| Summary: | We consider the disorders of arousal and sleep-related hypermotor epilepsy as genetic twin-conditions, one without, one with epilepsy. They share an augmented arousal-activity during NREM sleep with sleep-wake dissociations, culminating in sleep terrors and sleep-related hypermotor seizures with similar symptoms. The known mutations underlying the two spectra are different, but there are multifold population-genetic-, family- and even individual (the two conditions occurring in the same person) overlaps supporting common genetic roots. In the episodes of disorders of arousal, the anterior cingulate, anterior insular and pre-frontal cortices (shown to be involved in fear- and emotion processing) are activated within a sleeping brain. These regions overlap with the seizure-onset zones of successfully operated sleep-related hypermotor seizures, and notably, belong to the salience network being consistent with its hubs. The arousal-relatedness and the similar fearful confusion occurring in sleep terrors and hypermotor seizures, make them alike acute stress-responses emerging from sleep; triggered by false alarms. The activation of the anterior cingulate, prefrontal and insular regions in the episodes of both conditions, can easily mobilize the hypothalamo-pituitary-adrenal axis (preparing fight-flight responses in wakefulness); through its direct pathways to and from the salience network. This hypothesis has never been studied.
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