Life Sciences Database/Wikimedia Commons
Cerebellum (Latin for "little brain") 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 also 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. (Cerebellar is the sister word to cerebral and means "relating to or located in the cerebellum.")

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

In patients with schizophrenia, dopamine signaling in the frontal cortex tends to be abnormal. By blocking dopamine signaling in the frontal cortex of lab rats, the researchers at UI were able to reproduce schizophrenia-like cognitive and timing problems in animal models.

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."

Parker's lab is working with the lab of Nandakumar Narayanan at the University of Iowa. Together, they are unearthing previously unknown and enigmatic influences that the cerebellum has on cognition. Contrary to the long-held belief that the cerebellum wasn't involved in cognitive processes, it now appears that the cerebellum plays a complex role in executive function, creativity, attention, planning, emotional regulation, reward-seeking behavior, etc.

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, and Tourette's syndrome

The latest findings by Parker and colleagues provide fresh insights into how the cerebellum influences neural networks in the frontal lobes and the role of the cerebellum in cognitive processing. This study also suggests that delta-frequency cerebellar stimulation might help improve cognitive problems in human patients with schizophrenia.

Although this study focused on schizophrenia, the researchers point out that similar cognitive problems linked to cerebellar abnormalities are observed in autism spectrum disorders (ASD), Parkinson's disease, addiction, OCD, bipolar disorder, and depression. The researchers are optimistic that if cerebellar stimulation proves helpful for schizophrenia, it might also be beneficial for patients with any of these other conditions.

(For the record: Non-invasive deep brain stimulation is currently approved as a treatment for depression by the FDA. However, cerebellar stimulation is still in experimental phases and is not FDA approved as any type of cognitive therapy.)

Decoding the Cerebellum: A Neuroscience Holy Grail for the 21st Century

In 1504, Leonardo da Vinci made wax castings of the human brain and coined the term "cerebellum" (Latin for “little brain”) after identifying two small brain hemispheres tucked neatly under the relatively colossal left-right hemispheres of the "cerebrum" (Latin for "brain").

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

Notably, 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.

For centuries, most neuroscientists believed that the cerebellum was only responsible for “non-thinking” unconscious motor skills—such as coordinating fine-tuned muscle movements, balance, and proprioception. On the flip side, the "left brain-right brain" hemispheres of the cerebrum (which house the “thinking cap” of the cerebral cortex) were considered to be the sole domain of cognitive function and creativity. 

This outdated view of "cerebral-cerebellar" dynamics is changing at breakneck speed. In fact, every week, there seems to be another study (such as the new report from Parker et al. published yesterday) that puts the cognitive and behavioral influences of the cerebellum in the spotlight. 

Along this line, last week, neuroscientists at Stanford University serendipitously discovered (for the first time) that granule cells in the cerebellum encode and predict rewards. The Stanford study, "Cerebellar Granule Cells Encode the Expectation of Reward," was published March 20 online ahead of print in the journal Nature.

As another example, a few months ago, a different team of researchers at Stanford University, led by Manish Saggar, reported that optimizing cerebral-cerebellar connectivity increases creative capacity. Using fMRI neuroimaging, Saggar's team found that suppressing the executive-control functions of the cerebrum—while encouraging the cerebellum to become the “controller"—increased spontaneous creative capacity. These findings were published in the journal Cerebral Cortex

The Overshadowed "Little Brain" Is Finally Getting the Spotlight It Deserves

I've been researching and writing about the cerebellum for over a decade. As someone who keeps my finger on the pulse of the latest cerebellar research, it's clear that the frequency of new studies on the cerebellum is speeding up ... What was once a slow drip, drip, drip of new research on the cerebellum (being published sluggishly every few months) is now a steadier stream of new cerebellar research being published hastily online ahead of print.

Although the cerebellum is still bubbling under the radar in the mainstream, the neuroscience zeitgeist of today seems to be making the heretofore underappreciated cerebellum a trending topic. Most importantly, all of this trailblazing cerebellar research is revealing countless, previously unknown (and amazing) things that your powerful and mysterious "little brain" is probably doing day and night. 

Stay tuned for more exciting new research on the cerebellum. Hopefully, future research will continue to help us understand how cerebellum function and cerebral-cerebellar connectivity influence cognition, as well as various mental health disorders.

In the meantime, if you'd like to check out my previous Psychology Today blog posts on the cerebellum, click on this link

References

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

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

Manish Saggar, Eve-Marie Quintin, Nicholas T. Bott, Eliza Kienitz, Yin-hsuan Chien, Daniel W-C. Hong, Ning Liu, Adam Royalty, Grace Hawthorne, Allan L. Reiss; Changes in Brain Activation Associated with Spontaneous Improvization and Figural Creativity After Design-Thinking-Based Training: A Longitudinal fMRI Study. CerebCortex 2016 bhw171. doi: 10.1093/cercor/bhw171

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