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Concept: Electromyography


Despite partial success, communication has remained impossible for persons suffering from complete motor paralysis but intact cognitive and emotional processing, a state called complete locked-in state (CLIS). Based on a motor learning theoretical context and on the failure of neuroelectric brain-computer interface (BCI) communication attempts in CLIS, we here report BCI communication using functional near-infrared spectroscopy (fNIRS) and an implicit attentional processing procedure. Four patients suffering from advanced amyotrophic lateral sclerosis (ALS)-two of them in permanent CLIS and two entering the CLIS without reliable means of communication-learned to answer personal questions with known answers and open questions all requiring a “yes” or “no” thought using frontocentral oxygenation changes measured with fNIRS. Three patients completed more than 46 sessions spread over several weeks, and one patient (patient W) completed 20 sessions. Online fNIRS classification of personal questions with known answers and open questions using linear support vector machine (SVM) resulted in an above-chance-level correct response rate over 70%. Electroencephalographic oscillations and electrooculographic signals did not exceed the chance-level threshold for correct communication despite occasional differences between the physiological signals representing a “yes” or “no” response. However, electroencephalogram (EEG) changes in the theta-frequency band correlated with inferior communication performance, probably because of decreased vigilance and attention. If replicated with ALS patients in CLIS, these positive results could indicate the first step towards abolition of complete locked-in states, at least for ALS.

Concepts: Neuroscience, Amyotrophic lateral sclerosis, Electroencephalography, Evoked potential, Electromyography, Answer, Support vector machine, Neurofeedback


BackgroundCharcot-Marie-Tooth type 1A disease (CMT1A) is a rare orphan inherited neuropathy caused by an autosomal dominant duplication of a gene encoding for the structural myelin protein PMP22, which induces abnormal Schwann cell differentiation and dysmyelination, eventually leading to axonal suffering then loss and muscle wasting. We favour the idea that diseases can be more efficiently treated when targeting multiple disease-relevant pathways. In CMT1A patients, we therefore tested the potential of PXT3003, a low-dose combination of three already approved compounds (baclofen, naltrexone and sorbitol). Our study conceptually builds on preclinical experiments highlighting a pleiotropic mechanism of action that includes downregulation of PMP22. The primary objective was to assess safety and tolerability of PXT3003. The secondary objective aimed at an exploratory analysis of efficacy of PXT3003 in CMT1A, to be used for designing next clinical development stages (Phase 2b/3).Methods80 adult patients with mild-to-moderate CMT1A received in double-blind for 1 year Placebo or one of the three increasing doses of PXT3003 tested, in four equal groups. Safety and tolerability were assessed with the incidence of related adverse events. Efficacy was assessed using the Charcot-Marie-Tooth Neuropathy Score (CMTNS) and the Overall Neuropathy Limitations Scale (ONLS) as main endpoints, as well as various clinical and electrophysiological outcomes.ResultsThis trial confirmed the safety and tolerability of PXT3003. The highest dose (HD) showed consistent evidence of improvement beyond stabilization. CMTNS and ONLS, with a significant improvement of respectively of 8% (0.4% - 16.2%) and 12.1% (2% - 23.2%) in the HD group versus the pool of all other groups, appear to be the most sensitive clinical endpoints to treatment despite their quasi-stability over one year under Placebo. Patients who did not deteriorate over one year were significantly more frequent in the HD group.ConclusionsThese results confirm that PXT3003 deserves further investigation in adults and could greatly benefit CMT1A-diagnosed children, usually less affected than adults.Trial registrationEudraCT Number: 2010-023097-40. Identifier: NCT01401257. The Committee for Orphan Medicinal Products issued in February 2014 a positive opinion on the application for orphan designation for PXT3003 (EMA/OD/193/13).

Concepts: Clinical trial, Action potential, Electromyography, Myelin, Vincristine, Charcot-Marie-Tooth disease, Schwann cell, Jean-Martin Charcot


Recent findings suggest that not only the lack of physical activity, but also prolonged times of sedentary behaviour where major locomotor muscles are inactive, significantly increase the risk of chronic diseases. The purpose of this study was to provide details of quadriceps and hamstring muscle inactivity and activity during normal daily life of ordinary people. Eighty-four volunteers (44 females, 40 males, 44.1±17.3 years, 172.3±6.1 cm, 70.1±10.2 kg) were measured during normal daily life using shorts measuring muscle electromyographic (EMG) activity (recording time 11.3±2.0 hours). EMG was normalized to isometric MVC (EMG(MVC)) during knee flexion and extension, and inactivity threshold of each muscle group was defined as 90% of EMG activity during standing (2.5±1.7% of EMG(MVC)). During normal daily life the average EMG amplitude was 4.0±2.6% and average activity burst amplitude was 5.8±3.4% of EMG(MVC) (mean duration of 1.4±1.4 s) which is below the EMG level required for walking (5 km/h corresponding to EMG level of about 10% of EMG(MVC)). Using the proposed individual inactivity threshold, thigh muscles were inactive 67.5±11.9% of the total recording time and the longest inactivity periods lasted for 13.9±7.3 min (2.5-38.3 min). Women had more activity bursts and spent more time at intensities above 40% EMG(MVC) than men (p<0.05). In conclusion, during normal daily life the locomotor muscles are inactive about 7.5 hours, and only a small fraction of muscle's maximal voluntary activation capacity is used averaging only 4% of the maximal recruitment of the thigh muscles. Some daily non-exercise activities such as stair climbing produce much higher muscle activity levels than brisk walking, and replacing sitting by standing can considerably increase cumulative daily muscle activity.

Concepts: Mode, Muscle, Physical exercise, Knee, Electromyography, Arithmetic mean, Thigh, Extension


Duchenne muscular dystrophy (DMD) is a devastating genetic muscular disorder of childhood marked by progressive debilitating muscle weakness and wasting, and ultimately death in the second or third decade of life. Wnt7a signaling through its receptor Fzd7 accelerates and augments regeneration by stimulating satellite stem cell expansion through the planar cell polarity pathway, as well as myofiber hypertrophy through the AKT/mammalian target of rapamycin (mTOR) anabolic pathway. We investigated the therapeutic potential of the secreted factor Wnt7a for focal treatment of dystrophic DMD muscles using the mdx mouse model, and found that Wnt7a treatment efficiently induced satellite cell expansion and myofiber hypertrophy in treated mucles in mdx mice. Importantly, Wnt7a treatment resulted in a significant increase in muscle strength, as determined by generation of specific force. Furthermore, Wnt7a reduced the level of contractile damage, likely by inducing a shift in fiber type toward slow-twitch. Finally, we found that Wnt7a similarly induced myotube hypertrophy and a shift in fiber type toward slow-twitch in human primary myotubes. Taken together, our findings suggest that Wnt7a is a promising candidate for development as an ameliorative treatment for DMD.

Concepts: Energy, Muscle, Cardiac muscle, Electromyography, Muscular system, Muscular dystrophy, Atrophy, Muscle spindle


Identification of a systemically acting and universal small molecule therapy for Duchenne muscular dystrophy would be an enormous advance for this condition. Based on evidence gained from studies on mouse genetic models we have identified tyrosine phosphorylation and degradation of β-dystroglycan as a key event in the aetiology of Duchenne muscular dystrophy. Thus preventing tyrosine phosphorylation and degradation of β-dystroglycan presents itself as a potential therapeutic strategy. Using the dystrophic sapje zebrafish we have investigated the use of tyrosine kinase and other inhibitors to treat the dystrophic symptoms in this model of Duchenne muscular dystrophy. Dasatinib, a potent and specific Src tyrosine kinase inhibitor was found to decrease the levels of β-dystroglycan phosphorylation on tyrosine and increase the relative levels of non-phosphorylated β-dystroglycan in sapje zebrafish. Furthermore, dasatinib treatment resulted in the improved physical appearance of the sapje zebrafish musculature and increased swimming ability as measured by both duration and distance of swimming dasatinib treated fish compared to control animals. These data suggest great promise for pharmacological agents that prevent the phosphorylation of β-dystroglycan on tyrosine and subsequent steps in the degradation pathway as therapeutic targets for the treatment of Duchenne muscular dystrophy.

Concepts: Signal transduction, Protein kinase, Phosphorylation, Enzyme inhibitor, Electromyography, Muscular dystrophy, Duchenne muscular dystrophy, Morpholino


Combined pelvic floor electromyography (EMG) and videocystourethrography (VCUG) during urodynamic investigation are the most acceptable and widely agreed methods for diagnosing detrusor external sphincter dyssynergia (DESD). Theoretically, external urethral sphincter pressure (EUSP) measurement would provide enough information for the diagnosis of DESD and could simplify the urodynamic investigation replacing combined pelvic floor EMG and VCUG. Thus, we evaluated the diagnostic accuracy of EUSP measurement for DESD. PATIENTS #ENTITYSTARTX00026;

Concepts: Diagnosis, Measurement, Electromyography, Pelvic floor, Accuracy and precision, Urethral sphincter


The effects of hip muscle strength and activation on anterior cruciate ligament injury biomechanics, particularly knee valgus loading, have been reported in isolation and with equivocal results. However, the combination of these factors influences joint biomechanics. This investigation evaluated the influence of hip strength on gluteal activation and knee valgus motion. Maximal isometric hip abduction (ABD) and external rotation (ER) contractions were used to define High and Low strength groups. Knee kinematics and gluteus maximus (GMax) and medius (GMed) EMG amplitudes obtained during landing were compared between High and Low strength groups after controlling for the potential confounding influence of sex. Knee valgus motion did not differ between the High and Low hip ABD and ER strength groups. However, the Low ABD and ER strength groups displayed greater GMed and GMax EMG amplitudes, respectively, compared to the High strength groups. These findings suggest that weaker individuals compensate for a lack of force production via heightened neural drive. As such, hip muscle strength influences knee valgus motion indirectly by determining neural drive requirements.

Concepts: Knee, Anterior cruciate ligament, Electromyography, Muscular system, Ligament, Anterior cruciate ligament injury, Cruciate ligament, Gluteal muscles


OBJECTIVE: To investigate the efficacy of DA-8031, a novel compound for the treatment of premature ejaculation (PE), we performed in vivo pharmacological studies using 2 preclinical animal models, electrical stimulation of sensory branch of pudendal nerve (SBPdn) and para-chloroamphetamine (PCA)-induced ejaculation model. METHODS: First of all, in electrical stimulation of an SBPdn model, an SBPdn in the pelvic canal of the spinal cord transected from rats was identified. Then an electromyogram (EMG) of the bulbospongiosus (BS) muscle was recorded during electrical stimulation of SBPdn after single intravenous (IV) dosing of DA-8031 and its reference drug, dapoxetine. In the second model, both seminal vesicle pressure (SVP) and the EMG profile of the BS muscle were recorded in PCA-induced ejaculation animals after treated with the same dosing regimen. RESULTS: Area under the curve (AUC) of the BS muscle by EMG wave exhibited a significant reduction in the DA-8031 and dapoxetine 3 mg/kg treated groups, and maximum amplitudes were also significantly decreased in DA-8031 1, 3 mg/kg and dapoxetine 3 mg/kg dose level in the SBPdN stimulation model. Consistent with these findings, in a PCA-induced ejaculation model, SVP increase was significantly inhibited from DA-8031 0.3 mg/kg dose level, and AUC of BS muscle EMG significantly decreased in the DA-8031 1, 3 mg/kg groups. CONCLUSION: The present study implied that DA-8031 contributed to an effective co-coordinated inhibition of the expulsion phase of ejaculation by modulating BS muscle activity and the emission phase through blocking SVP rise. From these findings, DA-8031 is further expected to have clinical efficacy in human studies.

Concepts: Semen, Electromyography, Orgasm, Ejaculation, Penis, Premature ejaculation, Pudendal nerve, Bulbospongiosus muscle


BACKGROUND: Tendon transfers are essential for reconstruction of hand function in tetraplegic patients. To transfer the extensor carpi radialis longus (ECRL), the extensor carpi radialis brevis (ECRB) has to be sufficiently strong. However, there is currently no reliable clinical test to individually analyse both muscles. In order to develop a reliable preoperative clinical test, the anatomy of the muscle (innervation) areas of ECRB, ECRL and brachio-radialis (BR) was examined. METHODS: In 20 arms, the ECRB, ECRL and BR were dissected and localised. Subsequently, muscle-innervation points were mapped and categorised. A novel method, computer-assisted surgical anatomy mapping (CASAM), was used to visualise muscle areas and innervation points in a computed arm with average dimensions. RESULTS: For both ECRL and ECRB a 100% area could be identified, a specific area in the computed average arm in which the muscle was present for all 20 arms. For the ECRL, this area was situated at 16% of the distance between the lateral epicondyle and the deltoid muscle insertion. The ECRB 100% area was 5 times bigger than that of the ECRL and was located at 40% of the distance between the lateral epicondyle and the radial styloid process. The ECRL and BR showed one to three innervation points, the ECRB one to four. In 47% of the cases, there was a combined nerve branch innervating both the ECRL and the ECRB. CONCLUSIONS: It is feasible to develop a preoperative test; the 100% areas can be used for needle electromyography (EMG) or local anaesthetic muscle injections.

Concepts: Muscle, Electromyography, Nerve, Upper limb anatomy, Brachioradialis, Flexor carpi radialis muscle, Extensor carpi radialis brevis muscle, Extensor carpi radialis longus muscle


Training the bench press exercise on a traditional flat bench does not induce a level of instability as seen in sport movements and activities of daily living. Twenty participants were recruited to test two forms of instability: using one dumbbell rather than two and lifting on the COR bench compared to a flat bench. Electromyography (EMG) amplitudes of the pectoralis major, middle trapezius, external oblique, and internal oblique were recorded and compared. Differences in range of motion (ROM) were evaluated by measuring an angular representation of the shoulder complex. Four separate conditions of unilateral bench press were tested while lifting on a: flat bench with one dumbbell, flat bench with two dumbbells, COR Bench with one dumbbell, and COR Bench with two dumbbells. The results imply that there are no differences in EMG amplitude or ROM between the COR bench and traditional bench. However, greater ROM was found to be utilized in the single dumbbell condition, both in the COR bench and the flat bench.

Concepts: Fundamental physics concepts, Muscle, Electromyography, Bench press, Abdominal external oblique muscle, Pectoralis major muscle, Clavicle, Barbell