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.

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.

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.

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.

Heart Rate and Breathing Are Not Always in Phase During Resonance Frequency Breathing.

For many years it has been an axiom among practitioners of heart rate variability biofeedback that heart rate and breathing vary in phase with each other when people do resonance frequency breathing. When people breathe at the frequency of the baroreflex system, about 0.1 Hz, heart rate and blood pressure have been found to oscillate 180° out of phase, while heart rate and breathing are in phase (zero-degree phase). Thus breathing stimulates the baroreflex by augmenting the baroreflex response with each breath, an effect that is magnified by resonance properties in the baroreflex system. The original data on these relationships came from a study of highly athletic healthy young people. To test this relationship we analyzed phase relationship data between cardiac interbeat interval and breathing during 5-min periods of resonance frequency breathing among 24 adults from a recent study of heart rate variability biofeedback to treat adults with mild to moderate currently symptomatic asthma, ages between 18 and 70. For the specific frequency near 0.1 Hz with the highest amplitude of HRV we calculated coherence and phase between cardiac interbeat interval (IBI) and the respiration curve using the WinCPRS program. Among records with coherence > 0.8, we found a phase relationship of 109° rather than the expected 180°, with IBI changes leading breathing. We computed Spearman correlation coefficients between phase and various subject characteristics, including age, gender, height, and asthma severity. We found no relationship between phase and gender, height, or asthma physiology or symptoms. However, when controlled for gender and height, we found a moderate size significant correlation between phase and age, with younger participants having values closer to 180°, r = 0.47, p < 0.03. It is possible that cardiovascular characteristics of older people affect the phase relationship. Despite the deviation from the in-phase relationship among older individuals, breathing nevertheless stimulated the baroreflex and produced high-amplitude heart rate oscillations. Implications are discussed for HRV biofeedback training protocols. Replication in a healthy population is needed in order to determine the universality of these findings.

Further Exploration of Treatment Response in Latinos with Comorbid Asthma and Panic Disorder: A Brief Report of HRV and ETCO2 as Potential Mediators of Treatment Response.

Heart rate variability (HRV) and end tidal CO2 (ETCO2) in relation to treatment response have not been studied in Latino populations or in comorbid asthma and panic disorder (PD). An extension of previously published research, the current study explored psychophysiological variables as possible mediators of treatment response. Latino treatment completers (N = 32) in the Bronx with asthma-PD received either Cognitive-Behavioral Psychophysiological Therapy (CBPT) or Music Relaxation Therapy (MRT). CBPT included HRV-biofeedback (HRVB); in-the-moment heart rate data to help an individual learn to influence his/her own heart rate. The sample was primarily female (93.8%) and Puerto Rican (81.25%). Treatment groups did not differ on demographics, except for less education in CBPT. The Panic Disorder Severity Scale (PDSS) and Asthma Control Questionnaire (ACQ) assessed changes in symptoms. HRV and ETCO2 were measured at four of eight therapy sessions. Baseline ETCO2 and changes in HRV from first to last of psychophysiology sessions were investigated as mediators of change on ACQ and PDSS. Mixed model analyses indicated in the CPBT group, changes in both asthma control and PD severity were not mediated by changes in HRV. In the CBPT and MRT groups combined, changes in PD severity were not mediated by baseline ETCO2. These findings may be due to the brevity of HRVB in CBPT, multiple treatment components, ETCO2 not directly targeted, and/or unique physiological pathways in Latinos with asthma-PD.

Heart Rate Variability Biofeedback Does Not Substitute for Asthma Steroid Controller Medication.

Despite previous findings of therapeutic effects for heart rate variability biofeedback (HRVB) on asthma, it is not known whether HRVB can substitute either for controller or rescue medication, or whether it affects airway inflammation. Sixty-eight paid volunteer steroid naïve study participants with mild or moderate asthma were given 3 months of HRVB or a comparison condition consisting of EEG alpha biofeedback with relaxing music and relaxed paced breathing (EEG+), in a two-center trial. All participants received a month of intensive asthma education prior to randomization. Both treatment conditions produced similar significant improvements on the methacholine challenge test (MCT), asthma symptoms, and asthma quality of life (AQOL). MCT effects were of similar size to those of enhanced placebo procedures reported elsewhere, and were 65% of those of a course of a high-potency inhaled steroid budesonide given to a sub-group of participants following biofeedback training. Exhaled nitric oxide decreased significantly only in the HRVB group, 81% of the budesonide effect, but with no significant differences between groups. Participants reported becoming more relaxed during practice of both techniques. Administration of albuterol after biofeedback sessions produced a large improvement in pulmonary function test results, indicating that neither treatment normalized pulmonary function as a potent controller medication would have done. Impulse oscillometry showed increased upper airway (vocal cord) resistance during biofeedback periods in both groups. These data suggest that HRVB should not be considered an alternative to asthma controller medications (e.g., inhaled steroids), although both biofeedback conditions produced some beneficial effects, warranting further research, and suggesting potential complementary effects. Various hypotheses are presented to explain why HRVB effects on asthma appeared smaller in this study than in earlier studies. Clinical Trial Registration NCT02766374.

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.

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.

Psychophysiologic treatment for patients with medically unexplained symptoms: a randomized controlled trial.

BACKGROUND: Patients presenting with medically unexplained physical symptoms (MUPS) typically present with significant distress and marked impairment in functioning and pose a unique challenge to health care providers. The purpose of this study was to examine the efficacy of a psychophysiological treatment (PT) for MUPS. METHODS: Thirty-eight participants meeting criteria for subthreshold somatization disorder (abridged somatization) were randomly assigned to one of two conditions: (1) standard medical care augmented by a psychiatric consultation intervention (wait-list) or (2) a 10-session, manualized, individually-administered PT added to the psychiatric consultation intervention. Assessments were conducted at baseline, at midpoint (after four sessions), and after completing the last session. The primary outcome measure was the severity scale of the Clinical Global Impression Scale anchored for Somatic Symptoms (CGI-SD). Secondary outcome measures were responder status as determined by clinical ratings, self-report measures of mental and physical functioning. RESULTS: At the end of the trial, the severity (and frequency) of physical symptoms improved significantly more (p<0.05) in the intervention group. The average improvement in the CGI-SD was 0.80 points greater in the intervention group than in the wait-list group. PT was also associated with greater improvements in self-reported functioning and depressive symptomatology. The effect sizes at the final assessment point indicate that this intervention had a robust effect on complex somatic symptom presentations. CONCLUSION: For patients with high levels of MUPS (abridged somatization), PT produces significant improvements in symptoms and functional status.

Influence of acute epinephrine infusion on endotoxin-induced parameters of heart rate variability: a randomized controlled trial.

OBJECTIVE: To determine whether the acute anti-inflammatory influence of epinephrine (EPI) extends to changes in heart rate variability (HRV) induced by the prototypical inflammatory stimulus, endotoxin (lipopolysaccharide [LPS]). SUMMARY BACKGROUND DATA: HRV reflects fluctuating cardiac autonomic inputs and is acutely reduced during the systemic inflammation induced by LPS as well as during severe critical illnesses such as sepsis and traumatic injury. While EPI may diminish proinflammatory cytokine release, it is unknown whether this net anti-inflammatory activity extends to HRV. METHODS: Healthy volunteers (n = 17) were randomized to either saline + LPS (2 ng/kg) or LPS + antecedent EPI infusion (30 ng/kg/min) from -3 to 6 hours relative to LPS. HRV and blood samples were obtained before EPI and LPS as well as hourly afterward. Plasma cytokines were measured by ELISA. Statistical analysis was by repeated measures analysis of variance. This study was registered at Clinicaltrials.gov and is listed under the following ID number: NCT00753402. RESULTS: LPS acutely influenced all measured parameters of HRV including standard deviation of the average beat to beat intervals over a 5-minute period, percentage of interval differences of successive interbeat intervals greater than 50 milliseconds and square root of the mean squared differences, high frequency (HF), low frequency, low frequency/HF, and very low frequency (all P < 0.01). EPI infusion reduced the inflammatory cytokine response to LPS as measured by decreased TNFalpha, IL-6, and IL-8 (P < 0.01). Relative to the saline + LPS group, antecedent EPI infusion was associated with further reductions in parameters of HRV measuring vagal/parasympathetic activity including, percentage of interval differences of successive interbeat intervals greater than 50 milliseconds, square root of the mean squared differences, and HF (P < 0.05). CONCLUSION: Prior EPI exposure exerts anti-inflammatory influences but also may reduce vagus nerve activity. Hence, acute EPI administration may be protective against early inflammatory challenges but diminish vagal nerve responsiveness to subsequent stimuli.

The Effect of Heart Rate Variability Biofeedback Training on Mental Health of Pregnant and Non-Pregnant Women: A Randomized Controlled Trial.

In this study, we examined the efficacy of heart rate variability (HRV)-biofeedback on stress and stress-related mental health problems in women. Furthermore, we examined whether the efficacy differed between pregnant and non-pregnant women. Fifty women (20 pregnant, 30 non-pregnant; mean age 31.6, SD = 5.9) were randomized into an intervention (n = 29) or a waitlist condition (n = 21). All participants completed questionnaires on stress, anxiety, depressive symptoms, sleep, and psychological well-being on three occasions with 6-week intervals. Women in the intervention condition received HRV-biofeedback training between assessment 1 and 2, and women in the waitlist condition received the intervention between assessment 2 and 3. The intervention consisted of a 5-week HRV-biofeedback training program with weekly 60⁻90 min. sessions and daily exercises at home. Results indicated a statistically significant beneficial effect of HRV-biofeedback on psychological well-being for all women, and an additional statistically significant beneficial effect on anxiety complaints for pregnant women. No significant effect was found for the other stress-related complaints. These findings support the use of HRV-biofeedback as a stress-reducing technique among women reporting stress and related complaints in clinical practice to improve their well-being. Furthermore, it supports the use of this technique for reducing anxiety during pregnancy.

Psychological treatment of comorbid asthma and panic disorder: a pilot study.

We evaluated two protocols for treating adults with comorbid asthma and panic disorder. The protocols included elements of Barlow's panic control therapy and elements of Barlow's "panic control therapy" and several asthma education programs, as well as modules designed to teach participants how to differentiate asthma and panic symptoms, and how to apply specific home management strategies for each. Fifty percent of subjects dropped out of a 14-session protocol by the eighth session; however, 83% of patients were retained in an eight-session protocol. Clinical results were mostly equivalent: significant decreases of >50% in panic symptoms, clinically significant decreases in asthma symptoms, improvement in asthma quality of life, and maintenance of clinical stability in asthma. Albuterol use decreased significantly in the 14-session protocol and at a borderline level I the 8-session protocol, while pulmonary function was maintained. A controlled evaluation of this procedure is warranted.

Heart rate variability biofeedback and other psychophysiological procedures as important elements in psychotherapy.

Lang's distinction of psychophysiological, behavioral, and cognitive domains in psychological problems and therapies provides a useful heuristic for guiding psychotherapy. Much psychotherapy practice emphasizes the cognitive domain, but behavioral and psychophysiological interventions show at least equivalent effectiveness for some kinds of problems. Most descriptions of cognitive behavior therapy emphasize cognitive procedures, although most CBT approaches also incorporate behavioral interventions such as social skills training, exposure, and behavior activation. The contribution of psychophysiological methods is often underemphasized. Muscle relaxation and breathing interventions, particularly heart rate variability biofeedback, have been shown to have clinically significant therapeutic effects for a variety of problems. Although used more sporadically in the West, similar methods are part of traditional medical practice in Eastern countries. Examples are given for how these methods can be integrated into more generic psychotherapy practice, using Lang's distinctions, for a variety of psychological problems.

Rest, Reactivity, and Recovery: A Psychophysiological Assessment of Borderline Personality Disorder.

Difficulty regulating emotion is a cardinal feature of borderline personality disorder (BPD), yet little is known about the automatic psychophysiological processes involved in this phenotype. Inconsistent findings have emerged from studies that employed limited assessments (e.g., heart rate variability, skin conductance) of autonomic nervous system response to emotional contexts, and compared groups based on the presence or absence of BPD as a categorical diagnosis. This exploratory study assessed a comprehensive set of autonomic nervous system processes in 44 individuals (22 with BPD) at rest, in response to emotionally evocative stimuli, and during a subsequent recovery period. BPD was characterized with a dimensional measure of BPD symptom severity, as a well by categorical diagnosis. At baseline and across experimental tasks, higher heart rate was observed in those diagnosed with BPD compared to controls, and in those expressing greater BPD symptom severity. These effects, however, were fully mediated by differences in physical exercise. In contrast, during recovery from emotional activation, greater symptom severity predicted consistently higher levels of multiple sympathetic and parasympathetic processes compared to lower symptom severity. Overall, these findings suggest that the heart rate elevations sometimes observed in those diagnosed with BPD may be associated with individual and group differences in levels of physical exercise. Results further indicate that adaptive psychophysiological recovery responses following emotional challenge may be disrupted in proportion to BPD symptom severity, independently of exercise. Results highlight the utility of considering lifestyle factors and symptom severity in studies of emotional activation and regulation processes in BPD.

Low-dose steroid alters in vivo endotoxin-induced systemic inflammation but does not influence autonomic dysfunction.

Severe injury and infection are associated with autonomic dysfunction. Diminished heart rate variability (HRV) is also observed as a component of autonomic dysfunction and is induced by endotoxin administration to healthy subjects. It is established that low-dose glucocorticoid administration diminishes the systemic inflammatory manifestations of endotoxinemia but the influence of this anti-inflammatory intervention on overall autonomic dysfunction and HRV responses to endotoxin is unknown. This study was designed to assess the influence of a low-dose hydrocortisone infusion upon endotoxin-elicited systemic inflammatory responses including phenotypic features, cytokine production, and parameters of HRV. Of 19 subjects studied, nine received a continuous infusion of hydrocortisone (3 microg/kg/min continuously over 6 h) prior to intravenous administration of Escherichia coli endotoxin (2 ng/kg, CC-RE, Lot #2) while 10 healthy subjects received only the endotoxin after a 6-h period of saline control infusion. Serial determinations of vital signs, heart rate variability assessments, and cytokine levels were obtained over the subsequent 24 h. Prior cortisol infusion diminished the peak TNF-alpha (P < 0.01) and IL-6 (P < 0.0001) responses after endotoxin challenge, as compared to saline infusion controls and diminished the peak core temperature response to endotoxin (P < 0.01). In contrast to the influence of cortisol on the above parameters of systemic inflammation, the significant endotoxin-induced decreases in HRV time and frequency domains were not influenced by prior hydrocortisone treatment. Hence, alterations in autonomic dysfunction occur despite hydrocortisone attenuation of other traditional systemic manifestations of endotoxinemia. The maintenance or restoration of autonomic balance is not influenced by glucocorticoid administration.

Psychological treatment of comorbid asthma and panic disorder in Latino adults: Results from a randomized controlled trial.

Confusion between panic and asthma symptoms can result in serious self-management errors. A cognitive behavior psychophysiological therapy (CBPT) intervention was culturally adapted for Latinos consisting of CBT for panic disorder (PD), asthma education, differentiation between panic and asthma symptoms, and heart rate variability biofeedback. An RCT compared CBPT to music and relaxation therapy (MRT), which included listening to relaxing music and paced breathing at resting respiration rates. Fifty-three Latino (primarily Puerto Rican) adults with asthma and PD were randomly assigned to CBPT or MRT for 8 weekly sessions. Both groups showed improvements in PD severity, asthma control, and several other anxiety and asthma outcome measures from baseline to post-treatment and 3-month follow-up. CBPT showed an advantage over MRT for improvement in adherence to inhaled corticosteroids. Improvements in PD severity were mediated by anxiety sensitivity in CBPT and by depression in MRT, although earlier levels of these mediators did not predict subsequent improvements. Attrition was high (40%) in both groups, albeit comparable to CBT studies targeting anxiety in Latinos. Additional strategies are needed to improve retention in this high-risk population. Both CBPT and MRT may be efficacious interventions for comorbid asthma-PD, and CBPT may offer additional benefits for improving medication adherence.