This Brain Discovery Could Change How ADHD Is Treated

Attention disorders such as ADHD arise when the brain struggles to separate important signals from irrelevant noise. At any moment, the brain is flooded with information, and staying focused depends on filtering out distractions while responding to what matters most. Most current treatments address this problem by stimulating brain circuits involved in attention, particularly in the prefrontal cortex. These medications work by increasing neural activity.

New research points to a very different strategy. Instead of boosting activity, the study suggests that reducing background brain activity may help sharpen focus by lowering mental noise.

A Gene That Quietens the Brain

In a study published today (December 22) in Nature Neuroscience, scientists report that a gene called Homer1 plays a key role in regulating attention through this quieter approach. Mice with lower levels of two specific forms of the gene showed calmer brain activity and performed better on attention tasks.

The findings point toward a potential new direction for treating attention disorders. By calming neural activity rather than amplifying it, future therapies could offer an alternative way to improve focus. The research may also have broader relevance, since Homer1 has already been linked to conditions involving early sensory processing differences, including autism and schizophrenia.

“The gene we found has a striking effect on attention and is relevant to humans,” says Priya Rajasethupathy, head of the Skoler Horbach Family Laboratory of Neural Dynamics and Cognition at Rockefeller.

An Unexpected Genetic Discovery

When the research team began exploring the genetics behind attention, Homer1 was not their expected target. The gene is well known for its role in neurotransmission—and many interacting proteins of Homer1 have appeared in human genetic studies of attention disorders—but Homer1 itself had not previously been singled out as a major driver of attention.

To investigate further, the researchers analyzed the genomes of nearly 200 mice bred from eight different parental lines. Some of these mice had wild ancestry, a design meant to mirror the genetic diversity seen in humans. This wide range of variation allowed the team to detect genetic influences that are often missed in more uniform laboratory populations.

“It was a Herculean effort, and really novel for the field,” Rajasethupathy says, crediting PhD student Zachary Gershon for leading the work.

A Large Effect on Focus

This broad genetic scan revealed a striking pattern. Mice that performed best on attention tasks had much lower levels of Homer1 in the prefrontal cortex, the brain region most closely tied to attention. The gene was located in a stretch of DNA that explained nearly 20 percent of the differences in attention observed among the mice.

“That’s a huge effect,” Rajasethupathy says. “Even accounting for any overestimation here of the size of this effect, which can happy for many reasons, that’s a remarkable number. Most of the time, you’re lucky if you find a gene that affects even 1 percent of a trait.”

Timing Matters in Brain Development

Further experiments showed that not all forms of Homer1 were involved. Two specific versions, Homer1a and Ania3, stood out. Mice with naturally lower levels of these versions in the prefrontal cortex consistently performed better on attention tests.

When researchers experimentally reduced these gene variants in adolescent mice during a brief developmental window, the results were dramatic. The animals became faster, more accurate, and less easily distracted across several behavioral measures. Making the same genetic change in adult mice, however, produced no improvement, suggesting that Homer1 shapes attention during a critical period early in life.

Why Less Activity Leads to Better Focus

The most unexpected findings emerged when the team looked at how Homer1 affects brain cells. Lowering Homer1 levels caused neurons in the prefrontal cortex to increase their number of GABA receptors—the molecular brakes of the nervous system.

This change reduced unnecessary background activity while preserving strong, focused bursts of activity when meaningful cues appeared. Instead of firing constantly, neurons saved their activity for the right moments, leading to more precise and reliable responses.

“We were sure that the more attentive mice would have more activity in the prefrontal cortex, not less,” Rajasethupathy says. “But it made some sense. Attention is, in part, about blocking everything else out.”

A Calmer Approach to Treating Attention

For Gershon, the results felt intuitive. He lives with ADHD himself and says the project was personally meaningful. “It’s part of my story,” he says, “and one of the inspirations for me wanting to apply genetic mapping to attention.”

He was also the first to notice that reducing Homer1 improved focus by limiting distractions. In his view, the finding aligns with everyday experiences. “Deep breathing, mindfulness, meditation, calming the nervous system—people consistently report better focus following these activities,” he says.

Rethinking Future Treatments

Most existing treatments for attention disorders work by increasing excitatory signaling in the prefrontal cortex using stimulant medications. The new findings suggest another possibility: medications designed to calm neural activity instead.

Because Homer1 and its interacting proteins have been linked to ADHD, schizophrenia, and autism, further research could reshape how scientists think about multiple neurodevelopmental conditions.

Looking ahead, Rajasethupathy’s lab plans to continue exploring the genetic foundations of attention, with the goal of developing therapies that precisely adjust Homer1 levels.

“There is a splice site in Homer1 that can be pharmacologically targeted, which may be an ideal way to help dial the knob on brain signal-to-noise levels,” Rajasethupathy says. “This offers a tangible path toward creating a medication that has a similar quieting effect as meditation.”

Reference: “Genetic mapping identifies Homer1 as a developmental modifier of attention” by Zachary Gershon, Alessandra Bonito-Oliva, Matt Kanke, Andrea Terceros, Genelle Rankin, John Fak, Yujin Harada, Andrew F. Iannone, Millennium Gebremedhin, Brian Fabella, Natalia V. De Marco García, Praveen Sethupathy and Priya Rajasethupathy, 22 December 2025, Nature Neuroscience.
DOI: 10.1038/s41593-025-02155-2

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