Disrupted Effective Connectivity Underlying Self-Other Representation in Autism

Background:  

Disruption in interregional functional and anatomical connectivity has been at the center stage of the neurobiological accounts of autism spectrum disorder (ASD) (Just et al., 2012; Kana, Libero, & Moore, 2011). While the insights gained from these models are valuable, functional connectivity does not provide insight into the time-lagged causality and directionality of connectivity. Effective connectivity, on the other hand, provides information about the influence one system exerts over another with respect to a given experimental context (Büchel and Friston, 2000) and tests the direction of connectivity effects. Only a handful of studies have utilized effective connectivity in ASD (Shen et al., 2012; Shih et al., 2010; Wicker et al., 2008). The present study examined effective connectivity in ASD during a self-other judgment task.

Objectives:  The main objective of this fMRI study was to examine social information processing in ASD with specific focus on effective connectivity among different brain areas. 

Methods:  

18 high-functioning adolescents and adults with ASD and 18 age-and-IQ-matched typically developing control participants took part in this study. Participants made “yes” or “no” judgments of whether an adjective, presented visually, described them (self) or their favorite teacher (other). The data were collected using a 3T MRI scanner. Mean time series was extracted from 5 different regions of interest (ROIs) for all participants. These were the LIFG, LIPL, LMPFC, SMA, and the Caudate nucleus. The extracted time series were normalized and the hemodynamic response de-convolved using a cubature Kalman filter (Havliceck et al., 2011) to get the underlying neuronal response, which were input into the multivariate autoregressive model (Deshpande et al., 2010) and connectivity matrices were obtained for all participants. After this, a t-test was performed on the connectivities to examine the paths which were significantly different between the groups (p<0.05 corrected).

Results:  

We found an overall significant reduction in effective connectivity across the task in ASD participants relative to control participants. Group differences in connectivity were found primarily in the other condition, where the participants with ASD showed weaker effective connectivity from SMA to Caudate [t(34)=2.03, p<0.05], MPFC to LIFG [t(34)=2.04, p<0.05], LIPL to LIFG [t(34)=2.03, p<0.05], and between SMA and LIFG [t(34)=2.03, p<0.05], [t(34)=2.04, p<0.05]  bi-directionally. The only pathway in which effective connectivity was significantly greater for the ASD group was MPFC to Caudate [t(34)=2.03, p<0.05]. In whole-task comparisons, no pathway showed greater effective connectivity in ASD. 

Conclusions:  

Group differences in effective connectivity emerged only for the other condition, with significantly weaker connectivity in ASD in many regions. It should be noted that the connections that were weaker in ASD involved regions that are associated with self-other representation and social cognition. The MPFC has been associated with theory-of-mind and thoughts about others (Ebner et al., 2011), the IFG, IPL, and caudate have been found to have a role in self-other processing (Decety and Somerville, 2003; Kelley et al., 2002). Overall, the findings of this study underscore altered patterns of information flow in participants with ASD during social cognition and supplement functional connectivity findings in ASD.