NEURONAL SYNCHRONY IN RELATION TO BURST DISCHARGE IN EPILEPTIC HUMAN TEMPORAL LOBES

1. Synchronous interactions between neurons in mesial temporal structu res of patients with complex partial seizures were studied using cross -correlation analyses. We recorded spontaneous activity from 293 neuro ns in 24 patients during the interictal state. Patients had depth micr oelectrodes chronically implanted in amygdala, hippocampal formation. and parahippocampal gyrus to record epileptic activity. One hundred tw enty-five cells were recorded from the temporal lobe commonly initiati ng seizures (ipsilateral temporal lobe), and 168 cells from the contra lateral temporal lobe. Eight hundred forty-three cross-correlograms er e constructed between all pairs of simultaneously recorded neurons. Cr oss-correlogram peaks or troughs that exceeded confidence limits withi n 200 ms of the origin were considered evidence of synchronous neurona l interaction. 2. Synchronous neuronal interactions were observed in 2 23 of 843 cross-correlograms. Eighty-six percent of these 223 cross-co rrelograms showed significant central peaks (peak interactions), sugge sting excitatory interactions, whereas the remainder displayed signifi cant central troughs (trough interactions), suggesting inhibitory tory interactions. 3. Cross-correlograms constructed using cells from the ipsilateral temporal lobe (ipsilateral cross-correlograms) were more l ikely to display significant central troughs (14/262) than cross-corre lograms ams constructed using cells from the contralateral temporal lo be (6/376; contralateral cross-correlograms). Similarly, cross-correlo grams constructed using one cell from each hemisphere (11/205: bilater al cross-correlograms) were also more likely to display significant ce ntral troughs (trough interactions) than contralateral cross-correlogr ams. Both ipsilateral (77/262) and contralateral cross-correlograms (1 02/376) were more likely to display significant central peaks (peak in teractions) than bilateral cross-correlograms (13/205). 4. Cells from different structures in the ipsilateral temporal lobe were more likely to display significant trough interactions (10/114) than neurons in d ifferent contralateral structures. We also compared the proportion of significant peak interactions between cells within the ipsilateral and contralateral sides of each structure. Neurons in the contralateral e ntorhinal cortex were more likely to show peak interactions (21/55) th an cells from the ipsilateral entorhinal cortex (3/31). Also, cells in the ipsilateral presubiculum showed a higher proportion of peak inter actions (9/16) than their contralateral homologues (5/30). 5. Neuronal burst discharges were defined as three or more action potentials (or spikes) separated by interspike intervals of less than or equal to 30 ms, or two spikes separated by an interval of less than or equal to 15 ms. The contribution of burst discharge to synchronous peak interacti on a was compared between temporal lobes. Cells used to construct ipsi lateral cross-correlograms displaying significant central peaks (n = 1 54) were found to have significantly reduced burst discharge contribut ions to the observed synchronous peaks in comparison with their contra lateral homologues (n = 203). When cross-correlograms were separated b y regions, burst discharge contributions to synchronous peak interacti ons between cells in the ipsilateral hippocampus (n = 72) were signifi cantly smaller than the contributions from cells in the contralateral hippocampus (n = 44). 6. The results suggest that in the interictal sl ate, synchronous neuronal burst discharge is not a distinguishing feat ure of epileptogenic regions of patients with complex partial seizures , but inhibitory tory neuronal interactions are increased in regions o f seizure initiation. Increases in the strength and spread of local in hibition in seizure initiating regions in these patients may result in a greater proportion of inhibitory interactions and could also cause increased synchrony between isolated action potentials. These findings suggest that models of epilepsy displaying synchronous neuronal burst discharge may not be representative of the interictal stale of patien ts with complex partial seizures, and therefore may not appropriately reproduce the transition from the interictal to the ictal state.