with the principles and features disclosed herein.

[0033] Herein is disclosed an exemplary method and circuit for extracting values of components of a three-component electrode-tissue impedance model during an active current stimulation applied by a medical stimulation device to a body tissue via two active electrodes. An exemplary circuit may include a processor, a control logic circuitry, a current stimulation circuitry, a number of electrodes, and an impedance measurement circuitry. An exemplary control logic circuitry may generate a set of three stimulation control signals and another set of electrode-select control signals. An exemplary current stimulation circuitry may apply a biphasic stimulation to the tissue according to the set of three stimulation control signals. Each of exemplary resultant voltage signals at two active electrodes may be selected by a multiplexer controlled by the same control logic circuitry. Exemplary resultant voltage signals may be differentially amplified by a programmable-gain difference amplifier. Exemplary values of components of the three-component electrode-tissue impedance model may be extracted from the amplified voltages through a series of calculations performed by the processor.

[0034] FIG. 1A shows a flowchart of a method for measuring an electrode-tissue impedance during active current stimulation of a tissue of a subject’s body, consistent with one or more exemplary embodiments of the present disclosure. An exemplary method 100 may include placing a first electrode on the tissue (step 102), placing a second electrode on a region of the subject’s body (step 104), applying a biphasic current stimulation to the tissue (step 106), measuring a current-stimulus-response voltage signal of the tissue during the biphasic current stimulation (step 108), and calculating the electrode-tissue impedance based on the biphasic current stimulation and the current-stimulus-response voltage signal (step 110).

[0035] FIG. 2A shows a schematic of a circuit for measuring an electrode-tissue impedance during active current stimulation of a tissue of a subject’s body, consistent with one or more exemplary embodiments of the present disclosure. An exemplary circuit 200 may include a plurality of electrodes 202, a current stimulation circuitry 204, a voltage measurement circuitry 206, a control logic circuitry 208, and a processor 210. In an exemplary embodiment, different steps of method 100 may be implemented utilizing different components of circuit 200, as described below.

[0036] In further detail regarding step 102, in an exemplary embodiment, plurality of electrodes 202 may include an electrode array 212. Exemplary electrodes of electrode array 212 may have a same shape and contact area. In an exemplary embodiment, step 102 may include placing a first electrode 212A of electrode array 212 on a tissue 214 of the subject’s body.

[0037] For further detail with regards to step 104, an exemplary second electrode may be an electrode 212B of electrode array 212 or a reference electrode 216 of plurality of electrodes 202. An exemplary size of reference electrode 216 may be at least one order of magnitude larger than a size of first electrode 212A. In an exemplary embodiment, step 104 may include placing electrode 212B on tissue 214 to perform a bipolar stimulation of tissue 214. In an exemplary embodiment, “bipolar stimulation” may refer to a stimulation in which both active electrodes of the stimulation are placed in a same region of a subject’s body (for example, tissue 214). In an exemplary embodiment, step 104 may include placing reference electrode 216 on a region 218 of the subject’s body to perform a monopolar stimulation of tissue 214. In an exemplary embodiment, “monopolar stimulation” may refer to a stimulation in which active electrodes of the stimulation are placed in different regions (for example, tissue 214 and region 218) of a subject’s body.

[0038] For further detail with respect to step 106, FIG. IB shows a flowchart for applying a biphasic current stimulation to a tissue, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, applying the biphasic current stimulation to tissue 214 may include passing a stimulation current between the first electrode and the second electrode inside the tissue in a first direction for a first time period (step 112), stopping a passage of the stimulation current inside the tissue for a second time period (step 114), and passing the stimulation current between the first electrode and the second electrode inside the tissue in a second direction for a third time period after the second time period (step 116). An exemplary second direction may be opposite to the first direction.

[0039] In further detail regarding step 112, FIG. 1C shows a flowchart for passing a stimulation current in a first direction, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, passing the stimulation current in the first direction may include selecting the first electrode from the plurality of electrodes (step 118), coupling the first electrode to a power source (step 120), selecting the second electrode from the plurality of electrodes (step 122), and coupling the second electrode to a current source (step 124).

[0040] For further detail with respect to steps 118-124, FIG. 2B shows a schematic of a current stimulation circuitry, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, current stimulation circuitry 204 may include a first demultiplexer 220, a power source 222, a first switch 224, a second demultiplexer 226, a current source 228, and a second switch 230. In an exemplary embodiment, first switch 224 may be connected between plurality of electrodes 202 and power source 222. In an exemplary embodiment, second switch 230 may be connected between plurality of electrodes 202 and current source 228. An exemplary plurality of direct current (DC) blocking capacitors 223 may be connected between power source 222 and plurality of electrodes 202 to prevent causing possible tissue irritation. Each exemplary capacitor of plurality of DC blocking capacitors 223 may be connected to corresponding electrode of plurality of electrodes 202. In an exemplary embodiment, steps 118-124 may be implemented utilizing different components of current stimulation circuitry 204, as described below.

[0041] In an exemplary embodiment, step 118 may include selecting first electrode 212A from plurality of electrodes 202. In an exemplary embodiment, first demultiplexer 220 may be utilized for selecting first electrode 212A. Exemplary outputs of first demultiplexer 220 may be connected to plurality of electrodes 202. An exemplary electrode selection signal 227 may configure first demultiplexer 220 to select first electrode 212A by coupling an input of first demultiplexer 220 to first electrode 212A. In an exemplary embodiment, electrode selection signal 227 may be produced by control logic circuitry 208 in FIG. 2A. In an exemplary embodiment, a “control logic circuitry” may refer to a logic circuit that may be programmed (for example, via programmable hardware interconnects) to control different components (such as first demultiplexer 220) of a circuit (for example, circuit 200). An exemplary input of first demultiplexer 220 may be coupled to each of power source 222 and current source 228 through respective switches. As a result, in an exemplary embodiment, first demultiplexer 220 may couple power source 222 or current source 228 to first electrode 212A upon activation of a respective switch, as described below.

[0042] In further detail with regarding step 120, FIG. 3A shows a diagram of stimulation control signals, consistent with one or more exemplary embodiments of the present disclosure. Referring to FIGs. 1C, 2A, 2B, and 3, in an exemplary embodiment, step 120 may include coupling first electrode 212A to power source 222 by closing first switch 224 at a beginning (i.e., a moment 302) of a first time period 304. In an exemplary embodiment, control logic circuitry 208 may be utilized for closing first switch 224. An exemplary first control signal 306 may be applied to first switch 224 by control logic circuitry 208 to keep first switch 224 closed during first time period 304. For this purpose, in an exemplary embodiment, control logic circuitry 208 may apply a constant voltage to first switch 224 during first time period 304. An exemplary constant voltage may be higher than an activation threshold of first switch 224.

[0043] In an exemplary embodiment, step 122 may include selecting the second electrode from plurality of electrodes 202. In an exemplary embodiment, second demultiplexer 226 may be utilized for selecting electrode 212B for bipolar stimulation or selecting reference electrode 216 for monopolar stimulation, respectively Exemplary outputs of second demultiplexer 226 may be connected to plurality of electrodes 202. An exemplary electrode selection signal 229 may configure second demultiplexer 226 to select the second electrode (i.e., electrode 212B or reference electrode 216) by coupling an input of second demultiplexer 226 to the second electrode. In an exemplary embodiment, electrode selection signal 229 may be produced by control logic circuitry 208. An exemplary input of second demultiplexer 226 may be coupled to each of power source 222 and current source 228 through respective switches. As a result, in an exemplary embodiment, second demultiplexer 226 may couple power source 222 or current source 228 to the second electrode upon activation of a respective switch.

[0044] In an exemplary embodiment, step 124 may include coupling the second electrode to current source 228 by closing second switch 230 at moment 302. In an exemplary embodiment, control logic circuitry 208 may be utilized for closing second switch 230. An exemplary second control signal 308 may be applied to second switch 230 by control logic circuitry 208 to keep second switch 230 closed during first time period 304. For this purpose, in an exemplary embodiment, control logic circuitry 208 may apply a constant voltage to second switch 230 during first time period 304. An exemplary constant voltage may be higher than an activation threshold of second switch 230. As a result, an exemplary cross-pair 231 of first switch 224 and second switch 230 may provide a path between power source 222 and current source 228 to deliver the stimulation current to tissue 214 in the first direction through the first electrode and the second electrode during first time period 304. [0045] In further detail regarding step 114, FIG. ID shows a flowchart for stopping a passage of a stimulation current, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, stopping the passage of the stimulation current in step 114 may include decoupling the second electrode from the current source (step 126) and decoupling the first electrode from the power source (step 128).

[0046] In an exemplary embodiment, step 126 may include decoupling the second electrode from current source 228 by opening second switch 230 at an end (i.e., a moment 310) of first time period 304. In an exemplary embodiment, control logic circuitry 208 may be utilized for opening second switch 230. For this purpose, in an exemplary embodiment, control logic circuitry 208 may stop applying second control signal 308 to second switch 230 at moment 310

[0047] In an exemplary embodiment, step 128 may include decoupling first electrode 212A from power source 222 by opening first switch 224 at an end (i.e., a moment 312) of a second time period 314. In an exemplary embodiment, second time period 314 may start at moment 310. In an exemplary embodiment, control logic circuitry 208 may be utilized for opening first switch 224. For this purpose, in an exemplary embodiment, control logic circuitry 208 may stop applying first control signal 306 to first switch 224 at moment 312.

[0048] For further detail with regards to step 116, FIG. IE shows a flowchart for passing a stimulation current in a second direction, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, passing the stimulation current in the second direction may include coupling the first electrode to the current source (step 130) and coupling the second electrode to the power source (step 132).

[0049] Referring again to FIG. 2B, in an exemplary embodiment, current stimulation circuitry 204 may further include a third switch 232 and a fourth switch 234. In an exemplary embodiment, third switch 232 may be connected between plurality of electrodes 202 and current source 228. In an exemplary embodiment, fourth switch 234 may be connected between plurality of electrodes 202 and power source 222. In an exemplary embodiment, third switch 232 and fourth switch 234 may be utilized for implementing step 116, as described below.

[0050] Referring to FIGs. IE, 2A, 2B, and 3, in an exemplary embodiment, step 130 may include coupling first electrode 212A to current source 228 by closing third switch 232 at a beginning (i.e., a moment 316) of a third time period 318. In an exemplary embodiment, control logic circuitry 208 may be utilized for closing third switch 232. An exemplary third control signal 320 may be applied to third switch 232 by control logic circuitry 208 to keep third switch 232 closed during third time period 318. For this purpose, in an exemplary embodiment, control logic circuitry 208 may apply a constant voltage to third switch 232 during third time period 318. An exemplary constant voltage may be higher than an activation threshold of third switch 232.

[0051] In an exemplary embodiment, step 132 may include coupling the second electrode to power source 222 by closing fourth switch 234 at moment 316. In an exemplary embodiment, control logic circuitry 208 may be utilized for closing fourth switch 234. In an exemplary embodiment, third control signal 320 may be applied to fourth switch 234 by control logic circuitry 208 to keep fourth switch 234 closed during third time period 318. For this purpose, in an exemplary embodiment, control logic circuitry 208 may apply a constant voltage to fourth switch 234 during third time period 318. An exemplary constant voltage may be higher than an activation threshold of fourth switch 234. As a result, an exemplary cross-pair 235 of third switch 232 and fourth switch 234 may provide a path between power source 222 and current source 228 to deliver the stimulation current to tissue 214 in a direction opposite to the first direction through the first electrode and the second electrode during third time period 318. As a result, an exemplary biphasic stimulation of tissue 214 may be obtained.

[0052] Referring again to FIGs. 1A, in an exemplary embodiment, step 108 may include measuring the current-stimulus-response voltage signal. FIG. IF shows a flowchart for measuring a current-stimulus-response voltage signal, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, measuring the current- stimulus-response voltage signal may include obtaining a first attenuated voltage of the first electrode and a second attenuated voltage of the second electrode (step 134), selecting the first attenuated voltage from a plurality of attenuated voltages of the plurality of electrodes (step 136), selecting the second attenuated voltage from the plurality of attenuated voltages (step 138), obtaining an amplitude-altered voltage signal by differentially amplifying a voltage difference between the first attenuated voltage and the second attenuated voltage (step 140), and obtaining the current-stimulus-response voltage signal by digitizing the amplitude-altered voltage signal (step 142).

[0053] Referring again to FIG. 2A, in an exemplary embodiment, voltage measurement circuitry 206 may include a front end circuitry 236, a programmable-gain difference amplifier (PGDA) 238, and an analog-to-digital converter (ADC) 240. In an exemplary embodiment, step 108 may be implemented utilizing different components of voltage measurement circuitry 206, as described below.

[0054] For further detail with respect to step 134, FIG. 2C shows a schematic of a front end circuitry of a voltage measurement circuitry, consistent with one or more exemplary embodiments of the present disclosure. An exemplary front end circuitry 236 may include a plurality of resistive attenuators 242. Each exemplary resistive attenuator of plurality of resistive attenuators 242 may be connected to a respective electrode of plurality of electrodes 202. For example, a resistive attenuator 242A may be connected to reference electrode 216 and a resistive attenuator 242B may be connected to first electrode 212A. In an exemplary embodiment, step 134 may include obtaining a first attenuated voltage of first electrode 212A and a second attenuated voltage of the second electrode by equally attenuating voltages of plurality of electrodes 202. For this purpose, in an exemplary embodiment, a respective voltage of each of plurality of electrodes 202 may be passed through a respective resistive attenuator of plurality of resistive attenuators 242. For example, a voltage of reference electrode 216 may be passed through resistive attenuator 242A and a voltage of first electrode 212A may be passed through resistive attenuator 242B. Each exemplary attenuator of plurality of resistive attenuators 242 may be of passive resistive type and may provide an attenuated version of its input as an output. In an exemplary embodiment, all of plurality of resistive attenuators 242 may be identical. As a result, all exemplary voltages of plurality of electrodes 202 may be equally attenuated after passing through plurality of resistive attenuators 242.

[0055] In further detail regarding step 136, in an exemplary embodiment, front end circuitry 236 may further include a first multiplexer 244. In an exemplary embodiment, first multiplexer 244 may be utilized to obtain a first attenuated voltage 245. For this purpose, in an exemplary embodiment, first multiplexer 244 may select an attenuated voltage of first electrode 212A at an output node 246 of resistive attenuator 242B from a plurality of attenuated voltages of plurality of electrodes 202. An exemplary voltage selection signal 247 may configure first multiplexer 244 to select the attenuated voltage of first electrode 212A by coupling output node 246 to an output of first multiplexer 244. In an exemplary embodiment, electrode selection signal 247 may be produced by control logic circuitry 208 in FIG. 2A.

[0056] In further detail with regards to step 138, in an exemplary embodiment, front end circuitry 236 may further include a second multiplexer 248. In an exemplary embodiment, second multiplexer 248 may be utilized to obtain a second attenuated voltage 249. For this purpose, in an exemplary embodiment, second multiplexer 248 may select an attenuated voltage of electrode 212B at an output node 250 of resistive attenuator 242C from the plurality of attenuated voltages of plurality of electrodes 202 in a case of bipolar stimulation of tissue 214. In an exemplary embodiment, second multiplexer 248 may select an attenuated voltage of reference electrode 216 at an output node 252 of resistive attenuator 242A from the plurality of attenuated voltages of plurality of electrodes 202 in a case of monopolar stimulation of tissue 214. An exemplary voltage selection signal 251 may configure second multiplexer 248 to select the attenuated voltage of electrode 212B or the attenuated voltage of reference electrode 216 by coupling output node 250 or output node 252 to an output of second multiplexer 248, respectively. In an exemplary embodiment, voltage selection signal 251 may be produced by control logic circuitry 208 in FIG. 2A.

[0057] Referring again to FIGs. IF and 2A, in an exemplary embodiment, step 140 may include obtaining an amplitude-altered voltage signal 252 by differentially amplifying a voltage difference between first attenuated voltage 245 and second attenuated voltage 249. For this purpose, in an exemplary embodiment, PGDA 238 may be utilized for amplifying the voltage difference between first attenuated voltage 245 and second attenuated voltage 249. In an exemplary embodiment, PGDA 238 may be single supply or dual supply.

[0058] In an exemplary embodiment, step 142 may include obtaining a current-stimulus- response voltage signal 254 by digitizing amplitude-altered voltage signal 252. In an exemplary embodiment, ADC 240 may be utilized for digitizing amplitude-altered voltage signal 252. In an exemplary embodiment, ADC 240 may produce a digital number that may correspond to a value of amplitude-altered voltage signal 252.

[0059] Referring again to FIGs. 1A and 2A, in an exemplary embodiment, step 110 may include calculating the electrode-tissue impedance based on the biphasic current stimulation and current-stimulus-response voltage signal 254. FIG. 4 shows a schematic of an electrode- tissue-electrode impedance model, consistent with one or more exemplary embodiments of the present disclosure. An exemplary electrode-tissue-electrode impedance model 400 may model an electrical impedance between first electrode 212A and a second electrode 401. In an exemplary embodiment, second electrode 401 may be electrode 212B in a case of bipolar stimulation of tissue 214 or reference electrode 216 in a case of monopolar stimulation of tissue 214 [0060] FIG. 2D shows a schematic of a first implementation of a reference electrode, consistent with one or more exemplary embodiments of the present disclosure. An exemplary reference electrode 216A may be a first implementation of reference electrode 216 in FIG. 2A. In an exemplary embodiment, reference electrode 216A may have a cylindrical shape similar to electrodes of electrode array 212. However, an exemplary contact area of reference electrode 216A may be at least one order of magnitude larger than contact areas of electrodes of electrode array 212.

[0061] FIG. 2E shows a schematic of a second implementation of a reference electrode, consistent with one or more exemplary embodiments of the present disclosure. An exemplary reference electrode 216B may be a second implementation of reference electrode 216 in FIG. 2A. In an exemplary embodiment, reference electrode 216B may have a planar shape. An exemplary contact area of reference electrode 216A may be at least one order of magnitude larger than contact areas of electrodes of electrode array 212.

[0062] In an exemplary embodiment, electrode-tissue-electrode impedance model 400 may include a three-component electrode-tissue impedance 402 and an electrode impedance 404. In an exemplary embodiment, electrode impedance 404 may model an internal impedance of second electrode 401. In an exemplary embodiment, electrode-tissue impedance 402 may include an electrode impedance 406 and a tissue resistance 408. In an exemplary embodiment, tissue resistance 408 may model an internal resistance of tissue 214. In an exemplary embodiment, tissue resistance 408 may be connected in series to electrode impedance 406. In an exemplary embodiment, electrode impedance 406 may model an internal impedance of first electrode 212A. In an exemplary embodiment, electrode impedance 406 may include a resistive component 410 and a capacitive component 412. capacitive component 412 may be connected in parallel to resistive component 410. In an exemplary embodiment, calculating the electrodetissue impedance in step 110 may include estimating values of different components of three- component electrode-tissue impedance 402, as described below.

[0063] FIG. 3B shows a diagram of voltage signals, consistent with one or more exemplary embodiments of the present disclosure. Exemplary voltage signals may include first attenuated voltage 245, second attenuated voltage 249, and current-stimulus-response voltage signal 254. In an exemplary embodiment, current-stimulus-response voltage signal 254 may be obtained by calculating a difference between first attenuated voltage 245 and second attenuated voltage 249. Referring to FIGs. 3B and 4, in an exemplary embodiment, current-stimulus-response voltage signal 254 may be described according to the following: Equation (la) + T2 Equation (lb)

where:

V_t is an amplitude of current-stimulus-response voltage signal 254,

I_STIM is ^a value of the stimulation current,

R_B is the value of tissue resistance 408,

R_CT is the value of resistive component 410,

C_DL is the value of capacitive component 412, t is a time instance, k is a constant,

T- is a duration of first time period 304, and

T₂ is a duration of second time period 314.

[0064] If reference electrode 216 is selected as second electrode 401 in a case of an exemplary monopolar stimulation of tissue 214, a resultant voltage presented on electrode impedance 404 may be insignificant compared to a voltage on three-component electrode-tissue impedance 402 since reference electrode 216 may have a larger contact area with tissue 214 by a factor of at least one order of magnitude than first electrode 212A. As a result, constant k may be set to 1 in Equations (la) and (lb) in a case of an exemplary monopolar stimulation of tissue 214.

[0065] If electrode 212B is selected as second electrode 401 in a case of an exemplary bipolar stimulation of tissue 214, a resultant voltage presented on electrode impedance 404 may be equal to a voltage on electrode impedance 406 since first electrode 212A and electrode 212B may be identical in size and shape. Therefore, constant k may be set to 2 in Equations (la) and (lb) in a case of an exemplary bipolar stimulation of tissue 214.

[0066] To estimate three-component electrode-tissue impedance 402 based on Equations (la) and (lb), four exemplary voltage amplitudes may be sampled from current-stimulus-response voltage signal 254 at four sampling moments. An exemplary first voltage amplitude 324 may be sampled from current-stimulus-response voltage signal 254 at a first sampling moment 326. In an exemplary embodiment, first sampling moment 326 may be in first time period 304. An exemplary second voltage amplitude 328 may be sampled from current-stimulus-response voltage signal 254 at a second sampling moment 330. In an exemplary embodiment, second sampling moment 330 may be in first time period 304 after first sampling moment 326. An exemplary third voltage amplitude 332 may be sampled from current-stimulus-response voltage signal 254 at a third sampling moment 334. In an exemplary embodiment, third sampling moment 334 may be in second time period 314. An exemplary fourth voltage amplitude 336 may be sampled from current-stimulus-response voltage signal 254 at a fourth sampling moment 338. In an exemplary embodiment, fourth sampling moment 338 may be in second time period 314 after third sampling moment 334.

[0067] Based on Equations (la) and (lb), in an exemplary embodiment, calculating electrodetissue impedance 402 in step 110 may include calculating a value of resistive component 410 according to an operation defined by the following: Equation (2a)

where: t₁₅

^are values of first sampling moment 326, second sampling moment 330, third sampling moment 334, and fourth sampling moment 338, respectively, and

7_tl , ^t2 , ^t3 , and Vt4 are values of first voltage amplitude 324, second voltage amplitude 328, third voltage amplitude 332, and fourth voltage amplitude 336, respectively. [0068] In an exemplary embodiment, calculating electrode-tissue impedance 402 in step 110 may further include calculating a value of capacitive component 412 according to an operation defined by the following: Equation (2b)

[0069] In an exemplary embodiment, calculating electrode-tissue impedance 402 in step 110 may further include calculating a value of tissue resistance 408 according to an operation defined by the following: Equation (2c)

[0070] As described above, in an exemplary embodiment, a value of constant k may be set to 2 in Equations (2a) and (2c) in a case of bipolar stimulation of tissue 214 (i.e., electrode 212B in FIG. 2A is used as second electrode 401 in FIG. 4). In an exemplary embodiment, a value of constant k may be set to 1 in Equations (2a) and (2c) in a case of monopolar stimulation of tissue 214 (i.e., reference electrode 216 in FIG. 2A is used as second electrode 401 in FIG. 4). [0071] In an exemplary embodiment, first sampling moment 326 and second sampling moment 330 may be set according

= t₄ — t₃ and t₂ = 2t₁₅ respectively. As a result, Equations (2a)-(2c) may be simplified for an exemplary bipolar stimulation of tissue 214 as follows:

[0072] For an exemplary monopolar stimulation of tissue 214, Equations (2a)-(2c) may be simplified as follows:

[0073] FIG. 5 shows an example computer system 500 in which an embodiment of the present invention, or portions thereof, may be implemented as computer-readable code, consistent with exemplary embodiments of the present disclosure. For example, different steps of method 100 may be implemented in computer system 500 using hardware, software, firmware, tangible computer readable media having instructions stored thereon, or a combination thereof and may be implemented in one or more computer systems or other processing systems. Hardware, software, or any combination of such may embody any of the modules and components in FIGs. 1A-4, for example, processor 210 in FIG. 2A. [0074] If programmable logic is used, such logic may execute on a commercially available processing platform or a special purpose device. One ordinary skill in the art may appreciate that an embodiment of the disclosed subject matter can be practiced with various computer system configurations, including multi-core multiprocessor systems, minicomputers, mainframe computers, computers linked or clustered with distributed functions, as well as pervasive or miniature computers that may be embedded into virtually any device.

[0075] For instance, a computing device having at least one processor device and a memory may be used to implement the above-described embodiments. A processor device may be a single processor, a plurality of processors, or combinations thereof. Processor devices may have one or more processor “cores.”

[0076] An embodiment of the invention is described in terms of this example computer system 300. After reading this description, it will become apparent to a person skilled in the relevant art how to implement the invention using other computer systems and/or computer architectures. Although operations may be described as a sequential process, some of the operations may in fact be performed in parallel, concurrently, and/or in a distributed environment, and with program code stored locally or remotely for access by single or multiprocessor machines. In addition, in some embodiments the order of operations may be rearranged without departing from the spirit of the disclosed subject matter.

[0077] Processor device 504 may be a special purpose (e.g., a graphical processing unit) or a general -purpose processor device. As will be appreciated by persons skilled in the relevant art, processor device 504 may also be a single processor in a multi-core/multiprocessor system, such system operating alone, or in a cluster of computing devices operating in a cluster or server farm. Processor device 504 may be connected to a communication infrastructure 506, for example, a bus, message queue, network, or multi-core message-passing scheme.

[0078] In an exemplary embodiment, computer system 500 may include a display interface 502, for example a video connector, to transfer data to a display unit 530, for example, a monitor. Computer system 500 may also include a main memory 508, for example, random access memory (RAM), and may also include a secondary memory 510. Secondary memory 510 may include, for example, a hard disk drive 512, and a removable storage drive 514. Removable storage drive 514 may include a floppy disk drive, a magnetic tape drive, an optical disk drive, a flash memory, or the like. Removable storage drive 514 may read from and/or write to a removable storage unit 518 in a well-known manner. Removable storage unit 518 may include a floppy disk, a magnetic tape, an optical disk, etc., which may be read by and written to by removable storage drive 514. As will be appreciated by persons skilled in the relevant art, removable storage unit 518 may include a computer usable storage medium having stored therein computer software and/or data.

[0079] In alternative implementations, secondary memory 510 may include other similar means for allowing computer programs or other instructions to be loaded into computer system 500. Such means may include, for example, a removable storage unit 522 and an interface 520. Examples of such means may include a program cartridge and cartridge interface (such as that found in video game devices), a removable memory chip (such as an EPROM, or PROM) and associated socket, and other removable storage units 522 and interfaces 520 which allow software and data to be transferred from removable storage unit 522 to computer system 500. [0080] Computer system 500 may also include a communications interface 524. Communications interface 524 allows software and data to be transferred between computer system 500 and external devices. Communications interface 524 may include a modem, a network interface (such as an Ethernet card), a communications port, a PCMCIA slot and card, or the like. Software and data transferred via communications interface 524 may be in the form of signals, which may be electronic, electromagnetic, optical, or other signals capable of being received by communications interface 524. These signals may be provided to communications interface 524 via a communications path 526. Communications path 526 carries signals and may be implemented using wire or cable, fiber optics, a phone line, a cellular phone link, an RF link or other communications channels.

[0081] In this document, the terms “computer program medium” and “computer usable medium” are used to generally refer to media such as removable storage unit 518, removable storage unit 522, and a hard disk installed in hard disk drive 512. Computer program medium and computer usable medium may also refer to memories, such as main memory 508 and secondary memory 510, which may be memory semiconductors (e.g. DRAMs, etc.).

[0082] Computer programs (also called computer control logic) are stored in main memory 508 and/or secondary memory 510. Computer programs may also be received via communications interface 524. Such computer programs, when executed, enable computer system 500 to implement different embodiments of the present disclosure as discussed herein. In particular, the computer programs, when executed, enable processor device 504 to implement the processes of the present disclosure, such as the operations in method 100 illustrated by flowcharts of FIG. 1A-FIG. IF and particularly, calculations of step 110 discussed above. Accordingly, such computer programs represent controllers of computer system 500. Where an exemplary embodiment of method 100 is implemented using software, the software may be stored in a computer program product and loaded into computer system 500 using removable storage drive 514, interface 520, and hard disk drive 512, or communications interface 524.

[0083] Embodiments of the present disclosure also may be directed to computer program products including software stored on any computer useable medium. Such software, when executed in one or more data processing device, causes a data processing device to operate as described herein. An embodiment of the present disclosure may employ any computer useable or readable medium. Examples of computer useable mediums include, but are not limited to, primary storage devices (e.g., any type of random access memory), secondary storage devices (e.g., hard drives, floppy disks, CD ROMS, ZIP disks, tapes, magnetic storage devices, and optical storage devices, MEMS, nanotechnological storage device, etc.).

[0084] The embodiments have been described above with the aid of functional building blocks illustrating the implementation of specified functions and relationships thereof. The boundaries of these functional building blocks have been arbitrarily defined herein for the convenience of the description. Alternate boundaries can be defined so long as the specified functions and relationships thereof are appropriately performed.

[0085] While the foregoing has described what may be considered to be the best mode and/or other examples, it is understood that various modifications may be made therein and that the subject matter disclosed herein may be implemented in various forms and examples, and that the teachings may be applied in numerous applications, only some of which have been described herein. It is intended by the following claims to claim any and all applications, modifications and variations that fall within the true scope of the present teachings.

[0086] Unless otherwise stated, all measurements, values, ratings, positions, magnitudes, sizes, and other specifications that are set forth in this specification, including in the claims that follow, are approximate, not exact. They are intended to have a reasonable range that is consistent with the functions to which they relate and with what is customary in the art to which they pertain.

[0087] The scope of protection is limited solely by the claims that now follow. That scope is intended and should be interpreted to be as broad as is consistent with the ordinary meaning of the language that is used in the claims when interpreted in light of this specification and the prosecution history that follows and to encompass all structural and functional equivalents. Notwithstanding, none of the claims are intended to embrace subject matter that fails to satisfy the requirement of Sections 101, 102, or 103 of the Patent Act, nor should they be interpreted in such a way. Any unintended embracement of such subject matter is hereby disclaimed.

[0088] Except as stated immediately above, nothing that has been stated or illustrated is intended or should be interpreted to cause a dedication of any component, step, feature, object, benefit, advantage, or equivalent to the public, regardless of whether it is or is not recited in the claims.

[0089] It will be understood that the terms and expressions used herein have the ordinary meaning as is accorded to such terms and expressions with respect to their corresponding respective areas of inquiry and study except where specific meanings have otherwise been set forth herein. Relational terms such as first and second and the like may be used solely to distinguish one entity or action from another without necessarily requiring or implying any actual such relationship or order between such entities or actions. The terms “comprises,” “comprising,” or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. An element proceeded by “a” or “an” does not, without further constraints, preclude the existence of additional identical elements in the process, method, article, or apparatus that comprises the element.

[0090] The Abstract of the Disclosure is provided to allow the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. In addition, in the foregoing Detailed Description, it can be seen that various features are grouped together in various implementations. This is for purposes of streamlining the disclosure, and is not to be interpreted as reflecting an intention that the claimed implementations require more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive subject matter lies in less than all features of a single disclosed implementation. Thus, the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separately claimed subject matter. [0091] While various implementations have been described, the description is intended to be exemplary, rather than limiting and it will be apparent to those of ordinary skill in the art that many more implementations and implementations are possible that are within the scope of the implementations. Although many possible combinations of features are shown in the accompanying figures and discussed in this detailed description, many other combinations of the disclosed features are possible. Any feature of any implementation may be used in combination with or substituted for any other feature or element in any other implementation unless specifically restricted. Therefore, it will be understood that any of the features shown and/or discussed in the present disclosure may be implemented together in any suitable combination. Accordingly, the implementations are not to be restricted except in light of the attached claims and their equivalents. Also, various modifications and changes may be made within the scope of the attached claims.

Claims

What is claimed is:

1. A method for measuring an electrode-tissue impedance during active current stimulation of a tissue of a subject’s body, the method comprising: placing an electrode array on the tissue, the electrode array comprising a plurality of electrodes; applying a biphasic current stimulation to the tissue by: passing a stimulation current between a first electrode of the plurality of electrodes and a second electrode of the plurality of electrodes inside the tissue in a first direction for a first time period by: selecting, utilizing a first demultiplexer of a current stimulation circuitry, the first electrode from the plurality of electrodes; coupling the first electrode to a power source of the current stimulation circuitry by closing a first switch of the current stimulation circuitry at a beginning of the first time period through applying a first control signal to the first switch by a control logic circuitry, the first switch connected between the first electrode and the power source; selecting, utilizing a second demultiplexer of the current stimulation circuitry, the second electrode from the plurality of electrodes; and coupling the second electrode to a current source of the current stimulation circuitry by closing a second switch of the current stimulation circuitry at the beginning of the first time period through applying a second control signal to the second switch by the control logic circuitry, the second switch connected between the second electrode and the current source; stopping a passage of the stimulation current inside the tissue for a second time period starting at an end of the first time period by: decoupling the second electrode from the current source by opening, utilizing the control logic circuitry, the second switch at the end of the first time period; and decoupling the first electrode from the power source by opening, utilizing the control logic circuitry, the first switch at an end of the second time period; and

23 passing the stimulation current between the first electrode and the second electrode inside the tissue in a second direction opposite to the first direction for a third time period after the second time period by: coupling the first electrode to the current source by closing a third switch of the current stimulation circuitry at a beginning of the third time period through applying a third control signal to the third switch by the control logic circuitry, the third switch connected between the first electrode and the current source; and coupling the second electrode to the power source by closing a fourth switch of the current stimulation circuitry at the beginning of the third time period through applying the third control signal to the fourth switch by the control logic circuitry, the fourth switch connected between the second electrode and the power source; measuring a current-stimulus-response voltage signal of the tissue during the biphasic current stimulation by: obtaining a first attenuated voltage of the first electrode and a second attenuated voltage of the second electrode by equally attenuating voltages of the plurality of electrodes, equally attenuating the voltages comprising: passing a respective voltage of each of the plurality of electrodes through a respective resistive attenuator of a front end circuitry of a voltage measurement circuitry; selecting, utilizing a first multiplexer of the front end circuitry, the first attenated voltage from a plurality of attenated voltages of the plurality of electrodes; selecting, utilizing a second multiplexer of the front end circuitry, the second attenuated voltage from the plurality of attenuated voltages; obtaining an amplitude-altered voltage signal by amplifying, utilizing a programmable-gain difference amplifier (PGDA) of the voltage measurement circuitry, a voltage difference between the first attenuated voltage and the second attenuated voltage; and obtaining the current-stimulus-response voltage signal by digitizing, utilizing an analog-to-digital converter (ADC) of the voltage measurement circuitry, the amplitude- altered voltage signal; and calculating, utilizing one or more processors, the electrode-tissue impedance by: sampling a first voltage amplitude V_L1 from the current-stimulus-response voltage signal at a first sampling moment t₄ in the first time period; sampling a second voltage amplitude V_t2 from the current-stimulus-response voltage signal at a second sampling moment t₂ in the first time period where t₂ = 2t₄ sampling a third voltage amplitude V_t3 from the current-stimulus-response voltage signal at a third sampling moment t₃ in the second time period; sampling a fourth voltage amplitude V_t4 from the current-stimulus-response voltage signal at a fourth sampling moment t₄ in the second time period where t₄ = t₄ + t₃ calculating a value of a resistive component of an electrode impedance according to an operation defined by the following:

where R_CT is the value of the electrode resistance, ISTIM is a value of the stimulation current, and fc is a constant; calculating a value C_DL of a capacitive component of the electrode impedance according to an operation defined by the following:

wherein the capacitive component is connected in parallel to the resistive component; and calculating a value of a tissue resistance connected in series to the electrode impedance according to an operation defined by the following:

where R_B is the value of the tissue resistance.

2. A method for measuring an electrode-tissue impedance during active current stimulation of a tissue of a subject’s body, the method comprising: placing a first electrode on the tissue; placing a second electrode on a region of the subject’s body; applying a biphasic current stimulation to the tissue by: passing, utilizing a current stimulation circuitry, a stimulation current between the first electrode and the second electrode inside the tissue in a first direction for a first time period; stopping, utilizing the current stimulation circuitry, a passage of the stimulation current inside the tissue for a second time period starting at an end of the first time period; and passing, utilizing the current stimulation circuitry, the stimulation current between the first electrode and the second electrode inside the tissue in a second direction opposite to the first direction for a third time period after the second time period; measuring, utilizing a voltage measurement circuitry, a current-stimulus-response voltage signal of the tissue during the biphasic current stimulation; and calculating, utilizing one or more processors, the electrode-tissue impedance based on the stimulation current and the current-stimulus-response voltage signal.

3. The method of claim 2, wherein passing the stimulation current in the first direction comprises: selecting, utilizing a first demultiplexer of the current stimulation circuitry, the first electrode from a plurality of electrodes; coupling the first electrode to a power source of the current stimulation circuitry by closing, utilizing a control logic circuitry, a first switch of the current stimulation circuitry at a beginning of the first time period, the first switch connected between the first electrode and the power source; selecting, utilizing a second demultiplexer of the current stimulation circuitry, the second electrode from the plurality of electrodes; and coupling the second electrode to a current source of the current stimulation circuitry by closing, utilizing the control logic circuitry, a second switch of the current stimulation circuitry at the beginning of the first time period, the second switch connected between the second electrode and the current source.

4. The method of claim 3, wherein stopping the passage of the stimulation current comprises: decoupling the second electrode from the current source by opening, utilizing the control logic circuitry, the second switch at the end of the first time period; and

26 decoupling the first electrode from the power source by opening, utilizing the control logic circuitry, the first switch at an end of the second time period.

5. The method of claim 4, wherein passing the stimulation current in the second direction comprises: coupling the first electrode to the current source by closing, utilizing a control logic circuitry, a third switch of the current stimulation circuitry at a beginning of the third time period, the third switch connected between the first electrode and the current source; and coupling the second electrode to the power source by closing, utilizing the control logic circuitry, a fourth switch of the current stimulation circuitry at the beginning of the third time period, the fourth switch connected between the second electrode and the power source.

6. The method of claim 5, wherein: closing the first switch comprises applying a first control signal to the first switch by the control logic circuitry; closing the second switch comprises applying a second control signal to the second switch by the control logic circuitry; and closing the third switch and closing the fourth switch comprise applying a third control signal to each of the third switch and the fourth switch by the control logic circuitry.

7. The method of claim 3, wherein measuring the current-stimulus-response voltage signal comprises: obtaining a first attenuated voltage of the first electrode and a second attenuated voltage of the second electrode by equally attenuating voltages of the plurality of electrodes, equally attenuating the voltages comprising: passing a respective voltage of each of the plurality of electrodes through a respective resistive attenuator of a front end circuitry of the voltage measurement circuitry; selecting, utilizing a first multiplexer of the front end circuitry, the first attenated voltage from a plurality of attenated voltages of the plurality of electrodes; selecting, utilizing a second multiplexer of the front end circuitry, the second attenuated voltage from the plurality of attenuated voltages;

27 obtaining an amplitude-altered voltage signal by amplifying, utilizing a programmable- gain difference amplifier (PGDA) of the voltage measurement circuitry, a voltage difference between the first attenuated voltage and the second attenuated voltage; and obtaining the current-stimulus-response voltage signal by digitizing, utilizing an analog- to-digital converter (ADC) of the voltage measurement circuitry, the amplitude-altered voltage signal.

8. The method of claim 2, wherein calculating the electrode-tissue impedance comprises: sampling a first voltage amplitude V_tl from the current-stimulus-response voltage signal at a first sampling moment t₄ in the first time period; sampling a second voltage amplitude V_t2 from the current-stimulus-response voltage signal at a second sampling moment t₂ in the first time period after the first sampling moment t₄ sampling a third voltage amplitude V_t3 from the current-stimulus-response voltage signal at a third sampling moment t₃ in the second time period; sampling a fourth voltage amplitude V_t4 from the current-stimulus-response voltage signal at a fourth sampling moment t₄ in the second time period after the third sampling moment t₃ calculating a value of a resistive component of an electrode impedance according to an operation defined by the following:

where R_CT is the value of the resistive component, I_ST]M i^{s a} value of the stimulation current, and A: is a constant; calculating a value C_DL of a capacitive component of the electrode impedance according to an operation defined by the following:

28

where R_B is the value of the tissue resistance.

9. The method of claim 8, wherein: placing the first electrode and placing the second electrode comprise placing an electrode array on the tissue; and calculating the value of the resistive component and calculating the value of the tissue resistance comprise setting a value of the constant k to 2.

10. The method of claim 9, wherein calculating the electrode-tissue impedance further comprises: setting the first sampling moment t according to an operation defined by t = t₄ — t₃ setting the second sampling moment t₂ according to an operation defined by t₂ = 2t₄ obtaining the value of the capacitive component according to an operation defined by the following:

obtaining the value of the capacitive component according to an operation defined by the following:

obtaining the value of the tissue resistance according to an operation defined by the following:

11. The method of claim 8, wherein: placing the second electrode comprises placing an electrode of a size of at least one order of magnitude larger than a size of the first electrode on the region; and

29 calculating the value of the resistive component and calculating the value of the tissue resistance comprise setting a value of the constant k to 1.

12. The method of claim 11, wherein calculating the electrode-tissue impedance further comprises: setting the first sampling moment t according to an operation defined by t = t₄ — t₃ setting the second sampling moment t₂ according to an operation defined by t₂ = 2t_x; obtaining the value of the capacitive component according to an operation defined by the following:

13. A circuit for measuring an electrode-tissue impedance during active current stimulation of a tissue of a subject’s body, the circuit comprising: a plurality of electrodes comprising: an electrode array configured to be placed on the tissue; and a reference electrode configured to be placed on a region of the subject’s body and comprising a size of at least one order of magnitude larger than a size of each electrode of the electrode array; a current stimulation circuitry configured to apply a biphasic current stimulation to the tissue by:

30 passing a stimulation current inside the tissue between a first electrode of the electrode array and a second electrode of the plurality of electrodes in a first direction for a first time period; stopping a passage of the stimulation current inside the tissue for a second time period starting at an end of the first time period; and passing the stimulation current between the first electrode and the second electrode inside the tissue in a second direction opposite to the first direction for a third time period after the second time period; a voltage measurement circuitry configured to measure a current-stimulus-response voltage signal of the tissue during the biphasic current stimulation; a control logic circuitry configured to: apply a first control signal to the current stimulation circuitry during the first time period and the second time period; apply a second control signal to the current stimulation circuitry during the first time period; and apply a third control signal to the current stimulation circuitry during the third time period; a memory having processor-readable instructions stored therein; and one or more processors configured to access the memory and execute the processor- readable instructions, which, when executed by the one or more processors configures the one or more processors to perform a method, the method comprising: calculating the electrode-tissue impedance based on the stimulation current and the current-stimulus-response voltage signal.

14. The circuit of claim 13, wherein the current stimulation circuitry comprises: a power source; a current source; a first demultiplexer configured to select the first electrode from the electrode array; a second demultiplexer configured to select the second electrode from the plurality of electrodes;

31 a first switch connected between the first electrode and the power source, the first switch configured to: couple the first electrode to the power source by being closed responsive to receiving the first control signal from the control logic circuitry at a beginning of the first time period; and decouple the first electrode from the power source by being opened at an end of the second time period; a second switch connected between the second electrode and the current source, the second switch configured to: couple the second electrode to the current source by being closed responsive to receiving a second control signal from the control logic circuitry at the beginning of the first time period; and decouple the second electrode from the current source by being opened at the end of the first time period; a third switch connected between the first electrode and the current source, the third switch configured to couple the first electrode to the current source by being closed responsive to receiving the third control signal from the control logic circuitry at a beginning of the third time period; and a fourth switch connected between the second electrode and the power source, the fourth switch configured to couple the second electrode to the power source by being closed responsive to receiving the third control signal from the control logic circuitry at the beginning of the third time period.

15. The circuit of claim 13, wherein the voltage measurement circuitry comprises: a front end circuitry configured to obtain a first attenuated voltage of the first electrode and a second attenuated voltage of the second electrode by equally attenuating voltages of the plurality of electrodes, the front end circuitry comprising: a plurality of resistive attenuators, each respective resistive attenuator of the plurality of resistive attenuators configured to attenuate a respective voltage of each of the plurality of electrodes;

32 a first multiplexer configured to select the first attenated voltage from a plurality of attenated voltages of the plurality of electrodes; and a second multiplexer configured to select the second attenuated voltage from the plurality of attenuated voltages; a programmable-gain difference amplifier (PGDA) configured to obtain an amplitude- altered voltage signal by amplifying a voltage difference between the first attenuated voltage and the second attenuated voltage; and an analog-to-digital converter (ADC) configured to obtain the current-stimulus-response voltage signal by digitizing the amplitude-altered voltage signal.

16. The circuit of claim 13, wherein calculating the electrode-tissue impedance comprises: sampling a first voltage amplitude V_tl from the current-stimulus-response voltage signal at a first sampling moment t₄ in the first time period; sampling a second voltage amplitude V_t2 from the current-stimulus-response voltage signal at a second sampling moment t₂ in the first time period after the first sampling moment t₄ sampling a third voltage amplitude V_t3 from the current-stimulus-response voltage signal at a third sampling moment t₃ in the second time period; sampling a fourth voltage amplitude V_t4 from the current-stimulus-response voltage signal at a fourth sampling moment t₄ in the second time period after the third sampling moment t₃ calculating a value of a resistive component of an electrode impedance according to an operation defined by the following:

wherein the capacitive component is connected in parallel to the resistive component; and

33 calculating a value of a tissue resistance connected in series to the electrode impedance according to an operation defined by the following:

where R_B is the value of the tissue resistance.

17. The circuit of claim 16, wherein: the second electrode comprises an electrode of the electrode array; and calculating the value of the resistive component and calculating the value of the tissue resistance comprise setting a value of the constant k to 2.

18. The circuit of claim 17, wherein calculating the electrode-tissue impedance further comprises: setting the first sampling moment t according to an operation defined by t = t₄ — t₃ setting the second sampling moment t₂ according to an operation defined by t₂ = 2t₄ obtaining the value of the capacitive component according to an operation defined by the following:

19. The circuit of claim 16, wherein: the second electrode comprises the reference electrode; and

34 calculating the value of the resistive component and calculating the value of the tissue resistance comprise setting a value of the constant k to 1.

20. The circuit of claim 19, wherein calculating the electrode-tissue impedance further comprises: setting the first sampling moment t according to an operation defined by t = t₄ — t₃ setting the second sampling moment t₂ according to an operation defined by t₂ = 2t₄ obtaining the value of the capacitive component according to an operation defined by the following:

1 t₃ — t₄

•DL ~ ; and KCT