Parsing altered brain connectivity in neurodevelopmental disorders by integrating graph-based normative modeling and deep generative networks

Divergent brain connectivity is thought to underlie the behavioral and cognitive symptoms observed in many neurodevelopmental disorders. Quantifying divergence from neurotypical connectivity patterns offers a promising pathway to inform diagnosis and therapeutic interventions. While advanced neuroimaging techniques, such as diffusion MRI (dMRI), have facilitated the mapping of brain's structural connectome, the challenge lies in accurately modeling developmental trajectories within these complex networked structures to create robust neurodivergence markers. In this work, we present the Brain Representation via Individualized Deep Generative Embedding (BRIDGE) framework, which integrates normative modeling with a bio-inspired deep generative model to create a reference trajectory of connectivity transformation as part of neurotypical development. This will enable the assessment of neurodivergence by comparing individuals to the established neurotypical trajectory. BRIDGE provides a global neurodivergence score based on the difference between connectivity-based brain age and chronological age, along with region-wise neurodivergence maps that highlight localized connectivity differences. Application of BRIDGE to a large cohort of children with autism spectrum disorder demonstrates that the global neurodivergence score correlates with clinical assessments in autism, and the regional map offers insights into the heterogeneity at the individual level in neurodevelopmental disorders. Together, the neurodivergence score and map form powerful tools for quantifying developmental divergence in connectivity patterns, advancing the development of imaging markers for personalized diagnosis and intervention in various clinical contexts.