Summary: Researchers have discovered that a specific brain region, the mediodorsal thalamus, can trigger feelings of paranoia. By comparing data from monkey and human studies, they found that lesions in this area of the brain lead to erratic behavior and an increased perception of environmental instability.
The study offers 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 problems.
Key facts:
- The study focused on the orbitofrontal cortex and the mediodorsal thalamus.
- Lesions in these areas cause a variety of chaotic behaviors in monkeys.
- High paranoia in humans mirrors fluctuating perceptions in apes.
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. Impairment of this ability, however, can negatively affect cognitive abilities and behavior, leading to such states of mind 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 causally provoke these feelings of paranoia.
Their new approach—which involved equating data collected from monkeys with data from humans—also offers a new cross-species framework through which scientists could better understand human cognition by studying other species.
Their findings and the approach they used are described June 13 in the journal Cell reports.
While previous studies have implicated some areas of the brain 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 in both humans and monkeys.
In all previous studies, humans and monkeys performed the same task that captures how impermanent, or how unstable, the participant thinks their environment is. Participants in each study were given three options on the screen that were associated with different probabilities of receiving a reward.
If participants choose the option with the highest reward probability, they will receive a reward with fewer clicks across trials. The option with the lowest probability requires 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 find their best option by trial and error.
After a certain number of trials and without warning, the highest and lowest reward probability options are reversed.
“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 Yale’s School of Arts and Sciences and co-senior author of the study.
Participants’ clicking behavior before and after the reversal can reveal information about how unstable their environment is and how adaptive their behavior is in 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 Yale School of Medicine and co-author of research.
“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 the monkey data relating to human data.”
In the previous studies, some of the monkeys had small but specific lesions in one of two brain regions of interest: the orbitofrontal cortex, which is involved in making reward-related decisions, or the mediodorsal thalamus, which sends environmental information to decision-making control centers of the brain.
Among the human participants, some reported strong paranoia and others did not.
The researchers found that having lesions in both areas of the brain negatively affected the monkeys’ behavior, but in different ways.
Monkeys with lesions in the orbitofrontal cortex were more likely to stay with the same options even after not receiving a reward. Those with lesions in the mediodorsal thalamus, on the other hand, showed inconsistent switching behavior even after receiving a reward.
They seem to perceive their environment as particularly volatile, which is similar to what the researchers observed in human participants with high paranoia.
The findings offer new information about what happens in the human brain — and the role of the mediodorsal thalamus — when people experience paranoia, the researchers said. And they provide a pathway for how to study complex human behavior in simpler animals.
“This allows us to ask how we can translate what we’re learning to simpler species — like rats, mice, maybe even invertebrates — to understand human cognition,” said Corlett, who, along with Chang, is a member of the Wu Institute Tsai at Yale, which aims to accelerate the understanding of human cognition.
This approach will also allow researchers to assess how pharmaceutical treatments that affect conditions such as paranoia actually work in the brain.
“And maybe in the future we can use it to find new ways to reduce paranoia in people,” Chang said.
The work was led by co-authors Praveen Suthaharan, a graduate student in Corlett’s lab, and Summer Thompson, an associate research fellow in the Yale Department of Psychiatry. This was done in collaboration with Jane Taylor, Charles BG Murphy Professor of Psychiatry at Yale School of Medicine.
About this news about neuroscience research and paranoia
Author: Fred Mamun
source: Yale
Contact: Fred Mamun – Yale
Image: Image credit: Neuroscience News
Original research: Free access.
“Lesions of mediodorsal thalamus, but not orbitofrontal cortex, enhance paranoia-related impermanence beliefs” by Steve Chang et al. Cell reports
Summary
Lesions of the mediodorsal thalamus but not the orbitofrontal cortex enhance changeable beliefs associated with paranoia
Beliefs—attitudes toward some state of the environment—guide the choice of action and must be resistant to variability but sensitive to significant change.
Mutability beliefs (anticipation of change) are associated with paranoia in humans, but the brain regions responsible for mutability beliefs remain unknown.
The orbitofrontal cortex (OFC) is central to adaptive behavior, while the magnocellular mediodorsal thalamus (MDmc) is essential for arbitrating between perceptions and action policies.
We assessed belief updating in a three-option probabilistic reversal learning task following excitotoxic lesions of the MDmc (n = 3) or OFC (n = 3) and compared performance with that of unoperated monkeys (n = 14).
Computational analyzes show a double dissociation: MDmc, but not OFC, lesions are associated with chaotic switching behavior and increased beliefs about variability (as in paranoia in humans), whereas OFC, but not MDmc, lesions are associated with increased losing behavior stay and reward learning rates.
Given the fit between species and models, these results have implications for understanding paranoia.
