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The Journal of Neuroscience, September 15, 2004, 24(37):8075-8083; doi:10.1523/JNEUROSCI.1509-04.2004

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Neurobiology of Disease
Epilepsy in Small-World Networks

Theoden I. Netoff,1,3 Robert Clewley,2,3 Scott Arno,1,3 Tara Keck,1,3 and John A. White1,3

1Department of Biomedical Engineering, 2Department of Mathematics and 3Center for BioDynamics and Center for Memory and Brain, Boston University, Boston, Massachusetts 02215

In hippocampal slice models of epilepsy, two behaviors are seen: short bursts of electrical activity lasting 100 msec and seizure-like electrical activity lasting seconds. The bursts originate from the CA3 region, where there is a high degree of recurrent excitatory connections. Seizures originate from the CA1, where there are fewer recurrent connections. In attempting to explain this behavior, we simulated model networks of excitatory neurons using several types of model neurons. The model neurons were connected in a ring containing predominantly local connections and some long-distance random connections, resulting in a small-world network connectivity pattern. By changing parameters such as the synaptic strengths, number of synapses per neuron, proportion of local versus long-distance connections, we induced "normal," "seizing," and "bursting" behaviors. Based on these simulations, we made a simple mathematical description of these networks under well-defined assumptions. This mathematical description explains how specific changes in the topology or synaptic strength in the model cause transitions from normal to seizing and then to bursting. These behaviors appear to be general properties of excitatory networks.

Key words: epilepsy; networks; small-world networks; seizures; computational modeling; interictal burst


Received Dec 18, 2003; revised July 29, 2004; accepted July 30, 2004.




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