Heart rate variability, the vagus and calm.
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701 to 725 of 1,007The relationship between sexual concordance and interoception in anxious and nonanxious women.
Introduction: Sexual concordance refers to the association between physiological and self-reported sexual arousal. Women typically exhibit lower sexual concordance scores than men. There is also a sex difference in interoception--awareness of (nonsexual) physiological states or responses--such that women, compared with men, tend to be less aware of and less accurate at detecting changes in their physiological responses. Women with anxiety problems tend to have better interoceptive abilities than nonanxious women.
Aim: To investigate whether women's lower sexual concordance is associated with interoception using a sample likely to show high variation in interoceptive abilities.
Method: Sixteen anxious and 15 nonanxious women were presented with twelve 90 seconds sexual and nonsexual film clips while their genital response, heart rate, and respiration rate were measured. A heartbeat mental…
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Sympathetic nerve fibers in human cervical and thoracic vagus nerves.
Background: Vagus nerve stimulation (VNS) therapy has been used for chronic heart failure and is believed to improve imbalance of autonomic control by increasing parasympathetic activity. Although it is known that there is neural communication between the VN and the cervical sympathetic trunk, there are few data regarding the quantity and/or distribution of the sympathetic components within the vagus nerve (VN).
Objective: To examine the sympathetic components within the human VN and correlate them with the presence of cardiac and neurologic diseases.
Methods: We performed immunohistochemistry on 31 human cervical and thoracic VNs (total 104 VNs) from autopsies and reviewed the patients' records. We correlated the quantity of sympathetic nerve fibers within the VNs with cardiovascular and neurologic disease states.
Results: All 104 VNs contain tyrosine hydroxylase (TH)-positive (sympathe…
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Neuro-anatomical evidence indicating indirect modulation of macrophages by vagal efferents in the intestine but not in the spleen.
Background: Electrical stimulation of the vagus nerve suppresses intestinal inflammation and normalizes gut motility in a mouse model of postoperative ileus. The exact anatomical interaction between the vagus nerve and the intestinal immune system remains however a matter of debate. In the present study, we provide additional evidence on the direct and indirect vagal innervation of the spleen and analyzed the anatomical evidence for neuroimmune modulation of macrophages by vagal preganglionic and enteric postganglionic nerve fibers within the intestine.
Methods: Dextran conjugates were used to label vagal preganglionic (motor) fibers projecting to the small intestine and spleen. Moreover, identification of the neurochemical phenotype of the vagal efferent fibers and enteric neurons was performed by immunofluorescent labeling. F4/80 antibody was used to label resident macrophages.
Results…
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Neurostimulation of the cholinergic anti-inflammatory pathway ameliorates disease in rat collagen-induced arthritis.
Introduction: The inflammatory reflex is a physiological mechanism through which the nervous system maintains immunologic homeostasis by modulating innate and adaptive immunity. We postulated that the reflex might be harnessed therapeutically to reduce pathological levels of inflammation in rheumatoid arthritis by activating its prototypical efferent arm, termed the cholinergic anti-inflammatory pathway. To explore this, we determined whether electrical neurostimulation of the cholinergic anti-inflammatory pathway reduced disease severity in the collagen-induced arthritis model.
Methods: Rats implanted with vagus nerve cuff electrodes had collagen-induced arthritis induced and were followed for 15 days. Animals underwent active or sham electrical stimulation once daily from day 9 through the conclusion of the study. Joint swelling, histology, and levels of cytokines and bone metabolism m…
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Olofsson PS, Katz DA, Rosas-Ballina M, Levine YA, Ochani M, Valdés-Ferrer SI, Pavlov VA, Tracey KJ, Chavan SS (2012)MEDLINE-indexed journal, not yet read by usMolecular medicine (Cambridge, Mass.)136 citations α7 nicotinic acetylcholine receptor (α7nAChR) expression in bone marrow-derived non-T cells is required for the inflammatory reflex.
The immune response to infection or injury coordinates host defense and tissue repair, but also has the capacity to damage host tissues. Recent advances in understanding protective mechanisms have found neural circuits that suppress release of damaging cytokines. Stimulation of the vagus nerve protects from excessive cytokine production and ameliorates experimental inflammatory disease. This mechanism, the inflammatory reflex, requires the α7 nicotinic acetylcholine receptor (α7nAChR), a ligand-gated ion channel expressed on macrophages, lymphocytes, neurons and other cells. To investigate cell-specific function of α7nAChR in the inflammatory reflex, we created chimeric mice by cross-transferring bone marrow between wild-type (WT) and α7nAChR-deficient mice. Deficiency of α7nAChR in bone marrow-derived cells significantly impaired vagus nerve-mediated regulation of tumor necrosis factor …
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Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve.
There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABA(B1b) mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant reductions in expression in the hippocampus, amygdala, a…
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Vagus nerve stimulation modulates cortical synchrony and excitability through the activation of muscarinic receptors.
Vagus nerve stimulation (VNS) is an FDA approved treatment for drug-resistant epilepsy and depression. Recently, we demonstrated the capacity for repeatedly pairing sensory input with brief pulses of VNS to induce input specific reorganization in rat auditory cortex. This was subsequently used to reverse the pathological neural and perceptual correlates of hearing loss induced tinnitus. Despite its therapeutic potential, VNS mechanisms of action remain speculative. In this study, we report the acute effects of VNS on intra-cortical synchrony, excitability, and sensory processing in anesthetized rat auditory cortex. VNS significantly increased and decorrelated spontaneous multi-unit activity, and suppressed entrainment to repetitive noise burst stimulation at 6-8 Hz but not after application of the muscarinic antagonist scopolamine. Collectively, these experiments demonstrate the capacity…
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β2-Adrenoreceptors of regulatory lymphocytes are essential for vagal neuromodulation of the innate immune system.
The nervous system is classically organized into sympathetic and parasympathetic systems acting in opposition to maintain physiological homeostasis. Here, we report that both systems converge in the activation of β2-adrenoceptors of splenic regulatory lymphocytes to control systemic inflammation. Vagus nerve stimulation fails to control serum TNF levels in either β2-knockout or lymphocyte-deficient nude mice. Unlike typical suppressor CD25(+) cells, the transfer of CD4(+)CD25(-) regulatory lymphocytes reestablishes the anti-inflammatory potential of the vagus nerve and β2-agonists to control inflammation in both β2-knockout and nude mice. β2-Agonists inhibit cytokine production in splenocytes (IC(50)≈ 1 μM) and prevent systemic inflammation in wild-type but not in β2-knockout mice. β2-Agonists rescue wild-type mice from established polymicrobial peritonitis in a clinically relevant time …
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Li JV, Ashrafian H, Bueter M, Kinross J, Sands C, le Roux CW, Bloom SR, Darzi A, Athanasiou T, Marchesi JR, Nicholson JK, Holmes E (2011)MEDLINE-indexed journal, not yet read by usGut316 citations Metabolic surgery profoundly influences gut microbial-host metabolic cross-talk.
Background and aims: Bariatric surgery is increasingly performed worldwide to treat morbid obesity and is also known as metabolic surgery to reflect its beneficial metabolic effects especially with respect to improvement in type 2 diabetes. Understanding surgical weight loss mechanisms and metabolic modulation is required to enhance patient benefits and operative outcomes.
Methods: The authors applied a parallel and statistically integrated bacterial profiling and metabonomic approach to characterise Roux-en-Y gastric bypass (RYGB) effects in a non-obese rat model.
Results: Substantial shifts of the main gut phyla towards higher concentrations of Proteobacteria (52-fold), specifically Enterobacter hormaechei, are shown. Low concentrations of Firmicutes (4.5-fold) and Bacteroidetes (twofold) in comparison with sham-operated rats were also found. Faecal extraction studies revealed a decrea…
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Reversing pathological neural activity using targeted plasticity.
Brain changes in response to nerve damage or cochlear trauma can generate pathological neural activity that is believed to be responsible for many types of chronic pain and tinnitus. Several studies have reported that the severity of chronic pain and tinnitus is correlated with the degree of map reorganization in somatosensory and auditory cortex, respectively. Direct electrical or transcranial magnetic stimulation of sensory cortex can temporarily disrupt these phantom sensations. However, there is as yet no direct evidence for a causal role of plasticity in the generation of pain or tinnitus. Here we report evidence that reversing the brain changes responsible can eliminate the perceptual impairment in an animal model of noise-induced tinnitus. Exposure to intense noise degrades the frequency tuning of auditory cortex neurons and increases cortical synchronization. Repeatedly pairing t…
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The influence of carbon dioxide on brain activity and metabolism in conscious humans.
A better understanding of carbon dioxide (CO(2)) effect on brain activity may have a profound impact on clinical studies using CO(2) manipulation to assess cerebrovascular reserve and on the use of hypercapnia as a means to calibrate functional magnetic resonance imaging (fMRI) signal. This study investigates how an increase in blood CO(2), via inhalation of 5% CO(2), may alter brain activity in humans. Dynamic measurement of brain metabolism revealed that mild hypercapnia resulted in a suppression of cerebral metabolic rate of oxygen (CMRO(2)) by 13.4% ± 2.3% (N=14) and, furthermore, the CMRO(2) change was proportional to the subject's end-tidal CO(2) (Et-CO(2)) change. When using functional connectivity MRI (fcMRI) to assess the changes in resting-state neural activity, it was found that hypercapnia resulted in a reduction in all fcMRI indices assessed including cluster volume, cross-c…
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Chronic vagus nerve stimulation induces neuronal plasticity in the rat hippocampus.
Vagus nerve stimulation (VNS) is used to treat pharmacotherapy-resistant epilepsy and depression. However, the mechanisms underlying the therapeutic efficacy of VNS remain unclear. We examined the effects of VNS on hippocampal neuronal plasticity and behaviour in rats. Cell proliferation in the hippocampus of rats subjected to acute (3 h) or chronic (1 month) VNS was examined by injection of bromodeoxyuridine (BrdU) and immunohistochemistry. Expression of doublecortin (DCX) and brain-derived neurotrophic factor (BDNF) was evaluated by immunofluorescence staining. The dendritic morphology of DCX+ neurons was measured by Sholl analysis. Our results show that acute VNS induced an increase in the number of BrdU+ cells in the dentate gyrus that was apparent 24 h and 3 wk after treatment. It also induced long-lasting increases in the amount of DCX immunoreactivity and in the number of DCX+ neu…
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van der Zanden EP, Snoek SA, Heinsbroek SE, Stanisor OI, Verseijden C, Boeckxstaens GE, Peppelenbosch MP, Greaves DR, Gordon S, De Jonge WJ (2009)MEDLINE-indexed journal, not yet read by usGastroenterology107 citations Vagus nerve activity augments intestinal macrophage phagocytosis via nicotinic acetylcholine receptor alpha4beta2.
Background & aims: The vagus nerve negatively regulates macrophage cytokine production via the release of acetylcholine (ACh) and activation of nicotinic acetylcholine receptors (nAChR). In various models of intestinal inflammation, vagus nerve efferent stimulation ameliorates disease. Given the actively constrained cytokine responses of intestinal macrophages, we explored the effect of nAChR activation on endocytosis and phagocytosis by macrophages residing in the peritoneal and mucosal compartment.
Methods: The phagocytic uptake by intestinal and peritoneal macrophages was measured by fluorescence-activated cell sorter analysis, and the nAChR involved was determined by pharmacologic blockade, short hairpin RNA-assisted gene knockdown, and the use of specific nAChR knockout mice. The effect of electrical vagus nerve stimulation on epithelial translocation and macrophage uptake of lumina…
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[A novel transcutaneous vagus nerve stimulation leads to brainstem and cerebral activations measured by functional MRI].
Background: Left cervical vagus nerve stimulation (VNS) using the implanted NeuroCybernetic Prosthesis (NCP) can reduce epileptic seizures and has recently been shown to give promising results for treating therapy-resistant depression. To address a disadvantage of this state-of-the-art VNS device, the use of an alternative transcutaneous electrical nerve stimulation technique, designed for muscular stimulation, was studied. Functional magnetic resonance imaging (MRI) has been used to test non-invasively access nerve structures associated with the vagus nerve system. The results and their impact are unsatisfying due to missing brainstem activations. These activations, however, are mandatory for reasoning, higher subcortical and cortical activations of vagus nerve structures. The objective of this study was to test a new parameter setting and a novel device for performing specific (well-co…
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Cholinergic agonists attenuate renal ischemia-reperfusion injury in rats.
Inflammation plays a significant role in the pathophysiology of renal ischemia-reperfusion injury. Local inflammation is modulated by the brain via the vagus nerve and nicotinic acetylcholine receptors such that electrical or pharmacologic stimulation of this cholinergic anti-inflammatory pathway results in suppression of proinflammatory cytokine production. We examined the effects of cholinergic stimulation using agonists, nicotine or GTS-21, given before or after bilateral renal ischemia-reperfusion injury in rats. Pretreatment of rats with either agonist significantly attenuated renal dysfunction and tubular necrosis induced by renal ischemia. Similarly, tumor necrosis factor-alpha protein expression and leukocyte infiltration of the kidney were markedly reduced following treatment with cholinergic agonists. We found functional nicotinic acetylcholine receptors were present on rat pro…
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Vagus nerve stimulation potentiates hippocampal LTP in freely-moving rats.
Previous studies have demonstrated that electrical stimulation of the vagus nerve (VNS) delivered at a moderate intensity following a learning experience enhances memory in laboratory rats and human subjects, while VNS at lower or higher intensities has little or no effect. This finding suggests that VNS may affect memory processes by modulating neural plasticity in brain structures associated with memory storage such as the hippocampus. To test this hypothesis, the present study investigated the modulatory effect of VNS on the development of long-term potentiation (LTP) in the dentate gyrus of freely-moving rats. Rats receiving 0.4 mA VNS showed enhanced potentiation of the population spike amplitude for at least 24 h after tetanus relative to the sham-stimulation group. In contrast, no such effect was observed with 0.2 mA VNS. Stimulation at 0.8 mA had a short-term effect and tended to…
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Ghrelin down-regulates proinflammatory cytokines in sepsis through activation of the vagus nerve.
Objective: To test the hypothesis that administration of ghrelin attenuates inflammatory responses in sepsis through vagal nerve stimulation.
Summary background data: Ghrelin has been demonstrated to possess multiple functions, including stimulation of the vagus nerve. Our recent study has shown that plasma levels of ghrelin were significantly reduced in sepsis; and ghrelin administration improved organ perfusion and function. However, it remained unknown whether ghrelin also decreases proinflammatory cytokines in sepsis and, if so, whether the down-regulatory effect of ghrelin is mediated by activation of the vagus nerve.
Methods: Male rats were subjected to sepsis by cecal ligation and puncture (CLP). At 5 hours after CLP, a bolus intravenous injection of 2 nmol ghrelin was followed by a continuous infusion of 12 nmol ghrelin via a primed 200-microL Alzet mini-pump for 15 hours. At 20 …
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Vagus nerve stimulation increases norepinephrine concentration and the gene expression of BDNF and bFGF in the rat brain.
Vagus nerve stimulation therapy, effective for treatment-resistant epilepsy, has recently been approved also for treatment-resistant depression; nevertheless, the molecular mechanism(s) underlying its therapeutic action remains unclear. Given that neurotrophic factors and monoamines could play a crucial role in the pathophysiology of depression, we tested whether vagus nerve stimulation increases the expression of brain-derived neurotrophic factor, fibroblast growth factor, and nerve growth factor as well as the concentration of norepinephrine in the rat brain. Rats were implanted with a vagus nerve stimulator device and the effects of acute stimulation were evaluated on the growth factors mRNA levels and norepinephrine concentration by ribonuclease protection assay and microdialysis, respectively. We found that acute vagus nerve stimulation increased the expression of brain-derived neur…
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Activation of the cholinergic anti-inflammatory pathway ameliorates postoperative ileus in mice.
Background & aims: We previously showed that intestinal inflammation is reduced by electrical stimulation of the efferent vagus nerve, which prevents postoperative ileus in mice. We propose that this cholinergic anti-inflammatory pathway is mediated via alpha7 nicotinic acetylcholine receptors expressed on macrophages. The aim of this study was to evaluate pharmacologic activation of the cholinergic anti-inflammatory pathway in a mouse model for postoperative ileus using the alpha7 nicotinic acetylcholine receptor-agonist AR-R17779.
Methods: Mice were pretreated with vehicle, nicotine, or AR-R17779 20 minutes before a laparotomy (L) or intestinal manipulation (IM). Twenty-four hours thereafter gastric emptying was determined using scintigraphy and intestinal muscle inflammation was quantified. Nuclear factor-kappaB transcriptional activity and cytokine production was assayed in peritonea…
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Weight loss during chronic, cervical vagus nerve stimulation in depressed patients with obesity: an observation.
Fourteen patients were treated over 2 years with cervical vagus nerve stimulation (VNS) for adjunctive therapy of severe, treatment-resistant depression. Here, we report the serendipitous observation that this treatment was associated with highly significant, gradual weight loss despite the patients' report of not dieting or exercising. The weight loss was proportional to the initial BMI, that is, the more severe the obesity, the greater the weight loss. Weight loss did not correlate with changes in mood symptoms. The vagus nerve carries visceral information to and from the brain; modulation of its activity may alter eating behavior. Chronic cervical VNS may merit controlled study for the treatment of severe obesity.
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Dorr AE, Debonnel G (2006)MEDLINE-indexed journal, not yet read by usThe Journal of pharmacology and experimental therapeutics309 citations Effect of vagus nerve stimulation on serotonergic and noradrenergic transmission.
Vagus nerve stimulation (VNS) is an antiepileptic treatment, which has recently shown promise as an antidepressant. Yet, its antidepressant mechanisms of action are unknown. Serotonergic [5-hydroxytryptamine (5-HT, serotonin)] and noradrenergic [norepinephrine (NE)] systems are involved in the pathophysiology of depression and in the mechanisms of action of antidepressants. The present study analyzes 5-HT and NE neuronal firing rates in their brainstem nuclei: the dorsal raphe nucleus (DRN) and locus coeruleus (LC), respectively. The basal firing rates in the DRN and LC were significantly increased after long-term treatments with VNS. After short-term VNS treatments, firing rates were significantly higher for LC (at 1 h and 3 days). As changes in their firing rate may have been due to altered autoreceptor sensitivities, the responses of autoreceptors to the acute administration of their …
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Increased extracellular concentrations of norepinephrine in cortex and hippocampus following vagus nerve stimulation in the rat.
The vagus nerve is an important source of afferent information about visceral states and it provides input to the locus coeruleus (LC), the major source of norepinephrine (NE) in the brain. It has been suggested that the effects of electrical stimulation of the vagus nerve on learning and memory, mood, seizure suppression, and recovery of function following brain damage are mediated, in part, by the release of brain NE. The hypothesis that left vagus nerve stimulation (VNS) at the cervical level results in increased extracellular NE concentrations in the cortex and hippocampus was tested at four stimulus intensities: 0.0, 0.25, 0.5, and 1.0 mA. Stimulation at 0.0 and 0.25 mA had no effect on NE concentrations, while the 0.5 mA stimulation increased NE concentrations significantly in the hippocampus (23%), but not the cortex. However, 1.0 mA stimulation significantly increased NE concentr…
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Cheng C, Xue X, Jiao Y, You R, Zhang M, Jia M, Du M, Zeng X, Sun JB, Qin W, Yang XJ (2025)MEDLINE-indexed journal, not yet read by usNeuroscience3 citations External trigeminal nerve stimulation (eTNS) Exhibits relaxation effects in fatigue states following napping deprivation.
Background: In the face of inevitable declines in alertness and fatigue resulting from sleep deprivation, effective countermeasures are essential for maintaining performance. External trigeminal nerve stimulation (eTNS) presents a potential avenue for regulating alertness by activating the locus coeruleus and reticular activating system.
Methods: Here, we conducted a within-subject study with 66 habitual nappers, subjecting them to afternoon nap-deprivation and applying either 20-minute of 120 Hz eTNS or sham stimulation. We compared participants' performance in PVT and N-back tasks, subjective fatigue level and alertness ratings, and changes in heart rate variability, cortisol, and salivary alpha-amylase before and after stimulation.
Results: The results revealed a significant decline in PVT and N-back tasks performance, along with increased subjective fatigue levels in the sham stimula…
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Gritty Heart: Improved Heart Rate Variability Markers of Adaptive Physiological Response in Grit.
Grit is a personality trait, conceptualized as perseverance of effort and consistency of interests in long-term goals. Previous research has shown that grit is associated with various positive outcomes, including well-being. Despite extensive research on grit, most studies relied on self-reported measures rather than objective measures. To address this gap, our study investigated the relationship between grit and physiological responses, focusing on resting-state heart rate variability (HRV)-a physiological marker of well-being and adaptability. Additionally, we examined whether this relationship was unique to grit and not explained by other related psychological constructs (i.e., conscientiousness and self-control). A total of 206 healthy college students participated in this study (Mage = 21.03, SD = 2.48, age range = 18-33; 111 women). Results of hierarchical regression analyses showe…
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Yoo HJ, Nashiro K, Min J, Cho C, Mercer N, Bachman SL, Nasseri P, Dutt S, Porat S, Choi P, Zhang Y, Grigoryan V, Feng T, Thayer JF, Lehrer P, Chang C, Stanley JA, Head E, Rouanet J, Marmarelis VZ, Narayanan S, Wisnowski J, Nation DA, Mather M (2023)MEDLINE-indexed journal, not yet read by usScientific data15 citations Multimodal neuroimaging data from a 5-week heart rate variability biofeedback randomized clinical trial.
We present data from the Heart Rate Variability and Emotion Regulation (HRV-ER) randomized clinical trial testing effects of HRV biofeedback. Younger (N = 121) and older (N = 72) participants completed baseline magnetic resonance imaging (MRI) including T1-weighted, resting and emotion regulation task functional MRI (fMRI), pulsed continuous arterial spin labeling (PCASL), and proton magnetic resonance spectroscopy (1H MRS). During fMRI scans, physiological measures (blood pressure, pulse, respiration, and end-tidal CO2) were continuously acquired. Participants were randomized to either increase heart rate oscillations or decrease heart rate oscillations during daily sessions. After 5 weeks of HRV biofeedback, they repeated the baseline measurements in addition to new measures (ultimatum game fMRI, training mimicking during blood oxygen level dependent (BOLD) and PCASL fMRI). Participant…
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