Osteoporosis is mainly a geriatric disease with a high incidence, and the resulting spinal fractures and hip fractures cause great harm to patients. Anti-osteoporosis drugs are the main treatment for ...osteoporosis currently, but these drugs have potential clinical limitations and side effects, so the development of new therapies is of great significance to patients with osteoporosis. Electrical stimulation therapy mainly includes pulsed electromagnetic fields (PEMF), direct current (DC), and capacitive coupling (CC). Meanwhile, electrical stimulation therapy is clinically convenient without side effects. In recent years, many researchers have explored the use of electrical stimulation therapy for osteoporosis. Based on this, the role of electrical stimulation therapy in osteoporosis was summarized. In the future, electrical stimulation might become a new treatment for osteoporosis.
The stimulation paradigm for sacral neuromodulation has remained largely unchanged since its inception. We sought to determine, in rats, whether stimulation-induced increases in bladder capacity ...correlated with the proportion of sensory pudendal (PudS) neurons at each stimulated location (L6, S1). If supported, this finding could guide the choice of stimulation side (left/right) and level (S2, S3, S4) in humans. Unexpectedly, we observed that acute stimulation at clinically relevant (low) amplitudes 1-1.5 × motor threshold (T
), did not increase bladder capacity, regardless of stimulus location (L6 or S1). More importantly for the ability to test our hypothesis, there was little anatomic variation, and S1 infrequently contributed nerve fibers to the PudS nerve. During mapping studies we noticed that large increases in PudS nerve activation occurred at amplitudes exceeding 2T
. Thus, additional cystometric studies were conducted, this time with stimulation of the L6-S1 trunk, to examine further the relationship between stimulation amplitude and cystometric parameters. Stimulation at 1T
to 6T
evoked increases in bladder capacity and decreases in voiding efficiency that mirrored those produced by PudS nerve stimulation. Many animal studies involving electrical stimulation of nerves of the lower urinary tract use stimulation amplitudes that exceed those used clinically (∼1T
). Our results confirm that high amplitudes generate immediate changes in cystometric parameters; however, the relationship to low-amplitude chronic stimulation in humans remains unclear. Additional studies are needed to understand changes that occur with chronic stimulation, how these changes relate to therapeutic outcomes, and the contribution of specific nerve fibers to these changes.
Acute low-amplitude electrical stimulation of sacral nerve (sacral neuromodulation) did not increase bladder capacity in anesthetized CD, obese-prone, or obese-resistant rats. Increasing stimulation amplitude correlated with increases in bladder capacity and pudendal sensory nerve recruitment. It is unclear how the high-amplitude acute stimulation that is commonly used in animal experiments to generate immediate effects compares mechanistically to the chronic low-amplitude stimulation used clinically.
One of the ultimate goals of neurostimulation field is to design materials, devices and systems that can simultaneously achieve safe, effective and tether-free operation. For that, understanding the ...working mechanisms and potential applicability of neurostimulation techniques is important to develop noninvasive, enhanced, and multi-modal control of neural activity. Here, we review direct and transduction-based neurostimulation techniques by discussing their interaction mechanisms with neurons via electrical, mechanical, and thermal means. We show how each technique targets modulation of specific ion channels (e.g. voltage-gated, mechanosensitive, heat-sensitive) by exploiting fundamental wave properties (e.g. interference) or engineering nanomaterial-based systems for efficient energy transduction. Overall, our review provides a detailed mechanistic understanding of neurostimulation techniques together with their applications to
, and translational studies to guide the researchers toward developing more advanced systems in terms of noninvasiveness, spatiotemporal resolution, and clinical applicability.
The number of applications using neural prosthetic interfaces is expanding. Computer models are a valuable tool to evaluate stimulation techniques and electrode designs. Although our understanding of ...neural anatomy has improved, its impact on the effects of neural stimulation is not well understood. This study evaluated the effects of fascicle perineurial thickness, diameter, and position on axonal excitation thresholds and population recruitment using finite element models and NEURON simulations. The perineurial thickness of human fascicles was found to be 3.0% \pm 1.0% of the fascicle diameter. Increased perineurial thickness and fascicle diameter increased activation thresholds. The presence of a large neighboring fascicle caused a significant change in activation of a smaller target fascicle by as much as 80% \pm 11% of the total axon population. Smaller fascicles were recruited at lower amplitudes than neighboring larger fascicles. These effects were further illustrated in a realistic model of a human femoral nerve surrounded by a nerve cuff electrode. The data suggest that fascicular selectivity is strongly dependent upon the anatomy of the nerve being stimulated. Therefore, accurate representations of nerve anatomy are required to develop more accurate computer models to evaluate and optimize nerve electrode designs for neural prosthesis applications.
Introduction
Neuromuscular electrical stimulation (NMES) is an innovative and effective (re)training strategy to improve or restore neuromuscular function (Maffiuletti et al., 2018). Contractions ...induced by NMES differ in many aspects from voluntary contractions, as motor unit (MU) recruitment is random, synchronous and spatially fixed (mostly superficial; Maffiuletti, 2010). Consequently, several limitations, such as higher fatigability (Vanderthommen et al., 1999) and discomfort (Delitto et al., 1992) might restrain its clinical implementation. The use of specific stimulation parameters may partly overcome these limitations. Indeed, the use of wide pulses (≥ 1 ms) delivered at low stimulation intensity leads to a preferential recruitment of Ia sensory axons (Veale et al., 1973) which may promote MU central (reflexive) recruitment. Furthermore, the high stimulation frequencies (> 80 Hz) would facilitate the temporal summation of post-synaptic excitatory potentials and reflexively activate spinal motoneurons through Ia afferents (Dideriksen et al., 2015), which may increase force production. Another potential advantage of wide pulse high frequency (WPHF) NMES is that low stimulation intensities are required to limit antidromic collision, and these lower intensities are associated with less discomfort (Delitto et al., 1992). Therefore, by stimulating at intensities expected to generate ~10% of the maximal voluntary contraction (MVC) force, WPHF NMES induces, in some individuals, a progressive increase in force during the stimulation, called ‘extra force’. It can reach up to 80% of the MVC force in plantar flexors (Neyroud et al., 2018) but the response to WPHF NMES in other muscle groups is less documented. Extra force is usually accompanied by a prolongation of the surface electromyographic (EMG) activity after cessation of the stimulation, also called ‘sustained EMG activity’ which is interpreted as MU recruited through the central pathway (Neyroud et al, 2018). The main aim of the present study was to explore the effect of varying stimulation parameters on the NMES-evoked force and sustained EMG activity in the plantar flexors, knee extensors and elbow flexors. It was hypothesized that the plantar flexors would show higher centrally-mediated responses to NMES than knee extensors and elbow flexors, especially with large pulse duration.
Methods
Sixteen volunteers, 2 women and 14 men (29 ± 6 yr, 177 ± 6 cm, 74 ± 11 kg) participated to three experimental sessions - one for each muscle group - in a randomized order. The experimental protocol was similar for the three muscle groups and included twelve 10-s NMES trains separated by at least 2 min of rest and delivered at an intensity set initially to evoke 10% of the maximal voluntary contraction force. Stimulation trains were randomly delivered with a combination of frequencies (20, 50, 100 and 147 Hz) and pulse durations (0.2, 1 and 2 ms). Force was collected using specific isometric ergometers and EMG activity was recorded with bipolar electrodes on the soleus, vastus lateralis and biceps brachii muscles. Extra force was calculated as the relative force difference between the last second and the 2nd second of stimulation. Sustained EMG activity was identified as the visible activity on the EMG after the end of the stimulation and quantified over 500 ms as the root mean square (RMS) of this signal normalized by the RMS of the EMG activity measured during the MVC.
Results
Stimulation frequency. Extra force was significantly higher for the plantar flexors than for the elbow flexors at 50 Hz (69 ± 68% vs 38 ± 53%, p = 0.025), 100 Hz (84 ± 71% vs 21 ± 72%, p < 0.001) and 147 Hz (75 ± 84% vs 16 ± 82%, p < 0.001), but not at 20 Hz (p = 0.649). For all the tested frequencies, extra force was not significantly different between plantar flexors and knee extensors (p = 0.065 - 0.743). Extra force was significantly higher for the knee extensors than for the elbow flexors at 100 Hz (63 ± 106% vs 21 ± 72%, p = 0.012), but not at the other frequencies (p = 0.156 - 0.388). Sustained EMG activity was significantly higher for the plantar flexors than for the elbow flexors at all frequencies (p < 0.001) as well as compared to the knee extensors at 50 Hz, 100 Hz and 147 Hz (p = 0.010, p = 0.009, p = 0.003 respectively) but not at 20 Hz (p = 0.483). Finally, sustained EMG activity was significantly higher for the knee extensors than for the elbow flexors at for all the tested stimulation frequencies (p < 0.05).
Pulse duration. Extra force was significantly higher for the plantar flexors than for the elbow flexors with pulse durations of 1 ms (76 ± 74% vs 23 ± 48%, p < 0.001) and 2 ms (73 ± 70% vs 29 ± 88%, p < 0.001) but not with 0.2 ms (p = 0.064). Extra force was not significantly different between the plantar flexors and the knee extensors, and the knee extensors showed a higher extra force than elbow flexors with 1 ms (56 ± 99% vs 23 ± 48%, p = 0.002). Sustained EMG activity was significantly higher for the plantar flexors than the elbow flexors with all pulse durations (p < 0.001) and than the knee extensors with 1 and 2 ms (p < 0.001). Knee extensors showed a higher sustained EMG activity than elbow flexors with 0.2 ms and 2 ms (p < 0.001) but not with 1 ms.
Discussion/Conclusion
WPHF NMES is a promising tool for (re)training and the results of the present study suggest that its use to induce centrally-mediated force is more pertinent in lower limb muscles. The difference in responses between muscle groups could be explained by muscle typology and density in neuromuscular spindles. Indeed, muscles involved in precise movements and postural control have a greater number of neuromuscular spindles, which are mainly located in type 1 fibers (Botterman et al., 1978). The greater centrally-mediated responses in the plantar flexors compared with the elbow flexors can be explained by the difference in muscle typology (more type I muscle fibers in the postural lower limb muscles). It may also justify the absence of difference in extra force between plantar flexors and knee extensors as they both contribute to postural maintenance (Jusić et al., 1995). Since the effectiveness of NMES for neuromuscular adaptations depends on the amount of force generated during training (Maffiuletti et al., 2018), these results suggest that the use of WPHF NMES would be efficient on plantar flexors and knee extensors for training and rehabilitation and that wide pulses and high frequencies should be preferentially used when implementing this NMES modality in clinical settings.
References
Botterman, B. R., Binder, M. D., & Stuart, D. G. (1978). Functional anatomy of the association between motor units and muscle teceptors. American Zoologist, 18(1), 135–152. https://doi.org/10.1093/icb/18.1.135
Delitto, A., Strube, M. J., Shulman, A. D., & Minor, S. D. (1992). A study of discomfort with electrical stimulation. Physical Therapy, 72(6), 410–421. https://doi.org/10.1093/ptj/72.6.410
Dideriksen, J. L., Muceli, S., Dosen, S., Laine, C. M., & Farina, D. (2015). Physiological recruitment of motor units by high-frequency electrical stimulation of afferent pathways. Journal of Applied Physiology, 118(3), 365–376. https://doi.org/10.1152/japplphysiol.00327.2014
Jusić, A., Baraba, R., & Bogunović, A. (1995). H-reflex and F-wave potentials in leg and arm muscles. Electromyography and Clinical Neurophysiology, 35(8), 471–478.
Maffiuletti, N. A., Gondin, J., Place, N., Stevens-Lapsley, J., Vivodtzev, I., & Minetto, M. A. (2018). Clinical Use of Neuromuscular Electrical Stimulation for Neuromuscular Rehabilitation: What Are We Overlooking? Archives of Physical Medicine and Rehabilitation, 99(4), 806-812. https://doi.org/10.1016/j.apmr.2017.10.028
Maffiuletti, N. A. (2010). Physiological and methodological considerations for the use of neuromuscular electrical stimulation. European Journal of Applied Physiology, 110(2), 223–234. https://doi.org/10.1007/s00421-010-1502-y
Neyroud, D., Grosprêtre, S., Gondin, J., Kayser, B., & Place, N. (2018). Test–retest reliability of wide-pulse high-frequency neuromuscular electrical stimulation evoked force. Muscle & Nerve, 57(1), E70–E77. https://doi.org/10.1002/mus.25747
Vanderthommen, M., Gilles, R., Carlier, P., Ciancabilla, F., Zahlan, O., Sluse, F., & Crielaard, J. M. (1999). Human muscle energetics during voluntary and electrically induced isometric contractions as measured by 31P NMR spectroscopy. International Journal of Sports Medicine, 20(5), 279–283. https://doi.org/10.1055/s-2007-971131
Veale, J. L., Mark, R. F., & Rees, S. (1973). Differential sensitivity of motor and sensory fibres in human ulnar nerve. Journal of Neurology, Neurosurgery & Psychiatry, 36(1), 75–86.
JOURNAL/nrgr/04.03/01300535-202419110-00034/figure1/v/2024-03-08T184507Z/r/image-tiff Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors, leading to ...progressive photoreceptor loss. Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival. This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation (tcES) in mice affected by inherited retinal degeneration. Additionally, the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans. In this study, we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular, sine, and ramp waveforms. To investigate the functional effects of electrical stimulation on photoreceptors, we used human retinal explant cultures and rhodopsin knockout (Rho-/-) mice, demonstrating progressive photoreceptor degeneration with age. Human retinal explants isolated from the donors' eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro. Photoreceptor density was evaluated by rhodopsin immunolabeling. In vivo Rho-/- mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms. Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response (OMR), respectively. Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas. Oscilloscope recordings indicated effective delivery of rectangular, sine, and ramp waveforms to the retina by transcorneal electrical stimulation, of which the ramp waveform required the lowest voltage. Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes. The temperature recordings during and after electrical stimulation indicated no significant temperature change in vivo and only a subtle temperature increase in vitro (~0.5-1.5°C). Electrical stimulation increased photoreceptor survival in human retinal explant cultures, particularly at the ramp waveform. Transcorneal electrical stimulation (rectangular + ramp) waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results. Histology and immunolabeling demonstrated increased photoreceptor survival, improved outer nuclear layer thickness, and increased bipolar cell sprouting in Rho-/- mice. These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina, improves photoreceptor survival in both human and mouse retinas, and increases visual function in Rho-/- mice. Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion.
Diseases that affect the eye, including photoreceptor degeneration, diabetic retinopathy, and glaucoma, affect 11.8 million people in the US, resulting in vision loss and blindness. Loss of sight ...affects patient quality of life and puts an economic burden both on individuals and the greater healthcare system. Despite the urgent need for treatments, few effective options currently exist in the clinic. Here, we review research on promising neuroprotective strategies that promote neuronal survival with the potential to protect against vision loss and retinal cell death. Due to the large number of neuroprotective strategies, we restricted our review to approaches that we had direct experience with in the laboratory. We focus on drugs that target survival pathways, including bile acids like UDCA and TUDCA, steroid hormones like progesterone, therapies that target retinal dopamine, and neurotrophic factors. In addition, we review rehabilitative methods that increase endogenous repair mechanisms, including exercise and electrical stimulation therapies. For each approach, we provide background on the neuroprotective strategy, including history of use in other diseases; describe potential mechanisms of action; review the body of research performed in the retina thus far, both in animals and in humans; and discuss considerations when translating each treatment to the clinic and to the retina, including which therapies show the most promise for each retinal disease. Despite the high incidence of retinal diseases and the complexity of mechanisms involved, several promising neuroprotective treatments provide hope to prevent blindness. We discuss attractive candidates here with the goal of furthering retinal research in critical areas to rapidly translate neuroprotective strategies into the clinic.
•Neuroprotective strategies promote survival of retinal neurons.•Preserving functional vision supports independence and quality of life.•We present six strategies that preserve retinal neurons across multiple diseases.•Translation of TUDCA and progesterone can leverage several ongoing clinical trials.•Dopamine-related therapies and exercise are new strategies to prevent vision loss.
Objectives
The aim of the study was to increase muscle volume and improve phonation characteristics of the aged ovine larynx by functional electrical stimulation (FES) using a minimally invasive ...surgical procedure.
Methods
Stimulation electrodes were placed bilaterally near the terminal adduction branch of the recurrent laryngeal nerves (RLN). The electrodes were connected to battery powered pulse generators implanted subcutaneously at the neck region. Training patterns were programmed by an external programmer using a bidirectional radio frequency link. Training sessions were repeated automatically by the implant every other day for 1 week followed by every day for 8 weeks in the awake animal. Another group of animals were used as sham, with electrodes positioned but not connected to an implant. Outcome parameters included gene expression analysis, histological assessment of muscle fiber size, functional analysis, and volumetric measurements based on three‐dimensional reconstructions of the entire thyroarytenoid muscle (TAM).
Results
Increase in minimal muscle fiber diameter and an improvement in vocal efficiency were observed following FES, compared with sham animals.
Conclusion
This is the first study to demonstrate beneficial effects in the TAM of FES at molecular, histological, and functional levels. FES of the terminal branches of the RLN reversed the effects of age‐related changes and improved vocal efficiency.
Level of Evidence
NA Laryngoscope, 134:848–854, 2024
Bilateral functional electrical stimulation was applied to increase muscle volume and improve phonation characteristics of the aged sheep larynx. After 9 weeks of stimulation, an improvement in vocal efficiency as well as an increase in minimal muscle fiber diameter (type II fibers) was observed, compared with sham. Histology and gene expression analysis showed no significant muscle fiber type switching after stimulation.
This study investigated the neurologic symptoms and stimulus intensities in the stimulation of deep structures and subcortical fibers with the depth electrodes.
Seventeen patients with ...drug-refractory epilepsy who underwent functional brain mapping with the depth electrodes were enrolled. The 50 Hz electrical stimulation was applied, and the diffusion tensor image was used to identify subcortical fibers. The responsible structures and stimulus intensities for the induced neurologic symptoms were evaluated.
Neurologic symptoms were induced in 11 of 17 patients. The opercular stimulation elicited the neurologic symptoms in 6 patients at the median threshold of 4.0 mA (visceral/face/hand sensory, hand/throat motor, negative motor and auditory symptoms). The insular stimulation induced the neurologic symptoms in 4 patients at the median threshold of 4.0 mA (auditory, negative motor, and sensory symptoms). The stimulation of subcortical fibers was induced in 5 of 9 patients at the median threshold of 4.5 mA. The thresholds of depth electrodes were significantly lower than those of subdural electrodes in 8 patients who used both subdural and depth electrodes and induced symptoms with both electrodes.
The stimulation of depth electrodes can identify the function of deep structures and subcortical fibers with lower intensities than subdural electrodes.
Neuromuscular electrical stimulation (NMES) and Functional Electrical Stimulation (FES) are commonly prescribed rehabilitative therapies. Closed-loop NMES holds the promise to yield more accurate ...limb control, which could enable new rehabilitative procedures. However, NMES/FES can rapidly fatigue muscle, which limits potential treatments and presents several control challenges. Specifically, the stimulation intensity-force relation changes as the muscle fatigues. Additionally, the delayed response between the application of stimulation and muscle force production, termed electromechanical delay (EMD), may increase with fatigue. This paper quantifies these effects. Specifically, open-loop fatiguing protocols were applied to the quadriceps femoris muscle group of able-bodied individuals under isometric conditions, and the resulting torque was recorded. Short pulse trains were used to measure EMD with a thresholding method while long duration pulse trains were used to induce fatigue, measure EMD with a cross-correlation method, and construct recruitment curves. EMD was found to increase significantly with fatigue, and the control effectiveness (i.e., the linear slope of the recruitment curve) decreased with fatigue. Outcomes of these experiments indicate an opportunity for improved closed-loop NMES/FES control development by considering EMD to be time-varying and by considering the muscle recruitment curve to be a nonlinear, time-varying function of the stimulation input.
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