A groundbreaking study has revealed that the neural organization of the prefrontal cortex-an area crucial for complex cognitive functions-may not align with conventional tissue-based maps. Led by researchers at the Karolinska Institutet, this research challenges long-held views of brain architecture by presenting activity-based maps derived from the real-time behavior of thousands of individual neurons in awake mice.Thes findings could have significant implications for understanding mental health disorders linked to prefrontal cortex dysfunction.
Bild:
Rubrik:
Marie Carlén.
Foto: Magnus Bergström, KAW
– Med tanke på att avvikelser i prefrontalkortex funktion har kopplats till praktiskt taget alla psykiska sjukdomar vet man förvånansvärt lite om hur denna region fungerar, säger Marie Carlén, professor vid institutionen för neurovetenskap vid Karolinska Institutet.
Stämde inte överens med tidigare kartor
Table of Contents
Hennes forskargrupp registrerade och analyserade aktiviteten hos mer än 24 000 nervceller i vakna möss och skapade de första aktivitetsbaserade kartorna över prefrontalkortex. Kartorna över nervcellernas spontana och kognitionsrelaterade aktivitet stämde inte överens med de traditionella, vävnadsbaserade kartorna.
– Våra resultat utmanar det traditionella sättet att definiera hjärnregioner och har stor betydelse för hur hjärnans organisation kan utforskas, säger Marie Carlén.
Forskarna fann att nervcellernas aktivitetsmönster återspeglade hierarkin i hjärnans informationsflöde, och inte vävnadsstrukturen. Nervceller med långsam, regelbunden aktivitet visade sig vara karaktäristiskt för prefrontalkortex, som sitter högst upp i hierarkin. Samma aktivitetsmönster utmärkte även områden högst upp i prefrontalkortex egna hierarki. Långsam, regelbunden aktivitet anses känneteckna integrering av informationsflöden, en process som är central för kognitiva funktioner som planering och resonemang.
Nervcellers olika aktivitetsmönster samverkar
Carlén och hennes kollegor upptäckte att nervceller som är involverade i beslutsfattande var koncentrerade i områden högt i den prefrontala hierarkin. Överraskande så karaktäriserades dessa nervceller av mycket snabba aktivitetsmönster.
– Detta tyder på att kognitiva processer bygger på lokala interaktioner mellan nervceller med komplementerande aktivitetsmönster. Vissa nervceller verkar specialiserade på integration av informationsflöden och andra har hög spontan aktivitet som passar snabb och flexibel kodning av information, till exempel information som behövs för att fatta ett specifikt beslut, säger Marie Carlén.
Studien finansierades bland annat av Knut och Alice Wallenbergs Stiftelse, Wenner-Gren-stiftelsen, och Hjärnfonden.
Publikation
“A prefrontal cortex map based on single-neuron activity”, Pierre Le Merre, Katharina Heining, Marina Slashcheva, Felix Jung, Eleni Moysiadou, Nicolas Guyon, Ram Yahya, Hyunsoo Park, Fredrik Wernstal, Marie Carlén, Nature Neuroscience, online 20 januari 2026, doi: 10.1038/s41593-025-02190-z.
Researchers have created the first activity-based maps of the prefrontal cortex, a brain region critical for higher-level cognitive functions, potentially reshaping our understanding of mental health and neurological disorders. Understanding the prefrontal cortex is vital, as disruptions in its function are linked to nearly all psychiatric illnesses, yet surprisingly little is known about how it operates.
A team led by Marie Carlén, a professor at the Department of Neuroscience at Karolinska Institutet, recorded and analyzed the activity of over 24,000 neurons in awake mice. The resulting maps, which detail both spontaneous and cognition-related neural activity, differed significantly from traditional, tissue-based maps of the brain.
“Our results challenge the traditional way of defining brain regions and have major implications for how the brain’s organization can be explored,” said Carlén. The study, published online January 20, 2026, in Nature Neuroscience, suggests that the brain’s organization is better understood by examining information flow rather than physical structure.
The researchers discovered that patterns of neural activity mirrored the brain’s hierarchical information processing, rather than its tissue structure. Neurons exhibiting slow, regular activity were characteristic of the prefrontal cortex, which sits at the top of the brain’s hierarchy. This same activity pattern was also found in areas highest within the prefrontal cortex’s own hierarchy. Slow, regular activity is believed to be key to integrating information – a process central to cognitive functions like planning and reasoning.
Interestingly, neurons involved in decision-making were concentrated in the higher levels of the prefrontal hierarchy, but were characterized by very rapid activity patterns. “This suggests that cognitive processes are built on local interactions between neurons with complementary activity patterns,” Carlén explained. “Some neurons appear specialized in integrating information flows, while others have high spontaneous activity suited for rapid and flexible encoding of information, such as that needed to make a specific decision.”
The findings highlight the complex interplay between different types of neurons and could lead to new insights into the neural basis of cognitive function and mental illness. The research was supported by the Knut and Alice Wallenberg Foundation, the Wenner-Gren Foundation, and the Swedish Brain Foundation.
Publication
“A prefrontal cortex map based on single-neuron activity”, Pierre Le Merre, Katharina Heining, Marina Slashcheva, Felix Jung, Eleni Moysiadou, Nicolas Guyon, Ram Yahya, Hyunsoo Park, Fredrik Wernstal, Marie Carlén, Nature Neuroscience, online 20 januari 2026, doi: 10.1038/s41593-025-02190-z.
