Sleep and epilepsy: contribution of intracerebral EEG

Intracerebral EEG recording is an established method in the presurgical evalution of epileptic patients. It provides the unique opportunity to examine site-specific interactions between sleep and epilepsy. Only recently, intracerebral EEG demonstrated that sleep is not a generalized but a local phenomenon. This study aims to gain novel insights into physiological and pathological human sleep. We will elucidate 3 different perspectives, namely: 1.) Investigation of EEG pre- and postictal vigilance fluctuations in relation to diurnal seizures, 2.) Analysis of the relationships between High Frequency Oscillations (HFOs) an innovative biomarker for epileptogenic tissue -, epileptiform discharges and sleep transients, as both HFOs and sleep transients are assumed to be influenced by thalamic activity, 3.) Exploration of how different brain regions may differentially participate in sleep, given recent findings regarding the possible focal nature of sleep. Intracerebral EEG recordings of approximately 60 consecutive epileptic patients who will undergo at least 1 night of additional sleep recording will be analyzed. Project 1 will assess EEG vigilance fluctuations for the 30 minutes before and after diurnal partial seizures by both visual inspection and quantitative EEG analysis. Project 2 will investigate random 5-minute sleep samples gathered from different sleep stages and sleep cycles to assess the relationship between high frequency oscillations (HFOs), epileptiform discharges and sleep cycle, as well as type of NREM sleep stage, and stage-specific sleep transients. Project 3 will evaluate differences between conventional surface EEG sleep scoring and site-specific sleep pattern. In a subgroup of patients with depth electrodes in cortical motor areas, we will investigate whether physiological REM-sleep related minor movements are primarily cortically generated as in case of movements during wakefulness. The project is expected to contribute to gain novel insights on physiological and pathological sleep, and will open an innovative novel area of research at the interface between sleep and epilepsy. For the field of epileptology the acquired knowledge on distribution of HFOs will contribute to a better utilizability of this technique in clinical routine as ideal selection of candidate samples for HFO scoring saves a considerable amount of time. For the field of sleep medicine, the current study will help to further advance the understanding of the mechanisms of sleep and its motor control.

Intracerebral electroencephalographic (EEG) recording, used in the setting of presurgical epilepsy evaluation, provides the unique opportunity to study important clinical inter-relationships between sleep and epilepsy. This project applied the technique of intracerebral EEG in order to gain novel insights into sleep physiology and interactions between epileptic activity and sleep. The major findings were that i) sleep is indeed more locally regulated compared to the traditional view of sleep as a global phenomenon; ii) sleep slow waves and not NREM sleep itself trigger epileptic activity, and iii) synchronization as opposed to desynchronization is crucial for the generation of epileptic activity. Sleep spindles are important for memory consolidation and brain development. We found that spindles in the scalp were accompanied by widespread cortical sleep spindles. This intracranial involvement during scalp spindles showed no consistent pattern, and exhibited unexpectedly low synchrony across brain regions. We further investigated whether the transitions from NREM to REM sleep are synchronous across different brain areas. We found that the transitions from NREM to REM were significantly more spread in intracranial EEG compared to the scalp. No consistent patterns were found in intracranial channels, further underlining the concept of sleep as a local phenomenon. We hypothesized that sleep slow waves and not NREM sleep itself trigger epileptic spikes and pathological high frequency oscillations (HFOs), a novel biomarker for epilepsy. We found that epileptic spikes and HFOs were more frequently present during sleep slow waves compared to the rest of NREM sleep. In fact, both variables occurred at the transition from the activated to the deactivated state of the slow wave pointing to the importance of synchronization for the activation of epileptic activity. A further project investigated the role of desynchronization. We found that REM sleep with rapid eye movements, the sleep state with highest desynchronization, has even lower rates of spikes and HFOs compared to REM sleep without rapid eye movements. Both studies showed that epileptic HFOs are differently coupled to slow waves or rapid eye movements compared to HFOs in healthy brain regions. In summary, this project contributed to a better understanding of physiological sleep highlighting the importance of the local cortical influence for sleep generation. It also shed light into the mechanisms of sleep-related epileptogenesis.