Systems and methods for adjustable current individualized stimulation therapy

Abstract

Methods and systems are provided herein for an adjustable current individualized stimulation system. In one example, a stimulation system comprises a device comprising a plurality of stimulation electrodes and at least one isolated current source (ICS), wherein the device is configurable to adjust current parameters and a pulse pattern of pulses of stimuli applied to a patient.

Description

SYSTEMS AND METHODS FOR ADJUSTABLE CURRENT INDIVIDUALIZEDSTIMULATION THERAPYCROSS REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims priority to U.S. Provisional Application No. 63 / 656.515 entitled "SYSTEMS AND METHODS FOR ADJUSTABLE CURRENT INDIVIDUALIZED STIMULATION THERAPY”, filed June 05, 2024. The entire contents of the above-listed application is hereby incorporated by reference for all purposes.TECHNICAL FIELD

[0002] Embodiments of the subject matter disclosed herein relate to medical treatment, and more specifically to methods and system for adjustable current individualized stimulation therapy.BACKGROUND AND SUMMARY

[0003] Electroconvulsive therapy (ECT) is a commonly used treatment option for medicationresistant depression and / or other mental health disorders. In ECT, a generalized tonic-clonic seizure is elicited by inducing an electric field in the brain through delivery of current to electrodes placed on the scalp. ECT functions by delivering a series of brief pulses of current through a pair of electrodes affixed to a scalp of an anesthetized patient. Present clinical ECT practice uses limited fixed electrode placements, typically bitemporal or right unilateral, and fixed high current amplitudes, such as 800 or 900 mA, which induce strong electric fields. The electric fields are broadly distributed throughout the brain and the expected maximal effect of the generated ECT stimulus train is of those regions of the brain in proximity to the placement of the tw o electrodes. While widespread stimulation in this way may have powerful anti-depressant effects, it may also result in significant cognitive side effects, such as memory loss. These cognitive side effects may be due to overstimulation of the medial temporal brain regions.

[0004] Optimization of ECT is impeded by lack of a stimulation paradigm and technology to optimally induce the electric field in the brain in a w ay that maximizes the antidepressant action while minimizing cognitive side effects. Furthermore, conventional fixed current amplitude stimulation dosing may fail to account for inter-individual anatomical variability in patients. Variability' in anatomy from patient to patient may' produce inconsistent dosage when a fixed current amplitude is used, which may result in variable clinical outcomes. Systems and methods are therefore needed to provide technology for maximizing antidepressant efficacy of ECT while minimizing side effects.

[0005] In one example, the issues described above may be at least partially addressed by an adjustable current individualized stimulation therapy system.

[0006] It should be understood that the brief description above is provided to introduce in simplified form a selection of concepts that are further described in the detailed description. It is not meant to identify key or essential features of the claimed subject matter, the scope of which is defined uniquely by the claims that follow the detailed description. Furthermore, the claimed subject matter is not limited to implementations that solve any disadvantages noted above or in any part of this disclosure.BRIEF DESCRIPTION OF THE DRAWINGS

[0007] FIG. 1 shows an example adjustable current individualized stimulation system, according to an embodiment;

[0008] FIG. 2 shows an example H-bridge circuit topology stimulation system of FIG. 1;

[0009] FIG. 3 shows a flowchart illustrating a method for configuring the stimulation system;

[0010] FIG. 4 shows a flowchart illustrating a method for operating the stimulation system;

[0011] FIG. 5 shows a first example pulse waveform;

[0012] FIG. 6 shows a second example pulse waveform;

[0013] FIG. 7 shows a third example pulse waveform;

[0014] FIG. 8 shows a fourth example pulse waveform; and

[0015] FIG. 9 shows a fifth example pulse waveform.DETAILED DESCRIPTION

[0016] The following description relates to systems and methods for an adjustable current individualized stimulation system comprising a main control unit (MCU) comprising a microcomputer, one or more isolated current sources (ICSs) each powered by a battery source, and a cap comprising a plurality of electrodes. Current is delivered through the plurality of electrodes of the cap while a frontend amplifier unit (FEAU) reads physiology signals, for example electroencephalogram (EEG), electrocardiogram (ECG), and / or electromyogram (EMG) signals. The stimulation system herein described may be designed to deliver electrical stimulation to patients being treated for various neurological, psychological, and psychiatric disorders by electroconvulsive therapy (ECT). A diagram of the stimulation system is shown in FIG. 1. An example of current output of an isolated current source is shown in FIG. 2. A method for configuring the stimulation system, including current paradigms and pulse patterns is shown in a flowchart in FIG. 3. A method for operating the stimulation system is shown in a flowchart in FIG. 4. Various waveforms resultant from the stimulation system are shown in FIGS. 5-10.

[0017] Turning now to FIG. 1, a high-level block diagram of an adjustable current individualized stimulation system 100. also referred to herein as the stimulation system 100. is shown. The stimulation system 100 comprises an MCU 102, a power control unit (PCU) 104, and one or more ICSs 126. In some examples, the stimulation system 100 may comprise just one ICS 126, as is described herein,although it should be understood that in other examples the stimulation system 100 may comprise a plurality of ICSs 126. The MCU 102, PCU 104, and the ICS 126 may be configured as part of and / or within a chassis 138.

[0018] The MCU 102 may be operated by a microcontroller or microcomputer 106 that includes a field programmable gate array, a processor (e.g., a single-core or dual-core processor), one or more indicator lights (e.g., indicator light-emitting diodes (LEDs)), and multiple analog and digital input / output lines. In some examples, the MCU 102 may be WiFi-capable. In other examples, the MCU 102 may include wired communications. In yet further examples, the MCU 102 may be both WiFi- capable and include wired communications. The microcomputer 106 may control the PCU 104 and the ICS 126 through a serial peripheral interface (SPI) protocol and / or the field programmable gate array. The MCU 102 may control current path of the ICS 126 as well as current amplitude, pulse width, and other parameters as will be herein discussed.

[0019] In some examples, the MCU 102 further comprises a multiplexer, current / voltage measurement devices, safety relays, and one or more test loads. The microcomputer 106 may receive current / voltage measurements during a stimulation session on a pulse-by-pulse basis, as will be described with respect to FIG. 4.

[0020] Further, the microcomputer 106 may detect potential anomalies in real-time (e.g., without intentional time delay) and may abort a stimulation pulse train or stimulation session in the event of detected current amplitude or latency deviations.

[0021] The microcomputer 106 may send digital bits to activate gate drivers in the ICS 126, as well as to safety relays to allow stimulus delivery to a patient 124 via an electrode cap 122. During stimulation, the ICS 126 may be controlled by the field programmable gate array of the MCU 102, which may achieve precise and accurate timing of delivery. The ICS 126, as controlled by the MCU 102, may produce electrical stimulation pulses. The ICS 126 current / voltage measurements may communicate via separate communication busses. The safety relays may be controlled by the MCU 102.

[0022] In some examples, the electrode cap 122 may include a plurality of stimulation electrodes interleaved with one or more EEG electrodes (e g., high-density' EEG electrodes). An electrode box 121 may include one or more inputs and one or more outputs, wherein electrode cables from the electrode cap 122 are connected to the electrode box 121 and one or more connection cables from the electrode box 121 are connected to the ICS 126.

[0023] In some examples, the electrode cap 122 may comprise two electrodes, one corresponding to each node of the ICS 126. In other examples, for example when more than one ICS 126 is included in the stimulation system 100, additional electrodes may be included in the electrode cap 122, wherein each of the one or more ICSs 126 corresponds to designated pairs of electrodes. In some examples, a conduction gel may be applied between the cap and the patient’s head.

[0024] The ICS 126 may provide circuitry and power to deliver a pulse train stimulus to the electrodes of the electrode cap 122 (e.g., to a pair of electrodes). In addition to generating stimuli, the ICS 126 may monitor voltage present on the electrodes as well as monitoring current flowing during the pulse stimuli via the current / voltage measurements. For example, the ICS 126 may monitor accuracy of ICS current, while the MCU 102 monitors total energy that is delivered to the patient 124. In response to the total energy meeting and / or exceeding a predefined threshold, stimulus delivery is aborted.

[0025] In some examples, the ICS 126 may be coupled to an adapter configured to split the current delivered by the ICS 126. The adapter may be a passive resistive divider, in one example. Thus, current may be delivered for a first electrode configuration and then split by the adapter for a second electrode configuration, wherein the second electrode configuration is the configuration of the cap 122. As a nonlimiting example, the current may be delivered for a two electrode configuration and the adapter may split the current for a five electrode configuration.

[0026] A range of possible currents for stimulation may be defined, the range being from 1mA to 900mA, in some examples. As an example, current parameters, including current amplitude, may be defined for each of the pulses in a pulse train. A single pulse generated by the ICS 126 may be a square constant-current pulse characterized by rapid onset and offset, however the current may not be constant throughout the pulse train when such is defined for the system. As the stimulus is presented, some area of the patient 124‘s head between the stimulating electrodes of the electrode cap 122 may experience die current. In some examples, the stimulus delivered may be symmetrically bi-phasic, asymmetrically bi-phasic, or uni-phasic (e.g., unidirectional), as will be described with respect to FIGS. 5-10.

[0027] The microcomputer 106 is further communicatively coupled to an operator computer 120. A connection between the microcomputer 106 and the operator computer 12 may be an electrically isolated wired connection (e.g.. a universal serial bus (USB) cable) or a wireless connection (e g., over WiFi). The operator computer 120 may be a desktop computer, laptop computer, mobile device, and / or the like that includes a display device through which a graphical user interface (GUI) may be displayed. The GUI of the operator computer 120 may allow for a user to define stimulation parameters, enable stimulus delivery, and receive feedback on completion status of the stimulus train, battery health, and other device status indications. The stimulation parameters that may be defined by the user may include current dosimetry (e.g.. current amplitude), stimulus train duration, pulse polarity, pulse width (e.g., duration of each current pulse) and / or pulse-pair frequency for each pulse of the pulse train. In some examples, one or more of the parameters and stimulus patterns may be determined based on a computer implemented algorithm. The MCU 102 may store the stimulation parameters as indicated via the GUI in memory and the MCU 102 may control stimulation during the neurostimulation session according to the stored parameters. The stored parameters may not be updated or otherwise modified during the neurostimulation session, rather they are predefined via the GUI as herein described.

[0028] The operator computer 120 may be further communicatively coupled and / or operably coupled to an FEAU 116, for example via a wired connection such as a USB. The FEAU 116 may comprise an EEG protective circuit and an EEG amplifier / reader. In this way, the FEAU 116 may monitor signals, such as EEG, ECG, and / or EMG signals, during the neurostimulation session. Monitoring EMG electrodes may monitor for adequate paralysis during the neurostimulation session and monitoring ECG electrodes may monitor cardiac status during the neurostimulation session. The FEAU 116 may also protect EEG electrodes during stimulation and reduce EEG reading recovery time delay. The FEAU 116 may be communicatively and / or operably coupled to the electrode cap 122 that is positioned in direct contact with the patient 124 (e.g., the patient’s head). The operator computer 120 and / or a separate display device communicatively coupled to the FEAU 116 may display an EEG reading as provided by the EEG electrodes of the electrode cap 122. The operator computer 120 may store data recording settings and parameters of a neurostimulation session including state and status of software running on both the operator computer 120 and the MCU 102, and recorded timing, voltages, and currents measured by the MCU 102 for each delivered stimulus pulse. In this way, a user may be able to view recorded voltage and current parameters for a given session at a later time.

[0029] In some examples, during charging of the stimulation system 100. alternating current (AC) power 136 may provide power to the stimulation system 100. The AC power 136 may be converted into direct current (DC) power via an AC / DC converter 134. Power may be provided to a battery control unit (BCU) 132 which is operably coupled to the PCU 104. The PCU 104 comprises an MCU battery’ 128 and an ICS battery 130 to charge each of the batteries when in charging mode. In examples in which more than one ICS is included, multiple ICS batteries may also be included, one for each ICS. In some examples, the MCU battery’ 128 and the ICS battery 130 are rechargeable batteries such as nickel metal hydride batteries, nickel cadmium batteries, or lithium ion batteries.

[0030] Following charging of the batteries, the BCU 132 may be disconnected from the PCU 104.In some examples, the chassis 138 may include a mechanical guard that ensures that when stimulation electrode cables are plugged in, the battery charging connector (e.g., the wired connection between the BCU 132 and the PCU 104) is disconnected. Operating with battery power alone during a neurostimulation session may decrease possibility of patient to Earth ground shortage. For example, the PCU 104 may be configured to isolate the patient from any conductive surfaces of hardware of the stimulation system 100 and electrodes to Earth ground. As noted, the electrode cap 122 may include a plurality of stimulation electrodes that are interleaved with high-density EEG electrodes. The microcomputer 106 may provide control for the EEG protective circuit of the FEAU 116 to protect the EEG amplifier during stimulus current delivery. The EEG data may be sent to the operator computer 120 for signal digitation and display, as previously’ discussed. Alternatively, or additionally, a chart recorder for visual monitoring of the EEG seizure as well as other physiological signals during thetreatment session may be displayed by the operator computer 120 and / or by a separate display device not comrected to the MCU 102.

[0031] The stimulation system 100 may consider the finite limitations of energy and charge that can safely be delivered to a patient during stimulation. While the predicted charge value may not differ significantly from the measured value, the energy delivered may vary during stimulation as the energy calculated is based on a bulk resistor model that assumes a fixed resistance of 220 Ohms. During stimulation, the stimulation system 100 may continuously calculate accumulated energy for each pulse and automatically halts the stimulation if it reaches 100 Joules, as will be explained further below.

[0032] The stimulation system 100 may be configured to deliver current for treating a major depressive episode, a manic episode, catatonia, a psychotic subtype of depression, schizophrenia, schizoaffective disorder, Parkinson’s disease, epilepsy, status epilepticus, repetitive self-injury in an autism spectrum disorder, tardive dyskinesia, dystonia, and / or neuroleptic malignant syndrome. In some examples, current parameters and a pulse waveform pattern may be selected for the particular patient based on the intended treatment course. For example, current delivery for treatment of a major depressive episode may include a first set of current parameters and a first pulse pattern while current delivery for treatment of tardive dyskinesia may include a second set of current parameters and a second pulse pattern different from the first parameters and pattern. The stimulation system 100 herein described may be configmed to deliver current according to different parameters defined for a specific patient. The system may thus be adaptable to provide individualized stimulation treatment.

[0033] Turning now to FIG. 2, an example of an ICS 202 of the stimulation system 100 is shown. The ICS 202 may be the ICS 126 (or one of the one or more ICSs 126 in examples that include more than one ICS). The ICS 202 of the stimulation system 100 may be configmed as an H-bridge circuit to deliver current to the patient’s head via the electrode cap 122. The ICS 202 may have two output terminals, A and B. As discussed, stimuli delivered via the ICS 202 may be symmetrically biphasic, asymmetrically biphasic, or unidirectional. The H-bridge circuit comprises a plurality of switches QI, Q2. Q3. and Q4 that when in various configurations allow for current to flow across a load 208. The load 208 may be the head of the patient 124, in some examples. When the stimuli are biphasic, one of the A and B terminals serves as a voltage somce and the other of the terminals serves as a current sink. As such, the H-bridge circuit topology may include a positive phase and a negative phase of a pulse, for example as depicted in FIGS. 5 and 6. When the stimuli are unidirectional, only positive or only negative phases may be delivered.

[0034] In some examples, each of the terminals A and B may be assigned to an electrode of an electrode pair, for example one of the two electrodes in a tw o-electrode configmation of the electrode cap 122. The two electrodes that form the pair may thus define a path for the current pulse to travel. A first positive phase 204 and a second negative phase 206 of a pulse are depicted within the H-bridge circuit as moving in opposite directions, for example with the switches in different configurations, as isdie case for biphasic stimulation patterns. It should be understood, however, that different phases and phase directions may be feasible in other stimulation patterns. As an example, in unidirectional patterns, current may be delivered as repeated positive or repeated negative pulses where only the first phase 204 or second phase 206 are delivered.

[0035] The stimulation system 100 has herein disclosed may allow for varying pulse patterns, including unidirectional and bidirectional pulse trains, monophasic and biphasic pulses, bursting patterns, and modulated amplitude patterns. Turning briefly to FIGS. 5-9. various waveforms resulting from different configurations of the circuit of the ICS 202 as herein described are shown. FIG. 5 shows a first symmetric biphasic waveform 500. FIG. 6 shows an asymmetric biphasic waveform 600, FIG. 7 shows a first unidirectional waveform 700. FIG. 8 shows a second unidirectional waveform 800. and FIG. 9 shows a second symmetric biphasic waveform 900. The waveforms as herein shown may be produced by the adjustable current individualized stimulation system 100 herein disclosed.

[0036] Starting with FIG. 5, the first symmetric biphasic waveform 500 is shown. The first symmetric biphasic waveform 500 may be an example of a conventional ECT waveform that has a fixed frequency with bidirectional pulse pairs. The stimulation system as herein described may be configurable to produce conventional ECT waveforms as well as a variety7of other waveforms as herein described. Each pulse, and each phase of each pulse, may have the same current amplitude, pulse width, and frequency. For example, the first symmetric biphasic waveform 500 as shown may be generated with stimulation applied over a 200 Ohm resistor with pulse stimulation parameters including a pulse width of 1ms, a frequency of 100 Hz, and a current amplitude of 50 mA.

[0037] In contrast, biphasic stimulation addresses this issue by promptly introducing opposite polarity pulse right after the initial pulse. This effectively minimizes disruption of the charge balance. The biphasic pattern as shown in FIG. 5 may be generated with the ICS 202 of FIG. 2. For example, during the positive phase 204 of the pulse, depicted by a solid line in FIG. 2, switches QI. Q2 Q3, and Q4 may be in a first configuration. The first configuration may include switches QI and Q4 being closed while switches Q2 and Q3 are open. The first configuration may allow current to flow across the load 208 in a first direction. During the negative phase 206 of the pulse, depicted by a dotted line in FIG. 2, switches QI, Q2, Q3, and Q4 may be in a second configuration. The second configuration may include switches Q2 and Q3 being closed while switches QI and Q4 are open. The second configuration may allow current to flow in a second direction opposite the first direction across the load 208.

[0038] A resultant first phase 504 of a pulse 502 corresponds to the positive phase 204 and is consequently depicted as a positive pulse phase. A second pulse 506 of the pulse 502 corresponds to the negative phase 206 and is consequently depicted as a negative pulse phase. The first and second phases 504 and 506 may thus form the biphasic pulse 502. Multiple of these biphasic pulses are delivered in succession to generate the first symmetric biphasic waveform 500.

[0039] FIG. 6 shows the asymmetric biphasic waveform 600 comprising a plurality of asymmetric biphasic pulses. Asymmetric biphasic pulses are generated using unequal positive and negative current amplitudes and pulse widths while still maintaining charge balance. The charge may be calculated by multiplying the current amplitude with the pulse width. For example, as shown in the asymmetric biphasic waveform 600, a positive phase 604 of a pulse 602 (e.g., the positive charge) may have a first amplitude and a first pulse width, while a negative phase 606 of the pulse 602 has a second amplitude and a second pulse width, wherein Atx PW = A2X PW2. As a non-limiting example, the positive phase 602 may have a current amplitude of 50 mA and a pulse width of 1 ms while the negative phase 606 of the pulse 602 has a current amplitude of 10 mA and a pulse width of 5 ms. Thus, the total charge of both the positive phase 604 and the negative phase 606 may be 50 pC. Asymmetric biphasic stimulation allows for increased intensity on one side of the pulse polarity while maintaining charge balance.

[0040] FIG. 7 shows the first unidirectional waveform 700. The first unidirectional waveform 700. in contrast to the biphasic waveforms described above, may have pulses with only positive or negative phases rather than both. Unidirectional pulses as make up the first unidirectional waveform 700 may modulate brain activity more effectively than bidirectional pulses in some examples. The first unidirectional waveform 700 as shown may be a fixed frequency pulse train whereby each of the pulses has fixed pulse parameters including current amplitude, pulse width, and frequency . For example, the pulses of the waveform 700 as shown may have a pulse width of 1ms, a frequency of 100 Hz, and a current amplitude of 500 mA.

[0041] FIG. 8 shows the second unidirectional waveform 800. The second unidirectional waveform 800 may be a bursting pattern rather than a fixed pattern. The bursting pattern may more closely resemble the natural rhythms of activity in the neurons of the brain. For example, in theta-burst stimulation (TBS), a short burst of pulses are delivered at a 50 Hz frequency (gamma frequency), and the burst repeats at a 5 Hz frequency (theta frequency). The stimulation system as herein disclosed can deliver a range of bursting patterns with varying pulse waveforms (monophasic and / or biphasic pulses and unidirectional and / or bidirectional pulse trains), number of pulses per burst, current amplitudes, and nesting frequencies. The second unidirectional waveform 800 as shown in FIG. 8 is thus an example of a unidirectional bursting pattern. It should be understood that bursting patterns may also be generated that are biphasic / bidirectional. symmetrically and asymmetrically.

[0042] The second unidirectional waveform 800 as shown is a theta-burst pattern. The stimulation parameters thereof may include unidirectional pulses with a fixed current amplitude, a pulse frequency with a given burst, pulse widths within the burst, and a burst frequency. For example, the stimulation parameters of the waveform as shown include a pulse width of 1 ms, pulse frequency within a burst of 50 Hz, burst frequency of 5 Hz. and a current amplitude of 50 mA.

[0043] FIG. 9 shows the second symmetric biphasic waveform 900. The second symmetric biphasic waveform 900 may be a modulated amplitude pulse pattern wherein the stimulation current amplitude and / or the frequency during the pulse train are varied. For example, the current amplitude may be titrated up over time with each pulse. Similar to the bursting pattern described above, the modulated amplitude pulse pattern is applicable not only to biphasic / bidirectional symmetric patterns as shown in FIG. 9. but is also applicable unidirectional and asymmetric type patterns. Modulated amplitude pattern may facilitate new ECT seizure titration schemes, including for example amplitude titration.

[0044] Stimulation parameters of the modulated amplitude pulse patterns may include a variable current that ramps up with each subsequent pulse. As a non-limiting example, the pulse parameters of the second symmetric biphasic waveform 900 may include a pulse width of 1 ms. a frequency of 100 Hz, and a current amplitude with a step size of 2 mA with a starting amplitude of 0 mA. As a result, with each pulse phase, the current amplitude steps up by 2 mA. For example, a first pulse 902 may comprise a positive phase 904 and a negative phase 906 and a second pulse 910 may comprise a positive phase 912 and a negative phase 914. The first and second pulses 902. 910 may be adjacent pulses, where the second pulse 910 is delivered immediately subsequent to the first pulse 902. The positive phase 904 of the first pulse 902 may have a current amplitude of 8 mA, the negative phase 906 of the first pulse 902 may have a current amplitude of 10 mA, the positive phase 912 of the second pulse 910 may have a current amplitude of 12 mA, and the negative phase 914 of the second pulse 910 may have a current amplitude of 14 mA. Thus the step size of 2 mA with every pulse phase is demonstrated. Stimulation current amplitude may be up to 900 mA, meeting the total energy delivery requirement predicated on existing ECT devices. It should be understood that other amplitude step sizes, pulse widths, and frequencies not shown in the figures are possible, within system parameter constraints as herein described.

[0045] The stimulation system 100 as herein presented may thus be configured to generate the above varying current pulse patterns depending on the individual patient. In some examples, an individualized stimulation pattern may increase efficacy of stimulation while minimizing side effects.

[0046] Turning now to FIG. 3, a flowchart illustrating an example method 300 for configuration an adjustable current individualized stimulation system, such as the stimulation system 100 described with respect to FIG. 1. which includes an ICS configured to deliver current through electrodes of an electrode cap. Method 300 may be carried out according to instructions stored in memory of one or more controllers, processors, and / or computing devices included as part of an / or communicatively or operatively coupled to the stimulation system, for example microcomputer 106 of stimulation system 100 described with reference to FIG. 1.

[0047] At 302, method 300 includes obtaining data of a patient. The data may include structural data, such as magnetic resonance imaging (MRI) data, of the patient’s brain and / or brain mapping data,such as EEG data. The data of the patient may define patient-specific anatomy that may be used to generate a model of the patient’s anatomy. In some examples, structural data may be segmented and then meshed. For example, brain MRI data may be segmented into scalp, skull, cerebrospinal fluid, gray matter, and white matter.

[0048] At 304. method 300 includes generating a three-dimensional (3D) model of the patient’s head based on the segmented data. As noted, each of the segmented portions of the data may be meshed together to form the 3D model of the patient’s head. The 3D model may be configured for use in one or more methods and / or algorithms. For example, the 3D model may be used to compute an electric field and current flow that is to be provided by the stimulation system during a neurostimulation session. Computation of the electric field and / or current flow may be performed via application of a numerical stimulation model, such as a finite element method or a boundary element method. Computing the electric field via the numerical stimulation model may decrease time spent by the operator in determining parameters for the electric field and / or current flow. Computation of the electric field and / or current flow based on patient-specific anatomy may allow for individualized therapy.

[0049] At 306, method 300 optionally includes determining stimulation target(s). Determination, or specification, may be performed by a user of the stimulation system via an operator computer that is communicatively coupled and / or operatively coupled to the stimulation system. Determination of the stimulation target(s) may be based on the data of the patient, for example the spatial data provided by die 3D model, brain mapping data such as an EEG that may provide information for which areas of the patient’s brain arc to be targeted during the neurostimulation session, and the like. Further, specification of stimulation target(s) may allow for avoidance of certain brain areas that may contributed to side effects like memory loss and as such, specifying stimulation targets that do not include those areas may allow for decreased side effects for the patient. In addition to specifying targets, one or more non-targets (e.g., anti-targets) that are not to receive stimulation may also be determined, in some examples. In other examples, stimulation targets may be predefined for a given electrode cap configuration. For example, the electrode pair of the electrode cap may be pre-configured as a bitemporal or right unilateral configuration in which the current path is known based on the preset configuration of the cap.

[0050] At 308. method 300 optionally includes applying a computational optimization method for the electric field. In some examples, the computational optimization method may be applied in order to determine maximum electric field delivery to the specified stimulation target(s) and or to the planned stimulation target(s) between electrodes of the electrode cap. The computational optimization method may be carried out by instructions stored in non-transitory memory of the stimulation system.

[0051] At 310, method 300 includes determining current parameters and pulse pattern. In some examples, the current parameters and pulse waveform pattern may be based on user input indicating parameters and pattem(s). The current parameters may include current amplitude, pulse width, pulse frequency, stimulus train duration, and pattern specific parameters, such as pulse width within burst.The stimulation system may have predefined parameter constraints, including current amplitude up to 900 mA, pulse width up to 1.5 ms, pulse-pair frequency up to 120 Hz, and stimulus train duration up to 8 s. Within these predefined constraints, current pulse parameters may be defined, including current amplitude and pattern. As is described with respect to FIGS. 5-9, the patterns available may include symmetric biphasic, asymmetric biphasic, unidirectional symmetric, bursting bidirectional, bursting unidirectional, and modulated amplitude. In some examples, the user may define the current parameters and pulse pattern based on the patient specific data, including the 3D head model. MRI and EEG data, and clinical diagnoses. For example, 3D head models may be constructed from the patient’s MRI data. The electric field associated with a specific stimulus electrode placement can be simulated using numerical methods. The simulated electric field strength and distribution can be used to determine the current amplitude for the stimulus pulses. In additional, the patient’s demographics, such as age, can be included to further inform the current amplitude dose requirements.

[0052] As an example, a patient diagnosis that is being treated may indicate current parameters and pulse pattern chosen by the user. For example, an asymmetric biphasic wave pattern may be inputted by the user in the instance of treatment for medically resistant schizophrenia, while a bursting unidirectional wave pattern may be inputted by the user in the instance of treatment for repetitive selfinjury in an autism spectrum disorder.

[0053] At 312, method 300 includes operating the stimulation system to deliver current to the patient’s head based on the determined current parameters and pulse pattern. As described with respect to FIG. 2, the ICS may comprise two output terminals, A and B, and stimuli may be delivered as pulses w ith one or more phases. As an example, for a selected pulse pattern of asymmetric biphasic, stimuli may be delivered as pairs of alternating positive and negative current pulses, whereby one phase of each pair has a first current amplitude and first pulse width and the other phase of each pair has a second current amplitude and a second pulse width. In the determination of current parameters and pulse pattern, the parameters for the stimulus train are defined, including current amplitude, pulse width, pulse frequency, and the like. The current delivered to the patient’s head may thus be based on the defined parameters and patterns. In some examples, for example when the defined parameters and patterns are one of an asymmetric, unidirectional, bursting, and modulated amplitude pattern, the stimulation system may adjust delivery between each pulse and / or pulse phase in order to deliver the prescribed current in each pulse / phase.

[0054] Turning now to FIG. 4, a flowchart illustrating an example method 400 for operating an adjustable current individualized stimulation system is shown. The stimulation system herein described may be the stimulation system 100 of FIG. 1. Method 400 may be carried out at least in part according to instructions stored in memory of one or more controllers, processors, and / or computing devices included as part of and / or communicatively or operatively coupled to the stimulation system, for example microcomputer 106 of MCU 102 of the stimulation system 100 described with reference toFIG. 1. The stimulation system may comprise a chassis that includes an MCU, PCU, one or more ICSs, an FE AU, an operator computer removably coupled to the chassis via an isolated wired connection, and an electrode cap removably coupled to the chassis.

[0055] At 402, method 400 includes transitioning a current pulse from low to high at the start of a timer for pulse parameters. The current pulse may begin to rise once the timer starts. The timer may indicate the pulse width, thus when the timer starts, the pulse current rises from 0mA towards its defined current amplitude. Parameters of the current pulse may be predefined, as explained with respect to FIG. 3. In some examples, the current pulse may be the first pulse in a pulse train. In other examples, the current pulse may be one of a plurality of pulses delivered after the first pulse in the pulse train. The current pulse may be delivered as the pulse transitions from low to high, the time in between, as measured by the timer, may be the pulse width, and the amplitude and pulse width may be defined for the system as noted. The current pulse, as herein described, may be a full pulse, as in the case of unidirectional pulse patterns, or a pulse phase, as in the case of biphasic / bidirectional pulse patterns. The current pulse may transition from low to high within a timeframe of 10 ps, in some examples. The time it takes to transition from low to high may also be a predefined variable for the system. It should be understood that “low” as herein referenced for the current pulse refers to an amplitude of 0mA and “high” refers to the peak current amplitude. The peak current amplitude may be a positive or negative amplitude, depending on the current parameters, pulse pattern, and which pulse is currently being delivered.

[0056] At 404, method 400 includes measuring data of the pulse such as current amplitude of the pulse. As noted, the current amplitude may be a predefined parameter known to the system. While the pulse is at its peak, an analog-to-digital converter (ADC) of the ICS may measure the current amplitude of the pulse. For example, the ADC measurement may occur at halfway through the pulse width (e.g., at 50% of stimulation duration). Thus, the timing of the ADC measurement may be predefined as the pulse width is predefined. ADC measurement may be trigged by the rising edge of the pulse, and then may be executed at the midway point in the pulse width, in some examples. Other data may include pulse width, pulse frequency (e.g., duration since previous pulse), and the like. Pulse wave patterns may be independent of the ADC measurement. The pulse may rise to the current amplitude, maintain at the current amplitude for the pulse width, and the transition to low.

[0057] At 406, method 400 includes transitioning the pulse from high to low at the end of the timer. As noted, the timer may indicate the pulse width of the current pulse. When the timer ends, the current may drop from its current amplitude to 0mA. The duration of the transition from high to low may be equal to the transition from low to high as noted at 402.

[0058] At 408, method 400 includes processing the data to determine a plurality of metrics. The plurality' of metrics may include short-circuit, open-circuit, and delivered energy. The MCU of thestimulation system may process the data in real time after the pulse is low. For example, the data may be processed immediately after the stimulation pulse returns to OmA.

[0059] At 410, method 400 includes determining whether the data and the plurality of metrics are within a predefined threshold. The MCU may store in memory predefined ranges for acceptable short- circuits, open-circuits, delivered energy, amplitudes, widths, frequencies, and more. If the data and metrics are within the predefined threshold ranges, method 400 proceeds to 416. If any of the data and metrics are outside a respective predefined threshold range, method 400 ends. The method 400 ending following determination of the data being outside the threshold may be an abortion of the stimulus train as is described previously. In such an instance, a subsequent pulse may not be delivered to the patient.

[0060] At 412, method 400 includes determining if a next pulse is indicated. As discussed, each stimulus pulse train includes a plurality of pulses. In some cases, as with biphasic / bidirectional patterns, each pulse may comprise a positive and a negative phase of the pulse, a next pulse may refer to a next pulse phase of the pulse or the next pulse may refer to the next full pulse in the pulse train. A next pulse may be indicated when the pulse is not the last pulse or pulse phase in the pulse train. A next pulse may not be indicated when the pulse is the last pulse or pulse phase in the pulse train. If a next pulse is indicated, method 400 proceeds to 418. If a next pulse is not indicated, method 400 ends.

[0061] At 414, method 400 optionally includes modifying current parameters. In examples in which the pulse pattern is asymmetric biphasic, bursting, and / or modulated amplitude, the next pulse (or next pulse phase) may have different parameters than the preceding pulse or pulse phase. As a nonlimiting example, in an example asymmetric biphasic pattern, the positive pulse phase of each pulse may have a current amplitude of 50 mA and a pulse width of 1 ms while the negative pulse phase of each pulse may have a current amplitude of 10 mA and a pulse width of 5 ms. With a preceding positive pulse phase, the next pulse phase may be the corresponding negative pulse phase, and thus the current parameters may be modified from the parameters of the positive pulse phase to the parameters of the negative pulse phase. Some pulse patterns do not demand a change in current parameters. For example, unidirectional symmetric patterns, in which the same current amplitude, pulse width, and direction are repeated throughout the stimulation, no modifications are made.

[0062] The pulse current may change when the pulse amplitude is 0 mA, for example after the preceding pulse is finished and before the next pulse starts. To change the current amplitude, for example in asymmetric pulse patterns, the system may update to a new DAC output. Consequently, the adjustment of current parameters may affect the speed of the stimulation process. After the current parameters are modified, the pulse remains low (e.g., at 0 mA) until the DAC of the ICS registers the new output voltage, as noted at 4160. Once the ICS registers the new output voltage, method 400 returns to 402 to repeat the method 400 again for the next pulse. In examples in which the current parameters are not modified, method 400 may skip over 414 and 416 and proceed back to 402 from 412. Thus, method 400 may be performed for each pulse / pulse phase in the pulse train that is executed.

[0063] The technical effect of the adjustable current individualized stimulation system herein disclosed is that the system is configured to generate stimulation at various defined stimulation parameters. For example, the system can deliver stimulation at varying pulse parameters, including pulse frequency, current amplitude, pulse width, and pulse polarity, as well as the pulse pattern (e.g., biphasic, unidirectional, asymmetric, symmetric, etc.). In this way. the system is configured to deliver stimulation that is individualized to patients based on their diagnosis and physiology, which may reduce side effects from stimulation while maintaining treatment efficacy.

[0064] The following claims particularly point out certain combinations and sub-combinations regarded as novel and non-obvious. These claims may refer to “an” element or “a first” element or the equivalent thereof. Such claims should be understood to include incorporation of one or more such elements, neither requiring nor excluding two or more such elements. Other combinations and subcombinations of the disclosed features, functions, elements, and / or properties may be claimed through amendment of the present claims or through presentation of new claims in this or a related application. Such claims, whether broader, narrower, equal, or different in scope to the original claims, also are regarded as included within the subject matter of the present disclosure.

[0065] As used herein, an element or step recited in the singular and proceeded with the word “a” or “an” should be understood as not excluding plural of said elements or steps, unless such exclusion is explicitly stated. Furthermore, references to “one embodiment” of the present invention are not intended to be interpreted as excluding the existence of additional embodiments that also incorporate die recited features. Moreover, unless explicitly stated to the contrary, embodiments “comprising,” “including,” or “having” an element or a plurality of elements having a particular property may include additional such elements not having that property. The terms “including” and “in which" are used as the plain-language equivalents of the respective terms “comprising" and “wherein.” Moreover, the terms “first.” “second.” and “third,” etc. are used merely as labels, and are not intended to impose numerical requirements or a particular positional order on their objects.

[0066] This written description uses examples to disclose the invention, including the best mode, and also to enable a person of ordinary skill in the relevant art to practice the invention, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the invention is defined by the claims, and may include other examples that occur to those of ordinary' skill in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal languages of the claims.

Claims

CLAIMS1. A system, comprising: a device comprising a plurality of stimulation electrodes and at least one isolated current source (ICS), wherein the device is configurable to adjust current parameters and a pulse pattern of pulses of stimuli applied to a patient.

2. The system of claim 1, further comprising: a main control unit (MCU) comprising a microcomputer; a power control unit (PCU), comprising a plurality of batteries including an MCU battery and at least one ICS battery; and an electrode cap comprising the plurality of stimulation electrodes, wherein the at least one ICS delivers current according to defined current parameters and a defined pulse pattern through at least one pair of stimulation electrodes of the plurality of stimulation electrodes of the electrode cap.

3. The system of claim 2, wherein the defined current parameters and the defined pulse pattern are defined based on patient-specific anatomy.

4. The system of claim 2, wherein the electrode cap further comprises one or more electroencephalogram (EEG) electrodes interleaved with the plurality' of stimulation electrodes.

5. The system of claim 2, further comprising an operator computer communicatively and operatively coupled to the MCU.

6. The system of claim 5, wherein the operator computer display s a graphical user interface (GUI) through which the defined current parameters and the defined pulse pattern arc defined.

7. The system of claim 2, wherein the defined pulse pattern is one or more of symmetric biphasic, asymmetric biphasic, symmetric unidirectional, amplitude modulated, and bursting.

8. The system of claim 2, further comprising: a front-end amplifier unit (FEAU) that operably couples to the MCU, wherein the FEAU is coupled to the electrode cap including the plurality of EEG electrodes; and a plurality of additional monitoring electrodes including electrocardiograph (ECG) and electromyogram (EMG) electrodes.

9. The system of claim 8, wherein the FEAU is configured to protect the plurality of EEG electrodes during stimulation and to reduce EEG reading recovery time delay.

10. A method, comprising: delivering current pulses to one or more stimulation targets of a patient, wherein current parameters and a pulse pattern of the current pulses are variable and configurable based on patientspecific anatomy and the one or more stimulation targets.

11. The method of claim 10. comprising: obtaining data of the patient-specific anatomy; generating a three-dimensional (3D) model of a head of the patient based on the data of the patient-specific anatomy: determining the current parameters and pulse pattern for an adjustable current individualized stimulation system based on 3D model; and delivering current pulses according to the current parameters and pulse pattern via an isolated current source (ICS) of the adjustable current individualized stimulation system.

12. The method of claim 11, wherein the current parameters comprise current amplitude, pulse width, pulse frequency, and pulse polarity'.

13. The method of claim 11, wherein the pulse pattern is one or more of symmetric biphasic, asymmetric biphasic, symmetric unidirectional, amplitude modulated, and bursting.

14. The method of claim 11, wherein determining the current parameters comprises receiving user input an operator computer.

15. An adjustable current individualized stimulation system, comprising: an electrode cap operably coupled to one or more isolated current sources (ICSs), wherein die electrode cap comprises at least two electrodes and the one or more ICSs are configured to deliver current to the at least two electrodes; a mam control unit (MCU) operably coupled to the one or more ICSs; a power control unit (PCU) operably coupled to the MCU and the one or more ICSs, the PCU comprising an MCU battery' and one or more current source batteries, wherein the MCU battery is configured to provide power to the MCU and each of the one or more current source batteries is configured to provide power to one of the one or more ICSs, wherein the MCU is configured to control delivery of current through at least one pair of electrodes of the electrode cap via the one or more ICSs, wherein the current adjustable prior to delivery; and a battery control unit (BCU) operably coupled with the PCU during charging batteries.

16. The adjustable current individualized stimulation system of claim 15, wherein during a charge mode, the PCU is charged by the BCU that is operably coupled to the PCU and simultaneously disconnected from the MCU and patient electrode circuitry .

17. The adjustable current individualized stimulation system of claim 15. wherein during a stimulation mode, the BCU is disconnected from the PCU and electrodes of the electrode cap are operably coupled to the MCU.

18. The adjustable current individualized stimulation system of claim 15, further comprising a front-end amplifier unit (FEAU) that operably couples to the MCU. wherein the FEAU is coupled to the electrode cap including a plurality of electroencephalogram (EEG) electrodes, and a plurality of additional monitoring electrodes measuring physiology of a patient, the plurality of additional monitoring electrodes including electrocardiogram (ECG) and electromyogram (EMG) electrodes.

19. The adjustable current individualized stimulation system of claim 15, wherein current is delivered for treating one or more of a major depressive episode, a manic episode, catatonia, a psychotic subtype of depression, schizophrenia, schizoaffective disorder, Parkinson’s disease, epilepsy, status epilepticus, repetitive self-injury’ in an autism spectrum disorder, tardive dyskinesia, dystonia, and neuroleptic malignant syndrome.

20. The adjustable current individualized stimulation system of claim 15, wherein current parameters and a pulse pattern of the delivered current is defined based on the patient specific data.

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