Objective: Investigating non-manifesting carriers (NMC) of the TAF1 gene mutation causing X-linked dystonia-parkinsonism to reveal a potential change in the neural basis of cognitive control processes during the prodromal phase of the disease.

Background: XDP is a rare X-linked recessive degenerative movement disorder characterized by rapidly progressive adult-onset dystonia affecting Filipino men. Postmortem analyses and structural imaging point to degenerative processes affecting the basal ganglia with the striosomal compartment being most prominently involved in the early phase. The functional consequences of these neurodegenerative processes are described by recent EEG studies showing event-related potential (ERP) components to be associated with cognitive control and the detection of action errors. In the present study we are investigating a potential impairment of cognitive control processes and related neural underpinnings in the prodromal phase.

Method: Ten male NMC and 23 matched controls negative for the disease-causing mutation (HC) were investigated. Participants performed a stop signal reaction time task while EEG was recorded. The 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: While no significant differences were found at the fronto-central electrodes for the choice errors, TAF1 NMCs showed a significant amplitude decrease for the error-related negativity (ERN) associated to late inhibition errors (Asymptotic General Independence Test, Z=-2.01, p=0.045). NMCs also revealed an increased negativity to correct choice (CRN, Z=2.99, p=0.003) responses at Fz/Cz. In contrast to the ERP findings, no group differences were found in reaction times, error rates or the stop signal reaction time.

Conclusion: EEG recordings indicate a decline of cognitive control functions in the prodromal phase of TAF1 NMCs. This finding demonstrates that cognitive consequences are already present before the first motor symptoms occur indicating structural changes in the basal ganglia in the prodromal disease phase, as already described recently [1].

References: [1] Hanssen, Henrike et al. “Basal Ganglia Atrophy as a Marker for Prodromal X-Linked Dystonia-Parkinsonism.” Annals of neurology, 10.1002/ana.26606. 16 Jan. 2023, doi:10.1002/ana.26606

« Back to 2023 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/altered-cognitive-control-processes-in-the-prodromal-phase-of-x-linked-dystonia-parkinsonism-xdp/