Hypocapnia, eucapnia and hypercapnia during "Where's Waldo" search paradigms: Neurovascular coupling across the cardiac cycle and biological sexes

Abstract

This investigation explored the impact of partial pressure of end-tidal carbon dioxide (P_ETCO₂) alterations on temporal neurovascular coupling (NVC) responses across the cardiac cycle and the influence of biological sex via a complex visual scene-search task ("Where's Waldo?"). 10 females and 10 males completed five puzzles, each with 40 seconds of eyes open and 20 seconds of eyes closed, under P_ETCO₂ clamped at ∼40 mmHg (eucapnia), ∼55 mmHg (hypercapnia), and ∼25 mmHg (hypocapnia). Cerebral blood velocity (CBv) in the middle and posterior cerebral arteries (MCAv, PCAv) were measured via Transcranial Doppler ultrasound. Linear mixed-effects models with participants as a random effect analyzed NVC metrics, including baseline and peak CBv, relative increase, and area-under-the-curve (AUC30). During hypercapnic trials, reductions in PCAv and MCAv AUC30 were noted across the cardiac cycle (all p < 0.001). Hypocapnic PCAv AUC30 was reduced (all p < 0.012), as was systolic MCAv AUC30 (p = 0.003). Females displayed greater baseline PCA diastole (p = 0.048). No other biological sex differences were observed across conditions in baseline (all p > 0.050), peak (all p > 0.054), relative increase (all p > 0.511), and AUC30 metrics (all p > 0.514). Despite differences in responses to hypercapnic and hypocapnic stimuli, NVC responses to complex visual tasks remain robust, across the physiological CO₂ range.

Keywords: Biological sex differences; cerebral blood velocity; hypercapnia; hypocapnia; neurovascular coupling.