The physiological component of the BOLD signal: Impact of age and heart rate variability biofeedback training

Aging is associated with declines in autonomic nervous system (ANS) function, impaired neurovascular coupling, and diminished cerebrovascular responsiveness-factors that may contribute to cognitive decline and neurodegenerative diseases. Understanding how aging alters the integration of physiological signals in the brain is crucial for identifying potential interventions to promote brain health. This study examines age-related differences in coupling between low-frequency cardiac rate and respiratory volume fluctuations and the blood oxygenation level-dependent (BOLD) signal, using two independent resting-state fMRI datasets with concurrent physiological recordings from younger and older adults. Our findings reveal significant age-related reductions in the percent variance of the BOLD signal explained by heart rate (HR), respiratory variation (RV), and end-tidal CO², particularly in regions involved in autonomic regulation, including the orbitofrontal cortex, anterior cingulate cortex, insula, basal ganglia, and white matter. Cross-correlation analysis also revealed that younger adults exhibited stronger HR-BOLD coupling in white matter, as well as a more rapid BOLD response to RV and CO² in gray matter. Additionally, we investigated the effects of heart rate variability biofeedback (HRV-BF) training, a non-invasive intervention designed to modulate heart rate oscillations. The intervention modulated physiological-BOLD coupling in a manner dependent on both age and training condition: older adults who underwent HRV-BF to enhance HR oscillations exhibited a shift toward younger-like HR-BOLD coupling patterns. These findings suggest that HRV-BF may help mitigate age-related declines in autonomic or cerebrovascular function. Overall, this study underscores the role of physiological dynamics in brain aging and highlights the importance of considering autonomic function when interpreting BOLD signals. By demonstrating that HRV-BF can modulate physiological-BOLD interactions, our findings suggest a potential pathway for enhancing cerebrovascular function and preserving brain health across the lifespan.