Characterization and applications of evoked responses during epidural electrical stimulation

Nishant Verma; Ben Romanauski; Danny Lam; Luis Lujan; Stephan Blanz; Kip Ludwig; Scott Lempka; Andrew Shoffstall; Bruce Knudson; Yuichiro Nishiyama; Jian Hao; Hyun-Joo Park; Erika Ross; Igor Lavrov; Mingming Zhang

doi:10.1186/s42234-023-00106-5

Characterization and applications of evoked responses during epidural electrical stimulation

Bioelectron Med. 2023 Feb 28;9(1):5. doi: 10.1186/s42234-023-00106-5.

Authors

Nishant Verma^#^{1

2

3}, Ben Romanauski^#⁴, Danny Lam¹, Luis Lujan^{4

5}, Stephan Blanz^{2

3

6}, Kip Ludwig^{2

3

7}, Scott Lempka^{8

9

10}, Andrew Shoffstall^{8

9}, Bruce Knudson^{2

3}, Yuichiro Nishiyama¹¹, Jian Hao¹¹, Hyun-Joo Park¹, Erika Ross¹, Igor Lavrov¹², Mingming Zhang¹³

Affiliations

¹ Abbott Neuromodulation, 6901 Preston Rd, Plano, TX, 75024, USA.
² Department of Biomedical Engineering, University of Wisconsin Madison, Madison, USA.
³ Wisconsin Institute for Translational Neuroengineering (WITNe), Madison, WI, USA.
⁴ Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA.
⁵ Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
⁶ University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
⁷ Department of Neurosurgery, University of Wisconsin-Madison, Madison, WI, USA.
⁸ Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.
⁹ APT Center, Louis Stokes Cleveland VA Medical Center, OH, Cleveland, USA.
¹⁰ Department of Biomedical Engineering, Department of Anesthesiology, Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
¹¹ Department of Neurology, Department of Physiology and Biomedical Engineering, Mayo Clinic, 500 First Street SW, Rochester, MN, 55905, USA.
¹² Department of Neurology, Department of Physiology and Biomedical Engineering, Mayo Clinic, 500 First Street SW, Rochester, MN, 55905, USA. igor.lavrov@gmail.com.
¹³ Abbott Neuromodulation, 6901 Preston Rd, Plano, TX, 75024, USA. mingming.zhang1@abbott.com.

^# Contributed equally.

Abstract

Background: Epidural electrical stimulation (EES) of the spinal cord has been FDA approved and used therapeutically for decades. However, there is still not a clear understanding of the local neural substrates and consequently the mechanism of action responsible for the therapeutic effects.

Method: Epidural spinal recordings (ESR) are collected from the electrodes placed in the epidural space. ESR contains multi-modality signal components such as the evoked neural response (due to tonic or BurstDR™ waveforms), evoked muscle response, stimulation artifact, and cardiac response. The tonic stimulation evoked compound action potential (ECAP) is one of the components in ESR and has been proposed recently to measure the accumulative local potentials from large populations of neuronal fibers during EES.

Result: Here, we first review and investigate the referencing strategies, as they apply to ECAP component in ESR in the domestic swine animal model. We then examine how ECAP component can be used to sense lead migration, an adverse outcome following lead placement that can reduce therapeutic efficacy. Lastly, we show and isolate concurrent activation of local back and leg muscles during EES, demonstrating that the ESR obtained from the recording contacts contain both ECAP and EMG components.

Conclusion: These findings may further guide the implementation of recording and reference contacts in an implantable EES system and provide preliminary evidence for the utility of ECAP component in ESR to detect lead migration. We expect these results to facilitate future development of EES methodology and implementation of use of different components in ESR to improve EES therapy.

Keywords: Evoked compound action potential; Neuromodulation; Neuropathic pain; Neurophysiology; Spinal cord stimulation; Spinally evoked motor potentials.

Grants and funding

OT2 OD025340/OD/NIH HHS/United States