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Scientists at the Lieber Institute for Brain Development may have identified in mice a key mechanism of attention that could help develop attention-enhancing drugs in humans, according to new research published in the journal Neuropsychopharmacology.

“Paying attention for long periods of time takes a lot of work and is tiring,” says Gregory Carr, Ph.D., a co-author of the paper and a Lead Investigator in the Drug Discovery Division at the Lieber Institute for Brain Development. “Over time, your performance decreases.”

Cognitive dysfunction is a common symptom of schizophrenia, and difficulty paying attention is part of that. Scientists use touchscreen tests in humans and mice, including rewards for good performance, to measure attention.

“For all people, performance in sustained attention tasks is best at the beginning of a session and deteriorates over time,” says Dr. Carr. “One of the major deficits in schizophrenia is a faster onset of inattention and a steeper decrease in performance.”

A core tenet of translational science—the process of taking discoveries from the lab to the clinic, where they can improve the lives of actual patients—is finding animal models that mimic human responses and can tell us more about the biological mechanisms behind behavioral issues such as attention. If the mechanisms behind attention in mice correlate to the human brain, scientists could develop drugs to target and manipulate those mechanisms to improve attention and combat this cognitive deficit in humans.

“Mice have the same issues we do with maintaining focus over time during a task,” Dr. Carr says. “Their performance will be really high at the beginning and decrease over time.”

In their research just published in Neuropsychopharmacology, Dr. Carr and the team, including Lieber Institute Lead Investigator Keri Martinowich, Ph.D., looked for neural circuits that might play crucial roles in this process of attention and inattention. They found interesting electrical activity in the locus coeruleus (LC) and prelimbic cortex (PrL), two inter-connected regions previously implicated in attentional processes.

“We think we’ve identified a biomarker that correlates with performance and may provide a mechanism for maintaining focus over time,” says Dr. Carr.
The typical method of improving attention in humans is prescribing psychostimulants, such as amphetamine and methylphenidate, which are FDA-approved for attention-deficit/hyperactivity disorder (ADHD). “Unfortunately, for people with schizophrenia, these drugs can actually exacerbate any hallucinations and delusions they may have,” Dr. Carr explains.

Dr. Carr and his team hope their newly identified biomarker will allow them to screen novel compounds, chemicals that might be more effective at treating inattention in humans.

“We’d love to develop a new therapy for people who need it,” he said. “In patients, their attentional deficits are directly correlated with their quality of life. If you can’t maintain focus, it is very difficult to accomplish your goals. We have a chance of having an outsized effect on quality of life for patients.”