March 3, 2024

I, Science

The science magazine of Imperial College

Living with and without the cerebellum

A biological battery


Strolling along the Italian city of Como’s picturesque lakefront, you may eventually come across the Tempio Voltiano, an impressive building in neoclassical style, which houses a museum dedicated to one of Como’s favourite sons: Alessandro Volta. Among the museum’s collection of various scientific instruments used in Volta’s laboratory, you will find an early example of the physicist’s most famous invention – the voltaic pile – known in more colloquial terms as the first electrical battery.


To the modern eye, Volta’s device appears not unlike a French press rendered in a steampunk aesthetic – comprised of alternating zinc and copper discs, anchored by a central pole, with the entire column set between a wooden dais and lid, framed by four supporting rods equally spaced around the stack’s outer rim. The voltaic pile was a marvel of its time, and its introduction in 1800 heralded a new era of electrical ingenuity [1].


A few years later, at the University of Sassari on the island of Sardinia, the anatomist Luigi Rolando cogitated on the nature of biological movement. He thought of Volta, and his current-generating apparatus, and he thought of Luigi Galvani, Volta’s academic frenemy who had demonstrated the presence of bioelectrical muscular contraction by inducing a twitching response from dissected frog legs after prodding them with an electrostatic machine.


Rolando’s musings, abuzz with these electric advances, led him to a single conclusion: because movement requires electricity, and the brain is responsible for controlling said movement, the brain must therefore possess within it a device capable of generating electric current. Since voltaic piles were the only point of reference for electrical generators at the time, Rolando surmised that the body’s battery might take a similar stacked columnar form to Volta’s device. Can such a structure be found in the brain? After thinking on his own dissections and perusing numerous texts containing detailed neuroanatomical schematics and descriptions, Rolando eventually settled on one potential brain region: the cerebellum.


The cerebellum derives its name from the Latin for ‘little brain’, a fitting moniker for this posterior brain structure, which is simultaneously connected to but also separate from the cerebrum, its larger neural cousin. Even with a cursory glance at the cerebellum’s shape it is not difficult to follow Rolando’s logic: in mammals, the cerebellum is comprised of a many folds undulating in a regular pattern, resulting in highly ridged organ that could be said to resemble the stacked discs of Volta’s primitive battery.


Rolando surmised that if the cerebellum serves as the main source of the bioelectricity required for animal mobility, then its removal should result in the complete cessation of movement. Rolando proceeded to test his hypothesis by removing the cerebellum of a young goat, after which it could no longer stand up. The goat died shortly thereafter[2].


Rolando concluded that since this highly invasive, lethal procedure resulted in the paralysis of the subject, the cerebellum must therefore be the centre of motor function. While this notion is perhaps an overestimation given the experiment’s flaws, it still provided the first inkling of the cerebellum’s role in the control of movement.


A hole in the head


In the summer of 1981, Catherine and Richard Keleher from Concord, Massachusetts welcomed their son Jonathan into the world. Jonathan was the picture of a healthy baby boy, but after a few years, the Keleher’s noticed their son had yet to start walking and was unable to talk at the expected level for a child his age – Jonathan’s developmental milestones were delayed [3].


Jonathan was subsequently entered into intensive speech and physical therapy, but doctors remained unsure of the cause of his ailments during these early years. The particulars of Jonathan’s condition would remain a mystery until he was 5 years old, when he would be brought to a hospital and placed in the cavernous barrel of a computerised tomography scanner.


Catherine and Richard were hoping the CT scans would yield answers, and their eagerness was apparent when they returned for the test results. At first, the internist assigned to Jonathan’s case appeared reluctant to review the images themself, noting the high probability of missing subtle differences in Jonathan’s neural anatomy due to their lack of specialisation – the scans would likely require further assessment by a radiologist. The doctor needn’t have worried.


Gazing upon that series of monochromatic cross-sections, the internist marvelled at Jonathan’s brain. The cerebral hemispheres appeared normal, perfectly ensconced within the upper half of Jonathan’s cranium. The base of these mirrored lobes, however, gave way to something quite spectacular: instead of the expected whirling mass of folded neural tissue, there was only a large rhombus of darkness – Jonathan’s brain did not have a cerebellum.


Catherine and Richard sat patiently as the doctor elucidated their son’s affliction. Jonathan was born with cerebellar agenesis – a rare condition that meant his cerebellum had not properly formed during the early stages of development. But what did that mean for Jonathan going forward, the Keleher’s wondered. What is a cerebellum actually for? The cerebellum, the doctor explained, is an organ of refinement. It is not itself responsible for the initiation of movement but is essential for coordinating many aspects of mobility including balance and the execution of fine motor skills.


Alcohol has a particularly potent effect on cerebellar function, so if you want to get an idea of what the cerebellum does, think back to the last time you drank a little bit too much. In fact, testing for cerebellar malfunction is vaguely akin to the process of getting pulled over for drunk driving: walk, talk, touch your finger to your nose. A stumbling gait, slurred speech, and clumsy gesticulation are all classic signs of cerebellar impairment.


The cerebellum is also notable for containing more nerve cells within its compact size than all the other brain regions combined. Thus, Jonathan was effectively missing over half the usual number of neurons found in a human brain; this, coupled with the functional implications of an absent cerebellum, caused Jonathan’s physicians to fear that he would likely be unable to lead a normal life.


Fortunately, Jonathan has defied all expectations. Today, he works as an administrator for The Institute for Community Inclusion at the University of Massachusetts Boston. The only immediately apparent signifier of his cerebellar deficiency is the slight slurring when he speaks. Otherwise, he goes about his life in a very typical fashion: walking, talking and charming his way through the days. “I had a bit more obstacles and challenges”, Jonathan admits, “but you rise above it” [4].


A plastic brain


Jonathan’s condition is rare but not unique. In 2014, a 24-year old mother was admitted to a hospital in the Shandong province of China. She complained of a monthlong spell of nausea and vomiting, and when asked about other ailments, she admitted to frequent bouts of dizziness, and an unsteady gait for as long as she could remember. She spoke with a slur, but appeared to have no perturbations to her mental acuity. Like Jonathan, she amazed her doctors when her brain scans revealed a large, distinct shadow where a cerebellum should be. She had somehow managed to go over two decades without uncovering her anatomical deficit [5].


Although these cases may appear inexplicable, they serve as a testament to the brain’s astonishing ability to transfer functions between its different areas in order to optimally adjust to certain situations – an ability known as neuroplasticity.


It is thus likely that in individuals with cerebellar agenesis, a compensatory mechanism reallocates parts of the cerebrum to carry out roles that would normally be executed by the missing organ. One study posits that the supratentorial region (i.e. the cerebral areas directly abutting the cerebellum) may play a major role in this neuroplastic process, though it is difficult to assess the validity of such hypotheses given the rarity of this condition [6].


Only eleven living cases of cerebellar agenesis have been reported thus far, but despite their paucity, these instances have still managed to grant a greater understanding of the human cerebellum’s complex functions. Compelled by this notion, Jonathan Keleher continues to work with researchers, knowing that any new insights he might be able to provide could help countless people with damaged or malfunctioning cerebella.

Tristan Varela is currently studying for a MSc in Science Communication at Imperial College London.

Banner image: Computed Tomography of the Head, Wikipedia

  1. Piccolino, M., The bicentennial of the Voltaic battery (1800-2000): the artificial electric organ. Trends Neurosci, 2000. 23(4): p. 147-51.
  2. Coco, M. and V. Perciavalle, Where did the motor function of the cerebellum come from? Cerebellum & Ataxias, 2015. 2(1): p. 10.
  3. Hamilton, J. A Man’s Incomplete Brain Reveals Cerebellum’s Role In Thought And Emotion. 2015.
  4. Cordovez, J.C., “I’m the only me” – Jonathan Keleher. 2016.
  5. Yu, F., et al., A new case of complete primary cerebellar agenesis: clinical and imaging findings in a living patient. Brain, 2015. 138(Pt 6): p. e353.
  6. Ashraf, O., et al., Primary cerebellar agenesis presenting as isolated cognitive impairment. J Pediatr Neurosci, 2016. 11(2): p. 150-2.