Summary: Researchers have developed a potential diagnostic tool for schizophrenia by observing how patients process conflicting information. By analyzing neural activity between the cortex and thalamus, they found distinct patterns that make schizophrenia patients more sensitive to uncertainty. These neural markers could also help evaluate treatment effectiveness.
The study, which used decision-making tasks to test participants’ response to conflicting cues, reveals deficits in cognitive flexibility unique to schizophrenia. Future research aims to refine this tool, offering a new way to measure and monitor executive dysfunction.
Key Facts:
- Sensitivity to Uncertainty: Schizophrenia patients show heightened sensitivity to ambiguous information, impairing flexible thinking.
- Neural Markers: Distinct patterns of brain activity between the cortex and thalamus correlate with decision-making deficits.
- Clinical Potential: These neural patterns could serve as biomarkers for diagnosing and assessing treatment efficacy in schizophrenia.
Source: Tufts University
Scientists have known for decades that the classic symptoms of schizophrenia, such as jumping to conclusions or difficulty adjusting to new information, can be attributed to poor communication between the cerebral cortex and the thalamus, known as the brain’s central switchboard.
By measuring brain cell activity between these two regions as volunteers completed ambiguous tasks, a team of Tufts University School of Medicine and Vanderbilt University School of Medicine researchers found a way to use someone’s sensitivity to uncertainty as a diagnostic tool.
In a study published November 7 in the journal Cell Reports Medicine, the researchers show that people with schizophrenia generate distinct neural patterns when asked to make decisions based on conflicting information.
The work offers one of the first biological tests to assess whether someone is prone to inflexible thinking and, by monitoring changes in these patterns, a new way to measure whether treatments are working.
“Our goal was to derive a biomarker for executive dysfunction in schizophrenia, which only emerged when patients were taxed by an uncertain task,” says physician-scientist Michael Halassa, an associate professor of neuroscience and psychiatry at Tufts University School of Medicine who co-led the study with Neil Woodward, a neuropsychologist at Vanderbilt University School of Medicine.
“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.”
Over the course of evolution, the human brain has developed ways to “vote” on which bits of information are most relevant when making decisions. For example, if you go to your favorite restaurant but your meal isn’t the quality you’ve come to expect, you may think the chef is out or having a bad night, but it doesn’t prevent you from coming back.
In contrast, a person with schizophrenia may be unable to consider the evidence that the past 20 or 30 visits were great and will no longer want to return to the restaurant.
Animal studies have shown that this behavior is driven by deficits in how the part of the forebrain that helps animals make sense of complex inputs (the dorsolateral prefrontal cortex) interfaces with a subcortical region associated with conflict resolution and decision making (the mediodorsal thalamus).
Informed by the animal data, the research team developed a series of cognitive and imaging tests to better understand this neural circuitry in humans to establish more accurate diagnostics for patients.
The scientists asked about 40 study participants—a mixture of neurotypical individuals and patients with schizophrenia—to correctly choose a target’s location based on a sequence of cues that can be made more or less conflicting. For healthy people, performance was very good even when the conflict was high.
People with schizophrenia had comparable behavior to controls when there was little conflict, but they made many more errors with conflict levels that were tolerated well by controls.
“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,” said Anna Huang, a research assistant professor of psychiatry and behavioral sciences at Vanderbilt and co-first author of the study.
“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 validate their findings by replicating the methods with a wider range of subjects receiving brain scans as they process ambiguous cues. They also plan on administering hierarchical tasks to subjects, akin to the restaurant example above.
The study is part of a wider research initiative the Halassa Lab is pursuing to link neural activity to data that can be interpreted for clinical benefit.
Also contributing to this study were Ralf Wimmer, research assistant professor of neuroscience and co-first author, and Norman Lam, postdoctoral fellow, from Tufts University School of Medicine, as well as Sahil Suresh, a student in the MD/PhD Medical Scientist Training Program at Tufts University School of Medicine and the Graduate School of Biomedical Sciences at Tufts University.
Complete information on authors, funders, methodology, and conflicts of interest is available in the published paper. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.
About this schizophrenia research news
Author: Tara Pettinato
Source: Tufts University
Contact: Tara Pettinato – Tufts University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“A prefrontal thalamocortical readout for conflict-related executive dysfunction in schizophrenia” by Michael Halassa et al. Cell Reports Medicine
Abstract
A prefrontal thalamocortical readout for conflict-related executive dysfunction in schizophrenia
Executive dysfunction is a prominent feature of schizophrenia and may drive core symptoms. Dorsolateral prefrontal cortex (dlPFC) deficits have been linked to schizophrenia executive dysfunction, but mechanistic details critical for treatment development remain unclear.
Here, capitalizing on recent animal circuit studies, we develop a task predicted to engage human dlPFC and its interactions with the mediodorsal thalamus (MD).
We find that individuals with schizophrenia exhibit selective performance deficits when attention is guided by conflicting cues. Task performance correlates with lateralized MD-dlPFC functional connectivity, identifying a neural readout that predicts susceptibility to conflict during working memory in a larger independent schizophrenia cohort.
In healthy subjects performing a probabilistic reversal task, this MD-dlPFC network predicts switching behavior.
Overall, our three independent experiments introduce putative biomarkers for executive function in schizophrenia and highlight animal circuit studies as inspiration for the development of clinically relevant readouts.
