Variation within the visually evoked neurovascular coupling response of the posterior cerebral artery is not influenced by age or sex

Abstract

Neurovascular coupling (NVC) is the temporal and spatial coordination between local neuronal activity and regional cerebral blood flow. The literature is unsettled on whether age and/or sex affect NVC, which may relate to differences in methodology and the quantification of NVC in small sample-sized studies. The aim of this study was to 1) determine the relative and combined contribution of age and sex to the variation observed across several distinct NVC metrics (n = 125, 21-66 yr; 41 males) and 2) present an approach for the comprehensive systematic assessment of the NVC response using transcranial Doppler ultrasound. NVC was measured as the relative change from baseline (absolute and percent change) assessing peak, mean, and total area under the curve (tAUC) of cerebral blood velocity through the posterior cerebral artery (PCAv) during intermittent photic stimulation. In addition, the NVC waveform was compartmentalized into distinct regions, acute (0-9 s), mid (10-19 s), and late (20-30 s), following the onset of photic stimulation. Hierarchical multiple regression modeling was used to determine the extent of variation within each NVC metric attributable to demographic differences in age and sex. After controlling for differences in baseline PCAv, the R² data suggest that 1.6%, 6.1%, 1.1%, 3.4%, 2.5%, and 4.2% of the variance observed within mean, peak, tAUC, acute, mid, and late response magnitude is attributable to the combination of age and sex. Our study reveals that variability in NVC response magnitude is independent of age and sex in healthy human participants, aged 21-66 yr.NEW & NOTEWORTHY We assessed the variability within the neurovascular coupling response attributable to age and sex (n = 125, 21-66 yr; 41 male). Based on the assessment of posterior cerebral artery responses to visual stimulation, 0%-6% of the variance observed within several metrics of NVC response magnitude are attributable to the combination of age and sex. Therefore, observed differences between age groups and/or sexes are likely a result of other physiological factors.

Keywords: aging; cerebral blood flow; neurovascular coupling; sex.

Graphical abstract

Figure 1.

Group averaged PCAv waveform during visual stimulation showcasing the biphasic neurovascular coupling response. This waveform demonstrates the change in PCAv in response to 1) visual stimulation and 2) removal of visual stimulus. The waveform was developed from averaged values across our entire sample population (n = 125; n = 625 visual stimulation trials). This figure is informed by Hoiland et al. (47) and Iadecola et al. (9), highlighting the relative contribution of both feedforward and feedback mechanisms across various time domains of the NVC response. The initial rise in PCAv during visual stimulation is hypothesized as neural feedforward signaling pathways. In contrast, feedback metabolic signaling is thought to contribute to the later sustained elevation in PCAv. NVC, neurovascular coupling; PCAv, posterior cerebral artery velocity.

Figure 2.

Cardiorespiratory and autonomic variables during baseline and visual stimulation. Total group (n = 63 participants) averages for respiratory rate (R_R; breaths/min; A, i–iii), peripheral oxygen saturation ($\text{S}{\text{p}}_{{\text{O}}_2}$; %; B, i–iii), the partial pressure of end-tidal CO₂ ($\text{PE}{\text{T}}_{\text{C}{\text{O}}_2}$; mmHg; C, i–iii), heart rate (HR; beats/min; D, i–iii; n = 125), and mean arterial pressure (MAP; mmHg; E, i–iii; n = 125) are provided. Variable averages were calculated and plotted every 2 s for each participant to provide an average variable waveform for the entire sample population across each visual stimulus (left column) with grey bins representing 30-s visual stimulation trials. Respective absolute changes (middle column), and relative percentage changes (right column) between baseline and visual stimulation are provided for each variable with baseline and visual stimulation values presented in clear and light-grey boxes, respectively. Data are presented as violin plots showcasing the interquartile range, median, upper, and lower limits. ***P < 0.001 from baseline. ±SD of the group-averaged waveform is presented as the orange shaded region.

Figure 3.

NVC response magnitude across repeated visual stimulation trials. This waveform showcases the group averaged NVC waveform during repeated visual stimulation (A). ΔMean (B, i–ii), ΔPeak (C, i–ii), and ΔtAUC (D, i–ii) NVC response magnitudes across each visual trial are presented (clear boxes). Respective absolute changes for PCAv and tAUC (Δcm/s and Δcm.s², respectively) are presented along the left column whereas the relative percentage change (%) from baseline are presented in the right column. Data are presented as violin plots showcasing the interquartile range, median, upper and lower limits. ***P < 0.001 from V1. ±SD of the group-averaged waveform is presented as the orange shaded region. NVC, neurovascular coupling; PCAv, posterior cerebral artery velocity; ΔtAUC, Δ total area under the curve.

Figure 4.

Simple linear regression analysis demonstrating the relationship between age, cerebral hemodynamics, and NVC metrics. Simple Linear regressions are presented for the relationship between age and baseline PCAv (A), mean NVC response (B), acute NVC response (C), peak NVC response (D), mid NVC response (E), tAUC NVC response (F), and late NVC response (G). NVC metrics are presented as the % change from baseline along the y-axis. These models are unadjusted with respect to sex. Age (years) is presented along the x-axis. Text boxes imposed on each graph include sample size (n), P value, and Pearson’s correlation coefficient (r). NVC, neurovascular coupling; PCAv, posterior cerebral artery velocity; tAUC, total area under the curve.