Increase in heterogeneity of biceps brachii activation during isometric submaximal fatiguing contractions: a multichannel surface EMG study

The effects of fatigue emerge from the beginning of sustained submaximal contractions, as shown by an increase in the amplitude of the surface electromyogram (EMG). The increase in EMG amplitude is attributed to an augmentation of the excitatory drive to the motor neuron pool that, more importantly than increasing discharge rates, recruits additional motor units for the contraction. The aim of this study was to determine whether the spatiotemporal distribution of biceps brachii (BB) activity becomes more or less heterogeneous during a fatiguing isometric contraction sustained at a submaximal target force. Multiple electrodes were attached over the entire BB muscle, and principal component analysis (PCA) was used to extract the representative information from multiple monopolar EMG channels. The development of heterogeneity during the fatiguing contraction was quantified by applying a cluster algorithm on the PCA-processed EMG amplitudes. As shown previously, the overall EMG amplitude increased during the sustained contraction, whereas there was no change in coactivation of triceps brachii. However, EMG amplitude did not increase in all channels and even decreased in some. The change in spatial distribution of muscle activity varied across subjects. As found in other studies, the spatial distribution of EMG activity changed during the sustained contraction, but the grouping and size of the clusters did not change. This study showed for the first time that muscle activation became more heterogeneous during a sustained contraction, presumably due to a decrease in the strength of common inputs with the recruitment of additional motor units

Effect of tsDCS applied with different electrode configurations on the lumbar spinal circuits

Spinal Cord Injury (SCI) is a severe injury to the central nervous system (CNS) which, despite a heavy post injury rehabilitation regime, often leaves patients bound to a wheelchair or with other impairments diminishing their quality of life. Trans-spinal direct current stimulation (tsDCS) is a promising new technique for the treatment of SCI. During tsDCS a small direct current is applied to the spinal cord via two or more stimulation electrodes, placed over the backbone of a subject. The technique aims to alter the response of the neural pathways in the spinal cord, which is hypothesized to have a positive effect on the recovery of the damaged spinal cord neuronal networks. The objective of this study, is to assess how tsDCS modulates the excitability of the spinal cord and whether this modulation is dependent on the electrode placement configurations. The primary goal is to compare a new electrode placement configuration with one that is commonly used in previous tsDCS studies. This is assessed using the H- Reflex, whereby the novel configuration is hypothesized to have a larger modulatory effect on the spinal circuits. The two different configurations are: 1) cathode and anode placed on the T11 vertebra and the left shoulder blade respectively (commonly used) and 2) the two electrodes placed over the spinal cord, 7 centimeters apart and centered around the 11 thoracic vertebra. TsDCS is applied on the lumbar spinal cord for a period of 15 minutes with a current of 2,5mA. The ascending part of the H-reflex recruitment curve is measured before, during and after tsDCS. We hereby present the outcome of the aforementioned study as well as the current progress of our laboratory with respect to the effect of tsDCS on the spinal circuits. We hope that our work will be able to contribute to the effectivity of tsDCS, which could possibly be applied in the rehabilitation of spinal cord injured subjects in the future

Prospective, blind study of the triple stimulation technique in the diagnosis of ALS

Abstract Objective: To evaluate the diagnostic yield of magnetic cortical stimulation with the triple stimulation technique (TST) to identify upper motor neuron (UMN) involvement in patients suspected of having ALS. Methods: Fifty-nine patients were recruited to undergo TST in addition to the standard work-up for suspected motor neuron disease. TST combines transcranial magnetic stimulation of the motor cortex with collision studies, which results in a higher sensitivity in detecting UMN involvement. Primary outcome was the number of abnormal TST results in patients with possible ALS. The positivity rate was converted to the number needed to test with TST (NN-TST) for one extra diagnosis of ALS. Results: Fifty patients underwent TST. In the total group (n 059), 18 patients had a motor neuron disorder but did not fulfil criteria for 'probable' or 'definite' ALS. In four of these patients TST was abnormal (NN-TST, 4.5). One TST was erroneously interpreted as abnormal. TST findings were normal in inclusion body myositis and peripheral nerve disorders. Conclusion: This prospective and blind study confirms open studies of TST in the evaluation of ALS. We suggest that TST can be used to arrive at a diagnosis of 'probable' or 'definite' ALS in patients lacking UMN signs in the upper extremities

Combined N-of-1 trials to investigate mexiletine in non-dystrophic myotonia using a Bayesian approach; study rationale and protocol

Background: To obtain evidence for the clinical and cost-effectiveness of treatments for patients with rare diseases is a challenge. Non-dystrophic myotonia (NDM) is a group of inherited, rare muscle diseases characterized by muscle stiffness. The reimbursement of mexiletine, the expert opinion drug for NDM, has been discontinued in some countries due to a lack of independent randomized controlled trials (RCTs). It remains unclear however, which concessions can be accepted towards the level 1 evidence needed for coverage decisions, in rare diseases. Considering the large number of rare diseases with a lack of treatment evidence, more experience with innovative trial designs is needed. Both NDM and mexiletine are well suited for an N-of-1 trial design. A Bayesian approach allows for the combination of N-of-1 trials, which enables the assessment of outcomes on the patient and group level simultaneously. Methods/Design: We will combine 30 individual, double-blind, randomized, placebo-controlled N-of-1 trials of mexiletine (600 mg daily) vs. placebo in genetically confirmed NDM patients using hierarchical Bayesian modeling. Our results will be compared and combined with the main results of an international cross-over RCT (mexiletine vs. placebo in NDM) published in 2012 that will be used as an informative prior. Similar criteria of eligibility, treatment regimen, end-points and measurement instruments are employed as used in the international cross-over RCT. Discussion: The treatment of patients with NDM with mexiletine offers a unique opportunity to compare outcomes and efficiency of novel N-of-1 trial-based designs and conventional approaches in producing evidence of clinical and cost-effectiveness of treatments for patients with rare diseases

Enhanced low-threshold motor unit capacity during endurance tasks in patients with spinal muscular atrophy using pyridostigmine

Objective: To investigate the electrophysiological basis of pyridostigmine enhancement of endurance performance documented earlier in patients with spinal muscular atrophy (SMA). Methods: We recorded surface electromyography (sEMG) in four upper extremity muscles of 31 patients with SMA types 2 and 3 performing endurance shuttle tests (EST) and maximal voluntary contraction (MVC) measurements during a randomized, double blind, cross-over, phase II trial. Linear mixed effect models (LMM) were used to assess the effect of pyridostigmine on (i) time courses of median frequencies and of root mean square (RMS) amplitudes of sEMG signals and (ii) maximal RMS amplitudes during MVC measurements. These sEMG changes over time indicate levels of peripheral muscle fatigue and recruitment of new motor units, respectively. Results: In comparison to a placebo, patients with SMA using pyridostigmine had fourfold smaller decreases in frequency and twofold smaller increases in amplitudes of sEMG signals in some muscles, recorded during ESTs (p < 0.05). We found no effect of pyridostigmine on MVC RMS amplitudes. Conclusions: sEMG parameters indicate enhanced low-threshold (LT) motor unit (MU) function in upper-extremity muscles of patients with SMA treated with pyridostigmine. This may underlie their improved endurance. Significance: Our results suggest that enhancing LT MU function may constitute a therapeutic strategy to reduce fatigability in patients with SMA

Changes in corticospinal excitability and the direction of evoked movements during motor preparation: A TMS study

BACKGROUND: Preparation of the direction of a forthcoming movement has a particularly strong influence on both reaction times and neuronal activity in the primate motor cortex. Here, we aimed to find direct neurophysiologic evidence for the preparation of movement direction in humans. We used single-pulse transcranial magnetic stimulation (TMS) to evoke isolated thumb-movements, of which the direction can be modulated experimentally, for example by training or by motor tasks. Sixteen healthy subjects performed brisk concentric voluntary thumb movements during a reaction time task in which the required movement direction was precued. We assessed whether preparation for the thumb movement lead to changes in the direction of TMS-evoked movements and to changes in amplitudes of motor-evoked potentials (MEPs) from the hand muscles. RESULTS: When the required movement direction was precued early in the preparatory interval, reaction times were 50 ms faster than when precued at the end of the preparatory interval. Over time, the direction of the TMS-evoked thumb movements became increasingly variable, but it did not turn towards the precued direction. MEPs from the thumb muscle (agonist) were differentially modulated by the direction of the precue, but only in the late phase of the preparatory interval and thereafter. MEPs from the index finger muscle did not depend on the precued direction and progressively decreased during the preparatory interval. CONCLUSION: Our data show that the human corticospinal movement representation undergoes progressive changes during motor preparation. These changes are accompanied by inhibitory changes in corticospinal excitability, which are muscle specific and depend on the prepared movement direction. This inhibition might indicate a corticospinal braking mechanism that counteracts any preparatory motor activation

Distinct neural control of intrinsic and extrinsic muscles of the hand during single finger pressing

Single finger force tasks lead to unintended activation of the non-instructed fingers, commonly referred to as enslaving. Both neural and mechanical factors have been associated with this absence of finger individuality. This study investigates the amplitude modulation of both intrinsic and extrinsic finger muscles during single finger isometric force tasks. Twelve participants performed single finger flexion presses at 20% of maximum voluntary contraction, while simultaneously the electromyographic activity of several intrinsic and extrinsic muscles associated with all four fingers was recorded using 8 electrode pairs in the hand and two 30-electrode grids on the lower arm. The forces exerted by each of the fingers, in both flexion and extension direction, were recorded with individual force sensors. This study shows distinct activation patterns in intrinsic and extrinsic hand muscles. Intrinsic muscles exhibited individuation, where the agonistic and antagonistic muscles associated with the instructed fingers showed the highest activation. This activation in both agonistic and antagonistic muscles appears to facilitate finger stabilisation during the isometric force task. Extrinsic muscles show an activation independent from instructed finger in both agonistic and antagonistic muscles, which appears to be associated with stabilisation of the wrist, with an additional finger-dependent modulation only present in the agonistic extrinsic muscles. These results indicate distinct muscle patterns in intrinsic and extrinsic hand muscles during single finger isometric force pressing. We conclude that the finger specific activation of intrinsic muscles is not sufficient to fully counteract enslaving caused by the broad activation of the extrinsic muscles

Understanding the constraints of finger motor control

Biomechanical EngineeringBiomechatronics & Human-Machine Contro