The Development of Cognitive Control in Children with Autism Spectrum Disorders

Background: Individuals with autism spectrum disorders (ASDs) exhibit impairments in cognitive control which are associated with atypicalities in the dorsolateral prefrontal (DLPFC), anterior prefrontal (aPFC), anterior cingulate (ACC), and parietal cortices. As yet, there has been little study of the developmental trajectory of the neural correlates of cognitive control in ASDs.

Objectives: To investigate the developmental trajectory of cognitive control in adolescents and young adults with ASDs and typical development; to examine changes in functional connectivity with age; and to test whether network and other measures are related to symptoms of inflexible thoughts and/or behaviors, and attention deficits.

Methods: Participants included 4 groups of 15 individuals with ASDs and typical development (TYP) each divided into younger (ages 12-15) and older (ages 16-18) groups. Slow event-related functional magnetic resonance imaging (fMRI) was used to examine group differences in performance in the cue phase of the Preparing to Overcome Prepotency (POP) task, which is a stimulus response incompatibility paradigm. Beta series correlations between brain regions activated during previous studies of cognitive control, were used as seed regions in the investigation of age-relatd changes in functional connectivity between regions including anterior PFC (aPFC) and DLPFC in a multivariate method based on graph-theory and adapted from Dosenbach, Fair, Cohen, Schlaggar and Petersen (2008). A second multivariate “small world network- based” developmental connectivity analysis, adapted from Achard, Whitcher, Suckling, and Bullmore (2006), also was implemented in a whole brain analysis.

Results: Across both groups and methods, younger individuals exhibited higher levels of brain activation in frontal and parietal regions than older ones. Using the graph-theory approach, the ASD group showed a pattern of “catching up” to the TYPs. For example, the TYP group exhibited increased network integration over time between regions of the aPFC, the DLPFC, and the occipital cortex. In the young TYPs, aPFC connections were limited; however, integration with occipital cortex became evident for the older age group. For the DLPFC, younger TYPs exhibited connectivity with aPFC, thalamus and temporal parietal junction. Older TYP children did not exhibit prominent DLPFC connectivity during the task. For the young ASD group, connectivity with aPFC and DLPFC was limited, however, by the older group ASD group demonstrated patterns of regional connectivity comparable to younger TYPs. Small-world network analysis implemented for the whole brain, showed a similar pattern of findings related to overall network changes in both groups with development, and with deficits in fronto-parietal connectivity in the ASD group at both ages. TYPs also showed greater long-range connectivity, and better network integrity than ASDs. A measure of network integrity was significantly related to restricted and repetitive behaviors in the ASDs group.

Conclusions: Results suggest that ASDs involve developmental delay in connectivity in the aPFC and DLPFC and a general deficit in parietal connectivity. They also show that ASDs exhibit reduced long-range connectivity across both regions, and provide preliminay support for the hypothesis that individuals with ASDs “catch up” to TYPs with respect to the activation patterns found in neural networks during control tasks.