Showing papers on "Autonomic nervous system published in 2021"

Comparative physiology and evolution of the autonomic nervous system

Abstract: Comparative anatomy and evolution of the autonomic nervous system comparative aspects of the biochemical identity of neurotransmitters of autonomic neurons chromaffin systems the gastrointestinal canal glands the circulatory system the spleen lungs and swimbladders urino-genital organs chomatophores the iris.

Post-Acute Sequelae of COVID-19 and Cardiovascular Autonomic Dysfunction: What Do We Know?

Abstract: Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID syndrome, is emerging as a major health issue in patients with previous SARS-CoV-2 infection. Symptoms commonly experienced by patients include fatigue, palpitations, chest pain, dyspnea, reduced exercise tolerance, and “brain fog”. Additionally, symptoms of orthostatic intolerance and syncope suggest the involvement of the autonomic nervous system. Signs of cardiovascular autonomic dysfunction appear to be common in PASC and are similar to those observed in postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. In this review, we report on the epidemiology of PASC, discuss current evidence and possible mechanisms underpinning the dysregulation of the autonomic nervous system, and suggest nonpharmacological and pharmacological interventions to treat and relieve symptoms of PASC-associated dysautonomia.

Ageing promotes pathological alpha-synuclein propagation and autonomic dysfunction in wild-type rats.

Abstract: Neuronal aggregates of misfolded alpha-synuclein protein are found in the brain and periphery of patients with Parkinson's disease. Braak and colleagues have hypothesized that the initial formation of misfolded alpha-synuclein may start in the gut, and then spread to the brain via peripheral autonomic nerves hereby affecting several organs, including the heart and intestine. Age is considered the greatest risk factor for Parkinson's disease, but the effect of age on the formation of pathology and its propagation has not been studied in detail. We aimed to investigate whether propagation of alpha-synuclein pathology from the gut to the brain is more efficient in old versus young wild-type rats, upon gastrointestinal injection of aggregated alpha-synuclein. Our results demonstrate a robust age-dependent gut-to-brain and brain-to-gut spread of alpha-synuclein pathology along the sympathetic and parasympathetic nerves, resulting in age-dependent dysfunction of the heart and stomach, as observed in patients with Parkinson's disease. Moreover, alpha-synuclein pathology is more densely packed and resistant to enzymatic digestion in old rats, indicating an age-dependent maturation of alpha-synuclein aggregates. Our study is the first to provide a detailed investigation of alpha-synuclein pathology in several organs within one animal model, including the brain, skin, heart, intestine, spinal cord and autonomic ganglia. Taken together, our findings suggest that age is a crucial factor for alpha-synuclein aggregation and complete propagation to heart, stomach and skin, similar to patients. Given that age is the greatest risk factor for human Parkinson's disease, it seems likely that older experimental animals will yield the most relevant and reliable findings. These results have important implications for future research to optimize diagnostics and therapeutics in Parkinson's disease and other age-associated synucleinopathies. Increased emphasis should be placed on using aged animals in preclinical studies and to elucidate the nature of age-dependent interactions.

Comparative Anatomy and Evolution of the Autonomic Nervous System

Abstract: This chapter presents an overview of the functional anatomy of the peripheral autonomic nervous system of each of the vertebrate classes. When combined with developmental studies, there are several clues as to the likely course of evolution of the different divisions of the autonomic nervous system. The enteric nervous system probably is the most primitive division, with apparently homologous neurons occurring in cephalochordates. An oculomotor pathway to ocular tissues is present in all gnathostome classes. Cranial autonomic innervation of the upper jaw via the palatine branch of the facial nerve first appears in amphibians. The cranial autonomic innervation of the lower jaw is primitively derived from the post-trematic branches of the facial and glossopharyngeal nerves, as seen in elasmobranchs. In amphibians, the glossopharyngeal pathway predominates, but in amniotes, the facial pathway is dominant. The vagus provides autonomic pathways to the foregut and its derivatives, and to the heart, via pathways that seem to be highly conserved. The sympathetic division is likely to have evolved from aggregations of chromaffin tissue primarily associated with the origins of the segmental blood vessels and the posterior cardinal veins. The pelvic plexuses are a complex mixture of pathways containing sympathetic and sacral parasympathetic components, mainly involved with the control of the hindgut and its .derivatives. Overall, there is a clear evolutionary trend for an increase in the level of organisation of autonomic pathways. This trend presumably is related to a corresponding increase in the ability of vertebrates to flourish independently of environmental constraints.

Gastrointestinal motility disorders in neurologic disease.

Abstract: The extrinsic and autonomic nervous system intricately controls the major functions of the gastrointestinal tract through the enteric nervous system; these include motor, secretory, sensory, storage, and excretory functions. Disorders of the nervous system affecting gastrointestinal tract function manifest primarily as abnormalities in motor (rather than secretory) functions. Common gastrointestinal symptoms in neurologic disorders include sialorrhea, dysphagia, gastroparesis, intestinal pseudo-obstruction, constipation, diarrhea, and fecal incontinence. Diseases of the entire neural axis ranging from the cerebral hemispheres to the peripheral autonomic nerves can result in gastrointestinal motility disorders. The most common neurologic diseases affecting gastrointestinal function are stroke, parkinsonism, multiple sclerosis, and diabetic neuropathy. Diagnosis involves identification of the neurologic disease and its distribution, and documentation of segmental gut dysfunction, typically using noninvasive imaging, transit measurements, or intraluminal measurements of pressure activity and coordination of motility. Apart from treatment of the underlying neurologic disease, management focuses on restoration of normal hydration and nutrition and pharmacologic treatment of the gut neuromuscular disorder.

Maturation of the Cardiac Autonomic Nervous System Activity in Children and Adolescents

Abstract: Background Despite the increasing interest in cardiac autonomic nervous activity, the normal development is not fully understood The main aim was to determine the maturation of different cardiac s

Analysis of Heart rate Variability and Implication of Different Factors on Heart Rate Variability

Abstract: Background The heart is the central organ of the circulatory system which maintains the flow of blood along with the transport of nutrients to different cells and tissues. A well-functioning cardiac state is a complicated mode of changeability. A healthy heart is not only about oscillation as the rhythmometer is not the same in every circumstance. Heart rate shows variations so that it can be regulated according to psychophysiological conditions to maintain the effect of the internal-external stimulus. Objective The main objective of this review is to provide a piece of all-inclusive information about heart rate variability (HRV) and different variables affecting HRV. The direct interconnection among factors and so that HRV can be used in clinical practices. Methods This review article contains a detailed survey of literature about HRV available in different online sources such as; Google Scholar, Science Direct, PubMed, and Web of Science, etc. In this review, the authors have focused on the role of the autonomic nervous system in the regulation of HRV and the role of various factors affecting HRV. Results The variation in the time between two heartbeats is termed as HRV. It is one of the indicators of many pathological conditions related to cardiovascular health. It provided reliable information about the interaction of the sympathetic and parasympathetic nervous systems. The analysis of the variation of heart rate is a well-known non-invasive technique to identify the functioning of the autonomic nervous system. The autonomic nervous system (ANS) depends on the sympathetic and parasympathetic nervous system for transferring information. The cardio-accelerating center, lungs, and non-striated muscles are innervated by cardiac sympathetic nerves. This division of ANS latches upon the heart accordingly via the cervicothoracic ganglion and vagus nerve. It is found that cardiac normal variability depends upon this stimulation towards the sinoatrial node (pacemaker) which can be evaluated by analyzing the HRV. In human- based studies, it has been found that low level of HRV is one of the main causes of death rate among adults. Hence, HRV helps in identifying the risk of cardiac diseases and the state of ANS. Conclusion The heart plays a vital role in the human body and the well-functioning of the cardiac system is the need for a healthy life. The heart contains its nervous system termed as neurocardio system in which ANS plays a key role in which the sympathetic and parasympathetic system interplay to regulate HRV. High HRV is associated with healthy condition while low HRV is associated with pathological conditions. The HRV is influenced by various variables such as; pathological, physiological, psychological, environmental factors, lifestyle factors, and genetic factors, etc.

Sympathetic and parasympathetic innervation in cancer: therapeutic implications.

Abstract: The autonomic nervous system, consisting of sympathetic and parasympathetic/vagal nerves, is known to control the functions of any organ, maintaining whole-body homeostasis under physiological conditions. Recently, there has been increasing evidence linking sympathetic and parasympathetic/vagal nerves to cancers. The present review aimed to summarize recent developments from studies addressing the relationship between sympathetic and parasympathetic/vagal nerves and cancer behavior. Literature review. Human and animal studies have revealed that sympathetic and parasympathetic/vagal nerves innervate the cancer microenvironment and alter cancer behavior. The sympathetic nerves have cancer-promoting effects on prostate cancer, breast cancer, and melanoma. On the other hand, while the parasympathetic/vagal nerves have cancer-promoting effects on prostate, gastric, and colorectal cancers, they have cancer-suppressing effects on breast and pancreatic cancers. These neural effects may be mediated by β-adrenergic or muscarinic receptors and can be explained by changes in cancer cell behavior, angiogenesis, tumor-associated macrophages, and adaptive antitumor immunity. Sympathetic nerves innervating the tumor microenvironment promote cancer progression and are related to stress-induced cancer behavior. The parasympathetic/vagal nerves have variable (promoting or suppressing) effects on different cancer types. Approaches directed toward the sympathetic and parasympathetic/vagal nerves can be developed as a new cancer therapy. In addition to existing pharmacological, surgical, and electrical approaches, a recently developed virus vector-based genetic local neuroengineering technology is a powerful approach that selectively manipulates specific types of nerve fibers innervating the cancer microenvironment and leads to the suppression of cancer progression. This technology will enable the creation of "cancer neural therapy" individually tailored to different cancer types.

Autonomic dysfunction in SARS-COV-2 infection acute and long-term implications COVID-19 editor's page series.

Abstract: The autonomic nervous system (ANS) is a complex network of nerves originating in the brain, brain stem, spinal cord, heart and extracardiac organs that regulates neural and physiological responses to internal and external environments and conditions. A common observation among patients with the 2019 Coronavirus (CoV) (SARS-severe acute respiratory syndrome CoV-2) (SARS-CoV-2) or COVID-19 [CO for corona, VI for virus, D for disease and 19 for when the outbreak was first identified (31 December 2019)] in the acute and chronic phases of the disease is tachycardia, labile blood pressure, muscular fatigue and shortness of breath. Because abnormalities in the ANS can contribute to each of these symptoms, herein a review of autonomic dysfunction in SARS-COV-2 infection is provided to guide diagnostic testing, patient care and research initiatives. The autonomic nervous system is a complex network of nerves originating in the brain, brain stem, spinal cord, heart and extracardiac organs that regulates neural and physiological responses to internal and external environments and conditions. A common collection of signs and symptoms among patients with the 2019 Coronavirus (CoV) (SARS-severe acute respiratory syndrome CoV-2) (SARS-CoV-2) or COVID-19 [CO for corona, VI for virus, D for disease and 19 for when the outbreak was first identified (31 December 2019)] is tachycardia, labile blood pressure, muscular fatigue and shortness of breath. Abnormalities in the autonomic nervous system (ANS) can contribute to each of these identifiers, potentially offering a unifying pathobiology for acute, subacute and the long-term sequelae of SARS-CoV-2 infection (PASC) and a target for intervention.

Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health.

Abstract: Schizophrenia (SCZ) is a psychiatric disorder characterized by a wide range of positive, negative and cognitive symptoms, along with an increased risk of metabolic syndrome and cardiovascular disease that contribute to a 15-20-year reduced life expectancy. Autonomic dysfunction, in the form of increased sympathetic activity and decreased parasympathetic activity, is postulated to be implicated in SCZ and its treatment. The aim of this narrative review is to view SCZ through an autonomic lens and synthesize the evidence relating autonomic dysfunction to different domains of SCZ. Using various methods of assessing autonomic activity, autonomic dysfunction was found to be associated with multiple aspects of SCZ pathophysiology, including symptom severity, cognitive impairment, and the development of cardiometabolic comorbidities, such as metabolic syndrome and high BMI. The strongest association of low heart rate variability was noted among patients on antipsychotic treatment with high-affinity muscarinic antagonism (i.e., clozapine, olanzapine and quetiapine). The review will also suggest ways in which studying autonomic dysfunction can help reduce morbidity and mortality associated with SCZ and its treatment.

Central Autonomic Network

Abstract: The central autonomic network (CAN) consists of interconnected areas distributed throughout the central neuraxis. These areas not only control the activity of the preganglionic neurons but also participate in coordination of autonomic nervous system (ANS) activity with other homeostatic responses including respiration, arousal, and response to stress. These areas include the anterior cingulate and insular cortices, amygdala, periaqueductal gray, pedunculopontine nucleus (PPN), parabrachial nuclear complex, nucleus of solitary tract, ventrolateral medullary reticular formation, and rostral ventromedial medulla and raphe nuclei. The activity of neurons in these regions is regulated in a state-dependent manner during the sleep-wake cycle providing for changes in cardiovascular and respiratory functions during these states. Understanding of the functional organization of these autonomic structures is therefore of relevance to interpret cardiovascular, respiratory and other autonomic manifestation during normal sleep and in sleep disorders.

Autonomic manifestations of epilepsy: emerging pathways to sudden death?

Abstract: Epileptic networks are intimately connected with the autonomic nervous system, as exemplified by a plethora of ictal (during a seizure) autonomic manifestations, including epigastric sensations, palpitations, goosebumps and syncope (fainting). Ictal autonomic changes might serve as diagnostic clues, provide targets for seizure detection and help us to understand the mechanisms that underlie sudden unexpected death in epilepsy (SUDEP). Autonomic alterations are generally more prominent in focal seizures originating from the temporal lobe, demonstrating the importance of limbic structures to the autonomic nervous system, and are particularly pronounced in focal-to-bilateral and generalized tonic–clonic seizures. The presence, type and severity of autonomic features are determined by the seizure onset zone, propagation pathways, lateralization and timing of the seizures, and the presence of interictal autonomic dysfunction. Evidence is mounting that not all autonomic manifestations are linked to SUDEP. In addition, experimental and clinical data emphasize the heterogeneity of SUDEP and its infrequent overlap with sudden cardiac death. Here, we review the spectrum and diagnostic value of the mostly benign and self-limiting autonomic manifestations of epilepsy. In particular, we focus on presentations that are likely to contribute to SUDEP and discuss how wearable devices might help to prevent SUDEP. The close connection between epileptic networks and the autonomic nervous system is illustrated by a range of autonomic manifestations during a seizure. This article reviews the spectrum and diagnostic value of these manifestations, focusing on presentations that could contribute to sudden unexpected death in epilepsy.

Autonomic nervous system activity changes in patients with hypertension and overweight: role and therapeutic implications.

Abstract: The incidence and prevalence of hypertension is increasing worldwide, with approximately 1.13 billion of people currently affected by the disease, often in association with other diseases such as diabetes mellitus, chronic kidney disease, dyslipidemia/hypercholesterolemia, and obesity. The autonomic nervous system has been implicated in the pathophysiology of hypertension, and treatments targeting the sympathetic nervous system (SNS), a key component of the autonomic nervous system, have been developed; however, current recommendations provide little guidance on their use. This review discusses the etiology of hypertension, and more specifically the role of the SNS in the pathophysiology of hypertension and its associated disorders. In addition, the effects of current antihypertensive management strategies, including pharmacotherapies, on the SNS are examined, with a focus on imidazoline receptor agonists.

Intrinsic Cardiac Autonomic Nervous System: what do clinical electrophysiologists need to know about the ‘heart brain’?

Abstract: It is increasingly recognized that the autonomic nervous system (ANS) is a major contributor in many cardiac arrhythmias. Cardiac ANS can be divided into extrinsic and intrinsic parts according to the course of nerve fibers and localization of ganglia and neuron bodies. Although the role of the extrinsic part has historically gained more attention, the intrinsic cardiac ANS may affect cardiac function independently as well as influence the effects of the extrinsic nerves. Catheter-based modulation of the intrinsic cardiac ANS is emerging as a novel therapy for the management of patients with brady and tachyarrhythmias resulting from hyperactive vagal activation. However, the distribution of intrinsic cardiac nerve plexus in the human heart and the functional properties of intrinsic cardiac neural elements remain insufficiently understood. The present review aims to bring the clinical and anatomical elements of the immune effector cell-associated neurotoxicity together, by reviewing neuroanatomical terminologies and physiological functions, to guide the clinical electrophysiologist in the catheter lab and to serve as a reference for further research.

Signaling and function of cardiac autonomic nervous system receptors: Insights from the GPCR signalling universe.

Abstract: The two branches of the autonomic nervous system (ANS), adrenergic and cholinergic, exert a multitude of effects on the human myocardium thanks to the activation of distinct G protein-coupled receptors (GPCRs) expressed on the plasma membranes of cardiac myocytes, cardiac fibroblasts, and coronary vascular endothelial cells. Norepinephrine (NE)/epinephrine (Epi) and acetylcholine (ACh) are released from cardiac ANS terminals and mediate the biological actions of the ANS on the heart via stimulation of cardiac adrenergic or muscarinic receptors, respectively. In addition, several other neurotransmitters/hormones act as facilitators of ANS neurotransmission in the heart, taking part in the so-called nonadrenergic noncholinergic (NANC) part of the ANS's control of cardiac function. These NANC mediators also use several different cell membrane-residing GPCRs to exert their effects in the myocardium. Cardiac ANS dysfunction and an imbalance between the activities of its two branches underlie a variety of cardiovascular diseases, from heart failure and hypertension to coronary artery disease, myocardial ischemia, and arrhythmias. In this review, we present the main well-established signaling modalities used by cardiac autonomic GPCRs, including receptors for salient NANC mediators, and we also highlight the latest developments pertaining to cardiac cell type-specific signal transduction, resulting in cell type-specific cardiac effects of each of these autonomic receptors.

Parkinson's disease outside the brain: targeting the autonomic nervous system.

Abstract: Patients with Parkinson's disease present with signs and symptoms of dysregulation of the peripheral autonomic nervous system that can even precede motor deficits. This dysregulation might reflect early pathology and therefore could be targeted for the development of prodromal or diagnostic biomarkers. Only a few objective clinical tests assess disease progression and are used to evaluate the entire spectrum of autonomic dysregulation in patients with Parkinson's disease. However, results from epidemiological studies and findings from new animal models suggest that the dysfunctional autonomic nervous system is a probable route by which Parkinson's disease pathology can spread both to and from the CNS. The autonomic innervation of the gut, heart, and skin is affected by α-synuclein pathology in the early stages of the disease and might initiate α-synuclein spread via the autonomic connectome to the CNS. The development of easy-to-use and reliable clinical tests of autonomic nervous system function seems crucial for early diagnosis, and for developing strategies to stop or prevent neurodegeneration in Parkinson's disease.

A Review on the Vagus Nerve and Autonomic Nervous System During Fetal Development: Searching for Critical Windows

Abstract: The autonomic nervous system (ANS) is one of the main biological systems that regulates the body's physiology. Autonomic nervous system regulatory capacity begins before birth as the sympathetic and parasympathetic activity contributes significantly to the fetus' development. In particular, several studies have shown how vagus nerve is involved in many vital processes during fetal, perinatal, and postnatal life: from the regulation of inflammation through the anti-inflammatory cholinergic pathway, which may affect the functioning of each organ, to the production of hormones involved in bioenergetic metabolism. In addition, the vagus nerve has been recognized as the primary afferent pathway capable of transmitting information to the brain from every organ of the body. Therefore, this hypothesis paper aims to review the development of ANS during fetal and perinatal life, focusing particularly on the vagus nerve, to identify possible "critical windows" that could impact its maturation. These "critical windows" could help clinicians know when to monitor fetuses to effectively assess the developmental status of both ANS and specifically the vagus nerve. In addition, this paper will focus on which factors-i.e., fetal characteristics and behaviors, maternal lifestyle and pathologies, placental health and dysfunction, labor, incubator conditions, and drug exposure-may have an impact on the development of the vagus during the above-mentioned "critical window" and how. This analysis could help clinicians and stakeholders define precise guidelines for improving the management of fetuses and newborns, particularly to reduce the potential adverse environmental impacts on ANS development that may lead to persistent long-term consequences. Since the development of ANS and the vagus influence have been shown to be reflected in cardiac variability, this paper will rely in particular on studies using fetal heart rate variability (fHRV) to monitor the continued growth and health of both animal and human fetuses. In fact, fHRV is a non-invasive marker whose changes have been associated with ANS development, vagal modulation, systemic and neurological inflammatory reactions, and even fetal distress during labor.

Altered cardiac autonomic function after recovery from COVID-19.

Abstract: Background Autonomic dysfunction may occur during the acute phase of COVID-19. Heart rate variability (HRV) is a useful tool for the assessment of cardiac sympathetic and parasympathetic balance. We aimed to evaluate cardiac autonomic function by using HRV in subjects after recovery from COVID-19 who had previously symptomatic and were followed outpatiently. Methods The study group composed of 50 subjects with a confirmed history of COVID-19 and the control group composed of 50 healthy subjects without a history of COVID-19 and vaccination. All the study participants underwent 2-dimensional, pulsed- and tissue-Doppler echocardiographic examinations and 24-hour Holter monitoring for HRV analysis. Results Time domain parameters of SDNN, SDANN, SDNNi, RMSSD, pNN50, and HRV triangular index were all decreased in the study group when compared with the control group. Frequency domain parameters of TP, VLF, LF, HF, and HFnu were also decreased in the study group in comparison with the control group. LFnu was similar between groups. Nonlinear parameters of HRV including α1 and α2 decreased in the study group. By contrast, Lmax, Lmean, DET, REC, and Shannon entropy increased in the study population. Approximate and sample entropies also enhanced in the study group. Conclusions The present study showed that all three domain HRV significantly altered in patients after recovery from COVID-19 indicating some degree of dysfunction in cardiac autonomic nervous system. HRV may be a useful tool for the detection of preclinical autonomic dysfunction in this group of patients.

Identification of Novel Cross-Talk between the Neuroendocrine and Autonomic Stress Axes Controlling Blood Pressure.

Abstract: The hypothalamic paraventricular nucleus (PVN) controls neuroendocrine axes and the autonomic nervous system to mount responses that cope with the energetic burdens of psychological or physiological stress. Neurons in the PVN that express the angiotensin Type 1a receptor (PVNAgtr1a) are implicated in neuroendocrine and autonomic stress responses; however, the mechanism by which these neurons coordinate activation of neuroendocrine axes with sympathetic outflow remains unknown. Here, we use a multidisciplinary approach to investigate intra-PVN signaling mechanisms that couple the activity of neurons synthesizing corticotropin-releasing-hormone (CRH) to blood pressure. We used the Cre-Lox system in male mice with in vivo optogenetics and cardiovascular recordings to demonstrate that excitation of PVNAgtr1a promotes elevated blood pressure that is dependent on the sympathetic nervous system. Next, neuroanatomical experiments found that PVNAgtr1a synthesize CRH, and intriguingly, fibers originating from PVNAgtr1a make appositions onto neighboring neurons that send projections to the rostral ventrolateral medulla and express CRH type 1 receptor (CRHR1) mRNA. We then used an ex vivo preparation that combined optogenetics, patch-clamp electrophysiology, and Ca2+ imaging to discover that excitation of PVNAgtr1a drives the local, intra-PVN release of CRH, which activates rostral ventrolateral medulla-projecting neurons via stimulation of CRHR1(s). Finally, we returned to our in vivo preparation and found that CRH receptor antagonism specifically within the PVN lowered blood pressure basally and during optogenetic activation of PVNAgtr1a Collectively, these results demonstrate that angiotensin II acts on PVNAgtr1a to conjoin hypothalamic-pituitary-adrenal axis activity with sympathetically mediated vasoconstriction in male mice.SIGNIFICANCE STATEMENT The survival of an organism is dependent on meeting the energetic demands imposed by stressors. This critical function is accomplished by the CNS's ability to orchestrate simultaneous activities of neurosecretory and autonomic axes. Here, we unveil a novel signaling mechanism within the paraventricular nucleus of the hypothalamus that links excitation of neurons producing corticotropin-releasing-hormone with excitation of neurons controlling sympathetic nervous system activity and blood pressure. The implication is that chronic stress exposure may promote cardiometabolic disease by dysregulating the interneuronal cross-talk revealed by our experiments.

Effects of transcutaneous auricular vagus nerve stimulation on cardiovascular autonomic control in health and disease.

Abstract: Autonomic nervous system (ANS) dysfunction is a well-known feature of cardiovascular diseases (CVDs). Studies on heart rate variability (HRV), a non-invasive method useful in investigating the status of cardiovascular autonomic control, have shown that a predominance of sympathetic modulation not only contributes to the progression of CVDs but has a pivotal role in their onset. Current therapies focus more on inhibition of sympathetic activity, but the presence of drug-resistant conditions and the invasiveness of some surgical procedures are an obstacle to complete therapeutic success. On the other hand, targeting the parasympathetic branch of the autonomic nervous system through invasive vagus nerve stimulation (VNS) has shown interesting results as alternative therapeutic approach for CVDs. However, the invasiveness and cost of the surgical procedure limit the clinical applicability of VNS and hinder the research on the physiological pathway involved. Transcutaneous stimulation of the auricular branch of the vagus nerve (tVNS) seems to represent an important non-invasive alternative with effects comparable to those of VNS with surgical implant. Thus, in the present narrative review, we illustrate the main studies on tVNS performed in healthy subjects and in three key examples of CVDs, namely heart failure, hypertension and atrial fibrillation, highlighting the neuromodulatory effects of this technique.

Neuroscientific therapies for atrial fibrillation

Abstract: The cardiac autonomic nervous system (ANS) plays an integral role in normal cardiac physiology as well as in disease states that cause cardiac arrhythmias. The cardiac ANS, comprised of a complex neural hierarchy in a nested series of interacting feedback loops, regulates atrial electrophysiology and is itself susceptible to remodelling by atrial rhythm. In light of the challenges of treating atrial fibrillation (AF) with conventional pharmacologic and myoablative techniques, increasingly interest has begun to focus on targeting the cardiac neuraxis for AF. Strong evidence from animal models and clinical patients demonstrates that parasympathetic and sympathetic activity within this neuraxis may trigger AF, and the ANS may either induce atrial remodelling or undergo remodelling itself to serve as a substrate for AF. Multiple nexus points within the cardiac neuraxis are therapeutic targets, and neuroablative and neuromodulatory therapies for AF include ganglionated plexus ablation, epicardial botulinum toxin injection, vagal nerve (tragus) stimulation, renal denervation, stellate ganglion block/resection, baroreceptor activation therapy, and spinal cord stimulation. Pre-clinical and clinical studies on these modalities have had promising results and are reviewed here.

The Emerging Role of Nerves and Glia in Colorectal Cancer.

Abstract: The role of the nervous system as a contributor in the tumor microenvironment has been recognized in different cancer types, including colorectal cancer (CRC). The gastrointestinal tract is a highly innervated organ system, which is not only innervated by the autonomic nervous system, but also contains an extensive nervous system of its own; the enteric nervous system (ENS). The ENS is important for gut function and homeostasis by regulating processes such as fluid absorption, blood flow, and gut motility. Dysfunction of the ENS has been linked with multiple gastrointestinal diseases, such as Hirschsprung disease and inflammatory bowel disease, and even with neurodegenerative disorders. How the extrinsic and intrinsic innervation of the gut contributes to CRC is not fully understood, although a mutual relationship between cancer cells and nerves has been described. Nerves enhance cancer progression through the secretion of neurotransmitters and neuropeptides, and cancer cells are capable of stimulating nerve growth. This review summarizes and discusses the nervous system innervation of the gastrointestinal tract and how it can influence carcinogenesis, and vice versa. Lastly, the therapeutic potential of these novel insights is discussed.

The autonomic nervous system in its natural environment: Immersion in nature is associated with changes in heart rate and heart rate variability.

Abstract: Stress Recovery Theory (SRT) suggests that time spent in nature reduces stress. While many studies have examined changes in stress physiology after exposure to nature imagery, nature virtual reality, or nature walks, this study is the first to examine changes in heart rate (HR) and vagally mediated HR variability, as assessed by Respiratory Sinus Arrythmia (RSA), after a longer duration of nature exposure. Consistent with SRT, we hypothesized that immersion in nature would promote stress recovery, as indexed by an increase in RSA and a decrease in HR. We also predicted that exposure to nature would improve self-reported mood. We used a within-subjects design (N = 67) to assess changes in peripheral physiology before, during, and after a 5-day nature trip. Results demonstrated a significant decrease in RSA and a significant increase in HR during the trip compared to before or after the trip, suggesting that immersion in nature is associated with a shift toward parasympathetic withdrawal and possible sympathetic activation. These results were contrary to our hypotheses and may suggest increased attentional intake or presence of emotions associated with an increase in sympathetic activation. We also found an improvement in self-reported measures of mood during the trip compared to before or after the trip, confirming our hypotheses and replicating previous research. Implications of this study are discussed in the context of SRT.