Timing-dependent synergies between noninvasive motor cortex and spinal cord stimulation in chronic cervical spinal cord injury

Objective

Spinal cord sensory networks strongly interact with descending motor circuits. We targeted this interaction by pairing motor cortex stimulation with coordinated cervical spinal cord stimulation. Using separate non-invasive and epidural experiments, we tested the hypothesis that the strongest muscle response would occur when paired brain and spinal cord stimuli simultaneously converge within the spinal cord. Methods: For non-invasive experiments, we measured motor evoked potentials in response to transcranial magnetic stimulation (TMS) and transcutaneous spinal cord stimulation (TSCS). We compared this noninvasive approach to intraoperative paired stimulation experiments using dorsal epidural electrodes in individuals undergoing surgery for cervical myelopathy. Results: In 16 individuals with chronic spinal cord injury (SCI) and 15 uninjured individuals, suprathreshold TMS augmented target muscle responses (11.0%) when subthreshold TSCS stimuli converged synchronously in the spinal cord. Facilitation correlated with TSCS intensity. Facilitation did not correlate with SCI level or severity, indicating spared circuits were sufficient for this effect. Noninvasive pairing produced less facilitation compared to intraoperative (epidural) pairing. Conclusions: Sensorimotor interactions in the cervical spinal cord can be targeted with paired stimulation in individuals with and without SCI. Significance: Properly timed paired stimulation may enhance synaptic responsiveness after SCI.