Organization and control of epileptic circuits in temporal lobe epilepsy

When studying the pathological mechanisms of epilepsy, there are a seemingly endless number of approaches from the ultrastructural level-receptor expression by EM-to the behavioral level-comorbid depression in behaving animals. Epilepsy is characterized as a disorder of recurrent seizures, which are defined as "a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain" (Fisher et al., 2005). Such abnormal activity typically does not occur in a single isolated neuron; rather, it results from pathological activity in large groups-or circuits-of neurons. Here we choose to focus on two aspects of aberrant circuits in temporal lobe epilepsy: their organization and potential mechanisms to control these pathological circuits. We also look at two scales: microcircuits, ie, the relationship between individual neurons or small groups of similar neurons, and macrocircuits, ie, the organization of large-scale brain regions. We begin by summarizing the large body of literature that describes the stereotypical anatomical changes in the temporal lobe-ie, the anatomical basis of alterations in microcircuitry. We then offer a brief introduction to graph theory and describe how this type of mathematical analysis, in combination with computational neuroscience techniques and using parameters obtained from experimental data, can be used to postulate how microcircuit alterations may lead to seizures. We then zoom out and look at the changes which are seen over large whole-brain networks in patients and animal models, and finally we look to the future.