Paired Associative Transspinal and Transcortical Stimulation Produces Bidirectional Plasticity of Human Cortical and Spinal Motor Pathways

Anatomical, physiological, and functional connectivity exists between primary motor cortex (M1) and spinal cord neurons. Paired associative stimulation (PAS) produces enduring changes in M1 based on the Hebbian principle of associative plasticity. The present study aims to discover immediate neurophysiological changes on human corticomotor pathways by pairing noninvasive transspinal and transcortical stimulation via transcranial magnetic stimulation (TMS). We delivered paired transspinal and transcortical stimulation for 40-min at precise interstimulus intervals with TMS being delivered after (transspinal-transcortical PAS) or before (transcortical-transspinal PAS) transspinal stimulation. Transspinal-transcortical PAS markedly decreased intracortical inhibition, increased intracortical facilitation and M1 excitability with concomitant decreases of motor threshold. Conversely, transcortical-transspinal PAS did not affect intracortical circuits and decreased M1 excitability. Both protocols affected the recruitment gain of spinal motoneurons. Transcortical-transspinal PAS reduced the soleus H-reflex postactivation depression, and transspinal-transcortical PAS reduced the low-frequency soleus H-reflex depression. These findings clearly indicate that pairing transspinal with transcortical stimulation produces both cortical and spinal plasticity, but excitability changes (inhibition or facilitation) in the human brain and spinal cord are reversed based on the timing interval and functional network interactions between the two associated inputs. Transspinal-transcortical PAS can be used as a therapeutic intervention to strengthen cortical networks and corticospinal connections in neurological disorders and thus reduce impairment associated with dysfunction of these neuronal networks