Restriction spectrum imaging reveals brain microstructural correlates of obesity risk in early childhood.

Pediatric obesity is a growing public health concern, yet the early neurobiological correlates of obesity risk remain underexplored. 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 attention-deficit/hyperactivity disorder (ADHD) and 78 typically developing (TD) peers. We focused on RSI-derived measures of restricted diffusion-specifically restricted normalized isotropic (RNI) and total (RNT) signals-as indicators of cellular density in reward and salience circuitry. Body mass index (BMI) z-score, percent body fat, waist circumference, and obesity status were assessed. Higher BMI z-score, but not other adiposity measures, was significantly associated with increased RNI in the bilateral anterior insula, nucleus accumbens (NAcc), putamen, pallidum, and hippocampus, as well as increased RNT in the right anterior insula and pallidum. Furthermore, exploratory voxelwise analyses revealed a localized pattern of altered diffusion (increased restricted and decreased hindered signal) in the left hypothalamus. Contrary to hypotheses, ADHD diagnosis did not moderate these associations, suggesting shared neural pathways linking early adiposity and brain structure independent of diagnostic status. Rather than indicating unique biological sensitivity, the specificity of findings to BMI z-score likely reflects measurement constraints of other adiposity indices in this age group. These microstructural patterns are consistent with theories of diet-related neuroinflammation, though alternative neurodevelopmental mechanisms remain plausible. Ultimately, these results demonstrate that neural signatures of obesity risk are detectable as early as preschool age, highlighting a critical developmental window for preventive intervention.