Does a pharmacologically driven elevation in cerebral blood flow modulate cognition during combined hypoxic and...

Cognitive performance during environmental stress is highly variable, and the mechanisms underlying this heterogeneity remain unclear. Cerebral blood flow (CBF) has been proposed as a key determinant of neural performance during hypoxia and heat stress. However, whether experimentally increasing CBF modifies executive function during combined hypoxic and thermal stress has not been directly tested. Thirteen healthy young adults completed a randomized, double-blind, placebo-controlled crossover study. Participants ingested 1,000 mg of acetazolamide (ACZ) or a placebo (PLA) 4 h before testing. CBF was quantified from bilateral internal carotid and vertebral artery blood flow. Executive function was assessed using a Go/No-Go Flanker task during normothermia, hypoxia ([Formula: see text] ≈ 0.10), hyperthermia (+1.5°C to 2.0°C in core temperature), and combined hypoxic-hyperthermic conditions. ACZ increased CBF by ≈200 mL/min (+20% to 32%) across conditions (P < 0.05). Compared with PLA, ACZ shortened reaction time during normoxic-normothermia (-11 ms, P = 0.026) and combined hypoxic-hyperthermic exposure (-9 ms, P = 0.021). ACZ also reduced response variability during combined hypoxic-hyperthermic exposure (σ: 0.140 vs. 0.151, P = 0.041). Hyperthermia was associated with faster responses (P < 0.001), whereas hypoxia reduced response accuracy by approximately 1.5 percentage points (P = 0.027). Pharmacological augmentation of CBF modulated processing speed and response variability without improving response accuracy during environmental stress. These effects did not extend to response accuracy and were not consistently observed across environmental stress conditions, suggesting that increasing CBF alone is insufficient to preserve executive function during environmental strain.NEW & NOTEWORTHY Acetazolamide increases cerebral blood flow (CBF), but whether this perfusion "reserve" protects executive function during combined hypoxic and thermal stress is unknown. We tested cognition during normothermia, hypoxia, hyperthermia, and combined stress after acetazolamide or placebo in a randomized, double-blind crossover design. Although acetazolamide increased CBF, cognitive benefits were limited to faster, more consistent responses during normoxic-normothermic and hypoxic-hyperthermic exposures, suggesting that increasing cerebral perfusion alone is insufficient to protect executive function during environmental stress.