The "Little Brain" Inside the Heart

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A Moment in History

Marcia Crocker Noyes
(1869 – 1946)

Further to my comment on old books and research that started with an interesting bookplate (Ex-Libris). I continued my research and found that the person in charge of the Osler library bookplate was a fascinating individual that today maybe a ghost in the MedChi library and building in Baltimore... This is certainly an article that can be called "A Moment in History"

Marcia Crocker Noyes was the librarian at The Maryland State Medical Society from 1896 to 1946 and was a founding member of the Medical Library Association.[1][2][3]

Sir William Osler, MD. a famous Johns Hopkins surgeon was a noted bibliophile and had a large personal collection of books on various topics. When he became the President of MedChi in 1896, he was dismayed at the condition of the library and knew that with the right person and some stewardship, it could become a significant collection. Sir William asked his friend, Dr. Bernard Steiner, a physician and President of the Enoch Pratt Free Library in Baltimore for suggestions of a librarian, and Dr. Steiner recommended Marcia Crocker Noyes. A native of New York, and a graduate of Hunter College, Marcia had moved to Baltimore for a lengthy visit with her sister, and took a “temporary” position at the Pratt Library, which turned into three years. Although she had no medical experience or background, she was enthusiastic, and most importantly, she was willing to move into the apartment provided for the librarian, who needed to be available 24 hours a day.

The image in this article is Ms. Noyes on her first year on the job. Marcia developed a book classification system for medical books, based on the Index Medicus, and called it the Classification for Medical Literature. The system uses the alphabet with capital letters for the major divisions of medicine and lower-case ones for the sub-sections. The system was used for many years, but it's now dated and the Faculty's original shelving scheme was never changed. The card catalogs still reflect her classification and many of the cards are written in Marcia's back-slanting handwriting.

Marcia knew enough to ask the Faculty's members about medical questions, terminology and literature. She gradually won over the predominantly male membership and they became her greatest allies; Sir William at the start, and then for nearly 40 years, Dr. John Ruhräh, a wealthy pediatrician with no immediate family of his own. She made a point of attending almost every Faculty function, and in 1904, under guidelines from the American Medical Association, Marcia was made the Faculty Secretary. For much of her first 10 years, she was the Faculty's only full-time employee, only being assisted by Mr. Caution, the Faculty's janitor. Later in life Marcia would say that she hired him because of his name!

Within ten years, the library had outgrown its space, and plans, spearheaded by Marcia and Sir William before his move to Oxford, were made to build a headquarters building, mainly to house the library's growing collection of medical books and journals.

Marcia was instrumental in the design and building of the new headquarters. She travelled to Philadelphia, New York and Boston to look at their medical society buildings, and eventually, the Philadelphia architectural firm, Ellicott & Emmart was selected to design and build the new Faculty building. Every detail of the building held her imprimatur, from the graceful staircase, to the light-filled reading room, and all of the myriad details of the millwork, marble tesserae, and most of all, the four-story cast iron stacks. She was on-site, climbing up unfinished staircases, checking out the progress of the building, which was built in less than one year at a cost of $90,000.

Among the features of the new building was a fourth-floor apartment for her. She referred to it as the "first penthouse in Baltimore" and it had a garden and rooftop terrace. The library collection eventually grew to more than 65,000 volumes from medical and specialty societies around the world. Journals were traded back and forth, and physicians eagerly anticipated the arrival of each new issue. At the same time, Marcia was involved in the Medical Library Association as one of eight founding members. The MLA promotes medical libraries and the exchange of information. One of the earliest mandates of the MLA was the Exchange, a distribution and trade service for those who had duplicates or little-used books in their collections. Initially, the Exchange was run out of the Philadelphia medical society, but in 1900 it was moved to Baltimore and Marcia oversaw it. Several hundred periodicals and journals were received and sent each month, a huge amount of work for a tiny staff. In 1904, the Faculty had run out of room to manage the Exchange, so it was moved to the Medical Society of the Kings County (Brooklyn). But without Marcia's excellent administrative skills, it floundered and in 1908, the MLA asked Marcia to take charge once again.

In 1909, when the new Faculty building opened, there was enough room to run the Exchange and with the help of MLA Treasurer, noted bibliophile and close friend, Dr. John Ruhräh, it once again became successful. Additionally, Marcia and Dr. Ruhräh combined forces to revive the MLA's bulletin, which had all but ceased publication in 1908, taking the Exchange with it. This duo maintained editorial control from 1911 until 1926. In 1934, around the time of Dr. Ruhräh's death, Marcia became the first “unmedicated” professional to head the MLA. During her tenure, the MLA incorporated, the first seal was adopted, and the annual meeting was held in Baltimore. Marcia wanted to write the history of the MLA once she retired from full-time work at the Faculty, but her health was beginning to fail. She had back problems and had suffered a serious burn on her shoulder as a young woman, possibly from her time running a summer camp, Camp Seyon, for young ladies in the Adirondack Mountains. In 1946, a celebration was planned to honor Marcia's 50 years at the Faculty. But she was adamant that the physicians wait until November, the actual date of her 50 years. However, they knew she was gravely ill, and might not make it until then, so a huge party was held in April. More than 250 physicians attended the celebration, but the ones she was closest to in the early years, were long gone. She was presented with a suitcase, a sum of money to use for travelling, and her favorite painting of Dr. John Philip Smith, a founder of the Medical College in Winchester, Virginia. It was painted by Edward Caledon Smith, a Virginia painter who had been a student of the painter Thomas Sully.[4] She adored this painting and vowed, jokingly, to take it with her wherever she went.

The painting was not to stay with her for very long, for she died in November 1946, and left it to the Faculty in her will. Her funeral was held in the Faculty's Osler Hall, named for her dear friend. More than 60 physicians served as her pallbearers, and she was buried at Baltimore's Green Mount Cemetery. In 1948, the MLA decided to establish an award in the name of Marcia Crocker Noyes. It was for outstanding achievement in medical library field and was to be awarded every two years, or when a truly worthy candidate was submitted. In 2014, the Faculty began giving a bouquet of flowers to the winner of the award in Marcia's name, and in honor of her work. Much evidence exists for this tradition, as we know that the physicians, especially Drs. Osler and Ruhräh, frequently gave her bouquets of flowers. Marcia also cultivated flower gardens at the Faculty and decorated the rooms with her work.

Today, the MedChi building is open for tours and if the rumors are to be believed Ms. Marcia Crocker Noyes is still at work in her beloved library as the "resident ghost" [1][5]

NOTE: This article has been modified from the original Wikipedia article on Marcia Crocker Noyes. The article itself is well-written with interesting images of the subject. I would encourage you to visit it. The second insert is from book 00736 in my personal library and shows in pencil, the incredibly small handwriting of Marsha C. Noyes.

Sources:
1. "Marcia, Marcia, Marcia" MedChi Archives blog.
2. "Marcia C. Noyes, Medical Librarian" (PDF). Bulletin of the Medical Library Association. 35 (1): 108–109. 1947. PMC 194645
3. Smith, Bernie Todd (1974). "Marcia Crocker Noyes, Medical Librarian: The Shaping of a Career" (PDF). Bulletin of the Medical Library Association. 62 (3): 314–324. PMC 198800Freely accessible. PMID 4619344.
4. Edward Caledon BRUCE (1825-1901)"
5. Behind the scenes tour MedChiBuilding

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Anterior view of the heart

Personal Note: A few weeks ago, I came across a very interesting article in Spanish by Dr. Jose Manuel Revuelta from the University of Cantabria, Spain. The article (in Spanish) talked about the “small brain inside the heart”. One of my interests in the anatomy of the heart is the intrinsic system called the cardiac “ganglionated plexuses”, “ganglionated plexi”, or “GPs”.

It is our proposal that this nervous system inside the heart, which works autonomously (if needed to or forced to) and also dependent, of the autonomic nervous system, is responsible for the intrinsic working of the heart and its dysfunction is probably the root of cardiac dysrhythmias. We have several seminars on this topic here.

In a recent publication with Dr. Randall K. Wolf, we explained both the Wolf Procedure and the anatomical basis that underline atrial fibrillation.

The concept of the "small brain of the heart" is not new. It has been mentioned by Woolard (1926), Armour (1997), Pauza (2000), and others. These authors and others are referenced in this publication. Unfortunately, the diffusion of the concept of an intrinsic, interconnected mesh of clusters of neurons within the heart and other organs that have rhythmic activity, has many names used by the media. That is why you can find articles on the "little brain of the gut", the "gut brain", the "enteric nervous system", the "little brain of the heart", etc.

Dr. Revuelta's article shows that the interest on the GPs continues on, and more research is being done on this topic. He has graciously granted us permission to translate and publish his article in “Medical Terminology Daily”. He has also expressed interest in publishing some of his articles in this blog. Dr. Miranda

The “Little Brain” Inside the Heart

Dr. José Manuel Revuelta Soba
Professor of Surgery. Professor Emeritus, University of Cantabria, Spain

Dr. José Manuel Revuelta

In December 2024, the prestigious journal Nature Communications published that a group of researchers from the Karolinska Institute (Sweden) and Columbia University (United States) have discovered that the heart contains a small autonomous brain.

In general, scientific knowledge has been relating cardiac activity to the brain, as the only organ that regulates its functioning. This intimate bidirectional relationship regulates the adaptation of its rhythm and contractile force to changing energy demands, through impulses and signals transmitted by the autonomic nervous system. However, the heart surprises us again with new properties that go beyond what is known.

Autonomic nervous system

The neurovegetative nervous system of the human being is involuntary, comprising the sympathetic and parasympathetic nervous systems, essential for the functioning of the organism. They act in conjunction with the enteric nervous system, which also has involuntary action and regulates the activity of the gastrointestinal tract. The complex interactions between these autonomous systems, which have opposing actions, maintain cardiovascular homeostasis, that is, they provide the appropriate amount of oxygenated blood to the organs and tissues according to their demands.

The sympathetic nervous system regulates, among other functions, the body's response to any danger perceived as a threat to physical or mental health, known as the "fight or flight" reaction, described in 1915 by the physiologist Walter B. Cannon in the United States. This instinctive reaction leads to the immediate release of certain chemical substances into the blood, such as adrenaline and noradrenaline. These hormones act as neurotransmitters that produce an increase in the contractile force of the heart, tachycardia, contraction of blood vessels, hypertension and dilation of the airways. These neurotransmitters are released in the brain, facilitating the diffusion of their messages through the extensive network that forms this autonomous nervous system, increasing the state of alertness and eliminating any feeling of drowsiness. By producing an immediate tachycardia, it improves the supply of oxygen to the organs and tissues, enlarges the pupils and reduces the digestion of food to save energy and make it available for this reaction to an unexpected danger.

The parasympathetic nervous system controls the relaxation of the body at the end of the stress caused by the sudden “fight or flight” reaction, once the threat has passed, restoring the normal functioning of the organism. Its main function is the conservation and storage of energy through the release of acetylcholine, a powerful neurotransmitter, discovered by the English physiologist Henry H. Dale, for which he was awarded the Nobel Prize in Medicine in 1936. This substance produces vasodilation, reduction of blood pressure, decreased heart rate and increased intestinal motility.

The enteric nervous system has the exclusive mission of regulating the functioning of the gastrointestinal tract, which is completely covered by hundreds of millions of nerve fibers that transmit brain messages for digestive mobility and function, modifying the volume of blood flow via vasoconstriction or vasodilation.

The small brain of the heart

The innervation of the heart is more complex than previously thought, conditioned by messages from the autonomic nervous system and others from the organ itself. In the early 1990s, scientists described that the heart contained some neurons similar to those in the human brain, which led to speculation about the possible existence of independent neuronal activity within the heart that mediated its functioning and rhythm. This fascinating discovery soon became a priority objective of scientific research.

In 2021, James S. Schwaber and R. Vadigepalli, researchers at Thomas Jefferson University in Philadelphia, performed a three-dimensional mapping of the heart's neural center. They found that the heart receives constant information from the brain about the internal and external state of its environment, adjusting heart rate, blood pressure, and cardiac output. However, these messages also came from the heart's own neural system, called the "little brain," behaving as if there were an internal loop, something similar to what systems engineers call a programmable logic controller or PLC. Most of these neurons are located near the aortic and pulmonary valves, with their largest neuronal cluster (74 percent) located in the area of the sinoatrial plexus, on the upper lateral wall of the right atrium, in immediate relation to the mouth of the superior vena cava.

Using mathematical models, they observed that when this peculiar neural programmable logic controller was activated, it perfectly adjusted the heart's response to the various impulses and signals from the brain to improve cardiac performance, making its work more efficient. Without the presence of this "little brain" it would be impossible to eliminate or correct the possible errors and damage contained in some brain messages, so the heart could become erratic, causing irregular heartbeats or arrhythmias, as well as defects in its contractility.

As these scientists analyze their 3D heart models, obtained from various mammals, new questions arise about the actions of this "brain of the heart", its internal organization, its influence on the contractile force and rhythm of the heart, as well as its coordination and responses to the constant messages from the brain. Currently, these three-dimensional maps are being used to better understand how the vagus nerve connects with cardiac neurons, opening new opportunities for the greater integration of systems engineering into the field of cardiology.

Recent findings from the Karolinska Institutet and Columbia University have revealed that the heart does indeed have its own “mini-brain,” containing a nervous system that self-regulates its rhythm and function according to demand. This complex neurological center is made up of various types of neurons with different functions, some of which function as cardiac pacemakers.

This important research project was carried out in the zebrafish, an animal model that has great similarities with the human heart, both in terms of its heart rate and its general functioning. These scientists mapped the composition, organization and functions of neurons within this small intracardiac brain, using a combination of anatomical methods, electrophysiological techniques and neuronal RNA sequencing. They carried out a complete molecular and functional classification of intracardiac neurons, revealing a complex neuronal diversity within the heart itself.

This intracardiac neurological center is not part of the autonomic nervous system governed by the brain, contrary to what was believed. The data obtained in this interesting scientific investigation show that this “small brain” is made up of several types of independent sensory neurons with clear neurochemical and functional diversity. This population of neuronal cells allows the expression of various genes that encode various neurotransmitter receptors (glycine, glutamate, adrenergic, inotropic, GABA, muscarinic, serotonergic receptors, etc.), suggesting a complex network of neurotransmission specific to the heart, which ignores its total dependence on central orders from the brain.

“We were surprised to see the complexity of this small brain inside the heart, which has a key role in maintaining and controlling the heartbeat, similar to how the brain regulates other rhythmic functions such as locomotion and breathing. Better understanding this nervous system could lead to new insights into heart disease and help develop new treatments, such as for arrhythmias. We will continue to investigate how the heart’s brain interacts with the real brain to regulate cardiac functions under different conditions, such as exercise, stress or disease”, explains Konstantinos Ampatzis, a senior researcher at the Department of Neuroscience at Karolinska Institutet, Sweden, who led the study.

Future electrophysiological, pharmacological and molecular research will be critical to better understand the tangled interactions and complex regulatory mechanisms of the internal neurotransmission of this autonomous “small brain” and thus understand its overall regulation of cardiac rhythm, contraction and output in the face of the multiple physical and mental changes to which we are exposed throughout life.

“There is a wisdom of the head and a wisdom of the heart"
Charles Dickens (1812-1870), English writer

“Facts do not cease to exist because they are ignored”
Aldous Huxley (1894-1963), English writer and philosopher.

Sources:
1. “Decoding the molecular, cellular, and functional heterogeneity of zebrafish intracardiac nervous system”. Pedroni, A; Yilmaz, E; Del Vecchio,L; et al. Nature Communications, 2024; 15 (1) DOI: 10.1038/s41467-024-54830-w
2. Bodily changes in pain, hunger, fear, and rage; an account of recent researches into the function of emotional excitement” Cannon, W. 1915. D. Appleton and Co. USA.
3. “Mapping the little brain at the heart by an interdisciplinary systems biology team” Vadigepalli, Rajanikanth et al. iScience, Volume 24, Issue 5, 102433. https://doi.org/10.1016/j.isci.2021.102433
4. A comprehensive integrated anatomical and molecular atlas of rat intrinsic cardiac nervous system. Achanta S. et al. iScience 2020 Jun 26;23(6):101140 doi: 10.1016/j.isci.2020.101140
5. "Minimally Invasive Surgical Treatment of Atrial Fibrillation: A New Look at an Old Problem" Randall K. Wolf, Efrain A. Miranda, Operative Techniques in Thoracic and Cardiovascular Surgery, 2024, doi.org/10.1053/j.optechstcvs.2024.10.003
6 Valenza, G., Matić, Z. & Catrambone, V. The brain–heart axis: integrative cooperation of neural, mechanical and biochemical pathways. Nat Rev Cardiol 22, 537–550 (2025).