Individual variability in the relationship between physiological and resting-state fMRI metrics

Cerebrovascular Reactivity (CVR), the brains vascular response to a vasodilatory stimulus, can be measured using fMRI during breathing challenges that modulate arterial CO2 levels. CVR is an important indicator of cerebrovascular health, although its estimation can be challenging due to the extra experimental setup and/or the subject compliance required. To overcome these limitations, summary metrics based on resting state fluctuations (RSF), such as the (fractional) amplitude of low frequency fluctuations (f/ALFF) and the resting state fluctuation amplitude (RSFA), have been proposed as alternative estimates of CVR, as they are frequently associated with vascular and physiological factors. Previous studies have reported a significant relationship between CVR estimates obtained by means of respiratory paradigms and RSF metrics. However, the total sample sizes, considering both subjects and sessions, are typically small, and not all studies agree on the degree of the relationship. Furthermore, to our knowledge, these studies have only reported cross-sectional analyses, whereas intra-subject longitudinal relationships between CVR estimates and RSF metrics are unknown. Leveraging a unique dense sampling dataset in which resting state and breath-hold multi-echo fMRI were collected in 7 subjects with 10 sessions each, we provide evidence of high individual variability in the inter-session (i.e. intra-subject) relationship between RSF metrics and CVR. These results indicate that RSF metrics might not be a suitable proxy of CVR in clinical settings or for BOLD signal calibration as they may not properly account for intra-individual physiological variations in BOLD fMRI data.