Study On High-low Frequency Oscillations Of Hippocampal Network In Mice With Temporal Lobe Epilepsy

Temporal lobe epilepsy（TLE）is one of the most common types of epilepsy in humans.High-frequency oscillations（HFOs）refer to EEG signals with a frequency range above 80 Hz,which can be further subdivided into Ripple（Ripple;80-250 Hz）and Fast ripple（FR;250-500 Hz）.Studies suggest that HFOs may be an important biomarker of epilepsy,and the interaction between HFOs and low-frequency signals may be involved in the process of epilepsy.However,the exact neural mechanism of HFOs and high-low frequency coupling in the development of epilepsy is not fully understood.Therefore,based on the Li Cl-Pilocarpine epilepsy mouse model,this thesis conducts a statistical analysis of the characteristic distribution of HFOs in the hippocampal network,and analyzes the cross-frequency coupling relationship of high-low frequency signals in the hippocampal network in different states of epilepsy.By exploring characteristics of HFOs and high-low frequency signals coupling,it provides an experimental basis for further understanding the neural mechanism of epilepsy development.The main findings of this thesis are as follows:1.The characteristic statistics of HFOs show that the number of FR increases significantly during ictal state,so compared with Ripple,FR is more able to characterize epileptic seizures;at the same time,the change trend of FR number and Ripple number after ictal state are opposite,suggesting that FR and Ripple have different roles in epilepsy.2.The phase-locked coupling results based on Ripple and FR show that the significant phase-locking couplings between FR and low-frequency oscillations change more significantly during epilepsy states,which further proves that FR is a better indicator of epileptic states than Ripple;the significant phase-locking couplings of FR and lowfrequency oscillations increased during the ictal and postictal states,and the locations of the significant phase-locked angles of FR and low-frequency oscillations in various hippocampus regions tended to be consistent,indicating that cross-frequency coupling change in hippocampal brain regions is associated with epileptic seizures.3.The study of the synchronization of hippocampal network shows that the changes of the synchronization of hippocampal network in the Ripple and FR frequency bands are significantly different from those in the low-frequency band;the study of the effective connectivity of the hippocampal network shows that the information interaction of the hippocampal network during ictal state increase significantly,and the increased effective connectivity is mostly derived from the Entorhinal cortex（EC）,indicating that the EC region plays a key role in the process of seizures onset.In summary,this thesis reveals that the changes of Ripple and FR are involved in the process of epilepsy from the perspective of changes in HFOs during epilepsy and their coupling with low frequencies signals.The results can provide important reference for HFOs as a biomarker of epilepsy,and provide a new idea for further understanding the neural mechanism of epilepsy.