Enlargement of Thalamic Nuclei in Tourette Syndrome

Anatomical and functional disturbances in corticostriatothalamocortical (CSTC) circuits are thought to contribute to the pathogenesis of Tourette syndrome (TS). Previous imaging studies have suggested the presence of hypoplasia in motor portions of these loops, particularly in the caudate nucleus1,2 and in inferior portions of sensory, motor, and premotor cortices.3 Enlargement in other portions of CSTC circuits, including the frontal and parietal cortices, the hippocampus, and their associated commissural pathways,4–6 are thought to compensate for disturbances in motor pathways and thereby reduce the severity of tic symptoms in persons with TS. The thalamus is an integral component of the CSTC circuits that are involved in the genesis of tic symptoms and their associated compensatory responses. A previous functional magnetic resonance imaging study demonstrated activation of the thalamus, together with the basal ganglia and frontal and parietal cortices, during the willful suppression of tic symptoms.7 The change in activity of the thalamus correlated with the change inactivity of basal ganglia nuclei, suggesting that a coordinated effort between the thalamus and basal ganglia (defined as the striatum, globus pallidus, substantia nigra, and subthalamic nucleus)8 is required to suppress tics. In addition, inducing lesions in or stimulating thalamic subregions may attenuate tics,9,10 whereas space-occupying lesions of the thalamus seem to exacerbate them.11 These and other findings have prompted some to hypothesize that dysregulation of thalamocortical activity may generate tic behaviors.12 Several preliminary anatomical studies have yielded contradictory findings for overall thalamic volume. One reported an increased size of the left hemithalamus in 18 treatment-naive boys with TS.13 Another in which treatment history was unspecified found decreased thalamic volumes in 23 children with TS.14 A third study detected no morphological differences in the thalamus of 15 neuroleptic-naive adults.15 The small numbers of participants, their differing histories of medication use, the differing age and sex compositions of the samples, and the markedly differing image-processing techniques across these studies renders a coherent interpretation of their findings impossible. A large-scale study is needed to clarify the effects of TS on thalamic morphology. We assessed overall thalamic volumes and localized morphological features over individual thalamic subregions in a large sample of children and adults to improve our understanding of the role of the thalamus in the pathophysiological processes of TS. We hypothesized that the volumes of the thalamus and its subregions would differ between diagnostic groups.