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

## TL;DR

This study uses [18F]FDG microPET to examine brain metabolic networks in a mouse model of autism, finding patterns similar to those observed in human ASD.

## Contribution

The study introduces FDG-derived metabolic covariance networks as a novel approach to investigate ASD-related brain alterations in a mouse model.

## Key findings

- C58/J mice showed higher clustering and local cohesion in metabolic networks compared to controls.
- Olfactory bulb, hippocampus, and hypothalamus had reduced nodal degree in C58/J mice.
- Motor-related regions showed increased connectivity in C58/J mice, aligning with ASD metabolic patterns.

## Abstract

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.

The online version contains supplementary material available at 10.1007/s00429-026-03087-8.