Distinguishing reflex from non-reflex responses elicited by transcutaneous spinal stimulation targeting the lumbosacral cord in healthy individuals.

Transcutaneous spinal stimulation (TSS) studies rely on the depolarization of afferent fibers to provide input to the spinal cord; however, this has not been routinely ascertained. Thus, we aimed to characterize the types of responses evoked by TSS and establish paired-pulse ratio cutoffs that distinguish posterior root reflexes, evoked by stimulation of afferent nerve fibers, from motor responses, evoked by stimulation of efferent nerve fibers. Twelve neurologically intact participants (six women) underwent unipolar TSS (cathode over T11-12 spinal processes, anode paraumbilically) while resting supine. In six participants, unipolar TSS was repeated 2-3 months later and also compared to a bipolar TSS configuration (cathode 2.5 cm below T11-12, anode 5 cm above cathode). EMG signals were recorded from 16 leg muscles. A paired-pulse paradigm was applied at interstimulus intervals (ISIs) of 25, 50, 100, 200, and 400 ms. Responses were categorized by three assessors into reflexes, motor responses, or their combination (mixed responses) based on the visual presence/absence of paired-pulse suppression across ISIs. The paired-pulse ratio that best discriminated between response types was derived for each ISI. These cutoffs were validated by repeating unipolar TSS 2-3 months later and with bipolar TSS. Unipolar TSS evoked only reflexes (90%) and mixed responses (10%), which were mainly recorded in the quadriceps muscles (25-42%). Paired-pulse ratios of 0.51 (25-ms ISI) and 0.47 (50-ms ISI) best distinguished reflexes from mixed responses (100% sensitivity, > 99.2% specificity). These cutoffs performed well in the repeated unipolar TSS session (100% sensitivity, > 89% specificity). Bipolar TSS exclusively elicited reflexes which were all correctly classified. These results can be utilized in future studies to ensure that the input to the spinal cord originates from the depolarization of large afferents. This knowledge can be applied to improve the design of future neurophysiological studies and increase the fidelity of neuromodulation interventions.

Neuromodulation with transcutaneous spinal stimulation reveals different groups of motor profiles during robot-guided stepping in humans with incomplete spinal cord injury.

Neuromodulation via spinal stimulation has been investigated for improving motor function and reducing spasticity after spinal cord injury (SCI) in humans. Despite the reported heterogeneity of outcomes, few investigations have attempted to discern commonalities among individual responses to neuromodulation, especially the impact of stimulation frequencies. Here, we examined how exposure to continuous lumbosacral transcutaneous spinal stimulation (TSS) across a range of frequencies affects robotic torques and EMG patterns during stepping in a robotic gait orthosis on a motorized treadmill. We studied nine chronic motor-incomplete SCI individuals (8/1 AIS-C/D, 8 men) during robot-guided stepping with body-weight support without and with TSS applied at random frequencies between 1 and up to 100 Hz at a constant, individually selected stimulation intensity below the common motor threshold for posterior root reflexes. The hip and knee robotic torques needed to maintain the predefined stepping trajectory and EMG in eight bilateral leg muscles were recorded. We calculated the standardized mean difference between the stimulation conditions grouped into frequency bins and the no stimulation condition to determine changes in the normalized torques and the average EMG envelopes. We found heterogeneous changes in robotic torques across individuals. Agglomerative clustering of robotic torques identified four groups wherein the patterns of changes differed in magnitude and direction depending mainly on the stimulation frequency and stance/swing phase. On one end of the spectrum, the changes in robotic torques were greater with increasing stimulation frequencies (four participants), which coincided with a decrease in EMG, mainly due to the reduction of clonogenic motor output in the lower leg muscles. On the other end, we found an inverted u-shape change in torque over the mid-frequency range along with an increase in EMG, reflecting the augmentation of gait-related physiological (two participants) or pathophysiological (one participant) output. We conclude that TSS during robot-guided stepping reveals different frequency-dependent motor profiles among individuals with chronic motor incomplete SCI. This suggests the need for a better understanding and characterization of motor control profiles in SCI when applying TSS as a therapeutic intervention for improving gait.

Neurophysiology of epidurally evoked spinal cord reflexes in clinically motor-complete posttraumatic spinal cord injury.

Increased use of epidural Spinal Cord Stimulation (eSCS) for the rehabilitation of spinal cord injury (SCI) has highlighted the need for a greater understanding of the properties of reflex circuits in the isolated spinal cord, particularly in response to repetitive stimulation. Here, we investigate the frequency-dependence of modulation of short- and long-latency EMG responses of lower limb muscles in patients with SCI at rest. Single stimuli could evoke short-latency responses as well as long-latency (likely polysynaptic) responses. The short-latency component was enhanced at low frequencies and declined at higher rates. In all muscles, the effects of eSCS were more complex if polysynaptic activity was elicited, making the motor output become an active process expressed either as suppression, tonic or rhythmical activity. The polysynaptic activity threshold is not constant and might vary with different stimulation frequencies, which speaks for its temporal dependency. Polysynaptic components can be observed as direct responses, neuromodulation of monosynaptic responses or driving the muscle activity by themselves, depending on the frequency level. We suggest that the presence of polysynaptic activity could be a potential predictor for appropriate stimulation conditions. This work studies the complex behaviour of spinal circuits deprived of voluntary motor control from the brain and in the absence of any other inputs. This is done by describing the monosynaptic responses, polysynaptic activity, and its interaction through its input-output interaction with sustain stimulation that, unlike single stimuli used to study the reflex pathway, can strongly influence the interneuron circuitry and reveal a broader spectrum of connectivity.

Bipolar transcutaneous spinal stimulation evokes short-latency reflex responses in human lower limbs alike standard unipolar electrode configuration.

Noninvasive electrical stimulation targeting the posterior lumbosacral roots has been applied recently in reflexes studies and as a neuromodulation intervention for modifying spinal cord circuitry after an injury. Here, we characterized short-latency responses evoked by four bipolar electrode configurations placed longitudinally over the spinal column at different vertebral levels from L1 to T9. They were compared with the responses evoked by the standard unipolar (aka monopolar) electrode configuration (cathode at T11/12, anode over the abdominal wall). Short-latency responses were recorded in the rectus femoris, medial hamstrings, tibialis anterior, and soleus muscles, bilaterally, in 11 neurologically intact participants. The response recruitment characteristics (maximal amplitude, motor threshold) and amplitude-matched onset latencies and paired-pulse suppression (35-ms interstimulus interval) were assessed with 1-ms current-controlled pulses at intensities up to 100 mA. The results showed that short-latency responses can be elicited with all bipolar electrode configurations. However, only with the cathode at T11/12 and the anode 10 cm cranially (∼T9), the maximum response amplitudes were statistical equivalent (P < 0.05) in the medial hamstrings, tibialis anterior, and soleus but not the rectus femoris, whereas motor thresholds were not significantly different across all muscles. The onset latency and paired-pulse suppression were also not significantly different across the tested electrode configurations, thereby confirming the reflex nature of the bipolar short-latency responses. We conclude that the bipolar configuration (cathode T11/12, anode ∼T9) produces reflex responses that are ostensibly similar to those evoked by the standard unipolar configuration. This provides an alternative approach for neuromodulation intervention.NEW & NOTEWORTHY Transcutaneous spinal stimulation with the identified bipolar electrode configuration may offer several advantages for neuromodulation interventions over commonly used unipolar configurations: there are no associated abdominal contractions, which improves the participant's comfort; additional dermatomes are not stimulated as when the anode is over the abdominal wall or iliac crest, which may have unwanted effects; and, due to a more localized electrical field, the bipolar configuration offers the possibility of targeting cord segments more selectively.

Optimization of Interphase Intervals to Enhance the Evoked Muscular Responses of Transcutaneous Neuromuscular Electrical Stimulation.

Neuromuscular electrical stimulation (NMES) is a widely used technique for clinical diagnostic, treatment, and research. Normally, it applies charge-balanced biphasic pulses, which several publications have reported to be less efficient than monophasic pulses. A good alternative is the use of interphase intervals (IPI) on biphasic pulses that allows to achieve similar responses than those evoked by monophasic stimulation. This study analyzes the enhancing mechanism of the IPI and provides guidelines on how to optimize the IPI in order to reduce secondary effects such as the electrode corrosion. The tibial nerve was excited by NMES biphasic pulses with different IPI durations and polarities. Then, the elicited responses were recorded on the soleus muscle via electromyography. When cathodic-first pulses were applied, the responses increased proportionally to the IPI until the duration of 250 µs, where the increase saturated at 30% of the original amplitude. The responses evoked during anodic-first were 6% to 30% smaller than those evoked during cathodic-first pulses and continuously increased until the IPI duration of 2500 µs, where the responses reached an increase of around 30%. The results suggest that when a cathodic-first pulse is used, the IPI could be optimized (based on the setup geometry) to allow the action potentials to travel out of the hyperpolarization zone induced by the anodic phase. When anodic-first stimuli are applied, the IPI duration allows the fiber to recover from an apparent insensitive state induced by the anodic phase. The use of IPI is a viable option to improve the efficiency of actual stimulation systems, since only small modifications are required to significantly reduce the electrical charge required and boost the stimulation efficiency.

Epidural and transcutaneous spinal electrical stimulation for restoration of movement after incomplete and complete spinal cord injury.

PURPOSE OF REVIEW: The Purpose of this review is to outline and explain the therapeutic use of electrical spinal cord stimulation (SCS) for modification of spinal motor output. Central functional stimulation provides afferent input to posterior root neurons and is applied to improve volitional movements, posture and their endurance, control spasticity, and improve bladder function or perfusion in the lower limbs. Clinical accomplishments strongly depend on each individual's physiological state and specific methodical adaptation to that physiological state. RECENT FINDINGS: Effectiveness of this neuromodulory technique for changing motor control after spinal cord injury (SCI) continues to be explored along with the underlying mechanisms of its effect in people with complete and incomplete spinal cord injuries. There are extensive studies of tonic and rhythmical activity elicited from the lumbar cord as well as data demonstrating augmentation of residual volitional activity. Recent studies have focused on verifying if and how SCS can modify features of neurocontrol in ambulatory spinal cord patients. SUMMARY: In this review, we emphasize recent publications of research revealing that SCS can substitute for the reduced brain drive for control of excitability in people with SCI. Artificially replacing diminished or lost brain control over the spinal cord has limitations. A fundamental requirement for successful SCS application is analysis of each individual's residual postinjury neural function. This will allow a better understanding of the physiological interactions between SCS and spinal cord motor control below injury and provide criteria for its application. Finally, the publication of both successful and failed applications of SCS will be crucial for gaining future progress.

Motor Control of Human Spinal Cord Disconnected from the Brain and Under External Movement.

Motor control after spinal cord injury is strongly depending on residual ascending and descending pathways across the lesion. The individually altered neurophysiology is in general based on still intact sublesional control loops with afferent sensory inputs linked via interneuron networks to efferent motor outputs. Partial or total loss of translesional control inputs reduces and alters the ability to perform voluntary movements and results in motor incomplete (residual voluntary control of movement functions) or motor complete (no residual voluntary control) spinal cord injury classification. Of particular importance are intact functionally silent neural structures with residual brain influence but reduced state of excitability that inhibits execution of voluntary movements. The condition is described by the term discomplete spinal cord injury. There are strong evidences that artificial afferent input, e.g., by epidural or noninvasive electrical stimulation of the lumbar posterior roots, can elevate the state of excitability and thus re-enable or augment voluntary movement functions. This modality can serve as a powerful assessment technique for monitoring details of the residual function profile after spinal cord injury, as a therapeutic tool for support of restoration of movement programs and as a neuroprosthesis component augmenting and restoring movement functions, per se or in synergy with classical neuromuscular or muscular electrical stimulation.

Multi-Electrode Array for Transcutaneous Lumbar Posterior Root Stimulation.

Interest in transcutaneous electrical stimulation of the lumbosacral spinal cord is increasing in human electrophysiological and clinical studies. The stimulation effects on lower limb muscles depend on the depolarization of segmentally organized posterior root afferents and, thus, the rostro-caudal stimulation site. In previous studies, selective stimulation was achieved by varying the positions of single self-adhesive electrodes over the thoracolumbar spine. Here, we developed a multi-electrode surface array consisting of 3 × 8 electrode pads and tested its stimulation-site specificity. The array was placed longitudinally over the spine covering the T10-L2 vertebrae. Two different hydrogel layer configurations were utilized: a single layer adhered to all electrode pads of the array and a configuration comprised of eight separate strips attached to the three transverse electrode pads of each level. Voltage measurements demonstrated that an effectively focused field distribution along the longitudinal extent of the array was not accomplished when using the single continuous hydrogel layer, and segmental selective stimulation of the posterior root afferents was not possible. The separate strips produced a focused electric field distribution at the rostro-caudal level of the electrode pads selected for stimulation. This configuration allowed for the preferential elicitation of posterior root-muscle reflexes in either the L2-L4 innervated quadriceps or the L5-S2 innervated triceps surae muscle groups. Such multi-electrode array for transcutaneous spinal cord stimulation shall allow for improved control of stimulation conditions in electrophysiological studies and time-dependent and site-specific stimulation patterns for neuromodulation applications.

Comparison of Twitch Responses During Current- or Voltage-Controlled Transcutaneous Neuromuscular Electrical Stimulation.

Neuromuscular electrical stimulation (NMES) is an established method for functional restoration of muscle function, rehabilitation, and diagnostics. In this work, NMES was applied with surface electrodes placed on the anterior thigh to identify the main differences between current-controlled (CC) and voltage-controlled (VC) modes. Measurements of the evoked knee extension force and the myoelectric signal of quadriceps and hamstrings were taken during stimulation with different amplitudes, pulse widths, and stimulation techniques. The stimulation pulses were rectangular and symmetric biphasic for both stimulation modes. The electrode-tissue impedance influences the differences between CC and VC stimulation. The main difference is that for CC stimulation, variation of pulse width and amplitude influences the amount of nerve depolarization, whereas VC stimulation is only dependent on amplitude variations for pulse widths longer than 150 µs. An important remark is that these findings are strongly dependent on the characteristics of the electrode-skin interface. In our case, we used large stimulation electrodes placed on the anterior thigh, which cause higher capacitive effects. The controllability, voltage compliance, and charge characteristics of each stimulation technique should be considered during the stimulators design. For applications that require the activation of a large amount of nerve fibers, VC is a more suitable option. In contrast, if the application requires a high controllability, then CC should be chosen prior to VC.

Augmentation of Voluntary Locomotor Activity by Transcutaneous Spinal Cord Stimulation in Motor-Incomplete Spinal Cord-Injured Individuals.

The level of sustainable excitability within lumbar spinal cord circuitries is one of the factors determining the functional outcome of locomotor therapy after motor-incomplete spinal cord injury. Here, we present initial data using noninvasive transcutaneous lumbar spinal cord stimulation (tSCS) to modulate this central state of excitability during voluntary treadmill stepping in three motor-incomplete spinal cord-injured individuals. Stimulation was applied at 30 Hz with an intensity that generated tingling sensations in the lower limb dermatomes, yet without producing muscle reflex activity. This stimulation changed muscle activation, gait kinematics, and the amount of manual assistance required from the therapists to maintain stepping with some interindividual differences. The effect on motor outputs during treadmill-stepping was essentially augmentative and step-phase dependent despite the invariant tonic stimulation. The most consistent modification was found in the gait kinematics, with the hip flexion during swing increased by 11.3° ± 5.6° across all subjects. This preliminary work suggests that tSCS provides for a background increase in activation of the lumbar spinal locomotor circuitry that has partially lost its descending drive. Voluntary inputs and step-related feedback build upon the stimulation-induced increased state of excitability in the generation of locomotor activity. Thus, tSCS essentially works as an electrical neuroprosthesis augmenting remaining motor control.

Selective Tibial Neurotomy Outcomes for Spastic Equinovarus Foot: Patient Expectations and Functional Assessment.

BACKGROUND: Spastic equinovarus foot (SEF) is a common dysfunctional foot posture after stroke that impairs balance and mobility. Selective tibial neurotomy (STN) is a simple but underutilized surgical option that can effectively address critical aspects of SEF and thereby provide enduring quality of life gains. There are few studies that examine both functional outcomes and patient satisfaction with this treatment option. OBJECTIVE: To elucidate the patient goals that motivated their decision to undergo the procedure and compare subjective and objective changes in balance and functional mobility as a consequence of surgery. METHODS: Thirteen patients with problematic SEF who had previously failed conservative measures were treated with STN. Preoperative and postoperative (on average 6 months) assessments evaluated gait quality and functional mobility. In addition, a custom survey was conducted to investigate patient perspectives on STN intervention. RESULTS: The survey showed that participants who opted for STN were dissatisfied with their previous spasticity management. The most common preoperative expectation for STN treatment was to improve walking, followed by improving balance, brace comfort, pain, and tone. Postoperatively, participants rated the improvement in their expectations and were, on average, 71 on a 100-point scale, indicating high satisfaction. The gait quality, assessed with the Gait Intervention and Assessment Tool, improved significantly between preoperative and postoperative assessment (M = -4.1, P = .01) with a higher average difference in stance of -3.3 than in swing -0.5. Improvement in both gait endurance (M = 36 m, P = .01) and self-selected gait speed (M = .12 m/s, P = .03) was statistically significant. Finally, static balance (M = 5.0, P = .03) and dynamic balance (M = 3.5, P = .02) were also significantly improved. CONCLUSION: STN improved gait quality and functional mobility and was associated with high satisfaction in patients with SEF.

Safe neuromuscular electrical stimulator designed for the elderly.

A stimulator for neuromuscular electrical stimulation (NMES) was designed, especially suiting the requirements of elderly people with reduced cognitive abilities and diminished fine motor skills. The aging of skeletal muscle is characterized by a progressive decline in muscle mass, force, and condition. Muscle training with NMES reduces the degradation process. The discussed system is intended for evoked muscle training of the anterior and posterior thigh. The core of the stimulator is based on a microcontroller with two modular output stages. The system has two charge-balanced biphasic voltage-controlled stimulation channels. Additionally, the evoked myoelectric signal (M-wave) and the myokinematic signal (surface acceleration) are measured. A central controller unit allows using the stimulator as a stand-alone device. To set up the training sequences and to evaluate the compliance data, a personal computer is connected to the stimulator via a universal serial bus. To help elderly people handle the stimulator by themselves, the user interface is kept very simple. For safety reasons, the electrode impedance is monitored during stimulation. A comprehensive compliance management with included measurements of muscle activity and stimulation intensity enables a scientific use of the stimulator in clinical trials.

Influence of Spine Curvature on the Efficacy of Transcutaneous Lumbar Spinal Cord Stimulation.

Transcutaneous spinal cord stimulation is a non-invasive method for neuromodulation of sensorimotor function. Its main mechanism of action results from the activation of afferent fibers in the posterior roots-the same structures as targeted by epidural stimulation. Here, we investigated the influence of sagittal spine alignment on the capacity of the surface-electrode-based stimulation to activate these neural structures. We evaluated electromyographic responses evoked in the lower limbs of ten healthy individuals during extension, flexion, and neutral alignment of the thoracolumbar spine. To control for position-specific effects, stimulation in these spine alignment conditions was performed in four different body positions. In comparison to neutral and extended spine alignment, flexion of the spine resulted in a strong reduction of the response amplitudes. There was no such effect on tibial-nerve evoked H reflexes. Further, there was a reduction of post-activation depression of the responses to transcutaneous spinal cord stimulation evoked in spinal flexion. Thus, afferent fibers were reliably activated with neutral and extended spine alignment. Spinal flexion, however, reduced the capacity of the stimulation to activate afferent fibers and led to the co-activation of motor fibers in the anterior roots. This change of action was due to biophysical rather than neurophysiological influences. We recommend applying transcutaneous spinal cord stimulation in body positions that allow individuals to maintain a neutral or extended spine.

Transcutaneous Spinal Cord Stimulation Induces Temporary Attenuation of Spasticity in Individuals with Spinal Cord Injury.

Epidural spinal cord stimulation (SCS) is currently regarded as a breakthrough procedure for enabling movement after spinal cord injury (SCI), yet one of its original applications was for spinal spasticity. An emergent method that activates similar target neural structures non-invasively is transcutaneous SCS. Its clinical value for spasticity control would depend on inducing carry-over effects, because the surface-electrode-based approach cannot be applied chronically. We evaluated single-session effects of transcutaneous lumbar SCS in 12 individuals with SCI by a test-battery approach, before, immediately after and 2 h after intervention. Stimulation was applied for 30 min at 50 Hz with an intensity sub-threshold for eliciting reflexes in lower extremity muscles. The tests included evaluations of stretch-induced spasticity (Modified Ashworth Scale [MAS] sum score, pendulum test, electromyography-based evaluation of tonic stretch reflexes), clonus, cutaneous-input-evoked spasms, and the timed 10 m walk test. Across participants, the MAS sum score, clonus, and spasms were significantly reduced immediately after SCS, and all spasticity measures were improved 2 h post-intervention, with large effect sizes and including clinically meaningful improvements. The effect on walking speed varied across individuals. We further conducted a single-case multi-session study over 6 weeks to explore the applicability of transcutaneous SCS as a home-based therapy. Self-application of the intervention was successful; weekly evaluations suggested progressively improving therapeutic effects during the active period and carry-over effects for 7 days. Our results suggest that transcutaneous SCS can be a viable non-pharmacological option for managing spasticity, likely working through enhancing pre- and post-synaptic spinal inhibitory mechanisms, and may additionally serve to identify responders to treatments with epidural SCS.

Changes in motor cortex excitability following training of a novel goal-directed motor task.

Training of skilled movements leads to typical changes in motor evoked potentials (MEPs). To explore how such changes are related to motor performance and hand preference, a goal-directed movement task was implemented on a haptic interface. Right and left hands of right-handed subjects were trained in two sessions separated by a pause of 10 min. Transcranial magnetic stimulation (TMS) was applied contralaterally to the trained hand before and after each session. Effects of right hand training: after session #1 MEP-facilitation was +60%, intracortical inhibition (ICI) was reduced and task improvement was +37%. Following session #2 all variables remained unchanged. Left hand training: after session #1 MEP-facilitation was +59%, ICI remained unchanged and task improvement was +30%. Following session #2 all variables remained unchanged. It is concluded that mainly the early phase of skill acquisition induces neuroplastic changes. The asymmetry in ICI obviously reflects functional side differences in hand motor control.

Body Position Influences Which Neural Structures Are Recruited by Lumbar Transcutaneous Spinal Cord Stimulation.

Transcutaneous stimulation of the human lumbosacral spinal cord is used to evoke spinal reflexes and to neuromodulate altered sensorimotor function following spinal cord injury. Both applications require the reliable stimulation of afferent posterior root fibers. Yet under certain circumstances, efferent anterior root fibers can be co-activated. We hypothesized that body position influences the preferential stimulation of sensory or motor fibers. Stimulus-triggered responses to transcutaneous spinal cord stimulation were recorded using surface-electromyography from quadriceps, hamstrings, tibialis anterior, and triceps surae muscles in 10 individuals with intact nervous systems in the supine, standing and prone positions. Single and paired (30-ms inter-stimulus intervals) biphasic stimulation pulses were applied through surface electrodes placed on the skin between the T11 and T12 inter-spinous processes referenced to electrodes on the abdomen. The paired stimulation was applied to evaluate the origin of the evoked electromyographic response; trans-synaptic responses would be suppressed whereas direct efferent responses would almost retain their amplitude. We found that responses to the second stimulus were decreased to 14%±5% of the amplitude of the response to the initial pulse in the supine position across muscles, to 30%±5% in the standing, and to only 80%±5% in the prone position. Response thresholds were lowest during standing and highest in the prone position and response amplitudes were largest in the supine and smallest in the prone position. The responses obtained in the supine and standing positions likely resulted from selective stimulation of sensory fibers while concomitant motor-fiber stimulation occurred in the prone position. We assume that changes of root-fiber paths within the generated electric field when in the prone position increase the stimulation thresholds of posterior above those of anterior root fibers. Thus, we recommend conducting spinal reflex or neuromodulation studies with subjects lying supine or in an upright position, as in standing or stepping.

Physical exercise in aging human skeletal muscle increases mitochondrial calcium uniporter expression levels and affects mitochondria dynamics.

Age-related sarcopenia is characterized by a progressive loss of muscle mass with decline in specific force, having dramatic consequences on mobility and quality of life in seniors. The etiology of sarcopenia is multifactorial and underlying mechanisms are currently not fully elucidated. Physical exercise is known to have beneficial effects on muscle trophism and force production. Alterations of mitochondrial Ca2+ homeostasis regulated by mitochondrial calcium uniporter (MCU) have been recently shown to affect muscle trophism in vivo in mice. To understand the relevance of MCU-dependent mitochondrial Ca2+ uptake in aging and to investigate the effect of physical exercise on MCU expression and mitochondria dynamics, we analyzed skeletal muscle biopsies from 70-year-old subjects 9 weeks trained with either neuromuscular electrical stimulation (ES) or leg press. Here, we demonstrate that improved muscle function and structure induced by both trainings are linked to increased protein levels of MCU Ultrastructural analyses by electron microscopy showed remodeling of mitochondrial apparatus in ES-trained muscles that is consistent with an adaptation to physical exercise, a response likely mediated by an increased expression of mitochondrial fusion protein OPA1. Altogether these results indicate that the ES-dependent physiological effects on skeletal muscle size and force are associated with changes in mitochondrial-related proteins involved in Ca2+ homeostasis and mitochondrial shape. These original findings in aging human skeletal muscle confirm the data obtained in mice and propose MCU and mitochondria-related proteins as potential pharmacological targets to counteract age-related muscle loss.

Dynamic impedance model of the skin-electrode interface for transcutaneous electrical stimulation.

Transcutaneous electrical stimulation can depolarize nerve or muscle cells applying impulses through electrodes attached on the skin. For these applications, the electrode-skin impedance is an important factor which influences effectiveness. Various models describe the interface using constant or current-depending resistive-capacitive equivalent circuit. Here, we develop a dynamic impedance model valid for a wide range stimulation intensities. The model considers electroporation and charge-dependent effects to describe the impedance variation, which allows to describe high-charge pulses. The parameters were adjusted based on rectangular, biphasic stimulation pulses generated by a stimulator, providing optionally current or voltage-controlled impulses, and applied through electrodes of different sizes. Both control methods deliver a different electrical field to the tissue, which is constant throughout the impulse duration for current-controlled mode or have a very current peak for voltage-controlled. The results show a predominant dependence in the current intensity in the case of both stimulation techniques that allows to keep a simple model. A verification simulation using the proposed dynamic model shows coefficient of determination of around 0.99 in both stimulation types. The presented method for fitting electrode-skin impedance can be simple extended to other stimulation waveforms and electrode configuration. Therefore, it can be embedded in optimization algorithms for designing electrical stimulation applications even for pulses with high charges and high current spikes.

Long-term high-level exercise promotes muscle reinnervation with age.

The histologic features of aging muscle suggest that denervation contributes to atrophy, that immobility accelerates the process, and that routine exercise may protect against loss of motor units and muscle tissue. Here, we compared muscle biopsies from sedentary and physically active seniors and found that seniors with a long history of high-level recreational activity up to the time of muscle biopsy had 1) lower loss of muscle strength versus young men (32% loss in physically active vs 51% loss in sedentary seniors); 2) fewer small angulated (denervated) myofibers; 3) a higher percentage of fiber-type groups (reinnervated muscle fibers) that were almost exclusive of the slow type; and 4) sparse normal-size muscle fibers coexpressing fast and slow myosin heavy chains, which is not compatible with exercise-driven muscle-type transformation. The biopsies from the old physically active seniors varied from sparse fiber-type groupings to almost fully transformed muscle, suggesting that coexpressing fibers appear to fill gaps. Altogether, the data show that long-term physical activity promotes reinnervation of muscle fibers and suggest that decades of high-level exercise allow the body to adapt to age-related denervation by saving otherwise lost muscle fibers through selective recruitment to slow motor units. These effects on size and structure of myofibers may delay functional decline in late aging.