Sequential Oxygen Mismatch from Skeletal Muscle to Prefrontal Cortex Underpins the Rate of Exhaustion during All-Out Exercise

ABSTRACT – Purpose – We tested the overarching hypothesis that the expended rate of work above critical power (W′ Balance) during all-out whole-body exercise is related to a decline in prefrontal cortex (PFC) oxygenation secondary to an organized systemic outstripping of muscle O₂ supply relative to O₂ demand. Methods – We concomitantly measured (n = 16 males) skeletal muscle O₂ saturation (vastus lateralis near-infrared spectroscopy (NIRS); %S_mO₂), pulmonary O₂ uptake (V̇O₂), and hemoglobin (Hb) differential (∆[O₂Hb − HHb]) as an index of PFC O₂ mismatch (_pfcO₂) via functional NIRS bilaterally in the ventrolateral (VLPFC), dorsolateral (DLPFC), and orbitofrontal (OFC) cortices during brief all-out cycling exercise (highest instantaneous power for 3 min). Results – All-out exercise evoked significant changes in %S_mO₂ (∆ −28.8% ± 14.1%), V̇O₂ (∆27.7% ± 10.3%), and global _pfcO₂ (∆ −7.6% ± 4.8%). Decreases in regional _pfcO₂ were greater in the VLPFC (∆ −10.9 ± 6.1 μM) versus DLPFC (∆ −4.8 ± 4.5 μM) or OFC (∆ −5.9 ± 4.2 μM). Spatiotemporal analysis by O₂ measurement location revealed a steep rate of change transition phase followed by a maximal sustaining plateau, and progression of this pattern occurred sequentially first in muscle (~13 s) → pulmonary (~44 s) → PFC (~80 s). Transition phase O₂ indices were strongly correlated with the rate of W′ Balance expended (muscle, R² = 0.91; pulmonary, R² = 0.997; PFC, R² = 0.968), with crossover between regional O₂ mismatches occurring at the same %W′ Balance (end muscle = 71% vs start pulmonary = 65%, P = 0.56; end pulmonary = 26% vs start PFC = 30%, P = 0.83) and end PFC transition phase occurring at complete depletion of W′ (end PFC = −0.9%). Conclusions – We conclude that whole-body all-out exercise tolerance may arise from a progressive O₂ mismatch from skeletal muscle to the brain.