Melanin bias in pulse oximetry explained by light source spectral bandwidth.

BACKGROUND: Pulse oximetry uses noninvasive optical measurements of light transmission from each of two sources through vascularised living tissue over the cardiac cycle (SpO2). From those measurements, the relative amount of oxygenated haemoglobin (SaO2) in circulating blood can be deduced. Recent reports have shown that, compared with SaO2 measurements from blood samples, SpO2 measurements are biased erroneously high for patients with dark skin. METHODS: We developed a new method, spectrally resolved photoplethysmography (srPPG), to examine how spectral bandwidth affects the transmission of polychromatic light through the fingertip across the cardiac cycle. We measured and recorded the spectral transmission through the fingertip as the O2 concentration in inspired air was reduced. We applied digital spectral filters of two different bandwidths, narrow or broad, to the same srPPG recordings to determine whether SpO2 readings systematically varied for the two bandwidths. The srPPG method also allowed us to measure the fractional amount of melanin in the optical path. The effect of melanin content on the ratio of SpO2 readings for narrow and broad spectral bandwidths was analysed. RESULTS: We hypothesised, based upon the Beer-Lambert law, and then showed experimentally, that the light emission spectra of light-emitting diode light sources, as used in commercial pulse oximeters, result in erroneously high SpO2 measurements for patients having greater melanin concentrations in their skin than those of the subject pool used for instrument calibration. CONCLUSIONS: To eliminate melanin bias, pulse oximeters should use much narrower spectral bandwidths than those used in current models.

Evaluation of a Novel Ambient Light Survey Question in the Cancer Prevention Study-3.

Nighttime light exposure may increase cancer risk by disrupting the circadian system. However, there is no well-established survey method for measuring ambient light. In the Cancer Prevention Study-3, 732 men and women answered a light survey based on seven environments. The light environment in the past year was assessed twice, one year apart, and four one-week diaries were collected between the annual surveys. A total of 170 participants wore a meter to measure photopic illuminance and circadian stimulus (CS). Illuminance and CS values were estimated for lighting environments from measured values and evaluated with a cross validation approach. The kappas for self-reported light environment comparing the two annual surveys were 0.61 on workdays and 0.49 on non-workdays. Kappas comparing the annual survey to weekly diaries were 0.71 and 0.57 for work and non-workdays, respectively. Agreement was highest for reporting of darkness (95.3%), non-residential light (86.5%), and household light (75.6%) on workdays. Measured illuminance and CS identified three peaks of light (darkness, indoor lighting, and outdoor daytime light). Estimated illuminance and CS were correlated with the measured values overall (r = 0.77 and r = 0.67, respectively) but were less correlated within each light environment (r = 0.23-0.43). The survey has good validity to assess ambient light for studies of human health.

The circadian stimulus-oscillator model: Improvements to Kronauer's model of the human circadian pacemaker.

Modeling how patterns of light and dark affect circadian phase is important clinically and organizationally (e.g., the military) because circadian disruption can compromise health and performance. Limit-cycle oscillator models in various forms have been used to characterize phase changes to a limited set of light interventions. We approached the analysis of the van der Pol oscillator-based model proposed by Kronauer and colleagues in 1999 and 2000 (Kronauer99) using a well-established framework from experimental psychology whereby the stimulus (S) acts on the organism (O) to produce a response (R). Within that framework, using four independent data sets utilizing calibrated personal light measurements, we conducted a serial analysis of the factors in the Kronauer99 model that could affect prediction accuracy characterized by changes in dim-light melatonin onset. Prediction uncertainty was slightly greater than 1 h for the new data sets using the original Kronauer99 model. The revised model described here reduced prediction uncertainty for these same data sets by roughly half.

Corrigendum: Modeling Circadian Phototransduction: Quantitative Predictions of Psychophysical Data.

[This corrects the article DOI: 10.3389/fnins.2021.615322.].

Spatial sensitivity of human circadian response: Melatonin suppression from on-axis and off-axis light exposures.

A better understanding of the spatial sensitivity of the human circadian system to photic stimulation can provide practical solutions for optimized circadian light exposures. Two psychophysical experiments, involving 25 adult participants in Experiment 1 (mean age = 34.0 years [SD 15.5]; 13 females) and 15 adult participants in Experiment 2 (mean age = 43.0 years [SD 12.6]; 12 females), were designed to investigate whether varying only the spatial distribution of luminous stimuli in the environment while maintaining a constant spectrally weighted irradiance at the eye could influence nocturnal melatonin suppression. Two spatial distributions were employed, one where the luminous stimulus was presented On-axis (along the line of sight) and one where two luminous stimuli were both presented Off-axis (laterally displaced at center by 14°). Two narrowband LED light sources, blue (λmax  = 451 nm) for first experiment and green (λmax  = 522 nm) for second experiment, were used in both the On-axis and the Off-axis spatial distributions. The blue luminous stimulus targeting the fovea and parafovea (On-axis) was about three times more effective for suppressing melatonin than the photometrically and spectrally matched stimulus targeting the more peripheral retina (Off-axis). The green luminous stimulus targeting the fovea and parafovea (On-axis) was about two times more effective for suppressing melatonin than the photometrically and spectrally matched stimulus targeting the more peripheral retina (Off-axis).

Relative light sensitivities of four retinal hemi-fields for suppressing the synthesis of melatonin at night.

The magnitude of the stimulus to the biological clock will depend upon the distribution of circadian phototransduction circuits across the retinae and the spatial distribution of luminous stimuli in the environment. The present study compared nocturnal melatonin suppression for light exposures to the superior, inferior, nasal, and temporal retina in one eye independent of shading from the brow and the nose. The stimulus was a 40° diameter luminous disc, half of which was blue light (LED, λpeak = 470 nm) and the other amber light (LED, λpeak = 590 nm). Experimentally, the orientation of the bipartite disc was rotated to each of the four cardinal points of the visual field. A full, 40° blue disc was also employed by replacing the amber half-disc with another blue half-disc. The blue full- and half-discs always produced 100 photopic lx at the cornea. As hypothesized, nocturnal melatonin suppression was statistically greatest when the blue half-disc was delivered to the nasal hemi-field (35%); the other three hemi-fields were equally affected by the blue half-disc (≈20%). Melatonin suppression for the full-disc was 24%, which was not statistically different than the average suppression for the four hemi-fields of 27%.

Modeling Circadian Phototransduction: Quantitative Predictions of Psychophysical Data.

A revised computational model of circadian phototransduction is presented. The first step was to characterize the spectral sensitivity of the retinal circuit using suppression of the synthesis of melatonin by the pineal gland at night as the outcome measure. From the spectral sensitivity, circadian light was defined. Circadian light, thereby rectifies any spectral power distribution into a single, instantaneous photometric quantity. The second step was to characterize the circuit's response characteristic to different amounts of circadian light from threshold to saturation. By doing so a more complete instantaneous photometric quantity representing the circadian stimulus was defined in terms of both the spectral sensitivity and the response magnitude characteristic of the circadian phototransduction circuit. To validate the model of the circadian phototransduction circuit, it was necessary to augment the model to account for different durations of the circadian stimulus and distribution of the circadian stimulus across the retina. Two simple modifications to the model accounted for the duration and distribution of continuous light exposure during the early biological night. A companion paper (https://www.frontiersin.org/articles/10.3389/fnins.2020.615305/full) provides a neurophysiological foundation for the model parameters.

Long-Term, All-Day Exposure to Circadian-Effective Light Improves Sleep, Mood, and Behavior in Persons with Dementia.

BACKGROUND: Persons with Alzheimer's disease and related dementias (ADRD) frequently experience sleep-wake (circadian) cycle disturbances that lead them to remain awake at night, causing stress and fatigue for families and caregivers. Light therapy shows promise as a nonpharmacological treatment for regulating sleep in this population. OBJECTIVE: We investigated the long-term impact of a circadian-effective lighting intervention on sleep, mood, and behavior problems in persons with ADRD. METHODS: This 25-week clinical trial administered an all-day lighting intervention to 47 patients with ADRD in 9 senior-care facilities, employing wrist-worn actigraphy measures and standardized measures of sleep quality, mood, and behavior. RESULTS: The intervention significantly improved Pittsburgh Sleep Quality Index scores, from an estimated mean±SEM of 11.89±0.53 at baseline to 5.36±0.63 at the end of the intervention. Additional improvements were noted for sleep efficiency data from actigraph measurements. The intervention significantly reduced Cornell Scale for Depression in Dementia scores (mean±SEM of 11.36±0.74 at baseline and 4.18±0.88 at the end of the intervention) and Cohen-Mansfield Agitation Inventory scores (mean±SEM of 47.10±1.98 at baseline and 35.33±2.23 at the end of the intervention). CONCLUSION: A regular circadian-effective daytime lighting intervention can improve sleep at night and reduce depression and agitation in patients with dementia living in controlled environments. More importantly, the positive effects of the tailored lighting intervention on these outcomes appear to be cumulative over time.

Predictions of melatonin suppression during the early biological night and their implications for residential light exposures prior to sleeping.

The magnitude of nocturnal melatonin suppression depends upon the spectrum, amount, and duration of light exposure. The functional relationship between melatonin suppression and the light spectrum and amount have been previously described. Only one duration-dependent parameter was needed to extend this functional relationship to predict nocturnal melatonin suppression during the early biological night from a variety of published studies. Those predictions suggest that ambient lighting commonly found in North American homes will not suppress melatonin for durations up to 3 h, whereas extended use of self-luminous displays in the home prior to sleep can.

Declines in Wavelength Discrimination and Shifts in Unique Hue with Hypoxia.

INTRODUCTION: Hypoxia can be a problem for warfighters, compromising visual and cognitive performance. One area of study has been hypoxia-induced decrements in color vision.METHODS: The present study examined how hypoxia affected the perception of wavelengths associated with unique green and with unique yellow as well as discriminability by the blue vs. yellow (b-y) and the red vs. green (r-g) spectrally opponent color channels while breathing O2 levels found at sea level and at 5500 m. Measurements of wavelengths producing unique green (minimizing response by the b-y channel) and unique yellow (minimizing response by the r-g channel) preceded measurements of wavelength discriminability near those unique hues.RESULTS: Relative to sea level, unique yellow shifted to shorter wavelengths (0.54 nm) and unique green shifted to longer wavelengths (2.3 nm) under hypoxia. In terms of an equal psychophysical scale, both unique hues shifted by similar magnitudes. Wavelength discriminability of both color channels was compromised by statistically reliable amounts of 16-17% under hypoxia.DISCUSSION: These results were consistent with previous studies and the inference that postreceptor, M-cone neurons were differentially compromised by hypoxia. However, these measurable changes in color vision due to hypoxia were not perceived by the subjects.Bierman A, LaPlumm T, Rea MS. Declines in wavelength discrimination and shifts in unique hue with hypoxia. Aerosp Med Hum Perform. 2020; 91(5):394-402.

Modeling Circadian Phototransduction: Retinal Neurophysiology and Neuroanatomy.

The retina is a complex, but well-organized neural structure that converts optical radiation into neural signals that convey photic information to a wide variety of brain structures. The present paper is concerned with the neural circuits underlying phototransduction for the central pacemaker of the human circadian system. The proposed neural framework adheres to orthodox retinal neuroanatomy and neurophysiology. Several postulated mechanisms are also offered to account for the high threshold and for the subadditive response to polychromatic light exhibited by the human circadian phototransduction circuit. A companion paper, modeling circadian phototransduction: Quantitative predictions of psychophysical data, provides a computational model for predicting psychophysical data associated with nocturnal melatonin suppression while staying within the constraints of the neurophysiology and neuroanatomy offered here.

Effects of a Tailored Lighting Intervention on Sleep Quality, Rest-Activity, Mood, and Behavior in Older Adults With Alzheimer Disease and Related Dementias: A Randomized Clinical Trial.

STUDY OBJECTIVES: We investigated the effectiveness of a lighting intervention tailored to maximally affect the circadian system as a nonpharmacological therapy for treating problems with sleep, mood, and behavior in persons with Alzheimer disease and related dementias (ADRD). METHODS: This 14-week randomized, placebo-controlled, crossover design clinical trial administered an all-day active or control lighting intervention to 46 patients with ADRD in 8 long-term care facilities for two 4-week periods (separated by a 4-week washout). The study employed wrist-worn actigraphy measures and standardized measures of sleep quality, mood, and behavior. RESULTS: The active intervention significantly improved Pittsburgh Sleep Quality Index scores compared to the active baseline and control intervention (mean ± SEM: 6.67 ± 0.48 after active intervention, 10.30 ± 0.40 at active baseline, 8.41 ± 0.47 after control intervention). The active intervention also resulted in significantly greater active versus control differences in intradaily variability. As for secondary outcomes, the active intervention resulted in significant improvements in Cornell Scale for Depression in Dementia scores (mean ± SEM: 10.30 ± 1.02 at baseline, 7.05 ± 0.67 after active intervention) and significantly greater active versus control differences in Cohen-Mansfield Agitation Inventory scores (mean ± SEM: -5.51 ± 1.03 for the active intervention, -1.50 ± 1.24 for the control intervention). CONCLUSIONS: A lighting intervention tailored to maximally entrain the circadian system can improve sleep, mood, and behavior in patients with dementia living in controlled environments. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov, title: Methodology Issues in a Tailored Light Treatment for Persons With Dementia, URL: https://clinicaltrials.gov/ct2/show/NCT01816152, identifier: NCT01816152.

Sleep reductions associated with illicit opioid use and clinic-hour changes during opioid agonist treatment for opioid dependence: Measurement by electronic diary and actigraphy.

Sleep problems are commonly reported during opioid agonist treatment (OAT) for opioid use disorders. Inpatient studies have found both sleep disturbances and improved sleep during OAT. Illicit opioids can also disrupt sleep, but it is unclear how they affect sleep in outpatients receiving OAT. Therefore, we used electronic diary entries and actigraphy to measure sleep duration and timing in opioid-dependent participants (n = 37) treated with methadone (n = 15) or buprenorphine (n = 22). For 16 weeks, participants were assigned to attend our clinic under different operating hours in a crossover design: Early hours (07:00-09:00) vs. Late hours (12:00-13:00) for 4 weeks each in randomized order, followed for all participants by our Standard clinic hours (07:00-11:30) for 8 weeks. Throughout, participants made daily electronic diary self-reports of their sleep upon waking; they also wore a wrist actigraph for 6 nights in each of the three clinic-hour conditions. Drug use was assessed by thrice-weekly urinalysis. In linear mixed models controlling for other sleep-relevant factors, sleep duration and timing differed by drug use and by clinic hours. Compared to when non-using, participants slept less, went to bed later, and woke later when using illicit opioids and/or both illicit opioids and cocaine. Participants slept less and woke earlier when assigned to the Early hours. These findings highlight the role OAT clinic schedules can play in structuring the sleep/wake cycles of OAT patients and clarify some of the circumstances under which OAT patients experience sleep disruption in daily life.

Effects of red light on sleep inertia.

Introduction: Sleep inertia, broadly defined as decrements in performance and lowering of alertness following waking, lasts for durations ranging between 1 min and 3 hrs. This study investigated whether, compared to a dim light condition (the control), exposure to long-wavelength (red) light delivered to closed eyelids during sleep (red light mask) and to eyes open upon waking (red light goggles) reduced sleep inertia. Methods: Thirty participants (18 females, 12 males; mean age=30.4 years [SD 13.7]) completed this crossover, within-subjects, counterbalanced design study. Self-reported measures of sleepiness and objective measures of auditory performance and cortisol levels were collected on 3 Friday nights over the course of 3 consecutive weeks. Results: Performance improved significantly during the 30-min data collection period in all experimental conditions. Subjective sleepiness also decreased significantly with time awake in all experimental conditions. As hypothesized, performance of some tasks was significantly better in the red light mask condition than in the dim light condition. Performance scores in the red light goggles condition improved significantly after a few minutes of wearing the light goggles. Discussion: The results show that saturated red light delivered through closed eyelids at levels that do not suppress melatonin can be used to mitigate sleep inertia upon waking.

Effect of White Light Devoid of "Cyan" Spectrum Radiation on Nighttime Melatonin Suppression Over a 1-h Exposure Duration.

The intrinsically photosensitive retinal ganglion cells are the main conduit of the light signal emanating from the retina to the biological clock located in the suprachiasmatic nuclei of the hypothalamus. Lighting manufacturers are developing white light sources that are devoid of wavelengths around 480 nm ("cyan gap") to reduce their impact on the circadian system. The present study was designed to investigate whether exposure to a "cyan-gap," 3000 K white light source, spectrally tuned to reduce radiant power between 475 and 495 nm (reducing stimulation of the melanopsin-containing photoreceptor), would suppress melatonin less than a conventional 3000 K light source. The study's 2 phases employed a within-subjects experimental design involving the same 16 adult participants. In Phase 1, participants were exposed for 1 h to 3 experimental conditions over the course of 3 consecutive weeks: 1) dim light control (<5 lux at the eyes); 2) 800 lux at the eyes of a 3000 K light source; and 3) 800 lux at the eyes of a 3000 K, "cyan-gap" modified (3000 K mod) light source. The same protocol was repeated in Phase 2, but light levels were reduced to 400 lux at the eyes. As hypothesized, there were significant main effects of light level ( F1,12 = 9.1, p < 0.05, ηp² = 0.43) and exposure duration ( F1,12 = 47.7, p < 0.05, ηp² = 0.80) but there was no significant main effect of spectrum ( F1,12 = 0.16, p > 0.05, ηp² = 0.01). There were no significant interactions with spectrum. Contrary to our model predictions, our results showed that short-term exposures (≤ 1 h) to "cyan-gap" light sources suppressed melatonin similarly to conventional light sources of the same CCT and photopic illuminance at the eyes.

Nocturnal Melatonin Suppression by Adolescents and Adults for Different Levels, Spectra, and Durations of Light Exposure.

The human circadian system is primarily regulated by the 24-h LD cycle incident on the retina, and nocturnal melatonin suppression is a primary outcome measure for characterizing the biological clock's response to those light exposures. A limited amount of data related to the combined effects of light level, spectrum, and exposure duration on nocturnal melatonin suppression has impeded the development of circadian-effective lighting recommendations and light-treatment methods. The study's primary goal was to measure nocturnal melatonin suppression for a wide range of light levels (40 to 1000 lux), 2 white light spectra (2700 K and 6500 K), and an extended range of nighttime light exposure durations (0.5 to 3.0 h). The study's second purpose was to examine whether differences existed between adolescents' and adults' circadian sensitivity to these lighting characteristics. The third purpose was to provide an estimate of the absolute threshold for the impact of light on acute melatonin suppression. Eighteen adolescents (age range, 13 to 18 years) and 23 adults (age range, 24 to 55 years) participated in the study. Results showed significant main effects of light level, spectrum, and exposure duration on melatonin suppression. Moreover, the data also showed that the relative suppressing effect of light on melatonin diminishes with increasing exposure duration for both age groups and both spectra. The present results do not corroborate our hypothesis that adolescents exhibit greater circadian sensitivity to short-wavelength radiation compared with adults. As for threshold, it takes longer to observe significant melatonin suppression at lower CS levels than at higher CS levels. Dose-response curves (amount and duration) for both white-light spectra and both age groups can guide lighting recommendations when considering circadian-effective light in applications such as offices, schools, residences, and healthcare facilities.

Evaluating the blue-light hazard from solid state lighting.

PURPOSE: New light sources including light-emitting diodes (LEDs) have elicited questions about retinal damage, including the blue-light hazard. Some organizations have recommended avoiding using LEDs with correlated color temperatures exceeding 3000 K, since they tend to produce greater short-wavelength energy. This article provides quantitative comparisons among light sources and use cases as they affect the blue-light hazard. METHODS: The spectral radiant power characteristics of incandescent, fluorescent, LED and daylight sources were evaluated in terms of blue-light hazard using standard procedures for phakic, aphakic and pseudophakic eyes. RESULTS: Under most use cases, LEDs do not exhibit greater risk for the blue-light hazard than other sources (e.g., incandescent). Because they generally produce little to no ultraviolet energy, LEDs often present less risk to aphakic eyes. CONCLUSIONS: LEDs present no special concerns for the blue-light hazard over some other common sources in typical use cases because photophobic responses limit exposure to bright sources. Where photophobic responses might not occur (e.g., eye surgery patients or premature infants) or where individuals suppress these responses (e.g., stage actors), caution is necessary. Evidence remains inconsistent regarding the risk of human retinal damage from long-term exposures to light insufficient to reach acute blue-light hazard thresholds.

Investigation of flashing and intensity characteristics for vehicle-mounted warning beacons.

Reducing the potential for crashes involving front line service workers and passing vehicles is important for increasing worker safety in work zones and similar locations. Flashing yellow warning beacons are often used to protect, delineate, and provide visual information to drivers within and approaching work zones. A nighttime field study using simulated workers, with and without reflective vests, present outside trucks was conducted to evaluate the effects of different warning beacon intensities and flash frequencies. Interactions between intensity and flash frequency were also analyzed. This study determined that intensitiesof 25/2.5 cd and 150/15 cd (peak/trough intensity) provided the farthest detection distances of the simulated worker. Mean detection distances in response to a flash frequency of 1 Hz were not statistically different from those in response to 4 Hz flashing. Simulated workers wearing reflective vests were seen the farthest distances away from the trucks for all combinations of intensity and flash frequency.

The impact of daytime light exposures on sleep and mood in office workers.

BACKGROUND: By affecting the internal timing mechanisms of the brain, light regulates human physiology and behavior, perhaps most notably the sleep-wake cycle. Humans spend over 90% of their waking hours indoors, yet light in the built environment is not designed to affect circadian rhythms. OBJECTIVE: Using a device calibrated to measure light that is effective for the circadian system (circadian-effective light), collect personal light exposures in office workers and relate them to their sleep and mood. SETTING: The research was conducted in 5 buildings managed by the US General Services Administration. PARTICIPANTS: This study recruited 109 participants (69 females), of whom 81 (54 females) participated in both winter and summer. MEASUREMENTS: Self-reported measures of mood and sleep, and objective measures of circadian-effective light and activity rhythms were collected for 7 consecutive days. RESULTS: Compared to office workers receiving low levels of circadian-effective light in the morning, receiving high levels in the morning is associated with reduced sleep onset latency (especially in winter), increased phasor magnitudes (a measure of circadian entrainment), and increased sleep quality. High levels of circadian-effective light during the entire day are also associated with increased phasor magnitudes, reduced depression, and increased sleep quality. CONCLUSIONS: The present study is the first to measure personal light exposures in office workers using a calibrated device that measures circadian-effective light and relate those light measures to mood, stress, and sleep. The study's results underscore the importance of daytime light exposures for sleep health.