Cortico-motor excitability of the lower limb motor representation: a comparative study in Parkinson's disease and healthy controls.

OBJECTIVE: To compare indices of cortico-motor excitability derived from transcranial magnetic stimulation (TMS) of the lower limb motor representation in patients with Parkinson's diseases (PD) and healthy controls. METHODS: The cortico-motor excitability of the lower limb motor area was studied both at rest (motor threshold, amplitude of motor evoked potentials (MEPs)) and during active contraction of the quadriceps (Quad) muscle (MEPs facilitation and silent period) in 10 PD patients (11 legs) and 11 healthy controls using single pulse TMS. RESULTS: At rest, the motor threshold was found to be significantly lower and the amplitude of MEPs larger in patients than in controls. During active knee contraction, patients produced lower levels of MEP facilitation with respect to baseline values and the silent period was lengthened in comparison to controls. CONCLUSIONS: The present results provide further evidence from the lower limb motor area that enhanced cortico-spinal excitability is an important feature in the pathophysiology of PD.     

Facilitation and reciprocal inhibition by imagining thumb abduction.

It is well known that motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) of the motor cortex are facilitated by voluntary muscle contraction. We evaluated the effects of imagination of movements on MEP latencies of agonist and antagonist muscles in the hand using TMS. Twenty-two healthy volunteers were studied. TMS delivered at rest and while imagining tonic abduction of the right thumb. MEPs were recorded in response to magnetic stimulation over the scalp and cervical spine (C7-T1), and central motor conduction times (CMCT) were calculated. MEPs were recorded from right abductor pollicis brevis muscle (APB) and adductor pollicis muscle (AP) simultaneously. Imagination of abduction resulted in a shortened latency of MEPs in the APB muscle, and a prolonged latency in the AP muscle. But the imagination caused no significant change in the latency of MEPs elicited by stimulation over the cervical spine. The changes of the CMCT may account for these latency changes with imagination of movement. These findings indicate that imagination of thumb abduction facilitates motoneurons of agonist muscle and has an inhibitory effect on those of antagonist muscle (reciprocal inhibition).     

Intra-rater reliability of a transcranial magnetic stimulation technique to obtain motor evoked potentials

The purpose of this study was to determine the intra-rater reliability of motor evoked potentials (MEP) obtained through transcranial magnetic stimulation (TMS). TMS was applied over the primary motor cortex of 16 healthy subjects. Motor thresholds, MEP latencies, and amplitudes were recorded from the contralateral upper limb on 6 occasions over 15 days. An intraclass correlation coefficient (ICC 2,1) was used to estimate reliability. The ICCs ranged from 0.60 to 0.92 for all MEP measures except amplitude (ICC = 0.01 to 0.34). MEPs obtained with the TMS technique described are generally reliable, although MEP amplitudes demonstrated less consistency.     

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.     

INTRA-RATER RELIABILITY OF A TRANSCRANIAL MAGNETIC STIMULATION TECHNIQUE TO OBTAIN MOTOR EVOKED POTENTIALS

The purpose of this study was to determine the intra-rater reliability of motor evoked potentials (MEP) obtained through transcranial magnetic stimulation (TMS). TMS was applied over the primary motor cortex of 16 healthy subjects. Motor thresholds, MEP latencies, and amplitudes were recorded from the contralateral upper limb on 6 occasions over 15 days. An intraclass correlation coefficient (ICC 2,1) was used to estimate reliability. The ICCs ranged from 0.60 to 0.92 for all MEP measures except amplitude (ICC = 0.01 to 0.34). MEPs obtained with the TMS technique described are generally reliable, although MEP amplitudes demonstrated less consistency.     

Intraoperative neurophysiologic discovery of uncrossed sensory and motor pathways in a patient with horizontal gaze palsy and scoliosis.

OBJECTIVE: To report the intraoperative neurophysiologic discovery of clinically unsuspected non-decussation of the somatosensory and motor pathways. METHODS: We performed somatosensory evoked potential (SEP) and transcranial electric stimulation (TES) muscle motor evoked potential (MEP) monitoring during scoliosis surgery for a 16 year old patient with familial horizontal gaze palsy and progressive scoliosis. Our routine procedures included optimizing tibial cortical SEP monitoring derivations through saggital and coronal (C4', C2', Cz', C1', C3'-mastoid) P37 mapping, which surprisingly indicated non-decussation. Consequently, we also obtained coronal median nerve SEPs and simultaneous bilateral muscle recordings to lateralized TES (C3-Cz, C4-Cz) intraoperatively and focal hand area transcranial magnetic stimulation (TMS) postoperatively. RESULTS: For each nerve, tibial P37/N37 distribution was contralateral/ipsilateral and median N20 ipsilateral. For each hemisphere, ipsilateral TES MEPs had lower thresholds and TMS MEPs were exclusively ipsilateral. Accurate monitoring required reversed montages. Reevaluation of an MRI (previously reported normal) disclosed a ventral midline cleft of the medulla. CONCLUSIONS: The results indicate uncrossed dorsal column-medial lemniscal and corticospinal pathways due to brain-stem malformation with absent internal arcuate and pyramidal decussations. SIGNIFICANCE: Simultaneous bilateral recording to unilateral stimulation demonstrates SEP/MEP hemispheric origin and is important for accurate interpretation and monitoring because decussation anomalies exist.     

Long lasting effects of transcranial direct current stimulation on motor imagery

Transcranial magnetic stimulation (TMS) was employed to probe the modulatory effects of transcranial direct current stimulation of motor cortex on motor evoked responses (MEPs) produced during motor imagery. MEP amplitudes at rest and during motor imagery were assessed before and for a period of 60 min after transcranial direct current stimulation (tDCS) applied over the primary motor cortex at 1 mA for 5 min. Cathodal stimulation induced a decrease of about 30% of MEP amplitude at rest and a 50% reduction of MEP size during imagery. Ten minutes after tDCS, MEPs at rest returned to baseline values while MEPs during motor imagery were suppressed for up to 30 min. No changes in MEP amplitude during imagery were found after anodal stimulation. tDCS could represent a powerful tool to modulate the excitability of motor areas involved in mental practice and motor imagery.     

Nonspecific facilitation of responses to transcranial magnetic stimulation.

We examined the effect of facial muscle contraction and eye movements on motor evoked potentials (MEPs) from the abductor pollicis brevis muscle (APB) evoked by transcranial magnetic stimulation (TMS). The hypothesis was that activity of large cortical regions (face) influences the excitability of spinal motoneurons via cortical or subcortical pathways. MEPs were recorded in 12 healthy subjects during the following conditions: (1) rest; (2) facial muscle contraction; (3) eye movements; (4) 10% precontraction of the target muscle; and (5) simultaneous target muscle precontraction and facial muscle contraction. In 9 subjects, spinal motoneuron excitability was assessed by measurements of F waves during the same facilitation maneuvers. Activation of eye and facial muscles clearly facilitated MEPs from the APB. The facilitation of MEP size during nonspecific maneuvers was almost similar to that obtained by target muscle precontraction, whereas shortening of latencies was significantly smaller. The occurrence and amplitude of F waves increased in parallel with MEP size during specific and nonspecific facilitation, pointing to spinal motoneuronal threshold changes as a potential facilitatory mechanism by facial and eye muscle activation. The different MEP latencies during specific and nonspecific facilitation were not explained by different spinal motoneuron excitability, but raise the possibility that supraspinal mechanisms contributed to nonspecific facilitation.     

Inhibition of ipsilateral motor cortex during phasic generation of low force.

OBJECTIVE: To study the effect of different types of unilateral pinch grips on excitability of the ipsilateral motor cortex. METHODS: In 9 healthy volunteers, transcranial magnetic stimuli (TMS) were applied over one motor cortex while the subjects performed either phasic or tonic ipsilateral pinch grips with different force levels (range 1-40% maximum voluntary contraction, MVC). Motor evoked potentials (MEP) were recorded from the relaxed contralateral first dorsal interosseous muscle (FDI) and were compared to MEPs obtained during muscle relaxation of both hands. In additional experiments, transcranial electrical stimuli (TES) were administered and F waves were recorded after electrical stimulation of the ulnar nerve. RESULTS: Phasic pinch grips with low force (1 and 2% MVC) induced a significant decrease of TMS-induced MEP amplitudes. The effect lasted for about 100 ms after reaching the force level and was similar for both right and left-handed pinch grips. TES-induced MEPs and F waves remained unchanged. In contrast, tonic contractions (20 and 40% MVC) enhanced MEPs in the homologous FDI. CONCLUSIONS: Phasic pinch grips with low force inhibit the motor cortex responsible for the contralateral homologous hand muscle. This effect, which is probably mediated transcallosally, might act at the level of the motor cortex.     

Central changes in muscle fatigue during sustained submaximal isometric voluntary contraction as revealed by transcranial magnetic stimulation

Changes in responses to transcranial magnetic stimulation (TMS) during submaximal isometric voluntary contraction (60% of maximal voluntary contraction (MVC) of the adductor pollicis muscle and the subsequent recovery period have been studied in healthy volunteers. TMS at twice the motor threshold was applied during the sustained contraction, as well as at rest and during short-lasting (2 s) 60% MVCs before and immediately after the sustained contraction, and at 5 min intervals during the recovery period. Both motor evoked potential (MEP) magnitude (peak and area) and silent period (SP) duration in electromyographic activity (EMG) of the adductor pollicis muscle showed a gradual decrease up to the endurance point and an increase thereafter. MEPs elicited at rest immediately after the fatiguing contraction were larger, whereas those elicited later on during the recovery period did not differ significantly from the controls. It is suggested that the changes in responses to TMS, divergent from those in ongoing voluntary EMG during the sustained 60% MVC, indicate complex processes at levels preceding the motor cortex output cells in an attempt to maintain a submaximal contraction of the fatigued muscle. The increase in MEP magnitude after the sustained 60% MVC may indicate residual changes in cortical activity after fatiguing contraction.     

Excitability profile of motor evoked potentials and silent periods

The aim of this study was to confirm the excitability profile of human cortical circuits on the motor evoked potential (MEP) and the silent period (SP) after paired transcranial magnetic stimulation (TMS) with variable interstimulus intervals (ISI), and to compare the time courses of MEP and SP after paired TMS at variable ISIs. MEPs were elicited at the hypothenar muscles at rest, and during tonic muscle contraction by applying paired TMS to the motor cortex. The authors measured the MEP amplitude during rest and the duration of SP during tonic muscle contraction at various ISIs. The response to paired stimuli was inhibited by an ISI of 15 ms and facilitated by an ISI of 1020 ms. The SP at an ISI of 15 ms was shorter than that at the single suprathreshold stimulus, but the SP at an ISI of 1525 ms was longer than this. A significant correlation was observed between the MEP amplitude and the duration of SP at ISIs of 120 ms and for a CS of 80% of threshold. These results may provide useful data for the study of the function of cortical excitability in disease states and suggest that the neural circuits underlying MEP and SP differ partly.     

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.     

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.     

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.     

Role of intracortical mechanisms in the late part of the silent period to transcranial stimulation of the human motor cortex

Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) of the human motor cortex produce a silent period (SP) following motor evoked potentials (MEPs). The early part of the SP can be explained by decreased alpha motor neuron excitability, whereas the late part is presumably due to suprasegmental mechanisms. In order to determine the level of the suprasegmental contribution to the generation of SPs, we recorded excitatory and inhibitory responses to TMS, TES, and percutaneous electrical brainstem stimulation (PBS) in the voluntarily activated first dorsal interosseous muscle of the hand. Stimulus intensities were set so that PBS and TES induced MEPs with areas equal to or larger than those of MEPs obtained with TMS. This procedure revealed that SPs were 49% and 83% shorter with TES and PBS, respectively, than with TMS. As TMS is more effective than TES or PBS in activating cortical interneurons, these findings support the idea that a significant component of the SP arises from intracortical mechanisms.     

Differential modulation of motor evoked potential and silent period by activation of intracortical inhibitory circuits.

OBJECTIVES: To investigate the effect of activation of intracortical inhibitory circuits, as tested by short interval (3 ms) paired-pulse transcranial magnetic stimulation (TMS) with a conditioning-test paradigm, on the electromyographic (EMG) pause (silent period, SP) following the motor evoked potential (MEP) in normal subjects. METHODS: SPs and MEPs were recorded from the right first dorsal interosseous (FDI) muscle during a tonic voluntary contraction (from 70 to 90% of the maximum). Using a focal coil, we compared the SP duration after single-pulse TMS, paired-pulse TMS and single-pulse TMS of reduced intensity such as to evoke MEPs matched in size to the conditioned ones after paired-pulse TMS. In addition, we compared in a control experiment the duration of the SP following matched size MEPs evoked, respectively, by focal TMS with preferential activation of indirect I1- or I3-waves. RESULTS: SP duration after paired-pulse TMS was significantly longer than after single-pulse TMS evoking MEPs of a similar size. In no case the SP duration was longer when focal TMS preferentially activated I1-waves. CONCLUSIONS: The conditioning sub-threshold stimulus is more powerful in reducing the MEP size than in cutting down the subsequent EMG silence, suggesting that the neural circuits underlying MEP and SP are, at least in part, different.     

Excitability Profile of Motor Evoked Potentials and Silent Periods

The aim of this study was to confirm the excitability profile of human cortical circuits on the motor evoked potential (MEP) and the silent period (SP) after paired transcranial magnetic stimulation (TMS) with variable interstimulus intervals (ISI), and to compare the time courses of MEP and SP after paired TMS at variable ISIs. MEPs were elicited at the hypothenar muscles at rest, and during tonic muscle contraction by applying paired TMS to the motor cortex. The authors measured the MEP amplitude during rest and the duration of SP during tonic muscle contraction at various ISIs. The response to paired stimuli was inhibited by an ISI of 1–5 ms and facilitated by an ISI of 10–20 ms. The SP at an ISI of 1–5 ms was shorter than that at the single suprathreshold stimulus, but the SP at an ISI of 15–25 ms was longer than this. A significant correlation was observed between the MEP amplitude and the duration of SP at ISIs of 1–20 ms and for a CS of 80% of threshold. These results may provide useful data for the study of the function of cortical excitability in disease states and suggest that the neural circuits underlying MEP and SP differ partly.     

Motor evoked potentials from masseter muscle induced by transcranial magnetic stimulation of the pyramidal tract: the importance of coil orientation

BACKGROUND: Reliable recording of motor evoked potentials (MEPs) of the masseter muscle by transcranial magnetic stimulation (TMS) has proved more difficult than from facial or intrinsic hand muscles. Up to now it was unclear whether this difficulty was due to methodological and/or anatomical reasons. METHODS: The mechanism of pyramidal cell activation in masseter MEPs was investigated by using magnetic and electric transcranial stimulation. Analysing the effect of magnetic coil positioning and orientation over the scalp, and scrutinizing the masseter recording technique to avoid compound motor action potential (CMAP) contamination from facial muscles, an optimized method of masseter MEPs was developed. RESULTS: In particular, an antero-lateral inducing current orientation in the stimulating coil, approximately paralleling the central sulcus, proved clearly more effective for the masseter muscles than the postero-lateral orientation (P=0.005) found optimal for intrinsic hand muscles. The thus evoked masseter MEPs by transcranial magnetic stimulation (TMS) were found to be identical in shape, amplitude and latency as those evoked by transcranial electric stimulation (TES), evidencing a direct rather than trans-synaptic activation of the pyramidal cells. CONCLUSIONS: We conclude that in TMS evoked MEPs of masseter muscles, the direct stimulation of the pyramidal tract is more easily achieved than the trans-synaptic activation, which is in contrast to the intrinsic hand muscles. We hypothesize that the presynaptic projections to pyramidal cells of the masticatory muscles are less abundant than in hand muscles, and are therefore less accessible to trans-synaptic stimulation.     

Post-exercise facilitation and depression of motor evoked potentials to transcranial magnetic stimulation: a study in multiple sclerosis.

OBJECTIVE: To evaluate motor cortex excitability changes by transcranial magnetic stimulation (TMS) following repetitive muscle contractions in patients with multiple sclerosis (MS); to state whether a typical pattern of post-exercise motor evoked potentials (MEPs) is related to clinical fatigue in MS. METHODS: In 41 patients with definite MS (32 with fatigue and 9 without fatigue according to Fatigue Severity Scale) and 13 controls, MEPs were recorded at rest: at baseline condition, following repetitive contractions until fatigue, and after fatigue, to evaluate post-exercise MEP facilitation (PEF) and depression (PED). RESULTS: After exercise, MEP amplitude significantly increased both in patients and controls (PEF). When fatigue set in, MEP amplitude was significantly reduced in normal subjects (PED), but not in patients. Post-exercise MEP findings were similar both in patients with and without fatigue. CONCLUSIONS: Our findings suggest an intracortical motor dysfunction following a voluntary contraction in MS patients, possibly due to failure of depression of facilitatory cortical circuits, or alternatively of inhibitory mechanisms.     

Input-output organization of the foot motor area in humans.

OBJECTIVE: A well-organized input-output relation similar to that of the monkey motor cortex has been demonstrated in the human hand motor area (Terao Y, Ugawa Y, Uesaka Y, Hanajima R, Gemba-Shimizu K, Ohki Y, Kanazawa I. Input-output organization in the hand area of the human motor cortex, Electroenceph clin Neurophysiol 1995;97:375-381). The aim of this study is to investigate the input-output organization of the human foot motor area. METHODS: We studied the effect of tactile stimuli given to the toe tip on the sizes of following responses; motor evoked potentials (MEPs) elicited by transcranial magnetic or electrical stimulation (TMS or TES) over the motor cortex and magnetic stimulation at the foramen magnum level. RESULTS: Air stimuli applied to the toe tip facilitated magnetically evoked MEPs of mainly the muscle attached to that toe, although a less prominent facilitation was also noted in muscles attached to the adjacent toes. Neither responses evoked by TES, nor those by stimulation at the foramen magnum level, were affected by air stimuli. These results suggest that the observed facilitatory effect occurs at the cortical level. CONCLUSION: A fairly well-organized input-output relation is present also in the foot motor area in humans, although the facilitatory effect is not so topographically restricted as is noted for the hand motor area.