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Handbook of Clinical Neurology 2022Brain PCO is sensed primarily via changes in [H]. Small pH changes are detected in the medulla oblongata and trigger breathing adjustments that help maintain arterial... (Review)
Review
Brain PCO is sensed primarily via changes in [H]. Small pH changes are detected in the medulla oblongata and trigger breathing adjustments that help maintain arterial PCO constant. Larger perturbations of brain CO/H, possibly also sensed elsewhere in the CNS, elicit arousal, dyspnea, and stress, and cause additional breathing modifications. The retrotrapezoid nucleus (RTN), a rostral medullary cluster of glutamatergic neurons identified by coexpression of Phoxb and Nmb transcripts, is the lynchpin of the central respiratory chemoreflex. RTN regulates breathing frequency, inspiratory amplitude, and active expiration. It is exquisitely responsive to acidosis in vivo and maintains breathing autorhythmicity during quiet waking, slow-wave sleep, and anesthesia. The RTN response to [H] is partly an intrinsic neuronal property mediated by proton sensors TASK-2 and GPR4 and partly a paracrine effect mediated by astrocytes and the vasculature. The RTN also receives myriad excitatory or inhibitory synaptic inputs including from [H]-responsive neurons (e.g., serotonergic). RTN is silenced by moderate hypoxia. RTN inactivity (periodic or sustained) contributes to periodic breathing and, likely, to central sleep apnea. RTN development relies on transcription factors Egr2, Phox2b, Lbx1, and Atoh1. PHOX2B mutations cause congenital central hypoventilation syndrome; they impair RTN development and consequently the central respiratory chemoreflex.
Topics: Chemoreceptor Cells; Humans; Hypoxia; Medulla Oblongata; Respiration; Sleep Apnea, Central
PubMed: 35965033
DOI: 10.1016/B978-0-323-91534-2.00007-2 -
Cell Apr 2015Breathing 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...
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, other autonomic functions under vagal control. Thus, the vagus nerve contains intermingled sensory neurons constituting genetically definable labeled lines with different anatomical connections and physiological roles.
Topics: Animals; Brain Stem; Lung; Mice; Receptors, G-Protein-Coupled; Respiration; Sensory Receptor Cells; Vagus Nerve
PubMed: 25892222
DOI: 10.1016/j.cell.2015.03.022 -
Aging Cell Feb 2019Metformin and exercise independently improve insulin sensitivity and decrease the risk of diabetes. Metformin was also recently proposed as a potential therapy to slow... (Randomized Controlled Trial)
Randomized Controlled Trial
Metformin and exercise independently improve insulin sensitivity and decrease the risk of diabetes. Metformin was also recently proposed as a potential therapy to slow aging. However, recent evidence indicates that adding metformin to exercise antagonizes the exercise-induced improvement in insulin sensitivity and cardiorespiratory fitness. The purpose of this study was to test the hypothesis that metformin diminishes the improvement in insulin sensitivity and cardiorespiratory fitness after aerobic exercise training (AET) by inhibiting skeletal muscle mitochondrial respiration and protein synthesis in older adults (62 ± 1 years). In a double-blinded fashion, participants were randomized to placebo (n = 26) or metformin (n = 27) treatment during 12 weeks of AET. Independent of treatment, AET decreased fat mass, HbA1c, fasting plasma insulin, 24-hr ambulant mean glucose, and glycemic variability. However, metformin attenuated the increase in whole-body insulin sensitivity and VO max after AET. In the metformin group, there was no overall change in whole-body insulin sensitivity after AET due to positive and negative responders. Metformin also abrogated the exercise-mediated increase in skeletal muscle mitochondrial respiration. The change in whole-body insulin sensitivity was correlated to the change in mitochondrial respiration. Mitochondrial protein synthesis rates assessed during AET were not different between treatments. The influence of metformin on AET-induced improvements in physiological function was highly variable and associated with the effect of metformin on the mitochondria. These data suggest that prior to prescribing metformin to slow aging, additional studies are needed to understand the mechanisms that elicit positive and negative responses to metformin with and without exercise.
Topics: Adaptation, Physiological; Aged; Blood Glucose; Cardiorespiratory Fitness; Cell Respiration; Exercise; Female; Humans; Insulin Resistance; Male; Metformin; Middle Aged; Mitochondria; Muscle, Skeletal; Protein Biosynthesis; Signal Transduction; Telomere Homeostasis
PubMed: 30548390
DOI: 10.1111/acel.12880 -
The Journal of Pain 2020Slow deep breathing (SDB) is commonly employed in the management of pain, but the underlying mechanisms remain equivocal. This study sought to investigate effects of...
Slow deep breathing (SDB) is commonly employed in the management of pain, but the underlying mechanisms remain equivocal. This study sought to investigate effects of instructed breathing patterns on experimental heat pain and to explore possible mechanisms of action. In a within-subject experimental design, healthy volunteers (n = 48) performed 4 breathing patterns: 1) unpaced breathing, 2) paced breathing (PB) at the participant's spontaneous breathing frequency, 3) SDB at 6 breaths per minute with a high inspiration/expiration ratio (SDB-H), and 4) SDB at 6 breaths per minute with a low inspiration/expiration ratio (SDB-L). During presentation of each breathing pattern, participants received painful heat stimuli of 3 different temperatures and rated each stimulus on pain intensity. Respiration, heart rate, and blood pressure were recorded. Compared to unpaced breathing, participants reported less intense pain during each of the 3 instructed breathing patterns. Among the instructed breathing patterns, pain did not differ between PB and SDB-H, and SDB-L attenuated pain more than the PB and SDB-H patterns. The latter effect was paralleled by greater blood pressure variability and baroreflex effectiveness index during SDB-L. Cardiovascular changes did not mediate the observed effects of breathing patterns on pain. PERSPECTIVES: SDB is more efficacious to attenuate pain when breathing is paced at a slow rhythm with an expiration that is long relative to inspiration, but the underlying mechanisms remain to be elucidated.
Topics: Adult; Blood Pressure; Breathing Exercises; Electrocardiography; Female; Heart Rate; Humans; Male; Pain Management; Pain Measurement; Respiratory Rate; Time Factors; Young Adult
PubMed: 31978501
DOI: 10.1016/j.jpain.2019.12.010 -
Complementary Therapies in Medicine May 2023Slow breathing techniques are commonly used to reduce stress. While it is believed by mind-body practitioners that extending the exhale time relative to inhale increases... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Slow breathing techniques are commonly used to reduce stress. While it is believed by mind-body practitioners that extending the exhale time relative to inhale increases relaxation, this has not been demonstrated.
METHODS
We conducted a 12-week randomized, single-blinded trial among 100 participants to compare if yoga-based slow breathing with an exhale greater inhale versus an exhale equals inhale produces measurable differences in physiological and psychological stress among healthy adults.
RESULTS
Participants mean individual instruction attendance was 10.7 ± 1.5 sessions out of 12 offered sessions. The mean weekly home practice was 4.8 ± 1.2 practices per week. There was no statistical difference between treatment groups for frequency of class attendance, home practice, or achieved slow breathing respiratory rate. Participants demonstrated fidelity to assigned breath ratios with home practice as measured by remote biometric assessments through smart garments (HEXOSKIN). Regular slow breathing practice for 12 weeks significantly reduced psychological stress as measured by PROMIS Anxiety (-4.85 S.D. ± 5.53, confidence interval [-5.60, -3.00], but not physiological stress as measured by heart rate variability. Group comparisons showed small effect size differences (d = 0.2) with further reductions in psychological stress and physiological stress from baseline to 12 weeks for exhale greater than inhale versus exhale equals inhale, however these differences were not statistically significant.
CONCLUSION
While slow breathing significantly reduces psychological stress, breath ratios do not have a significant differential effect on stress reduction among healthy adults.
Topics: Adult; Humans; Respiratory Rate; Yoga; Meditation
PubMed: 36871835
DOI: 10.1016/j.ctim.2023.102937 -
Frontiers in Neural Circuits 2021Respiration paces brain oscillations and the firing of individual neurons, revealing a profound impact of rhythmic breathing on brain activity. Intriguingly,... (Review)
Review
Respiration paces brain oscillations and the firing of individual neurons, revealing a profound impact of rhythmic breathing on brain activity. Intriguingly, respiration-driven entrainment of neural activity occurs in a variety of cortical areas, including those involved in higher cognitive functions such as associative neocortical regions and the hippocampus. Here we review recent findings of respiration-entrained brain activity with a particular focus on emotional cognition. We summarize studies from different brain areas involved in emotional behavior such as fear, despair, and motivation, and compile findings of respiration-driven activities across species. Furthermore, we discuss the proposed cellular and network mechanisms by which cortical circuits are entrained by respiration. The emerging synthesis from a large body of literature suggests that the impact of respiration on brain function is widespread across the brain and highly relevant for distinct cognitive functions. These intricate links between respiration and cognitive processes call for mechanistic studies of the role of rhythmic breathing as a timing signal for brain activity.
Topics: Cognition; Fear; Hippocampus; Neurons; Respiration
PubMed: 34790100
DOI: 10.3389/fncir.2021.761812 -
Medical Hypotheses 2006Pranayamic breathing, defined as a manipulation of breath movement, has been shown to contribute to a physiologic response characterized by the presence of decreased...
Pranayamic breathing, defined as a manipulation of breath movement, has been shown to contribute to a physiologic response characterized by the presence of decreased oxygen consumption, decreased heart rate, and decreased blood pressure, as well as increased theta wave amplitude in EEG recordings, increased parasympathetic activity accompanied by the experience of alertness and reinvigoration. The mechanism of how pranayamic breathing interacts with the nervous system affecting metabolism and autonomic functions remains to be clearly understood. It is our hypothesis that voluntary slow deep breathing functionally resets the autonomic nervous system through stretch-induced inhibitory signals and hyperpolarization currents propagated through both neural and non-neural tissue which synchronizes neural elements in the heart, lungs, limbic system and cortex. During inspiration, stretching of lung tissue produces inhibitory signals by action of slowly adapting stretch receptors (SARs) and hyperpolarization current by action of fibroblasts. Both inhibitory impulses and hyperpolarization current are known to synchronize neural elements leading to the modulation of the nervous system and decreased metabolic activity indicative of the parasympathetic state. In this paper we propose pranayama's physiologic mechanism through a cellular and systems level perspective, involving both neural and non-neural elements. This theoretical description describes a common physiological mechanism underlying pranayama and elucidate the role of the respiratory and cardiovascular system on modulating the autonomic nervous system. Along with facilitating the design of clinical breathing techniques for the treatment of autonomic nervous system and other disorders, this model will also validate pranayama as a topic requiring more research.
Topics: Autonomic Nervous System; Breathing Exercises; Humans; Models, Biological; Respiration
PubMed: 16624497
DOI: 10.1016/j.mehy.2006.02.042 -
NeuroImage Jun 2020Slow changes in systemic brain physiology can elicit large fluctuations in fMRI time series, which manifest as structured spatial patterns of temporal correlations...
Slow changes in systemic brain physiology can elicit large fluctuations in fMRI time series, which manifest as structured spatial patterns of temporal correlations between distant brain regions. Here, we investigated whether such "physiological networks"-sets of segregated brain regions that exhibit similar responses following slow changes in systemic physiology-resemble patterns associated with large-scale networks typically attributed to remotely synchronized neuronal activity. By analyzing a large group of subjects from the 3T Human Connectome Project (HCP) database, we demonstrate brain-wide and noticeably heterogenous dynamics tightly coupled to either respiratory variation or heart rate changes. We show, using synthesized data generated from physiological recordings across subjects, that these physiologically-coupled fluctuations alone can produce networks that strongly resemble previously reported resting-state networks, suggesting that, in some cases, the "physiological networks" seem to mimic the neuronal networks. Further, we show that such physiologically-relevant connectivity estimates appear to dominate the overall connectivity observations in multiple HCP subjects, and that this apparent "physiological connectivity" cannot be removed by the use of a single nuisance regressor for the entire brain (such as global signal regression) due to the clear regional heterogeneity of the physiologically-coupled responses. Our results challenge previous notions that physiological confounds are either localized to large veins or globally coherent across the cortex, therefore emphasizing the necessity to consider potential physiological contributions in fMRI-based functional connectivity studies. The rich spatiotemporal patterns carried by such "physiological" dynamics also suggest great potential for clinical biomarkers that are complementary to large-scale neuronal networks.
Topics: Adult; Brain; Connectome; Female; Heart Rate; Humans; Magnetic Resonance Imaging; Male; Nerve Net; Respiration; Rest
PubMed: 32145437
DOI: 10.1016/j.neuroimage.2020.116707 -
Clinical Neurophysiology : Official... Dec 2023Infra-slow fluctuations (ISF, 0.008-0.1 Hz) characterize hemodynamic and electric potential signals of human brain. ISFs correlate with the amplitude dynamics of fast...
OBJECTIVE
Infra-slow fluctuations (ISF, 0.008-0.1 Hz) characterize hemodynamic and electric potential signals of human brain. ISFs correlate with the amplitude dynamics of fast (>1 Hz) neuronal oscillations, and may arise from permeability fluctuations of the blood-brain barrier (BBB). It is unclear if physiological rhythms like respiration drive or track fast cortical oscillations, and the role of sleep in this coupling is unknown.
METHODS
We used high-density full-band electroencephalography (EEG) in healthy human volunteers (N = 21) to measure concurrently the ISFs, respiratory pulsations, and fast neuronal oscillations during periods of wakefulness and sleep, and to assess the strength and direction of their phase-amplitude coupling.
RESULTS
The phases of ISFs and respiration were both coupled with the amplitude of fast neuronal oscillations, with stronger ISF coupling being evident during sleep. Phases of ISF and respiration drove the amplitude dynamics of fast oscillations in sleeping and waking states, with different contributions.
CONCLUSIONS
ISFs in slow cortical potentials and respiration together significantly determine the dynamics of fast cortical oscillations.
SIGNIFICANCE
We propose that these slow physiological phases play a significant role in coordinating cortical excitability, which is a fundamental aspect of brain function.
Topics: Humans; Electroencephalography; Sleep; Membrane Potentials; Brain; Respiration
PubMed: 37972532
DOI: 10.1016/j.clinph.2023.10.013 -
La Tunisie MedicaleThe main two functions of the lung are the respiratory functions, dependent on ventilatory mechanics and gas exchange, and the nonrespiratory functions such as...
The main two functions of the lung are the respiratory functions, dependent on ventilatory mechanics and gas exchange, and the nonrespiratory functions such as metabolic, immunological, and endocrine ones. Lung aging is secondary to the age-dependent impairment of one or more of these functions. Tobacco use accelerates lung aging and touches biological, structural and respiratory and non-respiratory functions. These changes contribute to the development of chronic pulmonary diseases and predispose to pulmonary infections in older individuals. The knowledge of these changes is very useful for better management of elderly. Lung health in aging can be improved by strategies that slow the age-related decline in lung function by acting on the environmental parameters. It is also possible to improve lung development in children and to strengthen the lungs' resistance to environmental challenges and thus to extrinsic lung aging.
Topics: Aged; Aging; Child; Humans; Lung; Pulmonary Gas Exchange; Respiration; Tobacco Use
PubMed: 36155900
DOI: No ID Found