The Development of Neural Correlates Associated with Visuo-Spatial Working Memory in Children with ASD: 2-Year Longitudinal fMRI Study

Background:  Prior research has shown persistent impairments in visuo-spatial working memory (WM) in individuals with Autism Spectrum Disorder (ASD), compared to normative populations. Existing neuroimaging studies suggest reduced brain activation in fronto-parietal regions during WM tasks in both children and adults with ASD. However, our understanding of the neurodevelopmental patterns accompanying WM is limited. It is suggested that social deficits related to ASD could be explained in part by degraded memory ability. Social and environmental demands become increasingly complex as children mature to adolescents, and thus it is important to consider the development of associated underlying neuropsychological systems, such as WM processing, that are vulnerable in ASD.

Objectives:  The purpose of the current study was to examine functional changes longitudinally, over 2 years, in neural correlates of WM in children and adolescents with and without ASD, and the impact of increasing cognitive load.

Methods: Measures of brain activity were acquired with functional magnetic resonance imaging (fMRI) during a visuo-spatial 1-back WM task with four levels of difficulty. A total of 14 children with ASD and 15 age- and sex-matched typically developing children (ages 7-13) were included at baseline and followed up approximately 2 years later. Diagnosis of ASD was confirmed using the Autism Diagnostic Observation Schedule (ADOS). Neural changes between the hardest and easiest difficulty level were analyzed, and the longitudinal change of this contrast was compared between children with and without ASD using a Group x Time interaction.

Results:  Although similar task performance was seen at baseline and follow-up across groups, differences were evident in the developmental trajectories of neural responses. Typically developing children showed greater load-dependent activation which increased with age in frontal, parietal and occipital lobes and the right fusiform gyrus, compared to those with ASD. In these areas, children with ASD showed little load dependent increases. However, the ASD group showed greater longitudinal load-dependent decreased activation in default-mode related areas (parahippocampal gyrus and ventro-medial prefrontal cortex) compared to controls.

Conclusions:  Our results suggest a lack of neural modulation with increasing cognitive demand in parietal-occipital cortical areas in children with ASD that showed no significant maturation into adolescence, in contrast to typically developing peers. Further, children with ASD demonstrated delayed, rather than arrested, maturation of DMN-related areas as observed by increased load-dependent suppression of brain activity across time, relative to typical children. Children with ASD may become quickly saturated and overwhelmed with incoming information, impacting their ability to balance multiple demands of their environment, which becomes increasingly more complex in adolescence. Thus, the period from childhood to adolescence is a critical time to support children with ASD by teaching them skills for facilitating WM (e.g., chunking strategies) and providing them with appropriate accommodations to compensate for WM deficits; this will allow them to benefit more from academic, social and/or behavioural interventions.