Brain Microstructure and Obesity Risk in Early Childhood: Insights from Restriction Spectrum Imaging.

Pediatric obesity is a growing public health concern, yet little is known about the neurobiological underpinnings of obesity risk in early childhood. Using restriction spectrum imaging (RSI), we examined associations between adiposity and brain microstructure in a cross-sectional sample of 159 children aged 4-7 years, including 81 with ADHD and 78 typically developing (TD) peers. We focused on RSI-derived measures of restricted diffusion-specifically restricted normalized isotropic (RNI), directional (RND), and total (RNT) signals-as indicators of cellular density in subcortical and cortical regions implicated in reward and salience processing. Body mass index (BMI), percent body fat, waist circumference, and obesity status were assessed. Higher BMI, but not other adiposity measures, was significantly associated with increased RNI in the right insula, nucleus accumbens (NAcc), and putamen, as well as increased RNT in the right insula and pallidum. These findings suggest early microstructural alterations in reward-related circuits, consistent with theories of diet-related neuroinflammation. Contrary to hypotheses, ADHD diagnosis did not moderate the associations, and anthropometric profiles were similar between groups. This suggests a shared neural pathway linking early adiposity and brain structure, independent of diagnostic status. Our findings replicate and extend prior work in older children, highlighting BMI as the most sensitive marker of obesity-related brain differences in early childhood. These results underscore the potential of RSI as a tool for identifying early neural risk markers of obesity and inform future efforts to design preventive interventions during critical developmental windows.