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1.
Clin Auton Res ; 34(2): 233-252, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38709357

ABSTRACT

PURPOSE: We conducted a meta-analysis to determine the effect of hyperoxia on muscle sympathetic nerve activity in healthy individuals and those with cardio-metabolic diseases. METHODS: A comprehensive search of electronic databases was performed until August 2022. All study designs (except reviews) were included: population (humans; apparently healthy or with at least one chronic disease); exposures (muscle sympathetic nerve activity during hyperoxia or hyperbaria); comparators (hyperoxia or hyperbaria vs. normoxia); and outcomes (muscle sympathetic nerve activity, heart rate, blood pressure, minute ventilation). Forty-nine studies were ultimately included in the meta-analysis. RESULTS: In healthy individuals, hyperoxia had no effect on sympathetic burst frequency (mean difference [MD] - 1.07 bursts/min; 95% confidence interval [CI] - 2.17, 0.04bursts/min; P = 0.06), burst incidence (MD 0.27 bursts/100 heartbeats [hb]; 95% CI - 2.10, 2.64 bursts/100 hb; P = 0.82), burst amplitude (P = 0.85), or total activity (P = 0.31). In those with chronic diseases, hyperoxia decreased burst frequency (MD - 5.57 bursts/min; 95% CI - 7.48, - 3.67 bursts/min; P < 0.001) and burst incidence (MD - 4.44 bursts/100 hb; 95% CI - 7.94, - 0.94 bursts/100 hb; P = 0.01), but had no effect on burst amplitude (P = 0.36) or total activity (P = 0.90). Our meta-regression analyses identified an inverse relationship between normoxic burst frequency and change in burst frequency with hyperoxia. In both groups, hyperoxia decreased heart rate but had no effect on any measure of blood pressure. CONCLUSION: Hyperoxia does not change sympathetic activity in healthy humans. Conversely, in those with chronic diseases, hyperoxia decreases sympathetic activity. Regardless of disease status, resting sympathetic burst frequency predicts the degree of change in burst frequency, with larger decreases for those with higher resting activity.


Subject(s)
Hyperoxia , Muscle, Skeletal , Sympathetic Nervous System , Humans , Hyperoxia/physiopathology , Sympathetic Nervous System/physiology , Sympathetic Nervous System/physiopathology , Muscle, Skeletal/physiology , Muscle, Skeletal/innervation , Heart Rate/physiology
2.
Skelet Muscle ; 14(1): 11, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38769542

ABSTRACT

BACKGROUND: Myotonic Dystrophy type I (DM1) is the most common muscular dystrophy in adults. Previous reports have highlighted that neuromuscular junctions (NMJs) deteriorate in skeletal muscle from DM1 patients and mouse models thereof. However, the underlying pathomechanisms and their contribution to muscle dysfunction remain unknown. METHODS: We compared changes in NMJs and activity-dependent signalling pathways in HSALR and Mbnl1ΔE3/ΔE3 mice, two established mouse models of DM1. RESULTS: Muscle from DM1 mouse models showed major deregulation of calcium/calmodulin-dependent protein kinases II (CaMKIIs), which are key activity sensors regulating synaptic gene expression and acetylcholine receptor (AChR) recycling at the NMJ. Both mouse models exhibited increased fragmentation of the endplate, which preceded muscle degeneration. Endplate fragmentation was not accompanied by changes in AChR turnover at the NMJ. However, the expression of synaptic genes was up-regulated in mutant innervated muscle, together with an abnormal accumulation of histone deacetylase 4 (HDAC4), a known target of CaMKII. Interestingly, denervation-induced increase in synaptic gene expression and AChR turnover was hampered in DM1 muscle. Importantly, CaMKIIß/ßM overexpression normalized endplate fragmentation and synaptic gene expression in innervated Mbnl1ΔE3/ΔE3 muscle, but it did not restore denervation-induced synaptic gene up-regulation. CONCLUSIONS: Our results indicate that CaMKIIß-dependent and -independent mechanisms perturb synaptic gene regulation and muscle response to denervation in DM1 mouse models. Changes in these signalling pathways may contribute to NMJ destabilization and muscle dysfunction in DM1 patients.


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Disease Models, Animal , Muscle, Skeletal , Myotonic Dystrophy , Neuromuscular Junction , Myotonic Dystrophy/genetics , Myotonic Dystrophy/metabolism , Myotonic Dystrophy/physiopathology , Animals , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics , Neuromuscular Junction/metabolism , Muscle, Skeletal/metabolism , Muscle, Skeletal/innervation , Muscle, Skeletal/pathology , Mice , Humans , Histone Deacetylases/metabolism , Histone Deacetylases/genetics , Receptors, Cholinergic/metabolism , Receptors, Cholinergic/genetics , Male , Mice, Inbred C57BL
3.
Sci Robot ; 9(90): eadl0085, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38809994

ABSTRACT

Sensory feedback for prosthesis control is typically based on encoding sensory information in specific types of sensory stimuli that the users interpret to adjust the control of the prosthesis. However, in physiological conditions, the afferent feedback received from peripheral nerves is not only processed consciously but also modulates spinal reflex loops that contribute to the neural information driving muscles. Spinal pathways are relevant for sensory-motor integration, but they are commonly not leveraged for prosthesis control. We propose an approach to improve sensory-motor integration for prosthesis control based on modulating the excitability of spinal circuits through the vibration of tendons in a closed loop with muscle activity. We measured muscle signals in healthy participants and amputees during different motor tasks, and we closed the loop by applying vibration on tendons connected to the muscles, which modulated the excitability of motor neurons. The control signals to the prosthesis were thus the combination of voluntary control and additional spinal reflex inputs induced by tendon vibration. Results showed that closed-loop tendon vibration was able to modulate the neural drive to the muscles. When closed-loop tendon vibration was used, participants could achieve similar or better control performance in interfaces using muscle activation than without stimulation. Stimulation could even improve prosthetic grasping in amputees. Overall, our results indicate that closed-loop tendon vibration can integrate spinal reflex pathways in the myocontrol system and open the possibility of incorporating natural feedback loops in prosthesis control.


Subject(s)
Amputees , Artificial Limbs , Feedback, Sensory , Hand , Muscle, Skeletal , Prosthesis Design , Reflex , Vibration , Humans , Adult , Hand/physiology , Male , Female , Feedback, Sensory/physiology , Reflex/physiology , Muscle, Skeletal/physiology , Muscle, Skeletal/innervation , Electromyography , Tendons/physiology , Motor Neurons/physiology , Middle Aged , Hand Strength/physiology , Young Adult
4.
Physiol Rep ; 12(9): e16039, 2024 May.
Article in English | MEDLINE | ID: mdl-38740563

ABSTRACT

Evaluating reciprocal inhibition of the thigh muscles is important to investigate the neural circuits of locomotor behaviors. However, measurements of reciprocal inhibition of thigh muscles using spinal reflex, such as H-reflex, have never been systematically established owing to methodological limitations. The present study aimed to clarify the existence of reciprocal inhibition in the thigh muscles using transcutaneous spinal cord stimulation (tSCS). Twenty able-bodied male individuals were enrolled. We evoked spinal reflex from the biceps femoris muscle (BF) by tSCS on the lumber posterior root. We examined whether the tSCS-evoked BF reflex was reciprocally inhibited by the following conditionings: (1) single-pulse electrical stimulation on the femoral nerve innervating the rectus femoris muscle (RF) at various inter-stimulus intervals in the resting condition; (2) voluntary contraction of the RF; and (3) vibration stimulus on the RF. The BF reflex was significantly inhibited when the conditioning electrical stimulation was delivered at 10 and 20 ms prior to tSCS, during voluntary contraction of the RF, and during vibration on the RF. These data suggested a piece of evidence of the existence of reciprocal inhibition from the RF to the BF muscle in humans and highlighted the utility of methods for evaluating reciprocal inhibition of the thigh muscles using tSCS.


Subject(s)
Spinal Cord Stimulation , Thigh , Humans , Male , Spinal Cord Stimulation/methods , Adult , Thigh/physiology , Thigh/innervation , Muscle, Skeletal/physiology , Muscle, Skeletal/innervation , Muscle Contraction/physiology , Transcutaneous Electric Nerve Stimulation/methods , Young Adult , H-Reflex/physiology , Femoral Nerve/physiology , Neural Inhibition/physiology , Quadriceps Muscle/physiology , Quadriceps Muscle/innervation , Hamstring Muscles/physiology , Electromyography
5.
J Exp Biol ; 227(10)2024 May 15.
Article in English | MEDLINE | ID: mdl-38699818

ABSTRACT

Little is known regarding the precise muscle, bone and joint actions resulting from individual and simultaneous muscle activation(s) of the lower limb. An in situ experimental approach is described herein to control the muscles of the rabbit lower hindlimb, including the medial and lateral gastrocnemius, soleus, plantaris and tibialis anterior. The muscles were stimulated using nerve-cuff electrodes placed around the innervating nerves of each muscle. Animals were fixed in a stereotactic frame with the ankle angle set at 90 deg. To demonstrate the efficacy of the experimental technique, isometric plantarflexion torque was measured at the 90 deg ankle joint angle at a stimulation frequency of 100, 60 and 30 Hz. Individual muscle torque and the torque produced during simultaneous activation of all plantarflexor muscles are presented for four animals. These results demonstrate that the experimental approach was reliable, with insignificant variation in torque between repeated contractions. The experimental approach described herein provides the potential for measuring a diverse array of muscle properties, which is important to improve our understanding of musculoskeletal biomechanics.


Subject(s)
Hindlimb , Muscle, Skeletal , Torque , Animals , Rabbits , Muscle, Skeletal/physiology , Muscle, Skeletal/innervation , Hindlimb/physiology , Biomechanical Phenomena , Electric Stimulation , Male
6.
J Hand Surg Eur Vol ; 49(6): 773-782, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38819009

ABSTRACT

Optimal recovery of muscle function after proximal nerve injuries remains a complex and challenging problem. After a nerve injury, alterations in the affected muscles lead to atrophy, and later degeneration and replacement by fat-fibrous tissues. At present, several different strategies for the preservation of skeletal muscle have been reported, including various sets of physical exercises, muscle massage, physical methods (e.g. electrical stimulation, magnetic field and laser stimulation, low-intensity pulsed ultrasound), medicines (e.g. nutrients, natural and chemical agents, anti-inflammatory and antioxidants, hormones, enzymes and enzyme inhibitors), regenerative medicine (e.g. growth factors, stem cells and microbiota) and surgical procedures (e.g. supercharge end-to-side neurotization). The present review will focus on methods that aimed to minimize the damage to muscles after denervation based on our present knowledge.


Subject(s)
Muscle, Skeletal , Peripheral Nerve Injuries , Humans , Muscle, Skeletal/innervation , Peripheral Nerve Injuries/surgery , Peripheral Nerve Injuries/therapy , Exercise Therapy/methods , Massage , Muscle Denervation
7.
Proc Natl Acad Sci U S A ; 121(19): e2313590121, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38683978

ABSTRACT

Myokines and exosomes, originating from skeletal muscle, are shown to play a significant role in maintaining brain homeostasis. While exercise has been reported to promote muscle secretion, little is known about the effects of neuronal innervation and activity on the yield and molecular composition of biologically active molecules from muscle. As neuromuscular diseases and disabilities associated with denervation impact muscle metabolism, we hypothesize that neuronal innervation and firing may play a pivotal role in regulating secretion activities of skeletal muscles. We examined this hypothesis using an engineered neuromuscular tissue model consisting of skeletal muscles innervated by motor neurons. The innervated muscles displayed elevated expression of mRNAs encoding neurotrophic myokines, such as interleukin-6, brain-derived neurotrophic factor, and FDNC5, as well as the mRNA of peroxisome-proliferator-activated receptor γ coactivator 1α, a key regulator of muscle metabolism. Upon glutamate stimulation, the innervated muscles secreted higher levels of irisin and exosomes containing more diverse neurotrophic microRNAs than neuron-free muscles. Consequently, biological factors secreted by innervated muscles enhanced branching, axonal transport, and, ultimately, spontaneous network activities of primary hippocampal neurons in vitro. Overall, these results reveal the importance of neuronal innervation in modulating muscle-derived factors that promote neuronal function and suggest that the engineered neuromuscular tissue model holds significant promise as a platform for producing neurotrophic molecules.


Subject(s)
Brain-Derived Neurotrophic Factor , Exosomes , Muscle, Skeletal , Exosomes/metabolism , Animals , Muscle, Skeletal/metabolism , Muscle, Skeletal/innervation , Brain-Derived Neurotrophic Factor/metabolism , Mice , Fibronectins/metabolism , Motor Neurons/metabolism , Interleukin-6/metabolism , MicroRNAs/metabolism , MicroRNAs/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Neurons/metabolism , Nerve Growth Factors/metabolism , Myokines
8.
Am J Physiol Regul Integr Comp Physiol ; 326(6): R472-R483, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38557152

ABSTRACT

The role of muscle mass in modulating performance and perceived fatigability across the entire intensity spectrum during cycling remains unexplored. We hypothesized that at task failure (Tlim), muscle contractile function would decline more following single- (SL) versus double-leg (DL) cycling within severe and extreme intensities, but not moderate and heavy intensities. After DL and SL ramp-incremental tests, on separate days, 11 recreationally active males (V̇o2max: 49.5 ± 7.7 mL·kg-1·min-1) completed SL and DL cycling until Tlim within each intensity domain. Power output for SL trials was set at 60% of the corresponding DL trial. Before and immediately after Tlim, participants performed an isometric maximal voluntary contraction (MVC) coupled with one superimposed and three resting femoral nerve stimulations [100 Hz; 10 Hz; single twitch (Qtw)] to measure performance fatigability. Perceived fatigue, leg pain, dyspnea, and effort were collected during trials. Tlim within each intensity domain was not different between SL and DL (all P > 0.05). MVC declined more for SL versus DL following heavy- (-42 ± 16% vs. -30 ± 18%; P = 0.011) and severe-intensity cycling (-41 ± 12% vs. -31 ± 15%; P = 0.036). Similarly, peak Qtw force declined more for SL following heavy- (-31 ± 12% vs. -22 ± 10%; P = 0.007) and severe-intensity cycling (-49 ± 13% vs. -40 ± 7%; P = 0.048). Except for heavy intensity, voluntary activation reductions were similar between modes. Similarly, except for dyspnea, which was lower for SL versus DL across all domains, ratings of fatigue, pain, and effort were similar at Tlim between exercise modes. Thus, the amount of muscle mass modulates the extent of contractile function impairment in an intensity-dependent manner.NEW & NOTEWORTHY We investigated the modulatory role of muscle mass on performance and perceived fatigability across the entire intensity spectrum. Despite similar time-to-task failure, single-leg cycling resulted in greater impairments in muscle contractile function within the heavy- and severe-intensity domains, but not the moderate- and extreme-intensity domains. Perceived fatigue, pain, and effort were similar between cycling modes. This indicates that the modulatory role of muscle mass on the extent of performance fatigability is intensity domain-dependent.


Subject(s)
Bicycling , Muscle Fatigue , Muscle, Skeletal , Humans , Male , Muscle, Skeletal/innervation , Muscle, Skeletal/physiology , Young Adult , Adult , Perception/physiology , Muscle Contraction , Isometric Contraction , Electric Stimulation , Physical Exertion
9.
J Physiol ; 602(9): 1987-2017, 2024 May.
Article in English | MEDLINE | ID: mdl-38593215

ABSTRACT

When the foot dorsum contacts an obstacle during locomotion, cutaneous afferents signal central circuits to coordinate muscle activity in the four limbs. Spinal cord injury disrupts these interactions, impairing balance and interlimb coordination. We evoked cutaneous reflexes by electrically stimulating left and right superficial peroneal nerves before and after two thoracic lateral hemisections placed on opposite sides of the cord at 9- to 13-week interval in seven adult cats (4 males and 3 females). We recorded reflex responses in ten hindlimb and five forelimb muscles bilaterally. After the first (right T5-T6) and second (left T10-T11) hemisections, coordination of the fore- and hindlimbs was altered and/or became less consistent. After the second hemisection, cats required balance assistance to perform quadrupedal locomotion. Short-latency reflex responses in homonymous and crossed hindlimb muscles largely remained unaffected after staggered hemisections. However, mid- and long-latency homonymous and crossed responses in both hindlimbs occurred less frequently after staggered hemisections. In forelimb muscles, homolateral and diagonal mid- and long-latency response occurrence significantly decreased after the first and second hemisections. In all four limbs, however, when present, short-, mid- and long-latency responses maintained their phase-dependent modulation. We also observed reduced durations of short-latency inhibitory homonymous responses in left hindlimb extensors early after the first hemisection and delayed short-latency responses in the right ipsilesional hindlimb after the first hemisection. Therefore, changes in cutaneous reflex responses correlated with impaired balance/stability and interlimb coordination during locomotion after spinal cord injury. Restoring reflex transmission could be used as a biomarker to facilitate locomotor recovery. KEY POINTS: Cutaneous afferent inputs coordinate muscle activity in the four limbs during locomotion when the foot dorsum contacts an obstacle. Thoracic spinal cord injury disrupts communication between spinal locomotor centres located at cervical and lumbar levels, impairing balance and limb coordination. We investigated cutaneous reflexes during quadrupedal locomotion by electrically stimulating the superficial peroneal nerve bilaterally, before and after staggered lateral thoracic hemisections of the spinal cord in cats. We showed a loss/reduction of mid- and long-latency responses in all four limbs after staggered hemisections, which correlated with altered coordination of the fore- and hindlimbs and impaired balance. Targeting cutaneous reflex pathways projecting to the four limbs could help develop therapeutic approaches aimed at restoring transmission in ascending and descending spinal pathways.


Subject(s)
Hindlimb , Locomotion , Muscle, Skeletal , Reflex , Spinal Cord Injuries , Animals , Cats , Hindlimb/innervation , Hindlimb/physiology , Hindlimb/physiopathology , Male , Female , Spinal Cord Injuries/physiopathology , Reflex/physiology , Locomotion/physiology , Muscle, Skeletal/innervation , Muscle, Skeletal/physiology , Muscle, Skeletal/physiopathology , Skin/innervation , Thoracic Vertebrae , Forelimb/physiopathology , Forelimb/physiology , Electric Stimulation
10.
J Plast Reconstr Aesthet Surg ; 92: 288-298, 2024 May.
Article in English | MEDLINE | ID: mdl-38599000

ABSTRACT

BACKGROUND: Globally, over 1 million lower limb amputations are performed annually, with approximately 75% of patients experiencing significant pain, profoundly impacting their quality of life and functional capabilities. Targeted muscle reinnervation (TMR) has emerged as a surgical solution involving the rerouting of amputated nerves to specific muscle targets. Originally introduced to enhance signal amplification for myoelectric prosthesis control, TMR has expanded its applications to include neuroma management and pain relief. However, the literature assessing patient outcomes is lacking, specifically for lower limb amputees. This systematic review aims to assess the effectiveness of TMR in reducing pain and enhancing functional outcomes for patients who have undergone lower limb amputation. METHODS: A systematic review was performed by examining relevant studies between 2010 and 2023, focusing on pain reduction, functional outcomes and patient-reported quality of life measures. RESULTS: In total, 20 studies were eligible encompassing a total of 778 extremities, of which 75.06% (n = 584) were lower limb amputees. Average age was 46.66 years and patients were predominantly male (n = 70.67%). Seven studies (35%) reported functional outcomes. Patients who underwent primary TMR exhibited lower average patient-reported outcome measurement information system (PROMIS) scores for phantom limb pain (PLP) and residual limb pain (RLP). Secondary TMR led to improvements in PLP, RLP and general limb pain as indicated by average numeric rating scale and PROMIS scores. CONCLUSION: The systematic review underscores TMR's potential benefits in alleviating pain, fostering post-amputation rehabilitation and enhancing overall well-being for lower limb amputees.


Subject(s)
Amputation, Surgical , Lower Extremity , Quality of Life , Humans , Amputation, Surgical/adverse effects , Lower Extremity/surgery , Nerve Transfer/methods , Muscle, Skeletal/innervation , Phantom Limb/prevention & control , Phantom Limb/etiology , Patient Reported Outcome Measures , Pain Management/methods , Amputees/rehabilitation
11.
Ann Plast Surg ; 92(4): 432-436, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38527350

ABSTRACT

PURPOSE: Combined targeted muscle reinnervation with regenerative peripheral nerve interfaces ("TMRpni") is a recently described nerve management strategy that leverages beneficial elements of targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) techniques. This study aimed to evaluate the effect of TMRpni on long-term opioid consumption after amputation. We hypothesize that TMRpni decreases chronic opioid consumption in amputees. METHODS: This is a retrospective cohort study of all patients who underwent TMRpni between 2019 and 2021. These patients were age-matched at a 1:1 ratio with a control group of patients who underwent amputation without TMRpni. Statistical analysis was performed using SPSS Version 28.0. RESULTS: Thirty-one age-matched pairs of patients in the TMRpni and control groups were included. At 30 days after surgery, there was no significant difference in number of patients who required an additional refill of their opioid prescriptions (45% vs 55%, P = 0.45) or patients who continued to actively use opioids (36% vs 42%, P = 0.60). However, at 90 days after surgery, there was a significantly lower number of patients from the TMRpni group who reported continued opioid use compared with the control group (10% vs 32%, P = 0.03). CONCLUSIONS: This study demonstrates that TMRpni may translate to decreased rates of chronic opiate use. Continued study is indicated to optimize TMRpni techniques and patient selection and to determine its long-term efficacy.


Subject(s)
Amputees , Humans , Case-Control Studies , Retrospective Studies , Analgesics, Opioid/therapeutic use , Peripheral Nerves/surgery , Peripheral Nerves/physiology , Muscles , Muscle, Skeletal/innervation
12.
Clin Auton Res ; 34(2): 297-301, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38502257

ABSTRACT

Increased sympathetic drive is of prognostic significance in chronic obstructive pulmonary disease (COPD) but its determinants remain poorly understood. One potential mechanism may be chemoreflex-mediated adrenergic stimulation caused by sustained hypercapnia. This study determined the impact of non-invasive ventilation (NIV) on muscle sympathetic nerve activity (MSNA) in patients with stable hypercapnic COPD. Ten patients (age 70 ± 7 years, GOLD stage 3-4) receiving long-term NIV (mean inspiratory positive airway pressure 21 ± 7 cmH2O) underwent invasive MSNA measurement via the peroneal nerve during spontaneous breathing and NIV. Compared with spontaneous breathing, NIV significantly reduced hypercapnia (PaCO2 51.5 ± 6.9 vs 42.6 ± 6.1 mmHg, p < 0.0001) along with the burst rate (64.4 ± 20.9 vs 59.2 ± 19.9 bursts/min, p = 0.03) and burst incidence (81.7 ± 29.3 vs 74.1 ± 26.9 bursts/100 heartbeats, p = 0.04) of MSNA. This shows for the first time that correcting hypercapnia with NIV decreases MSNA in COPD.


Subject(s)
Hypercapnia , Muscle, Skeletal , Noninvasive Ventilation , Pulmonary Disease, Chronic Obstructive , Sympathetic Nervous System , Humans , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/therapy , Hypercapnia/therapy , Hypercapnia/physiopathology , Noninvasive Ventilation/methods , Male , Aged , Sympathetic Nervous System/physiopathology , Female , Middle Aged , Muscle, Skeletal/physiopathology , Muscle, Skeletal/innervation
13.
J Electromyogr Kinesiol ; 76: 102873, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38518426

ABSTRACT

The ultimate neural signal for muscle control is the neural drive sent from the spinal cord to muscles. This neural signal comprises the ensemble of action potentials discharged by the active spinal motoneurons, which is transmitted to the innervated muscle fibres to generate forces. Accurately estimating the neural drive to muscles in humans in vivo is challenging since it requires the identification of the activity of a sample of motor units (MUs) that is representative of the active MU population. Current electrophysiological recordings usually fail in this task by identifying small MU samples with over-representation of higher-threshold with respect to lower-threshold MUs. Here, we describe recent advances in electrophysiological methods that allow the identification of more representative samples of greater numbers of MUs than previously possible. This is obtained with large and very dense arrays of electromyographic electrodes. Moreover, recently developed computational methods of data augmentation further extend experimental MU samples to infer the activity of the full MU pool. In conclusion, the combination of new electrode technologies and computational modelling allows for an accurate estimate of the neural drive to muscles and opens new perspectives in the study of the neural control of movement and in neural interfacing.


Subject(s)
Electromyography , Motor Neurons , Muscle, Skeletal , Humans , Muscle, Skeletal/physiology , Muscle, Skeletal/innervation , Electromyography/methods , Motor Neurons/physiology , Muscle Contraction/physiology , Action Potentials/physiology , Computer Simulation , Models, Neurological
14.
J Physiol ; 602(9): 2061-2087, 2024 May.
Article in English | MEDLINE | ID: mdl-38554126

ABSTRACT

Motoneuron properties and their firing patterns undergo significant changes throughout development and in response to neuromodulators such as serotonin. Here, we examined the age-related development of self-sustained firing and general excitability of tibialis anterior motoneurons in a young development (7-17 years), young adult (18-28 years) and adult (32-53 years) group, as well as in a separate group of participants taking selective serotonin reuptake inhibitors (SSRIs, aged 11-28 years). Self-sustained firing, as measured by ΔF, was larger in the young development (∼5.8 Hz, n = 20) compared to the young adult (∼4.9 Hz, n = 13) and adult (∼4.8 Hz, n = 8) groups, consistent with a developmental decrease in self-sustained firing mediated by persistent inward currents (PIC). ΔF was also larger in participants taking SSRIs (∼6.5 Hz, n = 9) compared to their age-matched controls (∼5.3 Hz, n = 26), consistent with increased levels of spinal serotonin facilitating the motoneuron PIC. Participants in the young development and SSRI groups also had higher firing rates and a steeper acceleration in initial firing rates (secondary ranges), consistent with the PIC producing a steeper acceleration in membrane depolarization at the onset of motoneuron firing. In summary, both the young development and SSRI groups exhibited increased intrinsic motoneuron excitability compared to the adults, which, in the young development group, was also associated with a larger unsteadiness in the dorsiflexion torque profiles. We propose several intrinsic and extrinsic factors that affect both motoneuron PICs and cell discharge which vary during development, with a time course similar to the changes in motoneuron firing behaviour observed in the present study. KEY POINTS: Neurons in the spinal cord that activate muscles in the limbs (motoneurons) undergo increases in excitability shortly after birth to help animals stand and walk. We examined whether the excitability of human ankle flexor motoneurons also continues to change from child to adulthood by recording the activity of the muscle fibres they innervate. Motoneurons in children and adolescents aged 7-17 years (young development group) had higher signatures of excitability that included faster firing rates and more self-sustained activity compared to adults aged ≥18 years. Participants aged 11-28 years of age taking serotonin reuptake inhibitors had the highest measures of motoneuron excitability compared to their age-matched controls. The young development group also had more unstable contractions, which might partly be related to the high excitability of the motoneurons.


Subject(s)
Motor Neurons , Humans , Motor Neurons/physiology , Motor Neurons/drug effects , Adult , Adolescent , Female , Male , Child , Young Adult , Middle Aged , Action Potentials/physiology , Muscle, Skeletal/physiology , Muscle, Skeletal/growth & development , Muscle, Skeletal/innervation , Selective Serotonin Reuptake Inhibitors/pharmacology
15.
J Vis Exp ; (205)2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38526122

ABSTRACT

Over the past decade, the field of prosthetics has witnessed significant progress, particularly in the development of surgical techniques to enhance the functionality of prosthetic limbs. Notably, novel surgical interventions have had an additional positive outcome, as individuals with amputations have reported neuropathic pain relief after undergoing such procedures. Subsequently, surgical techniques have gained increased prominence in the treatment of postamputation pain, including one such surgical advancement - targeted muscle reinnervation (TMR). TMR involves a surgical approach that reroutes severed nerves as a type of nerve transfer to "target" motor nerves and their accompanying motor end plates within nearby muscles. This technique originally aimed to create new myoelectric sites for amplified electromyography (EMG) signals to enhance prosthetic intuitive control. Subsequent work showed that TMR also could prevent the formation of painful neuromas as well as reduce postamputation neuropathic pain (e.g., Residual and Phantom Limb Pain). Indeed, multiple studies have demonstrated TMR's effectiveness in mitigating postamputation pain as well as improving prosthetic functional outcomes. However, technical variations in the procedure have been identified as it is adopted by clinics worldwide. The purpose of this article is to provide a detailed step-by-step description of the TMR procedure, serving as the foundation for an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394), including nine clinics in seven countries. In this trial, TMR and two other surgical techniques for managing postamputation pain will be evaluated.


Subject(s)
Neuralgia , Phantom Limb , Humans , Amputation, Surgical , Muscle, Skeletal/innervation , Neurosurgical Procedures , Phantom Limb/surgery , Randomized Controlled Trials as Topic
16.
Surg Radiol Anat ; 46(4): 413-424, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38480593

ABSTRACT

PURPOSE: In individuals who develop drop foot due to nerve loss, several methods such as foot-leg orthosis, tendon transfer, and nerve grafting are used. Nerve transfer, on the other hand, has been explored in recent years. The purpose of this study was to look at the tibial nerve's branching pattern and the features of its branches in order to determine the suitability of the tibial nerve motor branches, particularly the plantaris muscle motor nerve, for deep fibular nerve transfer. METHODS: There were 36 fixed cadavers used. Tibial nerve motor branches were observed and measured, as were the lengths, distributions, and thicknesses of the common fibular nerve and its branches at the bifurcation region. RESULT: The motor branches of the tibial nerve that supply the soleus muscle, lateral head, and medial head of the gastrocnemius were studied, and three distinct forms of distribution were discovered. The motor branch of the gastrocnemius medial head was commonly observed as the first branch to divide, and it appeared as a single root. The nerve of the plantaris muscle was shown to be split from many origins. When the thickness and length of the motor branches measured were compared, the nerve of the soleus muscle was determined to be the most physically suited for neurotization. CONCLUSION: In today drop foot is very common. Traditional methods of treatment are insufficient. Nerve transfer is viewed as an application that can both improve patient outcomes and hasten the patient's return to society. The nerve of the soleus muscle was shown to be the best candidate for transfer in our investigation.


Subject(s)
Leg , Peroneal Nerve , Humans , Leg/innervation , Tibial Nerve , Lower Extremity , Tibia , Muscle, Skeletal/innervation
17.
Clin Auton Res ; 34(1): 177-189, 2024 02.
Article in English | MEDLINE | ID: mdl-38308178

ABSTRACT

PURPOSE: Sympathetic nerve activity towards muscle (MSNA) and skin (SSNA) regulates various physiological parameters. MSNA primarily functions in blood pressure and flow, while SSNA operates in thermoregulation. Physical and cognitive stressors have been shown to have effects on both types of sympathetic activity, but there are inconsistencies as to what these effects are. This article aims to address the discrepancies in the literature and compare MSNA and SSNA responses. METHODS: Microelectrode recordings were taken from the common peroneal nerve in 29 participants: MSNA (n = 21), SSNA (n = 16) and both MSNA and SSNA (n = 8). Participants were subjected to four different 2-min stressors: two physical (isometric handgrip task, cold pressor test) and two cognitive (mental arithmetic task, Stroop colour-word conflict test), the latter of which saw participants separated into responders and non-responders to the stressors. It was hypothesised that the physical stressors would have a greater effect on MSNA than SSNA, while the cognitive stressors would operate conversely. RESULTS: Peristimulus time histogram (PSTH) analysis showed the mental arithmetic task to significantly increase both MSNA and SSNA; the isometric handgrip task and cold pressor test to increase MSNA, but not SSNA; and Stroop test to have no significant effects on changing MSNA or SSNA from baseline. Additionally, stress responses did not differ between MSNA and SSNA in participants who had both sets of data recorded. CONCLUSIONS: This study has provided evidence to support the literature which claims cognitive stressors increase sympathetic activity, and provides much needed SSNA data in response to stressors.


Subject(s)
Hand Strength , Skin , Humans , Skin/innervation , Muscles/innervation , Blood Pressure/physiology , Sympathetic Nervous System/physiology , Cognition , Muscle, Skeletal/innervation
18.
J Muscle Res Cell Motil ; 45(2): 79-86, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38367152

ABSTRACT

Neuromuscular junctions are the synapses between motor neurons and skeletal muscle fibers, which mediate voluntary muscle movement. Since neuromuscular junctions are also tightly associated with the capping function of terminal Schwann cells, these synapses have been classically regarded as tripartite chemical synapses. Although evidences from sympathetic innervation of neuromuscular junctions was described approximately a century ago, the essential presence and functional relevance of sympathetic contribution to the maintenance and modulation of neuromuscular junctions was demonstrated only recently. These findings shed light on the pathophysiology of different clinical conditions and can optimize surgical and clinical treatment modalities for skeletal muscle disorders.


Subject(s)
Muscle, Skeletal , Neuromuscular Junction , Sympathetic Nervous System , Neuromuscular Junction/metabolism , Humans , Muscle, Skeletal/innervation , Animals
19.
J Hand Surg Eur Vol ; 49(6): 783-791, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38366374

ABSTRACT

Selective nerve transfers are used in the setting of upper limb amputation to improve myoelectric prosthesis control. This surgical concept is referred to as targeted muscle reinnervation (TMR) and describes the rerouting of the major nerves of the arm onto the motor branches of the residual limb musculature. Aside from providing additional myosignals for prosthetic control, TMR can treat and prevent neuroma pain and possibly also phantom limb pain. This article reviews the history and current applications of TMR in upper limb amputation, with a focus on practical considerations. It further explores and identifies technological innovations to improve the man-machine interface in amputation care, particularly regarding implantable interfaces, such as muscle electrodes and osseointegration. Finally, future clinical directions and possible scientific avenues in this field are presented and critically discussed.


Subject(s)
Artificial Limbs , Bionics , Muscle, Skeletal , Nerve Transfer , Upper Extremity , Humans , Nerve Transfer/methods , Upper Extremity/innervation , Upper Extremity/surgery , Muscle, Skeletal/innervation , Muscle, Skeletal/surgery , Muscle, Skeletal/transplantation , Amputation, Surgical
20.
Int. j. morphol ; 42(1): 166-172, feb. 2024. ilus
Article in English | LILACS | ID: biblio-1528834

ABSTRACT

SUMMARY: Peripheral nerve injury is an extremely important medical and socio-economic problem. It is far from a solution, despite on rapid development of technologies. To study the effect of long-term electrical stimulation of peripheral nerves, we used a domestically produced electrical stimulation system, which is approved for clinical use. The study was performed on 28 rabbits. Control of regeneration was carried out after 3 month with morphologic techniques. The use of long-term electrostimulation technology leads to an improvement in the results of the recovery of the nerve trunk after an injury, both directly at the site of damage, when stimulation begins in the early period, and indirectly, after the nerve fibers reach the effector muscle.


La lesión de los nervios periféricos es un problema médico y socioeconómico extremadamente importante. Sin embargo, y a pesar del rápido desarrollo de las tecnologías, aún no tiene solución. Para estudiar el efecto de la estimulación eléctrica a largo plazo de los nervios periféricos, utilizamos un sistema de estimulación eléctrica de producción nacional, que está aprobado para uso clínico. El estudio se realizó en 28 conejos. El control de la regeneración se realizó a los 3 meses con técnicas morfológicas. El uso de tecnología de electro estimulación a largo plazo conduce a una mejora en los resultados de la recuperación del tronco nervioso después de una lesión, tanto directamente en el lugar del daño, cuando la estimulación comienza en el período temprano, como indirectamente, después de que las fibras nerviosas alcanzan el músculo efector.


Subject(s)
Animals , Rabbits , Electric Stimulation/methods , Peripheral Nerve Injuries/therapy , Peripheral Nerves , Muscle, Skeletal/innervation , Recovery of Function , Nerve Regeneration
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