Default mode network segregation and social deficits in autism spectrum disorder: Evidence from non-medicated children.

Functional pathology of the default mode network is posited to be central to social-cognitive impairment in autism spectrum disorders (ASD). Altered functional connectivity of the default mode network's midline core may be a potential endophenotype for social deficits in ASD. Generalizability from prior studies is limited by inclusion of medicated participants and by methods favoring restricted examination of network function. This study measured resting-state functional connectivity in 22 8-13 year-old non-medicated children with ASD and 22 typically developing controls using seed-based and network segregation functional connectivity methods. Relative to controls the ASD group showed both under- and over-functional connectivity within default mode and non-default mode regions, respectively. ASD symptoms correlated negatively with the connection strength of the default mode midline core-medial prefrontal cortex-posterior cingulate cortex. Network segregation analysis with the participation coefficient showed a higher area under the curve for the ASD group. Our findings demonstrate that the default mode network in ASD shows a pattern of poor segregation with both functional connectivity metrics. This study confirms the potential for the functional connection of the midline core as an endophenotype for social deficits. Poor segregation of the default mode network is consistent with an excitation/inhibition imbalance model of ASD.

Neural Correlates of Set-Shifting in Children With Autism.

Autism spectrum disorder (ASD) is often associated with high levels of inflexible thinking and rigid behavior. The neural correlates of these behaviors have been investigated in adults and older adolescents, but not children. Prior studies utilized set-shifting tasks that engaged multiple levels of shifting, and depended on learning abstract rules and establishing a strong prepotent bias. These additional demands complicate simple interpretations of the results. We used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of set-shifting in 20 children (ages 7-14) with ASD and 19 typically developing, matched, control children. Participants completed a set-shifting task that minimized nonshifting task demands through the use of concrete instructions that provide spatial mapping of stimuli-responses. The shift/stay sets were given an equal number of trials to limit the prepotent bias. Both groups showed an equivalent "switch cost," responding less accurately and slower to Switch stimuli than Stay stimuli, although the ASD group was less accurate overall. Both groups showed activation in prefrontal, striatal, parietal, and cerebellum regions known to govern effective set-shifts. Compared to controls, children with ASD demonstrated decreased activation of the right middle temporal gyrus across all trials, but increased activation in the mid-dorsal cingulate cortex/superior frontal gyrus, left middle frontal, and right inferior frontal gyri during the Switch vs. Stay contrast. The successful behavioral switching performance of children with ASD comes at the cost of requiring greater engagement of frontal regions, suggesting less efficiency at this lowest level of shifting.

Motor demands impact speed of information processing in autism spectrum disorders.

The apparent contradiction between preserved or even enhanced perceptual processing speed on inspection time tasks in autism spectrum disorders (ASD) and impaired performance on complex processing speed tasks that require motor output (e.g., Wechsler Processing Speed Index) has not yet been systematically investigated. This study investigates whether adding motor output demands to an inspection time task impairs ASD performance compared to that of typically developing control (TDC) children. The performance of children with ASD (n = 28; mean Full Scale IQ (FSIQ) = 115) and TDC (n = 25; mean FSIQ = 122) children was compared on processing speed tasks with increasing motor demand. Correlations were run between ASD task performance and Autism Diagnostic Observation Schedule (ADOS) Communication scores. Performance by the ASD and TDC groups on a simple perceptual processing speed task with minimal motor demand was equivalent, though it diverged (ASD worse than TDC) on 2 tasks with the same stimuli but increased motor output demands. ASD performance on the moderate but not the high speeded motor output demand task was negatively correlated with ADOS communication symptoms. These data address the apparent contradiction between preserved inspection time in the context of slowed "processing speed" in ASD. They show that processing speed is preserved when motor demands are minimized, but that increased motor output demands interfere with the ability to act on perceptual processing of simple stimuli. Reducing motor demands (e.g., through the use of computers) may increase the capacity of people with ASD to demonstrate good perceptual processing in a variety of educational, vocational, and social settings.