Responsiveness to distracting stimuli, though increased in Parkinson's disease, is decreased in asymptomatic PINK1 and Parkin mutation carriers

Rolf Verleger*, Johann Hagenah, Manuel Weiß, Thomas Ewers, Ilse Heberlein, Peter P. Pramstaller, Hartwig R. Siebner, Christine Klein

*Corresponding author for this work
14 Citations (Scopus)

Abstract

Patients with Parkinson's disease (PD) are more sensitive than healthy controls to response-triggering by irrelevant flanking stimuli in speeded choice-response tasks. This increased responsiveness may either indicate a lack of executive control or reflect compensatory efforts to cope with the reduced internal motor drive. Of interest in this context is whether responsiveness is already enhanced in the presymptomatic stage of PD. To address these questions, we studied a group of non-manifesting carriers of heterozygous Parkin and PINK1 mutations while they performed a choice-response task with response-compatible or incompatible flankers. These mutation carriers may be considered a model for pre-clinical PD because the mutant allele leads to a latent nigrostriatal dysfunction and may increase the risk for PD. For comparison, we studied groups of medicated patients with idiopathic PD and of healthy persons age-matched to the mutation carriers and to the patients. Measurements of reaction time, error rate, and the lateralized readiness potential of the EEG provided converging evidence that the mutation carriers were less responsive to distracting flankers than their healthy control group. In contrast, PD patients were more distractible by flankers than their control group, which replicated previous results. Mutation carriers also showed a smaller N2 component of the event-related EEG potential in trials with incompatible flankers relative to their control group, which might indicate reduced inhibitory control. We hypothesize that faulty executive control is the primary deficit, reflected by the reduced N2 component in the mutation carriers. To compensate for this deficit, mutation carriers change their strategy of speed-accuracy trade-off, in order to dampen the excitability of their lateral motor system. Disease progression might prevent symptomatic PD patients from using this compensatory mechanism, leading to increased disinhibition of their lateral motor system.

Original languageEnglish
JournalNeuropsychologia
Volume48
Issue number2
Pages (from-to)467-476
Number of pages10
ISSN0028-3932
DOIs
Publication statusPublished - 01.01.2010

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