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We used to think we could measure our circulatory health with a combination of blood pressure and heart rate. Low measures indicated healthy arteries, veins and heart.

However, recently researchers have begun to realise that there is another interesting and powerful measure of the strength of your nervous and circulatory systems and of your health in general. This measure is called heart rate variability (HRV) - and it turns out to be a better indicator than the more traditional notion of heart rate. HRV is increasingly being considered as a long term biomarker of health. Reduced HRV is associated with a number of ailments such as diabetes, cardiovascular disease, inflammation, obesity and psychiatric disorders. Conversely, increasing HRV can have a direct effect on capacity to exercise, promote weight loss, and positively affect mood, sleep, and recovery [1].

So what is HRV?

Simply put, HRV is the variability of the time between consecutive heart beats.

It turns out that healthy hearts do not have a consistent heart rate at all - so measuring the beats per minute doesn’t tell you everything. Your heart will regulate its beating to meet your body’s demands on an ongoing basis right down to the level of consecutive beats. So even as you breathe in and out, the interval between beats is changing in response to different levels of oxygen in your lungs.

HRV attempts to capture this by measuring the time between each heartbeat and measuring the degree to which this varies. To work this out, the exact moment of each heart beat must be recorded (down to millisecond precision) over a period of time that may range from at least 10 seconds all the way up to 24hours; then some clever maths is needed to convert this information into a single score for your HRV.

There are several different ways that this HRV score can be calculated, and for those of you who are more mathematically inclined, look out for our next post which will dive into a more in-depth analysis. For the rest of us, however, we don’t need to worry so much about how HRV is calculated so long as we can interpret the numbers and understand what it tells us about our health.

How is HRV linked to health?

Your heart rate is controlled by your Autonomic Nervous System (ANS), which is the part of your nervous system that works without direct conscious intervention from your brain. It is still signals from the brain that are controlling every beat of the heart, but it happens largely without you thinking about it or having much control over it.

The ANS actually has two branches which work in an opposing but complimentary fashion to keep the body in a balanced state, referred to as homeostasis. The Sympathetic Nervous System (SNS) branch stimulates the body in response to internal or environmental stressors. Activation of the SNS has the effect of preparing the body for what is sometimes referred to as it’s ‘fight or flight’ response. Heart rate and blood glucose levels are increased, pupils dilate and breathing quickens, while healing, digestion and reproduction systems are inhibited.

The Parasympathetic Nervous System (PNS) works in exactly the opposite direction and is sometimes referred to as the ‘rest and digest’ response of the body. It works to bring your stress level back down, slowing heart rate and breathing while stimulating digestion, healing and relaxation.

The ‘fight or flight’ vs the ‘rest and digestion’ description of these two branches is not a wholly accurate one, however, because it gives the impression that there are long periods when one is dominant over the other. But far more accurately, both are constantly active and attempting to keep the body in a balanced ‘homeostasis’, even when engaged in either fighting or relaxing.

Both branches are active even as we breathe in and out, with the SNS working to increase heart rate (along with other bodily functions) while the PSN is working to bring the heart rate right back down. Hence it is the strength and vibrancy of our nervous system that we are measuring when we measure our HRV.

Nervous System Health

Low heart rate variability is a sign that your body’s nervous system is not in proper balance. This can mean either that your sympathetic nervous system is dominant (over active) or that your parasympathetic nervous system is weak or under active. In extreme cases, this can result in serious health conditions, but in most cases, you can effectively bring yourself into balance by changes to your diet, exercise routines or by directly stimulating parts of the parasympathetic nervous system as is done with vagus nerve stimulation.

In other words, HRV is a proxy for measuring the health of your autonomic nervous system. Dysfunction in the ANS can have severe implications on the body’s ability to exercise, heal and fight disease.

That said, it’s also important to understand that HRV is not a direct measure of the health of the nervous system so even if your HRV varies, it doesn't necessarily mean that something is wrong. It’s best to get a longer term picture of your HRV and use it with other metrics to get an overall idea about your health.

What is normal HRV?

It’s very difficult to come up with an exact definition of what is normal, but scientists have studied population averages and give ranges that are common by age and gender. Below is a graph of HRV ranges from one such study [2].

As you can see, HRV tends to fall as we age and there is a considerable range.

HRV can fluctuate for an individual quite a lot even within a single day. Factors such as the amount of exercise you have recently done, how well you slept, how recently you ate and how stressed you feel can all have short term effects on your HRV. It is, therefore, generally considered better to examine the trend of your HRV and understand the different factors that can affect it. Long term trends are affected by health, diet, fitness, stress and age.

But generally speaking, within the ranges given, the higher your HRV at any age, the better. Your HRV will also increase after strenuous exercise and during recovery until it returns to your long term baseline.

Some good apps exist that can be used along with a regular heart rate monitor (such as polar or simply your phone camera), to get a measure of your HRV trends.

How to improve your HRV

If you do measure your HRV and find that it is a little on the low side for your age and gender, there is no need for immediate despair. There is a great deal you can do about it.

Given all the things that affect HRV, the ways to improve it all revolve around improvements in the same things: regular exercise, good sleep, good diet and limiting stress.

Additionally, ensuring that your nervous system is healthy and functioning as it should is very important. The vagus nerve is directly connected to your heart and good vagal tone is strongly correlated to good HVR. Stimulation is a good way to improve the tone of your vagus nerve, but there are also many natural ways that you could use. Look out for future posts where we will explore this.

Even if you decide to use stimulation to help maintain or improve your vagal tone, you should still always consider combining this with natural methods. Many of these methods will have a positive effect on your overall health and well being as well as your HRV.

References

[1] Young, Hayley A, and David Benton. “Heart-rate variability: a biomarker to study the influence of nutrition on physiological and psychological health?.” Behavioural pharmacology vol. 29,2 and 3-Spec Issue (2018): 140-151. doi:10.1097/FBP.0000000000000383

[2] van den Berg, Marten E et al. “Normal Values of Corrected Heart-Rate Variability in 10-Second Electrocardiograms for All Ages.” Frontiers in physiology vol. 9 424. 27 Apr. 2018, doi:10.3389/fphys.2018.00424

[3] Hayano, J., Yuda, E. Pitfalls of assessment of autonomic function by heart rate variability. J Physiol Anthropol 38, 3 (2019). https://doi.org/10.1186/s40101-019-0193-2

[4] Shaffer, Fred, and J P Ginsberg. “An Overview of Heart Rate Variability Metrics and Norms.” Frontiers in public health vol. 5 258. 28 Sep. 2017, doi:10.3389/fpubh.2017.00258

[5] Kiviniemi AM, Hautala AJ, Kinnunen H, Tulppo MP. Endurance training guided individually by daily heart rate variability measurements. Eur J Appl Physiol. 2007;101(6):743-751. doi:10.1007/s00421-007-0552-2

[6] Ernst, Gernot. “Heart-Rate Variability-More than Heart Beats?.” Frontiers in public health vol. 5 240. 11 Sep. 2017, doi:10.3389/fpubh.2017.00240

[7] Dong, Jin-Guo. “The role of heart rate variability in sports physiology.” Experimental and therapeutic medicine vol. 11,5 (2016): 1531-1536. doi:10.3892/etm.2016.3104

[8] Earnest CP, Jurca R, Church TS, et alRelation between physical exertion and heart rate variability characteristics in professional cyclists during the Tour of SpainBritish Journal of Sports Medicine 2004;38:568-575.

The term ‘vagus’ comes from Latin, meaning 'wandering,' which appropriately fits the description of the 10th cranial nerve or CN X as it wanders and branches throughout the body. Vagus nerve is the longest and most complicated of all 12 cranial nerves. It is a mixed nerve with both afferent (sensory) and efferent (motor) components, meaning it not only carries signals from the brain to the organs but also carries signals back from the organs to the brain. It contributes to the autonomic nervous system, with the parasympathetic nervous system being one of its most essential components, as well as some sympathetic influence.

The vagus nerve is an important component of the autonomic nervous system. It plays a vital role in the regulation of physiological homeostasis and maintaining the neuro-endocrine axis for homeostasis control through its afferent and efferent pathways. [1]

Throughout its course in the body, the vagus nerve gives off multiple branches, within the cranium, in the neck, in the thorax and in the abdomen.

Functions of the Vagus Nerve

The vagus nerve is an essential component of the parasympathetic nervous system as it oversees critical physiological functions of different organ systems, including heart rate, digestion, emotions, sweating, immune response, and articulation of speech. It transmits signals about the condition of various internal organs to the brainstem via afferent fibers from where the signals are relayed to different parts of the brain for different organ controls.[2] It plays a pivotal role in several involuntary activities and damage to it can cause multiple bodily functions to go haywire.

Constituent Fibers:

The vagus nerve specifically contains the following fibers:

 

  • General Afferent (Sensory) Fibers: They carry sensations of pain, vibration, touch, temperature, and proprioception (awareness of the position and the movement of the body) from the external ear and posterior part of the auricular canal.
  • Special Sensory Fibers: They carry the sensation of taste from palate and epiglottis. 
  • Visceral Afferent (Sensory) Fibers: They carry sensation, besides pain, from the viscera (internal organs in the main cavities of the body e-g those in the abdomen).
  • Brachial Efferent (Motor) Fibers: These provide innervation for muscles that arise from the branchial arches, such as muscles of mastication (chewing), tensor tympani, and tensor veli palitini (present in the head and neck region).
  • Visceral Efferent (Motor) Fibers: These innervate viscera including all smooth muscles (found in the walls of hollow organs such as intestines, stomach, and more) and glands (such as pancreas).

 

 The vagus nerve controls multiple organs and reflexes, including; digestion, respiratory rate, sweating, coughing, swallowing, as well as vasomotor activity (constriction ad dilation of blood vessels). [3] It is responsible for transmitting neural information from different parts of the body to the brain, making this peripheral nerve one of the most important nerves in the body.

Effects on the Body:

 

 

  • The Heart:

 

The heart receives its parasympathetic innervation through the vagus nerve, which acts by lowering the heart rate. The right vagus nerve innervates the SA node, whereas the left vagus nerve innervates the AV node as well as the atrial and ventricular myocardium. Vagal control is abnormal in cases of heart failure and it produces worse outcomes in cases of previous myocardial infarction and heart failure [4]. Over-stimulation of the vagus nerve may lead to bradyarrhythmias, AV block, or collapse due to a massive drop in blood pressure.

 

 

  • Gastrointestinal Tract:

 

There exists a bidirectional communication between the brain and the gastrointestinal tract, also called "brain-gut axis." It is based on a complex system, which includes the vagus nerve, but also other components including sympathetic, endocrine, immune, and humoral links as well as the influence of gut microbiota in order to regulate gastrointestinal homeostasis and to connect emotional and cognitive areas of the brain with gut functions. [5] The neural and endocrine pathways work together to communicate to the brain the internal environment of the gut, which in turn sends signals to the various functional effector cells, including enterochromaffin cells, intestinal cells of Cajal, immune cells, enteric neurons and epithelial cells. [6]. The vagus nerve innervates the myenteric plexus, which is responsible for gut motility. After means the vagal afferent fibers of the gut, liver, and pancreas, which rapidly provide nutrients to the alimentary canal, which in turn acts on the efferent vagal nerves, that work with a hormonal mechanism to determine the rate of nutrient absorption, storage, and mobilization [7].

 

 

  • Inflammatory Response:

 

The communication between the vagal nerve and brain is vital for mediating an immune response. It is a reflex phenomenon in which the vagus afferent nerve detects and is stimulated by pro-inflammatory factors like cytokines or other pathogen-derived products. A response is attenuated by the efferent fibers to counteract the inflammation and to regulate the production of pro-inflammatory factors[8.] The absence of which can result in excessive inflammation and cytokine toxicity. It, therefore, helps in regulating the body's immune response. 

 

Vagus Nerve Stimulation

Vagal nerve stimulation (VNS) is a medical procedure that involves placing an electrical device under the skin of the chest and connecting it to the left vagus nerve. When stimulated using electrical impulses, signals are sent along the nerve to the brainstem, which then stimulates certain areas of the brain.

Several dedicated clinical trials eventually led to approval by the United States Food and Drug Administration (FDA) in 1997, for an implanted VNS device indicated for the treatment of refractory epilepsy. [9] It is now successfully used to treat epilepsy and drug-resistant depression.

 

  • Depression

 

Depression is among the most common psychological disorders. According to the WHO, it affects more than 264 million people worldwide. Mostly, pharmaceutical therapy is used for the treatment; however, in resistant cases, VNS is employed with positive results.

The vagus nerve has direct and indirect connections to a neural circuit pertinent to emotional and cognitive functions relevant in depression. [10] Cytokine receptors present on the brain and along the hypothalamic-Pituitary-Adrenal (HPA) axis are activated by cytokines and are thought to be relevant for the pathogenesis of depression. [11] Patients with depression show elevated levels of pro-inflammatory cytokines in the plasma and CSF. VNS is thought to work by inhibiting the pro-inflammatory effect of cytokines[12] and by decreasing the levels of circulating pro-inflammatory cytokines[13.] The central role of the vagus nerve in the regulation of the neuro-endocrine-immune axis is a potential mechanism of action for VNS in the treatment of depression. [14]

 

 

  • Epilepsy

 

The device planted under the skin sends mild, regular pulses of electrical signals via the vagus nerve to the brain, which help prevent seizures. It is sometimes referred to as the pacemaker of the brain. There have been several studies suggesting that VNS affects the brain in such areas as the thalamus and other limbic structures. Vagal stimulation releases norepinephrine, which is thought to have an anti-epileptic effect. This procedure does not have any systemic side effects and is considered to be a good alternative for patients who have poor tolerance for anti-epileptic drugs[15]. VNS is not a cure for epilepsy, but it decreases the frequency of seizures by 50% and helps improves the quality of life.

Transcutaneous Vagus Nerve Stimulation (tVNS)

It is a relatively new, non-invasive approach for neural stimulation. It involves the stimulation of the vagus nerve through the skin and transiently increasing the levels of GABA and nor-adrenaline.  It has been demonstrated that tVNS targets three neurotransmitters, namely, norepinephrine, gamma-aminobutyric acid (GABA), and acetylcholine. All of these are thought to be directly involved in cognitive functioning [16]. tVNS is considered a better therapeutic alternative to invasive techniques of vagal nerve stimulation because of its lesser side effects and better safety profile17].

After the success of using VNS for the treatment of epilepsy and depression, it is considered that vagal nerve stimulation (VNS) can be used in the treatment of multiple diseases such as inflammatory bowel disease (IBD), cluster headache, multiple sclerosis and Alzheimer’s. While tVNS can be used in treating pain modalities, tinnitus, stroke recovery, and others. Other studies are also being conducted on these procedures as they improve treatment outcomes with fewer medications and less side effects.

 

References

[1] Howland R. H. (2014). Vagus Nerve Stimulation. Current behavioral neuroscience reports1(2), 64–73. 

[2] Breit, S., Kupferberg, A., Rogler, G., & Hasler, G. (2018). Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders. Frontiers in psychiatry9, 44. 

[3] Babic, T., & Browning, K. N. (2014). The role of vagal neurocircuits in the regulation of nausea and vomiting. European journal of pharmacology722, 38-47.

[4]Bibevski S, Dunlap ME. Evidence for impaired vagus nerve activity in heart failure. Heart Fail Rev. 2011;16(2):129‐135. doi:10.1007/s10741-010-9190-6

[5] Carabotti, M., Scirocco, A., Maselli, M. A., & Severi, C. (2015). The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Annals of gastroenterology: a quarterly publication of the Hellenic Society of Gastroenterology28(2), 203.

[6] Mayer, E. A., Savidge, T., & Shulman, R. J. (2014). Brain–gut microbiome interactions and functional bowel disorders. Gastroenterology146(6), 1500-1512.

[7] Berthoud, H. R. (2008). Vagal and hormonal gut–brain communication: from satiation to satisfaction. Neurogastroenterology & Motility20, 64-72.

[8] Pavlov, V. A., & Tracey, K. J. (2012). The vagus nerve and the inflammatory reflex--linking immunity and metabolism. Nature reviews. Endocrinology8(12), 743–754. 

[9] Morris, G. L., Gloss, D., Buchhalter, J., Mack, K. J., Nickels, K., & Harden, C. (2013). Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology81(16), 1453-1459.

[10] Ruffoli, R., Giorgi, F. S., Pizzanelli, C., Murri, L., Paparelli, A., & Fornai, F. (2011). The chemical neuroanatomy of vagus nerve stimulation. Journal of chemical neuroanatomy42(4), 288-296.

[11][14] Howland R. H. (2014). Vagus Nerve Stimulation. Current behavioral neuroscience reports1(2), 64–73. https://doi.org/10.1007/s40473-014-0010-5

[12] Suarez, E. C., Krishnan, R. R., & Lewis, J. G. (2003). The relation of severity of depressive symptoms to monocyte-associated pro-inflammatory cytokines and chemokines in apparently healthy men. Psychosomatic medicine65(3), 362-368.

[13] Corcoran, C., Connor, T. J., O’Keane, V., & Garland, M. R. (2005). The effects of vagus nerve stimulation on pro-and anti-inflammatory cytokines in humans: a preliminary report. Neuroimmunomodulation12(5), 307-309.

[15] Ben-Menachem E. (2002). Vagus-nerve stimulation for the treatment of epilepsy. The Lancet. Neurology1(8), 477–482. 

[16] Sellaro, R., Steenbergen, L., Verkuil, B., van IJzendoorn, M. H., & Colzato, L. S. (2015). Transcutaneous Vagus Nerve Stimulation (tVNS) does not increase prosocial behavior in Cyberball. Frontiers in psychology6, 499.

17 Anfinogenova Y. (2016). Vagus nerve stimulation: Invasive or non-invasive?. Anatolian journal of cardiology16(10), 811–812

Introduction

The autonomic nervous system is a part of the peripheral nervous system. This part is essential for regulation of the  involuntary physiological processes, including heart rate, blood pressure, respiration, digestion, and sexual arousal. It consists of three anatomically different divisions: sympathetic, parasympathetic and enteric.

The development of the autonomic nervous system

The development of the autonomic nervous system results from the migration of the neural crest cells like other portions of the nervous system. The migration of these neural cells takes the dorsolateral and ventromedial directions. The ventromedial direction forms the cells that will present the autonomic nervous system.                                                    

This process is found that it depends in an obvious way on the growth factors. These growth factors coordinate the migration and the growth of the axons. These growth factors also stimulate growth of others by releasing neurotransmitters.

The structure of the sympathetic nervous system

The  intermediolateral columns, or lateral horns, of the spinal cord have the cell bodies of the sympathetic neurons. The presynaptic fibers emergence from the spinal cord through anterior roots and enter the anterior rami of T1-L2 spinal nerves and onto the sympathetic trunks via white rami communicantes. 

Then the fibers may ascend or descend the sympathetic trunk to a superior or inferior paravertebral ganglion then pass to adjacent anterior spinal nerve rami via gray rami communicantes, or these fibers may arrive to prevertebral ganglia across the abdominolpelvic splanchnic nerve. 

Paravertebral ganglia present as nodules throughout the sympathetic trunk, adjacent to the spinal column, where pre- and postganglionic neurons synapse.

Generally, there are three cervical, twelve thoracic, four lumbar, and five sacral ganglia. This distribution may vary individually. Of these, only the cervical have names of superior, middle, and inferior cervical ganglia. There is the  stellate ganglion that forms by the fusion of the inferior cervical ganglion and the first thoracic ganglion. 

There are splanchnic nerves that  convey afferent and efferent fibers between the CNS and the viscera. Cardiopulmonary splanchnic nerves transfer the postsynaptic fibers for the thoracic cavity.

There are the abdominopelvic splanchnic nerves  include the greater, lesser, least, and lumbar splanchnic nerves. The presynaptic nerves finally synapse in prevertebral ganglia that are nearer to their target organ. 

Prevertebral ganglia includes the celiac, aorticorenal, and superior and inferior mesenteric ganglia. 

The celiac ganglion innervates organs derived from the foregut: distal esophagus, stomach, proximal duodenum, pancreas, liver, biliary system, adrenal glands, and the spleen. 

The superior mesenteric ganglion innervates organs derived from the midgut: distal duodenum, jejunum, ileum, cecum, appendix, ascending colon, and proximal transverse colon. 

The inferior mesenteric ganglion provides sympathetic innervation to the structures derived from the hindgut: distal transverse, descending, and sigmoid colon; rectum and upper anal canal; as well as the bladder and external genitalia.

The function of the sympathetic nervous system

The sympathetic nervous system enables the body to use energy appropriately to respond to stressful situations and emergencies, as in the “fight or flight” response. 

Activation of the sympathetic system leads to pupil dilation, piloerection, vasoconstriction of cutaneous blood vessels, sweating, release of adrenaline, bronchodilation, increased cardiac contraction and decreased digestion.

During normal conditions, blood vessels are existing in a resting state of moderate vasoconstriction.

 If sympathetic signals are sent, vasoconstriction increases and vice-versa. However, in coronary vessels, vessels of the external genitalia and the skeletal muscles sympathetic stimulation leads to vasodilation.

The structure of the parasympathetic nervous system

There are the parasympathetic fibers that emergences from  the central nervous system via cranial nerves III, VII, IX, and X, and also through the S2-4 nerve roots. There are four pairs of parasympathetic ganglia, and they are existing in the head.

The third cranial nerve, via the ciliary ganglion, innervates the iris and ciliary muscles of the eye.

The seventh cranial nerve innervates the lacrimal, nasal, palatine, and pharyngeal glands via the pterygopalatine ganglion, and also the sublingual and submandibular glands via the submandibular ganglion.

 The ninth cranial nerve innervates the parotid glands via the otic ganglion.

Each other presynaptic parasympathetic fiber synapses in a ganglion near or on the wall of the target tissue; this leads to the presynaptic fibers being obviously longer than the postsynaptic. 

The tenth cranial nerve (the vagus nerve) forms  about 75% of the PNS and supplies parasympathetic input to most of the thoracic and abdominal viscera, with the sacral parasympathetic fibers innervating the descending and rectum and the sigmoid colon.  The vagus nerve has four cell bodies in the medulla oblongata. These include the following:

  • Dorsal nucleus: supplies parasympathetic output to the viscera.
  • Nucleus ambiguus: produces motor fibers and neurons that innervate the heart.
  • Nucleus solitarius: receives afferents of taste sensation and that from the viscera.
  • Spinal trigeminal nucleus: receives information of touch, pain, and temperature of the outer ear, part of the dura and the mucosa of the larynx.

The function of the parasympathetic nervous system

The parasympathetic fibers are sent to various viscera to do different involuntary functions as:

  • Constriction of the pupil when the eyes are exposed to excessive bright light.
  • Contraction of the ciliary muscle to allow the lens to thicken for near vision.
  • Advancement of the secretion of the lacrimal glands, the secretion of the salivary glands, decreasing the rate and strength of contraction.
  • Constriction of the bronchi and the coronary vessels.
  • Advancement of bronchi mucus secretion of the lungs.
  • Sending impulses to stimulate peristalsis and secretion of digestive juices.
  • Contraction of the rectum during defecation and inhibition of the internal anal sphincter to cause defecation.
  • Advancement the building/conservation of glycogen.
  • Raising the secretion of bile.
  • Inhibition of the contraction of internal sphincter of urinary bladder and they are also responsible for contraction of the detrusor muscle of the urinary bladder wall causing urination.
  • Stimulation of engorgement (erection) of erectile tissues of the external genitalia.
  • In order to achieve the homeostasis in the activities of these organs, the sympathetic nervous system also innervates those structures in an antagonistic way.

The structure of the enteric nervous system

The enteric nervous system  consists of two ganglionated plexuses: 

The myenteric  and the submucosal. The myenteric plexus exists between the longitudinal and circular smooth muscle of the gastrointestinal tract, while the submucosal plexus presents within the submucosa.

The enteric nervous system neurons can be classified functionally into three groups: intrinsic primary afferent neurons, interneurons and motor neurons.

The intrinsic primary afferent neurons receive chemical and mechanical stimuli from ingestion, usually food and drink.

The motor neurons in the enteric nervous system coordinate peristalsis, rhythmic muscle contractions that move material along the digestive tract.

Enteric neurons are responsible for regulation the vomiting reflex, which is particularly critical in those cases in which vomiting results as a side-effect of medical treatments.

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