Altered coupling between resting-state glucose metabolism and functional activity in epilepsy

Abstract

Objective: Altered functional activities and hypometabolism have been found in medial temporal lobe epilepsy patients with hippocampal sclerosis (mTLE-HS). Hybrid PET/MR scanners provide opportunities to explore the relationship between resting-state energy consumption and functional activities, but whether repeated seizures disturb the bioenergetic coupling and its relationship with seizure outcomes remain unknown.

Methods: ¹⁸ F-FDG PET and resting-state functional MRI (rs-fMRI) scans were performed with hybrid PET/MR in 26 patients with mTLE-HS and in healthy controls. Energy consumption was quantified by ¹⁸ F-FDG standardized uptake value ratio(SUVR) relative to cerebellum. Spontaneous neural activities were estimated using regional homogeneity (ReHo), fractional amplitude of low frequency fluctuations (fALFF) from rs-fMRI. Between-group differences in SUVR and rs-fMRI derived metrics were evaluated by two-sample t test. Voxel-wise spatial correlations were explored between SUVR and ReHo, fALFF across gray matter and compared between groups. Furthermore, the relationships between altered fALFF/SUVR and ReHo/SUVR coupling and surgical outcomes were evaluated.

Results: Both the patients and healthy controls showed significant positive correlations between SUVR and rs-fMRI metrics. Spatial correlations between SUVR and fMRI-derived metrics across gray matter were significantly higher in patients with mTLE-HS compared with healthy controls (fALFF/SUVR, P < 0.001; ReHo/SUVR, P = 0.022). Higher fALFF/SUVR couplings were found in patients who had Engel class IA after surgery than all other (P = 0.025), while altered ReHo/SUVR couplings (P = 0.097) were not.

Conclusion: These findings demonstrated altered bioenergetic coupling across gray matter and its relationship with seizure outcomes, which may provide novel insights into pathogenesis of mTLE-HS and potential biomarkers for epilepsy surgery planning.