Objectives: This study examines posterior-anterior connectivity in the default network during rest in relation to ASD symptoms and 5-HTTLPR genotype. We hypothesized that (1) posterior-anterior default network connectivity would be altered in individuals with ASD compared to controls; (2) individuals with ASD with the low-expressing variant of 5-HTTLPR would show altered connectivity in regions that differed between individuals with ASD and controls; and (3) altered connectivity would be related to social symptom severity in individuals with ASD.
Methods: Forty-one individuals with ASD and 32 controls were instructed to “let your mind wander” while being presented with a fixation cross for 10 minutes during fMRI acquisition. To calculate connectivity, a self-organizing map algorithm was used to identify the cluster containing the posterior hubs (posterior cingulate and angular gyrus) of the default network for each subject. Then, this cluster’s average timecourse was correlated with all other voxels in the brain. PCR and DNA sequencing were performed on saliva samples to ascertain genotype.
Results: Individuals with ASD evidenced altered posterior-anterior connectivity compared to controls. Specifically, the right inferior frontal gyrus (rIFG) showed stronger connectivity with the posterior portion of the default network in individuals with ASD (xyz=46, 16, 6, t70=4.18, p=0.048 small volume corrected for right prefrontal cortex, controlling for age and IQ). With the 31 individuals with ASD genotyped to date, a preliminary analysis revealed that those with the low-expressing variant of 5-HTTLPR had stronger connectivity in the rIFG, compared to individuals with ASD without the low-expressing variant (xyz=50, 18, 22, t30=3.76, p<0.001 uncorrected). Genotyping is underway on the remaining 25 control and 10 ASD participants to address this hypothesis with the full set of participants. Lastly, connectivity in the rIFG was positively related to social impairment in individuals with ASD (xyz=50, 28, -6, t38=4.20, p=0.026, small volume corrected for rIFG, controlling for IQ).
Conclusions: Compared to controls, individuals with ASD exhibit stronger posterior-anterior connectivity in the default network during rest. Within the ASD group, stronger connectivity in the default network is related to both 5-HTTLPR genotype and social symptoms.