Systems and methods for evaluating neuromodulation based on evoked potentials
The present disclosure provides systems and methods relating to neuromodulation. In particular, the present disclosure provides systems and methods for evaluating the efficacy of neuromodulation therapy using evoked potential (EPs). The systems and methods disclosed herein facilitate the evaluation of both parameter-dependent and system-dependent changes in EPs as indicators of therapeutic efficacy.
1 . A method of determining efficacy of a neuromodulation therapy based on evoked potential (EP), the method comprising:
(i) administering a first functional stimulation train superimposed with a second probe stimulation train to neural tissue of a subject according to stimulation parameter settings, and obtaining a reference EP recording from the subject; and
(ii) altering at least one stimulation parameter of the first functional stimulation train with respect to the reference EP recording, and obtaining a variable EP recording from the subject;
wherein at least one different feature of the variable EP recording obtained by altering the at least one stimulation parameter correlates with a disease indication, a change in symptom, and/or a change in a side effect; and
wherein activation during stimulation of the subject's neural tissue for each of the reference EP recording and the variable EP recording is quantified on a per-second basis by summing individual responses to multiple repetitions of pulses within a stimulation train during a specified interval of time.
2 . The method of claim 1 , wherein the at least one different feature of the variable EP recording obtained by altering the at least one stimulation parameter correlates with charge, energy, and/or power required for stimulation.
3 . The method of claim 1 , wherein the variable EP recording is obtained from at least a second timepoint with respect to the reference EP recording.
4 . The method of claim 1 , wherein the at least one stimulation parameter comprises: (i) number and/or location of active electrode contacts; (ii) stimulation amplitude and polarity delivered to each contact; (iii) stimulation pulse repetition frequency; (iv) stimulation pulse duration; (v) stimulation pulse shape; and (vi) temporal pattern of stimulation.
5 . The method of claim 4 , wherein the temporal pattern of stimulation comprises duty cycle, bursts, random patterns, and non-random patterns.
6 . The method of claim 1 , wherein the at least one feature of the reference or variable EP recording comprises: (i) maximum peak voltage; (ii) peak latency; (iii) voltage differences from a maximum voltage; (iv) minimum trough value; (v) mean waveform value; (vi) voltage standard deviation; (vii) sum of voltage squared; (viii) voltage difference from the voltage at a set time point; and (ix) signal power present in specific spectral bands of the EP and any combinations thereof.
7 . The method of claim 1 , wherein the reference EP recording and the variable EP recording are obtained by averaging individual responses to multiple repetitions of pulses within a stimulation train.
8 . The method of claim 1 , wherein the reference EP recording and the variable EP recording are obtained as part of a closed-loop stimulation protocol.
9 . The method of claim 1 , wherein the method further comprises repeating steps (i) and (ii) to generate a variable EP signature that comprises a plurality of different features with respect to the reference EP.
10 . The method of claim 9 , wherein the variable EP signature: (i) correlates with a disease indication, a change in symptom, and/or a change in side effect; and/or (ii) correlates with charge, energy, and/or power required for stimulation.
11 . The method of claim 1 , wherein the method further comprises altering the at least one stimulation parameter to treat a symptom and/or reduce a side effect in the subject.
12 . The method of claim 11 , wherein the treatment is provided to the subject as part of deep brain stimulation (DBS), spinal cord stimulation (SCS), sacral nerve stimulation (SNS), vagus nerve stimulation (VNS), peripheral nerve stimulation (PNS), or cranial nerve stimulation.
13 . A method of determining efficacy of a neuromodulation therapy based on evoked potential (EP), the method comprising:
(i) administering a first functional stimulation train superimposed with a second probe stimulation train to neural tissue of a subject according to stimulation parameter settings, and obtaining a reference EP recording from the subject; and
(ii) obtaining a variable EP recording from the subject using stimulation parameters for the second probe stimulation train that are identical with respect to the reference EP recording;
wherein at least one different feature of the variable EP recording correlates with a disease indication, a change in symptom, and/or a change in a side effect; and
wherein activation during stimulation of the subject's neural tissue for each of the reference EP recording and the variable EP recording is quantified on a per-second basis by summing individual responses to multiple repetitions of pulses within a stimulation train during a specified interval of time.
14 . The method of claim 13 , wherein the disease indication, the change in symptom, and/or the change in a side effect comprises alterations in network state, ion accumulation, movement of the electrode, synaptic plasticity, neural excitability, changes in the surrounding tissue impedance, disease progression, the medication status of the patient, changes in the state of the patient, changes in the response to stimulation, and any combinations thereof.
15 . The method of claim 13 , wherein the at least one different feature of the variable EP recording correlates with charge, energy, and/or power required for stimulation.
16 . The method of claim 13 , wherein the at least one stimulation parameter comprises: (i) number and/or location of active electrode contacts; (ii) stimulation amplitude and polarity delivered to each contact; (iii) stimulation pulse repetition frequency; (iv) stimulation pulse duration; (v) stimulation pulse shape; and (vi) temporal pattern of stimulation.
17 . The method of claim 13 , wherein the at least one feature of the reference or variable EP recording comprises: (i) maximum peak voltage; (ii) peak latency; (iii) voltage differences from a maximum voltage; (iv) minimum trough value; (v) mean waveform value; (vi) voltage standard deviation; (vii) sum of voltage squared; (viii) voltage difference from the voltage at a set time point; and (ix) signal power present in specific spectral bands of the EP and any combinations thereof.
18 . The method of claim 13 , wherein the variable EP recording is obtained from at least a second timepoint with respect to the reference EP recording.
19 . The method of claim 13 , wherein the reference EP recording and the variable EP recording are obtained by averaging individual responses to multiple repetitions of pulses within a stimulation train.
20 . The method of claim 13 , wherein the reference EP recording and the variable EP recording are obtained as part of a closed-loop stimulation protocol.
21 . The method of claim 13 , wherein the method further comprises repeating steps (i) and (ii) to generate a variable EP signature that comprises a plurality of different features with respect to the reference EP.
22 . The method of claim 13 , wherein the method further comprises altering the at least one stimulation parameter to treat a symptom and/or reduce a side effect in the subject.
23 . A method of determining efficacy of a neuromodulation therapy based on evoked potential (EP), the method comprising:
(i) administering a first functional stimulation train superimposed with a second probe stimulation train to neural tissue of a subject according to stimulation parameter settings to obtain a reference EP recording; and
(ii) altering at least one stimulation parameter of the first functional stimulation train with respect to the reference EP recording to obtain a first variable EP recording; and obtaining a second variable EP recording using stimulation parameters for the second probe stimulation train that are identical with respect to the reference EP recording;
wherein at least one different feature of the first and/or second variable EP recording correlates with a disease indication, a change in symptom, and/or a change in a side effect.