[Toward a better understanding of fatigue in schizophrenia]. / Vers une meilleure compréhension de la fatigue dans la schizophrénie.

Despite being one of the most common complaints of people with schizophrenia, fatigue remains largely unexplored in this population. The lack of knowledge regarding this complex symptom makes it often underdiagnosed and undertreated in schizophrenia. The aim of this brief perspective review is to outline the potential origins (distinguishing primary and secondary fatigue) and consequences of fatigue and to explore some potential treatments in this population. The current literature in schizophrenia has mainly investigated fatigue as a trait, using a self-administered questionnaire. Beyond this observational approach, which does not allow to capture the symptom in real life situations where high levels of fatigue can emerge rapidly, we propose to consider the state level of fatigue, for instance occurring after a prolonged period of cognitive activity (i.e. mental fatigue). We elaborate on the potential relationships between mental fatigue and negative symptoms of schizophrenia and propose some research avenues to test the effects of acute fatigue on effort intentions and behaviours. The consideration of the multidimensional aspects of fatigue will allow to move beyond the sole pharmacological approach to treat fatigue in schizophrenia. Targeting the cognitive as well as the performance components of fatigue through interventions such as concomitant aerobic exercise - mental training offers attractive prospects to reduce fatigue in this population and minimize its functional negative impact.

Methodology and reliability of respiratory muscle assessment.

The optimal method for respiratory muscle endurance (RME) assessment remains unclear. This study assessed the test-retest reliability of two RME-test methodologies. Fifteen healthy adults attended the laboratory on four occasions, separated by 5 ± 2 days, and completed each test in a random, "one on two" order. They performed spirometry testing, maximal respiratory pressure assessment and two different RME tests: an inspiratory resistive breathing (IRB) and an isocapnic hyperpnea endurance (IHE) test. Typical error, expressed as coefficient of variation, for IRB maximal inspiratory pressure (MIP) and IHE maximal ventilation were 12.21 (8.85-19.67) % and 10.73 (7.78-17.29) %, respectively. Intraclass correlation coefficients for the same parameters were 0.83 (0.46-0.94) and 0.80 (0.41-0.93), respectively. No correlations were found between RME parameters derived from the IHE and IRB tests (all p > 0.05). Significant positive correlations were found between both IRB and IHE outcomes and spirometry parameters, MIP and maximal expiratory pressure (p < 0.05). Given these results, IRB and IHE appear to be suitable for RME testing in healthy people, although they may reflect different physiological mechanisms (respiratory mechanics and respiratory muscle capacity for IHE test vs. inspiratory muscle capacity for IRB test). Future studies are therefore warranted that compare IRB and IHE tests in clinical settings.

Absence of calf muscle metabolism alterations in active cystic fibrosis adults with mild to moderate lung disease.

BACKGROUND: Specific alterations in skeletal muscle related to genetic defects may be present in adults with cystic fibrosis (CF). Limb muscle dysfunction may contribute to physical impairment in CF. AIMS AND OBJECTIVES: We hypothesized that adults with CF would have altered calf muscle metabolism during exercise. METHODS: Fifteen adults with CF and fifteen healthy controls matched for age, gender and physical activity performed a maximal cycling test and an evaluation of calf muscle energetics by 31P magnetic resonance spectroscopy before, during and after plantar flexions to exhaustion. RESULTS: Maximal cycling test revealed lower exercise capacities in CF (VO2peak 2.44±0.11 vs. 3.44±0.23L·Min-1, P=0.03). At rest, calf muscle phosphorus metabolites and pHi were similar in CF and controls (P>0.05). Maximal power output during plantar flexions was significantly lower in CF compared to controls (7.8±1.2 vs. 6.6±2.4W; P=0.013). At exhaustion, PCr concentration was similarly reduced in both groups (CF -33±7%, controls -34±6%, P=0.44), while PCr degradation at identical absolute workload was greater in CF patients (P=0.04). These differences disappeared when power output was normalized for differences in calf size (maximal power output: 0.10±0.02 vs. 0.10±0.03W/cm2; P=0.87). Pi/PCr ratio and pHi during exercise as well as PCr recovery after exercise were similar between groups. CONCLUSION: Similar metabolic calf muscle responses during exercise and recovery were found in CF adults and controls. Overall, muscle anabolism rather than specific metabolic dysfunction may be critical regarding muscle function in CF.

Transcranial magnetic stimulation intensity affects exercise-induced changes in corticomotoneuronal excitability and inhibition and voluntary activation.

Transcranial magnetic stimulation (TMS) of the motor cortex during voluntary contractions elicits electrophysiological and mechanical responses in the target muscle. The effect of different TMS intensities on exercise-induced changes in TMS-elicited variables is unknown, impairing data interpretation. This study aimed to investigate TMS intensity effects on maximal voluntary activation (VATMS), motor-evoked potentials (MEPs), and silent periods (SPs) in the quadriceps muscles before, during, and after exhaustive isometric exercise. Eleven subjects performed sets of ten 5-s submaximal isometric quadriceps contractions at 40% of maximal voluntary contraction (MVC) strength until task failure. Three different TMS intensities (I100, I75, I50) eliciting MEPs of 53 ± 6%, 38 ± 5% and 25 ± 3% of maximal compound action potential (Mmax) at 20% MVC were used. MEPs and SPs were assessed at both absolute (40% baseline MVC) and relative (50%, 75%, and 100% MVC) force levels. VATMS was assessed with I100 and I75. When measured at absolute force level, MEP/Mmax increased during exercise at I50, decreased at I100 and remained unchanged at I75. No TMS intensity effect was observed at relative force levels. At both absolute and relative force levels, SPs increased at I100 and remained stable at I75 and I50. VATMS assessed at I75 tended to be lower than at I100. TMS intensity affects exercise-induced changes in MEP/Mmax (only when measured at absolute force level), SPs, and VATMS. These results indicate a single TMS intensity assessing maximal voluntary activation and exercise-induced changes in corticomotoneuronal excitability/inhibition may be inappropriate.

Stimulation of the motor cortex and corticospinal tract to assess human muscle fatigue.

This review aims to characterize fatigue-related changes in corticospinal excitability and inhibition in healthy subjects. Transcranial magnetic stimulation (TMS) has been extensively used in recent years to investigate modifications within the brain during and after fatiguing exercise. Single-pulse TMS reveals reduction in motor-evoked potentials (MEP) when measured in relaxed muscle following sustained fatiguing contractions. This modulation of corticospinal excitability observed in relaxed muscle is probably not specific to the fatigue induced by the motor task. During maximal and submaximal fatiguing contractions, voluntary activation measured by TMS decreases, suggesting the presence of supraspinal fatigue. The demonstration of supraspinal fatigue does not eliminate the possibility of spinal contribution to central fatigue. Concomitant measurement of TMS-induced MEP and cervicomedullary MEP in the contracting muscle, appropriately normalized to maximal muscle compound action potential, is necessary to determine the relative contribution of cortical and spinal mechanisms in the development of central fatigue. Recent studies comparing electromyographic (EMG) responses to paired-pulse stimuli at the cortical and subcortical levels suggest that impaired motoneuron responsiveness rather than intracortical inhibition may contribute to the development of central fatigue. This review examines the mechanical and EMG responses elicited by TMS (single- and paired-pulse) and cervicomedullary stimulation both during and after a fatiguing exercise. Particular attention is given to the muscle state and the type of fatiguing exercise when assessing and interpreting fatigue-induced changes in these parameters. Methodological concerns and future research interests are also considered.

Neuromuscular fatigue after maximal exercise in patients with cystic fibrosis.

The aim of this study was to determine whether patients with cystic fibrosis (CF), despite their ventilatory limitation, would develop neuromuscular fatigue of quadriceps muscles following a maximal cycling exercise. Eleven adults with CF (age=26.8±6.9years; forced expiratory volume in 1s=54.1±12.8% predicted) and 11 age-matched healthy subjects performed a maximal incremental cycle test with respiratory gas exchange measurements. Maximal voluntary contraction (MVC) and electromyographic (EMG) activity of the vastus medialis muscle were recorded before and after exercise. Neural and contractile properties of the quadriceps were also investigated using femoral nerve electrical stimulation. Patients had lower exercise capacity, peak oxygen uptake and MVC than controls. MVC fell significantly postexercise in both groups (CF: -20±10%, controls: -19±6%; p<0.01). EMG root mean square values, M-wave amplitude and duration were unchanged in both groups. Peak twitch (-46.9±13.8%), maximal rate of twitch torque development (-50.3±13.8%) and relaxation (-35.2±19.5%) were all reduced after exercise in CF patients. The control group followed the same pattern (-38.4±14.4%, -42.1±14.7% and -15±20.4%) but the statistical significance was not reached for the maximal rate of twitch torque relaxation. In conclusion, CF patients demonstrated lower limb fatigue following symptom-limited cycle exercise, which was comparable to that exhibited by healthy controls. This fatigue may be due to contractile impairments and not to transmission failure. Further studies should be conducted in a larger sample to confirm these preliminary results.

Clinical utility of the oxygen uptake efficiency slope in cystic fibrosis patients.

BACKGROUND: The present study investigated the validity and the reliability of the oxygen uptake efficiency slope (OUES) as a determinant of exercise tolerance in adults with cystic fibrosis (CF). METHODS: 31 CF patients and 34 healthy controls performed a maximal incremental cycle test with respiratory gas-exchange measurements. OUES was calculated from data taken from different percentages of the entire exercise duration, including 80% (OUES(80)) and 100% (OUES(100)). Peak oxygen uptake (VO(2peak)) and gas exchange threshold (GET) were also determined. The agreement between submaximal parameters and VO(2peak) was assessed using Bland Altman plots. Test retest reliability was evaluated in CF patients using absolute (SEM) and relative indices (ICC). RESULTS: On the contrary to the GET, which was undetectable in 16% of the CF patients, the OUES was easily determined in all patients. Among all the submaximal variables, OUES(80) had the best reliability (ICC=0.94, SEM=7.3%) and agreement with VO(2peak) (r(2)=0.83, P<0.01; limits of agreement: ±365mL min(-1)) and did not differ from OUES(100). CONCLUSIONS: OUES(80) is a reliable and more useful submaximal parameter than the GET and may find use in the interpretation of exercise studies in CF patients who are unable to perform maximal exercise.

Long term reliability of EMG measurements in adults with cystic fibrosis.

The aim of this study was to investigate the long term reliability of surface electromyography (sEMG) measurements in adults with cystic fibrosis (CF). Eighteen healthy subjects (CO) and sixteen adults with CF were tested on two occasions, six weeks apart. sEMG was recorded from the rectus femoris, vastus lateralis and vastus medialis obliquus muscles during maximal voluntary contraction (MVC) and 50% MVC until exhaustion. Quadriceps muscle activity during 50% MVC was described using four measures (initial, final, normalized and slope values) for both frequency and time domain. Relative (ICC) and absolute (SEM) reliabilities were applied to asses test-retest reliability. In CF group, median frequency (MDF) values for 100% MVC and initial, final and normalized final MDF for 50% MVC demonstrated moderate to very high relative reliability (ICC = 0.60-0.91) and low variability (SEM = 5.5-13%). MDF slope showed large variability in both groups. Root mean square (RMS) values were not reproducible in both groups whatever the intensity of exercise and can not be recommended as outcomes parameters. In conclusion, sEMG measurements during maximal and submaximal isometric contractions could be valid and reliable tools for clinical applications in cystic fibrosis patients but mainly in the frequency domain and from rectus femoris.

Growth kinetics of the granulosa cell population in ovarian follicles: an approach by mathematical modelling.

This paper describes, from a mathematical viewpoint, the cellular changes in the granulosa of ovarian follicles during their terminal development. A dynamic model takes into account the processes of (1) cell division, (2) exit from the cell cycle towards differentiation, and (3) apoptotic cell death. Proliferative cells leave the cycle in an irreversible way. The risk of entering apoptosis applies to non-cycling cells. Changes in the cell numbers and in the growth fraction are derived from differential equations. The transitions between the different cell states are ruled by time-dependent rates. Numerical applications of the model concern ovulating and degenerating ovarian follicles in the ewe. The main feature of the ovulating case is the progressive exhaustion of the proliferating compartment for the benefit of the non-cycling cells. From an initial mainly proliferative state the granulosa progressively switches to a highly differentiated state, so that the growth fraction continuously decreases. In the atretic cases, the pattern of changes in the total viable cell number is influenced by the follicular age at the onset of the apoptotic process and by the intensity of the cell death rate. As apoptosis affects the non-cycling cells, the growth fraction is no longer strictly decreasing. The sensitivity of the model to the parameters is studied in a more general framework than the granulosa cell population.