New Maps Challenge Traditional Way of Defining Brain Regions

For more than a hundred years, scientists have classified brain regions by their physical appearance under a microscope. These traditional maps divide the brain based on visible structural differences in tissue. A new study from Karolinska Institutet, published in Nature Neuroscience, challenges that view by focusing instead on the electrical behavior of neurons. The research suggests that maps drawn from tissue structure do not always reflect how the brain actually functions. 

Led by Professor Marie Carlén, the research team studied the prefrontal cortex, a region central to planning, decision-making, and other complex mental activities. “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,” says Carlén.

Using awake mice, the team recorded the activity of more than 24,000 neurons, producing the first maps of the prefrontal cortex based on real-time neuron firing patterns. These activity-based maps—covering both spontaneous and cognition-related activity—did not align with conventional, tissue-based models. “Our findings challenge the traditional way of defining brain regions and have major implications for understanding brain organization overall,” Carlén explains.

The study revealed that neuronal activity followed a hierarchy of information flow across the brain rather than structural boundaries. Regions near the top of this hierarchy, such as the prefrontal cortex, displayed neurons that fired slowly and regularly. This type of activity appeared to characterize areas responsible for integrating information, a critical process for higher reasoning and planning. Moreover, the same slow, steady firing pattern was observed in subregions at the top of the prefrontal cortex’s own internal hierarchy, indicating a consistent principle of organization.

The researchers also identified neurons involved in decision-making, concentrated in upper layers of this hierarchy. These neurons, in contrast, showed fast electrical activity. “This suggests that cognitive processes rely on local collaboration between neurons whose activity patterns complement one another,” says Carlén. “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.”