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 (ΔMCAv_T/ΔMAP_T and RelMCAv_T/RelMAP_T). 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, ΔMCAv_T/ΔMAP_T showed neither a MAP direction effect (P = 0.0714) nor a biological sex effect (P = 0.0629). RelMCAv_T/RelMAP_T showed a MAP direction effect (P = 0.0405) but no biological sex effect. At ∼0.10 Hz, ΔMCAv_T/ΔMAP_T 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 ΔMCAv_T/ΔMAP_T^INCREASE was lower than ΔMCAv_T/ΔMAP_T^DECREASE 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 ΔMCAv_T/ΔMAP_T, at ∼0.10-Hz OLBNP. We also provide evidence of a hysteresis-like pattern at ∼0.05-Hz OLBNP through the application of our RelMCAv_T/RelMAP_T metric. Together, these results underscore the importance of accounting for biological sex and employing a multimetric analytical approach when investigating dynamic cerebral autoregulation.