Comprendre l’interaction entre la douleur et le système moteur : une étude novatrice combinant la stimulation magnétique transcrânienne et l’électroencéphalographie

Résumé : L’interaction entre la douleur et le système moteur est bien connue en clinique et en réadaptation. Il est sans surprise que la douleur est un phénomène considérablement invalidant, affectant la qualité de vie de ceux et celles qui en souffrent. Toutefois, les bases neurophysiologiques qui sous-tendent cette interaction demeurent, encore aujourd’hui, mal comprises. Le but de la présente étude était de mieux comprendre les mécanismes corticaux impliqués dans l’interaction entre la douleur et le système moteur. Pour ce faire, une douleur expérimentale a été induite à l’aide d’une crème à base de capsaïcine au niveau de l’avant-bras gauche des participants. L'effet de la douleur sur la force des projections corticospinales ainsi que sur l’activité cérébrale a été mesuré à l’aide de la stimulation magnétique transcrânienne (TMS) et de l’électroencéphalographie (EEG), respectivement. L’analyse des données EEG a permis de révéler qu'en présence de douleur aiguë, il y a une augmentation de l’activité cérébrale au niveau du cuneus central (fréquence têta), du cortex dorsolatéral préfrontal gauche (fréquence alpha) ainsi que du cuneus gauche et de l'insula droite (toutes deux fréquence bêta), lorsque comparée à la condition initiale (sans douleur). Également, les analyses démontrent une augmentation de l'activité du cortex moteur primaire droit en présence de douleur, mais seulement chez les participants qui présentaient simultanément une diminution de leur force de projections corticales (mesurée avec la TMS t=4,45, p<0,05). Ces participants ont également montré une plus grande connectivité entre M1 et le cuneus que les participants dont la douleur n’a pas affecté la force des projections corticospinales (t=3,58, p<0,05). Ces résultats suggèrent qu’une douleur expérimentale induit, chez certains individus, une altération au niveau des forces de projections corticomotrices. Les connexions entre M1 et le cuneus seraient possiblement impliquées dans la survenue de ces changements corticomoteurs.

Unexpected Levels of Biological Activity during the Polar Night Offer New Perspectives on a Warming Arctic

The current understanding of Arctic ecosystems is deeply rooted in the classical view of a bottom-up controlled system with strong physical forcing and seasonality in primary-production regimes. Consequently, the Arctic polar night is commonly disregarded as a time of year when biological activities are reduced to a minimum due to a reduced food supply. Here, based upon a multidisciplinary ecosystem-scale study from the polar night at 79 degrees N, we present an entirely different view. Instead of an ecosystem that has entered a resting state, we document a system with high activity levels and biological interactions across most trophic levels. In some habitats, biological diversity and presence of juvenile stages were elevated in winter months compared to the more productive and sunlit periods. Ultimately, our results suggest a different perspective regarding ecosystem function that will be of importance for future environmental management and decision making, especially at a time when Arctic regions are experiencing accelerated environmental change [1].

MRI indices of functional recovery following intracerebral implantation of a human neural stem cell line in a pre-clinical model of ischaemic stroke

Stem cell therapy for ischaemic stroke is an emerging field in light of an increasing number of patients surviving with permanent disability. Several allogenic and autologous cells types are now in clinical trials with preliminary evidence of safety. Some clinical studies have reported functional improvements in some patients. After initial safety evaluation in a Phase 1 study, the conditionally immortalised human neural stem cell line CTX0E03 is currently in a Phase 2 clinical trial (PISCES-II). Previous pre-clinical studies conducted by ReNeuron Ltd, showed evidence of functional recovery in the Bilateral Asymmetry test up to 6 weeks following transplantation into rodent brain, 4 weeks after middle cerebral artery occlusion. Resting-state fMRI is increasingly used to investigate brain function in health and disease, and may also act as a predictor of recovery due to known network changes in the post-stroke recovery period. Resting-state methods have also been applied to non-human primates and rodents which have been found to have analogous resting-state networks to humans. The sensorimotor resting-state network of rodents is impaired following experimental focal ischaemia of the middle cerebral artery territory. However, the effects of stem cell implantation on brain functional networks has not previously been investigated. Prior studies assessed sensorimotor function following sub-cortical implantation of CTX0E03 cells in the rodent post-stroke brain but with no MRI assessments of functional improvements. This thesis presents research on the effect of sub-cortical implantation of CTX0E03 cells on the resting- state sensorimotor network and sensorimotor deficits in the rat following experimental stroke, using protocols based on previous work with this cell line. The work in this thesis identified functional tests of appropriate sensitivity for long-term dysfunction suitable for this laboratory, and investigated non-invasive monitoring of physiological variables required to optimize BOLD signal stability within a high-field MRI scanner. Following experimental stroke, rats demonstrated expected sensorimotor dysfunction and changes in the resting-state sensorimotor network. CTX0E03 cells did not improve post-stroke functional outcome (compared to previous studies) and with no changes in resting-state sensorimotor network activity. However, in control animals, we observed changes in functional networks due to the stereotaxic procedure. This illustrates the sensitivity of resting-state fMRI to stereotaxic procedures. We hypothesise that the damage caused by cell or vehicle implantation may have prevented functional and network recovery which has not been previously identified due to the application of different functional tests. The findings in this thesis represent one of few pre-clinical studies in resting-state fMRI network changes post-stroke and the only to date applying this technique to evaluate functional outcomes following a clinically applicable human neural stem cell treatment for ischaemic stroke. It was found that injury caused by stereotaxic injection should be taken into account when assessing the effectiveness of treatment.

Cocaine-specific neuroplasticity in the ventral striatum network is linked to delay discounting and drug relapse

AIMS: To contrast functional connectivity on ventral and dorsal striatum networks in cocaine dependence relative to pathological gambling, via a resting-state functional connectivity approach; and to determine the association between cocaine dependence-related neuroadaptations indexed by functional connectivity and impulsivity, compulsivity and drug relapse. DESIGN: Cross-sectional study of 20 individuals with cocaine dependence (CD), 19 individuals with pathological gambling (PG) and 21 healthy controls (HC), and a prospective cohort study of 20 CD followed-up for 12 weeks to measure drug relapse. SETTING AND PARTICIPANTS: CD and PG were recruited through consecutive admissions to a public clinic specialized in substance addiction treatment (Centro Provincial de Drogodependencias) and a public clinic specialized in gambling treatment (AGRAJER), respectively; HC were recruited through community advertisement in the same area in Granada (Spain). MEASUREMENTS: Seed-based functional connectivity in the ventral striatum (ventral caudate and ventral putamen) and dorsal striatum (dorsal caudate and dorsal putamen), the Kirby delay-discounting questionnaire, the reversal-learning task and a dichotomous measure of cocaine relapse indicated with self-report and urine tests. FINDINGS: CD relative to PG exhibit enhanced connectivity between the ventral caudate seed and subgenual anterior cingulate cortex, the ventral putamen seed and dorsomedial pre-frontal cortex and the dorsal putamen seed and insula (P≤0.001, kE=108). Connectivity between the ventral caudate seed and subgenual anterior cingulate cortex is associated with steeper delay discounting (P≤0.001, kE=108) and cocaine relapse (P≤0.005, kE=34). CONCLUSIONS: Cocaine dependence-related neuroadaptations in the ventral striatum of the brain network are associated with increased impulsivity and higher rate of cocaine relapse.

Increased corticolimbic connectivity in cocaine dependence versus pathological gambling is associated with drug severity and emotion-related impulsivity

Neural biomarkers for the active detrimental effects of cocaine dependence (CD) are lacking. Direct comparisons of brain connectivity in cocaine-targeted networks between CD and behavioural addictions (i.e. pathological gambling, PG) may be informative. This study therefore contrasted the resting-state functional connectivity networks of 20 individuals with CD, 19 individuals with PG and 21 healthy individuals (controls). Study groups were assessed to rule out psychiatric co-morbidities (except alcohol abuse and nicotine dependence) and current substance use or gambling (except PG). We first examined global connectivity differences in the corticolimbic reward network and then utilized seed-based analyses to characterize the connectivity of regions displaying between-group differences. We examined the relationships between seed-based connectivity and trait impulsivity and cocaine severity. CD compared with PG displayed increased global functional connectivity in a large-scale ventral corticostriatal network involving the orbitofrontal cortex, caudate, thalamus and amygdala. Seed-based analyses showed that CD compared with PG exhibited enhanced connectivity between the orbitofrontal and subgenual cingulate cortices and between caudate and lateral prefrontal cortex, which are involved in representing the value of decision-making feedback. CD and PG compared with controls showed overlapping connectivity changes between the orbitofrontal and dorsomedial prefrontal cortices and between amygdala and insula, which are involved in stimulus-outcome learning. Orbitofrontal-subgenual cingulate cortical connectivity correlated with impulsivity and caudate/amygdala connectivity correlated with cocaine severity. We conclude that CD is linked to enhanced connectivity in a large-scale ventral corticostriatal-amygdala network that is relevant to decision making and likely to reflect an active cocaine detrimental effect.

Prevalencia de síntomas de fatiga crónica / encefalomielitis miálgica (SFC/EM) y su relación con factores ocupacionales en trabajadores en una empresa de vigilancia en Bogotá, Colombia, 2016

Antecedentes: El síndrome de fatiga crónica/encefalomielitis miálgica (SFC/EM), un trastorno debilitante y complejo que se caracteriza por un cansancio intenso, ha sido estudiado en población general, sin embargo, su exploración en población trabajadora ha sido limitada. Objetivo: Determinar la prevalencia de síntomas asociados a SFC/EM y su relación con factores ocupacionales en personal de una empresa de vigilancia en Bogotá, durante el año 2016. Materiales y métodos: Estudio de corte transversal en una empresa de vigilancia, utilizando como instrumento para la recolección de datos la historia clínica-ocupacional. En las variables cualitativas se obtuvieron frecuencias simples y porcentajes y en las variables cuantitativas medidas de tendencia central y de dispersión. Se determinaron asociaciones entre variables (Ji-cuadrado de Pearson o test exacto de Fisher, valores esperados <5), (mann-whitney.y un modelo de regresión logística incondicional (p<0.05)). Resultados: Se evaluaron 162 trabajadores, los síntomas de SFC/EM con mayor prevalencia fueron sueño no reparador (38,3%) y dolor muscular (30,2%). Se encontró asociación estadísticamente significativa entre fatiga severa y crónica por al menos 6 meses con alteración en sistema nervioso (p=0,016) y consumo de medicamentos (p=0,043), así mismo entre el sueño no reparador con el número de horas de sueño de 5 a 7 horas (p=0,002). Conclusión: En los vigilantes el síntoma de SFC/EM más prevalente fue sueño no reparador y este se asoció con el número de horas de sueño de 5 a 7 horas. Con el estudio se pudieron determinar los casos probables de SFC/EM los cuales se beneficiarían de una valoración médica integral para un diagnóstico oportuno.

Reduced resting skeletal muscle protein synthesis is rescued by resistance exercise and protein ingestion following short-term energy deficit

The myofibrillar protein synthesis (MPS) response to resistance exercise (REX) and protein ingestion during energy deficit (ED) is unknown. We determined, in young men (n=8) and women (n=7), protein signaling, resting post-absorptive MPS during energy balance [EB: 45 kcal∙(kg FFM∙d)-1] and after 5d of ED [30 kcal∙(kg FFM∙d)-1] as well as MPS while in ED after acute REX in the fasted state and with the ingestion of whey protein (15 and 30 g). Post-absorptive rates of MPS were 27% lower in ED than EB (P<0.001), but REX stimulated MPS to rates equal to EB. Ingestion of 15 and 30 g of protein after REX in ED increased MPS ~16 and ~34% above resting EB, (P<0.02). p70 S6Kthr389 phosphorylation increased above EB only with combined exercise and protein intake (~2-7 fold; P<0.05). In conclusion, short-term ED reduces post-absorptive MPS, however, a bout of REX in ED restores MPS to values observed at rest in EB. The ingestion of protein after REX further increases MPS above resting EB in a dose-dependent manner. We conclude that combining REX with increased protein availability after exercise enhances rates of skeletal muscle protein synthesis during short term ED and could, in the long term, preserve muscle mass.

Never-resting microglia: physiological roles in the healthy brain and pathological implications

Microglia are largely known as the major orchestrators of the brain inflammatory response. As such, they have been traditionally studied in various contexts of disease, where their activation has been assumed to induce a wide range of detrimental effects. In the last few years, a series of discoveries have challenged the current view of microglia, showing their active and positive contribution to normal brain function. This Research Topic will review the novel physiological roles of microglia in the developing, mature and aging brain, under non-pathological conditions. In particular, this Research Topic will discuss the cellular and molecular mechanisms by which microglia contribute to the formation, pruning and plasticity of synapses; the maintenance of the blood brain barrier; the regulation of adult neurogenesis and hippocampal learning; and neuronal survival, among other important roles. Because these novel findings defy our understanding of microglial function in health as much as in disease, this Research Topic will also summarize the current view of microglial nomenclature, phenotypes, origin and differentiation, sex differences, and contribution to various brain pathologies. Additionally, novel imaging approaches and molecular tools to study microglia in their non-activated state will be discussed. In conclusion, this Research Topic seeks to emphasize how the current research in neuroscience is challenged by never-resting microglia.

Influence of a fed or fasted state on the s-IgA response to prolonged cycling in active men and women

This study investigated the effect of a fed or fasted state on the salivary immunoglobulin A (s-IgA) response to prolonged cycling. Using a randomized, crossover design, 16 active adults (8 men and 8 women) performed 2 hr of cycling on a stationary ergometer at 65% of maximal oxygen uptake on 1 occasion after an overnight fast (FAST) and on another occasion 2 hr after consuming a 2.2-MJ high-carbohydrate meal (FED). Timed, unstimulated whole saliva samples were collected immediately before ingestion of the meal, immediately preexercise, 5 min before cessation of exercise, immediately postexercise, and 1 hr postexercise. The samples were analyzed for s-IgA concentration, osmolality, and cortisol, and saliva flow rates were determined to calculate s-IgA secretion rate. Saliva flow rate decreased by 50% during exercise (p < .05), and s-IgA concentration increased by 42% (p < .05), but s-IgA secretion rate remained unchanged. There was a 37% reduction in s-IgA:osmolality postexercise (p < .05), and salivary cortisol increased by 68% (p < .05). There was no effect of FED vs. FAST on these salivary responses. The s-IgA concentration, secretion rate, and osmolality were found to be significantly lower in women than in men throughout the exercise protocol (p < .05); however, there was no difference between genders in saliva flow rate, s-IgA:osmolality ratio, or cortisol. These data demonstrate that a fed or fasted state 2 hr before exercise does not influence resting s-IgA or the response to prolonged cycling. Furthermore, these results show lower levels of s-IgA and osmolality in women than in men at rest.

Measuring the state of consciousness in a free-living diving sea turtle

We report on results from two types of data-logger attached to hawksbill turtles (Eretmochelys coriacea) in the breeding season at the Seychelles, Indian Ocean. Conventional time-depth recorders (TDRs) showed prolonged bouts of long dives to the seabed, consistent with benthic resting. This behaviour has been widely reported in sea turtles and appears to be a common feature for energy conservation. An Inter-Mandibular Angle Sensor (IMASEN) recorded mouth opening and buccal pumping by one turtle for 2.5 days. Buccal pumping occurred widely while the turtle was submerged, consistent with a function of olfactory sensory perception of the turtle's environment. However, buccal pumping stopped during the middle of long benthic dives consistent with the turtle entering a phase of sleep. It therefore appears that by recording buccal oscillations, it is possible to assess the state of consciousness of turtles allowing the eco-physiology of diving to be more fully explored. (C) 2007 Elsevier B.V. All rights reserved.

Resting metabolic rate and protein turnover in apparently healthy elderly Gambian men.

Body composition, resting energy expenditure (REE), and whole body protein metabolism were studied in 26 young and 28 elderly Gambian men matched for body mass index during the dry season in a rural village in The Gambia. REE was measured by indirect calorimetry (hood system) in the fasting state and after five successive meals. Rates of whole body nitrogen flux, protein synthesis, and protein breakdown were determined in the fed state from the level of isotopic enrichment of urinary ammonia over a period of 12 h after a single oral dose of [15N]glycine. Expressed in absolute value, REE was significantly lower in the elderly compared with the young group (3.21 +/- 0.07 vs. 4.04 +/- 0.07 kJ/min, P < 0.001) and when adjusted to body weight (3.29 +/- 0.05 vs. 3.96 +/- 0.05 kJ/min, P < 0.0001) and fat-free mass (FFM; 3.38 +/- 0.01 vs. 3.87 +/- 0.01 kJ/min, P < 0.0001). The rate of protein synthesis averaged 207 +/- 13 g protein/day in the elderly and 230 +/- 13 g protein/day in the young group, whereas protein breakdown averaged 184 +/- 13 g protein/day in the elderly and 203 +/- 13 g protein/day in the young group (nonsignificant). When values were adjusted for body weight or FFM, they did not reveal any difference between the two groups. It is concluded that the reduced REE adjusted for body composition observed in elderly Gambian men is not explained by a decrease in protein turnover.

Bifurcations and state changes in the human alpha rhythm: Theory and experiment

Despite many decades investigating scalp recordable 8–13-Hz (alpha) electroencephalographic activity, no consensus has yet emerged regarding its physiological origins nor its functional role in cognition. Here we outline a detailed, physiologically meaningful, theory for the genesis of this rhythm that may provide important clues to its functional role. In particular we find that electroencephalographically plausible model dynamics, obtained with physiological admissible parameterisations, reveals a cortex perched on the brink of stability, which when perturbed gives rise to a range of unanticipated complex dynamics that include 40-Hz (gamma) activity. Preliminary experimental evidence, involving the detection of weak nonlinearity in resting EEG using an extension of the well-known surrogate data method, suggests that nonlinear (deterministic) dynamics are more likely to be associated with weakly damped alpha activity. Thus rather than the “alpha rhythm” being an idling rhythm it may be more profitable to conceive it as a readiness rhythm.

THE INFLUENCE of RESTING PERIOD LENGTH on JUMPING PERFORMANCE

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Vagal control of heart rate and cardiac shunts in reptiles: Relation to metabolic state

The vagus is clearly of primary importance in the regulation of reptilian cardiorespiratory systems. Vagal control of pulmonary blood flow and cardiac shunts provides reptiles with an additional means of regulating arterial oxygen levels that is not present in endothermic vertebrates (birds and mammals). Within a given species, there exists a clear correlation between withdrawal of vagal tone on the cardiovascular system and elevated metabolic rate. Undisturbed and resting reptiles are normally characterised by high vagal tone, low pulmonary blood flow and large right-left (R-L) cardiac shunts. The low oxygen levels that result from the large R-L shunt may serve to regulate metabolism. However, when metabolism is increased by temperature, exercise or digestion, the R-L cardiac shunt is reduced, which serves to increase oxygen delivery. This response is partially elicit ed by reduction of vagal tone. Interspecies comparisons reveal a similar pattern. Thus, species that are able to sustain the highest metabolic rates possess the highest degree of anatomical ventricular separation and, therefore, less cardiac shunting. It is interesting to note that when cardiac shunts occur in mammals, due for example to developmental defects, they are associated with reduced maximal metabolic rates and impaired exercise tolerance. It appears, therefore, that full separation of ventricular blood flows was a prerequisite for the evolution of high aerobic metabolic rates and exercise stamina in mammals and birds.

Maximal lactate steady state in running mice: Effect of exercise training

1. Maximal lactate steady state (MLSS) corresponds to the highest blood lactate concentration (MLSSc) and workload (MLSSw) that can be maintained over time without continual blood lactate accumulation and is considered an important marker of endurance exercise capacity. The present study was undertaken to determine MLSSw and MLSSc in running mice. In addition, we provide an exercise training protocol for mice based on MLSSw.2. Maximal lactate steady state was determined by blood sampling during multiple sessions of constant-load exercise varying from 9 to 21 m/min in adult male C57BL/6J mice. The constant-load test lasted at least 21 min. The blood lactate concentration was analysed at rest and then at 7 min intervals during exercise.3. The MLSSw was found to be 15.1 +/- 0.7 m/min and corresponded to 60 +/- 2% of maximal speed achieved during the incremental exercise testing. Intra- and interobserver variability of MLSSc showed reproducible findings. Exercise training was performed at MLSSw over a period of 8 weeks for 1 h/day and 5 days/week. Exercise training led to resting bradycardia (21%) and increased running performance (28%). of interest, the MLSSw of trained mice was significantly higher than that in sedentary littermates (19.0 +/- 0.5 vs 14.2 +/- 0.5 m/min; P = 0.05), whereas MLSSc remained unchanged (3.0 mmol/L).4. Altogether, we provide a valid and reliable protocol to improve endurance exercise capacity in mice performed at highest workload with predominant aerobic metabolism based on MLSS assessment.