Epilepsy affects from 0.5-1% of the human population, with an estimated 1/3 to nearly 1/2 of patients unable to attain satisfactory seizure control. A majority of patients have seizures of focal onset, possibly with secondary generalization. Within a seizure focus, the behavior of neurons evolves in time and space: this is reflected in the occurrence of low-amplitude, high-frequency (gamma [30-70 Hz], or higher [>70 Hz]) oscillations in a subpopulation of neurons, just prior to initiation of more typical epileptiform waves that then spread. Spatiotemporal evolution has been reproduced in in vitro and in vivo seizure models, as has another nonuniformity: different neuronal firing patterns across cortical layers. An in vitro model of >100 Hz oscillations leading into an electrographic seizure also exists. A better understanding of the detailed pathophysiology of within-focus seizure initiation, followed by spread, is important: a) it might allow improved early warning of an impending seizure, and suggest alternative measures to abort the seizure;b) it could suggest drug treatments, for example binders to proteins constituting putative axonal gap junctions, or modulators of said junctions;c) it could possibly refine the preoperative evaluation of surgical candidates, by indicating the most physiologically based types of preoperative EEG monitoring, for example, concentrating on frequency bands not typically examined. This proposal describes how we can first adapt an existing single-column network model for the study of very fast oscillations and seizure initiation, and then build a multi-column cortical network model. Temporal evolution of a seizure can be studied in one column, and spatial evolution in multiple columns. We use detailed model neuronal elements, along with synaptic and gap junctional connectivity. Such models are necessary as tools for integrating diverse types of experimental measurements (field potentials, single-cell electrical and optical recordings), and for accounting for the contributions to population activity made by a) intrinsic properties of multiple cell types, b) within-column synaptic and electrical connectivity, and c) between-column synaptic connectivity. A successful model will generate specific and testable predictions useful to experimental collaborators, who have worked closely on this project in the past and continue to do so.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS044133-08
Application #
7617029
Study Section
Cognitive Neuroscience Study Section (COG)
Program Officer
Liu, Yuan
Project Start
2002-06-01
Project End
2012-04-30
Budget Start
2009-05-01
Budget End
2010-04-30
Support Year
8
Fiscal Year
2009
Total Cost
$305,649
Indirect Cost
Name
Ibm Thomas J. Watson Research Center
Department
Type
DUNS #
084006741
City
Yorktown Heights
State
NY
Country
United States
Zip Code
10598
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Traub, Roger D; Cunningham, Mark O; Whittington, Miles A (2014) What is a seizure network? Very fast oscillations at the interface between normal and epileptic brain. Adv Exp Med Biol 813:71-80
Carracedo, Lucy M; Kjeldsen, Henrik; Cunnington, Leonie et al. (2013) A neocortical delta rhythm facilitates reciprocal interlaminar interactions via nested theta rhythms. J Neurosci 33:10750-61
Vladimirov, Nikita; Tu, Yuhai; Traub, Roger D (2013) Synaptic gating at axonal branches, and sharp-wave ripples with replay: a simulation study. Eur J Neurosci 38:3435-47
Traub, Roger D; Schmitz, Dietmar; Maier, Nikolaus et al. (2012) Axonal properties determine somatic firing in a model of in vitro CA1 hippocampal sharp wave/ripples and persistent gamma oscillations. Eur J Neurosci 36:2650-60
Cunningham, Mark O; Roopun, Anita; Schofield, Ian S et al. (2012) Glissandi: transient fast electrocorticographic oscillations of steadily increasing frequency, explained by temporally increasing gap junction conductance. Epilepsia 53:1205-14
Vivar, Carmen; Traub, Roger D; Gutierrez, Rafael (2012) Mixed electrical-chemical transmission between hippocampal mossy fibers and pyramidal cells. Eur J Neurosci 35:76-82

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