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Objective: To assess the value of combining brain and autonomic measures to discriminate the subjective perception of pain from other sensory-cognitive activations., Methods: 20 healthy individuals received 2 types of tonic painful stimulation delivered to the hand: electrical stimuli and immersion in 10 Celsius degree (°C) water, which were contrasted with non-painful immersion in 15 °C water, and stressful cognitive testing. High-density electroencephalography (EEG) and autonomic measures (pupillary, electrodermal and cardiovascular) were continuously recorded, and the accuracy of pain detection based on combinations of electrophysiological features was assessed using machine learning procedures., Results: Painful stimuli induced a significant decrease in contralateral EEG alpha power. Cardiac, electrodermal and pupillary reactivities occurred in both painful and stressful conditions. Classification models, trained on leave-one-out cross-validation folds, showed low accuracy (61-73%) of cortical and autonomic features taken independently, while their combination significantly improved accuracy to 93% in individual reports., Conclusions: Changes in cortical oscillations reflecting somatosensory salience and autonomic changes reflecting arousal can be triggered by many activating signals other than pain; conversely, the simultaneous occurrence of somatosensory activation plus strong autonomic arousal has great probability of reflecting pain uniquely., Significance: Combining changes in cortical and autonomic reactivities appears critical to derive accurate indexes of acute pain perception., Competing Interests: Conflict of Interest Statement None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

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.)

The autonomic nervous system (ANS) harmoniously regulates all internal organic functions (heart rate, blood pressure, vasomotion, digestive tract motility, endocrinal secretions) and adapts them to the needs. It's the control of so-called vegetative functions, which allows homeostasis but also allostasis of our body. ANS is divided into two systems often understood as antagonistic and complementary: the sympathetic and the parasympathetic systems. However, we currently know of many situations of co-activation of the two systems. Long seen as acting through "reflex" control loops passing through the integration of peripheral information and the efferent response to the peripheral organ, more recent electrophysiological and brain functional imaging knowledge has been able to identify the essential role of the central autonomic network. This element complicates the understanding of the responses of the reflex loops classically used to identify and quantify dysautonomia. Finding the "ANS" tools best suited for the clinician in their daily practice is a challenge that we will attempt to address in this work., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

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.)

Empathetic verbal feedback from others has been shown to alleviate the intensity of experimental pain. To investigate the brain changes associated with this effect, we conducted 3T-fMRI measurements in 30 healthy subjects who received painful thermal stimuli on their left hand while overhearing empathetic, neutral or unempathetic comments, supposedly made by experimenters, via headsets. Only the empathetic comments significantly reduced pain intensity ratings. A whole-brain BOLD analysis revealed that both Empathetic and Unempathetic conditions significantly increased the activation of the right anterior insular and posterior parietal cortices to pain stimuli, while activations in the posterior cingulate cortex and precuneus (PCC/Prec) were significantly stronger during Empathetic compared to Unempathetic condition. BOLD activity increased in the DLPFC in the Empathetic condition and decreased in the PCC/Prec and vmPFC in the Unempathetic condition. In the Empathetic condition only, functional connectivity increased significantly between the vmPFC and the insular cortex. These results suggest that modulation of pain perception by empathetic feedback involves a set of high-order brain regions associated with autobiographical memories and self-awareness, and relies on interactions between such supra-modal structures and key nodes of the pain system.

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.)

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 (M age = 50.3) and 21 female matched controls (M age = 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., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

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.)

The physiological and behavioural effects of empathy for other's pain have been widely investigated, while the opposite situation, i.e. the influence on one's pain of empathetic feedback from others, remains largely unexplored. Here, we assessed whether and how empathetic and unempathetic comments from observers modulate pain and associated vegetative reactions. In Study 1, conversations between observers of a pain study were recorded by professional actors. Comments were prepared to be perceived as empathetic, unempathetic or neutral, and were validated in 40 subjects. In a subsequent pain experiment (Study 2), changes in subjective pain and heart rate were investigated in 30 naïve participants who could overhear the empathetic or unempathetic conversations pre-recorded in study 1. Subjective pain was significantly attenuated when hearing empathetic comments, as compared to both unempathetic and neutral conditions, while unempathetic comments failed to significantly modulate pain. Heart rate increased when hearing unempathetic remarks and when receiving pain stimuli, but heart acceleration to nociceptive stimulation was not correlated with pain ratings. These results suggest that empathetic feedback from observers has a positive influence on pain appraisal and that this effect may surpass the negative effect of unempathetic remarks. Negative remarks can either trigger feelings of guilt or induce irritation/anger, with antagonistic effects on pain that might explain inter-individual variation. As in basal conditions heart rate and pain perception are positively correlated, their dissociation here suggests that changes in subjective pain were linked to a cognitive bias rather than changes in sensory input., (© 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

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.

Alteration in cardiac autonomic activity during sleep is a common feature of sleep disorders. Diurnal sympathetic overactivity is a possible consequence and could contribute to future cardiovascular complications. The aim of this study is to assess the relationship between cardiac autonomic activity during sleep and diurnal autonomic cardiovascular control. In a large cohort (n = 1011) of subjects aged 65 years old (± 0.4) free of cardiac and cerebrovascular events and of sleep-related breathing disorders, we evaluated (cross-sectional study) the prevalence of unexpected alteration in sleep-related autonomic overactivity according to the presence of a cyclical nocturnal heart rate variability [quantified using the relative power spectral density of the very low-frequency band of the heart rate increment (VLFi%) from ECG Holter monitoring]. We tested its relationship with diurnal ambulatory blood pressure and spontaneous baroreflex sensitivity (sBRS). An abnormal cardiac autonomic activity during sleep was retained in 34.4% of this population according to a VLFi% >4. Using multiple logistic regression analysis, the severity of the autonomic alteration was mainly correlated after adjustment with lower sBRS (p = 0.01; OR: 0.94; 95% CI: 0.90-0.98). Diurnal baroreflex control alteration is associated with sleep-related autonomic overactivity elderly. Such alteration may contribute to the increased incidence of cardiovascular complications in sleep disorders.

The placebo effect is a neurobiological and psychophysiological process known to influence perceived pain relief. Optimization of placebo analgesia may contribute to the clinical efficacy and effectiveness of medication for acute and chronic pain management. We know that the placebo effect operates through two main mechanisms, expectations and learning, which is also influenced by sleep. Moreover, a recent study suggested that rapid eye movement (REM) sleep is associated with modulation of expectation-mediated placebo analgesia. We examined placebo analgesia following pharmacological REM sleep deprivation and we tested the hypothesis that relief expectations and placebo analgesia would be improved by experimental REM sleep deprivation in healthy volunteers. Following an adaptive night in a sleep laboratory, 26 healthy volunteers underwent classical experimental placebo analgesic conditioning in the evening combined with pharmacological REM sleep deprivation (clonidine: 13 volunteers or inert control pill: 13 volunteers). Medication was administered in a double-blind manner at bedtime, and placebo analgesia was tested in the morning. Results revealed that 1) placebo analgesia improved with REM sleep deprivation; 2) pain relief expectations did not differ between REM sleep deprivation and control groups; and 3) REM sleep moderated the relationship between pain relief expectations and placebo analgesia. These results support the putative role of REM sleep in modulating placebo analgesia. The mechanisms involved in these improvements in placebo analgesia and pain relief following selective REM sleep deprivation should be further investigated.

Key Points: Sleep spindle are usually considered to play a major role in inhibiting sensory inputs. Using nociceptive stimuli in humans, we tested the effect of spindles on behavioural, autonomic and cortical responses in two experiments using surface and intracerebral electroencephalographic recordings. We found that sleep spindles do not prevent arousal reactions to nociceptive stimuli and that autonomic reactivity to nociceptive inputs is not modulated by spindle activity. Moreover, neither the surface sensory, nor the insular evoked responses were modulated by the spindle, as detected at the surface or within the thalamus. The present study comprises the first investigation of the effect of spindles on nociceptive information processing and the results obtained challenge the classical inhibitory effect of spindles., Abstract: Responsiveness to environmental stimuli declines during sleep, and sleep spindles are often considered to play a major role in inhibiting sensory inputs. In the present study, we tested the effect of spindles on behavioural, autonomic and cortical responses to pain, in two experiments assessing surface and intracerebral responses to thermo-nociceptive laser stimuli during the all-night N2 sleep stage. The percentage of arousals remained unchanged as a result of the presence of spindles. Neither cortical nociceptive responses, nor autonomic cardiovascular reactivity were depressed when elicited within a spindle. These results could be replicated in human intracerebral recordings, where sleep spindle activity in the posterior thalamus failed to depress the thalamocortical nociceptive transmission, as measured by sensory responses within the posterior insula. Hence, the assumed inhibitory effect of spindles on sensory inputs may not apply to the nociceptive system, possibly as a result of the specificity of spinothalamic pathways and the crucial role of nociceptive information for homeostasis. Intriguingly, a late scalp response commonly considered to reflect high-order stimulus processing (the 'P3' potential) was significantly enhanced during spindling, suggesting a possible spindle-driven facilitation, rather than attenuation, of cortical nociception., (© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.)

Sleep is divided into two main sleep stages: (1) non-rapid eye movement sleep (non-REMS), characterized among others by reduced global brain activity; and (2) rapid eye movement sleep (REMS), characterized by global brain activity similar to that of wakefulness. Results of heart rate variability (HRV) analysis, which is widely used to explore autonomic modulation, have revealed higher parasympathetic tone during normal non-REMS and a shift toward sympathetic predominance during normal REMS. Moreover, HRV analysis combined with brain imaging has identified close connectivity between autonomic cardiac modulation and activity in brain areas such as the amygdala and insular cortex during REMS, but no connectivity between brain and cardiac activity during non-REMS. There is also some evidence for an association between HRV and dream intensity and emotionality. Following some technical considerations, this review addresses how brain activity during sleep contributes to changes in autonomic cardiac activity, organized into three parts: (1) the knowledge on autonomic cardiac control, (2) differences in brain and autonomic activity between non-REMS and REMS, and (3) the potential of HRV analysis to explore the sleeping brain, and the implications for psychiatric disorders.

The placebo response is a psychobiological phenomenon for clinical benefits following the administration of an inert substance whatever its form. This phenomenon can be attributed to a wide range of neurobiological processes, such as expectations of relief, the Pavlovian conditioning and learning, emotional regulation, and reward mechanisms, which are themselves under the influence of processes that take place during sleep. The study of placebo analgesia in healthy from a placebo conditioning associated with analgesic suggestions has highlighted a relationship between sleep, expectations of relief and placebo analgesia: when the induction is persuasive before sleep, expectations of relief modulate placebo response the next morning and paradoxical sleep correlates negatively with both expectations and the placebo response. When the analgesic experience before sleep is less persuasive, expectations of relief are still present but no longer interact with placebo analgesia while paradoxical sleep no longer correlates with the analgesic placebo response. Sleep-processes especially during paradoxical sleep seem to influence the relationship between expectations of relief and placebo analgesia. In this review, we describe the relationship between sleep and placebo analgesia, the mechanisms involved in the placebo response (e.g., conditioning, learning, memory, reward) and their potential link with sleep that could make it a special time for the building placebo response., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Objective: The present study provides a functional mapping of vestibular responses in the human insular cortex., Methods: A total of 642 electrical stimulations of the insula were performed in 219 patients, using stereotactically implanted depth electrodes, during the presurgical evaluation of drug-refractory partial epilepsy. We retrospectively identified 41 contacts where stimulation elicited vestibular sensations (VSs) and analyzed their location with respect to (1) their stereotactic coordinates (for all contacts), (2) the anatomy of insula gyri (for 20 vestibular sites), and (3) the probabilistic cytoarchitectonic maps of the insula (for 9 vestibular sites)., Results: VSs occurred in 7.6% of the 541 evoked sensations after electrical stimulations of the insula. VSs were mostly obtained after stimulation of the posterior insula, that is, in the granular insular cortex and the postcentral insular gyrus. The data also suggest a spatial segregation of the responses in the insula, with the rotatory and translational VSs being evoked at more posterior stimulation sites than other less definable VSs. No left-right differences were observed., Interpretation: These results demonstrate vestibular sensory processing in the insula that is centered on its posterior part. The present data add to the understanding of the multiple sensory functions of the insular cortex and of the cortical processing of vestibular signals. The data also indicate that lesion or dysfunction in the posterior insula should be considered during the evaluation of vestibular epileptic seizures., (© 2014 American Neurological Association.)

Despite the substantial advances in the understanding of pain mechanisms and management, postoperative pain relief remains an important health care issue. Surgical patients also frequently report postoperative sleep complaints. Major sleep alterations in the postoperative period include sleep fragmentation, reduced total sleep time, and loss of time spent in slow wave and rapid eye movement sleep. Clinical and experimental studies show that sleep disturbances may exacerbate pain, whereas pain and opioid treatments disturb sleep. Surgical stress appears to be a major contributor to both sleep disruptions and altered pain perception. However, pain and the use of opioid analgesics could worsen sleep alterations, whereas sleep disruptions may contribute to intensify pain. Nevertheless, little is known about the relationship between postoperative sleep and pain. Although the sleep-pain interaction has been addressed from both ends, this review focuses on the impact of sleep disruptions on pain perception. A better understanding of the effect of postoperative sleep disruptions on pain perception would help in selecting patients at risk for more severe pain and may facilitate the development of more effective and safer pain management programs., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Autonomic dysfunction is recognized to contribute to cardiovascular consequences in obstructive sleep apnea/hypopnea syndrome (OSAHS) patients who present predominant cardiovascular sympathetic activity that persists during wakefulness. Here, we examined 1) the factors that influence sympathetic cardiac modulation in response to apneas/hypopneas; and 2) the influence of autonomic activity during apneas/hypopneas on CA. Sixteen OSAHS patients underwent in-hospital polysomnography. RR interval (RR) and RR spectral analysis using wavelet transform were used to study parasympathetic (high frequency power: HF(WV)) and sympathetic (low frequency power: LF(WV) and LF(WV)/HF(WV) ratio) activity before and after apnea/hypopnea termination. Autonomic cardiac modulations were compared according to sleep stage, apnea/hypopnea type and duration, arterial oxygen saturation, and presence of CA. At apnea/hypopnea termination, RR decreased (p<0.001) while LF(WV) (p = 0.001) and LF(WV)/HF(WV) ratio (p = 0.001) increased. Only RR and LF(WV)/HF(WV) ratio changes were higher when apneas/hypopneas produced CA (p = 0.030 and p = 0.035, respectively) or deep hypoxia (p = 0.023 and p = 0.046, respectively). Multivariate statistical analysis showed that elevated LF(WV) (p = 0.006) and LF(WV)/HF(WV) ratio (p = 0.029) during apneas/hypopneas were independently related to higher CA occurrence. Both the arousal and hypoxia processes may contribute to sympathetic cardiovascular overactivity by recurrent cardiac sympathetic modulation in response to apneas/hypopneas. Sympathetic overactivity also may play an important role in the acute central response to apneas/hypopneas, and in the sleep fragmentation.

Aims: Sleep fragmentation is a landmark of sleep disorders, because microarousals are systematically associated with sympathetic surges (i.e., sympathetic arousals). However, the impact of sympathetic sleep fragmentation on blood pressure (BP) remains understudied. We assessed the relationships between 24 h ambulatory BP monitoring, the autonomic arousal index (AAI) derived from pulse transit time, and heart rate variability indices. We hypothesized that repeated sympathetic arousals during sleep are associated with elevated BP in a large population of elderly volunteers., Methods and Results: Volunteer subjects (n = 780, 57.4% women) with a mean age of 68.7 years and free of known sleep-disordered breathing, coronary heart diseases, and neurological disorders underwent polygraphy, 24 h ECG Holter monitoring, and 24 h ambulatory BP monitoring. Multivariate regressions showed that sleep fragmentation, expressed by AAI, was associated with elevated diurnal (P = 0.008) and 24 h (P = 0.005) systolic BP and higher risk for 24 h [odds ratio (OR): 1.70 (1.04-2.80), P = 0.036] systolic hypertension, independently of confounders such as sleep-disordered breathing, body mass index, sex, diabetes, hypercholesterolaemia, and self-reported sleep duration and quality. Increased AAI was associated with higher nocturnal and diurnal low-frequency power (P < 0.001) and low-to-high-frequency ratio (P < 0.001), suggesting nocturnal and diurnal sympathetic overactivity., Conclusion: In healthy elderly subjects, repetitive sympathetic arousals during sleep are associated with elevated systolic BP and higher risk of hypertension, after controlling for confounders. Sympathetic overactivity is the proposed underlying mechanism., Clinical Trial Registration: NCT00766584 and NCT00759304.

Chronic pain is a highly prevalent post-concussion symptom occurring in a majority of patients with mild traumatic brain injury (mTBI). About half of patients with mTBI report sleep-wake disturbances. It is known that pain can alter sleep quality in this population, but the interaction between pain and sleep is not fully understood. This study aimed to identify how pain affects subjective sleep (Pittsburgh Sleep Quality Index [PSQI]), sleep architecture, and quantitative electroencephalographic (qEEG) brain activity after mTBI. Twenty-four mTBI patients complaining of sleep-wake disturbances, with and without pain (8 and 16, respectively), were recruited 45 (±22.7) days post-trauma on average. Data were compared with those of 18 healthy controls (no sleep or pain complaints). The PSQI, sleep architecture, and qEEG activity were analyzed. Pain was assessed using questionnaires and a 100-mm visual analogue scale. Patients with mTBI reported three times poorer sleep quality than controls on the PSQI. Sleep architecture significantly differed between patients with mTBI and controls but was within normal range. Global qEEG showed lower delta (deep sleep) and higher beta and gamma power (arousal) at certain EEG derivations in patients with mTBI compared with controls (p<0.04). Patients with mTBI with pain, however, showed greater increase in rapid EEG frequency bands, mostly during REM sleep, and beta bands in non-REM sleep compared with patients with mTBI without pain and controls (p<0.001). Pain in patients with mTBI was associated with more rapid qEEG activity, mostly during REM sleep, suggesting that pain is associated with poor sleep and is a critical factor in managing post-concussion symptoms.

Background: Obstructive sleep apnea syndrome (OSA) has been recently considered as a cause and a component of the metabolic syndrome (MetS), previous studies showing the presence of OSA in about half of middle-aged patients having MetS. To date, no study has considered the association of OSA and MetS in the elderly. In this study we examine the prevalence of MetS and its strength association among healthy elderly OSA subjects., Methods: A cohort of 806 subjects aged 68.5 years, participants of a 7-year follow-up study, was examined. All subjects underwent clinical evaluation, blood sample measurements, and an at-home polygraphy. OSA was assessed as an apnea/hypopnea index (AHI) >15, and MetS was diagnosed according to the Adult Treatment Panel III., Results: In the total group, 9.8% of cases met criteria for MetS with a prevalence similar in men and women. Of the entire group with Mets, 51.3% were women and 48.7% men. OSA was diagnosed in 55.9% of the sample, and among the OSA group, 12.5% had MetS. Oxyhemoglobin desaturation index (ODI, p < 0.0001) and AHI (p = 0.003) were found significantly higher in subjects with MetS than in those without it. Most of MetS components were significantly associated with AHI and ODI, the relationship stronger with ODI. After adjustment for covariables such as obesity, gender, and presence of diabetes, ODI was independently associated with three MetS components, glycemia (p < 0.0001), hypertension (p = 0.002), and triglyceride levels (p = 0.02). Sleepiness, autonomic arousal index, and sleep duration had no effect on the metabolic parameters., Conclusions: In elderly subjects, the association between OSA and MetS was stronger for hyperglycemia and hypertension. Among factors explaining this association, hypoxemia appears to be the most important factor without any effect of indices of sleep fragmentation, sleep duration, and sleepiness.

After the age of 65 yrs the specific impact of unrecognised sleep-related breathing disorders (SRBD) on 24-h blood pressure (BP) levels remains under debate. We tested the cross-sectional relationship between the severity of obstructive sleep apnoea/hypopnoea (OSAH) and the increase of BP using ambulatory BP monitoring (ABPM) in the PROOF (PROgnostic indicator OF cardiovascular and cerebrovascular events study)-SYNAPSE (Autonomic Nervous System Activity, Aging and Sleep Apnea/Hypopnea study) cohort. 470 subjects (aged 68 yrs) neither treated for hypertension nor diagnosed for SRBD were included. All subjects underwent ABPM, and unattended at-home polygraphic studies. OSAH was defined by an apnoea/hypopnoea index (AHI) >15 · h(-1). The severity of the sleep apnoea was also quantified as the index of dips in oxyhaemoglobin saturation >3% (ODI). Results are expressed in per protocol analysis. Severe OSAH (AHI >30 · h(-1), 17% of subjects) was associated with a significant 5 mmHg increase in both diurnal and nocturnal systolic BP (SBP), and with a nocturnal 3 mmHg increase in diastolic BP (DBP). Systolic (mean SBP >135 mmHg) or diastolic (mean DBP >80 mmHg) hypertension were more frequently encountered in subjects suffering from moderate (AHI 15-30) or severe OSAH. After adjustment, the independent association between severe OSAH and 24-h systolic hypertension remained significant (OR 2.42, 95% CI 1.1-5.4). The relationship was further reinforced when SRBD severity was expressed using ODI >10 · h(-1). The impact of unrecognised SRBD on BP levels also exists at the age of 68 yrs. The hypoxaemic load appears to be the pathophysiological cornerstone for such a relationship.

Background: The high prevalence of sleep disordered breathing (SDB) among heart diseases patients becomes increasingly recognized. A reliable exploring tool of SDB well adapted to cardiologists practice would be very useful for the management of these patients., Methods: We assessed a novel multi-modal electrocardiogram (ECG) Holter which incorporated both thoracic impedance and pulse oximetry signals. We compared in a home setting, a standard condition for Holter recordings, results from the novel device to a classical ambulatory polygraph in subjects with suspected SDB. The analysis of cardiac arrhythmias in relationship with SDB is also presented. A total of 118 patients clinically suspected of having SDB were evaluated (mean age 57 ± 14 years, mean body mass index [BMI] 32 ± 6 kg/m(2)). The new device allows calculating a new index called thoracic impedance (TI) disturbance index (TIDI+) evaluated from TI and SpO(2) signals recorded from a Holter monitor., Results: In the population under study, 93% had more than 70% of usable TI signal and 95% had more than 90% for SpO(2) during sleep time recording. Screening performance results based on automatic analysis is accurate: TIDI + demonstrates a high level of sensitivity (96.8%), specificity (72.3%) as well as positive (82.4%) and negative (94.4%) predictive value for the detection of SDB. Moreover, detection of SDB periods permits us to observe a possible respiratory association of several nocturnal arrhythmias., Conclusions: The multi-modal Holter should be considered as a valuable evaluating tool for SDB screening and as a case selection technique for facilitating access to a full polysomnography for severe cases. Moreover, it offers a unique opportunity to study arrhythmia consequences with both respiratory and hypoxia disturbances.

Objective: To evaluate the ability of the heart rate power spectral density of the very low frequency component expressed as a percentage of the total power spectral band (%VLFI) to diagnose obstructive sleep apnoea (OSA) in the elderly., Patients and Methods: Eight hundred and thirty-two subjects aged 68.5±0.8 years were selected from the participants of a 7-year cross-sectional study on the association between OSA and vascular morbidity-mortality. All subjects underwent electrocardiogram Holter monitoring and an at-home polysomnogram to measure the apnoea/hypopnoea index (AHI). OSA was assessed as an AHI>15., Results: The very low, the low frequency powers, and the %VLFI increased in subjects with OSA and were correlated with the autonomic arousal index and AHI (p<0.0001). A %VLFI of 2.4% and 4% demonstrated a sensitivity of 62% and 69% and a specificity of 45% and 44% to predict OSA in the population., Conclusion: The %VLFI did not provide a high level of diagnostic sensitivity and specificity at different degrees of OSA severity in an elderly healthy population. The ability for prediction was lower in mild cases and in women. These findings suggest that the ageing-related changes in the autonomic nervous system reduce the applicability of HRV to diagnose OSA in older populations., (Copyright © 2011 Elsevier B.V. All rights reserved.)