Abstract
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.
Footnotes
The authors declare no competing financial interests. L.S. was supported by the Swiss National Science Foundation (Grant 323530-158125). G.B. was supported by the Swiss National Science Foundation (Grant 140332). C.M. was supported by the Swiss National Science Foundation (Grant 320030-159705), by the National Center of Competence in Research (NCCR) “SYNAPSY,” and by the Center for Biomedical Imaging (CIBM) from Geneva and Lausanne. C.Q. was supported by the Fondation Ernst et Lucie Schmidheiny and by the Swiss League Against Epilepsy.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.