Efficacy of neuromuscular electrical stimulation in improving ankle kinetics during walking in children with cerebral palsy

Neuromuscular electrical stimulation (NMES) applied to the triceps surae muscle is claimed to be effective in improving gait in children with cerebral palsy. The main aim of this study was to determine the effect of NMES on the triceps surae muscle in improving the gait and function of children with cerebral palsy. Twelve children with spastic diplegia or hemiplegia were recruited and randomly assigned to the two experimental groups. The period of the study was 8 weeks (2-4-2 week design). The initial 2 weeks was the control period, in which usual treatment was given to both groups of patients with a pre- and post-treatment assessment. The middle 4 weeks was the experimental period, in which the Treadmill+NMES group received NMES plus treadmill walking training and the Treadmill group underwent treadmill walking training only. Assessment was performed at 2-week intervals. The final 2 weeks was the carryover period, in which treatment to be tested was stopped and reassessment performed again at the end of week 8. An additional treatment and post-treatment assessment were given at weeks 2, 4 and 6 to test for the immediate effect of treatment. Altogether, eight repeated measures with three-dimensional gait analysis and five clinical measurements using the gross motor function measure (GMFM) were performed. Kinetic changes in ankle moment quotient (AMQ) and ankle power quotient (APQ) were not significant either immediately or cumulatively in both groups. Improvement in trend was observed in both groups immediately but not cumulatively. Using the GMFM, functional changes were detected in standing (GMST, p < 0.001) and in walking (GMWK, p = 0.003) using a 'time' comparison. Significant interaction was also detected in GMWK using 'treatment by time' (p = 0.035). The difference between the two groups was not significant on 'treatment' comparison of both GMST and GMWK. Both groups showed improvement in GMST and GMWK cumulatively but there was no difference between the two groups. The effects in both groups could be carried over to 2 weeks after interventions stopped. Both the Treadmill+NMES and Treadmill groups showed improvement in functional outcomes. The trend in the changes of the GMFM score suggested that improvements were greater in the Treadmill+NMES group. There was also a trend showing some immediate improvement in AMQ and APQ.

Electrical Stimulation of Myoblast Proliferation and Differentiation on Aligned Nanostructured Conductive Polymer Platforms

In this study, nanostructured conductive platforms synthesized from aligned multiwalled carbon nanotubes and polypyrrole are investigated as myo-regenerative scaffolds. Myotube formation follows a linear path on the platforms coinciding with extent of nanotopography. In addition, electrical stimulation enhances myo-nuclear number and differentiation. These studies demonstrate that conductive polymer platforms can be used to influence muscle cell behaviour through nanostructure and electrical stimulation.

Effects of increasing neuromuscular electrical stimulation current intensity on cortical sensorimotor network activation: a time domain fNIRS study

Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

Aligned nanofibers from polypyrrole/graphene as electrodes for regeneration of optic nerve via electrical stimulation

The damage of optic nerve will cause permanent visual field loss and irreversible ocular diseases, such as glaucoma. The damage of optic nerve is mainly derived from the atrophy, apoptosis or death of retinal ganglion cells (RGCs). Though some progress has been achieved on electronic retinal implants that can electrically stimulate undamaged parts of RGCs or retina to transfer signals, stimulated self-repair/regeneration of RGCs has not been realized yet. The key challenge for development of electrically stimulated regeneration of RGCs is the selection of stimulation electrodes with a sufficient safe charge injection limit (Q(inj), i.e., electrochemical capacitance). Most traditional electrodes tend to have low Q(inj) values. Herein, we synthesized polypyrrole functionalized graphene (PPy-G) via a facile but efficient polymerization-enhanced ball milling method for the first time. This technique could not only efficiently introduce electron-acceptor nitrogen to enhance capacitance, but also remain a conductive platform-the π-π conjugated carbon plane for charge transportation. PPy-G based aligned nanofibers were subsequently fabricated for guided growth and electrical stimulation (ES) of RGCs. Significantly enhanced viability, neurite outgrowth and antiaging ability of RGCs were observed after ES, suggesting possibilities for regeneration of optic nerve via ES on the suitable nanoelectrodes.

What has transcranial magnetic stimulation taught us about neural adaptations to strength training? A brief review

The evidence for neural mechanisms underpinning rapid strength increases has been investigated and discussed for over 30 years using indirect methods, such as surface electromyography, with inferences made toward the nervous system. Alternatively, electrical stimulation techniques such as the Hoffman reflex, volitional wave, and maximal wave have provided evidence of central nervous system changes at the spinal level. For 25 years, the technique of transcranial magnetic stimulation (TMS) has allowed for noninvasive supraspinal measurement of the human nervous system in a number of areas such as fatigue, skill acquisition, clinical neurophysiology, and neurology. However, it has only been within the last decade that this technique has been used to assess neural changes after strength training. The aim of this brief review is to provide an overview of TMS, discuss specific strength training studies that have investigated changes, after short-term strength training in healthy populations in upper and lower limbs, and conclude with further research suggestions and the application of this knowledge for the strength and conditioning coach.

Closed loop deep brain stimulation: an evolving technology

Deep brain stimulation is an effective and safe medical treatment for a variety of neurological and psychiatric disorders including Parkinson's disease, essential tremor, dystonia, and treatment resistant obsessive compulsive disorder. A closed loop deep brain stimulation (CLDBS) system automatically adjusts stimulation parameters by the brain response in real time. The CLDBS continues to evolve due to the advancement in the brain stimulation technologies. This paper provides a study on the existing systems developed for CLDBS. It highlights the issues associated with CLDBS systems including feedback signal recording and processing, stimulation parameters setting, control algorithm, wireless telemetry, size, and power consumption. The benefits and limitations of the existing CLDBS systems are also presented. Whilst robust clinical proof of the benefits of the technology remains to be achieved, it has the potential to offer several advantages over open loop DBS. The CLDBS can improve efficiency and efficacy of therapy, eliminate lengthy start-up period for programming and adjustment, provide a personalized treatment, and make parameters setting automatic and adaptive.

Antioxidant treatment with N-acetylcysteine regulates mammalian skeletal muscle Na+-K+-ATPase ∝ gene expression during repeated contractions

Exercise increases Na+–K+ pump isoform gene expression and elevates muscle reactive oxygen species (ROS). We investigated whether enhanced ROS scavenging induced with the antioxidant N-acetylcysteine (NAC) blunted the increase in Na+–K+ pump mRNA during repeated contractions in human and rat muscle. In experiment 1, well-trained subjects received saline or NAC intravenously prior to and during 45 min cycling. Vastus lateralis muscle biopsies were taken pre-infusion and following exercise. In experiment 2, isolated rat extensor digitorum longus muscles were pre-incubated without or with 10 mm NAC and then rested or stimulated electrically at 60 Hz for 90 s. After 3 h recovery, muscles were frozen. In both experiments, the muscles were analysed for Na+–K+ pump α1, α2, α3, β1, β2 and β3 mRNA. In experiment 1, exercise increased α2 mRNA by 1.0-fold (P = 0.03), but α2 mRNA was reduced by 0.40-fold with NAC (P = 0.03). Exercise increased α3, β1 and β2 mRNA by 2.0- to 3.4-fold (P < 0.05), but these were not affected by NAC (P > 0.32). Neither exercise nor NAC altered α1 or β3 mRNA (P > 0.31). In experiment 2, electrical stimulation increased α1, α2 and α3 mRNA by 2.3- to 17.4-fold (P < 0.05), but these changes were abolished by NAC (P > 0.07). Electrical stimulation almost completely reduced β1 mRNA but only in the presence of NAC (P < 0.01). Neither electrical stimulation nor NAC altered β2 or β3 mRNA (P > 0.09). In conclusion, NAC attenuated the increase in Na+–K+ pump α2 mRNA with exercise in human muscle and all α isoforms with electrical stimulation in rat muscle. This indicates a regulatory role for ROS in Na+–K+ pump α isoform mRNA in mammalian muscle during repeated contractions.

Comonitoring of adenosine and dopamine using the wireless instantaneous neurotransmitter concentration system : proof of principle : laboratory investigation

Object

The authors of previous studies have demonstrated that local adenosine efflux may contribute to the therapeutic mechanism of action of thalamic deep brain stimulation (DBS) for essential tremor. Real-time monitoring of the neurochemical output of DBS-targeted regions may thus advance functional neurosurgical procedures by identifying candidate neurotransmitters and neuromodulators involved in the physiological effects of DBS. This would in turn permit the development of a method of chemically guided placement of DBS electrodes in vivo. Designed in compliance with FDA-recognized standards for medical electrical device safety, the authors report on the utility of the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for real-time comonitoring of electrical stimulation–evoked adenosine and dopamine efflux in vivo, utilizing fast-scan cyclic voltammetry (FSCV) at a polyacrylonitrile-based (T-650) carbon fiber microelectrode (CFM).
Methods

The WINCS was used for FSCV, which consisted of a triangle wave scanned between −0.4 and +1.5 V at a rate of 400 V/second and applied at 10 Hz. All voltages applied to the CFM were with respect to an Ag/AgCl reference electrode. The CFM was constructed by aspirating a single T-650 carbon fiber (r = 2.5 μm) into a glass capillary and pulling to a microscopic tip using a pipette puller. The exposed carbon fiber (the sensing region) extended beyond the glass insulation by ~ 50 μm. Proof of principle tests included in vitro measurements of adenosine and dopamine, as well as in vivo measurements in urethane-anesthetized rats by monitoring adenosine and dopamine efflux in the dorsomedial caudate putamen evoked by high-frequency electrical stimulation of the ventral tegmental area and substantia nigra.
Results

The WINCS provided reliable, high-fidelity measurements of adenosine efflux. Peak oxidative currents appeared at +1.5 V and at +1.0 V for adenosine, separate from the peak oxidative current at +0.6 V for dopamine. The WINCS detected subsecond adenosine and dopamine efflux in the caudate putamen at an implanted CFM during high-frequency stimulation of the ventral tegmental area and substantia nigra. Both in vitro and in vivo testing demonstrated that WINCS can detect adenosine in the presence of other easily oxidizable neurochemicals such as dopamine comparable to the detection abilities of a conventional hardwired electrochemical system for FSCV.
Conclusions

Altogether, these results demonstrate that WINCS is well suited for wireless monitoring of high-frequency stimulation-evoked changes in brain extracellular concentrations of adenosine. Clinical applications of selective adenosine measurements may prove important to the future development of DBS technology.

Oxygen consumption and blood flow distribution in perfused skeletal muscle of chinook salmon

An isolated, perfused salmon tail preparation showed oxyconformance at low oxygen delivery rates. Addition of pig red blood cells to the perfusing solution at a haematocrit of 5 or 10% allowed the tail tissues to oxyregulate. Below ca. 60 ml O₂ kg⁻¹ h⁻¹ of oxygen delivery (DO₂), VO₂ was delivery dependent. Above this value additional oxygen delivery did not increase VO₂ of resting muscle above ca. 35 ml O₂ kg⁻¹ h⁻¹. Following electrical stimulation, VO₂ increased to ca. 65 ml O₂ kg⁻¹ h⁻¹, with a critical DO₂ of ca. 150 ml O₂ kg⁻¹ h⁻¹. Dorsal aortic pressure fell to 69% of the pre-stimulation value after 5 min of stimulation and to 54% after 10 min. Microspheres were used to determine blood flow distribution (BFD) to red (RM) and white muscle (WM) within the perfused myotome. Mass specific BFD ratio at rest was found to be 4.03 ± 0.49 (RM:WM). After 5 min of electrical stimulation the ratio did not change. Perfusion with saline containing the tetrazolium salt 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) revealed significantly more mitochondrial activity in RM. Formazan production from MTT was directly proportional to time of perfusion in both red and WM. The mitochondrial activity ratio (RM:WM) did not change over 90 min of perfusion.

Insulin entry into muscle involves a saturable process in the vascular endothelium

Aims/hypothesis : Insulin's rate of entry into skeletal muscle appears to be the rate-limiting step for muscle insulin action and is slowed by insulin resistance. Despite its obvious importance, uncertainty remains as to whether the transport of insulin from plasma to muscle interstitium is a passive diffusional process or a saturable transport process regulated by the insulin receptor. Methods : To address this, here we directly measured the rate of 125I-labelled insulin uptake by rat hindlimb muscle and examined how that is affected by adding unlabelled insulin at high concentrations. We used mono-iodinated [125I]TyrA14-labelled insulin and short (5 min) exposure times, combined with trichloroacetic acid precipitation, to trace intact bioactive insulin. Results : Compared with saline, high concentrations of unlabelled insulin delivered either continuously (insulin clamp) or as a single bolus, significantly raised plasma 125I-labelled insulin, slowed the movement of 125I-labelled insulin from plasma into liver, spleen and heart (p < 0.05, for each) but increased kidney 125I-labelled insulin uptake. High concentrations of unlabelled insulin delivered either continuously (insulin clamp), or as a single bolus, significantly decreased skeletal muscle 125I-labelled insulin clearance (p < 0.01 for each). Increasing muscle perfusion by electrical stimulation did not prevent the inhibitory effect of unlabelled insulin on muscle 125I-labelled insulin clearance. Conclusions/interpretation : These results indicate that insulin's trans-endothelial movement within muscle is a saturable process, which is likely to involve the insulin receptor. Current findings, together with other recent reports, suggest that trans-endothelial insulin transport may be an important site at which muscle insulin action is modulated in clinical and pathological settings.

Wet-Spun Biodegradable Fibers on Conducting Platforms: Novel Architectures for Muscle Regeneration

Novel biosynthetic platforms supporting ex vivo growth of partially differentiated muscle cells in an aligned linear orientation that is consistent with the structural requirements of muscle tissue are described. These platforms consist of biodegradable polymer fibers spatially aligned on a conducting polymer substrate. Long multinucleated myotubes are formed from differentiation of adherent myoblasts, which align longitudinally to the fiber axis to form linear cell-seeded biosynthetic fiber constructs. The biodegradable polymer fibers bearing undifferentiated myoblasts can be detached from the substrate following culture. The ability to remove the muscle cell-seeded polymer fibers when required provides the means to use the biodegradable fibers as linear muscle-seeded scaffold components suitable for in vivo implantation into muscle. These fibers are shown to promote differentiation of muscle cells in a highly organized linear unbranched format in vitro and thereby potentially facilitate more stable integration into recipient tissue, providing structural support and mechanical protection for the donor cells. In addition, the conducting substrate on which the fibers are placed provides the potential to develop electrical stimulation paradigms for optimizing the ex vivo growth and synchronization of muscle cells on the biodegradable fibers prior to implantation into diseased or damaged muscle tissue.

Altered responsiveness of the kidney to activation of the renal nerves in fat-fed rabbits

We tested whether mild adiposity alters responsiveness of the kidney to activation of the renal sympathetic nerves. After rabbits were fed a high-fat or control diet for 9 wk, responses to reflex activation of renal sympathetic nerve activity (RSNA) with hypoxia and electrical stimulation of the renal nerves (RNS) were examined under pentobarbital anesthesia. Fat pad mass and body weight were, respectively, 74% and 6% greater in fat-fed rabbits than controls. RNS produced frequency-dependent reductions in renal blood flow, cortical and medullary perfusion, glomerular filtration rate, urine flow, and sodium excretion and increased renal plasma renin activity (PRA) overflow. Responses of sodium excretion and medullary perfusion were significantly enhanced by fat feeding. For example, 1 Hz RNS reduced sodium excretion by 79 ± 4% in fat-fed rabbits and 46 ± 13% in controls. RNS (2 Hz) reduced medullary perfusion by 38 ± 11% in fat-fed rabbits and 9 ± 4% in controls. Hypoxia doubled RSNA, increased renal PRA overflow and medullary perfusion, and reduced urine flow and sodium excretion, without significantly altering mean arterial pressure (MAP) or cortical perfusion. These effects were indistinguishable in fat-fed and control rabbits. Neither MAP nor PRA were significantly greater in conscious fat-fed than control rabbits. These observations suggest that mild excess adiposity can augment the antinatriuretic response to renal nerve activation by RNS, possibly through altered neural control of medullary perfusion. Thus, sodium retention in obesity might be driven not only by increased RSNA, but also by increased responsiveness of the kidney to RSNA.

The impact of supplementing lambs with algae on growth, meat traits and oxidative status

The current study examined the effect of supplementing lambs with algae. Forty, three month old lambs were allocated to receive a control ration based on oats and lupins (n=20) or the control ration with DHA-Gold™ algae (~2% of the ration, n=20). These lambs came from dams previously fed a ration based on either silage (high in omega-3) or oats and cottonseed meal (OCSM: high in omega-6) at joining (dam nutrition, DN). Lamb performance, carcase weight and GR fat content were not affected by treatment diet (control vs algae) or DN (silage vs OSCM). Health claimable omega-3 fatty acids (EPA+DHA) were significantly greater in the LL of lambs fed algae (125±6mg/100g meat) compared to those not fed algae (43±6mg/100g meat) and this effect was mediated by DN. Supplementing with algae high in DHA provides a means of improving an aspect of the health status of lamb meat.

High-performance multifunctional graphene-PLGA fibers: toward biomimetic and conducting 3D scaffolds

The development of electrically conducting fibers based on known cytocompatible materials is of interest to those engaged in tissue regeneration using electrical stimulation. Herein, it is demonstrated that with the aid of rheological insights, optimized formulations of graphene containing spinnable poly(lactic-co-glycolic acid) (PLGA) dopes can be made possible. This helps extend the general understanding of the mechanics involved in order to deliberately translate the intrinsic superior electrical and mechanical properties of solution-processed graphene into the design process and practical fiber architectural engineering. The as-produced fibers are found to exhibit excellent electrical conductivity and electrochemical performance, good mechanical properties, and cellular affinity. At the highest loading of graphene (24.3 wt%), the conductivity of as-prepared fibers is as high as 150 S m-1 (more than two orders of magnitude higher than the highest conductivity achieved for any type of nanocarbon-PLGA composite fibers) reported previously. Moreover, the Young's modulus and tensile strength of the base fiber are enhanced 647- and 59-folds, respectively, through addition of graphene.

A diamond-based electrode for detection of neurochemicals in the human brain

Deep brain stimulation (DBS), a surgical technique to treat certain neurologic and psychiatric conditions, relies on pre-determined stimulation parameters in an open-loop configuration. The major advancement in DBS devices is a closed-loop system that uses neurophysiologic feedback to dynamically adjust stimulation frequency and amplitude. Stimulation-driven neurochemical release can be measured by fast-scan cyclic voltammetry (FSCV), but existing FSCV electrodes rely on carbon fiber, which degrades quickly during use and is therefore unsuitable for chronic neurochemical recording. To address this issue, we developed durable, synthetic boron-doped diamond-based electrodes capable of measuring neurochemical release in humans. Compared to carbon fiber electrodes, they were more than two orders-of-magnitude more physically-robust and demonstrated longevity in vitro without deterioration. Applied for the first time in humans, diamond electrode recordings from thalamic targets in patients (n = 4) undergoing DBS for tremor produced signals consistent with adenosine release at a sensitivity comparable to carbon fiber electrodes. (Clinical trials # NCT01705301).