Effect of apomorphine on cortical inhibition in Parkinson's disease patients: a transcranial magnetic stimulation study

In this study, transcranial magnetic stimulation (TMS) of the primary motor hand area was used to test cortical excitability in Parkinson's disease (PD) patients. Motor evoked potentials (MEPs) to TMS were studied at rest by utilising distinct paired-pulse TMS protocols. Out of 29 untreated PD patients and 29 healthy subjects, early cortical inhibition (1-6 ms) was studied in a first subgroup of 17 PD patients and 15 healthy subjects, whereas late cortical inhibition (20-200 ms) was studied in a second subgroup of 21 PD patients and 19 healthy subjects. In all PD patients the same TMS protocols were performed before and after 3 h of apomorphine infusion. In comparison to healthy subjects, untreated PD patients showed a significant reduction of both early and late cortical inhibition, which was maximal at 2-3 ms, and at 80-100 ms, respectively. Apomorphine administration consistently reversed all the MEP abnormalities found in PD patients. The lack of TMS effects on the Hoffman's reflex (HR), at those intervals revealing the reduced inhibition in PD patients, is compatible with a supraspinal origin of the observed MEP abnormalities. Our data suggest that the cortical and/or subcortical loss of dopaminergic transmission in PD patients is associated with impaired motor cortical inhibitory mechanisms, as tested by a decreased early and late MEP inhibition.