Brain Advance Access originally published online on December 3, 2007
Brain 2008 131(1):165-179; doi:10.1093/brain/awm278
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Neural correlates of tic severity and cognitive control in children with Tourette syndrome
1Center for Mind and Brain, 2Department of Psychiatry and Behavioral Sciences, 3MIND Institute, University of California at Davis, 4Department of Psychology, University of Illinois at Urbana-Champaign, 5Helen Wills Neuroscience Institute and 6Department of Psychology, University of California at Berkeley, USA
Correspondence to: Silvia A. Bunge, PhD, Department of Psychology &, Helen Wills Neuroscience Institute, University of California, Berkeley, 132 Barker Hall, Berkeley, CA 94720-3190, USA E-mail: sbunge{at}berkeley.edu
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.
Key Words: frontal; striatal; paediatric; brain imaging; disorder
Abbreviations: ADHD, attention deficit disorder; fMRI, functional magnetic resonance imaging; OCD, obsessive-compulsive disorder; PFC, prefrontal cortex; TS, Tourette syndrome
.
Received June 29, 2007. Revised September 20, 2007. Accepted October 5, 2007.
*These authors contributed equally to this work.