Behavioral Therapy for Functional Heartburn: Recommendation Statements.

BACKGROUND & AIMS: Brain-gut behavior therapies (BGBT) are increasingly recognized as effective therapeutic interventions for functional heartburn. However, recommendations regarding candidacy for treatment, initial treatment selection, and navigating treatment non-response have not been established for functional heartburn specifically. The aim of this study was to establish expert-based recommendations for behavioral treatment in patients with functional heartburn. METHODS: The validated RAND/University of California, Los Angeles Appropriateness Method was applied to develop recommendations. A 15-member panel composed of 10 gastrointestinal psychologists and 5 esophageal specialists ranked the appropriateness of a series of statements on a 9-point interval scale over 2 ranking periods. Statements were within the following domains: pre-therapy evaluation, candidacy criteria for BGBT, selection of initial BGBT, role of additional therapy for initial non-response to BGBT, and role of pharmacologic neuromodulation. The primary outcome was appropriateness of each intervention based on the recommendation statements. RESULTS: Recommendations for psychosocial assessment (eg, hypervigilance, symptom-specific anxiety, health-related quality of life), candidacy criteria (eg, motivated for BGBT, acknowledges the role of stress in symptoms), and treatment were established. Gut-directed hypnotherapy or cognitive behavioral therapy were considered appropriate BGBT for functional heartburn. Neuromodulation and/or additional BGBT were considered appropriate in the context of non-response. CONCLUSIONS: Gut-directed hypnotherapy and/or cognitive behavioral therapy are recommended as appropriate behavioral interventions for heartburn symptoms, depending on clinical indication, specific gut-brain targets, and preferred treatment modality (pharmacologic vs non-pharmacologic). Pre-therapy evaluation of psychosocial processes and candidacy for BGBT are important to determine eligibility for referral to psychogastroenterology services.

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.

Heart Rate Variability Biofeedback for Mild Traumatic Brain Injury: A Randomized-Controlled Study.

To determine whether heart rate variability biofeedback (HRV-BF) training, compared to a psychoeducation control condition can strengthen the integration of the central and autonomic nervous systems as measured by neuropsychological measures in patients with mild traumatic brain injury (mTBI). Participants were recruited from two university hospitals in Taipei, Taiwan. A total of 49 participants with mTBI were recruited for this study. Forty-one participants completed the study, 21 in the psychoeducation group and 20 in the HRV-BF group. Randomized controlled study. The Taiwanese Frontal Assessment Battery, the Semantic Association of Verbal Fluency Test, the Taiwanese version of the Word Sequence Learning Test, the Paced Auditory Serial Addition Test-Revised, and the Trail Making Test were used as performance-based neuropsychological functioning measures. The Checklist of Post-concussion Symptoms, the Taiwanese version of the Dysexecutive Questionnaire, the Beck Anxiety Inventory, the Beck Depression Inventory, and the National Taiwan University Irritability Scale were used as self-report neuropsychological functioning measures. Furthermore, heart rate variability pre- vs. post-training was used to measure autonomic nervous system functioning. Executive, information processing, verbal memory, emotional neuropsychological functioning, and heart rate variability (HRV) were improved significantly in the HRV-BF group at the posttest whereas the psychoeducation group showed no change. HRV biofeedback is a feasible technique following mild TBI that can improve neuropsychological and autonomic nervous system functioning. HRV-BF may be clinically feasible for the rehabilitation of patients with mTBI.

Heartbeat-Evoked Potential in Major Depressive Disorder: A Biomarker for Differential Treatment Prediction between Venlafaxine and rTMS?

INTRODUCTION: Currently, major depressive disorder (MDD) treatment plans are based on trial-and-error, and remission rates remain low. A strategy to replace trial-and-error and increase remission rates could be treatment stratification. We explored the heartbeat-evoked potential (HEP) as a biomarker for treatment stratification to either antidepressant medication or rTMS treatment. METHODS: Two datasets were analyzed: (1) the International Study to Predict Optimized Treatment in Depression (iSPOT-D; n = 1,008 MDD patients, randomized to escitalopram, sertraline, or venlafaxine, and n = 336 healthy controls) and (2) a multi-site, open-label rTMS study (n = 196). The primary outcome measure was remission. Cardiac field artifacts were removed from the baseline EEG using independent component analysis (ICA). The HEP-peak was detected in a bandwidth of 20 ms around 8 ms and 270 ms (N8, N270) after the R-peak of the electrocardiogram signal. Differences between remitters and non-remitters were statistically assessed by repeated-measures ANOVAs for electrodes Fp1, Cz, and Oz. RESULTS: In the venlafaxine subgroup, remitters showed a lower HEP around the N8 peak than non-remitters on electrode site Cz (p = 0.004; d = 0.497). The rTMS group showed a non-significant difference in the opposite direction (d = -0.051). Retrospective stratification to one of the treatments based on the HEP resulted in enhanced treatment outcome prediction for venlafaxine (+22.98%) and rTMS (+10.66%). CONCLUSION: These data suggest that the HEP could be used as a stratification biomarker between venlafaxine and rTMS; however, future out-of-sample replication is warranted.

The Role of the Autonomic Nervous System in Headache: Biomarkers and Treatment.

PURPOSE OF REVIEW: In this review, the role of the autonomic nervous system in tension-type headache and migraine is reviewed. RECENT FINDINGS: A pathophysiological model for tension-type headache is proposed that is compatible with most physiological and behavioral literature. A treatment protocol is described that follows from this model. For migraine, incorporating autonomic factors into the pathophysiology offers rationales for behavioral interventions that have been shown to be useful in migraine treatment and a biofeedback protocol is proposed.

Targeting autonomic flexibility to enhance cognitive training outcomes in older adults with mild cognitive impairment: study protocol for a randomized controlled trial.

IMPORTANCE: Cognitive training with components that can further enhance the transferred and long-term effects and slow the progress of dementia is needed for preventing dementia. OBJECTIVE: The goal of the study is to test whether improving autonomic nervous system (ANS) flexibility via a resonance frequency breathing (RFB) training will strengthen the effects of a visual speed of processing (VSOP) cognitive training on cognitive and brain function, and slow the progress of dementia in older adults with mild cognitive impairment (MCI). DESIGN: Stage II double-blinded randomized controlled trial. The study was prospectively registered at ClinicalTrials.gov, with registration approved on 21 August 2020 (No. NCT04522791). SETTING: Study-related appointments will be conducted on-site at University of Rochester Medical Center locations. Data collection will be conducted from August 2020 to February 2025. PARTICIPANTS: Older adults with MCI (n = 114) will be randomly assigned to an 8-week combined intervention (RFB+VSOP), VSOP with guided imagery relaxation (IR) control, and a IR-only control, with periodical booster training sessions at follow-ups. Mechanistic and distal outcomes include ANS flexibility, measured by heart rate variability, and multiple markers of dementia progress. Data will be collected across a 14-month period. DISCUSSION: This will be among the first RCTs to examine in older persons with MCI a novel, combined intervention targeting ANS flexibility, an important contributor to overall environmental adaptation, with an ultimate goal for slowing neurodegeneration. TRIAL REGISTRATION: ClinicalTrials.gov NCT04522791 . Registered on 21 August 2020 Protocol version: STUDY00004727; IRB protocol version 2, approved on 30 July 2020.

Pilot Study on Reducing Symptoms of Anxiety with a Heart Rate Variability Biofeedback Wearable and Remote Stress Management Coach.

We assessed the feasibility of using a consumer friendly, heart rate variability biofeedback (HRVB) wearable device in conjunction with a remote stress management coach to reduce symptoms of anxiety. We utilized a discreet, continuously wearable electrocardiogram device, the Lief Smart Patch, which measures and records heart rate and HRV in real time, and guides HRVB exercises using vibrations and visual cues. During the 8-week study, participants (N = 14) wore the Lief Smart Patch, participated in HRVB with the device, utilized the mobile app, and communicated with a remote stress management coach. We collected self-report survey responses to measure symptoms of anxiety (GAD-2) and depression (PHQ-2) every 2 weeks, as well as HRV data throughout the study. Participants' mean GAD-2 score began at 4.6 out of 6. By the trial's completion, the group's mean GAD-2 score dropped to 1.7 (t(13) = 11.0, p < .001) with only 2 of the 14 subjects remaining over the clinical threshold of high anxiety. Similarly, the group's mean PHQ-2 score dropped from 2.93 to 1.29 (t(13) = 3.54, p < .01). In addition, participants increased their HRV (RMSSD) by an average of + 11.4 ms after participating in a low dose biofeedback exercise. These findings suggest that engaging in HRVB through a discreet wearable device in conjunction with a remote stress management program may be effective for reducing symptoms of anxiety and depression.

Neurophysiological Approach by Self-Control of Your Stress-Related Autonomic Nervous System with Depression, Stress and Anxiety Patients.

BACKGROUND: Heart Rate Variability Biofeedback (HRVB) is a treatment in which patients learn self-regulation of a physiological dysregulated vagal nerve function. While the therapeutic approach of HRVB is promising for a variety of disorders, it has not yet been regularly offered in a mental health treatment setting. AIM: To provide a systematic review about the efficacy of HRV-Biofeedback in treatment of anxiety, depression, and stress related disorders. METHOD: Systematic review in PubMed and Web of Science in 2020 with terms HRV, biofeedback, Post-Traumatic Stress Disorder (PTSD), depression, panic disorder, and anxiety disorder. Selection, critical appraisal, and description of the Random Controlled Trials (RCT) studies. Combined with recent meta-analyses. RESULTS: The search resulted in a total of 881 studies. After critical appraisal, nine RCTs have been selected as well as two other relevant studies. The RCTs with control groups treatment as usual, muscle relaxation training and a "placebo"-biofeedback instrument revealed significant clinical efficacy and better results compared with control conditions, mostly significant. In the depression studies average reduction at the Beck Depression Inventory (BDI) scale was 64% (HRVB plus Treatment as Usual (TAU) versus 25% (control group with TAU) and 30% reduction (HRVB) at the PSQ scale versus 7% (control group with TAU). In the PTSD studies average reduction at the BDI-scale was 53% (HRV plus TAU) versus 24% (control group with TAU) and 22% (HRVB) versus 10% (TAU) with the PTSD Checklist (PCL). In other systematic reviews significant effects have been shown for HRV-Biofeedback in treatment of asthma, coronary artery disease, sleeping disorders, postpartum depression and stress and anxiety. CONCLUSION: This systematic review shows significant improvement of the non-invasive HRVB training in stress related disorders like PTSD, depression, and panic disorder, in particular when combined with cognitive behavioral therapy or different TAU. Effects were visible after four weeks of training, but clinical practice in a longer daily self-treatment of eight weeks is more promising. More research to integrate HRVB in treatment of stress related disorders in psychiatry is warranted, as well as research focused on the neurophysiological mechanisms.

Feasibility and Efficacy of the Addition of Heart Rate Variability Biofeedback to a Remote Digital Health Intervention for Depression.

A rise in the prevalence of depression underscores the need for accessible and effective interventions. The objectives of this study were to determine if the addition of a treatment component showing promise in treating depression, heart rate variability-biofeedback (HRV-B), to our original smartphone-based, 8-week digital intervention was feasible and whether patients in the HRV-B ("enhanced") intervention were more likely to experience clinically significant improvements in depressive symptoms than patients in our original ("standard") intervention. We used a quasi-experimental, non-equivalent (matched) groups design to compare changes in symptoms of depression in the enhanced group (n = 48) to historical outcome data from the standard group (n = 48). Patients in the enhanced group completed a total average of 3.86 h of HRV-B practice across 25.8 sessions, and were more likely to report a clinically significant improvement in depressive symptom score post-intervention than participants in the standard group, even after adjusting for differences in demographics and engagement between groups (adjusted OR 3.44, 95% CI [1.28-9.26], P = .015). Our findings suggest that adding HRV-B to an app-based, smartphone-delivered, remote intervention for depression is feasible and may enhance treatment outcomes.

A frontal-vagal network theory for Major Depressive Disorder: Implications for optimizing neuromodulation techniques.

Major Depressive Disorder (MDD) is a psychiatric disorder characterized by high comorbidity with cardiovascular disease. Furthermore, a combination of high heart rate (HR) and low heart rate variability (HRV) has been frequently reported in depressed patients. The present review proposes a frontal-vagal (brain-heart) network that overlaps with functional nodes of the depression network. Moreover, we summarize neuromodulation studies that have targeted key nodes in this depression network, with subsequent impact on heart rate (HR) or heart-rate-variability (HRV), such as the dorsolateral prefrontal cortex (DLPFC), subgenual anterior cingulate cortex (sgACC), and the vagus nerve (VN). Based on the interplay of this frontal-vagal network, we emphasize the importance of including HR and HRV measurements in human depression studies, in particular those that conduct neuromodulation, in order to obtain a better understanding of the pathways that are affected, and we explore the possibilities of using this frontal-vagal interplay as a method for target engagement in neuromodulation treatments. This frontal-vagal network theory opens-up the possibility for individualizing neuromodulation treatments such as rTMS. A recent development called Neuro-Cardiac-Guided TMS (NCG-TMS), was developed based on this theory, and an individual-participant meta-analysis is presented. Four studies provide consistent and replicable support for NCG-TMS as a target engagement method, with consistent HR deceleration during frontal TMS and HR acceleration during motor strip TMS.

Secondary outcomes of a behavioral sleep intervention: A randomized clinical trial.

OBJECTIVE: Nearly 80% of cancer patients struggle with insomnia, which is associated with decreased heart rate variability (HRV) and quality of life (QOL). The aim of this secondary analysis was to evaluate the possible effects of Brief Behavioral Therapy for Cancer-Related Insomnia (BBT-CI), delivered during chemotherapy visits, on QOL and HRV in patients with breast cancer (BC). METHOD: QOL and HRV data were obtained during a pilot clinical trial assessing the feasibility and effects of BBT-CI on insomnia. A total of 71 BC patients (mean age = 52.5 years) were randomly assigned to either BBT-CI or a healthy-eating control intervention (HEAL). BBT-CI and HEAL were delivered over 6 weeks (2 face-to-face sessions plus 4 phone calls) by trained staff at 4 National Cancer Institute-funded Community Oncology Research Program clinics. QOL was measured with the Functional Assessment of Cancer Therapy (FACT-G) and HRV with the Firstbeat device at baseline and after intervention. RESULTS: There were significant improvements in QOL after intervention for BBT-CI (FACT-G, p = .009; FACT-B, p = .016; ANCOVA) and 5-min supine HRV measures (SDNN, p = .005; rMSSD, p = .004; HF, p = .009; ANCOVA) compared with HEAL. CONCLUSIONS: Patients randomized to BBT-CI showed improvements in QOL and HRV, providing support for BBT-CI's possible benefit when delivered in the community oncology setting by trained staff. A more definitive efficacy trial of BBT-CI is currently being planned with sufficient statistical power to evaluate the intervention's clinical utility. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Contributing factors predicting nightmares in children: Trauma, anxiety, dissociation, and emotion regulation.

OBJECTIVE: There is little research in the current literature regarding contributing factors to nightmares in children. This study aimed to test potentially overlapping predictors of nightmare distress and severity, including anxiety, dissociation, trauma history, vagal tone, and parental processing of emotions. METHOD: Sixty parent-child dyads (children ages 6-11) filled out a variety of child-report and parent-observation inventories on nightmare frequency and distress, dissociation, anxiety, and trauma history of the child. Children were monitored on heart rate variability and vagal tone. Both parent and child participated in a discussion of positive and negative life events that were later coded for degree of parent processing of emotional information. RESULTS: Anxiety, trauma history, dissociation, and baseline vagal tone accounted for 39% of the variance in nightmare distress. Anxiety and dissociation were positive predictors of nightmare distress in the multiple regression. Parent processing variables were weak predictors in the current analysis. CONCLUSIONS: The predictive power of anxiety, dissociation, vagal tone, and trauma history was not entirely due to their overlap, as shown by uniquely significant beta weights in the prediction of distress. Treatment procedures with multiple intervention points targeting physiological and psychological sources of nightmare distress may be warranted. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Heart Rate Variability and Cognitive Bias Feedback Interventions to Prevent Post-deployment PTSD: Results from a Randomized Controlled Trial.

Introduction: There is a long history of pre-deployment PTSD prevention efforts in the military and effective pre-deployment strategies to prevent post-deployment PTSD are still needed. Materials and Methods: This randomized controlled trial included three arms: heart rate variability biofeedback (HRVB), cognitive bias modification for interpretation (CBM-I), and control. The hypothesis was that pre-deployment resilience training would result in lower post-deployment PTSD symptoms compared with control. Army National Guard soldiers (n = 342) were enrolled in the Warriors Achieving Resilience (WAR) study and analyzed. The outcome was PTSD symptom severity using the PTSD Checklist - Military version (PCL) measured at pre-deployment, 3- and 12-month post-deployment. Due to the repeated measures for each participant and cluster randomization at the company level, generalized linear mixed models were used for the analysis. This study was approved by the Army Human Research Protection Office, Central Arkansas Veterans Healthcare System Institutional Review Board (IRB), and Southeast Louisiana Veterans Health Care System IRB. Results: Overall, there was no significant intervention effect. However, there were significant intervention effects for subgroups of soldiers. For example, at 3-months post-deployment, the HRVB arm had significantly lower PCL scores than the control arm for soldiers with no previous combat zone exposure who were age 30 and older and for soldiers with previous combat zone exposure who were 45 and older (unadjusted effect size -0.97 and -1.03, respectively). A significant difference between the CBM-I and control arms was found for soldiers without previous combat zone exposure between ages 23 and 42 (unadjusted effect size -0.41). Similarly, at 12-months post-deployment, the HRVB arm had significantly lower PCL scores in older soldiers. Conclusion: Pre-deployment resilience training was acceptable and feasible and resulted in lower post-deployment PTSD symptom scores in subgroups of older soldiers compared with controls. Strengths of the study included cluster randomization at the company level, use of iPod device to deliver the resilience intervention throughout the deployment cycle, and minimal disruption of pre-deployment training by using self-paced resilience training. Weaknesses included self-report app use, study personnel not able to contact soldiers during deployment, and in general a low level of PTSD symptom severity throughout the study. In future studies, it would important for the study team and/or military personnel implementing the resilience training to be in frequent contact with participants to ensure proper use of the resilience training apps.

fMRI during Transcendental Meditation practice.

This study used a within group design to investigate blood flow patterns (fMRI) in 16 long-term practitioners of Transcendental Meditation (mean practice: 34.3 years with each having over 36,000 h of meditation practice). During Transcendental Meditation practice, blood flow patterns were significantly higher in executive and attention areas (anterior cingulate and dorsolateral prefrontal cortices) and significantly lower in arousal areas (pons and cerebellum). This pattern supports the understanding that Transcendental Meditation practice requires minimal effort. During Transcendental Meditation, the attentional system was active (heightened blood flow in anterior cingulate and dorsolateral prefrontal cortices) in an automatic manner-decreased blood flow in the pons and cerebellum. This pattern of heightened blood flow in attentional areas and decreased blood flow in arousal areas has not been reported during other meditation practices. Future research should investigate blood flow patterns in different meditation practices in the same study.

Heart Rate Variability Markers as Correlates of Survival in Recipients of Hematopoietic Cell Transplantation

OBJECTIVES: To assess pre-/post-transplantation changes in autonomic tone, as measured by heart rate variability (HRV), among patients undergoing hematopoietic cell transplantation (HCT) and to look at those changes as they relate to post-transplantation survival rates. 
. SAMPLE & SETTING: Data were derived from a sample of 27 English-speaking patients undergoing allogeneic or autologous HCT at Stanford University. 
. METHODS & VARIABLES: A survival analysis using the Kaplan-Meier estimator was employed to explore whether increased HRV would enhance survival probabilities over time among patients undergoing HCT.
. RESULTS: An increased probability of survival was significantly related to increases in two HRV indexes. IMPLICATIONS FOR NURSING: HRV may be a useful predictor of mortality among patients undergoing HCT. Interventions deliverable by nurses could be used to enhance HRV for patients identified as being at risk for early mortality.

Facilitating Neurofeedback in Children with Autism and Intellectual Impairments Using TAGteach.

Individuals with autism and intellectual impairments tend to be excluded from research due to their difficulties with methodological compliance. This study focuses on using Teaching with Acoustic Guidance-TAGteach-to behaviorally prepare children with autism and a IQ ≤ 80 to participate in a study on neurofeedback training (NFT). Seven children (ages 6-8) learned the prerequisite skills identified in a task analysis in an average of 5 h of TAGteach training, indicating that this is a feasible method of preparing intellectually-impaired children with autism to participate in NFT and task-dependent electroencephalography measures. TAGteach may thus have the potential to augment this population's ability to participate in less accessible treatments and behavioral neuroscientific studies.

Alcohol Use Disorder Moderates the Effect of Age on Heart Rate Variability in Veterans With Posttraumatic Stress Disorder.

Research on heart rate variability (HRV) in posttraumatic stress disorder (PTSD) and comorbid alcohol use disorder (AUD) is limited despite its use as a biomarker of both disorders. This study examined whether AUD comorbidity contributes an additive effect on HRV for veterans with PTSD. HRV was assessed in 70 male Operation Enduring Freedom/Operation Iraqi Freedom veterans with PTSD, including 32 with co-occurring AUD. Mean HRV values for both groups were below the mean for healthy adults, but additive effects of PTSD and AUD on HRV were not observed. Consistent with prior studies, hierarchical regressions showed that HRV decreased with age in the PTSD-only group. However, HRV increased slightly with age among veterans with both PTSD and AUD. This interaction remained significant after controlling for common HRV covariates. These findings support HRV as a biomarker of PTSD and extend research by demonstrating the complex relationship between PTSD and HRV in the context of co-occurring AUD.

Neuro-Cardiac-Guided TMS (NCG-TMS): Probing DLPFC-sgACC-vagus nerve connectivity using heart rate - First results.

BACKGROUND: Given that many studies suggest a role of DLPFC-sgACC connectivity in depression and prior research demonstrating that neuromodulation of either of these nodes modulates parasympathetic activity and results in a heart rate deceleration, a new method is proposed to individualize localization of the DLPFC. This can, among others, be useful for rTMS treatment of depression. METHODS: Ten healthy subjects received three trains of 10Hz rTMS randomly over 7 target regions (10-20 system). RESULTS: Overall, F3 and F4 expressed the largest heart rate deceleration, in line with studies suggesting these are the best 10-20 sites to target the DLPFC. On the individual level, 20-40% subjects expressed the largest heart rate deceleration at FC3 or FC4, indicating individual differences as to the 'optimal site for stimulation'. CONCLUSIONS: These results show that the NCG-TMS method is valid to localize the entry into the DLPFC-sgACC network.