Review Article
Volume 8 Issue 8 - 2021
The Human Heart as the "Little Brain"—the Intrinsic Cardiac Nervous System (ICNS)
Nicholas A Kerna1,2*, Joseph Anderson II3, John V Flores4,5, Hilary M Holets4,5, Emmanuella O Solomon6, Kevin D Pruitt7,8, ND Victor Carsrud9 and Uzoamaka Nwokorie10
1SMC–Medical Research, Thailand
2First InterHealth Group, Thailand
3International Institute of Original Medicine, USA
4Beverly Hills Wellness Surgical Institute, USA
5Orange Partners Surgicenter, USA
6Obafemi Awolowo University, Nigeria
7Kemet Medical Consultants, USA
8PBJ Medical Associates, LLC, USA
9Lakeline Wellness Center, USA
10University of Washington, USA
*Corresponding Author: Nicholas A Kerna, SMC–Medical Research, Thailand.
Received: August 17, 2021; Published: August 30, 2021


The heart is extensively supplied with nerves of the autonomic nervous system (ANS). These nerves allow the brain to have neural control of vital cardiac activity. The sympathetic and parasympathetic branches of ANS act antagonistically to regulate the mechanical and physiological functions of the heart, atrial and ventricular contractions, heartbeat, heart rhythm, blood flow, and blood pressure.

Nerves descending from the brain stem provide a continuous network of cardiac nerves and ganglia disseminated in the atrial and ventricular epicardial of the heart. This extensive system of nerves in the heart, termed the intrinsic cardiac nervous system (ICNS), controls local cardiac activity and is sometimes called the “little brain”. However, the little brain is not solely responsible for the cardiac activity, as is evident in various cardiovascular diseases.

A brain injury can affect heart function, indicating that the brain plays a significant role in modulation heart physiology. A scientific quest that has been continuing for more than a century has unraveled some of the factors responsible for heart functions. In recent years, crosstalk between the little brain and the brain's central nervous system has become a crucial topic of research as scientists have realized its clinical implications.

The high number of deaths from cardiovascular disease has made it imperative to explore this interactive signaling network to develop appropriate therapeutic interventions. In this review, the role played by this second brain is explicated, leading to a greater understanding not only of its function within the heart but also its connection to the human brain.

Keywords: Autonomic Nervous System; Intrinsic Cardiac Nervous System; Neural Crest Cells; Pulmonary; Sympathetic Nervous System


  1. Carter R. “The Brain Book An Illustrated Guide to Its Structure, Functions, and Disorders”. India: D K Publishing (2019): 1-264.
  2. Mesquita ET., et al. “Andreas Vesalius 500 years--A Renaissance that revolutionized cardiovascular knowledge”. Revista Brasileira de Cirurgia Cardiovascular2 (2015): 260-265.
  3. Aird WC. “Discovery of the cardiovascular system: from Galen to William Harvey”. Journal of Thrombosis and Haemostasis1 (2011): 118-129.
  4. Fye WB. “The origin of the heartbeat: A tale of frogs, jellyfish, and turtles”. Circulation3 (1987): 493-500.
  5. Friedman GW. “Medicine’S 10 Greatest Discoveries”. India: Universities Press (1999).
  6. Bolli R. “William Harvey and the Discovery of the Circulation of the Blood”. Circulation Research9 (2019): 1300-1302.
  7. Manfrini O., et al. “Baseline autonomic characteristics”. In: Malik M, edition. Sex and Cardiac Electrophysiology”. 1st edition. Academic Press (2020): 165-176.
  8. Valenti O., et al. “Fetal cardiac function during the first trimester of pregnancy”. Journal of Prenatal Medicine3 (2011): 59-62.
  9. McFarland J and Anders A. “The morbid Histology of the cardiac nervous Ganglia”. The Journal of Medical Research4 (1913): 425-435.
  10. Armour JA., et al. “Gross and microscopic anatomy of the human intrinsic cardiac nervous system”. The Anatomical Record2 (1997): 289-298.
  11. Fukuda K., et al. “Cardiac innervation and sudden cardiac death”. Circulation Research12 (2015): 2005-2019.
  12. Armour JA and Ardell JL. “Basic and Clinical Neurocardiology”. USA: Oxford University Press (2004): 1-478.
  13. Armour JA. “Potential clinical relevance of the 'little brain' on the mammalian heart”. Experimental Physiology2 (2008): 165-176.
  14. Horst GJ Ter. “Emotions and Heart-Activity Control”. In: The Nervous System and the Heart. NY: Humana Press (2000): 55-116.
  15. Pauza DH., et al. “Morphology, distribution, and variability of the epicardiac neural ganglionated subplexuses in the human heart”. The Anatomical Record4 (2000): 353-382.
  16. Achanta S., et al. “A Comprehensive Integrated Anatomical and Molecular Atlas of Rat Intrinsic Cardiac Nervous System”. iScience6 (2020): 101140.
  17. Hildreth V., et al. “Cells migrating from the neural crest contribute to the innervation of the venous pole of the heart”. Journal of Anatomy1 (2008): 1-11.
  18. Hasan W. “Autonomic cardiac innervation: development and adult plasticity”. Organogenesis3 (2013): 176-193.
  19. Jiang X., et al. “Fate of the mammalian cardiac neural crest”. Development8 (2000): 1607-1616.
  20. Kirby ML and Stewart DE. “Neural crest origin of cardiac ganglion cells in the chick embryo: identification and extirpation”. Developmental Biology2 (1983): 433-443.
  21. Miller Mr and Kasahara M. “Studies On The Nerve Endings In The Heart”. The American Journal of Anatomy 115 (1964): 217-233.
  22. McLean PD. “Psychosomatic disease and the visceral brain; recent developments bearing on the Papez theory of emotion”. Psychosomatic Medicine6 (1949): 338-353.
  23. McCraty R. “Heart-Brain Neurodynamics: The Making of Emotions”. Neuropsychother 6 (2003): 68-89.
  24. Davis AM and Natelson BH. “Brain-heart interactions. The neurocardiology of arrhythmia and sudden cardiac death”. Texas Heart Institute Journal3 (1993): 158-169.
  25. Gary Y and Vigier D. “Inhibitory effects in the cuneate nucleus produced by vago-aortic afferent fibers”. Brain Research2 (1974): 241-259.
  26. Boyett MR. “And the beat goes on.' The cardiac conduction system: the wiring system of the heart”. Experimental Physiology10 (2009): 1035-1049.
  27. Fedele L and Brand T. “The Intrinsic Cardiac Nervous System and Its Role in Cardiac Pacemaking and Conduction”. Journal of Cardiovascular Development and Disease4 (2020): 54.
  28. Franzoso M., et al. “Putting together the clues of the everlasting neuro-cardiac liaison”. Biochimica et Biophysica Acta7 (2016): 1904-1915.
  29. Kuder T and Nowak E. “Autonomic cardiac nerves: literature review”. Folia Morphologica1 (2015): 1-8.
  30. Chen PS., et al. “Role of the autonomic nervous system in atrial fibrillation: pathophysiology and therapy”. Circulation Research9 (2014): 1500-1515.
  31. Qin M., et al. “The cardiac autonomic nervous system: A target for modulation of atrial fibrillation”. Clinical Cardiology 6 (2019): 644-652.
  32. Chen W. “Anatomy and Molecular Basis of Autonomic Innervation of the Heart”. In: Dilsizian V. NJ, edition. Atlas of Cardiac Innervation. Cham: Springer (2017): 1-12.
  33. Beckers F., et al. “Different evolutions in heart rate variability after heart transplantation: 10-year follow-up”. Transplantation 10 (2004): 1523-1531.
  34. “Denervation of the transplanted heart: nursing implications for patient care”. Critical Care Nursing Quarterly 17 (1995): 1-14.
  35. Uberfuhr P., et al. “Incomplete sympathic reinnervation of the orthotopically transplanted human heart: observation up to 13 years after heart transplantation”. European Journal of Cardio-Thoracic Surgery2 (2000): 161-168.
  36. Murphy DA., et al. “The heart reinnervates after transplantation”. The Annals of Thoracic Surgery6 (2000): 1769-1781.
  37. Cardiovascular diseases. World Health Organization. URL (2021).
  38. Hanna P., et al. “Cardiac neuroanatomy - Imaging nerves to define functional control”. Autonomic Neuroscience 207 (2017): 48-58.
  39. Backs J., et al. “The neuronal norepinephrine transporter in experimental heart failure: evidence for a posttranscriptional downregulation”. Journal of Molecular and Cellular Cardiology3 (2001): 461-472.
  40. Zucker IH., et al. “Neurohumoral stimulation”. Heart Failure Clinics1 (2012): 87-99.
  41. Kimura K., et al. “Cardiac sympathetic rejuvenation: a link between nerve function and cardiac hypertrophy”. Circulation Research12 (2007): 1755-1764.
  42. Chiou CW and Zipes DP. “Selective vagal denervation of the atria eliminates heart rate variability and baroreflex sensitivity while preserving ventricular innervation”. Circulation4 (1998): 360-368.
  43. Schnell O., et al. “Reduced myocardial 123I-metaiodobenzylguanidine uptake in newly diagnosed IDDM patients”. Diabetes6 (1996): 801-805.
  44. Rajendran PS., et al. “Myocardial infarction induces structural and functional remodeling of the intrinsic cardiac nervous system”. The Journal of Physiology2 (2016): 321-341.
  45. Kingma JG., et al. “Influence of cardiac nerve status on cardiovascular regulation and cardioprotection”. World Journal of Cardiology6 (2017): 508-520.
  46. Hardwick JC., et al. “Dynamic remodeling of the guinea pig intrinsic cardiac plexus induced by chronic myocardial infarction”. But Neuroscience 181 (2014): 4-12.
  47. Durães Campos I., et al. “A brain within the heart: A review on the intracardiac nervous system”. Journal of Molecular and Cellular Cardiology 119 (2018): 1-9.
  48. Foreman RD., et al. “Integrative control of cardiac function by cervical and thoracic spinal neurons”. In: Armour JA, Ardell JL. editions. Basic and Clinical Neurocardiology. NY: Oxford University Press (2004): 153-186.
  49. Jänig W. “Neurocardiology: a neurobiologist's perspective”. The Journal of Physiology14 (2016): 3955-3962.
  50. Burnstock G. “Evolution of the autonomic innervation of visceral and cardiovascular systems invertebrates”. Pharmacological Reviews4 (1969): 247-324.
Citation: Kerna NA, Anderson II J, Flores JV, Holets HM, Solomon EO, Pruitt KD, Carsrud NDV, Nwokorie U. "The Human Heart as the "Little Brain"—the Intrinsic Cardiac Nervous System (ICNS)”. EC Cardiology 8.9 (2021): 26-34.

PubMed Indexed Article

EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005

EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777

EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347

EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478

EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253

EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033

EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992

EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505

EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793

EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211

EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047

EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560

EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318

EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819

EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840

EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344

EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476

EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658

EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489

EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278

EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108

EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571

EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333

EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883

EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001

EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937

EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723

EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726

EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603

EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646

EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616

EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290

EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226

EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812

EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268

News and Events

November Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the November issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for Upcoming Issue

ECronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before December 13, 2022.

Certificate of Publication

ECronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

ECronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.