Brain state-dependent high-frequency activity as a biomarker for abnormal neocortical networks in an epileptic spasms animal model.

OBJECTIVE: Epileptic spasms are a hallmark of a severe epileptic state. A previous study showed neocortical up and down states defined by unit activity play a role in the generation of spasms. However, recording unit activity is challenging in clinical settings, and more accessible neurophysiological signals are needed for the analysis of these brain states. METHODS: In the tetrodotoxin model, we used 16-channel microarrays to record electrophysiological activity in the neocortex during interictal periods and spasms. High-frequency activity (HFA) in the frequency range of fast ripples (200-500 Hz) was analyzed, as were slow wave oscillations (1-8 Hz), and correlated with the neocortical up and down states defined by multiunit activity (MUA). RESULTS: HFA and MUA had high temporal correlation during interictal and ictal periods. Both increased strikingly during interictal up states and ictal events but were silenced during interictal down states and preictal pauses, and their distributions were clustered at the peak of slow oscillations in local field potential recordings. In addition, both HFA power and MUA firing rates were increased to a greater extent during spasms than interictal up states. During non-rapid eye movement sleep, the HFA rhythmicity faithfully followed the MUA up and down states, but during rapid eye movement sleep when MUA up and down states disappeared the HFA rhythmicity was largely absent. We also observed an increase in the number of HFA down state minutes prior to ictal onset, consistent with the results from analyses of MUA down states. SIGNIFICANCE: This study provides evidence that HFA may serve as a biomarker for the pathological up states of epileptic spasms. The availability of HFA recordings makes this a clinically practical technique. These findings will likely provide a novel approach for localizing and studying epileptogenic neocortical networks not only in spasms patients but also in other types of epilepsy.