Identifying Microstructural Signatures of Brain Vulnerability in Early Development: A Multimodal Imaging Approach

• Applicant: Dr. Clara Weber
• Subject Area: Biological Psychiatry ; Human Cognitive and Systems Neuroscience
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 566655780

Throughout neurodevelopment, cognitive processing becomes increasingly organized along a central sensory-association axis. The microscale mechanisms contributing to refined hierarchical patterns are highly susceptible to internal and external stressors. Autism and hypoxia-related injuries like ischemic stroke and hypoxic-ischemic encephalopathy (HIE) affect brain maturation in distinct ways, but show similar connectome disruptions and developmental atypicality. Recent literature reports highlight increased autism prevalence in early stroke survivors, suggesting a potential mechanistic link between these conditions. I hypothesize that common patterns of vulnerability in early neurodevelopment anchor in perturbations along a sensory-association axis across etiologies. Underlying molecular profiles of early atypical neurodevelopment remain poorly understood to date. This project aims to identify common biomolecular signatures of brain vulnerability by integrating macro- and microscale data in a system-level framework. Specifically, this project aims to (i) characterize the spatial distribution of hypoxic lesions vis-à-vis cortical imaging marker changes in autism, and describe their location on hierarchical axes of brain organization; (ii) identify underlying transcriptomic, histologic, and receptor expression patterns as a common microscale signature of vulnerability in early neurodevelopment; and (iii) describe developmental trajectories by determining changes in macroscale cortical markers and communication efficiency measures over time. I aim to study neurodevelopmental vulnerability by understanding how disrupted neurodevelopment affects unfolding of sensory-association hierarchical processing patterns. In a computational approach, I will integrate multimodal neuroimaging and microstructural data to contextualize findings along this trajectory. Leveraging open data repositories containing data from typically developing neonates, children, and adults and data from autistic individuals and neonates after HIE and pediatric stroke, I will delineate changes using manual segmentation and surface-wide computational models. Heatmaps of developmental injury or atypicality will then be contextualized to organizational networks, histologic profiles, receptor density and gene expression atlases, with additional information leveraged from endothelial cell- and development-specific genetic atlases. By integrating multimodal imaging with cellular and transcriptomic data, this study bridges external neurological injury and neuropsychiatric outcomes through a combination of macro- and microscale perspectives on brain development. Findings will reveal shared molecular patterns of neurodevelopmental atypicality while potentially highlighting mechanistic differences that refine the understanding of syndromal versus idiopathic autism and the long-term impact of minor injuries, contributing to improved clinical guidelines for timely diagnosis and intervention.

• DFG Programme: WBP Position