The aim of the study was to determine whether abnormal connectivity of the fronto-striato-thalamic circuit underlies the morphological changes in subcortical structures of patients with Tourette syndrome and to correlate these changes with neurobehavioral measures. A total of 18 children with Tourette syndrome and 12 age-matched healthy controls underwent diffusion tensor magnetic resonance imaging. Tractography of the fronto-striato-thalamic circuit was achieved using probability distribution function of individual voxels. The Tourette syndrome group had significantly lower probability of connection between caudate nucleus and anterior-dorsolateral-frontal cortex on the left (P = .038). Obsessive-compulsive behavior was negatively associated with connectivity score of the left caudate and anterior dorsolateral frontal cortex (P = .01) and was positively associated with connectivity score for the subcallosal gyrus (P = .009) and for the lentiform nucleus (P = .008). The abnormal connectivity among components of the fronto-striato-thalamic circuit bilaterally (ie, seeds on the caudate and thalamus) in patients with Tourette syndrome provides direct evidence for the involvement of these circuits in the pathophysiology.
Leckman JF, Riddle MATourette's syndrome: when habit-forming systems form habits of their own? Neuron. 2000;28: 349-354.
2.
Rauch S., Whalen P., Curran T., et al. Probing striato-thalamic function in obsessive-compulsive disorder and Tourette syndrome using neuroimaging methods. Adv Neurol . 2001;85: 207-224.
3.
Peterson BS, Thomas P., Kane MJ, et al. Basal ganglia volumes in patients with Gilles de la Tourette syndrome. Arch Gen Psychiatry. 2003;60:415-424.
4.
Peterson BS, Staib L., Scahill L., et al. Regional brain and ventricular volumes in Tourette syndrome . Arch Gen Psychiatry. 2001;58:427-440.
5.
Fredericksen KA, Cutting LE, Kates WR, et al. Disproportionate increases of white matter in right frontal lobe in Tourette syndrome. Neurology . 2002;58:85-89.
6.
Ludolph AG, Juengling FD, Libal G., Ludolph AC, Fegert JM, Kassubek J.Grey-matter abnormalities in boys with Tourette syndrome: magnetic resonance imaging study using optimised voxel-based morphometry. Br J Psychiatry. 2006;188:484-485.
7.
Garraux G., Goldfine A., Bohlhalter S., Lerner A., Hanakawa T., Hallett M.Increased midbrain gray matter in Tourette's syndrome. Ann Neurol. 2006;59:381-385.
8.
Bloch MH, Leckman JF, Zhu H., Peterson BSCaudate volumes in childhood predict symptom severity in adults with Tourette syndrome. Neurology. 2005;65:1253-1258.
9.
Kates WR, Frederikse M., Mostofsky SH, et al. MRI parcellation of the frontal lobe in boys with attention deficit hyperactivity disorder or Tourette syndrome. Psychiatry Res. 2002;116:63-81.
10.
DeVito TJ, Drost DJ, Pavlosky W., et al. Brain magnetic resonance spectroscopy in Tourette's disorder. J Am Acad Child Adolesc Psychiatry . 2005;44:1301-1308.
11.
Peterson BS , Skudlarski P., Anderson AW, et al. A functional magnetic resonance imaging study of tic suppression in Tourette syndrome. Arch Gen Psychiatry . 1998;55:326-333.
12.
Singer HS, Reiss AL, Brown JE, et al. Volumetric MRI changes in basal ganglia of children with Tourette's syndrome. Neurology. 1993;43:950-956.
13.
Singer HSNeurobiology of Tourette syndrome. Neurol Clin. 1997;15:357-379.
14.
Behen M., Chugani HT, Juhász C., et al. Abnormal brain tryptophan metabolism and clinical correlates in Tourette syndrome. Mov Disord. 2007;22:2256-2262.
15.
Makki MI, Behen M., Bhatt A., Wilson B., Chugani HTMicrostructural abnormalities of striatum and thalamus in children with Tourette syndrome. Mov Disord. 2008;23:2349-2356.
16.
Behrens TEJ , Woolrich MW, Jenkinson M., et al. Characterization and propagation of uncertainty in diffusion-weighted MR imaging. Magn Reson Med . 2003;50:1077-1088.
17.
Ashburner J. , Neelin P., Collins DL, Evans A., Friston K.Incorporating prior knowledge into image registration . Neuroimage. 1997;6:344-352.
18.
Jones DK, Symms MR, Cercignani M., Howard RJThe effect of filter size on VBM analyses of DT-MRI data. Neuroimage. 2005;26:546-554.
19.
Friston KJ, Ashburner J., Frith CD, Poline JB, Heather JD, and Frackowiak RSJ . Spatial registration and normalization of images. Hum Brain Mapp. 1995;2:165-189.
20.
Worsley KJ, Marrett S., Neelin P., Vandal AC, Friston KJ, Evans ACA unified statistical approach for determining significant signals in images of cerebral activation. Hum Brain Mapp. 1996 ;4:58-73.
21.
Maguire EA, Gadian DG, Johnsrude IS, et al. Navigation-related structural change in the hippocampi of taxi drivers. Proc Natl Acad Sci U S A. 2000;97:4398-4403.
22.
Ashburner J. , Friston KJVoxel-based morphometry-the methods . Neuroimage. 2000;11:805-821.
23.
Good CD, Johnsrude IS, Ashburner J., Henson RN, Friston KJ, Frackowiak RSA voxel-based morphometric study of ageing in 465 normal adult human brains . Neuroimage. 2001;14(1 pt 1): 21-36.
24.
Wechsler D.Wechsler Intelligence Scale for Children-Fourth Edition. San Antonio, TX: Psycholgical Corporation;2003.
25.
DiSimoni F.The Token Test for Children Manual. Austin, TX : Pro Ed;1978.
26.
Semel E., Wiig E., Secord W.Clinical Evaluation of Language Fundamentals (CELF-4). San Antonio, TX: The Psychological Corporation; 2003.
27.
Sheslow D., Adams W.WRAML 2: Wide Range Assessment of Memory and Learning. Deleware, MD: Jastak Assessment Systems;2003.
28.
Wilkinson G.WRAT-3: Wide Range Achievement Test Administration Manual. Lutz, FL: Psychological Assessment Resources Inc; 2006.
29.
Gordon M.The Gordon Diagnostic System. DeWitt, NY: Gordon Systems;1983.
Reynolds C., Kamphaus R.Behavior Assessment System for Children (BASC). Circle Pines, MN: American Guidance Service; 1992.
32.
Gioia G., Isquith P., Guy S., Kenworthy L.Behavior Rating Inventory of Executive Function: BRIEF. Lutz, FL: Psychological Assessment Resources;2000.
33.
Leckman JF, Towbin KE, Ore SI, Cohen DJTourette Syndrome and Tic Disorders. New York, NY: Wiley; 1988.
34.
Scahill L., Riddle MA, McSwiggin-Hardin M., et al. Children's Yale-Brown Obsessive Compulsive Scale: reliability and validity. J Am Acad Child Adolesc Psychiatry. 1997;36:844-852.
35.
Mink JW. The basal ganglia: focused selection and inhibition of competing motor programs. Prog Neurobiol. 1996;50:381-425. 36. Harris K, Singer HS. Tic disorders: neural circuits, neurochemistry, and neuroimmunology. J Child Neurol. 2006;21:678-689. 37. Braun A, Stoetter B, Randolph C, et al. The functional neuroanatomy of Tourette's syndrome: an FDG-PET study. I. Regional changes in cerebral glucose metabolism differentiating patients and controls. Neuropsychopharmacology. 1993;9:277-291. 38. Braun A, Randolph C, Stoetter B, et al. The functional neuroanatomy of Tourette's syndrome: an FDG-PET study. II. Relationships between regional cerebral metabolism and associated behavioral and cognitive features of the illness. Neurpsychopharmacology. 1995;13:151-168.
36.
Singer HS, Minzer K.Neurobiology of Tourette's syndrome: concepts of neuroanatomic localization and neurochemical abnormalities. Brain Dev. 2003;25:S70-S84.
37.
Mink J.Neurobiology of basal ganglia and Tourette syndrome: basal ganglia circuits and thalamocortical outputs. Adv Neurol. 2006 ;99:89-98.
38.
Osmon DC, Smerz JMNeuropsychological evaluation in the diagnosis and treatment of Tourette's Syndrome. Behav Modif. 2005;29:746-783.
McGraw P., Liang L., Provenzale JMEvaluation of normal age-related changes in anisotropy during infancy and childhood as shown by diffusion tensor imaging . Am J Roentgenol. 2002;179: 1515-1522.
41.
Beaulieu C. , Allen P.Determinants of anisotropic water diffusion in nerves. Magn Reson Med. 1994;31:394-400.
42.
Gerard E., Peterson BSDevelopmental processes and brain imaging studies in Tourette syndrome . J Psychosom Res. 2003;55:13-22.
43.
Lee JS, Yoo SS, Cho SY, Ock SM, Lim MK, Panych LPAbnormal thalamic volume in treatment-naive boys with Tourette syndrome . Acta Psychiatr Scand. 2006;113:64-67.
