A "herculean" genetic study just found a new way to treat ADHD
Attention depends on the brain’s ability to filter out distractions, but new research suggests this works best when background brain activity is quieter. Scientists found that lowering certain versions of the Homer1 gene improved focus in mice by calming neural noise. The effect was strongest during a critical developmental window. This approach could inspire new treatments for ADHD that work by reducing mental clutter instead of increasing stimulation.
Attention disorders such as ADHD occur when the brain has trouble separating meaningful signals from constant background input. The brain continuously processes sights, sounds, and internal thoughts, and focus depends on its ability to ignore distractions while responding to what matters. Most current treatments improve attention by increasing activity in brain circuits that control focus, especially in the prefrontal cortex.
A new study suggests a different solution. Instead of increasing brain activity, the research points to reducing baseline activity as a way to lower mental noise and improve attention.
A Gene Linked to Calmer Focus
In research published in Nature Neuroscience, scientists report that a gene called Homer1 plays an important role in attention by shaping how quiet or noisy the brain is at rest. Mice with reduced levels of two specific forms of this gene showed calmer brain activity and performed better on tasks requiring focus.
These findings may represent an early step toward new treatments aimed at calming the mind rather than stimulating it. The implications extend beyond ADHD, since Homer1 has also been linked to disorders 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 Target
When the research team began exploring the genetics of attention, Homer1 was not an obvious candidate. Scientists have long known the gene for its role in neurotransmission, and many interacting proteins of Homer1 have appeared in genetic studies of attention disorders, but Homer1 itself had not previously stood out as a key driver.
To investigate more broadly, the researchers analyzed the genomes of nearly 200 mice bred from eight different parental strains, including some with wild ancestry. This approach was designed to reflect the genetic diversity seen in human populations and allowed subtle genetic influences to emerge.
"It was a Herculean effort, and really novel for the field," says Rajasethupathy, who credits PhD student Zachary Gershon for leading the work.
A Large Genetic Effect on Attention
This large-scale genetic analysis revealed a clear pattern. Mice that performed best on attention tasks had much lower levels of Homer1 in the prefrontal cortex, a brain region essential for focus. The gene was located within a stretch of DNA that explained nearly 20 percent of the variation in attention 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."