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

Hartman, Mark E; Kantor, Michael; Thornhill, Kirsten; Reiner, Susannah L; Winn, Brad J; Kramer, Mark; Pettitt, Robert W; Kirby, Brett S · Med Sci Sports Exerc · 2025

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Abstract

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 O 2 supply relative to O 2 demand. We concomitantly measured ( n = 16 males) skeletal muscle O 2 saturation (vastus lateralis near-infrared spectroscopy (NIRS); %S m O 2 ), pulmonary O 2 uptake (V̇O 2 ), and hemoglobin (Hb) differential (∆[O 2 Hb - HHb]) as an index of PFC O 2 mismatch ( pfc O 2 ) 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). All-out exercise evoked significant changes in %S m O 2 (∆ -28.8% ± 14.1%), V̇O 2 (∆27.7% ± 10.3%), and global pfc O 2 (∆ -7.6% ± 4.8%). Decreases in regional pfc O 2 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 O 2 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 O 2 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 O 2 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%). We conclude that whole-body all-out exercise tolerance may arise from a progressive O 2 mismatch from skeletal muscle to the brain.

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