Scientists identify an ancient brainstem network that acts as an attentional selection engine

A recent study published in Nature Communications provides evidence that an evolutionarily ancient group of brainstem neurons is required for the brain to filter out distractions and focus on important spatial information. The findings indicate that these specific inhibitory cells are specialized for helping animals select the correct target of attention, without affecting basic perception or physical movement. The discovery of these neurons in mice could represent an initial step toward developing targeted treatments for attention disorders.

To navigate a complex environment, animals must constantly filter sensory input to select the most important information. The importance of a stimulus, known as its priority, is a combination of two factors. One factor is physical salience, which is a bottom-up signal driven by how much an object stands out, like a bright flash of light. The other factor is behavioral relevance, which is a top-down signal driven by the animal’s current goals, such as searching for a specific shape that leads to a food reward.

Historically, the dominant view in neuroscience proposed that sophisticated spatial attention was managed primarily by advanced networks in the prefrontal cortex, a region highly developed in humans and other primates. However, animals with less developed outer brains, such as birds, fish, and rodents, still show impressive abilities to focus their attention. This observation suggests that an older, deep brain structure might be responsible for this fundamental cognitive skill across different vertebrate species.

“If we really go back in evolution, for hundreds of millions of years, birds have had this ability, fish have had this ability. And they do not typically have a highly developed prefrontal cortex, so how does the brain solve this problem?” said lead author Ninad Kothari, a postdoctoral fellow in the Department of Psychological and Brain Sciences at Johns Hopkins University. “We were able to identify an evolutionarily old region in the brainstem which affords this ability.”

The impetus to investigate these neurons in mammals stems from earlier studies of birds, frogs, and turtles conducted by Shreesh Mysore, a neuroscientist at Johns Hopkins University who studies neural circuits tied to behavior, and other scientists. Previous research indicates that a midbrain area called the superior colliculus is involved in processing spatial information. Because the superior colliculus is a major hub for both sensation and movement, disrupting it tends to impair basic sight and physical coordination.

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This makes it difficult to determine if the superior colliculus itself computes attention, or if another specialized brain module handles the competitive filtering of distractions. The authors of the new study focused on an older group of brain cells called the parabigemino-lateral tegmental inhibitory complex, or PLTi. These specific brainstem neurons produce a chemical messenger called GABA, which tends to reduce the electrical activity of other nearby neurons.

The researchers first mapped the anatomical connections of PLTi neurons in adult mice. Using fluorescent tracers, they found that these cells receive highly organized input from the superior colliculus and send long-range projections directly back to it. By using a technique called chemogenetics, which allows scientists to selectively activate or silence specific cells using a custom drug, the authors demonstrated that activating PLTi neurons directly inhibits the superior colliculus.

To test spatial attention, the researchers trained freely moving mice on a touchscreen test known as the flanker task. The mice had to interact with a screen through a custom mask with three holes. They learned to nose-touch the screen to report the orientation of a central target image, such as a vertical or horizontal striped pattern.

At the same time, a distracting peripheral image, called a flanker, appeared on the screen to compete for the animal’s attention. The flanker could be congruent, meaning it shared the target’s orientation, or incongruent, meaning it displayed the opposite orientation. The authors systematically altered the visual contrast of the flanker to change its physical salience.

The researchers then used chemogenetics to bilaterally silence the PLTi neurons in six genetically modified mice. The scientists administered a specific drug that turned off these targeted brain cells while the mice performed the flanker task. With the PLTi neurons deactivated, the mice showed severely impaired performance on the incongruent trials, indicating a massive increase in distractibility. “When we inactivate these neurons, the mice become hyper distractible,” Kothari said.

“A hallmark of ADHD is that even faint distractors draw attention away, and that’s exactly what we see here when these neurons are silenced,” said Mysore. “But the very next day, when the neurons are turned back on, the same animal can ignore distractors again, even very strong ones.”

Notably, the mice still performed accurately when the flanker matched the target, or when the target appeared alone. To check if the PLTi neurons merely reacted to raw visual intensity, the researchers replaced the task-relevant flanker with a simple block of light that held no task information. Under these conditions, silencing the PLTi neurons did not harm the animals’ performance. This provides evidence that PLTi neurons evaluate both physical intensity and goal-oriented relevance to guide behavior.

Because attention is closely tied to basic sensory processing and movement, the researchers checked if silencing the PLTi neurons simply broke the animals’ ability to see or move properly. They analyzed data from four mice performing a basic single-target visual test and found no changes in visual perception. Using calibrated 3D video cameras, the authors tracked the physical head movements of the mice and their choices between the upper and lower response ports.

The physical movement trajectories and the motor choices remained entirely unchanged. The only physical difference was that the mice reacted slightly faster across all task conditions when the PLTi neurons were silenced.

“The only thing impaired was their ability to take the competing pieces of information, compare them, and pay attention to the location with the most important information,” Mysore said. “This part of the brain is like an attentional selection engine. It helps solve the question: ‘What is most important information I should pay attention to right now?'”

Using mathematical models and brain recordings, the researchers determined that this faster reaction time occurred because the superior colliculus became generally overactive without the constant, calming inhibition from the PLTi neurons. This supports the idea that the PLTi acts as a specialized module specifically designed to filter out distractions.

In natural environments, the brain must make strict choices about which stimulus is the most important. This process relies on a subjective decision boundary, which is the exact point where a distractor suddenly overrides a target. The authors analyzed the precision of this boundary in the mice, finding that healthy animals display a sharp, highly precise transition point that acts like a winner-take-all filter.

When the PLTi neurons were silenced, this decision boundary shifted significantly, allowing much weaker distractors to inappropriately capture the animals’ attention. The boundary also became wider and less precise, meaning the animals’ choices were less categorical.

To understand the underlying brain mechanisms, the scientists recorded electrical activity directly from 16 individual neurons in the superior colliculus of head-fixed mice. They presented competing visual stimuli, which consisted of expanding dark dots on a screen, to see how the neurons processed conflicting information. Normal superior colliculus neurons showed a sharp, precise transition in their firing rates when a distracting stimulus outcompeted a central target.

When the researchers silenced the PLTi neurons during these recordings, the neural signals in the superior colliculus lost their sharp precision. The neural boundary shifted in the exact same way that the behavioral boundary did, with weaker distractors heavily suppressing the main target signal. This suggests that the PLTi orchestrates competitive interactions within the superior colliculus to create a precise signal for selective spatial attention.

While the study provides detailed evidence for the role of the PLTi in attention, there are potential limitations and areas for future exploration. The authors note that entirely silencing the PLTi still allowed the mice to perform slightly above random chance. This suggests that other brain regions likely contribute to comparing competing stimuli, even if they operate at a lower resolution without the PLTi.

Another potential misinterpretation is assuming that the PLTi acts as a passive relay station rather than an active computing center. The detailed structural logic of how the mammalian PLTi and the superior colliculus circuits communicate step-by-step remains unknown. Future research will need to map these exact local connections to fully grasp the underlying neural wiring.

In addition, scientists do not yet know how this deep brainstem network interacts with the highly evolved networks in the cortex. Understanding how these different brain circuits cooperate to drive spatial attention will be necessary to build a complete picture of sensory processing. Resolving these questions might help explain the attention deficits observed in atypical cognitive conditions, such as schizophrenia, autism, and ADHD.

The researchers plan to investigate the degree to which these specific neurons are involved in human attention. If their function is affected in neurodivergent conditions, it could lead to the development of novel, targeted drugs.

“All the evidence to date suggests that these neurons exist in humans too,” said Mysore. “But are they responsible for selective spatial attention in humans? An exciting hypothesis is that they play a crucial role.”

The study, “Evolutionarily old brainstem neurons are required for the control of selective spatial attention,” was authored by Ninad B. Kothari, Arunima Banerjee, Qingcheng Zhang, Wen-Kai You, and Shreesh P. Mysore.