In particular, this framework posits that social communication symptoms in autism spectrum disorder (ASD) reflect decreased motivation to engage in reciprocal social behaviors throughout the development that results in fewer experiences with social rewards 2. The social motivation hypothesis of autism proposes that functional disruptions in brain circuits supporting social motivation constitute a primary deficit that contributes to social communication impairments 1. PET-fMRI may be a suitable tool to evaluate novel ASD therapeutics targeting the striatal dopamine system. Our findings that ASD is characterized by impaired striatal phasic dopamine release to incentives provide support for the social motivation hypothesis of autism. Within the ASD group, decreased phasic dopamine release in the putamen was related to poorer theory-of-mind skills. Relative to controls, the ASD group demonstrated decreased phasic dopamine release to incentives in the bilateral putamen and left caudate, as well as increased functional connectivity between a PET-derived right putamen seed and the precuneus and insula. Striatal clusters showing significant between-group BP ND differences were used as seeds in whole-brain fMRI general functional connectivity analyses. Using a bolus + infusion protocol with the D2/D3 dopamine receptor antagonist raclopride, voxel-wise binding potential (BP ND) was compared between groups (controls = 12, ASD = 10) in the striatum. Here, we examined striatal functioning during monetary incentive processing in ASD and controls using simultaneous positron emission tomography (PET) and fMRI. Although this hypothesis is supported by functional magnetic resonance imaging (fMRI) studies, no molecular imaging study has evaluated striatal dopamine functioning in response to rewards in ASD. This framework suggests that impaired mesolimbic dopamine function underlies compromised responses to social rewards in ASD. These results have implications for using the IGT to study abnormal mechanisms of decision making in a variety of clinical populations.The social motivation hypothesis of autism posits that autism spectrum disorder (ASD) is characterized by impaired motivation to seek out social experience early in life that interferes with the development of social functioning. Specifically, a neural circuitry involving the dorsolateral prefrontal cortex (for working memory), the insula and posterior cingulate cortex (for representations of emotional states), the mesial orbitofrontal and ventromedial prefrontal cortex (for coupling the two previous processes), the ventral striatum and anterior cingulate/SMA (supplementary motor area) for implementing behavioral decisions was engaged. The activated regions were consistent with the neural circuitry hypothesized to underlie somatic marker activation and decision-making. Decision-making during the IGT was associated with activity in several brain regions in a group of healthy individuals. Here we report a method for exploring brain activity using fMRI during performance of the IGT. Very few studies have employed the IGT in functional magnetic resonance imaging (fMRI) investigations, in part, because the task is cognitively complex. The Iowa Gambling Task (IGT) is a sensitive test for the detection of decision-making impairments in several neurological and psychiatric populations.
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