Functional changes in the activity of cerebellum and frontostriatal regions during externally and internally timed movement in Parkinson's disease

We used fMRI to investigate the neurofunctional basis of externally and internally timed movements in Parkinson's disease (PD) patients. Ten PD patients whose medication had been withheld for at least 18 h and 11 age- and sex-matched healthy controls were scanned while performing continuation paradigm with a visual metronome. Compared with the controls, PD, patients displayed an intact capability to store and reproduce movement frequencies but with a significantly increased movement latencies. No differences in BOLD response were found in both groups when comparing the continuation with the preceding synchronization phase and viceversa, except for activity in visually related regions. Relative to healthy controls during the synchronization phase, PD patients exhibited an overall signal increase in the cerebellum and frontostriatal circuit (putamen, SMA and thalamus) activity together with specific brain areas (right inferior frontal gyrus and insula cortex) that are also implicated in primary timekeeper processes. By contrast, in the continuation phase the only neural network involved to a greater extent by the PD group was the cerebello-thalamic pathway. The lack of neurofunctional differences between the two timing phases suggests that rhythmic externally and internally guided movements engage similar neural networks in PD and matched healthy controls. Moreover, between-group comparison indicates that PD, patients OFF medication may compensate for their basal ganglia-cortical loop's dysfunction using different motor pathways involving cerebellum and basal ganglia relays during the two phases of rhythmic movement. (c) 2006 Elsevier Inc. All rights reserved.