Optimizing the Time and Dose of Melatonin as a Sleep-Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose-Response Meta-Analysis.

Previous studies have reported inconsistent results about exogenous melatonin's sleep-promoting effects. A possible explanation relies on the heterogeneity in administration schedule and dose, which might be accountable for differences in treatment efficacy. In this paper, we undertook a systematic review and meta-analysis of double-blind, randomized controlled trials performed on patients with insomnia and healthy volunteers, evaluating the effect of melatonin administration on sleep-related parameters. The standardized mean difference between treatment and placebo groups in terms of sleep onset latency and total sleep time were used as outcomes. Dose-response and meta-regression models were estimated to explore how time of administration, dose, and other treatment-related parameters might affect exogenous melatonin's efficacy. We included 26 randomized controlled trials published between 1987 and 2020, for a total of 1689 observations. Dose-response meta-analysis showed that melatonin gradually reduces sleep onset latency and increases total sleep time, peaking at 4 mg/day. Meta-regression models showed that insomnia status (ß = 0.50, p < 0.001) and time between treatment administration and the sleep episode (ß = -0.16, p = 0.023) were significant predictors of sleep onset latency, while the time of day (ß = -0.086, p < 0.01) was the only significant predictor of total sleep time. Our results suggest that advancing the timing of administration (3 h before the desired bedtime) and increasing the administered dose (4 mg/day), as compared to the exogenous melatonin schedule most used in clinical practice (2 mg 30 min before the desired bedtime), might optimize the efficacy of exogenous melatonin in promoting sleep.

Hypnotizability-related risky experience and behavior.

Risk is the probability of an adverse event. The proneness to take a risk and the risk taking behavior differ among the general population. Hypnotizability is a stable psychophysiological trait expressing the individual proneness to modify perception, memory and behavior following specific suggestions also in the ordinary state of consciousness. Some hypnotizability-related neurophysiological and behavioral correlates suggest that hypnotizability level, measured by standard scales classifying individuals as low (lows), medium (mediums) and high hypnotizable (highs) subjects, can be related to risk propensity and risk-taking. To study whether hypnotizability modulates risk propensity and behavior, we recruited healthy participants, classified through the Standford Hypnotic Susceptibility scale, form A, and compared lows' (n = 33), mediums' (n = 19) and highs'(n = 15) experiential and behavioral risk perception and propensity variables through the Domain-specific risk-taking scale and the Balloon Analogue Risk Task. MANOVA results indicated that different hypnotizability levels are not associated with different risky behavior and experience, except for higher expected financial benefits from risky behavior in lows. However, hypnotizability-related risk profiles were identified through correlational analyses. In fact, highs exhibited a negative association between risk perception and propensity to risk-taking, whereas mediums and lows displayed a positive association between risk propensity and expected benefit. In conclusion, the highs' profile indicates a more automatic behavior with respect to mediums and lows.

Actigraphic and self-reported characterization of sleep in systemic lupus erythematosus patients.

OBJECTIVES: In a cross-sectional study, we explored possible differences in sleep parameters between SLE patients and age- and gender-matched healthy controls through actigraphic and self-reported measures. Furthermore, we aimed to identify possible predictors of such disturbances in the patient cohort. METHODS: Participants' sociodemographic data and sleep parameters were collected. Sleep parameters were evaluated through the Pittsburgh Sleep Quality Index, the Insomnia Severity Index and 7-day actigraphic monitoring. The 10-item Perceived Stress Scale was used to investigate stress. Disease activity and daily glucocorticoid dose were assessed in SLE patients. Possible predictors of the SLE group were explored through two binomial logistic models. Within the SLE group, possible predictors of sleep parameters were tested estimating multiple linear regression models. RESULTS: A total of 40 SLE patients and 33 controls were included in the study. The SLE group showed worse sleep maintenance actigraphic parameters (i.e. sleep efficiency and wake after sleep onset), higher total sleep time and higher perceived stress. Within the SLE cohort, the daily glucocorticoids dose was associated with an impairment in sleep maintenance despite no reduction in sleep duration, typical of normal sleep duration insomnia, whereas perceived stress was associated with short sleep duration insomnia. CONCLUSION: Compared with healthy controls, SLE patients showed worse sleep quality and greater perceived stress severity. As glucocorticoids and perceived stress are associated with different types of insomnia in these patients, a multidimensional approach to both sleep characterization and therapy might be preferred.

Pointing in cervical dystonia patients.

Introduction: The normal hemispheric balance can be altered by the asymmetric sensorimotor signal elicited by Cervical Dystonia (CD), leading to motor and cognitive deficits. Methods: Directional errors, peak velocities, movement and reaction times of pointing towards out-of-reach targets in the horizontal plane were analysed in 18 CD patients and in 11 aged-matched healthy controls. Results: CD patients displayed a larger scatter of individual trials around the average pointing direction (variable error) than normal subjects, whatever the arm used, and the target pointed. When pointing in the left hemispace, all subjects showed a left deviation (constant error) with respect to the target position, which was significantly larger in CD patients than controls, whatever the direction of the abnormal neck torsion could be. Reaction times were larger and peak velocities lower in CD patients than controls. Discussion: Deficits in the pointing precision of CD patients may arise from a disruption of motor commands related to the sensorimotor imbalance, from a subtle increase in shoulder rigidity or from a reduced agonists activation. Their larger left bias in pointing to left targets could be due to an increased right parietal dominance, independently upon the direction of head roll/jaw rotation which expands the left space representation and/or increases left spatial attention. These deficits may potentially extend to tracking and gazing objects in the left hemispace, leading to reduced skills in spatial-dependent motor and cognitive performance.

Performance evaluation of the open-source Yet Another Spindle Algorithm sleep staging algorithm against gold standard manual evaluation of polysomnographic records in adolescence.

GOAL AND AIMS: To evaluate an automatic sleep scoring algorithm against manual polysomnography sleep scoring. FOCUS METHOD/TECHNOLOGY: Yet Another Spindle Algorithm automatic sleep staging algorithm. REFERENCE METHOD/TECHNOLOGY: Manual sleep scoring. SAMPLE: 327 nights (151 healthy adolescents), from the NCANDA study. DESIGN: Participants underwent one-to-three overnight polysomnography recordings, one consisting of an event-related-potential paradigm. CORE ANALYTICS: Epoch by Epoch and discrepancy analyses (Bland Altman plots) were conducted on the overall sample. ADDITIONAL ANALYTICS AND EXPLORATORY ANALYSES: Epoch by Epoch and discrepancy analysis were repeated separately on standard polysomnography nights and event-related potential nights. Regression models were estimated on age, sex, scorer, and site of recording, separately on standard polysomnography nights and event-related potential nights. CORE OUTCOMES: The Yet Another Spindle Algorithm sleep scoring algorithm's average sensitivity of 93.04% for Wake, 87.67% for N2, 84.46% for N3, 86.02% for rapid-eye-movement, and 40.39% for N1. Specificity was 96.75% for Wake, 97.31% for N1, 88.87% for N2, 97.99% for N3, and 97.70% for rapid-eye-movement. The Matthews Correlation Coefficient was highest in rapid-eye-movement sleep (0.85) while lowest in N1 (0.39). Cohen's Kappa mirrored Matthews Correlation Coefficient results. In Bland-Altman plots, the bias between Yet Another Spindle Algorithm and human scoring showed proportionality to the manual scoring measurement size. IMPORTANT ADDITIONAL OUTCOMES: Yet Another Spindle Algorithm performance was reduced in event-related-potential/polysomnography nights for N3 and rapid-eye-movement. According to the Matthews Correlation Coefficient, the Yet Another Spindle Algorithm performance was affected by younger age, male sex, recording sites, and scorers. CORE CONCLUSION: Results support the use of Yet Another Spindle Algorithm to score adolescents' polysomnography sleep records, possibly with classification outcomes supervised by an expert scorer.

Trigeminal Stimulation and Visuospatial Performance: The Struggle between Chewing and Trigeminal Asymmetries.

Chewing improves visuospatial performance through locus coeruleus (LC) activation. The effects of bilateral and unilateral mastication were investigated in subjects showing different degrees of asymmetry in masseter electromyographic (EMG) activity during clenching and in pupil size at rest (anisocoria), which is a proxy of LC imbalance. Correlations between performance changes and asymmetry values were found in males, but not in females. Among males, subjects with low asymmetry values (balanced-BAL) were more sensitive than those with high asymmetry values (imbalanced-IMB) to bilateral and unilateral chewing on the side with higher EMG activity (hypertonic). The opposite was true for hypotonic side chewing. BAL subjects were sensitive to unilateral chewing on both sides, while in IMB subjects, hypertonic side chewing did not influence performance in either males or females. Bilateral chewing elicited larger effects in BAL subjects than in IMB subjects, exceeding the values predicted from unilateral chewing in both groups. Finally, pupil size and anisocoria changes elicited by chewing were correlated with asymmetry values, independent of sex. Data confirmed the facilitation of visuospatial performance exerted by chewing. Trigeminal asymmetries modulate the chewing effects, making occlusal rebalancing an appropriate strategy to improve performance.

Effects of exogenous melatonin on sleep and circadian rhythm parameters in bipolar disorder with comorbid delayed sleep-wake phase disorder: An actigraphic study.

The present study evaluates the effect of exogenous melatonin (exo-MEL) on sleep and circadian parameters in patients with bipolar disorder (BD) and delayed sleep-wake phase disorder (DSWPD). BD euthymic patients (n = 83, mean age = 45.13 ± 13.68, males 56%) were evaluated for chronotype (reduced Morningness-Eveningness Questionnaire [rMEQ]), sleep quality (Pittsburgh Sleep Quality Index), sleep and circadian parameters (actigraphic monitoring). Patients that fulfilled criteria for DSWPD (n = 25) were treated for three months with exo-MEL 2 mg administered approximately 4 h before the sleep onset time (SOT) actigraphically-determined at baseline. Sleep and circadian parameters at baseline (T0) and after the exo-MEL treatment (T1) were compared using paired Wilcoxon test. In patients that completed the treatment (n = 19), the rMEQ score increased between T0 (median = 8.0 [IQR = 7.0, 11.0]) and T1 (median = 13.5 [IQR = 9.3, 15.0], p-value = 0.006), the SOT was advanced between T0 (median = 00:55 [IQR = 00:25, 01:39] and T1 (median = 00:09 [IQR = 23:41, 01:04], p-value = 0.039), the sleep efficiency and total sleep time increased (T0: median = 84.4 [IQR = 81.3, 89.4]; T1 (median = 90.3 [IQR = 85.5, 92.9] %, p-value = 0.01, and T0: median = 7.20 [IQR = 6.15, 8.15]; T1: median = 7.7 [IQR = 7.0, 9.3] hours, p-value = 0.04, respectively). These results indicate that in BD with comorbid DSWPD, the self-reported chronotype, the sleep onset time, and sleep efficiency and duration were modified after a personalized treatment with exo-MEL, suggesting its potential efficacy in improving sleep patterns in BD. The absence of proper control groups and of treatment randomization constitute limitations of our study and further randomized controlled trials are required to confirm our results.

Effects of a short period of postural training on postural stability and vestibulospinal reflexes.

The effects of postural training on postural stability and vestibulospinal reflexes (VSRs) were investigated in normal subjects. A period (23 minutes) of repeated episodes (n = 10, 50 seconds) of unipedal stance elicited a progressive reduction of the area covered by centre of pressure (CoP) displacement, of average CoP displacement along the X and Y axes and of CoP velocity observed in this challenging postural task. All these changes were correlated to each other with the only exception of those in X and Y CoP displacement. Moreover, they were larger in the subjects showing higher initial instability in unipedal stance, suggesting that they were triggered by the modulation of sensory afferents signalling body sway. No changes in bipedal stance occurred soon and 1 hour after this period of postural training, while a reduction of CoP displacement was apparent after 24 hours, possibly due to a beneficial effect of overnight sleep on postural learning. The same period of postural training also reduced the CoP displacement elicited by electrical vestibular stimulation (EVS) along the X axis up to 24 hours following the training end. No significant changes in postural parameters of bipedal stance and VSRs could be observed in control experiments where subjects were tested at identical time points without performing the postural training. Therefore, postural training led to a stricter control of CoP displacement, possibly acting through the cerebellum by enhancing feedforward mechanisms of postural stability and by depressing the VSR, the most important reflex mechanism involved in balance maintenance under challenging conditions.

Zebrafish as an Innovative Tool for Epilepsy Modeling: State of the Art and Potential Future Directions.

This article discusses the potential of Zebrafish (ZF) (Danio Rerio), as a model for epilepsy research. Epilepsy is a neurological disorder affecting both children and adults, and many aspects of this disease are still poorly understood. In vivo and in vitro models derived from rodents are the most widely used for studying both epilepsy pathophysiology and novel drug treatments. However, researchers have recently obtained several valuable insights into these two fields of investigation by studying ZF. Despite the relatively simple brain structure of these animals, researchers can collect large amounts of data in a much shorter period and at lower costs compared to classical rodent models. This is particularly useful when a large number of candidate antiseizure drugs need to be screened, and ethical issues are minimized. In ZF, seizures have been induced through a variety of chemoconvulsants, primarily pentylenetetrazol (PTZ), kainic acid (KA), and pilocarpine. Furthermore, ZF can be easily genetically modified to test specific aspects of monogenic forms of human epilepsy, as well as to discover potential convulsive phenotypes in monogenic mutants. The article reports on the state-of-the-art and potential new fields of application of ZF research, including its potential role in revealing epileptogenic mechanisms, rather than merely assessing iatrogenic acute seizure modulation.

Morning naps architecture and mentation recall complexity.

Mentation reports were collected after spontaneous awakenings from morning naps in 18 healthy participants, and associations between sleep stages duration and complexity of recalled mentation were investigated. Participants were continuously recorded with polysomnography and allowed to sleep for a maximum of 2 hr. Mentation reports were classified according to both their complexity (1-6 scale) and their perceived timing of occurrence (Recent or Previous Mentation with respect to the final awakening). The results showed a good level of mentation recall, including different types of mentation with lab-related stimuli. N1 + N2 duration was positively related to the complexity of Previous Mentation recall, while rapid eye movement sleep duration was negatively related. This suggests that the recall of complex mentation, such as dreaming with a plot, occurring far from awakening may depend on the length of N1 + N2. However, the duration of sleep stages did not predict the complexity of Recent Mentation recall. Nevertheless, 80% of participants who recalled Recent Mentation had a rapid eye movement sleep episode. Half of the participants reported incorporating lab-related stimuli in their mentation, which positively correlated with both N1 + N2 and rapid eye movement duration. In conclusion, nap sleep architecture is informative about the complexity of dreams perceived as having occurred early during the sleep episode, but not about those perceived as recent.

Chronotype is differentially associated with lifetime mood and panic-agoraphobic spectrum symptoms in patients with bipolar disorder and healthy controls.

OBJECTIVE: Although the association between chronotype and mood disorders has been consistently reported, conversely, attempts to measure the association between chronotype and anxiety symptoms have generated inconsistent results. We aimed at evaluating whether chronotype (assessed through subjective and objective measures) is associated with lifetime mood and panic-agoraphobic spectrum symptoms in healthy controls (HCs) and in patients with bipolar disorder (BD). METHODS: Overall, 173 subjects, patients with BD in euthymic phase (n = 76) and HC (n = 97), were evaluated through the reduced Morningness-Eveningness Questionnaire (rMEQ), actigraphy monitoring and mood and panic-agoraphobic spectrum self-report (MOODS-SR and PAS-SR). The discrepancy between objective (actigraphic-based) versus subjective (rMEQ-based) circadian typology was estimated through the Circadian Classification Discrepancy Index (CCDI). RESULTS: rMEQ-based evening chronotype (ET) was associated with higher scores in MOODS-SR depressive and rhythmicity and vegetative functions domains in HC and BD.Both ET and morning chronotypes (MT) were associated with higher PAS-SR scores in BD only. Actigraphic-based MT was associated with higher MOODS-SR depressive scores in HC. Likewise, the discrepancy between actigraphic-based and rMEQ-based circadian typology was associated with depressive symptoms in HC only. CONCLUSION: Self-reported ET was consistently associated with mood symptoms, while associations with panic-agoraphobic symptoms only emerged in BD and involved both extreme chronotypes. The discrepancy between the preferred circadian typology (rMEQ-based) and the actual one (actigraphic-based) could contribute to depressive symptoms in HC. These results pave the way for interventional studies targeting circadian typology in an attempt to prevent or treat mental health disorders.

The Central Noradrenergic System in Neurodevelopmental Disorders: Merging Experimental and Clinical Evidence.

The aim of this article is to highlight the potential role of the locus-coeruleus-noradrenergic (LC-NA) system in neurodevelopmental disorders (NdDs). The LC is the main brain noradrenergic nucleus, key in the regulation of arousal, attention, and stress response, and its early maturation and sensitivity to perinatal damage make it an interesting target for translational research. Clinical data shows the involvement of the LC-NA system in several NdDs, suggesting a pathogenetic role in the development of such disorders. In this context, a new neuroimaging tool, LC Magnetic Resonance Imaging (MRI), has been developed to visualize the LC in vivo and assess its integrity, which could be a valuable tool for exploring morphological alterations in NdD in vivo in humans. New animal models may be used to test the contribution of the LC-NA system to the pathogenic pathways of NdD and to evaluate the efficacy of NA-targeting drugs. In this narrative review, we provide an overview of how the LC-NA system may represent a common pathophysiological and pathogenic mechanism in NdD and a reliable target for symptomatic and disease-modifying drugs. Further research is needed to fully understand the interplay between the LC-NA system and NdD.

Exploratory Study on the Associations between Lifetime Post-Traumatic Stress Spectrum, Sleep, and Circadian Rhythm Parameters in Patients with Bipolar Disorder.

The present study aimed at exploring whether lifetime post-traumatic stress spectrum symptoms are associated with chronotype in patients with bipolar disorder (BD). Moreover, we explored whether the chronotype can moderate the potential associations between lifetime post-traumatic stress spectrum symptoms and rest-activity circadian and sleep-related parameters. A total of 74 BD patients were administered the Trauma and Loss Spectrum Self-Report (TALS-SR) lifetime version for lifetime post-traumatic stress spectrum symptoms, the Pittsburgh Sleep Quality Index (PSQI) for self-reported sleep quality, and the Reduced Morningness-Eveningness Questionnaire (rMEQ) to discriminate evening chronotypes (ETs), neither chronotype (NT), and morning chronotype (MT). Actigraphic monitoring was used to objectively evaluate sleep and circadian parameters. Patients classified as ET reported significantly higher scores in the re-experiencing domain, as well as poorer sleep quality, lower sleep efficiency, increased wake after sleep onset, and delayed mid-sleep point compared with both NT and MT (p-value ≤ 0.05). Moreover, ET presented significantly higher scores in the TALS-SR maladaptive coping domain than NT and lower relative amplitude than MT (p-value ≤ 0.05). Moreover, higher TALS-SR total symptomatic domains scores were significantly correlated with poor self-reported sleep quality. Regression analyses showed that the PSQI score maintained the association with the TALS total symptomatic domains scores after adjusting for potentially confounding factors (age and sex) and that no interaction effect was observed between the chronotype and the PSQI. Conclusions: This exploratory study suggests that patients with BD classified as ET showed significantly higher lifetime post-traumatic stress spectrum symptoms and more disrupted sleep and circadian rhythmicity with respect to other chronotypes. Moreover, poorer self-reported sleep quality was significantly associated with lifetime post-traumatic stress spectrum symptoms. Further studies are required to confirm our results and to evaluate whether targeting sleep disturbances and eveningness can mitigate post-traumatic stress symptoms in BD.

School Attendance, Chronotype, and Day-of-the-Week Effect in Adolescent Male Basketball Players.

Adolescents' conflict between circadian rhythm and early school start time is more pronounced in evening chronotypes, who tend to reduce sleep duration during school days compensating during the free days by oversleeping (i.e., social jetlag). Cumulative weekly sleep debt may impair sport performance, which relies on physical and cognitive skills modulated by sleep. We hypothesized that chronotype predicts sport performance, and that it may interact with the day of the week. Moreover, given the role sleep plays in motor memory consolidation, we tested the hypothesis that school attendance, and the related chronic sleep deprivation, might be detrimental for participants in a training phase. Ninety-three adolescent male basketball players performed multiple free throw sessions (n = 7880) during both the school and holiday periods. Chronotype and its interaction with the day of the week significantly predicted shooting accuracy when attending school, but not on holidays. Evening types' performance gradually decreased from Monday to Friday. Participants with a more unstable performance (i.e., who did not complete the acquisition of the free throw motor scheme) worsened their accuracy when attending school. Our results suggest that the impact of chronotype and day of the week on sport performance is related to the presence of an externally imposed sleep/wake schedule and is consistent with evening types' increased likelihood of experiencing social jetlag. Possibly due to early school start time, attending school worsened the performance of participants in a training phase. Further investigations are required to assess whether reducing the mismatch between biological and social clocks might improve sport performance, along with other aspects of adolescents' life.

Sleep disturbances in specific learning disorders: a qualitative and quantitative investigation.

BACKGROUND: The literature reports a significant association between sleep disorders and learning disabilities. Nevertheless, not all children with learning disorders have sleep alterations, and which sleep characteristics are associated with which learning difficulty is still unknown. The study aimed at acquiring new information on the relation between sleep disturbances or habits and the learning profiles of children with a specific learning disorder (SLD). METHODS: The Sleep Disturbance Scale for Children (SDSC) and an actigraph (the FitBit-Flex, FB-F) were used in 26 and 16 SLD children respectively; all children were also assessed for learning skills. RESULTS: Although parents' reports at the SDSC did not differentiate SLD from typical readers, the awakening, respiratory and arousal disturbances at the SDSC correlated with sleep duration at the FB-F. Sleep alterations at the FB-F actigraph characterize SLD with literacy difficulties: children with reading decoding difficulties showed shorter minimum amount of sleep than typical children, and severe SLDs showed shorter maximum sleep duration and a higher number of awakenings in comparison to SLDs with mild learning deficits. CONCLUSIONS: Mild alterations in the amount, duration and quality of sleep may characterize children with learning disorders and actigraphy proves to be a useful tool in starting the individual monitoring of sleep in these populations.

Melatonin as a Chronobiotic with Sleep-promoting Properties.

The use of exogenous melatonin (exo-MEL) as a sleep-promoting drug has been under extensive debate due to the lack of consistency of its described effects. In this study, we conduct a systematic and comprehensive review of the literature on the chronobiotic, sleep-inducing, and overall sleep-promoting properties of exo-MEL. To this aim, we first describe the possible pharmacological mechanisms involved in the sleep-promoting properties and then report the corresponding effects of exo-MEL administration on clinical outcomes in: a) healthy subjects, b) circadian rhythm sleep disorders, c) primary insomnia. Timing of administration and doses of exo-MEL received particular attention in this work. The exo-MEL pharmacological effects are hereby interpreted in view of changes in the physiological properties and rhythmicity of endogenous melatonin. Finally, we discuss some translational implications for the personalized use of exo-MEL in the clinical practice.

Handling shifts during an overnight sailing regatta: Comparison between sleep management strategies.

The study aims to investigate the association between different sleep management strategies and the final ranking during a one-night sailing race. A large sample of 190 teams participating in the overnight sailing regatta (151 Miglia) were included in the study. The experimental design consisted of two surveys, administered one before the start of the race and the other after the arrival. The questionnaires provided general information on the sailboat, its crew, and the strategy adopted to manage sleep during the race. In this one-night regatta, the self-management of sleep/wake timing emerged as the most successful strategy. Among participants who adopted a shift-based racing strategy, a short night shift duration (i.e., 2 h) significantly predicted a better placement. These findings confirmed the relevance of sleep management in sport performance and provided new insights into the most suitable sleep management strategy during a relatively short offshore regatta. The conclusions might apply also to similar continuous-cycle activities. Further investigations are needed to explore best sleep management strategy in team regattas of longer duration.

Sleep Deprivation-Induced Changes in Baseline Brain Activity and Vigilant Attention Performance.

Sleep deprivation (SD) negatively affects several aspects of cognitive performance, and one of the most widely-used tools to evaluate these effects is the Psychomotor Vigilance Test (PVT). The present study investigated the possibility of predicting changes induced by SD in vigilant attention performance by evaluating the baseline electroencephalographic (EEG) activity immediately preceding the PVT stimuli onset. All participants (n = 10) underwent EEG recordings during 10 min of PVT before and after a night of SD. For each participant, the root mean square (RMS) of the baseline EEG signal was evaluated for each 1 s time window, and the respective average value was computed. After SD, participants showed slower (and less accurate) performance in the PVT task. Moreover, a close relationship between the changes in the baseline activity with those in cognitive performance was identified at several electrodes (Fp2, F7, F8, P3, T6, O1, Oz, O2), with the highest predictive power at the occipital derivations. These results indicate that vigilant attention impairments induced by SD can be predicted by the pre-stimulus baseline activity changes.

Maximum downward slope of sleep slow waves as a potential marker of attention-deficit/hyperactivity disorder clinical phenotypes.

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly heterogeneous diagnostic category, encompassing several endophenotypes and comorbidities, including sleep problems. However, no predictor of clinical long-term trajectories or comorbidity has yet been established. Sleep EEG has been proposed as a potential tool for evaluating the synaptic strength during development, as well as the cortical thickness, which is presumed to be altered in ADHD. We investigated whether the slope of the Slow Waves (SWs), a microstructural parameter of the sleep EEG, was a potential predictive parameter for psychiatric comorbidities and neuropsychological dimensions in ADHD. METHODS: 70 children (58 m; 8.76 ± 2.77 y) with ADHD who underwent psychiatric and neurologic evaluations and a standard EEG recording during naps were investigated. After sleep EEG analysis, we grouped the extracted SWs in bins of equal amplitude and then measured the associations, through generalized linear regression, between their maximum downward slopes (MDS) and the individual scores obtained from clinical rating scales. RESULTS: The presence of Multiple Anxiety Disorders was positively associated with MDS of medium amplitude SWs in temporo-posterior left areas. The Child Behavior Checklist scores showed negative associations in the same areas for small SWs. The presence of autistic traits was positively associated with MDS of high amplitude SWs in bilateral anterior and temporal left areas. The WISC-IV Processing Speed Index showed negative associations with MDS of small-to-medium SWs in anterior and temporal right areas, while positive associations in posterior and temporal left areas. CONCLUSIONS: Consistency of association clusters' localization on the scalp suggests that variations in the local MDS, revealing alterations of local synaptic strength and/or in daytime use of certain cortical circuits, could underlie specific neurodevelopmental trajectories resulting in different ADHD clinical phenotypes.