Brain functional connectivity correlates of autism diagnosis and familial liability in 24-month-olds

BACKGROUND: fcMRI correlates of autism spectrum disorder (ASD) diagnosis and familial liability were studied in 24-month-olds at high (older affected sibling) and low familial likelihood for ASD. METHODS: fcMRI comparisons of high-familial-likelihood (HL) ASD-positive (HLP, N = 23) and ASD-negative (HLN, N = 91), and low-likelihood ASD-negative (LLN, N = 27) 24-month-olds from the Infant Brain Imaging Study (IBIS) Network were conducted, employing object oriented data analysis (OODA), support vector machine (SVM) classification, and network-level fcMRI enrichment analyses. RESULTS: OODA (alpha = 0.0167, 3 comparisons) revealed differences in HLP and LLN fcMRI matrices (p = 0.012), but none for HLP versus HLN (p = 0.047) nor HLN versus LLN (p = 0.225). SVM distinguished HLP from HLN (accuracy = 99%, PPV = 96%, NPV = 100%), based on connectivity involving many networks. SVM accurately classified (non-training) LLN subjects with 100% accuracy. Enrichment analyses identified a cross-group fcMRI difference in the posterior cingulate default mode network 1 (pcDMN1)- temporal default mode network (tDMN) pair (p = 0.0070). Functional connectivity for implicated connections in these networks was consistently lower in HLP and HLN than in LLN (p = 0.0461 and 0.0004). HLP did not differ from HLN (p = 0.2254). Secondary testing showed HL children with low ASD behaviors still differed from LLN (p = 0.0036). CONCLUSIONS: 24-month-old high-familial-likelihood infants show reduced intra-DMN connectivity, a potential neural finding related to familial liability, while widely distributed functional connections correlate with ASD diagnosis.