Thalamus-driven cortical and subcortical maturation trajectories from childhood to adolescence

Thalamo-cortical projections are formed during late embryonic development and are crucial for the maturation of cortical layers. Abnormalities in thalamic development have been implicated in atypical brain maturation and psychiatric vulnerability more broadly. Cross-sectional and longitudinal studies in large population-based and clinical samples suggest that thalamic volume in childhood is not static but dynamically related to later cortical development (Boedhoe et al., 2017; Weeland et al., 2022). Specifically, larger thalamic volume in childhood has been linked to a flatter trajectory of cortical thinning during adolescence, pointing to the thalamus as an early marker of altered neurodevelopment (Weeland et al., 2024). Leveraging longitudinal structural MRI data from the population-based Generation R cohort, a large prospective study with repeated neuroimaging assessments spanning mid-childhood through late adolescence, this study investigates whether normative deviations in thalamic volume at approximately 10 years of age are associated with altered developmental trajectories of cortical thickness, cortical surface area, and subcortical volumes across adolescence (ages ~10, 14, and 18 years). By adopting a normative modeling framework to quantify individual deviations from age-expected brain structure relative to a large reference population (Rutherford et al., 2022), and by using repeated-measures analyses, the project aims to clarify how early thalamic atypicality relates to downstream brain maturation during a critical developmental period.