Intraoperative electrical stimulation of the human dorsal spinal cord reveals a map of arm and hand muscle responses

Abstract

While epidural stimulation of the lumbar spinal cord has emerged as a powerful modality for recovery of movement, how it should be targeted to the cervical spinal cord to activate arm and hand muscles is not well-understood, particularly in humans. We sought to map muscle responses to posterior epidural cervical spinal cord stimulation in humans. We hypothesized that lateral stimulation over the dorsal root entry zone would be most effective, and responses would be strongest in the muscles innervated by the stimulated segment. Twenty-five people undergoing clinically indicated cervical spine surgery were consented to map motor responses. During surgery, stimulation was performed in midline and lateral positions at multiple exposed segments; six arm and three leg muscles were recorded on each side of the body. Across all segments and muscles tested, lateral stimulation produced stronger muscle responses than midline despite similar latency and shape of responses. Muscles innervated at a cervical segment had the largest responses from stimulation at that segment, but responses were also observed in muscles innervated at other cervical segments and in leg muscles. The cervical responses were clustered in rostral (C4-C6) and caudal (C7-T1) cervical segments. Strong responses to lateral stimulation are likely due to the proximity of stimulation to afferent axons. Small changes in response sizes to stimulation of adjacent cervical segments argues for local circuit integration, and distant muscle responses suggest activation of long propriospinal connections. This map can help guide cervical stimulation to improve arm and hand function.

Timing dependent synergies between motor cortex and posterior spinal stimulation in humans

“…When considering the targeted muscles of the arm and hand, 30,188 MEPs were analysed of which 2,949 (9.8%) were rejected. Note that this is higher than in our previous work with SCS (McIntosh et al 2023) due to the tES induced artefact being more extensive and the presence of additional sources of artefact induced by the ongoing surgery. Rejection was performed blinded to the ISI.…”

“…The location of the exiting or entering cervical nerve was estimated based on bony and neural anatomical landmarks. This method of hand placement of the electrode was previously validated by co-registering intraoperative computer tomography with pre-operative MRI and verifying the electrode placement relative to the DREZ (McIntosh et al 2023). In a subset of cases (n = 23), intraoperative imaging was required as part of the surgical procedure and this was subsequently utilised to confirm the location of the electrode contacts (e.g., Fig.…”

“…We employed the same method for rejecting MEPs as previously described (McIntosh et al 2023). Briefly, rejection was based on principal component analysis and human observer confirmation.…”

“…The selectivity for a particular muscle was calculated as its AUC divided by the sum of the AUCs of all other muscles recorded on the same side of the body (McIntosh et al 2023). This calculation ensures that the sum of selectivities across all muscles equals one.…”

“…To test this, we have used epidural electrodes to pair motor cortex stimulation with dorsal (sensory) spinal cord stimulation in rats. Epidural spinal cord stimulation recruits a large number of sensory axons as they enter the spinal cord (Capogrosso et al 2013; Liang et al 2023; McIntosh et al 2023). In one preclinical study, our group showed that timing motor cortex and dorsal epidural spinal stimulation to converge in the spinal cord markedly increased the motor evoked potential (MEP) (by 155%), while convergence in motor cortex resulted in a much smaller effect (17%) (Pal et al 2022).…”