Brain Advance Access originally published online on June 9, 2005
Brain 2005 128(10):2281-2290; doi:10.1093/brain/awh572
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Motor reorganization in asymptomatic carriers of a single mutant Parkin allele: a human model for presymptomatic parkinsonism
1 NeuroImage-Nord, Hamburg-Kiel-Lübeck, Germany, 2 Department of Neurology, University Hospital Hamburg-Eppendorf, Hamburg, Germany, 3 Department of Neurology, University of Lübeck, Lübeck, Germany, 4 Department of Neurology, Christian-Albrechts-University, Kiel, Germany and 5 Department of Neurology, Central Hospital and Department of Medical Genetics, Eurac Research, Bolzano/Bozen, Italy
Correspondence to: Hartwig Siebner, MD, Department of Neurology, Christian-Albrechts University, Schittenhelmstrasse 10, 24105 Kiel, Germany E-mail: h.siebner{at}neurologie.uni-kiel.de
Mutations in the Parkin gene are the most common known single cause of early-onset parkinsonism. It has been shown that asymptomatic carriers with a single mutant allele have latent presynaptic dopaminergic dysfunction in the striatum. Here we used functional MRI to map movement-related neuronal activity during internally selected or externally determined finger movements in 12 asymptomatic carriers of a Parkin mutation and 12 healthy non-carriers. Mean response times were 63 ms shorter during internally selected movements than during externally guided movements (P = 0.003). There were no differences in mean response times between groups (P > 0.2). Compared with externally determined movements, the internal selection of movements led to a stronger activation of rostral motor areas, including the rostral cingulate motor area (rCMA), rostral supplementary motor area, medial and dorsolateral prefrontal cortices. The genotype had a significant impact on movement-related activation patterns. Asymptomatic carriers showed a stronger increase in movement-related activity in the right rCMA and left dorsal premotor cortex, but only if movements relied on internal cues. In addition, synaptic activity in the rCMA had a stronger influence on activity in the basal ganglia in the context of internally selected movements in asymptomatic carriers relative to non-carriers. We infer that this reorganization of striatocortical motor loops reflects a compensatory effort to overcome latent nigrostriatal dysfunction.
Key Words: functional magnetic resonance imaging; motor reorganization; Parkin gene; Parkinson's disease; presymptomatic parkinsonism
Abbreviations: ANOVA = analysis of variance; BOLD = blood oxygen level-dependent; 18F-DOPA = 18F-fluorodopa; MPTP = N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; PET = positron emission tomography; PMd = dorsal premotor cortex; PPI = psycho-physiological interaction; rCMA = rostral cingulate motor area; SMA = supplementary motor area; SPMt = statistical parametric t-map; SVC = small volume correction
Received March 19, 2005. Revised May 17, 2005. Accepted May 19, 2005.
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