The primary goal of this proposal is to study the dynamics of the transition from interictal to ictal state (ictogenesis). Using novel recording methods developed in our laboratory we have accumulated significant experience and ability to investigate human epileptogenic brain across the relevant range of spatial and frequency scales involved in the transition from normal brain activity to seizures. Using hybrid electrodes containing clinical macroelectrodes and microwire arrays we have identified three quantitative signatures of epileptogenic brain that are outside the range of conventional clinical intracranial EEG (IEEG). Decades of clinical IEEG using a restricted spatial and frequency bandwidth have often frustrated epileptologists looking for discrete, resectable """"""""electrographic lesions"""""""" during evaluation for epilepsy surgery. Additionally, recent efforts to utilize direct brain stimulation t abort detected seizures have meet with only partial success. The inability to disrupt seizures after they are sufficiently established to be detected on millimeter scale macroelectrodes may explain the marginal efficacy of brain stimulation. Recent work by our group suggests that a significant impediment to localizing and """"""""controlling"""""""" epileptic networks may be the narrow recording bandwidth (~0.5 - 100 Hz) and large, widely spaced electrodes used in conventional IEEG that have led to the paradigm that seizures occur as large-scale paroxysmal events. In this application, we will analyze continuous, wide-bandwidth iEEG across the relevant range spatial scales in order to probe and localize human epileptic networks and track ictogenesis. This work builds on our established effort in Translational Neuroengineering, melding state of the art epilepsy care with Engineering and Neuroscience at the Mayo Clinic.

Public Health Relevance

Neocortical networks extend from sub-millimeter cortical columns to lobar structures measured in centimeters. These networks generate activity over a wide frequency range (DC - 1000 Hz). We hypothesize that the pathological network transition from normal brain activity to seizure (ictogenesis) occurs on a microscopic scale that is not detected by clinical intracranial EEG.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (NOIT)
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Stewart, Randall R
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Mayo Clinic, Rochester
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Cimbalnik, Jan; Brinkmann, Benjamin; Kremen, Vaclav et al. (2018) Physiological and pathological high frequency oscillations in focal epilepsy. Ann Clin Transl Neurol 5:1062-1076
Guragain, Hari; Cimbalnik, Jan; Stead, Matt et al. (2018) Spatial variation in high-frequency oscillation rates and amplitudes in intracranial EEG. Neurology 90:e639-e646
Cimbálník, Jan; Hewitt, Angela; Worrell, Greg et al. (2018) The CS algorithm: A novel method for high frequency oscillation detection in EEG. J Neurosci Methods 293:6-16
Bower, Mark R; Kucewicz, Michal T; St Louis, Erik K et al. (2017) Reactivation of seizure-related changes to interictal spike shape and synchrony during postseizure sleep in patients. Epilepsia 58:94-104
Kremen, Vaclav; Duque, Juliano J; Brinkmann, Benjamin H et al. (2017) Behavioral state classification in epileptic brain using intracranial electrophysiology. J Neural Eng 14:026001
Lundstrom, Brian Nils; Van Gompel, Jamie; Britton, Jeffrey et al. (2016) Chronic Subthreshold Cortical Stimulation to Treat Focal Epilepsy. JAMA Neurol 73:1370-1372
Stead, Matt; Halford, Jonathan J (2016) Proposal for a Standard Format for Neurophysiology Data Recording and Exchange. J Clin Neurophysiol 33:403-413
Klimes, Petr; Duque, Juliano J; Brinkmann, Ben et al. (2016) The functional organization of human epileptic hippocampus. J Neurophysiol 115:3140-5
Bower, Mark R; Stead, Matt; Bower, Regina S et al. (2015) Evidence for consolidation of neuronal assemblies after seizures in humans. J Neurosci 35:999-1010
Staba, Richard J; Stead, Matt; Worrell, Gregory A (2014) Electrophysiological biomarkers of epilepsy. Neurotherapeutics 11:334-46

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