Background: Myoclonus-dystonia (MD) is a movement disorder characterized by myoclonic jerks, dystonic postures and psychiatric co-morbidity. A mutation in the DYT11 gene underlies half of MD cases. We hypothesize that MD results from a dysfunctional basal ganglia network causing insufficient inhibitory motor control. To test this hypothesis functional MRI (fMRI) was performed using a validated "Go/No go" task, in order to localize blood-oxygen-level dependence (BOLD) effects corresponding to Response Inhibition (RI).
Methods: Twenty-four MD patients (fifteen DYT11 positive) and 24 matched controls responded with a button press to Go (Go-Response) or No go (referred to as 'Stop') cues, resulting in analyses of accurate response suppression to Stop cues (Stop-Inhibit), and incorrect responses to Go cues (Go-Inhibit), or to Stop cues (Stop-Response).
Results: Response accuracy in patients was impaired due to frequent Go-Inhibit errors. Image analysis of the Stop-Inhibit contrast demonstrated frontal, caudate and cingular activity in both groups. Compared to controls, MD patients showed increased primary motor cortex and insular activation. During Go-Inhibit trials, patients revealed increased activity in the contralateral thalamus (ventral lateral nucleus) and dorso-lateral-prefrontal cortex. In a post-hoc analysis comparing MD patients, DYT11 positive patients demonstrated anterior cerebellum hyperactivation on all contrasts and increased putaminal activation in the Stop-Response contrast.
Conclusions: This study demonstrates a distinct association of motor symptoms in MD with the ventral lateral nucleus of the thalamus. Cerebellar dysfunction distinguishes DYT11 positive from negative patients. We suggest that MD might be best considered as a disorder of the cortico-ponto-cerebello-thalamo-cortical system.
Keywords: Dystonia; Executive functioning; Functional MRI; Myoclonus; Response inhibition.
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