dc.contributor.author
Kübler, Dorothee
dc.contributor.author
Schroll, Henning
dc.contributor.author
Hamker, Fred H.
dc.contributor.author
Joutsa, Juho
dc.contributor.author
Buchert, Ralph
dc.contributor.author
Kühn, Andrea A.
dc.date.accessioned
2021-08-12T09:23:50Z
dc.date.available
2021-08-12T09:23:50Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/31486
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-31218
dc.description.abstract
Introduction: Motor but also non-motor effects are modulated by dopamine (DA) in Parkinson's disease (PD). Impaired inhibition has been related to dopamine overdosing of the associative striatum. We compared effects of dopaminergic medication on inhibitory control in patients with young (age at onset <50 years, YOPD) and late onset PD (LOPD) and related them to nigrostriatal degeneration.
Methods: 27 patients (10 YOPD, 17 LOPD) underwent a Go/NoGo paradigm comprising a global and specific NoGo condition ON and OFF DA. The ratio of dopamine transporter availability (DAT) in the associative relative to the sensorimotor striatum according to [123I]FP-CIT SPECT was compared between YOPD and LOPD (n = 8/12). Neuro-computational modeling was used to identify pathway activation during Go/NoGo performance.
Results: Patients made more errors ON compared to OFF in the global NoGo. This DA effect on global NoGo errors correlated with disease duration (r = 0.489, p = 0.010). YOPD made more errors in the specific NoGo ON-OFF compared to LOPD (p = 0.015). YOPD showed higher associative-to-sensorimotor DAT ratios compared to LOPD (p < 0.001). Neuro-computational modeling revealed DA overdosing of the associative striatum in YOPD resulting in excess activation of the direct basal ganglia pathway triggering incorrect responses.
Conclusions: Depending on the age of symptom onset, DA differentially modulated inhibition in PD with detrimental effects on specific NoGo performance in YOPD but increased performance in LOPD. YOPD showed relatively less degeneration in the associative striatum suggesting DA overdosing that is supported by our neuro-computational model. Reduced inhibition in the global NoGo condition suggests different pathway activation.
en
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
Dopamine overdose hypothesis
en
dc.subject
FP-CIT SPECT
en
dc.subject
Young and late onset Parkinson's disease
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
The effect of dopamine on response inhibition in Parkinson's disease relates to age-dependent patterns of nigrostriatal degeneration
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1016/j.parkreldis.2019.02.003
dcterms.bibliographicCitation.journaltitle
Parkinsonism & Related Disorders
dcterms.bibliographicCitation.originalpublishername
Elsevier
dcterms.bibliographicCitation.pagestart
185
dcterms.bibliographicCitation.pageend
190
dcterms.bibliographicCitation.volume
63
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.note.author
Original article first published: 2019-02-05.
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
30765262
dcterms.isPartOf.eissn
1873-5126