Long-term electrical stimulation of muscles in children with Duchenne and Becker muscular dystrophy.

Nine children suffering from progressive muscular dystrophy (7 Duchenne and 2 Becker) were included in a program of low-frequency electrical stimulation (LFES) of the right tibialis anterior (TA) muscle. Muscle strength and muscle fatigue were estimated by measuring torques in the ankle during attempts of maximal voluntary contraction (MVC) in the direction of dorsal flexion of the foot and during electrically evoked contractions (EEC). No important increase in the strength of the stimulated muscles was noticed in 4 boys whose muscles were stimulated for 3 months. The muscles of 5 boys who were subjected to electrical stimulation for 9 months showed an improvement; 6 measurements made during the stimulation program revealed that changes of torques in the ankle of the right stimulated extremity were significantly different (P less than 0.001) from the changes of torques in the ankle of the left nonstimulated extremity.     

Electrophysiological characteristics of motor units and muscle fibers in trained and untrained young male subjects

We hypothesized that the amplitudes of compound muscle action potentials (CMAPs) and interference pattern analysis (IPA) would be larger in trained subjects compared with untrained subjects, possibly due to hypertrophy of muscle fibers and/or increased central drive. Moreover, we hypothesized that the untrained muscle is less excitable compared with the trained muscle. An electromyographic (EMG) needle electrode was used to record the IPA at maximal voluntary effort. The CMAP was obtained by stimulating the musculocutaneous nerve and recording the brachial biceps muscle using surface electrodes. CMAPs were obtained by direct muscle stimulation (DMS) with two stainless‐steel subdermal electrodes placed subcutaneously in the distal third of the muscle. Amplitudes of CMAP and IPA were significantly larger in trained subjects compared with untrained subjects. We found no differences between trained and untrained subjects in IPA power spectrum and turns per second or amplitude of the CMAPs obtained by DMS. Muscle fiber hypertrophy and/or altered central drive may account for our results, but there was no indication of changes in muscle fiber excitability. Muscle Nerve, 2010     

Recovery of long-term denervated human muscles induced by electrical stimulation

We investigated the restorative potential of intensive electrical stimulation in a patient with long-standing quadriceps denervation. Stimulation started 18 months after injury. After 26 months, the thighs were visibly less wasted. Muscle cross-sectional areas, measured by computerized tomography, increased from 36.0 cm(2) to 57.9 cm(2) (right) and from 36.1 cm(2) to 52.4 cm(2) (left). Knee torque had become sufficient to maintain standing without upper extremity support. Biopsies revealed evidence of both growth and regeneration of myofibers. The results suggest that electrical stimulation may offer a route to the future development of mobility aids in patients with lower motor neuron lesions.     

骨骼肌生长与适应的机械信号与途径

背景：骨骼肌作为一种机械组织,具有机械收缩的功能,但外界力学机械信号如何转变成生物体的化学信号,从而影响肌肉的生长和代谢仍不是很明确。 目的：了解机械刺激与骨骼肌适应的信号途径,为摸索改善骨骼肌质量与适应提供理论依据及实验方案。 方法：应用计算机检索Pubmed数据库和中国期刊网1980-01/2008-12相关文献。英文检索词为“skeletal muscle、mechanical stimulation、signal transduction”;中文检索词为“骨骼肌,运动,信号传导”。纳入标准：①具有原创性,论点论据可靠的实验性文章。②与骨骼肌肥大相关内容的文章。③观点明确,分析全面的文章。排除标准：与文章目的无关的内容和重复性研究。 结果与结论：骨骼肌作为一种机械组织,具有机械收缩的功能,但外界力学机械信号如何转变成生物体的的化学信号,从而影响肌肉的生长和代谢仍不是很明确。研究表明,机械刺激通过诱导Akt/mTOR途径,从而促进骨骼肌生长与适应的机制;骨骼肌纤维在机械运动刺激作用下,神经冲动的传递,随后开放Ca2+及相关离子通道,引起胞浆中的钙离子增加,使钙调神经磷酸酶的活性上升,催化NFAT 去磷酸化,激活的NFAT 进入肌细胞核,作用于相应的靶基因,最终使骨骼肌产生运动适应性变化。结果表明,肌肉机械信号刺激促进胰岛素样生长因子1的释放,进而通过生物信号传导通路来实现。机械刺激促进离子浓度的改变,从而影响钙调磷酸酶/对核因子活化T细胞途径以增加肌肉质量。对于机械运动的物理信号与生物体的化学信号通路的机制研究还有待继续深入探索。     

Repetitive nerve stimulation of facial muscles in MuSK antibody-positive myasthenia gravis

To better define electrophysiological abnormalities in myasthenia gravis (MG) patients with muscle-specific tyrosine kinase (MuSK) antibodies (Ab), we compared electrophysiological features of 14 MuSK Ab-positive, 73 acetylcholine receptor antibody (AChR Ab)-positive, and 22 MuSK and AChR Ab-negative (seronegative) patients with generalized disease. Repetitive nerve stimulation (RNS) abnormalities were observed in 86% of MuSK Ab-positive and 82% of AChR Ab-positive patients but in only 55% of seronegative patients. RNS decrements in the orbicularis oculi were more common and severe in the MuSK Ab-positive patients than the other two groups. Single-fiber electromyography (SFEMG) of the extensor digitorum communis was abnormal in 90% of MuSK Ab-positive patients. The high frequency of RNS abnormalities in facial muscles in the MuSK Ab-positive population reflects the propensity for facial muscle involvement in this form of MG and emphasizes the importance of including facial muscles in RNS protocols when evaluating these patients.     

Mapping of multiple muscles with transcranial magnetic stimulation: absolute and relative test–retest reliability

The spatial accuracy of transcranial magnetic stimulation (TMS) may be as small as a few millimeters. Despite such great potential, navigated TMS (nTMS) mapping is still underused for the assessment of motor plasticity, particularly in clinical settings. Here, we investigate the within‐limb somatotopy gradient as well as absolute and relative reliability of three hand muscle cortical representations (MCRs) using a comprehensive grid‐based sulcus‐informed nTMS motor mapping. We enrolled 22 young healthy male volunteers. Two nTMS mapping sessions were separated by 5–10 days. Motor evoked potentials were obtained from abductor pollicis brevis (APB), abductor digiti minimi, and extensor digitorum communis. In addition to individual MRI‐based analysis, we studied normalized MNI MCRs. For the reliability assessment, we calculated intraclass correlation and the smallest detectable change. Our results revealed a somatotopy gradient reflected by APB MCR having the most lateral location. Reliability analysis showed that the commonly used metrics of MCRs, such as areas, volumes, centers of gravity (COGs), and hotspots had a high relative and low absolute reliability for all three muscles. For within‐limb TMS somatotopy, the most common metrics such as the shifts between MCR COGs and hotspots had poor relative reliability. However, overlaps between different muscle MCRs were highly reliable. We, thus, provide novel evidence that inter‐muscle MCR interaction can be reliably traced using MCR overlaps while shifts between the COGs and hotspots of different MCRs are not suitable for this purpose. Our results have implications for the interpretation of nTMS motor mapping results in healthy subjects and patients with neurological conditions.     

Functional magnetic stimulation of the respiratory muscles in dogs

This study assessed the ability of functional magnetic stimulation (FMS) to activate the respiratory muscles in dogs. With the animal supine, FMS of the phrenic nerves using a high-speed magnetic stimulator was performed by placing a round magnetic coil (MC) at the carotid triangle. Following hyperventilation-induced apnea, changes in volume (ΔV) and airway pressure (ΔP) against an occluded airway were determined. FMS of the phrenic nerves produced substantial inspired function (ΔV = 373 ± 20.5 mL and ΔP = −20 ± 2.0 cm H₂O). After bilateral phrenectomies, maximal inspired ΔV (219 ± 12.2 mL) and ΔP (−10 ± 1.0 cm H₂O) were produced when the MC was placed near the C6–C7 spinous processes, while maximal expired ΔV (−199 ± 22.5 mL) and ΔP (11 ± 2.3 cm H₂O) were produced following stimulation near the T9–T10 spinous processes. We conclude: (1) FMS of either the phrenic or upper intercostal nerves results in inspired volume production; (2) FMS of the lower intercostal nerves generates expired volume production; and (3) FMS of the respiratory muscles may be a useful noninvasive tool for artificial ventilation and assisted cough in patients with spinal cord injuries or other neurological disorders. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:1048–1057, 1998.     

Glycogenosomes in fibres of human normal skeletal muscles

Summary Analysis of muscle biopsies from five patients, with no clinical evidence of neuromuscular disorders, showed the presence of membrane-bound structures containing glycogen (glycogenosomes). Occurrence of these structures within human muscle fibres has been usually considered a pathological finding, common to various types of metabolic diseases. Our results provide evidence that glycogenosomes are a normal constituent of human muscle fibre, thereby emphasizing that any relationship between glycogenosomes and a specific pathological condition should be established with great care.Supported by a grant from CDCH of UCV (no. C-01.3/82)     

Surface‐distributed low‐frequency asynchronous stimulation delays fatigue of stimulated muscles

Introduction: One important reason why functional electrical stimulation (FES) has not gained widespread clinical use is the limitation imposed by rapid muscle fatigue due to non‐physiological activation of the stimulated muscles. We aimed to show that asynchronous low‐pulse‐rate (LPR) electrical stimulation applied by multipad surface electrodes greatly postpones the occurrence of muscle fatigue compared with conventional stimulation (high pulse rate, HPR). Methods: We compared the produced force vs. time of the forearm muscles responsible for finger flexion in 2 stimulation protocols, LPR (f_L = 10 Hz ) and HPR (f_H = 40 Hz ). Results: Surface‐distributed low‐frequency asynchronous stimulation (sDLFAS) doubles the time interval before the onset of fatigue (104 ± 80%) compared with conventional synchronous stimulation. Conclusions: Combining the performance of multipad electrodes (increased selectivity and facilitated positioning) with sDLFAS (decreased fatigue) can improve many FES applications in both the lower and upper extremities. Muscle Nerve 48 : 930–937, 2013     

Changes in skeletal muscles of young women with anorexia nervosa

Summary Biopsies from four young women with advanced anorexia nervosa were examined to investigate the effect of malnutrition on skeletal muscles. None of the patients showed signs of neuromuscular disease and all were physically active at the time of examination.Cryostat sections from the vastus lateralis muscle were stained with hematoxylin-azophloxin-safran and with stains for myofibrillar ATP-ase activity. In addition to routine examination of the sections, the size and distribution of the type 1 and type 2 fibres were calculated by means of a Kontron Digiplan MOP 02.Routine stained sections showed a small grouped atrophy in three cases and a more diffuse atrophy in the fourth. Enzyme histochemical stains revealed a distinct type 2 atrophy, a finding which should serve to distinguish the changes of pure malnutrition from those of conventional denervation.Exact measurements confirmed the predominant type 2 atrophy but showed definite atrophy also of the type 1 fibres. Compared with normal controls the type 1 fibres were reduced by 46% and the type 2 fibres by 75%. These findings are largely in agreement with the recent observations by Essén et al. (1981) on anorexia nervosa. However, in contrast to Essén et al. we did not find any change in the numerical distribution of the fibre types, especially no increase in type 1 fibres. Thus, we could not confirm the hypotheses of a conversion of the fibre types in cachexia.     

Homocysteine activates calcium-mediated cell signaling mechanisms targeting the cytoskeleton in rat hippocampus

Homocysteine is considered to be neurotoxic and a risk factor for neurodegenerative diseases. Despite the increasing evidences of excitotoxic mechanisms of homocysteine (Hcy), little is known about the action of Hcy on the cytoskeleton. In this context, the aim of the present work was to investigate the signaling pathways involved in the mechanism of action of Hcy on cytoskeletal phosphorylation in cerebral cortex and hippocampus of rats during development. Results showed that 100 μM Hcy increased the intermediate filament (IF) phosphorylation only in 17-day-old rat hippocampal slices without affecting the cerebral cortex from 9- to 29-day-old animals. Stimulation of ⁴⁵Ca²⁺ uptake supported the involvement of NMDA receptors and voltage-dependent channels in extracellular Ca²⁺ flux, as well as Ca²⁺ release from intracellular stores through inositol-3-phosphate and ryanodine receptors. Moreover, the mechanisms underlying the Hcy effect on hippocampus cytoskeleton involved the participation of phospholipase C, protein kinase C, mitogen-activated protein kinase, phosphoinositol-3 kinase and calcium/calmodulin-dependent protein kinase II. The Hcy-induced IF hyperphosphorylation was also related to G_i protein and inhibition of cAMP levels. These findings demonstrate that Hcy at a concentration described to induce neurototoxicity activates the IF-associated phosphorylating system during development in hippocampal slices of rats through different cell signaling mechanisms. These results probably suggest that hippocampal rather than cortical cytoskeleton is succeptible to neurotoxical concentrations of Hcy during development and this could be involved in the neural damage characteristic of mild homocystinuric patients.     

Specific impulse patterns regulate acetylcholinesterase activity in skeletal muscles of rats and rabbits

In rats, acetylcholinesterase (AChE) activity in the fast muscles is several times higher than in the slow soleus muscle. The hypothesis that specific neural impulse patterns in fast or slow muscles are responsible for different AChE activities was tested by altering the neural activation pattern in the fast extensor digitorum longus (EDL) muscle by chronic low-frequency stimulation of its nerve. In addition, the soleus muscle was examined after hind limb immobilization, which changed its neural activation pattern from tonic to phasic. Myosin heavy-chain (MHC) isoforms were analyzed by gel electrophoresis. Activity of the molecular forms of AChE was determined by velocity sedimentation. Low-frequency stimulation of the rat EDL for 35 days shifted the profile of MHC II isoforms toward a slower MHCIIa isoform. Activity of the globular G₁ and G₄ molecular forms of AChE decreased by a factor of 4 and 10, respectively, and became comparable with those in the soleus muscle. After hind limb immobilization, the fast MHCIId isoform, which is not normally present, appeared in the soleus muscle. Activity of the globular G₁ form of AChE increased approximately three times and approached the levels in the fast EDL muscle. In the rabbit, on the contrary to the rat, activity of the globular forms of AChE in a fast muscle increased after low-frequency stimulation. The results demonstrate that specific neural activation patterns regulate AChE activity in muscles. Great differences, however, exist among different mammalian species in regard to muscle AChE regulation. J. Neurosci. Res. 47:49–57, 1997. © 1997 Wiley-Liss, Inc.     

Increased truncated TrkB receptor expression and decreased BDNF/TrkB signaling in the frontal cortex of reeler mouse model of schizophrenia

Heterozygous reeler mouse has been used as an animal model for schizophrenia based on several neuropathological and behavioral abnormalities homologous to schizophrenia. Since some of these abnormalities are primarily associated with altered BDNF signaling we investigated BDNF signaling in the frontal cortex of reeler mice in order to shed some light on the neuropathology and treatment of schizophrenia. BDNF, TrkB receptor isoforms (full-length and truncated), reelin, GAD67, GAD65, p75NTR, and NRH-2 levels were measured in the frontal cortex samples from reeler (B6C3Fe a/a-Reln^rl/+) and wild-type (WT) mice. BDNF protein levels were significantly higher in reeler compared to WT. The protein levels of full-length TrkB were not altered in reeler mice, but both mRNA and protein levels of truncated TrkB were significantly higher. Protein analysis showed that TrkB activity, as indicated by the levels of tyrosine-phosphorylated TrkB, was lower in reeler mice. We did not find any significant change in the levels of p75NTR and NRH-2, regulatory proteins of TrkB signaling, in the reeler mice. Furthermore, we found significant reduction in reelin and GAD67 expressions, but not GAD65 expression in reeler compared to WT mice. In summary, molecular processes associated with defective BDNF signaling in reeler mice provide new therapeutic targets for neuroprotective pharmacotherapy for schizophrenia.     

Depression of involuntary activity in muscles paralyzed by spinal cord injury

Involuntary muscle contractions are common after spinal cord injury (SCI). Increased sensitivity to Ia muscle afferent input may contribute to the development of these spasms. Since tendon vibration results in a period of postactivation depression of the Ia synapse, we sought to determine whether Achilles tendon vibration (80 HZ for 2 s) altered involuntary contractions evoked by superficial peroneal nerve (SPN) stimulation (5 pulses at 300 HZ) in paralyzed leg muscles of subjects with chronic (>1 year) SCI. Responses to SPN stimulation that were conditioned by vibration were reduced in 66% of trials (by 33+/-12% in tibialis anterior and 40+/-16% in soleus). These reductions in electromyographic activity are unlikely to be mediated by changes at the Ia synapse or motoneuron because vibration did not alter the magnitude of the soleus H reflex. The electromyographic reductions may involve long-lasting neuromodulatory effects on spinal inhibitory interneurons or synapses involved in the flexor reflex pathway. Vibration-evoked depression of electromyographic activity may be clinically useful in controlling involuntary muscle contractions after SCI.     

Concurrent excitation of the opposite motor cortex during transcranial magnetic stimulation to activate the abdominal muscles

The study investigated the potential for stimulation of both motor cortices during transcranial magnetic stimulation (TMS) to evoke abdominal muscle responses. Electromyographic activity (EMG) of transversus abdominis (TrA) was recorded bilaterally in eleven healthy volunteers using fine-wire electrodes. TMS at 120% motor threshold (MT) was delivered at rest and during 10% activation at 1 cm intervals from the midline to 5 cm lateral, along a line 2 cm anterior to the vertex. The optimal site to evoke responses in TrA is located 2 cm lateral to the vertex. When bilateral abdominal responses were evoked at or lateral to this site, onset of ipsilateral motor evoked potentials (MEPs) were 3–4 ms longer than contralateral MEPs. The difference between latencies is consistent with activation of faster crossed-, and slower uncrossed-corticospinal pathways from one hemisphere. However, latencies of MEPs were similar between sides when stimulation was applied more medially and were consistent with concurrent activation of crossed corticospinal tracts on both sides. The findings suggest that stimulation of both motor cortices is possible when TMS is delivered less than 2 cm from midline. Concurrent stimulation of both motor cortices can be minimised if TMS is delivered at least 2 cm lateral to midline.     

Elicitability of muscle cramps in different leg and foot muscles

To explore the efficacy of muscle motor point stimulation in eliciting muscle cramps, 11 subjects underwent eight sessions of electrical stimulation of the following muscles bilaterally: abductor hallucis flexor hallucis brevis, and both heads of the gastrocnemius muscles. Bursts of 150 square wave stimuli (duration: 152 μs; current intensity: 30% supramaximal) were applied. The stimulation frequency was increased from 4 pulses per second (pps) at increments of 2 pps until a cramp was induced. The number of cramps that could be elicited was smaller in flexor hallucis brevis than in abductor hallucis (16 vs. 22 out of 22 trials each; P < 0.05) and in the lateral gastrocnemius than in the medial gastrocnemius (5 vs. 20 out of 22 trials each; P < 0.0001). We show that leg and foot muscles have different cramp susceptibility, and the intermuscle variability in the elicitability profile for electrically induced cramps supports the use of the proposed method for cramp research. Muscle Nerve, 2009     

External recording of twitch time course in cat ankle muscles

In chronic experiments concerning the activity-dependent plasticity of muscle properties, a simple and noninvasive method was used for monitoring changes of twitch speed in conscious adult cats. The animals had been provided with implanted electrodes for nerve stimulation, and a hand-held force transducer was pressed against the fully extended ankle joint while single test pulses were delivered to the common peroneal nerve. In the present report, this technique for the recording of ankle twitches is subjected to critical analysis and evaluation. The measurements were highly reproducible with respect to contraction time (time-to-peak) but less so for half-relaxation time and twitch amplitude; other methods should be used for the long-term monitoring of contractile force. The total force (torque) of the ankle twitch was mainly produced by tibialis anterior (about 45%), peroneus longus (PerL; 27%) and extensor digitorum longus (23%). The ankle twitch produced by PerL alone had about the same contraction time as that of all the muscles together. Among muscles that had become changed as a result of long-term electrical stimulation there was, in general, a good correspondence between the contraction times from simple external recordings of ankle twitches and those separately measured for PerL under general anesthesia (force transducer then directly connected to PerL tendon).     

Appropriate stimulation in visual evoked potential to evaluate visual perception state of athletes★

BACKGROUND: Several studies have demonstrated that visual evoked potentials can be influenced by sport events. To the best of our knowledge, there are no specific parameters for the most appropriate stimulation for evaluating the functional state of athletes. OBJECTIVE: To investigate the best stimulation in visual evoked potential to apply to functional evaluation of athletes. DESIGN, TIME AND SETTING: Ninety-five, healthy students from the Shandong Normal University took part in an observational, contrast study. PARTICIPANTS: All active participants were male. Sixty-five students majored in physical education, and had participated in exercise for the duration of (4.26 ± 3.08) years. An additional 30 students majored in other subjects. METHODS: The neural electricity tester, NDI-200, was adapted to examine and record visual evoked potential with varying probes using bipolar electrodes attached to the head of all the participants in a dark room. The visual evoked potential values were analyzed transversally. A chessboard pattern reversal method was applied with the following parameters: 2 Hz stimulation frequency, brightness of 90 cdp, 80% contrast, 1–100 Hz bandpass filters, and 10 μV sensitivity; 100 responses were averaged. MAIN OUTCOME MEASURES: latency, peak latencies, and inter-peak latencies were measured in N75, P100, N145 with varying probe stimulations. RESULTS: (1) Comparisons between the little check, middle check, and big check stimulation, demonstrated that the common tendencies in visual evoked potential indexes of the two groups of N75 latency were successively shorter and N145 were longer. P100-N145 peak latency was decreased and each inter-peak latency was longer. (2) Changes of N75, P100, and N145 with different check stimulations in the physical education student group: after compared with the middle check stimulation, N75 latency was significantly longer (P < 0.01), and N75-P100 inter-peak latency (P < 0.05) and N75-N145 inter-peak latency were both shorter (P < 0.05). N75-P100 inter-peak latency was shorter (P < 0.01) in the little check stimulation. When compared with the big check stimulation, N75 latency was significantly longer (P < 0.01) and N145 was shorter (P < 0.01). Compared with the big check stimulation, N145 latency was significantly shorter (P < 0.05). (3) Changes of N75, P100, and N145 with different check stimulations in the normal students: when compared with the big check stimulation, N75 latency was significantly longer (P < 0.05) and N145 latency was shorter (P < 0.05). Each inter-peak latency was shorter (P < 0.05) in the little check stimulation. When comparing the middle check stimulation, N75-N145 inter-peak latency was shorter (P < 0.05). CONCLUSION: Large visual evoked potential differences were observed between students majoring in physical education and other subjects when medium probe stimulation was applied. These results suggest that the use of medium probe stimulation (25 mm×25 mm) should be adopted when evaluating the functional state of athletes. Key Words: visual evoked potential; functional evaluation; probe stimulation     

Anodal and cathodal transcranial direct current stimulation can decrease force output of knee extensors during an intermittent MVC fatiguing task in young healthy male participants

Transcranial direct current stimulation (tDCS) has the capacity to enhance force output during a short‐lasting maximal voluntary contraction (MVC) as well as during a long‐lasting submaximal voluntary contraction until task failure. However, its effect on an intermittent maximal effort is not known. We hypothesized that anodal tDCS applied during or before a maximal fatigue task increases the amplitude of maximal voluntary contraction (aMVC) and voluntary activation (VA) in young healthy male participants. We measured VA, potentiated twitch at rest (Ptw), root mean square electromyogram (EMG), and aMVC during a fatiguing task that consisted of 35 × 5 s MVC of knee extensors and was performed during tDCS or 10 min after the end of tDCS (sham, anodal, or cathodal treatments). No effect of tDCS was detected on the first MVC but, when compared to sham tDCS, both anodal tDCS and cathodal tDCS reduced aMVC when tDCS was applied during the task (p < .001) and only anodal tDCS reduced aMVC when applied 10 min before the task (p = .03). The reductions in aMVC were accompanied by reductions in EMG of M. vastus lateralis for both tDCS treatments as well as in Ptw only during anodal tDCS and in VA only during cathodal tDCS. Both cathodal tDCS and anodal tDCS impaired force production during an intermittent fatiguing MVC task. The detrimental effects were stronger when tDCS was applied during the task. Here, cathodal and anodal tDCS specifically affected Ptw and VA indicating different underlying mechanisms.