During non-rapid eye movement (NREM) sleep (stage N3), when consciousness fades, cortico-cortical interactions are impaired while neurons are still active and reactive. Why is this? We compared cortico-cortical evoked-potentials recorded during wakefulness and NREM by means of time-frequency analysis and phase-locking measures in 8 epileptic patients undergoing intra-cerebral stimulations/recordings for clinical evaluation. We observed that, while during wakefulness electrical stimulation triggers a chain of deterministic phase-locked activations in its cortical targets, during NREM the same input induces a slow wave associated with an OFF-period (suppression of power>20Hz), possibly reflecting a neuronal down-state. Crucially, after the OFF-period, cortical activity resumes to wakefulness-like levels, but the deterministic effects of the initial input are lost, as indicated by a sharp drop of phase-locked activity. These findings suggest that the intrinsic tendency of cortical neurons to fall into a down-state after a transient activation (i.e. bistability) prevents the emergence of stable patterns of causal interactions among cortical areas during NREM. Besides sleep, the same basic neurophysiological dynamics may play a role in pathological conditions in which thalamo-cortical information integration and consciousness are impaired in spite of preserved neuronal activity.

Non-rapid eye movement (NREM) sleep parasomnias (or NREM parasomnias) are fascinating disorders with mysterious neurobiological substrates. These conditions are common and often severe, with social, personal and forensic implications. The NREM parasomnias include sleepwalking, sleep terrors and confusional arousals - collectively termed disorders of arousal (DOAs) - as well as less well-known entities such as sleep-related sexual behaviours and eating disorders. Affected patients can exhibit waking behaviours arising abruptly out of NREM sleep. Although the individual remains largely unresponsive to the external environment, their EEG shows both typical sleep-like and wake-like features, and they occasionally report dreaming afterwards. Therefore, these disorders offer a unique natural model to explore the abnormal coexistence of local sleep and wake brain activity and the dissociation between behaviour and various aspects of consciousness. In this article, we critically review major findings and updates on DOAs, focusing on neurophysiological studies, and offer an overview of new clinical frontiers and promising future research areas. We advocate a joint effort to inform clinicians and the general public about the management and follow-up of these conditions. We also strongly encourage collaborative multicentre studies to add more objective polysomnographic criteria to the current official diagnostic definitions and to develop clinical practice guidelines, multidisciplinary research approaches and evidence-based medical care.

SUMMARYPurpose: Sleep-related complex motor seizures are a common feature of nocturnal frontal lobe epilepsy. Nevertheless, recent studies also suggest that sleeprelated hypermotor seizures can originate in the insula. The present study describes the electroclinical features of eight drug-resistant epileptic patients with insularopercular seizures manifesting with nocturnal complex motor seizures. Methods: Patients underwent a comprehensive presurgical evaluation, which included history, interictal electroencephalography (EEG), scalp video-EEG monitoring, high-resolution magnetic resonance imaging (MRI), and intracerebral recording by stereo-EEG. Key Findings: Almost all patients reported an initial sensation consisting of viscerosensitive or somatosensory symptoms. Ictal clinical signs were represented by tonicdystonic asymmetric posturing and/or hyperkinetic automatisms, including bimanual/bipedal activity and ballistic movements. Some patients exhibited dysarthric speech, hypersalivation, and apnea. Interictal and ictal EEG provided lateralizing information in the majority of patients. In three patients, MRI showed a focal anatomical abnormality in the insular-opercular region. Stereo-EEG ictal recordings demonstrated that the epileptic discharge involved simultaneously the insular cortex and the opercular region. Complex motor manifestations appeared when the ictal discharge showed an extrainsular spreading to frontomesial regions (cingulum, superior frontal gyrus, and supplementary motor area) and/or to internal and neocortical temporal lobe structures. Six patients received an insular-opercular cortical resection; three of them are seizure free (minimum follow-up 24 months) and in one a marked reduction in seizure frequency was obtained. Two patients have been operated on recently. Histology revealed a focal cortical dysplasia in three patients. One patient excluded from surgery died for sudden unexpected death in epilepsy during sleep. Significance: Our data strengthen the concept that sleeprelated complex motor attacks can originate in the insula, and provide useful electroclinical information to differentiate this localization from those with similar clinical characteristics. Furthermore, this study indicates that in these drug-resistant patients, surgical treatment represents a highly effective treatment option.