Research ArticleEpilepsy

Cognitive refractory state caused by spontaneous epileptic high-frequency oscillations in the human brain

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Science Translational Medicine  16 Oct 2019:
Vol. 11, Issue 514, eaax7830
DOI: 10.1126/scitranslmed.aax7830

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A brief refractory state

Patients with epilepsy present abnormal activity in specific brain areas, resulting in the development of seizures. The removal of these epileptic regions is often the best treatment available. Seizure-originating tissue is thought to be chronically dysfunctional; however, it is unclear how epileptic tissue responds to cognitive stimuli before, during, and after seizures. Now, Liu et al. detected and analyzed brain oscillations in nonlesional epileptic tissue of patients while performing cognitive tasks. The author found that the epileptic tissue generated physiological responses to cognitive stimuli except when the stimulus arrived at the 1-s window preceding seizure. The results suggest that the epileptic tissue might not be as chronically impaired as previously thought.


Epileptic brain tissue is often considered physiologically dysfunctional, and the optimal treatment of many patients with uncontrollable seizures involves surgical removal of the epileptic tissue. However, it is unclear to what extent the epileptic tissue is capable of generating physiological responses to cognitive stimuli and how cognitive deficits ensuing surgical resections can be determined using state-of-the-art computational methods. To address these unknowns, we recruited six patients with nonlesional epilepsies and identified the epileptic focus in each patient with intracranial electrophysiological monitoring. We measured spontaneous epileptic activity in the form of high-frequency oscillations (HFOs), recorded stimulus-locked physiological responses in the form of physiological high-frequency broadband activity, and explored the interaction of the two as well as their behavioral correlates. Across all patients, we found abundant normal physiological responses to relevant cognitive stimuli in the epileptic sites. However, these physiological responses were more likely to be “seized” (delayed or missed) when spontaneous HFOs occurred about 850 to 1050 ms before, until about 150 to 250 ms after, the onset of relevant cognitive stimuli. Furthermore, spontaneous HFOs in medial temporal lobe affected the subjects’ memory performance. Our findings suggest that nonlesional epileptic sites are capable of generating normal physiological responses and highlight a compelling mechanism for cognitive deficits in these patients. The results also offer clinicians a quantitative tool to differentiate pathological and physiological high-frequency activities in epileptic sites and to indirectly assess their possible cognitive reserve function and approximate the risk of resective surgery.

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