Background: Autism spectrum disorder (ASD) is a heritable condition related to brain development that affects a person’s perception and socialization with others. Here, we examined variability in the brain morphology in ASD children and adolescent individuals at the level of brain cortical structural profiles and the level of each brain regional measure. Methods: We selected brain structural MRI data in 600 ASDs and 729 normal controls (NCs) from Autism Brain Imaging Data Exchange (ABIDE). The personalized estimate of similarity between gray matter volume (GMV) profiles of an individual to that of others in the same group was assessed by using the person-based similarity index (PBSI). Regional contributions to PBSI score were utilized for brain age gap estimation (BrainAGE) prediction model establishment, including support vector regression (SVR), relevance vector regression (RVR), and Gaussian process regression (GPR). The association between BrainAGE prediction in ASD and clinical performance was investigated. We further explored the related inter‐regional profiles of gene expression from the Allen Human Brain Atlas with variability differences in the brain morphology between groups. Results: The PBSI score of GMV was negatively related to age regardless of the sample group, and the PBSI score was significantly lower in ASDs than in NCs. The regional contributions to the PBSI score of 126 brain regions in ASDs showed significant differences compared to NCs. RVR model achieved the best performance for predicting brain age. Higher inter-individual brain morphology variability was related to increased brain age, specific to communication symptoms. A total of 430 genes belonging to various pathways were identified as associated with brain cortical morphometric variation. The pathways, including short-term memory, regulation of system process, and regulation of nervous system process, were dominated mainly by gene sets for manno midbrain neurotypes. Limitations: There is a sample mismatch between the gene expression data and brain imaging data from ABIDE. A larger sample size can contribute to the model training of BrainAGE and the validation of the results. Conclusions: ASD has personalized heterogeneity brain morphology. The brain age gap estimation and transcription-neuroimaging associations derived from this trait are replenished in an additional direction to boost the understanding of the ASD brain.

Approximately 36% of patients with neuromyelitis optica spectrum disorders (NMOSD) suffer from severe visual and motor disability (blindness or light perception or unable to walk) with abnormalities of whole-brain functional networks. However, it remains unclear how whole-brain functional networks and their dynamic properties are related to clinical disability in patients with NMOSD. Our study recruited 30 NMOSD patients (37.70 ± 11.99 years) and 45 healthy controls (HC, 41.84 ± 11.23 years). The independent component analysis, sliding-window approach and graph theory analysis were used to explore the static strength, time-varying and topological properties of large-scale functional networks and their associations with disability in NMOSD. Compared to HC, NMOSD patients showed significant alterations in dynamic networks rather than static networks. Specifically, NMOSD patients showed increased occurrence (fractional occupancy; P < 0.001) and more dwell times of the low-connectivity state (P < 0.001) with fewer transitions (P = 0.028) between states than HC, and higher fractional occupancy, increased dwell times of the low-connectivity state and lower transitions were related to more severe disability. Moreover, NMOSD patients exhibited altered small-worldness, decreased degree centrality and reduced clustering coefficients of hub nodes in dynamic networks, related to clinical disability. NMOSD patients exhibited higher occurrence and more dwell time in low-connectivity states, along with fewer transitions between states and decreased topological organizations, revealing the disrupted communication and coordination among brain networks over time. Our findings could provide new perspective to help us better understand the neuropathological mechanism of the clinical disability in NMOSD.