Decreased Muscle Strength in Children With Repaired Tetralogy of Fallot: Relation With Exercise Capacity.

Background The aim of this study is to describe muscle strength in pediatric patients with repaired tetralogy of Fallot compared with healthy peers and to analyze the correlation between muscle strength and peak oxygen uptake, exercise capacity (mL/min). Methods and Results A prospective, cross-sectional study was carried out in the University Medical Center Groningen between March 2016 and December 2019, which included 8 -to-19-year-old patients with repaired tetralogy of Fallot. Exclusion criteria comprised the following: Down syndrome, unstable pulmonary disease and severe scoliosis affecting pulmonary function, neuromuscular disease, and mental or physical limitations that prohibit the execution of the functional tests. Muscle strength was compared with 2 healthy pediatric cohorts from the Northern Netherlands. Handgrip strength, maximal voluntary isometric contraction, and dynamic muscle strength in correlation with peak oxygen uptake, exercise capacity (mL/min) were the main outcomes of the study. The 67 patients with repaired tetralogy of Fallot (42% female; aged 12.9 [interquartile range, 10.0-16.3] years old) were compared with healthy children. The patients showed reduced grip strength (z-score [mean±SD] -1.5±1.2, P<0.001), and total muscle strength (z-score -0.9±1.3, P<0.001). Dynamic strength (Bruininks-Oseretsky test) was significantly reduced (z-score -0.3±0.8, P=0.001), but running, speed, and agility were normal (z-score 0.1±0.7, P=0.4). Univariate correlation analyses showed strong correlations between absolute peak oxygen uptake, exercise capacity (mL/min), and muscle strength (grip strength r=0.83, total muscle strength r=0.88; P<0.001). In multivariate analyses, including correction for age and sex, total muscle strength (B 0.3; P=0.009), and forced vital capacity (B 0.5; P=0.02) correlated with peak oxygen uptake, exercise capacity (mL/min), independent of conventional cardiovascular parameters. Conclusions Children with repaired tetralogy of Fallot show reduced muscle strength, which strongly correlated with their exercise performance.

Exercise capacity in patients with repaired Tetralogy of Fallot aged 6 to 63 years.

OBJECTIVES: This study aimed to provide a perspective for the interpretation of exercise capacity (peakVO2) in patients with repaired Tetralogy of Fallot (patients with rTOF) by describing the course of peakVO2 from patients aged 6-63 years. METHODS: A retrospective study was performed between September 2001 and December 2016 in the German Heart Centre Munich, Germany, and in the University Medical Centre Groningen, the Netherlands. A total of 1175 cardiopulmonary exercise tests (CPETs) were collected from 586 patients with rTOF, 46% female. Maximal exertion was verified using a respiratory exchange ratio ≥1.00. PeakVO2 was modelled using time-dependent multilevel models for repeated measurements (n=889 in 300 patients), and compared with subject-specific reference values calculated by the models of Bongers et al and Mylius et al. RESULTS: The peakVO2 of patients with rTOF was reduced at all ages. At the age of 6, the peakVO2 was 614 mL/min (70% of predicted (95% CI 67 to 73)). The reduced increase in peakVO2 during adolescence resulted in a significant lower maximum peakVO2 of 1209 mL/min at 25 years (65% predicted, p<0.001). A linear decline after 25 years was observed in patients and references, although patients showed an accelerated decline, with a -0.24% point of predicted (95% CI 0.11 to 0.38) per year without differences between sexes (p=0.263). CONCLUSIONS: This study provides a context for peakVO2 across ages in patients with rTOF under contemporary treatment strategies. It showed that the reduction in peakVO2 originates from childhood and declines over time. Sex differences in patients with rTOF were similar to natural existing sex differences.

Training in a ballistic task but not a visuomotor task increases responses to stimulation of human corticospinal axons.

Short periods of training in motor tasks can increase motor cortical excitability. This study investigated whether changes also occur at a subcortical level. Subjects trained in ballistic finger abduction or visuomotor tracking. The right index finger rotated around the metacarpophalangeal (MCP) joint in a splint. Surface EMG was recorded from the first dorsal interosseous. Transcranial magnetic stimulation over the back of the head (double-cone coil) elicited cervicomedullary motor evoked potentials (CMEPs) by stimulation of corticospinal axons. Responses were recorded from the relaxed muscle before, between, and after two sets of training. In study 1 (n = 7), training comprised two sets of 150 maximal finger abductions. Feedback of acceleration was provided. With training, acceleration increased significantly. CMEPs increased to 248 ± 152% (± SD) of baseline immediately after training (P = 0.007) but returned to control level (155 ± 141%) 10 min later. In study 2 (n = 7), subjects matched MCP joint angle to a target path on a computer screen. After ∼30 min of training, tracking improved as shown by increased correlation between joint angle and the target pathway, reduced time lag, and reduced EMG(rms). However, CMEPs remained unchanged. These results show that transmission through the corticospinal pathway at a spinal level increased after repeated ballistic movements but not after training in a visuomotor task. Thus, changes at a spinal level may contribute to improved performance in some motor tasks.

Constraints for control of the human hand.

More than 30 muscles drive the hand to perform a multitude of essential dextrous tasks. Here we consider new views on the evolution of hand structure and on peripheral and central constraints for independent control of the digits of the hand. The human hand is widely assumed to have evolved from hands like those of African apes, yet recent studies have shown that our hands and those of the earliest hominids are very similar and unlike those of living apes. Understanding the limits of hand function may come from investigation of our last common ancestor with the great apes, rather than the great apes themselves. In the periphery, movement across the full range of joint space can be limited by mechanical linkages among the extrinsic muscles. Further, peripheral limits occur when the hand adopts some positions in which the contraction of muscles fails to move the joints on which they usually act; there is muscle 'disengagement' and functional paralysis for some actions. Surprisingly, the central nervous system drives the hand seamlessly through this landscape of mechanical limits. Central constraints on control of the individual digits include the spillover of neural drive to neighbouring muscles and their 'compartments', and the inability to make maximal muscle forces when multiple digits contract strongly which produces a force deficit. The pattern of these latter constraints correlates with amounts of daily use of each digit and favours enslaved extension to lift fingers from an object but selective flexion of fingers to contact it.

Voluntary activation of the different compartments of the flexor digitorum profundus.

Flexor digitorum profundus (FDP), the sole flexor of the fingertips, is critical for tasks such as grasping. It is a compartmentalized multitendoned muscle with both neural and mechanical links between the fingers. We determined whether voluntary activation (VA), the level of neural drive to muscle, could be measured separately in its four compartments, whether VA differed between the fingers, and whether maximal voluntary contraction (MVC) force and VA changed when the non-test fingers were extended from full flexion to 90° flexion to partially "disengage" the test finger. Transcranial magnetic stimulation (TMS) of the motor cortex was used to measure VA, in a position in which only FDP generated force at the fingertip. Despite differences among the fingers in MVCs, VA for each finger was ∼92% (n = 8), with no differences between fingers. When the test finger was partially disengaged by extending the other fingers to 90° flexion, performance was more variable both within and between subjects. MVCs decreased significantly by about 25-40% for the four fingers. However, VA was not significantly changed (n = 6) and was similar for the four fingers. In both positions, there were strong linear relationships between the voluntary forces and the superimposed twitch sizes, indicating that the method to measure VA was very reliable. Our results indicate that maximal VA is similar for all four compartments of FDP when force production by the other fingers is unconstrained. When altered mechanical connections between the compartments decrease voluntary force output there is little difference in neural drive.

Limited ability to extend the digits of the human hand independently with extensor digitorum.

While the human hand has an extraordinary capacity to manipulate objects, movement of its digits is usually not completely independent. These limits have been documented for extrinsic flexor muscles, although hand skills also require selectivity for extension movements. Hence, we measured the degree of independent control of the major extrinsic extensor (extensor digitorum, ED). Subjects grasped a cylinder, with the thumb perpendicular to the fingers. Load cells were connected to the proximal phalanges of the fingers and the thumb's distal phalanx. Intramuscular recordings using needle electrodes were made from the individual digital compartments of ED. Subjects were instructed to extend each digit isometrically in a voluntary ramp contraction to 50% maximal force. In total, the behaviour of 283 single motor units was analysed. More than half of the units associated with one 'test' finger were recruited inadvertently when another digit contracted to 50% maximum, with most units being recruited by extension of the adjacent digits. Usually, test motor units were recruited at higher forces by extension of fingers further from the test finger. Unexpectedly, extension of the thumb recruited many motor units acting on the little finger. Across tasks, at recruitment of the test motor units, the force produced by the test finger often differed between the voluntary and inadvertent contractions. Overall, the independent control of the output of ED is limited; this may reflect 'spill-over' of motor commands to other digital extensor compartments. This level of control of the extrinsic extensor muscles is more independent than the control of the deep extrinsic flexor muscle but less independent than that of the superficial extrinsic flexor muscle.

Relation between muscle and brain activity during isometric contractions of the first dorsal interosseus muscle.

We studied the relationship between muscle activity (electromyography, EMG), force, and brain activity during isometric contractions of the index finger, on a group and individual level. Ten subjects contracted their right or left index finger at 5, 15, 30, 50, and 70% of their maximal force. Subjects received visual feedback of the produced force. We focused our analysis on brain activation that correlated with EMG. Brain activity of specific anatomical areas (region-of-interest analysis, ROI) was quantified and correlated with EMG activity. Furthermore, we tried to distinguish between brain areas in which activity was modulated by the amount of EMG and areas that were active during the task but in which the activity was not modulated. Therefore, we used two regressors simultaneously: (1) the produced EMG and (2) the task (a categorical regressor). As expected, activity in the motor areas (contralateral sensorimotor cortex, premotor areas, and ipsilateral cerebellum) strongly correlated with the amount of EMG. In contrast, activity in frontal and parietal areas (inferior part of the right precentral sulcus, ipsilateral supramarginal gyrus, bilateral inferior parietal lobule, bilateral putamen, and insular cortex) correlated with activation per se, independently of the amount of EMG. Activity in these areas was equal during contractions of the right or left index finger. We suppose that these areas are more involved in higher order motor processes during the preparatory phase or monitoring feedback mechanisms. Furthermore, our ROI analysis showed that muscle and brain activity strongly correlate in traditional motor areas, both at group and at subject level.

The psychobiology of burnout: are there two different syndromes?

BACKGROUND: Plasma prolactin levels are sensitive to dopamine and serotonin function, and fatigue. Low cortisol, dopamine and/or serotonin may be involved in burnout and detachment. METHODS: In this double-blind within-subject study, we treated 9 female burnout subjects and 9 controls with 35 mg cortisol and placebo orally. We measured state affect and plasma prolactin, oxytocin, cortisol and adrenocorticotropic hormone levels, and administered an attachment questionnaire. RESULTS: The burnout subjects displayed an extreme distribution of basal prolactin levels, displaying higher or lower levels compared to the controls. The low prolactin burnouts had profoundly low attachment scores and tended to have low oxytocin levels. The high prolactin burnout subjects tended to show cortisol-induced decreased prolactin and fatigue, and increased vigor. CONCLUSION: Results are consistent with the hypothesis that burnout subjects are either characterized by low serotonergic function or by low dopaminergic function, and that the latter group benefits from cortisol replacement. These preliminary results suggest that differentiating between two syndromes may resolve inconsistencies in research on burnout, and be necessary for selecting the right treatment strategy.

MR compatible strain gauge based force transducer.

In order to evaluate brain activation during motor tasks accurately one must also measure output parameters such as muscle force or muscle activity. Especially in clinical situations where the force output can be compromised by changes at different levels of the motor system, it is essential to standardize the task or force level. We have therefore developed a magnetic resonance compatible force transducer that is capable of recording index finger abduction force and to display the produced force in real-time. This transducer is based on strain-gauges techniques and designed to measure both small and large forces accurately (range 0.7-60N) as well as fast force fluctuations. Experiments showed that the MR environment did not affect the force measurements or vice versa. Although, this transducer is developed for measuring index finger forces, detailed schematic diagrams are provided such that the transducer can easily be adapted for measuring forces of other muscle groups.

Effects of motor fatigue on human brain activity, an fMRI study.

The main purpose of this study was to investigate effects of motor fatigue on brain activation in humans, using fMRI. First, we assessed brain activation that correlated with muscle activity during brief contractions at different force levels (force modulation). Second, a similar analysis was done for sustained contractions inducing motor fatigue. Third, we studied changes in brain activation due to motor fatigue over time. And fourth, we investigated cross-over effects of fatigue by comparing brain activation before and after the fatiguing condition during simple and high-order motor tasks (reaction time tasks). Several motor areas in the brain showed increased activity with increased muscle activity, both during force modulation and motor fatigue. Interestingly, the cerebellum showed a smaller increase in activation, during compensatory activation due to fatigue, while additional activation was found in the pre-supplementary motor area and in a frontal area. During motor fatigue, there was a decrease in force production, an increase in force variability, and an increase in muscle activity. Brain areas comparable with the aforementioned areas also showed stronger activation over time. After fatigue, reaction time task performance remained the same (compared to before fatigue), while increased activation in orbitofrontal areas was found. Furthermore, there was a reduction in subjects' maximal voluntary contraction force, accompanied by a decrease in activation of the supplementary motor area (SMA). These results suggest that especially the activity in the SMA and frontal areas is affected by motor fatigue.

Reduced cortical activity during maximal bilateral contractions of the index finger.

The bilateral deficit refers to the phenomenon in which homologous muscles produce per muscle less force when contracting simultaneously than when contracting individually. The mechanism underlying the bilateral deficit is still unknown, but the most likely cause is a decline in the activation of motor units during bilateral contractions. In the present study, we used functional magnetic resonance imaging (fMRI) to measure the degree of brain activity during unilateral and bilateral maximal contractions in combination with force and EMG measurements. Subjects performed, in a semi-randomized order, maximal isometric contractions (MVC) with the right index finger, the left index finger and with both fingers simultaneously. During the task, brain activation was measured with a 3 T MR scanner, in combination with force and EMG recordings. The most important activated areas in the brain during the contractions were the sensorimotor cortex (precentral and postcentral gyrus), cerebellum, premotor cortex and supplementary motor area. During bilateral contractions, a significant decline in force and EMG values was found and detailed analysis of the brain activation data showed that this decline was accompanied with a significant decline in the activation of the precentral gyrus. This result suggests that the bilateral decline is the resultant of a decline in input to the primary motor area and shows that the main source of the bilateral deficit lies upstream of the primary motor cortex.

Interaction between force production and cognitive performance in humans.

OBJECTIVE: A dual task paradigm was used to examine the effects of the generation of force on cognitive performance. METHODS: Subjects (n=22) were asked to respond to auditory stimuli with their left middle or index finger and concurrently maintain a sub-maximal contraction with their right index finger at one of two different force levels. The contraction was maintained for approximately 12s and the target force level was alternated between 30 and 60% of the maximal force. Force production was the primary task of interest; performance of the (secondary) choice reaction time task (reaction times and accuracy) was used as an index of the amount of interference between the two tasks. RESULTS: All subjects were capable of performing the force tasks adequately. Significant interference was observed between the level of force production and cognitive performance. At the higher force level, subjects performed the cognitive task more slowly and less accurately compared to the lower force level. CONCLUSION: Our results show that the execution of high-effort motor behaviour interacts with cognitive task performance. However, comparison with the data obtained during fatiguing contractions in a previous study [Lorist MM, Kernell D, Meijman TF, Zijdewind I. Motor fatigue and cognitive task performance in humans. J Physiol 2002;545:313-319.] showed that the interference was stronger during fatiguing contractions than during the present high-effort motor behaviour. SIGNIFICANCE: The results suggest that force-related factors can explain part of the fatigue-related interference between force production and cognitive performance. This result could have consequences for interpreting cognitive deficits observed in patients suffering from motor dysfunction.

Surface EMG measurements during fMRI at 3T: accurate EMG recordings after artifact correction.

In this experiment, we have measured surface EMG of the first dorsal interosseus during predefined submaximal isometric contractions (5, 15, 30, 50, and 70% of maximal force) of the index finger simultaneously with fMRI measurements. Since we have used sparse sampling fMRI (3-s scanning; 2-s non-scanning), we were able to compare the mean amplitude of the undisturbed EMG (non-scanning) intervals with the mean amplitude of the EMG intervals during scanning, after MRI artifact correction. The agreement between the mean amplitudes of the corrected and the undisturbed EMG was excellent and the mean difference between the two amplitudes was not significantly different. Furthermore, there was no significant difference between the corrected and undisturbed amplitude at different force levels. In conclusion, we have shown that it is feasible to record surface EMG during scanning and that, after MRI artifact correction, the EMG recordings can be used to quantify isometric muscle activity, even at very low activation intensities.

The effect of caffeine on cognitive task performance and motor fatigue.

RATIONALE: In everyday life, people are usually capable of performing two tasks simultaneously. However, in a previous study we showed that during a fatiguing motor task, cognitive performance declined progressively. There is extensive literature on the (positive) effects of caffeine on cognitive and motor performance. These effects are most pronounced under suboptimal conditions, for example during fatigue. However, little is known about the effects of caffeine on cognitive performance during a fatiguing motor task. OBJECTIVE: This study was aimed to investigate whether a moderate dose of caffeine could attenuate the decline in cognitive performance during a fatiguing motor task. METHODS: The study consisted of a placebo and a caffeine (3 mg/kg) session. A total of 23 subjects completed these sessions in a semi-randomized and double-blind order. In each session, subjects performed maximal voluntary contractions of the index finger, a choice reaction time (CRT) task and a dual task consisting of a fatiguing motor task concomitantly with the same CRT task. After the fatiguing dual task, the CRT task was repeated. RESULTS: Caffeine improved cognitive task performance, in both the single and dual task, as shown by decreased reaction times together with unchanged accuracy. Cognitive performance in the dual task deteriorated with increasing fatigue. However, the decrease in cognitive performance in the beginning of the dual task, as observed in the placebo condition, was partly prevented by caffeine administration (i.e., no increase in reaction times). We found no effects of caffeine on motor parameters (absolute force, endurance time or electromyographic amplitude). CONCLUSIONS: Caffeine improved cognitive performance. This effect also extends under demanding situations, as was shown by the performance during the dual task, even during progressive motor fatigue.