Neurodevelopmental Plasticity as a Window into Youth Mental Health Vulnerability

• Applicant: Dr. Meike Hettwer
• Subject Area: Biological Psychiatry
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 572317568

Mental health challenges often emerge during adolescence, a period of marked brain network refinement and heightened susceptibility to environmental influences. This elevated susceptibility has been linked to the prolonged malleability, i.e., plasticity, of the association cortex. Adversity exposure, such as abuse, neglect, or trauma, may disrupt brain development and shape mental health outcomes, particularly when it coincides with periods of heightened plasticity. Understanding when and where the brain is most plastic is thus key to identifying both periods of increased vulnerability and opportunities for targeted intervention. This project aims to chart the spatiotemporal progression of plasticity across the cortex and to investigate how its disruption by adversity may confer risk for mental illness. The first work package (WP1) will aggregate large-scale neuroimaging datasets (N > 7,000 individuals) to establish normative developmental charts of cortical plasticity. Plasticity will be indexed using the amplitude of low-frequency fluctuations (ALFF), a non-invasive fMRI marker recently validated as a correlate of neuroplasticity in animals and humans. WP1 will model regional ALFF trajectories across development and release the resulting human plasticity charts as a public resource. A multimodal extension will further examine whether these plasticity trajectories are constrained by intracortical myelination - a biological plasticity regulator - across three cortical depths. The second work package (WP2) will investigate whether individuals exposed to adversity show deviations from normative plasticity development. I will first apply multivariate analyses to identify plasticity patterns associated with experiences of abuse, neglect, or trauma. I will then test whether these deviation patterns predict mental health symptoms, focusing on transdiagnostic dimensions of psychopathology. Together, this project aims to elucidate the timing and spatial progression of cortical plasticity during human development and its association with youth mental health vulnerability. These insights may pave the way for neurodevelopmentally informed interventions that are tailored to individuals’ plasticity profiles to enhance effectiveness and risk mitigation. The project will be conducted under the mentorship of Prof. Dr. Satterthwaite, a leading expert in developmental psychopathology and neuroplasticity, at the University of Pennsylvania, USA. It will deepen my expertise in psychiatric neuroimaging while training me in big data integration, normative modeling, multivariate brain-behavior analysis, and open science practices. In addition to expanding my international network, this fellowship will lay the conceptual and technical foundation for my transition to academic independence and the future establishment of my own research group.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Ted Satterthwaite