Circadian rhythms in cognitive performance: Methodological constraints, protocols, theoretical underpinnings

Abstract The investigation of time-of-day effects on cognitive performance began in the early days of psychophysiological performance assessments. Since then, standardised, highly controlled protocols (constant routine and forced desynchrony) and a standard performance task (psychomotor vigilance task) have been developed to quantify sleep-wake homeostatic and internal circadian time-dependent effects on human cognitive performance. However, performance assessment in this field depends on a plethora of factors. The roles of task difficulty, task duration and complexity, the performance measure per se, practice effects, inter-individual differences, and ageing are all relevant aspects. Therefore, welldefined theoretical approaches and standard procedures are needed for tasks pinpointing higher cortical functions along with more information about time-dependent changes in the neural basis of task performance. This promises a fascinating challenge for future research on sleep-wake related and circadian aspects of different cognitive domains

In Athletes, the Diurnal Variations in Maximum Oxygen Uptake Are More Than Twice as Large as the Day-to-Day Variations

In competitive sports any substantial individual differences in diurnal variations in maximal performance are highly relevant. Previous studies have exclusively focused on how the time of day affects performance and disregarded the maximal individual diurnal variation of performance. Thus, the aims of this study were (1) to investigate the maximum diurnal variation in maximum oxygen uptake (VO2max), (2) to compare the diurnal variation of VO2max during the day to the day-to-day variation in VO2max, and (3) to investigate if there is a time-of-day effect on VO2max. Ten male and seven female athletes (mean VO2max: 58.2 ± 6.9 ml/kg/min) performed six maximal cardiopulmonary exercise tests including a verification-phase at six different times of the day (i.e., diurnal variation) and a seventh test at the same time the sixth test took place (i.e., day-to-day variation). The test times were 7:00, 10:00, 13:00, 16:00, 19:00, and 21:00. The order of exercise tests was the same for all participants to ensure sufficient recovery but the time of day of the first exercise test was randomized. We used paired t-tests to compare the nadir and peak of diurnal variations, day-to-day variations and the difference between diurnal and day-to-day variations. The mean difference in VO2max was 5.0 ± 1.9 ml/kg/min (95% CI: 4.1, 6.0) for the diurnal variation and 2.0 ± 1.0 ml/kg/min (95% CI: 1.5, 2.5) for the day-to-day variation. The diurnal variation was significantly higher than the day-to-day variation with a mean difference of 3.0 ± 2.1 ml/kg/min (95% CI: 1.9, 4.1). The linear mixed effects model revealed no significant differences in VO2max for any pairwise comparison between the different times of the day (all p > 0.11). This absence of a time-of-day effect is explained by the fact that peak VO2max was achieved at different times of the day by different athletes. The diurnal variations have meaningful implications for competitive sports and need to be considered by athletes. However, the results are also relevant to research. To increase signal-to-noise-ratio in intervention studies it is necessary to conduct cardiopulmonary exercise testing at the same time of the day for pre- and post-intervention exercise tests

Non-24-Hour Sleep-Wake Disorder Revisited – A Case Study

The human sleep-wake cycle is governed by two major factors: a homeostatic hourglass process (process S), which rises linearly during the day, and a circadian process C, which determines the timing of sleep in a ~24-h rhythm in accordance to the external light–dark (LD) cycle. While both individual processes are fairly well characterized, the exact nature of their interaction remains unclear. The circadian rhythm is generated by the suprachiasmatic nucleus (“master clock”) of the anterior hypothalamus, through cell-autonomous feedback loops of DNA transcription and translation. While the phase length (tau) of the cycle is relatively stable and genetically determined, the phase of the clock is reset by external stimuli (“zeitgebers”), the most important being the LD cycle. Misalignments of the internal rhythm with the LD cycle can lead to various somatic complaints and to the development of circadian rhythm sleep disorders (CRSD). Non-24-hour sleep-wake disorders (N24HSWD) is a CRSD affecting up to 50% of totally blind patients and characterized by the inability to maintain a stable entrainment of the typically long circadian rhythm (tau > 24.5 h) to the LD cycle. The disease is rare in sighted individuals and the pathophysiology less well understood. Here, we present the case of a 40-year-old sighted male, who developed a misalignment of the internal clock with the external LD cycle following the treatment for Hodgkin’s lymphoma (ABVD regimen, four cycles and AVD regimen, four cycles). A thorough clinical assessment, including actigraphy, melatonin profiles and polysomnography led to the diagnosis of non-24-hour sleep-wake disorders (N24HSWD) with a free-running rhythm of tau = 25.27 h. A therapeutic intervention with bright light therapy (30 min, 10,000 lux) in the morning and melatonin administration (0.5–0.75 mg) in the evening failed to entrain the free-running rhythm, although a longer treatment duration and more intense therapy might have been successful. The sudden onset and close timely connection led us to hypothesize that the chemotherapy might have caused a mutation of the molecular clock components leading to the observed elongation of the circadian period

Predicting melatonin suppression by light in humans:Unifying photoreceptor-based equivalent daylight illuminances, spectral composition, timing and duration of light exposure

Light‐induced melatonin suppression data from 29 peer‐reviewed publications was analysed by means of a machine‐learning approach to establish which light exposure characteristics (ie photopic illuminance, five α‐opic equivalent daylight illuminances [EDIs], duration and timing of the light exposure, and the dichotomous variables pharmacological pupil dilation and narrowband light source) are the main determinants of melatonin suppression. Melatonin suppression in the data set was dominated by four light exposure characteristics: (1) melanopic EDI, (2) light exposure duration, (3) pupil dilation and (4) S‐cone‐opic EDI. A logistic model was used to evaluate the influence of each of these parameters on the melatonin suppression response. The final logistic model was only based on the first three parameters, since melanopic EDI was the best single (photoreceptor) predictor that was only outperformed by S‐cone‐opic EDI for (photopic) illuminances below 21 lux. This confirms and extends findings on the importance of the metric melanopic EDI for predicting biological effects of light in integrative (human‐centric) lighting applications. The model provides initial and general guidance to lighting practitioners on how to combine spectrum, duration and amount of light exposure when controlling non‐visual responses to light, especially melatonin suppression. The model is a starting tool for developing hypotheses on photoreceptors’ contributions to light's non‐visual responses and helps identifying areas where more data are needed, like on the S‐cone contribution at low illuminances

Effects of scale, question location, order of response alternatives, and season on self-reported noise annoyance using ICBEN scales : a field experiment

The type of noise annoyance scale and aspects of its presentation such as response format or location within a questionnaire and other contextual factors may affect self-reported noise annoyance. By means of a balanced experimental design, the effect of type of annoyance question and corresponding scale (5-point verbal vs. 11-point numerical ICBEN (International Commission on Biological Effects of Noise) scale), presentation order of scale points (ascending vs. descending), question location (early vs. late within the questionnaire), and survey season (autumn vs. spring) on reported road traffic noise annoyance was investigated in a postal survey with a stratified random sample of 2386 Swiss residents. Our results showed that early appearance of annoyance questions was significantly associated with higher annoyance scores. Questionnaires filled out in autumn were associated with a significantly higher annoyance rating than in the springtime. No effect was found for the order of response alternatives. Standardized average annoyance scores were slightly higher using the 11-point numerical scale whereas the percentage of highly annoyed respondents was higher based on the 5-point scale, using common cutoff points. In conclusion, placement and presentation of annoyance questions within a questionnaire, as well as the time of the year a survey is carried out, have small but demonstrable effects on the degree of self-reported noise annoyance

Blue blocker glasses as a countermeasure for alerting effects of evening LED - screen exposure in teenagers

peer reviewe

Brain activity during a working memory task after daily caffeine intake and caffeine withdrawal: a randomized double-blind placebo-controlled trial

Acute caffeine intake has been found to increase working memory (WM)-related brain activity in healthy adults without improving behavioral performances. The impact of daily caffeine intake-a ritual shared by 80% of the population worldwide-and of its discontinuation on working memory and its neural correlates remained unknown. In this double-blind, randomized, crossover study, we examined working memory functions in 20 young healthy non-smokers (age: 26.4 ± 4.0 years; body mass index: 22.7 ± 1.4 kg/m$^{2}$; and habitual caffeine intake: 474.1 ± 107.5 mg/day) in a 10-day caffeine (150 mg × 3 times/day), a 10-day placebo (3 times/day), and a withdrawal condition (9-day caffeine followed by 1-day placebo). Throughout the 10th day of each condition, participants performed four times a working memory task (N-Back, comprising 3- and 0-back), and task-related blood-oxygen-level-dependent (BOLD) activity was measured in the last session with functional magnetic resonance imaging. Compared to placebo, participants showed a higher error rate and a longer reaction time in 3- against 0-back trials in the caffeine condition; also, in the withdrawal condition we observed a higher error rate compared to placebo. However, task-related BOLD activity, i.e., an increased attention network and decreased default mode network activity in 3- versus 0-back, did not show significant differences among three conditions. Interestingly, irrespective of 3- or 0-back, BOLD activity was reduced in the right hippocampus in the caffeine condition compared to placebo. Adding to the earlier evidence showing increasing cerebral metabolic demands for WM function after acute caffeine intake, our data suggest that such demands might be impeded over daily intake and therefore result in a worse performance. Finally, the reduced hippocampal activity may reflect caffeine-associated hippocampal grey matter plasticity reported in the previous analysis. The findings of this study reveal an adapted neurocognitive response to daily caffeine exposure and highlight the importance of classifying impacts of caffeine on clinical and healthy populations

Sleep Disruption and Daytime Sleepiness Correlating with Disease Severity and Insulin Resistance in Non-Alcoholic Fatty Liver Disease: A Comparison with Healthy Controls

BACKGROUND & AIMS: Sleep disturbance is associated with the development of obesity, diabetes and hepatic steatosis in murine models. Hepatic triglyceride accumulation oscillates in a circadian rhythm regulated by clock genes, light-dark cycle and feeding time in mice. The role of the sleep-wake cycle in the pathogenesis of human non-alcoholic fatty liver disease (NAFLD) is indeterminate. We sought to detail sleep characteristics, daytime sleepiness and meal times in relation to disease severity in patients with NAFLD. METHODS: Basic Sleep duration and latency, daytime sleepiness (Epworth sleepiness scale), Pittsburgh sleep quality index, positive and negative affect scale, Munich Chronotype Questionnaire and an eating habit questionnaire were assessed in 46 patients with biopsy-proven NAFLD and 22 healthy controls, and correlated with biochemical and histological parameters. RESULTS: In NAFLD compared to healthy controls, time to fall asleep was vastly prolonged (26.9 vs. 9.8 min., p = 0.0176) and sleep duration was shortened (6.3 vs. 7.2 hours, p = 0.0149). Sleep quality was poor (Pittsburgh sleep quality index 8.2 vs. 4.7, p = 0.0074) and correlated with changes in affect. Meal frequency was shifted towards night-times (p = 0.001). In NAFLD but not controls, daytime sleepiness significantly correlated with liver enzymes (ALAT [r = 0.44, p = 0.0029], ASAT [r = 0.46, p = 0.0017]) and insulin resistance (HOMA-IR [r = 0.5, p = 0.0009]) independent of cirrhosis. In patients with fibrosis, daytime sleepiness correlated with the degree of fibrosis (r = 0.364, p = 0.019). CONCLUSIONS: In NAFLD sleep duration was shortened, sleep onset was delayed and sleep quality poor. Food-intake was shifted towards the night. Daytime sleepiness was positively linked to biochemical and histologic surrogates of disease severity. The data may indicate a role for sleep-wake cycle regulation and timing of food-intake in the pathogenesis of human NAFLD as suggested from murine models