Four Sessions of Combining Wearable Devices and Heart Rate Variability (HRV) Biofeedback are Needed to Increase HRV Indices and Decrease Breathing Rates.

Heart rate variability biofeedback (HRVB) is a behavioral intervention that uses resonance frequency breathing to synchronize the heart rate and breathing patterns. This study aimed to explore how many sessions of wearable HRVB devices are needed to increase the HRV index and decrease breathing rates and to compare the HRVB protocol with other psychological intervention programs in HRV indices and breathing rates. Sixty-four participants were randomly assigned to either the HRVB or relaxation training (RT) group. Both groups received interbeat intervals (IBIs) and breathing rates measurement at the pre-training baseline, during training, and post-training baseline from weeks 1 to 4. IBIs were transformed into HRV indices as the index of the autonomic nervous system. The Group × Week interaction effects significantly in HRV indices and breathing rates. The between-group comparison found a significant increase in HRV indices and decreased breathing rates in the HRVB group than in the RT group at week 4. The within-session comparison in the HRVB group revealed significantly increased HRV indices and decreased breathing rates at weeks 3 and 4 than at weeks 1 and 2. There was a significant increase in HRV indices and a decrease in breathing rates at mid- and post-training than pre-training in the HRVB group. Therefore, 4 weeks of HRVB combined with a wearable device are needed in increasing HRV indices and decrease breathing rates compared to the relaxation training. Three weeks of HRVB training are the minimum requirement for increasing HRV indices and reducing breathing rates compared to the first week of HRVB.

The learning effects and curves during high beta down-training neurofeedback for patients with major depressive disorder.

BACKGROUND: Electroencephalography (EEG) has revealed increased beta activity in patients with comorbid major depressive disorder (MDD) and anxiety symptoms. Negative emotions and high beta activity could be decreased by a high beta down-training neurofeedback (NFB) protocol. The present study utilized three objective parameters - trainability, independence, and interpretability - to validate the effects of high beta down-training sessions. METHODS: EEG data were collected from 23 patients with comorbid MDD and anxiety symptoms during high beta down-training sessions. Participants received five weeks of training, two sessions per week, to down-train high beta amplitude (20-32 Hz) at EEG sites P3 and P4. Three efficacy parameters were examined by comparing pre-training and post-training EEG. RESULTS: The trainability index revealed the learning curves of reduced high beta activity at P3 and P4, confirming training effects across and within sessions. The independence index revealed only beta band activity decreased. The interpretability index revealed the decreased high beta activity was positively correlated with decreased severity of depression, especially for cognitive depression. LIMITATIONS: With only ten sessions in this study, it is unknown whether the NFB training caused extended and stable learning effects. Additionally, combining high beta down-training protocol with enhancing another target band could better ensure the desired changes in brain activity. Finally, the effect of medication on EEG cannot be excluded in present study. CONCLUSIONS: The trainability, independence and interpretability of the high beta down-training NFB protocol were confirmed, supporting the protocol's use in future research and clinical applications.

NPFFR2 Activates the HPA Axis and Induces Anxiogenic Effects in Rodents.

Neuropeptide FF (NPFF) belongs to the RFamide family and is known as a morphine-modulating peptide. NPFF regulates various hypothalamic functions through two receptors, NPFFR1 and NPFFR2. The hypothalamic-pituitary-adrenal (HPA) axis participates in physiological stress response by increasing circulating glucocorticoid levels and modulating emotional responses. Other RFamide peptides, including neuropeptide AF, neuropeptide SF and RFamide related peptide also target NPFFR1 or NPFFR2, and have been reported to activate the HPA axis and induce anxiety- or depression-like behaviors. However, little is known about the action of NPFF on HPA axis activity and anxiety-like behaviors, and the role of the individual receptors remains unclear. In this study, NPFFR2 agonists were used to examine the role of NPFFR2 in activating the HPA axis in rodents. Administration of NPFFR2 agonists, dNPA (intracerebroventricular, ICV) and AC-263093 (intraperitoneal, IP), time-dependently (in rats) and dose-dependently (in mice) increased serum corticosteroid levels and the effects were counteracted by the NPFF receptor antagonist, RF9 (ICV), as well as corticotropin-releasing factor (CRF) antagonist, α-helical CRF(9-41) (intravenous, IV). Treatment with NPFFR2 agonist (AC-263093, IP) increased c-Fos protein expression in the hypothalamic paraventricular nucleus and induced an anxiogenic effect, which was evaluated in mice using an elevated plus maze. These findings reveal, for the first time, that the direct action of hypothalamic NPFFR2 stimulates the HPA axis and triggers anxiety-like behaviors.

Chronic activation of NPFFR2 stimulates the stress-related depressive behaviors through HPA axis modulation.

Neuropeptide FF (NPFF) is a morphine-modulating peptide that regulates the analgesic effect of opioids, and also controls food consumption and cardiovascular function through its interaction with two cognate receptors, NPFFR1 and NPFFR2. In the present study, we explore a novel modulatory role for NPFF-NPFFR2 in stress-related depressive behaviors. In a mouse model of chronic mild stress (CMS)-induced depression, the expression of NPFF significantly increased in the hypothalamus, hippocampus, medial prefrontal cortex (mPFC) and amygdala. In addition, transgenic (Tg) mice over-expressing NPFFR2 displayed clear depression and anxiety-like behaviors with hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis, reduced expression of glucocorticoid receptor (GR) and neurogenesis in the hippocampus. Furthermore, acute treatment of NPFFR2 agonists in wild-type (WT) mice enhanced the activity of the HPA axis, and chronic administration resulted in depressive and anxiety-like behaviors. Chronic stimulation of NPFFR2 also decreased the expression of hippocampal GR and led to persistent activation of the HPA axis. Strikingly, bilateral intra-paraventricular nucleus (PVN) injection of NPFFR2 shRNA predominately inhibits the depressive-like behavior in CMS-exposed mice. Antidepressants, fluoxetine and ketamine, effectively relieved the depressive behaviors of NPFFR2-Tg mice. We speculate that persistent NPFFR2 activation, in particular in the hypothalamus, up-regulates the HPA axis and results in long-lasting increases in circulating corticosterone (CORT), consequently damaging hippocampal function. This novel role of NPFFR2 in regulating the HPA axis and hippocampal function provides a new avenue for combating depression and anxiety-like disorder.