Decreased Delta/Beta ratio index as the sleep state-independent electrophysiological signature of sleep state misperception in Insomnia disorder: A focus on the sleep onset and the whole night.

PURPOSE: Sleep State Misperception (SSM) is described as the tendency of Insomnia Disorder (ID) patients to overestimate Sleep Latency (SL) and underestimate Total Sleep Time (TST). Literature exploring topographical components in ID with SSM is scarce and does not allow us to fully understand the potential mechanisms underlying this phenomenon. This study aims to evaluate the existence of sleep EEG topography alterations in ID patients associated with SSM compared to Healthy Controls (HC), focusing on two distinct periods: the Sleep Onset (SO) and the whole night. METHODS: Twenty ID patients (mean age: 43.5 ± 12.7; 7 M/13F) and 18 HCs (mean age: 41.6 ± 11.9; 8 M/10F) underwent a night of Polysomnography (PSG) and completed sleep diaries the following morning upon awakening. Two SSM indices, referring to the misperception of SL (SLm) and TST (TSTm), were calculated by comparing objective and subjective sleep indices extracted by PSG and sleep diary. According to these indices, the entire sample was split into 4 sub-groups: ID +SLm vs HC -SLm; ID +TSTm vs HC -TSTm. RESULTS: Considering the SO, the two-way mixed-design ANOVA showed a significant main effect of Groups pointing to a decreased delta/beta ratio in the whole scalp topography. Moreover, we found a significant interaction effect for the sigma and beta bands. Post Hoc tests showed higher sigma and beta power in anterior and temporo-parietal sites during the SO period in IDs +SLm compared to HC -SLm. Considering the whole night, the unpaired t-test revealed in IDs +TSTm significantly lower delta power during NREM, and lower delta/beta ratio index during NREM and REM sleep compared to HCs -TSTm. Finally, we found diffuse significant negative correlations between SSM indices and the delta/beta ratio during SO, NREM, and REM sleep. CONCLUSION: The main finding of the present study suggests that higher SL overestimation and TST underestimation are both phenomena related to diffuse cortical hyperarousal interpreted as a sleep state-independent electrophysiological correlate of the SSM, both during the SO and the whole night.

A systematic review of dreams and nightmares recall in patients with rapid eye movement sleep behaviour disorder.

Rapid eye movement (REM) sleep behaviour disorder is a REM sleep parasomnia characterised by the loss of the physiological muscle atonia during REM sleep, resulting in dream enactment behaviours that may cause injuries to patients or their bed partners. The nocturnal motor episodes seem to respond to the dream contents, which are often vivid and violent. These behavioural and oneiric features make the REM sleep behaviour disorder a potential model to study dreams. This review aims to unify the literature about dream recall in REM sleep behaviour disorder as a privileged approach to study dreams, systematically reviewing studies that applied retrospective and prospective experimental designs to provide a comprehensive overview of qualitative and quantitative aspects of dream recall in this REM sleep parasomnia. The present work highlights that the study of dreaming in REM sleep behaviour disorder is useful to understand unique aspects of this pathology and to explore neurobiological, electrophysiological, and cognitive mechanisms of REM sleep and dreaming.

Challenging subjective excessive daytime sleepiness as an insomnia symptom: a retrospective study.

Diagnostic manuals describe insomnia disorder (ID) characterised by fatigue and sleepiness as diurnal consequences of nocturnal symptoms. However, patients with ID do not frequently report sleepiness in the clinical setting. The present study aimed to investigate subjective sleepiness in ID measured through the Epworth Sleepiness Scale (ESS) and its independence towards daytime functioning and fatigue, and to evaluate cognitive behavioural therapy for insomnia (CBT-I) improvement in daytime consequences and their relationship to sleepiness and fatigue. We retrospectively collected the ESS evaluation in a large sample of 105 healthy controls (HCs), 671 patients with ID, and 602 patients with sleep disorders characterised by excessive daytime sleepiness (EDS). Moreover, we conducted a pre-post evaluation of the ESS in a sub-sample of patients with ID who underwent CBT-I. Component 2 of the Insomnia Severity Index and Profile of Mood States-Fatigue Inertia Scale was used to evaluate daytime functioning and fatigue. Patients with ID reported ESS levels comparable to that observed in HCs and significantly lower than the EDS group. No significant correlation arose between ESS and the diurnal impact of the disorder, suggesting the independence between daytime functioning and sleepiness in ID. Contrarily, insomnia severity and diurnal impact significantly correlated with fatigue. Data showed a statistically significant increase in sleepiness after CBT-I, despite significantly improving daytime consequences and fatigue. Although diagnostic manuals report sleepiness and fatigue as daytime consequences of sleep symptoms in patients with ID, these retrospective data indicate a dissociation between these entities. This evidence aligns with the core feature of ID: the hyperarousal status that pervades patients also during wakefulness.

The association between emotional dysregulation and REM sleep features in insomnia disorder.

Rapid Eye Movement (REM) sleep is involved in nightly emotional processing; therefore, its disruption might be associated with an impaired ability of emotional regulation during daytime. Accordingly, the aim of the present study was to evaluate the presence of emotional dysregulation in insomnia patients and to test its correlation with REM sleep features. Forty-six subjects (23 insomnia patients and 23 healthy controls) were enrolled. All subjects underwent an assessment for the evaluation of emotion dysregulation (Difficulties in Emotion Regulation Scale, DERS), sleep quality, insomnia severity, excessive daytime sleepiness, worry, rumination, depressive and anxious symptomatology. Insomnia patients underwent a nocturnal polysomnographic recording to characterize sleep macrostructure and REM sleep microstructure variables. Insomnia patients reported increased values of emotional dysregulation. REM sleep percentage and REM sleep latency significantly correlated with DERS total score, and with the subscales "Lack of Confidence in Emotional Regulation Skills", "Difficulties in Behavioral Control" and "Difficulty in recognizing emotions". Furthermore, positive correlations between REM arousal index and emotion dysregulation were found, whereas REM density negatively correlated with DERS. Our results suggest the presence of a relationship between REM sleep and emotional regulation in insomnia patients.

Neurophysiological Parameters Influencing Sleep-Wake Discrepancy in Insomnia Disorder: A Preliminary Analysis on Alpha Rhythm during Sleep Onset.

Sleep state misperception (SSM) is a common issue in insomnia disorder (ID), causing a discrepancy between objective and subjective sleep/wake time estimation and increased daytime impairments. In this context, the hyperarousal theory assumes that sustained central nervous system activation contributes to the SSM. This study investigates factors influencing SSM during sleep latency (SL) and total sleep time (TST). Objective polysomnographic sleep variables (the alpha density index, latency-to-sleep stages and the first K-complex, and Rapid Eye Movement (REM) arousal density) and subjective sleep indices, taken from sleep diaries, were analyzed in 16 ID patients. Correlation analyses revealed a positive association between the degree of SL misperception (SLm) and the percentage of epochs that contained a visually scored stereotyped alpha rhythm during objective SL. A regression analysis showed that the REM arousal density and alpha density index significantly predicted TST misperception (TSTm). Furthermore, the degree of SLm was associated with an increased probability of transitioning from stage 1 of non-REM sleep to wakefulness during subjective SL. These findings support the role of hyperarousal in SSM and highlight the importance of alpha activity in unravelling the heterogeneous underpinnings of SSM.

Dreaming in Parasomnias: REM Sleep Behavior Disorder as a Model.

Sleep parasomnias have drawn the interest of sleep experts because they represent a valuable window to directly monitor dream activity and sleep mentation associated with nocturnal events. Indeed, parasomnias and their manifestations are helpful in investigating dream activity and features, overcoming methodological limits that affect dream study. Specifically, REM sleep Behavior Disorder (RBD) is a parasomnia characterized by enacted dream episodes during Rapid Eye Movements (REM) sleep, caused by the loss of physiological atonia. Patients suffering from RBD report a peculiar oneiric activity associated with motor episodes characterized by high Dream Recall Frequency (DRF) and vivid dreams. Additionally, isolated RBD (iRBD) represents a prodromal stage of neurodegeneration preceding the development of α-synucleinopathies. This narrative review aims to combine evidence describing dream activity in RBD and similarities and differences with other NREM parasomnias. Moreover, a special focus has been reserved for those conditions in which RBD is associated with α-synucleinopathies to clarify the potential role of dreams in neurodegenerative processes.

Functional connectivity changes in insomnia disorder: A systematic review.

Insomnia (ID) is the most common sleep disorder; however pathogenetic mechanisms underlying ID symptoms are not fully understood. Adopting a multifactorial view and considering ID a condition that involves interregional neuronal coordination would be useful to understand the ID pathophysiology. Functional connectivity (FC) may help to shed light on functional processes and neural correlates underlying ID symptoms. Despite a growing number of studies assessing FC anomalies, insight into ID pathophysiology is still fragmentary. This systematic review aims to search empirical evidence regarding FC changes in ID during resting-state. Thirty-one studies involving 1052 ID participants met the inclusion criteria for this review. Results suggested several associations between ID symptoms and impaired intra- and inter-hemispheric interactions of principal resting-state networks. Overall, evidence supported the hypothesis that a disrupted organization of the brain functional connectome characterizes ID, resulting in a decline in sleep, cognition, emotion, and memory. However, the wide methodological heterogeneity between reviewed studies and limitations in terms of study protocols and statistical approaches raised from this systematic review, makes it difficult to provide a univocal framework of ID pathophysiology. Future researches in this field should lead towards shared and rigorous search designs to ensure solid research evidence in the ID pathophysiology.

The Oneiric Activity during and after the COVID-19 Total Lockdown in Italy: A Longitudinal Study.

A growing body of evidence highlights that the COVID-19 pandemic affected oneiric activity. However, only a few studies have assessed the longitudinal changes in dream phenomenology during different phases of the pandemic, often focused on a limited number of dream variables. The aim of the present study was to provide an exhaustive assessment of dream features during total lockdown (TL) and a post-lockdown (PL) period characterized by eased restrictive measures in Italy. We performed a longitudinal study using a web-based survey to collect demographic, COVID-19 related, clinical, sleep, and dream data at TL and PL. Our final sample included 108 participants. The high frequency of poor sleep quality, anxiety, and depressive symptoms observed during TL remained stable at PL, while sleep latency (t = −4.09; p < 0.001) and PTSD-related disruptive nocturnal behaviors (t = −5.68; p < 0.001) exhibited a reduction at PL. A PL decrease in time spent with digital media was observed (t = −2.77; p = 0.007). We found a strong PL reduction in dream frequency (t = −5.49; p < 0.001), emotional load (t = −2.71; p = 0.008), vividness (t = −4.90; p < 0.001), bizarreness (t = −4.05; p < 0.001), length (t = −4.67; p < 0.001), and lucid dream frequency (t = −2.40; p = 0.018). Fear was the most frequently reported emotion in dreams at TL (26.9%) and PL (22.2%). Only the frequency of specific lockdown-related dream contents exhibited a reduction at PL. These findings highlight that the end of the home confinement had a strong impact on the oneiric activity, in the direction of reduced dream frequency, intensity, and lockdown-related contents. The co-occurrence of such changes with a decline in nocturnal PTSD-related symptoms, sleep latency, and time with digital media suggests an influence of post-traumatic stress levels, lifestyle modifications, and sleep pattern on dream changes during different phases of the pandemic. The stable prevalence of fear in dreams and the large frequency of poor sleep quality, depressive symptoms, and anxiety are probably related to the persistence of many negative consequences of the pandemic. Overall, these results are consistent with the continuity hypothesis of dreams.

Exploring the functional role and neural correlates of K-complexes in isolated rapid eye movement sleep behavior disorder.

Underlying neural mechanisms and cognitive implications of non-Rapid Eye Movement (NREM) sleep in isolated Rapid Eye Movement (REM) sleep behavior disorder (iRBD) are not yet fully elucidated. This study aims to evaluate brain metabolic connectivity of the anterior default mode network (ADMN) underlying a waveform that is an hallmark of NREM sleep, namely K-complex (KC) and their implication for neuropsychological functioning in iRBD patients. Combining polysomnographic and multivariate molecular imaging (FDG-PET) approaches may provide crucial insights regarding KCs role in the prodromal stages of synucleinopathies. We applied a seed-based interregional correlation analysis on FDG-PET data. iRBD patients with cognitive decline displayed a reduced KC density (KCd) in comparison to patients without cognitive impairments. KCd showed a significant positive correlation with global cognitive functioning, specifically with visuo-spatial and executive performances, two cognitive domains known to be relevant in predicting conversion into neurodegenerative disorders. Increased KCd was associated with a more preserved ADMN connectivity. Our study underlines the importance of NREM sleep in prodromal stages of synucleinopathies, and future investigations might clarify its role in iRBD.

Neuropsychological, electrophysiological, and neuroimaging biomarkers for REM behavior disorder.

Introduction: Rapid eye movement (REM) sleep behavior disorder (RBD) is a REM sleep parasomnia characterized by dream enacting behaviors allowed by the loss of physiological atonia during REM sleep. This disorder is recognized as a prodromal stage of neurodegenerative disease, in particular Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB). Therefore, a timely identification of biomarkers able to predict an early conversion into neurodegeneration is of utmost importance. Areas covered: In this review, the authors provide updated evidence regarding the presence of neuropsychological, electrophysiological and neuroimaging markers in isolated RBD (iRBD) patients when the neurodegeneration is yet to come. Expert opinion: Cognitive profile of iRBD patients is characterized by the presence of impairment in visuospatial abilities and executive function that is observed in α-synucleinopathies. However, longitudinal studies showed that impaired executive functions, rather than visuospatial abilities, augmented conversion risk. Cortical slowdown during wake and REM sleep suggest the presence of an ongoing neurodegenerative process paralleled by cognitive decline. Neuroimaging findings showed that impairment nigrostriatal dopaminergic system might be a good marker to identify those patients at higher risk of short-term conversion. Although a growing body of evidence the identification of biomarkers still represents a critical issue in iRBD.

Impact Of Phenotypic Heterogeneity Of Insomnia On The Patients' Response To Cognitive-Behavioral Therapy For Insomnia: Current Perspectives.

Insomnia is one of the most common mental disorders and the most frequent sleep disorder encountered in clinical practice, with a prevalence of about 7% in the European population. Insomnia Disorder (ID) is defined as a disturbance of sleep initiation or maintenance, followed by a feeling of non-restorative sleep and several diurnal consequences ranging from occupational and social difficulties to cognitive impairment. Cognitive-Behavioral Therapy for Insomnia (CBT-I) is considered the first-choice therapy for this disorder because its effectiveness has been proven to be greater in the long term with fewer side effects in comparison to pharmacotherapy. Although its effectiveness has been well established, it has been reported that nearly 40% of patients do not achieve remission after treatment. This finding could be the consequence of heterogeneity of ID between patients. It has been proposed that this heterogeneity might be ascribable to indices that are not related to sleep quality and quantity, such as comorbidities, life events, and personality traits. However, several works focused on the role of sleep markers, in particular objective total sleep time, for the phenotypization of ID and treatment response. The aim of this work is to summarize the available scientific literature regarding the impact of ID subtype on CBT-I response.