Alterations in the functional neural circuitry supporting flexible choice behavior in autism spectrum disorders.

A-M D'Cruz,J A Sweeney,M E Ragozzino,E H Cook,M W Mosconi

doi:10.1038/tp.2016.161

A-M D'Cruz, J A Sweeney + Show 3 more

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https://doi.org/10.1038/tp.2016.161

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Abstract

Restricted and repetitive behaviors, and a pronounced preference for behavioral and environmental consistency, are distinctive characteristics of autism spectrum disorder (ASD). Alterations in frontostriatal circuitry that supports flexible behavior might underlie this behavioral impairment. In an functional magnetic resonance imaging study of 17 individuals with ASD, and 23 age-, gender- and IQ-matched typically developing control participants, reversal learning tasks were used to assess behavioral flexibility as participants switched from one learned response choice to a different response choice when task contingencies changed. When choice outcome after reversal was uncertain, the ASD group demonstrated reduced activation in both frontal cortex and ventral striatum, in the absence of task performance differences. When the outcomes of novel responses were certain, there was no difference in brain activation between groups. Reduced activation in frontal cortex and ventral striatum suggest problems in decision-making and response planning, and in processing reinforcement cues, respectively. These processes, and their integration, are essential for flexible behavior. Alterations in these systems may therefore contribute to a rigid adherence to preferred behavioral patterns in individuals with an ASD. These findings provide an additional impetus for the use of reversal learning paradigms as a translational model for treatment development targeting the domain of restricted and repetitive behaviors in ASD.

Highlights

Much research has focused on social deficits in autism spectrum disorders (ASD), but understanding of the restricted and repetitive behaviors symptom domain remains limited, despite the significant burden it places on affected individuals and their caregivers.[1,2] A neurocognitive deficit in disengaging from preferred behavioral patterns may contribute to this behavioral aspect of ASD.[3,4,5] Because few treatment options for behavioral rigidity in ASD are currently available, defining the neural substrate of behavioral inflexibility has the potential to inform new treatment targets for this understudied feature of the disorder.Reversal learning tasks provide a well-established and translational approach to examining flexible choice behavior
For controls in the two-choice reversal learning task, in which the requirements for planning a new response were minimal as the necessary alternative response was clear, non-reinforcement of learned responses relative to expected reinforcement of correct responses at reversal trials led to significant activation in bilateral primary visual cortex only
Our findings suggest that alterations in the function of the pre-supplementary motor area may result in difficulty in deciding to shift behavior and subsequently in planning new responses, which may contribute to reduced behavioral flexibility in ASD

Summary

Introduction

Much research has focused on social deficits in autism spectrum disorders (ASD), but understanding of the restricted and repetitive behaviors symptom domain remains limited, despite the significant burden it places on affected individuals and their caregivers.[1,2] A neurocognitive deficit in disengaging from preferred behavioral patterns may contribute to this behavioral aspect of ASD.[3,4,5] Because few treatment options for behavioral rigidity in ASD are currently available, defining the neural substrate of behavioral inflexibility has the potential to inform new treatment targets for this understudied feature of the disorder.Reversal learning tasks provide a well-established and translational approach to examining flexible choice behavior. In contrast to extradimensional set-shifting tasks such as the Wisconsin Card Sorting Test[6] in which the criterion for choosing a correct response might switch from color, to shape, to location, reversal learning tasks assess simple intradimensional shifts in behavior, for example, shifting from choosing one spatial location to another. This is accomplished by requiring subjects to learn a behavioral response using performance feedback, and to reverse that response to an alternative option when a learned response preference is no longer the correct choice.

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