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Circadian phase asessment by ambulatory monitoring in humans: Correlation with dim light melatonin onset
Abstract
The increased prevalence of circadian disruptions due to abnormal coupling between internal and external time makes the detection of circadian phase in humans by ambulatory recordings a compelling need. Here, we propose an accurate practical procedure to estimate circadian phase with the least possible burden for the subject, that is, without the restraints of a constant routine protocol or laboratory techniques such as melatonin quantification, both of which are standard procedures. In this validation study, subjects (N = 13) wore ambulatory monitoring devices, kept daily sleep diaries and went about their daily routine for 10 days. The devices measured skin temperature at wrist level (WT), motor activity and body position on the arm, and light exposure by means of a sensor placed on the chest. Dim light melatonin onset (DLMO) was used to compare and evaluate the accuracy of the ambulatory variables in assessing circadian phase. An evening increase in WT: WTOnset (WTOn) and "WT increase onset" (WTiO) was found to anticipate the evening increase in melatonin, while decreases in motor activity (Activity Offset or AcOff), body position (Position Offset (POff)), integrative TAP (a combination of WT, activity and body position) (TAPOffset or TAPOff) and an increase in declared sleep propensity were phase delayed with respect to DLMO. The phase markers obtained from subjective sleep (R = 0.811), WT (R = 0.756) and the composite variable TAP (R = 0.720) were highly and significantly correlated with DLMO. The findings strongly support a new method to calculate circadian phase based on WT (WTiO) that accurately predicts and shows a temporal association with DLMO. WTiO is especially recommended due to its simplicity and applicability to clinical use under conditions where knowing endogenous circadian phase is important, such as in cancer chronotherapy and light therapy.
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“Our results indicate that the temperature traces in the UKBB study capture biological signal compellingly and agree with field studies13,23,32.”
From Diurnal rhythms of wrist temperature are associated with future disease risk in the UK Biobank (2023) · cites this paper as [13]
In the citing paper
“and are therefore suitable to estimate circadian entrainment, comparable to melatonin or core body temperature, as marker rhythms12,13.”
From Diurnal rhythms of wrist temperature are associated with future disease risk in the UK Biobank (2023) · cites this paper as [13]
In the citing paper
“To underscore the value of wrist temperature as a potential biomarker, we refer to a study in 13 healthy volunteers showing that phase determined by wrist temperature readings correlated strongly (R = 0.756) with the circadian phase assessed by dim light melatonin onset (DLMO), which is the gold standard in the field13.”
From Diurnal rhythms of wrist temperature are associated with future disease risk in the UK Biobank (2023) · cites this paper as [13]
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“Wrist temperature (WT), one of the components of the TAP variable, is a marker of peripheral vasodilation mediated by the sympathetic/parasympathetic balance (Rubinstein and Sessler, 1990; Charkoudian, 2003; Sarabia et al., 2008), with a stable phase relationship with DLMO (Bonmati-Carrion et al., 2014b) and core body…”
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“…(DST) has recently been proposed as a noninvasive, robust, comfortable, and easy-to-register tool for CS assessment (Blazquez et al. 2012; Bonmati-Carrion et al. 2014; Kräuchi 2002; Kräuchi et al. 2005; Martinez-Nicolas et al. 2013, 2014; Romejin and Van Someren 2011; Zornoza-Moreno et…”
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“It has been previously demonstrated that WT phase indexes are capable of accurately detecting the phase of the circadian system in subjects recorded under normal living conditions as compared to DLMO (Bonmati-Carrion et al., 2014).”
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Physical activity, and not fat mass is a primary predictor of circadian parameters in young men
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“Decreases in activity, changes in body position and increases in declared sleep propensity were delayed with respect to increases in dim light melatonin (Bonmati-Carrion et al., 2014; Corbalán-Tutau et al., 2011; Gompper et al., 2010; Kripke et al., 2005; Morgan et al., 1998; Nováková et al., 2013; Sarabia et al., 200…”
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“…and position provides a reliable evaluation of circadian system status, since it includes a variable with an endogenous component (skin temperature) but also variables reactive to behavioral demands (motor activity and body position) (Ortiz-Tudela et al., 2010, 2014; Bonmati-Carrion et al., 2014b).”
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“DST measurement has shown validity in detecting the sleep–wake [12] cycle, ability to discern among the three circadian typologies [13] and its stable phase relationship with melatonin secretion pattern [14].”
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“A study in which suspected SAD was confirmed by a specialist and circadian functions was measured using a range of sophisticated techniques and indicators (e.g. actigraphy, dim light melatonin onset and/or morning cortisol levels; Bonmati-Carrion et al. 2014) would consolidate the presented results and verify whether…”
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“…as sleep fragmentation or short sleep duration, apart from contributing to excessive daytime sleepiness, affect the amplitude of other rhythms (Martinez-Nicolas et al., 2011) and alter the balance between homeostatic and circadian processes involved in sleep–wake regulation (Borbély et al., 2016).”
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“76).(68) Wrist skin temperature will be measured on the inside of the wrist, near the radial artery of the non-”
BackgroundBonmatí‐Carrión, M., Middleton, B., Revell, V. L., Skene, D. J., Rol, M. A., & Madrid, J. A. (2015) · Chronobiology International · doi:10.3109/07420528.2015.1016613 · Cited by 18
“Alternative methods based on simple changes in tilt position have been previously explored (Bonmati-Carrion et al., 2013; Ortiz-Tudela et al., 2010) but they have not yet been validated for chronobiological assessment by comparing them with another wellestablished actigraphy method.”
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“Studies using MCA devices have reported that the evening increase in WT shows a high correlation with dim light melatonin onset, preceding the rise in melatonin (Bonmati-Carrion et al., 2014).”
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Bonmatí‐Carrión, M., Santhi, N., Atzori, G., Mendis, J. R., Kaduk, S. I., Dijk, D., & Archer, S. N. (2024) · npj Microgravity · doi:10.1038/s41526-024-00387-3 · Cited by 15
“Besides,theaveragetimingofourMOn(21:16to22:12)iswithin the normal range of previously obtained DLMO timings 52 – 54 .”
InfluentialIntegrating wearable data into circadian models
Hannay, K. M., & Moreno, J. P. (2020) · Current Opinion in Systems Biology · doi:10.1016/j.coisb.2020.08.001 · Cited by 13
Would you allow a sleepy surgeon operate on you? A narrative review.
Whelehan, D. F., Alexander, M., & Ridgway, P. (2020) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2020.101341 · Cited by 11
Castaldo, R., Chappell, M. J., Byrne, H. M., Innominato, P. F., Hughes, S., Pescapè, A., & Pecchia, L. (2020) · Biomedical Signal Processing and Control · doi:10.1016/j.bspc.2020.102386 · Cited by 13
“These results confirmed that activity level shows a robust circadian pattern [30], reinforcing the idea that motor activity is generally high during the day and decreases during the evening [28 – 30], when a rise of melatonin levels is expected.”
BackgroundChronodisruption and Ambulatory Circadian Monitoring in Cancer Patients: Beyond the Body Clock
Pagán, P., Torrente, M., Campos, M., Provencio, M., Madrid, J. A., Franco, F., Morilla, B. R., Cantos, B., Sousa, P., Martínez-Madrid, M. J., et al. (2022) · Current Oncology Reports · doi:10.1007/s11912-021-01158-z · Cited by 15
Self-citationAcosta, F. M., Martínez‐Téllez, B., Blondin, D. P., Haman, F., Rensen, P. C. N., Elvira, J. M. L., Martínez-Nicolás, A., & Ruiz, J. R. (2019) · Journal of Biological Rhythms · doi:10.1177/0748730419865400 · Cited by 13
“This is supported by the fact (among others) that an increase in DST coincides with the onset of the release of dim-light melatonin (Bonmati-Carrion et al., 2014) and that it may lead to vasodilation (inducing heat loss) and an eventual fall in core body temperature that helps initiate sleep (Kräuchi and Wirz-Justice,…”
BackgroundMammalian NREM and REM sleep: Why, when and how
Rial, R. V., Akaârir, M., Cañellas, F., Barceló, P., Díaz, J. Á. R., Martin-Reina, A., Gamundí, A., & Nicolau, M. C. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105041 · Cited by 12
Zerón-Rugerio, M. F., Zaragozá, M. C., Domingo, J. C., Sentañes, R. S., Alegre, J., Castro‐Marrero, J., & Cambras, T. (2024) · Chronobiology International · doi:10.1080/07420528.2024.2380020 · Cited by 11
Saeki, K., Obayashi, K., Nishi, T., Miyata, K., Maruoka, S., Ueda, T., Okamoto, M., Hasegawa, T., Matsuura, T., Tone, N., et al. (2014) · Trials · doi:10.1186/1745-6215-15-514 · Cited by 10
Circadian rhythms measured by actigraphy during oncological treatments: a systematic review
Huang, C., Madsen, M. T., & Gögenür, I. (2015) · Biological Rhythm Research · doi:10.1080/09291016.2015.1004840 · Cited by 10
“Preliminary studies applying integrated circadian variable derived from both skin temperature and activity showed promising results (Ortiz-Tudela et al. 2010; Bonmati-Carrion et al. 2014), but for now, the actigraphy remains the most suitable and proven method for larger clinical populations.”
MethodAdamsson, M., Laike, T., & Morita, T. (2018) · LEUKOS The Journal of the Illuminating Engineering Society of North America · doi:10.1080/15502724.2017.1391101 · Cited by 11
“…for explaining the non-image-forming effects of light radiation as well as for generating new research questions that can be further studied in controlled laboratory experiments (Bonmati-Carrion et al. 2014; Figueiro and Rea 2016; Kolodyazhniy et al. 2012; Lucas et al. 2014; Miller et al. 2010).”
BackgroundLiving at the Wrong Time: Effects of Unmatching Official Time in Portugal and Western Spain
Bonmatí‐Carrión, M., Casado‐Ramírez, E., Moreno‐Casbas, T., Campos, M., Madrid, J. A., & Rol, M. A. (2022) · Biology · doi:10.3390/biology11081130 · Cited by 9
Self-citationArgüelles-Prieto, R., Madrid, J. A., Rol, M. A., & Bonmatí‐Carrión, M. (2022) · Biology · doi:10.3390/biology11111584 · Cited by 6
Self-citationAdán, A., Navarro, J. F., & on behalf of ADDISCHRONO Group (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11071846 · Cited by 7
Circadian Phase Prediction From Non-Intrusive and Ambulatory Physiological Data
Suarez, A., Núñez, F., & Rodriguez-Fernández, M. (2020) · IEEE Journal of Biomedical and Health Informatics · doi:10.1109/jbhi.2020.3019789 · Cited by 8
“position, known as TAP [24], but all these models were linear regressions and not multivariate regression models similar to in the present work.”
BackgroundMethodResultInfluentialWhat Wrist Temperature Tells Us When We Sleep Late: A New Perspective of Sleep Health
Wei, J., Zhang, J., & Boger, J. N. (2018) · IEEE SmartWorld, Ubiquitous Intelligence & Computing, Advanced & Trusted Computing, Scalable Computing & Communications, Cloud & Big Data Computing, Internet of People and Smart City Innovation (SmartWorld/SCALCOM/UIC/ATC/CBDCom/IOP/SCI) · doi:10.1109/smartworld.2018.00145 · Cited by 5
“standard phase marker CBT and DLMO [15], [16].”
BackgroundMethodInfluentialCircadian Timing: From Genetics to Behavior
Agostino, P. V., Bussi, I. L., & Caldart, C. S. (2018) · BRILL eBooks · doi:10.1163/9789004280205_002 · Cited by 6
Llenas, A., Hurlbert, A. C., Lam, F., Manudhane, R., Gupta, G., Giddings, J., & Carreras, J. (2019) · Quadrennial Session of the International Commission on Illumination (CIE Session) · doi:10.25039/x46.2019.pp29 · Cited by 5
The Light–Eye–Brain Axis: Neurobiological Links Between Mood Disorders and Myopia—A Narrative Review
Li, C.-Y., Song, Q.-Q., Xu, W., Li, X.-Y., Huang, Y., Wang, N.-L., & Li, S. (2026) · Ophthalmology and Therapy · doi:10.1007/s40123-026-01315-2 · Cited by 6
Haghayegh, S., Parker, R. A., Montano, M. A., Katz, I. T., Hu, K., & Li, P. (2025) · SLEEP Advances · doi:10.1093/sleepadvances/zpaf055 · Cited by 4
“Previous research has shown moderate corr elations between rest-activity phase measures and endogenous circadian phase markers, such as DLMO [13], supporting the use of actigraphy-derived measures as practical proxies for circadian timing in large epidemiological studies where direct measurement of…”
Towards Classifying Human Circadian Rhythm Using Multiple Modalities
Riani, K., Sharak, S., Das, K., Abouelenien, M., Burzo, M. G., Mihalcea, R. F., Elson, J., Maranville, C. W., Prakah-Asante, K. O., & Manzoor, W. A. (2021) · International Conference on Affective Computing and Intelligent Interaction and workshops · doi:10.1109/acii52823.2021.9597391 · Cited by 4
A non-parametric model: free analysis of actigraphic recordings of acute insomnia patients
Marín-García, A., Fossión, R., Müller, M., Ríos-Herrera, W. A., & Rivera, A. L. (2022) · Royal Society Open Science · doi:10.1098/rsos.210463 · Cited by 4
“Other components also present a significant phase differences; however, correct interpretation of these differences should be accompanied by the simultaneous study of several biological markers such as blood pressure, heart rate, skin temperature among others, in order to provide a clear association between physiologi…”
Martínez‐Cayuelas, E., Merino-Andreu, M., Pozo, R. L.-D., Gavela‐Pérez, T., Garcés, C., & Soriano‐Guillén, L. (2023) · Journal of Child Neurology · doi:10.1177/08830738231173606 · Cited by 4
The Pineal Gland and Melatonin
Klein, D. C. (2015) · Elsevier eBooks · doi:10.1016/b978-0-323-18907-1.00019-6 · Cited by 4
Sensor-Based Estimation of Dim Light Melatonin Onset Using Features of Two Time Scales
Wan, C., McHill, A. W., Klerman, E. B., & Sano, A. (2021) · ACM Transactions on Computing for Healthcare · doi:10.1145/3447516 · Cited by 6
Actigraphic and melatonin alignment in older adults with varying dementia risk
Schrire, Z. M., Gordon, C. J., Palmer, J. R., Murray, J. M., Hickie, I. B., Rogers, N. L., Lewis, S. J. G., Terpening, Z., Pye, J., Naismith, S. L., et al. (2022) · Chronobiology International · doi:10.1080/07420528.2022.2144744 · Cited by 4
Delayed sleep phase disorder during the COVID-19 pandemic and its health implications
Jiménez‐Correa, U., Bonilla, N., Álvarez-García, H. B., Alonzo, G. M., Barrera-Medina, A., Santana-Miranda, R., Poblano, A., & Agudelo, H. A. M. (2023) · CNS Spectrums · doi:10.1017/s109285292300007x · Cited by 4
Integral Analysis of Circadian Rhythms
Vicente-Martínez, J., González-Romero, P., Pagán, P., Martínez-Nicolás, A., Madrid, J. A., Rol, M. A., & Bonmatí‐Carrión, M. (2023) · Springer eBooks · doi:10.1007/978-3-031-32729-2_9 · Cited by 3
Self-citationAssessment of time window for sleep onset on the basis of continuous wrist temperature measurement
Partonen, T., Haukka, J. K., Kuula, L., & Pesonen, A. (2020) · Biological Rhythm Research · doi:10.1080/09291016.2020.1802160 · Cited by 4
Fast tuning of observer-based circadian phase estimator using biometric data
Ike, C. O., Wen, J. T.-Y., Oishi, M., Brown, L. K., & Julius, A. A. (2022) · Heliyon · doi:10.1016/j.heliyon.2022.e12500 · Cited by 3
“With the aim of eliminating the pitfalls of melatonin assessment and similarly invasive genetic assay techniques, recent research has focused on the use of easily accessible biometric data, most prominently activity levels, heart rate, skin temperature, and light exposure [11, 12, 13].”
MethodCompensating for Sensor Error in the Model Predictive Control of Circadian Clock Phase
Brown, L. S., Klerman, E. B., & Doyle, F. J. (2019) · IEEE Control Systems Letters · doi:10.1109/lcsys.2019.2919438 · Cited by 3
“1 h [13], [14], [15], [16].”
Colitta, A., & Faraguna, U. (2025) · Journal of Pineal Research · doi:10.1111/jpi.70085 · Cited by 2
“More complex mathematical methods to predict DLMO which require combinations of the afore-mentioned tools have been proposed, reaching moderate ‐ to ‐ high accuracy [8, 10, 11], albeit remaining unemployed in most clinical settings.”
InfluentialBorges, M. A., Alves, D. A. G., & Guimarães, L. H. D. C. T. (2021) · Revista Neurociências · doi:10.34024/rnc.2021.v29.12290 · Cited by 9
Non-Contact Based Modeling of Enervation
Riani, K., Sharak, S., Abouelenien, M., Burzo, M. G., Mihalcea, R. F., Elson, J., Maranville, C. W., Prakah-Asante, K. O., & Manzoor, W. A. (2023) · International Conference on Automatic Face and Gesture Recognition · doi:10.1109/fg57933.2023.10042529 · Cited by 2
“Existing work in this area mainly focused on contact-based physiological data analysis [6], [23].”
BackgroundMartínez-Alarcón, L., Martínez-Nicolás, A., Jover-Aguilar, M., López‐López, V., Alconchel, F., Ríos, A., Madrid, J. A., Rol, M. A., Ramírez, P., & Ramis, G. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13154529 · Cited by 2
“This statement is based on its strong endogenous component [19–24], ease of monitoring [25–28], ability to assess the circadian phase [20,23], and validation against polysomnography [15,29].”
BackgroundSelf-citationPhysiologic Methods of Assessment Relevant to Circadian Rhythm Sleep-Wake Disorders
LaBarbera, V. A., & Sharkey, K. M. (2020) · Springer eBooks · doi:10.1007/978-3-030-43803-6_4 · Cited by 2
Wei, J., & Boger, J. N. (2019) · doi:10.4108/eai.20-5-2019.2282879 · Cited by 2
Evaluating the Accuracy of Declared Eating Schedules by Continuous Glucose Monitoring
González-Romero, P., Madrid, J. A., Pagán, P., & Rol, M. A. (2026) · Nutrients · doi:10.3390/nu18050772 · Cited by 1
Self-citationMarchesano, M., Silva, A. C., & Tassino, B. (2026) · Journal of Biological Rhythms · doi:10.1177/07487304261428332 · Cited by 1
“As validated elsewhere, acrophase, L5c, and M10c were considered as proxies of the circadian phase (Bonmati-Carrion et al., 2014; Mitchell et al., 2017; Ruiz et al., 2020).”
La hora de nuestro cuerpo. Monitorización Ambulatoria Circadiana
Martínez-Nicolás, A., & Manzanera, A. L. B. (2015) · Digitum: Institutional Repository of the University of Murcia (University of Murcia) · Cited by 1
Metadata
- Authors
- Bonmati-Carrion, M. A., Middleton, B., Revell, V., Skene, D. J., Rol, M. A., & Madrid, J. A.
- Affiliations
- University of Surrey (GB)
- Universidad de Murcia (ES)
- Corresponding author
- Rol, M. A.
- Venue
- Chronobiology International
- Publisher
- Informa UK Limited
- Published
- 2013-10-28
- Volume
- 31
- Issue
- 1
- Pages
- 37-51
- ISSN
- 0742-0528 (ISSN-L)
- 1525-6073
- OpenAlex
- W2082096003
- Cited by
- 116
- References
- 76
- Citations by year
- 2026: 11 · 2025: 6 · 2024: 5 · 2023: 11 · 2022: 10 · 2021: 9 · 2020: 11 · 2019: 11 · 2018: 11 · 2017: 7 · 2016: 6 · 2015: 10 · 2014: 6 · 2013: 2
- FWCI
- 4.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Chronobiology International (publishedVersion)
- PubMed (publishedVersion)
- Hispana (publishedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Keywords
- circadian phase, dim light melatonin onset, ambulatory monitoring, motor activity, posture, sleep propensity, circadian misalignment, cancer chronotherapy, phototherapy, sleep diary
- MeSH terms
- Adult, Body Temperature, Circadian Rhythm, Female, Humans, Light, Male, Melatonin, Surveys and Questionnaires, Radioimmunoassay, Saliva, Sleep, Monitoring, Ambulatory, Young Adult, Actigraphy
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