Heart rate variability, the vagus and calm.
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676 to 700 of 1,007Interoceptive awareness declines with age.
Aging has been shown to increase sensory thresholds for a variety of exteroceptive and proprioceptive stimuli. However, the influence of aging on interoceptive awareness has received relatively little empirical attention. Here we report an inverse association between aging and interoception, as indexed by the ability to sense the heartbeat at rest. In a group of 59 participants ranging in age from 22 to 63 years, age inversely predicted heartbeat detection ability, both within and across several measurement sessions. On average, age accounted for 30% of the variance in heartbeat detection accuracy. Other attribute variables including body mass index and sex were not related to heartbeat detection ability. These findings provide clear empirical evidence that interoception, much like exteroception and proprioception, declines with age.
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Baumert M, Porta A, Vos MA, Malik M, Malik M, Couderc JP, Laguna P, Piccirillo G, Smith GL, Tereshchenko LG, Volders PG (2016)MEDLINE-indexed journal, not yet read by usEuropace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology154 citations QT interval variability in body surface ECG: measurement, physiological basis, and clinical value: position statement and consensus guidance endorsed by the European Heart Rhythm Association jointly with the ESC Working Group on Cardiac Cellular Electrophysiology.
This consensus guideline discusses the electrocardiographic phenomenon of beat-to-beat QT interval variability (QTV) on surface electrocardiograms. The text covers measurement principles, physiological basis, and clinical value of QTV. Technical considerations include QT interval measurement and the relation between QTV and heart rate variability. Research frontiers of QTV include understanding of QTV physiology, systematic evaluation of the link between QTV and direct measures of neural activity, modelling of the QTV dependence on the variability of other physiological variables, distinction between QTV and general T wave shape variability, and assessing of the QTV utility for guiding therapy. Increased QTV appears to be a risk marker of arrhythmic and cardiovascular death. It remains to be established whether it can guide therapy alone or in combination with other risk factors. QT inte…
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Bush NR, Jones-Mason K, Coccia M, Caron Z, Alkon A, Thomas M, Coleman-Phox K, Wadhwa PD, Laraia BA, Adler NE, Epel ES (2017)MEDLINE-indexed journal, not yet read by usDevelopment and psychopathology93 citations Effects of pre- and postnatal maternal stress on infant temperament and autonomic nervous system reactivity and regulation in a diverse, low-income population.
We examined the prospective associations of objective and subjective measures of stress during pregnancy with infant stress reactivity and regulation, an early-life predictor of psychopathology. In a racially and ethnically diverse low-income sample of 151 mother-infant dyads, maternal reports of stressful life events (SLE) and perceived stress (PS) were collected serially over gestation and the early postpartum period. Infant reactivity and regulation at 6 months of age was assessed via maternal report of temperament (negativity, surgency, and regulation) and infant parasympathetic nervous system physiology (respiratory sinus arrhythmia [RSA]) during the Still Face Paradigm. Regression models predicting infant temperament showed higher maternal prenatal PS predicted lower surgency and self-regulation but not negativity. Regression models predicting infant physiology showed higher number…
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Helping from the heart: Voluntary upregulation of heart rate variability predicts altruistic behavior.
Our various daily activities continually require regulation of our internal state. These regulatory processes covary with changes in High Frequency Heart Rate Variability (HF-HRV), a marker of parasympathetic activity. Specifically, incidental increases in HF-HRV accompany positive social engagement behavior and prosocial action. Little is known about deliberate regulation of HF-HRV and the role of voluntary parasympathetic regulation in prosocial behavior. Here, we present a novel biofeedback task that measures the ability to deliberately increase HF-HRV. In two large samples, we find that a) participants are able to voluntarily upregulate HF-HRV, and b) variation in this ability predicts individual differences in altruistic prosocial behavior, but not non-altruistic forms of prosociality, assessed through 14 different measures. Our findings suggest that self-induction of parasympatheti…
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Cardiac inotropic and hypertrophic effects of Nigella sativa supplementation in rats.
The intrinsic cardiac responses to 2-months Nigella sativa (black seed) oral supplementation (800 mg/kg) in rats were investigated. The isolated hearts were perfused in a Langendorff preparation to demonstrate the effects of N. sativa on the baseline inotropic and chronotropic functions and the myocardial flow rate. N. sativa supplementation induced moderate global (homogenous) cardiac hypertrophy, evident by significant increases in left ventricular and whole heart weights as well as the relative heart weight/body weight ratio. The isolated perfused hearts of Nigella-treated rats showed enhanced levels of baseline peak tension, maximum rate of tension development, heart rate and myocardial flow rate. Moreover, there was a significant increase in the tension developed per gram left ventricular weight. The present study provides the first evidence of a physiological cardiac hypertrophy in…
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Sharon O, Fahoum F, Nir Y (2021)MEDLINE-indexed journal, not yet read by usThe Journal of neuroscience : the official journal of the Society for Neuroscience167 citations Transcutaneous Vagus Nerve Stimulation in Humans Induces Pupil Dilation and Attenuates Alpha Oscillations.
Vagus nerve stimulation (VNS) is widely used to treat drug-resistant epilepsy and depression. While the precise mechanisms mediating its long-term therapeutic effects are not fully resolved, they likely involve locus coeruleus (LC) stimulation via the nucleus of the solitary tract, which receives afferent vagal inputs. In rats, VNS elevates LC firing and forebrain noradrenaline levels, whereas LC lesions suppress VNS therapeutic efficacy. Noninvasive transcutaneous VNS (tVNS) uses electrical stimulation that targets the auricular branch of the vagus nerve at the cymba conchae of the ear. However, the extent to which tVNS mimics VNS remains unclear. Here, we investigated the short-term effects of tVNS in healthy human male volunteers (n = 24), using high-density EEG and pupillometry during visual fixation at rest. We compared short (3.4 s) trials of tVNS to sham electrical stimulation at …
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The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential.
Background: Transcutaneous vagus nerve stimulation (tVNS) is a new, non-invasive technique being investigated as an intervention for a variety of clinical disorders, including epilepsy and depression. It is thought to exert its therapeutic effect by increasing central norepinephrine (NE) activity, but the evidence supporting this notion is limited.
Objective: In order to test for an impact of tVNS on psychophysiological and hormonal indices of noradrenergic function, we applied tVNS in concert with assessment of salivary alpha amylase (SAA) and cortisol, pupil size, and electroencephalograph (EEG) recordings.
Methods: Across three experiments, we applied real and sham tVNS to 61 healthy participants while they performed a set of simple stimulus-discrimination tasks. Before and after the task, as well as during one break, participants provided saliva samples and had their pupil size recor…
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Effects of Concomitant Stimulation of the GABAergic and Norepinephrine System on Inhibitory Control - A Study Using Transcutaneous Vagus Nerve Stimulation.
Background: Inhibitory control processes are a central executive function. Several lines of evidence suggest that the GABAergic and the norepinephrine (NE) system modulate inhibitory control processes. Yet, the effects of conjoint increases in the GABAergic and NE system activity on inhibitory control have not been examined.
Objective/hypothesis: We examine the conjoint effects of the GABA and NE system for inhibitory control.
Methods: We used transcutaneous vagus nerve stimulation (tVNS), which has been shown to modulate both the GABAergic and NE system. We examine the effects of tVNS in two experimental paradigms examining different aspect of inhibitory control; i.e. a backward inhibition paradigm and a response inhibition paradigm modulating working memory load.
Results: There were no effects of tVNS on backward inhibition processes, but on response inhibition processes. Yet, these on…
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Developmental changes in hypothalamus-pituitary-adrenal activity over the transition to adolescence: normative changes and associations with puberty.
Home baseline and laboratory stressor (Trier Social Stress Test for Children) measures of salivary cortisol were obtained from 82 participants (40 girls) aged 9, 11, 13, and 15 years. Measures of pubertal development, self-reported stress, parent reports of child depressive symptoms and fearful temperament, and cardiac measures of sympathetic and parasympathetic activity were also obtained. Significant increases in the home cortisol baselines were found with age and pubertal development. Cortisol stress reactivity differed by age group with 11-year-olds and 13-year-old boys showing blunted reactivity and 9-year-olds, 13-year-old girls, and 15-year-olds showing significant cortisol reactions. Cortisol reactivity correlated marginally with sexual maturation. Measures of sympathetic activity revealed increased sympathetic modulation with age. Higher sympathetic tone was associated with more…
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Influence of a 30-Day Slow-Paced Breathing Intervention Compared to Social Media Use on Subjective Sleep Quality and Cardiac Vagal Activity.
Breathing techniques are part of traditional relaxation methods; however, their influence on psychophysiological variables related to sleep is still unclear. Consequently, the aim of this paper was to investigate the influence of a 30-day slow-paced breathing intervention compared to social media use on subjective sleep quality and cardiac vagal activity (CVA, operationalized via high-frequency heart rate variability). Healthy participants (n = 64, 33 male, 31 female, M = 22.11, SD = 3.12) were randomly allocated to an experimental or control group. In the experimental group, they had to perform slow-paced breathing for 15 min each evening across a 30-day period. This was administered through a smartphone application. The control group used social media (e.g., Facebook, Instagram, Whatsapp) for the same duration. The night before and after the intervention, their CVA was assessed via a l…
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Accuracy of the StressEraser in the detection of cardiac rhythms.
StressEraser is a commercially marketed biofeedback device designed to enhance heart rate variability. StressEraser makes its internal calculations on beat-to-beat measures of finger pulse intervals. However, the accuracy and precision of StressEraser in quantifying interbeat intervals using finger pulse intervals has not been evaluated against standard laboratory equipment using R-R intervals. Accuracy was assessed by simultaneously recording interbeat intervals using StressEraser and a standard laboratory ECG system. The interbeat intervals were highly correlated between the systems. The average deviation in interbeat interval recordings between the systems was approximately 6 ms. Moreover, correlations approached unity between the systems on estimates of heart period, heart rate, and heart rate variability. Feedback from StressEraser is based on an interbeat time series that provides …
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Corazzol M, Lio G, Lefevre A, Deiana G, Tell L, André-Obadia N, Bourdillon P, Guenot M, Desmurget M, Luauté J, Sirigu A (2017)editorial or commentMEDLINE-indexed journal, not yet read by usCurrent biology : CB103 citations Restoring consciousness with vagus nerve stimulation.
Patients lying in a vegetative state present severe impairments of consciousness [1] caused by lesions in the cortex, the brainstem, the thalamus and the white matter [2]. There is agreement that this condition may involve disconnections in long-range cortico-cortical and thalamo-cortical pathways [3]. Hence, in the vegetative state cortical activity is 'deafferented' from subcortical modulation and/or principally disrupted between fronto-parietal regions. Some patients in a vegetative state recover while others persistently remain in such a state. The neural signature of spontaneous recovery is linked to increased thalamo-cortical activity and improved fronto-parietal functional connectivity [3]. The likelihood of consciousness recovery depends on the extent of brain damage and patients' etiology, but after one year of unresponsive behavior, chances become low [1]. There is thus a need …
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Gut microbiota changes require vagus nerve integrity to promote depressive-like behaviors in mice.
Chronic stress constitutes a major risk factor for depression that can disrupt various aspects of homeostasis, including the gut microbiome (GM). We have recently shown that GM imbalance affects adult hippocampal (HPC) neurogenesis and induces depression-like behaviors, with the exact mechanisms being under active investigation. Here we hypothesized that the vagus nerve (VN), a key bidirectional route of communication between the gut and the brain, could relay the effects of stress-induced GM changes on HPC plasticity and behavior. We used fecal samples derived from mice that sustained unpredictable chronic mild stress (UCMS) to inoculate healthy mice and assess standard behavioral readouts for anxiety- and depressive-like behavior, conduct histological and molecular analyses for adult HPC neurogenesis and evaluate neurotransmission pathways and neuroinflammation. To study the potential …
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Nikolova N, Harrison O, Toohey S, Brændholt M, Legrand N, Correa C, Vejlø M, Jensen MS, Fardo F, Allen M (2022)MEDLINE-indexed journal, not yet read by usBiological psychology43 citations The respiratory resistance sensitivity task: An automated method for quantifying respiratory interoception and metacognition.
The ability to sense, monitor, and control respiration - e.g., respiratory interoception (henceforth, respiroception) is a core homeostatic ability. Beyond the regulation of gas exchange, enhanced awareness of respiratory sensations is directly related to psychiatric symptoms such as panic and anxiety. Indeed, chronic breathlessness (dyspnea) is associated with a fourfold increase in the risk of developing depression and anxiety, and the regulation of the breath is a key aspect of many mindfulness-based approaches to the treatment of mental illness. Physiologically speaking, the ability to accurately monitor respiratory sensations is important for optimizing cardiorespiratory function during athletic exertion, and can be a key indicator of illness. Given the important role of respiroception in mental and physical health, it is unsurprising that there is increased interest in the quantifi…
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A multidimensional coding architecture of the vagal interoceptive system.
Interoception, the ability to timely and precisely sense changes inside the body, is critical for survival1-4. Vagal sensory neurons (VSNs) form an important body-to-brain connection, navigating visceral organs along the rostral-caudal axis of the body and crossing the surface-lumen axis of organs into appropriate tissue layers5,6. The brain can discriminate numerous body signals through VSNs, but the underlying coding strategy remains poorly understood. Here we show that VSNs code visceral organ, tissue layer and stimulus modality-three key features of an interoceptive signal-in different dimensions. Large-scale single-cell profiling of VSNs from seven major organs in mice using multiplexed projection barcodes reveals a 'visceral organ' dimension composed of differentially expressed gene modules that code organs along the body's rostral-caudal axis. We discover another 'tissue layer' di…
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A key role of the subdiaphragmatic vagus nerve in the depression-like phenotype and abnormal composition of gut microbiota in mice after lipopolysaccharide administration.
The vagus nerve plays a role in the cross talk between the brain and gut microbiota, which could be involved in depression. The subdiaphragmatic vagus nerve serves as a major modulatory pathway between the brain and gut microbiota. Here, we investigated the effects of subdiaphragmatic vagotomy (SDV) on the depression-like phenotype and the abnormal composition of gut microbiota in mice after lipopolysaccharide (LPS) administration. LPS caused a depression-like phenotype, inflammation, increase in spleen weight, and downregulation of synaptic proteins in the medial prefrontal cortex (mPFC) in the sham-operated mice. In contrast, LPS did not produce a depression-like phenotype and downregulated synaptic proteins in the mPFC after SDV. The spleen weight and plasma levels of pro-inflammatory cytokines in the SDV + LPS group were lower than those of the sham + LPS group. Interestingly, there …
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Teratani T, Mikami Y, Nakamoto N, Suzuki T, Harada Y, Okabayashi K, Hagihara Y, Taniki N, Kohno K, Shibata S, Miyamoto K, Ishigame H, Chu PS, Sujino T, Suda W, Hattori M, Matsui M, Okada T, Okano H, Inoue M, Yada T, Kitagawa Y, Yoshimura A, Tanida M, Tsuda M, Iwasaki Y, Kanai T (2020)MEDLINE-indexed journal, not yet read by usNature216 citations The liver-brain-gut neural arc maintains the Treg cell niche in the gut.
Recent clinical and experimental evidence has evoked the concept of the gut-brain axis to explain mutual interactions between the central nervous system and gut microbiota that are closely associated with the bidirectional effects of inflammatory bowel disease and central nervous system disorders1-4. Despite recent advances in our understanding of neuroimmune interactions, it remains unclear how the gut and brain communicate to maintain gut immune homeostasis, including in the induction and maintenance of peripheral regulatory T cells (pTreg cells), and what environmental cues prompt the host to protect itself from development of inflammatory bowel diseases. Here we report a liver-brain-gut neural arc that ensures the proper differentiation and maintenance of pTreg cells in the gut. The hepatic vagal sensory afferent nerves are responsible for indirectly sensing the gut microenvironment …
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Chu C, Murdock MH, Jing D, Won TH, Chung H, Kressel AM, Tsaava T, Addorisio ME, Putzel GG, Zhou L, Bessman NJ, Yang R, Moriyama S, Parkhurst CN, Li A, Meyer HC, Teng F, Chavan SS, Tracey KJ, Regev A, Schroeder FC, Lee FS, Liston C, Artis D (2019)MEDLINE-indexed journal, not yet read by usNature346 citations The microbiota regulate neuronal function and fear extinction learning.
Multicellular organisms have co-evolved with complex consortia of viruses, bacteria, fungi and parasites, collectively referred to as the microbiota1. In mammals, changes in the composition of the microbiota can influence many physiologic processes (including development, metabolism and immune cell function) and are associated with susceptibility to multiple diseases2. Alterations in the microbiota can also modulate host behaviours-such as social activity, stress, and anxiety-related responses-that are linked to diverse neuropsychiatric disorders3. However, the mechanisms by which the microbiota influence neuronal activity and host behaviour remain poorly defined. Here we show that manipulation of the microbiota in antibiotic-treated or germ-free adult mice results in significant deficits in fear extinction learning. Single-nucleus RNA sequencing of the medial prefrontal cortex of the br…
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McVey Neufeld KA, Bienenstock J, Bharwani A, Champagne-Jorgensen K, Mao Y, West C, Liu Y, Surette MG, Kunze W, Forsythe P (2019)MEDLINE-indexed journal, not yet read by usScientific reports101 citations Oral selective serotonin reuptake inhibitors activate vagus nerve dependent gut-brain signalling.
The vagus nerve can transmit signals to the brain resulting in a reduction in depressive behavior as evidenced by the long-term beneficial effects of electrical stimulation of the vagus in patients with intractable depression. The vagus is the major neural connection between gut and brain, and we have previously shown that ingestion of beneficial bacteria modulates behaviour and brain neurochemistry via this pathway. Given the high levels of serotonin in the gut, we considered if gut-brain signaling, and specifically the vagal pathway, might contribute to the therapeutic effect of oral selective serotonin reuptake inhibitors (SSRI). Mesenteric nerve recordings were conducted in mice after treatment with SSRI to ascertain if this class of drugs resulted in increased vagal excitability. Patch clamp recordings of enteric neurons were carried out to measure activity of primary afferent neuro…
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A Nigro-Vagal Pathway Controls Gastric Motility and Is Affected in a Rat Model of Parkinsonism.
Background & aims: In most patients with Parkinson's disease, gastrointestinal (GI) dysfunctions, such as gastroparesis and constipation, are prodromal to the cardinal motor symptoms of the disease. Sporadic Parkinson's disease has been proposed to develop after ingestion of neurotoxicants that affect the brain-gut axis via the vagus nerve, and then travel to higher centers, compromising the substantia nigra pars compacta (SNpc) and, later, the cerebral cortex. We aimed to identify the pathway that connects the brainstem vagal nuclei and the SNpc, and to determine whether this pathway is compromised in a rat model of Parkinsonism.
Methods: To study this neural pathway in rats, we placed tracers in the dorsal vagal complex or SNpc; brainstem and midbrain were examined for tracer distribution and neuronal neurochemical phenotype. Rats were given injections of paraquat once weekly for 3 wee…
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Changes in interoceptive processes following brain stimulation.
The processing and perception of individual internal bodily signals (interoception) has been differentiated to comprise different levels and processes involved. The so-called heartbeat-evoked potential (HEP) offers an additional possibility to examine automatic processing of cardiac signals. Knowledge on neural structures potentially supporting different facets of interoception is still sparse. One way to get insights into neuroanatomical function is to manipulate the activity of different brain structures. In this study, we used repetitive transcranial magnetic stimulation (rTMS) and a continuous theta-burst protocol to inhibit specific central locations of the interoceptive network including the right anterior insula and the right somatosensory cortices and assessed effects on interoceptive facets and the HEP in 18 male participants. Main results were that inhibiting anterior insula re…
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How the heart speaks to the brain: neural activity during cardiorespiratory interoceptive stimulation.
Prominent theories emphasize key roles for the insular cortex in the central representation of interoceptive sensations, but how this brain region responds dynamically to changes in interoceptive state remains incompletely understood. Here, we systematically modulated cardiorespiratory sensations in humans using bolus infusions of isoproterenol, a rapidly acting peripheral beta-adrenergic agonist similar to adrenaline. To identify central neural processes underlying these parametrically modulated interoceptive states, we used pharmacological functional magnetic resonance imaging (phMRI) to simultaneously measure blood-oxygenation-level dependent (BOLD) and arterial spin labelling (ASL) signals in healthy participants. Isoproterenol infusions induced dose-dependent increases in heart rate and cardiorespiratory interoception, with all participants endorsing increased sensations at the high…
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Interoceptive dimensions across cardiac and respiratory axes.
Interoception refers to the sensing of signals concerning the internal state of the body. Individual differences in interoceptive sensitivity are proposed to account for differences in affective processing, including the expression of anxiety. The majority of investigations of interoceptive accuracy focus on cardiac signals, typically using heartbeat detection tests and self-report measures. Consequently, little is known about how different organ-specific axes of interoception relate to each other or to symptoms of anxiety. Here, we compare interoception for cardiac and respiratory signals. We demonstrate a dissociation between cardiac and respiratory measures of interoceptive accuracy (i.e. task performance), yet a positive relationship between cardiac and respiratory measures of interoceptive awareness (i.e. metacognitive insight into own interoceptive ability). Neither interoceptive a…
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Knockdown of GLP-1 Receptors in Vagal Afferents Affects Normal Food Intake and Glycemia.
Nutrient stimulation of enteroendocrine L cells induces the release of the incretin and satiating peptide glucagon-like peptide 1 (GLP-1). The vagus nerve innervates visceral organs and may contribute to the mediation of gut-derived GLP-1's effects on food intake, energy homeostasis, and glycemic control. To test the hypothesis that vagal afferent neuron (VAN) GLP-1 receptors (GLP-1Rs) are necessary for these effects of endogenous GLP-1, we established a novel bilateral nodose ganglia injection technique to deliver a lentiviral vector and to knock down VAN GLP-1Rs in male Sprague Dawley rats. We found that a full expression of VAN GLP-1Rs is not necessary for the maintenance of long-term energy balance in normal eating conditions. VAN GLP-1R knockdown (kd) did, however, increase meal size and accelerated gastric emptying. Moreover, postmeal glycemia was elevated and insulin release was b…
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Vagal Sensory Neuron Subtypes that Differentially Control Breathing.
Breathing is essential for survival and under precise neural control. The vagus nerve is a major conduit between lung and brain required for normal respiration. Here, we identify two populations of mouse vagus nerve afferents (P2ry1, Npy2r), each a few hundred neurons, that exert powerful and opposing effects on breathing. Genetically guided anatomical mapping revealed that these neurons densely innervate the lung and send long-range projections to different brainstem targets. Npy2r neurons are largely slow-conducting C fibers, while P2ry1 neurons are largely fast-conducting A fibers that contact pulmonary endocrine cells (neuroepithelial bodies). Optogenetic stimulation of P2ry1 neurons acutely silences respiration, trapping animals in exhalation, while stimulating Npy2r neurons causes rapid, shallow breathing. Activating P2ry1 neurons did not impact heart rate or gastric pressure, othe…
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