Distinct neurobiological alterations during hedonic experience of rewards in attention deficit hyperactivity disorder and autism spectrum disorder: Multimodal evidence from neuroimaging meta-analyses

While aberrant responsiveness to rewards represents a core transdiagnostic feature across attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), it remains unclear whether those deficits are underpinned by shared or distinct neurobiological signatures. Here we leveraged pre-registered task-based functional neuroimaging meta-analyses to identify shared and specific neurofunctional alterations during hedonic processing of rewards in ADHD and ASD, and further validated the distinctions by integrating behavioral decoding, brain network and neurotransmitter linkage analyses. Our coordinate-based meta-analysis of 29 studies (468 ADHD patients, 424 ASD patients, and 1027 healthy controls, HCs) revealed that both disorders shared abnormal subcortical activation patterns in the putamen and amygdala, whereas the disorder-specific neurofunctional alterations were primarily localized to the prefrontal cortex. Such segregate neurofunctional patterns were further associated with differential behavioral manifestations, brain network connectivity changes and anatomical expression of specific neurotransmitter systems. Overall, those findings suggest that impaired responses to rewards in ADHD and ASD are mediated by shared subcortical dysfunction and distinct prefrontal functional abnormalities. The disorder-specific prefrontal activations characterized by divergent functional and neurochemical profiles may explain different motivational symptoms of ADHD and ASD, and further inform treatments on distinct cortico-subcortical circuits for precision therapeutics.