The relationship between glucose metabolism, resting-state fMRI BOLD signal, and GABAA-binding potential: a preliminary study in healthy subjects and those with temporal lobe epilepsy

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00931619.

Figures

Figure 1

(A–E) Regional metabolic rate of glucose (rMRGlu), amplitude of low frequency functional magnetic resonance imaging fluctuation (ALFF), global connectivity (GC), regional homogeneity (ReHo), and gamma-aminobutyric acid A–binding potential (GABAA BPND), respectively, for a single subject. (F–I) Scatterplots of ALFF, GC, and GABAA BPND plotted versus rMRGlu for the same subject.

Figure 2

Scatterplots illustrating group differences in the z-transformed correlation coefficients for (A) global connectivity (GC) versus regional metabolic rate of glucose (rMRGlu); (B) amplitude of low frequncy functional magnetic resonance imaging fluctuation (ALFF) versus rMRGlu; and (C) partial correlation coefficients for ALFF versus gamma-aminobutyric acid A–binding potential (GABAA BPND), controlling for rMRGlu. Within-group correlations significantly different from zero by one sample t-test are indicated by *. P values are given for group differences.

Figure 3

Voxelwise t-maps for the regression of glucose metaboolism (rMRGlu) and gamma-aminobutyric acid A–binding potential (GABAA BPND), in (A) healthy controls and (B) subjects with temporal lobe epilepsy (TLE). Voxel-wise threshold is P<0.005 uncorrected, and only clusters surviving a Pcorr<0.05 threshold are shown.