Navigating Pubertal Goldilocks: The Optimal Pace for Hierarchical Brain Organization.

Adolescence is a timed process with an onset, tempo, and duration. Nevertheless, the temporal dimension, especially the pace of maturation, remains an insufficiently studied aspect of developmental progression. The primary objective is to estimate the precise influence of pubertal maturational tempo on the configuration of associative brain regions. To this end, the connection between maturational stages and the level of hierarchical organization of large-scale brain networks in 12-13-year-old females is analyzed. Skeletal maturity is used as a proxy for pubertal progress. The degree of maturity is defined by the difference between bone age and chronological age. To assess the level of hierarchical organization in the brain, the temporal dynamic of closed eye resting state high-density electroencephalography (EEG) in the alpha frequency range is analyzed. Different levels of hierarchical order are captured by the measured asymmetry in the directionality of information flow between different regions. The calculated EEG-based entropy production of participant groups is then compared with accelerated, average, and decelerated maturity. Results indicate that an average maturational trajectory optimally aligns with cerebral hierarchical order, and both accelerated and decelerated timelines result in diminished cortical organization. This suggests that a "Goldilocks rule" of brain development is favoring a particular maturational tempo.

The adolescent pattern of sleep spindle development revealed by HD-EEG.

Sleep spindles are developmentally relevant cortical oscillatory patterns; however, they have mostly been studied by considering the entire spindle frequency range (11-15 Hz) without a distinction between the functionally and topographically different slow and fast spindles, using relatively few electrodes and analysing wide age-ranges. Here, we employ high-density night sleep electroencephalography in three age-groups between 12 and 20 years of age (30 females and 30 males) and analyse the adolescent developmental pattern of the four major parameters of slow and fast sleep spindles. Most of our findings corroborate those very few previous studies that also make a distinction between slow and fast spindles in their developmental analysis. We find spindle frequency increasing with age. A spindle density change is not obvious in our study. We confirm the declining tendencies for amplitude and duration, although within narrower, more specific age-windows than previously determined. Spindle frequency seems to be higher in females in the oldest age-group. Based on the pattern of our findings, we suggest that high-density electroencephalography, specifically targeting slow and fast spindle ranges and relatively narrow age-ranges would advance the understanding of both adolescent cortical maturation and development and the functional relevance of sleep spindles in general.

Overnight dynamics in scale-free and oscillatory spectral parameters of NREM sleep EEG.

Unfolding the overnight dynamics in human sleep features plays a pivotal role in understanding sleep regulation. Studies revealed the complex reorganization of the frequency composition of sleep electroencephalogram (EEG) during the course of sleep, however the scale-free and the oscillatory measures remained undistinguished and improperly characterized before. By focusing on the first four non-rapid eye movement (NREM) periods of night sleep records of 251 healthy human subjects (4-69 years), here we reveal the flattening of spectral slopes and decrease in several measures of the spectral intercepts during consecutive sleep cycles. Slopes and intercepts are significant predictors of slow wave activity (SWA), the gold standard measure of sleep intensity. The overnight increase in spectral peak sizes (amplitudes relative to scale-free spectra) in the broad sigma range is paralleled by a U-shaped time course of peak frequencies in frontopolar regions. Although, the set of spectral indices analyzed herein reproduce known age- and sex-effects, the interindividual variability in spectral slope steepness is lower as compared to the variability in SWA. Findings indicate that distinct scale-free and oscillatory measures of sleep EEG could provide composite measures of sleep dynamics with low redundancy, potentially affording new insights into sleep regulatory processes in future studies.

Analysis of slow and fast sleep spindle properties in Parkinson's disease - A comparative EEG study.

STUDY OBJECTIVES: Sleep disturbances and altered sleep macrostructure are common in Parkinson's disease (PD). Few studies have addressed the changes in sleep spindle (SS) properties in this movement disorder so far. SS seem to be fundamental of both sleep architecture and memory consolidation. The aim of our comparative study was to investigate the changes of SS characteristics in PD, and reveal the relationship between SS properties and cognitive function. METHODS: We investigated 20 PD patients and 18 age-matched controls. All participants underwent a 24-hour-long polygraphic EEG recording after extensive clinical investigation. We detected slow and fast SS properties automatically using individual adjusting method (IAM). The data were statistically evaluated. RESULTS: We found significantly lower fast spindle amplitude in PD comparing with controls. We did not find significant differences in SS densities, duration and oscillatory frequency between the groups. We detected significant positive correlation between fast SS amplitude and memory in PD, and between fast SS density and retrograde memory in controls. The total Addenbrooke's cognitive score correlated negatively with slow SS density and duration in controls. CONCLUSIONS: By the time clinical diagnosis of PD is established, the pathological process is already spreading. Changes in sleep macrostructure and SS properties might become a useful biomarker of the neurodegenerative process in PD. In addition, decreased fast SS amplitude might predict further cognitive deterioration and indicate early involvement of corresponding cortical area. Our study results strengthen the importance of EEG examination in PD, and the use of IAM method in SS analysis.

Scale-free and oscillatory spectral measures of sleep stages in humans.

Power spectra of sleep electroencephalograms (EEG) comprise two main components: a decaying power-law corresponding to the aperiodic neural background activity, and spectral peaks present due to neural oscillations. "Traditional" band-based spectral methods ignore this fundamental structure of the EEG spectra and thus are susceptible to misrepresenting the underlying phenomena. A fitting method that attempts to separate and parameterize the aperiodic and periodic spectral components called "fitting oscillations and one over f" (FOOOF) was applied to a set of annotated whole-night sleep EEG recordings of 251 subjects from a wide age range (4-69 years). Most of the extracted parameters exhibited sleep stage sensitivity; significant main effects and interactions of sleep stage, age, sex, and brain region were found. The spectral slope (describing the steepness of the aperiodic component) showed especially large and consistent variability between sleep stages (and low variability between subjects), making it a candidate indicator of sleep states. The limitations and arisen problems of the FOOOF method are also discussed, possible solutions for some of them are suggested.

Maturation-dependent vulnerability of emotion regulation as a response to COVID-19 related stress in adolescents.

BACKGROUND: The COVID-19 pandemic created unpredictable circumstances resulting in increased psychological strain. Here we investigate pandemic-related alterations in emotion regulation in adolescents assessed before and during the pandemic. We also take biological age into account in the response to the pandemic. METHODS: Mann-Whitney U tests were conducted to compare baseline data on the Difficulties in Emotion Regulation Scale (DERS) total scores of a pre-pandemic adolescent cohort (n = 241) with those obtained during the second wave of the pandemic (n = 266). We estimated biological age based on an ultrasonic boneage assessment procedure in a subgroup of males, including grammar school and vocational school students in the 9th and 10th grades, and analyzed their data independently. FINDINGS: There is a gender difference in the timing of vulnerability for pandemic-related stress in grammar school students: females are affected a year earlier than males. Vocational school male students mature faster than grammar school male students, and the timing of emotional vulnerability also precedes that of the grammar school students'. DISCUSSION: We interpret our findings within a developmental model suggesting that there might be a window of highest vulnerability in adolescent emotion regulation. The timing of the window is determined by both chronological and biological age, and it is different for females and males. APPLICATION TO PRACTICE: Defining the exact temporal windows of vulnerability for different adolescent cohorts allows for the timely integration of preventive actions into adolescent care to protect mental health during future chronic stressful situations.

Visual imagery vividness declines across the lifespan.

The capacity to elicit vivid visual mental images varies within an extensive range across individuals between hyper- and aphantasia. It is not clear, however, whether imagery vividness is constant across the lifespan or changes during development and later in life. Without enforcing the constraints of strict experimental procedures and representativity across the entire population, our purpose was to explore the self-reported level of imagery vividness and determine the relative proportions of aphantasic/hyperphantasic participants in different age groups. Relying on the frequently used Vividness of Visual Imagery Questionnaire, we collected data on a random sample of 2252 participants between the ages of 12-60 years. We found a novel developmental pattern that describes a declining ability to elicit vivid visual mental images in the group averages of different age groups from adolescence to middle age. This effect involves both a decreasing proportion of individuals with vivid visual imagery vividness and an increasing proportion of individuals with low imagery vividness as maturation (based on bone age assessments in adolescents) and ageing progress. These findings may shed some light on the developmental mechanisms of our internal, stimulus-independent processes, and might also help to determine genetic, maturational, and age-dependent factors in the cases of hyper- and aphantasia.

Musical training improves fine motor function in adolescents.

BACKGROUND: Adolescence is a sensitive period in motor development but little is known about how long-term learning dependent processes shape hand function in tasks of different complexity. PROCEDURE: We mapped two fundamental aspects of hand function: simple repetitive and complex sequential finger movements, as a function of the length of musical instrumental training. We controlled maturational factors such as chronological and biological age of adolescent female participants (11 to 15 years of age, n = 114). RESULTS: We demonstrated that experience improves performance as a function of task complexity, the more complex task being more susceptible for experience driven performance changes. CONCLUSION: Overall, these results suggest that fine motor skills involving cognitive control and relying on long-range functional brain networks are substantially shaped by experience. On the other hand, performance in a simple repetitive task that explains fine motor speed is primarily determined by white matter development driven by maturational factors.

Topographical relocation of adolescent sleep spindles reveals a new maturational pattern in the human brain.

Current theories of human neural development emphasize the posterior-to-anterior pattern of brain maturation. However, this scenario leaves out significant brain areas not directly involved with sensory input and behavioral control. Suggesting the relevance of cortical activity unrelated to sensory stimulation, such as sleep, we investigated adolescent transformations in the topography of sleep spindles. Sleep spindles are known to be involved in neural plasticity and in adults have a bimodal topography: slow spindles are frontally dominant, while fast spindles have a parietal/precuneal origin. The late functional segregation of the precuneus from the frontoparietal network during adolescence suggests that spindle topography might approach the adult state relatively late in development, and it may not be a result of the posterior-to-anterior maturational pattern. We analyzed the topographical distribution of spindle parameters in HD-EEG polysomnographic sleep recordings of adolescents and found that slow spindle duration maxima traveled from central to anterior brain regions, while fast spindle density, amplitude and frequency peaks traveled from central to more posterior brain regions. These results provide evidence for the gradual posteriorization of the anatomical localization of fast sleep spindles during adolescence and indicate the existence of an anterior-to-posterior pattern of human brain maturation.

Ultrasonic bone age fractionates cognitive abilities in adolescence.

Adolescent development is not only shaped by the mere passing of time and accumulating experience, but it also depends on pubertal timing and the cascade of maturational processes orchestrated by gonadal hormones. Although individual variability in puberty onset confounds adolescent studies, it has not been efficiently controlled for. Here we introduce ultrasonic bone age assessment to estimate biological maturity and disentangle the independent effects of chronological and biological age on adolescent cognitive abilities. Comparing cognitive performance of female participants with different skeletal maturity we uncover the impact of biological age on both IQ and specific abilities. We find that biological age has a selective effect on abilities: more mature individuals within the same age group have higher working memory capacity and processing speed, while those with higher chronological age have better verbal abilities, independently of their maturity. Based on our findings, bone age is a promising biomarker of adolescent maturity.

Sleep alterations are related to cognitive symptoms in Parkinson's disease: A 24-hour ambulatory polygraphic EEG study.

BACKGROUND: Sleep disorders are frequent and early non-motor symptoms of Parkinson's disease (PD). As a consequence of histopathological changes, the regulation of rapid eye movement (REM) sleep is affected in PD causing REM sleep behaviour disorder in about half of the patients. Considering the well-known role of sleep in memory formation processes, our aim was to investigate the relationship between sleep alterations and cognitive performance to elucidate the possible association between sleep, and especially REM sleep changes and cognitive dysfunction in PD. METHODS: We investigated 25 PD patients and 20 healthy controls. All participants underwent a 24-hour-long 19-channel polygraphic EEG recording, neurological, neuroimaging and neuropsychological examination. The visually analysed sleep-EEG and neuropsychological data were statistically evaluated. RESULTS: The intergroup analysis showed significant decrease of REM and N3, but increase of N2 sleep ratio, and significantly lower scores in the verbal fluency in PD compared to healthy controls. While we found significant negative correlation between verbal fluency and REM-sleep in the whole sample, we observed a marginal significant correlation between phonemic fluency and REM sleep in the PD group. CONCLUSION: The negative correlation between verbal fluency performance and REM sleep duration suggests the role of decreased REM sleep in cognitive dysfunction in PD. The early involvement of REM sleep regulation with parallel executive dysfunction in PD emphasise the important role of REM sleep deterioration in the neurodegenerative process of PD.

Sleep-spindle frequency: Overnight dynamics, afternoon nap effects, and possible circadian modulation.

Homeostatic and circadian processes play a pivotal role in determining sleep structure, timing, and quality. In sharp contrast with the wide accessibility of the electroencephalogram (EEG) index of sleep homeostasis, an electrophysiological measure of the circadian modulation of sleep is still unavailable. Evidence suggests that sleep-spindle frequencies decelerate during biological night. In order to test the feasibility of measuring this marker in common polysomnographic protocols, the Budapest-Munich database of sleep records (N = 251 healthy subjects, 122 females, age range: 4-69 years), as well as an afternoon nap sleep record database (N = 112 healthy subjects, 30 females, age range: 18-30 years) were analysed by the individual adjustment method of sleep-spindle analysis. Slow and fast sleep-spindle frequencies were characterised by U-shaped overnight dynamics, with highest values in the first and the fourth-to-fifth sleep cycle and the lowest values in the middle of the sleeping period (cycles two to three). Age-related attenuation of sleep-spindle deceleration was evident. Estimated phases of the nadirs in sleep-spindle frequencies were advanced in children as compared to other age groups. Additionally, nap sleep spindles were faster than night sleep spindles (0.57 and 0.39 Hz difference for slow and fast types, respectively). The fine frequency resolution analysis of sleep spindles is a feasible method of measuring the assumed circadian modulation of sleep. Moreover, age-related attenuation of circadian sleep modulation might be measurable by assessing the overnight dynamics in sleep-spindle frequency. Phase of the minimal sleep-spindle frequency is a putative biomarker of chronotype.

REM Sleep Microstates in the Human Anterior Thalamus.

Rapid eye movement (REM) sleep is an elusive neural state that is associated with a variety of functions from physiological regulatory mechanisms to complex cognitive processing. REM periods consist of the alternation of phasic and tonic REM microstates that differ in spontaneous and evoked neural activity. Although previous studies indicate, that cortical and thalamocortical activity differs across phasic and tonic microstates, the characterization of neural activity, particularly in subcortical structures that are critical in the initiation and maintenance of REM sleep is still limited in humans. Here, we examined electric activity patterns of the anterior nuclei of the thalamus as well as their functional connectivity with scalp EEG recordings during REM microstates and wakefulness in a group of epilepsy patients (N = 12, 7 females). Anterothalamic local field potentials (LFPs) showed increased high-α and ß frequency power in tonic compared with phasic REM, emerging as an intermediate state between phasic REM and wakefulness. Moreover, we observed increased thalamocortical synchronization in phasic compared with tonic REM sleep, especially in the slow and fast frequency ranges. Wake-like activity in tonic REM sleep may index the regulation of arousal and vigilance facilitating environmental alertness. On the other hand, increased thalamocortical synchronization may reflect the intrinsic activity of frontolimbic networks supporting emotional and memory processes during phasic REM sleep. In sum, our findings highlight that the heterogeneity of phasic and tonic REM sleep is not limited to cortical activity, but is also manifested by anterothalamic LFPs and thalamocortical synchronization.SIGNIFICANCE STATEMENT REM sleep is a heterogeneous sleep state that features the alternation of two microstates, phasic and tonic rapid eye movement (REM). These states differ in sensory processing, awakening thresholds, and cortical activity. Nevertheless, the characterization of these microstates, particularly in subcortical structures is still limited in humans. We had the unique opportunity to examine electric activity patterns of the anterior nuclei of the thalamus (ANTs) as well as their functional connectivity with scalp EEG recordings during REM microstates and wakefulness. Our findings show that the heterogeneity of phasic and tonic REM sleep is not limited to cortical activity, but is also manifested in the level of the thalamus and thalamocortical networks.

A set of composite, non-redundant EEG measures of NREM sleep based on the power law scaling of the Fourier spectrum.

Features of sleep were shown to reflect aging, typical sex differences and cognitive abilities of humans. However, these measures are characterized by redundancy and arbitrariness. Our present approach relies on the assumptions that the spontaneous human brain activity as reflected by the scalp-derived electroencephalogram (EEG) during non-rapid eye movement (NREM) sleep is characterized by arrhythmic, scale-free properties and is based on the power law scaling of the Fourier spectra with the additional consideration of the rhythmic, oscillatory waves at specific frequencies, including sleep spindles. Measures derived are the spectral intercept and slope, as well as the maximal spectral peak amplitude and frequency in the sleep spindle range, effectively reducing 191 spectral measures to 4, which were efficient in characterizing known age-effects, sex-differences and cognitive correlates of sleep EEG. Future clinical and basic studies are supposed to be significantly empowered by the efficient data reduction provided by our approach.

The laminar profile of sleep spindles in humans.

Sleep spindles are functionally important NREM sleep EEG oscillations which are generated in thalamocortical, corticothalamic and possibly cortico-cortical circuits. Previous hypotheses suggested that slow and fast spindles or spindles with various spatial extent may be generated in different circuits with various cortical laminar innervation patterns. We used NREM sleep EEG data recorded from four human epileptic patients undergoing presurgical electrophysiological monitoring with subdural electrocorticographic grids (ECoG) and implanted laminar microelectrodes penetrating the cortex (IME). The position of IMEs within cortical layers was confirmed using postsurgical histological reconstructions. Many spindles detected on the IME occurred only in one layer and were absent from the ECoG, but with increasing amplitude simultaneous detection in other layers and on the ECoG became more likely. ECoG spindles were in contrast usually accompanied by IME spindles. Neither IME nor ECoG spindle cortical profiles were strongly associated with sleep spindle frequency or globality. Multiple-unit and single-unit activity during spindles, however, was heterogeneous across spindle types, but also across layers and patients. Our results indicate that extremely local spindles may occur in any cortical layer, but co-occurrence at other locations becomes likelier with increasing amplitude and the relatively large spindles detected on ECoG channels have a stereotypical laminar profile. We found no compelling evidence that different spindle types are associated with different laminar profiles, suggesting that they are generated in cortical and thalamic circuits with similar cortical innervation patterns. Local neuronal activity is a stronger candidate mechanism for driving functional differences between spindles subtypes.

REM versus Non-REM sleep disturbance specifically affects inter-specific emotion processing in family dogs (Canis familiaris).

Dogs have outstanding capabilities to read human emotional expressions, both vocal and facial. It has also been shown that positively versus negatively valenced dog-human social interactions substantially affect dogs' subsequent sleep. In the present study, we manipulated dogs' (N = 15, in a within subject design) sleep structure by specifically disrupting REM versus Non-REM sleep, while maintaining equal sleep efficiency (monitored via non-invasive polysomnography). We found that both the number of awakenings as well as relative Non-REM (but not relative REM) duration influenced dogs' viewing patterns in a task where sad and happy human faces were simultaneously projected with sad or happy human voice playbacks. In accordance with the emotion laterality hypothesis, the interaction between sound valence and Non-REM sleep duration was specific to images projected to the left (regardless of image-sound congruency). These results reveal the first evidence of a causal link between sleep structure and inter-specific emotion-processing in the family dog.

Reliability of Family Dogs' Sleep Structure Scoring Based on Manual and Automated Sleep Stage Identification.

Non-invasive polysomnography recording on dogs has been claimed to produce data comparable to those for humans regarding sleep macrostructure, EEG spectra and sleep spindles. While functional parallels have been described relating to both affective (e.g., emotion processing) and cognitive (e.g., memory consolidation) domains, methodologically relevant questions about the reliability of sleep stage scoring still need to be addressed. In Study 1, we analyzed the effects of different coders and different numbers of visible EEG channels on the visual scoring of the same polysomnography recordings. The lowest agreement was found between independent coders with different scoring experience using full (3 h-long) recordings of the whole dataset, and the highest agreement within-coder, using only a fraction of the original dataset (randomly selected 100 epochs (i.e., 100 × 20 s long segments)). The identification of drowsiness was found to be the least reliable, while that of non-REM (rapid eye movement, NREM) was the most reliable. Disagreements resulted in no or only moderate differences in macrostructural and spectral variables. Study 2 targeted the task of automated sleep EEG time series classification. Supervised machine learning (ML) models were used to help the manual annotation process by reliably predicting if the dog was sleeping or awake. Logistic regression models (LogREG), gradient boosted trees (GBT) and convolutional neural networks (CNN) were set up and trained for sleep state prediction from already collected and manually annotated EEG data. The evaluation of the individual models suggests that their combination results in the best performance: ~0.9 AUC test scores.

Repeated afternoon sleep recordings indicate first-night-effect-like adaptation process in family dogs.

The importance of dogs (Canis familiaris) in sleep research is primarily based on their comparability with humans. In spite of numerous differences, dogs' comparable sleep pattern, as well as several phenotypic similarities on both the behavioural and neural levels, make this species a most feasible model in many respects. Our aim was to investigate whether the so-called first-night effect, which in humans manifests as a marked macrostructure difference between the first and second sleep occasions, can be observed in family dogs. We used a non-invasive polysomnographic method to monitor and compare the characteristics of dogs' (N = 24) 3-hr-long afternoon naps on three occasions at the same location. We analysed how sleep macrostructure variables differed between the first, second and third occasions, considering also the effects of potential confounding variables such as the dogs' age and sleeping habits. Our findings indicate that first-night effect is present in dogs' sleep architecture, although its specifics somewhat deviate from the pattern observed in humans. Sleep macrostructure differences were mostly found between occasions 1 and 3; dogs slept more, had less wake after the first drowsiness episode, and reached drowsiness sleep earlier on occasion 3. Dogs, which had been reported to sleep rarely not at home, had an earlier non-rapid eye movement sleep, a shorter rapid eye movement sleep latency, and spent more time in rapid eye movement sleep on occasion 3, compared with occasion 1. Extending prior dog sleep data, these results help increase the validity of further sleep electroencephalography investigations in dogs.

Cortical hyperarousal in NREM sleep normalizes from pre- to post- REM periods in individuals with frequent nightmares.

STUDY OBJECTIVES: Frequent nightmares have a high prevalence and constitute a risk factor for psychiatric conditions, but their pathophysiology is poorly understood. Our aim was to examine sleep architecture and electroencephalographic markers-with a specific focus on state transitions-related to sleep regulation and hyperarousal in participants with frequent nightmares (NM participants) versus healthy controls. METHODS: Healthy controls and NM participants spent two consecutive nights in the sleep laboratory. Second night spectral power during NREM to REM sleep (pre-REM) and REM to NREM (post-REM) transitions as well as during NREM and REM periods were evaluated for 22 NM participants compared to 22 healthy controls with a similar distribution of age, gender, and dream recall frequency. RESULTS: We found significant differences between the groups in the pre-REM to post-REM changes in low- and high-frequency domains. NM participants experienced a lower amount of slow-wave sleep and showed increased beta and gamma power during NREM and pre-REM periods. No difference was present during REM and post-REM phases. Furthermore, while increased pre-REM high-frequency power seems to be mainly driven by post-traumatic stress disorder (PTSD) symptom intensity, decreased low-frequency activity occurred regardless of PTSD symptom severity. CONCLUSION: Our findings indicate that NM participants had increased high-frequency spectral power during NREM and pre-REM periods, as well as relatively reduced slow frequency and increased fast frequency spectral power across pre-and post-REM periods. This combination of reduced sleep-protective activity and increased hyperarousal suggests an imbalance between sleep regulatory and wake-promoting systems in NM participants.

Hyperarousal captured in increased number of arousal events during pre-REM periods in individuals with frequent nightmares.

The aim of this study was to investigate hyperarousal in individuals with frequent nightmares (NM participants) by calculating arousal events during nocturnal sleep. We hypothesized an increased number of arousals in NM participants compared with controls, especially during those periods where the probability of spontaneous arousal occurrence is already high, such as non-rapid eye movement to rapid eye movement transitions (pre-rapid eye movement periods). Twenty-two NM participants and 23 control participants spent two consecutive nights in our sleep laboratory, monitored by polysomnography. Arousal number and arousal length were calculated only for the second night, for 10 min before rapid eye movement (pre-rapid eye movement) and 10 min after rapid eye movement (post-rapid eye movement) periods, as well as non-rapid eye movement and rapid eye movement phases separately. Repeated-measures ANOVA model testing revealed significant Group (NM participants, controls) × Phase (pre-rapid eye movement, post-rapid eye movement) interaction in case of the number of arousals. Furthermore, post hoc analysis showed a significantly increased number of arousals during pre-rapid eye movement periods in NM participants, compared with controls, a difference that disappeared in post-rapid eye movement periods. We propose that focusing the analyses of arousals specifically on state transitory periods offers a unique perspective into the fragile balance between the sleep-promoting and arousal systems. This outlook revealed an increased number of arousals in NM participants, reflecting hyperarousal during pre-rapid eye movement periods.