Evaluation of low vagally-mediated heart rate variability as an early marker of depression risk.

BACKGROUND: Both low vagally-mediated heart rate variability (HRV) and depression have been shown to be risk factors for cardiovascular disease (CVD). We recently identified an HRV cutpoint below which persons have an increased risk for several cardiometabolic disorders. However, no cutpoint exists to identify those at risk for depression. METHODS: The association between daytime HRV and diagnostically validated depression cutoffs using the five-item World Health Organization Well-being Index (WHO-5) was examined in adults from the Mannheim Industrial Cohort Study (n = 9973; Mage = 41.9[10.9]; 20 % women [n = 1934]). The aim was to identify HRV cutpoints for individuals who may have clinical depression. RESULTS: Regression adjusting for age, sex, and linear trend showed a significant quadratic association between depression, indexed by WHO-5 scores and HRV, indexed by the root mean square successive differences (RMSSD) in milliseconds (ms) (p < 0.001). Logistic regression models adjusting for age, sex, and heart period (i.e., inter-beat intervals) compared the clinically depressed (WHO-5 ≤ 28) and those with a screening diagnosis of depression (WHO-5 ≤ 50) to the rest of the population. Significant odds ratios suggested two RMSSD values 25 ±â€¯2 ms (OR = 1.39 [1.17, 1.64]) and 35 ±â€¯2 ms (OR = 1.17 [1.02, 1.34]) that may be used to identify those with an elevated risk for depression. LIMITATIONS: The sample was primarily German men. Fitness and anti-depressant use were not available. CONCLUSIONS: As HRV is a brief measure that can be used in clinical settings, our HRV cutpoints have implications for the early detection of those at risk for psychological and cardiometabolic disorders.

Associations of luteal phase changes in vagally mediated heart rate variability with premenstrual emotional changes.

BACKGROUND: A recent meta-analysis revealed that vagally mediated heart rate variability (vmHRV; a biomarker of emotion regulation capacity) significantly decreases in the luteal phase of the menstrual cycle. As two follow-up studies suggest, these vmHRV decreases are driven primarily by increased luteal progesterone (P4). However, analyses also revealed significant interindividual differences in vmHRV reactivity to the cycle, which is in line with longstanding evidence for interindividual differences in mood sensitivity to the cycle. The present study begins to investigate whether these interindividual differences in vmHRV cyclicity can explain who is at higher risk of showing premenstrual emotional changes. We expected a greater degree of midluteal vmHRV decrease to be predictive of a greater premenstrual increase in negative affect. METHODS: We conducted an observational study with a naturally cycling community sample (N = 31, M = 26.03 years). Over a span of six weeks, participants completed (a) daily ratings of negative affect and (b) counterbalanced lab visits in their ovulatory, midluteal, and perimenstrual phases. Lab visits were scheduled based on positive ovulation tests and included assessments of baseline vmHRV and salivary ovarian steroid levels. RESULTS: In line with previous research, multilevel models suggest that most of the sample shows ovulatory-to-midluteal vmHRV decreases which, however, were not associated with premenstrual emotional changes. Interestingly, it was only the subgroup with luteal increases in vmHRV whose negative affect markedly worsened premenstrually and improved postmenstrually. CONCLUSION: The present study begins to investigate cyclical changes in vmHRV as a potential biomarker of mood sensitivity to the menstrual cycle. The results demonstrate a higher level of complexity in these associations than initially expected, given that only atypical midluteal increases in vmHRV are associated with greater premenstrual negative affect. Potential underlying mechanisms are discussed, among those the possibility that luteal vmHRV increases index compensatory efforts to regulate emotion in those with greater premenstrual negative affect. However, future studies with larger and clinical samples and more granular vmHRV assessments should build on these findings and further explore associations between vmHRV cyclicity and menstrually related mood changes.

Central autonomic network dysfunction and plasma Alzheimer's disease biomarkers in older adults.

BACKGROUND: Higher order regulation of autonomic function is maintained by the coordinated activity of specific cortical and subcortical brain regions, collectively referred to as the central autonomic network (CAN). Autonomic changes are frequently observed in Alzheimer's disease (AD) and dementia, but no studies to date have investigated whether plasma AD biomarkers are associated with CAN functional connectivity changes in at risk older adults. METHODS: Independently living older adults (N = 122) without major neurological or psychiatric disorder were recruited from the community. Participants underwent resting-state brain fMRI and a CAN network derived from a voxel-based meta-analysis was applied for overall, sympathetic, and parasympathetic CAN connectivity using the CONN Functional Toolbox. Sensorimotor network connectivity was studied as a negative control. Plasma levels of amyloid (Aß42, Aß40), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed using digital immunoassay. The relationship between plasma AD biomarkers and within-network functional connectivity was studied using multiple linear regression adjusted for demographic covariates and Apolipoprotein E (APOE) genotype. Interactive effects with APOE4 carrier status were also assessed. RESULTS: All autonomic networks were positively associated with Aß42/40 ratio and remained so after adjustment for age, sex, and APOE4 carrier status. Overall and parasympathetic networks were negatively associated with GFAP. The relationship between the parasympathetic CAN and GFAP was moderated by APOE4 carrier status, wherein APOE4 carriers with low parasympathetic CAN connectivity displayed the highest plasma GFAP concentrations (B = 910.00, P = .004). Sensorimotor connectivity was not associated with any plasma AD biomarkers, as expected. CONCLUSION: The present study findings suggest that CAN function is associated with plasma AD biomarker levels. Specifically, lower CAN functional connectivity is associated with decreased plasma Aß42/40, indicative of cerebral amyloidosis, and increased plasma GFAP in APOE4 carriers at risk for AD. These findings could suggest higher order autonomic and parasympathetic dysfunction in very early-stage AD, which may have clinical implications.

Neuropsychobiology of fear-induced bradycardia in humans: progress and pitfalls.

In the last century, the paradigm of fear conditioning has greatly evolved in a variety of scientific fields. The techniques, protocols, and analysis methods now most used have undergone a progressive development, theoretical and technological, improving the quality of scientific productions. Fear-induced bradycardia is among these techniques and represents the temporary deceleration of heart beats in response to negative outcomes. However, it has often been used as a secondary measure to assess defensive responding to threat, along other more popular techniques. In this review, we aim at paving the road for its employment as an additional tool in fear conditioning experiments in humans. After an overview of the studies carried out throughout the last century, we describe more recent evidence up to the most contemporary research insights. Lastly, we provide some guidelines concerning the best practices to adopt in human fear conditioning studies which aim to investigate fear-induced bradycardia.

Racial differences in baroreflex function: Implications for the cardiovascular conundrum.

Study objective: African Americans (AAs) show early signs of vascular dysfunction paired with elevated blood pressure (BP) and total peripheral resistance (TPR), which is thought to underlie their increased rates of cardiovascular health complications relative to European Americans (EAs). AAs paradoxically have higher cardiac vagal tone, indexed by heart rate variability (HRV), which is cardio-protective. This paradox has been termed the Cardiovascular Conundrum. The physiological mechanism underlying this phenomenon is not well understood. We examined race differences in baroreflex function, which might be an important mechanism underlying the Cardiovascular Conundrum. Design: Participants completed a 5-minute baseline period where resting cardiac metrics were assessed. Setting: Laboratory. Participants: 130 college-aged individuals (54 women, 57 AAs). Main outcome measures: Baroreflex function was indexed as baroreflex sensitivity (BRS; the magnitude of changes in cardiovascular activity in accordance with BP changes) and effectiveness (BEI; the ratio of BP changes that elicit changes in cardiovascular activity) in the cardiac, vascular, and myocardial limbs. Results and conclusions: Results showed AAs to have higher HRV and cardiac BRS in comparison to EAs, suggesting the baroreflex is more sensitive to correcting the heart period for changes in BP among AAs compared to EAs. However, AAs showed lower vascular BEI relative to EAs, suggesting less effective control of TPR. In sum, lower BEI in the vascular branch might be an important mechanism underlying the Cardiovascular Conundrum (i.e., higher HRV and BP) and by extension, health disparities in cardiovascular diseases between AAs and EAs.

Perceptions of HIV-Related Comorbidities and Usability of a Virtual Environment for Cardiovascular Disease Prevention Education in Sexual Minority Men With HIV: Formative Phases of a Pilot Randomized Controlled Trial.

BACKGROUND: Sexual minority men with HIV are at an increased risk of cardiovascular disease (CVD) and have been underrepresented in behavioral research and clinical trials. OBJECTIVE: This study aims to explore perceptions of HIV-related comorbidities and assess the interest in and usability of a virtual environment for CVD prevention education in Black and Latinx sexual minority men with HIV. METHODS: This is a 3-phase pilot behavioral randomized controlled trial. We report on formative phases 1 and 2 that informed virtual environment content and features using qualitative interviews, usability testing, and beta testing with a total of 25 individuals. In phase 1, a total of 15 participants completed interviews exploring HIV-related illnesses of concern that would be used to tailor the virtual environment. In phase 2, usability testing and beta testing were conducted with 10 participants to assess interest, features, and content. RESULTS: In phase 1, we found that CVD risk factors included high blood pressure, myocardial infarction, stroke, and diabetes. Cancer (prostate, colon, and others) was a common concern, as were mental health conditions. In phase 2, all participants completed the 12-item usability checklist with favorable feedback within 30 to 60 minutes. Beta-testing interviews suggested (1) mixed perceptions of health and HIV, (2) high risk for comorbid conditions, (3) virtual environment features were promising, and (4) the need for diverse avatar representations. CONCLUSIONS: We identified several comorbid conditions of concern, and findings carry significant implications for mitigating barriers to preventive health screenings, given the shared risk factors between HIV and related comorbidities. Highly rated aspects of the virtual environment were anonymity; meeting others with HIV who identify as gay or bisexual; validating lesbian, gay, bisexual, transgender, queer, and others (LGBTQ+) images and content; and accessibility to CVD prevention education. Critical end-user feedback from beta testing suggested more options for avatar customization in skin, hair, and body representation. Our next phase will test the virtual environment as a new approach to advancing cardiovascular health equity in ethnic and racial sexual minority men with HIV. TRIAL REGISTRATION: ClinicalTrials.gov NCT04061915; https://clinicaltrials.gov/study/NCT05242952. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/38348.

High-Frequency Heart Rate Variability Is Prospectively Associated With Sleep Complaints in a Healthy Working Cohort.

OBJECTIVE: Vagus nerve functioning, as indexed by high-frequency heart rate variability (HF-HRV), has been implicated in a wide range of mental and physical health conditions, including sleep complaints. This study aimed to test associations between HF-HRV measured during sleep (sleep HF-HRV) and subjective sleep complaints 4 years later. METHODS: One hundred forty-three healthy employees (91% male; MAge = 47.8 years [time 2], SD = 8.3 years) of an industrial company in Southern Germany completed the Jenkins Sleep Problems Scale, participated in a voluntary health assessment, and were given a 24-hour ambulatory heart rate recording device in 2007. Employees returned for a health assessment and completed the Jenkins Sleep Problems Scale 4 years later. RESULTS: Hierarchical regression analyses showed that lower sleep HF-HRV measured in 2007 was associated with higher self-reported sleep complaints 4 years later after controlling for covariates (rab,c = -0.096, b = -0.108, 95% CI, -0.298 to 0.081, ΔR2 = 0.009, p = .050). CONCLUSIONS: These data are the first to show that lower sleep HF-HRV predicted worse sleep 4 years later, highlighting the importance of vagus nerve functioning in adaptability and health.

The association between perceived social functioning and heart rate variability is mediated by subclinical depressive symptomatology and moderated by gender.

Chronic loneliness and low perceived social support have been recognized as risk factors for both mental and cardiovascular disorders. It has been proposed that their link to psychophysiological problems may involve changes in parasympathetic activity. However, the exact underlying psychopathological mechanisms and the moderating effects of gender are still not thoroughly examined. Thus, the present study investigated associations between perceived social functioning and resting vagal tone in the context of potential cognitive and subclinical mediators and gender differences. Three hundred twenty-five young adults (aged 18-35, 180 women) underwent an electrocardiogram measurement of 6-minute resting heart rate variability (HRV). They also completed questionnaires assessing loneliness, perceived social support, social cognitive biases, depressive and social anxiety symptoms, and general mental health. In men, HRV was significantly and negatively associated with poorer perceived social functioning, depressive symptoms, and self-reported social cognitive biases, while in women, there was a quadratic link between HRV and depressive symptoms and HRV and general mental health. Moderated mediation analysis revealed that depressive symptoms fully mediated the relationship between perceived social functioning and HRV in men. The results suggest that decreased resting vagal tone in lonely individuals is linked to depressive symptomatology rather than to specific social cognitive biases and that this association is significant only in men.

Reliability of beat-to-beat blood pressure variability in older adults.

Blood pressure variability (BPV) is emerging as an important risk factor across numerous disease states, including cerebrovascular and neurodegenerative disease in older adults. However, there is no current consensus regarding specific use cases for the numerous available BPV metrics. There is also little published data supporting the ability to reliably measure BPV across metrics in older adults. BPV metrics were derived from continuous beat-to-beat blood pressure monitoring data. Two sequential 7-minute waveforms were analyzed. Absolute and relative reliability testing was performed. Differences between antihypertensive medication users and non-users on BPV metric reliability was also assessed. All sequence and dispersion based BPV metrics displayed good test-retest reliability. A measure of BP instability displayed only moderate reliability. Systolic and diastolic average real variability displayed the highest levels of reliability at ICC= .87 and .82 respectively. Additionally, systolic average real variability was the most reliable metric in both the antihypertensive use group, and the no antihypertensive use group. Beat-to-beat dispersion and sequence-based metrics of BPV can be reliably obtained from older adults using noninvasive continuous blood pressure monitoring. Average real variability may be the most reliable and specific beat-to-beat blood pressure variability metric due to its decreased susceptibility to outliers and low frequency blood pressure oscillations.

Oscillatory Coupling Between Neural and Cardiac Rhythms.

Oscillations serve a critical role in organizing biological systems. In the brain, oscillatory coupling is a fundamental mechanism of communication. The possibility that neural oscillations interact directly with slower physiological rhythms (e.g., heart rate, respiration) is largely unexplored and may have important implications for psychological functioning. Oscillations in heart rate, an aspect of heart rate variability (HRV), show remarkably robust associations with psychological health. Mather and Thayer proposed coupling between high-frequency HRV (HF-HRV) and neural oscillations as a mechanism that partially accounts for such relationships. We tested this hypothesis by measuring phase-amplitude coupling between HF-HRV and neural oscillations in 37 healthy adults at rest. Robust coupling was detected in all frequency bands. Granger causality analyses indicated stronger heart-to-brain than brain-to-heart effects in all frequency bands except gamma. These findings suggest that cardiac rhythms play a causal role in modulating neural oscillations, which may have important implications for mental health.

Heart rate and breathing effects on attention and memory (HeartBEAM): study protocol for a randomized controlled trial in older adults.

BACKGROUND: In healthy people, the "fight-or-flight" sympathetic system is counterbalanced by the "rest-and-digest" parasympathetic system. As we grow older, the parasympathetic system declines as the sympathetic system becomes hyperactive. In our prior heart rate variability biofeedback and emotion regulation (HRV-ER) clinical trial, we found that increasing parasympathetic activity through daily practice of slow-paced breathing significantly decreased plasma amyloid-ß (Aß) in healthy younger and older adults. In healthy adults, higher plasma Aß is associated with greater risk of Alzheimer's disease (AD). Our primary goal of this trial is to reproduce and extend our initial findings regarding effects of slow-paced breathing on Aß. Our secondary objectives are to examine the effects of daily slow-paced breathing on brain structure and the rate of learning. METHODS: Adults aged 50-70 have been randomized to practice one of two breathing protocols twice daily for 9 weeks: (1) "slow-paced breathing condition" involving daily cognitive training followed by slow-paced breathing designed to maximize heart rate oscillations or (2) "random-paced breathing condition" involving daily cognitive training followed by random-paced breathing to avoid increasing heart rate oscillations. The primary outcomes are plasma Aß40 and Aß42 levels and plasma Aß42/40 ratio. The secondary outcomes are brain perivascular space volume, hippocampal volume, and learning rates measured by cognitive training performance. Other pre-registered outcomes include plasma pTau-181/tTau ratio and urine Aß42. Recruitment began in January 2023. Interventions are ongoing and will be completed by the end of 2023. DISCUSSION: Our HRV-ER trial was groundbreaking in demonstrating that a behavioral intervention can reduce plasma Aß levels relative to a randomized control group. We aim to reproduce these findings while testing effects on brain clearance pathways and cognition. TRIAL REGISTRATION: ClinicalTrials.gov NCT05602220. Registered on January 12, 2023.

High Heart Rate Variability Buffers the Effect of Attachment Insecurity on Sleep Quality.

OBJECTIVE: Sleep quality is an important health-protective factor. Psychosocial factors, including attachment orientation, may be valuable for understanding who is at risk of poor sleep quality and associated adverse health outcomes. High attachment anxiety is reliably associated with adverse health outcomes, whereas high attachment avoidance is associated with adverse health outcomes when co-occurring with poor self-regulatory capacity, indexed by heart rate variability (HRV). We examined the associations between attachment anxiety, attachment avoidance, HRV, and sleep quality. METHODS: Using longitudinal data from a sample of 171 older adults measured four times over 1 year ( M = 66.18 years old; 67.83% women), we separated the between-person variance (which we call "trait") and within-person variance (which we call "state") for attachment anxiety, attachment avoidance, and HRV (via the root mean square of successive differences). Sleep quality was measured with the Pittsburgh Sleep Quality Index. RESULTS: Higher trait attachment anxiety was associated with poorer global sleep quality ( B = 0.22, p = .005). Higher state attachment avoidance was associated with poorer sleep quality ( B = -0.13, p = .01), except for those with higher trait HRV. Higher state attachment anxiety was associated with poorer sleep quality ( B = -0.15, p = .002), except for those with higher or mean trait HRV. Higher trait attachment anxiety was associated with poorer sleep quality ( B = -0.31, p = .02), except for those with higher trait HRV. CONCLUSIONS: High trait HRV mitigated the adverse effects of attachment insecurity on sleep quality. Our results suggest that people with high trait HRV had greater self-regulation capacity, which may enable them to enact emotion regulation strategies effectively.

Negative emotions enhance memory-guided attention in a visual search task by increasing frontoparietal, insular, and parahippocampal cortical activity.

Previous literature demonstrated that long-term memory representations guide spatial attention during visual search in real-world pictures. However, it is currently unknown whether memory-guided visual search is affected by the emotional content of the picture. During functional magnetic resonance imaging (fMRI), participants were asked to encode the position of high-contrast targets embedded in emotional (negative or positive) or neutral pictures. At retrieval, they performed a visual search for targets presented at the same location as during encoding, but at a much lower contrast. Behaviorally, participants detected more accurately targets presented in negative pictures compared to those in positive or neutral pictures. They were also faster in detecting targets presented at encoding in emotional (negative or positive) pictures than in neutral pictures, or targets not presented during encoding (i.e., memory-guided attention effect). At the neural level, we found increased activation in a large circuit of regions involving the dorsal and ventral frontoparietal cortex, insular and parahippocampal cortex, selectively during the detection of targets presented in negative pictures during encoding. We propose that these regions might form an integrated neural circuit recruited to select and process previously encoded target locations (i.e., memory-guided attention sustained by the frontoparietal cortex) embedded in emotional contexts (i.e., emotional contexts recollection supported by the parahippocampal cortex and emotional monitoring supported by the insular cortex). Ultimately, these findings reveal that negative emotions can enhance memory-guided visual search performance by increasing neural activity in a large-scale brain circuit, contributing to disentangle the complex relationship between emotion, attention, and memory.

Resting heart rate variability is associated with neural adaptation when repeatedly exposed to emotional stimuli.

Higher heart rate variability (HRV) at rest is associated with better emotion regulation ability. While the neurovisceral integration model explains this by postulating that HRV can index how the brain adaptively modulates responses to emotional stimuli, neuroimaging studies directly supporting this idea are scarce. We examined the neural correlates of regulating negative and positive emotion in relation to resting HRV based on the neuroimaging and heart rate data of one hundred young adults. The results showed that those with higher HRV better recruit the medial prefrontal cortex while intensifying positive compared to negative emotion. We also examined how individual differences in resting HRV are associated with adjusting brain activity to repeated emotional stimuli. During repeated viewing of emotional images, subjects with higher resting HRV better reduced activity in the medial prefrontal cortex, posterior cingulate gyrus, and angular gyrus, most of which overlapped with the default mode network. This HRV-DMN association was observed during passively viewing emotional images rather than during actively regulating emotion. While the regulating trials can better detect task-induced changes, the viewing trials might approximate resting state, better revealing individual differences. These findings suggest two possibilities: people with higher resting HRV might have a tendency to spontaneously engage with emotion regulation or possess a trait helping emotional arousal fade away.

Genetic differences associated with dopamine and serotonin release mediate fear-induced bradycardia in the human brain.

Fear-induced bradycardia, a transient heartbeat deceleration following exposure to threat, is a physiological index observable in humans, especially in fear conditioning experiments. While gaining interest in recent years, it is still currently underemployed in neuroscientific research compared to more popular physiological indices. Besides its use in research, it could also constitute a valuable resource in a clinical psychiatry setting, as many disorders are also characterized by altered heart rate responses. However, differences in fear-induced bradycardia may also be subtended by genetic interindividual differences, thus suggesting precaution when recommending its use in the clinical setting. Here, we discussed the first endeavors that aimed at clarifying the genetic underpinnings of heart rate variations, which suggest that individual genetic differences have a role in defining the characteristics of heart rate responses. Given this, translating heart rate measurements in the clinical setting must be implemented with caution. Future endeavors in this field will aim at identifying these differences even further, thus allowing for more precise clinical interventions.

Multi-ethnic variation in the ties that bind rumination and heart rate variability: Implications for health disparities.

Higher self-reported rumination, a common form of trait perseverative cognition, is linked with lower resting heart rate variability (HRV), which indicates poorer cardiac function and greater disease risk. A meta-analysis and systematic review indicated that in samples with fewer European Americans, the association of rumination with both heart rate and blood pressure was stronger. Thus, trait rumination may be more strongly associated with resting HRV among ethnically minoritized populations. The current study investigated whether differences in the association of self-reported rumination with resting HRV varied by ethnicity in a sample (N = 513; Mage = 19.41; 226 Women) of self-identified African Americans (n = 110), Asian Americans (n = 84), and European Americans (n = 319). Participants completed a five-minute baseline period to assess resting HRV, followed by the Ruminative Responses Scale, which contains three facets of rumination including brooding, depressive, and reflective rumination. On average, Asian Americans reported higher levels of rumination relative to European Americans. African Americans had higher resting HRV than Asian Americans. Adjusting for covariates, higher self-reported rumination was significantly associated with lower resting HRV in both African and Asian Americans, but not significantly so in European Americans. This finding was consistent for brooding and reflective, but not depressive rumination. Overall, this study lends insight into a psychological mechanism-rumination-that may impact health disparities among ethnically minoritized individuals, contributing to an understanding of how stress gets under the skin among such minoritized populations.

Error-related cardiac deceleration: Functional interplay between error-related brain activity and autonomic nervous system in performance monitoring.

Coordinated interactions between the central and autonomic nervous systems are crucial for survival due to the inherent propensity for human behavior to make errors. In our ever-changing environment, when individuals make mistakes, these errors can have life-threatening consequences. In response to errors, specific reactions occur in both brain activity and heart rate to detect and correct errors. Specifically, there are two brain-related indicators of error detection and awareness known as error-related negativity and error positivity. Conversely, error-related cardiac deceleration denotes a momentary slowing of heart rate following an error, signaling an autonomic response. However, what is the connection between the brain and the heart during error processing? In this review, we discuss the functional and neuroanatomical connections between the brain and heart markers of error processing, exploring the experimental conditions in which they covary. Given the current limitations of available data, future research will continue to investigate the neurobiological factors governing the brain-heart interaction, aiming to utilize them as combined markers for assessing cognitive control in healthy and pathological conditions.