Associations Between Age, Heart Rate Variability, and BOLD fMRI Signal Variability

Numerous studies report that BOLD fMRI signal variance (SD_BOLD) decreases with age. However, these associations may partly reflect cardiovascular contributions to the BOLD signal. For example, heart rate variability (HRV) has been positively associated with Resting State Fluctuation Amplitude (RSFA), which captures low frequency components of BOLD fMRI variability. HRV is also negatively associated with age, which could potentially confound age-SD_BOLD associations. Yet, limited research has examined HRV-SD_BOLD associations or tested within-person HRV-SD_BOLD coupling using sliding window analyses of simultaneous HRV and SD_BOLD. We analyzed resting-state fMRI data from two independent Midlife in the United States (MIDUS) samples: Core at M3 (n=115) and Refresher at MR1 (n=101). Partial Least Squares (PLS) analyses revealed significant positive HRV-SD_BOLD associations (Core: permutation p=0.018; Refresher: permutation p<0.001). Whole brain age-SD_BOLD PLS associations were non-significant via permutation tests across several models (Core: permutation p=0.201; Refresher: permutation p=0.121). We found age-related decreases in SD_BOLD across ~70% of voxels in both samples. Concordance analyses showed 67-69% of brain voxels exhibited negative age-SD_BOLD but positive HRV-SD_BOLD relationships, suggesting that regions showing age-related decreases in SD_BOLD also showed HRV-related increases in SD_BOLD. Sliding-window analyses demonstrated robust positive within-person associations between person-centered HRV and SD_BOLD via different HRV metrics: SDNN (Core: p < 0.001; Refresher: p < 0.001), RMSSD (Core: p = 0.072; Refresher: p = 0.009), and low frequency (Core: p < 0.001; Refresher: p < 0.001), with non-significant effects of high frequency (Core: p = 0.516; Refresher: p = 0.12) HRV. Thus, regardless of baseline levels, windows with higher HRV corresponded to higher SD_BOLD, suggesting that cardiovascular factors partially explain age-SD_BOLD associations and HRV may mechanistically influence SD_BOLD. These results suggest that controlling for HRV, especially low-frequency HRV or SDNN, may be necessary when analyzing SD_BOLD to isolate neural effects.