Disrupted memory pathways uncovered in epilepsy patients

By Eleanor McDermid

A study in rats, backed up by results in patients, has revealed how interictal epileptiform discharges (IEDs) may lead to memory impairments in patients with epilepsy.

"Long-term memory requires a prolonged consolidation period, which is thought to be mediated by three prominent network patterns: hippocampal ripples, neocortical slow oscillations and thalamocortical sleep spindles", write the researchers in Nature Medicine.

Under normal circumstances, hippocampal ripples (brief, high-frequency oscillations; 100-200 Hz) coordinate with sleep spindles (9-16 Hz) in the medial prefrontal cortex (mPFC), via neocortical slow oscillations, during non-REM sleep.

But in rats with epilepsy caused by kindling (repeated electrically induced seizures), the team observed that IEDs in the hippocampus also coordinated with sleep spindles, and as the frequency of IEDs increased, so that of ripples decreased.

The IEDs slightly preceded sleep spindles, as did physiological hippocampal ripples, but the IEDs were significantly more likely to provoke sleep spindles than were the ripples. So the coordinated spiking in the mPFC provoked by ripples - required for memory consolidation - was partly replaced by "nonsense" information carried by IEDs, say the researchers.

And, indeed, the kindling-induced IEDs were associated with impaired memory performance in the rats, which recovered after the kindling period had ended.

Similar to their findings in rats, the team detected strong correlations between IEDs and sleep spindles during non-REM sleep in four patients with epilepsy who had electrodes implanted during evaluation for surgery.

In both rats and epilepsy patients, the researchers found that hippocampal IEDs provoked a positive delta wave in the mPFC - characteristic of cortical down states (ie, non-REM sleep or during anaesthesia). In line with this, there was a simultaneous marked reduction in neuronal firing, followed by an increase, relative to that before the IED.

"These results support the hypothesis that the synchronous hippocampal output generated by an IED can reset the mPFC slow-oscillation phase, forcing a cortical down state that is characterized by [a local field potential] delta wave and decreased neuronal firing", say György Buzsáki (New York University School of Medicine, USA) and study co-authors.

"Recovery from this down state induces thalamocortical spindles."

But this "recruits mPFC neurons into events that carry no learning-related information and that thereby may compete with true informational events", they say.

Licensed from medwireNews with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.