Thomas Rupp

Prefrontal cortex oxygenation and neuromuscular responses to exhaustive exercise

Near-infrared spectroscopy (NIRS) allows non-invasive monitoring of central and peripheral changes in oxygenation during exercise and may provide valuable insight into the factors affecting fatigue. This study aimed to explore the changes in oxygenation of prefrontal cortex and active muscle tissue as limiting factors of incremental exercise performance in trained cyclists. Thirteen trained healthy subjects (meanxa0±xa0SE: age 24.9xa0±xa01.5xa0years, body mass 70.1xa0±xa01.2xa0kg, training 6.1xa0±xa00.9xa0hxa0week−1) performed a progressive maximal exercise to exhaustion on a cycling ergometer. Prefrontal cortex (Cox) and vastus lateralis muscle (Mox) oxygenation were measured simultaneously by NIRS throughout the exercise. Maximal voluntary isometric knee torques and quadriceps neuromuscular fatigue (M-wave properties and voluntary activation ratio) were evaluated before and after exercise. Maximal power output and oxygen consumption were 380.8xa0±xa07.9xa0W and 75.0xa0±xa02.2xa0mlxa0min−1xa0kg−1, respectively. Mox decreased significantly throughout exercise while Cox increased in the first minutes of exercise but decreased markedly from the workload corresponding to the second ventilatory threshold up to exhaustion (Pxa0<xa00.05). No significant difference was noted 6xa0min after maximal exercise in either the voluntary activation ratio or the M-wave properties. These findings are compatible with the notion that supraspinal modulation of motor output precedes exhaustion.

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.

Altitude-induced changes in muscle contractile properties.

Because of its high energetic demand, skeletal muscle is sensitive to changes in the partial pressure of oxygen. Most human studies on in vivo skeletal muscle function during hypoxia were performed with voluntary contractions. However, skeletal muscle function is not only characterized by voluntary maximal or repeated force- generating capacity, but also by force generated by evoked muscle contractions (i.e., force-frequency properties). This mini-review reports on the effects of acute or prolonged exposure to hypoxia on human skeletal muscle performance and contractile properties. The latter depend on both the amount and type of contractile proteins and the efficiency of the cellular mechanism of excitation-contraction coupling. Observations on humans indicate that hypoxia (during simulated ascent or brief exposure) exerts modest influences on the membrane propagation of the muscle action potentials during voluntary contractions. Overall in humans, in physiological conditions, including that of climbing Mt. Everest, there is extraordinarily little that changes with regard to maximal force-generating capacity. Interestingly, it appears that the adaptations to chronic hypoxia minimize the effects on skeletal muscle dysfunction (i.e., impairment during fatigue resistance exercise and in muscle contractile properties) that may occur during acute hypoxia for some isolated muscle exercises. Only sustained isometric exercise exceeding a certain intensity (30% MVC) and causing substantial and sustained ischemia is not affected by acute hypoxia.

Dynamics of corticospinal changes during and after high-intensity quadriceps exercise

What is the central question of this study? Progressive development of the supraspinal component of central fatigue and increases in corticospinal excitability and inhibition have been demonstrated during fatiguing contractions of the elbow flexors. However, the kinetics of mechanical and EMG responses induced by transcranial magnetic stimulation during and after single‐joint fatiguing knee‐extensor exercise remains unknown. What is the main finding and its importance? Our results show that single‐joint knee‐extensor isometric exercise induces late supraspinal fatigue with increased intracortical inhibition, both of which recover quickly after task failure, and unchanged corticospinal excitability. This indicates that fatigue‐induced corticospinal changes are muscle and/or limb specific and reinforces the need to measure corticospinal changes within seconds after task failure to avoid their underestimation.

EFFECT OF SEVERE HYPOXIA ON PREFRONTAL CORTEX AND MUSCLE OXYGENATION RESPONSES AT REST AND DURING EXHAUSTIVE EXERCISE

Near infrared spectroscopy (NIRS) may provide valuable insight into the determinants of exercise performance. We examined the effects of severe hypoxia on cerebral (prefrontal lobe) and muscle (gastrocnemius) oxygenation at rest and during a fatiguing task. After a 15-min rest, 15 healthy subjects (age 25.3 +/- 0.9 yr) performed a sustained contraction of the ankle extensors at 40% of maximal voluntary force until exhaustion. The contraction was performed at two different fractions of inspired O2 fraction (F(IO2) = 0.21/0.11) in randomized and single-blind fashion. Cerebral and muscle oxy-(HbO2) deoxy-(HHb) total-hemoglobin (HbTot) and tissue oxygenation index (TOI) were monitored continuously by NIRS. Arterial O2 saturation (SpO2) was estimated by pulse oximetry throughout the protocol. Muscle TOI did not differ between normoxia and hypoxia after the 15-min rest, whereas SpO2 and cerebral TOI significantly dropped (-6.5 +/- 0.9% and -3.9 +/- 1.0%, respectively, P<0.05) in hypoxia. The muscle NIRS changes during exercise were similar in normoxia and hypoxia, whereas the increased cerebral HbTot and HbO2 near exhaustion were markedly reduced in hypoxia. In conclusion, although F(IO2) had no significant effect on endurance time, NIRS patterns near exhaustion in hypoxia differed from normoxia.

Resting and active motor thresholds versus stimulus-response curves to determine transcranial magnetic stimulation intensity in quadriceps femoris.

BackgroundTranscranial magnetic stimulation (TMS) is a widely-used investigative technique in motor cortical evaluation. Recently, there has been a surge in TMS studies evaluating lower-limb fatigue. TMS intensity of 120-130% resting motor threshold (RMT) and 120% active motor threshold (AMT) and TMS intensity determined using stimulus–response curves during muscular contraction have been used in these studies. With the expansion of fatigue research in locomotion, the quadriceps femoris is increasingly of interest. It is important to select a stimulus intensity appropriate to evaluate the variables, including voluntary activation, being measured in this functionally important muscle group. This study assessed whether selected quadriceps TMS stimulus intensity determined by frequently employed methods is similar between methods and muscles.MethodsStimulus intensity in vastus lateralis, rectus femoris and vastus medialis muscles was determined by RMT, AMT (i.e. during brief voluntary contractions at 10% maximal voluntary force, MVC) and maximal motor-evoked potential (MEP) amplitude from stimulus–response curves during brief voluntary contractions at 10, 20 and 50% MVC at different stimulus intensities.ResultsStimulus intensity determined from a 10% MVC stimulus–response curve and at 120 and 130% RMT was higher than stimulus intensity at 120% AMT (lowest) and from a 50% MVC stimulus–response curve (pu2009<u20090.05). Stimulus intensity from a 20% MVC stimulus–response curve was similar to 120% RMT and 50% MVC stimulus–response curve. Mean stimulus intensity for stimulus–response curves at 10, 20 and 50% MVC corresponded to approximately 135, 115 and 100% RMT and 180, 155 and 130% AMT, respectively. Selected stimulus intensity was similar between muscles for all methods (pu2009>u20090.05).ConclusionsSimilar optimal stimulus intensity and maximal MEP amplitudes at 20 and 50% MVC and the minimal risk of residual fatigue at 20% MVC suggest that a 20% MVC stimulus–response curve is appropriate for determining TMS stimulus intensity in the quadriceps femoris. The higher selected stimulus intensities at 120-130% RMT have the potential to cause increased coactivation and discomfort and the lower stimulus intensity at 120% AMT may underestimate evoked responses. One muscle may also act as a surrogate in determining optimal quadriceps femoris stimulation intensity.

Changes in Voluntary Activation Assessed by Transcranial Magnetic Stimulation during Prolonged Cycling Exercise

Maximal central motor drive is known to decrease during prolonged exercise although it remains to be determined whether a supraspinal deficit exists, and if so, when it appears. The purpose of this study was to evaluate corticospinal excitability and muscle voluntary activation before, during and after a 4-h cycling exercise. Ten healthy subjects performed three 80-min bouts on an ergocycle at 45% of their maximal aerobic power. Before exercise and immediately after each bout, neuromuscular function was evaluated in the quadriceps femoris muscles under isometric conditions. Transcranial magnetic stimulation was used to assess voluntary activation at the cortical level (VATMS), corticospinal excitability via motor-evoked potential (MEP) and intracortical inhibition by cortical silent period (CSP). Electrical stimulation of the femoral nerve was used to measure voluntary activation at the peripheral level (VAFNES) and muscle contractile properties. Maximal voluntary force was significantly reduced after the first bout (13±9%, P<0.01) and was further decreased (25±11%, P<0.001) at the end of exercise. CSP remained unchanged throughout the protocol. Rectus femoris and vastus lateralis but not vastus medialis MEP normalized to maximal M-wave amplitude significantly increased during cycling. Finally, significant decreases in both VATMS and VAFNES (∼8%, P<0.05 and ∼14%, P<0.001 post-exercise, respectively) were observed. In conclusion, reductions in VAFNES after a prolonged cycling exercise are partly explained by a deficit at the cortical level accompanied by increased corticospinal excitability and unchanged intracortical inhibition. When comparing the present results with the literature, this study highlights that changes at the cortical and/or motoneuronal levels depend not only on the type of exercise (single-joint vs. whole-body) but also on exercise intensity and/or duration.

Time-dependent effect of acute hypoxia on corticospinal excitability in healthy humans

Contradictory results regarding the effect of hypoxia on cortex excitability have been reported in healthy subjects, possibly depending on hypoxia exposure duration. We evaluated the effects of 1- and 3-h hypoxia on motor corticospinal excitability, intracortical inhibition, and cortical voluntary activation (VA) using transcranial magnetic stimulation (TMS). TMS to the quadriceps cortex area and femoral nerve electrical stimulations were performed in 14 healthy subjects. Motor-evoked potentials (MEPs at 50-100% maximal voluntary contraction; MVC), recruitment curves (MEPs at 30-100% maximal stimulator power output at 50% MVC), cortical silent periods (CSP), and VA were measured in normoxia and after 1 (n = 12) or 3 (n = 10) h of hypoxia (Fi(O(2)) = 0.12). One-hour hypoxia did not modify any parameters of corticospinal excitability but reduced slightly VA, probably due to the repetition of contractions 1 h apart (96 ± 4% vs. 94 ± 4%; P = 0.03). Conversely, 3-h hypoxia significantly increased 1) MEPs of the quadriceps muscles at all force levels (+26 ± 14%, +24 ± 12%, and +27 ± 17% at 50, 75, and 100% MVC, respectively; P = 0.01) and stimulator power outputs (e.g., +21 ± 14% at 70% maximal power), and 2) CSP at all force levels (+20 ± 18%, +18 ± 19%, and +14 ± 22% at 50, 75, and 100% MVC, respectively; P = 0.02) and stimulator power outputs (e.g., +9 ± 8% at 70% maximal power), but did not modify VA (98 ± 1% vs. 97 ± 3%; P = 0.42). These data demonstrate a time-dependent hypoxia-induced increase in motor corticospinal excitability and intracortical inhibition, without changes in VA. The impact of these cortical changes on physical or psychomotor performances needs to be elucidated to better understand the cerebral effects of hypoxemia.

Changes in cerebral blood flow and vasoreactivity to CO2 measured by arterial spin labeling after 6 days at 4350 m

Changes in cerebral perfusion and CO2 cerebrovascular reactivity during and immediately after a sojourn at high altitude remain unclear but may be critical for acclimatization. The aim of the present study was to assess the effects of 6days at 4350m on cerebral perfusion and cerebrovascular reactivity (CVR) to CO2 by arterial spin labeling (ASL) magnetic resonance imaging at sea level and to compare it with transcranial Doppler (TCD) results at altitude. Eleven healthy male subjects, non-acclimatized to altitude, stayed for 6days at 4350m (Observatoire Vallot, massif du Mont-Blanc). Prior to the stay and within 6h after returning to sea level, subjects were investigated using pseudo-continuous ASL at 3T during a block-design inhalation paradigm to measure basal cerebral blood flow (CBF) and CO2 CVR. End-tidal CO2 (PetCO2), respiratory rate, heart rate and oxygen saturation were recorded during the exam. Subjects were also examined using TCD prior to and on day 5 of the stay at altitude to measure blood velocity in the middle cerebral artery (MCAv) and CO2 CVR. CO2 CVR was expressed as percent change in ASL CBF or TCD MCAv per mmHg change in PetCO2. PetCO2 was significantly decreased during and after altitude. Significant increases in TCD MCAv compared to before altitude measurements were observed on day 5 at altitude (+20.5±15.5%). Interestingly, ASL CBF remained increased in the MCA and anterior vascular territories (+22.0±24.1% and 20.5±20.3%, respectively) after altitude under normoxic conditions. TCD CVR tended to decrease on day 5 at 4350m (-12.3±54.5% in the MCA) while the ASL CVR was significantly decreased after altitude (-29.5±19.8% in the MCA). No correlation was observed between cerebral hemodynamic changes and symptoms of acute mountain sickness at high altitude. In conclusion, prolonged exposure to high altitude significantly increases blood flow during the altitude stay and within 6h after returning to sea level. Decreased CO2 CVR after prolonged altitude exposure was also observed using ASL. Changes in cerebral hemodynamics with altitude exposure probably involve other mechanisms than the vasodilatory effect of hypoxia only, since it persists under normoxia several hours following the descent.

Cerebral Hemodynamic and Ventilatory Responses to Hypoxia, Hypercapnia, and Hypocapnia during 5 Days at 4,350 m

This study investigated the changes in cerebral near-infrared spectroscopy (NIRS) signals, cerebrovascular and ventilatory responses to hypoxia and CO2 during altitude exposure. At sea level (SL), after 24u2009hours and 5 days at 4,350u2009m, 11 healthy subjects were exposed to normoxia, isocapnic hypoxia, hypercapnia, and hypocapnia. The following parameters were measured: prefrontal tissue oxygenation index (TOI), oxy- (HbO2), deoxy- and total hemoglobin (HbTot) concentrations with NIRS, blood velocity in the middle cerebral artery (MCAv) with transcranial Doppler and ventilation. Smaller prefrontal deoxygenation and larger ΔHbTot in response to hypoxia were observed at altitude compared with SL (day 5: ΔHbO2−0.6±1.1 versus −1.8±1.3u2009μmol/cmper mmu2009Hg and ΔHbTot 1.4±1.3 versus 0.7±1.1u2009μmol/cm per mmu2009Hg). The hypoxic MCAv and ventilatory responses were enhanced at altitude. Prefrontal oxygenation increased less in response to hypercapnia at altitude compared with SL (day 5: ΔTOI 0.3±0.2 versus 0.5±0.3% mmu2009Hg). The hypercapnic MCAv and ventilatory responses were decreased and increased, respectively, at altitude. Hemodynamic responses to hypocapnia did not change at altitude. Short-term altitude exposure improves cerebral oxygenation in response to hypoxia but decreases it during hypercapnia. Although these changes may be relevant for conditions such as exercise or sleep at altitude, they were not associated with symptoms of acute mountain sickness.