RECHERCHE & DEVELOPPEMENT
La recherche occupe une place essentielle à Physip.
Elle nous permet de faire avancer en permanence les algorithmes d’analyse existants et d’en développer de nouveaux pour répondre à de nouveaux besoins scientifiques et industriels.
La R&D à Physip est essentiellement collaborative. C’est en travaillant avec des équipes médicales compétentes, reconnues que nous avons pu amener nos solutions d’analyse à leur niveau de performance actuel.
PROJETS DE RECHERCHE
Nos projets de recherche se répartissent entre deux grands domaines, le sommeil et l’éveil, et entre les projets de développement -validation des algorithmes, et ceux où nos analyses sont utilisées sur des thématiques larges : cognition, vieillissement, syndrome post traumatique, performances, monitoring de la somnolence dans les transports.
Berthomier C, Brandewinder M, EOG-based auto-staging: less is more, Sleep Breath. Sleep Breath. 19 (3):791-793, 2015
This issue of Sleep and Breathing presents the validation results of a new automated wake/sleep staging method based on EOG activity, developed by Jussi Virkkala from the Finnish Institute of Occupational Health. Classically, the automated method is compared to visual analysis, on an epoch by epoch basis. It reaches a level of global concordance of 88 % with a Kappa of 0.57. In other words, on the 248,696 epochs of the validation dataset, 212,138 were scored correctly in wake/sleep, that is as the human expert did it, and on 36,558 epochs, the two scorings differ.
Berthomier C, Brandewinder M, Sleep scoring: man vs. machine ?, Sleep Breath. 17 (2):461-462, 2013
The automated analysis of sleep has grown in interest in the past decade. Advances in computing have brought the needed intensive calculations within reach ; while simultaneously, there is an increasing demand for sleep diagnosis and analysis. The prevalence of sleep troubles is high, and the awareness of their consequences is spreading among patients, health authorities, and clinicians. This awareness is directing more and more patients to sleep centers. The upward trend in demand for sleep evaluations concerns not only sleep specialists. Sleep appears to be an extremely promising territory for other fields, such as cardiology and nutrition for example . Needs exceed capacities by this far. Data analysis has been identified as one of the bottlenecks in the sleep evaluation process, making clear the importance of developing tools to facilitate analysis. These developments have an impact that is medical, as well as economical and social.
Maire M, Reichert CF, Gabel V, Viola AU, Phillips C, Berthomier C, Borgwardt S, Cajochen C, Schmidt C. Human brain patterns underlying vigilant attention: impact of sleep debt, circadian phase and attentional engagement. Sci Rep. 2018 Jan 17;8(1):970. doi: 10.1038/s41598-017-17022-9.
Sleepiness and cognitive function vary over the 24-h day due to circadian and sleep-wake-dependent mechanisms. However, the underlying cerebral hallmarks associated with these variations remain to be fully established. Using functional magnetic resonance imaging (fMRI), we investigated brain responses associated with circadian and homeostatic sleep-wake-driven dynamics of subjective sleepiness throughout day and night. Healthy volunteers regularly performed a psychomotor vigilance task (PVT) in the MR-scanner during a 40-h sleep deprivation (high sleep pressure) and a 40-h multiple nap protocol (low sleep pressure). When sleep deprived, arousal-promoting thalamic activation during optimal PVT performance paralleled the time course of subjective sleepiness with peaks at night and troughs on the subsequent day. Conversely, task-related cortical activation decreased when sleepiness increased as a consequence of higher sleep debt. Under low sleep pressure, we did not observe any significant temporal association between PVT-related brain activation and subjective sleepiness. Thus, a circadian modulation in brain correlates of vigilant attention was only detectable under high sleep pressure conditions. Our data indicate that circadian and sleep homeostatic processes impact on vigilant attention via specific mechanisms; mirrored in a decline of cortical resources under high sleep pressure, opposed by a subcortical « rescuing » at adverse circadian times.
> Accéder à l’article complet : Human brain patterns underlying vigilant attention: impact of sleep debt, circadian phase and attentional engagement
Dang-Vu TT, Hatch B, Salimi A, Mograss M, Boucetta S, O’byrne J, Brandewinder M, Berthomier C, Gouin JP, Sleep spindles may predict response to cognitive behavioral therapy for chronic insomnia, Sleep Medicine 39 (2017) 54-61
• Spindles may predict responsiveness to cognitive-behavioral therapy for insomnia (CBT-I).
• Lower spindle density was prospectively associated with smaller responses to CBT-I.
• Spindles might thus constitute a biomarker identifying patients less responsive to CBT-I.
Reichert CF, Maire M, Gabel V, Viola AU, Götz T, Scheffler K, Klarhöfer M, Berthomier C, Strobel W, Phillips C, Salmon E, Cajochen C, Schmidt C, Cognitive brain responses during circadian wake-promotion: evidence for sleep-pressure-dependent hypothalamic activation, Sci Rep. 2017 Jul 17;7(1):5620. doi: 10.1038/s41598-017-05695-1.
The two-process model of sleep-wake regulation posits that sleep-wake-dependent homeostatic processes interact with the circadian timing system to affect human behavior. The circadian timing system is fundamental to maintaining stable cognitive performance, as it counteracts growing homeostatic sleep pressure during daytime. Using magnetic resonance imaging, we explored brain responses underlying working memory performance during the time of maximal circadian wake-promotion under varying sleep pressure conditions. Circadian wake-promoting strength was derived from the ability to sleep during an evening nap. Hypothalamic BOLD activity was positively linked to circadian wake-promoting strength under normal, but not under disproportionally high or low sleep pressure levels. Furthermore, higher hypothalamic activity under normal sleep pressure levels predicted better performance under sleep loss. Our results reappraise the two-process model by revealing a homeostatic-dose-dependent association between circadian wake-promotion and cognition-related hypothalamic activity.
Raphael Vallat, Tarek Lajnef, Jean-Baptiste Eichenlaub, Christian Berthomier, Karim Jerbi, Dominique Morlet and Perrine M. Ruby, Increased Evoked Potentials to Arousing Auditory Stimuli during Sleep: Implication for the Understanding of Dream Recall, Front. Hum. Neurosci., 21 March 2017 | https://doi.org/10.3389/fnhum.2017.00132
High dream recallers (HR) show a larger brain reactivity to auditory stimuli during wakefulness and sleep as compared to low dream recallers (LR) and also more intra-sleep wakefulness (ISW), but no other modification of the sleep macrostructure. To further understand the possible causal link between brain responses, ISW and dream recall, we investigated the sleep microstructure of HR and LR, and tested whether the amplitude of auditory evoked potentials (AEPs) was predictive of arousing reactions during sleep. Participants (18 HR, 18 LR) were presented with sounds during a whole night of sleep in the lab and polysomnographic data were recorded. Sleep microstructure (arousals, rapid eye movements (REMs), muscle twitches (MTs), spindles, KCs) was assessed using visual, semi-automatic and automatic validated methods. AEPs to arousing (awakenings or arousals) and non-arousing stimuli were subsequently computed. No between-group difference in the microstructure of sleep was found. In N2 sleep, auditory arousing stimuli elicited a larger parieto-occipital positivity and an increased late frontal negativity as compared to non-arousing stimuli. As compared to LR, HR showed more arousing stimuli and more long awakenings, regardless of the sleep stage but did not show more numerous or longer arousals. These results suggest that the amplitude of the brain response to stimuli during sleep determine subsequent awakening and that awakening duration (and not arousal) is the critical parameter for dream recall. Notably, our results led us to propose that the minimum necessary duration of an awakening during sleep for a successful encoding of dreams into long-term memory is approximately 2 min.
Dang-Vu T. T., Salimi A., Boucetta S., Wenzel K., O’Byrne J., M. Brandewinder M., Berthomier C. and Gouin J.-P.. Sleep spindles predict stress-related increases in sleep disturbances. Front. Hum. Neurosci., 10 February 2015 | doi: 10.3389/fnhum.2015.00068
The aim of this study was to prospectively assess whether spindle density would predict the worsening of sleep disturbances in response to a standardized stressor. We chose to follow a population of undergraduate university students during a period of increasing academic stress. In this context, assessing students at the beginning of the semester, corresponding to a lower stress period, and reevaluating them during a follow-up in the week preceding the final examinations, a period of higher stress, provides a unique opportunity to examine individual differences in the evolution of insomnia symptoms in response to a standardized stressor.
O’Byrne J, Boucetta S, Reed L,Malhi O, Zhang V, Arcelin A, Wenzel K, Brandewinder M, Berthomier C, Gouin J-P, Dang-Vu TT. Spindles and slow waves predict treatment responses to cognitive-behavioural therapy for chronic primary insomnia. J. Sleep Res., 23 Suppl. 1:209, 2014
Sagaspe P, Taillard J, Chaufton C, Berthomier C, Brandewinder M, Amiéva H, Dartigues J-F, Philip P. Polysomnographic data in patients with isolated memory complaints or mild cognitive impairment. J. Sleep Res., 23 Suppl. 1:240, 2014
Eichenlaub JB, Bertrand O, Morlet D, Ruby P. Brain Reactivity Differentiates Subjects with High and Low Dream Recall Frequencies during Both Sleep and Wakefulness. Cereb. Cortex 24 (5): 1206-1215. 2014
The neurophysiological correlates of dreaming remain unclear. According to the « arousal-retrieval » model, dream encoding depends on intrasleep wakefulness. Consistent with this model, subjects with high and low dream recall frequency (DRF) report differences in intrasleep awakenings. This suggests a possible neurophysiological trait difference between the 2 groups. To test this hypothesis, we compared the brain reactivity (evoked potentials) of subjects with high (HR, N = 18) and low (LR, N = 18) DRF during wakefulness and sleep. During data acquisition, the subjects were presented with sounds to be ignored (first names randomly presented among pure tones) while they were watching a silent movie or sleeping. Brain responses to first names dramatically differed between the 2 groups during both sleep and wakefulness. During wakefulness, the attention-orienting brain response (P3a) and a late parietal response were larger in HR than in LR. During sleep, we also observed between-group differences at the latency of the P3a during N2 and at later latencies during all sleep stages. Our results demonstrate differences in the brain reactivity of HR and LR during both sleep and wakefulness. These results suggest that the ability to recall dreaming is associated with a particular cerebral functional organization, regardless of the state of vigilance.
Ruby P, Blochet C, Eichenlaub J-B, Bertrand O, Morlet D, Bidet-Caulet A. Alpha Reactivity to Complex Sounds Differs during REM Sleep and Wakefulness. PLoS ONE 8(11): e79989, 2013.
We aimed at better understanding the brain mechanisms involved in the processing of alerting meaningful sounds during sleep, investigating alpha activity. During EEG acquisition, subjects were presented with a passive auditory oddball paradigm including rare complex sounds called Novels (the own first name – OWN, and an unfamiliar first name – OTHER) while they were watching a silent movie in the evening or sleeping at night. During the experimental night, the subjects’ quality of sleep was generally preserved. During wakefulness, the decrease in alpha power (8–12 Hz) induced by Novels was significantly larger for OWN than for OTHER at parietal electrodes, between 600 and 900 ms after stimulus onset. Conversely, during REM sleep, Novels induced an increase in alpha power (from 0 to 1200 ms at all electrodes), significantly larger for OWN than for OTHER at several parietal electrodes between 700 and 1200 ms after stimulus onset. These results show that complex sounds have a different effect on the alpha power during wakefulness (decrease) and during REM sleep (increase) and that OWN induce a specific effect in these two states. The increased alpha power induced by Novels during REM sleep may 1) correspond to a short and transient increase in arousal; in this case, our study provides an objective measure of the greater arousing power of OWN over OTHER, 2) indicate a cortical inhibition associated with sleep protection. These results suggest that alpha modulation could participate in the selection of stimuli to be further processed during sleep.
Ruby P, Blochet C, Eichenlaub JB, Bertrand O, Morlet D, Bidet-Caulet A. Alpha reactivity to first names differs in subjects with high and low dream recall frequency. Front Psychol.;4:419, 2013.
Studies in cognitive psychology showed that personality (openness to experience, thin boundaries, absorption), creativity, nocturnal awakenings, and attitude toward dreams are significantly related to dream recall frequency (DRF). These results suggest the possibility of neurophysiological trait differences between subjects with high and low DRF. To test this hypothesis we compared sleep characteristics and alpha reactivity to sounds in subjects with high and low DRF using polysomnographic recordings and electroencephalography (EEG). We acquired EEG from 21 channels in 36 healthy subjects while they were presented with a passive auditory oddball paradigm (frequent standard tones, rare deviant tones and very rare first names) during wakefulness and sleep (intensity, 50 dB above the subject’s hearing level). Subjects were selected as High-recallers (HR, DRF = 4.42 ± 0.25 SEM, dream recalls per week) and Low-recallers (LR, DRF = 0.25 ± 0.02) using a questionnaire and an interview on sleep and dream habits. Despite the disturbing setup, the subjects’ quality of sleep was generally preserved. First names induced a more sustained decrease in alpha activity in HR than in LR at Pz (1000–1200 ms) during wakefulness, but no group difference was found in REM sleep. The current dominant hypothesis proposes that alpha rhythms would be involved in the active inhibition of the brain regions not involved in the ongoing brain operation. According to this hypothesis, a more sustained alpha decrease in HR would reflect a longer release of inhibition, suggesting a deeper processing of complex sounds than in LR during wakefulness. A possibility to explain the absence of group difference during sleep is that increase in alpha power in HR may have resulted in awakenings. Our results support this hypothesis since HR experienced more intra sleep wakefulness than LR (30 ± 4 vs. 14 ± 4 min). As a whole our results support the hypothesis of neurophysiological trait differences in high and low-recallers.
Schmidt C, Maire M, Reichert C F, Scheffler K, Klarhoefer M, Strobel W, Krebs J, Berthomier P, Berthomier C, Cajochen C. Circadian and homeostatic modulation of cognition-related cerebral activity in humans. J. Sleep Res. 21 (Suppl. 1), 1-371, 2012.
Schmidt C, Peigneux P, Leclercq Y, Sterpenich V, Vandewalle G, Philips C, Berthomier P, Berthomier C, Tinguely G, Gais S, Schabus M, Desseilles M, Dang-Vu T, Salmon E, Degueldre C, Balteau E, Luxen A, Cajochen C, Maquet P, Collette F. Circadian preference modulates the neural substrate of conflict processing across the day. PLoS One. 2012;7(1):e29658. 2012 Jan 4. PLoS One. 2012;7(1):e29658. 2012 Jan 4.
Human morning and evening chronotypes differ in their preferred timing for sleep and wakefulness, as well as in optimal daytime periods to cope with cognitive challenges. Recent evidence suggests that these preferences are not a simple by-product of socio-professional timing constraints, but can be driven by inter-individual differences in the expression of circadian and homeostatic sleep-wake promoting signals. Chronotypes thus constitute a unique tool to access the interplay between those processes under normally entrained day-night conditions, and to investigate how they impinge onto higher cognitive control processes. Using functional magnetic resonance imaging (fMRI), we assessed the influence of chronotype and time-of-day on conflict processing-related cerebral activity throughout a normal waking day. Sixteen morning and 15 evening types were recorded at two individually adapted time points (1.5 versus 10.5 hours spent awake) while performing the Stroop paradigm. Results show that interference-related hemodynamic responses are maintained or even increased in evening types from the subjective morning to the subjective evening in a set of brain areas playing a pivotal role in successful inhibitory functioning, whereas they decreased in morning types under the same conditions. Furthermore, during the evening hours, activity in a posterior hypothalamic region putatively involved in sleep-wake regulation correlated in a chronotype-specific manner with slow wave activity at the beginning of the night, an index of accumulated homeostatic sleep pressure. These results shed light into the cerebral mechanisms underlying inter-individual differences of higher-order cognitive state maintenance under normally entrained day-night conditions.
Schmidt C, Peigneux P, Leclercq Y, Sterpenich V, Van Dewalle G, Philips C, Tinguely G, Gais S, Schabus M, Desseilles M, Dang-Vu T, Salmon E, Balteau E, Luxen A, Cajochen C, Maquet P, Collette F. Working memory load affects chronotype- and time-of-day dependent cerebral activity modulations. J. Sleep Res., 19: P541,2010.
Sterpenich V, Schmidt C, Albouy G, Matarazzo L, Van Haudenhuyse A, Boveroux P, Vaessen N, Berthomier P, Berthomier C, Degueldre C, Leclercq Y, Balteau E, Collette F,Luxen A, Philips C, Maquet P. Conditioned auditory cues delivered during phasic REM sleep enhance adult human brain plasticity. J. Sleep Res., 19: O310,2010.
Schmidt C, Collette F, Leclercq Y, Sterpenich V, Vandewalle G, Berthomier P, Berthomier C, Philipps C, Tinguely G, Darsaud A, Gais S, Schabus M, Desseilles M, Dang-Vu T, Salmon E, Balteau E, Degueldre C, Luxen A, Maquet P, Cajochen C, Peigneux P. Homeostatic sleep pressure and responses to sustained attention in the suprachiasmatic area. Science, 324 (5926):516-9, 2009.
Throughout the day, cognitive performance is under the combined influence of circadian processes and homeostatic sleep pressure. Some people perform best in the morning, whereas others are more alert in the evening. These chronotypes provide a unique way to study the effects of sleep-wake regulation on the cerebral mechanisms supporting cognition. Using functional magnetic resonance imaging in extreme chronotypes, we found that maintaining attention in the evening was associated with higher activity in evening than morning chronotypes in a region of the locus coeruleus and in a suprachiasmatic area (SCA) including the circadian master clock. Activity in the SCA decreased with increasing homeostatic sleep pressure. This result shows the direct influence of the homeostatic and circadian interaction on the neural activity underpinning human behavior.
Schmidt C, Peigneux P, Leclercq Y, Sterpenich V, Vandewalle G, Berthomier P, Berthomier C, Philipps C, Tinguely G, Gais S, Schabus M, Balteau E, Luxen A, Maquet P, Cajochen C and Collette F. Stroop-related cerebral activity is modulated by time of day and chronotype. NeuroImage, 47:S39-S41, 2009.
Berthomier C, Berthomier P, Brandewinder M, Mattout J, Philip P, Taillard J. Assessment of an automatic analysis method of the Karolinska drowsiness test. J. Sleep Res. 21 (Suppl. 1), 1-371, 2012.
Van Beers P, Berthomier C, Prado J, Berthomier P, Coste O. HRV Analysis during Sleep: Clinical Interest of a New Automatic Sleep Analysis. Sleep, 32:A374, 2009.
Berthomier C, Muzet A, Berthomier P, Prado J, Mattout J, Real-Time Automatic Measure of Drowsiness based on a Single EEG Channel. J. Sleep Res., 17:P434, 2008.
Berthomier C, Herman-Stoïca M, Berthomier P, Drouot X, Prado J, Mattout J, d’Ortho MP, Real-Time Automatic Wake/Sleep Scoring based on a Single EEG Channel. Sleep, 31:A338, 2008.
Berthomier C, Drouot X, Herman-Stoïca M, Berthomier P, Prado J, Bokar-thiré D, Benoit O, Mattout J, d’Ortho M-P, Automatic Analysis of Single-Channel Sleep EEG: Validation in Healthy Individuals. Sleep, 30(11):1587-95, 2007.
STUDY OBJECTIVE: To assess the performance of automatic sleep scoring software (ASEEGA) based on a single EEG channel comparatively with manual scoring (2 experts) of conventional full polysomnograms.
DESIGN: Polysomnograms from 15 healthy individuals were scored by 2 independent experts using conventional R&K rules. The results were compared to those of ASEEGA scoring on an epoch-by-epoch basis.
SETTING: Sleep laboratory in the physiology department of a teaching hospital.
PARTICIPANTS: Fifteen healthy volunteers.
MEASUREMENTS AND RESULTS: The epoch-by-epoch comparison was based on classifying into 2 states (wake/sleep), 3 states (wake/REM/ NREM), 4 states (wake/REM/stages 1-2/SWS), or 5 states (wake/REM/ stage 1/stage 2/SWS). The obtained overall agreements, as quantified by the kappa coefficient, were 0.82, 0.81, 0.75, and 0.72, respectively. Furthermore, obtained agreements between ASEEGA and the expert consensual scoring were 96.0%, 92.1%, 84.9%, and 82.9%, respectively. Finally, when classifying into 5 states, the sensitivity and positive predictive value of ASEEGA regarding wakefulness were 82.5% and 89.7%, respectively. Similarly, sensitivity and positive predictive value regarding REM state were 83.0% and 89.1%.
CONCLUSIONS: Our results establish the face validity and convergent validity of ASEEGA for single-channel sleep analysis in healthy individuals. ASEEGA appears as a good candidate for diagnostic aid and automatic ambulant scoring.
Berthomier C, Berthomier P, Herman-Stoïca M, Drouot X, Prado J, Benoit O, Mattout J, d’Ortho MP, Real-Time Automatic Measurement of Recorded Sleep Time. Chest, 132(4):649S, 2007.
Berthomier C, Drouot X, Herman-Stoïca M, Berthomier P, Prado J, Benoit O, Mattout J, d’Ortho M-P, Wake-REM-NREM Automatic Classification based on a Single EEG Channel: Epoch-by-Epoch Comparison with Human Sleep Scoring in Patients. J. Sleep Res., 15:P295, 2006.
Berthomier C, Drouot X, Herman-Stoïca M, Berthomier P, Prado J, Mattout J, d’Ortho M-P, Single Channel based Brain Monitoring: Sleep/Wakefulness classification. Int. conf. of SENSATION/ESRS on Monitoring sleep and sleepiness – from physiology to new sensors, 2006.
Berthomier C, Drouot X, Herman-Stoïca M, Berthomier P, Prado J, Mattout J, d’Ortho MP, A Wake-REM-NREM Automatic Analysis Using a Single EEG Channel: Epoch by Epoch Comparison with Human Sleep Scoring in Healthy Subjects. Sleep Medicine, 6:S194, 2005.
Berthomier C, Prado J and Benoit O, Automatic sleep EEG analysis using filter banks, in Biomedical Sciences Instrumentation, 35():241-6, 1999.
Filter banks analysis is an easy and quick computing way to implement time-scale methods, these being well suited for short events as well as for large waveforms detection tasks. We propose a non-uniform oversampled filter banks to analyze sleep EEG single channel signal, the different subbands matching the classical EEG rhythms. In order to preserve the temporal shapes information, filter banks are oversampled. Coupling the informations conveyed by the different outputs allow to perform an automatic hypnogram.
Berthomier C, Prado J and Benoit O, EEG analysis using non-uniform oversampled filter banks, in Biomedical Sciences Instrumentation, 34():119-24, 1997.
Time-frequency or time-scale methods are well suited for short events as well as for large waveforms detection tasks. Filter banks analysis is an easy and quick computing way to implement these methods. We propose a non-uniform oversampled filter banks to analyze EEG single channel signal, the different subbands matching the classical EEG rhythms. We use oversampled filter banks to preserve the temporal shapes information. In order to illustrate this method, we show different spindle temporal structures as also their meaning in terms of sleep stage detection.