GABA, resting-state connectivity and the developing brain.

ABSTRACT

BACKGROUND: Preclinical data demonstrate that gamma-aminobutyric acid (GABA) interneurons initiate connectivity in the developing brain. OBJECTIVES: The goal of this study was to compare GABA concentration and its relationship to functional connectivity in the brains of term and preterm infants at term-equivalent age. METHODS: Infants received both magnetic resonance spectroscopy (MRS) and functional magnetic resonance imaging (fMRI) scans at term-equivalent age. Whole brain functional connectivity MRI data using intrinsic connectivity distribution maps were compared to identify areas with differences in resting-state functional connectivity between the preterm and term control groups. MRS measured concentrations of GABA, glutamate, N-acetyl-aspartate (NAA) and choline; NAA/choline was then calculated for comparison between the 2 groups. RESULTS: Preterm infants had lower right frontal GABA and glutamate concentrations than term controls and showed a significantly different relationship between connectivity and GABA concentration in the right frontal lobe. Preterm infants had a positive correlation between GABA concentration and connectivity, while term controls demonstrated a negative correlation between these two developmentally regulated parameters. CONCLUSION: These results suggest that regional GABA concentrations are associated with normal and altered neonatal resting-state connectivity.