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Lookup NU author(s): Kimberley Ladner, Eline Versantvoort, Dave Mugan, Professor Stuart BakerORCiD, Dr Sasha KraskovORCiD, Dr Quoc VuongORCiD, Dr Birte Dietz, Dr Ilona ObaraORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The Authors.Objectives Epidural stimulation of the spinal cord evokes distinct electrophysiologic responses that can be recorded epidurally. Here, we characterized evoked compound action potentials (ECAPs), doublets (secondary or tertiary ECAPs, probably of different physiologic origin from primary ECAPs), evoked synaptic activity potentials (ESAPs), and electromyographic (EMG) signals in preclinical models. Our objective was to clarify the features and distinct physiologic origins of these signals, to advance mechanistic studies and support clinical applications of spinal cord stimulation (SCS) therapy. Materials and Methods Adult male Sprague-Dawley rats (300–440 g) were implanted with two epidural leads (caudal and rostral; each with eight electrodes) and received monopolar, biphasic stimulation (200-μs pulse width) at 2 and 50 Hz, with current increased stepwise to motor threshold. Rhesus macaques (11.5 and 10.2 kg) were implanted with a single 12-electrode epidural lead and stimulated using either tripolar, triphasic pulses at 10 Hz (100 μs) or tripolar, biphasic pulses at 3 Hz (80 μs) up to 3 × ECAP threshold. Recordings were taken from nonstimulating electrodes. Results ECAPs and EMG signals were recorded across multiple spinal segments in both rats (L1–T7) and macaques (L2–T11). Doublets presented as complex waveforms with multiple negative peaks, two in rats and three in macaques, likely representing distinct ECAPs at T11–T6 in a rat and L1–T11 in macaques. ESAPs, detectable in rats, showed anatomical specificity over the L1/T13 vertebrae, with peak responses at L1. Signal analysis included activation thresholds, amplitudes, latencies, and conduction velocities. Conclusions This study outlines electrophysiologic signals evoked by SCS in terms of their waveform, recruitment thresholds, and putative physiologic origins. We propose that to some extent, these signals reflect different aspects of spinal processing and may serve as biomarkers of dysregulated nociceptive pathways, and as indicators of SCS efficacy or potential side effects.
Author(s): Ladner K, Versantvoort EM, Thijssen MEG, Mugan D, Baker SN, Kraskov A, Vuong QC, Sharma M, Bikson M, Dietz BE, Palmisani S, Obara I
Publication type: Article
Publication status: Published
Journal: Neuromodulation
Year: 2026
Pages: epub ahead of print
Online publication date: 09/02/2026
Acceptance date: 06/01/2026
Date deposited: 23/02/2026
ISSN (print): 1094-7159
ISSN (electronic): 1525-1403
Publisher: International Neuromodulation Society
URL: https://doi.org/10.1016/j.neurom.2026.01.001
DOI: 10.1016/j.neurom.2026.01.001
Data Access Statement: The data sets used and/or analyzed during the present study are available from the corresponding author on reasonable request.
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