Evolving Viewpoints on the Cerebellum

Historical aspects of cerebellar nonmotor functions have changed over time.

By Peter J. Koehler

Figure 1. Cell doctrine depicted in Gregor Reisch’s Margarita Philosophica Woodcut of head showing cerebral ventricles (1508 edition; public domain).

With respect to the history of functions successively attributed to it, the cerebellum is perhaps one of the most remarkable parts of the central nervous system. Five years ago, I wrote about vital functions attributed to the cerebellum (“Early Ideas on the Localization of Vital Functions: From Cerebellum to Medulla Oblongata,” World Neurology, Winter 2019). This was particularly true in the 17th and 18th centuries when it was initially thought that the cerebellum was a vital organ. More careful experiments gradually revealed that this was not the case. The ideas regarding nonmotor functions of the cerebellum, however, are more numerous than that.

Memory

In classical antiquity, the pneuma psychikon, a supposed volatile substance that was transmitted from the cerebral ventricles to the nerves, was considered the instrument of the soul. In the early medieval period, the cerebral ventricles (called “cells” rather than the cerebral substance) were considered important. Nemesius of Emesa (c. 390) connected Greek physiology with Christian concepts and localized the psychic pneuma in these hollow spaces in the head. (See Figure 1.) The localization was as follows:

• First cell: Imagination (the present lateral ventricles)
• Second cell: Thought (now third ventricle)
• Third cell: Memory (the present fourth ventricle, below the cerebellum)

In this way, “the balanced conception of human nature inherited from the Greeks was gradually eroded as Christianization of the ancient world advanced, with most of the attention being now focused only on the soul.” The material seat of the divine spirit and sensorium commune (the place where the information from all the senses converges) were localized as follows:

• First cell: Phantasia, sensus communis, and imaginativa
• Second cell: Mogitati[v]a and estimatia
• Third cell: Memorativa

Figure 2. The anatomy lesson of Dr. Nicolaes Tulp, Rembrandt van Rijn, 1632, oil on canvas, 169.5 x 216.5 cm (public domain © Mauritshuis, The Hague).

Memory was still localized at the back of the head by Nicolaes Tulp (1593-1674; see Figure 2), who described two cases of memory loss in his Observationes Medicae of 1641. In the first case, a person fell on one of Amsterdam’s slippery bridges, hitting the back of their head and suffering severe memory loss with only partial recovery. In the second case, a person was found with a wound to the back of the head and did not know what had happened.

A Musical Ear

The Italian physician and anatomist Costanzo Variolo (1543-1575) associated the cerebellum with movement, but also with hearing, taste, and touch, as he believed some cranial nerves had their origin there. As written in the World Neurology article mentioned above, the cerebellum was attributed a vital function due to observations of severe occipital injuries. Moreover, several 17th century experimenters reported the fatal effect of the removal of the cerebellum.

Thomas Willis (1721-1775) believed the vagus nerve had its origin in the cerebellum and therefore played a role in breathing, heartbeat, bowel movement, etc. However, he also associated the cerebellum with the musical faculty.

“Audible sounds pass through the cerebellum, they leave behind some traces of their passage in certain men who live in this country … they are endowed with a musical ear.”

During the subsequent century, several experimenters observed that animals did not always die upon removal of the cerebellum, if more precise and careful experiments were conducted.

Figure 3. Vicenzo Malacarne (public domain © Wellcome Collection, London).

Intelligence

The Italian surgeon and anatomist Vincenzo Malacarne (1744-1816; see Figure 3), who introduced terms for several cerebellar parts including tonsil, pyramid, lingual, and uvula, noticed a relationship between intelligence and the number of cerebellar lamellae. He numbered the lamellae to be able to provide a systematic description of the organ. He noted that the size and number of lamellae were reduced in patients suffering from cretinism, a condition of severe physical and mental retardation due to iodine deficiency. In normal persons, he counted between 500 and 780 folia, while in “idiots,” it could be as low as 340. He believed scientists could predict the development of folia before the dissection of a deceased person, based on the manifestation of intelligence during life.

Figure 4. Franz Joseph Gall. Lithograph by A. F. Kunike (public domain © Wellcome Collection, London).

Reproductive Instinct

Franz Joseph Gall (1758-1828; see Figure 4) is well known for having introduced the concept of cortical cerebral localization. He believed that bumps or indentations in the skull reflected growth or underdevelopment of brain regions associated with specific functions. Of the 27 faculties he distinguished, eight were considered distinctly human faculties. He localized the highest faculties — for instance, wit (XXII) and religion (XXVI) — in the top of the front of the brain. In contrast, he located successively more primitive functions to brain organs more posteriorly. The most primitive faculty, that of reproductive instinct (I), was localized in the cerebellar cortex. (See Figure 5a.)

Figure 5a. Plate V from Gall & Spurzheim’s Atlas.⁷ Anatomical drawing with the cerebellum below.

In his writings, Gall provided evidence of this localization with several examples (both positive and negative) in animals and humans. (See Figure 5b.) Some cases were drawn from sick or damaged brains, while others came from studying healthy brains. He examined people and animals with naturally occurring disorders, acute injuries, or surgical procedures including castration. Depending on the age at which this happened, he believed there was an association with the cerebellum: “The lobe of the cerebellum, on the opposite side, visibly decays, or is altered in some way in its substance.”^,,

Figure 5b. Plate XL. From Gall & Spurzheim’s Atlas.⁷ “Son crâne prouve que son cervelet avait acquis un développement très considérable [His skull proves that his cerebellum had undergone considerable development].”

Gall was not the only researcher to refer to this association. In a chapter on the cerebellum in his book Leçons sur la Physiologie Générale Et Comparée du Système Nerveux Faites au Muséum d’Histoire Naturelle, the French physician Alfred Vulpian (1826-1887) reviewed the influence of the cerebellum on the intestines, stomach, heart, and the genito-urinary organs. With respect to the latter influence, he referred to this famous example of a girl:

“Cette jeune fille a vécu jusqu’à l’âge de onze ans, bien que son cervelet fût entièrement atrophié des les premiers temps de sa vie; et par conséquent l’influence du cervelet sur ces divers organes ne peut pas être considérée comme indispensable [This young girl lived to the age of 11, although her cerebellum was completely atrophied from the beginning of her life; and consequently the influence of the cerebellum on these various organs cannot be considered indispensable].”

He returned to the case at several places in the book. The girl had no sensory loss. However, “la petite fille sans cervelet (observation de Combettes) se livrait à l’onanisme. [The little girl without cerebellum (observed by Combettes) indulged in onanism].” With respect to another case “la femme dont le cervelet avait subi une atrophie complète de toute son écorce grise, et dont j’ai déjà dit un mot, avait été, d’après certains détails de ses antécédents, atteinte d’un léger degré d’érotomanie [the woman whose cerebellum had undergone a complete atrophy of all its grey cortex, and of whom I have already said a word, had been, according to certain details of her antecedents, affected by a slight degree of erotomania].”⁶

Vulpian’s remarks on these cases in fact did not support Gall’s hypothesis. More importantly, he added another sign that was observed in the young girl. “L’observation, incomplète du reste, signale un embarras assez grand de la parole, et constate que l’enfant se laissait tomber souvent [The observation, incomplete in any case, points to a fairly great embarrassment of speech, and notes that the child often fell].”⁶

The Scottish/English physician David Ferrier (1843-1928) was another researcher of the period who referred to the Combettes case: “… there still remain numerous well-authenticated and carefully recorded instances, which, though not opposed to Flourens’ data, are not capable of being harmonized with his theory — stated without modification — that the cerebellum is the organ of the coordination of movements of locomotion. Many such cases might be quoted, but I select only one or two.”

A closer look at the source, the 1831 report by Combettes (intern at St. Antoine Hospital) reveals that the girl had more abnormalities than just atrophy of the cerebellum. The full title of the article was “Absence Complète du Cervelet, des Pédoncules Postérieurs Et de la Protubérance Cérébrale Chez Une Jeune Fille Morte [Complete Absence of Cerebellum, Posterior Peduncles, and Cerebral Protuberance in a Dead Girl].”

When she was hospitalized at age 9, “elle avait extrêmement peu d’intelligence [she had extremely little intelligence],” and before she died, she was suffering from “convulsions épileptiformes.” Part of the brain dissection, after her death at age 11, was done by the Paris physiologist François Magendie (1783-1855).

In his 1997 book “The Cerebellum and Cognition,” Jeremy Schmahmann, neurologist at Massachusetts General Hospital and professor of neurology at Harvard Medical School, added a table of “selected clinical reports” with descriptions of cerebellar disorders related primarily to mental retardation.

He noted that “perhaps it should not be surprising that the cerebellum may contribute to sensory, affective, autonomic, and cognitive functions as well as to motor control.” He referred to English physician John Hughlings Jackson (1835-1911), who wrote on the continuum from movement to thought. Schmahmann also referred to Ferrier, who wrote that “mental operations, in the last analysis, must be merely the subjective side of sensory and motor substrata.”¹¹

Robert S. Dow (University of Oregon. Medical School, public domain; Robert S. Dow, MD, PhD).

Henrietta C. Leiner: The Mathematical Analyst

In 1958, neurologist and neuroscientist Robert S. Dow (1908-1995) published a review on the past 100 years of cerebellar physiology and pathology in cooperation with Giuseppe Moruzzi ([1910-1986], co-discoverer of the reticular arousal system with Horace Magoun [1907-1991]). Meanwhile Henrietta C. Leiner (1914-2012) worked as a mathematical analyst in Washington, D.C., where she contributed to the capabilities of the pioneering computers used by the National Bureau of Standards (now known as the National Institute of Standards and Technology). In 1960, her husband, Alan L. Leiner (1914-2010), accepted an offer of employment from the IBM Research Center in New York City.

Interested in neural anatomy, Leiner took courses in neuroanatomy and then dissected brains at Columbia University in New York. From the intensive cerebro-cerebellar connections, she wondered why the cerebral cortex would send so much high-level information down to the “low-level” cerebellum. She hypothesized that the connection “enables the cerebellum to improve the speed and skill of cognitive and language performance in much the same way that the older circuitry enables the cerebellum to improve the speed and skill of motor performance.”

Henrietta C. and Alan L. Leiner (from interview at Oral History Museum available at Oral History of Alan and Henrietta Leiner).

She then moved with her husband to Palo Alto, California, where she continued her studies at Stanford University and read the work of Robert S. Dow, to whom she presented her hypothesis. They met in Portland, Oregon, and Dow decided to undertake the clinical testing of patients to find out whether damage restricted to the cerebellum ever resulted in a cognitive deficit.

A series of articles on the subject, written by Henrietta, her husband Alan, who was a computer expert, and Dow followed in the 1986 to 1995 period. They postulated that in the human brain newly acquired cerebro-cerebellar loops could contribute to skilled mental performance in much the same way that the older loops contribute to skilled motor performance. The Leiners also contributed a chapter to Schmahmann’s book: “How Fibers Subserve Computing Capabilities: Similarities Between Brains and Machines.”¹¹

Interest in the role of the cerebellum in emotion and cognition increased after Schmahmann’s 1997 book and subsequent publications. Looking back on her career two years before she died at age 98, Henrietta Leiner noted that “the concept of the cerebellum as a motor mechanism has not helped to solve the mystery of why the human cerebellum enlarged so dramatically in the last million years of human evolution.” The syndrome is now known as cerebellar cognitive affective syndrome (CCAS) or Schmahmann syndrome. •