Most of us have experienced the feeling that when we switch from one task to another, our brain temporarily becomes stuck in an old mode of thinking. In some cases, even after realizing that a strategy no longer works, the mind keeps returning to it anyway.
Neuroscientists refer to the ability to adapt and change strategies as “cognitive flexibility.” This is a core function of advanced cognition that allows the brain to abandon outdated rules and respond to changing circumstances. Impairments in cognitive flexibility are associated with disorders such as attention-deficit/hyperactivity disorder (ADHD), depression, obsessive-compulsive disorder (OCD), schizophrenia, and Alzheimer’s disease.
Now, researchers at the University of California, Riverside have identified a key neural circuit that helps the brain “shift gears.” This study e-lifeshow that a small brainstem structure called the locus coeruleus (LC) plays a central role in helping the brain switch behavioral rules and maintain flexible thinking.
The brain faces constantly changing environments and demands. Our study shows that the locus coeruleus functions as an important regulator that helps the brain efficiently transition between behavioral states. ”
Hongdian Yang, senior author of the study and associate professor of molecular, cell, and systems biology
Although small, LC has a significant impact on the entire brain. It is the main source of norepinephrine, a neuromodulator involved in attention, alertness, learning, stress responses, and decision-making. Scientists have long suspected that LC contributes to cognitive flexibility, but it remained unclear exactly how it shapes brain activity during behavioral switches.
To investigate, researchers at the University of California, Riverside trained mice in a rule-switching task designed to test attentional flexibility. The animals first learned to use certain sensory signals, such as the texture of bedding materials, to find food rewards. Then, without warning, the rules changed and the mice had to ignore the old cues and rely on smell instead.
The team then used chemical genetic techniques to selectively suppress LC activity. The research team found that the mice struggled to adapt to the new rules, continued to rely on outdated strategies, and required significantly more trials to learn the switch.
“We found that LC signals help reorganize neural activity patterns in the prefrontal cortex, freeing the brain from old rules and allowing it to engage with new rules,” Yang said.
The prefrontal cortex is a brain region involved in planning and decision-making. The researchers recorded neural activity in the prefrontal cortex using a miniature microscope implanted in mice, allowing them to track hundreds of neurons during the task.
Rather than simply reducing brain activity, disrupting the LC had the opposite effect. That is, more prefrontal neurons were active, and individual neurons responded to a wider range of more mixed information.
“Networks have become louder and less selective,” Yang said. “This suggests that rather than simply amplifying activity, LC helps keep the prefrontal cortex organized and maintain a high neural ‘signal-to-noise ratio’ during complex decision-making.”
The findings add to a growing body of evidence that brains in many psychiatric and neurological disorders may have problems not just with too much or too little activity, but with their ability to reconfigure neural networks when conditions change.
The researchers also found that during normal learning, the brain shifts between different “modes” of activity as it discovers new rules. In the prefrontal cortex, groups of neurons reorganized into distinct, well-defined patterns as the mice learned. But when the researchers suppressed LC, those patterns became more vague and difficult to distinguish, as if the brain could no longer clearly switch to the correct learning mode.
Using machine learning tools to analyze the data, the scientists found that the brain activity did not clearly reflect the mouse’s learning stage or what choice it was likely to make next. They found that the prefrontal cortex, which keeps track of the current rules the mice should follow, was worsened.
“Since LC is affected in the early stages of neurodegeneration, our findings also have implications for aging and Alzheimer’s disease,” Yang said. “More broadly, our study provides a potential new target for therapeutic intervention by identifying neural circuits that may help restore cognitive flexibility and adaptive behavior.”
Yan was also joined in the research by Marco Nigro, Lucas Silva Tortorelli, Mahindra Galad and Natalie Zrebnik.
This research was supported by grants from the National Institute of Neurological Disorders and Stroke and the National Institute on Drug Abuse.
sauce:
University of California, Riverside
Reference magazines:
Nigro, M. others. (2026). Locus coeruleus modulation of prefrontal dynamics during attention switching in mice. e-life. DOI: 10.7554/eLife.105911.4. https://elifesciences.org/articles/105911
