Differences in Dopaminergic Modulation to Motor Cortical Plasticity between Parkinson's Disease and Multiple System Atrophy

Abstract

Dopamine modulates the synaptic plasticity in the primary motor cortex (M1). To evaluate whether the functioning of the cortico-striatal circuit is necessary for this modulation, we applied a paired associative stimulation (PAS) protocol that comprised an electric stimulus to the right median nerve at the wrist and subsequent transcranial magnetic stimulation of the left M1, to 10 patients with Parkinson's disease (PD) and 10 with multiple system atrophy of the parkinsonian type (MSA-P) with and without dopamine replacement therapy (-on/off). To investigate the M1 function, motor-evoked potentials (MEPs) were measured before and after the PAS. In both patient groups without medication, the PAS protocol failed to increase the averaged amplitude of MEPs. The dopamine replacement therapy in PD, but not in MSA-P effectively restored the PAS-induced MEP increase. This suggests that not the existence of dopamine itself but the activation of cortico-striatal circuit might play an important role for cortical plasticity in the human M1.

Transcranial magnetic stimulation follow‐up study in early Parkinson's disease: A decline in compensation with disease progression?

“…Therefore our results challenge the classical view of generally reduced sensorimotor cortical plasticity in PD . We show that enhanced response to PAS in PD may be detected when clinical signs are minimal, becoming less pronounced with worsening of motor signs.…”

“…Therefore our results challenge the classical view of generally reduced sensorimotor cortical plasticity in PD. 32, [34][35][36][37][38] We show that enhanced response to PAS in PD may be detected when clinical signs are minimal, becoming less pronounced with worsening of motor signs. In PD, motor symptoms emerge only after a prolonged period of dompaminergic loss, on account of activity of adaptive or compensatory mechanisms.…”

The interindividual variability of transcranial magnetic stimulation effects: Implications for diagnostic use in movement disorders

“…Plasticity in atypical parkinsonism has also been tested using PAS and TBS protocols. There is one report of absent responses to PAS in MSA‐P patients both on and off l ‐dopa . In PSP, cTBS causes MEP facilitation instead of inhibition, and iTBS induces greater MEP facilitation when compared with healthy individuals .…”

“…There is one report of absent responses to PAS in MSA-P patients both on and off L-dopa. 89 In PSP, cTBS causes MEP facilitation instead of inhibition, 70 and iTBS induces greater MEP facilitation when compared with healthy individuals. 70 It has been suggested that the latter might result from the loss of M1 inhibitory interneurons.…”

Neurophysiological correlates of bradykinesia in Parkinson’s disease

“…Neurophysiological studies in humans using transcranial magnetic stimulation (TMS) have revealed changes in resting measures of excitability and plasticity in M1. There is enhanced corticospinal excitability and reduced M1 inhibition (Cantello et al, 2002;Currà et al, 2002;Lefaucheur et al, 2005;Berardelli et al, 2008;Bologna et al, 2016b), together with reduced long-term potentiation (LTP)-like plasticity in M1 (Morgante et al, 2006;Ueki et al, 2006;Schwingenschuh et al, 2010;Suppa et al, 2011;Kojovic et al, 2012 andKawashima et al, 2013;Kishore et al, 2017).…”