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BOSTON — Schizophrenia, a complex mental health disorder, profoundly impacts a patient’s cognitive abilities. Now, a new study finds that a schizophrenic’s brain activity displays unique signs when they’re trying to handle conflicting information. In other words, their brains don’t work in the same way as someone without schizophrenia when confronted with information that they believe isn’t true.
A recent study published in Cell Reports Medicine has identified key neural processes underlying these deficits, including impaired connectivity between two brain regions — the dorsolateral prefrontal cortex (dlPFC) and the mediodorsal thalamus (MD). Researchers pinpointed how these disruptions impair executive function, particularly under conditions like uncertainty. This groundbreaking work not only provides a potential marker for examining cognitive rigidity among schizophrenia patients, but it also lays the foundation for developing new treatments for brain disorders.
“Our goal was to derive a biomarker for executive dysfunction in schizophrenia, which only emerged when patients were taxed by an uncertain task,” says lead study author Michael Halassa, an associate professor of neuroscience and psychiatry at Tufts University School of Medicine, in a media release. “We make decisions that are hierarchical in nature all the time as humans—meaning that we often need to account for misinformation at different levels—but this breaks down in schizophrenia and here is a way we can begin measuring that attribute.”
Animal studies mimicking the schizophrenic brain have shown impairments in the dorsolateral prefrontal cortex, which is responsible for making sense of complex information. What’s more, the prefrontal cortex poorly communicates with another brain region called the mediodorsal thalamus, which is important for memory and cognition. Reduced connectivity between the two regions results in people with schizophrenia jumping to conclusions or having trouble processing new information.
For example, if you’re out to eat at your favorite restaurant but your meal was subpar, you likely wouldn’t write off the place as terrible. Since you’ve enjoyed their food before, you might justify the poor experience as the chef having a bad night. Meanwhile, someone with schizophrenia would be incapable of taking in other evidence to justify why the food was lousy. Despite going to this restaurant a dozen times, a person with schizophrenia would not consider other explanations and would no longer want to come back.
In the current study, scientists developed several cognitive and imaging tests to determine people’s level of uncertainty and whether it was because of schizophrenia. They measured people’s brain cell activity between the prefrontal cortex and thalamus while they completed ambiguous tasks. The study participants were a mix of neurotypical individuals and people with confirmed cases of schizophrenia.
People were asked to choose a target’s location using a series of cues, which were more or less conflicting. Neurotypical people had no issue with the tasks, even when presented with conflicting cues. People with schizophrenia showed similar results when the cues were not ambiguous and conflicting. However, they made more mistakes with conflicting cues than the neurotypical participants.
“When you look at the behavior, there’s an increased susceptibility to sensory noise, so the patients with schizophrenia don’t do as well when things become more ambiguous,” says Anna Huang, a research assistant professor of psychiatry and behavioral sciences at Vanderbilt University School of Medicine. “These results correlated with thalamus and frontal cortex deficits that we could capture in brain activity readouts, predicting a person’s ability to process conflicting information in perceptual as well as memory tasks.”
The researchers plan to repeat the experiment using a larger participant pool that is willing to undergo brain scans when processing ambiguous cues. They also want to add more tasks where participants are placed in scenarios similar to the restaurant example, where people face conflicting information.
Paper Summary
Methodology
The researchers aimed to understand how schizophrenia affects a person’s ability to handle conflicting information. They used a special task where participants had to focus on either visual or auditory cues, sometimes mixed to create uncertainty. Healthy individuals and those with schizophrenia completed the task while their brain activity was monitored using functional MRI. The study also examined how brain regions involved in decision-making and attention (like the prefrontal cortex and thalamus) interacted during these tasks.
Key Results
People with schizophrenia struggled more with tasks involving conflicting information compared to healthy participants. When cues were unclear, their performance dropped significantly. The study found that this difficulty was linked to weaker connections between two brain regions: the right mediodorsal thalamus and the dorsolateral prefrontal cortex. These connections are crucial for managing complex tasks and resolving conflicts.
Study Limitations
First, the sample size for neuroimaging was small, which could limit how broadly the results apply. Second, not all tasks were performed while the participants’ brain activity was recorded, making it harder to see real-time brain-behavior connections. Lastly, the third experiment, which examined task-related brain activity, didn’t include participants with schizophrenia, reducing the study’s direct relevance to that group.
Discussion & Takeaways
This study shines a light on why individuals with schizophrenia face challenges in situations requiring high mental flexibility. The findings suggest that targeting the connection between the thalamus and prefrontal cortex could help improve cognitive deficits in schizophrenia. This could lead to new treatment strategies, such as brain stimulation therapies, focusing on strengthening these brain circuits.
Funding & Disclosures
This research was supported by grants from the National Institutes of Health (NIH) and various international scientific organizations. The authors have declared no competing financial interests, ensuring the integrity of their findings. Specific funding details include contributions from the German Research Foundation and the Vanderbilt University Medical Center.