Rosalind Franklin University of Medicine and Science researcher William Frost, PhD, director of the Stanson Toshok Center for Brain Function and Repair within the university’s Brain Science Institute, has been awarded a $1.95 million grant from the National Institutes of Health to study how the brain develops and sustains focus when responding to novel stimuli.

“We hope insights gained from this study of the principles of rapid network focusing will help promote novel approaches for treating or preventing declines in cognitive function in aging and disease,” said Dr. Frost, an electrophysiologist, professor and discipline chair of Cell Biology and Anatomy.

Dr. Frost and his team are in the vanguard of scientists using large-scale recordings to watch how neurons interact and participate in networks to process information, store memory and generate behavior. The grant will allow them to test their hypothesis that neurons’ variable network participation, even when presented with identical inputs, is an adaptive feature that reflects a “focusing” mechanism innate to many networks. They theorize that focusing allows networks to rapidly and flexibly rearrange which neurons are called upon to process specific information in the context of the moment.

“We hope to uncover the mechanisms underlying what may be an important versatility process for healthy function in many brain networks — one that allows them to rapidly reallocate neurons to suit a specific context,” said Dr. Frost, who has authored more than 50 peer-reviewed articles on neural networks and related topics.

The hypothesis emerged unexpectedly from the team’s large-scale recordings of the rhythmic escape swim network of the marine mollusk Tritonia diomedea. During the initial seconds of responding to an unexpected aversive sensory input, Tritonia's swim motor program rapidly tunes itself, pulling many initially-silent neurons into the bursting population and driving others out, apparently optimizing itself for escape. Researchers observed that this focused state remained as a memory for the stimulus for several minutes, enabling a stronger, faster-onset motor program should the same stimulus recur.

Many studies in vertebrates have reported rapid growth in the size of responding networks with repeated stimulation, but the mechanisms and purpose of such phenomena are poorly understood.

“Mechanisms of stimulus-induced network focusing,” a five-year, NIH R01 grant, was awarded by the National Institute of Neurological Disorders and Stroke (NINDS).

Dr. Frost is also the recipient of a three-year, $600,000 NIH Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) subcontract to create the first transgenic mollusc model for neuroscience research. While the award ended in August 2021, the work by the five-lab team continues under a no-cost extension until August, 2022. The BRAIN subcontract was part of a large award to researchers from five institutions, which in addition to RFU, include the University of Massachusetts, Harvard University, the University of California San Diego and the University of Maryland.

Twenty million Americans and 16% of households are experiencing some form of brain disease or neurological condition, according to the United Brain Association. One in five U.S. adults experience mental illness, reports the National Alliance on Mental Health. Neurological and mental illness often overlap and many such diseases have no effective treatment. The annual economic impact is more than $800 billion.

“We’re grateful for the support of the NIH and programs like the BRAIN Initiative, as our neuroscientists and labs employ state-of-the-art tools that allow us to inch closer to understanding how the brain functions in health and disease,” said RFU Executive Vice President for Research Ronald Kaplan, PhD. “We are energized by the novel research underway in our Brain Science Institute and its three centers, including Dr. Frost’s area of brain function and repair.”