Summary: Researchers discovered that a specific area of the brain, the mediodorsal thalamus, can provoke feelings of paranoia. Comparing data from monkey and human studies, they found that lesions in this brain region led to disordered behavior and increased perceptions of environmental instability.
The study provides a new framework for understanding human cognition through cross-species research. These findings could pave the way for the development of targeted treatments for paranoia and other cognitive issues.
Key facts:
- The study focused on the orbitofrontal cortex and the mediodorsal thalamus.
- Lesions in these areas caused various disordered behaviors in the monkeys.
- High paranoia in humans mirrored unstable perceptions in monkeys.
Source: Yale
The ability to adjust beliefs about one’s actions and their consequences in a constantly changing environment is a defining characteristic of advanced cognition. Disruptions to this ability, however, can negatively affect cognition and behavior, leading to such mental states as paranoia, or the belief that others intend to harm us.
In a new study, Yale scientists reveal how a specific area of the brain can provoke these feelings of paranoia.
Their new approach – which involved aligning data collected from monkeys with human data – also provides a new cross-species framework through which scientists can better understand human cognition by studying other species.
Their findings, and the approach they used, are described June 13 in the journal Nature Cell reports.
While past studies have implicated several brain regions in paranoia, understanding of the neural bases of paranoia remains limited.
For the new study, Yale researchers analyzed existing data from previous studies, conducted by multiple laboratories, in both humans and monkeys.
In all the previous studies, humans and monkeys performed the same task, which indicates how unstable or unstable a participant believes their environment to be. Participants in each study were presented with three options on a screen, which were associated with different probabilities of receiving a reward.
If participants chose the option with the highest reward probability, they would receive a reward with fewer clicks across trials. The option with the lowest probability required more clicks to receive a reward.
The third option, meanwhile, was somewhere in between. Participants had no information on reward probability and had to discover their best option by trial and error.
After a certain number of trials and without warning, the highest and lowest reward probability options return.
“So participants have to figure out what the best target is, and when there’s a perceived change in the environment, the participant has to find the new best target,” said Steve Chang, associate professor of psychology and neuroscience in the Faculty of Yale Arts. and Science and co-senior author of the study.
Participants’ clicker behavior before and after flipping can reveal information about how unstable they perceive their environment to be and how adaptive their behavior is within that changing environment.
“Not only did we use data in which monkeys and humans performed the same task, we also applied the same computational analysis to both sets of data,” said Philip Corlett, an associate professor of psychiatry at Yale School of Medicine. and co-senior author of the study.
“A computational model is essentially a series of equations that we can use to try to explain behavior, and here it serves as a common language between the human and monkey data and allows us to compare the two and see how monkey data relates to human data.”
In previous studies, some of the monkeys had small but specific lesions in one of two brain regions of interest: the orbitofrontal cortex, which has been associated with reward-related decision-making, or the mediodorsal thalamus, which sends environmental information to reward centers. brain decision-making control.
Among the human participants, some reported high paranoia and some did not.
The researchers found that the presence of lesions in both brain regions negatively affected the behavior of the monkeys, but in different ways.
Monkeys with lesions in the orbitofrontal cortex more often stuck with the same options even after not receiving a reward. Those with lesions in the mediodorsal thalamus, on the other hand, displayed erratic switching behavior, even after receiving the reward.
They seemed to perceive their environments as particularly unstable, which was similar to what the researchers observed in human participants with high paranoia.
The findings provide new information about what’s happening in the human brain — and the role the mediodorsal thalamus may play — when people experience paranoia, the researchers say. And they provide a way to study complex human behavior in simpler animals.
“This allows us to ask how we can translate what we learn in simpler species — like mice, rats, maybe even invertebrates — to understand human cognition,” said Corlett, who, along with Chang, is a member of the Yale’s Wu Tsai Institute. which aims to accelerate the understanding of human cognition.
This approach will also allow researchers to assess how pharmaceutical treatments that affect conditions like paranoia actually work in the brain.
“And maybe we can use that to find new ways to reduce paranoia in people,” Chang said.
The work was led by first authors Praveen Suthaharan, a graduate student in Corlett’s lab, and Summer Thompson, an associate research scientist in the Yale Department of Psychiatry. It was done in collaboration with Jane Taylor, the Charles BG Murphy Professor of Psychiatry at the Yale School of Medicine.
About this neuroscience and paranoia research news
Author: Fred Mamoun
Source: Yale
Contact: Fred Mamoun – Yale
Image: Image is credited to Neuroscience News
Original research: Open access.
“Lesions to the mediodorsal thalamus, but not the orbitofrontal cortex, increase paranoia-related instability beliefs” by Steve Chang et al. Cell reports
ABSTRACT
Lesions in the mediodorsal thalamus, but not the orbitofrontal cortex, increase paranoia-related instability beliefs
Beliefs—attitudes toward some state of the environment—guide the selection of actions and must be stable to variability but sensitive to meaningful change.
Beliefs about instability (expectation of change) are associated with paranoia in humans, but the brain regions responsible for instability beliefs remain unknown.
The orbitofrontal cortex (OFC) is central to adaptive behavior, while the magnocellular mediodorsal thalamus (MDmc) is central to arbitrating between perceptions and action policies.
We assessed belief updating in a three-choice probabilistic reversal learning task after excitotoxic lesions of the MDmc (n = 3) or OFC (n = 3) and compared performance with that of unoperated monkeys (n = 14).
Computational analyzes showed a double dissociation: MDmc, but not OFC, lesions were associated with erratic switching behavior and increased instability belief (as in paranoia in humans), whereas OFC, but not MDmc, lesions were associated with increased loss behavior and compensation. learning rates.
Given the consistency across species and models, these results have implications for understanding paranoia.