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Spontaneous ripples in the hippocampus correlate with epileptogenicity and not memory function in patients with refractory epilepsy
Institution:1. Department of Neuropediatrics and Muscular Diseases, Epilepsy Center Clinic, Medical Center, University of Freiburg, Germany;2. Montreal Neurological Institute, Canada;3. University Medical Center Utrecht, Netherlands;4. SEIN — Stichting Epilepsie Instellingen Nederland, Netherlands;1. Epilepsy Unit, Department of Neurology, Hospital Universitario y Politécnico La Fe, Avinguda de Fernando Abril Martorell, 106, 46026 Valencia, Spain;2. Department of Psychobiology/IDOCAI, University of Valencia, Av. de Blasco Ibáñez, 13, 46010 Valencia, Spain. Valencian International University. Carrer del Pintor Sorolla, 21, 46002 Valencia, Spain;3. Epilepsy Unit, Department of Neurosurgery, Hospital Universitario y Politécnico La Fe, Avinguda de Fernando Abril Martorell, 106, 46026 Valencia, Spain.;1. Montreal Neurological Institute, Canada;2. Departments of Neurology & Neurosurgery, and of Physiology, McGill University, Montréal, H3A 2B4 Québec, Canada;3. Department of Experimental Medicine, Facoltà di Medicina e Odontoiatria, Sapienza University of Rome, 00185 Roma, Italy
Abstract:IntroductionHigh-frequency oscillations (HFOs, 80–500 Hz) are newly-described EEG markers of epileptogenicity. The proportion of physiological and pathological HFOs is unclear, as frequency analysis is insufficient for separating the two types of events. For instance, ripples (80–250 Hz) also occur physiologically during memory consolidation processes in medial temporal lobe structures. We investigated the correlation between HFO rates and memory performance.MethodsPatients investigated with bilateral medial temporal electrodes and an intellectual capacity allowing for memory testing were included. High-frequency oscillations were visually marked, and rates of HFOs were calculated for each channel during slow-wave sleep. Patients underwent three verbal and three nonverbal memory tests. They were grouped into severe impairment, some impairment, mostly intact, or intact for verbal and nonverbal memory. We calculated a Pearson correlation between HFO rates in the hippocampi and the memory category and compared HFO rates in each hippocampus with the corresponding (verbal — left, nonverbal — right) memory result using Wilcoxon rank-sum test.ResultsTwenty patients were included; ten had bilateral, five had unilateral, and five had no memory impairment. Unilateral memory impairment was verbal in one patient and nonverbal in four. There was no correlation between HFO rates and memory performance in seizure onset areas. There was, however, a significant negative correlation between the overall memory performance and ripple rates (r =  0.50, p = 0.03) outside the seizure onset zone.ConclusionOur results suggest that the majority of spontaneous hippocampal ripples, as defined in the present study, may reflect pathological activity, taking into account the association with memory impairment. The absence of negative correlation between memory performance and HFO rates in seizure onset areas could be explained by HFO rates in the SOZ being generally so high that differences between areas with remaining and impaired memory function cannot be seen.
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