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Brain Advance Access originally published online on October 24, 2008
Brain 2009 132(1):225-238; doi:10.1093/brain/awn223
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© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Control networks in paediatric Tourette syndrome show immature and anomalous patterns of functional connectivity

Jessica A. Church1, Damien A. Fair1, Nico U. F. Dosenbach2, Alexander L. Cohen1, Francis M. Miezin1,2, Steven E. Petersen1,2,3,4 and Bradley L. Schlaggar1,2,3,5

1 Department of Neurology, School of Medicine, Washington University in St Louis, St Louis, MO, USA 2 Department of Radiology, School of Medicine, Washington University in St Louis, St Louis, MO, USA 3 Department of Anatomy Neurobiology, School of Medicine, Washington University in St Louis, St Louis, MO, USA 4 Department of Psychology, School of Medicine, Washington University in St Louis, St Louis, MO, USA 5 Department of Pediatrics, School of Medicine, Washington University in St Louis, St Louis, MO, USA

Correspondence to: Jessica A. Church, Department of Neurology, Box 8111, 4525 Scott Avenue, Washington University School of Medicine, St Louis, MS 63110, USA E-mail: jchurch{at}wustl.edu

Tourette syndrome (TS) is a developmental disorder characterized by unwanted, repetitive behaviours that manifest as stereotyped movements and vocalizations called ‘tics’. Operating under the hypothesis that the brain's control systems may be impaired in TS, we measured resting-state functional connectivity MRI (rs-fcMRI) between 39 previously defined putative control regions in 33 adolescents with TS. We were particularly interested in the effect of TS on two of the brain's task control networks—a fronto-parietal network likely involved in more rapid, adaptive online control, and a cingulo-opercular network apparently important for set-maintenance. To examine the relative maturity of connections in the Tourette subjects, functional connections that changed significantly over typical development were examined. Age curves were created for each functional connection charting correlation coefficients over age for 210 healthy people aged 7–31 years, and the TS group correlation coefficients were compared to these curves. Many of these connections were significantly less ‘mature’ than expected in the TS group. This immaturity was true not only for functional connections that grow stronger with age, but also for those that diminish in strength with age. To explore other differences between Tourette and typically developing subjects further, we performed a second analysis in which the TS group was directly compared to an age-matched, movement-matched group of typically developing, unaffected adolescents. A number of functional connections were found to differ between the two groups. For these identified connections, a large number of connectional differences were found where the TS group value was out of range compared to typical developmental age curves. These anomalous connections were primarily found in the fronto-parietal network, thought to be important for online adaptive control. These results suggest that in adolescents with TS, immature functional connectivity is widespread, with additional, more profound deviation of connectivity in regions related to adaptive online control.

Key Words: Tourette syndrome; functional connectivity; attentional control; adolescence; cognitive development

Abbreviations: ADHD, Attention deficit-hyperactivity disorder; BOLD, blood-oxygenation-level dependent; COIs, connections of interest; CSTC, cortico-striatal-thalamo-cortical; OCD, obsessive-compulsive disorder; ROI, region of interest; rs-fcMRI, resting-state functional connectivity MRI; TS, Tourette syndrome

Received April 9, 2008. Revised August 15, 2008. Accepted August 18, 2008.


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