['Obesity and decreased physical health are linked to deficits in several cognitive domains. The broad range of cognitive problems linked to obesity suggests a global mechanism that may interfere with multiple neural systems. We examined how variation in body mass index (BMI) is associated with the microstructural integrity of fiber connections in the human brain.', 'White matter structure was measured using diffusion tensor imaging in 28 participants (mean age = 30 years) with BMI scores ranging from normal weight to obese (19.5-45.7 kg/m(2)) based on standard BMI criteria.', 'Using a whole-brain voxelwise analysis, we found that, across participants, the fractional anisotropy of white matter voxels parametrically decreased with increasing BMI (63% of white matter voxels). Midbrain and brainstem tracts were among the pathways most strongly associated with obesity (r = -0.18 to -0.33, df = 27, all p values < .05). We also observed a weaker overall diffusion signal in individuals with higher BMI than controls with normal weight (r = -0.14 to -0.71, df = 27, for 67% of fiber pathways tested, all p values < .05). After controlling for this decrease in general diffusivity, we found that decreases in fractional anisotropy stemmed from both a decrease in axial diffusivity (p < .05) and an increase in radial diffusivity (p < .05).'] Is increased body mass index associated with a global and distributed decrease in white matter microstructural integrity?