Resting-state neuroimaging is a dominant paradigm for studying brain function in health and disease. It is attractive for clinical research because of its simplicity for patients, straightforward standardization, and sensitivity to brain disorders. Importantly, non-sensory experiences like mind wandering may arise from ongoing brain activity. However, little is known about the link between ongoing brain activity and cognition, as phenotypes of resting-state cognition—and tools to quantify them—have been lacking. To facilitate rapid and structured measurements of resting-state cognition we developed a 50-item self-report survey, the Amsterdam Resting-State Questionnaire (ARSQ). Based on ARSQ data from 813 participants assessed after 5 min eyes-closed rest in their home, we identified seven dimensions of resting-state cognition using factor analysis: Discontinuity of Mind, Theory of Mind, Self, Planning, Sleepiness, Comfort, and Somatic Awareness. Further, we showed that the structure of cognition was similar during resting-state fMRI and EEG, and that the test-retest correlations were remarkably high for all dimensions. To explore whether inter-individual variation of resting-state cognition is related to health status, we correlated ARSQ-derived factor scores with psychometric scales measuring depression, anxiety, and sleep quality. Mental health correlated positively with Comfort and negatively with Discontinuity of Mind. Finally, we show that sleepiness may partially explain a resting-state EEG profile previously associated with Alzheimer's disease. These findings indicate that the ARSQ readily provides information about cognitive phenotypes and that it is a promising tool for research on the neural correlates of resting-state cognition in health and disease.

Meta-analyses and systematic reviews have reported surprisingly few consistent insomnia-characteristics with respect to cognitions, mood, traits, history of life events and family history. One interpretation of this limited consistency is that different subtypes of insomnia exist, each with its own specific multivariate profile of characteristics. Because previously unrecognized subtypes will be differentially represented in individual studies and dilute effect sizes of subtype-dependent characteristics of importance, they are unlikely to be reported consistently in individual studies, let alone in meta-analyses. This review therefore aims to complement meta-analyses by listing previously reported psychometric characteristics of insomnia, irrespective of the degree of consistency over studies. The review clearly indicates that characteristics of insomnia may not be limited to sleep. Reports suggest that at least some individuals with insomnia may deviate from people without sleep complaints with respect to demographics, mental and physical health, childhood trauma, life events, fatigue, sleepiness, hyperarousal, hyperactivity, other sleep disorders, lifetime sleep history, chronotype, depression, anxiety, mood, quality of life, personality, happiness, worry, rumination, self-consciousness, sensitivity, dysfunctional beliefs, self-conscious emotion regulation, coping, nocturnal mentation, wake resting-state mentation, physical activity, food intake, temperature perception and hedonic evaluation. The value of this list of characteristics is that 1) internet has now made it feasible to asses them all in a large sample of people suffering from insomnia, and 2) statistical methods like latent class analysis and community detection can utilize them for a truly bottom-up data-driven search for subtypes. The supplement to this review provides a blueprint of this multivariate approach as implemented in the Sleep registry platform (www.sleepregistry.nl), that allows for bottom-up subtyping and fosters cross-cultural comparison and worldwide collaboration on insomnia subtype finding - and beyond.

The mechanisms underlying hyperarousal, the key symptom of insomnia, have remained elusive, hampering cause-targeted treatment. Recently, restless rapid-eye-movement (REM) sleep emerged as a robust signature of sleep in insomnia. Given the role of REM sleep in emotion regulation, we hypothesized that restless REM sleep could interfere with the overnight resolution of emotional distress, thus contributing to accumulation of arousal. Participants (n = 1,199) completed questionnaires on insomnia severity, hyperarousal, self-conscious emotional distress, and thought-like nocturnal mentation that was validated to be a specific proxy for restless REM sleep (selective fragmentation: R = 0.57, P < 0.001; eye movement density: R = 0.46, P < 0.01) in 32 polysomnographically assessed participants. The experience of distress lasting overnight increased with insomnia severity (β = 0.29, P < 10⁻²³), whereas short-lasting distress did not (β = −0.02, P = 0.41). Insomnia severity was associated with hyperarousal (β = 0.47, P < 10⁻⁶³) and with the thought-like nocturnal mentation that is specifically associated with restless REM sleep (β = 0.31, P < 10⁻²⁶). Structural equation modeling showed that 62.4% of the association between these key characteristics of insomnia was mediated specifically by reduced overnight resolution of emotional distress. The model outperformed all alternative mediation pathways. The findings suggest that restless REM sleep reflects a process that interferes with the overnight resolution of distress. Its accumulation may promote the development of chronic hyperarousal, giving clinical relevance to the role of REM sleep in emotion regulation in insomnia, depression, and posttraumatic stress disorder. Significance Decades of research into the cause of chronic insomnia have identified hyperarousal as the key factor, but mechanisms underlying hyperarousal have remained elusive. The present findings suggest that hyperarousal can result from an inadequate resolution of emotional distress, which, in turn, is likely due to restless rapid-eye-movement sleep.

Sleep complaints increase profoundly with age; prevalence estimates of insomnia in the elderly reach up to 37%. The three major types of nocturnal complaints are difficulties initiating (DIS) and maintaining (DMS) sleep and early morning awakening (EMA), of which the latter appears most characteristic for aging. The neural correlates associated with these complaints have hardly been investigated, hampering the development of rational treatment and prevention. A recent study on structural brain correlates of insomnia showed that overall severity, but not duration, of insomnia complaints is associated with lower gray matter (GM) density in part of the left orbitofrontal cortex (OFC). Following up on this, we investigated, in an independent sample of people not diagnosed with insomnia, whether individual differences in GM density are associated with differences in DIS, DMS, and EMA. Sixty five healthy participants (mean age = 41 years, range 18–56) filled out questionnaires and underwent structural magnetic resonance imaging. Three compound Z-scores were computed for questionnaire items relating to DIS, DMS, and EMA. Whole-brain voxel-based morphometry was used to investigate their association with GM density. Results show that participants with lower GM density in a region where the left inferior OFC borders the insula report more EMA, but not DIS or DMS. This is the first study to investigate structural brain correlates of specific sleep characteristics that can translate into complaints in insomniacs. The selective association of EMA with orbitofrontal GM density makes our findings particularly relevant to elderly people, where EMA represents the most characteristic complaint. It is hypothesized that low GM density in aforementioned orbitofrontal area affects its role in sensing comfort. An intact ability to evaluate comfort may be crucial to maintain sleep, especially at the end of the night when sleep is vulnerable because homeostatic sleep propensity has dissipated.