Layer 6b may be a key circuit in the brain for the control of attention. Credit: Timothy Zolnik and Matthew Larkum.

A layer deep in the cerebral cortex, which is the innermost layer of the mammalian brain, has recently been found to play a role in the regulation of brain states associated with wakefulness and attention.

This previously overlooked layer of the brain, known as layer 6b, has since become the focus of a growing number of research studies, yet its unique contribution to different mental processes has not yet been clearly elucidated.

Building on the findings of experiments involving mice, researchers at Humboldt University of Berlin and the Charité University of Medicine in Berlin devised a new theory that offers a possible explanation for the role of layer 6b in attention, consciousness and potentially other advanced mental functions.

This theory, available online as a preprint and set to be published in Neuron, suggests that neurons in layer 6b integrate internal state signals, such as those related to arousal and motivation, with goal-driven instructions from higher brain regions.

Via synaptic excitation (i.e., the activation of connected neurons), layer 6b is hypothesized to control reciprocal circuits interconnecting the cortex and the thalamus, known as thalamocortical loops.

"The theory grew out of years of work and discussions in Berlin during experiments we were conducting to understand a mysterious, almost ignored group of neurons buried deep in the cortex, called layer 6b, " Timothy Adam Zolnik, co-author of the paper, told Medical Xpress.

"When we finally revealed their connections and influence, we were surprised to find that, despite making up only a tiny fraction of cortical neurons, layer 6b neurons could powerfully 'light up' huge parts of the brain and even generate the rhythms linked to focused attention."

The newly uncovered association between layer 6b neurons and crucial attention processes inspired the researchers to continue exploring the contribution of this poorly understood region.

Ultimately, this led to the introduction of a new theory suggesting that layer 6b is a missing link in models of attention and cognition, which could improve the understanding of various neuropsychiatric disorders.

"The hypothesis that layer 6b controls attention is still under investigation, but our published results provide strong clues, " explained Zolnik.

"In mice, we used light to switch on layer 6b neurons and watched how the brain responded. In addition, we traced their connections with new mapping techniques that we developed, and we studied how their synapses behave and communicate with other brain circuits."

Combining these different experimental methods, the researchers gathered evidence that confirmed the key role of layer 6b in the regulation of brain states that are strongly associated with attention. The findings of their experiments with mice suggest that this previously ignored section of the cortex could be the central "controller" of attention.

"The biggest contribution of our theory is that it suggests that the brain's deepest layer, which has been largely ignored in neuroscience, may actually be a keystone for attention and other higher cognitive functions, " said Zolnik.

"If that's true, it changes how we think about perception and our everyday experience, as well as disorders where attention goes awry, like ADHD or autism."

In the future, Zolnik and his colleagues plan to conduct further experiments to help refine and adjust their theory, potentially deepening the present understanding of layer 6b and its contribution to attention.

Concurrently, their work could inspire other research teams to study layer 6b and assess its possible role in attention deficit hyperactivity disorder (ADHD) or other neuropsychiatric conditions.

"We're now running targeted experiments to pin down just how far layer 6b's influence on cognition goes, " added Zolnik. "At the same time, we're examining human layer 6b neurons in great detail, asking whether they have special features that might help explain what makes human thought unique."

Written for you by our author Ingrid Fadelli, edited by Sadie Harley, and fact-checked and reviewed by Robert Egan—this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive. If this reporting matters to you, please consider a donation (especially monthly). You'll get an ad-free account as a thank-you.

More information: Timothy Zolnik et al, The Layer 6b Theory of Attention. (2025). DOI: 10.20944/preprints202506.2342.v1  Journal information: Neuron

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