Actigraphic multi-night home-recorded sleep estimates reveal three types of sleep misperception in Insomnia Disorder and good sleepers.

People with Insomnia Disorder tend to underestimate their sleep compared with polysomnography or actigraphy, a phenomenon known as paradoxical insomnia or sleep-state misperception. Previous studies suggested that night-to-night variability could be an important feature differentiating subtypes of misperception. This study aimed for a data-driven definition of misperception subtypes revealed by multiple sleep features including night-to-night variability. We assessed features describing the mean and dispersion of misperception and objective and subjective sleep duration from 7-night diary and actigraphy recordings of 181 people with Insomnia Disorder and 55 people without sleep complaints. A minimally collinear subset of features was submitted to latent class analysis for data-driven subtyping. Analysis revealed three subtypes, best discriminated by three of five selected features: an individual's shortest reported subjective sleep duration; and the mean and standard deviation of misperception. These features were on average 5.4, -0.0 and 0.5 hr in one subtype accommodating the majority of good sleepers; 4.1, -1.4 and 1.0 hr in a second subtype representing the majority of people with Insomnia Disorder; and 1.7, -2.2 and 1.5 hr in a third subtype representing a quarter of people with Insomnia Disorder and hardly any good sleepers. Subtypes did not differ on an individual's objective sleep duration mean (6.9, 7.2 and 6.9 hr) and standard deviation (0.8, 0.8 and 0.9 hr). Data-driven analysis of naturalistic sleep revealed three subtypes that markedly differed in misperception features. Future studies may include misperception subtype to investigate whether it contributes to the unexplained considerable individual variability in treatment response.

Internet-guided cognitive, behavioral and chronobiological interventions in depression-prone insomnia subtypes: protocol of a randomized controlled prevention trial.

BACKGROUND: Major depressive disorder is among the most burdening and costly chronic health hazards. Since its prognosis is poor and treatment effectiveness is moderate at best, prevention would be the strategy of first choice. Insomnia may be the best modifiable risk factor. Insomnia is highly prevalent (4-10%) and meta-analysis estimates ±13% of people with insomnia to develop depression within a year. Among people with insomnia, recent work identified three subtypes with a particularly high lifetime risk of depression. The current randomized controlled trial (RCT) evaluates the effects of internet-guided Cognitive Behavioral Therapy for Insomnia (CBT-I), Chronobiological Therapy (CT), and their combination on insomnia and the development of depressive symptoms. METHODS: We aim to include 120 participants with Insomnia Disorder (ID) of one of the three subtypes that are more prone to develop depression. In a two by two factorial repeated measures design, participants will be randomized to CBT-I, CT, CBT-I + CT or treatment as usual, and followed up for one year. The primary outcome is the change, relative to baseline, of the severity of depressive symptoms integrated over four follow-ups spanning one year. Secondary outcome measures include a diagnosis of major depressive disorder, insomnia severity, sleep diaries, actigraphy, cost-effectiveness, and brain structure and function. DISCUSSION: Pre-selection of three high-risk insomnia subtypes allows for a sensitive assessment of the possibility to prevent the development and worsening of depressive symptoms through interventions targeting insomnia. TRIAL REGISTRATION: Netherlands Trial Register (NL7359). Registered on 19 October 2018.

Sustained effects of prior red light on pupil diameter and vigilance during subsequent darkness.

Environmental light can exert potent effects on physiology and behaviour, including pupil size, vigilance and sleep. Previous work showed that these non-image forming effects can last long beyond discontinuation of short-wavelength light exposure. The possible functional effects after switching off long-wavelength light, however, have been insufficiently characterized. In a series of controlled experiments in healthy adult volunteers, we evaluated the effects of five minutes of intense red light on physiology and performance during subsequent darkness. As compared to prior darkness, prior red light induced a subsequent sustained pupil dilation. Prior red light also increased subsequent heart rate and heart rate variability when subjects were asked to perform a sustained vigilance task during the dark exposure. While these changes suggest an increase in the mental effort required for the task, it could not prevent a post-red slowing of response speed. The suggestion that exposure to intense red light affects vigilance during subsequent darkness, was confirmed in a controlled polysomnographic study that indeed showed a post-red facilitation of sleep onset. Our findings suggest the possibility of using red light as a nightcap.

Post-illumination pupil response after blue light: Reliability of optimized melanopsin-based phototransduction assessment.

Melanopsin-containing retinal ganglion cells have recently been shown highly relevant to the non-image forming effects of light, through their direct projections on brain circuits that regulate alertness, mood and circadian rhythms. A quantitative assessment of functionality of the melanopsin-signaling pathway could be highly relevant in order to mechanistically understand individual differences in the effects of light on these regulatory systems. We here propose and validate a reliable quantification of the melanopsin-dependent Post-Illumination Pupil Response (PIPR) after blue light, and evaluated its sensitivity to dark adaptation, time of day, body posture, and light exposure history. Pupil diameter of the left eye was continuously measured during a series of light exposures to the right eye, of which the pupil was dilated using tropicamide 0.5%. The light exposure paradigm consisted of the following five consecutive blocks of five minutes: baseline dark; monochromatic red light (peak wavelength: 630 nm, luminance: 375 cd/m(2)) to maximize the effect of subsequent blue light; dark; monochromatic blue light (peak wavelength: 470 nm, luminance: 375 cd/m(2)); and post-blue dark. PIPR was quantified as the difference between baseline dark pupil diameter and post-blue dark pupil diameter (PIPR-mm). In addition, a relative PIPR was calculated by dividing PIPR by baseline pupil diameter (PIPR-%). In total 54 PIPR assessments were obtained in 25 healthy young adults (10 males, mean age ± SD: 26.9 ± 4.0 yr). From repeated measurements on two consecutive days in 15 of the 25 participants (6 males, mean age ± SD: 27.8 ± 4.3 yrs) test-retest reliability of both PIPR outcome parameters was calculated. In the presence of considerable between-subject differences, both outcome parameters had very high test-retest reliability: Cronbach's α > 0.90 and Intraclass Correlation Coefficient > 0.85. In 12 of the 25 participants (6 males, mean age ± SD: 26.5 ± 3.6 yr) we examined the potential confounding effects of dark adaptation, time of the day (morning vs. afternoon), body posture (upright vs. supine position), and 24-h environmental light history on the PIPR assessment. Mixed effect regression models were used to analyze these possible confounders. A supine position caused larger PIPR-mm (ß = 0.29 mm, SE = 0.10, p = 0.01) and PIPR-% (ß = 4.34%, SE = 1.69, p = 0.02), which was due to an increase in baseline dark pupil diameter; this finding is of relevance for studies requiring a supine posture, as in functional Magnetic Resonance Imaging, constant routine protocols, and bed-ridden patients. There were no effects of dark adaptation, time of day, and light history. In conclusion, the presented method provides a reliable and robust assessment of the PIPR to allow for studies on individual differences in melanopsin-based phototransduction and effects of interventions.

Sleep, vigilance, and thermosensitivity.

The regulation of sleep and wakefulness is well modeled with two underlying processes: a circadian and a homeostatic one. So far, the parameters and mechanisms of additional sleep-permissive and wake-promoting conditions have been largely overlooked. The present overview focuses on one of these conditions: the effect of skin temperature on the onset and maintenance of sleep, and alertness. Skin temperature is quite well suited to provide the brain with information on sleep-permissive and wake-promoting conditions because it changes with most if not all of them. Skin temperature changes with environmental heat and cold, but also with posture, environmental light, danger, nutritional status, pain, and stress. Its effect on the brain may thus moderate the efficacy by which the clock and homeostat manage to initiate or maintain sleep or wakefulness. The review provides a brief overview of the neuroanatomical pathways and physiological mechanisms by which skin temperature can affect the regulation of sleep and vigilance. In addition, current pitfalls and possibilities of practical applications for sleep enhancement are discussed, including the recent finding of impaired thermal comfort perception in insomniacs.

Sleep classification from wrist-worn accelerometer data using random forests.

Accurate and low-cost sleep measurement tools are needed in both clinical and epidemiological research. To this end, wearable accelerometers are widely used as they are both low in price and provide reasonably accurate estimates of movement. Techniques to classify sleep from the high-resolution accelerometer data primarily rely on heuristic algorithms. In this paper, we explore the potential of detecting sleep using Random forests. Models were trained using data from three different studies where 134 adult participants (70 with sleep disorder and 64 good healthy sleepers) wore an accelerometer on their wrist during a one-night polysomnography recording in the clinic. The Random forests were able to distinguish sleep-wake states with an F1 score of 73.93% on a previously unseen test set of 24 participants. Detecting when the accelerometer is not worn was also successful using machine learning ([Formula: see text]), and when combined with our sleep detection models on day-time data provide a sleep estimate that is correlated with self-reported habitual nap behaviour ([Formula: see text]). These Random forest models have been made open-source to aid further research. In line with literature, sleep stage classification turned out to be difficult using only accelerometer data.

Optimizing actigraphic estimates of polysomnographic sleep features in insomnia disorder.

STUDY OBJECTIVES: Actigraphy is a useful tool for estimating sleep, but less accurately distinguishes sleep and wakefulness in patients with insomnia disorder (ID) than in good sleepers. Specific algorithm parameter settings have been suggested to improve the accuracy of actigraphic estimates of sleep onset or nocturnal sleep and wakefulness in ID. However, a direct comparison of how different algorithm parameter settings affect actigraphic estimates of sleep features has been lacking. This study aimed to define the optimal algorithm parameter settings for actigraphic estimates of polysomnographic sleep features in people suffering from ID and matched good sleepers. METHODS: We simultaneously recorded actigraphy and polysomnography without sleep diaries during 210 laboratory nights of people with ID (n = 58) and matched controls (CTRL) without sleep complaints (n = 56). We analyzed cross-validation errors using 150 algorithm parameter configurations and Bland-Altman plots of sleep features using the optimal settings. RESULTS: Optimal sleep onset latency and total sleep time (TST) errors were lower in CTRL (8.9 ± 2.1 and 16.5 ± 2.1 min, respectively) than in ID (11.7 ± 0.8 and 29.1 ± 3.4 min). The sleep-wake algorithm, a period duration of 5 min, and a wake sensitivity threshold of 40 achieved optimal results in ID and near-optimal results in CTRL. Bland-Altman plots were nearly identical for ID and controls for all common all-night sleep features except for TST. CONCLUSION: This systematic evaluation shows that actigraphic sleep feature estimation can be improved by using uncommon parameter settings. One specific parameter setting provides (near-)optimal estimation of sleep onset and nocturnal sleep across ID and controls.

Environmental light and time of day modulate subjective liking and wanting.

Several studies demonstrated effects of light on affect via projections from the retina of the eye to the circadian clock or via projections to areas involved in mood and reward. Few field studies investigated how naturally fluctuating light levels affect positive and negative mood in everyday life, but none addressed two key components of the reward system: wanting and liking. To elucidate diurnal profiles and immediate effects of dynamically changing light intensity in everyday life, subjective wanting and liking were assessed using experience sampling, while continuously monitoring environmental illuminance. Using a smartphone and light sensors, healthy volunteers (n = 27, 14 females, 23.7 ± 3.8 [M ± SD] years of age) were probed for 1 week, 9 times a day, to rate positive and negative mood, and 6 novel dedicated questions each on subjective liking and wanting. The multiband light spectrum was continuously recorded from sensors worn on the chest and intensities were averaged over the intervals between subsequent probes. Mixed effect models were used to evaluate how time of day and light intensity modulated subjective ratings. A total of 1,102 valid observations indicated that liking and wanting peaked around 6 p.m. and increased, respectively, by 13 ± 4% and 11 ± 4% across an individual's range of experienced light intensities. More traditional mood questions were less sensitive to modulation by light intensity. Combined experience sampling and environmental monitoring opens up the possibility for field studies on light in disorders in which the reward system is highly relevant, like addiction, depression and insomnia. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Objectively measured sleep and body mass index: a prospective bidirectional study in middle-aged and older adults.

BACKGROUND: In recent years, short sleep has been increasingly recognized as a risk factor for obesity. However, current evidence has so far been limited to cross-sectional studies or longitudinal studies using self-reported sleep. Therefore, we explored the directionality of the association between objectively measured sleep and body mass index (BMI). METHODS: The study consists of 1031 participants from the general population (52% women, 45-91 years at baseline). Sleep, BMI and waist circumference (WC) were measured twice across a follow-up of six years. BMI and WC were measured at the research center. Total sleep time (TST, hrs), sleep onset latency (SOL, min), sleep efficiency (SE, %) and wake after sleep onset (WASO, min) were estimated by a wrist-worn actigraph. In addition, cross-sectional and longitudinal associations in both directions were explored. RESULTS: An hour shorter TST was cross-sectionally associated with approximately 0.5 kg/m2 higher BMI. Longitudinally, longer TST and higher SE were associated with lower BMI (ßTST = -0.75, 95% CI: -1.08, -0.42; ßSE = -0.04, 95% CI: -0.08, -0.01). Conversely, one kg/m2 higher BMI was prospectively associated with 0.02 h shorter TST (95% CI: -0.03, -0.01), and this association was more pronounced over time. Results from analyses with WC were in line with those of BMI. CONCLUSIONS: This is the first study to explore bidirectionality in the association between objectively measured sleep and BMI in a large population of middle-aged and older adults. Indices of poor sleep were associated with higher and less stable BMI across time. Conversely, a high BMI was associated with a decrease in sleep duration. This confirms that the relation between sleep and body size is bidirectional, and changes in either sleep or BMI are likely to co-occur with changes in health through multiple pathways.

Skin temperature, sleep, and vigilance.

A large number of studies have shown a close association between the 24-hour rhythms in core body temperature and sleep propensity. More recently, studies have have begun to elucidate an intriguing association of sleep with skin temperature as well. The present chapter addresses the association of sleep and alertness with skin temperature. It discusses whether the association could reflect common underlying drivers of both sleep propensity and skin vasodilation; whether it could reflect efferents of sleep-regulating brain circuits to thermoregulatory circuits; and whether skin temperature could provide afferent input to sleep-regulating brain circuits. Sleep regulation and concomitant changes in skin temperature are systematically discussed and three parallel factors suggested: a circadian clock mechanism, a homeostatic hourglass mechanism, and a third set of sleep-permissive and wake-promoting factors that gate the effectiveness of signals from the clock and hourglass in the actual induction of sleep or maintenance of alert wakefulness. The chapter moreover discusses how the association between skin temperature and arousal can change with sleep deprivation and insomnia. Finally it addresses whether the promising laboratory findings on the effects of skin temperature manipulations on vigilance can be applied to improve sleep in everyday life.

EEG Microstates Indicate Heightened Somatic Awareness in Insomnia: Toward Objective Assessment of Subjective Mental Content.

People with Insomnia Disorder (ID) not only experience abundant nocturnal mentation, but also report altered spontaneous mental content during daytime wakefulness, such as an increase in bodily experiences (heightened somatic awareness). Previous studies have shown that resting-state EEG can be temporally partitioned into quasi-stable microstates, and that these microstates form a small number of canonical classes that are consistent across people. Furthermore, the microstate classes have been associated with individual differences in resting mental content including somatic awareness. To address the hypothesis that altered resting mental content in ID would be reflected in an altered representation of the corresponding EEG microstates, we analyzed resting-state high-density EEG of 32 people with ID and 32 age- and sex-matched controls assessed during 5-min eyes-closed wakefulness. Using data-driven topographical k-means clustering, we found that 5 microstate classes optimally explained the EEG scalp voltage map sequences across participants. For each microstate class, 3 dynamic features were obtained: mean duration, frequency of occurrence, and proportional coverage time. People with ID had a shorter mean duration of class C microstates, and more frequent occurrence of class D microstates. The finding is consistent with previously established associations of these microstate properties with somatic awareness, and increased somatic awareness in ID. EEG microstate assessment could provide objective markers of subjective experience dimensions in studies on consciousness during the transition between wake and sleep, when self-report is not possible because it would interfere with the very process under study. Addressing somatic awareness may benefit psychotherapeutic treatment of insomnia.

Bright environmental light ameliorates deficient subjective 'liking' in insomnia: an experience sampling study.

Study Objectives: Altered comfort sensing and reduced gray matter volume in the orbitofrontal cortex of the brain in people suffering from insomnia disorder (ID) suggest compromised processes of motivation and hedonia. The experience sampling (ES) method was used to evaluate whether, in naturalistic conditions, people with ID differ from those without sleep complaints with respect to subjective Wanting and Liking, two major dimensions of the reward system. Since light affects brain circuits involved in affect and reward, ES was combined with ambulatory monitoring of light intensity fluctuations to evaluate their effect on subjective Wanting and Liking. Methods: Participants with ID (n = 17, 12 females, 56.8 ± 6.5 mean ± standard deviation years of age) and matched controls without sleep complaints (n = 18, 12 females, 57.0 ± 8.6 years of age) were probed by a smartphone alarm to log their subjective Wanting, Liking, and mood nine times a day for 7 days. Using an ambulatory light recorder, light intensity exposure was sampled simultaneously and averaged over the intervals between subsequent ES alarms. Mixed-effect models were used to evaluate how ID and varying light intensity affected subjective assessments. Results: The results indicated significantly lower subjective Liking and Wanting in people suffering from ID, particularly at low environmental light intensity. Conclusions: Wanting and Liking, rather than more commonly used mood adjectives, showed an increased sensitivity to detect deficient hedonic and reward processing in insomnia during everyday life. Deficient Liking may in part be rescued by exposure to bright environmental light.

Insomnia heterogeneity: Characteristics to consider for data-driven multivariate subtyping.

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.

Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits.

Persistent insomnia is among the most frequent complaints in general practice. To identify genetic factors for insomnia complaints, we performed a genome-wide association study (GWAS) and a genome-wide gene-based association study (GWGAS) in 113,006 individuals. We identify three loci and seven genes associated with insomnia complaints, with the associations for one locus and five genes supported by joint analysis with an independent sample (n = 7,565). Our top association (MEIS1, P < 5 × 10-8) has previously been implicated in restless legs syndrome (RLS). Additional analyses favor the hypothesis that MEIS1 exhibits pleiotropy for insomnia and RLS and show that the observed association with insomnia complaints cannot be explained only by the presence of an RLS subgroup within the cases. Sex-specific analyses suggest that there are different genetic architectures between the sexes in addition to shared genetic factors. We show substantial positive genetic correlation of insomnia complaints with internalizing personality traits and metabolic traits and negative correlation with subjective well-being and educational attainment. These findings provide new insight into the genetic architecture of insomnia.

The experienced temperature sensitivity and regulation survey.

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.

I Keep a Close Watch on This Heart of Mine: Increased Interoception in Insomnia.

STUDY OBJECTIVES: Whereas both insomnia and altered interoception are core symptoms in affective disorders, their neural mechanisms remain insufficiently understood and have not previously been linked. Insomnia Disorder (ID) is characterized by sensory hypersensitivity during wakefulness and sleep. Previous studies on sensory processing in ID addressed external stimuli only, but not interoception. Interoceptive sensitivity can be studied quantitatively by measuring the cerebral cortical response to one's heartbeat (heartbeat-evoked potential, HEP). We here investigated whether insomnia is associated with increased interoceptive sensitivity as indexed by the HEP amplitude. METHODS: Sixty-four participants aged 21-70 years were recruited through www.sleepregistry.nl including 32 people suffering from ID and 32 age- and sex-matched controls without sleep complaints. HEPs were obtained from resting-state high-density electroencephalography (HD-EEG) recorded during evening wakeful rest in eyes-open (EO) and eyes-closed (EC) conditions of 5-minute duration each. Significance of group differences in HEP amplitude and their topographical distribution over the scalp were assessed by means of cluster-based permutation tests. RESULTS: In particular during EC, and to a lesser extent during EO, people with ID had a larger amplitude late HEP component than controls at frontal electrodes 376-500 ms after the R-wave peak. Source localization suggested increased neural activity time-locked to heartbeats in people with ID mainly in anterior cingulate/medial frontal cortices. CONCLUSIONS: People with insomnia show insufficient adaptation of their brain responses to the ever-present heartbeats. Abnormalities in the neural circuits involved in interoceptive awareness including the salience network may be of key importance to the pathophysiology of insomnia.

Individual Differences in Sleep Timing Relate to Melanopsin-Based Phototransduction in Healthy Adolescents and Young Adults.

STUDY OBJECTIVES: Individual differences in sleep timing have been widely recognized and are of particular relevance in adolescents and young adults who often show mild to severely delayed sleep. The biological mechanisms underlying the between-subject variance remain to be determined. Recent human genetics studies showed an association between sleep timing and melanopsin gene variation, but support for functional effects on downstream pathways and behavior was not demonstrated before. We therefore investigated the association between the autonomic (i.e., pupil diameter) and behavioral (i.e., sleep timing) readouts of two different downstream brain areas, both affected by the same melanopsin-dependent retinal phototransduction: the olivary pretectal nucleus (OPN) and the suprachiasmatic nucleus (SCN). METHODS: Our study population included 71 healthy individuals within an age range with known vulnerability to a delayed sleep phase (16.8-35.7 y, 37 males, 34 females). Pupillometry was performed to estimate functionality of the intrinsic melanopsin-signaling circuitry based on the OPN-mediated post-illumination pupil response (PIPR) to blue light. Sleep timing was quantified by estimating the SCN-mediated mid-sleep timing in three different ways in parallel: using a chronotype questionnaire, a sleep diary, and actigraphy. RESULTS: All three measures consistently showed that those individuals with a later mid-sleep timing had a more pronounced PIPR (0.03 < P < 0.05), indicating a stronger blue-light responsiveness of the intrinsic melanopsin-based phototransduction circuitry. CONCLUSIONS: Trait-like individual differences in the melanopsin phototransduction circuitry contribute to individual differences in sleep timing. Blue light-sensitive young individuals are more prone to delayed sleep.

Individual Differences in the Post-Illumination Pupil Response to Blue Light: Assessment without Mydriatics.

Melanopsin-containing retinal ganglion cells play an important role in the non-image forming effects of light, through their direct projections on brain circuits involved in circadian rhythms, mood and alertness. Individual differences in the functionality of the melanopsin-signaling circuitry can be reliably quantified using the maximum post-illumination pupil response (PIPR) after blue light. Previous protocols for acquiring PIPR relied on the use of mydriatics to dilate the light-exposed eye. However, pharmacological pupil dilation is uncomfortable for the participants and requires ophthalmological expertise. Hence, we here investigated whether an individual's maximum PIPR can be validly obtained in a protocol that does not use mydriatics but rather increases the intensity of the light stimulus. In 18 participants (5 males, mean age ± SD: 34.6 ± 13.6 years) we evaluated the PIPR after exposure to intensified blue light (550 µW/cm²) provided to an undilated dynamic pupil. The test-retest reliability of the primary PIPR outcome parameter was very high, both between day-to-day assessments (Intraclass Correlation Coefficient (ICC) = 0.85), as well as between winter and summer assessments (ICC = 0.83). Compared to the PIPR obtained with the use of mydriatics and 160 µW/cm² blue light exposure, the method with intensified light without mydriatics showed almost zero bias according to Bland-Altman plots and had moderate to strong reliability (ICC = 0.67). In conclusion, for PIPR assessments, increasing the light intensity is a feasible and reliable alternative to pupil dilation to relieve the participant's burden and to allow for performance outside the ophthalmological clinic.

Sleep estimates using microelectromechanical systems (MEMS).

STUDY OBJECTIVES: Although currently more affordable than polysomnography, actigraphic sleep estimates have disadvantages. Brand-specific differences in data reduction impede pooling of data in large-scale cohorts and may not fully exploit movement information. Sleep estimate reliability might improve by advanced analyses of three-axial, linear accelerometry data sampled at a high rate, which is now feasible using microelectromechanical systems (MEMS). However, it might take some time before these analyses become available. To provide ongoing studies with backward compatibility while already switching from actigraphy to MEMS accelerometry, we designed and validated a method to transform accelerometry data into the traditional actigraphic movement counts, thus allowing for the use of validated algorithms to estimate sleep parameters. DESIGN: Simultaneous actigraphy and MEMS-accelerometry recording. SETTING: Home, unrestrained. PARTICIPANTS: Fifteen healthy adults (23-36 y, 10 males, 5 females). INTERVENTIONS: None. MEASUREMENTS: Actigraphic movement counts/15-sec and 50-Hz digitized MEMS-accelerometry. ANALYSES: Passing-Bablok regression optimized transformation of MEMS-accelerometry signals to movement counts. Kappa statistics calculated agreement between individual epochs scored as wake or sleep. Bland-Altman plots evaluated reliability of common sleep variables both between and within actigraphs and MEMS-accelerometers. RESULTS: Agreement between epochs was almost perfect at the low, medium, and high threshold (kappa = 0.87 ± 0.05, 0.85 ± 0.06, and 0.83 ± 0.07). Sleep parameter agreement was better between two MEMS-accelerometers or a MEMS-accelerometer and an actigraph than between two actigraphs. CONCLUSIONS: The algorithm allows for continuity of outcome parameters in ongoing actigraphy studies that consider switching to MEMS-accelerometers. Its implementation makes backward compatibility feasible, while collecting raw data that, in time, could provide better sleep estimates and promote cross-study data pooling.