5 New Studies Report Previously Unknown Cerebellum Functions

Neuroscientists made radical new discoveries about the cerebellum in March 2017.

Posted Apr 03, 2017

Life Sciences Database/Wikimedia Commons
Cerebellum (Latin for "little brain") in red. 
Source: Life Sciences Database/Wikimedia Commons

In March 2017, neuroscientists from around the globe published five different studies in various peer-reviewed journals detailing radical new discoveries about the cerebellum. In this Psychology Today blog post, I will provide a brief history of the cerebellum and chronicle the latest research in a succinct timeline.

I've been writing about the mysterious interplay between the cerebral cortex and cerebellum for over a decade. Since 2007, I've had my antennae up for new scientific evidence to help better inform my "Bergland split-brain model" hypothesis that both hemispheres of the cerebellum and both hemispheres of the cerebral cortex play a historically underestimated role in cognition, reward-seeking behavior, and creative capacity. The pioneering research of the past month adds valuable insights into everything our enigmatic and powerful "little brain" is actually doing.  

Courtesy of Larry Vandervert
The number of neurons in the cerebellum versus the number in the cerebral cortex. (Lent et.al.)
Source: Courtesy of Larry Vandervert

In 1504, Leonardo da Vinci coined the term “cerebellum” (Latin for “little brain”) after making wax castings of the human brain and observing two small hemispheres neatly tucked under the much larger "cerebrum" (Latin for “brain”). The cerebellum is only 10 percent of brain volume but houses about 80 percent of your brain’s total neurons, most of which are granule cells. Cerebellar is the sister word to cerebral and means “relating to or located in the cerebellum.”

For centuries, the cerebellum was considered by most experts to be the seat of unconscious "non-thinking" activities that had nothing to do with cognition—such as maintaining balance, fine-tuning motor coordination, and proprioception.

However, in recent months, revolutionary advances in brain imaging technology and computer science have allowed researchers to peer deeply into the densely packed neurons of the cerebellum in ways that were previously impossible. The latest empirical evidence using state-of-the-art methods suggests that the cerebellum plays a complex—and previously underestimated—role in various cognitive processes involving the cerebral cortex as well as other subcortical brain structures including the basal ganglia.

In this blog post, I'll give you a quick recap of each March 2017 study and create a chronological timeline of the latest cerebellar research, which is being published at a dizzying breakneck speed lately. This is not a meta-analysis of the various research but simply an overview that threads together current trends in cerebellar research and puts this research in the spotlight.

The studies are numbered and listed in chronological order based on their date of publication in March 2017:

1. Right Hand Task Training Transfers Motor Knowledge to Right Foot

Neuroscientists at Johns Hopkins University School of Medicine discovered that the cerebellum can transfer skill-based motor learning from one part of the body to another. This illustrates previously unknown plasticity between the motor cortex and the cerebellum. Notably, the motor cortex in the right hemisphere of the cerebrum controls the left side of the body; the right hemisphere of the cerebellum controls the right side of the body (and vice versa.) 

The primary goal of this study was to demonstrate the value of a brain stimulation technique called "cerebellar inhibition" that is used to investigate how neural connections in the brain change as people learn new motor skills. The Johns Hopkins findings were published in the Journal of Neuroscience on March 1. 

During one part of this experiment, the researchers investigated whether cerebellar changes were exclusive to learning a new task. Interestingly, when measuring the connectivity between the motor cortex and the cerebellum, the researchers found that cerebellar-cerebral brain activity did not change when executing a familiar task, but did change when learning a new task.

In a statement, Danny Spampinato, a biomedical engineering graduate student at the Johns Hopkins School of Medicine said, "This shows us there is something special about learning something new that changes how areas of the brain interact that does not happen when we do a movement we already knew how to do.”

2. When Learning a New Task, Cerebellar Granule Cells Display Surprising Levels of Activity

Courtesy of the Princeton Neuroscience Institute
Researchers captured images of individual granule neurons (orange circle-like objects) in the cerebellum using laser two-photon microscopy. Each colored line represents the activity of a different neuron as a mouse learned to predict an imminent event -- a puff of air to the eye. The researchers found that, contrary to existing theories of cerebellar function, many neurons were active at once. The study indicates that the cerebellum carries a rich representation of messages arriving from outside the body as well as from other parts of the brain.
Source: Courtesy of the Princeton Neuroscience Institute

An international team including researchers from the Princeton Neuroscience Institute and Baylor College of Medicine used an advanced brain imaging technology called “laser two-photon microscopy” and computer algorithms to decrypt the signals of granule cells in the cerebellum.

The researchers said this is the first study to look at the neuronal activity of cerebellar granule cells in the brains of living animals while they were learning a task in ways that were previously impossible. These findings were published March 20 in the journal Nature Neuroscience

According to prevailing historical theories about granule cells that date back to the 1960s, it was believed that subdued firing patterns of these neurons convey information to other parts of the cerebellum, which processed the information and sent it on to other parts of the brain for more processing, or to the motor neurons that told the body what to do. But, this appears not to be the case. The researchers were surprised to discover that a lot more granule cells were firing simultaneously to encode sensory information, and these firing patterns encoded both external sensory information and signals from other parts of the brain.

In a statement to Princeton, Sam Wang, professor of molecular biology at the Princeton Neuroscience Institute, and a senior co-author on the study said: 

"People used to think that the cerebellum's input layer of neurons was only sparsely active, and encoded only information collected from the external world. It turns out that they light up like a Christmas tree, and they convey information both from outside the body and from other areas within the brain . . . Your brain is constantly talking to itself. We found that the granule cells are not just producing the prediction but also receiving it. They are in an ongoing conversation, constantly processing information to update moment-by-moment the situation, leading to a dynamic, back-and-forth conversation within the brain."

The study reaffirms that the cerebellum—which was once believed to only control fine-tuned motor skills and physical movements—is increasingly being viewed by thought leaders as playing a complex role in various cognitive processes both in adulthood and when learning something new.

3. Cognitive Process in Cerebellar Granule Cells Encodes the Expectation of Reward

Courtesy of Mark Wagner/Stanford University
Stanford researchers have identified a previously unknown cognitive role of the cerebellar granule cells (in green). 
Source: Courtesy of Mark Wagner/Stanford University

In a serendipitous discovery, neuroscientists at Stanford University recently stumbled on previously unknown cognitive functions of the cerebellum. In a series of complex mice experiments using a state-of-the-art brain imaging technology called "two-photon calcium imaging," the Stanford researchers found that specific granule cells within the cerebellum learn and respond to anticipated rewards, or the lack thereof.

The new study from the Stanford Neuroscience Institute, "Cerebellar Granule Cells Encode the Expectation of Reward," was published March 20 online ahead of print in the journal Nature.

When Mark Wagner began this experiment with his colleagues at Stanford, he was only expecting to find that granule cell activity was related to planning and executing physical movements. But in a Eureka! moment, Wagner et al. observed that only some granule cells fired when a mouse pushed a lever to receive a sugary reward. Surprisingly, other granule cells fired when a mouse was waiting for his or her sugary reward. And, yet another subset of granule cells fired when Wagner sneakily took away the anticipated Pavlovian rewards. The scientists wrote in the Nature abstract of their study:

"Tracking the same granule cells over several days of learning revealed that cells with reward-anticipating responses emerged from those that responded at the start of learning to reward delivery, whereas reward-omission responses grew stronger as learning progressed. The discovery of predictive, non-sensorimotor encoding in granule cells is a major departure from the current understanding of these neurons and markedly enriches the contextual information available to postsynaptic Purkinje cells, with important implications for cognitive processing in the cerebellum."

Moving forward, Wagner and his team at Stanford are optimistic that this discovery could lead to something much bigger in terms of understanding how the cerebellum is involved in cognition. Wagner wants to unify their cerebellar research with other studies that focus on brain regions such as the cerebral cortex. 

4. Delta-Wave Cerebellum Stimulation Influences Frontal Cortex Functioning

Life Sciences Database/Wikimedia Commons
Frontal cortex in red. 
Source: Life Sciences Database/Wikimedia Commons

Non-invasive stimulation of the cerebellum at a delta frequency normalizes brain activity in the frontal cortex of lab rats with schizophrenia-like thinking disorders, according to a first-of-its-kind new study from the University of Iowa Carver College of Medicine. These findings were published online ahead of print March 28 in the journal Molecular Psychiatry.

In this experiment, the researchers used optogenetics to stimulate the rats’ cerebellum at the precise delta-wave frequency of 2 Hertz, which restored normal delta wave activity in the rats’ frontal cortex and normalized the rats’ performance on a timing test. This cerebellar stimulation also improved a lab animal's ability to estimate the passage of time, which is a cognitive deficit often observed in human beings with schizophrenia.

This cutting-edge research was led by Krystal Parker, who says, "My long-term goal is to understand the cerebellar contribution to cognition." In a statement, Parker, who is a University of Iowa assistant professor of psychiatry and the first faculty hire to the brand new Iowa Neuroscience Institute, said:

"Cerebellar interactions with the frontal cortex in cognitive processes has never been shown before in animal models. In addition to showing that the signal travels from the cerebellum to the frontal cortex, the study also showed that normal timing behavior was rescued when the signal was restored . . . We think timing is a window into cognitive function. It allows us to probe executive processes like working memory, attention, planning—all those things are abnormal in schizophrenia."

Dysfunctions or abnormalities within the structure of the cerebellum—or atypical cerebellar functional connectivity with other brain regions—appears to be linked to disorders such as schizophrenia, autism spectrum disorders (ASD), and Tourette syndrome (TS).

The latest findings by Parker and colleagues at the University of Iowa provide fresh insights into how the cerebellum influences neural networks in the frontal lobes and the role of the cerebellum in cognitive processing. 

5. Tourette Syndrome "Tics" Reveal New Clues About Cerebellum Connectivity

Figure realized by Beste Özcan, used with permission.
Key brain areas forming the "basal ganglia-cerebellar-thalamo-cortical system" underlying Tourette tic production.
Source: Figure realized by Beste Özcan, used with permission.

An international team of researchers used advanced computer-based brain simulation to identify that Tourette syndrome motor tics may arise from the interplay between various cortical and subcortical areas of the brain; rather than a single area of dysfunction as previously believed. These findings were published March 30 in the journal PLOS Computational Biology.

Historically, the involuntary motor tics associated with Tourette syndrome (clapping, eye blinking, sniffing, uncontrollable vocalization, etc.) were believed to result from abnormalities solely in the basal ganglia. However, various recent studies on humans, monkeys, and rats suggest that the cerebellum, cerebral cortex, and thalamus are also involved in generating these tics.


Based on this recent evidence, Daniele Caligiore of the National Research Council in Italy, and colleagues at the University of Southern California in Los Angeles created a computer simulation of brain activity which identified that dysfunctions of the four-tiered “basal ganglia-cerebellar-thalamo-cortical system” produce motor tics in Tourette syndrome

The new model suggests that abnormal dopamine activity in the basal ganglia may work in conjunction with activity of the thalamo-cortical system to trigger an initial tic. Additionally, it appears that bidirectional interplay between the basal ganglia and cerebellum allows the cerebellum to influence tic production as well. In a statement, Caligiore said, "This model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links.”

The researchers also found that their new computer model can be used to predict the number of tics generated when there are dysfunctions in the neural circuitry connecting the basal ganglia, thalamus, cortex, and cerebellum.

The "Little Brain" Is No Longer Being Completely Overshadowed by "Goliath"

The cerebellum has been overshadowed by the goliath size of the cerebrum for too long. After decades of slow progress, 21st-century breakthroughs in computer and neuroimaging technology are finally allowing scientists to better understand our mysterious and powerful "little brain." Growing empirical evidence on the dynamics of "cerebellum-cerebrum" interplay is advancing quickly and gaining momentum. These are exciting times for groundbreaking cerebellar research! 

Stay tuned for updates about future research on the cerebellum. In the meantime, if you'd like to read my previous Psychology Today blog posts on this topic, please click here

References

Danny A. Spampinato, Hannah J. Block, Pablo A. Celnik. Cerebellar–M1 Connectivity Changes Associated with Motor Learning Are Somatotopic Specific. The Journal of Neuroscience, 2017; 37 (9): 2377 DOI: 10.1523/JNEUROSCI.2511-16.2017

Andrea Giovannucci, Aleksandra Badura, Ben Deverett, Farzaneh Najafi, Talmo D Pereira, Zhenyu Gao, Ilker Ozden, Alexander D Kloth, Eftychios Pnevmatikakis, Liam Paninski, Chris I De Zeeuw, Javier F Medina, Samuel S-H Wang. Cerebellar granule cells acquire a widespread predictive feedback signal during motor learning. Nature Neuroscience, 2017; DOI: 10.1038/nn.4531

Mark J. Wagner, Tony Hyun Kim, Joan Savall, Mark J. Schnitzer & Liqun Luo Cerebellar granule cells encode the expectation of reward. Nature (2017) DOI: 10.1038/nature21726

K L Parker, Y C Kim, R M Kelley, A J Nessler, K-H Chen, V A Muller-Ewald, N C Andreasen, N S Narayanan. Delta-frequency stimulation of cerebellar projections can compensate for schizophrenia-related medial frontal dysfunction. Molecular Psychiatry, 2017; DOI: 10.1038/mp.2017.50

Caligiore D, Mannella F, Arbib MA, Baldassarre G (2017) Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome. PLoS Comput Biol 13(3): e1005395. doi: 10.1371/journal.pcbi.1005395

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