Modulation of motor evoked potentials by muscle vibration: the role of vibration frequency.

Augmentation of motor evoked potentials (MEPs) by muscle vibration (MV) was studied in 10 healthy subjects with regard to the vibration frequency (VF). The extensor carpi radialis muscle (ECR) was vibrated using VFs of 80, 120, and 160 Hz. Motor evoked potentials following transcranial magnetic stimulation were recorded simultaneously from the vibrated ECR and the antagonist flexor carpi radialis muscle (FCR) without MV, 0.5 s and 3 s after onset of MV and 1 s after offset. Only the VFs of 80 Hz and 120 Hz caused MEP augmentation and latency shortening in ECR, whereas depression of MEPs in FCR was induced by all VFs used. It appears that MEP augmentation and latency shortening in ECR are mediated by the primary muscle spindle endings which respond with optimal discharge rates to VFs of up to 100 Hz. Motor evoked potential depression in FCR, being well expressed also with VF 160 Hz, seems to involve other dynamic mechanoreceptors.     

Alteration of sensorimotor integration in musician's cramp: impaired focusing of proprioception.

OBJECTIVE: The influence of muscle vibration (MV) as a strong proprioceptive input on motorcortical excitability was studied in 5 patients with musician's cramp, 5 musician controls and 5 non-musician controls. METHODS: The relaxed flexor carpi radialis (FCR), involved in the dystonic movement in all patients, was vibrated using low frequency (80 Hz) and low amplitude (0.5 mm). Transcranial magnetic stimulation (TMS; intensity, 120% of motor threshold) was applied without MV, 3 and 9 s after the onset of MV. Motor-evoked potentials (MEPs) in the FCR and in the antagonistic extensor carpi radialis (ECR) were recorded. RESULTS: With MV, musician and non-musician controls showed a facilitation of MEPs in the FCR and a decrease of MEPs in the ECR. In musician's cramp, both phenomena were significantly less pronounced. CONCLUSIONS: The reduced facilitation of MEPs in musician's cramp indicates a reduced MV-induced activation of motorcortical areas representing the FCR. The less pronounced inhibition by MV reflects a reduced inhibitory control of the antagonistic ECR. As there were no differences between musician and non-musician controls, the observed changes in musician's cramp refer to this special form of focal dystonia. An impairment of focused motorcortical activation by proprioceptive input from a muscle involved in the dystonic movement is suggested.     

Effect of antagonistic voluntary contraction on motor responses in the forearm.

OBJECTIVE: We investigated the effects of voluntary contraction of agonist and antagonist muscles on motor evoked potentials (MEP) and on myoelectric activities in the target (agonist) muscle following transcranial magnetic stimulation (TMS). METHODS: The left extensor carpi radialis (ECR) and flexor carpi radialis (FCR) muscles were studied in 16 healthy subjects. H reflexes, MEP induced by TMS, and background electromyographic (EMG) activity were recorded using surface electrodes at rest and during voluntary contraction of either agonist or antagonist muscles. RESULTS: Voluntary contraction of antagonist muscles (at 10% of maximum contraction) enhanced the amplitudes of MEP for both muscles. The H reflex of the FCR muscle was inhibited by contraction (10% of maximum) of the ECR muscle. Background EMG activity did not differ between H-reflex trials and TMS trials. Enhancement of MEP amplitudes and background EMG activity during voluntary antagonist contraction was comparable in the two muscles. Appearance rate of MEP recorded by needle electrodes in response to subthreshold TMS was increased by antagonistic voluntary contraction. CONCLUSION: Facilitation occurs during voluntary contraction of antagonist muscles. Differences between the effects of voluntary contraction of the ECR muscle for the MEP and the H reflex of the FCR suggest that cortical facilitatory spread occurs between agonist and antagonist muscles.     

Vibration prolongs the cortical silent period in an antagonistic muscle

We tested whether the silent period, an indicator of inhibitory neuronal activity, is modulated by muscle vibration. Vibration was applied to the right extensor carpi radialis (ECR) muscle in 17 healthy subjects and, as a control experiment, to the dorsal terminal phalanges in 5 subjects. Data before vibration were compared with those during vibration. The cortical silent period (CSP) was evoked by transcranial magnetic stimuli (TMS) during voluntary wrist flexion or during voluntary wrist extension. TMS‐evoked motor potentials (MEPs) of the flexor carpi radialis (FCR) muscle were recorded during muscle relaxation. The mixed nerve silent period (MNSP) was obtained by electrical stimulation of the median nerve during wrist flexion. ECR vibration induced a significant prolongation of the CSP in FCR. CSP increases induced by vibration of the dorsal terminal phalanges were significantly less pronounced. In ECR, the CSP tended to be shortened. MEPs and MNSP remained unchanged. We conclude that vibration enhances inhibitory neuronal properties in a non‐vibrated antagonistic muscle, presumably at a supraspinal level. These results may be relevant for the treatment of spasticity of the upper extremity. Muscle Nerve, 2009     

Different patterns of excitation and inhibition of the small hand and forearm muscles from magnetic brain stimulation in humans.

OBJECTIVES: The objective of the present study is to quantify the effects of voluntary muscle contraction of the small hand (abductor pollicis brevis, first dorsal interosseus (FDI)) and forearm muscles (extensor carpi radialis (ECR), extensor carpi ulnaris (ECU), flexor carpi radialis (FCR) and flexor carpi ulnaris (FCU)) on motor evoked potentials (MEPs). METHODS: MEPs were recorded in 12 healthy subjects by a circular coil placed over the vertex at 1.2 times the resting motor threshold at different levels of the muscle contraction (0-100% of maximum voluntary contraction (MVC)). The effects of transcranial magnetic stimulation (TMS) on the onset latency, MEP area and silent period (SP) as a function of the %MVC were evaluated using a piecewise linear regression analysis. RESULTS: The MEP areas for the small hand muscles were almost completely saturated at 20% of MVC. In contrast, the MEP areas for radial muscles (ECR, FCR) had a dual increase at 40% of MVC while the ulnar muscles (ECU, FCU) had a dual increase at 20% of MVC. A uniform latency shift (1.5-3 ms reduction) was observed in all muscles with a changing point at 10% of MVC. The SPs were the longest for FDI and were not significantly influenced by MVC for any muscles. CONCLUSIONS: The excitatory and inhibitory effects of TMS on the MEPs differed for the small hand and forearm muscles and also between the ulnar and radial muscles. These results probably resulted from the different degrees of direct corticomotoneuronal inputs to each muscle and the inherent properties of the spinal motoneurons.     

Muscle vibration and prefrontal repetitive transcranial magnetic stimulation

We previously demonstrated that prefrontal subthreshold repetitive transcranial magnetic stimulation (rTMS) may reduce motor cortex excitability. We have now examined whether muscle vibration (MV) can compensate for this depression. We enrolled 25 healthy volunteers (aged 22 to 37 years) who received 5 HZ, 10% subthreshold prefrontal rTMS for 12 s. The extensor carpi radialis muscle was vibrated with an electromagnetic mechanical stimulator with a stimulation frequency of 120 HZ and 0.5 mm amplitude. Motor evoked potentials (MEPs) from the flexor carpi radialis muscle (FCR) following single-pulse transcranial magnetic stimulation (TMS) were recorded at baseline, and after 4, 8, and 12 s. During prefrontal rTMS, MEPs of the FCR exhibited a serial depression (P = 0.001). This effect did not occur during MV. We conclude that rTMS of the prefrontal cortex may inhibit the corticospinal system. This depression may be compensated by MV, suggesting that vibration changes motor cortex excitability. The underlying mechanism might be an input from Ia sensory afferents to the motor and prefrontal cortex.     

Evidence for facilitation of motor evoked potentials (MEPs) induced by motor imagery

This study examined the extent to which motor imagery can facilitate to specific pools of motoneurons. Motor commands induced by motor imagery were subthreshold for muscle activity and were presumably not associated with any change in background afferent activity. To estimate excitability changes of flexor carpi radialis (FCR) muscle motoneuron in spinal and cortical level, electric stimuli for recording H-reflex and transcranial magnetic stimulation (TMS) for recording motor evoked potentials (MEPs) were used. During motor imagery of wrist flexion, remarkable increases in the amplitude of the MEP of FCR were observed with no change in the H-reflex. Furthermore, facilitation of antagonist (extensor carpi radialis; ECR) was also observed. Therefore, it is concluded that internal motor command can activate precisely cortical excitability with no change in spinal level without recourse to afferent feedback.     

Absence of facilitation or depression of motor evoked potentials after contralateral homologous muscle activation

We have previously described post-exercise facilitation and post-exercise depression of motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS). To determine the presence of post-exercise facilitation after exercise of a contralateral muscle, MEPs were recorded from the resting right extensor carpi radialis (ECR) muscle while the left ECR muscle was activated, then immediately after brief left ECR activation, and, finally, immediately after brief right ECR activation. We repeated the experiment using the first dorsal interosseous (FDI) muscle. To determine the presence of post-exercise depression after exercise of a contralateral muscle, MEPs were recorded from the right ECR after prolonged exercise of the left ECR, followed by right ECR recording after its fatigue. The mean MEP amplitudes from the right ECR and the right FDI after brief activation were 187% and 266% of their pre-exercise values, respectively. There were no significant changes in MEPs recorded from the right ECR or FDI muscles during or immediately after brief activation of their left counterparts. The mean amplitude of MEPs recorded from the right ECR after it fatigued was approximately half the pre-exercise value, but there was no significant change in MEPs recorded from the right ECR after prolonged exercise of the left ECR. Therefore, neither post-exercise facilitation nor post-exercise depression occurred after contralateral homologous muscle exercise.     

Effects of transcutaneous electrical nerve stimulation on motor cortex excitability in writer's cramp: neurophysiological and clinical correlations.

We recently reported that transcutaneous electrical nerve stimulation (TENS) applied over forearm flexor muscles, a paradigm producing in physiological conditions transient changes in corticomotoneuronal excitability of forearm muscles, may improve motor symptoms in writer's cramp (WC). In the present study, we explored the possibility that one or repeated sessions of TENS might have beneficial effects on handwriting in WC by remodulating cortical excitability of forearm agonist and antagonist muscles. Motor evoked potentials (MEPs) after transcranial magnetic stimulation of the left motor cortex were recorded from the right flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles, before and after 1 and 15 sessions of TENS applied over flexor muscles in patients and in a control group. One session of TENS induced a significant smaller reduction of MEPs from the FCR and a smaller increase of the MEPs from the ECR in patients than in normal subjects. In WC, repeated sessions of TENS had the effect to decrease MEP amplitude in the FCR and to increase it in the ECR. This modulation was paralleled by a handwriting improvement. In conclusion, repeated TENS sessions may have the effect to re-modulate excitability of the motor cortex in WC and this modulation might partially play a role in temporarily improving the handwriting.     

Muscle vibration: different effects on transcranial magnetic and electrical stimulation.

Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) were applied before and 3 s after onset of vibration (0.5 mm, 80 Hz) of the right extensor carpi radialis muscle in 5 healthy subjects. Vibration induced significant augmentation and latency shortening of motor evoked potentials elicited by TMS, but not TES. This provides evidence for an involvement of cortical mechanisms by muscle vibration in the augmentation of MEPs following TMS.     

Changes in corticomotor excitability following prolonged muscle tendon vibration

The present experiment addressed whether increases in corticospinal excitability following sensory stimulation with muscle tendon vibration are accompanied by reorganization of the forearm musculature representation within the primary motor cortex. Using transcranial magnetic stimulation, we mapped the corticomotor projection to the dominant flexor carpi radialis (FCR) and extensor carpi radialis brevis (ECR) muscle before and after interventional sensory stimulation obtained via muscle tendon vibration (80Hz, 60 min) to the dominant distal wrist flexor tendons. Following vibration, MEP amplitude at the optimal stimulation position, motor output area, as well as map volume, increased significantly for the ECR. None of these effects reached significance for the FCR. These results suggest that the antagonistic vibratory response (AVR), which is considered to be of cortical origin, induces a delayed facilitation of musculature that is antagonistic to the site of the directly activated Ia afferent pathways. This example demonstrates that peripheral sensory stimulation can induce lasting increases in corticospinal excitability in the absence of actual movements.     

Changes in processing of proprioceptive information in Parkinson's disease and multiple system atrophy.

OBJECTIVE: Changes in processing of proprioceptive information are known in idiopathic Parkinson's disease (IPD) and may contribute to motor deficits. This study used transcranial magnetic stimulation (TMS) to investigate the processing of proprioceptive information induced by muscle vibration (MV) in 10 patients with IPD and 10 patients with multiple system atrophy of the parkinsonian type (MSA-P) in comparison to 10 controls. METHODS: Single and paired-pulses were used, and motor evoked potentials (MEPs) were recorded in the extensor and flexor carpi radialis muscles (ECR and FCR) without and with MV (80Hz) to the ECR. Cortical silent periods (SP) were also studied. RESULTS: Controls showed the known MV-induced focal MEP augmentation which was lacking in IPD and intermediate and less focal in MSA-P. Intracortical inhibition and facilitation were not influenced by MV. SP was not changed by MV in controls and IPD while it was significantly prolonged in MSA-P. CONCLUSIONS: Processing of proprioceptive information is differently changed in IPD and MSA-P. Cortical facilitation by MV is more impaired in IPD than MSA-P, and these changes are less focal in MSA-P than in controls. SIGNIFICANCE: Our results support the view that changes in processing of proprioceptive information may contribute to motor deficits in patients with IPD and MSA-P.     

Hand preference and transcranial magnetic stimulation asymmetry of cortical motor representation

Human handedness may be associated with asymmetry in the corticospinal motor system. Previous studies measuring the threshold for eliciting motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) have provided evidence consistent with this hypothesis. However, TMS asymmetry observed in previous studies may have reflected cortical or spinal differences. We therefore undertook this investigation to test the hypothesis that handedness is associated with asymmetry in cortical motor representations. We used TMS to map contralateral cortical motor representations of the right and left abductor pollicis brevis (APB) and flexor carpi radialis (FCR) muscles in nine normal subjects (three left-handed). Using focal stimulation with a figure-of-8 shaped magnetic coil, we found no differences in MEP threshold or MEP size between the preferred and the nonpreferred hand. However, we observed that the number of scalp stimulation sites eliciting MEPs was statistically greater for APB and FCR muscles of the preferred limb. We found significant asymmetry between right-handed and left-handed subjects, such that in right-handers, the representation of the right APB was larger than that of the left APB, but in left-handers the representation of right APB was smaller than that of the left APB. These results suggest that handedness is associated with asymmetry in cortical motor representation.     

Effects of remote muscle contraction on transcranial magnetic stimulation-induced motor evoked potentials and silent periods in humans.

OBJECTIVE: To determine to what extent tonic contraction of the testing muscle modulates the effect of remote muscle contraction on motor evoked potentials (MEPs) and cortical silent periods (CSPs) in resting and active proximal and distal muscles following transcranial magnetic stimulation (TMS). In addition, we tested whether the remote effect on MEP was observable when the test MEP was small. METHODS: While performing tonic abductions of the first dorsal interosseous (FDI), flexor carpi radialis, or anterior deltoid muscles, subjects made phasic dorsiflexions of the right ankle at various forces. MEPs and CSPs were induced by separately optimized TMS intensities and locations in the left motor cortex and recorded electromyographically. RESULTS: Phasic dorsiflexion increased MEP amplitude and shortened CSP duration in a dorsiflexion intensity-dependent manner in all muscles tested. At test MEPs <10% of Mmax, remote effects on MEP amplitude and CSP duration were significantly attenuated while the testing muscle was active. CONCLUSIONS: Phasic contraction of remote muscles potentiates excitatory- and suppresses inhibitory intracortical neuronal pathways converging on corticospinal tract cells innervating the upper limb muscles even when they are active. However, the magnitude of the remote effect on MEP amplitude strongly depends on the test MEP amplitude. SIGNIFICANCE: Although remote effects on MEP amplitude and CSP duration are observed even when the test muscle is active, the magnitude of the remote effect strongly depends on TMS intensity.     

Scaling of motor cortical excitability during unimanual force generation

During performance of a unimanual force generation task primary motor cortices (M1s) experience clear functional changes. Here, we evaluated the way in which M1s interact during parametric increases in right wrist flexion force in healthy volunteers. We measured the amplitude and the slope of motor evoked potentials (MEP) recruitment curves to transcranial magnetic stimulation (TMS) in the left and right flexor carpi radialis (FCR) muscles at rest and during 10%, 30% and 70% of maximal wrist flexion force. At rest, no differences were observed in the amplitude and slope of MEP recruitment curves in the left and right FCR muscles. With increasing right wrist flexion force, MEP amplitudes increased in both FCR muscles, with larger amplitudes in the right FCR. We found a significant correlation between the left and right MEP amplitudes across conditions. The slope of right and left FCR MEP recruitment curve was significantly steeper at 70% of force compared to rest and 10% of force. A significant correlation between the slope of left and right FCR MEP amplitudes was found at 70% of force only. Our results indicate a differential scaling of excitability in the corticospinal system controlling right and left FCR muscles at increasing levels of unimanual force generation. Specifically, these data highlights that at strong levels of unimanual force the increases in motor cortical excitability with increasing TMS stimulus intensities follow a similar pattern in both M1s, while at low levels of force they do not.     

Vision modulates corticospinal suppression in a functionally specific manner during movement of the opposite limb

The effect of vision on the excitability of corticospinal projections to the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles of right human forearm was investigated before and during discrete movement of the opposite limb. An external force opposed the initial phase of the movement (wrist flexion) and assisted the reverse phase, so that recruitment of the wrist extensors was minimized. Three conditions were used as follows: viewing the inactive right limb (Vision), viewing the mirror image of the moving left limb (Mirror), and with vision of the right limb occluded (No Vision). Transcranial magnetic stimulation was delivered to the left motor cortex: before, at the onset of, or during the left limb movement to obtain motor evoked potentials (MEPs) in the muscles of the right forearm. At and following movement onset, MEPs obtained in the right FCR were smaller in the Vision condition than in the Mirror and No Vision conditions. A distinct pattern of variation was obtained for the ECR. In all conditions, MEPs in this muscle were elevated upon or following movement of the opposite limb. An additional analysis of ipsilateral silent periods indicated that interhemispheric inhibition plays a role in mediating these effects. Activity-dependent changes in corticospinal output to a resting limb during discrete actions of the opposite limb are thus directly contingent upon where one looks. Furthermore, the extent to which vision exerts an influence upon projections to specific muscles varies in accordance with the functional contribution of their homologs to the intended action.     

How repeatable are the physiological effects of TENS?

OBJECTIVE: Several studies suggest that transcutaneous electrical stimulation (TENS) can have a variety of effects on the central nervous system (CNS). In this study, we tried to replicate the physiological effects of TENS and to explore its effects on intracortical circuits. METHODS: We used transcranial magnetic stimulation (TMS) and spinal reflex testing to examine excitability of intracortical and spinal cord circuits before and after a 30-min period of TENS over the flexor carpi radialis (FCR) muscle. We measured the amplitude of TMS-evoked muscle responses (MEP), short interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical antagonist inhibition (CAI) in flexor and extensor carpial radialis (FCR, ECR) muscles as well as spinal reciprocal inhibition (RI) and presynaptic inhibition (PI) from ECR to FCR. RESULTS: TENS had no significant effect on any of these measures apart from a reduction in median nerve induced facilitation of FCR when testing CAI. CONCLUSIONS: When compared with previous studies, our results suggest that the effects of TENS are highly variable and unreliable, likely by the difficulty in defining precise parameters of stimulation in individual subjects. SIGNIFICANCE: Care should be taken in assuming that effects after TENS observed in small populations of subjects will apply equally to a wider population.     

Amplitude of muscle stretch modulates corticomotor gain during passive movement

Previous studies have shown that the excitability of corticomotor projections to forearm muscles exhibit phasic modulation during passive movement (flexion-extension) about the wrist joint. We examined the stimulus-response properties of flexor carpi radialis (FCR) and extensor carpi radialis (ECR) to transcranial magnetic stimulation (TMS) applied over the contralateral motor cortex while the wrist was moved passively at two different sinusoidal frequency-amplitude relationships. Movement velocity (and therefore, the rate of change in muscle length) at the time of stimulation was held constant. Motor evoked potential (MEP) amplitudes were facilitated during passive muscle shortening and suppressed during passive muscle lengthening with suppression being more evident at higher stimulation intensities. For both FCR and ECR, during the shortening phase, responses were facilitated during the large amplitude movement relative to the small amplitude movement. It is suggested that the altered gain may be related to the thixotropic properties of muscle.     

Inhibition of motor system excitability at cortical and spinal level by tonic muscle pain.

OBJECTIVE: To assess whether the motor system excitability can be modified by experimental tonic pain induced either in muscles or in subcutis. METHODS: Transcranial magnetic stimulation of the left primary motor cortex was used to record motor evoked potentials (MEPs) from the right abductor digiti minimi (ADM) muscle. Recordings were made before, during and after experimental pain induced by (1) injection of hypertonic (5%) saline into the right ADM, the right first dorsal interosseum (FDI) and the left ADM muscles, and (2) injection of hypertonic saline in the subcutaneous region of the right ADM. Both MEPs and H-reflex were recorded also from the right flexor carpi radialis (FCR) before, during and after muscle pain. RESULTS: MEPs recorded from the ADM muscle were significantly reduced in amplitude during pain induced in the right ADM and right FDI muscles, but not during pain in the left ADM muscle or during subcutaneous pain. This inhibitory effect was observed during the peak-pain and persisted also after the disappearance of the pain sensation. In the FCR muscle, the MEP inhibition was observed during the peak-pain, while a significant reduction of the H-reflex's amplitude was observed starting 1 min after the peak-pain. CONCLUSIONS: Tonic muscle pain can inhibit the motor system. The motor cortex inhibition observed at an early phase is followed by a reduction of the excitability of both cortical and spinal motoneurones.     

Investigation of paroxysmal dystonia in a patient with multiple sclerosis: a transcranial magnetic stimulation study.

OBJECTIVE: To study the pathogenesis of paroxysmal dystonia affecting the right body side in a patient with a demyelinating lesion in the descending motor pathways, also involving the basal ganglia. METHODS: Single-pulse transcranial magnetic stimulation (TMS) was applied to study motor evoked potentials (MEPs) and the following silent periods (SPs) in the first dorsal interosseous muscle (FDI) of both sides and in the right extensor carpi radialis muscle (ECR) during voluntary contractions performed outside the dystonic attacks. During the dystonic paroxysms, single-pulse TMS was used to investigate the time course of MEPs and SPs in both FDI and ECR of the right side. Furthermore, paired-pulse TMS was applied at rest to investigate short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in both FDI muscles. RESULTS: At rest SICI and ICF were normal in both motor cortices. During voluntary contraction the MEP was smaller and the SP was longer in the affected FDI than in the contralateral. During the paroxysms, the MEPs and SPs were suppressed in comparison with the responses elicited during voluntary contraction. CONCLUSIONS: These results fit well with the theory of ephaptic excitement of corticospinal axons for the pathogenesis of paroxysmal dystonia due to a demyelinating lesion. SIGNIFICANCE: Identification of the mechanisms underlying paroxysmal dystonia in demyelinating disorders extends our knowledge on the pathophysiology of dystonia.