Abstracts

High frequency oscillations have been recorded in the hippocampus of patients with mesial temporal lobe epilepsy (MTLE) and in animal models of chronic recurrent seizures. In patients with MTLE, bursts of high frequency oscillatory activity in the range of 150-500 Hz called Fast Ripples (FR) are found in localized hippocampal areas of the temporal lobe generating seizure onsets (Staba et al., 2002, J Neurophysiol, 88:1743-1752). In order to investigate the anatomical substrates of FR oscillations in MTLE, we used surface contour mapping to reveal patterns of hippocampal atrophy and then evaluated their association with local areas generating FR. Wideband hippocampal microelectrode recordings of FR were carried out in 15 MTLE patients with unilateral temporal onsets. Surface contour modeling was used to generate 3D parametric mesh models of hippocampi in these patients and in 19 age- and sex-matched controls, based on preoperative T1 MRI scans (Thompson et al., Neuroimage, 2004, 22:1754-1766). Patient and control models were divided into Ipsilateral (Ipsi) and Contralateral (Contra) groups based on side of seizure onset. MRI scans of implanted depth electrodes were used to localize microelectrode tips to the nearest hippocampal surface point. Thickness measurements at these points were compared to control group averages and Z score levels of local atrophy were determined. Patients with bilateral hippocampal recordings (n=6) were used to correlate FR rates and side of seizure onset with local atrophy at those 12 hippocampal recording sites. ANOVA of whole hippocampal volumes showed significant atrophy in MTLE patients compared to controls in Ipsi (p=.0001), but not in Contra (p=.34) hippocampi. Within the patient group, Ipsi volumes were, on average, 23.1% smaller than Contra volumes, and in those patients with bilateral EEG recordings, Ipsi volumes were 27.3% smaller (p=.01). Similar deficits in surface atrophy Z-scores were seen in this group (p=.04), demonstrating concordance between whole hippocampal volume measures and surface model measurements of local atrophy. Multiple regression analysis of the 12 hippocampi showed a significant relationship between atrophy scores and both FR rate and side of seizure onset (r=.72, F=.04). These preliminary data using MRI based surface contour maps provide a novel and promising method for quantifying atrophy in specific hippocampal regions and for correlating these anatomical changes with local FR oscillations recorded from hippocampal depth electrodes. (Supported by NIH grants NS 02808 and NS 33310.)