Neural Mechanisms of Uncertainty Processing in Children with Autism Spectrum Disorder

Background: Autism spectrum disorder (ASD) is often characterized by a preference for predictability and difficulty coping with unpredictable or unexpected circumstances referred to as insistence on sameness.  This behavioral tendency may also have an impact on other core symptoms of ASD as a preference for sameness and aversion towards uncertainty may bias individuals with ASD to prefer predictable circumscribed interests versus inherently unpredictable social interactions.  Yet, despite the prevalence of such symptoms and their potential role in core ASD symptomatology, uncertainty processing and its neurobiological mechanisms have yet to be studied empirically in children with ASD

Objectives: The present study had the following aims: (1) to better understand the neural circuitry involved in processing uncertainty using functional magnetic resonance imaging (fMRI) in both a social and non-social context and (2) to investigate how neural activation during uncertainty processing might be related to caregiver-reported aversion to uncertainty (i.e., intolerance of uncertainty) and insistence on sameness symptoms.   

Methods: This study included 25 children with ASD and 21 typically developing (TD) children who were matched on age, IQ, and gender.  An fMRI task previously used to measure neural responses to uncertainty (Grupe & Nitschke, 2011; Sarinopoulos et al., 2010) was adapted to include positively valenced social stimuli (i.e., faces with positive affect) and positive non-social stimuli (i.e., monetary compensation).  All fMRI analyses were corrected for multiple comparisons to obtain a cluster-corrected threshold of p< .05 using a frontolimbic small volume correction.  Structurally defined frontolimbic regions of interest were also correlated with caregiver-reported measures of intolerance of uncertainty and insistence on sameness.

Results: During the processing of uncertainty in a non-social context, the ASD group demonstrated attenuated activation of the bilateral putamen, nucleus accumbens, insula, and anterior cingulate cortex relative to the TD group.  During uncertainty in social context, the ASD group demonstrated enhanced activation of the bilateral anterior cingulate cortex and frontal medial cortex.  Frontolimbic activation during uncertainty processing was also found to be positively correlated with caregiver-reported levels of intolerance of uncertainty and insistence on sameness in children with ASD.

Conclusions: These results suggest that differential neural mechanisms are involved in the processing of uncertainty in children with ASD versus TD children and that these mechanisms may be influenced by a social versus nonsocial context.  In addition, atypical processing of uncertainty may be related to elevated intolerance of uncertainty and insistence on sameness symptoms.  An improved understanding of the mechanisms underlying atypical processing of uncertainty in ASD may ultimately provide insight into core ASD symptomatology, help differentiate these symptoms in ASD versus other clinical populations, and work towards developing interventions to address this symptom domain in ASD.