The brain ‘learns’ to have seizures more efficiently and frequently over time, mouse study shows

Calculus. Ballroom dancing. The words to your favorite song. There’s practically no limit to what your brain can learn. But a new study suggests that the same process that allows you to hold onto new information and skills could also make certain neurological diseases worse.

Scientists found that mice and rats that suffered from seizures commonly seen in people with epilepsy developed changes in the wiring of their brains that advanced the disease. A closer look showed that the cementing of these signals was driven by a process that also supports learning, memory, and attention.

The study, published Monday in the journal Nature Neuroscience, is the first to report that a key feature of the brain’s ability to change and adapt, known as activity-dependent myelination, can contribute to disease. Researchers found that blocking this process reduced the number of seizures in the animals they studied.

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They’re now following up to see if these findings hold true in people. Scientists are also exploring whether these results apply to other conditions, such as substance use and mental health disorders. It’s all part of an effort to better understand and treat patients for whom current medications aren’t effective.

“Prior to this, we didn’t know such a thing existed,” said Juliet Knowles, a Stanford physician-scientist and the study’s lead author. “This is perhaps a new frontier.”

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The study is the latest evidence that the mind is malleable. Learning Arabic or how to play the trombone forges connections between neurons, and repetition strengthens those links (so practice really does make perfect).

That’s not the only change that happens. Neurons have snaking tendrils that run from one cell to the next to relay signals. These extensions are swaddled in a blubbery layer of fat and protein known as myelin. In 2014, a team led by Stanford neuroscientist Michelle Monje, who is the senior author of the new study, found that myelin thickens along neural pathways that get repeatedly stimulated. This activity-dependent myelination protects and supports electrical messages pinging back and forth — a bit like the wiring wrapped around your computer cords.

But is that always a good thing?

To answer the question, scientists in the new research studied seizures as an example of brain signaling gone wrong. They focused on absence seizures, which account for about 10% of seizures in children with epilepsy. These aren’t the violent convulsions you may picture. Instead, patients briefly go still and silent, often losing consciousness for a few moments. These episodes can gradually become more frequent, sometimes happening hundreds of times a day.

“You can imagine for a child that would really interfere with things like learning in the classroom, and could also be dangerous if you’re crossing a street or playing on a jungle gym,” said Knowles, who treats children with epilepsy.

Researchers examined animals with a similar problem, including a strain of rats that begin developing seizures at two months and eventually suffer from 20 to 30 episodes an hour. They found clear signs of increased myelin along neural circuits linked to seizures as the disease wore on. And they also saw that the cells in the brain that produce myelin, known as oligodendrocytes, increased in the rats over time.

Blocking seizures with the anti-epilepsy drug ethosuximide (sold under the name Zarontin by Pfizer) reduced the thickening of the myelin. But researchers wanted to know if the opposite was true: Would blocking myelination improve disease? So they treated seizure-prone mice with a drug that blocks the formation of myelin-making oligodendrocytes. Doing so cut the number of seizures by about 35%.

In other diseases, such as multiple sclerosis and Alzheimer’s, it’s the loss of myelin that’s the problem; the new study suggests that too much in the wrong place can also be an issue.

“The work is really interesting and novel,” said Joseph Gleeson, a University of California, San Diego, neurologist who was not involved in the study. “The gap is really how the neurons firing talk to the supporting cells next to them. How does that happen? What does that conversation look like?”

It’s unclear whether these findings in rodents apply to people. But Knowles is working on that. Researchers plan to use MRI to see whether children with epilepsy also have increased myelin in areas of the brain associated with their seizures.

And the study’s authors are exploring whether the findings apply to other seizure types. Monje’s group is also looking at whether activity-dependent myelination happens in substance use and mental health disorders.

The ultimate hope, Monje said, is to treat patients for whom current therapies aren’t effective or who don’t have any treatment options. Researchers aren’t there yet, in part because the drug they used to block myelination in this study is a chemotherapy agent with side effects too harsh for most cases of neurologic disease. But she said the current findings are something to build on.

“I don’t know that we have the perfect way with an existing drug to interfere with this biology,” Monje said. “But now we understand some of the targets and can move down the right therapeutic path.”