Background Contraction Research Articles

#1621 Quantifying ureter smooth muscle electrophysiology from calcium transient images to understand abnormal peristaltic contraction

Abstract Background and Aims Abnormal peristaltic contraction of the ureter smooth muscle (USM) causes acute kidney stone episodes. Intracellular electrical activities like membrane depolarization and action potentials play important roles in modulating the USM contraction by releasing intracellular calcium from the sarcoplasmic reticulum. Therefore, an electrophysiological study will help to assess the USM cell's electrical activities and in diagnosing abnormal USM contraction. The objective of this study is to quantify the contribution of ionic currents in shaping experimental calcium transient profiles using in-silico electrophysiological modeling. Method The simultaneous experimental recording of action potential (AP) and intracellular calcium transient images from the mouse ureter is obtained. The single isolated USM cell model comprises several voltage-gated ion channels, such as two voltage-gated calcium (T—type, and L—type) channels, one voltage-gated fast potassium (KA) channel, one calcium-dependent large conductance potassium channel, and an HCN channel. To describe the calcium-dependent gating of Ca2+-dependent potassium channels and to update the equilibrium potential of the Ca2+ ion, the intracellular Ca2+ concentration is updated during the simulation period. Results Simulation of simultaneous recordings of AP and cytosolic calcium [Ca2+]i are done on a single isolated cell. The model shows [Ca2+]i as a function of synaptic input-induced AP to simulate extracted experimental data, where Ca2+ transient is recorded simultaneously during AP in mouse USM cells. Fig. 1 shows both experimental and simulation of AP (A) and Calcium transient (B) in the USM cell. In our model, the radius “r” and time constant τ of the shell influence the Ca2+ transient profile. In the USM cell model, the submembrane calcium transient occurs from a depth of 0.1 μm to a depth of 0.6 μm. We have investigated whether Ca2+ current via the L-type Ca2+ channel is responsible for the firing of APs with fast upstroke generation. The AP and calcium transients are demolished with the absence of the L-type Ca2+ channel. Conclusion From this study, it is found that inhibition of the L-type Ca2+ channel not only prevented AP generation, it also reduced the cytosolic Ca2+ transient. This study supports the application of L-type Ca2+ channel inhibitor as a potential drug for abnormal peristaltic contraction of the ureter smooth muscle.

Quadriceps motor evoked torque is a reliable measure of corticospinal excitability in individuals with anterior cruciate ligament reconstruction

This study comprehensively evaluated the test–retest reliability of raw and normalized quadriceps motor evoked responses elicited by transcranial magnetic stimulation (TMS) in individuals with anterior cruciate ligament (ACL) reconstruction. Fifteen participants were tested on three different days that were separated at least by 24 h. Motor evoked responses were collected during a small background contraction on the reconstructed leg across a range of TMS intensities using torque (MEPTORQUE) and electromyographic (MEPEMG) responses. MEPTORQUE and MEPEMG were evaluated using different normalization procedures (raw, normalized to maximum voluntary isometric contraction [MVIC], peak MEP, and background contraction). MEPTORQUE was also normalized to the magnetically-evoked peripheral resting twitch torque. The area under the recruitment curve was computed for both raw and normalized MEPs. Intraclass correlation coefficients (ICCs) were determined to assess test–retest reliability. Results indicated that MEPTORQUE generally showed greater reliability than MEPEMG for all normalization procedures. Vastus medialis MEPEMG generally showed greater reliability than rectus femoris MEPEMG. Finally, both MEPTORQUE and MEPEMG exhibited good reliability, even when not normalized. These findings indicate that MEPTORQUE and MEPEMG offer reliable measures of corticospinal function and suggest that MEPTORQUE is a suitable alternative to MEPEMG for measuring quadriceps corticospinal excitability in individuals with ACL reconstruction.

Comparison of the Effects of Matching and Normalization on the Cervical Vestibular Evoked Myogenic Potential

We compared two means of mitigating the effect of sternocleidomastoid (SCM) contraction strength on the cervical vestibular evoked myogenic potential (cVEMP): contraction matching and amplitude normalization. SCM muscle contraction strength affects the amplitude of the cVEMP which can impact measures of inter-side asymmetry and diagnostic outcomes. In 19 normal subjects, we investigated the effect of muscle contraction variation within a cVEMP recording. We then compared cVEMP recordings on the right and left sides with matched and unmatched muscle contraction strength using raw amplitudes and amplitude ratios (i.e., normalized amplitudes). Contraction variability had significant effects on small sections of a cVEMP recording, but there was no significant effect on overall cVEMP amplitude, suggesting that the cVEMP is relatively unaffected by variable effort during a recording. Matching the contraction across the two sides (d = 0.53, p = 0.016) and amplitude normalization (d = 0.43, p = 0.004) both significantly reduced inter-side asymmetry, but normalization had no additional benefit once the sides were matched (interaction effect, p = 0.019). cVEMPs recorded with matched contractions had the smallest range of asymmetry values. The study shows that controlling the background contraction during a cVEMP recording, either by using similar contractions for each trial or by normalizing the amplitude, reduces cVEMP asymmetry and can prevent incorrect results in the minority of subjects who make asymmetric muscle contractions.

Esophageal contraction during cryoablation: A possible protective mechanism.

Contraction of the esophagus was observed during cryoablation for paroxysmal atrial fibrillation (PAF). The purpose of this study is to investigate the mechanism of esophageal contraction and the correlation between the contraction and esophageal thermal lesions. This prospective study enrolled 64 patients with PAF undergoing second-generation cryoballoon (CB2) ablation for pulmonary vein isolation (PVI). During PVI for the left inferior pulmonary vein, contrast esophagography was performed before and during cryoablation. The sample population was divided into two groups: A (31 patients) and B (33 patients). Group A consisted of patients in whom the distal half of the CB was in proximity to the esophagus, while for group B the esophagus was away from the distal half of the CB. Esophageal contraction was recorded as a variation in the width of the esophageal lumen during PVI. Postablation esophageal endoscopy was done on all patients. The reduction in the width of the esophageal lumen in group A was greater than in group B during freezing (40.12±23.24% vs 8.14±10.35%, P<.001). Following endoscopy, no apparent esophageal lesion was detected in all patients. The extent of esophageal contraction is correlated with the positioning of the esophagus at the distal half of the CB. The findings of this study indicate that esophageal contraction during freezing may be a self-protective mechanism.

Geometrical features for premature ventricular contraction recognition with analytic hierarchy process based machine learning algorithms selection

Background and ObjectivePremature ventricular contraction is associated to the risk of coronary heart disease, and its diagnosis depends on a long time heart monitoring. For this purpose, monitoring through Holter devices is often used and computational tools can provide essential assistance to specialists. This paper presents a new premature ventricular contraction recognition method based on a simplified set of features, extracted from geometric figures constructed over QRS complexes (Q, R and S waves). MethodsInitially, a preprocessing stage based on wavelet denoising electrocardiogram signal scaling is applied. Then, the signal is segmented taking into account the ventricular depolarization timing and a new set of geometrical features are extracted. In order to validate this approach, simulations encompassing eight different classifiers are presented. To select the best classifiers, a new methodology is proposed based on the Analytic Hierarchy Process. ResultsThe best results, achieved with an Artificial Immune System, were 98.4%, 91.1% and 98.7% for accuracy, sensitivity and specificity, respectively. When artificial examples were generated to balance the dataset, the recognition performance increased to 99.0%, 98.5% and 99.5%, employing the Support Vector Machine classifier. ConclusionsThe proposed approach is compared with some of latest references and results indicate its effectiveness as a method for recognizing premature ventricular contraction. Besides, the overall system presents low computation load.

The effect of rolling massage on the excitability of the corticospinal pathway.

The aim of the present study was to investigate the alterations of corticospinal excitability (motor evoked potential, MEP) and inhibition (silent period, SP) following rolling massage of the quadriceps muscles. Transcranial magnetic and femoral nerve electrical stimuli were used to elicit MEPs and compound muscle action potential (Mmax) in the vastus lateralis and vastus medialis muscles prior to and following either (i) 4 sets of 90-s rolling massage (ROLLING) or (ii) rest (CONTROL). One series of neuromuscular evaluations, performed after each set of ROLLING or CONTROL, included 3 MEPs and 1 Mmax elicited every 4 s during 15-s submaximal contractions at 10% (experiment 1, n = 16) and 50% (experiment 2, n = 10) of maximal voluntary knee extensions (MVC). The MEP/Mmax ratio and electromyographic activity recorded from vastus lateralis at 10% MVC demonstrated significantly lower values during ROLLING than CONTROL (P < 0.05). The ROLLING did not elicit any significant changes in muscle excitability (Mmax area) and duration of transcranial magnetic stimulation-induced SP recorded from any muscle or level of contraction (P > 0.05). The findings suggest that rolling massage can modulate the central excitability of the circuitries innervating the knee extensors; however, the observed effects are dependent on the background contraction intensity during which the neuromuscular measurements are recorded.

Effects of intermittent theta burst stimulation on spasticity after spinal cord injury.

Spasticity is a common disorder in patients with spinal cord injury (SCI). The aim of this study was to investigate whether intermittent theta burst stimulation (iTBS), a safe, non-invasive and well-tolerated protocol of excitatory repetitive transcranial magnetic stimulation (rTMS), is effective in modulating spasticity in SCI patients. In this randomized, double-blind, crossover, sham-controlled study, ten subjects with incomplete cervical or thoracic SCI received 10 days of daily sessions of real or sham iTBS. The H/M amplitude ratio of the Soleus H reflex, the amplitude of the motor evoked potentials (MEPs) at rest and during background contraction, as well as Modified Ashworth Scale (MAS) and the Spinal Cord Injury Assessment Tool for Spasticity (SCAT) were compared before and after the stimulation protocols. Patients receiving real iTBS showed significant increased resting and active MEPs amplitude and a significant reduction of the H/M amplitude ratio. In these patients also the MAS and SCAT scores were significantly reduced after treatment. These changes persisted up to 1 week after the end of the iTBS treatment, and were not observed under the sham-TBS condition. These findings suggest that iTBS may be a promising therapeutic tool for the spasticity in SCI patients.

Short‐latency crossed responses in the human biceps femoris muscle

The present study is the first to show short-latency crossed-spinal reflexes in the human upper leg muscles following mechanical rotations to the ipsilateral knee (iKnee) joint. The short-latency reflex in the contralateral biceps femoris (cBF) was inhibitory following iKnee extension perturbations, and facilitatory following iKnee flexion perturbations. The onset latency was 44ms, indicating that purely spinal pathways mediate the cBF reflexes. The short-latency cBF inhibitory and facilitatory reflexes followed the automatic gain control principle, becoming larger as the level of background contraction in the cBF increased. The short-latency cBF reflexes were observed at the motor unit level using i.m. electromyography recordings, and the same population of cBF motor units that was inhibited following iKnee extensions was facilitated following iKnee flexions. Parallel interneuronal pathways from ipsilateral afferents to common motoneurons in the contralateral leg can therefore probably explain the perturbation direction-dependent reversal in the sign of the short-latency cBF reflex. Interlimb reflexes contribute to the central neural co-ordination between different limbs in both humans and animals. Although commissural interneurons have only been directly identified in animals, spinally-mediated interlimb reflexes have been discovered in a number of human lower limb muscles, indicating their existence in humans. The present study aimed to investigate whether short-latency crossed-spinal reflexes are present in the contralateral biceps femoris (cBF) muscle following ipsilateral knee (iKnee) joint rotations during a sitting task, where participants maintained a slight pre-contraction in the cBF. Following iKnee extension joint rotations, an inhibitory reflex was observed in the surface electromyographic (EMG) activity of the cBF, whereas a facilitatory reflex was observed in the cBF following iKnee flexion joint rotations. The onset latency of both cBF reflexes was 44ms, which is too fast for a transcortical pathway to contribute. The cBF inhibitory and facilitatory reflexes followed the automatic gain control principle, with the size of the response increasing as the level of background pre-contraction in the cBF muscle increased. In addition to the surface EMG, both short-latency inhibitory and facilitatory cBF reflexes were recorded directly at the motor unit level by i.m. EMG, and the same population of cBF motor units that were inhibited following iKnee extension joint rotations were facilitated following iKnee flexion joint rotations. Therefore, parallel interneuronal pathways (probably involving commissural interneurons) from ipsilateral afferents to common motoneurons in the contralateral leg can probably explain the perturbation direction-dependent reversal in the sign of the short-latency cBF reflex.

Effects of transcranial magnetic stimulation coil orientation and pulse width on short-latency afferent inhibition

Purpose We used a controllable pulse parameter transcranial magnetic stimulation (cTMS) device to assess whether adjusting pulse width and coil orientation would allow more selective stimulation of different neuronal populations. Methods Young healthy subjects participated in experiments involving single pulse stimulation over the hand motor area elicited by a cTMS device connected to a figure-of-eight coil. Experiment 1 (n=10) evaluated the effect of coil orientation (posterior-anterior, PA; anterior-posterior, AP) and pulse width (30, 60 and 120 μs) on the strength-duration curve, the input-output (IO) curve and the latency of the motor evoked potentials (MEPs) in the first dorsal interosseous muscle. Experiment 2 (n=12) evaluated the effect of coil orientations (PA, AP) and pulse width (30 and 120 μs) on short-latency afferent inhibition (SAI), tested with electrical median nerve stimulation at the wrist prior to TMS (inter-stimulus intervals: N20 latency +2 and +4 ms). All tests were completed during background contraction (∼10% maximum). Results The mean strength-duration time constants were shorter for PA than AP directed currents when estimated using motor threshold data (231 vs. 294 μs; t-test, p = 0.008) and IO data (252 vs. 296 μs; t-test, p < 0.001). ANOVA revealed an interaction of pulse width and orientation on MEP latencies (p = 0.001), due mainly to the increase in latencies with short duration AP stimuli. A similar pulse width and orientation interaction was observed for SAI (p = 0.011), resulting from the stronger inhibition with AP stimuli of short duration. Conclusion PA and AP oriented pulses appear to activate neural populations with different time constants. The AP-sensitive neural populations that elicit the longest latency MEPs are more readily stimulated by short than by long duration pulses, and appear more sensitive to SAI. Manipulating pulse width may improve the selectivity of AP stimulation.

Modeling left atrial volume, shape, and contraction patterns in normal subjects by cardiac magnetic resonance imaging

Left atrial three-dimensional shape and contraction patterns are not well described. We quantified the LA using three-dimensional cardiac MRI (CMR) in a group of normal subjects. Three-dimensional vectors were used to quantitate atrial shape and contraction using a geometric model as a three-dimensional prolate ellipsoid. Atrial area and length at end-systole and end-diastole were made in the horizontal long axis (HLA) and vertical long axis (VLA) planes. Biplane area-length products and the orthogonal LA long axis vector comprised 3 orthogonal vector lengths composed of axis measures for shape and volume calculations at end-diastole and end-systole. Vector fractional shortening in 3 dimensions was calculated for each 3-space orthogonal vector. Echocardiograms were used for comparison. The normal LA is an oblate ellipsoid with significantly longer HLA short axis than the vertical VLA short axis (p<0.001). LA contraction in the long axis dimension is smaller than both HLA and VLA short axis dimensional changes (p<0.001). Linear correlations between LAEDV vs. LASV and LAESV vs. LAEF were highly significant. This dimensional analysis quantitates normal left atrial shape for the first time, modeled as a prolate 3-D ellipsoid. LA contractile functions and derives mostly from contraction in the HLA and VLA short axis directions. Though LA end-diastolic volume is considered the marker of left atrial health or disease, this notion should be reconsidered in view of LA static and functional modeling in 3 dimensions.

A landmark publication in movement disorders

I went to do a fellowship with David Marsden in July 1975, after finishing my neurology residency, because I was fascinated by the work that he was doing together with Pat Merton and Bert Morton on the long-latency stretch reflex. This was landmark work that laid the groundwork for reflex loops that involved the brain, much beyond the spinal reflexes of Sherrington. Sherrington’s work was primarily in the spinalized cat; therefore, he could not appreciate that some reflexes might involve higher centres. The long-latency stretch reflexes required not only an intact nervous system but also a voluntary background contraction. Pat Merton was a physiologist who had been studying how movement might be controlled by feedback mechanisms and the long-latency reflexes seemed appropriate for the task. Bert Morton was a clever engineer who built the equipment that was housed in a special laboratory at the National Hospital in Queen Square. The three Ms would get together, often on the weekend, to do their experiments, typically with Pat or David as the experimental subject. Pat was a meticulous experimenter. In one experiment that I conducted with him, he corrected his reaction time to auditory stimulation taking into account the speed of sound from the speaker on one side of the room to his ear. It was likely that David, the neurologist of the group, recognized that hyperexcitability of the long loop might be responsible for certain forms of myoclonus. They spent considerable time studying the myoclonus of a single patient with post-hypoxic myoclonus. They collected huge amounts of data and David wanted to publish them, but Pat, being typically meticulous, did not allow it, as he wanted to make sure that the calibration of the data was correct; they could never finish the calibration, and the article was never published. There is …

Electromyographic bursting following the cortical silent period induced by transcranial magnetic stimulation

In subjects performing voluntary background contraction, transcranial magnetic stimulation (TMS) induces an interruption of electromyographic (EMG) activity known as the silent period (SP). This is thought to be mediated through the action of inhibitory cortical neurons, in particular involving γ-aminobutyric acid type B (GABAB) receptors. In some studies of the SP, a post-SP increase in EMG activity has been reported but not described in detail. In the present study we have sought to determine the presence and persistence of late EMG bursting associated with the return of voluntary drive after the SP, and to characterize the relationship to background contraction level, stimulus intensity, and SP duration. TMS was delivered at 3 levels of intensity (120, 140 and 160% of active motor threshold) and during 3 levels of voluntary contraction of the first dorsal interosseous muscle (10, 30 and 50% of maximum contraction) in a pseudo-randomized order in 11 healthy participants. The SP was followed by a brief (~60ms) burst of EMG up to 290±42% of the pre-stimulus EMG level. Both SP duration and the amplitude of the EMG burst increased with TMS intensity (p<0.001). Burst amplitude correlated with SP duration (r2=0.750; p=0.003). We conclude that post-SP EMG bursting is a quantifiable phenomenon that depends on the strength of TMS and the duration of the SP. This bursting may correspond with the post inhibitory period of disinhibition that has recently been identified in human motor cortex.

Stretch reflex responses in Complex Regional Pain Syndrome-related dystonia are not characterized by hyperreflexia

ObjectiveTo evaluate if hyperreflexia (exaggerated reflexes) due to disinhibition is associated with dystonia in Complex Regional Pain Syndrome (CRPS). MethodsStretch reflexes at the wrist were assessed in healthy controls (n=10) and CRPS-patients with dystonia (n=10). Subjects exerted a wrist flexion torque of 5% of maximum voluntary contraction torque (TMVC) to a manipulandum which applied ramp-and-hold stretches to the wrist flexors. Since reflex responses scale with background contraction, controls additionally performed the task at 1% and 3% TMVC to attain similar torques as patients who have reduced TMVC.The M1 onset and the magnitudes of the short latency M1 and long latency M2 were assessed using the electromyographic signals (EMG) of the flexor carpi radialis. EMG of the extensor carpi radialis was recorded to monitor cocontraction. ResultsCompared to controls, patients had a substantially reduced TMVC. Ramp velocity had a significant effect on M1 onset time and magnitude. ConclusionsSince M1 magnitude decreased with flexion torque, no significant difference was found between patients and controls at 5% TMVC, while comparison at similar absolute torques (controls at 1% TMVC) resulted in significantly smaller M1 magnitudes for patients with dystonia. SignificanceThis study suggests that CRPS-patients with dystonia are not hyperreflexive.

Gravitational force modulates muscle activity during mechanical oscillation of the tibia in humans

Mechanical oscillation (vibration) is an osteogenic stimulus for bone in animal models and may hold promise as an anti-osteoporosis measure in humans with spinal cord injury (SCI). However, the level of reflex induced muscle contractions associated with various loads ( g force) during limb segment oscillation is uncertain. The purpose of this study was to determine whether certain gravitational loads ( g forces) at a fixed oscillation frequency (30 Hz) increases muscle reflex activity in individuals with and without SCI. Nine healthy subjects and two individuals with SCI sat with their hip and knee joints at 90° and the foot secured on an oscillation platform. Vertical mechanical oscillations were introduced at 0.3, 0.6, 1.2, 3 and 5 g force for 20 s at 30 Hz. Non-SCI subjects received the oscillation with and without a 5% MVC background contraction. Peak soleus and tibialis anterior (TA) EMG were normalized to M-max. Soleus and TA EMG were <2.5% of M-max in both SCI and non-SCI subjects. The greatest EMG occurred at the highest acceleration (5 g). Low magnitude mechanical oscillation, shown to enhance bone anabolism in animal models, did not elicit high levels of reflex muscle activity in individuals with and without SCI. These findings support the g force modulated background muscle activity during fixed frequency vibration. The magnitude of muscle activity was low and likely does not influence the load during fixed frequency oscillation of the tibia.

Postactivation depression and recovery of reflex transmission during repetitive electrical stimulation of the human tibial nerve

H-reflexes are progressively depressed, relative to the first response, at stimulation frequencies above 0.1 Hz (postactivation depression; PAD). Presently, we investigated whether H-reflexes "recover" from this depression throughout 10-s trains of stimulation delivered at physiologically relevant frequencies (5-20 Hz) during functionally relevant tasks (sitting and standing) and contraction amplitudes [relaxed to 20% maximum voluntary contraction (MVC)]. When participants held a 10% MVC, reflex amplitudes did not change during 5-Hz stimulation. During stimulation at 10 Hz, reflexes were initially depressed by 43% but recovered completely by the end of the stimulation period. During 20-Hz stimulation, reflexes were depressed to 10% and recovered to 36% of the first response, respectively. This "postactivation depression and recovery" (PAD&R) of reflex amplitude was not different between sitting and standing. In contrast, PAD&R were strongly influenced by contraction amplitude. Reflexes were depressed to 10% of the first response during the relaxed condition (10-Hz stimulation) and showed no depression during a 20% MVC contraction. A partial recovery of reflex amplitude occurred when participants were relaxed and during contractions of 1-5% MVC. Surprisingly, reflexes could recover completely by the third pulse within a stimulation train when participants held a contraction between 5 and 10% MVC during stimulation at 10 Hz, a finding that challenges classical ideas regarding PAD mechanisms. Our results support the idea that there is an ongoing interplay between depression and facilitation when motoneurons receive trains of afferent input. This interplay depends strongly on the frequency of the afferent input and the magnitude of the background contraction but is relatively insensitive to changes in task.

Role of mitochondria in contraction and pacemaking in the mouse uterus

Uterine spontaneous contraction and pacemaking are poorly understood. This study investigates the role of the mitochondrial Ca(2+) store in uterine activity. We investigated the effects of mitochondrial and sarco-endoplasmic reticulum (SER) inhibitors on contraction, membrane potential (Vm) and cytosolic Ca(2+) concentration ([Ca(2+) ](c) ) in longitudinal smooth muscle of the mouse uterus. The mitochondrial agents rotenone, carbonylcyanide-3-chlorophenylhydrazone (CCCP), 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP37157) and kaempferol decreased the force of contractions. The ATP synthase inhibitor oligomycin had no significant effect. The effects of these agents were compared with those of SER inhibitors cyclopiazonic acid (CPA), 2-amino ethoxyphenylborate (2-APB) and caffeine. All agents, except CPA and oligomycin, decreased contractile force. CPA and CCCP transiently increased contraction frequency, which returned to control levels, whereas rotenone, CGP37157, kaempferol and 2-APB decreased frequency and caffeine had no significant effect. Application of the mitochondrial agents when CPA functionally inhibited stores did not change contraction frequency but, with the exception of kaempferol, decreased force. CCCP caused depolarization and maintained increase in [Ca(2+) ](c) or depolarization/transient hyperpolarization and transient increase in [Ca(2+) ](c) for oestrus and di-oestrus tissues respectively. Rotenone caused hyperpolarization and maintained increase in [Ca(2+) ](c) . CGP37157 and kaempferol caused hyperpolarization but no measurable change in [Ca(2+) ](c) . Application of a range of K(+) channel blockers indicated a role of Ca(2+) -activated K(+) (K(Ca) ) channels in the CCCP- and CGP37157-induced actions. Mitochondria have a modulatory role on uterine contractions, with mitochondrial inhibition reducing contraction amplitude and pacemaker frequency by changes in Vm, [Ca(2+) ](c) and/or Ca(2+) influx.

Inhibitory mechanisms following electrical stimulation of tendon and cutaneous afferents in the lower limb

Electrical stimulation of the Achilles tendon (TES) produced strong reflex depression (duration>250 ms) of a small background contraction in both heads of gastrocnemius (GA) via large diameter electrodes localized to the tendon. The inhibitory responses were produced without electrical (M wave) or mechanical (muscle twitch) signs of direct muscle stimulation. In this study, the contribution of presynaptic and postsynaptic mechanisms to the depression was investigated by studying conditioning effects of tendon afferent stimulation on the mechanical tendon reflex (TR) and magnetic motor evoked potential (MEP). TES completely inhibited the TR over an ISI of 300 ms that commenced before and continued during and after the period of voluntary EMG depression. Tendon afferent conditioning stimuli also partially inhibited the MEP, but over a short time course confined to the period of voluntary EMG depression. The strength and extended time course of tendon afferent conditioning of the TR and its failure to produce a similar depression of the MEP are consistent with a mechanism involving presynaptic inhibition of Ia terminals. Cutaneous (sural nerve) afferent conditioning partially inhibited the TR and MEP over a short time course (ISI <100 ms) resembling the inhibition seen in the voluntary EMG. This was consistent with the postsynaptic origin of cutaneous inhibition of the motoneurons.

Muscle imaging: Mapping responses to transcranial magnetic stimulation with high-density surface electromyography

Representations of different body parts or muscles in the human primary motor cortex overlap extensively. At the effector level, most muscles are surrounded by and overlap with several neighbours as well. This hampers the assessment of excitability in individual muscles with transcranial magnetic stimulation (TMS), even if so-called “focal” stimulating coils are used. Here we used a novel mapping paradigm based on high-density surface electromyography (HD-sEMG) to investigate the spatial selectivity of TMS in the forearm musculature. In addition, we tested the hypothesis that selective stimulation can be improved by a voluntary background contraction of the target muscle. We mapped and compared the topographies of motor evoked potential (MEP) amplitudes during rest and during background contractions of two forearm muscles (extensor carpi radialis and extensor digitorum communis). The MEP topographies were also compared to the amplitude topography of voluntary EMG. The results indicate that under many conditions a large proportion of the MEP activity recorded at the surface originated from the target muscle's neighbours. There was a systematic relationship between TMS intensity and the topographic distribution of MEP responses during voluntary contraction. With increasing stimulus intensity, the MEP topography deviated increasingly more from the topography of voluntary EMG. We conclude that when standard EMG montages are used, the recorded MEPs are not necessarily evoked in the target muscle alone. Stimulation during a voluntary background contraction of the target muscle may enhance the selectivity of TMS. It however remains essential to use stimulus intensities as low as possible, to minimize the contribution of surrounding non-target muscles to the MEP.

Effects of transcranial direct current stimulation on the excitability of the leg motor cortex

Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA has been shown to be efficacious in increasing (via anodal tDCS) or decreasing (via cathodal tDCS) the excitability of corticospinal projections to muscles of the hand. In this study, we examined whether tDCS at currents of 2 mA could effect similar changes in the excitability of deeper cortical structures that innervate muscles of the lower leg. Similar to the hand area, 10 min of stimulation with the anode over the leg area of the motor cortex increased the excitability of corticospinal tract projections to the tibialis anterior (TA) muscle, as reflected by an increase in the amplitude of the motor evoked potentials (MEPs) evoked by transcranial magnetic stimulation. MEP amplitudes recorded at rest and during a background contraction were increased following anodal tDCS and remained elevated at 60 min compared to baseline values by 59 and 35%, respectively. However, in contrast to the hand, hyperpolarizing cathodal stimulation at equivalent currents had minimal effect on the amplitude of the MEPs recorded at rest or during background contraction of the TA muscle. These results suggest that it is more difficult to suppress the excitability of the leg motor cortex with cathodal tDCS than the hand area of the motor cortex.

Ankle position and voluntary contraction alter maximal M waves in soleus and tibialis anterior

Compound muscle action potentials (CMAPs) recorded using surface electrodes are often used to assess the excitability of neural pathways to skeletal muscle. However, the amplitude of CMAPs can be influenced by changes at the recording site, independent of mechanisms within the central nervous system. We quantified how joint angle and background contraction influenced CMAP amplitude. In seven subjects CMAPs evoked by supramaximal transcutaneous electrical stimulation of motor axons (M(max)) were recorded using surface electrodes from soleus and tibialis anterior (TA) at static positions over the full range of ankle movement at 5 degrees intervals. Across subjects the peak-to-peak amplitude of M(max) was 155% and 159% larger at the shortest than longest muscle lengths for soleus and TA, respectively. In five subjects the effect of ankle position and voluntary contraction on M-wave/H-reflex recruitment curves was assessed in the soleus. Both ankle position and level of contraction significantly influenced M(max), H(max), and the H(max) to M(max) ratio, but there were no interactions between the two parameters. These peripheral changes that influence M(max) will also impact other CMAPs such as submaximal M-waves, H-reflexes, and responses to transcranial magnetic stimulation. As such, during experimental studies CMAPs evoked at a given joint angle and contraction level should be normalized to M(max) recorded at similar joint angle and contraction strength.