Abstracts

Rationale: In experimental animal models of chronic epilepsy, morphological changes, e.g. neuron loss and synaptic reorganization, are believed to contribute to synchronous neuronal burst firing within epileptogenic brain areas. In contrast, studies in patients with temporal lobe epilepsy (TLE) have not provided consistent evidence for the occurrence of abnormal burst firing in seizure generating brain areas. While hippocampal atrophy (HA) is commonly observed in surgical TLE patients, the extent of atrophy often is not uniformly distributed within hippocampal areas. In many of these previous patient studies, atrophy was not evaluated in relation to recording site, which may explain the inconsistent findings regarding neuronal excitability. In the present study, single neuron activity was analyzed in relation to areas of epileptogenicity and HA to identify single neuron correlates of seizure generating brain areas. Methods: Patients with medically intractable complex partial seizures of probable temporal lobe origin were implanted with intracranial depth electrodes for localization of the site of seizure onset. Continuous wide bandwidth interictal EEG was recorded from microelectrodes extending beyond the tip of each depth electrode, and neuronal action potentials were detected and separated into single neuron activity. High-resolution 3T T2-weighted MR images combined with two-dimensional computational unfolding of hippocampal subregions was used to identify the position of microelectrodes, and measure thickness of each hippocampal subregion that included DG/CA3/CA2, CA1, subicular and entorhinal cortices, and parahippocampal gyrus in order to determine the extent of atrophy in patients with respect to control subjects. Results: Results showed that when hippocampal subregions were combined, hippocampal thickness in patients in relation to control subjects was significantly reduced in areas ipsilateral to seizure onset (p=.006). In contrast, no significant difference in hippocampal thickness was observed in patients with respect to controls in areas contralateral to seizure onset (p=.10). Analysis of 217 single neurons recorded from 19 sites revealed that mean firing rates were significantly higher in areas ipsilateral to seizure onset compared to firing rates in contralateral areas (2.05±.26 vs. 1.00±.15; p=.005). Burst rates were higher in ipsilateral than contralateral sites (bursts/min, 1.38±.16 vs. 0.75±.11; p=.01). In areas ipsilateral to seziure onset, correlation analysis revealed a strong, but non-significant, association between hippocampal atrophy and mean firing rates (r=-0.44; p=.13), and between atrophy and burst rates (r=-.53; p=.06). Conclusions: In surgical patients with TLE, higher single neuron mean firing and burst rates are associated with atrophic seizure generating areas. These results indicate that pathological alterations linked with hippocampal atrophy may contribute to abnormal neuronal excitability in primary epileptogenic areas. Research support provided by NINDS NS33310 & NS02808.