The motor inhibition system in Parkinson's disease with levodopa-induced dyskinesias

Abstract

Background: Parkinson's disease is primarily a disorder of response initiation characterized by an excessive motor inhibition, whereas levodopa-induced dyskinesias are clearly a clinical expression of disinhibition of movements.

Objective: That levodopa-induced dyskinesias are linked to dysfunctions of inhibitory brain network has recently been proposed, but no investigation of behavioral performance during action inhibition task in these patients has been published.

Methods: Twenty-four Parkinson's disease patients with or without levodopa-induced dyskinesias tested on or off their medications underwent functional magnetic resonance imaging investigation during the execution of a stop-signal inhibition task. In particular, we were interested in evaluating the neural correlates of stop-related conditions: StopInhibit task (in which patients had to successfully inhibit their responses) and StopRespond task (Stop trials with erroneous button press). Both tasks were compared against Go trials.

Results: Levodopa intake in dyskinetic patients tended to worsen inhibitory control during the StopInhibit task, while significantly affecting the ability to monitor motor responses when patients failed to stop (StopRespond task). Functional analysis showed that, during the StopInhibit task, dyskinetic patients were characterized by decreased activity of the right inferior frontal cortex after levodopa intake, whereas patients without dyskinesias showed a reverse effect. A similar group × levodopa interaction effect was detected in the medial frontal cortex during the execution of the StopRespond task, in which dyskinetic patients showed increased activity after dopaminergic therapy

Conclusions: Our study demonstrated that levodopa intake in dyskinetic patients tends to alter the functioning of some parts of the neural network involved in motor inhibition.

Keywords: inferior frontal cortex; levodopa-induced dyskinesias; medial frontal cortex; motor inhibition; stop-signal reaction time.