Thesis defense Annika Rausch (Donders series 402)
8 November 2019
Promotors: prof. dr.J. Buitelaar, prof. dr.C. Beckmann
Co-promotors: dr. K. Haak, dr. W. Groen
System Connectomics in Autism Spectrum Disorder. Exploring the role of the Amygdala and the Thalamus
The thalamus maintains connections throughout the brain and its dysfunction has been associated with Autism Spectrum Disorders (ASD). However, robust neural markers for abnormal thalamic involvement in ASD are lacking. In a previous study in a small adolescent male sample we observed hyperconnectivity between the right prefrontal thalamic nucleus and the right ventromedial prefrontal cortex (TPF-CvmPFC FC strength). Here, we aimed to replicate this effect in a large heterogeneous sample. We extracted the mean time series of both regions of interest and calculated its correlations in resting-state fMRI scans of 15 neuroimaging cohorts with a total sample size of N=707 individuals with ASD and N=679 controls. In line with previous findings, a permutation test on FC strength group differences confirmed significantly higher TPF-CvmPFC FC strength in ASD than in controls, using a linear mixed effects model permutation test with study-site as random factor and age and gender as covariate. The between group effect was more pronounced but yet less significant, when repeating the analysis with a sub-selection of adolescent boys that match the characteristics of the discovery sample (12-23y, males only). Furthermore, within the ASD group higher TPF-CvmPFC FC strength was associated with lower repetitive and stereotypic behaviour (RRB). This suggests that the thalamic-PFC hyperconnectivity marker may reflect a compensatory mechanism in ASD. Our study is the first to provide reproducible evidence of higher prefrontal thalamic-vmPFC FC strength in ASD and links this effect to RRB symptom severity.