Recovery of Dexterous Motor Control via Non-Monosynaptic Corticospinal Pathways

SUMMARY Fine motor control of the human arm is assumed to depend on monosynaptic connections between the motor cortex and spinal motoneurons. We report that people with post-stroke hemiparesis could regain dexterous control using non-monosynaptic corticospinal tract (CST) projections during epidural cervical spinal cord stimulation (SCS). Participants in our pilot clinical study demonstrated the ability to improve strength, reaching smoothness, and fine force control of the arm and hand while receiving continuous stimulation. Detailed electrophysiology of corticospinal connectivity with transcranial magnetic stimulation, electromyography spectral analysis, and single motor-unit firing showed that SCS did not reliably strengthen CST-activation of motoneurons. Instead, residual CST axons sculpted the strength of spinal reflexes produced by each pulse of SCS via polysynaptic mechanisms, including presynaptic gating of sensory afferent excitability, to promote functionally relevant muscle activation patterns. Our findings reveal the ability of non-monosynaptic CST pathways to finely tune spinal motor output in humans after stroke.