Objective: Investigating heterozygous Parkin gene (PRKN) mutation carriers to evaluate the potential association of this mutation with an alteration of cognitive control processes.

Background: Recessively inherited biallelic mutations in the PRKN gene lead to monogenic Parkinson’s disease (PD). Heterozygous mutations have been associated with subtle Parkinsonian traits and are thus discussed as a risk factor for the development of PD, albeit with very reduced penetrance. Alterations in the dopaminergic system [1], amongst other factors, may compromise cognitive control functions in asymptomatic heterozygous carriers (P+) compared to non-mutation carriers (P-).

Method: 100 individuals were recruited from the Cooperative Health Research in South Tyrol (CHRIS) study [2], a long-term population study in northern Italy, as part of the PAREGEN2 sub-study. 26 P+ and 31 P- were included in the present analysis. EEG was recorded while performing a stop-signal reaction time task. Investigator and participant were blind to the participant’s genetic status. Mean amplitudes of the ERPs time locked to correct and incorrect choice reactions and to non-inhibited responses to the stop signal were analyzed.

Results: Time-locking ERPs to incorrect choice reactions revealed an increased amplitude for the error-related negativity (ERN) in P+ compared to P- at fronto-central electrode sites. There were no ERN group differences in non-inhibited responses to the stop signal. In both groups, expected amplitude latency differences between non-inhibited fast and slow responses to the stop signal could be shown, without significant differences between groups. The analysis of stop signal reaction times, reaction times to the flanker stimulus and error rates showed no group differences.

Conclusion: Response-locked ERPs indicate a difference in the neural functionality of cognitive control processes in P+. This can be interpreted as a potential alteration of the dopaminergic system in cognitive control processes. Our study thus provides further evidence for an impact of heterozygous Parkin mutations on brain function.

References: [1] Song P, Peng W, Sauve V, et al. Parkinson’s disease-linked parkin mutation disrupts recycling of synaptic vesicles in human dopaminergic neurons. Neuron. 2023;111(23):3775-3788.e7. doi:10.1016/j.neuron.2023.08.018
[2] Pattaro C, Gögele M, Mascalzoni D, et al. The Cooperative Health Research in South Tyrol (CHRIS) study: rationale, objectives, and preliminary results. J Transl Med. 2015;13:348. doi:10.1186/s12967-015-0704-9

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MDS Abstracts - https://www.mdsabstracts.org/abstract/alterations-in-neural-processes-of-cognitive-control-in-asymptomatic-heterozygous-mutation-carriers-in-the-parkin-gene/