
Am J Psychiatry 161:2028-2037, November 2004
© 2004 American Psychiatric Association
Altered Interhemispheric Connectivity in Individuals With Tourettes Disorder
Kerstin J. Plessen, M.D.,
Tore Wentzel-Larsen, M.Sc.,
Kenneth Hugdahl, Ph.D.,
Patricia Feineigle, Ph.D.,
Joel Klein, M.D.,
Lawrence H. Staib, Ph.D.,
James F. Leckman, M.D.,
Ravi Bansal, Ph.D., and
Bradley S. Peterson, M.D.
OBJECTIVE: The corpus callosum is the major commissure connecting the cerebral hemispheres. Prior evidence suggests involvement of the corpus callosum in the pathophysiology of Tourettes disorder. The authors assessed corpus callosum size and anatomical connectivity across the cerebral hemispheres in persons with Tourettes disorder. METHOD: The size of the corpus callosum was determined on the true midsagittal slices of reformatted, high-resolution magnetic resonance imaging scans and compared across groups in a cross-sectional case-control study of 158 subjects with Tourettes disorder and 121 healthy comparison subjects, ages 565 years. RESULTS: In the context of increasing midsagittal corpus callosum area from childhood to age 30 years, children with Tourettes disorder had smaller overall corpus callosum size, whereas adults with Tourettes disorder on average had larger corpus callosum size, yielding a prominent interaction of diagnosis with age. Corpus callosum size correlated positively with tic severity. Corpus callosum size also correlated inversely with dorsolateral prefrontal and orbitofrontal cortical volumes in both the subjects with Tourettes disorder and the comparison subjects, but the magnitudes of the correlations were significantly greater in the group with Tourettes disorder. The effects of medication and comorbid illnesses had no appreciable influence on the findings. CONCLUSIONS: Given prior evidence for the role of prefrontal hypertrophy in the regulation of tic symptoms, the current findings suggest that neural plasticity may contribute to smaller corpus callosum size in persons with Tourettes disorder, which thereby limits neuronal trafficking across the cerebral hemispheres and reduces input to cortical inhibitory interneurons within the prefrontal cortices. Reduced inhibitory input may in turn enhance prefrontal excitation, thus helping to control tics and possibly contributing to the cortical hyperexcitatibility reported previously in patients with Tourettes disorder.
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