[18F]FDG metabolic brain network in C58/J strain: an autism murine model

Autism spectrum disorder (ASD) is associated with atypical brain network organization. Functional connectivity has been extensively studied using fMRI, which often reports reduced long-range connectivity alongside local hyperconnectivity. However, BOLD-based connectivity reflects neurovascular coupling and therefore provides an indirect estimate of neuronal activity. Complementary information may be obtained from [18F]FDG microPET, which quantifies regional glucose uptake—an index of synaptic energy demand integrated over minutes—although FDG-derived network organization has been scarcely examined in ASD. Here, “metabolic connectivity” refers to between-subject covariance in regional [18F]FDG uptake (group-level metabolic covariance networks), not within-subject temporal coupling as in BOLD-fMRI functional connectivity. We tested whether the C58/J mouse strain—an ASD-relevant model with social deficits and repetitive behaviors—recapitulates ASD-relevant metabolic network-level alterations. Using [18F]FDG microPET, we constructed ROI-wise metabolic covariance networks by correlating uptake values across animals and compared C58/J mice with C57BL/6 controls. The C58/J network exhibited higher clustering and a more locally cohesive organization than the C57BL/6 network. Nodal degree/edge density was reduced in the olfactory bulb, hippocampus, and hypothalamus. In contrast, the motor-related regions—including the striatum, brainstem, and superior and inferior colliculi—showed a higher degree/denser covariance. These findings suggest that C58/J mice display FDG-derived metabolic covariance network features qualitatively consistent with those reported in ASD FDG-PET studies, supporting this strain as a tool to investigate ASD-relevant pathophysiological mechanisms and to evaluate candidate interventions.