Motor reorganization in asymptomatic carriers of a single mutant Parkin allele: a human model for presymptomatic parkinsonism.
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.
Buhmann
C
C
NeuroImage-Nord, Hamburg-Kiel-Lübeck, Germany.
Binkofski
F
F
Klein
C
C
Büchel
C
C
van Eimeren
T
T
Erdmann
C
C
Hedrich
K
K
Kasten
M
M
Hagenah
J
J
Deuschl
G
G
Pramstaller
P P
PP
Siebner
H R
HR
D000328:Adult; D017668:Age of Onset; D000483:Alleles; D005260:Female; D005385:Fingers; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008957:Models, Genetic; D009044:Motor Cortex / Q000473:pathology* / Q000503:physiopathology; D009068:Movement / Q000502:physiology; D009154:Mutation; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000473:pathology / Q000503:physiopathology; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D044767:Ubiquitin-Protein Ligases; C111567:parkin protein