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. Author manuscript; available in PMC: 2025 Feb 1.
Published in final edited form as: Sleep Health. 2023 Sep 23;10(1 Suppl):S34–S40. doi: 10.1016/j.sleh.2023.08.012

A pilot study of light exposure as a countermeasure for menstrual phase-dependent neurobehavioral performance impairment in women

Leilah K Grant 1,2,3,*, Joshua J Gooley 1,2, Melissa A St Hilaire 1,2,4, Hadine Joffe 2,3,5, George C Brainard 5, Eliza Van Reen 1,2, Melanie Rüger 1,2, Shantha MW Rajaratnam 1,2, Steven W Lockley 1,2, Charles A Czeisler 1,2, Shadab A Rahman 1,2,3
PMCID: PMC10959759  NIHMSID: NIHMS1933417  PMID: 37748973

Abstract

Objective:

To examine effects of menstrual phase and nighttime light exposure on subjective sleepiness and auditory Psychomotor Vigilance Task performance.

Methods:

Twenty-nine premenopausal women (12=Follicular; 17=Luteal) completed a 6.5-h nighttime monochromatic light exposure with varying wavelengths (420–620 nm) and irradiances (1.03–14.12 μW/cm2). Subjective sleepiness, reaction time and attentional lapses were compared between menstrual phases in women with minimal (<33%) or substantial (≥33%) light-induced melatonin suppression.

Results:

When melatonin was not suppressed, women in the follicular phase had significantly worse reaction time (mean difference=145.1 ms, 95% CI 51.8–238.3, p<.001, Cohen’s D=1.9) and lapses (mean difference=12.9 lapses, 95% CI 4.37–21.41, p<.001, Cohen’s D=1.7) compared to women in the luteal phase. When melatonin was suppressed, women in the follicular phase had significantly better reaction time (mean difference=152.1 ms, 95% CI 43.88–260.3, p<.001, Cohen’s D=1.7) and lapses (mean difference=12.3 lapses, 95% CI 1.14–25.6, p<.01, Cohen’s D=1.6) compared to when melatonin was not suppressed, such that their performance was not different (p>.9) from women in the luteal phase. Subjective sleepiness did not differ by menstrual phase (mean difference=0.6, p>.08) or melatonin suppression (mean difference=0.2, p>.4).

Conclusions:

Nighttime light exposure sufficient to suppress melatonin can also mitigate neurobehavioral performance deficits associated with the follicular phase. Despite the relatively small sample size, these data suggests that nighttime light may be a valuable strategy to help reduce errors and accidents in female shift workers.

Keywords: Women, Menstrual Phase, Night work, Shift work, Neurobehavioral performance, Light, Melatonin

INTRODUCTION

In 1890, Massachusetts was the first state in the United States to ban women from working at night; 17 states and the Territory of Puerto Rico soon followed suit with similar laws prohibiting or regulating night work for women [1]. In 1914, arguing that women were more susceptible to the adverse effects of night work, Attorney Louis Brandeis and his sister-in-law, labor reformer Josephine Goldmark, submitted a brief on behalf of the People to support a successful effort to defend these sex-based night work prohibition laws [2] that were being challenged in the State of New York. Evidence supporting their claims was largely anecdotal and suffused with prejudice about the role of women in society. Due to the need for munitions, laws restricting the rights of women to work at night were suspended during the World War I, and then reinstated before being suspended again during World War II [3,4], after which time there was building opposition to the return of the ban on night work for women. With support from the 20th century feminist movement, the US laws were ended in the 1970s [5], but it was not until 2017 that the International Labour Organization finally renounced its official position recommending prohibition of night work for women [6].

The original premise underlying paternalistic restrictions on the right of women to work at night–i.e., that women were especially vulnerable to the hazards of night work–has found support from recent findings from controlled laboratory experiments indicating that women, on average, experience greater neurobehavioral performance impairment compared to men when awake overnight [7,8]. Importantly, these laboratory findings are reflected in real-world work-related injury data [9–11]: for example, a study in Canada showed that women, compared to men, had an increased risk of injury (HR 1.85, 95% CI 1.44, 2.37) when working non-standard shifts [9]. Closer inspection of the laboratory data shows that these differences are not simply due to a sex difference. When data were analyzed separately based on menstrual phase, women in the luteal phase of the menstrual cycle outperformed both women in the follicular phase and men [8], whereas women in the follicular phase, had significantly greater neurobehavioral impairment, on average, than both men and women in the luteal phase [8].

While this finding could seem counterproductive in promoting equality between sexes, we should embrace it as an opportunity to investigate the underlying biology driving this effect and begin testing appropriate countermeasures to promote safety for all. To that end, in a recent study of 16 premenopausal women, we showed that the ratio between the temperature-regulating female sex-steroids progesterone and estradiol may contribute to the neurobehavioral performance vulnerabilities during the follicular phase of the menstrual cycle via their influence on overnight body temperature [12]. We also showed preliminary evidence that nighttime light exposure increased body temperature and could be a potential countermeasure to improve neurobehavioral performance during the follicular phase of the menstrual cycle. We therefore expanded these analyses in a larger sample to allow for a more robust statistical approach and also assessed the effects of light exposure on subjective sleepiness, in order to understand whether self-ratings are useful in identifying impairment and assessing the impact of countermeasures.

METHODS

Thirty naturally cycling premenopausal women (mean±SD age = 23.4±2.9 years), 12 in the follicular and 18 in the luteal phase of the menstrual cycle, were studied in a 9-day inpatient protocol in an environment free of time cues, the details of which have been described elsewhere [13–15]. A subset of these data was published in 16 women in whom serum progesterone was available to determine menstrual phase [12]. In the current study, menstrual phase on the light exposure day was estimated using self-reported last menstrual cycle date and average cycle length [8]. Menstrual phase was defined as follicular if the light exposure occurred on a cycle day in the first half of the cycle (e.g., days 0–14 of a 28 day cycle), or luteal if in the second half of the cycle. There was >80% (14/16) agreement with menstrual phase determined using progesterone levels in the subset of 16 participants in whom data were previously reported [12]. The study was approved by the Partners Human Research Committee and written informed consent was given by participants before commencing the study.

On day 6 of the protocol, participants underwent a 6.5-hour monochromatic nighttime light exposure starting ~9.25-hours prior to their habitual waketime on baseline days. Participants were randomized across a series of studies to light wavelength (dark control, 420, 460, 480, 507, 555, or 620 nm) and irradiance (1.03–14.12 μW/cm2, half peak bandwidths 10 – 14 nm) conditions that were selected as part of different studies to investigate the spectral sensitivity of circadian, neuroendocrine and neurobehavioral responses to light [13–15]. Details of the lighting conditions are detailed in [15] and briefly in Table 1, which reports the number of participants randomized to each wavelength condition by menstrual phase. As analysis by the different light exposure conditions was precluded by sample size, in the current analysis, we compared subjective sleepiness, neurobehavioral performance, and temperature between women in whom the light exposure either did or did not induce a robust physiological response, namely melatonin suppression, regardless of wavelength or irradiance. Melatonin suppression was used as a biomarker of whether the light exposure induced either a minimal (<33%) or robust (≥33%) response (Figure 1A), using a threshold consistent with our prior studies [12,16].

Table 1.

Demographic variables and the number of participants randomized to each wavelength condition by menstrual phase †

Follicular Luteal p-value
Age, years 22.58 ± 2.19 23.94 ± 3.19 0.99
Chronotype, MEQ score 52.06 ± 8.24 53.29 ± 10.26 0.73
Bedtime, hh:mm 23:26 ± 1:04 23:02 ± 1:04 0.31
DLMO, hh:mm 22:35 ± 1:22 22:05 ± 1:25 0.36
Phase angle, hours 0.97 ± 1.08 0.99 ± 1.02 0.98
Wavelength of light exposure*
 420 nm (11.55 – 13.45 μ/cm2) 3 1 -
 460 nm (11.54 – 14.11 μ/cm2) 2 7 -
 480 nm (13.45 – 13.84 μ/cm2) 1 1 -
 507 nm (12.25 – 13.45 μ/cm2) 1 1 -
 555 nm (1.03 – 13.44 μ/cm2) 4 6 -
 620 nm (13.45 – 14.12 μ/cm2) 1 1 -
 Dark, 0 nm (0 μ/cm2) 0 1 -
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†

Values are presented as mean±SD, except for wavelength which reports the number (n) of participants per condition; a two-tailed t-test or Mann-Whitney U test, where appropriate, was used to compare age, chronotype, bedtime, DLMO and phase angle (between DLMO and bedtime) between menstrual phases. MEQ = Morningness Eveningness Questionnaire; DLMO = dim light melatonin onset.

*

Monochromatic light generated by a Xenon arc lamp and grating monochromator, and the wavelength and bandwidth were verified by measurement with a spectrophotometer [15].

Figure 1. Effects of menstrual phase and melatonin suppression on neurobehavioral performance and body temperature.

Figure 1.

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Mean ± Standard error (SE) of plasma melatonin levels (A), subjective sleepiness (E), Psychomotor Vigilance Task (PVT) reaction time (I), PVT attentional lapses (M), and core body temperature (Q) for women in the follicular (black circles, ●) and luteal (grey squares, ■) phases of the menstrual cycle in whom there was <33% (closed symbols) or ≥ 33% melatonin suppression (open symbols) in response to 6.5-hour monochromatic light exposures with varying wavelengths and irradiances. Saliva was used to calculate melatonin suppression in 3 women (1=Follicular, 2=Luteal) whose melatonin data were not included in the plasma melatonin levels shown in panel A. Significance of Tukey-adjusted post-hoc analyses are denoted by * p<0.05; ** p<0.01; *** p<0.001 for the comparison between menstrual phases (follicular vs. luteal) in women with <33% suppression, and # p<0.05; # # p<0.01; # # # p<0.001 for the comparison between suppression groups (<33% vs. ≥ 33%) in women in the follicular phase. In panels E, I, M, and Q, data shown before lights on and after lights off are for illustrative purposes only and were not included in the analyses. Least square means ± SE of the main effects of menstrual phase, melatonin suppression status and time since lights on for Karolinska Sleepiness Scale (KSS) subjective sleepiness (B-D), and Psychomotor PVT reaction time (F-H), PVT attentional lapses (J-L) and core body temperature (N-P). Significant main effects are denoted by * p<0.05; ** p<0.01; *** p<0.001. Non-significant effects are denoted by ‘ns’

The Karolinska Sleepiness Scale (KSS) and an auditory version of the 10-minute Psychomotor Vigilance Task (PVT) were completed hourly throughout the light exposure to assess subjective sleepiness and neurobehavioral performance, respectively. Core body temperature (CBT) was collected each minute via rectal thermistor and melatonin was measured from plasma samples collected every 20 minutes via intravenous catheter (n=26) or from saliva samples (n=3). Generalized linear mixed models with participant-level random effects were used to investigate main and interaction effects of time within the light exposure (7 hourly time points for KSS and PVT, 13 half-hourly timepoints for CBT), menstrual phase (follicular, luteal), and melatonin suppression (<33%, ≥33%) on KSS scores, PVT mean reaction time and attentional lapses (reaction time > 500ms), and CBT. Analyses were conducted on n=29 women, as one participant was excluded from all analyses due to missing melatonin data (22A7V) and another was excluded only from analyses of PVT data due to missing data during the light exposure (22E6V, for PVT analyses n=28). All analyses and graphical representations were conducted in SAS 9.4 (SAS Inc., Cary, NC, USA) and GraphPad Prism 9.1.0. (GraphPad Software La Jolla, CA, USA).

RESULTS

The main effects of time within the light exposure, menstrual phase, and melatonin suppression, and the time course profiles the primary outcomes are reported in Table 1 and shown in Figure 1. Subjective sleepiness, reaction time and attentional lapses increased with time since the overnight light exposure began. Reaction time and attentional lapses, but not sleepiness, were significantly higher in the follicular compared to luteal phase of the menstrual cycle, and in women with minimal compared to robust melatonin suppression irrespective of menstrual phase. CBT significantly decreased with increasing time since lights on and was significantly lower in women in the follicular phase and in those with minimal melatonin suppression.

For subjective sleepiness, there was a significant three-way interaction between time into light exposure, menstrual phase and suppression status. Among women with minimal suppression, in the first assessment at the start of the light exposure, sleepiness was highest in women in the luteal phase, whereas at the end of the exposure, during the second-to-last assessment, women in the follicular phase reported greater sleepiness. There was no difference in sleepiness between menstrual phases or suppression groups, at any other timepoints.

For reaction time, there was a significant two-way interaction between menstrual phase and suppression status, such that reaction time was significantly slower in the follicular compared to luteal phase, but only in women with minimal melatonin suppression (t=3.9, p-adj<.001). Furthermore, in the follicular, but not in the luteal phase, reaction time was faster in women who had robust compared to minimal melatonin suppression (t=3.8, p-adj=.001).

For attentional lapses, there was a significant three-way interaction between time into light exposure, menstrual phase and suppression status. With minimal melatonin suppression, women in the follicular compared to luteal phase had more attentional lapses, except during the first testing session (i.e., at lights on). In the follicular, but not luteal phase, attentional lapses were higher in women who had minimal compared to robust melatonin suppression in all except the first and third testing sessions.

There was a non-significant trend toward a two- and three-way interaction for temperature, such that CBT increased more in the follicular compared to luteal phase when melatonin suppression was high, especially in the second half of the light exposure.

DISCUSSION

The data in the current study demonstrate that menstrual phase-dependent differences in neurobehavioral performance at night can be mitigated by exposure to light that suppresses melatonin. Additionally, we found that these differences in neurobehavioral performance and their mitigation by light exposure were observed despite women not perceiving a difference in their level of subjective sleepiness between menstrual phases. These findings indicate that strategically timed exposure to light in the workplace at night may be valuable to help reduce errors and accidents in female shift workers during the follicular phase even when higher levels of sleepiness are not perceived.

Consistent with previous studies [8,12,17], we found that in women with minimal or no melatonin suppression, neurobehavioral performance was worse, and temperature was lower in women in the follicular, compared to the luteal phase of the menstrual cycle. Despite these objective differences in performance and CBT, both groups reported similar levels of subjective sleepiness, suggesting that, consistent with data in men [18,19], women may not perceive their level of impairment nor their response to effective countermeasures. Furthermore, nighttime light exposure that suppressed melatonin and increased CBT was able to improve performance of women in the follicular phase to the same level as women in the luteal phase, confirming our preliminary report [12]. Based on these findings, a large-scale clinical trial should be conducted to evaluate the efficacy and safety of a photic countermeasure to mitigate menstrual phase-dependent differences in overnight performance impairment.

During the 19th- to mid-20th-century prohibition of night work for women, factory lighting was so poor for vision that it was often the direct cause of injuries and accidents [2,3], although today minimum illuminance standards (e.g., [20]) reduce this risk. Adequate illuminance, while important for safety from a visual perspective, is only part of the solution, however. Light is a direct stimulant while also having melatonin suppressing and thermoregulating effects [21]–often termed ‘non-visual’ effects of light–and this mechanism is likely as important as good vision for minimizing workplace injuries and accidents. Lighting standards should therefore set minima for both the visual and non-visual effects of light [22]. While the monochromatic light exposures are a limitation of the current study, we expect that polychromatic white light, which also suppresses melatonin and increases temperature [23], would have a similar beneficial effect on performance in the follicular phase. Nonetheless, future studies investigating the optimal illuminance and spectral composition of white light that can improve performance and also meet visual and color-rendering standards are needed prior to the initiation of large-scale clinical trials.

While beyond the scope of the current study, it should be acknowledged that light exposure at night, and melatonin suppression in particular, has been hypothesized as a risk factor for hormone-dependent breast and prostate cancers [24,25]. All night shiftwork, by definition, requires light exposure for vision, but light can also be used to elevate alertness and therefore safety at a time when the risk of accidents and injuries are highest [26]. It remains to be determined whether the lifetime risk of a serious injury that accumulates for each and every nightshift worked, and can be attenuated by appropriate lighting, outweighs the lifetime risk of a shift worker developing cancer. Epidemiological studies suggest that decades of exposure to shiftwork are needed to increase a risk of cancer [27,28], whereas even one nightshift can cause substantial decrements in performance and safety. Shiftwork also increases sleep loss, sleep variability and disruption to sleep structure, as well as disruption to the internal circadian milieu and a multitude of other hormonal, feeding and behavioral patterns, many of which are themselves potential risk factors for cancer. In its latest review, the International Agency for Research on Cancer (IARC) designated ‘nightshift work’ as a probable carcinogen, reflecting this multifaceted risk profile [29]. Future work is needed to quantify the relative risks of shift work to short-term safety versus long-term health, which would enable evaluation of the trade-off between elevated risk of cancer, metabolic and cardiovascular disease associated with night shift work and the necessity of working at night in a particular occupation. Additionally, development and testing of lighting technology and protocols that can sustain alerting effects while minimizing melatonin suppression are also needed.

While this study suggests that light exposure may be a countermeasure for menstrual-phase dependent performance impairment at night, it had several limitations. First, we determined menstrual phase based on self-report measures, but future work is needed using objective as well as more granular assessments of menstrual phase (i.e., early/late follicular, mid/late luteal), which each have different hormonal profiles. In the current study, however, our self-report method had an 80% agreement with menstrual phase classifications based on hormone levels measured in a subset (~55%) of participants. Second, this study was not originally designed to examine differences in neurobehavioral performance between menstrual phases. Future work should implement a larger sample size with adequate statistical power and examine these relationships using a cross-over design that would allow for within-subject analysis of differences in neurobehavioral performance due to menstrual phase. Third, to improve generalizability to a shift working population, it will be important to study these relationships in women across a wider age range and in women using different types of hormonal contraception. Additionally, future studies should also implement a wider range of cognitive tests, in addition to neurobehavioral performance, to determine whether menstrual phase differences extend to other cognitive domains, particularly those sensitive to circadian phase and sleep loss. Furthermore, additional work using different lapse thresholds (e.g., 400ms [30], 3000 ms [8]) and statistical approaches (e.g., reaction time distributions [8], Weibull analysis [31]) may provide a more comprehensive characterization of sustained attention deficits due to menstrual phase.

Given the historical precedent for discrimination against women in the workplace, the emerging evidence that women in the follicular phase are more susceptible to the adverse neurobehavioral performance and safety effects of night shift work may risk further unwarranted discrimination. We should not hide from these findings, however, but should embrace this opportunity to educate and inform both workplace regulators and women on the nature of this hazard and empower them to be able to deploy appropriate countermeasures during times of increased susceptibility to impaired neurobehavioral performance. Light exposure is a necessary aspect of shift work, and when appropriately deployed, is a passive and effective intervention to reduce risk of safety and performance impairment. It also has the advantage of conferring universal benefits to the entire workforce that would avoid the risk of discrimination against women, and specially women in the follicular phase of their menstrual phase.

Table 2.

Results of statistical analyses †

Outcome Main effects Interaction effects
Menstrual phase Follicular vs. Luteal Suppression status < 33% vs. ≥ 33% Time since lights on Menstrual phase * suppression status Menstrual * Suppression * Time
F stat p-value F stat p-value F stat p-value F stat p-value F stat p-value
KSS sleepiness 3.02 .08 0.68 .41 14.97 <.001 0.19 .67 3.78 .002
Reaction time 10.45 .002 12.72 <.001 2.58 .02 5.66 .02 0.79 .57
Attentional lapses 8.16 .005 11.79 <.001 21.83 <.001 3.06 .08 3.60 .002
Core body temp. 14.93 <.001 16.18 <.001 26.94 <.001 2.94 0.09 1.67 .07
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†

KSS = Karolinska Sleepiness Scale; Temp. = temperature.

Acknowledgments.

We thank the technical, dietary and laboratory staff, nurses and physicians, participant recruiters, and the study participants at the Center for Clinical Investigation and Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital; and Ralph Todesco (Brigham and Women’s Hospital), John P. Hanifin, PhD, and Bill Coyle (Thomas Jefferson University), Ron Kovak, and Jon Cooke (Photon Technology Inc., Lawrenceville, NJ) for technical support of the monochromatic light equipment.

Funding.

This work was supported by the National Institute of Neurological Disorders and Stroke (R01 NS36590 to G.C.B.), the National Institute of Mental Health (R01 MH45130-11A1 to C.A.C. and S.W.L.), the National Center for Complementary and Alternative Medicine (R01 AT002129 to C.A.C. and S.W.L.), and the National Institute of Environmental Health Sciences (R21 ES017112-01A1 to S.W.L.). L.K.G. was supported in part by the Mary Ann Tynan Research Fund, Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital; L.K.G., M.S.H., H.J., S.W.L. and S.A.R. were supported in part by the National Heart, Lung and Blood Institute (R01 HL162102-01 to M.S.H.); H.J. was supported in part by the National Institute on Aging (R01 AG053838 to H.J.); G.C.B, C.A.C., and S.W.L. were supported in part by the National Space Biomedical Research Institute through NASA NCC 9–58; G.C.B. was supported, in part, by the Nova Institute. The project was supported by the National Center for Research Resources through grants to Brigham and Women’s Hospital General Clinical Research Center (NCRR M01 RR02635) and the Harvard Clinical and Translational Science Center (NCRR UL1 RR025758).

Disclosures.

Dr. Grant has nothing to disclose; Dr. Gooley has nothing to disclose. Dr. St. Hilaire has nothing to disclose; Dr. Joffe reports grants from National Institutes of Health, grants from Merck, grants from Pfizer, personal fees from Bayer, personal fees from Merck, personal fees from Hello Therapeutics, outside the submitted work; and Spouse conflicts: Employee at Arsenal Biosciences, Equity from Merck; Dr. Brainard reports personal fees from PhotoPharmics Inc, personal fees from Lutron, Inc., personal fees from McCullough Hill LLC, personal fees from The Institution for Functional Medicine, grants and other from Toshiba Materials, grants from Seoul Semiconductor, grants and other from BIOS Inc., grants from Robern, grants from PhotoPharmics Company, other from Nova Institute, other from Philadelphia Chapter of the Illuminating Engineering Society, outside the submitted work; In addition, Dr. Brainard has a patent USPTO 7678140 B2 licensed to Litebook Company Ltd.; Dr. Van Reen reports being a full-time employee and owner of Circadian Positioning Systems, Inc.; Dr. Ruger has nothing to disclose; Dr. Rajaratnam reports grants from Vanda Pharmaceuticals, grants from Philips Respironics, grants from Cephalon, grants from Rio Tinto, grants from BHP Billiton, grants from Shell, other from Optalert, other from Compumedics, other from Teva Pharmaceuticals, other from Circadian Therapeutics, personal fees from National Sleep Foundation Sleep Timing Variability Consensus Panel, outside the submitted work; and has unpaid appointments at CRC for Alertness, Safety and Productivity, Australia and the Sleep Health Foundation; Dr. Lockley reports personal fees from Hintsa Performance AG, personal fees from Rec Room, personal fees from Stantec, personal fees from View Inc, personal fees from Absolute Rest, personal fees from Akili Interactive, personal fees from Apex 2100 Ltd, personal fees from Ashurst Risk Advisory, personal fees from Consumer Sleep Solutions, personal fees from KBR Wyle Services, personal fees from Light Cognitive, personal fees from Lighting Science Group Corporation/HealthE, personal fees from Mental Workout/Timeshifter, personal fees from Bloxhub, personal fees from Clifton College, personal fees from Danish Centre for Lighting, personal fees from University of Toronto, personal fees from Wiley, other from Oxford University Press, other from iSleep pty, grants and other from F. Lux Software LLC, grants from Vanda Pharmaceuticals Inc, non-financial support from Midwest Lighting Institute, outside the submitted work; In addition, Dr. Lockley has a patent US2019366032A1 pending, a patent USD943612S1 pending, and a patent US2021162164A1 pending and he has served as a paid expert in legal proceedings related to light, sleep and health. He is part-time adjunct professor at the University of Surrey, UK. His interests are reviewed and managed by Brigham and Women’s Hospital and Partners HealthCare in accordance with their conflict-of-interest policies; Dr. Czeisler reports personal fees from National Sleep Foundation, during the conduct of the study; grants from Mary Ann & Stanley Snider via Combined Jewish Philanthropies, grants from National Football League Charities, grants from Optum, grants from Philips Respironics Inc, grants from ResMed Foundation, grants from San Francisco Bar Pilots, grants from Sysco Corp, grants from Teva Pharmaceuticals Industries Ltd, grants from Jazz Pharmaceuticals Plc Inc, grants from Regeneron Pharmaceuticals, grants from Sanofi SA, grants from Dayzz Ltd, grants from Teva Pharma Australia PTY Ltd, personal fees from Bose Corporation, personal fees from Boston Red Sox, personal fees from Columbia River Bar Pilots, personal fees from Institute of Digital Media and Child Development, personal fees from Klarman Family Foundation, personal fees from Samsung Electronics, grants, personal fees and other from Vanda Pharmaceuticals Inc, personal fees from Zurich Insurance Company Ltd, personal fees from McGraw Hill, personal fees from Washington State Board of Pilotage Commissioners, personal fees from Ganésco Inc, personal fees from New England Journal of Medicine, personal fees from Teva Pharma Australia, personal fees from AARP, personal fees from American Academy of Dental Sleep Medicine, personal fees from Eisenhower Medical Center, personal fees from M. Davis and Company, personal fees from Physician’s Seal, personal fees from UC San Diego, personal fees from University of Washington, personal fees from Guy A. Ricciardulli, Attorney at Law, personal fees from Kessinger Law Group PLLC, personal fees from Law Offices Of Robert Hamparyan, personal fees from Law Offices of Rossman, Baumberger, Reboso & Spier, P.A., personal fees from Mcelfish Law Firm, personal fees from Millberg Gordon Stewart PLLC, personal fees from Hupy and Abram, SC, personal fees from King & Spalding LLP, personal fees from Law Offices of Power, Rogers & Smith LLP, personal fees from Lewis Brisbois Bisgaard Smith LLP, personal fees from Nurenberg Paris Heller & McCarthy, personal fees from United States Aircraft Insurance Group, personal fees from University of Michigan, personal fees from Zehl and Associates PC, personal fees from Cole, Cole & Easley PC, personal fees from Haglund Kelley LLP, personal fees from Marshall Dennehey Warner Coleman Goggin, personal fees from Maryland Sleep Society, personal fees from Morgan & Meyers PLC, personal fees from National Sleep Foundation, personal fees from Nurenberg Paris Heller & McCarthy, personal fees from Ostroff Injury Law PC, personal fees from Pratt Clay LLC, personal fees from Lyon Gorsky Gilbert Livingston LLP, personal fees from Drake Law Firm, personal fees from Segal Law Firm, personal fees from Clement Law Firm, personal fees from Sleep Research Society, personal fees from Tencent Holdings Ltd, personal fees from Casper Sleep Inc, non-financial support from Boston Celtics, non-financial support from CurtCo Media Labs LLC, other from Schneider Inc, other from Cephalon Inc, grants from NHLBI, grants from NIA, grants from NIOSH, grants from DOD, other from Whoop, Inc., grants from US Centers for Disease Control and Prevention, other from Delta Airlines, grants from Axome Therapeutics, Inc., grants from Puget Sound Pilots, personal fees and other from With Deep, Inc., personal fees and other from Signos, Inc., personal fees from Bryte Foundation, personal fees from Simpson & Simpson, personal fees and other from Associated Professional Sleep Societies, personal fees from Massachusetts Medical Society, personal fees from University of Colorado, personal fees from Atty Yolanda Huang and Kaitlyn Murphy. Esq.Ýeputy City Attorney, City of San Francisco, personal fees from Law Office of Daniel D. Horowitz III, P.C., personal fees from Paul, Weiss, Rifkind, Wharton & Garrison LLP, personal fees from The Armstrong Firm, PLLC and Rabb and Rabb PLLC, personal fees from Shaked Law Firm, P.A., personal fees from Law Offices of James L Mitchell, other from Stanley Ho Medical Development Foundation, other from UK Biotechnology and Biological Services Research Council, other from Journal of Biological Rhythms, grants from Johnson & Johnson, grants from Alexandra Drane, grants from DR Capital, grants from Harmony Biosciences LLC, grants from Eisai Co., LTD, grants from Idorsia Pharmaceuticals LTD, grants from Sleep Number Corp., grants from Apnimed, Inc., grants from Avadel Pharmaceuticals, grants from Bryte Foundation, grants from f.lux Software, LLC, grants from Stuart F. and Diana L. Quan Charitable Fund, grants from Casey Feldman Foundation, grants from Roman Catholic Archdiocese of Boston, grants from Summus, Inc., grants from Takeda Pharmaceutical Co., LTD, grants from Abbaszadeh Foundation, grants from Sharon and John Loeb, grants from CDC Foundation, grants from Centers for Disease Control and Prevention, grants and other from ResMed, Inc., outside the submitted work; In addition, Dr. Czeisler has a patent Actiwatch-2 and Actiwatch-Spectrum devices with royalties paid to Philips Respironics Inc., a patent Assessment and Modification of a Subject’s Endogenous Circadian Cycle. issued, a patent Test for Evaluation of Visual Functioning in Visually Impaired Subjects. issued, a patent Assessment and Modification of a Subject’s Endogenous Circadian Cycle. issued, a patent Assessment and Modification of Endogenous Circadian Phase and Amplitude. issued, a patent Assessment and Modification of Circadian Phase and Amplitude. issued, a patent Assessment and Modification of a Subject’s Endogenous Circadian Cycle issued, a patent Assessment and Modification of a Human Subject’s Circadian Cycle. issued, a patent Apparatus for Producing and Delivering High-Intensity Light to a Subject. issued, a patent Intermittent Use of Bright Light to Modify the Circadian Phase. issued, a patent Method of Facilitating the Physiological Adaption to an Activity/Rest Schedule and Apparatus for Prescribing a Substantially Optimum Stimulus Regimen of Pulses of Bright Light to Allow a Subject’s Circadian Cycle to be Modified to a Desired State. issued, a patent Method and Device for Modifying the Circadian Cycle in Humans. issued, a patent Assessment and Modification of a Subject’s Endogenous Circadian Cycle. issued, a patent Modification of Endogenous Circadian Pacemaker. issued, a patent Test for evaluation of visual functioning in visually impaired subjects issued, a patent Method for modifying or resetting the circadian cycle using short wavelength light issued, and a patent High sensitivity of the human circadian pacemaker to resetting by short wavelength light. issued and Dr. Czeisler has served as an expert witness on a number of civil matters, criminal matters, and arbitration cases, including those involving the following commercial and government entities: Advanced Power Technologies; Alvarado Hospital, LLC; Amtrak; Bombardier, Inc.; C&J Energy Services; Casper Sleep, Inc.; Columbia River Bar Pilots; Complete General Construction Company; Dallas Police Department; Delta Airlines/Comair; Fédération des Médecins Résidents du Québec (FMRQ); FedEx; Greyhound Lines, Inc./Motor Coach Industries/FirstGroup America; H.G. Energy LLC; Maricopa County, Arizona, Sheriff’s Office; Murrieta Valley Unified School District; Pomerado Hospital, Palomar Health District; Puckett EMS; Purdue Pharma; South Carolina Central Railroad Company, LLC.; Steel Warehouse, Inc.; Union Pacific Railroad; United Parcel Service. Dr. Czeisler’s interests were reviewed and managed by Brigham and Women’s Hospital and Partners HealthCare in accordance with their conflict of interest policies; Dr. Rahman reports other from Melcort Inc., personal fees from Sultan & Knight Limited, personal fees from Bambu Vault LLC, personal fees from Lucidity Lighting Inc., personal fees from Starry Skies Lake Superior, personal fees from University of Minnesota Medical School, personal fees from PennWell Corp., personal fees from Seoul Semiconductor Co. Ltd., personal fees from FALK FOUNDATION E.V., grants from Seoul Semiconductor Co. Ltd., grants from Biological Innovation and Optimization Systems, LLC, grants from Merck & Co., Inc., grants from Pfizer Inc., grants from Vanda Pharmaceuticals Inc., grants from Lighting Science Group, grants from National Institutes of Health, grants from National Aeronautics and Space Administration, outside the submitted work; In addition, Dr. Rahman has a patent U.S. patent application Ser. No. 10/525,958 issued, and a patent U.S. Application No. 61/810,985 issued and These interests were reviewed and managed by Brigham and Women’s Hospital and MassGeneralBrigham in accordance with their conflict of interest policies.

Footnotes

CRediT author statement. LKG: Formal analysis, Data curation, Visualization, Writing original draft; JJG: Conceptualization, Investigation, Writing review and editing; MSH: Data curation, Writing review and editing; HJ: Writing review and editing; GCB: Conceptualization, Funding acquisition, Methodology, Resources, Writing review and editing; EVR: Investigation, Writing review and editing; MR: Investigation, Writing review and editing; SMWR: Investigation, Writing review and editing; SWL: Conceptualization, Funding acquisition, Methodology, Investigation, Supervision, Project administration, Writing review and editing; CAC: Conceptualization, Funding acquisition, Methodology, Supervision, Writing original draft; SAR: Formal analysis, Visualization, Writing review and editing

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