Electrode position, size, and orientation determine efficacy of cervical epidural stimulation to recruit forelimb muscles in rats

Objective: Cervical epidural spinal cord stimulation (SCS) can facilitate upper-limb motor recovery, but electrode configurations that optimally recruit motor circuits remain unclear. This study systematically evaluated how electrode position, size, orientation, and waveform influence the efficacy of forelimb motor activation in rats, with the goal of identifying configurations that minimize stimulation thresholds of evoked responses across multiple muscles. Approach: Custom microfabricated arrays of electrodes were implanted over the C6 dorsal root entry zone (DREZ) in eight adult female Sprague Dawley rats. A circular array was used to vary current orientation in 45 degree increments, while a linear array was used to optimize mediolateral electrode position. The linear array included both small (0.25 mm) and large (0.5 mm) contacts to assess size effects at mediolateral positions. Stimulation consisted of biphasic and pseudomonophasic waveforms with bipolar or distant return, and a high-definition montage to probe spatial focality around the DREZ. Motor-evoked potentials (MEPs) recorded via implanted EMG electrodes were analyzed in six forelimb muscles. Thresholds, estimated from recruitment curves using a hierarchical Bayesian model, were compared within-rat using pairwise t-tests with correction for multiple comparisons. Results: Stimulation over the DREZ yielded the lowest thresholds and efficacy decreased progressively with medial or lateral displacement relative to DREZ. In the circular array, rostro-caudal current orientation was most effective, reducing thresholds by up to 58% relative to latero-medial orientation (p = 0.0007). In the linear array, large contacts were significantly more effective than small contacts at the lateral position, reducing thresholds by 45% (p = 0.034). Cathodal stimulation was more effective than anodal, and high-definition montages reduced efficacy compared to distant returns. Across all tested parameters, position and orientation had the greatest influence on efficacy, with optimal conditions combining DREZ targeting and rostro-caudal oriented current flow. Significance: Maximum efficacy was achieved for cervical SCS with electrodes positioned over the DREZ, rostro-caudal current flow, larger contacts, and cathodal stimulation. These design principles that more effectively engage spinal circuitry could reduce the current required and thereby improve SCS systems for upper-limb motor restoration.