Epidural Spinal Cord Recordings (ESRs): Sources of Artifact in Stimulation Evoked Compound Action Potentials

Introduction Evoked compound action potentials (ECAPs) measured using epidural spinal recordings (ESRs) during epidural spinal cord stimulation (SCS) can help elucidate fundamental mechanisms for the treatment of pain, as well as inform closed-loop control of SCS. Previous studies have used ECAPs to characterize the neural response to various neuromodulation therapies and have demonstrated that ECAPs are highly prone to multiple sources of artifact, including post-stimulus pulse capacitive artifact, electromyography (EMG) bleed-through, and motion artifact resulting from disturbance of the electrode/tissue interface during normal behavior. However, a thorough characterization has yet to be performed for how these sources of artifact may contaminate recordings within the temporal window commonly used to determine activation of A-beta fibers in a large animal model. Methods We characterized the sources of artifacts that can contaminate the recording of ECAPs in an epidural SCS swine model using the Abbott Octrode™ lead. Muscle paralytics were administered to block muscle activation preventing EMG from contaminating the recorded ECAPs. Concurrent EMG recordings of the longissimus, a long muscle of the back, were used to confirm a 2-4 millisecond (ms) latency source of EMG bleed-through that frequently contaminated the A-beta temporal window. Additionally, we obtained recordings approximately 5-10 minutes post-mortem after clear evoked A-beta and associated EMG responses ceased to characterize the representation of stimulation artifact across the array. Results Spinal ECAP recordings can be contaminated by capacitive artifact, short latency EMG from nearby long muscles of the back, and motion artifact from multiple sources. In many cases, the capacitive artifact can appear nearly identical in duration and waveshape to evoked A-beta responses. These sources of EMG can have phase shifts across the electrode array, very similar to the phase shift anticipated by propagation of an evoked A-beta fiber response across the array. This short latency EMG is often evident at currents similar to those needed to activate A-beta fibers associated with the treatment of pain. Changes in cerebrospinal fluid between the cord and dura, and motion induced during breathing created a cyclic oscillation in all evoked components of the recorded ECAP signal. Conclusion Careful controls must be implemented to accurately separate neural signal from the sources of artifact in spinal cord ECAPs. To address this, we suggest experimental procedures and associated reporting requirements necessary to disambiguate the underlying neural response from these confounds. These data are important to better understand the conceptual framework for recorded ESRs, with components such as ECAPs, EMG responses and artifacts, and have important implications for closed-loop control algorithms to account for transient motion such as postural changes and cough. ### Competing Interest Statement This study was funded by Abbott Neuromodulation. JKT is a paid consultant for Presidio Medical, Inc. NV was an employee of Abbott Neuromodulation and BioCircuit Technologies during the completion of this work. NV is a stockholder in NeuronOff and NeuraWorx. NV is currently an employee of Presidio Medical. KAL is a co-founder and equity holder for Neuronoff, Inc. KAL is also a co-founder and equity holder of NeuraWorx. KAL is a scientific board member and has stock interests in NeuroOne Medical Inc. KAL is also a paid member of the scientific advisory board of Abbott and Presidio Medical, and a paid consultant for the Alfred Mann Foundation, ONWARD and Restora Medical. KAL and AJS are co-founders of Neuronoff Inc. AJS is a consultant to Neuronoff Inc. SFL receives research support from Abbott Neuromodulation, Medtronic plc, Neuromodulation Specialists LLC, and Presidio Medical Inc.; is a shareholder in CereGate, Hologram Consultants LLC, and Presidio Medical Inc., and is a member of the scientific advisory boards for Abbott Neuromodulation, CereGate, and Presidio Medical Inc. IL receives research support from Abbott Neuromodulation; DJW is a co-founder and shareholder of Reach Neuro, Inc. and Bionic Power, Inc. DJW has stock interests in NeuroOne Medical, Inc., Neuronoff, Inc. DJW receives research support from Meta, Inc.