Increased Local Connectivity and Decreased Long Range Connectivity In Autism Is Consistent with Immaturity of Cortical Networks

Background: A growing body of evidence suggests that autism spectrum disorders (ASDs) are related to altered communication between brain regions. Specifically, there are reports of reduced long-range connectivity across networks required for complex social behavior (e.g., Just 2004 2007; Koshino et al., 2005;Kleinhans et al., 2008; Kana et al., 2009). In an emotional facial processing task, we have previously found that, compared to typically developing children, children with ASD display increased local connectivity between different frontal regions and reduced long range connectivity between frontal and parietal cortex, as well as between amygdala and visual areas (Rudie et al. under review). Interestingly, recent work has shown that, during the course of typical development, functional brain networks show increases in long-range functional connectivity among nodes within a given network as well as reduced local (i.e., intralobar) connectivity among nodes in different networks (e.g. Fair et al 2009). Thus, the differences observed when comparing ASD and neurotypical individuals resemble the changes observed as a function of development.

Objectives: Here we sought to examine the hypothesis that individuals with ASD display an “immature” (as opposed to deviant) pattern of brain connectivity by examining how age may be related to altered connectivity patterns in ASD.

Methods: The data used in this study were collected in a sample of 23 high-functioning children and adolescents with ASD  (mean age: 12.61, range 8.22-17.35) who passively observed faces displaying different emotions (angry, fearful, happy, sad, and neutral) while undergoing functional Magnetic Resonance Imaging (fMRI). Here we focused our analyses on correlating chronological age in children with ASD and connectivity for two brain regions (amygdala and right pars opercularis) where we previously observed reduced long-range connectivity and increased local connectivity in this ASD sample vs.  to typically-developing (TD) matched controls.

Results: In regions where the ASD group showed greater local connectivity with the right pars opercularis as compared to TD controls, a significant correlation with age was observed such that younger children with ASD showed greater local connectivity (i.e., the younger the children, the more ASD-like the pattern of connectivity). Furthermore, in regions where TD controls showed greater long-range connectivity with the amygdala, a significant correlation with age was also observed such that older children with ASD showed greater connectivity between with the fusiform gyrus and occipital cortex (i.e., the older the ASD children, the more typical the pattern of connectivity).

Conclusions: Within a sample of children and adolescents with ASD in which we previously observed increased local and decreased long range connectivity, we found that age was significantly related to such altered patterns. More specifically, younger ages were associated with greater local connectivity with the right pars opercularis, whereas increasing age was associated  with greater long-range connectivity with the amygdala. Taken together, these findings provide support for the notion that altered functional connectivity in autism may in part reflect delayed or more immature patterns of brain connectivity.