Reconceptualizing functional brain connectivity in autism from a developmental perspective

Abstract

While there is almost universal agreement amongst researchers that autism is associated with alterations in brain connectivity, the precise nature of these alterations continues to be debated. Theoretical and empirical work is beginning to reveal that autism is associated with a complex functional phenotype characterized by both hypo- and hyper-connectivity of large-scale brain systems. It is not yet understood why such conflicting patterns of brain connectivity are observed across different studies, and the factors contributing to these heterogeneous findings have not been identified. Developmental changes in functional connectivity have received inadequate attention to date. We propose that discrepancies between findings of autism related hypo-connectivity and hyper-connectivity might be reconciled by taking developmental changes into account. We review neuroimaging studies of autism, with an emphasis on functional magnetic resonance imaging studies of intrinsic functional connectivity in children, adolescents and adults. The consistent pattern emerging across several studies is that while intrinsic functional connectivity in adolescents and adults with autism is generally reduced compared with age-matched controls, functional connectivity in younger children with the disorder appears to be increased. We suggest that by placing recent empirical findings within a developmental framework, and explicitly characterizing age and pubertal stage in future work, it may be possible to resolve conflicting findings of hypo- and hyper-connectivity in the extant literature and arrive at a more comprehensive understanding of the neurobiology of autism.

Keywords: autism spectrum disorders; brain development; fMRI; functional connectivity; puberty.

Figure 1

Schematic model of two scenarios that could explain a developmental shift from intrinsic hyper-to hypo-connectivity in ASD. In scenario 1 (solid red line), the ASD group shows a less steep developmental increase in functional connectivity over the age span compared with the TD group. In scenario 2 (dashed red line), the ASD group shows anomalous patterns of connectivity across the pubertal period. Resting-state functional connectivity MRI studies provide evidence for widespread hyper-connectivity in children with ASD in contrast to hypo-connectivity observed in adolescents and adults with ASD. To reconcile these findings, it will be necessary to conduct longitudinal studies that span the developmental period surrounding puberty (gray oval). ASD, autism spectrum disorders; TD, typical development.