Metabolic underpinnings of activated and deactivated cortical areas in human brain

Neuroimaging with functional MRI (fMRI) identifies activated and deactivated brain regions in task-based paradigms. These patterns of (de)activation are altered in diseases, motivating research to understand their underlying biochemical/biophysical mechanisms. Essentially, it remains unknown how aerobic metabolism of glucose to lactate (aerobic glycolysis) and excitatory-inhibitory balance of glutamatergic and GABAergic neuronal activities vary in these areas. In healthy volunteers, we investigated metabolic distinctions of activating visual cortex (VC, a task-positive area) using a visual task and deactivating posterior cingulate cortex (PCC, a task-negative area) using a cognitive task. We used fMRI-guided J-edited functional MRS (fMRS) to measure lactate, glutamate plus glutamine (Glx) and γ-aminobutyric acid (GABA), as indicators of aerobic glycolysis and excitatory-inhibitory balance, respectively. Both lactate and Glx increased upon activating VC, but did not change upon deactivating PCC. Basal GABA was negatively correlated with BOLD responses in both brain areas, but during functional tasks GABA decreased in VC upon activation and GABA increased in PCC upon deactivation, suggesting BOLD responses in relation to baseline are impacted oppositely by task-induced inhibition. In summary, opposite relations between BOLD response and GABAergic inhibition, and increases in aerobic glycolysis and glutamatergic activity distinguish the BOLD response in (de)activated areas.