BACKGROUND:Post-traumatic stress disorder (PTSD), in its partial or full forms, is frequently observed in military populations. It is therefore important to predict the risk of PTSD prior to deployment. OBJECTIVE:Since elevated allostatic load markers have been described in PTSD, we investigated whether these alterations pre-exist before PTSD onset. Our objective was to explore the ability of four allostatic load markers (urinary and blood cortisol, BDNF and 8-iso-PGF2α) to predict partial/full PTSD onset after a 6-month deployment. METHODS:We conducted a prospective study in a French military cohort deployed to Afghanistan. PTSD was assessed before (M0) and after (M6) deployment using PTSD Checklist Scale (PCLS). At M0, only subjects who were medically fit and who scored healthy at PCLS were considered. We evaluated whether biological markers of allostatic load at M0 would predict partial/full PTSD at M6. Psychological correlates were assessed, including anxious-depressive symptoms (HAD; Hospital Anxiety and Depression), burnout (BMS; Burnout Measure-Short version), anxiety (STAI; Spielberger State-Trait Anxiety Inventory), general mood (POMS; Profile of Mood State), perceived stress (PSS; Perceived Stress Scale), alexithymia (TAS; Toronto Alexithymia scale) and mental health-related scores (GHQ-28; General Health Questionnaire-28 items). RESULTS:After controlling for age, pre-deployment PCLS scores, and the number of missions, we found that elevated M0 nocturnal urinary cortisol excretion predicted M6 partial/full PTSD. CONCLUSIONS:Asymptomatic subjects at risk of partial/full PTSD exhibit a common pattern of hypothalamic-pituitary axis dysregulation, similar to that observed in established PTSD.

BACKGROUND:Caregivers in intensive care units are exposed to high levels of stress, which were exacerbated during the COVID-19 pandemic, increasing the incidence of stress-related disorders, including burnout. METHODS:We evaluated the influence of mindfulness and coping flexibility in the early days of burnout development in a prospective study of 50 military caregivers working in a mobile resuscitation unit during the COVID-19 pandemic. We visited the participants at the end of deployment (day 0; D0) and three weeks later (D21). On D0, the participants completed questionnaires assessing mindfulness (Freiburg Mindfulness Inventory; FMI), coping flexibility (Flexcop), and burnout (Burnout Measure, Short Version; BMS). Subjective sleep symptoms were also assessed to evaluate their relationship with burnout. The BMS was repeated on D21. RESULTS:Four short-term burnout evolutions were observed: (i) "healthy" on D0 and D21; (ii) "exhausted," healthy on D0 and burnout on D21; (iii) "resilient," burnout on D0 and healthy on D21; and (iv) "burnout" on D0 and D21. Compared with healthy participants on D0, only resilient participants had lower FMI (η2 = 0.22; p = 0.032). Exhausted participants had more difficulty waking, and burnout participants had higher daytime fatigue than healthy participants. FMI scores on D0 negatively correlated with BMS scores on D21 (r = ‒0.40 r2 = 0.16 p = 0.009) for the entire population, and also after excluding burnout status at D0 (r = ‒0.41 r2 = 0.17 p = 0.02). Flexcop scores on D0 did not correlate with BMS scores on D21. CONCLUSIONS:This study underlines the importance of mindfulness in the early days of burnout onset, and suggests considering its reinforcement for prevention of burnout and its measurement as a potential biomarker of burnout risk.

Auricular neuromodulation (ANM) is a non-invasive method of stimulating the trigeminal, spinal, and vagal nerves that innervate the auricle, the outer part of the ear. ANM, and the vagal nerve stimulation in particular, has been shown to be effective in treating a number of symptoms, including pain and anxiety. However, the mechanisms by which ANM exerts its beneficial effects are still under investigation. We hypothesized that ANM produces its effects by modulating interoception, a physiological function involved in homeostatic regulation and awareness of internal physical and emotional sensations. Interoception, activated by visceral and sensory afferences, in turn modulates body function by regulating the autonomic nervous system (ANS). Therefore, we reviewed the anatomical, physiological, and pathophysiological evidence linking ANM to interoception, ultimately defining an auricle-brain axis. We propose two functional pathways that are activated directly or indirectly by the auricular nerves. The first pathway processes the sensory information coming from the parabrachial and solitary tract nuclei. The second pathway activates the monoaminergic and cholinergic pathways, thereby regulating the interoceptive response. ANM modulates the two outputs of interoception - that is, the ANS and the stress response - and changes the body response. We hypothesized that ANM provides new sensory information for interoception and thereby improves body-brain interactions previously compromised by ongoing pathological processes. Therefore, we assessed the effects of ANM on interoception-related pathologies. Finally, we evaluated whether empirical features of ANM can be explained by interoceptive mechanisms.

Background Posttraumatic stress disorder (PTSD) is a psychiatric disease that may follow traumatic exposure. Current treatments fail in about 30% of patients. Although repeated transcranial magnetic stimulation (rTMS) applied to the prefrontal cortex has been shown to be effective in the treatment of PTSD, the mechanisms need further investigation. Objective Using a PTSD animal model, we verify the beneficial effect of rTMS, and explore the changes it induces on two putative PTSD mechanisms, GABA/ glutamate neurotransmission and neuroinflammation. Methods PTSD-like symptoms were elicited in twenty-six mice using a foot-shock conditioning procedure. Fourteen of the 26 were then treated using rTMS (12 were untreated). In the control group (n=30), 18 were treated with rTMS and 12 were untreated. Animals were sacrificed after re-exposure. The infralimbic (IL) cortex, basolateral amygdala (BLA) and ventral CA1 (vCA1) were isolated using laser microdissection. mRNA was then investigated using PCR array analysis targeting GABA/ glutamate and inflammatory pathways. Results The rTMS treatment significantly decreased the contextual fear memory phenotype. These changes were associated with reduced mRNA expression related to inflammation in the IL cortex and the vCA1, and lowered mRNA-related glutamate neurotransmission and increased GABA neurotransmission in the BLA. Conclusion Our results suggest that our rTMS treatment was associated with local anti-inflammatory effects and limbic effects, which seemed to counteract PTSD effects. Several of these changes (both stress- and rTMS-induced) have implications for the drug sensitivity of limbic brain areas, and may help in the design of future therapeutic protocols.

Les défis éthiques sont des situations dans lesquelles un individu doit choisir obligatoirement entre plusieurs options, aucune n’étant satisfaisante pour lui. Il en résulte un dilemme éthique. Ces situations, quoique courantes dans les vies quotidienne et professionnelle, ont été modélisées en laboratoire afin de comprendre les dynamiques comportementales et neurobiologiques. Après la réaction rapide intuitive s’installe une réaction plus lente, mêlant émotion et cognition rationnelle, le tout dans une interaction corporelle et sous la pression du stress. Une réponse non éthique à un défi peut résulter en séquelles psychiques allant de la désadaptation, au burn-out , aux sentiments de honte et de culpabilité, voire au trouble de stress post -traumatique.

Stress can push individuals close to the threshold to depression. An individual's intrinsic vulnerability before a stressful event determines how close they come to the threshold of depression. Identification of vulnerability biomarkers at early (before the stressful event) and late (close to the threshold after the stressful event) stages would allow for corrective actions. Social defeat is a stressful event that triggers vulnerability to depression in half of exposed rats. We analyzed the sleep properties of rats before (baseline) and after (recovery) social defeat by telemetry electroencephalogram recordings. Using Gaussian partitioning, we identified three non-rapid eye movement stages (N-S1, N-S2, and N-S3) in rats based on a sleep depth index (relative δ power) and a cortical activity index (fractal dimension). We found (1) that, at baseline, N-S3 lability and high-θ relative power in wake identified, with 82% accuracy, the population of rats that will become vulnerable to depression after social defeat, and (2) that, at recovery, N-S1 instability identified vulnerable rats with 83% accuracy. Thus, our study identified early and late sleep biomarkers of vulnerability to depression, opening the way to the development of treatments at a prodromal stage for high sensitivity to stress, and for stress-induced vulnerability to depression.

IntroductionInjuries induced by falls represent the main cause of failure in the French Navy Special Forces selection course. In the present study, we made the assumption that probing the posture might contribute to predicting the risk of fall-related injury at the individual level.MethodsBefore the start of the selection course, the postural signals of 99 male soldiers were recorded using static posturography while they were instructed to maintain balance with their eyes closed. The event to be predicted was a fall-related injury during the selection course that resulted in the definitive termination of participation. Following a machine learning methodology, we designed an artificial neural network model to predict the risk of fall-related injury from the descriptors of postural signal.ResultsThe neural network model successfully predicted with 69.9% accuracy (95% CI 69.3-70.5) the occurrence of a fall-related injury event during the selection course from the selected descriptors of the posture. The area under the curve value was 0.731 (95% CI 0.725-0.738), the sensitivity was 56.8% (95% CI 55.2-58.4) and the specificity was 77.7% (95% CI 76.8-0.78.6).ConclusionIf confirmed with a larger sample, these findings suggest that probing the posture using static posturography and machine learning-based analysis might contribute to inform risk assessment of fall-related injury during military training, and could ultimately lead to the development of novel programmes for personalised injury prevention in military population.

Le stress est la réaction biologique aspécifique et automatique observée lors de l’exposition à un stresseur et qui s’articule autour du système nerveux autonome et de l’axe corticotrope. Ils sont contrôlés par un réseau cérébral centré par l’amygdale. L’agression induit un stress dont l’intensité dépend de la violence et de la proximité du stresseur, de la capacité d’action de la victime. Un stresseur proche, une victime sans capacité d’action rend probable l’apparition d’un Trouble de stress post -traumatique (TSPT). L’exposition répétée à des stresseurs conduit à l’usure (anxiété, burn-out , dépression). L’aguerrissement qui module le stress peut être guidé par des marqueurs biologiques. D’autres indicateurs pourraient suivre la récupération.

IntroductionDepending on the individual, exposure to an intense stressor may, or may not, lead to a stress-induced pathology. Predicting the physiopathological evolution in an individual is therefore an important challenge, at least for prevention. In this context, we developed an ethological model of simulated predator exposure in rats: we call this the multisensorial stress model (MSS). We hypothesized that: (i) MSS exposure can induce stress-induced phenotypes, and (ii) an electrocorticogram (ECoG) recorded before stress exposure can predict phenotypes observed after stress.MethodsForty-five Sprague Dawley rats were equipped with ECoG telemetry and divided into two groups. The Stress group (n = 23) was exposed to an MSS that combined synthetic fox feces odor deposited on filter paper, synthetic blood odor, and 22 kHz rodent distress calls; the Sham group (n = 22) was not exposed to any sensorial stimulus. Fifteen days after initial exposure, the two groups were re-exposed to a context that included a filter paper soaked with water as a traumatic object (TO) reminder. During this re-exposure, freezing behavior and avoidance of the filter paper were measured.ResultsThree behaviors were observed in the Stress group: 39% developed a fear memory phenotype (freezing, avoidance, and hyperreactivity); 26% developed avoidance and anhedonia; and 35% made a full recovery. We also identified pre-stress ECoG biomarkers that accurately predicted cluster membership. Decreased chronic 24 h frontal Low θ relative power was associated with resilience; increased frontal Low θ relative power was associated with fear memory; and decreased parietal β2 frequency was associated with the avoidant-anhedonic phenotype.DiscussionThese predictive biomarkers open the way to preventive medicine for stress-induced diseases.

Les situations dans lesquelles on peut ne pas bien dormir, même s’il faut dormir, sont souvent la conséquence d’un excès d’activation durant la journée précédente (chaleur, exercice excessif, peur…) ou d’un environnement agressif durant le sommeil (chaleur, froid, bruit…). Un mauvais sommeil peut également s’expliquer par un excès de réactivité de l’individu à un environnement pourtant modérément agressif. La qualité du sommeil, reflet de l’interaction entre individu et environnement, a donc le stress pour médiateur. Les contre-mesures dépendent alors du contexte et des mécanismes de l’insomnie et peuvent associer nouvelles technologies et recettes éprouvées.

INTRODUCTION:Over the past two decades, overseas deployments of the French Army have been characterized by the exposure of its service personnel to sustained, high levels of combat stress. There is a need to assess their mental health throughout the deployment cycle, identify risk factors associated with stress-related disorders, and characterize the factors that promote long-term well-being.METHODS:We conducted two pilot studies within four units of the French Army: a conventional combat unit, a counterterrorist unit, a combat service support unit, and a medical support unit. Study 1 (n = 65) analyzed the psychological functioning of service personnel with respect to their personality and stress management characteristics. Study 2 (n = 40) analyzed the impact of overseas deployment on stress-related psychological outcomes.RESULTS:Overall, results from study 1 showed that service personnel have a protective psychological functioning, which is particularly developed in the counterterrorist unit. In study 2, although no stress-related disorder symptoms were observed with the psychometric tools used, a certain degree of psychological dysfunction (social dysfunction and lower positive affect) was detected post-deployment.CONCLUSIONS:These two complementary studies are key elements in developing a better understanding of unmet, medico-military needs that lie on the pathway that links exposure to stressors to impaired health. Certain personnel enrolled in the French Army (notably, the counterterrorist unit) were found to have a high level of protective psychological functioning, largely due to the training they receive. Nevertheless, overall, overseas deployment was associated with poorer psychological functioning and the emergence of social dysfunction, especially in units responsible for the care of service personnel (medical support and combat service support units).

The fast reaction of the autonomic nervous system (ANS) to an emotional challenge (EC) is the result of a functional coupling between parasympathetic (PNS) and sympathetic (SNS) branches. This coupling can be characterized by measures of cross-correlations between electrodermal activity (EDA) (under the influence of the SNS) and the RR interval (the interval between R peaks) (under the influence of the PNS and the SNS). Significant interindividual variability has previously been reported in SNS-PNS coupling in emotional situations, and the present study aimed to identify interindividual cross-correlation variability in ANS reactivity. We therefore studied EDA and the RR interval in 62 healthy subjects, recorded during a 24-minute EC. A Gaussian Mixture Model was used to cluster tonic EDA-RR cross-correlations during the EC. This identified two clusters that were characterized by significant or non-significant cross-correlations (SCC and NCC clusters, respectively). The SCC cluster reported higher negative emotion after the EC, while the NCC cluster reported higher scores on the Center for Epidemiologic Studies-Depression scale. The latter finding suggests that NCC is a pathological mood pattern with altered negative perception. Furthermore, a machine learning model that included three parameters indexing the functionality of both branches of the ANS, measured at baseline, predicted cluster membership. Our results are a first step in detecting dysfunctional ANS reactivity in general population.

(1) Background: While a number of studies among military personnel focus on specific pathologies such as post-traumatic stress disorder (PTSD), anxiety, and depression, they do not address the cumulative impact on mental health of stressors related to the profession. The present study aims to determine the relationship between allostatic load and mental health status in a cohort of fit-for-duty soldiers prior to their deployment to Afghanistan. The aim is to better-define the consequences of stressor adjustment. (2) Methods: A cohort of 290 soldiers was evaluated in a cross-sectional study with respect to psychopathology (PTSD, anxiety, depression), psychological functioning (stress reactivity, psychological suffering), and allostatic profile (urinary cortisol and 8-iso-PGF2α, blood cortisol and BDNF). A hierarchical cluster analysis was used to identify allostatic patterns. (3) Results: Around 10% of the cohort reported high scores for psychopathology, and biological alterations were identified. For the remainder, four allostatic profiles could be identified by their psychological functioning. (4) Conclusions: Both biological and psychological assessments are needed to characterize subthreshold symptomatology among military personnel. The psychological significance of allostatic load should be considered as a way to improve health outcomes.

The enhancement of body awareness is proposed as one of the cognitive mechanisms that characterize mindfulness. To date, this hypothesis is supported by self-report and behavioral measures but still lacks physiological evidence. The current study investigated relation between trait mindfulness (i.e., individual differences in the ability to be mindful in daily life) and body awareness in combining a self-report measure (Multidimensional Assessment of Interoceptive Awareness [MAIA] questionnaire) with analysis of the heartbeat evoked potential (HEP), which is an event-related potential reflecting the cortical processing of the heartbeat. The HEP data were collected from 17 healthy participants under five minutes of resting-state condition. In addition, each participant completed the Freiburg Mindfulness Inventory and the MAIA questionnaire. Taking account of the important variability of HEP effects, analyses were replicated with the same participants three times (in three distinct sessions). First, group-level analyses showed that HEP amplitude and trait mindfulness do not correlate. Secondly, we observed that HEP amplitude could positively correlate with self-reported body awareness; however, this association was unreliable over time. Interestingly, we found that HEP measure shows very poor reliability over time at the individual level, potentially explaining the lack of reliable association between HEP and psychological traits. Lastly, a reliable positive correlation was found between self-reported trait mindfulness and body awareness. Taken together, these findings provide preliminary evidence that the HEP might not support the increased subjective body awareness in trait mindfulness, thus suggesting that perhaps objective and subjective measures of body awareness could be independent.

Studies focusing on the interaction of dietary and acute emotional stress on oxidative stress in cortex frontal and in brain mitochondria are scarce. Dietary-induced insulin resistance, as observed in Western diets, has been associated with increased oxidative stress causing mitochondrial dysfunction. We hypothesized that acute emotional stress could be an aggravating factor by impacting redox status in cortex and brain mitochondria. Thus, the aim of the present study was to evaluate the combination of an insulin resistance inducing high-fat/high-fructose (HF/HFr) diet and acute emotional stress on brain oxidative stress in rats. We measured several oxidative stress parameters (carbonyls, FRAP, TBARS assays, GSH, GSSG, oxidized DNA, mRNA expression of redox proteins (Nrf2), and uric acid). The HF/HFr diet resulted in increased oxidative stress both in the brain mitochondria and in the frontal cortex and decreased expression of the Nrf2 gene. The emotional stress induced an oxidative response in plasma and in brain mitochondria of the control group. In the HF/HFr group it triggered an increase expression of the redox transcription factor Nrf2 and its downstream antioxidant genes. This suggests an improvement of the redox stress tolerance in response to an enhanced production of reactive oxygen species. Accordingly, a blunted oxidative effect on several markers was observed in plasma and brain of HF/HFr-stressed group. This was confirmed in a parallel study using lipopolysaccharide as a stress model. Beside the Nrf2 increase, the stress induced a stronger UA release in HF/HFr which could take a part in the redox stress.

Editor—Acute stress has been shown to decrease performance of cognitive tasks. Health professionals are often required to make cognitive decisions during stressful situations. Residents trained in stress management strategies (tactics to optimise potential [TOP]) show improved performance when coping with critical situations during high-fidelity simulation (HFS).1Sigwalt F. Petit G. Evain J.-N. et al.Stress management training improves overall performance during critical simulated situations: a prospective randomized controlled trial.Anesthesiology. 2020; 133: 198-211Crossref PubMed Scopus (1) Google Scholar Performance enhancement might result from the effect of TOP on stress regulation, leading to a more controlled biological stress reaction or balanced arousal with the subject being better prepared for action. Separating electrodermal activity (EDA) into its tonic (i.e. slow variation) and phasic (i.e. fast variation) components identifies the arousal phenomenon and sympathetic nervous system activity.2Greco A. Valenza G. Lanata A. Scilingo E.P. Citi L. cvxEDA: a convex optimization approach to electrodermal activity processing.IEEE Trans Biomed Eng. 2016; 63: 797-804PubMed Google Scholar These EDA components are under the influence of two neuroanatomical networks.3Nagai Y. Critchley H.D. Featherstone E. Trimble M.R. Dolan R.J. Activity in ventromedial prefrontal cortex covaries with sympathetic skin conductance level: a physiological account of a "default mode" of brain function.Neuroimage. 2004; 22: 243-251Crossref PubMed Scopus (316) Google Scholar The tonic component is influenced by the orbitofrontal and ventromedial prefrontal cortices, whilst the phasic component is influenced by various brain areas, including the thalamus, hypothalamus, striate and extra-striate cortices, anterior cingulate and insular cortices, and some lateral regions of the prefrontal cortex.3Nagai Y. Critchley H.D. Featherstone E. Trimble M.R. Dolan R.J. Activity in ventromedial prefrontal cortex covaries with sympathetic skin conductance level: a physiological account of a "default mode" of brain function.Neuroimage. 2004; 22: 243-251Crossref PubMed Scopus (316) Google Scholar Both are mobilised during stress: tonic EDA increases, whilst the phasic EDA bursts increase in both amplitude and frequency.4McNeal K.S. Spry J.M. Mitra R. Tipton J.L. Measuring student engagement, knowledge, and perceptions of climate change in an introductory environmental geology course.J Geosci Educ. 2014; 62: 655-667Crossref Google Scholar Both stress dimensions were better controlled in senior residents, indicating that experience reduces perceived stress.5Abdulghani H.M. Al-Harbi M.M. Irshad M. Stress and its association with working efficiency of junior doctors during three postgraduate residency training programs.Neuropsychiatr Dis Treat. 2015; 11: 3023-3029Crossref PubMed Scopus (21) Google Scholar As TOP decreases perceived stress in residents,1Sigwalt F. Petit G. Evain J.-N. et al.Stress management training improves overall performance during critical simulated situations: a prospective randomized controlled trial.Anesthesiology. 2020; 133: 198-211Crossref PubMed Scopus (1) Google Scholar we wanted to explore the impact of TOP on the EDA components. The effect of TOP on the performance of 128 anaesthesia residents facing a critical situation in HFS was studied in a prospective RCT.1Sigwalt F. Petit G. Evain J.-N. et al.Stress management training improves overall performance during critical simulated situations: a prospective randomized controlled trial.Anesthesiology. 2020; 133: 198-211Crossref PubMed Scopus (1) Google Scholar Assessment of the mechanism of action of TOP through EDA analysis was an ancillary objective. The study protocol was pre-registered on October 6, 2016 on ClinicalTrials.gov (NCT02926599) and was approved by the Institutional Review Board of the Comité de Protection des Personnes SUD-EST II (2016-089). Residents received general information about the study and then gave their written individual informed consent. They were randomised into two parallel arms: TOP or control. The TOP training consisted of five 60 min sequences given once a week for five consecutive weeks by two instructors and ending 1 month before the high-fidelity simulation. TOP consist of techniques, such as mental imagery, cardiac coherence biofeedback, and sensory relaxation.6Trousselard M. Dutheil F. Ferrer M.-H. Babouraj N. Canini F. Tactics to optimize the potential and CardioBioFeedback in stress management: the French experience.Med Acupunct. 2015; 27: 367-375Crossref Scopus (4) Google Scholar In our study, TOP was focused on breathing control using relaxing and revitalising breathing techniques and on optimisation of readiness through mental rehearsal of the upcoming actions (Supplementary material 1.A). The control group did not have any training. Senior residents were defined as those having responsibility for on-call duty (which in France means >3 yr experience). On the day of the high-fidelity simulation, participants were equipped with a wristband measuring device (E4 Empatica Srl, Milan, Italy) on their dominant hand for continuous measurements of EDA at a sampling rate of 4 Hz. The high-fidelity simulation was explained to the participants (briefing). The TOP group participants were then asked to sit down and perform the previously learned TOP exercises for 5 min (Supplementary material 1.B), whilst the control group participants only read laboratory test results. Thereafter, all participants did one critical simulated scenario followed by a debriefing. EDA was measured over four distinct time periods: briefing, intervention, scenario, and debriefing. We considered that 93 out of the 128 participants had complete EDA recordings, whilst the remainder had incomplete recordings because of technical problems. EDA was normalised using the z-score. Its phasic and tonic components were extracted using a validated convex optimisation algorithm that defines EDA as the sum of a tonic, phasic, and noise component.2Greco A. Valenza G. Lanata A. Scilingo E.P. Citi L. cvxEDA: a convex optimization approach to electrodermal activity processing.IEEE Trans Biomed Eng. 2016; 63: 797-804PubMed Google Scholar This algorithm solves EDA deconstruction by a quadratic optimisation approach.2Greco A. Valenza G. Lanata A. Scilingo E.P. Citi L. cvxEDA: a convex optimization approach to electrodermal activity processing.IEEE Trans Biomed Eng. 2016; 63: 797-804PubMed Google Scholar The mean tonic EDA (mtEDA) and the maximum phasic EDA (mapEDA) were calculated for each subject during each period of the high-fidelity simulation. Statistical analysis was performed using analysis of variance for repeated measures comparing conditioning (TOP [n=43] or control [n=50]) and experience (junior [<3 yr; n=47] or senior [≥3 yr; n=46]). The interaction conditioning∗experience corresponded to the combined effects of the TOP and experience. The statistical threshold was set at P<0.05, and post hoc Bonferroni tests for all pairs were performed if necessary. The mtEDA showed a significant experience effect (F[3267]=4.12; P<0.01) unrelated to conditioning. Post hoc analysis showed that seniors exhibited a lower mtEDA than juniors during the scenario and debriefing periods (P<0.01 and P<0.05, respectively; Fig. 1a). The mapEDA showed a significant intervention effect (F[3267]=3.45; P<0.05) without an experience effect or any interaction. Compared with the control participants, the TOP participants did not have a mapEDA increase during the intervention or other periods (Fig. 1b). During the debriefing, the mapEDA of control participants was higher than that of control and TOP participants during intervention (P<0.001 and P<0.05, respectively). Depending on which component is considered, EDA may also indicate the brain networks involved. Experience has a major effect on the tonic EDA. Senior residents had a lower sympathetic tone than juniors. Moreover, seniors, in contrast to juniors, did not experience an increase of tonic EDA during the scenario. Thus, experience may modulate the orbitofrontal and ventromedial prefrontal cortices in agreement with the known role of the ventromedial prefrontal cortex in coding the latent structures of experience, the causal links, and the task-related cognitive maps.7Mack M.L. Preston A.R. Love B.C. Ventromedial prefrontal cortex compression during concept learning.Nat Commun. 2020; 11: 46Crossref PubMed Scopus (26) Google Scholar The mapEDA is a reliable marker of sympathetic activity,2Greco A. Valenza G. Lanata A. Scilingo E.P. Citi L. cvxEDA: a convex optimization approach to electrodermal activity processing.IEEE Trans Biomed Eng. 2016; 63: 797-804PubMed Google Scholar which has been reported to increase in residents practising high-fidelity simulation.8Phitayakorn R. Minehart R.D. Hemingway M.W. Pian-Smith M.C.M. Petrusa E. Relationship between physiologic and psychological measures of autonomic activation in operating room teams during a simulated airway emergency.Am J Surg. 2015; 209: 86-92Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar As the mapEDA was steady in TOP participants but not in controls during the simulation scenario,1Sigwalt F. Petit G. Evain J.-N. et al.Stress management training improves overall performance during critical simulated situations: a prospective randomized controlled trial.Anesthesiology. 2020; 133: 198-211Crossref PubMed Scopus (1) Google Scholar it appears that TOP contributes to stress regulation and reduced sympathetic activation. This is in agreement with the decreased subjective feeling of stress in TOP participants.1Sigwalt F. Petit G. Evain J.-N. et al.Stress management training improves overall performance during critical simulated situations: a prospective randomized controlled trial.Anesthesiology. 2020; 133: 198-211Crossref PubMed Scopus (1) Google Scholar Furthermore, the better regulation of phasic EDA in TOP participants reinforces the concept of downregulation of the amygdala observed with functional MRI after other cognitive therapy,9Gingnell M. Frick A. Engman J. et al.Combining escitalopram and cognitive-behavioural therapy for social anxiety disorder: randomised controlled fMRI trial.Br J Psychiatry. 2016; 209: 229-235Crossref PubMed Scopus (24) Google Scholar as the amygdala, part of the limbic system, controls the phasic component of the sympathetic nervous system.10Sinha G.R. Suri J.S. Cognitive informatics, computer modelling, and cognitive science: volume 2: application to neural engineering, robotics, and STEM. Elsevier, London2020Google Scholar Using the components of EDA, we show for the first time that experience and stress management strategies may modulate two different pathways controlling the stress reaction. The authors thank Jacques Escarment (Direction Régionale du Service de Santé des Armées) for his support and encouragement for the tactics to optimise potential (TOP) training study; Carole Sage for her help with scheduling residents for TOP training and for simulation; students, simulation instructors, and simulation technicians of Université Claude-Bernard Lyon 1 Simulation Centre, Lyon, France; and Christopher Blakeley (London, UK) for substantial English revision of the paper. The authors declare that they have no conflicts of interest. 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STUDY OBJECTIVES:The regulation of sleep-wake cycles is crucial for the brain's health and cognitive skills. Among the various substances known to control behavioral states, intraventricular injection of neuropeptide S (NPS) has already been shown to promote wakefulness. However, the NPS signaling pathway remains elusive. In this study, we characterized the effects of NPS in the ventrolateral preoptic nucleus (VLPO) of the hypothalamus, one of the major brain structures regulating non-rapid eye movement (NREM) sleep.METHODS:We combined polysomnographic recordings, vascular reactivity, and patch-clamp recordings in mice VLPO to determine the NPS mode of action.RESULTS:We demonstrated that a local infusion of NPS bilaterally into the anterior hypothalamus (which includes the VLPO) significantly increases awakening and specifically decreases NREM sleep. Furthermore, we established that NPS application on acute brain slices induces strong and reversible tetrodotoxin (TTX)-sensitive constriction of blood vessels in the VLPO. This effect strongly suggests that the local neuronal network is downregulated in the presence of NPS. At the cellular level, we revealed by electrophysiological recordings and in situ hybridization that NPSR mRNAs are only expressed by non-Gal local GABAergic neurons, which are depolarized by the application of NPS. Simultaneously, we showed that NPS hyperpolarizes sleep-promoting neurons, which is associated with an increased frequency in their spontaneous IPSC inputs.CONCLUSION:Altogether, our data reveal that NPS controls local neuronal activity in the VLPO. Following the depolarization of local GABAergic neurons, NPS indirectly provokes feed-forward inhibition onto sleep-promoting neurons, which translates into a decrease in NREM sleep to favor arousal.

'We are at war', French President Emmanuel Macron said in an address to the nation on 16 March 2020. As part of this national effort, the French Military Medical Service (FMMS) is committed to the fight against COVID-19. This original report aimed to describe and detail actions that the FMMS has carried out in the nationwide fight against the COVID-19 pandemic in France, as well as overseas. Experts in the field reported major actions conducted by the FMMS during the COVID-19 pandemic in France. In just few weeks, the FMMS developed ad hoc medical capabilities to support national health authorities. It additionally developed adaptive, collective en route care via aeromedical and naval units and deployed a military intensive care field hospital. A COVID-19 crisis cell coordinated the French Armed Forces health management. The French Military Centre for Epidemiology and Public Health provided all information needed to guide the decision-making process. Medical centres of the French Armed Forces organised the primary care for military patients, with the widespread use of telemedicine. The Paris Fire Brigade and the Marseille Navy Fire Battalion emergency departments ensured prehospital management of patients with COVID-19. The eight French military training hospitals cooperated with civilian regional health agencies. The French military medical supply chain supported all military medical treatment facilities in France as well as overseas, coping with a growing shortage of medical equipment. The French Armed Forces Biomedical Research Institute performed diagnostics, engaged in multiple research projects, updated the review of the scientific literature on COVID-19 daily and provided expert recommendations on biosafety. Finally, even students of the French military medical academy volunteered to participate in the fight against the COVID-19 pandemic. In conclusion, in an unprecedented medical crisis, the FMMS engaged multiple innovative and adaptive actions, which are still ongoing, in the fight against COVID-19. The collaboration between military and civilian healthcare systems reinforced the shared objective to achieve the goal of 'saving the greatest number'.

Alexithymia is usually described by three main dimensions difficulty identifying feelings (DIF), difficulty describing feelings (DDF), and externally oriented thinking (EOT). The most commonly used questionnaire investigating alexithymia, the Toronto Alexithymia Scale (TAS-20), supports this three-factor structure. One important assumption is that alexithymia severity is associated to vulnerability to somatic diseases, among them gastrointestinal disorders. However, the association between alexithymia and gastrointestinal disorders is not systematic, thus questioning the role of alexithymia as a vulnerability factor for those illnesses. A recent factor analysis suggested another four-factor structure for the TAS-20: difficulties in awareness of feelings (DAF), difficulties in interoceptive abilities (DIA), externally oriented thinking (EOT), and poor affective sharing (PAS). We assume that DIA and DAF might be more relevant to investigate the association between alexithymia and gastrointestinal disorders. The rationale is that DIA and DAF reflect impairments in emotion regulation that could contribute to an inappropriate autonomic and HPA axis homeostasis in irritable bowel syndrome (IBS), ulcerative colitis (UC), or Crohn’s disease (CD). The aim of this study was to investigate whether DIA and DAF are associated with the presence of IBS, UC or CD, while checking for anxiety, depression, parasympathetic (vagus nerve) activity and cortisol levels. We recruited control participants (n=26), and patients in remission who were diagnosed with IBS (n=24), UC (n=18), or CD (n=21). Participants completed questionnaires to assess anxiety, depression, and alexithymia. A blood sample and an electrocardiogram were used to measure the level of cortisol and parasympathetic activity, respectively. Logistic regressions with the four-factor structure of the TAS-20 revealed that DIA was a significant predictor of IBS (W(1)=6.27, p=.01). Conversely, DIA and DAF were not significant predictors in CD and UC patients. However, low cortisol level was a significant predictor of UC (W(1)=4.67, p=.035). Additional logistic regressions based on the original 3-factor structure of TAS-20 (DIF, DDF, and EOT) showed that only DDF was a significant predictor of CD [W(1)=6.16, p < .001]. The present study suggests that DIA is an important dimension for assessing potential risk for gastrointestinal diseases, in particular for IBS.