Excess BMI in early adolescence adversely impacts maturating functional circuits supporting high-level cognition and their structural correlates

Background/Objectives Adverse effects of excess BMI (affecting 1 in 5 children in the US) on brain circuits during neurodevelopmentally vulnerable periods are incompletely understood. This study investigated BMI-related alterations in maturating functional networks and their underlying brain structures, and high-level cognition in early adolescence. Subjects/Methods Cross-sectional resting-state fMRI, structural sMRI, neurocognitive task scores, and BMI from 4922 youth [median (IQR) age = 120.0 (13.0) months, 2572 females (52.25%)] from the Adolescent Brain Cognitive Development (ABCD) cohort were analyzed. Comprehensive topological and morphometric network properties were estimated from fMRI and sMRI, respectively. Cross-validated linear regression models assessed correlations with BMI. Results were reproduced across multiple fMRI datasets. Results Almost 30% of youth had excess BMI, including 736 (15.0%) with overweight and 672 (13.7%) with obesity, and statistically more Black and Hispanic compared to white, Asian and non-Hispanic youth ( p < 0.01). Those with obesity or overweight were less physically active, slept less than recommended, snored more frequently, and spent more time using an electronic device ( p < 0.01). They also had lower topological efficiency, resilience, connectivity, connectedness and clustering in Default-Mode, dorsal attention, salience, control, limbic, and reward networks ( p ≤ 0.04, Cohen’s d: 0.07-0.39). Lower cortico-thalamic efficiency and connectivity were estimated only in youth with obesity ( p < 0.01, Cohen’s d: 0.09-0.19). Both groups had lower cortical thickness, volume and white matter intensity in these networks’ constituent structures, particularly anterior cingulate, entorhinal, prefrontal, and lateral occipital cortices ( p < 0.01, Cohen’s d: 0.12-0.30), which also mediated inverse relationships between BMI and regional functional topologies. Youth with obesity or overweight had lower scores in a task measuring fluid reasoning - a core aspect of cognitive function, which were partially correlated with topological changes ( p ≤ 0.04). Conclusions Excess BMI in early adolescence may be associated with profound aberrant topological alterations in maturating functional circuits and underdeveloped brain structures that adversely impact core aspects of cognitive function.