Theory Proposes Key Role for Cortex Layer 6b in Attention and Higher Mental Functions
A new theory from researchers at Humboldt University of Berlin and the Charité University of Medicine in Berlin is turning heads in neuroscience. It suggests that layer 6b, a deep and often ignored part of the cerebral cortex, could be central to how the brain manages attention, wakefulness, and advanced mental functions like motivation and consciousness.
Layer 6b sits at the very base of the cortex — the outer layer of the brain responsible for perception, reasoning, memory, and voluntary action. For decades, scientists paid little attention to this layer because it’s small, hard to study, and thought to be a leftover from early brain development. But new work is showing that this unassuming layer may be a crucial control center in the brain’s attention system.
The Overlooked Layer of the Brain
The cerebral cortex has six layers, each with unique cell types and functions. Layer 6b is the deepest one, bordering the white matter that connects different brain regions. It makes up only a small fraction of the cortex’s neurons, yet the new theory suggests its influence is far greater than its size implies.
Researchers have found that layer 6b neurons are special for several reasons. First, they respond strongly to orexin (also known as hypocretin), a neurochemical that regulates arousal and wakefulness. This connection links layer 6b directly to the systems that determine whether we are alert or drowsy. Second, its neurons send long-range connections to other parts of the cortex and the thalamus, a key hub that relays sensory and cognitive information.
The thalamus and cortex work together in loops — called thalamocortical circuits — that are essential for attention and consciousness. The Berlin research team believes that layer 6b helps control these loops, fine-tuning how information flows depending on what the brain is focusing on.
Building a Theory from Experiments
This new theory — called “The Layer 6b Theory of Attention” — is built on years of experiments, mainly involving mice. By using techniques like optogenetics (which allows scientists to switch neurons on or off with light) and detailed neural mapping, the team studied how layer 6b interacts with other brain areas.
When they activated layer 6b neurons, they noticed that large parts of the brain “lit up” with synchronized activity. This activation also triggered gamma brain waves, the fast electrical rhythms associated with focused attention and cognitive processing. Conversely, when layer 6b was quiet, the brain produced slow oscillations, typical of sleep-like or inattentive states.
These results led the researchers to propose that layer 6b may act like a “volume dial” for attention — helping the brain shift between low-attention and high-focus modes. Its signals could merge internal states (such as motivation and arousal) with goal-directed commands from higher cortical regions, creating a bridge between how we feel and what we choose to focus on.
A Key Player in Thalamocortical Communication
One of the most striking parts of the theory is how layer 6b might regulate communication between the cortex and the thalamus. The cortex depends on the thalamus not just for sensory information but also for coordinating activity across brain regions.
Layer 6b is thought to influence these thalamocortical loops by sending fast excitatory signals that can activate or stabilize the network. Unlike typical neuromodulators, which work slowly, layer 6b neurons appear capable of rapid, precise control.
Moreover, the team suggests that layer 6b synapses — the connections between neurons — behave differently from most cortical synapses. Instead of weakening with repeated activity (a process called depression), these may strengthen with ongoing activation (known as facilitation). This means that when layer 6b is repeatedly engaged, it could sustain attention and stabilize brain rhythms even during long periods of focus.
Implications for Attention and Mental Disorders
If this theory is correct, it could reshape how scientists understand attention, consciousness, and cognitive control. For instance, disorders like ADHD, autism, and schizophrenia all involve irregular patterns of attention and brain-state regulation. If layer 6b helps maintain stable attention through its influence on thalamocortical loops, then malfunctions in this layer could contribute to these conditions.
The findings could also shed light on sleep disorders, such as narcolepsy, which are linked to disruptions in orexin signaling — the same neurochemical system that layer 6b interacts with.
Future research aims to test these ideas in more detail. The Berlin team plans to conduct further experiments to see how far layer 6b’s influence on cognition extends, and whether similar mechanisms exist in the human brain. They’re also examining human layer 6b neurons under the microscope to look for special structural or molecular traits that might explain the uniqueness of human thought.
Why Layer 6b Matters
The discovery that such a thin and neglected layer could hold a key role in attention is exciting because it fills a long-standing gap in neuroscience. Scientists have long known that attention depends on both neuromodulatory systems (like dopamine, acetylcholine, and orexin) and cortical feedback circuits. What has been missing is an explanation of how these two systems interact.
Layer 6b might be that missing link — integrating chemical signals about the brain’s internal state with the precise wiring of cortical and thalamic circuits. In this view, attention is not just a psychological state but a biological balancing act between motivation, sensory input, and cortical coordination.
Broader Context: Understanding the Layers of the Cortex
To understand why layer 6b is so intriguing, it helps to look at the cortex’s layered organization.
- Layers 1–3 handle communication across different cortical regions.
- Layer 4 is the main input zone for sensory information.
- Layer 5 sends outputs to motor areas and subcortical structures.
- Layer 6 connects back to the thalamus, forming a loop that shapes perception and cognition.
Layer 6b, at the very bottom, may be a developmental remnant of the brain’s early subplate, which helps guide wiring in embryos. But in adults, evidence is emerging that it continues to function — helping to set and stabilize global brain states.
Recent reviews, such as “Structure and Function of Neocortical Layer 6b” (Feldmeyer et al., 2023), have highlighted its unique cell types and connectivity. Some of its neurons reach far across cortical areas, and others connect directly to subcortical regions like the superior colliculus, which is involved in attention and eye movements.
All of this paints a picture of layer 6b as a strategic control layer, capable of influencing multiple systems simultaneously — from sensory processing to conscious awareness.
The Road Ahead
While this theory is still under investigation and needs validation in primates and humans, it opens new paths for research. Neuroscientists could explore targeted stimulation or modulation of layer 6b neurons to see how it affects attention and cognition. Neuroimaging experts might also look for signatures of layer 6b activity in the human cortex using high-resolution MRI or electrophysiology.
If proven true, the Layer 6b Theory of Attention could mark a shift in how we understand brain organization. It reminds us that sometimes, the smallest and most overlooked structures can hold the biggest secrets about how the mind works.
Research Paper: The Layer 6b Theory of Attention (Zolnik & Larkum, 2025)
