Preliminary fMRI findings in experimentally sleep-restricted adolescents engaged in a working memory task

Here we report preliminary findings from a small-sample functional magnetic resonance imaging (fMRI) study of healthy adolescents who completed a working memory task in the context of a chronic sleep restriction experiment. Findings were consistent with those previously obtained on acutely sleep-deprived adults. Our data suggest that, when asked to maintain attention and burdened by chronic sleep restriction, the adolescent brain responds via compensatory mechanisms that accentuate the typical activation patterns of attention-relevant brain regions. Specifically, it appeared that regions that are normally active during an attention-demanding working memory task in the well-rested brain became even more active to maintain performance after chronic sleep restriction. In contrast, regions in which activity is normally suppressed during such a task in the well-rested brain showed even greater suppression to maintain performance after chronic sleep restriction. Although limited by the small sample, study results provide important evidence of feasibility, as well as guidance for future research into the functional neurological effects of chronic sleep restriction in general, the effects of sleep restriction in children and adolescents, and the neuroscience of attention and its disorders in children

The role of depressive symptoms and symptom dimensions in actigraphy-assessed sleep, circadian rhythm, and physical activity

BACKGROUND: Considering the heterogeneity of depression, distinct depressive symptom dimensions may be differentially associated with more objective actigraphy-based estimates of physical activity (PA), sleep and circadian rhythm (CR). We examined the association between PA, sleep, and CR assessed with actigraphy and symptom dimensions (i.e. mood/cognition, somatic/vegetative, sleep).METHODS: Fourteen-day actigraphy data of 359 participants were obtained from the Netherlands Study of Depression and Anxiety. PA, sleep, and CR estimates included gross motor activity (GMA), sleep duration (SD), sleep efficiency (SE), relative amplitude between daytime and night-time activity (RA) and sleep midpoint. The 30-item Inventory of Depressive Symptomatology was used to assess depressive symptoms, which were categorised in three depression dimensions: mood/cognition, somatic/vegetative, and sleep.RESULTS: GMA and RA were negatively associated with higher score on all three symptom dimensions: mood/cognition (GMA: β = -0.155, p &lt; 0.001; RA: β = -0.116, p = 0.002), somatic/vegetative (GMA: β = -0.165, p &lt; 0.001; RA: β = -0.133, p &lt; 0.001), sleep (GMA: β = -0.169, p &lt; 0.001; RA: β = -0.190, p &lt; 0.001). The association with sleep was more pronounced for two depression dimensions: longer SD was linked to somatic/vegetative (β = 0.115, p = 0.015) dimension and lower SE was linked to sleep (β = -0.101, p = 0.011) dimension.CONCLUSION: As three symptom dimensions were associated with actigraphy-based low PA and dampened CR, these seem to be general indicators of depression. Sleep disturbances appeared more linked to the somatic/vegetative and sleep dimensions; the effectiveness of sleep interventions in patients reporting somatic/vegetative symptoms may be explored, as well as the potential of actigraphy to monitor treatment response to such interventions.</p

The role of depressive symptoms and symptom dimensions in actigraphy-assessed sleep, circadian rhythm, and physical activity

BACKGROUND: Considering the heterogeneity of depression, distinct depressive symptom dimensions may be differentially associated with more objective actigraphy-based estimates of physical activity (PA), sleep and circadian rhythm (CR). We examined the association between PA, sleep, and CR assessed with actigraphy and symptom dimensions (i.e. mood/cognition, somatic/vegetative, sleep).METHODS: Fourteen-day actigraphy data of 359 participants were obtained from the Netherlands Study of Depression and Anxiety. PA, sleep, and CR estimates included gross motor activity (GMA), sleep duration (SD), sleep efficiency (SE), relative amplitude between daytime and night-time activity (RA) and sleep midpoint. The 30-item Inventory of Depressive Symptomatology was used to assess depressive symptoms, which were categorised in three depression dimensions: mood/cognition, somatic/vegetative, and sleep.RESULTS: GMA and RA were negatively associated with higher score on all three symptom dimensions: mood/cognition (GMA: β = -0.155, p &lt; 0.001; RA: β = -0.116, p = 0.002), somatic/vegetative (GMA: β = -0.165, p &lt; 0.001; RA: β = -0.133, p &lt; 0.001), sleep (GMA: β = -0.169, p &lt; 0.001; RA: β = -0.190, p &lt; 0.001). The association with sleep was more pronounced for two depression dimensions: longer SD was linked to somatic/vegetative (β = 0.115, p = 0.015) dimension and lower SE was linked to sleep (β = -0.101, p = 0.011) dimension.CONCLUSION: As three symptom dimensions were associated with actigraphy-based low PA and dampened CR, these seem to be general indicators of depression. Sleep disturbances appeared more linked to the somatic/vegetative and sleep dimensions; the effectiveness of sleep interventions in patients reporting somatic/vegetative symptoms may be explored, as well as the potential of actigraphy to monitor treatment response to such interventions.</p

Toda Fields on Riemann Surfaces: remarks on the Miura transformation

We point out that the Miura transformation is related to a holomorphic foliation in a relative flag manifold over a Riemann Surface. Certain differential operators corresponding to a free field description of $W$--algebras are thus interpreted as partial connections associated to the foliation.Comment: AmsLatex 1.1, 10 page

The day-to-day bidirectional longitudinal association between objective and self-reported sleep and affect:An ambulatory assessment study

Background: Ambulatory assessments offer opportunities to evaluate daily dynamics of sleep and momentary affect using mobile technologies. This study examines day-to-day bidirectional associations between sleep and affect using mobile monitoring, and evaluates whether these associations differ between people without and with current or remitted depression/anxiety. Methods: Two-week ecological momentary assessment (EMA) and actigraphy data of 359 participants with current (n = 93), remitted (n = 176) or no (n = 90) CIDI depression/anxiety diagnoses were obtained from the Netherlands Study of Depression and Anxiety. Objective sleep duration (SD) and efficiency were obtained from actigraphy data. Self-reported SD, sleep quality (SQ), positive affect (PA) and negative affect (NA) were assessed by electronic diaries through EMA. Results: A bidirectional longitudinal association was found between self-reported SQ and affect, while no association was found for self-reported SD and objective SD and efficiency. Better SQ predicted affect the same day (higher PA: b = 0.035, p < 0.001; lower NA: b = -0.022, p < 0.001), while lower NA on the preceding day predicted better SQ (b = -0.102, p = 0.001). The presence of current depression/anxiety disorders moderated the association between better SQ and subsequent lower NA; it was stronger for patients compared to controls (p = 0.003). Limitations: Observational study design can only point to areas of interest for interventions. Conclusions: This 2-week ambulatory monitoring study shows that, especially among depression/anxiety patients, better self-reported SQ predicts higher PA and lower NA the same day, while lower NA predicts better self-reported SQ. The value of mobile technologies to monitor and potentially intervene in patients to improve their affect should be explored

Cyclic dinucleotides bind the C-linker of HCN4 to control channel cAMP responsiveness

cAMP mediates autonomic regulation of heart rate by means of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which underlie the pacemaker current If. cAMP binding to the C-terminal cyclic nucleotide binding domain enhances HCN open probability through a conformational change that reaches the pore via the C-linker. Using structural and functional analysis, we identified a binding pocket in the C-linker of HCN4. Cyclic dinucleotides, an emerging class of second messengers in mammals, bind the C-linker pocket (CLP) and antagonize cAMP regulation of the channel. Accordingly, cyclic dinucleotides prevent cAMP regulation of If in sinoatrial node myocytes, reducing heart rate by 30%. Occupancy of the CLP hence constitutes an efficient mechanism to hinder β-adrenergic stimulation on If. Our results highlight the regulative role of the C-linker and identify a potential drug target in HCN4. Furthermore, these data extend the signaling scope of cyclic dinucleotides in mammals beyond their first reported role in innate immune system

Sleep, circadian rhythm, and physical activity patterns in depressive and anxiety disorders:A 2-week ambulatory assessment study

BACKGROUND: Actigraphy may provide a more valid assessment of sleep, circadian rhythm (CR), and physical activity (PA) than self-reported questionnaires, but has not been used widely to study the association with depression/anxiety and their clinical characteristics. METHODS: Fourteen-day actigraphy data of 359 participants with current (n = 93), remitted (n = 176), or no (n = 90) composite international diagnostic interview depression/anxiety diagnoses were obtained from the Netherlands Study of Depression and Anxiety. Objective estimates included sleep duration (SD), sleep efficiency, relative amplitude (RA) between day-time and night-time activity, mid sleep on free days (MSF), gross motor activity (GMA), and moderate-to-vigorous PA (MVPA). Self-reported measures included insomnia rating scale, SD, MSF, metabolic equivalent total, and MVPA. RESULTS: Compared to controls, individuals with current depression/anxiety had a significantly different objective, but not self-reported, PA and CR: lower GMA (23.83 vs. 27.4 milli-gravity/day, p = .022), lower MVPA (35.32 vs. 47.64 min/day, p = .023), lower RA (0.82 vs. 0.83, p = .033). In contrast, self-reported, but not objective, sleep differed between people with current depression/anxiety compared to those without current disorders; people with current depression/anxiety reported both shorter and longer SD and more insomnia. More depressive/anxiety symptoms and number of depressive/anxiety diagnoses were associated with larger disturbances of the actigraphy measures. CONCLUSION: Actigraphy provides ecologically valid information on sleep, CR, and PA that enhances data from self-reported questionnaires. As those with more severe or comorbid forms showed the lowest PA and most CR disruptions, the potential for adjunctive behavioral and chronotherapy interventions should be explored, as well as the potential of actigraphy to monitor treatment response to such interventions

Sociodemographic, Health and Lifestyle, Sampling, and Mental Health Determinants of 24-Hour Motor Activity Patterns:Observational Study

Background: Analyzing actigraphy data using standard circadian parametric models and aggregated nonparametric indices may obscure temporal information that may be a hallmark of the circadian impairment in psychiatric disorders. Functional data analysis (FDA) may overcome such limitations by fully exploiting the richness of actigraphy data and revealing important relationships with mental health outcomes. To our knowledge, no studies have extensively used FDA to study the relationship between sociodemographic, health and lifestyle, sampling, and psychiatric clinical characteristics and daily motor activity patterns assessed with actigraphy in a sample of individuals with and without depression/anxiety. Objective: We aimed to study the association between daily motor activity patterns assessed via actigraphy and (1) sociodemographic, health and lifestyle, and sampling factors, and (2) psychiatric clinical characteristics (ie, presence and severity of depression/anxiety disorders). Methods: We obtained 14-day continuous actigraphy data from 359 participants from the Netherlands Study of Depression and Anxiety with current (n=93), remitted (n=176), or no (n=90) depression/anxiety diagnosis, based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. Associations between patterns of daily motor activity, quantified via functional principal component analysis (fPCA), and sociodemographic, health and lifestyle, sampling, and psychiatric clinical characteristics were assessed using generalized estimating equation regressions. For exploratory purposes, function-on-scalar regression (FoSR) was applied to quantify the time-varying association of sociodemographic, health and lifestyle, sampling, and psychiatric clinical characteristics on daily motor activity. Results: Four components of daily activity patterns captured 77.4% of the variability in the data: overall daily activity level (fPCA1, 34.3% variability), early versus late morning activity (fPCA2, 16.5% variability), biphasic versus monophasic activity (fPCA3, 14.8% variability), and early versus late biphasic activity (fPCA4, 11.8% variability). A low overall daily activity level was associated with a number of sociodemographic, health and lifestyle, and psychopathology variables: older age (P<.001), higher education level (P=.005), higher BMI (P=.009), greater number of chronic diseases (P=.02), greater number of cigarettes smoked per day (P=.02), current depressive and/or anxiety disorders (P=.05), and greater severity of depressive symptoms (P<.001). A high overall daily activity level was associated with work/school days (P=.02) and summer (reference: winter; P=.03). Earlier morning activity was associated with older age (P=.02), having a partner (P=.009), work/school days (P<.001), and autumn and spring (reference: winter; P=.02 and P<.001, respectively). Monophasic activity was associated with older age (P=.005). Biphasic activity was associated with work/school days (P<.001) and summer (reference: winter; P<.001). Earlier biphasic activity was associated with older age (P=.005), work/school days (P<.001), and spring and summer (reference: winter; P<.001 and P=.005, respectively). In FoSR analyses, age, work/school days, and season were the main determinants having a time-varying association with daily motor activity (all P<.05). Conclusions: Features of daily motor activity extracted with fPCA reflect commonly studied factors such as the intensity of daily activity and preference for morningness/eveningness. The presence and severity of depression/anxiety disorders were found to be associated mainly with a lower overall activity pattern but not with the time of the activity. Age, work/school days, and season were the variables most strongly associated with patterns and time of activity, and thus future epidemiological studies on motor activity in depression/anxiety should take these variables into account

Microscopic Selection of Fluid Fingering Pattern

We study the issue of the selection of viscous fingering patterns in the limit of small surface tension. Through detailed simulations of anisotropic fingering, we demonstrate conclusively that no selection independent of the small-scale cutoff (macroscopic selection) occurs in this system. Rather, the small-scale cutoff completely controls the pattern, even on short time scales, in accord with the theory of microscopic solvability. We demonstrate that ordered patterns are dynamically selected only for not too small surface tensions. For extremely small surface tensions, the system exhibits chaotic behavior and no regular pattern is realized.Comment: 6 pages, 5 figure

Electrophysiology Model for a Human Heart with Ischemic Scar and Realistic Purkinje Network

The role of Purkinje fibres in the onset of arrhythmias is controversial and computer simulations may shed light on possible arrhythmic mechanisms involving the Purkinje fibres. However, few computational modelling studies currently include a detailed Purkinje network as part of the model. We present a coupled Purkinje-myocardium electrophysiology model that includes an explicit model for the ischemic scar plus a detailed Purkinje network, and compare simulated activation times to those obtained by electro-anatomical mapping in vivo during sinus rhythm pacing. The results illustrate the importance of using sufficiently dense Purkinje networks in patient-specific studies to capture correctly the myocardial early activation that may be influenced by surviving Purkinje fibres in the infarct region