The Evoked Compound Action Potential as a Predictor for Perception in Chronic Pain Patients: Tools for Automatic Spinal Cord Stimulator Programming and Control

Abstract

ObjectivesSpinal cord stimulation (SCS) is a drug free treatment for chronic pain. Recent technological advances have enabled sensing of the evoked compound action potential (ECAP), a biopotential that represents neural activity elicited from SCS. The amplitudes of many SCS paradigms – both sub- and supra-threshold – are programmed relative to the patient’s perception of SCS. The objective of this study, then, is to elucidate relationships between the ECAP and perception thresholds across posture and SCS pulse width. These relationships may be used for the automatic control and perceptually referenced programming of SCS systems.MethodsECAPs were acquired from 14 subjects across a range of postures and pulse widths with swept amplitude stimulation. Perception (PT) and discomfort (DT) thresholds were recorded. A stimulation artifact reduction scheme was employed, and growth curves were constructed from the sweeps. An estimate of the ECAP threshold (ET), was calculated from the growth curves using a novel approach. Relationships between ET, PT, and DT were assessed.ResultsETs were estimated from 112 separate growth curves. For the postures and pulse widths assessed, the ET tightly correlated with both PT (r = 0.93; p < 0.0001) and DT (r = 0.93; p < 0.0001). The median accuracy of ET as a predictor for PT across both posture and pulse width was 0.5 dB. Intra-subject, ECAP amplitudes at DT varied up to threefold across posture.ConclusionWe provide evidence that the ET varies across both different positions and varying pulse widths and suggest that this variance may be the result of postural dependence of the recording electrode-tissue spacing. ET-informed SCS holds promise as a tool for SCS parameter configuration and may offer more accuracy over alternative approaches for neural and perceptual control in closed loop SCS systems.

Spinal Evoked Compound Action Potentials in Rats With Clinically Relevant Stimulation Modalities

“…Growth curves are a common graphical means for depicting neural activation, ECAP amplitudes, and the relationship between ECAPs and psychometric measures such as the PT. 15 From each growth curve, we calculated the ECAPT by fitting a regression line to the first three ECAPs above a threshold of 10 μV; additional points were iteratively included for more accuracy if the calculated slope did not decrease by >1%. The ECAPT was defined as the x-intercept of the regression line.…”

“…ECAPs are a clinically valuable tool for quantifying changes in electrophysiologic state, whether as a means to relate perception to a direct measure of neural activation or as feedback signal for controlling the volume of tissue activated with SCS waveforms on a pulse-by-pulse basis. 15,26 And, as first described (albeit in a single animal) by Kent et al, 17 ECAPs may be used to advance understanding of neural activation with both tonic and more modern SCS waveforms in rats, a commonly used preclinical model for SCS research. Our work builds on this concept in several important ways.…”

“…Previous work has demonstrated that the ECAPT closely approximates the PT in human subjects across postures and stimulation parameters. 15 Accordingly, ECAP recording holds promise as an electrophysiologically derived point of perceptual reference for both preclinical and clinical SCS use.…”

Surround Inhibition Mediates Pain Relief by Low Amplitude Spinal Cord Stimulation: Modeling and Measurement

“…Supporting DC activation during low-amplitude SCS, prior studies recorded evoked compound action potentials (ECAPs) from the DCs below 50% of MT (or 100% of PT) in a preclinical model (Yang et al, 2015), and clinical reports with closed-loop SCS showed that ECAPs occur below sensory threshold in some patients (Pilitsis et al, 2021). A study of continuous 50 Hz subperception SCS found decreased mechanical hypersensitivity and altered theta rhythms in awake freely moving rats (Koyama et al, 2018).…”

A New Direction for Closed-Loop Spinal Cord Stimulation: Combining Contemporary Therapy Paradigms with Evoked Compound Action Potential Sensing

“…Moreover, the two may work additively, for instance by scaling the ECAP target based on body position. 43 Thus, the two approaches are not mutually exclusive but instead may readily integrate.…”