Convergent functional, white-matter microstructural, and cerebral perfusion abnormalities in overweight and obese adults: a multimodal MRI study

Abstract

Background Obesity affects the brain, but most neuroimaging studies examine a single modality, leaving it unclear whether obesity-related functional, microstructural, and perfusion abnormalities co-localize. We combined three modalities across the normal-weight–overweight–obese spectrum. Methods Of 80 adults enrolled, 10 were excluded (sleep, incomplete acquisition, artifacts), leaving 70 (normal-weight, n = 27; overweight, n = 21; obese, n = 22), who did not differ in age, sex, or education. All underwent resting-state functional MRI, diffusion tensor imaging, and 3D arterial spin labeling at 3.0 T, yielding amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), functional connectivity (FC), fractional anisotropy (FA), mean (MD), axial, and radial diffusivity (RD), and cerebral blood flow (CBF). Group differences were assessed with covariate-adjusted models; diffusion metrics were tested across all 48 atlas regions with false-discovery-rate (FDR) correction, and body mass index (BMI) relationships by whole-sample regression without prior region selection. Spatial convergence was tested by minimum-statistic conjunction and random-displacement permutation. Results Obese participants showed lower ALFF than controls in the cerebellar posterior lobe (vermis, left lobule VIII, right Crus II) and left superior frontal gyrus, higher ALFF in the bilateral parahippocampal gyri, lower ReHo in the left superior frontal gyrus, and lower ReHo than overweight participants in the left middle cingulate gyrus. No regional diffusion difference survived FDR correction, but BMI predicted FA, MD, and RD in the right inferior cerebellar peduncle in whole-sample regression (all q < 0.015), the only associations to survive. CBF was reduced in the cerebellar posterior lobe and increased in the left inferior frontal and right postcentral gyri. ALFF–CBF overlap there exceeded chance at every threshold, reaching 43.1-fold at P < 0.001, confirmed by conjunction and permutation (P = 0.0002–0.0008); peak-level in the left lobule VIII and right Crus II, but atlas-level only at the vermis. FC showed no group differences. Conclusion Overweight and obesity are associated with spatially convergent functional, microstructural, and perfusion abnormalities preferentially involving cerebellar and cortico-limbic regions, scaling continuously with BMI in the right inferior cerebellar peduncle. Because cognition was assessed only by the MMSE, these roles suggest hypotheses rather than conclusions about cognition.