Abnormal Functional Activation and Maturation of Ventromedial Prefrontal Cortex and Cerebellum during Temporal Discounting in Adolescents and Adults with Autism Spectrum Disorder: A Cross-Sectional Developmental fMRI Investigation

Background:

People with autism spectrum disorder (ASD) report having problems with, and avoidance of, decision making and have poor temporal foresight. This may adversely impact on their everyday life, mental health and productivity. However, the neural substrates underlying poor choice behaviour in people with ASD, or its’ neurofunctional development from childhood to adulthood, are unknown. Despite evidence of atypical structural brain development in ASD, investigation of functional brain maturation in people with ASD is lacking.

Objectives:

1. To investigate the neural substrates underlying performance on a temporal discounting task in 38 healthy (11 - 35 years old) male adolescents and adults with ASD and 40 age, sex and IQ-matched typically developing healthy controls using fMRI.

2. To assess group differences in the neurofunctional maturation of temporal discounting across childhood and adulthood using cross-sectional fMRI investigation.

Methods:

The fMRI temporal discounting task measures the choice between a small reward that is immediately available or a larger delayed reward and requires both inhibition of immediate reward and temporal foresight (forward thinking/future consideration of current choice).

Seventy eight right handed medication-naive healthy adolescent and adult males with IQ > 70 (N = 38 with non-comorbid ASD and N = 40 age and IQ matched typically developing controls) completed the event related fMRI temporal discounting task on a 3T MRI scanner (General Electric, Milwaukee, USA).

fMRI data analyses compared groups in brain activation and tested for group by age interaction effects using non-parametric fMRI data analyses (XBAM: www.brainmap.co.uk). Correlations were tested between performance measures and ASD severity measures and brain activation differences.

Results:

Males with ASD had significantly poorer task performance and significantly lower brain activation in typical right hemispheric regions that mediate temporal discounting for delayed choices, including right ventrolateral, dorsolateral and ventromedial prefrontal cortices, striato-limbic regions and cerebellum. Importantly, differential activation in ventromedial frontal cortex and cerebellum was associated with abnormal functional brain maturation; controls, in contrast to people with ASD, showed progressively increasing activation with increasing age in these regions; which furthermore was associated with task performance and clinical severity measures of ASD (stereotyped/restricted interests).

Conclusions:

This cross-sectional develomental fMRI investigation provides first evidence that reduced activation in people with ASD of ventromedial frontal and cerebellar brain regions that typically mediate temporal discounting is associated with, and may be caused by, abnormal functional brain development in these regions between childhood and adulthood. Furthermore, both abnormal activation and functional maturation appear to be related to poor task performance and clinical severity of ASD.