Event-Related Functional Neuroimaging of Reversal Learning in Autism Spectrum Disorders
thesisposted on 24.10.2013, 00:00 by Anna-Maria D'Cruz
Many individuals with autism spectrum disorders (ASD) demonstrate Insistence on Sameness, which is characterized by restricted and repetitive patterns of thinking and behavior, and distress associated with disrupting preferred routines. Whether a primary impairment in neurocognitive processes supporting behavioral flexibility exist that could contribute to Insistence on Sameness is not well understood. Animal and human neuroimaging studies indicate that frontostriatal circuitry supports flexible behavior, but few studies have directly examined this functional neural circuitry in ASD during performance of a task requiring instances of behavioral flexibility. We used functional brain imaging during a task requiring flexible shifts in behavior to assess two possible neurobiological mechanisms of behavioral rigidity in ASD. One hypothesis was that altered activity in dorsal striatum and dorsal frontal motor and cognitive systems could impair shifting and sustaining novel response choices. A second hypothesis was that alterations in ventral striatum and associated limbic circuitry could cause problems interpreting the reinforcement cues that guide shifts in behavior. Further, uncertainty associated with response choices could exacerbate behavioral flexibility deficits in ASD, paralleling the increased distress and disability that may be seen clinically in novel or ambiguous situations. To test this third hypothesis, behavioral flexibility was examined in conditions in which the outcomes of future choice behaviors were either certain or uncertain. Seventeen individuals with an ASD, and 23 age-, gender-, and IQ-matched control participants performed reversal learning studies during functional neuroimaging. When shifting from learned to novel responses when the outcome of responses was uncertain, the ASD group showed reduced activation of both dorsal and ventral frontostriatal circuits. This impairment was present in the absence of task performance deficits in the ASD group relative to controls that might have confounded data interpretation. When the outcomes of novel responses were certain, there was no difference in brain activation between the groups, nor was there any difference in task performance measures. Deficits present in both dorsal and ventral frontostriatal circuits suggest problems in integrating information from reinforcement cues with motor planning and decision making, which are essential in flexible responding. The specificity of these deficits to shifting behavior under uncertain circumstances may indicate problems responding appropriately to ambiguous reinforcement cues, and the integration of this information with multiple alternative response plans. Clinically, this may contribute to compulsive adherence to preferred behavioral patterns, and difficulty adapting to new environments and routines in individuals with an ASD. These findings provide a promising translational platform for better understanding the neurobiological substrates of Insistence on Sameness in ASD.