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Dr Victoria Revell

Lecturer in Translational Sleep and Circadian Physiology
+44 (0)1483 689383
03 MA 00

My publications


Bonmati-Carrion MA, Hild K, Isherwood C, Sweeney SJ, Revell VL, Skene DJ, Rol MA, Madrid JA (2016) Relationship between Human Pupillary Light Reflex and Circadian System Status, PLoS One 11 (9) e0162476 Public Library of Science (PLoS)
Intrinsically photosensitive retinal ganglion cells (ipRGCs), whose photopigment melanopsin
has a peak of sensitivity in the short wavelength range of the spectrum, constitute a common
light input pathway to the olivary pretectal nucleus (OPN), the pupillary light reflex
(PLR) regulatory centre, and to the suprachiasmatic nuclei (SCN), the major pacemaker of
the circadian system. Thus, evaluating PLR under short wavelength light (»max 500 nm)
and creating an integrated PLR parameter, as a possible tool to indirectly assess the status
of the circadian system, becomes of interest. Nine monochromatic, photon-matched light
stimuli (300 s), in 10 nm increments from »max 420 to 500 nm were administered to 15
healthy young participants (8 females), analyzing: i) the PLR; ii) wrist temperature (WT) and
motor activity rhythms (WA), iii) light exposure (L) pattern and iv) diurnal preference (Horne-
Östberg), sleep quality (Pittsburgh) and daytime sleepiness (Epworth). Linear correlations
between the different PLR parameters and circadian status index obtained from WT, WA
and L recordings and scores from questionnaires were calculated. In summary, we found
markers of robust circadian rhythms, namely high stability, reduced fragmentation, high
amplitude, phase advance and low internal desynchronization, were correlated with a
reduced PLR to 460?490 nm wavelengths. Integrated circadian (CSI) and PLR (cp-PLR)
parameters are proposed, that also showed an inverse correlation. These results demonstrate,
for the first time, the existence of a close relationship between the circadian system
robustness and the pupillary reflex response, two non-visual functions primarily under melanopsin-ipRGC
Revell VL, Skene DJ (2007) Light-induced melatonin suppression in humans with polychromatic and monochromatic light, CHRONOBIOLOGY INTERNATIONAL 24 (6) pp. 1125-1137 TAYLOR & FRANCIS INC
Revell VL (2005) How to trick Mother Nature into letting you fly around and stay out all night, Journal of Biological Rhythms 20 (4) pp. 353-365
Benloucif S, Burgess HJ, Klerman EB, Lewy AJ, Middleton B, Murphy PJ, Parry BL, Revell VL (2008) Measuring melatonin in humans, Journal of Clinical Sleep Medicine 4 (1) pp. 66-69
Revell VL, Skene DJ (2010) Impact of age on human non-visual responses to light, SLEEP AND BIOLOGICAL RHYTHMS 8 (2) pp. 84-94 WILEY-BLACKWELL
Pagani L, Semenova EA, Moriggi E, Revell VL, Hack LM, Lockley SW, Arendt J, Skene DJ, Meier F, Izakovic J (2010) The physiological period length of the human circadian clock in vivo is directly proportional to period in human fibroblasts., PLoS One 5 (10) Public Library of Science
Diurnal behavior in humans is governed by the period length of a circadian clock in the suprachiasmatic nuclei of the brain hypothalamus. Nevertheless, the cell-intrinsic mechanism of this clock is present in most cells of the body. We have shown previously that for individuals of extreme chronotype ("larks" and "owls"), clock properties measured in human fibroblasts correlated with extreme diurnal behavior.
Sletten TL, Revell VL, Middleton B, Lederle KA, Skene DJ (2009) Age-Related Changes in Acute and Phase-Advancing Responses to Monochromatic Light, JOURNAL OF BIOLOGICAL RHYTHMS 24 (1) pp. 73-84 SAGE PUBLICATIONS INC
Burgess HJ, Revell VL, Molina TA, Eastman CI (2010) Human Phase Response Curves to Three Days of Daily Melatonin: 0.5 mg Versus 3.0 mg, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 95 (7) pp. 3325-3331 ENDOCRINE SOC
Ackermann K, Sletten TL, Revell VL, Archer SN, Skene DJ (2009) Blue-Light Phase Shifts PER3 Gene Expression in Human Leukocytes, CHRONOBIOLOGY INTERNATIONAL 26 (4) PII 911212256 pp. 769-779 TAYLOR & FRANCIS INC
Revell VL, Arendt J, Terman M, Skene DJ (2005) Short-wavelength sensitivity of the human circadian system to phase-advancing light, JOURNAL OF BIOLOGICAL RHYTHMS 20 (3) pp. 270-272 SAGE PUBLICATIONS LTD
Revell VL, Kim H, Tseng CY, Crowley SJ (2005) Circadian phase determined from melatonin profiles is reproducible after one week in subjects who sleep later on weekends, Journal of Pineal Research 39
Burgess HJ, Revell VL, Eastman CI (2008) A three pulse phase response curve to three milligrams of melatonin in humans, JOURNAL OF PHYSIOLOGY-LONDON 586 (2) pp. 639-647 BLACKWELL PUBLISHING
Revell VL, Arendt J, Louis FF, Skene DJ (2006) Alerting effects of light are sensitive to very short wavelengths, NEUROSCIENCE LETTERS 399 (1-2) pp. 96-100 ELSEVIER IRELAND LTD
Ackermann K, Revell VL, Lao O, Rombouts EJ, Skene DJ (2012) Diurnal rhythms in blood cell populations and the effect of acute sleep deprivation in healthy young men, Sleep 35 (7)
Sletten TL, Revell VL, Middleton B, Lederle KA, Skene DJ (2008) Short wavelength light exposure in the elderly: acute and phase shifting effects, JOURNAL OF SLEEP RESEARCH 17 pp. 79-79 WILEY-BLACKWELL PUBLISHING, INC
Al Enezi J, Revell VL, Brown T, Wynne J, Schlangen LJM, Lucas R (2011) A 'melanopic' spectral efficiency function predicts the sensitivitiy of melanopsin photoreceptors to diverse polychromatic lights, Journal of Biological Rhythms 26 pp. 314-323
Revell VL, Burgess HJ, Gazda CJ, Smith MR, Fogg LF, Eastman CI (2006) Advancing human circadian rhythms with afternoon melatonin and monring intermittent bright light, Journal of Clinical Endocrinology and Metabolism 91 (1) pp. 54-59
Papamichael C, Skene DJ, Revell VL (2012) Human non-visual responses to simultaneous presentation of blue and red monochromatic light., Journal of Biological Rhythms 27 (1) pp. 70-78 Sage
Blue light sensitivity of melatonin suppression and subjective mood and alertness responses in
humans is recognised as being melanopsin based. Observations that long wavelength (red) light
can potentiate responses to subsequent short wavelength (blue) light have been attributed to the
bistable nature of melanopsin whereby it forms stable associations with both 11-cis and alltrans
isoforms of retinaldehyde and uses light to transition between these states. The current
study examined the effect of concurrent administration of blue and red monochromatic light, as
would occur in real-world white light, on acute melatonin suppression and subjective mood and
alertness responses in humans. Young healthy males (18-35 years; n = 21) were studied in
highly controlled laboratory sessions that included an individually timed 30 min light stimulus
of blue (»max 479 nm) or red (»max 627 nm) monochromatic light at varying intensities (1013 -
1014 photons/cm2/s) presented, either alone or in combination, in a within-subject randomised
design. Plasma melatonin levels and subjective mood and alertness were assessed at regular
intervals relative to the light stimulus. Subjective alertness levels were elevated after light onset
irrespective of light wavelength or irradiance. For melatonin suppression, a significant
irradiance response was observed with blue light. Co-administration of red light, at any of the
irradiances tested, did not significantly alter the response to blue light alone. Under the current
experimental conditions the primary determinant of the melatonin suppression response was
the irradiance of blue 479 nm light and this was unaffected by simultaneous red light
Lederle KA, Middleton B, Sletten TL, Revell VL, Skene DJ (2008) Subjective and actigraphic sleep in older people with control and 'blue-enriched' white light, JOURNAL OF SLEEP RESEARCH 17 pp. 120-120 WILEY-BLACKWELL PUBLISHING, INC
Smith MR, Revell VL, Eastman CI (2009) Phase advancing the human circadian clock with blue-enriched polychromatic light, SLEEP MEDICINE 10 (3) pp. 287-294 ELSEVIER SCIENCE BV
Revell VL, Skene DJ (2008) Authors' response, Chronobiology International 25 (4) pp. 655-656
Lall GS, Revell VL, Momiji H, El Enazi J, Altimus CM, Guler AD, Aguilar C, Cameron MA, Allender S, Hankins MW, Lucas RJ (2010) Distinct contributions of rod, cone and melanopsin photoreceptors to encoding irradiance, Neuron 66 pp. 417-428
Ang JE, Pal A, Asad YJ, Henley AT, Valenti M, Box G, de haven Brandon A, Revell Victoria, Skene Debra, Venturi M, Rueger R, Meresse V, Eccles SA, de Bono JS, Kaye SB, Workman P, Banerji U, Raynaud FI (2017) Modulation of plasma metabolite biomarkers of MAPK pathway with the MEK
inhibitor RO4987655: pharmacodynamic and predictive potential in metastatic
Molecular Cancer Therapeutics American Association for Cancer Research
MAPK pathway activation is frequently observed in human malignancies, including
melanoma, and is associated with sensitivity to MEK inhibition and changes in cellular
metabolism. Using quantitative mass spectrometry-based metabolomics, we identified in
preclinical models 21 plasma metabolites including amino acids, propionylcarnitine,
phosphatidylcholines and sphingomyelins that were significantly altered in two B-RAF
mutant melanoma xenografts and that were reversed following a single dose of the potent
and selective MEK inhibitor RO4987655. Treatment of non-tumour bearing animals and mice
bearing the PTEN null U87MG human glioblastoma xenograft elicited plasma changes only
in amino acids and propionylcarnitine. In patients with advanced melanoma treated with
RO4987655, on-treatment changes of amino acids were observed in patients with disease
progression and not in responders. In contrast, changes in phosphatidylcholines and
sphingomyelins were observed in responders. Furthermore, pre-treatment levels of 7 lipids
identified in the preclinical screen were statistically significantly able to predict objective
responses to RO4987655. The RO4987655 treatment-related changes were greater than
baseline physiological variability in non-treated individuals. This study provides evidence of a
translational exo-metabolomic plasma readout predictive of clinical efficacy together with
pharmacodynamic utility following treatment with a signal transduction inhibitor.
Gunn P, Middleton BA, Davies S, Revell VL, Skene DJ (2016) Sex differences in the circadian profiles of melatonin and cortisol in plasma and urine matrices under constant routine conditions, CHRONOBIOLOGY INTERNATIONAL 33 (1) pp. 39-50 TAYLOR & FRANCIS INC
Conflicting evidence exists as to whether there are differences between males and females in circadian timing. The aim of the current study was to assess whether sex differences are present in the circadian regulation of melatonin and cortisol in plasma and urine matrices during a constant routine protocol. Thirty-two healthy individuals (16 females taking the oral contraceptive pill (OCP)), aged 23.8 ± 3.7 (mean ± SD) years, participated. Blood (hourly) and urine (4-hourly) samples were collected for measurement of plasma melatonin and cortisol, and urinary 6-sulfatoxymelatonin (aMT6s) and cortisol, respectively. Data from 28 individuals (14 females) showed no significant differences in the timing of plasma and urinary circadian phase markers between sexes. Females, however, exhibited significantly greater levels of plasma melatonin and cortisol than males (AUC melatonin: 937 ± 104 (mean ± SEM) vs. 642 ± 47 pg/ml.h; AUC cortisol: 13581 ± 1313 vs. 7340 ± 368 mmol/L.h). Females also exhibited a significantly higher amplitude rhythm in both hormones (melatonin: 43.8 ± 5.8 vs. 29.9 ± 2.3 pg/ml; cortisol: 241.7 ± 23.1 vs. 161.8 ± 15.9 mmol/L). Males excreted significantly more urinary cortisol than females during the CR (519.5 ± 63.8 vs. 349.2 ± 39.3 mol) but aMT6s levels did not differ between sexes. It was not possible to distinguish whether the elevated plasma melatonin and cortisol levels observed in females resulted from innate sex differences or the OCP affecting the synthetic and metabolic pathways of these hormones. The fact that the sex differences observed in total plasma concentrations for melatonin and cortisol were not reproduced in the urinary markers challenges their use as a proxy for plasma levels in circadian research, especially in OCP users.
Lech K, Liu F, Ackermann K, Revell VL, Lao O, Skene DJ, Kayser M (2016) Evaluation of mRNA markers for estimating blood deposition time: Towards alibi testing from human forensic stains with rhythmic biomarkers, FORENSIC SCIENCE INTERNATIONAL-GENETICS 21 pp. 119-125 ELSEVIER IRELAND LTD
Determining the time a biological trace was left at a scene of crime reflects a crucial aspect of forensic investigations as ? if possible ? it would permit testing the sample donor?s alibi directly from the trace evidence, helping to link (or not) the DNA-identified sample donor with the crime event. However, reliable and robust methodology is lacking thus far. In this study, we assessed the suitability of mRNA for the purpose of estimating blood deposition time, and its added value relative to melatonin and cortisol, two circadian hormones we previously introduced for this purpose. By analysing 21 candidate mRNA markers in blood samples from 12 individuals collected around the clock at 2?h intervals for 36?h under real-life, controlled conditions, we identified 11 mRNAs with statistically significant expression rhythms. We then used these 11 significantly rhythmic mRNA markers, with and without melatonin and cortisol also analysed in these samples, to establish statistical models for predicting day/night time categories. We found that although in general mRNA-based estimation of time categories was less accurate than hormone-based estimation, the use of three mRNA markers HSPA1B, MKNK2 and PER3 together with melatonin and cortisol generally enhanced the time prediction accuracy relative to the use of the two hormones alone. Our data best support a model that by using these five molecular biomarkers estimates three time categories, i.e. night/early morning, morning/noon, and afternoon/evening with prediction accuracies expressed as AUC values of 0.88, 0.88, and 0.95, respectively. For the first time, we demonstrate the value of mRNA for blood deposition timing and introduce a statistical model for estimating day/night time categories based on molecular biomarkers, which shall be further validated with additional samples in the future. Moreover, our work provides new leads for molecular approaches on time of death estimation using the significantly rhythmic mRNA markers established here.
Lech K, Ackermann K, Revell VL, Lao O, Skene DJ, Kayser M (2016) Dissecting Daily and Circadian Expression Rhythms of Clock-Controlled Genes in Human Blood, JOURNAL OF BIOLOGICAL RHYTHMS 31 (1) pp. 68-81 SAGE PUBLICATIONS INC
The identification and investigation of novel clock-controlled genes (CCGs) has been conducted thus far mainly in model organisms such as nocturnal rodents, with limited information in humans. Here, we aimed to characterize daily and circadian expression rhythms of CCGs in human peripheral blood during a sleep/sleep deprivation (S/SD) study and a constant routine (CR) study. Blood expression levels of 9 candidate CCGs (SREBF1, TRIB1, USF1, THRA1, SIRT1, STAT3, CAPRIN1, MKNK2, and ROCK2), were measured across 48 h in 12 participants in the S/SD study and across 33 h in 12 participants in the CR study. Statistically significant rhythms in expression were observed for STAT3, SREBF1, TRIB1, and THRA1 in samples from both the S/SD and the CR studies, indicating that their rhythmicity is driven by the endogenous clock. The MKNK2 gene was significantly rhythmic in the S/SD but not the CR study, which implies its exogenously driven rhythmic expression. In addition, we confirmed the circadian expression of PER1, PER3, and REV-ERB± in the CR study samples, while BMAL1 and HSPA1B were not significantly rhythmic in the CR samples; all 5 genes previously showed significant expression in the S/SD study samples. Overall, our results demonstrate that rhythmic expression patterns of clock and selected clock-controlled genes in human blood cells are in part determined by exogenous factors (sleep and fasting state) and in part by the endogenous circadian timing system. Knowledge of the exogenous and endogenous regulation of gene expression rhythms is needed prior to the selection of potential candidate marker genes for future applications in medical and forensic settings.
Santhi N, Ramsey D, Phillipson G, Hull D, Revell V, Dijk D (2017) Efficacy of a Topical Aromatic Rub
(Vicks VapoRub®) on Effects on Self-Reported
and Actigraphically Assessed Aspects of
Sleep in Common Cold Patients,
Open Journal of Respiratory Diseases 7 (2) 76608 pp. 83-101 Scientific Research Publishing
Common cold sufferers frequently report sleep disruption during the symptomatic
period of infections. We examined the effects of treatment with a
topical aromatic pharmaceutical ointment (Vicks VapoRub®), on associated
sleep disturbances. The effects of Vicks VapoRub® versus placebo (petrolatum
ointment) on subjective and objective measured sleep parameters were assessed
in an exploratory study of 100 common cold patients, in a randomized,
single blind, controlled, two-arm, parallel design study. The primary efficacy
variable was subjective sleep quality measured with the SQSQ (Subjective
Quality of Sleep Questionnaire). Additional measures included, ease of falling
asleep and depth of sleep (measured with a post-sleep Visual Analog Scale),
total sleep time, sleep onset latency, activity score, percentage of sleep, sleep
efficiency (measured with actigraphy and SQSQ) and sleep quality index
measured with a modified Karolinska Sleep Diary (KSD). The primary endpoint,
?How was the quality of your sleep last night?? showed a statistically
significant difference in change from baseline in favour of VapoRub treatment
(p = 0.0392) versus placebo. Positive effects of VapoRub versus placebo were
also observed for ?How refreshed did you feel upon waking up?? (p = 0.0122)
(SQSQ), ?Did you get enough sleep?? (p = 0.0036) (KSD), ?How was it to get
up?? (p = 0.0120) (KSD) and ?Do you feel well-rested?? (p = 0.0125) (KSD).
No statistically significant changes from baseline versus placebo were detected
in the Actiwatch endpoints. Vicks VapoRub®when applied before retiring to bed can reduce subjective sleep disturbances during a common cold. The results
of this exploratory study support the belief among patients that the use
of VapoRub improves subjective sleep quality during common cold which was
associated with more refreshing sleep.
Lech Karolina, Liu Fan, Davies Sarah K., Ackermann Katrin, Ang Joo Ern, Middleton Benita, Revell Victoria L., Raynaud Florence I., Hoveijn Igor, Hut Roelof A., Skene Debra J., Kayser Manfred (2017) investigation of metabolites for estimating blood deposition time, International Journal of Legal Medicine 132 (1) pp. 25-32 Springer Verlag
Trace deposition timing reflects a novel concept in forensic molecular biology involving the use of rhythmic biomarkers for estimating the time within a 24-h day/night cycle a human biological sample was left at the crime scene, which in principle allows verifying a sample donor?s alibi. Previously, we introduced two circadian hormones for trace deposition timing and recently demonstrated that messenger RNA (mRNA) biomarkers significantly improve time prediction accuracy. Here, we investigate the suitability of metabolites measured using a targeted metabolomics approach, for trace deposition timing. Analysis of 171 plasma metabolites collected around the clock at 2-h intervals for 36 h from 12 male participants under controlled laboratory conditions identified 56 metabolites showing statistically significant oscillations, with peak times falling into three day/night time categories: morning/noon, afternoon/evening and night/early morning. Time prediction modelling identified 10 independently contributing metabolite biomarkers, which together achieved prediction accuracies expressed as AUC of 0.81, 0.86 and 0.90 for these three time categories respectively. Combining metabolites with previously established hormone and mRNA biomarkers in time prediction modelling resulted in an improved prediction accuracy reaching AUCs of 0.85, 0.89 and 0.96 respectively. The additional impact of metabolite biomarkers, however, was rather minor as the previously established model with melatonin, cortisol and three mRNA biomarkers achieved AUC values of 0.88, 0.88 and 0.95 for the same three time categories respectively. Nevertheless, the selected metabolites could become practically useful in scenarios where RNA marker information is unavailable such as due to RNA degradation. This is the first metabolomics study investigating circulating metabolites for trace deposition timing, and more work is needed to fully establish their usefulness for this forensic purpose.
Bonmati-Carrion María Ángeles, Hild Konstanze, Isherwood Cheryl, Sweeney Stephen J, Revell Victoria, Madrid Juan Antonio, Rol María Ángeles, Skene Debra (2018) Effect of single and combined monochromatic light on the human pupillary light response, Frontiers in Neurology 9 1019 Frontiers Media
The pupillary light reflex (PLR) is a neurological reflex driven by rods, cones, and melanopsin-containing retinal ganglion cells. Our aim was to achieve a more precise picture of the effects of 5-min duration monochromatic light stimuli, alone or in combination, on the human PLR, to determine its spectral sensitivity and to assess the importance of photon flux. Using pupillometry, the PLR was assessed in 13 participants (6 women) aged 27.2 ± 5.41 years (mean ± SD) during 5-min light stimuli of purple (437 nm), blue (479 nm), red (627 nm), and combinations of red+purple or red+blue light. In addition, nine 5-min, photon-matched light stimuli, ranging in 10 nm increments peaking between 420 and 500 nm were tested in 15 participants (8 women) aged 25.7 ± 8.90 years. Maximum pupil constriction, time to achieve this, constriction velocity, area under the curve (AUC) at short (0?60 s), and longer duration (240?300 s) light exposures, and 6-s post-illumination pupillary response (6-s PIPR) were assessed. Photoreceptor activation was estimated by mathematical modeling. The velocity of constriction was significantly faster with blue monochromatic light than with red or purple light. Within the blue light spectrum (between 420 and 500 nm), the velocity of constriction was significantly faster with the 480 nm light stimulus, while the slowest pupil constriction was observed with 430 nm light. Maximum pupil constriction was achieved with 470 nm light, and the greatest AUC0?60 and AUC240?300 was observed with 490 and 460 nm light, respectively. The 6-s PIPR was maximum after 490 nm light stimulus. Both the transient (AUC0?60) and sustained (AUC240?300) response was significantly correlated with melanopic activation. Higher photon fluxes for both purple and blue light produced greater amplitude sustained pupillary constriction. The findings confirm human PLR dependence on wavelength, monochromatic or bichromatic light and photon flux under 5-min duration light stimuli. Since the most rapid and high amplitude PLR occurred within the 460?490 nm light range (alone or combined), our results suggest that color discrimination should be studied under total or partial substitution of this blue light range (460?490 nm) by shorter wavelengths (~440 nm). Thus for nocturnal lighting, replacement of blue light with purple light might be a plausible solution to preserve color discrimination while minimizing melanopic activation.
Christou Skevoulla, Wehrens Sophie M T, Isherwood Cheryl, Moller-Levet Carla S, Wu Huihai, Revell Victoria L, Bucca Giselda, Skene Debra J, Laing Emma E, Archer Simon N, Johnston Jonathan D (2019) Circadian regulation in human white adipose tissue revealed by transcriptome and metabolic network analysis, Scientific Reports Nature Research
Studying circadian rhythms in most human tissues is hampered by difficulty in collecting serial samples. Here we reveal circadian rhythms in the transcriptome and metabolic pathways of human white adipose tissue. Subcutaneous adipose tissue was taken from seven healthy males under highly controlled ?constant routine? conditions. Five biopsies per participant were taken at six-hourly intervals for microarray analysis and in silico integrative metabolic modelling. We identified 837 transcripts exhibiting circadian expression profiles (2% of 41619 transcript targeting probes on the array), with clear separation of transcripts peaking in the morning (258 probes) and evening (579 probes). There was only partial overlap of our rhythmic transcripts with published animal adipose and human blood transcriptome data. Morning-peaking transcripts associated with regulation of gene expression, nitrogen compound metabolism, and nucleic acid biology; evening-peaking transcripts associated with organic acid metabolism, cofactor metabolism and redox activity. In silico pathway analysis further indicated circadian regulation of lipid and nucleic acid metabolism; it also predicted circadian variation in key metabolic pathways such as the citric acid cycle and branched chain amino acid degradation. In summary, in vivo circadian rhythms exist in multiple adipose metabolic pathways, including those involved in lipid metabolism, and core aspects of cellular biochemistry.
Sterr Annette, Ebajemito James, Mikkelsen Kaare B., Bonmati-Carrion Maria, Santhi Nayantara, della Monica Ciro, Grainger Lucinda, Atzori Giuseppe, Revell Victoria, Debener Stefan, Dijk Derk-Jan, DeVos Maarten (2018) Sleep EEG Derived From Behind-the-Ear Electrodes (cEEGrid) Compared to Standard Polysomnography: A Proof of Concept Study, Frontiers in Human Neuroscience 12 452 Frontiers Research Foundation
Electroencephalography (EEG) recordings represent a vital component of the
assessment of sleep physiology, but the methodology presently used is costly, intrusive
to participants, and laborious in application. There is a recognized need to develop more
easily applicable yet reliable EEG systems that allow unobtrusive long-term recording
of sleep-wake EEG ideally away from the laboratory setting. cEEGrid is a recently
developed flex-printed around-the-ear electrode array, which holds great potential for
sleep-wake monitoring research. It is comfortable to wear, simple to apply, and minimally
intrusive during sleep. Moreover, it can be combined with a smartphone-controlled
miniaturized amplifier and is fully portable. Evaluation of cEEGrid as a motion-tolerant
device is ongoing, but initial findings clearly indicate that it is very well suited for cognitive
research. The present study aimed to explore the suitability of cEEGrid for sleep
research, by testing whether cEEGrid data affords the signal quality and characteristics
necessary for sleep stage scoring. In an accredited sleep laboratory, sleep data from
cEEGrid and a standard PSG system were acquired simultaneously. Twenty participants
were recorded for one extended nocturnal sleep opportunity. Fifteen data sets were
scored manually. Sleep parameters relating to sleep maintenance and sleep architecture
were then extracted and statistically assessed for signal quality and concordance. The
findings suggest that the cEEGrid system is a viable and robust recording tool to capture
sleep and wake EEG. Further research is needed to fully determine the suitability of
cEEGrid for basic and applied research as well as sleep medicine.
Mikkelsen Kaare, Ebajemito James K., Bonmati?Carrion Mari, Santhi Nayantara, Revell Victoria, Atzori Giuseppe, della Monica Ciro, Debener Stefan, Dijk Derk-Jan, Sterr Annette, Vos Maarte (2019) Machine?learning?derived sleep?wake staging from around?the?ear electroencephalogram outperforms manual scoring and actigraphy, Journal of Sleep Research 28 (2) e12786 Wiley-Blackwell Publishing
Quantification of sleep is important for the diagnosis of sleep disorders and sleep research. However, the only widely accepted method to obtain sleep staging is by visual analysis of polysomnography (PSG), which is expensive and time consuming. Here, we investigate automated sleep scoring based on a low?cost, mobile electroencephalogram (EEG) platform consisting of a lightweight EEG amplifier combined with flex?printed cEEGrid electrodes placed around the ear, which can be implemented as a fully self?applicable sleep system. However, cEEGrid signals have different amplitude characteristics to normal scalp PSG signals, which might be challenging for visual scoring. Therefore, this study evaluates the potential of automatic scoring of cEEGrid signals using a machine learning classifier (?random forests?) and compares its performance with manual scoring of standard PSG. In addition, the automatic scoring of cEEGrid signals is compared with manual annotation of the cEEGrid recording and with simultaneous actigraphy. Acceptable recordings were obtained in 15 healthy volunteers (aged 35 ± 14.3 years) during an extended nocturnal sleep opportunity, which induced disrupted sleep with a large inter?individual variation in sleep parameters. The results demonstrate that machine?learning?based scoring of around?the?ear EEG outperforms actigraphy with respect to sleep onset and total sleep time assessments. The automated scoring outperforms human scoring of cEEGrid by standard criteria. The accuracy of machine?learning?based automated scoring of cEEGrid sleep recordings compared with manual scoring of standard PSG was satisfactory. The findings show that cEEGrid recordings combined with machine?learning?based scoring holds promise for large?scale sleep studies.
Bonmati-Carrion Maria-Angeles, Revell Victoria, Cook Tom J., Welch Thomas R.E, Rol Maria-Angeles, Skene Debra, Madrid Juan Antonio (2020) Living Without Temporal Cues: A Case Study, Frontiers in Physiology Frontiers Media
Isolation from external time cues allows endogenous circadian rhythmicity to be
demonstrated. In this study, also filmed as a television documentary, we assessed
rhythmic changes in a healthy man time isolated in a bunker for 9 days/nights. During
this period the lighting conditions were varied between: (1) self-selected light/dark
cycle, (2) constant dim light, and (3) light/dark cycle with early wake up. A range
of variables was assessed and related to the sleep-wake cycle, psychomotor and
physical performance and clock-time estimation. This case study using modern
non-invasive monitoring techniques emphasizes how different physiological circadian
rhythms persist in temporal isolation under constant dim light conditions with different
waveforms, free-running with a period (t) between 24 and 25 h. In addition, a significant
correlation between time estimation and mid-sleep time, a proxy for circadian phase,
was demonstrated.