Functional Brain Maturation of Attention and Temporal Discounting in Children and Adults with ASD: An fMRI Investigation

Background:  

Individuals with autistic spectrum disorder (ASD) have cognitive and behavioural difficulties with sustained attention as well as with temporal foresight and forward planning. However, little is known of the neurofunctional substrates underlying these deficits, nor of potential abnormalities in functional brain maturation during these functions in people with ASD.

Objectives:  

We used fMRI across a large age range of 86 children and adults with ASD and typically developing controls between 11-35 years old to investigate 1) differences in brain activation in children and adults with ASD relative to controls during two tasks that measure sustained attention and temporal discounting, respectively and 2) differences in the neurofunctional maturation in people with ASD relative to controls.

Methods:  

46 males (11-35 years old) with ASD and 40 age/IQ matched typically developing male controls completed two event-related fMRI tasks on a 3T MRI scanner. All participants were right-handed, medication-naïve, IQ >70.  All individuals with ASD were diagnosed with autism or Asperger (ICD-10) and met ADI and ADOS cut-offs for autism. The 12 minute parametric sustained attention task (SAT) requires subjects to respond as quickly as possible to a timer that appears under two delay conditions: 1) short, frequent, predictable delays (500ms), 2) randomly interspersed long, unpredictable delays (2s, 5s, 8s). Long unpredictable delays place a higher load on sustained attention (parametrically modulated with increasing delays); short predictable delays place a higher load on sensorimotor timing.  The 12 minute temporal discounting task (TD) measures the effect of delay on reward-related decision making and temporal foresight. Subjects choose between small immediate rewards and larger delayed rewards. Data were analysed using non-parametric image analysis (XBAM: www.brainmap.co.uk).  To investigate whether group differences in brain activation were associated with differential neurofunctional development, we performed a conjunction analysis between group differences in activation and group differences in whole-brain age correlations.

Results:  

SAT: Individuals with ASD had slower MRT and greater intrasubject variability than controls and underactivated dorsolateral and inferior prefrontal, striato-thalamic, temporal and cerebellar regions. The conjunction analysis showed that most of these regions that differed significantly between groups also differed in functional maturation; they increased progressively with age in controls, but not in ASD. Furthermore, activation in these areas showed significant negative correlations with ADI and ADOS scores (social, communication and restricted interests/repetitive behaviour) and positively with task performance.

TD: TD data will be presented at the conference

Conclusions:  

SAT: The findings suggest that individuals with ASD have significant differences from controls in the functional activation of brain networks central to sustained attention. Importantly, this study shows for the first time that functional activation deficits in ASD are associated with underlying abnormalities in functional brain maturation, suggesting that abnormal brain function may be due to abnormal functional maturation.