Victims of head injuries or brain disease often become epileptic later in life, says Yevgeny Berdichevsky, but anticonvulsant drugs do not treat the underlying cause of seizures and have negative side effects. Moreover, three of 10 seizure patients develop intractable epilepsy that is unresponsive to drugs and requires brain surgery.
Researchers seeking methods of preventing seizures have treated animals with drugs, says Berdichevsky, assistant professor of electrical and computer engineering. But these studies are expensive and often require months of work to acquire one data point.
While working at Massachusetts General Hospital, Berdichevsky found he could take a brain slice from a rat, monitor its neural signals and observe the development of epilepsy in just a few weeks. At Lehigh, where he directs the Neural Engineering Lab, Berdichevsky tests drugs on animal brain slices in hopes of finding a medication that can treat posttraumatic epilepsy.
He and his group take samples from the hippocampus, the part of the brain where learning and memory are controlled and where epilepsy is typically found. The researchers cause trauma to mimic a penetrative head injury and then take electrical recordings of the brain sample to test the ability of drugs to delay or prevent seizures.
Borrowing from techniques used in microelectronics, they can fit four brain slices into a small space on a neural recording chip. The extremely dense experiments are tracked by computer and automated algorithms that can yield meaningful data within two weeks.
The brain slice cultures preserve connections between neurons. The group has designed multiple electrode array chips, or MEAs, to record electrical activity continuously. Parallel recording of several cultures speeds the experiments. Berdichevsky’s goal is to perform as many as 100 experiments on a chip.
Electrical recordings show abnormal neural activity in an epileptic hippocampus, he says. The same activity can be observed in a culture of brain slice. The signal typically is an excessively strong and continuous neural activity that lasts more than 10 seconds, much as an epileptic fit might.
“When we inject an anticonvulsant drug into the sample, the excessive neural activity disappears,” says Berdichevsky. “We are testing drugs before the epileptic activity appears to try to find one that prevents epilepsy from even starting.”
The group has also developed microfluidic chips with channels the width of a human hair. These devices control the chemical microenvironments of brain slices and examine the connections between the slice cultures in the compartments.
This sheds light on the dynamics of neural pathways, revealing how brains integrate sensory information and memory, while improving the understanding of brain disorders. Knowing how abnormal neural activity spreads in an epileptic brain can lead to more targeted drug treatment.
“I have always been interested in neural circuits, and my specialty is digital electronic circuits,” he says. “It’s fascinating that neural circuits perform very much like electronic circuits. There is much more we can learn about the human body and cures for diseases if we can better understand the body’s complex ‘electrical system.’”
