
Am J Psychiatry 164:955-966, June 2007
doi: 10.1176/appi.ajp.164.6.955
© 2007 American Psychiatric Association
A Developmental fMRI Study of Self-Regulatory Control in Tourettes Syndrome
Rachel Marsh, Ph.D.,
Hongtu Zhu, Ph.D.,
Zhishun Wang, Ph.D.,
Pawel Skudlarski, Ph.D., and
Bradley S. Peterson, M.D.
OBJECTIVE: Disturbances in the maturation of neural systems that mediate self-regulatory processes may contribute to the development of Tourettes syndrome by releasing motor and vocal tics from regulatory control. The purpose of this study was to examine the age correlates of functional activity in neural circuits that subserve self-regulatory control in children and adults with Tourettes syndrome. METHOD: The participants were 136 children and adults, which included 66 Tourettes syndrome patients and 70 healthy comparison subjects. During performance of the Stroop interference task, the authors compared the functional magnetic resonance imaging (fMRI) blood-oxygen-level dependent response in patients with Tourettes syndrome with that of healthy comparison subjects. General linear modeling of Stroop-related activations was used to compare the differential effects of age and behavioral performance on changes in self-regulatory control between the two diagnostic groups. RESULTS: Although the correlations of age with behavioral performance on the Stroop task were similar between patients with Tourettes syndrome and healthy comparison subjects, the two groups differed significantly in their correlations of age with the magnitude of regional brain activation during the task. Interactions of age with diagnosis were detected in the ventral prefrontal (Brodmanns areas 10 and 24) and posterior cingulate cortices (Brodmanns area 31), and post hoc analyses indicated that subjects with Tourettes syndrome deactivated these regions less with advancing age. Greater activation of bilateral frontostriatal regions (Brodmanns areas 9/46, 45/46; lenticular nucleus; and thalamus) accompanied poorer performance in the patient group, whichin the presence of normal behavioral performance on the Stroop tasksuggests that greater activation of the frontostriatal systems helps to maintain task performance in individuals with Tourettes syndrome. CONCLUSIONS: Normative developmental correlates of activity in frontostriatal circuits that subserve self-regulatory control are disturbed in persons with Tourettes syndrome. These aberrant developmental correlates are likely a consequence of greater anatomical and functional disturbances in these circuits in adults with Tourettes syndrome, which leads to impaired regulation of tic behaviors. Reduced default-mode processing in ventral prefrontal and posterior cingulate cortices in adults with Tourettes syndrome suggests the presence of greater difficulty in engaging mental processes that become active when freed from the demands of more challenging cognitive tasks. However, individuals with Tourettes syndrome appear to co-opt normal developmental processes in circuits that subserve age-related improvement in self-regulatory control while presumably struggling to maintain adequate task performance.
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