From genes to brain structure and function in TS (WP2)

Objectives: 1.Identification of cognitive and structural and functional correlates of TS, contrasted against comorbid ADHD and OCD. 2. Assessment of functional implications of TS, OCD, and ADHD risk alleles. 3. Establishment of patterns of multivariate brain activation and connectivity for TS. 4. Performance of multivariate analysis of brain activation patterns to cognitive tasks that takes account of the whole temporal-spatial pattern of activated voxels instead of focusing on predefined regions of interest (ROIs).

Fellow ESR8
Host institution: University Medical Centre Groningen
Duration: 36 months    
Supervisor: P.J. Hoekstra, UMCG; Co-supervisor:  P. Paschou, DUTH (genetic part) & J. Glennon / J. Buitelaar, RUNMC and SENSA (imaging part)

Tasks and methodology:  The  uncertain phenotypic boundaries of  TS is one of the most scientifically challenging features of TS, not only constraining identification of the genes underlying TS and comorbid neurodevelopmental disorders but also the involved neurocognitive pathways. Through studying unaffected but at-risk individuals, it can be seen whether the neuroanatomic alterations are cause or consequence of the disorder. Unaffected relatives allow for the identification of endophenotypes, which lie in the etiologic pathway between gene and disorder. So far, studies using relatives of TS probands are completely lacking. This project will compare TS participants and their unaffected siblings with matched comorbid groups from the NeuroImage consortium of ADHD and Autism spectrum disorder and their unaffected siblings. We will use identical measurements as in the large Dutch NeuroImage cohort of probands with ADHD, their siblings, and healthy controls. We aim to do these measurements in (1) 30 children with TS and (2) 30 as yet unaffected siblings of probands with TS. Another important goal will be to clarify the association between TS, ADHD, and OCD risk alleles and brain function and structure. The project will be fully embedded within the FP7-funded European Multicentre Tics in Children Studies (EMTICS).

  • Task 1: Establishment of neuroimaging & assessment battery and study protocol, obtaining ethical approval. Measurements will be obtained on inhibitory control, working memory, reward anticipation, resting state connectivity, and Diffusion Tensor Imaging.
  • Task 2: Recruitment of participants and obtaining measurements.
  • Task 3: Data analyses. Linear mixed models (performed in SPSS) will be used for the analyses. The linear mixed model expands the general linear model so that the data are permitted to exhibit correlated variability. This model allows for the investigation of group differences while correcting for the non-independency of data (i.e. more than one child participated per family, which resulted in related measurements within groups and between groups). Sibling correlations and cross-sibling correlations will be calculated using SAGE.
  • Task 4:  linking brain imaging findings to genetic risk factors for TS, OCD, ADHD.




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