Altered plasticity of the human motor cortex in Parkinson's disease

TLDR

Interventional paired associative stimulation can enhance primary motor cortex excitability through synchronous peripheral nerve and cortical inputs. The study examined whether dopamine contributes to IPAS‑induced associative long‑term potentiation‑like effects in Parkinson’s disease patients. Eighteen right‑handed Parkinson’s patients (12 h off levodopa) and eleven age‑matched healthy controls received IPAS consisting of 240 paired median‑nerve and left M1 TMS stimuli at 25 ms intervals over 20 min, with ten patients also tested while on medication. IPAS increased motor‑evoked potentials in healthy volunteers but not in Parkinson’s patients, and dopamine replacement increased the pre‑to‑post IPAS MEP ratio in patients, indicating dopamine modulates cortical plasticity. Published in Annals of Neurology, 2006.

Abstract

Abstract Interventional paired associative stimulation (IPAS) to the contralateral peripheral nerve and cerebral cortex can enhance the primary motor cortex (M1) excitability with two synchronously arriving inputs. This study investigated whether dopamine contributed to the associative long‐term potentiation–like effect in the M1 in Parkinson's disease (PD) patients. Eighteen right‐handed PD patients and 11 right‐handed age‐matched healthy volunteers were studied. All patients were studied after 12 hours off medication with levodopa replacement (PD‐off). Ten patients were also evaluated after medication (PD‐on). The IPAS comprised a single electric stimulus to the right median nerve at the wrist and subsequent transcranial magnetic stimulation of the left M1 with an interstimulus interval of 25 milliseconds (240 paired stimuli every 5 seconds for 20 minutes). The motor‐evoked potential amplitude in the right abductor pollicis brevis muscle was increased by IPAS in healthy volunteers, but not in PD patients. IPAS did not affect the motor‐evoked potential amplitude in the left abductor pollicis brevis. The ratio of the motor‐evoked potential amplitude before and after IPAS in PD‐off patients increased after dopamine replacement. Thus, dopamine might modulate cortical plasticity in the human M1, which could be related to higher order motor control, including motor learning. Ann Neurol 2006