Cortical Thickness and Resting State Cardiac Function Across the Lifespan: A Cross-Sectional Pooled Mega Analysis

Abstract

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest that the decline in HRV with increasing age is related to a decline in prefrontal CT, particularly in the orbitofrontal cortex. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS. Nonetheless, in the absence of longitudinal data, alternative explanations need to be considered. Findings reveal an important association between cortical thickness and cardiac parasympathetic activity with implications for healthy aging and longevity.

The autonomic brain: Multi-dimensional generative hierarchical modelling of the autonomic connectome

“…We identify regions whose shapes differ contingent on autonomic tone, including the thalamus, nucleus accumbens and basal ganglia. Our univariate findings at both the cortex and subcortex reproduce those of other published studies ( Ruffle, Coen, Giampietro, Williams, Apkarian, et al., 2018 ), including a large multi-site study of brain structure ( Koenig, Abler, Agartz, et al, 2021 ). We advance current knowledge in identifying gray matter morphometric networks ( Raamana & Strother, 2018 ) subserving autonomic regulation, with high-degree nodes including the orbitofrontal cortex, cingulate, insula, basal ganglia, thalamus, nucleus accumbens, amygdala and hippocampus.…”

Increasing coordination and responsivity of emotion-related brain regions with a heart rate variability biofeedback randomized trial

“…Hundreds of previous studies have identified vagal HRV (usually assessed using HF-HRV or RMSSD) at rest as one of the best indicators of well-being [28][29][30] . In addition, individual differences in vagal HRV have been linked with brain structures and circuits associated with emotion regulation 3,20,31,32 . However, we need more than observational correlations to better understand the causal dynamics of the relationships.…”

“…One potential explanation is that many of the same brain regions are involved in coordinating heart rhythms and in regulating emotions (5). Indeed, individual differences in vagal HRV have been linked with brain structures and circuits associated with emotion regulation (5)(6)(7)(8). However, heart rate oscillations may go beyond signaling the functioning of regulatory brain regions.…”

Aging and cerebrovascular health: Structural, functional, cognitive, and methodological implications

“…Resting‐state autonomic nervous system activity, indexed by heart rate variability (HRV) has been associated with cortical thinning, but with some mixed results, partly due to relatively small sample sizes that prevented a close examination of sex‐ and age‐related individual differences. In a very large empirical study combining HRV and cortical thickness data from many existing samples (for a total N > 1,200) Koenig and colleagues (2021) confirm the existence of an association between HRV and cortical thickness, especially in orbitofrontal areas, and discuss the possible causal direction and interpretation of this association.…”