Dissociation of Structural and Functional Connectivity and Metabolism in the Neocortex of Idiopathic Generalized Epilepsy: A Simultaneous PET/MRI Multimodal Study

BACKGROUND AND PURPOSE: Idiopathic generalized epilepsy (IGE) accounts for approximately 20% of epilepsy cases. Characterized by generalized spike-wave discharge, IGE is increasingly recognized as a network disorder with potential metabolic underpinnings. This study leverages the advantages of simultaneous PET/MRI, which enables the concurrent acquisition of MRI and PET data, to integrate structural connectivity (SC), functional connectivity (FC), and glucose metabolism into a unified framework. This study aims to elucidate the multimodal abnormalities of the neocortex in IGE, to analyze the correlations between these abnormalities and clinical presentations, and to investigate the interactions among different imaging modalities.

MATERIALS AND METHODS: Twenty-one patients with IGE and 34 healthy controls (HCs) were recruited. Simultaneous PET/MRI scans were performed, incorporating DTI, resting-state fMRI, and [¹⁸F]FDG-PET. DTI generated a neocortical connectivity blueprint, while resting-state fMRI provided a whole-brain connectivity matrix. [¹⁸F]FDG-PET data were processed to obtain standardized uptake value ratios (SUVRs). Multivariate distance matrix regression was used to identify abnormal neocortical regions in SC and FC. Differences in SUVRs were identified by using least absolute shrinkage and selection operator regression. Statistical analyses, including t tests, linear models, mediation analysis, and Pearson correlations, were conducted to compare values of each technique between groups and explore relationships with clinical features.

RESULTS: SC abnormalities were primarily found in the limbic (40% of all abnormal neocortical regions) and visual networks (31%), while FC abnormalities were mostly in the default mode network (DMN, 45%). Metabolic abnormalities were predominantly in the frontoparietal (26%) and somatomotor (22%) networks. SC in the limbic was positively correlated with onset age, while seizure frequency was negative correlated with DMN FC and positively correlated with frontoparietal metabolism. Mediation analysis showed that DMN FC mediated the relationship between limbic SC and frontoparietal and somatomotor metabolism.

CONCLUSIONS: A multimodal approach reveals distinct and interrelated abnormalities in IGE, with different modalities reflecting various aspects of the disease, thus enhancing our understanding of its complex mechanisms. This integrative analysis could inform more effective treatments.