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Céline Borg,1–3 Florian Chouchou,4 Jenny Dayot-Gorlero,3 Perrine Zimmerman,1 Delphine Maudoux,5 Bernard Laurent,1,4 George A Michael3 1Neurology/Neuropsychology CMRR Unit, Hospital Nord, Saint-Priest-en-Jarez, France; 2Department of Psychology, University of Lyon, Lyon, France; 3Université de Lyon, Université Lyon 2, Laboratory EMC (EA 3082), Bron, France; 4Central Integration of Pain (NeuroPain), Inserm U1028, UCB Lyon1, Saint-Etienne, France; 5EA SNA-EPIS, Department of Clinical and Exercise Physiology, CHU de Saint-Etienne, Saint-Etienne, France Introduction: This study investigated interoception in fibromyalgia (FM), a disorder characterized by chronic pain accompanied by mood deregulation. Based on observations on the relationship between somatosensory processing and pain in FM and considering the affective symptoms of this disorder, we tested in FM three dimensions of interoception: interoceptive accuracy (IA), interoceptive awareness (IAW) and interoceptive sensibility (IS).Materials and methods: Twenty-one female FM patients (Mage = 50.3) and 21 female matched controls (Mage = 46.3) completed a heartbeat tracking task as an assessment of IA, rated confidence in their responses as a measure of IAW and completed the Multidimensional Assessment of Interoceptive Awareness as a measure of IS. Furthermore, they completed self-report scales that, according to a principal component analysis, targeted anxiety, emotional consciousness and pain-related affect and reactions.Results: Multiple regression analyses showed that increased pain-related affect and reactions decrease IA in FM. When the results of each group were examined separately, such effect was found only in FM patients. On its turn, IS was predicted by emotional consciousness and pain-related affect and reactions, but these effects did not differ between FM and controls. Finally, none of the variables we used predicted IAW.Discussion: Pain-related affect and reactions in FM patients can reduce their interoceptive ability. Our results help to better understand the integration between bodily signals and emotional processing in chronic pain. Keywords: fibromyalgia, interoception, heartbeat perception, pain, emotion

Homeostatic regulation plays a fundamental role in maintenance of multicellular life. At different scales and in different biological systems, this principle allows a better understanding of biological organization. Consequently, a growing interest in studying cause-effect relations between physiological systems has emerged, such as in the fields of cardiovascular and cardiorespiratory regulations. For this, mathematical approaches such as Granger causality (GC) were applied to the field of cardiovascular physiology in the last 20 years, overcoming the limitations of previous approaches and offering new perspectives in understanding cardiac, vascular and respiratory homeostatic interactions. In clinical practice, continuous recording of clinical data of hospitalized patients or by telemetry has opened new applicability for these approaches with potential early diagnostic and prognostic information. In this review, we describe a theoretical background of approaches based on linear GC in time and frequency domains applied to detect couplings between time series of RR intervals, blood pressure and respiration. Interestingly, these tools help in understanding the contribution of homeostatic negative feedback and the anticipatory feedforward mechanisms in homeostatic cardiovascular and cardiorespiratory controls. We also describe experimental and clinical results based on these mathematical tools, consolidating previous experimental and clinical evidence on the coupling in cardiovascular and cardiorespiratory studies. Finally, we propose perspectives allowing to complete the understanding of these interactions between cardiovascular and cardiorespiratory systems, as well as the interplay between brain and cardiac, and vascular and respiratory systems, offering a high integrative view of cardiovascular and cardiorespiratory homeostatic regulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pichot, Corbier and Chouchou.)

Insomnia treatment among individuals with comorbid insomnia and obstructive sleep apnea is suboptimal. In a pilot randomized controlled trial, 19 individuals with comorbid insomnia and obstructive sleep apnea were allocated to one of two arms: EX + EX, consisting of two 8-week phases of exercise training (EX), or RE + CBTiEX, encompassing 8 weeks of relaxation training (RE) followed by 8 weeks of combined cognitive-behavioral therapy and exercise (CBTiEX). Outcomes included Insomnia Severity Index (ISI), polysomnography, and cardiorespiratory fitness measures. A mixed-model analysis of variance revealed a Group × Time interaction on peak oxygen consumption change, F(1, 14) = 10.1, p = .007, and EX increased peak oxygen consumption (p = .03, g' = -0.41) and reduced ISI (p = .001, g' = 0.82) compared with RE (p = .49, g = 0.16) post-8 weeks. Post-16 weeks, there was a significant Group × Time interaction (p = .014) driven by RE + CBTiEX yielding a larger improvement in ISI (p = .023, g' = 1.48) than EX + EX (p = .88, g' < 0.1). Objective sleep was unchanged. This study showed promising effects of regular EX alone and combined with cognitive-behavioral therapy for insomnia on ISI in comorbid insomnia and obstructive sleep apnea.

Objective: Sudden and unexpected deaths in epilepsy (SUDEP) pathophysiology may involve an interaction between respiratory dysfunction and sleep/wake state regulation. We investigated whether patients with epilepsy exhibit impaired sleep apnea-related arousals., Methods: Patients with drug-resistant (N = 20) or drug-sensitive (N = 20) epilepsy and obstructive sleep apnea, as well as patients with sleep apnea but without epilepsy (controls, N = 20) were included. We explored (1) the respiratory arousal threshold based on nadir oxygen saturation, apnea-hypopnea index, and fraction of hypopnea among respiratory events; (2) the cardiac autonomic response to apnea/hypopnea quantified as percentages of changes from the baseline in RR intervals (RRI), high (HF) and low (LF) frequency powers, and LF/HF., Results: The respiratory arousal threshold did not differ between groups. At arousal onset, RRI decreased (-9.42%) and LF power (179%) and LF/HF ratio (190%) increased. This was followed by an increase in HF power (118%), p < 0.05. The RRI decrease was lower in drug-resistant (-7.40%) than in drug-sensitive patients (-9.94%) and controls (-10.91%), p < 0.05. LF and HF power increases were higher in drug-resistant (188%/126%) than in drug-sensitive patients (172%/126%) and controls (177%/115%), p < 0.05., Conclusions: Cardiac reactivity following sleep apnea is impaired in drug-resistant epilepsy., Significance: This autonomic dysfunction might contribute to SUDEP pathophysiology., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Recent evidence suggests that the autonomic nervous system can contribute to memory consolidation during sleep. Whether fluctuations in cardiac autonomic activity during sleep following physical exercise contribute to the process of memory consolidation has not been studied. We assessed the effects of a non-rapid eye movement (NREM) nap following acute exercise on cardiac autonomic regulation assessed with heart rate variability (HRV) to examine if HRV influences memory processes. Fifty-six (59% female) healthy young adults (23.14 ± 3.74 years) were randomly allocated to either the exercise plus nap (ExNap, n = 27) or nap alone (NoExNap, n = 29) groups. The ExNap group performed a 40-minute moderate-intensity cycling, while the NoExNap group was sedentary prior to learning 45 neutral pictures for a later test. Subsequently, participants underwent a 60-minute NREM nap while measuring EKG, followed by a visual recognition test. Our results indicated that heart rate did not significantly differ between the groups (p = .243), whereas vagally mediated HRV indices were lower in the ExNap group compared to the NoExNap group (p < .05). There were no significant differences in sleep variables between the groups (p > .05). Recognition accuracy was significantly higher in the ExNap group than in the NoExNap group (p = .027). In addition, the recognition accuracy of the ExNap group was negatively associated with vagally mediated HRV (p < .05). Pre-nap acute exercise appears to attenuate parasympathetic activity and to alter the relationship between memory and cardiac autonomic activity., (© 2023 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Introduction: Simultaneous beat-to-beat R-R intervals, blood pressure and respiration signals are routinely analyzed for the evaluation of autonomic cardiovascular and cardiorespiratory regulations for research or clinical purposes. The more recognized analyses are i) heart rate variability and cardiac coherence, which provides an evaluation of autonomic nervous system activity and more particularly parasympathetic and sympathetic autonomic arms; ii) blood pressure variability which is mainly linked to sympathetic modulation and myogenic vascular function; iii) baroreflex sensitivity; iv) time-frequency analyses to identify fast modifications of autonomic activity; and more recently, v) time and frequency domain Granger causality analyses were introduced for assessing bidirectional causal links between each considered signal, thus allowing the scrutiny of many physiological regulatory mechanisms. Methods: These analyses are commonly applied in various populations and conditions, including mortality and morbidity predictions, cardiac and respiratory rehabilitation, training and overtraining, diabetes, autonomic status of newborns, anesthesia, or neurophysiological studies. Results: We developed CVRanalysis , a free software to analyze cardiac, vascular and respiratory interactions, with a friendly graphical interface designed to meet laboratory requirements. The main strength of CVRanalysis resides in its wide scope of applications: recordings can arise from beat-to-beat preprocessed data (R-R, systolic, diastolic and mean blood pressure, respiration) or raw data (ECG, continuous blood pressure and respiratory waveforms). It has several tools for beat detection and correction, as well as setting of specific areas or events. In addition to the wide possibility of analyses cited above, the interface is also designed for easy study of large cohorts, including batch mode signal processing to avoid running repetitive operations. Results are displayed as figures or saved in text files that are easily employable in statistical softwares. Conclusion: CVRanalysis is freely available at this website: anslabtools.univ-st-etienne.fr. It has been developed using MATLAB ® and works on Windows 64-bit operating systems. The software is a standalone application avoiding to have programming skills and to install MATLAB. The aims of this paper area are to describe the physiological, research and clinical contexts of CVRanalysis , to introduce the methodological approach of the different techniques used, and to show an overview of the software with the aid of screenshots., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pichot, Corbier, Chouchou, Barthélémy and Roche.)

Some of the most important integrative control centers for the autonomic nervous system are located in the brainstem and the hypothalamus. However, growing recent neuroimaging evidence support that a set of cortical regions, named the central autonomic network (CAN), is involved in autonomic control and seems to play a major role in continuous autonomic cardiac adjustments to high-level emotional, cognitive or sensorimotor cortical activities. Intracranial explorations during stereo-electroencephalography (SEEG) offer a unique opportunity to address the question of the brain regions involved in heart-brain interaction, by studying: (i) direct cardiac effects produced by the electrical stimulation of specific brain areas; (ii) epileptic seizures inducing cardiac modifications; (iii) cortical regions involved in cardiac interoception and source of cardiac evoked potentials. In this review, we detail the available data assessing cardiac central autonomic regulation using SEEG, address the strengths and also the limitations of this technique in this context, and discuss perspectives. The main cortical regions that emerge from SEEG studies as being involved in cardiac autonomic control are the insula and regions belonging to the limbic system: the amygdala, the hippocampus, and the anterior and mid-cingulate. Although many questions remain, SEEG studies have already demonstrated afferent and efferent interactions between the CAN and the heart. Future studies in SEEG should integrate these afferent and efferent dimensions as well as their interaction with other cortical networks to better understand the functional heart-brain interaction., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

When exposed to a viral infection, the attacked cells promptly set up defense mechanisms. As part of the antiviral responses, the innate immune interferon pathway and associated interferon-stimulated genes notably allow the production of proteins bearing antiviral activity. Numerous viruses are able to evade the interferon response, highlighting the importance of controlling this pathway to ensure their efficient replication. Several viruses are also known to manipulate the metabolism of infected cells to optimize the availability of amino acids, nucleotides, and lipids. They then benefit from a reprogramming of the metabolism that favors glycolysis instead of mitochondrial respiration. Given the increasingly discussed crosstalk between metabolism and innate immunity, we wondered whether this switch from glycolysis to mitochondrial respiration would be beneficial or deleterious for an efficient antiviral response. We used a cell-based model of metabolic reprogramming. Interestingly, we showed that increased mitochondrial respiration was associated with an enhanced interferon response following polyriboinosinic:polyribocytidylic acid (poly:IC) stimulation. This suggests that during viral infection, the metabolic reprogramming towards glycolysis is also part of the virus' strategies to inhibit the antiviral response.

Objective: fibromyalgia is a complex chronic pain syndrome characterized by widespread musculoskeletal pain, insomnia and autonomic alterations. Cognitive-behavioral therapy (CBT) is regarded as a promising treatment in fibromyalgia, but its impact on autonomic function remains uncertain. In this research, we studied the effect of CBT on autonomic functions in fibromyalgia. Methods: Twenty-five participants underwent overnight polysomnographic recordings before and after CBT programs focused on pain (CBT-P) or a hybrid modality focused on pain and insomnia (CBT-C). Sleep quality, daily pain, depression and anxiety were assessed by self-reported questionnaires. We analyzed heart rate variability (HRV) using high-frequency power (HF) as a marker for parasympathetic activity, and low-frequency power (LF) and the LF/HF ratio as relative sympathetic markers during wakefulness and at each sleep stage. Results: After treatment, 14 patients (/25, 58.0%) reported improvement in their sleep: 6 in the CBT-P condition (/12, 50%), and 8 in the CBT-C condition (/13, 61.5%). We found that, regardless of the type of CBT, patients who reported improvement in sleep quality (n = 14, 58%) had an increase in HF during stages N2 (p < 0.05) and N3 (p < 0.05). These changes were related to improvement in sleep quality (N2, r = −0.43, p = 0.033) but not to pain, depression or anxiety. Conclusions: This study showed an improvement in parasympathetic cardiac control during non-rapid-eye-movement sleep following CBT in fibromyalgia participants who reported better sleep after this therapy. CBT may have a cardio-protective effect and HRV could be used as a sleep monitoring tool in fibromyalgia.

Background: Insomnia has been associated with decreased academic performance and unhealthy behaviors in university students. Although many studies have analyzed sleep phenomenology among this population, only few have focused on insomnia and its related variables. In addition, such studies do not always include a clinical interview or a specific and validated instrument for measuring insomnia. This study aimed to explore the prevalence of insomnia symptoms and the relationship between insomnia and health habits, mental health, and academic performance in a large university student sample., Methods: Five hundred and eighty-two students were recruited from the University of Granada, Spain. Data were collected through an online survey with questions on sociodemographic and academic data and health habits as well as the Pittsburgh Sleep Quality Index, Insomnia Severity Index, Sleep Hygiene Index, and Sleepiness, Depression, Anxiety, and Stress Scales. A multiple regression analysis explored the relationship between academic performance, health habits, mood state, and insomnia symptoms., Results: The prevalence of students with symptoms of insomnia was high (39.7%). A multiple logistic regression analysis revealed that depression, sleep hygiene, stress and anxiety were significant predictors of insomnia symptoms. Multivariate analyses revealed that subjective insomnia symptoms, sleep efficiency, and depression were significantly correlated with academic performance in a dependent way., Conclusions: In university students, anxiety, stress, and poor sleep hygiene are risk factors for insomnia, which plays an important role in academic performance. Promoting sleep and mental health could be a potentially effective way to improve their academic performance.

To understand the variable response to pain, researchers have examined the change in cardiovascular measures to a uniform painful stimulation. Pain catastrophizing is the tendency to magnify or exaggerate pain sensations, and it affects the outcome of rehabilitation in a clinical setting. Its effect on cardiovascular changes during a painful stimulus is unclear. Twenty-four healthy human participants completed the study. All participants completed a cold pressor test while subjective pain intensity was measured with a numeric pain scale from 0-10. Continuous cardiac output measurements were obtained with finger-pulse plethysmograph waveform analysis. The measurements included systolic and diastolic blood pressure, heart rate averaged over 30 s intervals. Pain catastrophizing and anxiety were assessed using the pain catastrophizing scale (PCS), and Spielberger's State-Trait Anxiety Inventories, respectively. Peak pain was correlated to pain catastrophizing (r = 0.628, p < 0.01). There was a strong correlation between change in heart rate (HR) and subjective peak pain (r = 0.805, p < 0.01), total PCS (r = 0.474, p < 0.05), and the helplessness subscale of the PCS (r = 0.457, p < 0.05). Peak pain and catastrophizing explained a significant amount of the variance for the change in HR during the cold pressor test (R 2 of 0.649 and 0.224 respectively, p = 0.019). These novel findings demonstrate a psycho-physiological relationship between cardiovascular changes and pain catastrophizing. Further research should include participants with subacute or persistent pain., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Heart rate variability biofeedback (HRVB) is a non-pharmacological intervention used in the management of chronic diseases., Method: A systematic search was performed according to eligibility criteria including adult chronic patients, HRVB as main treatment with or without control conditions, and psychophysiological outcomes as dependent variables., Results: In total, 29 articles were included. Reported results showed the feasibility of HRVB in chronic patients without adverse effects. Significant positive effects were found in various patient profiles on hypertension and cardiovascular prognosis, inflammatory state, asthma disorders, depression and anxiety, sleep disturbances, cognitive performance and pain, which could be associated with improved quality of life. Improvements in clinical outcomes co-occurred with improvements in heart rate variability, suggesting possible regulatory effect of HRVB on autonomic function., Conclusions: HRVB could be effective in managing patients with chronic diseases. Further investigations are required to confirm these results and recommend the most effective method., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: Suppression of alpha and enhancement of gamma electroencephalographic (EEG) power have both been suggested as objective indicators of cortical pain processing. While gamma activity has been emphasized as the best potential marker, its spectral overlap with pain-related muscular responses is a potential drawback. Since muscle contractions are almost universal concomitants of physical pain, here we investigated alpha and gamma scalp-recorded activities during either tonic pain or voluntary facial grimaces mimicking those triggered by pain., Methods: High-density EEG (128 electrodes) was recorded while 14 healthy participants either underwent a cold pressor test (painful hand immersion in 10 °C water) or produced stereotyped facial/nuchal contractions (grimaces) mimicking those evoked by pain. The scalp distribution of spectral EEG changes was quantified via vector-transformation of maps and compared between the pain and grimacing conditions by calculating the cosine of the angle between the two corresponding topographies., Results: Painful stimuli significantly enhanced gamma power bilaterally in fronto-temporal regions and decreased alpha power in the contralateral central scalp. Sustained cervico-facial contractions (grimaces) gave also rise to significant gamma power increase in fronto-temporal regions but did not decrease central scalp alpha. While changes in alpha topography significantly differed between the pain and grimace situations, the scalp topography of gamma power was statistically indistinguishable from that occurring during grimaces., Conclusion: Gamma power induced by painful stimuli or voluntary facial-cervical muscle contractions had overlapping topography. Pain-related alpha decrease in contralateral central scalp was less disturbed by muscle activity and may therefore prove more discriminant as an ancillary pain biomarker., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

The Sleep Hygiene Index (SHI) has shown adequate psychometric properties in samples from several countries but has not been validated in Spanish. The aims of the study were to translate the original (i.e., English) version of the SHI into Spanish and to evaluate the psychometric properties of this instrument (i.e., factor structure, internal consistency reliability, and concurrent, predictive, and discriminant validity) in Spanish adults. The overall sample, comprising 548 university students, was divided into two groups based on their self-reported insomnia symptoms (Insomnia Severity Index) because sleep hygiene has been shown to be closely related to insomnia. The Pittsburgh Sleep Quality Index and the Stanford Sleepiness Scale were used for testing concurrent validity. The Depression, Anxiety, and Stress Scale was used for testing predictive validity. Three items were dropped from the original SHI scale due to their low factor loadings. The principal component analysis revealed a four-factor solution for the SHI, accounting for 65.58% of the total variance in the overall sample, for 65.34% in the noninsomnia group, and for 63.50% in the insomnia group. Factor 1 comprised items regarding sleep-disrupting behaviors; Factor 2 comprised items regarding cognitive activation; Factor 3 comprised items about bedroom comfort; and Factor 4 comprised items on sleep/wake time. Omega coefficient indices for the SHI ranged from 0.751 to 0.878 in the overall sample, from 0.734 to 0.822 in the noninsomnia group, and from 0.724 to 0.835 in the insomnia group. The Spanish version of the SHI can be regarded as a reliable tool with adequate concurrent and predictive validity for assessing sleep hygiene in Spanish people with or without insomnia symptoms., (© 2021 Wiley Periodicals LLC.)

Background: Lockdown has been one of the major worldwide strategies to control the spread of coronavirus disease 2019 (COVID-19). Its consequences on the well-being of individuals needs to be better understood. The objective of this work was to evaluate the impact of lockdown on the well-being of a general population and the factors associated with this potential impairment of well-being in a population that has been only lightly affected by COVID-19 such as in Reunion island, an overseas French department., Methods: An online survey was proposed to the population of Reunion Island between the 35th and 54th days of lockdown relative to pre- and per-lockdown periods. Well-being was measured by the 5-item World Health Organization Well-Being Index, with some questions about sleep habits (Pittsburgh questionnaire), weekly physical activity (IPAQ), health, and lifestyle., Results: Four hundred volunteers answered the survey. They reported a 15.7% decrease in well-being (p < 0.001), accompanied by increased anxiety (p < 0.001), decreased weekly physical activity (p < 0.001), delayed and poorer quality sleep (p < 0.001). Multivariate logistical analysis showed that impairment in well-being during lockdown was independently associated with an increase in anxiety (odds ratio (OR): 4.77 (3.26-6.98), p < 0.001), decrease in weekly physical activity (OR: 0.58 (0.43-0.79), p < 0.001), and poor-quality sleep (OR: 0.29 (0.19-0.43), p < 0.001)., Conclusions: This study suggested an impairment in well-being during lockdown, associated with anxiety, lack of physical activity and sleep disruptions. Public policies must consider these factors as levers for improving the well-being of the population in order to effectively combat the spread of COVID-19., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Although emotion regulation has been proposed to be crucial for empathy, investigations on emotion regulation have been primarily limited to intrapersonal processes, leaving the interpersonal processes of self-regulation rather unexplored. Moreover, studies showed that emotion regulation and empathy are related with increased autonomic activation. How emotion regulation and empathy are related at the autonomic level, and more specifically during differently valenced social situations remains an open question. Healthy adults viewed a series of short videos illustrating a target who was expressing positive, negative, or no emotions during a social situation (Positive, Negative, or Neutral Social Scenes). Prior to each video, participants were instructed to reappraise their own emotions (Up-regulation, Down-regulation, or No-regulation). To assess autonomic activation, RR intervals (RRI), high frequency (HF) components of heart rate variability (HRV), and electrodermal activity phasic responses (EDRs) were calculated. Situational empathy was measured through a visual analogue scale. Participants rated how empathic they felt for a specific target. Up- and Down-regulation were related to an increase and a decrease in situational empathy and an increase in RRI and HF, respectively, compared to the control condition (No-regulation). This suggests increased activity of the parasympathetic branch during emotion regulation of situational empathic responses. Positive compared to Negative Social Scenes were associated with decreased situational empathy, in addition to a slightly but non-significantly increased HF. Altogether, this study demonstrates that emotion regulation may be associated with changes in situational empathy and autonomic responses, preferentially dominated by the parasympathetic branch and possibly reflecting an increase of regulatory processes. Furthermore, the current study provides evidence that empathy for different emotional valences is associated with distinct changes in situational empathy and autonomic responses., Competing Interests: The authors have declared that no competing interests exist.

New Findings: What is the central question of this study? Can Granger causality analysis of R-R intervals, systolic blood pressure and respiration provide evidence for the different physiological mechanisms induced during thermoneutral water immersion, 6 deg head-down tilt and supine position tests that are not accessible using traditional heart rate variability and baroreflex methods? What is the main finding and its importance? The Granger analysis demonstrated a significant difference in the causal link from R-R intervals to respiration between water immersion and head-down tilt. The underlying physiological mechanism explaining this difference could be the variation in peripheral resistances., Abstract: Thermoneutral head-out water immersion (WI) and 6 deg head-down tilt (HDT) are used to simulate SCUBA diving, swimming and microgravity, because these models induce an increase in central blood volume. Standard methods to analyse autonomic regulation have demonstrated an increase in parasympathetic activity and baroreflex sensitivity during these experimental conditions. However, such methods are not adapted to quantify all closed-loop interactions involved in respiratory and cardiovascular regulation. To overcome this limitation, we used Granger causality analysis between R-R intervals (RR), systolic blood pressure (SBP) and respiration (RE) in eight young, healthy subjects, recorded during 30 min periods in the supine position, WI and HDT. For all experimental conditions, we found a bidirectional causal relationship between RE and RR and between RR and SBP, with a dominant direction from RR to SBP, and a unidirectional causality from RE to SBP. These causal relationships remained unchanged for the three experimental tests. Interestingly, there was a lower causal relationship from RR to RE during WI compared with HDT. This causal link from RR to RE could be modulated by peripheral resistances. These results highlight differences in cardiovascular regulation during WI and HDT and confirm that Granger causality might reveal physiological mechanisms not accessible with standard methods., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)

Purpose: Thermoneutral head-out water immersion (WI) and 6° head-down tilt (HDT) have been considered as suitable models to increase central blood volume and simulate autonomic cardiovascular adaptations to microgravity, swimming or scuba diving. However, any differences in autonomic cardiovascular adaptations are still unclear. In this study, we hypothesized that WI induces a higher activation of arterial baroreceptors and the parasympathetic system., Methods: Ten healthy men underwent 30 min of WI, HDT, and a supine position (SP). RR intervals (RRI) and blood pressure (BP) were continuously monitored. High frequency power (HF), low frequency power (LF) and LF/HF ratio were calculated to study sympathetic and parasympathetic activities, and a spontaneous baroreflex method was used to study arterial baroreflex sensitivity (aBRS). Lung transfer of nitric oxide and carbon monoxide (TLNO/TLCO), vital capacity and alveolar volume (Vc/VA) were measured to study central blood redistribution., Results: We observed (1) a similar increase in RRI and decrease in BP; (2) a similar increase in HF power during all experimental conditions, whereas LF increased after; (3) a similar rise in aBRS; (4) a similar increase in Vc/VA and decrease in TLNO/TLCO in all experimental conditions., Conclusions: These results showed a cardiac parasympathetic dominance to the same extent, underpinned by a similar arterial baroreflex activation during WI and HDT as well as control SP. Future studies may address their association with cold or hyperoxia to assess their ability to replicate autonomic cardiovascular adaptations to microgravity, swimming or scuba diving.

Pain sensation is characterized by abrupt changes in central nervous system activity producing autonomic reactivity. While clinical hypnosis has demonstrated its benefits for children in pain management, it is not clear whether hypnosis modulated autonomic pain response in children in clinical conditions. Here, we studied autonomic responses under hypnosis to sutures in pediatric emergencies. For that, 42 children (mean age: 6.5 years, range 1.5 to 13) were divided into two groups consecutively (hypnosis and control groups), according to their choice. Time-frequency analysis was applied on RR intervals (heart rate interbeat intervals, or RRI) to estimate parasympathetic reactivity based on high frequency power (HF) and the Analgesia Nociception Index (ANI®) and on sympathetic reactivity (low frequency power [LF]) and LF/HF ratio). We observed that RRI and LF/HF ratio varied according to suture and hypnosis ( p < 0.05): RRI was higher and LF/HF ratio was lower during sutures in the hypnosis group in comparison to the control group whereas HF and ANI® increased only during hypnosis. To conclude, hypnosis in pediatric emergencies reduces sympathetic cardiac pain reactivity and could be a marker of pain relief under hypnosis, while parasympathetic activity seems to be a better marker of hypnosis.

Objectives: This study examined the differences in cognitive function between middle-aged and older adults with insomnia disorder, insomnia symptoms only (ISO) or no insomnia symptoms (NIS), in the context of other health and lifestyle factors., Methods: Twenty-eight thousand four hundred eighty-five participants >45 years completed questionnaires, physical examinations, and neuropsychological testing across domains of processing speed, memory, and executive functions. An eight-question instrument assessed participants' sleep, defining subjects with insomnia symptoms, probable insomnia disorder (PID), or NIS. The associations between these three groups and cognitive performance were examined with linear regression models adjusted for lifestyle and clinical factors., Results: PID was identified in 1,068 participants (3.7% of the sample) while 7,813 (27.5%) experienced ISO. Participants with PID exhibited greater proportions of adverse medical and lifestyle features such as anxiety, depression, and diabetes than both other groups. Analyses adjusting for age, sex, education, as well as medical and lifestyle factors demonstrated that adults with PID exhibited declarative memory deficits (Rey Auditory Verbal Learning Test) compared with ISO or NIS. Adults with insomnia symptoms exhibited better performance on a task of mental flexibility than both other groups., Conclusions: These findings suggest that insomnia disorder in middle-aged and older adults is associated with poorer health outcomes and worse memory performance than adults with insomnia symptoms alone or without any sleep complaints, even after adjustment for comorbidities. The assessment of longitudinal data within this cohort will be critical to understand if insomnia disorder may increase the risk of further cognitive decline., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Despite numerous studies suggesting the role of insular cortex in the control of autonomic activity, the exact location of cardiac motor regions remains controversial. We provide here a functional mapping of autonomic cardiac responses to intracortical stimulations of the human insula. The cardiac effects of 100 insular electrical stimulations into 47 epileptic patients were divided into tachycardia, bradycardia, and no cardiac response according to the magnitude of RR interval (RRI) reactivity. Sympathetic (low frequency, LF, and low to high frequency powers ratio, LF/HF ratio) and parasympathetic (high frequency power, HF) reactivity were studied using RRI analysis. Bradycardia was induced by 26 stimulations (26%) and tachycardia by 21 stimulations (21%). Right and left insular stimulations induced as often a bradycardia as a tachycardia. Tachycardia was accompanied by an increase in LF/HF ratio, suggesting an increase in sympathetic tone; while bradycardia seemed accompanied by an increase of parasympathetic tone reflected by an increase in HF. There was some left/right asymmetry in insular subregions where increased or decreased heart rates were produced after stimulation. However, spatial distribution of tachycardia responses predominated in the posterior insula, whereas bradycardia sites were more anterior in the median part of the insula. These findings seemed to indicate a posterior predominance of sympathetic control in the insula, whichever the side; whereas the parasympathetic control seemed more anterior. Dysfunction of these regions should be considered when modifications of cardiac activity occur during epileptic seizures and in cardiovascular diseases., (© 2019 Wiley Periodicals, Inc.)

Background: The use of quantitative sensory testing (QST) in multicenter studies has been quite limited, due in part to lack of standardized procedures among centers., Aim: The aim of this study was to assess the application of the capsaicin pain model as a surrogate experimental human model of neuropathic pain in different centers and verify the variation in reports of QST measures across centers., Methods: A multicenter study conducted by the Quebec Pain Research Network in six laboratories allowed the evaluation of nine QST parameters in 60 healthy subjects treated with topical capsaicin to model unilateral pain and allodynia. The same measurements (without capsaicin) were taken in 20 patients with chronic neuropathic pain recruited from an independent pain clinic., Results: Results revealed that six parameters detected a significant difference between the capsaicin-treated and the control skin areas: (1) cold detection threshold (CDT) and (2) cold pain threshold (CPT) are lower on the capsaicin-treated side, indicating a decreased in cold sensitivity; (3) heat pain threshold (HPT) was lower on the capsaicin-treated side in healthy subjects, suggesting an increased heat pain sensitivity; (4) dynamic mechanical allodynia (DMA); (5) mechanical pain after two stimulations (MPS2); and (6) mechanical pain summation after ten stimulations (MPS10), are increased on the capsaicin-treated side, suggesting an increased in mechanical pain ( P  < 0.002). CDT, CPT and HPT showed comparable effects across all six centers, with CPT and HPT demonstrating the best sensitivity. Data from the patients showed significant difference between affected and unaffected body side but only with CDT., Conclusion: These results provide further support for the application of QST in multicenter studies examining normal and pathological pain responses., Competing Interests: The authors have no conflict of interest to declare., (Published with license by Taylor & Francis Group, LLC.)

Objective: Differential diagnosis between sleep-related epileptic seizures and NREM parasomnia remains challenging. Pathophysiological markers to differentiate both conditions are needed. Activation of autonomic system is present in arousal reactions and epileptic seizures. Our study investigated whether cardiac reactivity differed between arousal disorders and sleep-related seizures., Methods: Nocturnal recordings of 50 patients (10 in each group: frontal lobe epilepsy [FLE], temporal lobe epilepsy [TLE], nocturnal terror [NT], confusional arousal [CA], normal arousals [NA]) were retrospectively selected. Timing of the first motor sign and description of behaviours were assessed. Beat-to-beat RR intervals (RRI) as well as heart rate variability were analysed over a period of 60 heartbeats before and after first motor manifestation. The slope and area under the curve (AUC) of RRI were calculated., Results: A significant decrease in RRI was observed at the onset of all events. Statistical analysis revealed: lower RRI in TLE than in other groups; higher slope of RRI in FLE than in NA and TLE, and higher AUC in NT and FLE than in TLE, and in NT than in NA. Sleep stage, episode duration, vocalization characteristics, lateralized or abnormal posture, exploratory behaviour differed between epileptic and parasomnia groups., Discussion: Analysis of cardiac reactivity seems to be a useful objective tool, together with clinical features, for diagnosing abnormal behaviour during sleep. Cardiac reactivity in TLE could reflect epileptic discharge propagation to brain areas involved in autonomic control, while FLE and NT might involve a strong non-specific activation of the sympathetic system., (Copyright © 2018. Published by Elsevier Masson SAS.)

Although modulation of cardiac activity may be influenced by several factors, interaction between autonomic nociceptive responses and the high-level of cortical processes is not clearly understood. Here, we studied in 26 subjects whether empathetic or unempathetic contexts could interact with autonomic pain responses. RR intervals variability was used to approach parasympathetic and sympathetic responses to painful thermal stimulations, according to contexts evoked by experimenters' comments. We observed that unempathetic context increased sympathetic reactivity to comments and to painful stimulations without any parasympathetic change. These results show an interaction between context and nociceptive processes in cardiovascular control., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: To identify structural changes in gray matter in suspected migraine generators (the hypothalamus and/or brainstem nuclei) and pain pathways and to evaluate whether structural changes in migraine are definitive or resolve with age., Methods: Voxel-based morphometry (VBM) was used to assess differences in gray matter between 39 healthy controls (HC), 25 episodic migraine (EM) subjects, and 37 subjects with a history of migraine (HM). In addition, morphometric changes were specifically investigated in suspected migraine generators and/or pain pathways. For statistical analyses, t tests between the groups were performed, and a correction for multiple comparisons was used., Results: Whole-brain analysis did not reveal any gray or white matter changes. However, when the analysis was limited to the pain matrix, a lower gray matter volume was observed in the left second somatosensory (SII) cortex in EM subjects compared to HC subjects. This volume was significantly reduced in the EM group compared to the HC group and to the HM group, but not in the HM group compared to the HC group., Conclusion: Morphometric abnormalities in the SII in subjects with ongoing migraine but not in subjects with a resolved migrainous disease are likely to characterize a migrainous state rather than be a marker of brain susceptibility to migraine.

The placebo effect is a psychobiological phenomenon producing clinical benefits attributed to a wide range of neurobiological mechanisms. Independently from placebo effects, these mechanisms may also be under the influence of processes that can take place during sleep. The relationship between sleep and placebo effects has received very little attention. Three experimental studies, conducted on healthy subjects, have examined sleep changes following placebo conditioning associated with analgesic suggestions and the effects of sleep deprivation on placebo effects. A relation between rapid eye movement (REM) sleep, expectations of relief and placebo analgesia was observed in which REM sleep deprivation seems to improve placebo-induced expectations and analgesia. Moreover, analgesic expectations developed before sleep produced a reduction in cortical arousals evoked by noxious stimuli during REM sleep. In this article, we describe sleep and pain/analgesia interactions, the relationship between sleep and placebo analgesia, and finally the potential mechanisms underlying this relationship., (© 2018 Elsevier Inc. All rights reserved.)

Pupillary diameter (PD) varies under the influence of the sympathetic as well as parasympathetic systems, increasing proportionally with pain intensity. Such variations however, should not be confused with pupillary fluctuations, which refer to the fast and permanent PD fluctuations induced by the ongoing interplay between the sympathetic and parasympathetic systems, which we propose to measure using the variation coefficient of PD (VCPD). This study aimed first at correlating PD, PD increase during a contraction, and VCPD, with pain rated using a numeric rating scale (NRS) during obstetrical labor, and then at comparing such correlations with each other. Forty patients were included in the study, and 160 simultaneous ratings (NRS, PD, and VCPD) were taken: 40 in the presence of uterine contractions and 40 in the absence of such contractions, before and 20 minutes after epidural analgesia. VCPD correlates more strongly (r = .77) than PD increase (r = .42) with pain rated using a NRS. The ability of VCPD to predict the occurrence of NRS scores ≥4 during obstetrical labor is .97 (confidence interval, .93-1.0). When measured over 10 seconds during contraction, VCPD correlates more strongly than PD increase with pain rated using the NRS. Such stronger correlation allows for an easy assessment of antinociception-nociception balance., Perspective: The VCPD allows for an objective assessment of pain in laboring women. It could allow for an easy assessment of pain in noncommunicating patients: newborns or very old patients, patients with serious psychological conditions, assessment during the immediate postoperative period, or in intensive care units., (Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Objective: Due to limited information from scalp electroencephalographic (EEG) recordings, brain areas driving changes in cardiac rhythm during Temporal lobe (TL) seizures are not clearly identified. Using stereotactic EEG (SEEG) recordings, we aimed at identifying which of the brain regions involved in autonomic control trigger ictal tachycardia., Methods: The neural activity of several mesial temporal lobe structures including amygdala, hippocampus, insula, and lateral temporal lobe recorded with SEEG were collected during 37 TL seizures in 9 patients, using indices based on High Frequency Activity (HFA). R-R intervals (RR) monitoring and time-frequency spectral analysis were performed to assess parasympathetic (High frequency power (HF)) and sympathetic (Low frequency/High frequency (LF/HF) ratio) reactivities., Results: Tachycardia was associated with a significant increase in LF/HF ratio and decrease in HF. Autonomic cardiac changes were accompanied by simultaneous SEEG signal changes with an increase in seizure-related HFA in anterior hippocampal formation and amygdala, but not in insula., Conclusion: In our sample, TL seizures are thus accompanied by an early decrease in parasympathetic control of cardiac rhythm and by an increase of sympathetic tone, concomitant to seizure activity in anterior hippocampus and amygdala., Significance: These results support a pivotal role of hippocampus and amygdala in tachycardia occurring during TL seizures., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Since the pioneering studies of the 1960s, heart rate variability (HRV) has become an increasingly used non-invasive tool for examining cardiac autonomic functions and dysfunctions in various populations and conditions. Many calculation methods have been developed to address these issues, each with their strengths and weaknesses. Although, its interpretation may remain difficult, this technique provides, from a non-invasive approach, reliable physiological information that was previously inaccessible, in many fields including death and health prediction, training and overtraining, cardiac and respiratory rehabilitation, sleep-disordered breathing, large cohort follow-ups, children's autonomic status, anesthesia, or neurophysiological studies. In this context, we developed HRVanalysis , a software to analyse HRV, used and improved for over 20 years and, thus, designed to meet laboratory requirements. The main strength of HRVanalysis is its wide application scope. In addition to standard analysis over short and long periods of RR intervals, the software allows time-frequency analysis using wavelet transform as well as analysis of autonomic nervous system status on surrounding scored events and on preselected labeled areas. Moreover, the interface is designed for easy study of large cohorts, including batch mode signal processing to avoid running repetitive operations. Results are displayed as figures or saved in TXT files directly employable in statistical softwares. Recordings can arise from RR or EKG files of different types such as cardiofrequencemeters, holters EKG, polygraphs, and data acquisition systems. HRVanalysis can be downloaded freely from the Web page at: https://anslabtools.univ-st-etienne.fr HRVanalysis is meticulously maintained and developed for in-house laboratory use. In this article, after a brief description of the context, we present an overall view of HRV analysis and we describe the methodological approach of the different techniques provided by the software.