Real-time heart rate variability biofeedback amplitude during a large-scale digital mental health intervention differed by age, gender, and mental and physical health.

Heart rate variability biofeedback (HRVB) is an efficacious treatment for depression and anxiety. However, translation to digital mental health interventions (DMHI) requires computing and providing real-time HRVB metrics in a personalized and user-friendly fashion. To address these gaps, this study validates a real-time HRVB feedback algorithm and characterizes the association of the main algorithmic summary metric-HRVB amplitude-with demographic, psychological, and health factors. We analyzed HRVB data from 5158 participants in a therapist-supported DMHI incorporating slow-paced breathing to treat depression or anxiety symptoms. A real-time feedback metric of HRVB amplitude and a gold-standard research metric of low-frequency (LF) power were computed for each session and then averaged within-participants over 2 weeks. We provide HRVB amplitude values, stratified by age and gender, and we characterize the multivariate associations of HRVB amplitude with demographic, psychological, and health factors. Real-time HRVB amplitude correlated strongly (r = .93, p < .001) with the LF power around the respiratory frequency (~0.1 Hz). Age was associated with a significant decline in HRVB (ß = -0.46, p < .001), which was steeper among men than women, adjusting for demographic, psychological, and health factors. Resting high- and low-frequency power, body mass index, hypertension, Asian race, depression symptoms, and trauma history were significantly associated with HRVB amplitude in multivariate analyses (p's < .01). Real-time HRVB amplitude correlates highly with a research gold-standard spectral metric, enabling automated biofeedback delivery as a potential treatment component of DMHIs. Moreover, we identify demographic, psychological, and health factors relevant to building an equitable, accurate, and personalized biofeedback user experience.

Daily biofeedback to modulate heart rate oscillations affects structural volume in hippocampal subregions targeted by the locus coeruleus in older adults but not younger adults.

Using data from a clinical trial, we tested the hypothesis that daily sessions modulating heart rate oscillations affect older adults' volume of a region-of-interest (ROI) comprised of adjacent hippocampal subregions with relatively strong locus coeruleus (LC) noradrenergic input. Younger and older adults were randomly assigned to one of two daily biofeedback practices for 5 weeks: 1) engage in slow-paced breathing to increase the amplitude of oscillations in heart rate at their breathing frequency (Osc+); 2) engage in self-selected strategies to decrease heart rate oscillations (Osc-). The interventions did not significantly affect younger adults' hippocampal volume. Among older adults, the two conditions affected volume in the LC-targeted hippocampal ROI differentially as reflected in a significant condition x time-point interaction on ROI volume. These condition differences were driven by opposing changes in the two conditions (increased volume in Osc+ and decreased volume in Osc-) and were mediated by the degree of heart rate oscillation during training sessions.

Daily biofeedback to modulate heart rate oscillations affects structural volume in hippocampal subregions targeted by the locus coeruleus in older adults but not younger adults.

Using data from a clinical trial, we tested the hypothesis that daily sessions modulating heart rate oscillations affect older adults' volume of a region-of-interest (ROI) comprised of adjacent hippocampal subregions with relatively strong locus coeruleus (LC) noradrenergic input. Younger and older adults were randomly assigned to one of two daily biofeedback practices for 5 weeks: (1) engage in slow-paced breathing to increase the amplitude of oscillations in heart rate at their breathing frequency (Osc+); (2) engage in self-selected strategies to decrease heart rate oscillations (Osc-). The interventions did not significantly affect younger adults' hippocampal volume. Among older adults, the two conditions affected volume in the LC-targeted hippocampal ROI differentially as reflected in a significant condition × time-point interaction on ROI volume. These condition differences were driven by opposing changes in the two conditions (increased volume in Osc+ and decreased volume in Osc-) and were mediated by the degree of heart rate oscillation during training sessions.

Daily heart rate variability biofeedback training decreases locus coeruleus MRI contrast in younger adults in a randomized clinical trial.

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.

Multimodal neuroimaging data from a 5-week heart rate variability biofeedback randomized clinical trial.

We present data from the Heart Rate Variability and Emotion Regulation (HRV-ER) randomized clinical trial testing effects of HRV biofeedback. Younger (N = 121) and older (N = 72) participants completed baseline magnetic resonance imaging (MRI) including T1-weighted, resting and emotion regulation task functional MRI (fMRI), pulsed continuous arterial spin labeling (PCASL), and proton magnetic resonance spectroscopy (1H MRS). During fMRI scans, physiological measures (blood pressure, pulse, respiration, and end-tidal CO2) were continuously acquired. Participants were randomized to either increase heart rate oscillations or decrease heart rate oscillations during daily sessions. After 5 weeks of HRV biofeedback, they repeated the baseline measurements in addition to new measures (ultimatum game fMRI, training mimicking during blood oxygen level dependent (BOLD) and PCASL fMRI). Participants also wore a wristband sensor to estimate sleep time. Psychological assessment comprised three cognitive tests and ten questionnaires related to emotional well-being. A subset (N = 104) provided plasma samples pre- and post-intervention that were assayed for amyloid and tau. Data is publicly available via the OpenNeuro data sharing platform.

Changes in Medial Prefrontal Cortex Mediate Effects of Heart Rate Variability Biofeedback on Positive Emotional Memory Biases.

Previous research suggests that implicit automatic emotion regulation relies on the medial prefrontal cortex (mPFC). However, most of the human studies supporting this hypothesis have been correlational in nature. In the current study, we examine how changes in mPFC-left amygdala functional connectivity relate to emotional memory biases. In a randomized clinical trial examining the effects of heart rate variability (HRV) biofeedback on brain mechanisms of emotion regulation, we randomly assigned participants to increase or decrease heart rate oscillations while receiving biofeedback. After several weeks of daily biofeedback sessions, younger and older participants completed an emotional picture memory task involving encoding, recall, and recognition phases as an additional measure in this clinical trial. Participants assigned to increase HRV (Osc+) (n = 84) showed a relatively higher rate of false alarms for positive than negative images than participants assigned to decrease HRV (Osc-) (n = 81). Osc+ participants also recalled relatively more positive compared with negative items than Osc- participants, but this difference was not significant. However, a summary bias score reflecting positive emotional memory bias across recall and recognition was significantly higher in the Osc+ than Osc- condition. As previously reported, the Osc+ manipulation increased left amygdala-mPFC resting-state functional connectivity significantly more than the Osc- manipulation. This increased functional connectivity significantly mediated the effects of the Osc+ condition on emotional bias. These findings suggest that, by increasing mPFC coordination of emotion-related circuits, daily practice increasing heart rate oscillations can increase implicit emotion regulation.

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

Previous research suggests that higher heart rate variability (HRV) is associated with better cognitive function. However, since most previous findings on the relationship between HRV and cognitive function were correlational in nature, it is unclear whether individual differences in HRV play a causal role in cognitive performance. To investigate whether there are causal relationships, we used a simple breathing manipulation that increases HRV through a 5-week HRV biofeedback intervention and examined whether this manipulation improves cognitive performance in younger and older adults (N = 165). The 5-week HRV biofeedback intervention did not significantly improve inhibitory control, working memory and processing speed across age groups. However, improvement in the Flanker score (a measure of inhibition) was associated with the amplitude of heart rate oscillations during practice sessions in the younger and older intervention groups. Our results suggest that daily practice to increase heart rate oscillations may improve inhibitory control, but future studies using longer intervention periods are warranted to replicate the present finding.

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

Heart rate variability is a robust biomarker of emotional well-being, consistent with the shared brain networks regulating emotion regulation and heart rate. While high heart rate oscillatory activity clearly indicates healthy regulatory brain systems, can increasing this oscillatory activity also enhance brain function? To test this possibility, we randomly assigned 106 young adult participants to one of two 5-week interventions involving daily biofeedback that either increased heart rate oscillations (Osc+ condition) or had little effect on heart rate oscillations (Osc- condition) and examined effects on brain activity during rest and during regulating emotion. While there were no significant changes in the right amygdala-medial prefrontal cortex (MPFC) functional connectivity (our primary outcome), the Osc+ intervention increased left amygdala-MPFC functional connectivity and functional connectivity in emotion-related resting-state networks during rest. It also increased down-regulation of activity in somatosensory brain regions during an emotion regulation task. The Osc- intervention did not have these effects. In this healthy cohort, the two conditions did not differentially affect anxiety, depression, or mood. These findings indicate that modulating heart rate oscillatory activity changes emotion network coordination in the brain.

Heart rate variability (HRV) changes and cortical volume changes in a randomized trial of five weeks of daily HRV biofeedback in younger and older adults.

Previous studies indicate that the structure and function of medial prefrontal cortex (PFC) and lateral orbitofrontal cortex (OFC) are associated with heart rate variability (HRV). Typically, this association is assumed to reflect the PFC's role in controlling HRV and emotion regulation, with better prefrontal structural integrity supporting greater HRV and better emotion regulation. However, as a control system, the PFC must monitor and respond to heart rate oscillatory activity. Thus, engaging in regulatory feedback during heart rate oscillatory activity may over time help shape PFC structure, as relevant circuits and connections are modified. In the current study with younger and older adults, we tested whether 5 weeks of daily sessions of biofeedback to increase heart rate oscillations (Osc+ condition) vs. to decrease heart rate oscillations (Osc- condition) affected cortical volume in left OFC and right OFC, two regions particularly associated with HRV in prior studies. The left OFC showed significant differences in volume change across conditions, with Osc+ increasing volume relative to Osc-. The volume changes in left OFC were significantly correlated with changes in mood disturbance. In addition, resting low frequency HRV increased more in the Osc+ than in the Osc- condition. These findings indicate that daily biofeedback sessions regulating heart rate oscillatory activity can shape both resting HRV and the brain circuits that help control HRV and regulate emotion.

Effects of a randomised trial of 5-week heart rate variability biofeedback intervention on mind wandering and associated brain function.

Previous research suggests that excessive negative self-related thought during mind wandering involves the default mode network (DMN) core subsystem and the orbitofrontal cortex (OFC). Heart rate variability (HRV) biofeedback, which involves slow paced breathing to increase HRV, is known to promote emotional well-being. However, it remains unclear whether it has positive effects on mind wandering and associated brain function. We conducted a study where young adults were randomly assigned to one of two 5-week interventions involving daily biofeedback that either increased heart rate oscillations via slow paced breathing (Osc+ condition) or had little effect on heart rate oscillations (active control or Osc- condition). The two intervention conditions did not differentially affect mind wandering and DMN core-OFC functional connectivity. However, the magnitude of participants' heart rate oscillations during daily biofeedback practice was associated with pre-to-post decreases in mind wandering and in DMN core-OFC functional connectivity. Furthermore, the reduction in the DMN core-OFC connectivity was associated with a decrease in mind wandering. Our results suggested that daily sessions involving high amplitude heart rate oscillations may help reduce negative mind wandering and associated brain function.

My Life in HRV Biofeedback Research.

This paper reviews the published work of me along with my students and close colleagues on the topic of heart rate variability biofeedback (HRVB). It includes early research by Vaschillo documenting resonance characteristics of the baroreflex system that causes large oscillations in heart rate when breathing at resonance frequency, research on heart rate variability as a marker of parasympathetic stress response in asthma, and HRVB as a treatment for asthma and depression. Many questions about HRVB remain unresolved, and important questions for future research are listed.

Meditation and Aerobic Exercise Enhance Mental Health Outcomes and Pattern Separation Learning Without Changing Heart Rate Variability in Women with HIV.

Mental and physical (MAP) training targets the brain and the body through a combination of focused-attention meditation and aerobic exercise. The following feasibility pilot study tested whether 6 weeks of MAP training improves mental health outcomes, while enhancing discrimination learning and heart rate variability (HRV) in a group of women living with human immunodeficiency virus (HIV) and other stress-related conditions. Participants were assigned to training (n = 18) or no-training control (n = 8) groups depending on their ability and willingness to participate, and if their schedule allowed. Training sessions were held once a week for 6 weeks with 30 min of meditation followed by 30 min of aerobic exercise. Before and after 6 weeks of training, participants completed the Behavioral Pattern Separation Task as a measure of discrimination learning, self-report questionnaires of ruminative and trauma-related thoughts, depression, anxiety, and perceived stress, and an assessment of HRV at rest. After training, participants reported fewer ruminative and trauma-related thoughts, fewer depressive and anxiety symptoms, and less perceived stress (p's < 0.05). The positive impact on ruminative thoughts and depressive symptoms persisted 6 months after training. They also demonstrated enhanced discrimination of similar patterns of information (p < 0.05). HRV did not change after training (p > 0.05). Combining mental and physical training is an effective program for enhancing mental health and aspects of cognition in women living with HIV, although not necessarily through variance in heart rate.

A Method for More Accurate Determination of Resonance Frequency of the Cardiovascular System, and Evaluation of a Program to Perform It.

This study validated a more exact automated method of determining cardiovascular resonance frequency (RF) against the "stepped" protocol described by Lehrer et al. (Appl Psychophysiol Biofeedback 25(3):177-191, https://doi.org/10.1023/a:1009554825745 , 2000; in Foundations of heart rate variability biofeedback: A book of readings, The Association for Applied Psychophysiology and Biofeedback, pp 9-19, 2016). Thirteen participants completed a 15-min RF determination session by each method. The "stepped" protocol assesses HRV in five 3-min stationary windows from 4.5 to 6.5 breaths per minute (bpm), decreasing in 0.5 bpm steps. Multiple criteria, subjectively weighted by the clinician, determines RF. For this study, the proposed method used a sliding window with a fixed rate of change (67.04 ms per breath) at each of 78 breath cycles ranging from 4.25 to 6.75 bpm. Its algorithm analyzes IBI to locate the midpoint of the 1-min region of stable maximum peak-trough variability. RF is quantified from breath duration at that point. The software generates a visual display of superimposed HR and breathing data. Thus, the new method fully automates RF determination. Eleven of the 13 matched pairs fell within the 0.5 bpm resolution of the stepped method. Comparisons of LF power generated by the autoregressive (AR) spectral method showed a strong correlation in LF power production by the stepped and sliding methods (R = 0.751, p = 0.000). The "sliding" pacing protocol was favored by 69% of participants (p < 0.02). The new, fully-automated, method may facilitate both in-person and remote HRV biofeedback training. Software is available open-source.

Relationships among pulmonary function, anxiety and depression in mild asthma: An exploratory study.

In a secondary analysis of data from a prior study, we calculated the relationships among depression (PHQ-8), anxiety (GAD-7), and measures of asthma in 69 steroid-naïve patients with mild and moderate symptomatic asthma. Average levels of pulmonary function, depression and anxiety tended to be in the normal range, and asthma tended to be well controlled (Asthma Control Test). Nevertheless, PHQ-8 scores were significantly correlated with forced oscillation (FO) measures of airway reactance (AX) and resistance at a low frequency of stimulation (Rrs5 Hz). GAD-7 scores also were significantly related to Rrs5 Hz. Exploratory analyses in Supplementary data provide no evidence for vagal mediation of the association. Further research is necessary to discover mechanisms for the associations found here. Future studies might examine the utility of assessing and treating mild anxiety and depression in mild to moderate asthma.