Age-atypical brain functional networks in autism spectrum disorder: a normative modeling approach.

BACKGROUND: Despite extensive research into the neural basis of autism spectrum disorder (ASD), the presence of substantial biological and clinical heterogeneity among diagnosed individuals remains a major barrier. Commonly used case‒control designs assume homogeneity among subjects, which limits their ability to identify biological heterogeneity, while normative modeling pinpoints deviations from typical functional network development at individual level. METHODS: Using a world-wide multi-site database known as Autism Brain Imaging Data Exchange, we analyzed individuals with ASD and typically developed (TD) controls (total n = 1218) aged 5-40 years, generating individualized whole-brain network functional connectivity (FC) maps of age-related atypicality in ASD. We then used local polynomial regression to estimate a networkwise normative model of development and explored correlations between ASD symptoms and brain networks. RESULTS: We identified a subset exhibiting highly atypical individual-level FC, exceeding 2 standard deviation from the normative value. We also identified clinically relevant networks (mainly default mode network) at cohort level, since the outlier rates decreased with age in TD participants, but increased in those with autism. Moreover, deviations were linked to severity of repetitive behaviors and social communication symptoms. CONCLUSIONS: Individuals with ASD exhibit distinct, highly individualized trajectories of brain functional network development. In addition, distinct developmental trajectories were observed among ASD and TD individuals, suggesting that it may be challenging to identify true differences in network characteristics by comparing young children with ASD to their TD peers. This study enhances understanding of the biological heterogeneity of the disorder and can inform precision medicine.

Wanting-liking dissociation and altered dopaminergic functioning: Similarities between internet gaming disorder and tobacco use disorder.

Background: Although internet gaming disorder (IGD) has been included in the DSM-5 for approximately 10 years, debate remains regarding its existence and classification. Methods: The current research incorporated three approaches. First, implicit association tests were used to examine for potential dissociation between wanting and liking in IGD. Second, brain features in wanting and liking circuits were tested and compared with tobacco use disorder (TUD) when performing a cue-craving task to explore the neural features of wanting and liking. Third, dopaminergic systems were investigated in IGD and TUD using neuromelanin-sensitive MRI. Results: The implicit association test results supported a wanting-liking dissociation in IGD participants. Functional MRI data suggested neural correlates underlying wanting-liking dissociation in IGD and TUD participants, with positive correlations suggesting greater dissociation with increasing addiction severity. Neuromelanin results suggest dopaminergic differences in IGD and TUD relative to healthy control participants. Conclusions: A wanting-liking dissociation in IGD participants suggests gaming motivations in IGD relating to incentive sensitization rather than hedonic responses. The neuromelanin-sensitive MRI results suggest dopaminergic involvement in IGD and TUD. The findings suggest similar brain-behaviour mechanisms for IGD and TUD based on an incentive-sensitization model for addiction, having implications for potential therapeutic strategies and policy-based interventions.