γ-Aminobutyric acid (GABA) concentration inversely correlates with basal perfusion in human occipital lobe

Commonly used neuroimaging approaches in humans exploit hemodynamic or metabolic indicators of brain function. However, fundamental gaps remain in our ability to relate such henno-metabolic reactivity to neurotransmission, with recent reports providing paradoxical information regarding the relationship among basal perfusion, functional imaging contrast, and neurotransmission in awake humans. Here, sequential magnetic resonance spectroscopy (MRS) measurements of the primary Inhibitory neurotransmitter, y-aminobutyric add (GABA + macromolecules normalized by the complex N-acetyl aspartate-N-acetyl aspartyl glutamic add: [GABA]/[NAA NAAG]), and magnetic resonance imaging (MRI) measurements of perfusion, fractional gray-matter volume, and arterial arrival time (AAT) are recorded in human visual cortex from a controlled cohort of young adult male volunteers with neurocognitive battery-confirmed comparable cognitive capacity (3T; n=16; age= 23 +/- 3 years). Regression analyses reveal an inverse correlation between [GABA+1/[NAA NAAGj and perfusion (R= 0.46; P=0.037), yet no relationship between MT and [GABA(+)NNAA NAAG1 (R= 0.12; P=0.33). Perfusion measurements that do not control for AAT variations reveal reduced correlations between [GABA(+)]/{NAA NAAG1 and perfusion (R= 0.13; P=0.32). These findings largely reconcile contradictory reports between perfusion and inhibitory tone, and underscore the physiologic origins of the growing literature relating functional imaging signals, hemodynamics, and neurotransmission.