504, Leonardo da Vinci made wax castings of the brain and coined the term “cerebellum (link is external)” which is Latin for “little brain.” A groundbreaking study released today reports that Purkinje cells (link is external) in the cerebellum are responsible for controlling the accurate execution of rapid eye movements. Coincidentally, da Vinci also painted the Mona Lisa, which is world-renowned for appearing to have roving eyes that follow viewers around the Louvre.
My father, Richard M. Bergland, was a neurosurgeon, neuroscientist, nationally ranked tennis player, and author of The Fabric of Mind (Viking). My dad was obsessed with Purkinje cells and the cerebellum. He passed this obsession on to me.
In 2007, my father died unexpectedly of a heart attack leaving his quest to find some type of “holy grail” in neuroscience incomplete. I made a vow at his funeral that I would pick up the torch and try to find answers to his hypotheses about Purkinje cells and the cerebellum. Every morning, I wake up hoping there will be new research that helps to decrypt the mysteries of the cerebellum. Needless to say, I was thrilled to read about the new study on eye movements and Purkinje cells released this morning.
The October 2015 study, “Encoding of Action by the Purkinje Cells of the Cerebellum (link is external),” was published in the journal Nature. The researchers found the combined neuronal activity of two seemingly opposite types of Purkinje cell in the brain’s cerebellum appear to control quick eye movements known as saccades.
In a summary of the findings, the editors describe this study saying, “The Purkinje cells are inhibitory neurons in the cerebellum with a central role in coordinating the body’s motor function. It has long been thought that they encode eye motion saccades, but how this is achieved was not known.
Recording from Purkinje cells in monkeys, David Herzfeld et al. find that the combined simple-spike responses of bursting and pausing Purkinje cells, but not either population alone, predicted the real-time speed of the saccade. Moreover, when Purkinje cells were organized according to their complex-spike field, the population responses encoded both speed and direction via a gain field.”
Purkinje cells are named after Johannes Purkinje, who first identified these neurons in 1837. Dr. Purkinje was also the first person to identify the individuality of the human fingerprint. Among many other duties, Purkinje cells are responsible for communicating sensory motor information from the cerebellum to the cerebral cortex.
The Cerebellum Is a Primal Powerhouse
The cerebellum is one of our most ancient brain regions. From an evolutionary perspective, the ability to hone in on a target and focus one’s gaze as hunters was necessary for killing prey. The cerebellum is a primitive and intuitive brain region that we relied on to target moving prey with a bow and arrow, or a spear.
Over millenia, both hemispheres of cerebellum have evolved to work seamlessly with both hemispheres of the cerebrum (link is external) to create peak human performance. From an athletic perspective, the cerebellum makes it possible to simultaneously run while locking your eyes onto a moving target. The cerebellum is the primary brain area associated for hand-eye coordination used when catching a baseball, hitting a tennis ball, shooting a hockey puck, etc.
When you shift the direction of your gaze, your head and eye movements are automatically coordinated with each other via the vestibulo-ocular reflex (link is external) (VOR) which is a part of the vestibular system connected to the cerebellum. The VOR is a reflex eye movement that stabilizes images on the retina during head movements by automatically producing an eye movement in the opposite direction of the head movement.
My father often said, “Of this I am absolutely certain, becoming a neurosurgeon was a direct consequence of my eye for the ball.” When my dad spoke of having an “eye for the ball” he was referring to his VOR system.
The vestibulo-ocular reflex needs to work very quickly to maintain clear vision and focus. Head movements must be compensated for almost immediately—otherwise, your vision would look like a video taken with a shaky hand or in motion. Hypothetically, abnormalities of the VOR would make the world a very disorienting place, as might be the case in people with autism spectrum disorder.
As this most recent study illustrates, the execution of accurate eye movements depends critically on the cerebellum. The combined neuronal activity of two seemingly opposite types of Purkinje cell in the brain’s cerebellum was recently found to control the jerky eye movements known as saccades in monkeys by David Herzfeld et al.
What Is a “Saccade”?
A saccade is a quick, simultaneous movement of both eyes between two phases of fixation in the same direction. As visual information is received from the retina it is translated into spatial information and then transferred to motor centers for appropriate motor responses.
We rely on the accuracy of saccadic eye movements every millisecond of our lives. During normal day-to-day conditions, you make about 3-5 saccades per second which amounts to about a half-million saccades a day.
Someone with saccadic dysmetria produces uncontrollable eye movements including microsaccades, ocular flutter, and square wave jerks even when the eye is at rest. The cause of dysmetria is thought to be lesions in the cerebellum or lesions in the proprioceptive nerves that lead to the cerebellum. Your cerebellum is responsible for the coordination of visual, spatial and other sensory information with motor control.
What Is the Link Between Purkinje Cells, Eye Movements, and Autism?
Recently, there has been a groundswell of research linking Purkinje cells, the cerebellum, and autism spectrum disorders (ASD). The recent findings by Herzfeld et al add to a growing body of evidence that potentially correlates abnormalities of Purkinje cells with autism. Although the recent study by Herzfeld doesn’t refer to autism specifically, the latest findings on the role of Purkinje cells in controlling eye movements supports previous research linking the eye movements, the cerebellum, and autism.
In autism spectrum disorders, the brain consistently shows defects in Purkinje cells, which have a single axon that projects from the cerebellum and creates connectivity from the cerebellum to most other brain regions. Previous research has found cerebellar dysfunction in people with ASD through postmortem studies of brain samples that showed loss of Purkinje cell volume. Over the past few years, a variety of studies have confirmed this phenomenon in the majority of autistic brains.
A 2013 study (link is external), published in the journal Nature, found that eye contact during early infancy may be the earliest indication of ASD. Babies typically begin to focus on human faces within the first few hours of life. Children with autism, however, don’t exhibit interest in making eye contact which makes it difficult to read faces. Learning how to pick up social cues unconsciously by paying attention to another person’s eyes is key to social connectivity.
Another study from August 2013 found that atypical visual orientation in 7-month-olds could be a sign of risk for autism. The study titled “White Matter Microstructure and Atypical Visual Orienting in 7-Month-Olds at Risk for Autism (link is external)” was published in American Journal of Psychiatry. White matter in the corpus callosum connects the left and right hemispheres of your cerebrum.
In 2014, researchers reported that the whites of our eyes communicate important social cues that are key to our bonding and survival both at a conscious and subconscious level. The study, “Unconscious Discrimination of Social Cues from Eye Whites in Infants (link is external),” was published in the online journal Proceedings of the National Academy of Sciences. The researchers from the University of Virginia and Max Planck Institute found that the ability to respond to eye cues typically begins to develop during infancy around the age of seven months.
In another study (link is external) from March 2013, a research team honed in on the gene Tsc2 in Purkinje cells of the cerebellum and found that a loss of Tsc2 in Purkinje cells lead to autistic-like behavioral deficits. The researchers provide compelling evidence that Purkinje cell loss in the cerebellum and/or dysfunction may be an important link between ASD as well as a “general anatomic phenomenon that contributes to the ASD phenotype,” according to researchers.
In August of 2014, Samuel Wang and his colleagues at Princeton University reported that early cerebellum abnormalities hinder neural development and could be a possible root of autism. In August 2014, they published their theory, “The Cerebellum, Sensitive Periods, and Autism (link is external),” in the journal Neuron.
Sam Wang (link is external), Associate Professor of Molecular Biology at Princeton University, is doing fascinating research on information processing in the cerebellum, including its contributions to motor learning, the role of the cerebellum in cognitive and affective function, and autism spectrum disorder.
Conclusion: The Cerebellum May Take Center Stage in the 21st Century
My father often said, “We don’t know exactly what the cerebellum is doing. But whatever its doing, it’s doing a lot of it.” My dad would be thrilled to see the growing new evidence that helps explain everything the powerful and mysterious cerebellum is actually doing.
Purkinje cells and the cerebellum remain enigmatic. That said, neuroscientists are making steady progress using 21st century technology to help us better understand the “little brain” that Leonardo da Vinci first identified over five hundred years ago. We still have a long way to go before completely decrypting these mysteries, therefore, more research is needed.