Brain Topography

, Volume 22, Issue 3, pp 176–184 | Cite as

Thinning of the Motor–Cingulate–Insular Cortices in Siblings Concordant for Tourette Syndrome

  • Cherine Fahim
  • Uicheul Yoon
  • Paul Sandor
  • Kirk Frey
  • Alan C. Evans
Original Paper

Abstract

Fraternal twin studies on normal subjects have demonstrated low heritability (intra-class correlation coefficient) estimates for frontal brain regions (r = 0.43). Here we aimed to investigate the relatedness/similarity estimates of the frontal brain regions in fraternal subjects concordant for Tourette syndrome (TS). We sought to identify regional brain similarities between siblings concordant for TS as an exploratory step towards the identification of potential brain structures involved in the TS phenotype. The identified brain structures may then serve in subsequent molecular genetic and linkage studies. In addition, we regressed cortical thickness and TS clinical severity scores to assess the relation between TS clinical symptoms and cortical structures. Sixteen sibling pairs concordant for TS were scanned using a 1.5 T magnetic resonance imaging scanner (age range 10–25, mean 17.19 ± 4.1). Brain morphology was assessed using the fully automated Civet pipeline at the Montreal Neurological Institute. TS was assessed using the Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Yale Global Tic Severity Scale (YGTSS) and the Goetz Tic Scale. We report high relatedness/similarity estimates for fraternal siblings concordant for TS (r = 0.86–0.60) in the middle frontal-motor/cingulate/insular cortices. Regression analysis revealed significant negative correlations in the right insula with the YGTSS (r = −0.41, F = 6.09, P < 0.02) and the left cingulated cortex with the (CY-BOCS) (r = −0.35, F = 4.30, P < 0.05). Since previous findings have concluded that normal fraternal siblings are less alike in frontal cortices, the present findings may be attributed to TS. We speculate that the high ICC between siblings and the negative correlation between TS symptoms severity and cortical thickness measurements are related to the disturbances in the maturation of the motor–cingulate–insular cortical neural system that mediate self-regulatory processes. Such delayed maturation may consequently contribute to the development of TS by releasing motor and vocal tics from regulatory control. These findings may have important genetic implications.

Keywords

Tourette syndrome Cortical thickness Neuroimaging Anterior cingulate Insula Motor Similarity Intra class correlations 

Notes

Acknowledgments

We thank the subjects who participated in this study. C·F. is a post-doctoral fellow of the Canadian Institutes of Health Research (CIHR), of the CIHR Genes, Mind, Behavior Training Program (M. Meany, PI) and the Jeanne Timmins Costello at the Montreal Neurological Institute.

References

  1. American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington, DCGoogle Scholar
  2. Aruga J, Yokota N, Mikoshiba K (2003) Human SLITRK family genes: genomic organization and expression profiling in normal brain and brain tumor tissue. Gene 315(2):87–94PubMedCrossRefGoogle Scholar
  3. Bohlhalter S, Goldfine A, Matteson S, Garraux G, Hanakawa T, Kansaku K, Wurzman R, Hallett M (2006) Neural correlates of tic generation in Tourette syndrome: an event-related functional MRI study. Brain 129(Pt 8):2029–2037PubMedCrossRefGoogle Scholar
  4. Chung MK, Worsley KJ, Robbins S, Paus T, Taylor J, Giedd JN, Rapoport JL, Evans AC (2003) Deformation-based surface morphometry applied to gray matter deformation. Neuroimage 18(2):198–213PubMedCrossRefGoogle Scholar
  5. Devinsky O, Morrell MJ, Vogt BA (1995) Contributions of anterior cingulate cortex to behaviour. Brain 118:279–306PubMedCrossRefGoogle Scholar
  6. Giedd JN, Schmitt JE, Neale MC (2007) Structural brain magnetic resonance imaging of pediatric twins. Hum Brain Mapp 28(6):474–481PubMedCrossRefGoogle Scholar
  7. Goetz CG, Tanner CM, Wilson RS, Shannon KM (1987) A rating scale for Gilles de la Tourette’s syndrome: description, reliability, and validity data. Neurology 7:1542–1544Google Scholar
  8. Hilgetag CC, Barbas H (2005) Developmental mechanics of the primate cerebral cortex. Anat Embryol (Berl) 210(5-6):411–417CrossRefGoogle Scholar
  9. Kawohl W, Bruhl A, Krowatschek G, Ketteler D, Herwig U (2008) Functional magnetic resonance imaging of tics and tic suppression in Gilles de la Tourette syndrome. World J Biol Psychiatry 3:1–4. Retrieved August 27, 2009 from http://www.informaworld.com/10.1080/15622970802118356 Google Scholar
  10. Laurin N, Wigg KG, Feng Y, Sandor P, Barr CL (2009) Chromosome 5 and Gilles de la Tourette syndrome: linkage in a large pedigree and association study of six candidates in the region. Am J Med Genet B Neuropsychiatr Genet 150B(1):95–103PubMedCrossRefGoogle Scholar
  11. Leckman JF, Riddle MA, Hardin MT, Ort SI, Swartz KL, Stevenson J, Cohen DJ (1989) The Yale Global Tic severity scale: initial testing of a clinician-rated scale of tic-severity. J Am Acad Child Adolesc Psychiatry 28:566–573PubMedCrossRefGoogle Scholar
  12. Leckman JF, Knorr AM, Rasmusson AM, Cohen DJ (1991) Basal ganglia research and Tourette’s syndrome. Trends Neurosci 14:94PubMedCrossRefGoogle Scholar
  13. Leckman JF, Zhang H, Vitale Lahnin F, Lynch K, Bondi C, Kim YS, Peterson BS (1998) Course of tic severity in Tourette’s syndrome: the first two decades. Pediatrics 102:14–19PubMedCrossRefGoogle Scholar
  14. Leckman JF, Cohen DJ, Goetz CG, Jankovic J (2001) Tourette syndrome: pieces of the puzzle. Adv Neurol 85:369–390PubMedGoogle Scholar
  15. Lenroot RK, Schmitt JE, Ordaz SJ, Wallace GL, Neale MC, Lerch JP, Kendler KS, Evans AC, Giedd JN (2009) Differences in genetic and environmental influences on the human cerebral cortex associated with development during childhood and adolescence. Hum Brain Mapp 30(1):163–174PubMedCrossRefGoogle Scholar
  16. Lerch JP, Evans AC (2005) Cortical thickness analysis examined through power analysis and a population simulation. Neuroimage 24:163–173PubMedCrossRefGoogle Scholar
  17. Lyttelton O, Boucher M, Robbins S, Evans A (2007) An unbiased iterative group registration template for cortical surface analysis. Neuroimage 34:1535–1544PubMedCrossRefGoogle Scholar
  18. Marsh R, Zhu H, Wang Z, Skudlarski P, Peterson BS (2007) A developmental fMRI study of self-regulatory control in Tourette’s syndrome. Am J Psychiatry 164(6):955–966PubMedCrossRefGoogle Scholar
  19. Miodonski A (1974) The angioarchitectonics and cytoarchitectonics (impregnation modo Golgi-Cox) structure of the fissural frontal neocortex in dog. Folia Biol (Krakow) 22:237–279Google Scholar
  20. Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9:97–113PubMedCrossRefGoogle Scholar
  21. Pauls DL (2003) An update on the genetics of Gilles de la Tourette syndrome. J Psychosom Res 55(1):7–12PubMedCrossRefGoogle Scholar
  22. Peper JS, Schnack HG, Brouwer RM, Van Baal GC, Pjetri E, Székely E, van Leeuwen M, van den Berg SM, Collins DL, Evans AC, Boomsma DI, Kahn RS, Hulshoff Pol HE (2009). Heritability of regional and global brain structure at the onset of puberty: a magnetic resonance imaging study in 9-year-old twin pairs. Hum Brain Mapp 30(7):2184–2196PubMedCrossRefGoogle Scholar
  23. Plomin R, Kosslyn SM (2001) Genes, brain and cognition. Nat Neurosci 4(12):1253–1258CrossRefGoogle Scholar
  24. Rakic P (1995) A small step for the cell, a giant leap for mankind: a hypothesis of neocortical expansion during evolution. Trends Neurosci 18:383–388PubMedCrossRefGoogle Scholar
  25. Robbins S, Evans AC, Collins DL, Whitesides S (2004) Tuning and comparing spatial normalization methods. Med Image Anal 8(3):311–323PubMedCrossRefGoogle Scholar
  26. Robertson MM (1989) The Gilles de la Tourette syndrome: the current status. Br J Psychiatry 154:147–169PubMedCrossRefGoogle Scholar
  27. Robertson MM, Cavanna AE (2007) The disaster was my fault! Neurocase 13(5):446–451PubMedGoogle Scholar
  28. Robertson MM, Eapen V (1992) Pharmacologic controversy of CNS stimulants in Gilles de la Tourette’s syndrome. Clin Neuropharmacol 15(5):408–425PubMedCrossRefGoogle Scholar
  29. Scahill L, Riddle MA, McSwiggin-Hardin M, Ort SI, King RA, Goodman WK, Cicchetti D, Leckman JF (1997) Children’s Yale-Brown Obsessive Compulsive Scale: reliability and validity. J Am Acad Child Adolesc Psychiatry 36:844–852PubMedCrossRefGoogle Scholar
  30. Sled JG, Zijdenbos AP, Evans AC (1998) A nonparametric method for automatic correction of intensity nonuniformity in MRI data. IEEE Trans Med Imaging 17:87–97PubMedCrossRefGoogle Scholar
  31. Speed WC, O’Roak BJ, Tárnok Z, Barta C, Pakstis AJ, State MW, Kidd KK (2008) Haplotype evolution of SLITRK1, a candidate gene for Gilles de la Tourette syndrome. Am J Med Genet B Neuropsychiatr Genet 147B(4):463–466PubMedCrossRefGoogle Scholar
  32. The Tourette Syndrome Association International Consortium for Genetics (2007) Genome scan for Tourette disorder in affected-sibling-pair and multigenerational families. Am J Hum Genet 80:265–272CrossRefGoogle Scholar
  33. Thompson PM, Cannon TD, Narr KL, van Erp T, Poutanen VP, Huttunen M, Lönnqvist J, Standertskjöld-Nordenstam CG, Kaprio J, Khaledy M, Dail R, Zoumalan CI, Toga AW (2001) Genetic influences on brain structure. Nat Neurosci 4(12):1253–1258PubMedCrossRefGoogle Scholar
  34. Verkerk AJ, Cath DC, van der Linde HC, Both J, Heutink P, Breedveld G, Aulchenko YS, Oostra BA (2006) Genetic and clinical analysis of a large Dutch Gilles de la Tourette family. Mol Psychiatry 11(10):954–964PubMedCrossRefGoogle Scholar
  35. Wallace GL, Eric Schmitt J, Lenroot R, Viding E, Ordaz S, Rosenthal MA, Molloy EA, Clasen LS, Kendler KS, Neale MC, Giedd JN (2006) A pediatric twin study of brain morphometry. J Child Psychol Psychiatry 47(10):987–993PubMedCrossRefGoogle Scholar
  36. Yoon U, Fahim C, Perusse D, Evans A (2008). Genetic analysis of cortical thickness in 8-year-old twins. In: The 14th international conference on funtional mapping of the human brain, Melbourne, Australia. NeuroImage, vol 41, p S55Google Scholar
  37. Zijdenbos AP, Forghani R, Evans AC (2002) Automatic pipeline analysis of 3-D MRI data for clinical trials: application to multiple sclerosis. IEEE Trans Med Imaging 21:1280–1291PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Cherine Fahim
    • 1
    • 2
    • 3
    • 4
    • 5
  • Uicheul Yoon
    • 1
    • 4
  • Paul Sandor
    • 7
  • Kirk Frey
    • 8
  • Alan C. Evans
    • 1
    • 4
    • 6
  1. 1.Department of Neurology and NeurosurgeryMcGill UniversityMontrealCanada
  2. 2.Laboratory for the Experimental Research in Behavior (LERB), Faculty of SSP, Institute of PsychologyUniversity of LausanneLausanneSwitzerland
  3. 3.Department of PsychiatryUniversity of MontrealMontrealCanada
  4. 4.McConnell Brain Imaging Center, Montreal Neurological InstituteMcGill UniversityMontrealCanada
  5. 5.Sainte-Justine Hospital Research CentreMontrealCanada
  6. 6.Department of Biomedical EngineeringMcGill UniversityMontrealCanada
  7. 7.Division of Brain Imaging & Behaviour Systems—Neuroscience Toronto Western Research InstituteUniversity of TorontoTorontoCanada
  8. 8.Departments of Radiology and of Neurology, Mental Health Research InstituteUniversity of MichiganAnn ArborUSA

Personalised recommendations