Damage to a part of the brain that regulates hyperactivity can contribute to both memory problems and seizures in the most common form of epilepsy, according to a new research.

The study, published recently in the Journal of Neuroscience, may lead to earlier diagnosis of epilepsy and possibly new ways to treat epilepsy and other disorders that share symptoms, like Alzheimer’s disease, traumatic brain injury and autism spectrum disorder.

Temporal lobe epilepsy, marked by seizures in the brain’s centers for learning and memory, affects more than half of the 3.4 million people in the U.S. diagnosed with epilepsy. One part of the temporal lobe, called the dentate gyrus, has long been suspected to work as a gate — helping to manage brain activity by getting choosy about which patterns of brain cells are active and which are silenced.

“You can think of each pattern as representing one memory,” says the lead author. “One pattern represents the first time you visited an art museum. Another, similar pattern is going to represent the second time you went to the museum.”

The unique features of each memory may be subtle — from the specific art you admired, different friends along for the experience or even the time of day — but they are important for guiding specific recollections. Researchers the dentate gyrus helps to discriminate between similar memories, withholding all but the appropriate patterns to prevent confusion.

“In epilepsy, there is this huge rewiring of the dentate gyrus. Some cells die, some new neurons and new connections between neurons are added in the wrong places” the author says. “It’s a dramatic difference from a healthy dentate gyrus.”

This rewiring, along with molecular changes inside each cell, allows seizures to develop. But it’s unclear what effect this reorganization of the dentate gyrus has on memory.

The researchers studied patients asking them to take image recognition tests. These tests revealed the trouble they had discriminating between similar memories relative to healthy people of similar age and gender.

The researchers also studied a mouse model of epilepsy and tested their memory by releasing them repeatedly into an arena with a pair of identical objects. Each time a mouse returned to the arena, one of the objects had been moved to a different location.

“Normal mice noticed and acted like something was different. They spent extra time exploring the object that was in a new location,” the senior author said. “Mice with epilepsy explored, but they did not show a preference for any object; they behaved as if nothing had changed, confusing the new situation with their memory of the old one.”

Looking for the cause of that confusion, the lead examined brain tissue taken from the mice that had undergone memory testing. With a series of specific electrical pulses, the author stimulated the nerve fibers that serve as inputs to the dentate gyrus and recorded the patterns of neuronal activity at the output of the dentate gate.

In healthy mice, similar input patterns were transformed by the dentate gyrus network into easily distinguishable patterns of output activity. The input patterns simulated different but similar memories. In epileptic mice, that process was broken. A subset of the neurons was not doing its job to separate patterns. Instead of transmitting a single impulse from the electrodes, the epileptic neurons would pass along bursts of pulses.

“We wonder if the same deficits in dentate gyrus function that cause memory problems are simultaneously causing susceptibility to these seizures,” the senior author says. “That abnormal activity leads to over-excitation, and that’s how seizures happen.”

“Identifying markers to specifically target pathological neurons could allow treatment of both seizures and memory symptoms with fewer side effects than current anti-seizure drugs,” the lead says.

Because memory problems often precede the seizure that leads to an epilepsy diagnosis, they could be used to diagnose patients earlier.

“Take a person who's had a head injury: They could evaluate their own memory regularly, using inexpensive and noninvasive computer-based tests like we used,” the senior author says. “If they start showing progressive deficits, a clinician could propose treatment to make sure they never have a first seizure.”

https://news.wisc.edu/seizures-and-memory-problems-in-epilepsy-may-have-a-common-cause/

https://www.jneurosci.org/content/41/46/9669