Hebbian priming of human spinal motor learning

Learning or relearning of motor skills requires plasticity in relevant neural circuits. Motor recovery following lesions to the corticospinal system can be augmented through neuromodulation techniques targeting the affected or compensatory neural circuits. By repeatedly pairing transcranial magnetic stimulation of the primary motor cortex (M1) and motoneuronal electrical stimulation (i.e., paired corticomotoneuronal stimulation, PCMS) timed to arrive at the corticomotoneuronal (CM) synapses in close temporal proximity, spike-timing-dependent bidirectional changes in CM transmission can be induced in humans (Taylor & Martin, 2009). PCMS-induced increases in CM transmission have been demonstrated to transiently improve motor control in patients with spinal cord injury (Bunday & Perez 2012), whereas effects on the malleability of neural circuits are entirely unexplored. We hypothesized that PCMS can prime mechanisms of subsequent motor learning exclusively when directed to the neural circuitry underpinning the motor behavior. In three experiments, we provide the first evidence (‘Experiment I’) and a double-blinded, sham-controlled replication (‘Experiment II’) that PCMS targeting the spinal CM synapses can prime subsequent learning of rapid finger movements relying on spinal neuroplasticity. Finally, we demonstrate that the effects of PCMS are circuit-specific and bidirectional. When PCMS was timed to arrive at a facilitatory interval in M1 but an inhibitory interval at the CM synapses subsequent learning was transiently impeded (‘Experiment III’). Taken together, our results provide proof-of-principle that non-invasively induced plasticity governed by Hebbian learning rules interacts with experience-dependent plasticity in the spinal cord with positive implications for motor learning. Our results offer a mechanistic rationale for priming sensorimotor training with individualized PCMS to enhance the effects of motor practice in neurorehabilitation.