<p>Sensing Evoked Compound Action Potentials from the Spinal Cord: Novel Preclinical and Clinical Considerations for the Pain Management Researcher and Clinician</p>

Abstract

Spinal cord stimulation (SCS) is a drug-free treatment for chronic neuropathic pain. Recent SCS technology can record evoked compound action potentials (ECAPs) in the spinal cord during therapy and utilize features of the sensed ECAP to optimize the SCS. The purpose of this work is to characterize the relevant parameters that govern the integrity and morphology of acquired ECAPs, and the implications for pain management clinicians and researchers working with ECAPs. Materials and Methods: Eight-contact percutaneous SCS leads were implanted into sheep, and a prototype ECAP-sensing system was used to record spinal cord activity across a range of electrode configurations, pulse widths, and stimulus amplitudes. Similar iterative testing was then completed in human subjects who were undergoing trials of commercial SCS systems. Results: Longer pulse width stimulation results in a progressive increase in ECAP latency, a neurophysiologic effect that enables ECAP sensing with longer pulses despite more encroachment by stimulation artifact. ECAPs may manifest a polyphasic morphology-an effect not seen in all subjects studied-with longer pulse width stimulation; these later phases may be used to assess ECAP amplitude when earlier features are effaced by artifact. Triphasic stimulation limits artifact from spinal cord ECAPs at the expense of potentially higher activation thresholds. If applied, alternating polarity stimulation must account for the ECAP latency differences resulting from alternating sites of neural activation. Conclusion: Together, this information can allow the ECAP to be readily distinguished from the stimulation artifact, although movement may continue to be a confounder; caution is inculcated for ECAP signal processing techniques that rely on the stability of the artifact to avoid clinically misleading results. The promise of closed-loop, ECAP-servoed neuromodulation relies on accurate and proper sensing of the ECAP, while clearly elucidating the clinically relevant trade-offs and design choices made to enable these novel features.

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

“…This analysis relied on small amplitude ECAP detection at the edge of perception. Even with the robust stimulation artifact reduction scheme employed here, shorter pulse widths were utilized to limit opportunity for artifact misclassification by the ECAP amp estimator ( Chakravarthy et al, 2020 ). Third, all testing was performed in-clinic under controlled experimental settings; different assessments of perception may be offered by the subjects if they were at home and engaged in everyday activities.…”

“…The ECAPs and associated stimulation artifact are digitized and stored off-line for further processing (Biopac MP160). Both the performance – pre-clinical and clinical – and design of the research system are detailed more fully elsewhere ( Chakravarthy et al, 2020 ).…”

“…Artifact reduction is an important consideration for ECAP estimation, as waveforms recorded from the spinal cord may be partially corrupted by stimulation artifact ( Parker et al, 2012 ; Chakravarthy et al, 2020 ). The application of an appropriate artifact reduction scheme is particularly important when assessing small amplitude ECAPs close to the perceptual threshold.…”

“…The spinal ECAP is described as a triphasic bipotential, the amplitude of which represents the extent of synchronous activation in the dorsal column axons in response to SCS ( Parker et al, 2012 ). The morphology of the ECAP is influenced by the SCS pulse width employed ( Chakravarthy et al, 2020 ). As the ECAP consists of the superposition of multiple fiber types firing together, changes in pulse width shifts the overall composition of the individual fiber types contributing to the ECAP ( Anaya et al, 2020 ).…”

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

“… 29 The amplitude of the ECAP—defined here as the differential voltage between the N1 and P2 features of the ECAP—is indicative of the presumed spinal volume of tissue activation (VTA) elicited with the stimulation. 29 , 30 Although a volumetric measure, VTA is often conceptualized in cross-section. The VTA in the dorsal columns contains ascending dorsal column fibers.…”