Region-specific uncoupling of oxygen and glucose metabolism in the human cortex during visual stimulation

The brain is fueled by oxidative glucose metabolism, yet activation may uncouple oxygen and glucose consumption. Because the two have never been measured simultaneously in humans across conditions, we combined multiparametric quantitative BOLD (mqBOLD) imaging with functional PET (fPET) during rest and visual stimulation. Participants (n = 12 with complete data) were scanned on an integrated PET/MR system during alternating six-minute blocks of checkerboard stimulation and fixation, with continuous arterial sampling. Cerebral metabolic rates of oxygen (CMRO2) and glucose (CMRglc), and cerebral blood flow (CBF) were quantified per condition and combined into the oxygen-to-glucose index (OGI = CMRO2/CMRglc), where six indicates fully oxidative glucose use. At rest, OGI was 4.6-5.0 in task-responsive visual regions and 4.9 elsewhere. Stimulation increased CMRglc (12-26%) and CBF (10-22%) more than CMRO2; (3-10%, not significant), lowering OGI by 12% in metabolically defined visual regions. Beyond the visual cortex, OGI fell 8%, significantly in 47% of cortical regions. The mechanisms differed, however: glycolytic upregulation in visual cortex (CBF, CMRglc up) versus oxidative downregulation elsewhere (CBF, CMRO2; down; CMRglc unchanged). Simultaneous imaging thus shows that focal activation shifts metabolism toward glycolysis across the cortex, with consequences for interpreting metabolic contrasts outside engaged regions.