Jeroen S. Benjamins

The Amsterdam resting-state questionnaire reveals multiple phenotypes of resting-state cognition.

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 Alzheimers 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.

Orbitofrontal gray matter relates to early morning awakening: a neural correlate of insomnia complaints?

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.

The ARSQ 2.0 reveals age and personality effects on mind-wandering experiences

The human brain frequently generates thoughts and feelings detached from environmental demands. Investigating the rich repertoire of these mind-wandering experiences is challenging, as it depends on introspection and mapping its content requires an unknown number of dimensions. We recently developed a retrospective self-report questionnaire—the Amsterdam Resting-State Questionnaire (ARSQ)—which quantifies mind wandering along seven dimensions: “Discontinuity of Mind,” “Theory of Mind,” “Self,” “Planning,” “Sleepiness,” “Comfort,” and “Somatic Awareness.” Here, we show using confirmatory factor analysis that the ARSQ can be simplified by standardizing the number of items per factor and extending it to a 10-dimensional model, adding “Health Concern,” “Visual Thought,” and “Verbal Thought.” We will refer to this extended ARSQ as the “ARSQ 2.0.” Testing for effects of age and gender revealed no main effect for gender, yet a moderate and significant negative effect for age on the dimensions of “Self,” “Planning,” and “Visual Thought.” Interestingly, we observed stable and significant test-retest correlations across measurement intervals of 3–32 months except for “Sleepiness” and “Health Concern.” To investigate whether this stability could be related to personality traits, we correlated ARSQ scores to proxy measures of Cloningers Temperament and Character Inventory, revealing multiple significant associations for the trait “Self-Directedness.” Other traits correlated to specific ARSQ dimensions, e.g., a negative association between “Harm Avoidance” and “Comfort.” Together, our results suggest that the ARSQ 2.0 is a promising instrument for quantitative studies on mind wandering and its relation to other psychological or physiological phenomena.

Slow dissolving of emotional distress contributes to hyperarousal

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. 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.

Wake High-Density Electroencephalographic Spatiospectral Signatures of Insomnia.

STUDY OBJECTIVES Although daytime complaints are a defining characteristic of insomnia, most EEG studies evaluated sleep only. We used high-density electroencephalography to investigate wake resting state oscillations characteristic of insomnia disorder (ID) at a fine-grained spatiospectral resolution. METHODS A case-control assessment during eyes open (EO) and eyes closed (EC) was performed in a laboratory for human physiology. Participants (n = 94, 74 female, 21-70 y) were recruited through www.sleepregistry.nl: 51 with ID, according to DSM-5 and 43 matched controls. Exclusion criteria were any somatic, neurological or psychiatric condition. Group differences in the spectral power topographies across multiple frequencies (1.5 to 40 Hz) were evaluated using permutation-based inference with Threshold-Free Cluster-Enhancement, to correct for multiple comparisons. RESULTS As compared to controls, participants with ID showed less power in a narrow upper alpha band (11-12.7 Hz, peak: 11.7 Hz) over bilateral frontal and left temporal regions during EO, and more power in a broad beta frequency range (16.3-40 Hz, peak: 19 Hz) globally during EC. Source estimates suggested global rather than cortically localized group differences. CONCLUSIONS The widespread high power in a broad beta band reported previously during sleep in insomnia is present as well during eyes closed wakefulness, suggestive of a round-the-clock hyperarousal. Low power in the upper alpha band during eyes open is consistent with low cortical inhibition and attentional filtering. The fine-grained HD-EEG findings suggest that, while more feasible than PSG, wake EEG of short duration with a few well-chosen electrodes and frequency bands, can provide valuable features of insomnia.

Genome-wide Analysis of Insomnia (N=1,331,010) Identifies Novel Loci and Functional Pathways

Insomnia is the second-most prevalent mental disorder, with no sufficient treatment available. Despite a substantial role of genetic factors, only a handful of genes have been implicated and insight into the associated neurobiological pathways remains limited. Here, we use an unprecedented large genetic association sample (N=1,331,010) to allow detection of a substantial number of genetic variants and gain insight into biological functions, cell types and tissues involved in insomnia. We identify 202 genome-wide significant loci implicating 956 genes through positional, eQTL and chromatin interaction mapping. We show involvement of the axonal part of neurons, of specific cortical and subcortical tissues, and of two specific cell-types in insomnia: striatal medium spiny neurons and hypothalamic neurons. These cell-types have been implicated previously in the regulation of reward processing, sleep and arousal in animal studies, but have never been genetically linked to insomnia in humans. We found weak genetic correlations with other sleep-related traits, but strong genetic correlations with psychiatric and metabolic traits. Mendelian randomization identified causal effects of insomnia on specific psychiatric and metabolic traits. Our findings reveal key brain areas and cells implicated in the neurobiology of insomnia and its related disorders, and provide novel targets for treatment.

The experienced temperature sensitivity and regulation survey

ABSTRACT Individuals differ in thermosensitivity, thermoregulation, and zones of thermoneutrality and thermal comfort. Whereas temperature sensing and -effectuating processes occur in part unconsciously and autonomic, awareness of temperature and thermal preferences can affect thermoregulatory behavior as well. Quantification of trait-like individual differences of thermal preferences and experienced temperature sensitivity and regulation is therefore relevant to obtain a complete understanding of human thermophysiology. Whereas several scales have been developed to assess instantaneous appreciation of heat and cold exposure, a comprehensive scale dedicated to assess subjectively experienced autonomic or behavioral thermoregulatory activity has been lacking so far. We constructed a survey that specifically approaches these domains from a trait-like perspective, sampled 240 volunteers across a wide age range, and analyzed the emergent component structure. Participants were asked to report their thermal experiences, captured in 102 questions, on a 7-point bi-directional Likert scale. In a second set of 32 questions, participants were asked to indicate the relative strength of experiences across different body locations. Principal component analyses extracted 21 meaningful dimensions, which were sensitive to sex-differences and age-related changes. The questions were also assessed in a matched sample of 240 people with probable insomnia to evaluate the sensitivity of these dimensions to detect group differences in a case-control design. The dimensions showed marked mean differences between cases and controls. The survey thus has discriminatory value. It can freely be used by anyone interested in studying individual or group differences in thermosensitivity and thermoregulation.

Memory effects of sleep, emotional valence, arousal and novelty in children

Effectiveness of memory consolidation is determined by multiple factors, including sleep after learning, emotional valence, arousal and novelty. Few studies investigated how the effect of sleep compares with (and interacts with) these other factors, of which virtually none are in children. The present study did so by repeated assessment of declarative memory in 386 children (45% boys) aged 9–11 years through an online word‐pair task. Children were randomly assigned to either a morning or evening learning session of 30 unrelated word‐pairs with positive, neutral or negative valenced cues and neutral targets. After immediately assessing baseline recognition, delayed recognition was recorded either 12 or 24 h later, resulting in four different assessment schedules. One week later, the procedure was repeated with exactly the same word‐pairs to evaluate whether effects differed for relearning versus original novel learning. Mixed‐effect logistic regression models were used to evaluate how the probability of correct recognition was affected by sleep, valence, arousal, novelty and their interactions. Both immediate and delayed recognition were worse for pairs with negatively valenced or less arousing cue words. Relearning improved immediate and delayed word‐pair recognition. In contrast to these effects, sleep did not affect recognition, nor did sleep moderate the effects of arousal, valence and novelty. The findings suggest a robust inclination of children to specifically forget the pairing of words to negatively valenced cue words. In agreement with a recent meta‐analysis, children seem to depend less on sleep for the consolidation of information than has been reported for adults, irrespective of the emotional valence, arousal and novelty of word‐pairs.

Erratum to: The sleep registry. An international online survey and cognitive test assessment tool and database for multivariate sleep and insomnia phenotyping [Sleep Medicine 14S (2013) e293–e294]

The authors would like to inform you that the name of the seventh author was incorrectly listed as “L. Hartescu” in their published article. Dr Hartescus affiliation to Loughborough University was also missed. We apologise for these errors, which have been corrected above.

Temperament moderates the association between sleep duration and cognitive performance in children

The importance of sufficient sleep for cognitive performance has been increasingly recognized. Individual differences in susceptibility to effects of sleep restriction have hardly been investigated in children. We investigated whether individual differences in temperament moderate the association of sleep duration with sustained attention, inhibition, and working memory in 123 children (42% boys) aged 9 to 11 years. Sleep duration was assessed using parental diaries, and temperament traits of extraversion and negative affectivity were assessed by child self-report (Early Adolescent Temperament Questionnaire-Revised). Computerized assessment of sustained attention (short-form Psychomotor Vigilance Task, PVT), inhibition (PVT Go/No-Go adaptation), and working memory (visual Digit Span) were performed at school. Our findings demonstrate that long-sleeping introverted and negatively affective children show worse sustained attention and working memory than short-sleeping children with these temperaments.