Mathematical models for fatigue minimization during functional electrical stimulation

We previously reported the development of a force- and fatigue-model system that predicted accurately forces during repetitive fatiguing activation of human skeletal muscles using brief duration (six-pulse) stimulation trains. The model system was tested in the present study using force responses produced by longer duration stimulation trains, containing up to 50 pulses. Our results showed that our model successfully predicted the peak forces produced when the muscle was repetitively activated with stimulation trains of frequencies ranging from 20 to 40 Hz, train durations ranging from 0.5 to 1 s, and varied pulse patterns. The predicted peak forces throughout each protocol matched the experimental peak forces with r² values above 0.9 and predicted successfully the forces at the end of each protocol with <15% error for all protocols tested. The success of our model system further supports its potential use for the design of optimal stimulation patterns for individual users during functional electrical stimulation.     

跨颅电刺激对大鼠抑郁症的治疗作用

目的：探讨跨颅电刺激对大鼠抑郁症的治疗作用。方法：跨颅电刺激抑郁症大鼠左侧前额叶皮层,敞箱实验测定大鼠行为学变化,荧光法测定单胺类递质含量的变化。结果：跨颅直流电和低频脉冲电刺激后,大鼠敞箱实验中垂直和水平运动得分均较模型组显著升高（P〈0.05）;且大鼠左侧前额叶皮层和海马5-HT、NE含量较模型组显著升高（P〈0.05）,而前额叶皮层DA含量无显著变化（P〉0.05）。结论：直流电和低频脉冲电跨颅刺激左侧前额叶皮层,对抑郁症均有显著治疗作用。     

Pulsed subcutaneous electrical stimulation in spinal cord injury: preliminary results

The treatment of long-term, stable para- and quadriplegics with pulsed electrical stimulation for pain control resulted in, anecdotally, a significant number of these individuals showing increased motor function as well as sensory awareness. This small pilot study was conducted in order to assess the hypothesis that pulsed electrical fields can effect diseased neurological function. Thirteen para- and quadriplegic subjects with 18 months of stable neurological signs and symptoms were exposed daily to pulsed electrical stimulation for a 6-month period and assessed for any improvement in motor function or sensory perception. The hypothesis is that pulsed electromagnetic fields can normalize viable but dysfunctional neuronal structures. Results were encouraging.     

Time-dependent effects of neuromuscular electrical stimulation on changes in spinal excitability are dependent on stimulation frequency: A preliminary study in healthy adults

Neuromuscular electrical stimulation (NMES) can be used as treatment for spasticity. The present study examined differences in time-dependent effects of NMES depending on stimulation frequency. Forty healthy subjects were separated into four groups (no-stim, NMES of 50, 100, and 200?Hz). The un-conditioned H-reflex amplitude and the H-reflex conditioning-test paradigm were used to measure the effectiveness on monosynaptic Ia excitation of motoneurons in the soleus (SOL) muscle, disynaptic reciprocal Ia inhibition from tibialis anterior (TA) to SOL, and presynaptic inhibition of SOL Ia afferents. Each trial consisted of a 30-min period of NMES applied to the deep peroneal nerve followed by a 30-min period with no stimulation to measure prolonged effects. Measurements were performed periodically. Stimulation applied at all frequencies produced a significant reduction in monosynaptic Ia excitation of motoneurons in the SOL muscle, however, only stimulation with 50?Hz showed prolonged reduction after NMES. NMES frequency did not affect the amount of disynaptic reciprocal Ia inhibition and presynaptic inhibition of Ia afferents. The results show a frequency-dependent effect of NMES on the monosynaptic Ia excitation of motoneurons. This result has implications for selecting the optimal NMES frequency for treatment in patients with spasticity.     

Optimizing neuromuscular electrical stimulation for hand opening

Aim: To investigate the effect of introducing an interphase interval to a biphasic pulse on force production and muscle fatigue, during stimulation of the wrist and finger extensors and to determine whether the IPI effect on force is dependent on electrode position.

Methods: Electrically-induced contraction forces of the wrist and finger extensors were measured in 15 healthy subjects undergoing stimulation. These forces were assessed with interphase interval settings at 0, 100, and 200μs, with both electrodes located just distal to common extensor origin (proximal placement) or with the distal electrode placed over the extensor and abductor policies longus muscles (distal placement). The degree of discomfort related to stimulation sensation was evaluated using a numeric rating scale. Muscle fatigue was measured during proximal placement.

Results: Under both electrode locations, introduction of 100 or 200?μs interphase interval enhanced force production; yet, only the 100μs interphase interval increased force without increasing discomfort. Additionally, stimulation sensation was more comfortable with proximal placement. Introducing interphase interval significantly increased the muscle force output during a repetitive stimulation fatigue protocol.

Conclusions: When using neuromuscular electrical stimulation to activate the wrist and finger extensors, clinicians should consider locating both stimulating electrodes proximally over the extensor surface of the forearm and apply a 100?µs interphase interval to a biphasic pulse. Future research that should establish these findings in individuals with various pathologies, especially in patients with residual hand spasticity.     

不同频率电刺激膈神经导致膈肌肌浆网Ca~(2 )-ATPase和Ca~(2 )释放-摄取动力学改变

研究不同频率慢性电刺激（ＣＥＳ）后兔膈肌肌浆网（ＳＲ）Ｃａ２＋－ＡＴＰａｓｅ活性以及ＳＲ Ｃａ２＋摄取－释放动力学对不同频率ＣＥＳ的适应性变化。建立不同频率ＣＥＳ组;用定磷法测定ＳＲ Ｃａ２＋－ＡＴＰａｓｅ活性;用Ｆｕｒａ－２荧光法测定ＳＲ　Ｃａ２＋摄取－释放动力学。与对照组比较,慢性低频电刺激１０ Ｈｚ和２０Ｈｚ组的ＳＲ　Ｃａ２＋－ＡＴＰａｓｅ活性明显降低（Ｐ＜０．０１）,Ｃａ２＋释放－摄取动力学也显著降低（Ｐ＜０．０１）;慢性高频电刺激５０ Ｈｚ和１００Ｈｚ组的ＳＲ Ｃａ２＋－ＡＴＰａｓｅ活性则显著升高（Ｐ＜０．０１）,Ｃａ２＋释放－摄取动力学亦明显升高（Ｐ＜０．０１）。实验提示,ＣＥＳ后不同频率ＣＥＳ导致膈肌ＳＲＣａ２＋－ＡＴＰａｓｅ、Ｃａ２＋摄取－释放动力学产生不同的适应性变化;对不同功能状态的膈肌应用不同频谱的慢性电刺激可能具有重要的临床意义。     

Greater osteoblast proliferation on anodized nanotubular titanium upon electrical stimulation

Currently used orthopedic implants composed of titanium have a limited functional lifetime of only 10–15 years. One of the reasons for this persistent problem is the poor prolonged ability of titanium to remain bonded to juxtaposed bone. It has been proposed to modify titanium through anodization to create a novel nanotubular topography in order to improve cytocompatibility properties necessary for the prolonged attachment of orthopedic implants to surrounding bone. Additionally, electrical stimulation has been used in orthopedics to heal bone non-unions and fractures in anatomically difficult to operate sites (such as the spine). In this study, these two approaches were combined as the efficacy of electrical stimulation to promote osteoblast (bone forming cell) density on anodized titanium was investigated. To do this, osteoblast proliferation experiments lasting up to 5 days were conducted as cells were stimulated with constant bipolar pulses at a frequency of 20 Hz and a pulse duration of 0.4 ms each day for 1 hour. The stimulation voltages were 1 V, 5 V, 10 V, and 15 V. Results showed for the first time that under electrical stimulation, osteoblast proliferation on anodized titanium was enhanced at lower voltages compared to what was observed on conventional (nonanodized) titanium. In addition, compared to nonstimulated conventional titanium, osteoblast proliferation was enhanced 72% after 5 days of culture on anodized nanotubular titanium at 15 V of electrical stimulation. Thus, results of this study suggest that coupling the positive influences of electrical stimulation and nanotubular features on anodized titanium may improve osteoblast responses necessary for enhanced orthopedic implant efficacy.     

Release of vasoactive intestinal polypeptide by electrical field stimulation of rabbit ileum

The release of vasoactive intestinal polypeptide (VIP) induced by electrical field stimulation (EFS) of rabbit ileum was studied in vitro. EFS parallel to the muscularis propria caused a significant increase in VIP concentration in the buffer bathing the serosal surface of full-thickness ileum. This effect was blocked by 10^?7 M tetrodotoxin. When circular and longitudinal muscle was removed, the amount of measurable VIP in the tissue decreased to about one-half that of full-thickness ileum, and EFS no longer caused release of VIP into the serosal or mucosal buffers. Our data indicate that EFS of rabbit ileum causes release of VIP, presumably from VIP-containing nerves present in the tissue. These results support the idea that VIP may be a physiological neuroregulator of intestinal function.     

电刺激大鼠脚内核对脚桥核神经元放电的影响

目的:观察电刺激大鼠脚内核(EP)对大鼠脚桥核(PPN)神经元自发放电的影响,进一步探讨脑内电刺激治疗帕金森病(PD)的机制。方法:应用细胞外记录的方法观察不同频率电刺激(强度0.6 mA,波宽0.06 ms,时程5 s,频率5 Hz、10Hz、20Hz、50Hz、100Hz、150Hz、200Hz)大鼠EP对PPN神经元放电的影响。结果:实验记录了大鼠33个神经元的自发放电,其放电频率在3.6~52.2Hz之间,平均为(15.95±8.56)Hz;当刺激频率为100Hz时,抑制效应最显著(P<0.05)。结论:高频电刺激大鼠EP对PPN神经元自发放电的影响主要为抑制作用,提示高频刺激EP可通过抑制PPN神经元活动参与PD的治疗。     

Activation of striatal tyrosine hydroxylase by in vivo electrical stimulation: Comparison with cyclic AMP-mediated activation

These studies were carried out to characterize the activation of rat striatal tyroxine hydroxylase produced by depolarization of the medial forebrain bundle and to evaluate the possible role of cyclic AMP as a mediator of this activation. The enzymatic properties of tyrosine hydroxylase following in vivo depolarization were compared to those produced by treatment of striatal synaptosomes with dibutyryl cyclic AMP (dbcAMP). Similar effects were observed with regard to enzyme distribution, altered sensitivity to dopamine-induced inhibition, and activity as a function of tyrosine concentration. However, differences between the two treatments were also apparent. First, treatment with dbcAMP shifted the pH optimum from 6.2 to 7.0. In contrast, electrical stimulation decreased the rate of decline in activity as the pH was increased above the optimum, but did not shift the pH optimum. Second, plots of tyrosine hydroxylase activity versus cofactor concentration revealed two enzyme forms for both control and electrically stimulated preparations. However, dbcAMP treatment converted the enzyme to a single high affinity form. These results can be explained by one of the following: (1) cyclic AMP is the sole mediator of enzyme activation, but does not produce a maximally activated enzyme following in vivo depolarization (2) cyclic AMP is only one of several mediators involved or (3) cyclic AMP is not involved in depolarization-induced activation, with activation occurring via the mediation of other intracellular messengers, such as calcium.     

Simple micropatterning method for enhancing fusion efficiency and responsiveness to electrical stimulation of C2C12 myotubes

Cultured myotubes induced in vitro from myoblast cell lines have been widely used to investigate muscle functional properties and disease‐related biological phenotypes. Until now, several cell patterning techniques have been applied to regulate in vitro myotube structures. However, these previous studies required specific geometry patterns or soft materials for inducing efficient myotube formation. Thus, more simple and easy handling method will be promising. In this study, we aimed to provide a method to form C2C12 myotubes with regulated sizes and orientations in simple line patterns. We used a poly(dimethylsiloxane) (PDMS) stamp and a 2‐methacryloyloxyethyl phosphorylcholine (MPC) polymer solution to fabricate line patterns for myotube formation onto a culture dish. We confirmed that C2C12 myotubes of well‐defined size and orientation were reproducibly formed. In particular, myotubes formed in the micropatterned lines showed the increased fusion efficiency. Then, functional dynamics in the micropatterned myotubes were detected and analyzed using a calcium imaging method. We confirmed micropatterning in line patterns enhanced the responsiveness of myotubes to external electrical stimulations. These results indicate that micropatterning myoblasts with the MPC polymer is a simple and effective method to form functional myotube networks. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:220–225, 2015     

Influence of transcutaneous electrical nerve stimulation conditions on disynaptic reciprocal Ia inhibition and presynaptic inhibition in healthy adults

This study investigated the influence of stimulus conditions of transcutaneous electrical nerve stimulation (TENS) on disynaptic reciprocal Ia inhibition (RI) and presynaptic inhibition (D1 inhibition) in healthy adults. Eight healthy participants received TENS (stimulus frequencies of 50, 100, and 200?Hz) over the deep peroneal nerve and tibialis anterior (TA) muscle in the resting condition for 30?min. At pre- and post-intervention, the RI from the TA to the soleus (SOL) and D1 inhibition of the SOL alpha motor neuron were assessed by evoked electromyography. The results showed that RI was not changed by TENS at any stimulus frequency condition. Conversely, D1 inhibition was significantly changed by TENS regardless of the stimulus frequency. The present results and previous studies pertaining to RI suggest that the resting condition might strongly influence the lack of pre- vs. post-intervention change in the RI. Regarding the D1 inhibition, the present results suggest that the effect of TENS might be caused by post-tetanic potentiation. The knowledge gained from the present study might contribute to a better understanding of fundamental studies of TENS in healthy adults and its clinical application for stroke survivors.     

Post-lesional cerebral reorganisation: Evidence from functional neuroimaging and transcranial magnetic stimulation

Reorganisation of cerebral representations has been hypothesised to underlie the recovery from ischaemic brain infarction. The mechanisms can be investigated non-invasively in the human brain using functional neuroimaging and transcranial magnetic stimulation (TMS). Functional neuroimaging showed that reorganisation is a dynamic process beginning after stroke manifestation. In the acute stage, the mismatch between a large perfusion deficit and a smaller area with impaired water diffusion signifies the brain tissue that potentially enables recovery subsequent to early reperfusion as in thrombolysis. Single-pulse TMS showed that the integrity of the cortico-spinal tract system was critical for motor recovery within the first four weeks, irrespective of a concomitant affection of the somatosensory system. Follow-up studies over several months revealed that ischaemia results in atrophy of brain tissue adjacent to and of brain areas remote from the infarct lesion. In patients with hemiparetic stroke activation of premotor cortical areas in both cerebral hemispheres was found to underlie recovery of finger movements with the affected hand. Paired-pulse TMS showed regression of perilesional inhibition as well as intracortical disinhibition of the motor cortex contralateral to the infarction as mechanisms related to recovery. Training strategies can employ post-lesional brain plasticity resulting in enhanced perilesional activations and modulation of large-scale bihemispheric circuits.     

Modulation of the rate of force development in hip abductor muscles by neuromuscular electrical stimulation during gait

Abstract

Purpose/aim of the study: An increase of hip abductor muscle strength contributes to the increase in gait speed. It is known that the rate of force development (RFD), an indicator of muscle strength, is increased by the combined use of low-intensity neuromuscular electrical stimulation (NMES) to the glutaeus medius (GM) and low-load resistance training (RT). However, it is unclear whether low-intensity neuromuscular electrical stimulation of the glutaeus medius during walking also increases the rate of force development. The aim of this study was to clarify whether NMES to the GM during gait modulates the RFD of the hip abductor muscles in healthy adults.

Materials and methods: Twenty-two healthy adults randomly received both gait with sub-motor threshold NMES and gait with sham NMES conditions. The RFD was assessed at pre- and post-intervention. A two-way repeated measures analysis of variance was used to analyse the effects of time and intervention.

Results: Gait with sub-motor threshold NMES condition significantly increased the RFD in shorter time interval (0–50 and 0–100?ms) compared to gait with sham NMES condition.

Conclusions: These findings suggest that the adding low-intensity NMES of the GM to gait is effective in increasing the RFD of the hip abductor muscles.     

不同频率慢性电刺激膈神经对兔膈肌骨骼肌型二氢吡啶受体α1亚单位、ryanodine受体mRNA和蛋白表达的影响

测定不同频率慢性电刺激(chronic electrical stimulation,CES)膈神经5周后对兔膈肌钙释放单位中骨骼肌型二氢吡啶受体(DHPR)α1亚单位和ryanodine受体(RyRs)的mRNA和蛋白表达水平的影响,探讨CES后兔膈肌钙释放单位结构组成的变化和可能的临床应用价值.封闭群日本大耳白兔30只,随机分为正常对照组、10、20、50和100Hz,每组6只;以10和20 Hz为慢性低频电刺激组,50和100Hz为慢性高频电刺激组.CES参数为波宽0.2 ms 3～6个波/次,45次/min,电压10～20 V.刺激时间2×2 h/日,每周刺激6 d,连续刺激5周.分别采用RT-PCR和免疫组织化学法测定兔膈肌骨骼肌型DHPRα1-亚单位和RyR1、RyR2和RyR3的mRNA和蛋白表达.结果显示与对照组比较,慢性低频电刺激10和20 Hz组骨骼肌型DHPRα1、RyR的mRNA和蛋白表达明显降低(P＜0.01),有低度的RyR,mRNA的表达出现;慢性高频电刺激50和100Hz组骨骼肌型DHPRα1、RyR1的mRNA和蛋白表达明显升高(P＜0.01),未检测到RyR2mRNA的阳性表达.本实验提示慢性低频电刺激膈神经5周后,膈肌质膜上DHPR与RyRs之间的信号转导方式已从变构耦联为主转变为以Ca2+诱导Ca2+释放耦联为主.     

Efficacy of transcutaneous electrical nerve stimulation combined with therapeutic exercise on hand function in children with hemiplegic cerebral palsy

Purpose: Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological method used to reduce spasticity. It was also assumed that TENS reduces pain and therefore improves limb function. Most of the previous studies about the effect of TENS were done in the lower limb and in stroke patients. There is a lack of enough literature about the direct and indirect effects of TENS in the upper limb. Hence, our study aimed to determine whether TENS combined with therapeutic exercises helps to improves hand function by reducing spasticity in children with hemiplegic cerebral palsy (CP).

Materials and methods: Twenty-nine children with hemiplegic CP were randomly assigned to the TENS group (n?=?15) or the control group (n?=?14). The TENS group received traditional physical therapy with the adjunct application of conventional TENS for 30?minutes (pulse duration, 250 µs; pulse rate, 100?Hz) on the wrist extensors, once daily, 3?days a week, for 8?weeks, while the control group received traditional physical therapy.

Results: The results showed a significant intergroup difference in handgrip strength over the 8-week period. The time to accomplish the Jebsen Taylor Hand Function Test (JTHFT) task decreased by 48% and the ABILHAND-Kids questionnaire scores improved by 23% in the TENS group.

Conclusions: The use of TENS in combination with therapeutic exercise may improve strength and hand function.     

电刺激大鼠束旁核对底丘脑核和丘脑腹内侧核神经元的影响

本工作旨在探讨电刺激束旁核（parafascicular nucleus,PF）对帕金森病模型（Parkinson’s disease,PD）大鼠神经行为的改善作用及其机制。成年雄性Sprague—Dawley大鼠黑质致密部注射6一羟基多巴胺建立PD大鼠模型。采用行为学方法观察电刺激PF对阿朴吗啡诱发的大鼠旋转行为的作用,并应用在体细胞外记录法观察电刺激PF对大鼠底丘脑核（subthalamic nucleus,STN）及丘脑腹内侧核（ventromedial nucleus,VM）神经元放电的影响。结果发现,高频电刺激（130Hz,0．4mA,5s）PF一周,明显改善PD大鼠旋转行为。细胞外放电记录显示,高频电刺激PF使PD大鼠STN神经元自发放电减少,且该作用具有频率依赖性。另外,高频电刺激PF可使VM神经元兴奋,该作用也是频率依赖性的。我们在实验中同时观察到微电泳谷氨酸（glutamicacid,Glu）受体拮抗剂MK-801使STN神经元放电频率减少或完全抑制,微电泳t氨基丁酸（T-amino butyricacid,GABA）受体拮抗剂印防己毒素（picrotoxin,Pic）则使神经元放电频率增加。以上结果表明,GABA能和GIu能传入纤维可会聚于同-STN神经元,并对后者有紧张性作用。高频刺激PF,使该核团到STN神经元的Glu能兴奋性输出减少,导致STN的失活。这一作用通过基底神经节的间接通路,最终释放了丘脑运动核团VM的活性。高频刺激PF经PF,STN和VM的神经通路而改善PD大鼠神经行为。