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

Cedeño, David L.; Vallejo, Ricardo; Kelley, Courtney A.; Platt, D; Litvak, Leonid M.; Straka, Małgorzata; Dinsmoor, David

doi:10.1016/j.neurom.2022.06.006

Cited by 8 publications

(20 citation statements)

References 32 publications

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“…In a minority of experiments, N2 was composed of dual peaks (not shown). Taken together, these recordings indicate that epidural stimulation was functional and could evoke ECAP responses indicative of dorsal column activity consistent with prior observations (Cedeño et al, 2022; Dietz et al, 2022).…”

Section: Resultssupporting

confidence: 90%

“…Despite the absolute variability, ECAP generally had lower thresholds than ESAP (Fig. 5) and EMG thresholds are approximately ∼2x above even S1, and our reported EMG thresholds being 3x above ECAPs are consistent (or conservative) compared to prior studies (Cedeño et al, 2022; Dietz et al, 2022).…”

Section: Discussionsupporting

confidence: 77%

“…The copyright holder for this preprint this version posted February 19, 2023. ; https://doi.org/10.1101/2023.02.18.528981 doi: bioRxiv preprint consistent (or conservative) compared to prior studies (Cedeño et al, 2022;Dietz et al, 2022).…”

Section: Limitationsmentioning

confidence: 92%

“…Epidural spinal cord stimulation (SCS) for neuropathic pain is thought to engage inhibitory dorsal horn mechanisms, whether via synaptic activation following antidromic stimulation of dorsal column fibers, consistent with Gate Control Theory (Shealy et al, 1970), or through more subtle, slower acting mechanisms (Titus et al, 2021). Dorsal column stimulation is sensed by evoked electrical responses representing the summed activity of dorsal column (Aβ) axons, whose synchronous activation produces a propagating evoked compound action potential (ECAP) characterized by P1, N1, and P2 waves, with latencies <2 ms proximal to the stimulation site (Cedeño et al, 2022; Cioni and Meglio, 1986; Dietz et al, 2022; Parker et al, 2013). The stimulation current threshold for ECAPs correlates with patient reported paresthesia and discomfort thresholds, and ECAP recording can be performed using contacts on the therapeutic stimulation leads, supporting the use of ECAPs in closed-loop SCS systems (Parker et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Novel Evoked Synaptic Activity Potentials (ESAPs) elicited by Spinal Cord Stimulation

Sharma

Bhaskar

Yang

et al. 2023

Preprint

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Spinal cord stimulation (SCS) evokes fast epidural Evoked Compound Action Potential (ECAPs) that represent activity of dorsal column axons, but not necessarily a spinal circuit response. Using a multimodal approach, we identified and characterized a delayed and slower potential evoked by SCS that reflects synaptic activity within the spinal cord. Anesthetized female Sprague Dawley rats were implanted with an epidural SCS lead, epidural motor cortex stimulation electrodes, an epidural spinal cord recoding lead, an intraspinal penetrating recording electrode array, and intramuscular electromyography (EMG) electrodes in the hindlimb and back. We stimulated the motor cortex or the epidural spinal cord and recorded epidural, intraspinal, and EMG responses. SCS pulses produced characteristic propagating ECAPs (composed of P1, N1, and P2 waves with latencies <2 ms) and an additional wave (S1) starting after the N2. We verified the S1-wave was not a stimulation artifact and was not a reflection of hindlimb/back EMG. The S1-wave has a distinct stimulation-intensity dose response and spatial profile compared to ECAPs. CNQX (a selective competitive antagonist of AMPA receptors) significantly diminished the S1-wave, but not ECAPs. Furthermore, cortical stimulation, which did not evoke ECAPs, produced epidurally detectable and CNQX-sensitive responses at the same spinal sites, confirming epidural recording of an evoked synaptic response. Finally, applying 50 Hz SCS resulted in dampening of ESAPs, but not ECAPs. Therefore, we hypothesize that the S1-wave is synaptic in origin, and we term the S1-wave type responses: Evoked Synaptic Activity Potentials (ESAPs). The identification and characterization of epidurally recorded ESAPs from the dorsal horn may elucidate SCS mechanisms.

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Section: Resultssupporting

confidence: 90%

Section: Discussionsupporting

confidence: 77%

Section: Limitationsmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Novel Evoked Synaptic Activity Potentials (ESAPs) elicited by Spinal Cord Stimulation

Sharma

Bhaskar

Yang

et al. 2023

Preprint

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“…After placing the SCS leads using an anatomical placement scheme, 2 we set the SCS amplitudes relative to the sheep ECAP thresholds (ECAPTs); an approach previously demonstrated to relate SCS PTs to ECAPTs in both rodents (by the visual motor threshold) and humans. 3 , 23 Then, using a first-of-its-kind method, we used a separate lead to assess changes in ALS activation with swept amplitude burst and conventional SCS. We conclude with a discussion on the comparative dosing and mechanistic implications for both burst and conventional SCS.…”

Section: Introductionmentioning

confidence: 99%

Using evoked compound action potentials to quantify differential neural activation with burst and conventional, 40 Hz spinal cord stimulation in ovines

Dinsmoor

Usoro

Barka

et al. 2022

PR9

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Introduction and Objectives: Unlike conventional dorsal spinal cord stimulation (SCS)-which uses single pulses at a fixed rate-burst SCS uses a fixed-rate, five-pulse stimuli cluster as a treatment for chronic pain; mechanistic explanations suggest burst SCS differentially modulate the medial and lateral pain pathways vs conventional SCS. Neural activation differences between burst and conventional SCS are quantifiable with the spinal-evoked compound action potential (ECAP), an electrical measure of synchronous neural activation. Methods: We implanted 7 sheep with a dorsal stimulation lead at T9/T10, a dorsal ECAP sensing lead at T6/T7, and a lead also at T9/T10 but adjacent to the anterolateral system (ALS). Both burst and conventional SCS with stimulation amplitudes up to the visual motor threshold (vMT) were delivered to 3 different dorsal spinal locations, and ECAP thresholds (ECAPTs) were calculated for all combinations. Then, changes in ALS activation were assessed with both types of SCS.Results: Evoked compound action potential thresholds and vMTs were significantly higher (P , 0.05) with conventional vs burst SCS, with no statistical difference (P . 0.05) among stimulation sites. However, the vMT2ECAPT window (a proxy for the useable therapeutic dosing range) was significantly wider (P , 0.05) with conventional vs burst SCS. No significant difference (P . 0.05) in ALS activation was noted between conventional and burst SCS. Conclusion: When dosed equivalently, no differentially unique change in ALS activation results with burst SCS vs conventional SCS; in addition, sub-ECAPT burst SCS results in no discernable excitability changes in the neural pathways feeding pain relevant supraspinal sites.

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Evoked compound action potentials during spinal cord stimulation: effects of posture and pulse width on signal features and neural activation within the spinal cord

Brucker-Hahn,

Zander,

Will

et al. 2023

J. Neural Eng.

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Objective. Evoked compound action potential (ECAP) recordings have emerged as a quantitative measure of the neural response during spinal cord stimulation (SCS) to treat pain. However, utilization of ECAP recordings to optimize stimulation efficacy requires an understanding of the factors influencing these recordings and their relationship to the underlying neural activation.Approach. We acquired a library of ECAP recordings from 56 patients over a wide assortment of postures and stimulation parameters, and then processed these signals to quantify several aspects of these recordings (e.g., ECAP threshold, amplitude, latency, growth rate). We compared our experimental findings against a computational model that examined the effect of variable distances between the spinal cord and the SCS electrodes.Main results. Postural shifts strongly influenced the experimental ECAP recordings, with a 65.7% lower ECAP threshold and 178.5% higher growth rate when supine versus seated. The computational model exhibited similar trends, with a 71.9% lower ECAP threshold and 231.5% higher growth rate for a 2.0-mm cerebrospinal fluid layer (representing a supine posture) versus a 4.4-mm cerebrospinal fluid layer (representing a prone posture). Furthermore, the computational model demonstrated that constant ECAP amplitudes may not equate to a constant degree of neural activation.Significance. These results demonstrate large variability across all ECAP metrics and the inability of a constant ECAP amplitude to provide constant neural activation. These results are critical to improve the delivery, efficacy, and robustness of clinical SCS technologies utilizing these ECAP recordings to provide closed-loop stimulation.

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

Cited by 8 publications

References 32 publications

Novel Evoked Synaptic Activity Potentials (ESAPs) elicited by Spinal Cord Stimulation

Novel Evoked Synaptic Activity Potentials (ESAPs) elicited by Spinal Cord Stimulation

Using evoked compound action potentials to quantify differential neural activation with burst and conventional, 40 Hz spinal cord stimulation in ovines

Evoked compound action potentials during spinal cord stimulation: effects of posture and pulse width on signal features and neural activation within the spinal cord

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