Abstracts

Rationale: Our recent presurgical patient studies found gray matter (GM) loss correlates with higher mesial temporal lobe (MTL) single neuron firing rates, and after controlling for differences in GM loss revealed significantly higher interictal firing and burst rates inside than outside the seizure onset zone (SOZ). Yet, it is not known whether MTL firing rates inside the SOZ are associated with abnormal principal or non-principal cell firing or both. Therefore, the present study used in vivo microelectrode recordings of MTL single neurons and cluster analysis to identify putative principal and non-principal cells to evaluate firing rates in relation to cell type, MTL subregion, and epileptogenicity.Methods: Ten consecutive patients with medically refractory focal seizures of probable temporal and/or frontal lobe origin were surgically implanted with depth electrodes for localization of the SOZ. Wide bandwidth, high frequency interictal EEG was recorded from microelectrodes extending beyond the tip of each depth electrode. Extracellular neuronal action potentials were detected and single neuron firing properties and waveform features used in a hierarchical cluster analysis to produce two groups of cells. 3-Tesla T2-weighted MRI combined with computational unfolding of MTL subregions was used to identify the position of microelectrodes in patients and compute GM loss with respect to controls for each MTL subregion that included a combined area of dentate gyrus/CA3/CA2, CA1, subicular cortex (SUB), entorhinal cortex (EC), and parahippocampal gyrus (PHG).Results: Cluster analysis of 405 single neurons produced two groups of putative principal and non-principal cells that were significantly different in terms of firing and burst rates, spike duration, slope asymmetry, and ratios of spike amplitude. In patients, MRI GM loss was found inside and outside the SOZ. GM loss correlated with higher principal cell firing rates in CA23DG, CA1, EC, and PHG inside the SOZ, whereas the effect of GM loss on firing rates was smaller and statistically equivalent for SUB principal cells inside the SOZ, all principal cells outside the SOZ, and non-principal cells inside and outside the SOZ. Mean firing rates adjusted for effects of GM loss were significantly higher for principal cells in all MTL subregions (except PHG) inside than outside the SOZ. In contrast, only CA23DG non-principal cells firing rates were higher inside versus outside the SOZ.Conclusions: In the human MTL, properties of putative principal and non-principal cells strongly resemble those corresponding to excitatory and inhibitory cells respectively in non-primate hippocampal areas. Inside the SOZ, the correlation between GM loss and higher principal cell, but not non-principal cell, firing rates could reflect stronger synaptic coupling among principal cells and weaker interactions between non-principal and principal cells. The proposed conditions of synaptic reorganization associated with GM loss could contribute to the significantly higher principal cell firing rates found in most MTL subregions inside the SOZ. Supported by NINDS NS071048.