Recently, in the past decade, high-frequency oscillations (HFOs), very high-frequency oscillations (VHFOs), and ultra-fast oscillations (UFOs) were reported in epileptic patients with drug-resistant epilepsy. However, to this day, the physiological origin of these events has yet to be understood. Our study establishes a mathematical framework based on bifurcation theory for investigating the occurrence of VHFOs and UFOs in depth EEG signals of patients with focal epilepsy, focusing on the potential role of reduced connection strength between neurons in an epileptic focus. We demonstrate that synchronization of a weakly coupled network can generate very and ultra high-frequency signals detectable by nearby microelectrodes. In particular, we show that a bistability region enables the persistence of phase-shift synchronized clusters of neurons. This phenomenon is observed for different hippocampal neuron models, including Morris-Lecar, Destexhe-Paré, and an interneuron model. The mechanism seems to be robust for small coupling, and it also persists with random noise affecting the external current. Our findings suggest that weakened neuronal connections could contribute to the production of oscillations with frequencies above 1000 Hz, which could advance our understanding of epilepsy pathology and potentially improve treatment strategies. However, further exploration of various coupling types and complex network models is needed.

We have built a mathematical framework to examine how a reduced neuronal coupling within an epileptic focus could lead to very high-frequency (VHFOs) and ultra-fast oscillations (UFOs) in depth EEG signals. By analyzing weakly coupled neurons, we found a bistability synchronization region where in-phase and anti-phase synchrony persist. These dynamics can be detected as very high-frequency EEG signals. The principle of weak coupling aligns with the disturbances in neuronal connections often observed in epilepsy; moreover, VHFOs are important markers of epileptogenicity. Our findings point to the potential significance of weakened neuronal connections in producing VHFOs and UFOs related to focal epilepsy. This could enhance our understanding of brain disorders. We emphasize the need for further investigations of weakly coupled neurons.

• Klíčová slova
• Bifurcations, Epilepsy, Neuronal network model, Phase-shift synchrony, Ultra-fast oscillations, Very high-frequency oscillations,
• Publikační typ
• časopisecké články MeSH

The electrophysiological EEG features such as high frequency oscillations, spikes and functional connectivity are often used for delineation of epileptogenic tissue and study of the normal function of the brain. The epileptogenic activity is also known to be suppressed by cognitive processing. However, differences between epileptic and healthy brain behavior during rest and task were not studied in detail. In this study we investigate the impact of cognitive processing on epileptogenic and non-epileptogenic hippocampus and the intracranial EEG features representing the underlying electrophysiological processes. We investigated intracranial EEG in 24 epileptic and 24 non-epileptic hippocampi in patients with intractable focal epilepsy during a resting state period and during performance of various cognitive tasks. We evaluated the behavior of features derived from high frequency oscillations, interictal epileptiform discharges and functional connectivity and their changes in relation to cognitive processing. Subsequently, we performed an analysis whether cognitive processing can contribute to classification of epileptic and non-epileptic hippocampus using a machine learning approach. The results show that cognitive processing suppresses epileptogenic activity in epileptic hippocampus while it causes a shift toward higher frequencies in non-epileptic hippocampus. Statistical analysis reveals significantly different electrophysiological reactions of epileptic and non-epileptic hippocampus during cognitive processing, which can be measured by high frequency oscillations, interictal epileptiform discharges and functional connectivity. The calculated features showed high classification potential for epileptic hippocampus (AUC = 0.93). In conclusion, the differences between epileptic and non-epileptic hippocampus during cognitive processing bring new insight in delineation between pathological and physiological processes. Analysis of computed iEEG features in rest and task condition can improve the functional mapping during pre-surgical evaluation and provide additional guidance for distinguishing between epileptic and non-epileptic structure which is absolutely crucial for achieving the best possible outcome with as little side effects as possible.

• Klíčová slova
• cognitive processing, functional connectivity, high frequency oscillation (HFO), hippocampus, interictal epileptiform discharge, pharmacoresistant epilepsy,
• Publikační typ
• časopisecké články MeSH