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

Your cerebellum may be part of a reality-check system that plays a central anti-hallucination role in the brain, according to a recent study conducted at Yale University. The new report, “Pavlovian Conditioning–Induced Hallucinations Result from Overweighting of Perceptual Priors,” was published August 11 in the journal Science.

Historically, the cerebellum was considered a sub-cortical brain region responsible for fine-tuning coordinated muscle movements that did not play a role in cognition. 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.

For example, in April 2017, Duke University researchers reported a previously unrecognized correlation between cerebellar circuitry and an increased risk of multiple forms of mental illness. (Cerebellar is the sister word to cerebral and means "relating to or located in the cerebellum.")

This first-of-its-kind paper, "Structural Alterations Within Cerebellar Circuitry Are Associated with General Liability for Common Mental Disorders," was published in Molecular Psychiatry. Lead author Adrienne Romer conducted this research with senior author Ahmad Hariri and other colleagues in the Hariri Lab at Duke's Laboratory of NeuroGenetics. (To read excerpts from my interview with the research team, check out this PT post: "A Wide Range of Mental Disorders May Have Link to Cerebellum.")

As another example, in May 2017, a groundbreaking paper by Torgeir Moberget, Lars Tjelta Westlye, and colleagues from the Norwegian Center for Mental Disorders Research (NORMENT), reported that total gray matter volume in the cerebellum was significantly reduced in patients with schizophrenia. These findings were based on a mega-analysis of MRI data from 14 different countries and published in Molecular Psychiatry. (I reported on this study in a Psychology Today blog post, "Little Brain Plays a Surprisingly Big Role in Mental Health.")

The latest eye-opening study about the cerebellum was led by Albert Powers, Clinical Instructor at the Yale University Department of Psychiatry and Medical Director of the PRIME Psychosis Research Clinic at Yale. Co-author, Philip Robert Corlett is director of The Belief, Learning, & Memory Lab at Yale. Powers and Corlett are on a mission to better understand delusions through the lens of brain structure and function. Their research aims to identify the neural mechanisms of hallucinations and associative learning as it relates to delusional beliefs in various populations. 

For their latest study on conditioning-induced hallucinations, the researchers recruited four participant groups that included: (1) people with a diagnosed psychotic illness (such as schizophrenia) who heard voices; (2) those with a similar illness who did not hear voices; (3) an active control group who heard voices daily, but had no diagnosed mental illness (as self-described psychics, they attributed their experiences metaphysically); (4) healthy controls without diagnosis who did not hear voices.

During the experiment, the researchers designed a classic Pavlovian learning task which conditioned an association between a checkerboard image and a 1000-Hz tone. Over time, they conditioned potential task-induced hallucinations by pairing the image with and without the actual tone in the four groups of people who differed in their voice-hearing and treatment-seeking statuses.

In the study abstract, the authors describe the next phase of the experiment: “Using functional neuroimaging and computational modeling of perception, we identified processes that differentiated voice-hearers from non–voice-hearers and treatment-seekers from non–treatment-seekers and characterized a brain circuit that mediated the conditioned hallucinations.”

After analyzing the data, Powers et al. found that participants who were more prone to hear voices were also more susceptible to the induced auditory hallucinations of thinking they heard the tone anytime they saw the checkerboard. In fact, the self-described psychics and patients with schizophrenia were roughly five times more likely to hear the tone when it was actually silent than the control group. They were also about 28 percent more confident that their auditory hallucinations were real.

Notably, participants who were more prone to these hallucinations also showed less activity in the cerebellum. Various degrees of cerebellar activity were linked to the severity of hallucinations on a continuum. i.e. The more severe a person’s hallucinations were, the less activity the team observed in that person’s cerebellum. Although more research is needed before drawing any ironclad conclusions, the researchers speculate that these findings suggest that the cerebellum might act as a type of watchdog that protects against the brain’s potential to distort reality.

The authors conclude: “These data demonstrate the profound and sometimes pathological impact of top-down cognitive processes on perception and may represent an objective means to discern people with a need for treatment from those without.” Adding, “Our observations support an explanation of hallucinations based on strong perceptual priors. They suggest precision treatments for hallucinations, such as targeting cholinergically mediated priors, and interventions to mollify psychosis more broadly, such as cerebellar transcranial magnetic stimulation.”

These are exciting times for cerebellar research. In the future, findings from this type of research might be used by clinicians to better predict those at a higher risk of developing schizophrenia, which could lead to earlier interventions and more effective treatments.

Please stay tuned for upcoming clinical studies on the cerebellum that will undoubtedly help us better understand the heretofore underappreciated role the "little brain" plays in our everyday lives and mental health

References

A. R. Powers, C. Mathys, P. R. Corlett. "Pavlovian conditioning–induced hallucinations result from overweighting of perceptual priors" Science. Aug. 11, 2017. Vol. 357, Issue 6351, pp. 596-600. DOI: 10.1126/science.aan3458

"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.2017.57

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 May 16, 2017. DOI: 10.1038/mp.2017.106

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