Wayne State researcher receives $1.6 million NIH grant to study epileptic brain activity

June 4, 2008

DETROIT- Dr. Jeffrey Loeb, associate professor of Neurology, member of the Wayne State University/DMC Comprehensive Epilepsy Program, and associate director of the Center for Molecular Medicine and Genetics in WSU's School of Medicine, received a grant for $1.6 million from the National Institutes of Health to study abnormal epileptic brain activities present in patients with recurrent seizures.

Patients who do not respond to medicines for their seizures often benefit from the surgical removal of brain regions that produce seizures. "Our research program has taken an entirely novel approach to understand what is different about human brain regions that display abnormal epileptic brain activities," Dr. Loeb said. "This is an extraordinary opportunity to learn not only about epilepsy, but also how the human brain works normally. This project is made possible by the generosity of our patients who have consented to donate their removed brain tissues for our studies."

Though the removal of brain tissue has been used to cure epilepsy for decades, Loeb's lab is the first in the world to study the tissue in relation to a particular abnormal activity called "interictal spiking" - the minor, more frequent electrical discharges in the brain that occur between seizures. Though they're not fully understood, research suggests interictal spikes are closely related to epileptic seizures in the brain. Loeb's research program has identified many new genes from human epileptic brain tissues and shown that the amount of these gene activations in epileptic parts of a patient's brain directly correlates with the amount of interictal spiking.

"It is amazing that these tiny discharges actually have more influence over the genes associated with epilepsy than seizures do," Loeb said. "Up until now, they've been a bit of a mystery and under-appreciated. What they're doing, nobody really knows, but there's no piece of brain tissue that has seizures that doesn't have interictal spiking."

Funds from the NIH will be used to take a detailed inventory of a patient's interictal spikes, including frequency, amplitude, and correlation with the genes that underlie these activities. Using this information, the spikes will be mapped onto a 3-dimensional rendering of the human brain and used to investigate the relationship between interictal spikes and seizures, as well as the reasons for why the spikes sometimes spread to other parts of the brain.

In addition to learning valuable information on interictal spikes, Loeb also expects to gain a better understanding of the effects of brain tissue removal, which could improve surgical procedures for those with epilepsy.

Epilepsy is one of the most frequently diagnosed neurological disorders, affecting approximately one percent of the world's population. Though rare cases are hereditary, the majority of patients develop the disease from stroke, tumor or some head impact where the brain is injured. If the patient is going to develop epilepsy, it usually takes 6 months to a year for seizures to start.

"Once interictal spikes are better understood, we plan to develop new treatments that for the first time could prevent epilepsy from ever occurring after any injury to the brain," Loeb said. "Right now there are no treatments to prevent epilepsy. If you hit your head, wouldn't it be nice to take a morning after pill and never get this debilitating and often lifelong disease?"

In addition to Dr. Loeb, Wayne State collaborators include Drs. Aashit Shah and Darren Fuerst of the Department of Neurology, and Dr. Jing Hua from the Department of Computer Science. Dr. Rajeev Agarwal from Concordia University in Montreal Canada is also a part of this international, multidisciplinary team.

Wayne State University is one of the nation's pre-eminent public research universities in an urban setting. Through its multidisciplinary approach to research and education, and its ongoing collaboration with government, industry and other institutions, the university seeks to enhance economic growth and improve the quality of life in the city of Detroit, state of Michigan and throughout the world.