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Glucose metabolism has been associated with magnitude of blood oxygen level-dependent (BOLD) signal and connectivity across subjects within the default mode and dorsal attention networks. Similar correlations within subjects across the entire brain remain unexplored. [(18)F]-fluorodeoxyglucose positron emission tomography ([(18)F]-FDG PET), [(11)C]-flumazenil PET, and resting-state functional magnetic resonance imaging (fMRI) scans were acquired in eight healthy individuals and nine with temporal lobe epilepsy (TLE). Regional metabolic rate of glucose (rMRGlu) was correlated with amplitude of low frequency fluctuations (ALFFs) in the fMRI signal, global fMRI connectivity (GC), regional homogeneity (ReHo), and gamma-aminobutyric acid A-binding potential (GABAA BP(ND)) across the brain. Partial correlations for ALFFs, GC, and ReHo with GABAA BP(ND) were calculated, controlling for rMRGlu. In healthy subjects, significant positive correlations were observed across the brain between rMRGlu and ALFF, ReHo and GABAA BP(ND), and between ALFFs and GABAA BP(ND), controlling for rMRGlu. Brain-wide correlations between rMRGlu and ALFFs were significantly lower in TLE patients, and correlations between rMRGlu and GC were significantly greater in TLE than healthy subjects. These results indicate that the glutamatergic and GABAergic systems are coupled across the healthy human brain, and that ALFF is related to glutamate use throughout the healthy human brain. TLE may be a disorder of altered long-range connectivity in association with glutamate function.

Patients with seizure disorders have an increased incidence of depression. This may be due in part to psychosocial factors; or side effects of antiepileptic drugs. However, there may be underlying physiologic mechanisms for the relationship. Neuroimaging studies, including structural magnetic resonance imaging, positron emission tomography measurements of cerebral glucose metabolism, and, more recently, imaging of serotonin 1A receptors, may provide additional data to explain overlapping clinical manifestations of epilepsy and depression.

Studies in experimental models have suggested a potential role for serotonergic transmission in epilepsy, and interest in this research has been increased by the development of positron emission tomography (PET) ligands that can be used to study 5-hydroxytryptamine (5-HT) receptors and transporters. The serotonergic system is very complex. At least 13 distinct G protein-coupled 5-HT receptors and one ligand-gated ion channel receptor (5-HT(3)) are divided into seven distinct classes (5-HT(1) to 5-HT(7)) ((1)). The receptors vary widely in their distribution and effects, innervating vascular structures and gut smooth muscle as well as neuronal tissue. Several receptor subtypes may be relevant to epilepsy.

We used serial positron emission tomography scans with [18F]2-deoxyglucose to study the effect of phenytoin on human cerebral glucose metabolism in 10 patients with seizure disorders. Local CMRglu for each patient was measured in 10 regions of interest. EEGs were performed during each procedure to match scans for state of consciousness and exclude data from scans with ictal activity. Serial scans without a drug change were performed in six control patients. Metabolic rates were significantly lower in two cortical regions while patients were taking phenytoin. No significant changes on repeat scan were seen in the control population. Measured across all regions of interest, metabolic rates were 13% higher when patients were off phenytoin (p less than 0.02).