Objective. Cervical transcutaneous spinal cord stimulation (tSCS) is a promising technology that can support motor function recovery of upper-limbs after spinal cord injury. Its efficacy may depend on the ability to recruit sensory afferents, conveying excitatory inputs onto motoneurons. Therefore, understanding its physiological mechanisms is critical to accelerate its development towards clinical applications. In this study, we used an anatomically realistic cervical tSCS computational model to compare α-motor, Aα-sensory, and Aβ-sensory fiber activation thresholds and activation sites. Approach. We developed a 3D geometry of the cervical body and tSCS electrodes with a cathode centred at the C7 spinous process and an anode placed over the anterior neck. The geometrical model was used to estimate the electric potential distributions along motor and sensory fiber trajectories at the C7 spinal level using a finite element method. We implemented dedicated motor and sensory fiber models to simulate the α-motor and Aα-sensory fibers using 12, 16, and 20 µm diameter fibers, and Aβ-sensory fibers using 6, 9, and 12 µm diameter fibers. We estimated nerve fiber activation thresholds and sites for a 2 ms monophasic stimulating pulse and compared them across the fiber groups. Main results. Our results showed lower activation thresholds of Aα- and Aβ-sensory fibers compared with α-motor fibers, suggesting preferential sensory fiber activation. We also found no differences between activation thresholds of Aα-sensory and large Aβ-sensory fibers, implying their co-activation. The activation sites were located at the dorsal and ventral root levels. Significance. Using a realistic computational model, we demonstrated preferential activation of dorsal root Aα- and Aβ-sensory fibers compared with ventral root α-motor fibers during cervical tSCS. These findings suggest high proprioceptive and cutaneous contributions to neural activations during cervical tSCS, which inform the underlying mechanisms of upper-limb functional motor recovery.

Cervical transcutaneous spinal cord stimulation (tSCS) has been utilized in applications for improving upper-limb sensory and motor function in patients with spinal cord injury. Although therapeutic effects of continuous cervical tSCS interventions have been reported, neurophysiological mechanisms remain largely unexplored. Specifically, it is not clear whether sub-threshold intensity and 10-min duration continuous cervical tSCS intervention can affect the central nervous system excitability. Therefore, the purpose of this study was to investigate effects of sub-motor-threshold 10-min continuous cervical tSCS applied at rest on the corticospinal and spinal reflex circuit in ten able-bodied individuals. Neurophysiological assessments were conducted to investigate (1) corticospinal excitability via transcranial magnetic stimulation applied on the primary motor cortex to evoke motor-evoked potentials (MEPs) and (2) spinal reflex excitability via single-pulse tSCS applied at the cervical level to evoke posterior root muscle (PRM) reflexes. Measurements were recorded from multiple upper-limb muscles before, during, and after the intervention. Our results showed that low-intensity and short-duration continuous cervical tSCS intervention applied at rest did not significantly affect corticospinal and spinal reflex excitability. The stimulation duration and/or intensity, as well as other stimulating parameters selection, may therefore be critical for inducing neuromodulatory effects during cervical tSCS.

Chronic arm and hand hemiparesis is a major cause of disability after stroke. Unfortunately, standard-of-care rehabilitation falls well short of the high doses required to experience improvements. In this feasibility study, we explored the use of cervical epidural spinal cord stimulation (SCS) to assist motor function and provide meaningful functional improvements without the need of a high-dose rehabilitation program. Here we report the final outcomes of this study testing safety, feasibility and preliminary efficacy of cervical SCS as a neuroprosthetic approach for chronic post-stroke upper limb hemiparesis. We implanted seven participants with profound motor deficits (Fugl-Meyer Assessment (FMA) scores 15–35) using two leads implanted unilaterally in the cervical spinal cord for 4 weeks. No serious adverse events occurred. Under SCS ON, motor function immediately improved regardless of impairment severity (average +32% strength and +5.6 FMA points). Notably, three of seven participants with residual corticospinal connectivity to finger muscles improved hand/finger movement with SCS. Despite performing only 8.6 hours of motor activity (5.5 hours with SCS ON), participants improved by an average of +6.6 FMA points at the end of the study compared to baseline, and spasticity decreased in all participants. Although all benefited, our preliminary analysis indicates that spared sensory function may be a determinant of responsiveness to SCS. These findings provide preliminary evidence of the safety, feasibility and efficacy of cervical SCS for chronic post-stroke hemiparesis, suggesting its potential as a fully implantable neuroprosthetic solution for assisting upper limb function in daily living. ClinicalTrials.gov identifier: NCT04512690.

Here, we report the final outcomes of a pilot clinical trial testing preliminary efficacy and safety of cervical epidural spinal cord stimulation (SCS) for chronic post-stroke upper-limb hemiparesis ( NCT04512690 ). We implanted seven participants with profound motor deficits (Fugl-Meyer Assessment [FMA] scores 15–35) using two leads implanted unilaterally in the cervical spinal cord for 4 weeks. Under SCS ON, motor function immediately improved regardless of impairment severity (average +32% strength and +5.6 FMA-points). Notably, 3/7 participants with residual corticospinal connectivity to finger muscles regained hand/finger function with SCS. Despite performing only 8.6hrs of motor activity (5.5hrs with SCS ON), participants improved by average +6.6 FMA-points at the end of the study compared to baseline and spasticity decreased in all participants. While all benefited, our preliminary analysis indicates that spared sensory function may be a determinant of responsiveness to SCS. No serious adverse events occurred.

Transcutaneous spinal cord stimulation (tSCS) applied over the cervical or lumbar spinal cord facilitates motor function after paralysis. However, emerging electrophysiological evidence indicates mechanistic differences between cervical and lumbar tSCS and across different cervical tSCS paradigms. To clarify these discrepancies, we developed and validated a multi-scale, whole-body computational model of tSCS-induced volume conduction, axonal recruitment, and synaptic transmission. Across 24 cervical and four lumbar tSCS paradigms, simulations showed that somatosensory afferents consistently exhibit lower stimulation thresholds than motor efferents. In turn, region-specific synaptic transmission differences may explain electrophysiological discrepancies between cervical and lumbar tSCS. Across cervical tSCS paradigms, substantial volume conduction and axonal recruitment differences were observed that explain electrophysiological discrepancies. Specifically, clinically-prevalent paradigms, including those with anodes placed over the clavicles or iliac crests, engaged peripheral nerves in addition to spinal roots. This effect was amplified by multiphasic waveforms, which introduced recruitment sites near the anodes. By integrating simulations with electrophysiological recordings in 14 able-bodied individuals, we investigated previously unexplored cervical tSCS paradigms on their capacity to recruit somatosensory afferents relative to motor threshold.