Precursors of Parkinsonistic Impairment in Making Distinct Decisions: An Event-Related Brain Potential Study in Asymptomatic Carriers of Parkin and PINK1 Mutations and in Patients with Idiopathic Parkinson's Disease

Abstract

Patients affected with Parkinson's disease (PD) are more distracted than healthy persons by irrelevant flanking stimuli in speeded choice-response tasks. This presumed hyperexcitability of the pre-motor cortex might be related to the frontal-lobe-type syndrome occurring in this disease. Here we investigated whether this sign, or alternatively some mechanism of compensation, might be at play in middle-aged carriers of Parkin and PINK1 mutations which mutations may increase susceptibility to develop parkinsonism. Mutation carriers were compared to family members without the mutation, and to patients with idiopathic PD and their age-matched controls. In contrast to the diseased patients, the mutation carriers were less affected by flanking stimuli, both in their overt behavior and in their motor-cortex activation, as measured by the lateralized readiness potential. The frontal N2 component of the event-related potential, indicating executive control, tended to be dimini-shed both in diseased patients and in mutation carriers. Thus, middle-aged carriers of heterozygous mutations that may be associated with parkinsonism already tended to have a Parkinson-like deficit in the mechanisms of cognitive control but possibly compensated for behavioral-relevant effects of this deficit by some other mechanism, resulting in overcompensation of parkinsonistic hypersensitivity of the motor system to irrelevant stimulation.