Daily heart rate variability biofeedback training decreases locus coeruleus MRI contrast in younger adults

Abstract

As an arousal hub region in the brain, the locus coeruleus (LC) has bidirectional connections with the autonomic nervous system. Magnetic resonance imaging (MRI)-based measures of LC structural integrity have been linked to cognition and arousal, but less is known about factors that influence LC structure and function across time. Here, we tested the effects of heart rate variability (HRV) biofeedback, an intervention targeting the autonomic nervous system, on LC MRI contrast and sympathetic activity. Younger and older participants completed daily HRV biofeedback training for five weeks. Those assigned to an experimental condition performed biofeedback involving slow, paced breathing designed to increase heart rate oscillations, whereas those assigned to a control condition performed biofeedback to decrease heart rate oscillations. At the pre- and post-training timepoints, LC contrast was assessed using turbo spin echo MRI scans, and RNA sequencing was used to assess cAMP-responsive element binding protein (CREB)-regulated gene expression in circulating blood cells, an index of sympathetic nervous system signaling. We found that left LC contrast decreased in younger participants in the experimental group, and across younger participants, decreases in left LC contrast were related to the extent to which participants increased their heart rate oscillations during training. Furthermore, decreases in left LC contrast were associated with decreased expression of CREB-associated gene transcripts. On the contrary, there were no effects of biofeedback on LC contrast among older participants in the experimental group. These findings provide novel evidence that in younger adults, HRV biofeedback involving slow, paced breathing can decrease both LC contrast and sympathetic nervous system signaling.

Effects of a Randomised Trial of 5-Week Heart Rate Variability Biofeedback Intervention on Cognitive Function: Possible Benefits for Inhibitory Control

“…For instance, engaging in a bout of moderate intensity exercise tends to increase processing speed (McMorris & Hale, 2015 ), which may be due to activation of the locus coeruleus (LC) and associated noradrenergic activity (McMorris, 2016 ). As we report elsewhere (Bachman et al, 2022 ), among younger adults the Osc+ intervention significantly decreased left LC magnetic resonance imaging contrast. a measure reflecting locus coeruleus magnetic properties.…”

“…LC contrast is influenced by the accumulation of neuromelanin, a by-product of catecholamine metabolism (Keren et al, 2015 ). Among the younger cohort, relative to the Osc− condition, the Osc+ condition also decrease cAMP-responsive element binding protein (CREB)-regulated gene expression in circulating blood cells, an index of sympathetic nervous system signaling (Bachman et al, 2022 ). Thus, one possibility that should be examined in future research is whether the Osc+ intervention influences processing speed via its suppression of noradrenergic activity.…”

The integrity of dopaminergic and noradrenergic brain regions is associated with different aspects of late-life memory performance

“…We applied a previously established semi-automatic analysis procedure to extract individual LC and SN– VTA intensity values from structural imaging data (for a detailed description and validation, see [87], for applications, see [88,89,127]; for an independent validation see [91]). The following procedure was performed separately for TP1 and TP2 imaging data.…”

The Central Noradrenergic System in Neurodevelopmental Disorders: Merging Experimental and Clinical Evidence

“…However, it is worth noting that in studies performed in adults, LC-MRI signal has been shown to be associated with LC-related cognitive and autonomic functions, even in the absence of brain pathology [ 160 , 161 , 162 , 171 , 172 ]. Furthermore, in a very interesting recent pre-print, Bachman and colleagues found that LC signal can vary in follow-up assessments, after autonomic biofeedback training [ 173 ]. Those studies suggest that LC-MRI parameters are associated with LC functioning and plasticity, even in the absence of morphological alterations, which might be a potential scenario occurring in NdD.…”