Regional balance between glutamate+glutamine and GABA+ in the resting human brain

Models of healthy brain function and psychiatric conditions assume that excitatory and inhibitory activity are balanced in the human brain at multiple spatial and temporal scales. In human neuroimaging, concentrations of the major excitatory (glutamate) and inhibitory (γ-aminobutyric acid, GABA) neurotransmitters are measured in vivo using magnetic resonance spectroscopy (MRS). However, despite the central importance of E/I balance to theories of brain function, a relationship between regional glutamate and GABA levels in the human brain has not been shown. We addressed this question in a large corpus of edited MRS data collected at 19 different sites (n = 220). Consistent with the notion of E/I balance, we found that levels of glutamate+glutamine (Glx) and GABA+ were highly correlated (R = 0.52, p = 2.86 x 10(−14)). This relationship held when controlling for site, scanner vendor, and demographics. Controlling for neurochemicals associated with neuronal density and metabolism (i.e. N-acetylaspartate and creatine) significantly reduced the correlation between GABA+ and Glx, suggesting that the levels of GABA+ and Glx may be critically linked to regional metabolism. These results are consistent with the notion that excitation and inhibition are balanced in the human brain.