Lag-optimized BOLD cerebrovascular reactivity derived from breathing task data has a stronger relationship with baseline cerebral blood flow

Cerebrovascular reactivity (CVR) is an important indicator of cerebrovascular health and is commonly studied with the Blood Oxygenation Level Dependent functional MRI (BOLD-fMRI) response to a vasoactive stimulus. There is theoretical and empirical evidence to suggest that baseline cerebral blood flow (CBF) modulates the BOLD signal amplitude, and that baseline CBF may influence BOLD-CVR estimates. We address how some pertinent data acquisition and modelling choices affect the relationship between baseline CBF and BOLD-CVR: whether BOLD-CVR is modelled with breathing task data or just resting-state data, and whether BOLD-CVR amplitudes are optimized for hemodynamic lag effects. For the relationship between baseline CBF and BOLD-CVR, we assessed both between-subject correlations of average GM values and within-subject spatial correlations across cortical regions. Our results suggest that a simple breathing task addition to a resting-state scan, alongside lag-optimization within BOLD-CVR modelling, can improve BOLD-CVR correlations with baseline CBF, both between- and within-subjects, likely because these CVR estimates are more physiologically accurate. We report positive coupling between baseline CBF and BOLD-CVR, both between and within subjects; the physiological explanation of this positive coupling is unclear, and future research with larger sample sizes and more tightly controlled vasoactive stimuli is needed. Understanding how baseline vascular physiology relates to dynamic cerebrovascular processes will bring further insights into what drives between and within subject participant variability in BOLD-CVR measurements and related measurements of cerebrovascular function. These insights are particularly relevant when interpreting results in populations with altered vascular and/or metabolic baselines or impaired cerebrovascular reserve. ### Competing Interest Statement The authors have declared no competing interest. * (ALFF) : amplitude of low-frequency fluctuation (bCBF) : baseline cerebral blood flow (BOLD) : blood oxygenation dependent signal (BH) : breath-holding (CBF) : cerebral blood flow (CVR) : cerebrovascular reactivity (CDB) : cued deep breathing (FDR) : false discovery rate (fALFF) : fractional amplitude of low-frequency fluctuation (FWHM) : full width half maximum (fMRI) : functional magnetic resonance imaging (GM) : gray matter (lag optimization) : Lag-Opt (no lag optimization) : No-Op (PETCO2) : partial pressure of end tidal carbon dioxide (pCASL) : pseudo-continuous arterial spin labelling (RSFA) : resting-state fluctuation amplitude