Timing is everything when it comes to humans functioning.
Our ability to guide our behaviors according to how we mentally keep track of time is based in the brain’s prefrontal cortex. Historically, this helped us find food and evade predators. Today, it enables everyday tasks like driving, crossing the street, and answering a phone.
For people with mental health disorders such as schizophrenia or neurological conditions like Parkinson’s disease, the inability to complete these types of everyday but high-order cognitive processes can be devastating. The location of this function in the prefrontal cortex is also why these conditions have been traditionally difficult to treat.
New findings from researchers at the University of Iowa Carver College of Medicine provide a clearer understanding of the cognitive processes that occur in the prefrontal cortex that guide timing-related thinking and behaviors. In a study published May 6 online in the Proceedings of the National Academy of Sciences, UI researchers mapped out the exact motion and direction of neurons in different parts of the prefrontal cortex during timed activities. It’s knowledge that could ultimately guide the development of new and more precise treatments for diseases that affect the prefrontal cortex.
“These findings illuminate the circuits that are involved in a temporal controlled action,” says Nandakumar Narayanan, MD, PhD, UI professor of neurology. “If we can understand where and how to deliver highly effective interventions, we might be able to make meaningful progress in some of these very difficult-to-treat brain disorders.”
In the study, the researchers looked at neurological activity in the prefrontal cortex of mice who were given a timed task. They found that neurons are active in different ways within the prefrontal cortex: In the mediodorsal thalamus, neurological activity ramps down while in the dorsomedial striatum, activity ramps up.
“The activity is like an alarm clock that, instead of going off at the right time, it slowly ramps up its activity until the time you’re supposed to wake up,” Narayanan says.
This kind of progression of movement was a surprise to the research team and not something that they had been able to measure before. Narayanan credits Xi Ding, a graduate student in molecular medicine in his lab and the research paper’s lead author, with developing the technology to allow this kind of measurement to happen.
In addition to the activity of neurons, the team also identified the molecular “fingerprints” left by the movement of neurons in this way. Together, these two findings create a map of what happens in the brain during timing-related activities and help advance the fundamental understanding of prefrontal cortex function and dysfunction. By knowing specifically where things go wrong in the brain that disrupt a person’s ability to perceive and measure the passage of time, they can target the broken systems with drug treatments and intervention therapies.
Having this map also adds more ways that researchers and clinicians can identify brain diseases and conditions.
“Patients with brain diseases have a variety of dysfunction in the prefrontal cortex, and looking at the timing of movements — even something as subtle as the way you use a phone, the way you walk, or the way you move through the world — may provide insight into how the frontal cortex is doing,” says Narayanan, who also is the associate director of the Iowa Neuroscience Institute.
With these findings, researchers and clinicians may look to the prefrontal cortex for signs of disease or impairment through electroencephalography (EEG), a well-established technique that records real-time electrical activity in the brain.
The study was funded through grants from the National Institute of Neurological Disorders and Stroke, the Fraternal Order of Eagles Neurodegeneration Fund, and the Athens Fund.