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.

Figure 1.

Baseline cerebral blood velocities (cm/s) obtained from participants’ posterior cerebral artery (PCA) and middle cerebral artery (MCA) across the cardiac cycle during a “Where's Waldo” neurovascular coupling (NVC) challenge. The NVC challenge was performed under three separate conditions: hypocapnia, eucapnia, and hypercapnia. The data are categorized by sex, with females represented in red (n = 10) and males in black (n = 10). The Phi symbol (Φ) indicates a stage significantly different from the eucapnia stage, determined by linear regressions with stages (eucapnia as reference) and sex (female as reference) predictor variables. The Psi (Ψ) highlights sex differences observed across the three stages (hypocapnia, eucapnia, hypercapnia).

Figure 2.

Peak cerebral blood velocities (cm/s) obtained from participants’ posterior cerebral artery (PCA) and middle cerebral artery (MCA) across the cardiac cycle during a “Where's Waldo” neurovascular coupling (NVC) challenge. The NVC challenge was performed under three separate conditions: hypocapnia, eucapnia, and hypercapnia. The data are categorized by sex, with females represented in red (n = 10) and males in black (n = 10). The Phi symbol (Φ) indicates a stage significantly different from the eucapnia stage, determined by linear regressions with stages (eucapnia as reference) and sex (female as reference) predictor variables. The Psi (Ψ) highlights sex differences observed across the three stages (hypocapnia, eucapnia, hypercapnia).

Figure 3.

Relative increase (%) obtained from participants’ posterior cerebral artery (PCA) and middle cerebral artery (MCA) across the cardiac cycle during a “Where's Waldo” neurovascular coupling (NVC) challenge. The NVC challenge was performed under three separate conditions: hypocapnia, eucapnia, and hypercapnia. The data are categorized by sex, with females represented in red (n = 10) and males in black (n = 10). The Phi symbol (Φ) indicates a stage significantly different from the eucapnia stage, determined by linear regressions with stages (eucapnia as reference) and sex (female as reference) predictor variables. The Psi (Ψ) highlights sex differences observed across the three stages (hypocapnia, eucapnia, hypercapnia).

Figure 4.

Area under the curve during 30 seconds of task engagement (AUC30) obtained from participants’ posterior cerebral artery (PCA) and middle cerebral artery (MCA) across the cardiac cycle during a “Where's Waldo” neurovascular coupling (NVC) challenge. The NVC challenge was performed under three separate conditions: hypocapnia, eucapnia, and hypercapnia. The data are categorized by sex, with females represented in red (n = 10) and males in black (n = 10). The Phi symbol (Φ) indicates a stage significantly different from the eucapnia stage, determined by linear regressions with stages (eucapnia as reference) and sex (female as reference) predictor variables. The Psi (Ψ) highlights sex differences observed across the three stages (hypocapnia, eucapnia, hypercapnia).