Attention disorders such asADHDarise 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) inNature Neurosciencescientists report that a gene calledHomer1plays 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.

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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, sinceHomer1has 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,Homer1was not their expected target. The gene is well known for its role in neurotransmission—and many interacting proteins ofHomer1have appeared in human genetic studies of attention disorders—butHomer1itself 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 uniform laboratory populations.

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“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 ofHomer1in the prefrontal cortex, the brain region most closely tied to attention. The gene was located in a stretch ofDNAthat 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 ofHomer1were involved. Two specific versions,Homer1aand Ania3, stood out. Mice with naturally lower levels of these versions in the prefrontal cortex consistently performed better on attention tests.

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When researchers experimentally reduced these gene variants in adolescent mice during a brief developmental window, the results were dramatic. The animals became faster, accurate, and less easily distracted across several behavioral measures. Making the same genetic change in adult mice, however, produced no improvement, suggesting thatHomer1shapes 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 howHomer1affects brain cells. LoweringHomer1levels 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 precise and reliable responses.

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

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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 reducingHomer1improved 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.

BecauseHomer1and its interacting proteins have been linked to ADHD, schizophrenia, and autism, further research could reshape how scientists think about multiple neurodevelopmental conditions.

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Looking ahead, Rajasethupathy’s lab plans to continue exploring the genetic foundations of attention, with the goal of developing therapies that precisely adjustHomer1levels.

“There is a splice site inHomer1that 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: 22 December 2025,Nature Neuroscience.
DOI: 10.1038/s41593-025-02155-2

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