We aimed to review shared brain localizations and morphological changes across NREM parasomnias as well as specific ones in their subtypes. The EEG changes described in the literature, were sorted to ones found in the waking periods of NREM parasomnia patients; changes in timely relation with the episodes, and those far from the episodes in sleep. The results found were highly inconsistent due to multiple types of patient selection (mixed or specific DOA populations) and methodological issues such as EEG sampling times (before, during, or between behavioural episodes); connectivity, spectral power, and eLORETA studies as well as heterogeneous imaging methods. Most publications have dealt with sleepwalking, some with mixed types of DOA, and a few with just specific types such as sleep talking, sexsomnia, confusional arousals, or sleep-related eating disorders.

During different DOA-episodes, the predominantly involved activated regions included the anterior cingulate and the motor cortex, confirming the early SPECT study of Bassetti et al. showing the highest increases of regional cerebral blood flow during sleepwalking in the anterior cerebellum and in the posterior cingulate cortex contrasting large frontal and parietal association cortices with less blood flow deactivated; in sleep. Additional regions of interest were the centro-parietal, visual, associative parietal, fronto-central regions, and the cuneus [29].

In certain studies, the EEG beta-connectivity increased between the motor and cingulate cortices and between frontal and parietal alpha frequency bands, as well as the thalamus and the occipital cortex, even during non-behavioural arousals [45], indicating permanently increased motor readiness, likely due to dysregulated cortical-subcortical interactions [54]. Conversely, reduced connectivity within cingulate segments suggested Default Mode Network (DMN) disorganization, potentially disrupting motor and cognitive regulation during NREM sleep [55].

The early stereo-EEG study of Terzaghi et al., evidencing the sleep-wake dissociation concept; local arousal of the motor and cingulate cortices versus increased delta activity in the frontoparietal associative cortices immediately before and during confusional arousal [28]; has been confirmed by the eLORETA study of Januszko et al. They have shown locally increased 24–30 Hz activity in the anterior cingulate cortex before several sleepwalking episodes of multiple patients [31], confirming “fluid boundaries” between sleep and wakefulness; local cingulate arousal within sleeping brains. The study of Castelnovo et al. has pointed out that roughly the same set of regions was affected by state-dissociation in NREM and REM sleep as well as in wakefulness, far from clinical episodes. The sleep-wake dissociation during waking has been confirmed by another study as well: DOA persons’ waking states were scattered by slow waves; suggesting permanently unstable state-boundaries in this group of disorders [45].

Therefore, we feel it justified to consider overall NREM parasomnias as ‘state-dissociation conditions’ characterized by a trait-like sleep-wake-dissociation; i.e., one occurring in each vigilance-state of the affected patient’. This could account for their unexpected neuropsychological changes and daytime sleepiness [45].

The results seem to converge to a central role of the cingulate gyrus. The anterior cingulate cortex is the main site of K-complex generation [25]. This region is linked to emotional processing, voluntary motor control, and decision-making and is closely interlinked with the salience network [56], which in turn may activate the hypothalamo-pituitary-adrenal axis, driving stress responses [57]. Therefore, its local (dissociated) activation in line with prevailing sleep in most parts of the brain may result in complex motor activities with partial or lacking awareness to the episodes; as well as emotional and fearful outbursts emerging in sleep terrors [58].

Certain studies have shown HSD just before or at the very onset of sleepwalking episodes [39, 40], possibly indicating a build-up of neural activity disrupting sleep architecture and triggering DOA episodes with sensory and spatial processing [28, 59]. The existence of HSD might confirm the hypothesis of DOA resulting from an imbalance of sleep-promoting and arousal processes [60, 61].

The reported increase in slow wave activity during the partial arousals of sleep terror episodes underscores the unique neural bases that distinguish parasomnias from ‘‘normal’’ arousals and typical sleep-wake transitions [41, 62].

A study on EEG differences in verbal versus non-verbal sleep talking found reduced theta and alpha power in the left centro-parieto-occipital regions, disrupting normal oscillatory rhythms and enabling speech-related processes during sleep [63].

Studies on cerebral blood flow point to the exposure of key areas in the generation of slow wave sleep and DOA episodes, as well as of those regions involved in impaired awareness and the reduced pain perception during sleepwalking episodes [21, 51, 64]. Those studies highlighting the hypo-perfusion in frontal and temporal areas and hyperperfusion in the parahippocampal gyrus confirm that sleepwalking involves complex, state-dependent brain dysfunctions as well as state-dissociations [65].

We found but a single morphological study in NREM parasomnia patients. In convergence with other imaging methods, it has revealed reduced grey matter volume in the left dorsal posterior cingulate and posterior mid-cingulate cortex [48]. Such cortical volume-reduction could be involved in the dysregulation of arousal and sleep-stage transitions, contributing to the wake-like motor activity with impaired consciousness in sleep [66, 67]. Additionally, structural abnormalities in these regions might hinder the normal suppression of the DMN during NREM sleep, promoting parasomnias [68].

While this single study identifies intriguing morphological alterations in individuals with NREM parasomnias, it requires confirmation by other, preferably systematic trials on higher number of DOA-patients. This highlights a significant gap in the literature and underscores the importance of future research using larger samples and multimodal imaging approaches to explore the neuroanatomical underpinnings of NREM parasomnia subtypes.

Limitations.

A major limitation of this review is the small number (just one) of studies investigating structural brain changes in individuals with NREM parasomnias. As such, any interpretations regarding brain morphology remain speculative and should be approached with caution.

Another notable limitation is the significant heterogeneity across the included studies, encompassing differences in study design, sample size, neuroimaging modalities (e.g., EEG, fMRI, PET), participant populations (heterogeneous patient population), as well as the timing of data acquisition relative to parasomnia episodes. This variability precluded a meta-analytic approach and limits the generalizability of our conclusions.

As a possible limitation of the study, language restrictions and database selection may have resulted in the omission of relevant studies published in non-English languages or those indexed in less commonly used databases. Another limitation might be that the study was conducted following the steps of the systematic review, through which we didn’t perform a quality appraisal for each step.