May 3, 2016

Seizures disrupt memory network

At a Glance

  • A study of rat and human brains revealed how seizure-like activity may disrupt memory consolidation.
  • The findings advance our understanding of memory and suggest a time frame to apply potential approaches to improve memory deficits in people with epilepsy.
Stylized illustration of human brain and neurons. In people with epilepsy, abnormal bursts of electrical activity in the brain can interfere with memory. Svisio/iStock/Thinkstock

Epilepsies are a spectrum of brain disorders in which surges of electrical activity in clusters of brain cells cause seizures. At least 2.3 million adults and nearly 500,000 children in the U.S. live with some form of epilepsy. Partial, or focal, seizures occur in just one part of the brain. In temporal lobe epilepsy, the most common form of the disorder in adults, seizures usually begin in the hippocampus, a brain structure essential for memory. People with this form of epilepsy often experience memory impairments.

Memory depends on a process called consolidation, in which different brain regions coordinate their activities during sleep. This process involves “ripples” of electrical activity in the hippocampus that are sometimes followed by bursts of activity in the prefrontal cortex called “spindles.” Abnormal electrical activity may disrupt normal brain activity patterns.

A group led by Dr. György Buzsáki at New York University took a closer look at how temporal lobe epilepsy affects the brain’s memory network. Their research was funded in part by NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Mental Health (NIMH). Results were published online on April 25, 2016, in Nature Medicine.

In people with temporal lobe epilepsy, spontaneous bursts of abnormal brain activity can sometimes occur even between seizures. These are called interictal epileptiform discharges (IEDs). Buzsáki’s group first looked at whether seizure- and IED-like activity that starts in the hippocampus impairs memory in a rat model of epilepsy. They trained the rats to find 3 hidden rewards in a maze and assessed their ability to remember the locations the following day. The rats showed memory deficits that were largely associated with the more frequently occurring IEDs rather than with the rare seizures.

The researchers found that hippocampal IEDs were followed by spindles in the prefrontal cortex. Normally, such spindles only follow hippocampal ripples during non-rapid-eye-movement (non-REM) stages of sleep. In rats that experienced seizures, hippocampal IEDs also elicited cortical spindles during REM and an awake state. These findings suggest that seizures may alter how the prefrontal cortex responds to hippocampal activity and thus interfere with normal memory consolidation.

The group next studied brain activity in 4 patients with epilepsy. IEDs were followed by cortical spindles at time intervals similar to that seen in the rats. The results suggest that these mistimed IEDs disrupt a brain network that’s essential for memory and reveal a time window for potential intervention in the altered communication between brain regions.

“Our study sheds the first light on the mechanisms by which epilepsy hijacks a normal brain process, disrupting the signals needed to form memories,” says lead author Dr. Jennifer Gelinas.

Since spindles can be detected noninvasively with EEG, a test that measures brain waves, the authors suggest that these findings may also be useful for diagnosing temporal lobe epilepsy. Spindles that occur outside normal non-REM sleep (while awake or during REM) could suggest IED activity in the temporal lobe.

—by Tianna Hicklin, Ph.D.

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Reference: Interictal epileptiform discharges induce hippocampal-cortical coupling in temporal lobe epilepsy. Gelinas JN, Khodagholy D, Thesen T, Devinsky O, Buzsáki G. Nat Med. 2016 Apr 25. doi: 10.1038/nm.4084. [Epub ahead of print] PMID: 27111281.

Funding: NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Mental Health (NIMH); National Science Foundation; Mathers Foundation; March of Dimes Foundation; and Simons Foundation.