Laminar cortical interactions during epileptic spikes studied with principal component analysis and physiological modeling

The direct cortical responses (DCR) to electrical stimulation and electrically evoked interictal penicillin spikes (EIIS) were studied in the same rats using current source-density (CSD) analysis to directly compare regions of neuronal depolarization and hyperpolarization in neocortex. Principal component analysis (PCA) was further used to evaluate patterns of covariance in the CSD that were characteristic of interactions between pyramidal cell populations with spatially and temporally distinct transmembrane currents. A physical model was applied to the physiological interpretation of PCA results and the optimal model parameters used to estimate neuronal generators of recorded laminar field potentials. The data suggested that the DCR and EIIS were produced by the same neuronal circuit which could be represented by two anatomically distinct populations of pyramidal cells. The first of these populations was situated in the upper and middle layers (supragranular pyramidal neurons) and formed a dipolar CSD pattern that reversed polarity in layers II and III. The second deeper population (infragranular pyramidal neurons) extended throughout most of the cortical thickness and formed a dipolar CSD pattern that reversed polarity in layer V. We propose that excitatory intracortical connections of supragranular pyramidal cells may pathologically synchronize depolarization within the epileptic focus. In this way, supragranular pyramidal cells may provide a trigger mechanism for interictal spikes in neocortex.