Contralesional paired associative stimulation increases paretic lower limb motor excitability post-stroke

Following stroke, an abnormally high interhemispheric inhibitory drive from the contralesional to the ipsilesional primary motor cortex (M1) is evident during voluntary movement. Down-regulating motor excitability of the contralesional M1 using inhibitory neuromodulatory protocols has demonstrated a correlation between balanced interhemispheric interactions and increased motor recovery. In 2005, our laboratory first reported bidirectional modulation of healthy subjects' tibialis anterior (TA) motor excitability during walking, using a stimulation paradigm known as paired associative stimulation (PAS). Suprathreshold transcranial magnetic stimulation (TMS) of the lower limb M1 paired with electrical stimulation of the common peroneal nerve produced a persistent modulation of TA corticomotor excitability. The present study tested the hypothesis that the excitability of the ipsilesional lower limb motor cortex during walking is increased when inhibitory PAS is applied to the contralesional motor cortex in chronic stroke survivors. We applied inhibitory PAS (120 pairs at 0.5 Hz) to the quiescent paretic TA of ten chronic stroke patients and the right TA of ten age-matched healthy subjects. Post intervention excitability measures were taken immediately following PAS, and again 5, 10 and 15 min later. When inhibitory PAS was applied to the non-paretic TA of chronic stroke subjects, the non-paretic TA motor evoked potential (MEP) amplitude decreased to 91% and paretic TA MEP amplitude increased to 130% (of pre-PAS values) during post-PAS walking. In healthy subjects, MEPs in response to TMS revealed that mean MEP amplitude from the stimulated TA decreased to 87% and the mean MEP amplitude from the non-stimulated TA increased to 126%. This is the first study to demonstrate that inhibitory PAS applied to the contralesional lower limb motor system of stroke survivors increases motor excitability of the paretic lower limb assessed during walking. This finding suggests that inhibitory PAS may be a useful tool to study how the human lower limb motor cortex recovers after neural injury, and that PAS may be a candidate adjuvant therapy for patients with neurological walking impairments.