Altered Working Memory-Related Brain Activation and Connectivity in Adolescents with Autism Spectrum Disorder

Background: Recent studies have reported atypical functional brain connectivity (i.e., correlations in neural activity between brain regions) in individuals with autism spectrum disorder (ASD; Koshino et al., 2005; Cherkassky et al., 2006). Research on healthy non-ASD individuals suggests that the degree of functional connectivity between brain regions is often not static but rather varies as a function of the task being performed. For example, when transitioning from a period of rest to the performance of a working memory task, the synchronization of activity within the ‘working memory’ network of brain regions may increase. One such working memory-related region is the left intraparietal sulcus (IPS), which previous research suggests is a ‘core’ critical region for working memory (Cowan et al., 2010).

Objectives: The goal of the present study was to evaluate potential ASD-related disruptions in patterns of rest-based and task-based activation and interrelations involving the left IPS. To accomplish this, functional activation and psychophysiological interaction (PPI) connectivity analyses were utilized in individuals with and without ASD during rest and during performance of a non-verbal working memory task.

Methods: A sample of 19 adolescents with ASD (mean age = 13.1 yrs; range: 11-15 yrs) and 21 typically developing adolescents without ASD (mean age = 13.2 yrs; range: 11-16 yrs) participated. Functional MRI scans were obtained while participants completed two conditions (2-back and 0-back) of an n-back non-verbal working memory task using a series of novel face stimuli. Each participant completed two functional runs, with each including 6 counterbalanced task epochs (3 per condition). PPI connectivity analysis was conducted to assess for differences in patterns of functional connectivity between a seed region, the left IPS, and the rest of the brain during task versus rest periods.

Results: Whole brain analysis revealed several regions-of-interest (ROIs) demonstrating significant condition (0-back and 2-back) x group (ASD and non-ASD) interactions in neural activation.  ROIs included the left IPS, left ventrolateral prefrontal cortex, right superior temporal cortex, and left fusiform gyrus [F(1,38) > 7.94, p < .005 cluster-thresholded, in all instances]. A significant PPI was observed between the left IPS and the anterior cingulate cortex (ACC) [F(1,38) = 14.59, p< .005 thresholded]. Whereas the non-ASD group showed a decrease in functional connectivity between the aforementioned regions during task performance compared to rest, the ASD group showed the opposite pattern (increased connectivity during task compared to rest).

Conclusions: Consistent with past neuroimaging studies, individuals with ASD demonstrated altered neural activation and functional connectivity compared to individuals without ASD both during a non-verbal working memory task and during resting period. Results of the current analysis further suggest ASD-related disruptions in the extent to which connectivity between regions changes as a function of task demands. Further analyses will examine the potential relationship between this phenomenon and cognitive, social, and behavioral functioning.