Functional MRI study of response inhibition in myoclonus dystonia

• Published in: Experimental neurology Vol. 247; pp. 623 - 629
• Main Authors: van der Salm, Sandra M.A., van der Meer, Johan N., Nederveen, Aart J., Veltman, Dick J., van Rootselaar, Anne- Fleur, Tijssen, Marina A.J.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-09-2013; Elsevier
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Brain Mapping; Case-Control Studies; Cerebral Cortex - blood supply; Cerebral Cortex - pathology; Diseases of striated muscles. Neuromuscular diseases; Dystonia; Dystonic Disorders - genetics; Dystonic Disorders - pathology; Dystonic Disorders - physiopathology; Executive Function - physiology; Executive functioning; Female; Functional MRI; Humans; Image Processing, Computer-Assisted; Inhibition (Psychology); Linear Models; Magnetic Resonance Imaging; Male; Medical sciences; Middle Aged; Myoclonus; Neurology; Oxygen - blood; Response inhibition; Statistics, Nonparametric; Young Adult; Response inhibition; Functional MRI; Dystonia; Myoclonus; Executive functioning; Nervous system diseases; Nuclear magnetic resonance imaging; Involuntary movement; Cerebral disorder; Striated muscle disease; Central nervous system disease; Neurological disorder; Extrapyramidal syndrome
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2013.02.017

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).
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).
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.
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.
•Cognitive control of response inhibition is normal in myoclonus dystonia (MD).•Presence of motor symptoms causes specific RI errors in patients.•The thalamus (VLN) has a distinct association with MD motor symptoms.•DYT11 gene positive patients show consistent cerebellar hyperactivation.•MD presumably is a disorder of the cortico-ponto-cerebello-thalamo-cortical system.