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Yale researchers link brain regions to paranoia through a study of human and monkey behaviors.
The ability to adjust beliefs about one’s actions and their consequences in a constantly changing environment is a hallmark of advanced cognition. Disruptions to this ability can negatively impact cognition and behavior, leading to states of mind such as paranoia—the belief that others intend to harm us.
In a groundbreaking study, Yale scientists have identified a specific brain region that might causally provoke feelings of paranoia. Their novel approach, which involved aligning data collected from monkeys with human data, offers a new cross-species framework through which scientists might better understand human cognition through the study of other species. The findings and the approach were recently published in the journal Cell Reports.
While past studies have implicated some brain regions in paranoia, understanding its neural underpinnings remains limited. This new study sheds light on the complex mechanisms involved.
Study Methodology and Findings
The Yale researchers analyzed existing data from previous studies conducted by multiple labs on both humans and monkeys. In these studies, participants performed a task designed to measure how volatile they perceived their environment to be. They were given three options on a screen, each associated with different probabilities of receiving a reward. Participants had to uncover the best option by trial and error, and the probabilities were periodically and unpredictably flipped.
“Participants have to figure out the best target, and when there’s a perceived change in the environment, they have to find the new best target,” explained Steve Chang, associate professor of psychology and neuroscience at Yale and co-senior author of the study.
Participants’ clicking behavior before and after the flip revealed information about how volatile they viewed their environment and how adaptive their behavior was within that changing environment. The researchers applied the same computational analysis to both human and monkey datasets to compare the two and understand the correlations.
Linking Animal and Human Data
In previous studies, some monkeys had specific lesions in either the orbitofrontal cortex, associated with reward-related decision-making, or the mediodorsal thalamus, which sends environmental information to the brain’s decision-making control centers. Among human participants, some reported high paranoia, while others did not.
The researchers found that lesions in both brain regions negatively affected the monkeys’ behavior, but in different ways. Monkeys with orbitofrontal cortex lesions often stuck with the same options despite not receiving a reward, while those with mediodorsal thalamus lesions displayed erratic switching behavior, even after receiving a reward. They appeared to perceive their environments as especially volatile, similar to human participants with high paranoia.
Implications and Future Research
The findings provide new insights into what occurs in the human brain—particularly the role of the mediodorsal thalamus—when people experience paranoia. They also offer a pathway to study complex human behaviors in simpler animals.
“It allows us to translate what we learn in simpler species to understand human cognition,” said Philip Corlett, associate professor of psychiatry at Yale School of Medicine and co-senior author of the study.
This approach will enable researchers to assess how pharmaceutical treatments affecting states like paranoia work in the brain and potentially lead to new ways to reduce paranoia in humans.
The study, titled “Lesions to the mediodorsal thalamus, but not orbitofrontal cortex, enhance volatility beliefs linked to paranoia,” was led by co-first authors Praveen Suthaharan, a graduate student in Corlett’s lab, and Summer Thompson, an associate research scientist in Yale’s Department of Psychiatry. The work was done in collaboration with Jane Taylor, the Charles B.G. Murphy Professor of Psychiatry at Yale School of Medicine.
Reference: Suthaharan, P., Thompson, S. L., Rossi-Goldthorpe, R. A., Rudebeck, P. H., Walton, M. E., Chakraborty, S., Noonan, M. P., Costa, V. D., Murray, E. A., Mathys, C. D., Groman, S. M., Mitchell, A. S., Taylor, J. R., Corlett, P. R., & Chang, S. W.C. (2024). Lesions to the mediodorsal thalamus, but not orbitofrontal cortex, enhance volatility beliefs linked to paranoia. Cell Reports. DOI: 10.1016/j.celrep.2024.114355
