Brain Advance Access published online on January 9, 2009
Brain, doi:10.1093/brain/awn339
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Structural changes in the somatosensory system correlate with tic severity in Gilles de la Tourette syndrome
1 Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg 2 Department of Neurology, Christian-Albrechts-University Kiel 3 Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg 4 Department of Neurology, MEG Laboratory, Düsseldorf University Hospital, Düsseldorf 5 Department of Clinical Neuroscience and Medical Psychology, Heinrich-Heine-University, Düsseldorf 6 Clinic of Psychiatry, Socialpsychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany
Correspondence to:
Dr Götz Thomalla, Department of Neurology, University Medial Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany E-mail: thomalla{at}uke.uni-hamburg.de
Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder characterized by multiple motor and vocal tics. Previous structural MRI studies have identified regional abnormalities in grey matter, especially in the basal ganglia. These findings are consistent with the assumption of alterations in cortico-striato-thalamo-cortical circuits and dopaminergic neurotransmission playing a major role in the pathophysiology of GTS. Additionally, recent imaging studies suggested an involvement of sensory-motor cortices in the pathophysiology of GTS. However, little is known about the role of white matter changes in GTS. In this study, we aimed to examine whether GTS is associated with abnormalities in white matter microstructure and whether these changes are correlated with tic severity. In a morphometric study based on diffusion tensor MRI of the whole brain, we compared brain tissue diffusion characteristics between 15 unmedicated adults with GTS without psychiatric co-morbidity and 15 healthy age- and sex-matched controls. We performed voxel-based morphometry (VBM) of regional fractional anisotropy (FA) values to identify regional differences in white matter microstructure between the groups. We also tested for a linear relationship between regional FA values and clinical scores of tic severity. Probabilistic fibre tracking was applied to characterize anatomical connectivity of those areas showing differences in regional FA. Compared with healthy controls, GTS patients showed bilateral FA increases in white matter underlying the post- and precentral gyrus, below the left supplementary motor area, and in the right ventro-postero-lateral part of the thalamus. The peak increase in FA was located below the left postcentral gyrus. Probabilistic tractography identified transcallosal and ipsilateral cerebello-thalamo-cortical pathways of the somatosensory system passing through this subcortical region. In patients, regional FA in this region showed an inverse linear relationship with tic severity. These findings demonstrate, for the first time, structural alterations in somatosensory pathways in GTS. Changes of water diffusion characteristics point towards reduced branching in somatosensory pathways in GTS patients. The negative correlation between higher regional FA values and fewer tics suggests that these alterations of white matter microstructure represent adaptive reorganization of somatosensory processing in GTS.
Key Words: Gilles de la Tourette Syndrome; tics; diffusion tensor imaging; fractional anisotropy; somatosensory system
Abbreviations:
ADHD, attention deficit hyperactivity disorder; BA, Brodmann area; CC, corpus callosum; CSF, corticospinal fluid; DCI, diagnostic confidence index; DTI, diffusion tensor imaging; DSM-IV-TR, Text Revision of the Diagnostic and Statistical Manual of Mental Disorders 4th edition; EPI, echo planar imaging; FA, fractional anisotropy; FDR, False Discovery Rate; FLAIR, fluid attenuation inversion recovery; FMRIB, Oxford Centre for Functional MRI of the Brain; FLIRT, FMRIBs Linear Image Registration Tool; FSL, FMRIB Software Library; FWHM, full width at half maximum; GTS, Gilles de la Tourette syndrome; 
1, first eigenvalue; 2, second eigenvalue; 3, third eigenvalue; MNI, Montreal Neurological Institute; MRI, magnetic resonance imaging; MD, mean diffusivity; MRVS, Modified Rush Video Scale; OCD, obsessive-compulsive disorder; SPM, Statistical Parametric Mapping; TE, echo time; TI, inversion time; TR, repetition time; VBM, voxel-based morphometry; VL, ventral lateral thalamus; VOI, volume of interest; VPL, ventral posterolateral thalamus; YGTSS, Yale Global Tic Severity Scale
Received September 9, 2008. Revised November 5, 2008. Accepted November 10, 2008.