Seizures and memory problems in epilepsy may have a common cause

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 research from the University of Wisconsin-Madison.

The study, published recently in the Journal of Neuroscience, may lead to an earlier diagnosis of epilepsy and possibly new ways of treating epilepsy and other disorders that share symptoms, such as dementia. ‘Alzheimer’s, traumatic brain injury and autism spectrum disorders.

Temporal lobe epilepsy, marked by seizures in the brain’s centers of learning and memory, affects more than half of the 3.4 million people in the United States diagnosed with epilepsy. Part of the temporal lobe, called the dentate gyrus, has long been suspected of functioning as a gate – helping to manage brain activity by choosing which brain cell patterns are active and which are silenced.

Antoine Madar

Portrait of Matt Jones

Matt jones

“You can think of each model as representing a memory,” says Antoine Madar, now a postdoctoral researcher at the University of Chicago, who conducted the research while earning his doctorate at UW-Madison in the laboratory of neuroscience professor Matt. Jones. “A motif represents the first time that you have visited an art museum. Another similar motif will represent the second time you have been to the museum.

The unique characteristics of each memory can be subtle – from the specific art you admired, different friends for the experience, or even the time of day – but they are important in guiding specific memories. Researchers like Madar suspected that the dentate gyrus helped distinguish between similar memories, retaining all but the appropriate patterns to avoid confusion.

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

This rewiring, along with the molecular changes inside each cell, allows seizures to develop. But it is not known what effect this reorganization of the dentate gyrus has on memory.

With the help of neurologists Bruce Hermann and Rama Maganti of UW-Madison, the researchers studied patients from the Epilepsy Surveillance Unit at UW School of Medicine and Public Health, their asking to pass image recognition tests. These tests revealed their difficulty in distinguishing between similar memories compared to healthy people of similar age and sex.

The study may lead to an earlier diagnosis of epilepsy and possibly new ways of treating epilepsy, Alzheimer’s disease, traumatic brain injury, and autism spectrum disorders.

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

“Normal mice noticed and acted like something was different. They spent more time exploring the object that was in a new location, ”says Jones, whose work is supported by the National Institutes of Health. “Epileptic mice have been explored, but they have shown no preference for any object; they behaved as if nothing had changed, mistaking the new situation for their memory of the old one.

In search of the cause of this confusion, Madar examined brain tissue taken from the mice that had undergone memory tests. With a series of specific electrical impulses, it stimulated the nerve fibers that serve as inputs to the dentate gyrus and recorded the patterns of neural activity as it exits the dentate gate.

In healthy mice, similar input patterns were transformed by the dentate gyrus network into easily distinguishable output activity patterns. The input models simulated different but similar memories. In epileptic mice, this process was interrupted. A subset of neurons was not doing its job to separate the patterns. Instead of transmitting a single pulse from Madar’s electrodes, epileptic neurons would transmit bursts of pulses.

“We wonder if the same deficits in dentate gyrus function that cause memory problems simultaneously cause susceptibility to these seizures,” says Jones. “This abnormal activity leads to over-arousal, and this is how seizures occur.”

The new study, which received support from Lily’s Fund for Epilepsy Research, based in Madison, improves our understanding of the mechanisms of memory, linking the biological function of the dentate gyrus and the ability to avoid memory confusion. This could lead to better care for patients with epilepsy and similar disorders who have poor memory or seizures, especially if the new findings help researchers differentiate damaged brain cells from those that retain normal function. .

“Identifying markers to specifically target pathologic neurons could make it possible to treat both seizures and memory symptoms with fewer side effects than current anti-seizure drugs,” says Madar.

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

“Take a person who has suffered a head injury: they could assess their own memory on a regular basis, using inexpensive, non-invasive computer tests as we have used it,” says Jones. “If they start to show progressive deficits, a clinician might suggest treatment to make sure they never have a first attack.”

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