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.

Decreased body mass index during treatment with sodium oxybate in narcolepsy type 1.

Narcolepsy type 1 is characterised by an increase in body weight after disease onset, frequently leading to obesity. It was suggested that this weight gain may be counteracted by treatment with sodium oxybate. We here provide longitudinal body mass index data of patients with narcolepsy type 1 after starting treatment with sodium oxybate, compared with patients in whom treatment with modafinil was initiated. Eighty-one individuals with narcolepsy type 1 fulfilled the entry criteria for this retrospective study: 59 had newly started treatment with sodium oxybate and 22 had newly started modafinil. Gender-specific differences between both treatment groups were compared using Student's t tests and mixed effect modeling. Patients using sodium oxybate lost weight, with a mean body mass index decrease of 2.56 kg/m2 between the first and last measurement (women; p = .001) and 0.84 kg/m2 (men; p = .006). Patients using modafinil, however, gained weight, with a mean body mass index increase of 0.57 kg/m2 (women; p = .033) and 0.67 kg/m2 (men; p = .122). Medication (p = .006) and baseline body mass index (p = .032) were predictors for body mass index decrease. In conclusion, treatment with sodium oxybate is associated with a body mass index reduction in narcolepsy type 1, whereas modafinil treatment is not. This effect is most pronounced in those who already have a higher baseline body mass index.

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.

Time- and state-dependent analysis of autonomic control in narcolepsy: higher heart rate with normal heart rate variability independent of sleep fragmentation.

Narcolepsy with hypocretin deficiency is known to alter cardiovascular control during sleep, but its aetiology is disputed. As cardiovascular control differs between sleep states, and narcolepsy affects sleep architecture, controlling for both duration and transitions of sleep states is necessary. This study therefore aimed to assess heart rate and its variability in narcolepsy during sleep taking these factors into account. The study included 12 medication-naïve patients with narcolepsy with cataplexy and hypocretin deficiency (11 male, 16-53 years old), and 12 sex- and age-matched healthy controls (11 male, 19-55 years). All subjects underwent 1-night ambulatory polysomnography recording. Cardiovascular parameters were calculated for each 30-s epoch. Heart rate was significantly higher in patients with narcolepsy than in controls in all sleep states and during wakefulness prior to sleep. Groups did not differ in heart rate variability measures. The effects of sleep state duration on heart rate and its variability were similar between patients and controls. In conclusion, heart rate was consistently higher in patients with narcolepsy than controls, independent of sleep stage and sleep fragmentation. A direct effect of hypocretin deficiency therefore seems probable.

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.

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).

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.

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.

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 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.