Neuronal Activity Maps Challenge Traditional Anatomical Divisions of Prefrontal Cortex

For more than a century, maps of the brain have been based on how brain tissue looks under the microscope. These anatomical maps divide the brain into regions according to structural variations in the tissue. But do these divisions really reflect how the brain works? A new study on mice from Karolinska Institutet, published in Nature Neuroscience, suggests that this is often not the case.

By describing the brain in terms of electrical activity of its neurons, the researchers have found a new way to understand the functional organisation of the prefrontal cortex, the brain region responsible for planning, decision-making, and other advanced cognitive functions.

Considering that deviations in prefrontal cortex function have been linked to virtually all psychiatric disorders, it is surprising how little is known about how this region actually works."

Marie Carlén, Professor, Department of Neuroscience, Karolinska Institutet, Sweden

Did Not Align With Previous Maps

Her research group recorded and analysed the activity of more than 24,000 neurons in awake mice and created the first activity-based maps of the prefrontal cortex. The maps of spontaneous and cognition-related neuron activity did not match the traditional, tissue-based maps.

"Our findings challenge the traditional way of defining brain regions and have major implications for understanding brain organization overall," says Marie Carlén.

The researchers found that the activity patterns of neurons reflected the hierarchy of information flow in the brain rather than the structure of the tissue. Neurons with slow, regular activity turned out to be characteristic of the prefrontal cortex, which sits at the top of this hierarchy. The same activity pattern also marked regions at the top of the prefrontal cortex's own internal hierarchy. Slow, regular activity is thought to characterize the integration of information flows, a process that is central to cognitive functions such as planning and reasoning.

Different Neuronal Activity Patterns Work Together

Professor Carlén and her colleagues discovered that neurons involved in decision-making were concentrated in regions high up in the prefrontal hierarchy. Surprisingly, these neurons were characterised by very fast activity patterns.

"This suggests that cognitive processes rely on local collaboration between neurons whose activity patterns complement one another. Some neurons appear to specialize in integrating information streams, while others have high spontaneous activity that supports quick and flexible encoding of information, for instance, information needed to make a specific decision," says Marie Carlén."

The study was funded by, among others, the Knut and Alice Wallenberg Foundation, the Wenner-Gren Foundation, and the Swedish Brain Foundation. 

Source:
Journal reference:

Le Merre, P., et al. (2026). A prefrontal cortex map based on single-neuron activity. Nature Neuroscience. doi: 10.1038/s41593-025-02190-z. https://www.nature.com/articles/s41593-025-02190-z

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