Biological sex modulates dynamic cerebral autoregulation and its directional sensitivity.

Dynamic cerebral autoregulation (dCA) exhibits directional sensitivity, characterized by greater buffering capacity of cerebral blood flow when mean arterial pressure (MAP) increases than when MAP decreases. Although dCA is known to differ between sexes, it remains unclear whether its hysteresis-like pattern is sex-dependent. In 35 healthy participants (17 females and 18 males; age: 29 ± 7 yr), we assessed the influence of sex on dCA and its directional sensitivity. Participants underwent 7 min of oscillatory lower body negative pressure (OLBNP) at ∼0.05 Hz (20-s cycles) and ∼0.10 Hz (10-s cycles) while middle cerebral artery mean blood velocity (MCAv) and MAP were recorded. dCA was quantified using transfer function analysis (TFA), and absolute and relative directional sensitivity was assessed using time-corrected ratios of MCAv to MAP changes (ΔMCAvT/ΔMAPT and RelMCAvT/RelMAPT). TFA metrics did not differ between sexes at either oscillation frequency except TFA phase at ∼0.10 Hz OLBNP, which was higher in females (1.14 ± 0.38 vs. 0.85 ± 0.35 rad; P = 0.0431). At ∼0.05-Hz OLBNP, ΔMCAvT/ΔMAPT showed neither a MAP direction effect (P = 0.0714) nor a biological sex effect (P = 0.0629). RelMCAvT/RelMAPT showed a MAP direction effect (P = 0.0405) but no biological sex effect. At ∼0.10 Hz, ΔMCAvT/ΔMAPT demonstrated significant effects of MAP direction (P < 0.0001), biological sex (P = 0.0150), and their interaction (P = 0.0075). Post hoc analysis revealed that ΔMCAvT/ΔMAPTINCREASE was lower than ΔMCAvT/ΔMAPTDECREASE in females only. These findings indicate that females exhibit better dCA and greater directional sensitivity at ∼0.10-Hz OLBNP.NEW & NOTEWORTHY The novel finding of this study is that females exhibit improved dynamic cerebral autoregulation and demonstrate greater directional sensitivity when assessed using ΔMCAvT/ΔMAPT, at ∼0.10-Hz OLBNP. We also provide evidence of a hysteresis-like pattern at ∼0.05-Hz OLBNP through the application of our RelMCAvT/RelMAPT metric. Together, these results underscore the importance of accounting for biological sex and employing a multimetric analytical approach when investigating dynamic cerebral autoregulation.