Resume: Researchers found that a specific brain region, the mediodorsal thalamus, can cause feelings of paranoia. Aligning data from studies in monkeys and humans, they found that lesions in this brain region led to erratic behavior and increased perception of the volatility of the environment.
The study provides a new framework for understanding human cognition through cross-species research. These findings could pave the way for developing targeted treatments for paranoia and other cognitive problems.
Key Facts:
- The study focused on the orbitofrontal cortex and the mediodorsal thalamus.
- Lesions in these areas caused various erratic behaviors in monkeys.
- High paranoia in humans mirrored fleeting perceptions in monkeys.
Source: Jale
The ability to adapt beliefs about one’s actions and their consequences in a constantly changing environment is a defining characteristic of advanced cognition. However, disruptions to this ability can negatively impact cognition and behavior, leading to mental states such as paranoia, or the belief that others intend to harm us.
In a new study, Yale scientists discover how a specific part of the brain can causally trigger these feelings of paranoia.
Their new approach – which matched data collected from monkeys with human data – also provides a new cross-species framework that allows scientists to better understand human cognition through the study of other species.
Their findings and the approach they used will be described in the journal on June 13 Cell reports.
Although previous studies have implicated some brain regions in paranoia, understanding of the neural underpinnings of paranoia remains limited.
For the new study, the Yale researchers analyzed existing data from previous studies conducted by multiple laboratories on both humans and monkeys.
In all previous studies, humans and monkeys performed the same task, which records how volatile or how unstable a participant thinks their environment is. Participants in each study were presented with three options on a screen, which were associated with different probabilities of receiving a reward.
If participants selected the option with the highest probability of reward, they would receive a reward with fewer clicks during the trial periods. The lowest probability option required more clicks to receive a reward.
The third option, meanwhile, was somewhere in the middle. Participants had no information about reward probability and had to discover their best option through trial and error.
After a certain number of attempts and without warning, the options with the highest and lowest reward probability are flipped.
“So participants have to figure out what the best target is, and when a change in the environment is observed, the participant has to find the new best target,” says Steve Chang, associate professor of psychology and neuroscience at Yale’s Faculty of Arts. and Sciences and co-senior author of the study.
Participants’ clicking behavior before and after the flip can reveal information about how volatile they view their environment 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 data sets,” said Philip Corlett, associate professor of psychiatry at the Yale School of Medicine and co-senior author of the study.
“The computational model is essentially a set of equations that we can use to explain behavior, and here it serves as the common language between the human and monkey data and allows us to compare the two and see how the data of monkeys relate to human data.”
In the previous studies, some monkeys had small but specific lesions in one of two brain areas of interest: the orbitofrontal cortex, which is associated with reward-related decision-making, or the mediodorsal thalamus, which sends environmental information to the brain. decision-making control centers of the brain.
Among the human participants, some had reported high levels of paranoia, and others had not.
The researchers found that the presence of lesions in both brain areas negatively affected the monkeys’ behavior, but in different ways.
Monkeys with lesions in the orbitofrontal cortex were more likely to stick with the same options, even after receiving no reward. In contrast, those with lesions in the mediodorsal thalamus showed erratic switching behavior even after receiving a reward.
They seemed to view their environment as particularly volatile, which was similar to what the researchers observed in the human participants with high paranoia.
The findings provide new information about what happens in the human brain – and the role the mediodorsal thalamus might play – when people experience paranoia, the researchers say. And they provide a way to study complex human behavior in simpler animals.
“It allows us to ask how we can translate what we learn in simpler species – such as rats, mice and perhaps even invertebrates – to understand human cognition,” says Corlett, who along with Chang is a member of the Wu Tsai Yale 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 in the future we can use it to find new ways to reduce paranoia in people,” says Chang.
The work was led by co-first authors Praveen Suthaharan, a graduate student in Corlett’s lab, and Summer Thompson, a principal investigator 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: Jale
Contact: Fred Mamoun – Yale
Image: The image is credited to Neuroscience News
Original research: Open access.
“Lesions to the mediodorsal thalamus, but not the orbitofrontal cortex, enhance volatility beliefs associated with paranoia” by Steve Chang et al. Cell reports
Abstract
Lesions to the mediodorsal thalamus, but not the orbitofrontal cortex, enhance volatility beliefs associated with paranoia
Beliefs (attitudes toward a particular state of the environment) determine the choice of actions and must be robust to variability but sensitive to meaningful changes.
Beliefs about volatility (expectation of change) are associated with paranoia in humans, but the brain regions responsible for volatility beliefs remain unknown.
The orbitofrontal cortex (OFC) is central to adaptive behavior, while the magnocellular mediodorsal thalamus (MDmc) is essential for the arbitration between perceptions and action policies.
We assessed belief updating in a three-choice probabilistic 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 indicated a double dissociation: MDmc, but not OFC, lesions were associated with erratic switching behavior and increased belief in volatility (as in paranoia in humans), while OFC, but not MDmc, lesions were associated with increased lose-stay behavior and reward. learning rates.
Given the consistency across species and models, these results have implications for understanding paranoia.