Multifractal Multiscale Analysis of Human Movements during Cognitive Tasks.

Continuous adaptations of the movement system to changing environments or task demands rely on superposed fractal processes exhibiting power laws, that is, multifractality. The estimators of the multifractal spectrum potentially reflect the adaptive use of perception, cognition, and action. To observe time-specific behavior in multifractal dynamics, a multiscale multifractal analysis based on DFA (MFMS-DFA) has been recently proposed and applied to cardiovascular dynamics. Here we aimed at evaluating whether MFMS-DFA allows identifying multiscale structures in the dynamics of human movements. Thirty-six (12 females) participants pedaled freely, after a metronomic initiation of the cadence at 60 rpm, against a light workload for 10 min: in reference to cycling (C), cycling while playing "Tetris" on a computer, alone (CT) or collaboratively (CTC) with another pedaling participant. Pedal revolution periods (PRP) series were examined with MFMS-DFA and compared to linearized surrogates, which attested to a presence of multifractality at almost all scales. A marked alteration in multifractality when playing Tetris was evidenced at two scales, τ ≈ 16 and τ ≈ 64 s, yet less marked at τ ≈ 16 s when playing collaboratively. Playing Tetris in collaboration attenuated these alterations, especially in the best Tetris players. This observation suggests the high sensitivity to cognitive demand of MFMS-DFA estimators, extending to the assessment of skill/demand interplay from individual behavior. So, by identifying scale-dependent multifractal structures in movement dynamics, MFMS-DFA has obvious potential for examining brain-movement coordinative structures, likely with sufficient sensitivity to find echo in diagnosing disorders and monitoring the progress of diseases that affect cognition and movement control.

Guiding Breathing at the Resonance Frequency with Haptic Sensors Potentiates Cardiac Coherence.

Cardiac coherence is a state achieved when one controls their breathing rate during the so-called resonance frequency breathing. This maneuver allows respiratory-driven vagal modulations of the heart rate to superimpose with sympathetic modulations occurring at 0.1 Hz, thereby maximizing autonomous power in heart-to-brain connections. These stimulations have been shown to improve vagal regulations, which results in obvious benefits for both mental and organic health. Here, we present a device that is able to deliver visual and haptic cues, as well as HRV biofeedback information to guide the user in maintaining a 0.1 Hz breathing frequency. We explored the effectiveness of cardiac coherence in three guidance conditions: visual, haptic and visuo-haptic breathing. Thirty-two healthy students (sixteen males) were divided into three groups that experienced five minutes of either visual, haptic and visuo-haptic guided breathing at 0.1 Hz. The effects of guidance on the (adequate) breathing pattern and heart rate variability (HRV) were analyzed. The interest of introducing haptic breathing to achieve cardiac coherence was shown in the haptic and visuo-haptic groups. Especially, the P0.1 index, which indicates how the autonomous power is 'concentrated' at 0.1 Hz in the PSD spectrum, demonstrated the superiority of combining haptic with visual sensory inputs in potentiating cardiac coherence (0.55 ± 0.20 for visuo-haptic vs. 0.28 ± 0.14 for visual only guidance; p < 0.05) haptic-induced effectiveness could be an asset for a more efficient and time-saving practice, allowing improved health and well-being even under tight time constraints.

A Single Session of SMR-Neurofeedback Training Improves Selective Attention Emerging from a Dynamic Structuring of Brain-Heart Interplay.

Research on sensorimotor rhythms (SMR) based on neurofeedback (NFb) emphasizes improvements in selective attention associated with SMR amplification. However, the long-term training proposed in most studies posed the question of acceptability, which led to the evaluation of the potential of a single NFb session. Based on cognitive and autonomic controls interfering with attention processes, we hypothesized changes in selective attention after a single SMR-NFb session, along with changes in brain-heart interplay, which are reflected in the multifractality of heartbeat dynamics. Here, young healthy participants (n = 35, 20 females, 21 ± 3 years) were randomly assigned either to a control group (Ctrl) watching a movie or to a neurofeedback (NFb) group performing a single session of SMR-NFb. A headset with EEG electrodes (positioned on C3 and C4) connected to a smartphone app served to guide and to evaluate NFb training efficacy. A Stroop task was performed for 8 min by each group before and after the intervention (movie vs. SMR-NFb) while collecting heart rate variability and C4-EEG for 20 min. When compared to Ctrl, the NFb group exhibited better Stroop performance, especially when facing incongruent trials. The multifractality and NFb training efficacy were identified as strong predictors of the gain in global Stroop performance, while multifractality was the only predictor regarding incongruent trials. We conclude that a single session of SMR-NFb improves selective attention in healthy individuals through the specific reorganization of brain-heart interplay, which is reflected in multifractal heartbeat dynamics.

Degraded Psychophysiological Status in Caregivers and Human Resources Staff during a COVID-19 Peak Unveiled by Psychological and HRV Testing at Workplace.

During COVID-19 pandemic peaks, healthcare professionals are a frontline workforce that deals with death on an almost daily basis and experiences a marked increase in workload. Returning home is also associated with fear of contaminating or be contaminated. An obvious consequence is stress accumulation and associated risks, especially in caregivers in mobility and possibly in human resource teams managing mobility. Here, during the second pandemic peak, we designed a 15-min testing procedure at the workplace, combining HADS and Brief COPE questionnaires with heart rate variability (HRV) recordings to evaluate psychophysiological status in four groups: caregivers in mobility (MOB); human resources teams managing mobility (ADM); caregivers without mobility (N-MOB); and university researchers teaching online (RES). Anxiety, depression, coping strategies, vagally-mediated heart rate regulation, and nonlinear dynamics (entropy) in cardiac autonomic control were quantified. Anxiety reached remarkably high levels in both MOB and ADM, which was reflected in vagal and nonlinear HRV markers. ADM maintained a better problem-solving capacity. MOB and N-MOB exhibited degraded problem-solving capacity. Multivariate approaches show how combining psychological and physiological markers helps draw highly group-specific psychophysiological profiles. Entropy in HRV and problem-solving capacity were highly relevant for that. Combining HADS and Brief COPE questionnaires with HRV testing at the workplace may provide highly relevant cues to manage mobility during crises as well as prevent health risks, absenteeism, and more generally malfunction incidents at hospitals.

Fast Hand Movements Unveil Multifractal Roots of Adaptation in the Visuomotor Cognitive System.

Beyond apparent simplicity, visuomotor dexterity actually requires the coordination of multiple interactions across a complex system that links the brain, the body and the environment. Recent research suggests that a better understanding of how perceptive, cognitive and motor activities cohere to form executive control could be gained from multifractal formalisms applied to movement behavior. Rather than a central executive "talking" to encapsuled components, the multifractal intuition suggests that eye-hand coordination arises from multiplicative cascade dynamics across temporal scales of activity within the whole system, which is reflected in movement time series. Here we examined hand movements of sport students performing a visuomotor task in virtual reality (VR). The task involved hitting spatially arranged targets that lit up on a virtual board under critical time pressure. Three conditions were compared where the visual search field changed: whole board (Standard), half-board lower view field (LVF) and upper view field (UVF). Densely sampled (90 Hz) time series of hand motions captured by VR controllers were analyzed by a focus-based multifractal detrended fluctuation analysis (DFA). Multiplicative rather than additive interactions across temporal scales were evidenced by testing comparatively phase-randomized surrogates of experimental series, which confirmed nonlinear processes. As main results, it was demonstrated that: (i) the degree of multifractality in hand motion behavior was minimal in LVF, a familiar visual search field where subjects correlatively reached their best visuomotor response times (RTs); (ii) multifractality increased in the less familiar UVF, but interestingly only for the non-dominant hand; and (iii) multifractality increased further in Standard, for both hands indifferently; in Standard, the maximal expansion of the visual search field imposed the highest demand as evidenced by the worst visuomotor RTs. Our observations advocate for visuomotor dexterity best described by multiplicative cascades dynamics and a system-wide distributed control rather than a central executive. More importantly, multifractal metrics obtained from hand movements behavior, beyond the confines of the brain, offer a window on the fine organization of control architecture, with high sensitivity to hand-related control behavior under specific constraints. Appealing applications may be found in movement learning/rehabilitation, e.g., in hemineglect people, stroke patients, maturing children or athletes.

Entropy and Multifractal-Multiscale Indices of Heart Rate Time Series to Evaluate Intricate Cognitive-Autonomic Interactions.

Recent research has clarified the existence of a networked system involving a cortical and subcortical circuitry regulating both cognition and cardiac autonomic control, which is dynamically organized as a function of cognitive demand. The main interactions span multiple temporal and spatial scales and are extensively governed by nonlinear processes. Hence, entropy and (multi)fractality in heart period time series are suitable to capture emergent behavior of the cognitive-autonomic network coordination. This study investigated how entropy and multifractal-multiscale analyses could depict specific cognitive-autonomic architectures reflected in the heart rate dynamics when students performed selective inhibition tasks. The participants (N=37) completed cognitive interference (Stroop color and word task), action cancellation (stop-signal) and action restraint (go/no-go) tasks, compared to watching a neutral movie as baseline. Entropy and fractal markers (respectively, the refined composite multiscale entropy and multifractal-multiscale detrended fluctuation analysis) outperformed other time-domain and frequency-domain markers of the heart rate variability in distinguishing cognitive tasks. Crucially, the entropy increased selectively during cognitive interference and the multifractality increased during action cancellation. An interpretative hypothesis is that cognitive interference elicited a greater richness in interactive processes that form the central autonomic network while action cancellation, which is achieved via biasing a sensorimotor network, could lead to a scale-specific heightening of multifractal behavior.

Integrative Methods for Studying Cardiac Energetics.

The more recent studies of human pathologies have essentially revealed the complexity of the interactions involved at the different levels of integration in organ physiology. Integrated organ thus reveals functional properties not predictable by underlying molecular events. It is therefore obvious that current fine molecular analyses of pathologies should be fruitfully combined with integrative approaches of whole organ function. It follows that an important issue in the comprehension of the link between molecular events in pathologies and whole organ function/dysfunction is the development of new experimental strategies aimed at the study of the integrated organ physiology. Cardiovascular diseases are a good example as heart submitted to ischemic conditions has to cope both with a decreased supply of nutrients and oxygen, and the necessary increased activity required to sustain whole body-including the heart itself-oxygenation.By combining the principles of control analysis with noninvasive 31P NMR measurement of the energetic intermediates and simultaneous measurement of heart contractile activity, we developed MoCA (for Modular Control and regulation Analysis), an integrative approach designed to study in situ control and regulation of cardiac energetics during contraction in intact beating perfused isolated heart (Diolez et al., Am J Physiol Regul Integr Comp Physiol 293(1):R13-R19, 2007). Because it gives real access to integrated organ function, MoCA brings out a new type of information-the "elasticities," referring to integrated internal responses to metabolic changes-that may be a key to the understanding of the processes involved in pathologies. MoCA can potentially be used not only to detect the origin of the defects associated with the pathology, but also to provide the quantitative description of the routes by which these defects-or also drugs-modulate global heart function, therefore opening therapeutic perspectives. This review presents selected examples of the applications to isolated intact beating heart that evidence different modes of energetic regulation of cardiac contraction. We also discuss the clinical application by using noninvasive 31P cardiac energetics examination under clinical conditions for detection of heart pathologies.

Physiological Resonance in Empathic Stress: Insights from Nonlinear Dynamics of Heart Rate Variability.

Because most humans live and work in populated environments, researchers recently took into account that people may not only experience first-hand stress, but also second-hand stress related to the ability to empathically share another person's stress response. Recently, researchers have begun to more closely examine the existence of such empathic stress and highlighted the human propensity to physiologically resonate with the stress responses of others. As in case of first-hand stress, empathic stress could be deleterious for health if people experience exacerbated activation of hypothalamic-pituitary-adrenal and autonomic nervous systems. Thus, exploring empathic stress in an observer watching someone else experiencing stress is critical to gain a better understanding of physiological resonance and conduct strategies for health prevention. In the current study, we investigated the influence of empathic stress responses on heart rate variability (HRV) with a specific focus on nonlinear dynamics. Classic and nonlinear markers of HRV time series were computed in both targets and observers during a modified Trier social stress test (TSST). We capitalized on multiscale entropy, a reliable marker of complexity for depicting neurovisceral interactions (brain-to-heart and heart-to-brain) and their role in physiological resonance. State anxiety and affect were evaluated as well. While classic markers of HRV were not impacted by empathic stress, we showed that the complexity marker reflected the existence of empathic stress in observers. More specifically, a linear model highlighted a physiological resonance phenomenon. We conclude on the relevance of entropy in HRV dynamics, as a marker of complexity in neurovisceral interactions reflecting physiological resonance in empathic stress.

Reliability of the Dynavision task in virtual reality to explore visuomotor phenotypes.

Daily-life behaviors strongly rely on visuomotor integration, a complex sensorimotor process with obvious plasticity. Visual-perceptive and visual-cognitive functions are degraded by neurological disorders and brain damage, but are improved by vision training, e.g. in athletes. Hence, developing tools to evaluate/improve visuomotor abilities has found echo among psychologists, neurophysiologists, clinicians and sport professionals. Here we implemented the Dynavision visuomotor reaction task in virtual reality (VR) to get a flexible tool to place high demands on visual-perceptive and visual-cognitive processes, and explore individual abilities in visuomotor integration. First, we demonstrated high test-retest reliability for the task in VR among healthy physically-active students (n = 64, 32 females). Second, the capture of head movements thanks to the VR-headset sensors provided new and reliable information on individual visual-perceptual strategies, which added significant value to explore visuomotor phenotypes. A factor analysis of mixed data and hierarchical clustering on principal components points to head movements, video-games practice and ball-tracking sports as critical cues to draw visuomotor phenotypes among our participants. We conclude that the visuomotor task in VR is a reliable, flexible and promising tool. Since VR nowadays can serve e.g. to modulate multisensorial integration by creating visual interoceptive-exteroceptive conflicts, or placing specifically designed cognitive demand, much could be learned on complex integrated visuomotor processes through VR experiments. This offers new perspectives for post brain injury risk evaluation, rehabilitation programs and visual-cognitive training.

Entropy in Heart Rate Dynamics Reflects How HRV-Biofeedback Training Improves Neurovisceral Complexity during Stress-Cognition Interactions.

Despite considerable appeal, the growing appreciation of biosignals complexity reflects that system complexity needs additional support. A dynamically coordinated network of neurovisceral integration has been described that links prefrontal-subcortical inhibitory circuits to vagally-mediated heart rate variability. Chronic stress is known to alter network interactions by impairing amygdala functional connectivity. HRV-biofeedback training can counteract stress defects. We hypothesized the great value of an entropy-based approach of beat-to-beat biosignals to illustrate how HRVB training restores neurovisceral complexity, which should be reflected in signal complexity. In thirteen moderately-stressed participants, we obtained vagal tone markers and psychological indexes (state anxiety, cognitive workload, and Perceived Stress Scale) before and after five-weeks of daily HRVB training, at rest and during stressful cognitive tasking. Refined Composite Multiscale Entropy (RCMSE) was computed over short time scales as a marker of signal complexity. Heightened vagal tone at rest and during stressful tasking illustrates training benefits in the brain-to-heart circuitry. The entropy index reached the highest significance levels in both variance and ROC curves analyses. Restored vagal activity at rest correlated with gain in entropy. We conclude that HRVB training is efficient in restoring healthy neurovisceral complexity and stress defense, which is reflected in HRV signal complexity. The very mechanisms that are involved in system complexity remain to be elucidated, despite abundant literature existing on the role played by amygdala in brain interconnections.

Alterations in heart-brain interactions under mild stress during a cognitive task are reflected in entropy of heart rate dynamics.

Many people experience mild stress in modern society which raises the need for an improved understanding of psychophysiological responses to stressors. Heart rate variability (HRV) may be associated with a flexible network of intricate neural structures which are dynamically organized to cope with diverse challenges. HRV was obtained in thirty-three healthy participants performing a cognitive task both with and without added stressors. Markers of neural autonomic control and neurovisceral complexity (entropy) were computed from HRV time series. Based on individual anxiety responses to the experimental stressors, two subgroups were identified: anxiety responders and non-responders. While both vagal and entropy markers rose during the cognitive task alone in both subgroups, only entropy decreased when stressors were added and exclusively in anxiety responders. We conclude that entropy may be a promising marker of cognitive tasks and acute mild stress. It brings out a new central question: why is entropy the only marker affected by mild stress? Based on the neurovisceral integration model, we hypothesized that neurophysiological complexity may be altered by mild stress, which is reflected in entropy of the cardiac output signal. The putative role of the amygdala during mild stress, in modulating the complexity of a coordinated neural network linking brain to heart, is discussed.

Fractal properties and short-term correlations in motor control in cycling: influence of a cognitive challenge.

Fluctuations in cyclic tasks periods is a known characteristic of human motor control. Specifically, long-range fractal fluctuations have been evidenced in the temporal structure of these variations in human locomotion and thought to be the outcome of a multicomponent physiologic system in which control is distributed across intricate cortical, spinal and neuromuscular regulation loops. Combined with long-range correlation analyses, short-range autocorrelations have proven their use to describe control distribution across central and motor components. We used relevant tools to characterize long- and short-range correlations in revolution time series during cycling on an ergometer in 19 healthy young adults. We evaluated the impact of introducing a cognitive task (PASAT) to assess the role of central structures in control organization. Autocorrelation function and detrending fluctuation analysis (DFA) demonstrated the presence of fractal scaling. PSD in the short range revealed a singular behavior which cannot be explained by the usual models of even-based and emergent timing. The main outcomes are that (1) timing in cycling is a fractal process, (2) this long-range fractal behavior increases in persistence with dual-task condition, which has not been previously observed, (3) short-range behavior is highly persistent and unaffected by dual-task. Relying on the inertia of the oscillator may be a way to distribute more control to the periphery, thereby allocating less resources to central process and better managing additional cognitive demands. This original behavior in cycling may explain the high short-range persistence unaffected by dual-task, and the increase in long-range persistence with dual-task.

Corrigendum: Frequency-Specific Fractal Analysis of Postural Control Accounts for Control Strategies.

[This corrects the article DOI: 10.3389/fphys.2018.00293.].

Effects of heart rate variability biofeedback training in athletes exposed to stress of university examinations.

INTRODUCTION: Heart rate variability biofeedback (HRV-BFB) training, a method whereby one controls an unusually low breathing rate to reach cardiac coherence, has been shown to reduce anxiety and improve cardiac autonomic markers in diseased people, but much less is known about HRV-BFB benefits in healthy people. Here we investigated potential benefits in young competitors experiencing stress during university examinations as well as persistence of benefits after HRV-BFB training cessation. METHODS: A group of sports students (n = 12) practiced 5-min HRV-BFB training twice a day for 5-weeks using URGOfeel® (URGOTECH) and was compared to a control group (n = 6). University examinations occurred immediately after HRV-BFB training (Exam1), then 12-weeks later (Exam2). Anxiety markers and cardiac autonomic markers were assessed at baseline, Exam1 and Exam2. Principal Component Analyses (PCA) that combined all these markers were computed at Exam1 and Exam2 to emphasize covariations. RESULTS: At Exam 1, immediately after HRV-BFB training cessation, the experimental group demonstrated greater autonomic markers but similar states of anxiety when compared to the Control group. Twelve weeks later at Exam2, autonomic markers were greater and anxiety scores were lesser among the experimental group. PCA highlighted covariations only within cardiac autonomic markers at Exam1. Rather, variations in cardiac markers were associated with anxiety markers at Exam2. CONCLUSION: Short sessions of HRV-BFB training for a brief period of 5 weeks bring substantial benefits to autonomic markers and anxiety levels in young competitors. Here beneficial effects persisted for 12 weeks. Dissociated profiles of anxiety and cardiac autonomic adaptations shed new light on the role of the amygdala in heart-brain interactions after cardiac coherence training.

Detrended fluctuation analysis in a simple spreadsheet as a tool for teaching fractal physiology.

Fractal physiology demonstrated growing interest over the last decades among physiologists, neuroscientists, and clinicians. Many physiological systems coordinate themselves for reducing variability and maintain a steady state. When recorded over time, the output signal exhibits small fluctuations around a stable value. It is becoming increasingly clear that these fluctuations, in most free-running healthy systems, are not simply due to uncorrelated random errors and possess interesting properties, one of which is the property of fractal dynamics. Fractal dynamics model temporal processes in which similar patterns occur across multiple timescales of measurement. Smaller copies of a pattern are nested within larger copies of the pattern, a property termed scale invariance. It is an intriguing process that may deserve attention for implementing curricular development for students to reconsider homeostasis. Teaching fractal dynamics needs to make calculating resources available for students. The present paper offers a calculating resource that uses a basic formula and is executable in a simple spreadsheet. The spreadsheet allows computing detrended fluctuation analysis (DFA), the most frequently used method in the literature to quantify the fractal-scaling index of a physiological time series. DFA has been nicely described by the group at Harvard that designed it; the authors made the C language source available. Going further, it is suggested here that a guide to build DFA step by step in a spreadsheet has many advantages for teaching fractal physiology and beyond: 1) it promotes the DIY (do-it-yourself) in students and highlights scaling concepts; and 2) it makes DFA available for people not familiarized with executing code in C language.

Frequency-Specific Fractal Analysis of Postural Control Accounts for Control Strategies.

Diverse indicators of postural control in Humans have been explored for decades, mostly based on the trajectory of the center-of-pressure. Classical approaches focus on variability, based on the notion that if a posture is too variable, the subject is not stable. Going deeper, an improved understanding of underlying physiology has been gained from studying variability in different frequency ranges, pointing to specific short-loops (proprioception), and long-loops (visuo-vestibular) in neural control. More recently, fractal analyses have proliferated and become useful additional metrics of postural control. They allowed identifying two scaling phenomena, respectively in short and long timescales. Here, we show that one of the most widely used methods for fractal analysis, Detrended Fluctuation Analysis, could be enhanced to account for scalings on specific frequency ranges. By computing and filtering a bank of synthetic fractal signals, we established how scaling analysis can be focused on specific frequency components. We called the obtained method Frequency-specific Fractal Analysis (FsFA) and used it to associate the two scaling phenomena of postural control to proprioceptive-based control loop and visuo-vestibular based control loop. After that, convincing arguments of method validity came from an application on the study of unaltered vs. altered postural control in athletes. Overall, the analysis suggests that at least two timescales contribute to postural control: a velocity-based control in short timescales relying on proprioceptive sensors, and a position-based control in longer timescales with visuo-vestibular sensors, which is a brand-new vision of postural control. Frequency-specific scaling exponents are promising markers of control strategies in Humans.

Energy Deregulation Precedes Alteration in Heart Energy Balance in Young Spontaneously Hypertensive Rats: A Non Invasive In Vivo31P-MR Spectroscopy Follow-Up Study.

INTRODUCTION: Gradual alterations in cardiac energy balance, as assessed by the myocardial PCr/ATP-ratio, are frequently associated with the development of cardiac disease. Despite great interest for the follow-up of myocardial PCr and ATP content, cardiac MR-spectroscopy in rat models in vivo is challenged by sensitivity issues and cross-contamination from other organs. METHODS: Here we combined MR-Imaging and MR-Spectroscopy (Bruker BioSpec 9.4T) to follow-up for the first time in vivo the cardiac energy balance in the SHR, a genetic rat model of cardiac hypertrophy known to develop early disturbances in cytosolic calcium dynamics. RESULTS: We obtained consistent 31P-spectra with high signal/noise ratio from the left ventricle in vivo by using a double-tuned (31P/1H) surface coil. Reasonable acquisition time (<3.2min) allowed assessing the PCr/ATP-ratio comparatively in SHR and age-matched control rats (WKY): i) weekly from 12 to 21 weeks of age; ii) in response to a bolus injection of the ß-adrenoreceptor agonist isoproterenol at age 21 weeks. DISCUSSION: Along weeks, the cardiac PCr/ATP-ratio was highly reproducible, steady and similar (2.35±0.06) in SHR and WKY, in spite of detectable ventricular hypertrophy in SHR. At the age 21 weeks, PCr/ATP dropped more markedly (-17.1%±0.8% vs. -3,5%±1.4%, P<0.001) after isoproterenol injection in SHR and recovered slowly thereafter (time constant 21.2min vs. 6.6min, P<0.05) despite similar profiles of tachycardia among rats. CONCLUSION: The exacerbated PCr/ATP drop under ß-adrenergic stimulation indicates a defect in cardiac energy regulation possibly due to calcium-mediated abnormalities in the SHR heart. Of note, defects in energy regulation were present before detectable abnormalities in cardiac energy balance at rest.

Integrative methods for studying cardiac energetics.

The more recent studies of human pathologies have essentially revealed the complexity of the interactions involved at the different levels of integration in organ physiology. Integrated organ thus reveals functional properties not predictable by underlying molecular events. It is therefore obvious that current fine molecular analyses of pathologies should be fruitfully combined with integrative approaches of whole organ function. It follows an important issue in the comprehension of the link between molecular events in pathologies, and whole organ function/dysfunction is the development of new experimental strategies aimed at the study of the integrated organ physiology. Cardiovascular diseases are a good example as heart submitted to ischemic conditions has to cope both with a decreased supply of nutrients and oxygen, and the necessary increased activity required to sustain whole body-including the heart itself-oxygenation.By combining the principles of control analysis with noninvasive (31)P NMR measurement of the energetic intermediates and simultaneous measurement of heart contractile activity, we developed MoCA (for Modular Control and Regulation Analysis), an integrative approach designed to study in situ control and regulation of cardiac energetics during contraction in intact beating perfused isolated heart (Diolez et al., Am J Physiol Regul Integr Comp Physiol 293(1):R13-R19, 2007). Because it gives real access to integrated organ function, MoCA brings out a new type of information-the "elasticities," referring to internal responses to metabolic changes-that may be a key to the understanding of the processes involved in pathologies. MoCA can potentially be used not only to detect the origin of the defects associated with the pathology, but also to provide the quantitative description of the routes by which these defects-or also drugs-modulate global heart function, therefore opening therapeutic perspectives. This review presents selected examples of the applications to isolated intact beating heart and a wider application to cardiac energetics under clinical conditions with the direct study of heart pathologies.

Mitochondrial energetics is impaired in vivo in aged skeletal muscle.

With aging, most skeletal muscles undergo a progressive loss of mass and strength, a process termed sarcopenia. Aging-related defects in mitochondrial energetics have been proposed to be causally involved in sarcopenia. However, changes in muscle mitochondrial oxidative phosphorylation with aging remain a highly controversial issue, creating a pressing need for integrative approaches to determine whether mitochondrial bioenergetics are impaired in aged skeletal muscle. To address this issue, mitochondrial bioenergetics was first investigated in vivo in the gastrocnemius muscle of adult (6 months) and aged (21 months) male Wistar rats by combining a modular control analysis approach with (31) P magnetic resonance spectroscopy measurements of energetic metabolites. Using this innovative approach, we revealed that the in vivo responsiveness ('elasticity') of mitochondrial oxidative phosphorylation to contraction-induced increase in ATP demand is significantly reduced in aged skeletal muscle, a reduction especially pronounced under low contractile activities. In line with this in vivo aging-related defect in mitochondrial energetics, we found that the mitochondrial affinity for ADP is significantly decreased in mitochondria isolated from aged skeletal muscle. Collectively, the results of this study demonstrate that mitochondrial bioenergetics are effectively altered in vivo in aged skeletal muscle and provide a novel cellular basis for this phenomenon.

Influence of individual energy cost on running capacity in warm, humid environments.

PURPOSE: Challenging environmental conditions including heat and humidity are associated with particular risks to the health of runners and triathletes during prolonged events. The heat production of a runner is the product of its energy cost of running (C r) by its velocity. Since C r varies greatly among humans, those individuals with high C r are more exposed to heat stress in warm and humid conditions. Although risk factor awareness is crucial to the prevention of heat stroke and potential fatalities associated therewith, how C r affects the highest sustainable velocity (V) at which maximal heat loss matches heat production has not been quantified to date. METHODS: Here, we computed in virtual runners weighting 45-75 kg, the influence of C r variability from 3.8 to 4.4 J·m(-1)·kg(-1) on V. Heat loss by radiation, convection, and conduction was assessed from known equations including body dimensions, running velocity (3.4-6.2 m·s(-1)), air temperature (T a, 10-35 °C) and relative humidity (r h, 50, 70 and 90 %). RESULTS: We demonstrated a marked and almost linear influence of C r on V in hot and humid conditions: +0.1 J·kg(-1)·m(-1) in C r corresponded to -4 % in V. For instance, in conditions 25 °C r h 70 %, 65-kg runners with low C r could sustain a running speed of 5.7 m·s(-1) as compared to only 4.3 m·s(-1) in runners with high C r, which is huge. CONCLUSION: We conclude that prior knowledge of individual C r in athletes exposed to somewhat warm and humid environments during prolonged running is one obvious recommendation for minimizing heat illness risk.