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

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 ("<i>Where's Waldo?</i>"). 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 <i>p < 0.001</i>). Hypocapnic PCAv AUC30 was reduced (all <i>p < 0.012</i>), as was systolic MCAv AUC30 (<i>p = 0.003</i>). Females displayed greater baseline PCA diastole (<i>p = 0.048</i>). No other biological sex differences were observed across conditions in baseline (all <i>p > 0.050</i>), peak (all <i>p</i> > <i>0.054</i>), relative increase (all <i>p > 0.511</i>), and AUC30 metrics (all <i>p > 0.514</i>). Despite differences in responses to hypercapnic and hypocapnic stimuli, NVC responses to complex visual tasks remain robust, across the physiological CO₂ range.