ObjectiveTo investigate the relationship between glucose metabolism and functional activity in the epileptogenic network of patients with mesial temporal lobe epilepsy (MTLE) and to determine whether this relationship is associated with surgical outcomes.Methods18F-FDG PET and resting-state functional MRI (rs-fMRI) scans were performed on a hybrid PET/MR scanner in 38 MTLE patients with hippocampal sclerosis (MR-HS), 35 MR-negative patients and 34 healthy controls (HC). Glucose metabolism was measured using18F-FDG PET standardized uptake value ratio (SUVR) relative to cerebellum; Functional activity was obtained by fractional amplitude of low-frequency fluctuation (fALFF). The betweenness centrality (BC) of metabolic covariance network and functional network were calculated using graph theoretical analysis. Differences in SUVR, fALFF, BC and the spatial voxel-wise SUVR-fALFF couplings of the epileptogenic network, consisting of default mode network (DMN) and thalamus, were evaluated by Mann-Whitney U test (using the false discovery rate [FDR] for multiple comparison correction). The top ten SUVR-fALFF couplings were selected by Fisher score to predict surgical outcomes using logistic regression model.ResultsThe results showed decreased SUVR-fALFF coupling in the bilateral middle frontal gyrus (PFDR= 0.0230,PFDR= 0.0296) in MR-HS patients compared to healthy controls. Coupling in the ipsilateral hippocampus was marginally increased (PFDR= 0.0802) in MR-HS patients along with decreased BC of metabolic covariance network and functional network (PFDR= 0.0152;PFDR= 0.0429). With Fisher score ranking, the top ten SUVR-fALFF couplings in regions from DMN and thalamic subnuclei could predict surgical outcomes with the best performance being a combination of ten SUVR-fALFF couplings with an AUC of 0.914.ConclusionThese findings suggest that the altered neuroenergetic coupling in the epileptogenic network is associated with surgical outcomes of MTLE patients, which may provide insight into their pathogenesis and help with preoperative evaluation.