Fatigue in primary Sjögren's syndrome is associated with an objective decline in physical performance, pain and depression.

OBJECTIVES: Fatigue is a major complaint in primary Sjögren's syndrome (pSS). To acquire a better understanding of fatigue in pSS, we investigated objective measures of performance decline (performance fatigability). Furthermore, we evaluated the relationship of self-reported fatigue with performance fatigability and factors modulating perceptions of fatigability (perceived fatigability). METHODS: Thirty-nine pSS patients and 27 healthy controls were included. To assess performance fatigability, force decline was measured during a sustained (124s) maximal voluntary contraction (MVC) with the index finger abductor muscle, and voluntary muscle activation was indexed using peripheral nerve stimulation. Self-reported fatigue was quantified using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). Pain, depression, and anxiety assessed using questionnaires and inflammatory biomarkers measured in blood were used as factors relating to perceived fatigability. RESULTS: Voluntary muscle activation was reduced in pSS (p=0.030), but force decline during the sustained MVC did not differ between groups. Self-reported fatigue was significantly higher in pSS than in controls (FSS: 4.4 vs. 2.6, p<0.001). Multivariable linear regression showed that both performance fatigability (force decline) and perceived fatigability (pain and depression) were associated with the MFIS physical domain in pSS (total explained variance of 47%). Negative associations with fatigue were observed for two interferon-associated proteins: MxA and CXCL10. CONCLUSIONS: This study demonstrates that performance fatigability in pSS was compromised by a reduced capacity of the central nervous system to drive the muscle. Furthermore, self-reported fatigue is a multifactorial symptom associated with both performance fatigability and perceived fatigability in patients with pSS.

Voluntary suppression of associated activity decreases force steadiness in the active hand.

Unilateral muscle contractions are often accompanied by the activation of the ipsilateral hemisphere, producing associated activity (AA) in the contralateral homologous muscles. However, the functional role of AA is not fully understood. We determined the effects of voluntary suppression of AA in the first dorsal interosseous (FDI), on force steadiness during a constant force isometric contraction of the contralateral FDI. Participants (n = 17, 25.5 years) performed two trials of isometric FDI contractions as steadily as possible. In Trial 1, they did not receive feedback or explicit instructions for suppressing the AA in the contralateral homologous FDI. In Trial 2, participants received feedback and were asked to voluntarily suppress the AA in the contralateral nontarget FDI. During both trials, corticospinal excitability and motor cortical inhibition were measured. The results show that participants effectively suppressed the AA in the nontarget contralateral FDI (-71%), which correlated with reductions in corticospinal excitability (-57%), and the suppression was also accompanied by increases in inhibition (27%) in the ipsilateral motor cortex. The suppression of AA impaired force steadiness, but the decrease in force steadiness did not correlate with the magnitude of suppression. The results show that voluntary suppression of AA decreases force steadiness in the active hand. However, due to the lack of association between suppression and decreased steadiness, we interpret these data to mean that specific elements of the ipsilateral brain activation producing AA in younger adults are neither contributing nor detrimental to unilateral motor control during a steady isometric contraction.

Neurophysiological impairments in multiple sclerosis-Central and peripheral motor pathways.

A systematic review of the literature was conducted comparing neurophysiological outcomes in persons with multiple sclerosis (PwMS) to healthy controls (HC), in studies of the central nervous system (CNS) function comprising motor evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS) and in studies of the peripheral nervous system (PNS) function comprising electroneuronography (ENG) outcomes elicited by peripheral nerve stimulation. Studies comparing neuromuscular function, assessed during maximal voluntary contraction (MVC) of muscle, were included if they reported muscle strength along with muscle activation by use of electromyography (EMG) and/or interpolated twitch technique (ITT). Studies investigating CNS function showed prolonged central motor conduction times, asymmetry of nerve conduction motor pathways, and prolonged latencies in PwMS when compared to HC. Resting motor threshold, amplitude, and cortical silent periods showed conflicting results. CNS findings generally correlated with disabilities. Studies of PNS function showed near significant prolongation in motor latency of the median nerve, reduced nerve conduction velocities in the tibial and peroneal nerves, and decreased compound muscle action potential amplitudes of the tibial nerve in PwMS. ENG findings did not correlate with clinical severity of disabilities. Studies of neuromuscular function showed lower voluntary muscle activation and increased central fatigue in PwMS, whereas EMG showed divergent muscle activation (ie, EMG amplitude) during MVC. When comparing the existing literature on neurophysiological motor examinations in PwMS and HC, consistent and substantial impairments of CNS function were seen in PwMS, whereas impairments of the PNS were less pronounced and inconsistent. In addition, impairments in muscle activation were observed in PwMS.

Cross-education does not improve early and late-phase rehabilitation outcomes after ACL reconstruction: a randomized controlled clinical trial.

PURPOSE: Limited evidence suggests that cross-education affords clinical benefits in the initial 8 weeks after anterior cruciate ligament (ACL) reconstruction, but it is unknown if such cross-education effects are reproducible and still present in later phases of rehabilitation. We examined whether cross-education, as an adjuvant to standard therapy, would accelerate the rehabilitation up to 26 weeks after ACL reconstruction by attenuating quadriceps weakness. METHODS: ACL-reconstructed patients were randomized into experimental (n = 22) and control groups (n = 21). Both groups received standard care after ACL reconstruction. In addition, the experimental group strength trained the quadriceps of the non-operated leg during weeks 1-12 after surgery (i.e., cross-education). Self-reported knee function was assessed with the Hughston Clinic Knee score as the primary outcome. Secondary outcomes were maximal quadriceps and hamstring strength and single leg hop distance. All outcomes were measured 29 ± 23 days prior to surgery, as a reference, and at 5-week, 12-week, and 26-week post-surgery. RESULTS: Both groups scored 12% worse on self-reported knee function 5-week post-surgery (95% CI 7-17) and showed 15% improvement 26-week post-surgery (95% CI - 20 to - 10). No cross-education effect was found. Interestingly, males scored 8-10% worse than females at each time point post-surgery. None of 33 secondary outcomes showed a cross-education effect. At 26-week post-surgery, both legs improved maximal quadriceps (5-14%) and hamstring strength (7-18%), and the non-injured leg improved 2% in hop distance. The ACL recovery was not affected by limb dominance and age. CONCLUSION: 26 weeks of standard care improved self-reported knee function and maximal leg strength relative to pre-surgery and adding cross-education did not further accelerate ACL recovery. LEVEL OF EVIDENCE: I. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION: This randomized controlled clinical trial is registered at the Dutch trial register ( http://www.trialregister.nl ) under NTR4395.

Somatosensory electrical stimulation improves skill acquisition, consolidation, and transfer by increasing sensorimotor activity and connectivity.

The interaction between the somatosensory and motor systems is important for normal human motor function and learning. Enhancing somatosensory input using somatosensory electrical stimulation (SES) can increase motor performance, but the neuronal mechanisms underlying these effects are largely unknown. With EEG, we examined whether skill acquisition, consolidation, and interlimb transfer after SES was related to increased activity in sensorimotor regions, as assessed by the N30 somatosensory evoked potential or rather increased connectivity between these regions, as assessed by the phase slope index (PSI). Right- and left-hand motor performance and EEG measures were taken before, immediately after, and 24 h ( day 2) after either SES ( n = 12; 5 men) or Control ( n = 12; 5 men). The results showed skill acquisition and consolidation in the stimulated right hand immediately after SES (6%) and on day 2 (9%) and interlimb transfer to the nonstimulated left hand on day 2 relative to Control (8%, all P < 0.05). Increases in N30 amplitudes correlated with skill acquisition while PSI from electrodes that represent the posterior parietal and primary somatosensory cortex to the electrode representing the primary motor cortex correlated with skill consolidation. In contrast, interlimb transfer did not correlate with the EEG-derived neurophysiological estimates obtained in the present study, which may indicate the involvement of subcortical structures in interlimb transfer after SES. In conclusion, weak peripheral somatosensory inputs in the form of SES improve skill acquisition, consolidation, and interlimb transfer that coincide with different cortical adaptations, including enhanced N30 amplitudes and PSI. NEW & NOTEWORTHY The relationship between adaptations in synaptic plasticity and motor learning following somatosensory electrical stimulation (SES) is incompletely understood. Here, we used for the first time a multifactorial approach that examined skill acquisition, consolidation, and interlimb transfer following 20 min of SES. In addition, we quantified sensorimotor integration and the magnitude and direction of connectivity with EEG. Following artificial electrical stimulation, increases in sensorimotor integration and connectivity were found to correlate with skill acquisition and consolidation, respectively.

Cross-education does not accelerate the rehabilitation of neuromuscular functions after ACL reconstruction: a randomized controlled clinical trial.

PURPOSE: Cross-education reduces quadriceps weakness 8 weeks after anterior cruciate ligament (ACL) surgery, but the long-term effects are unknown. We investigated whether cross-education, as an adjuvant to the standard rehabilitation, would accelerate recovery of quadriceps strength and neuromuscular function up to 26 weeks post-surgery. METHODS: Group allocation was randomized. The experimental (n = 22) and control (n = 21) group received standard rehabilitation. In addition, the experimental group strength trained the quadriceps of the non-injured leg in weeks 1-12 post-surgery (i.e., cross-education). Primary and secondary outcomes were measured in both legs 29 ± 23 days prior to surgery and at 5, 12, and 26 weeks post-surgery. RESULTS: The primary outcome showed time and cross-education effects. Maximal quadriceps strength in the reconstructed leg decreased 35% and 12% at, respectively, 5 and 12 weeks post-surgery and improved 11% at 26 weeks post-surgery, where strength of the non-injured leg showed a gradual increase post-surgery up to 14% (all p ≤ 0.015). Limb symmetry deteriorated 9-10% more for the experimental than control group at 5 and 12 weeks post-surgery (both p ≤ 0.030). One of 34 secondary outcomes revealed a cross-education effect: Voluntary quadriceps activation of the reconstructed leg was 6% reduced for the experimental vs. control group at 12 weeks post-surgery (p = 0.023). Both legs improved force control (22-34%) and dynamic balance (6-7%) at 26 weeks post-surgery (all p ≤ 0.043). Knee joint proprioception and static balance remained unchanged. CONCLUSION: Standard rehabilitation improved maximal quadriceps strength, force control, and dynamic balance in both legs relative to pre-surgery but adding cross-education did not accelerate recovery following ACL reconstruction.

An anterior cruciate ligament injury does not affect the neuromuscular function of the non-injured leg except for dynamic balance and voluntary quadriceps activation.

PURPOSE: The function of the anterior cruciate ligament (ACL) patients' non-injured leg is relevant in light of the high incidence of secondary ACL injuries on the contralateral side. However, the non-injured leg's function has only been examined for a selected number of neuromuscular outcomes and often without appropriate control groups. We measured a broad array of neuromuscular functions between legs of ACL patients and compared outcomes to age, sex, and physical activity matched controls. METHODS: Thirty-two ACL-deficient patients (208 ± 145 days post-injury) and active and less-active controls (N = 20 each) participated in the study. We measured single- and multi-joint neuromuscular function in both legs in each group and expressed the overall neuromuscular function in each leg by calculating a mean z-score across all neuromuscular measures. A group by leg MANOVA and ANOVA were performed to examine group and leg differences for the selected outcomes. RESULTS: After an ACL injury, duration (-4.3 h/week) and level (Tegner activity score of -3.9) of sports activity decreased and was comparable to less-active controls. ACL patients showed bilateral impairments in the star excursion balance test compared to both control groups (P ≤ 0.004) and for central activation ratio compared to active controls (P ≤ 0.002). There were between-leg differences within each group for maximal quadriceps and hamstring strength, voluntary quadriceps activation, star excursion balance test performance, and single-leg hop distance (all P < 0.05), but there were no significant differences in quadriceps force accuracy and variability, knee joint proprioception, and static balance. Overall neuromuscular function (mean z-score) did not differ between groups, but ACL patients' non-injured leg displayed better neuromuscular function than the injured leg (P < 0.05). CONCLUSIONS: Except for poorer dynamic balance and reduced quadriceps activation, ACL patients had no bilateral neuromuscular deficits despite reductions in physical activity after injury. Therapists can use the non-injured leg as a reference to assess the injured leg's function for tasks measured in the present study, excluding dynamic balance and quadriceps activation. Rehabilitation after an ACL injury should be mainly focused on the injured leg. LEVEL OF EVIDENCE: III.

Knee jerk responses in infants at high risk for cerebral palsy: an observational EMG study.

BACKGROUND: Following our clinical observation of tonic responses in response to the knee jerk in infants at very high risk for cerebral palsy (VHR infants), we systematically studied tonic responses, clonus, and reflex irradiation. We questioned (i) whether these responses occurred more often in VHR infants than in typically developing (TD) infants, and (ii) whether they were associated with abnormal general movement quality. METHODS: Twenty-four VHR and 26 TD infants were assessed around 3 mo corrected age. Surface electromyograms of leg, trunk, neck, and arm muscles were recorded while eliciting the knee jerk. All assessments were video-recorded. RESULTS: VHR infants more often than TD infants showed tonic responses in the ipsilateral quadriceps and hamstring (Mann-Whitney U; P = 0.0005 and P = 0.0009), clonus (Chi-square; P = 0.0005) and phasic responses in the contralateral quadriceps and hamstring (Mann-Whitney U; P = 0.002 and P = 0.0003, respectively). Widespread reflex irradiation occurred in VHR and TD infants. Definitely abnormal general movements and stiff movements were associated with tonic responses (Mann-Whitney U; P = 0.0005, P = 0.007, respectively) and clonus (Mann-Whitney U; P = 0.003 and P = 0.0005) in the ipsilateral quadriceps. CONCLUSION: Similar to clonus, tonic responses may be regarded as a marker of a loss of supraspinal control. Reflex irradiation primarily is a neurodevelopmental phenomenon of early ontogeny.

Short-latency afferent inhibition as a biomarker of cholinergic degeneration compared to PET imaging in Parkinson's disease.

INTRODUCTION: Short-latency afferent inhibition (SAI) is a relatively cheap and non-invasive method that has been proposed as a cholinergic marker in Parkinson's disease (PD). We aim to verify the clinical feasibility of SAI as a cholinergic marker in PD using positron emission tomography (PET) with the tracer (2R,3R)-5-(2-[18F]fluoroethoxy)benzovesamicol ([18F]FEOBV) as a reference. METHODS: We examined relations between SAI and [18F]FEOBV PET using linear regression analysis, with the primary motor cortex (M1) as primary region of interest. Additionally, we examined relations of both measures with clinical features. RESULTS: 30 PD patients with varying degrees of cognitive dysfunction and 10 healthy controls (HC) were included in the analysis. SAI was not related to tracer uptake in M1 in the PD group (p = .291) or the HC group (p = .206). We could not replicate the previously published relations between SAI and cholinergic symptoms, such as cognition, psychotic experiences and olfactory function. CONCLUSION: SAI was not related to [18F]FEOBV imaging parameters, nor to clinical measures of cholinergic dysfunction. Therefore, SAI may not be feasible as a clinically applied cholinergic marker in PD.

Firing patterns of spontaneously active motor units in spinal cord-injured subjects.

Involuntary motor unit activity at low rates is common in hand muscles paralysed by spinal cord injury. Our aim was to describe these patterns of motor unit behaviour in relation to motoneurone and motor unit properties. Intramuscular electromyographic activity (EMG), surface EMG and force were recorded for 30 min from thenar muscles of nine men with chronic cervical SCI. Motor units fired for sustained periods (>10 min) at regular (coefficient of variation ≤ 0.15, CV, n =19 units) or irregular intervals (CV>0.15, n =14). Regularly firing units started and stopped firing independently suggesting that intrinsic motoneurone properties were important for recruitment and derecruitment. Recruitment (3.6 Hz, SD 1.2), maximal (10.2 Hz, SD 2.3, range: 7.5-15.4 Hz) and derecruitment frequencies were low (3.3 Hz, SD 1.6), as were firing rate increases after recruitment (~20 intervals in 3 s). Once active, firing often covaried, promoting the idea that units received common inputs.Half of the regularly firing units showed a very slow decline (>40 s) in discharge before derecruitment and had interspike intervals longer than their estimated after hyperpolarisation potential (AHP) duration (estimated by death rate and breakpoint analyses). The other units were derecruited more abruptly and had shorter estimated AHP durations. Overall, regularly firing units had longer estimated AHP durations and were weaker than irregularly firing units, suggesting they were lower threshold units. Sustained firing of units at regular rates may reflect activation of persistent inward currents, visible here in the absence of voluntary drive, whereas irregularly firing units may only respond to synaptic noise.

Muscle Fatigability After Hex-Bar Deadlift Exercise Performed With Fast or Slow Tempo.

PURPOSE: To examine the differences in muscle fatigability after resistance exercise performed with fast tempo (FT) compared with slow tempo (ST). METHODS: A total of 8 resistance-trained males completed FT and ST hexagonal-barbell deadlifts, consisting of 8 sets of 6 repetitions at 60% 3-repetition maximum, using a randomized crossover design. Each FT repetition was performed with maximal velocity, while each repetition during ST was performed with a 3-1-3 (eccentric/isometric/concentric) tempo (measured in seconds). Isometric maximal voluntary contraction, voluntary muscle activation, and evoked potentiated twitch torque of the knee extensors were determined using twitch interpolation before, during (set 4), and after exercise. Displacement-time data were measured during the protocols. RESULTS: The mean bar velocity and total concentric work were higher for FT compared with ST (995 [166] W vs 233 [52] W; 0.87 [0.05] m/s vs 0.19 [0.05] m/s; 4.8 [0.8] kJ vs 3.7 [1.1] kJ). Maximal voluntary contraction torque, potentiated twitch, and voluntary muscle activation were significantly reduced after FT (-7.8% [9.2%]; -5.2% [9.2%], -8.7% [12.2%]) and ST (-11.2% [8.4%], -13.3% [8.1%], -1.8% [3.6%]). CONCLUSION: The decline in maximal voluntary force after both the FT and ST hexagonal-barbell deadlifts exercise was accompanied by a similar decline in contractile force and voluntary muscle activation.

Fatigue following mild traumatic brain injury relates to visual processing and effort perception in the context of motor performance.

INTRODUCTION: Following mild traumatic brain injury (mTBI), a substantial number of patients experience disabling fatigue for months after the initial injury. To date, the underlying mechanisms of fatigue remain unclear. Recently, it was shown that mTBI patients with persistent fatigue do not demonstrate increased performance fatigability (i.e., objective performance decline) during a sustained motor task. However, it is not known whether the neural activation required to sustain this performance is altered after mTBI. METHODS: Blood oxygen level-dependent (BOLD) fMRI data were acquired from 19 mTBI patients (>3 months post-injury) and 19 control participants during two motor tasks. Force was recorded from the index finger abductors of both hands during submaximal contractions and a 2-minute maximal voluntary contraction (MVC) with the right hand. Voluntary muscle activation (i.e., CNS drive) was indexed during the sustained MVC using peripheral nerve stimulation. Fatigue was quantified using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). Questionnaire, task, and BOLD data were compared across groups, and linear regression was used to evaluate the relationship between BOLD-activity and fatigue in the mTBI group. RESULTS: The mTBI patients reported significantly higher levels of fatigue (FSS: 5.3 vs. 2.6, p < 0.001). Both mTBI- and control groups demonstrated significant performance fatigability during the sustained MVC, but no significant differences in task performance or BOLD-activity were observed between groups. However, mTBI patients reporting higher FSS scores showed increased BOLD-activity in the bilateral visual cortices (mainly extrastriate) and the left midcingulate gyrus. Furthermore, across all participants mean voluntary muscle activation during the sustained MVC correlated with long lasting post-contraction BOLD-activation in the right insula and midcingulate cortex. CONCLUSION: The fMRI findings suggest that self-reported fatigue in mTBI may relate to visual processing and effort perception. Long lasting activation associated with high levels of CNS drive might be related to changes in cortical homeostasis in the context of high effort.

Increased Ipsilateral M1 Activation after Incomplete Spinal Cord Injury Facilitates Motor Performance.

Incomplete spinal cord injury (SCI) may result in muscle weakness and difficulties with force gradation. Although these impairments arise from the injury and subsequent changes at spinal levels, changes have also been demonstrated in the brain. Blood-oxygen-level dependent (BOLD) imaging was used to investigate these changes in brain activation in the context of unimanual contractions with the first dorsal interosseous muscle. BOLD- and force data were obtained in 19 individuals with SCI (AISA Impairment Scale [AIS] C/D, level C4-C8) and 24 able-bodied controls during maximal voluntary contractions (MVCs). To assess force modulation, participants performed 12 submaximal contractions with each hand (at 10, 30, 50, and 70% MVC) by matching their force level to a visual target. MVCs were weaker in the SCI group (both hands p < 0.001), but BOLD activation did not differ between SCI and control groups. For the submaximal contractions, force (as %MVC) was similar across groups. However, SCI participants showed increased activity of the ipsilateral motor cortex and contralateral cerebellum across all contractions, with no differential effect of force level. Activity of ipsilateral M1 was best explained by force of the target hand (vs. the non-target hand). In conclusion, the data suggest that after incomplete cervical SCI, individuals remain capable of producing maximal supraspinal drive and are able to modulate this drive adequately. Activity of the ipsilateral motor network appears to be task related, although it remains uncertain how this activity contributes to task performance and whether this effect could potentially be harnessed to improve motor functioning.

Older Compared With Younger Adults Performed 467 Fewer Sit-to-Stand Trials, Accompanied by Small Changes in Muscle Activation and Voluntary Force.

Background: Repetitive sit-to-stand (rSTS) is a fatigue perturbation model to examine the age-effects on adaptability in posture and gait, yet the age-effects on muscle activation during rSTS per se are unclear. We examined the effects of age and exhaustive rSTS on muscle activation magnitude, onset, and duration during ascent and descent phases of the STS task. Methods: Healthy older (n = 12) and younger (n = 11) adults performed rSTS, at a controlled frequency dictated by a metronome (2 s for cycle), to failure or for 30 min. We assessed muscle activation magnitude, onset, and duration of plantar flexors, dorsiflexors, knee flexors, knee extensors, and hip stabilizers during the initial and late stages of rSTS. Before and after rSTS, we measured maximal voluntary isometric knee extension force, and rate of perceived exertion, which was also recorded during rSTS task. Results: Older vs. younger adults generated 35% lower maximum voluntary isometric knee extension force. During the initial stage of rSTS, older vs. younger adults activated the dorsiflexor 60% higher, all 5 muscle groups 37% longer, and the hip stabilizers 80% earlier. Older vs. younger adults completed 467 fewer STS trials and, at failure, their rate of perceived exertion was ~17 of 20 on the Borg scale. At the end of the rSTS, maximum voluntary isometric knee extension force decreased 16% similarly in older and younger, as well as the similar age groups decline in activation of the dorsiflexor and knee extensor muscles (all p < 0.05). Conclusion: By performing 467 fewer STS trials, older adults minimized the potential effects of fatigability on muscle activation, voluntary force, and motor function. Such a sparing effect may explain the minimal changes in gait after rSTS reported in previous studies, suggesting a limited scope of this perturbation model to probe age-effects on muscle adaptation in functional tasks.

Inadvertent contralateral activity during a sustained unilateral contraction reflects the direction of target movement.

Strong unilateral contractions are accompanied by excitatory effects to the ipsilateral cortex. This activity can even result in overt contractions of muscles in the contralateral limb. We used this inadvertent, associated activity to study whether the cortical presentation of movements is organized in a directional-related or a muscle-related reference frame. We assessed the contralateral activation for the left index finger during a sustained maximal abduction of the right index finger. In the first experiment, both hands were held vertically in a symmetrical orientation, and in the second experiment the hands were in an asymmetrical orientation (left hand, palm downward; right hand, vertical). In both experiments, the direction of the contralateral associated contraction was upward, i.e., in the symmetrical hand orientation the contralateral force increased mainly in abduction direction, whereas in the asymmetrical hand orientation the contralateral force increased in the extension direction. Thus, the contralateral contractions reflected the direction of the target movement rather than simply the activity of the muscles activated on the target side. These observations provide strong evidence that motor commands are organized in an extrinsic, direction-related reference frame, as opposed to an internal muscle-related reference frame.

A cross-sectional comparison of performance, neurophysiological and MRI outcomes of responders and non-responders to fampridine treatment in multiple sclerosis - An explorative study.

OBJECTIVE: To compare baseline physical and cognitive performance, neurophysiological, and magnetic resonance imaging (MRI) outcomes and examinetheir interrelationship inparticipants with Multiple Sclerosis (MS), already established aseither responder or non-responder to Fampridine treatment, andto examine associationswiththe expanded disability status scale (EDSS) and 12-item MS walking scale (MSWS-12). METHODS: Baseline data from an explorative longitudinal observational study were analyzed. Participants underwent the Timed 25-Foot Walk Test (T25FW), Six Spot Step Test (SSST), Nine-Hole Peg Test, Five Times Sit-to-Stand Test, Symbol Digit Modalities Test (SDMT), neurophysiological testing, including central motor conduction time (CMCT), peripheral motor conduction time (PMCT), motor evoked potential (MEP) amplitudesand electroneuronographyof the lower extremities, and brain MRI (brain volume, number and volume of T2-weighted lesions and lesion load normalized to brain volume). RESULTS: 41 responders and 8 non-responders were examined. There were no intergroup differences inphysical performance, cognitive, neurophysiological, andMRI outcomes (p > 0.05).CMCT was associated withT25FW, SSST, EDSS, and MSWS-12,(p < 0.05). SDMT was associated with the number and volume of T2-weighted lesions, and lesion load normalized to brain volume (p < 0.05). CONCLUSION: No differences were identified between responders and non-responders to Fampridine treatment regarding physical and cognitive performance, neurophysiological or MRI outcomes. The results call for cautious interpretation and further large-scale studies are needed to expand ourunderstanding of underlying mechanisms discriminating Fampridine responders and non-responders.CMCT may be used as a marker of disability and walking impairment, while SDMT was associated with white matter lesions estimated by MRI. ClinicalTrials.gov identifier: NCT03401307.

Age-specific modulation of intermuscular beta coherence during gait before and after experimentally induced fatigue.

We examined the effects of age on intermuscular beta-band (15-35 Hz) coherence during treadmill walking before and after experimentally induced fatigue. Older (n = 12) and younger (n = 12) adults walked on a treadmill at 1.2 m/s for 3 min before and after repetitive sit-to-stand, rSTS, to induce muscle fatigability. We measured stride outcomes and coherence from 100 steps in the dominant leg for the synergistic (biceps femoris (BF)-semitendinosus, rectus femoris (RF)-vastus lateralis (VL), gastrocnemius lateralis (GL)-Soleus (SL), tibialis anterior (TA)-peroneus longus (PL)) and for the antagonistic (RF-BF and TA-GL) muscle pairs at late swing and early stance. Older vs. younger adults had 43-62% lower GL-SL, RF-VL coherence in swing and TA-PL and RF-VL coherence in stance. After rSTS, RF-BF coherence in late swing decreased by ~ 20% and TA-PL increased by 16% independent of age (p = 0.02). Also, GL-SL coherence decreased by ~ 23% and increased by ~ 23% in younger and older, respectively. Age affects the oscillatory coupling between synergistic muscle pairs, delivered presumably via corticospinal tracts, during treadmill walking. Muscle fatigability elicits age-specific changes in the common fluctuations in muscle activity, which could be interpreted as a compensation for muscle fatigability to maintain gait performance.

Voluntary activation and cortical activity during a sustained maximal contraction: an fMRI study.

Motor fatigue is an exercise-induced reduction in the force-generating capacity. The underlying mechanisms can be separated into factors residing in the periphery or in the central nervous system. We designed an experiment in which we investigated central processes underlying motor fatigue by means of magnetic resonance imaging in combination with the twitch interpolation technique. Subjects performed a sustained maximal abduction (2 min) with the right index finger. Brain activation was recorded with an MR scanner, together with index finger abduction force, EMG of several hand muscles and interpolated twitches. Mean activity per volume was calculated for the primary motor cortex and the secondary motor areas (supplementary motor, premotor, and cingulate areas) as well as mean force and mean rectified EMG amplitude. Results showed a progressive decline in maximal index finger abduction force and EMG of the target muscles combined with an increase in brain activity in the contralateral primary motor cortex and secondary motor areas. Analysis of the twitches superimposed on the sustained contraction revealed that during the contraction the voluntary drive decreased significantly. In conclusion, our data showed that despite an increase in brain activity the voluntary activation decreased. This suggests that, although the CNS increased its input to the relevant motor areas, this increase was insufficient to overcome fatigue-related changes in the voluntary drive.

Force decline after low and high intensity contractions in persons with multiple sclerosis.

OBJECTIVE: Force decline during strong contractions is dominated by changes in the periphery whereas during weaker contraction changes in voluntary activation become more important. We compared force decline and contributing factors in persons with multiple sclerosis (PwMS) during low and high intensity contractions. METHODS: Index finger abduction force, force evoked by electrical stimulation of the ulnar nerve at rest (RTw), and during MVCs were investigated in 19 PwMS and 19 controls. Participants performed contractions in sets of six contractions (7 s-on, 3 s-off) at 25% or 80% MVC. After each set, a 5 s-MVC was performed with superimposed nerve stimulation followed by RTw. Contractions were repeated until MVC dropped below 80% of initial MVC. RESULTS: Low compared to high intensity contractions caused a greater decline in voluntary activation and a smaller decline in RTw. Compared to controls, PwMS accomplished equal sets of contractions but showed a smaller decline in RTw. Female PwMS showed poorer voluntary activation. The number of low intensity contractions was associated with sense of fatigue in PwMS. CONCLUSION: Although, no difference in fatigability was observed, the mechanism contributing to force decline differed between PwMS and controls during submaximal contractions. SIGNIFICANCE: During weak contractions, fatigue and fatigability are associated in PwMS.