Do mean values tell the full story? Cardiac cycle and biological sex comparisons in temporally derived neurovascular coupling metrics

Previous reports have noted cerebrovascular regulation differs across the cardiac cycle, with greater regulation occurring within systole. However, this methodological notion has not been meticulously scrutinized during temporally deduced neurovascular coupling (NVC) metrics with additional respect to biological sex. Analyses of 111 healthy individuals (40 females/71 males) were performed where participants engaged in the "Where's Waldo?" paradigm. All NVC parameters were quantified in the posterior and middle cerebral arteries at 310 unique timepoints. Several individuals completed repeat testing which enabled for betweenday (3 timepoints) and within-day (7 timepoints) reliability comparisons in 17 and 11 individuals, respectively. One-way analysis of variance compared NVC metrics between diastole, mean, and systole values, as well as differences between biological sexes. Greater absolute cerebral blood velocity (CBv; baseline and peak) and total activation (area under the curve) were noted within systole for both posterior cerebral artery (PCA; P < 0.001) and middle cerebral artery (MCA; P < 0.001) values; however, the relative percent increase in CBv was greater within diastole (P < 0.001). Females had an elevated diastolic and mean CBv and a greater diastolic cerebrovascular conductance (P < 0.050). No sex differences were present for systolic CBv measures and within parameters quantifying the NVC response (area under the curve/relative CBv increase) across the cardiac cycle (P > 0.072). Future investigations seeking to differentiate cerebral regulatory mechanisms between clinical populations may benefit by performing their analyses across the cardiac cycle, as certain pathogenesis may affect one aspect of the cardiac cycle independently. Minimal differences were noted between females and males for metrics characterizing the NVC response across the cardiac cycle. NEW & NOTEWORTHY Neurovascular coupling (NVC) studies commonly assess the mean cerebral hemodynamic response with little consideration for diastole, systole, and biological sex. Greater total activation expressed as the area under the curve was seen within systole compared with mean and diastole. Resting cerebral blood velocity sex differences were more prevalent during diastole when the cerebrovasculature was pressure-passive. Future studies should assess the NVC response across the cardiac cycle as it may help delineate the underlying pathophysiology of various clinical populations.