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Duke University researchers have identified a previously unknown correlation between cerebellar circuitry and an increased risk of multiple forms of mental illness. Their groundbreaking study, "Structural Alterations within Cerebellar Circuitry are Associated with General Liability for Common Mental Disorders," was published April 11 in Molecular Psychiatry. (Cerebellar is the sister word to cerebral and means “relating to or located in the cerebellum.")
The study was led by Adrienne Romer and conducted with senior author Ahmad Hariri and other colleagues in the Hariri Lab at Duke's Laboratory of NeuroGenetics.
According to the researchers, this study is the first to link gray matter brain volume in specific regions of the cerebellum and integrity of the white matter (the communication lines that create connectivity between various brain regions) with a wide range of mental disorders.
In 1504, Leonardo da Vinci made wax castings of the human brain and noticed a total of four distinct brain hemispheres within the cranial globe. The wax castings made by da Vinci clearly illustrated that there were two large hemispheres in the cerebrum (Latin for "brain") and two smaller hemispheres neatly tucked underneath the left and right hemispheres of the cerebrum. Based on his unique observations, da Vinci coined the term cerebellum which is Latin for "little brain." Just as you have a left and right cerebral hemisphere with various lobes, you also have a left and right cerebellar hemisphere with various lobes.
For centuries, most neuroscientists believed that the cerebellum was solely responsible for noncognitive functions such as fine-tuning motor coordination, balance, and proprioception.
Until very recently, the notion that the cerebellum might play any type of role in cognition or mental health disorders was considered outlandish. But, the new study adds to a groundswell of cutting-edge research that is putting the potential cognitive influence of the cerebellum in the spotlight. The cerebellum is only 10 percent of brain volume, but houses about 80 percent of the brain's total neurons.
Independently, Jeremy Schmahmann has been conducting neurologic research on the cerebellum at Harvard Medical School’s Massachusetts General Hospital (MGH), particularly the condition known as ataxia, the loss of fine-tuned muscle coordination rooted in the cerebellum. In the course of his research, he developed a hypothesis known as “Dysmetria of Thought.” It posits that various microzones within cerebellar hemispheres might fine-tune our thoughts and cognition much the same way they fine-tune coordinated muscle movements.
As he describes in the video below, decades ago, Schmahmann had a very difficult time convincing any of his peers that the cerebellum might be involved in cognition or mental disorders. That is beginning to change, thanks to the recent publication of various studies linking cerebellar structure and connectivity with cognition and mental health.
In an email exchange I had with the Duke researchers, Hariri told me that “the take-home message of this work is that the cerebellum supports the integration and coordination of thought, and fundamental alterations in a brain circuitry centered on the cerebellum may give rise to the broad risk of an individual for developing any of the major categories of mental illness. In other words, if the brain isn't able to effectively coordinate information flow there may be an increased general risk for developing mental illness.”
He also told me that the Duke team "relied heavily on Schmahmann's pioneering work on the cerebellum and extensively reference his 'dysmetria of thought' model in the discussion of our findings. We likewise were influenced by the work of Narandren and as well as Ito on the importance of corticocerebellar circuits in thought.”
Romer added: “Schmahmann's 'dysmetria of thought' model certainly influenced our understanding of our findings of multiple mental disorders linked to structural alterations in the cerebellum. In particular, the part of the cerebellum that we find reduced gray matter volume (lobule VIIb) has previously been shown to be part of a network of brain regions that are involved in cognitive control. Using Schmahmann's model, we hypothesize that this region of the cerebellum, through its connections with other brain regions, may compare intention with execution, essentially working to help guide behavior to be consistent with our intentions based on external feedback, a cognitive process that may be deficient to varying degrees in multiple forms of mental illness.”
The researchers also told me that they are conducting further studies exploring whether the reductions in gray matter in the left cerebellar lobule VIIb are associated with functional connectivity to prefrontal regions of the right cerebral hemisphere that support cognitive control. "We plan to examine the functional connectivity of the cerebellum with prefrontal regions involved in cognitive control using fMRI tasks that require updating behavior based on external feedback,” said Romer.
These are exciting times for cerebellar research. Stay tuned for more cutting-edge findings on the link between the cerebellum, cognition, and our mental health.
References
"Structural Alterations within Cerebellar Circuitry are Associated with General Liability for Common Mental Disorders," Adrienne L. Romer, Annchen R. Knodt, Renate Houts, Bartholomew D. Brigidi, Terrie E. Moffitt, Avshalom Caspi and Ahmad R. Hariri. Molecular Psychiatry, April 11, 2017. DOI: 10.1038/MP.2017.5
