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Publication year
2015Author(s)
Number of pages
8 p.
Source
Neurology, 84, 4, (2015), pp. 399-406ISSN
Publication type
Article / Letter to editor

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Organization
Neurology
PI Group Systems Neurology
SW OZ DCC CO
PI Group Intention and Action
Journal title
Neurology
Volume
vol. 84
Issue
iss. 4
Languages used
English (eng)
Page start
p. 399
Page end
p. 406
Subject
111 000 Intention & Action; Action, intention, and motor control; DI-BCB_DCC_Theme 2: Perception, Action and Control; Radboudumc 3: Disorders of movement DCMN: Donders Center for Medical NeuroscienceAbstract
OBJECTIVE: We investigated system-level corticostriatal changes in a human model of premotor Parkinson disease (PD), i.e., healthy carriers of the G2019S LRRK2 mutation that is associated with a markedly increased, age-dependent risk of developing PD. METHODS: We compared 37 asymptomatic LRRK2 G2019S mutation carriers (age range 30-78 years) with 32 matched, asymptomatic nonmutation carriers (age range 30-74 years). Using fMRI, we tested the hypothesis that corticostriatal connectivity in premotor PD shifts from severely affected to less affected striatal subregions, as shown previously in symptomatic PD. Specifically, we predicted that in premotor PD, the shift in corticostriatal connectivity would follow the same gradient of striatal dopamine depletion known from overt PD, with the dorsoposterior putamen being more affected than the ventroanterior putamen. RESULTS: The known parallel topology of corticostriatal loops was preserved in each group, but the topography of putamen connectivity shifted. In LRRK2 G2019S mutation carriers, the right inferior parietal cortex had reduced functional connectivity with the dorsoposterior putamen but increased connectivity with the ventroanterior putamen, as compared with noncarriers. This shift in functional connectivity increased with age in LRRK2 G2019S mutation carriers. CONCLUSIONS: Asymptomatic LRRK2 G2019S mutation carriers show a reorganization of corticostriatal circuits that mirrors findings in idiopathic PD. These changes may reflect premotor basal ganglia dysfunction or circuit-level compensatory changes.
This item appears in the following Collection(s)
- Academic publications [203856]
- Donders Centre for Cognitive Neuroimaging [3391]
- Electronic publications [102287]
- Faculty of Medical Sciences [80326]
- Faculty of Social Sciences [27309]
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