Neural correlates of tic severity and cognitive control in children with Tourette syndrome.
Tourette syndrome (TS) is a neurodevelopmental disorder characterized by involuntary motor and phonic tics. It is hypothesized that excess dopamine leads to an imbalance in the pathways through the basal ganglia, resulting in unchecked movements via thalamic disinhibition. It has been unclear whether TS is associated with cognitive control deficits as well as pure motor control deficits, or whether cognitive deficits are associated with the presence of comorbid conditions. Furthermore, little is known about the neural underpinnings of TS in childhood, prior to the long-term effects of medication on brain function. Here, children with TS and typically developing children performed a cognitive control task during event-related fMRI data acquisition. The study included 18 native English-speaking 7-13-year-old children with TS (M = 10.42; 15 males), and 19 healthy, age-matched native English-speaking volunteers (M = 10.33; 11 males). The task involved three separate manipulations of cognitive control. Behaviourally, higher tic severity was correlated with slower task performance on the most demanding task conditions. Neurally, higher tic severity was associated with enhanced activation of dopaminergic nuclei (substantia nigra/ventral tegmental area) and cortical, striatal and thalamic regions in the direct pathway. Heightened tic severity was also associated with greater engagement of the subthalamic nucleus area, suggestive of a compensatory mechanism. Overall, patients engaged left prefrontal cortex more strongly than typicals during task performance. These data suggest that children aged 7-13 unmedicated for TS exhibit increased activation in the direct pathway through the basal ganglia, as well as increased compensatory activation in prefrontal cortex and the subthalamic nucleus.
Center for Mind and Brain, University of California at Davis, USA.
C L
CL
Baym
B A
BA
Corbett
S B
SB
Wright
S A
SA
Bunge
D000293:Adolescent; D001479:Basal Ganglia / Q000503:physiopathology; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods; D002648:Child; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology; D003342:Corpus Striatum / Q000503:physiopathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009483:Neuropsychological Tests; D011597:Psychomotor Performance; D012720:Severity of Illness Index; D013378:Substantia Nigra / Q000503:physiopathology; D013788:Thalamus / Q000503:physiopathology; D005879:Tourette Syndrome / Q000503:physiopathology* / Q000523:psychology*; D017557:Ventral Tegmental Area / Q000503:physiopathology