Sleep insufficiency and bedtime irregularity in children with ADHD: A population-based analysis.

BACKGROUND: Sleep is impaired in children with attention-deficit/hyperactivity disorder (ADHD). However, population-based examination of indicators of sleep insufficiency and bedtime irregularity is limited. This investigation examined associations between ADHD, weeknight sleep insufficiency, and bedtime irregularity in a nationally-representative child sample, and indicators of these sleep outcomes in ADHD. METHODS: Parents of children aged 3-17 years with ADHD (n = 7671) were surveyed through the 2020-2021 National Survey of Children's Health. Inverse probability of treatment weighting generated a weighted matched control sample (n = 51,572). Weighted generalized linear models were performed without and with age-stratification to examine associations between ADHD and sleep, adjusting for sociodemographics in the full sample, and between nineteen sociodemographic and clinical variables and sleep in ADHD. RESULTS: Having ADHD was associated with increased odds of sleep insufficiency and bedtime irregularity relative to controls, even after adjusting for sociodemographic variables. In ADHD, older age was associated with lower sleep insufficiency and greater bedtime irregularity. Black race, increased poverty, higher ADHD severity, depression, and increased screen time were associated with greater sleep insufficiency and bedtime irregularity. Adverse childhood experiences (ACEs) were associated with greater sleep insufficiency. Behavioral/conduct problems, female sex, and absence of both ADHD medication use and ASD diagnosis were associated with poorer bedtime irregularity. Age-stratified results are reported in text. CONCLUSIONS: Children with ADHD face heightened risk for insufficient sleep and irregular bedtimes. Findings suggest intervention targets (e.g., Black race, poverty, depression, screen time) to improve both sleep insufficiency and bedtime irregularity. Results highlight ACEs and behavioral/conduct problems as targets to improve sleep insufficiency and bedtime regularity, respectively. Age-stratified findings are discussed.

Human-Centric Lighting Research and Policy in the Melanopsin Age.

Beyond visual function, specialized light-sensitive retinal circuits involving the photopigment melanopsin drive critical aspects of human physiology and behavior, including sleep-wake rhythms, hormone production, mood, and cognition. Fundamental discoveries of visual neurobiology dating back to the 1990s have given rise to strong interest from the lighting industry in optimizing lighting to benefit health. Consequently, evidence-based recommendations, regulations, and policies need to translate current knowledge of neurobiology into practice. Here, reviewing recent advances in understanding of NIF circuits in humans leads to proposed strategies to optimize electric lighting. Highlighted knowledge gaps must be addressed urgently, as well as the challenge of developing personalized, adaptive NIF lighting interventions accounting for complex individual differences in physiology, behavior, and environment. Finally, lighting equity issues appear in the context of marginalized groups, who have traditionally been underserved in research on both fundamental visual processes and applied lighting. Biologically optimal light is a fundamental environmental right.

Optimizing Light Flash Sequence Duration to Shift Human Circadian Phase.

Unlike light input for forming images, non-image-forming retinal pathways are optimized to convey information about the total light environment, integrating this information over time and space. In a variety of species, discontinuous light sequences (flashes) can be effective stimuli, notably impacting circadian entrainment. In this study, we examined the extent to which this temporal integration can occur. A group of healthy, young (n = 20) individuals took part in a series of 16-day protocols in which we examined the impact of different lengths of light flash sequences on circadian timing. We find a significant phase change of -0.70 h in response to flashes that did not differ by duration; a 15-min sequence could engender as much change in circadian timing as 3.5-h sequences. Acute suppression of melatonin was also observed during short (15-min) exposures, but not in exposures over one hour in length. Our data are consistent with the theory that responses to light flashes are mediated by the extrinsic, rod/cone pathway, and saturate the response of this pathway within 15 min. Further excitation leads to no greater change in circadian timing and an inability to acutely suppress melatonin, indicating that this pathway may be in a refractory state following this brief light stimulation.

Electric lighting, adolescent sleep and circadian outcomes, and recommendations for improving light health.

Light is a potent circadian entraining agent. For many people, daily light exposure is fundamentally dysregulated with reduced light during the day and increased light into the late evening. This lighting schedule promotes chronic disruption to circadian physiology resulting in a myriad of impairments. Developmental changes in sleep-wake physiology suggest that such light exposure patterns may be particularly disruptive for adolescents and further compounded by lifestyle factors such as early school start times. This narrative review describes evidence that reduced light exposure during the school day delays the circadian clock, and longer exposure durations to light-emitting electronic devices in the evening suppress melatonin. While home lighting in the evening can suppress melatonin secretion and delay circadian phase, the patterning of light exposure across the day and evening can have moderating effects. Photic countermeasures may be flexibly and scalably implemented to support sleep-wake health; including manipulations of light intensity, spectra, duration and delivery modality across multiple contexts. An integrative approach addressing physiology, attitudes, and behaviors will support optimization of light-driven sleep-wake outcomes in adolescents.

Impact of daytime spectral tuning on cognitive function.

Light at night can improve alertness and cognition. Exposure to daytime light, however, has yielded less conclusive results. In addition to direct effects, daytime light may also mitigate the impact of nocturnal light exposure on alertness. To examine the impact of daytime lighting on daytime cognitive performance, and evening alertness, we studied nine healthy individuals using a within subject crossover design. On four visits, participants were exposed to one of four lighting conditions for 10 h (dim fluorescent, room fluorescent, broad-spectrum LED, standard white LED; the latter three conditions were matched for 100 lx) followed by an exposure to bright evening light. Cognitive performance, subjective and objective measures of alertness were regularly obtained. While daytime alertness was not impacted by light exposure, the broad-spectrum LED light improved several aspects of daytime cognition. The impact of evening light on alertness was not mitigated by the pre-exposure to different daytime lighting conditions. Results suggest that daytime exposure to white light with high melanopic efficacy has the potential to improve daytime cognitive function and that such improvements are likely to be direct rather than a consequence of light-induced changes in alertness.

Duration invariance and intensity dependence of the human circadian system phase shifting response to brief light flashes.

The melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are characterized by a delayed off-time following the cessation of light stimulation. Here, we exploited this unusual physiologic property to characterize the exquisite sensitivity of the human circadian system to flashed light. In a 34 h in-laboratory between-subjects design, we examined phase shifting in response to variable-intensity (3-9500 photopic lux) flashes at fixed duration (2 ms; n = 28 participants) and variable-duration (10 µs-10 s) flashes at fixed intensity (2000 photopic lux; n = 31 participants). Acute melatonin suppression, objective alertness and subjective sleepiness during the flash sequence were also assessed. We find a dose-response relationship between flash intensity and circadian phase shift, with an indication of a possible threshold-like behaviour. We find a slight parametric relationship between flash duration and circadian phase shift. Consistent with prior studies, we observe no dose-response relationship to either flash intensity or duration and the acute impact of light on melatonin suppression, objective alertness or subjective sleepiness. Our findings are consistent with circadian responses to a sequence of flashes being mediated by rod or cone photoreceptors via ipRGC integration.

Color perception and compensation in color deficiencies assessed with hue scaling.

Anomalous trichromats have three classes of cone receptors but with smaller separation in the spectral sensitivities of their longer-wave (L or M) cones compared to normal trichromats. As a result, the differences in the responses of the longer-wave cones are smaller, resulting in a weaker input to opponent mechanisms that compare the LvsM responses. Despite this, previous studies have found that their color percepts are more similar to normal trichromats than the smaller LvsM differences predict, suggesting that post-receptoral processes might amplify their responses to compensate for the weaker opponent inputs. We evaluated the degree and form of compensation using a hue-scaling task, in which the appearance of different hues is described by the perceived proportions of red-green or blue-yellow primary colors. The scaling functions were modeled to estimate the relative salience of the red-green to blue-yellow components. The red-green amplitudes of the 10 anomalous observers were 1.5 times weaker than for a group of 26 normal controls. However, their relative sensitivity at threshold for detecting LvsM chromatic contrast was on average 6 times higher, consistent with a 4-fold gain in the suprathreshold hue-scaling responses. Within-observer variability in the settings was similar for the two groups, suggesting that the suprathreshold gain did not similarly amplify the noise, at least for the dimension of hue. While the compensation was pronounced it was nevertheless partial, and anomalous observers differed systematically from the controls in the shapes of the hue-scaling functions and the corresponding loci of their color categories. Factor analyses further revealed different patterns of individual differences between the groups. We discuss the implications of these results for understanding both the processes of compensation for a color deficiency and the limits of these processes.

Effect of Suvorexant vs Placebo on Total Daytime Sleep Hours in Shift Workers: A Randomized Clinical Trial.

Importance: Many shift workers have difficulty sleeping during the daytime owing to an inappropriately timed circadian drive for wakefulness. Objective: To determine whether a dual hypocretin receptor antagonist would enable shift workers to have more daytime sleep. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial included 2 weeks of baseline data and 3 weeks of intervention data, from March 2016 to December 2018. Individuals were recruited through poster advertisements in the broader San Francisco Bay area in California. From an initial voluntary recruitment cohort of 38 shift workers, 19 individuals with self-reported difficulty sleeping during the daytime following night work shift were included. Data were analyzed from Janaury to March 2019. Interventions: 1 week of 10 mg suvorexant or placebo, titrated upward to 20 mg suvorexant or placebo for 2 additional weeks. Main Outcomes and Measures: Objective (ie, actigraphy) and subjective (ie, sleep logs) measures of sleep. Results: Among 19 participants who completed the study (mean [SD] age, 37.7 [11.1] years; 13 [68%] men), 8 participants (42%) were assigned to the suvorexant group and 11 participants (58%) were assigned to the placebo group. Compared with individuals in the placebo group, individuals in the suvorexant group increased their objective total sleep time by a mean (SE) of 1.04 (0.53) hours (P = .05) at the end of 1 week of 10-mg doses and by 2.16 (0.75) hours (P = .004) by the end of the 2 weeks of 20-mg doses. Subjective sleep was similarly improved as, compared with the placebo group, individuals in the suvorexant group increased their subjective total sleep time by a mean (SE) of 2.08 (0.47) hours (P < .001) at the end of 1 week of 10-mg doses and by 2.97 (0.56) hours (P < .001) by the end of the 2 weeks of 20-mg doses. Physician ratings of daytime sleep aligned with these measures, as there was no change in the placebo group and a much improved change in the suvorexant group. No adverse events were reported in the suvorexant group. Conclusions and Relevance: This pilot study found that the use of a dual hypocretin receptor antagonist in shift workers under real-world conditions resulted in more than 2 extra hours of daytime sleep per episode. Future research should confirm this pilot finding in a larger sample size and examine whether, over the long term, use of this medication has a concomitant improvement in medical and psychiatric health as well as workplace performance and safety. Trial Registration: ClinicalTrials.gov Identifier: NCT02491788.

Plasticity in perception: insights from color vision deficiencies.

Inherited color vision deficiencies typically result from a loss or alteration of the visual photopigments absorbing light and thus impact the very first step of seeing. There is growing interest in how subsequent steps in the visual pathway might be calibrated to compensate for the altered receptor signals, with the possibility that color coding and color percepts might be less severely impacted than the receptor differences predict. These compensatory adjustments provide important insights into general questions about sensory plasticity and the sensory and cognitive processes underlying how we experience color.

The accuracy of artificial and natural light measurements by actigraphs.

Actigraphs are the reference standard for measuring light exposure in human non-laboratory experiments due to their portability and long battery lives. However, actigraphs typically have a limited illuminance operating range not representative of real-world conditions, and for many actigraphs, the accuracy of their light measurement has not been verified independently. We assessed the illuminances recorded by Activinsights GENEActiv Original and Philips Actiwatch 2 actigraphs in comparison to a calibrated, laboratory-standard photometer, under both artificial light-emitting diode (LED) and natural sunlight illuminations that might be encountered by a person under real-world conditions. We show that in response to ~20,000 lux white LED light, the GENEActiv and Actiwatch 2 underestimate illuminance by recording 50% and 25% of the true value, respectively. Under ~30,000 lux sunlight, the GENEActiv readily saturates whereas the Actiwatch 2 reports ~46% of the true illuminance. These underestimations are highly linear and we provide correction factors to estimate the illuminance levels of the ambient environment measured by the actigraphs. We also evaluate the application of neutral density filters for extending the operating range of both devices in natural sunlight illuminations (as high as 30,000 lux during our measurements) and demonstrate that this may be a viable approach for increasing the operating range of the Actiwatch 2 but not the GENEActiv. We conclude that both actigraphs provide good performance in monitoring the temporal patterning of light, whereas the absolute illuminance values require correction to accurately evaluate the effects of light intensity on human health and behaviours.

Auditory psychomotor vigilance testing in older and young adults: a revised threshold setting procedure.

BACKGROUND: One of the most common ways to examine the daytime impact of sleep loss is the use of the psychomotor vigilance test (PVT). PVT metrics, including median reaction time (RT) and number of lapses, have been examined in a variety of studies in which both acute and chronic sleep times are manipulated. Most of these studies involve young, healthy individuals and use a visual stimulus. As light is a possible countermeasure to sleep loss, and sometimes incompatible with the use of visual PVT, PVT with auditory cues (aPVT) has been used. A threshold of 400 ms is commonly used to delineate lapses from normal RT in the aPVT. As aging can influence a variety of brain functions, we wanted to examine whether this lapse threshold was accurate for use in older adults. METHODS: Twenty-eight young and 19 healthy older participants performed a 10-min auditory PVT approximately 90 min before habitual bedtime. The occurrence of lapses was determined by five objective RT thresholds: (1) 400 ms, (2) 500 ms, (3) 2 × median, (4) mean + 2 × SD, and (5) method 4 without outliers. Results of these methods were compared with a triplicate visual inspection of RT histograms to determine RT outside of the expected log normal distribution. RESULTS: In both groups, methods 1, 4, and 5 performed poorly, while methods 2 and 3 were adequate, though method 3 was statistically superior. CONCLUSION: In both age groups, the use of twice the median as an objective threshold had the best concurrence with visual scoring.

Melanopsin-mediated pupil function is impaired in Parkinson's disease.

Parkinson's disease (PD) is characterised by non-motor symptoms including sleep and circadian disruption. Melanopsin-expressing intrinsically photosensitive Retinal Ganglion Cells (ipRGC) transmit light signals to brain areas controlling circadian rhythms and the pupil light reflex. To determine if non-motor symptoms observed in PD are linked to ipRGC dysfunction, we evaluated melanopsin and rod/cone contributions to the pupil response in medicated participants with PD (n = 17) and controls (n = 12). Autonomic tone was evaluated by measuring pupillary unrest in darkness. In the PD group, there is evidence for an attenuated post-illumination pupil response (PIPR) amplitude and reduced pupil constriction amplitude, and PIPR amplitudes did not correlate with measures of sleep quality, retinal nerve fibre layer thickness, disease severity, or medication dosage. Both groups exhibited similar pupillary unrest. We show that melanopsin- and the rod/cone-photoreceptor contributions to the pupil control pathway are impaired in people with early-stage PD who have no clinically observable ophthalmic abnormalities. Given that ipRGCs project to brain targets involved in arousal, sleep and circadian rhythms, ipRGC dysfunction may underpin some of the non-motor symptoms observed in PD.

A feasibility study of 2-mm bolus for postmastectomy radiation therapy.

PURPOSE: The purpose of this study was to prospectively evaluate the use of daily 2-mm bolus in patients undergoing postmastectomy radiation without reconstruction using optically stimulated luminescence dosimetry and weekly assessment of skin toxicity. METHODS AND MATERIALS: We prospectively collected data from the first 49 women treated with a daily 2-mm Superflab bolus during their postmastectomy radiation therapy from 2013 to 2016 at The University of Chicago Comprehensive Cancer Center at Silver Cross. Within the first 3 days of starting radiation therapy, we measured the surface dose in vivo at 5 anatomical locations under the 2-mm bolus on the chest wall. We assessed weekly the acute skin toxicity during radiation using the National Cancer Institute Common Toxicity Criteria. Patients with reconstruction before radiation therapy were excluded. RESULTS: Forty-nine women with a mean age of 54.3 years were treated with daily 2-mm bolus to the chest wall following mastectomy. Median follow-up was 32.7 weeks. The mean percentages of prescribed dose (standard deviation) for the median, central, lateral, superior, and inferior optically stimulated luminescence dosimeters were 100.1% (5.6%), 108.1% (6.7%), 98.1% (6.5%), 102.6% (8.9%), and 106.3% (6.6%), respectively. The majority (71.4%) of women experienced a maximum acute National Cancer Institute Common Toxicity Criteria skin toxicity score of 2, with only 12.2% experiencing a score of 3. There were no grade 4 toxicities. There were no local recurrences during our follow-up period. CONCLUSIONS: A daily 2-mm bolus is a feasible regimen for chest wall bolus during postmastectomy radiation therapy with acceptable dose buildup and skin toxicity.

The Effects of Short-Term Light Adaptation on the Human Post-Illumination Pupil Response.

PURPOSE: We determine the effect of short-term light adaptation on the pupil light reflex and the melanopsin mediated post-illumination pupil response (PIPR). Inner and outer retinal photoreceptor contributions to the dark-adapted pupil response were estimated. METHODS: In Experiment A, light adaptation was studied using short wavelength lights ranging from subthreshold to suprathreshold irradiances for melanopsin signaling that were presented before (5-60 seconds) and after (30 seconds) a melanopsin-exciting stimulus pulse. We quantified the pupil constriction and the poststimulus response amplitudes during dark (PIPR) and light (poststimulus pupil response, PSPR) adaptation. In Experiment B, colored prestimulus adapting lights were univariant for melanopsin or rod excitation. RESULTS: Increasing the prestimulus duration and irradiance of adapting lights increased the pupil constriction amplitude when normalized to the dark-adapted baseline but reduced its amplitude when normalized to the light-adapted baseline. Light adaptation at irradiances suprathreshold for melanopsin activation increased the PIPR amplitude, with larger changes at longer adaptation durations, whereas the PSPR amplitude became more attenuated with increasing irradiances, independent of duration. Rod versus melanospin univariant adaptation did not alter the constriction amplitude but increased the PIPR amplitude in the rod condition. Correlations between millimeter pupil constriction and PIPR amplitudes were eliminated when normalized to the baseline diameter. CONCLUSIONS: The findings have implications for standardizing light adaptation paradigms and the choice of pupil metrics in both laboratory and clinical settings. Light and dark adaptation have opposite effects on the pupil metrics, which should be normalized to baseline to minimize significant correlations between constriction and PIPR amplitudes.

Melanopsin-mediated post-illumination pupil response in the peripheral retina.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) regulate pupil size by integrating extrinsic rod and cone signals with intrinsic melanopsin-mediated phototransduction. Light adapted pupil diameter is determined by the corneal flux density (CFD), and for central visual field stimulation the melanopsin-mediated post-illumination pupil response (PIPR) follows this same CFD relationship. Rods, cones, and ipRGCs vary in size, density, and distribution across the retina, but how these differences affect the amplitude and timing of the extrinsic and intrinsic pupil light reflex in the central and peripheral retina is unknown. We determined the relationship between stimulus area and photon flux with stimuli constant for CFD, irradiance, or area at central (0°) and peripheral (20°) eccentricities with high and low melanopsin excitation. We show that the pupil constriction amplitude was similar at both eccentricities and the time to minimum diameter increased as melanopsin excitation increased. In contrast, the peripheral PIPR follows a CFD relationship but with lower amplitude compared with that at the fovea. This indicates differences in the spatial and temporal characteristics of extrinsic and intrinsic ipRGC inputs to the pupil control pathway for the central and peripheral retina. The eccentricity-dependent change in PIPR amplitude may be analogous to the hill of vision observed in visual perimetry; such knowledge is an important precursor to the development of pupil perimetry paradigms to measure the PIPR in select regions of the visual field.

Temporal characteristics of melanopsin inputs to the human pupil light reflex.

Rods, cones and melanopsin containing intrinsically photosensitive retinal ganglion cells (ipRGCs) operate in concert to regulate pupil diameter. The temporal properties of intrinsic ipRGC signalling are distinct to those of rods and cones, including longer latencies and sustained signalling after light offset. We examined whether the melanopsin mediated post-illumination pupil response (PIPR) and pupil constriction were dependent upon the inter-stimulus interval (ISI) between successive light pulses and the temporal frequency of sinusoidal light stimuli. Melanopsin excitation was altered by variation of stimulus wavelength (464 nm and 638 nm lights) and irradiance (11.4 and 15.2 log photons cm(-2) s(-1)). We found that 6s PIPR amplitude was independent of ISI and temporal frequency for all melanopsin excitation levels, indicating complete summation. In contrast to the PIPR, the maximum pupil constriction increased with increasing ISI with high and low melanopsin excitation, but time to minimum diameter was slower with high melanopsin excitation only. This melanopsin response to briefly presented pulses (16 and 100 ms) slows the temporal response of the maximum pupil constriction. We also demonstrate that high melanopsin excitation attenuates the phasic peak-trough pupil amplitude compared to conditions with low melanopsin excitation, indicating an interaction between inner and outer retinal inputs to the pupil light reflex. We infer that outer retina summation is important for rapidly controlling pupil diameter in response to short timescale fluctuations in illumination and may occur at two potential sites, one that is presynaptic to extrinsic photoreceptor input to ipRGCs, or another within the pupil control pathway if ipRGCs have differential temporal tuning to extrinsic and intrinsic signalling.

Effect of rod-cone interactions on mesopic visual performance mediated by chromatic and luminance pathways.

We studied the effect of rod-cone interactions on mesopic visual reaction time (RT). Rod and cone photoreceptor excitations were independently controlled using a four-primary photostimulator. It was observed that (1) lateral rod-cone interactions increase the cone-mediated RTs; (2) the rod-cone interactions are strongest when rod sensitivity is maximal in a dark surround, but weaker with increased rod activity in a light surround; and (3) the presence of a dark surround nonselectively increased the mean and variability of chromatic (+L-M, S-cone) and luminance (L+M+S) RTs independent of the level of rod activity. The results demonstrate that lateral rod-cone interactions must be considered when deriving mesopic luminous efficiency using RT.