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Brain Advance Access published online on June 9, 2005
Brain, doi:10.1093/brain/awh572
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© The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received March 19, 2005
Revised May 17, 2005
Accepted May 19, 2005

Article

Motor reorganization in asymptomatic carriers of a single mutant Parkin allele: a human model for presymptomatic parkinsonism

C. Buhmann 1, F. Binkofski 2, C. Klein 3, C. Büchel 1, T. van Eimeren 1, C. Erdmann 3, K. Hedrich 3, M. Kasten 3, J. Hagenah 3, G. Deuschl 4, P. P. Pramstaller 5, and H. R. Siebner 6*

1 NeuroImage-Nord, Hamburg-Kiel-Lübeck, Germany; Department of Neurology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
2 NeuroImage-Nord, Hamburg-Kiel-Lübeck, Germany; Department of Neurology, University of Lübeck, Lübeck, Germany
3 Department of Neurology, University of Lübeck, Lübeck, Germany
4 Department of Neurology, Christian-Albrechts-University, Kiel, Germany
5 Department of Neurology, Central Hospital and Department of Medical Genetics, Eurac Research, Bolzano/Bozen, Italy
6 NeuroImage-Nord, Hamburg-Kiel-Lübeck, Germany; Department of Neurology, Christian-Albrechts-University, Kiel, Germany

* To whom correspondence should be addressed.
H. R. Siebner, E-mail: h.siebner{at}neurologie.uni-kiel.de


  Abstract

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.

Keywords: functional magnetic resonance imaging; motor reorganization; Parkin gene; Parkinson's disease; presymptomatic parkinsonism.
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