Maximal Compound Action Potential Research Articles

Inducing ipsilateral motor-evoked potentials in the biceps brachii muscle in healthy humans.

To assess reticulospinal tract excitability, high-intensity transcranial magnetic stimulation (TMS) has been used to elicit ipsilateral motor-evoked potentials (iMEPs). However, there is no consensus on robust and valid methods for use in human studies. The present study proposes a standardized method for eliciting and analysing iMEPs in the biceps brachii. Twenty-four healthy young adults participated in this study. Electromyography (EMG) electrodes recorded contralateral MEPs (cMEPs) from the right and iMEPs from the left biceps brachii. A dynamic preacher curl task was used with ~15% of the subject's one-repetition maximum load. The protocol included maximal compound action potential (M-max) determination of the right biceps brachii muscle, TMS hotspot determination, and four sets of five repetitions where 100% stimulator output was delivered at an elbow angle of 110° of flexion. We normalized cMEP amplitude by M-max (% M-max) and iMEP by cMEP amplitude ratio (ICAR). Clear iMEPs above background EMG were observed in 21 subjects (88%, ICAR = .31 ± .19). Good-to-excellent agreement (intraclass correlation coefficient [ICC] = .795-1.000) and low bias (.01-.08 mV and .60-1.11 ms) were demonstrated when comparing two different analysis methods (i.e. fixed time-window vs. manual onset detection) to determine the cMEP and iMEP amplitude and latency, respectively. Most subjects demonstrated clear iMEPs above background EMG triggered at a pre-determined joint angle during a light-load dynamic preacher curl exercise. Similar results were obtained when comparing a single-trial manual identification of iMEP and a semi-automated time-window data analysis approach.

Cryoneurolysis of the saphenous nerve in the pig: A proof-of-principle investigation

ObjectiveTo determine if in vivo cryoneurolysis inhibits ex vivo compound action potential (CAP) conduction in the porcine saphenous nerve and if this occurs rapidly enough to justify performing the technique before stifle surgery. Study designBlinded, controlled, randomized, preclinical study. AnimalsA group of eight healthy, 8 weeks old, intact, female pigs anesthetized for an unrelated terminal study. MethodsBoth saphenous nerves of each pig were exposed surgically, and 15 mm of a 20 gauge, closed-tip, commercial cryoneurolysis cannula were inserted cranial to each nerve within the neurovascular fascial sheath along its long axis. The cannula was only actuated on one limb, according to random allocation. Nerves were excised within 15 minutes of actuation and underwent testing in a nerve conduction chamber, where stimulus voltage was increased sequentially (from 0.1 to ≤ 1.9 V). An anesthesiologist blinded to treatment viewed recordings of time versus voltage for each nerve and answered ‘yes’ or ‘no’ when asked if an evoked CAP was observed. Fisher’s exact test evaluated the incidence of CAP conduction between groups (p < 0.05 considered significant). Nerves were submitted for hematoxylin and eosin staining for blinded histopathological examination. ResultsA CAP was conducted in 8/8 and 1/8 of the control and treated nerves, respectively (p = 0.001). Maximal responses in control nerves were 1.92 ± 0.19 mV (mean ± standard error). In the single treated nerve that conducted a CAP, the maximal CAP amplitude was 0.4 mV, lower than the lowest maximal CAP (1.19 mV) in the control nerves. All control nerves were histologically normal, and all treated nerves displayed mild perivascular and perineural inflammation (cuffs of lymphocytes, plasma cells and eosinophils, and edema). Conclusions and clinical relevanceThe rapid inhibition of CAP conduction warrants clinical investigation of saphenous cryoneurolysis for both intraoperative antinociception and postoperative analgesia in pigs undergoing experimental stifle surgery.

Cortical and spinal responses to short-term strength training and detraining in young and older adults in rectus femoris muscle

IntroductionStrength training mitigates the age-related decline in strength and muscle activation but limited evidence exists on specific motor pathway adaptations.MethodsEleven young (22–34 years) and ten older (66–80 years) adults underwent five testing sessions where lumbar-evoked potentials (LEPs) and motor-evoked potentials (MEPs) were measured during 20 and 60% of maximum voluntary contraction (MVC). Ten stimulations, randomly delivered, targeted 25% of maximum compound action potential for LEPs and 120, 140, and 160% of active motor threshold (aMT) for MEPs. The 7-week whole-body resistance training intervention included five exercises, e.g., knee extension (5 sets) and leg press (3 sets), performed twice weekly and was followed by 4 weeks of detraining.ResultsYoung had higher MVC (~ 63 N·m, p = 0.006), 1-RM (~ 50 kg, p = 0.002), and lower aMT (~ 9%, p = 0.030) than older adults at baseline. Young increased 1-RM (+ 18 kg, p < 0.001), skeletal muscle mass (SMM) (+ 0.9 kg, p = 0.009), and LEP amplitude (+ 0.174, p < 0.001) during 20% MVC. Older adults increased MVC (+ 13 N·m, p = 0.014), however, they experienced decreased LEP amplitude (− 0.241, p < 0.001) during 20% MVC and MEP amplitude reductions at 120% (− 0.157, p = 0.034), 140% (− 0.196, p = 0.026), and 160% (− 0.210, p = 0.006) aMT during 60% MVC trials. After detraining, young and older adults decreased 1-RM, while young adults decreased SMM.ConclusionHigher aMT and MEP amplitude in older adults were concomitant with lower baseline strength. Training increased strength in both groups, but divergent modifications in cortico-spinal activity occurred. Results suggest that the primary locus of adaptation occurs at the spinal level.

Test-retest reliability of cortico-spinal measurements in the rectus femoris at different contraction levels.

Single-pulse Transcranial Magnetic Stimulation (TMS) and, very recently, lumbar stimulation (LS) have been used to measure cortico-spinal excitability from various interventions using maximal or submaximal contractions in the lower limbs. However, reliability studies have overlooked a wide range of contraction intensities for MEPs, and no reliability data is available for LEPs. This study investigated the reliability of motor evoked potentials and lumbar evoked potentials at different stimulation intensities and contraction levels in m.rectus femoris. Twenty-two participants performed non-fatiguing isometric knee extensions at 20 and 60% of maximum voluntary contraction (MVC). LS induced a lumbar-evoked potential (LEP) of 25 and 50% resting maximal compound action potential (M-max). TMS stimulator output was adjusted to 120, 140, and 160% of active motor threshold (aMT). In each contraction, a single MEP or LEP was delivered. Ten contractions were performed at each stimulator intensity and contraction level in random order. Moderate-to-good reliability was found when LEP was normalized to M-max/Root Mean Square in all conditions (ICC:0.74-0.85). Excellent reliability was found when MEP was normalized to Mmax for all conditions (ICC > 0.90) at 60% of MVC. Good reliability was found for the rest of the TMS conditions. Moderate-to-good reliability was found for silent period (SP) elicited by LS (ICC: 0.71-0.83). Good-to-excellent reliability was found for SP elicited by TMS (ICC > 0.82). MEPs and LEPs elicited in m.rectus femoris appear to be reliable to assess changes at different segments of the cortico-spinal tract during different contraction levels and stimulator output intensities. Furthermore, the TMS- and LS- elicited SP was a reliable tool considered to reflect inhibitory processes at spinal and cortical levels.

Acute effect of tendon vibration applied during isometric contraction at two knee angles on maximal knee extension force production

The aim of the current study was to investigate the effect of a single session of prolonged tendon vibration combined with low submaximal isometric contraction on maximal motor performance. Thirty-two young sedentary adults were assigned into two groups that differed based on the knee angle tested: 90° or 150° (180° = full knee extension). Participants performed two fatigue-inducing exercise protocols: one with three 10 min submaximal (10% of maximal voluntary contraction) knee extensor contractions and patellar tendon vibration (80 Hz) another with submaximal knee extensor contractions only. Before and after each fatigue protocol, maximal voluntary isometric contractions (MVC), voluntary activation level (assessed by the twitch interpolation technique), peak-to-peak amplitude of maximum compound action potentials of vastus medialis and vastus lateralis (assessed by electromyography with the use of electrical nerve stimulation), peak twitch amplitude and peak doublet force were measured. The knee extensor fatigue was significantly (P<0.05) greater in the 90° knee angle group (-20.6% MVC force, P<0.05) than the 150° knee angle group (-8.3% MVC force, P = 0.062). Both peripheral and central alterations could explain the reduction in MVC force at 90° knee angle. However, tendon vibration added to isometric contraction did not exacerbate the reduction in MVC force. These results clearly demonstrate that acute infrapatellar tendon vibration using a commercial apparatus operating at optimal conditions (i.e. contracted and stretched muscle) does not appear to induce knee extensor neuromuscular fatigue in young sedentary subjects.

Alterations of peripheral nerve excitability in an experimental autoimmune encephalomyelitis mouse model for multiple sclerosis

BackgroundExperimental autoimmune encephalomyelitis (EAE) is the most commonly used and clinically relevant murine model for human multiple sclerosis (MS), a demyelinating autoimmune disease characterized by mononuclear cell infiltration into the central nervous system (CNS). The aim of the present study was to appraise the alterations, poorly documented in the literature, which may occur at the peripheral nervous system (PNS) level.MethodsTo this purpose, a multiple evaluation of peripheral nerve excitability was undertaken, by means of a minimally invasive electrophysiological method, in EAE mice immunized with the myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide, an experimental model for MS that reproduces, in animals, the anatomical and behavioral alterations observed in humans with MS, including CNS inflammation, demyelination of neurons, and motor abnormalities. Additionally, the myelin sheath thickness of mouse sciatic nerves was evaluated using transmission electronic microscopy.ResultsAs expected, the mean clinical score of mice, daily determined to describe the symptoms associated to the EAE progression, increased within about 18 days after immunization for EAE mice while it remained null for all control animals. The multiple evaluation of peripheral nerve excitability, performed in vivo 2 and 4 weeks after immunization, reveals that the main modifications of EAE mice, compared to control animals, are a decrease of the maximal compound action potential (CAP) amplitude and of the stimulation intensity necessary to generate a CAP with a 50% maximum amplitude. In addition, and in contrast to control mice, at least 2 CAPs were recorded following a single stimulation in EAE animals, reflecting various populations of sensory and motor nerve fibers having different CAP conduction speeds, as expected if a demyelinating process occurred in the PNS of these animals. In contrast, single CAPs were always recorded from the sensory and motor nerve fibers of control mice having more homogeneous CAP conduction speeds. Finally, the myelin sheath thickness of sciatic nerves of EAE mice was decreased 4 weeks after immunization when compared to control animals.ConclusionsIn conclusion, the loss of immunological self-tolerance to MOG in EAE mice or in MS patients may not be only attributed to the restricted expression of this antigen in the immunologically privileged environment of the CNS but also of the PNS.

SPARC: A Hybrid Computational Approach to Classify Vagal C Fiber Functions

Neuroscience conventionally categorizes all unmyelinated fibers into an undifferentiated C fiber classification, implying a common function and impeding further classification. This is highly problematic, especially for autonomic nerves like the abdominal vagus, which contains &gt;99% unmyelinated C fibers. We require a modern classification framework to discriminate differences among these important, underappreciated messengers. One important and easily measurable property of C fibers is their conduction speed, which relates directly to their morphology or caliber. We present a hybrid computational modeling approach, integrating biophysical (HH‐type) and classical (e.g., Gasser, Erlanger and Grundfest) methods, to enable the classification of C fiber function according to fiber caliber/speed.The Hybrid Nerve Response Modeling and Classification System is a tool to classify C fiber functions with respect to fiber caliber and radial location within a nerve. Biophysical models of HH axons contribute a bottom‐up model of fiber activation that explains the influence of the electrode configuration and other factors on fiber activation threshold and the measured compound action potential (CAP) profile. Alternatively, modeled CAPs can be generated through superposition of individual axon contributions (single fiber action potentials; SFAPs), relating fiber caliber distribution data to SFAP shape and conduction properties; this classical model of the CAP accurately predicts the experimentally measured maximal CAP shape. Using published and novel nerve ultrastructure data, we unified the biophysical and classical modeling approaches in a new simulation framework that predicts graded CAP profiles in response to bipolar, constant‐current stimuli delivered through various cuff electrode configurations.In this work, we demonstrate how the Hybrid Model can be used to discern the spatial and size distribution of unmyelinated C fibers from the CAP of the ventral gastric branch of the rat vagus nerve. Through our web‐based user interface (Fig. 1), we will show how our system can predict the activation threshold of unmyelinated fibers in any nerve cross section as a function of the individual fiber size and spatial location within a common set of electrode geometries. We will provide examples of how this information may be used to accelerate our delineation of the various functions of C fibers using measured associations between nerve and organ responses to stimulation.Support or Funding InformationFunding AcknowledgmentsThis work was supported by NIH SPARC OT2 OD023847 (PI: Powley), NIH SPARC OT2 OD025340 (PI: Grill) and NIH SPARC OT2 OD026585 01 (PI: Havton)[LEFT] Web‐based interface for the Hybrid Model. [FAR RIGHT] Segmented electron micrograph of n = 4776 C fibers from a rat ventral vagal gastric branch. The user interface lets users track the location (e.g., spatial location in the nerve cross section and temporal location in the CAP response) and relative activation thresholds of C fibers with respect to observed changes in the downstream physiology of the organs and tissues they supply.Figure 1

Hyperexcitability in synaptic and firing activities of spinal motoneurons in an adult mouse model of amyotrophic lateral sclerosis

Hyperexcitability is hypothesized to contribute to the degeneration of spinal motoneurons (MNs) in amyotrophic lateral sclerosis (ALS). Studies, thus far, have not linked hyperexcitability to the intrinsic properties of MNs in the adult ALS mouse model with the G93A-mutated SOD1 protein (mSOD1G93A). In this study, we obtained two types of measurements: ventral root recordings to assess motor output and intracellular recordings to assess synaptic properties of individual MNs. All studies were carried out in an in vitro preparation of the sacral spinal cords of mSOD1G93A mice and their non-transgenic (NT) littermates, both in the age range of 50–90days. Ventral root recordings revealed that maximum compound action potentials (coAPs) evoked by a short-train stimulation of corresponding dorsal roots were similar between the two types of mice. Although the progressive depression of coAPs was present during the train stimulation in all recordings, the coAP depression in mSOD1G93A mice was to a lesser extent, which suggests an increased firing tendency in mSOD1G93A MNs. Intracellular recordings showed no changes in fast excitatory postsynaptic potentials (EPSPs) in mSOD1G93A MNs. However, recording did show that oscillating EPSPs (oEPSPs) were induced by poly-EPSPs at a higher frequency and by less-intense electrical stimulation in mSOD1G93A MNs. These oEPSPs were dependent upon the activities of spinal network and N-methyl-d-aspartate receptors (NMDARs), and were subjected to riluzole modulation. Taken together, these findings revealed abnormal electrophysiology in mSOD1G93A MNs that could underlie ALS excitotoxicity.

S70 Estimating motor unit number from CMAP scans – MScanFIT MUNE

Objectives There is no method that can measure the exact number of motor units, therefore motor unit number estimation (MUNE) methods have been developed. Most MUNE methods are based on estimating the size of an average surface-recorded motor unit potential and dividing that value into maximal compound action potential (CMAP). This makes the estimates strongly influenced by any bias in unit selection. Other limitations of the existing MUNE methods are the presence of subjectivity in the estimation process, the failure to sample enough units or the long time to perform the test or analyse. To overcome these limitations, a new MUNE method was recently developed, so-called ‘MScanFit MUNE‘, (MScan). Methods MScan meets the above-mentioned criticisms by fitting a model to a detailed stimulus-response curve (∼500 stimuli) or ‘CMAP scan’, taking into account the threshold variability of all the units, and avoiding subjectivity. Results The method has been found to be accurate (mean absolute error 7%) for simulated data.The reproducibility and the diagnostic utility of MScan were found to be good in healthy controls and in patients with amyotrophic lateral sclerosis (ALS) and different types of polyneuropathy. Discussion MScan revealed in neurofibromatosis-type-2 patients denervation and reinnervation in peripheral nerves suggesting that it may be used to quantify and monitor disease progression. Conclusions MScan is a novel method with good reproducibility, and may be performed in less than five minutes. Significance Preliminary results suggest MScan as a promising MUNE method with potential to be used in diagnoses and monitoring disease progression, particularly in ALS.

18. Dysfunctional properties of single motor units in ALS

Background Abnormalities in the excitability of lower motor neurons in amyotrophic lateral sclerosis have been extensively examined using threshold tracking techniques. Several studies have found evidence for a down-regulation of K+, and an up-regulation of Na+ conductances. The results as a whole however have been somewhat mixed. Threshold-tracking studies test the excitability of a fixed fraction of the maximal compound action potential, and for most disease processes this accurately reflects the excitability of all axons of the same modality within a nerve. However, in ALS such a relationship is unreliable. The slow inexorable process of degeneration of individual motor units is likely to change their excitability, with hyperexcitability and reinnervation believed to impact on their viability. In ALS the disease process itself presents the opportunity to study single motor units identifiable in the recruitment curve, and in particular the large units which result from reinnervation of muscle fibres from motor units that have undergone degeneration. Such measurements provide an unequivocal snapshot of the excitability of an individual motor unit. Methods Measurements of the excitability of single motor units in the intrinsic muscles of the split hand were undertaken in 7 subjects, and mathematical modelling was performed to examine the nature of changes in individual motor units. Results As expected, the ALS single motor unit recordings were more varied in nature when compared to normal single motor units from a previous study. Significant differences were observed with a greater rheobasic current and lower resting I/V slope, relative refractory period and ‘fanned out’ threshold electrotonus in the ALS single motor units compared to the normal controls. Conclusions The excitability of individual motor units in ALS is heterogeneous in nature, with axonal abnormalities correlated with disease progression. The underlying biophysical mechanisms of these abnormal motor units were best modelled by an increase in the Na+/K+-ATPase pump current, and a near halving of slow K+ conductances. The relative proportions of changes to the Na+/K+-ATPase pump and slow K+ conductances are likely to vary between individual motor units, and with disease progression.

Transcranial magnetic stimulation intensity affects exercise-induced changes in corticomotoneuronal excitability and inhibition and voluntary activation

Transcranial magnetic stimulation (TMS) of the motor cortex during voluntary contractions elicits electrophysiological and mechanical responses in the target muscle. The effect of different TMS intensities on exercise-induced changes in TMS-elicited variables is unknown, impairing data interpretation. This study aimed to investigate TMS intensity effects on maximal voluntary activation (VATMS), motor-evoked potentials (MEPs), and silent periods (SPs) in the quadriceps muscles before, during, and after exhaustive isometric exercise. Eleven subjects performed sets of ten 5-s submaximal isometric quadriceps contractions at 40% of maximal voluntary contraction (MVC) strength until task failure. Three different TMS intensities (I100, I75, I50) eliciting MEPs of 53±6%, 38±5% and 25±3% of maximal compound action potential (Mmax) at 20% MVC were used. MEPs and SPs were assessed at both absolute (40% baseline MVC) and relative (50%, 75%, and 100% MVC) force levels. VATMS was assessed with I100 and I75. When measured at absolute force level, MEP/Mmax increased during exercise at I50, decreased at I100 and remained unchanged at I75. No TMS intensity effect was observed at relative force levels. At both absolute and relative force levels, SPs increased at I100 and remained stable at I75 and I50. VATMS assessed at I75 tended to be lower than at I100. TMS intensity affects exercise-induced changes in MEP/Mmax (only when measured at absolute force level), SPs, and VATMS. These results indicate a single TMS intensity assessing maximal voluntary activation and exercise-induced changes in corticomotoneuronal excitability/inhibition may be inappropriate.

The Effect of Creatine Loading on Neuromuscular Fatigue in Women

This study aimed to examine the effects of intermittent isometric fatigue on maximal voluntary contraction (MVC) strength, percent voluntary activation (%VA), peak twitch force (PTF), peak rate of force development (PRFD), half relaxation time (HRT), and maximal compound action potential (M-wave) amplitude of the soleus and medial gastrocnemius muscles before and after creatine (Cr) loading. Using a double-blinded, placebo-controlled, randomized design, 12 women were assigned to a Cr (n = 6; mean age ± SD = 23.3 ± 3.0 yr) or placebo (PL; n = 6; mean age ± SD = 21.3 ± 1.6 yr) group. Participants supplemented four times daily for 5 d with 5 g of Cr + 10 g of fructose or 10 g of fructose. At baseline and after testing, an isometric MVC and the twitch interpolation procedure were used before and after a 4-min isometric fatigue protocol of the plantarflexor muscles, which consisted of six intermittent duty cycles per minute (7-s contraction, 3-s relaxation) at 70% MVC. There were no interactions between the Cr and PL groups (P > 0.05) for any dependent variable. The fatigue protocol reduced voluntary strength (-17.8%, P < 0.001) and %VA (-3.7%, P = 0.005). Baseline PTF (P < 0.005) and PRFD (P < 0.001) values were less than those of all respective time points, but PTF value decreased from 3 min to 4 min and after testing (P < 0.005). HRT increased from baseline to minutes 1 and 2 and then returned to baseline at minutes 3 and 4 and after testing. The M-wave did not change (P > 0.05). Five days of Cr loading did not influence isometric force, %VA, evoked twitch properties, or the central and peripheral aspects of fatigue measured in this study.

The Neuroprotective Ability of Polyethylene Glycol is Affected by Temperature in Ex Vivo Spinal Cord Injury Model

Immediate membrane sealing after spinal cord injury (SCI) can prevent further degradation and result in ultimate functional recovery. It has been reported that polyethylene glycol (PEG) can repair membrane damage caused by mechanical insults to the spinal cord. Furthermore, membrane fluidity and its sealing process vary at different temperatures. Here, we have assessed the possible synergistic effects of PEG and temperature on the repair of neural membranes in an SCI model. The effects of PEGs (400, 1,000 and 2,000 Da) were studied at different temperatures (25, 37 and 40 °C) by means of compound action potential (CAP) recovery and a lactate dehydrogenase (LDH) assay. Isolated spinal cords were mounted in a double sucrose gap chamber, where the amplitude and area of CAPs were recorded after implementing injury, in the presence and absence of PEG. Moreover, the LDH assay was used to assess the effects of PEG on membrane resealing. Data showed that the least CAP recovery occurred at 25 °C, followed by 37 and 40 °C, in all treated groups. Moreover, maximum CAP amplitude recovery, 65.46 ± 5.04 %, was monitored in the presence of PEG400 at 40 °C, followed by 41.49 ± 2.41 % in PEG1000 and 37.36 ± 1.62 % in PEG2000. Furthermore, raising the temperature from 37 to 40 °C significantly increased CAP recovery in the PEG2000 group. Similar recovery patterns were obtained by CAP area measurements and LDH assay. The results suggest that application of low-molecular weight PEG (PEG400) in mild hyperthermia conditions (40 °C) provides the optimum condition for membrane sealing in SCI model.

Mechanisms of vincristine-induced neurotoxicity: Possible reversal by erythropoietin

Vincristine (VCR) is a potent anticancer drug, but neurotoxicity is one of its most important dose-limiting toxicities. In this study, we investigated the neurotoxic effect of VCR, the possible mechanisms and the role of erythropoietin (EPO) in the protection against VCR-induced neurotoxicity in a rat model. The neurotoxicity of VCR and protective effect of EPO were examined using the tail flick test and by recording electrophysiological characteristics in isolated sciatic nerve. To elucidate the underlying mechanisms, mRNA expression of N-methyl-D-aspartate (NMDA) receptor, an index of glutamate excitotoxicity, and calcitonin gene-related peptide (CGRP), an important regulator of vascular tone, were measured in both spinal cord and sciatic nerves using an RT-PCR method. After intraperitoneal injection at a dose of 150 μg/kg three times weekly for five consecutive weeks, VCR significantly decreased the latency of tail withdrawal reflex, the amplitude of maximum compound action potential (MCAP) and chronaxie, and prolonged the duration of action potential (AP) and relative refractory period (RRP), but it had no effect on conduction velocity. VCR increased NMDA receptor expression and decreased CGRP expression. Forty μg/kg of EPO improved all VCR-induced changes, except chronaxie, while a higher dose of 80 μg/kg reversed all parameters and its effect was more prominent on tail flick test latency and NMDA receptor expression. These results suggested that VCR might cause increased nerve excitability and induce a state of glutamate excitotoxicity through enhancing NMDA receptor expression and diminishing CGRP expression, thus resulting in axonal degeneration. EPO had an obvious neuroprotective effect probably through decreasing NMDA receptor expression and increasing CGRP expression both centrally and peripherally.

Voluntary activation of the triceps surae in prepubertal children

The activation capacities and neuromuscular efficiency (NME) of the triceps surae (TS) of prepubescent children (7–11 years) and adults were evaluated during submaximal and maximal (MVC) isometric plantarflexion to determine whether they varied with age. TS-EMG were obtained by summing-up the rectified electromyograms of the soleus and gastrocnemii muscles; these data were quantified using a sliding average method and normalized with reference to the TS maximal compound action potential (TS-M-wave). The maximal EMG increased significantly with age in the children, but less than MVC, what led to a significant increase in NME Max (MVC/TS-EMG max ratio). The EMG–torque relationship indicated an age-related overactivation of TS at low torque, what led to a lower NME Sub-max (inverse of the slope of the EMG–torque relationship) for the youngest children. The overactivation of TS was accompanied by contraction of the TA, which decreased with age. The youngest children were also less able to maintain a target torque and muscle activation. Finally, the twitch interpolated method revealed an age-dependant activation deficit. We conclude that central mechanisms are the main cause of the lower torques developed by children and they appear to vary with age in prepubertal children.

Further prospective findings with compound action potentials from Nucleus 24 cochlear implants

The purpose of this study was to gain greater understanding of compound action potential (CAP) specific characteristics including: slope of the growth function, P1–N1 amplitude, threshold and latencies of P1 and N1 measured in cochlear implant users. Experienced adult subjects underwent behavioral threshold (T) measurement and electrically elicited stapedial reflex (eSR) recording, followed by CAP measurements on six selected electrodes. Based on the electrically elicited stapedial reflex threshold (eSRT), maximum stimulation level for each measured electrode was set. Relationships among the three thresholds of the above measures and maximum CAP P1–N1 amplitude and slope of the growth function were statistically evaluated for each measured electrode. Threshold of the CAP response showed relationships of similar strength with eSRT and T ( r=0.69 and 0.61, respectively). For both slope of the growth function and CAP P1–N1 amplitude, a statistically significant relationship with cochlear place was found. Both specific characteristics of CAP measurement for the most apical electrodes were roughly double those for the most basal electrode ( α=0.05). This may be partially explained by cochlear anatomy and is consistent with prior mammalian and human studies showing increasing density and survival of spiral ganglion cells in the regions corresponding to intracochlear electrode placement from basal to apical electrodes (90–360°).

Conduction failure of action potentials in sensory sural nerves of undernourished rats

In order to determine possible functional and morphometrical alterations produced by perinatal undernourishment on peripheral nerves, sensory sural nerves from control and undernourished rats of 30 and 90 postnatal days of age were dissected and divided in two segments, one for recording the compound action potential (CAP) and the other for histological examination. Nerves from undernourished animals showed maximal CAP responses of smaller amplitude and area, larger trial-to-trial variability in area, and a significant reduction in axonal myelin sheath thickness than nerves from control animals. It is suggested that perinatal undernourishment produces changes in axonal myelin sheath structure, resulting in severe alterations in the generation and propagation of action potentials (block and/or intermittent conduction) in sensory afferent fibers in the rat.

Facial electroneurography on the contralateral side in unilateral Bell's palsy

In this study, ten patients who exhibited severe unilateral Bell's palsy of the House-Brackmann grade V underwent facial electroneurography (ENoG) on the contralateral, healthy side. Serial ENoG was conducted in seven consecutive sessions within 6 months at a given current intensity level of stimulation. According to our results, all the patients presented a rise in the maximum compound-action potential (MCAP) amplitude on the healthy side within 20 to 45 days from the onset of the palsy and shortly after the onset of the recovery of the facial function. This was attributed to the central contralateral compensatory process, which restores balanced facial function. Based on our data, a hypothetical model is shown, which demonstrates the clinical course of the contralateral MCAP values and reflects the plasticity effect of the central nervous system after the onset of Bell's palsy.

Attenuation of the electrophysiological function of the corpus callosum after fluid percussion injury in the rat.

This study describes a new method used to evaluate axonal physiological dysfunction following fluid percussion induced traumatic brain injury (TBI) that may facilitate the study of the mechanisms and novel therapeutic strategies of posttraumatic diffuse axonal injury (DAI). Stimulated compound action potentials (CAP) were recorded extracellularly in the corpus callosum of superfused brain slices at 3 h, and 1, 3, and 7 days following central fluid percussion injury and demonstrated a temporal pattern of functional deterioration. The maximal CAP amplitude (CAPA) covaried with the intensity of impact 1 day following sham, mild (1.0-1.2 atm), and moderate (1.8-2.0 atm) injury (p < 0.05; 1.11 +/- 0.10, 0.82 +/- 0.11, and 0.49 +/- 0.08 mV, respectively). The CAPA in sham animals were approximately 1.1 mV and did not vary with survival interval (3 h, and 1, 3, and 7 days); however, they were significantly decreased at each time point following moderate injury (p < 0.05; 0.51 +/- 0.11, 0.49 +/- 0.08, 0.46 +/- 0.10, and 0.75 +/- 0.13 mV, respectively). The CAPA at 7 days in the injured group were higher than at 3 h, and 1 and 3 days. H&E and amyloid precursor protein (APP) light microscopic analysis confirmed previously reported trauma-induced axonal injury in the corpus callosum seen after fluid percussion injury. Increased APP expression was confirmed using Western blotting showing significant accumulation at 1 day (IOD 913.0 +/- 252.7; n = 3; p = 0.05), 3 days (IOD 753.1 +/- 159.1; n = 3; p = 0.03), and at 7 days (IOD 1093.8 = 105.0; n = 3; p = 0.001) compared to shams (IOD 217.6 +/- 20.4; n = 3). Thus, we report the characterization of white matter axonal dysfunction in the corpus callosum following TBI. This novel method was easily applied, and the results were consistent and reproducible. The electrophysiological changes were sensitive to the early effects of impact intensity, as well as to delayed changes occurring several days following injury. They also indicated a greater degree of attenuation than predicted by APP expression changes alone.

Improved functional recovery of denervated skeletal muscle after temporary sensory nerve innervation

Prolonged muscle denervation results in poor functional recovery after nerve repair. The possible protective effect of temporary sensory innervation of denervated muscle, prior to motor nerve repair, has been examined in the rat. Soleus and gastrocnemius muscles were denervated by cutting the tibial nerve, and the peroneal nerve was then sutured to the transected distal tibial nerve stump either immediately or after two, four or six months. In half of the animals with delayed repair, the saphenous (sensory) nerve was temporarily attached to the distal nerve stump. Muscles were evaluated three months after the peroneal-to-tibial union, and were compared with each other, with unoperated control muscles and with untreated denervated muscles. After four to six months of sensory “protection”, gastrocnemius muscles weighed significantly more than unprotected muscles, and both gastrocnemius and soleus muscles exhibited better preservation of their structure, with less fiber atrophy and connective tissue hyperplasia. The maximum compound action potentials were significantly larger in gastrocnemius and soleus muscles following sensory protection, irrespective of the delay in motor nerve union. Isometric force, although less than in control animals and in those with immediate nerve repair, remained reasonably constant after sensory protection, while in unprotected muscles there was a progressive and significant decline as the period of denervation lengthened. We interpret these results as showing that, although incapable of forming excitable neuromuscular junctions, sensory nerves can nevertheless exert powerful trophic effects on denervated muscle fibers. We propose that these findings indicate a useful strategy for improving the outcome of peripheral nerve surgery.