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eNeuro. 2019 Feb 12;6(1). pii: ENEURO.0494-18.2019. doi: 10.1523/ENEURO.0494-18.2019. eCollection 2019 Jan-Feb.

Large-Scale 3-5 Hz Oscillation Constrains the Expression of Neocortical Fast Ripples in a Mouse Model of Mesial Temporal Lobe Epilepsy.

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Functional Brain Mapping Laboratory, Department of Fundamental Neuroscience, University of Geneva, 1202 Geneva, Switzerland.
Neurology Clinic, Department of Clinical Neuroscience, University Hospital Geneva, 1206 Geneva, Switzerland.
Medical Image and Signal Processing Group, Ghent University, 9052 Ghent, Belgium.
Center for Biomedical Imaging (CIBM), 1015 Lausanne, Switzerland.
Center for Biomedical Imaging (CIBM), Geneva, Switzerland.


Large-scale slow oscillations allow the integration of neuronal activity across brain regions during sensory or cognitive processing. However, evidence that this form of coding also holds for pathological networks, such as for distributed networks in epileptic disorders, does not yet exist. Here, we show in a mouse model of unilateral hippocampal epilepsy that epileptic fast ripples generated in the neocortex distant from the primary focus occur during transient trains of interictal epileptic discharges. During these epileptic paroxysms, local phase-locking of neuronal firing and a phase-amplitude coupling of the epileptic discharges over a slow oscillation at 3-5 Hz are detected. Furthermore, the buildup of the slow oscillation begins in the bihippocampal network that includes the focus, which synchronizes and drives the activity across the large-scale epileptic network into the frontal cortex. This study provides the first functional description of the emergence of neocortical fast ripples in hippocampal epilepsy and shows that cross-frequency coupling might be a fundamental mechanism underlying the spreading of epileptic activity.


cross-frequency coupling; epilepsy; epileptic network; fast-ripples; oscillation

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