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Fatigue is one of the most common debilitating symptoms reported by persons with multiple sclerosis (MS). It reflects feelings of tiredness, lack of energy, low motivation, and difficulty in concentrating. It can be measured at a specific instant in time as a perception that arises from interoceptive networks involved in the regulation of homeostasis. Such ratings indicate the state level of fatigue and likely reflect an inability to correct deviations from a balanced homeostatic state. In contrast, the trait level of fatigue is quantified in terms of work capacity (fatigability), which can be either estimated (perceived fatigability) or measured (objective fatigability). Clinically, fatigue is most often quantified with questionnaires that require respondents to estimate their past capacity to perform several cognitive, physical, and psychosocial tasks. These retrospective estimates provide a measure of perceived fatigability. In contrast, the change in an outcome variable during the actual performance of a task provides an objective measure of fatigability. Perceived and objective fatigability do not assess the same underlying construct. Persons with MS who report elevated trait levels of fatigue exhibit deficits in interoceptive networks (insula and dorsal anterior cingulate cortex), including increased functional connectivity during challenging tasks. The state and trait levels of fatigue reported by an individual can be modulated by reward and pain pathways. Understanding the distinction between fatigue and fatigability is critical for the development of effective strategies to reduce the burden of the symptom for individuals with MS.

Declines in motor function are closely associated with decreases in sensory function in multiple sclerosis (MS). The purpose of our study was to assess the changes in motor function and disability status elicited by transcutaneous electrical nerve stimulation (TENS) to limb muscles of individuals with MS. Fifteen persons with MS and 11 age-matched healthy controls were evaluated before and after receiving 9 treatment sessions during which TENS was applied over the tibialis anterior and rectus femoris muscles of each leg, and over the median nerve and the thenar eminence of each hand. Each evaluation session involved completing two questionnaires (fatigue and walking limitations) and assessing walking performance (2-min test and 25-ft test), dynamic balance (chair-rise test), manual dexterity (grooved pegboard test), and muscle function of hands and legs (strength and force steadiness tests). The MS group exhibited improvements in the 25-ft test (P = 0.001), 2-min test (P = 0.002), chair-rise test (P = 0.008), grooved pegboard test (P = 0.008), and reductions in the self-reported levels of fatigue and walking limitation scores (P = 0.02, d = 0.52; P = 0.008, r = 0.50 respectively). In contrast, there were no statistically significant changes in the Control group. There were no significant changes in either muscle strength or force steadiness for either group. TENS elicited significant improvements in motor function and self-reported disability status in persons with MS. Some improvements reached clinically meaningful levels.

Individuals with multiple sclerosis (MS) experience progressive declines in movement capabilities, especially walking performance. The purpose of our study was to compare the amount of variance in walking performance that could be explained by the functional capabilities of lower leg muscles in persons with MS and a sex- and age-matched control group. Participants performed two walking tests (6-min walk and 25-ft walk), strength tests for the plantar flexor and dorsiflexor muscles, and steady submaximal (10% and 20% maximum) isometric contractions. High-density electromyography (EMG) was recorded during the steady contractions, and the signals were decomposed to identify the discharge times of concurrently active motor units. There were significant differences between the two groups in the force fluctuations during the steady contractions (force steadiness), the strength of the plantar flexor and dorsiflexor muscles, and the discharge characteristics during the steady contractions. Performance on the two walking tests by the MS group was moderately associated with force steadiness of the plantar flexor and dorsiflexor muscles; worse force steadiness was associated with poorer walking performance. In contrast, the performance of the control group was associated with muscle strength (25-ft test) and force steadiness of the dorsiflexors and variance in common input of motor units to the plantar flexors (6-min test). These findings indicate that a reduction in the ability to maintain a steady force during submaximal isometric contractions is moderately associated with walking performance of persons with MS. NEW & NOTEWORTHY The variance in walking endurance and walking speed was associated with force control of the lower leg muscles during submaximal isometric contractions in individuals with multiple sclerosis (MS). In contrast, the fast walking speed of a sex- and age-matched control group was associated with the strength of lower leg muscles. These findings indicate that moderate declines in the walking performance of persons with MS are more associated with impairments in force control rather than decreases in muscle strength.

The purpose of our study was to compare the influence of five types of electrical nerve stimulation delivered through electrodes placed over the right biceps brachii on motor unit activity in the left biceps brachii during an ongoing steady isometric contraction. The electrical stimulation protocols comprised different combinations of pulse duration (0.2 and 1.0 ms), stimulus frequency (50 and 90 Hz), and stimulus current (greater or less than motor threshold). The electrical nerve stimulation protocols were applied over the muscle of the right elbow flexors of 13 participants (26 ± 3 yr) while they performed voluntary contractions with the left elbow flexors to match a target force set at 10% of maximum. All five types of electrical nerve stimulation increased the absolute amplitude of the electromyographic (EMG) signal recorded from the left biceps brachii with high-density electrodes. Moreover, one stimulation condition (1 ms, 90 Hz) had a consistent influence on the centroid location of the EMG amplitude distribution and the average force exerted by the left elbow flexors. Another stimulation condition (0.2 ms, 90 Hz) reduced the coefficient of variation for force during the voluntary contraction, and both low-frequency conditions (50 Hz) increased the duration of the mean interspike interval of motor unit action potentials after the stimulation had ended. The findings indicate that the contralateral effects of electrical nerve stimulation on the motor neuron pool innervating the homologous muscle can be influenced by both stimulus pulse duration and stimulus frequency. NEW & NOTEWORTHY Different types of electrical nerve stimulation delivered through electrodes placed over the right biceps brachii modulated the ongoing motor unit activity in the left biceps brachii. Although the effects varied with stimulus pulse duration, frequency, and current, all five types of electrical nerve stimulation increased the amplitude of the electromyographic activity in the left biceps brachii. Moreover, most of the effects in the left arm occurred after the electrical nerve stimulation of the right arm had been terminated.

Declines in manual dexterity are frequently quantified as the time it takes to complete the grooved pegboard test. The test requires individuals to manipulate 25 pegs, one at a time, by removing them from a well and inserting them into a prescribed hole. The manipulation of each peg involves four phases: selection, transport, insertion, and return. The purpose of our study was to compare the times to complete the four phases of peg manipulation and the forces applied to the pegboard during peg insertion as young, middle-aged, and old adults performed the grooved pegboard test. The relative significance of the peg-manipulation attributes for 30 young (24.0 ± 4.4 years), 15 middle-aged (46.5 ± 6.5 years), and 15 old (70.4 ± 4.0 years) adults was assessed with a multiple-regression analysis. The grooved pegboard test was performed on a force plate. Pegboard times for the old adults (81 ± 17 s) were longer than those for young (56 ± 7 s) and middle-aged (58 ± 11 s) adults. Regression analysis indicated that the explanatory variables for the pegboard times of young (R2 = 0.33) and middle-aged (R2 = 0.78) adults were the times for the peg insertion and return phases, whereas the predictors for old adults (R2 = 0.49) were the times for the peg selection and transport phases. The relative influence of peg-manipulation capabilities on a pegboard test of manual dexterity was greater for middle-aged adults than for young and old adults.

Manual dexterity declines with advancing age and the development of neurological disorders. Changes in manual dexterity are frequently quantified as the time it takes to complete the grooved pegboard test, which requires individuals to manipulate 25 pegs. The manipulation of each peg involves four phases: selection, transport, insertion, and return. The purpose of the study was to compare the times to complete the four phases of manipulating each peg and the forces applied to the pegboard during peg selection and insertion in persons with multiple sclerosis (MS) and age- and sex-matched healthy adults. Multiple-regression models that could explain the variance in pegboard times for each group of participants were compared to assess the relative significance of the peg-manipulation attributes. The performance of 17 persons with MS (52.2 ± 8.3 years) was compared with 17 control subjects (52.2 ± 11.5 years). The grooved pegboard test was performed on a force plate. Pegboard times for the MS group (104 ± 40 s) were longer than those for the Control group (61 ± 15 s). Regression analysis indicated that the pegboard times for the MS group could be predicted by the time for the peg-selection phase (R 2 = 0.78), whereas the predictors for Control group (R 2 = 0.77) were the times for the peg-transport (partial r = 0.80) and selection (partial r = 0.58) phases. The variance in the time it took the MS participants to complete the grooved pegboard test was strongly related to the time required to select each peg, whereas the pegboard times for the Control subjects depended mostly on the duration of the transport phase but also on the time to select each peg.

Background: Multiple sclerosis (MS) symptoms reported in the first year of the disease include sensory impairment, fatigue, reduced mobility, and declines in hand function. The progressive reduction in motor function experienced by persons living with MS is invariably preceded by changes in sensory processing, which are strongly associated with the declines in both walking performance and manual dexterity. Aims: To assess the influence of concurrent sensory stimulation using augmented transcutaneous electrical nerve stimulation (aTENS) applied to leg and hand muscles on clinical tests of motor function in individuals whose mobility was compromised by MS. Methods: Thirteen persons with MS (52 ± 8 years; 6 women) and 12 age- and sex-matched healthy adults (52 ± 9 years) met the inclusion criteria. Participants visited the lab on two occasions with one week between visits. Each visit involved the participant performing four tests of motor function and completing two health-related questionnaires (PDDS and MSWS-12). The tests assessed walking performance (6-min test and 25-ft test), dynamic balance (chair-rise tes, and manual dexterity (grooved pegboard test). aTENS was applied through pads attached to the limbs over the tibialis anterior and rectus femoris muscles of the affected leg, and over the median nerve and the thenar eminence of the dominant hand. The pads were attached during both visits, but the current was only applied during the second visit. The stimulation comprised continuous asymmetrical biphasic pulses (0.2 ms) at a rate of 50 Hz and an intensity that elicited slight muscle contractions. Results: At baseline and during both treatment sessions, the performance on all four tests of motor function was worse for the MS group than the Control group. The MS group experienced significant improvements in all outcomes during the aTENS session with medium-to-large effect sizes. PDDS ratings improved (from 2.8 ± 1.3 to 2.0 ± 1.5; effect size d = –0.70) and the MSWS–12 scores declined (from 36 ± 11 to 28 ± 12; effect size d = –1.52). The concurrent application of aTENS enabled the MS group to walk further during the 6-min test (from 397 ± 174 m to 415 ± 172 m; effect size d = 0.81), to complete the 25-ft test in less time (6.7 ± 3.0 s to 6.3 ± 2.9 s; effect size d = –0.76), to increase the counts in the chair-rise test (from 11.2 ± 3.8 to 13.6 ± 4.8; effect size d = 1.52), and to perform the grooved pegboard test more quickly (from 110 ± 43 s to 99 ± 37 s; effect size d = –0.98). The only significant effect for the Control group was a significant increase in the 6-min walk distance (from 725 ± 79 to 740 ± 82 m; effect size d = 0.87). Conclusions: Stimulation of sensory fibers with aTENS evoked clinically significant improvements in four tests of motor function and the self-reported level of walking limitations in persons who were moderately disabled by MS. Moreover, the improvements in function elicited by the concurrent application of aTENS were immediate.

The purpose of the study was to determine the influence of neuromuscular electrical stimulation (NMES) current intensity and pulse width applied to the right elbow flexors on the discharge characteristics of motor units in the left biceps brachii. Three NMES current intensities were applied for 5 s with either narrow (0.2 ms) or wide (1 ms) stimulus pulses: one at 80% of motor threshold and two that evoked contractions at either ∼10% or ∼20% of maximal voluntary contraction (MVC) force. The discharge times of 28 low-threshold (0.4–21.6% MVC force) and 16 high-threshold (31.7–56.3% MVC force) motor units in the short head of biceps brachii were determined before, during, and after NMES. NMES elicited two main effects: one involved transient deflections in the left-arm force at the onset and offset of NMES and the other consisted of nonuniform modulation of motor unit activity. The force deflections, which were influenced by NMES current intensity and pulse width, were observed only when low-threshold motor units were tracked. NMES did not significantly influence the discharge characteristics of tracked single-threshold motor units. However, a qualitative analysis indicated that there was an increase in the number of unique waveforms detected during and after NMES. The findings indicate that activity of motor units in the left elbow flexors can be modulated by NMES current and pulse width applied to right elbow flexors, but the effects are not distributed uniformly to the involved motor units.

Background. Multiple sclerosis (MS) eventually compromises the walking ability of most individuals burdened with the disease. Treatment with neuromuscular electrical stimulation (NMES) can restore some functional abilities in persons with MS, but its effectiveness may depend on stimulus-pulse duration. Objective. To compare the effects of a 6-week intervention with narrow- or wide-pulse NMES on walking performance, neuromuscular function, and disability status of persons with relapsing-remitting MS. Methods. Individuals with MS (52.6 ± 7.4 years) were randomly assigned to either the narrow-pulse (n = 13) or wide-pulse (n = 14) group. The NMES intervention was performed on the dorsiflexor and plantar flexor muscles of both legs (10 minutes each muscle, 4 s on and 12 s off) at a tolerable level for 18 sessions across 6 weeks. Outcomes were obtained before (week 0) and after (week 7) the intervention and 4 weeks later (week 11). Results. There was no influence of stimulus-pulse duration on the outcomes ( P > .05); thus, the data were collapsed across groups. The NMES intervention improved ( P < .05) gait speed and walking endurance, dorsiflexor strength in the more-affected leg, plantar flexor strength in the less-affected leg, force control for plantar flexors in the less-affected leg, and self-reported levels of fatigue and walking limitations. Conclusion. There was no influence of stimulus-pulse duration on the primary outcomes (gait speed and walking endurance). The 6-week NMES intervention applied to the lower leg muscles of persons with mild to moderate levels of disability can improve their walking performance and provide some symptom relief.

Walking performance of persons with multiple sclerosis (MS) is strongly influenced by the activation signals received by lower leg muscles. We examined the associations between force steadiness and motor unit discharge characteristics of lower leg muscles during submaximal isometric contractions with tests of walking performance and disability status in individuals who self-reported walking difficulties due to MS. We expected that worse walking performance would be associated with weaker plantar flexor muscles, worse force steadiness, and slower motor unit discharge times. Twenty-three individuals with relapsing-remitting MS (56 ± 7 yr) participated in the study. Participants completed one to three evaluation sessions that involved two walking tests (25-ft walk and 6-min walk), a manual dexterity test (grooved pegboard), health-related questionnaires, and measurement of strength, force steadiness, and motor unit discharge characteristics of lower leg muscles. Multiple regression analyses were used to construct models to explain the variance in measures of walking performance. There were statistically significant differences (effect sizes: 0.21–0.60) between the three muscles in mean interspike interval (ISI) and ISI distributions during steady submaximal contractions with the plantar flexor and dorsiflexor muscles. The regression models explained 40% of the variance in 6-min walk distance and 47% of the variance in 25-ft walk time with two or three variables that included mean ISI for one of the plantar flexor muscles, dorsiflexor strength, and force steadiness. Walking speed and endurance in persons with relapsing-remitting MS were reduced in individuals with longer ISIs, weaker dorsiflexors, and worse plantar flexor force steadiness.NEW & NOTEWORTHY The walking endurance and gait speed of persons with relapsing-remitting multiple sclerosis (MS) were worse in individuals who had weaker dorsiflexor muscles and greater force fluctuations and longer times between action potentials discharged by motor units in plantar flexor muscles during steady isometric contractions. These findings indicate that the control of motor unit activity in lower leg muscles of individuals with MS is associated with their walking ability.

The purpose of our study was to examine the associations between the performance of older adults on four tests of mobility and the physical capabilities of the lower leg muscles. The assessments included measures of muscle strength, muscle activation, and perceived fatigability. Muscle activation was quantified as the force fluctuations—a measure of force steadiness—and motor unit discharge characteristics of lower leg muscles during submaximal isometric contractions. Perceived fatigability was measured as the rating of perceived exertion achieved during a test of walking endurance. Twenty participants (73 ± 4 yr) completed one to four evaluation sessions that were separated by at least 3 wk. The protocol included a 400-m walk, a 10-m walk at maximal and preferred speeds, a chair-rise test, and the strength, force steadiness, and discharge characteristics of motor units detected by high-density electromyography of lower leg muscles. Multiple-regression analyses yielded statistically significant models that explained modest amounts of the variance in the four mobility tests. The variance explained by the regression models was 39% for 400-m walk time, 33% for maximal walk time, 42% for preferred walk time, and 27% for chair-rise time. The findings indicate that differences in mobility among healthy older adults were partially associated with the level of perceived fatigability (willingness of individuals to exert themselves) achieved during the test of walking endurance and the discharge characteristics of soleus, medial gastrocnemius, and tibialis anterior motor units during steady submaximal contractions with the plantar flexor and dorsiflexor muscles.NEW & NOTEWORTHY Differences among healthy older adults in walking endurance, walking speed, and ability to rise from a chair can be partially explained by the performance capabilities of lower leg muscles. Assessments comprised the willingness to exert effort (perceived fatigability) and the discharge times of action potentials by motor units in calf muscles during submaximal isometric contractions. These findings indicate that the nervous system contributes significantly to differences in mobility among healthy older adults.

The primary purpose of our study was to assess the influence of modulating sensory input with either transcutaneous electrical nerve stimulation (TENS) or self-massage with therapy balls on the maximal range of motion (ROM) about the ankle joint when stretching the calf muscles. We also investigated the influence of these two conditions on the force capacity and force control of plantar flexor muscles. Twenty healthy adults (25 ± 3 yr) performed three sessions of ankle plantar flexor stretching (three stretches of 30 s each): stretching alone (SS), stretching with concurrent TENS (TENS), and stretching after self-massage using therapy balls (SM). TENS was applied for 60 s prior to and during each stretch, and SM was performed for 60 s prior to each of the three stretches. Maximal voluntary contraction (MVC) torque and force steadiness at 20% MVC were recorded before and at 15 min after the final stretch. Ankle dorsiflexion ROM was assessed before, after, and at 5, 10, and 15 min after the last stretch. The increase in ROM was greater after SM (24%) than after SS (13%) and TENS (9%; p .001). Maximal discomfort level (0-10 VAS) during stretching was similar for all conditions. MVC torque increased after SM only (p .001, Cohen's D = 1.5): SM, 16%; SS, -1%; TENS, -3%. Force steadiness did not change. The sensory fibres that contribute to stretch tolerance were engaged by self-massage but not by TENS, resulting in greater increases in flexibility and MVC torque after self-massage.

Declines in mobility with advancing age are often associated with a reduction in the use of lower leg muscles. We examined the influence of two interventions that involved neuromuscular electrical stimulation (NMES) applied to the triceps surae muscles on the mobility and muscle function of older adults. Thirty healthy older adults (73.5 ± 4.8 yrs) participated in a 6-week intervention comprising 3 weekly sessions of either narrow- or wide-pulse NMES. Motor function was assessed at Weeks 0, 4, 7, and 10. There were no statistically significant differences in the changes in mobility for the two groups of participants, so the data for the two groups were combined to examine changes across time. Time to walk 400 m decreased and maximal walking speed increased after 3 wks of NMES (Week 4) but did not change further at Weeks 7 and 10. In contrast, time to complete the chair-rise and rapid-step tests decreased progressively up to Week 7 but did not change further at Week 10. Moreover, the increase in plantar flexor strength was only observed at Week 7. NMES can elicit improvements in the motor function of older adults, but the time course of the adaptations differs across the mobility tests.

Time to complete two tests of manual dexterity, the 9-hole Peg Test and Grooved Pegboard Test, increases with advancing age. However, the adaptations responsible for the differences in pegboard times betweenmiddle-aged and older adults are largely unknown. Potential mechanisms include neuromuscular characteristics, cognitive function, and cutaneous sensation. To provide a tractable framework to address these gaps in knowledge, the purpose of the current study was to identify the latent variables underlying age-associated differences in time to complete the 9-hole and grooved pegboard tests. The approach involved an independent component analysis that identified associations between the two pegboard times for the two groups of participants with two to six secondary outcomes. The common association across three of the four conditions (two groups and two pegboard tests) was features derived from force-matching tasks requiring submaximal isometric contraction. In addition, there were significant associations for older adults between age, measures of cognitive function, and pegboard times. Nonetheless, the significant associations were unique for each age group and pegboard test. The results provide a framework for subsequent mechanistic studies to identify the adaptations underlying age-associated declines in manual dexterity. (C) 2017 Elsevier Inc. All rights reserved.

Force trajectories during isometric force-matching tasks involving isometric contractions vary substantially across individuals. In this study, we investigated if this variability can be explained by discrete time proportional, integral, derivative (PID) control algorithms with varying model parameters. To this end, we analyzed the pinch force trajectories of 24 subjects performing two rapid force-matching tasks with visual feedback. Both tasks involved isometric contractions to a target force of 10% maximal voluntary contraction. One task involved a single action (pinch) and the other required a double action (concurrent pinch and wrist extension). 50,000 force trajectories were simulated with a computational neuromuscular model whose input was determined by a PID controller with different PID gains and frequencies at which the controller adjusted muscle commands. The goal was to find the best match between each experimental force trajectory and all simulated trajectories. It was possible to identify one realization of the PID controller that matched the experimental force produced during each task for most subjects (average index of similarity: 0.87 ± 0.12; 1 = perfect similarity). The similarities for both tasks were significantly greater than that would be expected by chance (single action: p = 0.01; double action: p = 0.04). Furthermore, the identified control frequencies in the simulated PID controller with the greatest similarities decreased as task difficulty increased (single action: 4.0 ± 1.8 Hz; double action: 3.1 ± 1.3 Hz). Overall, the results indicate that discrete time PID controllers are realistic models for the neural control of force in rapid force-matching tasks involving isometric contractions.

The purpose of the study was to evaluate the capacity of an expanded set of force steadiness tasks to explain the variance in the time it takes young men and women to complete the grooved pegboard test. In a single experimental session, 30 participants (mean ± SD) (24.2 ± 4.0 yr; 15 women) performed the grooved pegboard test, two tests of hand speed, measurements of muscle strength, and a set of submaximal, steady contractions. The steadiness tasks involved single and double actions requiring isometric contractions in the directions of wrist extension, a pinch between the index finger and thumb, and index finger abduction. Time to complete the grooved pegboard test ranged from 41.5 to 67.5 s. The pegboard times (53.9 ± 6.2 s) were not correlated with any of the strength measurements or the reaction time test of hand speed. A stepwise, multiple-regression analysis indicated that much of the variance ( R2 = 0.70) in pegboard times could be explained by a model that comprised two predictor variables derived from the steadiness tasks: time to match the target during a rapid force-matching task and force steadiness (coefficient of variation for force) during a single-action task. Moreover, the pegboard times were significantly faster for women (51.7 ± 6.8 s) than men (56.1 ± 4.9 s). Participants with slower pegboard times seemed to place a greater emphasis on accuracy than speed as they had longer times to match the target during the rapid force-matching task and exhibited superior force steadiness during the single-action task.