"Little Brain" Plays Surprisingly Big Role in Mental Health
Mega-analysis reveals prominent role of the cerebellum in severe mental illness.
Posted Jun 12, 2017
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 neatly tucked under the relatively colossal left-right hemispheres of the cerebrum (Latin for "brain"). Cerebellar is the sister word to cerebral and means “relating to or located in the cerebellum.”
Historically, the cerebellum has been considered the seat of muscle memory, with the primary “non-thinking” task of fine-tuning coordinated movement. Until recently, the majority of textbooks on anatomy, neurology, and neuroscience have limited discussion of the cerebellum to chapters dedicated solely to motor control and sensorimotor learning without mentioning a possible cerebellar role in higher cognition or mental disorders. Because of this, the cerebellum has been overlooked by the mainstream as playing any type of role in psychological functions, mental health, or schizophrenia for way too long.
However, in recent years it’s become increasingly obvious that our “little brain” plays a surprisingly large role in higher order cognitive functions as well as psychopathology. Interestingly, it appears that just as cerebellar damage or dysfunction creates ataxia (as marked by uncoordinated physical movements) cerebellar abnormalities may also lead to uncoordinated thought processes—such as those observed in mental health disorders such as schizophrenia.
In fact, over the past few months, there's been a groundswell of cutting edge research that corroborates Jeremy Schmahmann’s “Dysmetria of Thought” hypothesis first published in the summer of 2004. Schmahmann's revolutionary hypothesis is that microzones within the cerebellum fine-tune and coordinate our thoughts much like they fine-tune muscle movements. Schmahmann is Professor of Neurology at Harvard Medical School and director of the Massachusetts General Hospital Ataxia Unit and Laboratory for Neuroanatomy and Cerebellar Neurobiology.
Earlier this spring, Duke University researchers reported a previously unrecognized correlation between cerebellar circuitry and an increased risk of multiple forms of mental illness. Their first-of-its-kind study, "Structural Alterations within Cerebellar Circuitry are Associated with General Liability for Common Mental Disorders," was published April 11 in Molecular Psychiatry. This 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 Romer and Hariri, this study is the first to link gray matter brain volume in specific regions of the cerebellum and the integrity of white matter (the communication lines that create connectivity between various cerebellar-cerebral brain regions) as being correlated with a wide range of mental disorders.
Along this same line, Norwegian researchers recently conducted the largest and most extensive meta-analysis of MRI brain imaging to date. They discovered that the cerebellum is among brain regions with the strongest and most consistent differences in schizophrenia when compared to healthy individuals.
A groundbreaking paper by Torgeir Moberget, Lars Tjelta Westlye and colleagues, “Cerebellar volume and cerebellocerebral structural covariance in schizophrenia: a multisite mega-analysis of 983 patients and 1349 healthy controls,” was released on May 16 as an advance access publication before print in Molecular Psychiatry.
The authors of this study used highly sophisticated tools which allowed them to analyze the volume and shape of the entire brain—including both hemispheres of the cerebrum and both hemispheres of the cerebellum.
The vastness of the data (which came from 14 different countries) allowed Moberget and his team to pinpoint very nuanced differences in cerebral and cerebellar brain volume in patients with schizophrenia compared to healthy controls. This study was part of an ongoing collaboration headed by Ole Andreassen of the Norwegian Centre for Mental Disorders Research (NORMENT) at the University of Oslo and Oslo University Hospital along with the Department of Psychology at the University of Oslo in Norway.
The Norwegian findings show that patients with schizophrenia as a collective group had smaller cerebellar volumes compared with healthy controls. More specifically, the researchers found that that total gray matter volume in the cerebellum was significantly reduced in schizophrenia with the strongest effects observed in cerebellar regions with functional connectivity to the frontoparietal region of the cerebral cortex. Notably, changes in cerebellar volumes were consistently associated with cerebral structural changes (e.g., hippocampus gray matter volume and frontotemporal cortical thickness).
The Norwegian researchers also observed a positive correlation between cerebellar volume and cerebral cortical thickness in frontotemporal regions (i.e., overlapping with areas that also showed reductions in schizophrenia). This cerebellocerebral structural covariance was strongest in schizophrenia, suggesting a common underlying disease process that jointly affects both the cerebellum and cerebrum. Taken together, the researchers believe these novel findings establish the cerebellum as a key node in the distributed brain networks underlying schizophrenia.
In an email correspondence, Torgeir Moberget shared statements with me about his latest study on cerebellar volume and schizophrenia. Moberget said:
"These findings reveal a prominent role of the cerebellum in severe mental illness, but it is important to emphasize that the brain differences we see in schizophrenia are generally very subtle. You would not be able to spot a difference between the brain scan of a patient and a healthy participant just by looking at them, and the differences among patients are also large. When we saw the same pattern repeated across many groups of patients and controls from different countries, the findings became much more convincing."
Moberget emphasizes that large collaborative studies are especially important because they improve the ability to detect small, but potentially important, effects, and allow researchers to evaluate the consistency of their findings.
Most severe mental disorders begin to emerge during childhood and adolescence. Having a better understanding of the cerebellar-cerebral structural covariances in schizophrenia could lead to better patient care and outcomes. Senior author Lars Westlye addressed this by saying, “To develop treatments that could reverse or even prevent the disease we need to understand why some children are at risk of developing these serious illnesses in the first place. The brain seems to be a good place to start looking, and we are now trying to identify environmental and genetic factors that influence brain development."
These are exciting times for cerebellar-cerebral research. Please stay tuned for upcoming findings that will undoubtedly help us better understand the heretofore underappreciated role the "little brain" plays in our mental health.
T. Moberget, N. T. Doan, D. Alnæs, T. Kaufmann, A. Córdova-Palomera, T. V. Lagerberg, J. Diedrichsen, E. Schwarz, M. Zink, S. Eisenacher, P. Kirsch, E. G. Jönsson, H. Fatouros-Bergman, L. Flyckt, KaSP, G. Pergola, T. Quarto, A. Bertolino, D. Barch, A. Meyer-Lindenberg, I. Agartz, O. A. Andreassen and L. T. Westlye. Cerebellar volume and cerebellocerebral structural covariance in schizophrenia: a multisite mega-analysis of 983 patients and 1349 healthy controls. Molecular Psychiatry. Advance online publication 16 May 2017. DOI: 10.1038/mp.2017.106
Adrienne L. Romer, Annchen R. Knodt, Renate Houts, Bartholomew D. Brigidi, Terrie E. Moffitt, Avshalom Caspi and Ahmad R. Hariri. "Structural Alterations within Cerebellar Circuitry are Associated with General Liability for Common Mental Disorders," Molecular Psychiatry. Online publication 11 April 2017. DOI: 10.1038/MP.2017.5
D.P. Hibar, O. A. Andreassen, et al. Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group. Molecular Psychiatry. Advance online publication 02 May 2017. DOI: 10.1038/mp.2017.73