A Simultaneous [¹¹C]Raclopride Positron Emission Tomography and Functional Magnetic Resonance Imaging Investigation of Striatal Dopamine Binding in Autism

AbstractBackgroundThe social motivation hypothesis of autism suggests 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. This framework posits that impaired mesolimbic dopamine (DA) function underlies compromised responses to social rewards in ASD. 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.MethodsThis study evaluated striatal dopaminergic functioning during incentive processing in ASD using simultaneous positron emission tomography (PET) and fMRI using the D2/D3 dopamine receptor antagonist [11C]raclopride. Using a bolus + infusion protocol, voxel-wise binding potential (BPND) was compared between groups (Controls=12, ASD=10) in the striatum.ResultsRelative to controls, the ASD group demonstrated relatively decreased phasic DA release to incentives in the right and left putamen and left caudate. Striatal clusters showing significant between-group BPNDdifferences were used as seeds in whole-brain fMRI general functional connectivity analyses. This revealed increased connectivity between the PET-derived right putamen seed and clusters in the precuneus and right insula in the ASD group. Within the ASD group, decreased phasic DA release in the left putamen was related to poorer theory-of-mind skills.ConclusionsASD was characterized by impaired striatal phasic DA release and abnormally increased functional connectivity, providing support for the social motivation hypothesis of autism. PET measures of dopamine receptor target occupancy may be suitable to evaluate novel ASD therapeutics targeting the striatal dopamine system.