Sleep and circadian rhythms in the acute phase of moderate to severe traumatic brain injury

Les traumatismes craniocérébraux (TCC) sont la principale cause d’invalidité chez les jeunes adultes, engendrant d’importantes séquelles cognitives, physiologiques et comportementales. Les perturbations du cycle veille-sommeil sont parmi les symptômes les plus persistants à la suite d’un TCC et pourraient nuire à la récupération. En effet, le sommeil est nécessaire à l’apprentissage, la plasticité cérébrale et la génération de nouveaux neurones dans le cerveau adulte. Les observations cliniques suggèrent que ces perturbations apparaissent dès les premières semaines suivant le TCC et pourraient suggérer une altération de l’horloge circadienne. Cependant, aucune étude n’a encore documenté comment les perturbations du cycle veille-sommeil émergent et évoluent dans la phase aiguë du TCC, ni leur association à la récupération fonctionnelle et cognitive à court-terme. Conséquemment, cette thèse vise à caractériser le sommeil et les rythmes circadiens des patients hospitalisés avec un TCC modéré ou sévère et déterminer si les perturbations du cycle veille-sommeil sont causées par un dérèglement de l’horloge circadienne. Pour ce faire, nous avons utilisé des mesures objectives et quantitatives de sommeil et des rythmes circadiens, incluant l’actigraphie, la polysomnographie (PSG) et la mélatonine, dès la phase d’éveil aux soins intensif. Afin de comprendre le rôle du TCC dans ces perturbations, nous avons comparé les patients TCC à des patients hospitalisés avec blessures orthopédiques graves, sans TCC. Ce protocole a mené à cinq articles de recherche. En premier lieu, nous démontrons que le cycle veille-sommeil des patients TCC est sévèrement perturbé, mais s’améliore chez 50% d’entre eux au cours de leur séjour hospitalier. Les patients avec une amélioration de la consolidation du cycle veille-sommeil ont un meilleur fonctionnement cognitif et fonctionnel au congé de l’hôpital. Ensuite, dans une étude de cas, nous démontrons qu’un patient TCC peut avoir un cycle veille-sommeil complètement différent dans un même environnement, selon son stade de récupération. Notre troisième article confirme que la consolidation du cycle veille-sommeil évolue en synchronie avec la récupération de la conscience et des fonctions cognitives dans la phase aiguë du TCC. Notre quatrième article compare le sommeil des patients TCC à celui des blessés orthopédiques graves, sans TCC, en utilisant un système de PSG ambulatoire au chevet. Nous démontrons que, contrairement à notre hypothèse, le sommeil des patients TCC comprend tous les éléments et stades d’un sommeil normal. Cependant, ces patients s’endorment plus tôt et ont un sommeil de plus longue durée, mais plus fragmenté, que les patients sans TCC. Dans les deux groupes, le sommeil est de mauvaise qualité, reflétant probablement l’effet de facteurs non-spécifiques associés avec les blessures physiques et l’environnement hospitalier. Conséquemment, la PSG en phase aiguë permet difficilement de distinguer les patients TCC des patients sans TCC. Notre dernier article confirme que les patients avec TCC ont une consolidation du cycle veille-sommeil et une qualité de sommeil nocturne inférieures à celles des patients sans TCC, ce qui confirme le rôle du TCC dans les perturbations du cycle veille-sommeil. Cependant, malgré ces perturbations plus sévères, les patients TCC ont un rythme normal de la mélatonine et celui-ci n’est pas associé aux perturbations observées. Cet article suggère que des mécanismes neuronaux autres que l’horloge circadienne seraient responsables des perturbations du cycle veille-sommeil à la suite d’un TCC. Cette thèse est la première à évaluer le sommeil et le fonctionnement de l’horloge circadienne de patients hospitalisés avec un TCC modéré ou sévère ayant atteint la stabilité médicale. En isolant le rôle du TCC de celui du traumatisme physique et du milieu hospitalier, ces études contribuent à comprendre les caractéristiques, les conséquences et la pathophysiologie des perturbations du cycle veille-sommeil à la suite d’un TCC, ouvrant la voie à de possibles interventions visant à améliorer le sommeil et optimiser la récupération.Traumatic brain injuries (TBI) are the leading cause of disability among young adults, causing debilitating cognitive, psychological and behavioural impairments. Sleep-wake disturbances (SWD) are among the most persistent sequelae following TBI, and could impede recovery. Indeed, sleep is essential to learning, plasticity and neurogenesis. Clinical observations suggest that these disturbances arise in the first weeks following injury, and could suggest a circadian disturbance. However, no study has yet documented how SWD arise and evolve in the acute phase of TBI, or how they are associated to short-term cognitive and functional recovery. Consequently, this thesis aims to characterize the sleep and circadian rhythms of patients hospitalized with moderate or severe TBI, and determine whether SWD are caused by a deregulation of the circadian clock. To achieve this goal, we used objective and quantitative measures of sleep and circadian rhythms including actigraphy, polysomnography (PSG), and melatonin, beginning in the awakening stage in the Intensive Care Unit. In order to understand the specific role of TBI on SWD, we compared TBI patients to other hospitalized trauma patients, without TBI. Our comprehensive study protocol led to five research articles. First, we show that the sleep-wake cycle of TBI patients is severely disturbed, but improves for 50% of patients during their hospital stay. Patients whose sleep-wake cycle consolidation improves have better cognitive and functional outcome at hospital discharge. Then, in a single case study, we demonstrate how a patient can have drastically different sleep-wake patterns in the same environment, according to recovery stage. In our third research article, we show that the consolidation of sleep and wake states evolves synchronously with the recovery of consciousness and cognition in the acute phase of TBI. Our fourth article compares the sleep of TBI patients to that of non-TBI trauma patients using ambulatory PSG at bedside. Contrary to our hypothesis, TBI patients have normal sleep elements and normal proportions of each sleep stages. However, they have earlier sleep onset and longer nighttime sleep duration, but with greater fragmentation, than non-TBI patients. In both groups, sleep quality is poor, which most likely reflects non-specific factors associated with the physical trauma and hospital environment. Therefore, PSG reveals little information able to distinguish TBI patients from other non-TBI trauma patients at this stage post-injury. Our final article shows that TBI patients have poorer sleep-wake cycle consolidation and nighttime sleep quality than non-TBI patients, confirming the role of the TBI in altering sleep and wake states. However, despite having more severe SWD, TBI patients have a normal melatonin rhythm, and this rhythm is not associated with the observed SWD. This article suggests that neural mechanisms other than the circadian clock may be responsible for post-TBI SWD. This thesis is the first to investigate the sleep and circadian clock of hospitalized moderate to severe TBI patients who are medically stable. By isolating the role of the injured brain from that of overall trauma and the hospital setting, these studies contribute to understanding the characteristics, consequences and pathophysiology of post-TBI SWD, unlocking the possibility to design interventions aiming to improve sleep and optimize recovery

A semi-automatic semantic method for mapping SNOMED CT concepts to VCM Icons

VCM (Visualization of Concept in Medicine) is an iconic language for representing key medical concepts by icons. However, the use of this language with reference terminologies, such as SNOMED CT, will require the mapping of its icons to the terms of these terminologies. Here, we present and evaluate a semi-automatic semantic method for the mapping of SNOMED CT concepts to VCM icons. Both SNOMED CT and VCM are compositional in nature; SNOMED CT is expressed in description logic and VCM semantics are formalized in an OWL ontology. The proposed method involves the manual mapping of a limited number of underlying concepts from the VCM ontology, followed by automatic generation of the rest of the mapping. We applied this method to the clinical findings of the SNOMED CT CORE subset, and 100 randomly-selected mappings were evaluated by three experts. The results obtained were promising, with 82 of the SNOMED CT concepts correctly linked to VCM icons according to the experts. Most of the errors were easy to fix

Mise à disposition des spectres d'activité des antibiotiques pour le médecin généraliste : méthode et résultats.

International audienceLes médecins généralistes ne maîtrisent pas comme des spécialistes les connaissances en bactériologie. Il peut leur apparaître difficile d'utiliser des documents rédigés par des experts en microbiologie. Nous proposons un outil qui leur permet de s'affranchir de ces savoirs pour utiliser efficacement un document sur les spectres d'activité des antibiotiques. Le développement de cet outil est supporté par une extraction automatique des connaissances contenues dans le document initial, l'élaboration d'une ontologie et d'un module de raisonnement utilisant l'algorithme de classification OWL-DL. Le résultat final est un site web permettant la recherche de spectres antibactériens au moyen de tableaux. Les sensibilités des bactéries peuvent y être rapidement comparées grâce à l'utilisation d'une convention graphique

Dream and emotion regulation: insight from the ancient art of memory.

During dreaming, as well as during wakefulness, elaborative encoding, indexing and ancient art of memory (AAOM) techniques, such as the method of loci, may coincide with emotion regulation. These techniques shed light on the link between dreaming and emotional catharsis, post-traumatic stress disorder, supermemorization during sleep as opposed to wakefulness, and the developmental role of rapid eye movement (REM) sleep in children

Trois méthodes d'analyse pour conceptualiser le contenu de différentes sections des monographies des médicaments

National audienceA partir de l'expérience issue de travaux de modélisation conceptuelle des connaissances contenues dans trois sections différentes des monographies des médicaments (indication, pharmacodynamie, pharmacocinétique), une analyse des méthodes de modélisation est proposée. Les différentes méthodes (pattern matching, modélisation ascendante et approche mixte) et les modalités de leur choix sont analysées en mettant en lumière des différences de nature entre les textes et l'existence de connaissances sur le domaine. Ceci nous conduit à proposer plusieurs indicateurs descriptifs de la nature du texte qui nous semblent susceptibles d'aider au choix d'une des trois méthodes proposées. Nous proposons aussi plusieurs méthodologies d'évaluation des modèles obtenus, elles aussi étant liées aux caractéristiques des textes initiaux

Analyse et structuration automatique des guides de bonnes pratiques cliniques : essai d'évaluation

National audienceHealth Practice Guideliens are supposed to unify practices and propose recommendations to physicians. This paper describes GemFrame, a system capable of semi-automatically filling an XML template from free texts in the clinical domain. The XML template includes semantic information not explicitly encoded in the text (pairs of conditions and ac-tions/recommendations). Therefore, there is a need to compute the exact scope of condi-tions over text sequences expressing the re-quired actions. We present a system developped for this task. We show that it yields good performance when applied to the analysis of French practice guidelines. We conclude with a precise evaluation of the tool.Les guides de bonnes pratiques cliniques (GBPC) sont des textes constitués de recommandations valides dont le but est de diffuser des synthèses de résultats démontrés et de normaliser des conduites à tenir dans des situations cliniques données. L'adhésion des médecins à ces guides doit conduire à une médecine de qualité basée sur des preuves scientifiques. Cet article présente un outil appelé GemFrame, destiné à faciliter la consultation des guides en proposant de nouveaux modes d'accès sur support électronique. Pour ce faire, un travail d'analyse et de structuration des GBPC est nécessaire. Nous présentons le système GemFrame, permettant cette structuration suite à une analyse semi-automatisée. Les GBPC étant des textes d'« incitation à l'action », ils sont principalement constitués de conditions et d'actions dépendant de ces conditions. Le système GemFrame vise à reconnaître automatiquement les segments « conditions » et les « segments incitation à l'action », puis à calculer la portée des conditions sur les actions. Nous présentons ici une évaluation détaillée sur plusieurs guides. Nous montrons d'abord l'intérêt de l'approche puis nous détaillons le processus d'évaluation fondé sur la comparaison des résultats obtenus automatiquement avec ceux obtenus manuellement (suite à l'élaboration de « référence »)

Differential classification of states of consciousness using envelope- and phase-based functional connectivity

The development of sophisticated computational tools to quantify changes in the brain\u27s oscillatory dynamics across states of consciousness have included both envelope- and phase-based measures of functional connectivity (FC), but there are very few direct comparisons of these techniques using the same dataset. The goal of this study was to compare an envelope-based (i.e. Amplitude Envelope Correlation, AEC) and a phase-based (i.e. weighted Phase Lag Index, wPLI) measure of FC in their classification of states of consciousness. Nine healthy participants underwent a three-hour experimental anesthetic protocol with propofol induction and isoflurane maintenance, in which five minutes of 128-channel electroencephalography were recorded before, during, and after anesthetic-induced unconsciousness, at the following time points: Baseline; light sedation with propofol (Light Sedation); deep unconsciousness following three hours of surgical levels of anesthesia with isoflurane (Unconscious); five minutes prior to the recovery of consciousness (Pre-ROC); and three hours following the recovery of consciousness (Recovery). Support vector machine classification was applied to the source-localized EEG in the alpha (8-13 Hz) frequency band in order to investigate the ability of AEC and wPLI (separately and together) to discriminate i) the four states from Baseline; ii) Unconscious ( deep unconsciousness) vs. Pre-ROC ( light unconsciousness); and iii) responsiveness (Baseline, Light Sedation, Recovery) vs. unresponsiveness (Unconscious, Pre-ROC). AEC and wPLI yielded different patterns of global connectivity across states of consciousness, with AEC showing the strongest network connectivity during the Unconscious epoch, and wPLI showing the strongest connectivity during full consciousness (i.e., Baseline and Recovery). Both measures also demonstrated differential predictive contributions across participants and used different brain regions for classification. AEC showed higher classification accuracy overall, particularly for distinguishing anesthetic-induced unconsciousness from Baseline (83.7 ± 0.8%). AEC also showed stronger classification accuracy than wPLI when distinguishing Unconscious from Pre-ROC (i.e., deep from light unconsciousness) (AEC: 66.3 ± 1.2%; wPLI: 56.2 ± 1.3%), and when distinguishing between responsiveness and unresponsiveness (AEC: 76.0 ± 1.3%; wPLI: 63.6 ± 1.8%). Classification accuracy was not improved compared to AEC when both AEC and wPLI were combined. This analysis of source-localized EEG data demonstrates that envelope- and phase-based FC provide different information about states of consciousness but that, on a group level, AEC is better able to detect relative alterations in brain FC across levels of anesthetic-induced unconsciousness compared to wPLI

The impact of poor sleep on cognition and activities of daily living after traumatic brain injury : a review

Background/aim : Patients frequently report sleep disrup-tions or insomnia during their hospital stay, particularlyafter a traumatic brain injury (TBI). The consequences ofthese sleep disturbances on everyday activities are not welldocumented and are therefore not considered in the evalu-ation of independence in activities of daily living (ADLs).The goal of this narrative review is to explore the conse-quences of poor sleep quality on cognition and ADLs inthe acute and subacute stages of a moderate and severeTBI, when patients are in acute care or inpatient rehabili-tation.Methods:We will present an overview of normal sleepand its role in cognitive functioning, and then present thefindings of studies that have investigated sleep characteris-tics in hospital settings and the consequences of sleep dis-turbances on ADLs.Results:During hospitalisation, TBI patients presentsevere sleep disturbances such as insomnia and sleepfragmentation, which are probably influenced by both themedical condition and the hospital or rehabilitation environ-ment. Sleep disruption is associated with several cognitivedeficits, including attention, memory and executive func-tion impairments. Poor quality and/or insufficient quantityof sleep in acute TBI probably affect general functioningand ADLs calling for these cognitive functions.Conclusions and Significance:The cognitive impair-ments present following TBI are probably exacerbated bypoor sleep quality and sleep deprivation during hospitali-sation, which in turn impact ADLs among this popula-tion. Health-care personnel should further consider sleepdisturbances among people with TBI and a sleep protocolshould be established

Hippocampal spatial mechanisms relate to the development of arithmetic symbol processing in children

Understanding the meaning of abstract mathematical symbols is a cornerstone of arithmetic learning in children. Studies have long focused on the role of spatial intuitions in the processing of numerals. However, it has been argued that such intuitions may also underlie symbols that convey fundamental arithmetic concepts, such as arithmetic operators. In the present cross-sectional study, we used fMRI to investigate how and when associations between arithmetic operators and brain regions processing spatial information emerge in children from 3rd to 10th grade. We found that the mere perception of a ‘+’ sign elicited grade-related increases of spatial activity in the right hippocampus. That is, merely perceiving ‘+’ signs – without any operands – elicited enhanced hippocampal activity after around 7th grade (12–13 years old). In these children, hippocampal activity in response to a ‘+’ sign was further correlated with the degree to which calculation performance was facilitated by the preview of that sign before an addition problem, an effect termed operator-priming. Grade-related increases of hippocampal spatial activity were operation-specific because they were not observed with ‘×’ signs, which might evoke rote retrieval rather than numerical manipulation. Our study raises the possibility that hippocampal spatial mechanisms help build associations between some arithmetic operators and space throughout age and/or education

Sleep and wake disturbances following traumatic brain injury

Traumatic brain injury (TBI) is a major health concern in industrialised countries. Sleep and wake disturbances are among the most persistent and disabling sequelae after TBI. Yet, despite the widespread complaints of post-TBI sleep and wake disturbances, studies on their etiology, pathophysiology, and treatments remain inconclusive. This narrative review aims to summarise the current state of knowledge regarding the nature of sleep and wake disturbances following TBI, both subjective and objective, spanning all levels of severity and phases postinjury. A second goal is to outline the various causes of post-TBI sleep-wake disturbances. Globally, although sleep-wake complaints are reported in all studies and across all levels of severity, consensus regarding the objective nature of these disturbances is not unanimous and varies widely across studies. In order to optimize recovery in TBI survivors, further studies are required to shed light on the complexity and heterogeneity of post-TBI sleep and wake disturbances, and to fully grasp the best timing and approach for intervention