Change in the Ipsilateral Motor Cortex Excitability Is Independent from a Muscle Contraction Phase during Unilateral Repetitive Isometric Contractions

The aim of this study was to investigate the difference in a muscle contraction phase dependence between ipsilateral (ipsi)- and contralateral (contra)-primary motor cortex (M1) excitability during repetitive isometric contractions of unilateral index finger abduction using a transcranial magnetic stimulation (TMS) technique. Ten healthy right-handed subjects participated in this study. We instructed them to perform repetitive isometric contractions of the left index finger abduction following auditory cues at 1 Hz. The force outputs were set at 10, 30, and 50% of maximal voluntary contraction (MVC). Motor evoked potentials (MEP) were obtained from the right and left first dorsal interosseous muscles (FDI). To examine the muscle contraction phase dependence, TMS of ipsi-M1 or contra-M1 was triggered at eight different intervals (0, 20, 40, 60, 80, 100, 300, or 500 ms) after electromyogram (EMG) onset when each interval had reached the setup triggering level. Furthermore, to demonstrate the relationships between the integrated EMG (iEMG) in the active left FDI and the ipsi-M1 excitability, we assessed the correlation between the iEMG in the left FDI for the 100 ms preceding TMS onset and the MEP amplitude in the resting/active FDI for each force output condition. Although contra-M1 excitability was significantly changed after the EMG onset that depends on the muscle contraction phase, the modulation of ipsi-M1 excitability did not differ in response to any muscle contraction phase at the 10% of MVC condition. Also, we found that contra-M1 excitability was significantly correlated with iEMG in all force output conditions, but ipsi-M1 excitability was not at force output levels of below 30% of MVC. Consequently, the modulation of ipsi-M1 excitability was independent from the contraction phase of unilateral repetitive isometric contractions at least low force output.     

Excitability of the Primary Motor Cortex Increases More Strongly with Slow- than with Normal-Speed Presentation of Actions

Introduction

The aim of the present study was to investigate how the speed of observed action affects the excitability of the primary motor cortex (M1), as assessed by the size of motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS).

Methods

Eighteen healthy subjects watched a video clip of a person catching a ball, played at three different speeds (normal-, half-, and quarter-speed). MEPs were induced by TMS when the model''s hand had opened to the widest extent just before catching the ball (“open”) and when the model had just caught the ball (“catch”). These two events were locked to specific frames of the video clip (“phases”), rather than occurring at specific absolute times, so that they could easily be compared across different speeds. MEPs were recorded from the thenar (TH) and abductor digiti minimi (ADM) muscles of the right hand.

Results

The MEP amplitudes were higher when the subjects watched the video clip at low speed than when they watched the clip at normal speed. A repeated-measures ANOVA, with the factor VIDEO-SPEED, showed significant main effects. Bonferroni''s post hoc test showed that the following MEP amplitude differences were significant: TH, normal vs. quarter; ADM, normal vs. half; and ADM, normal vs. quarter. Paired t-tests showed that the significant MEP amplitude differences between TMS phases under each speed condition were TH, “catch” higher than “open” at quarter speed; ADM, “catch” higher than “open” at half speed.

Conclusions

These results indicate that the excitability of M1 was higher when the observed action was played at low speed. Our findings suggest that the action observation system became more active when the subjects observed the video clip at low speed, because the subjects could then recognize the elements of action and intention in others.     

A Higher Number of TMS-Elicited MEP from a Combined Hotspot Improves Intra- and Inter-Session Reliability of the Upper Limb Muscles in Healthy Individuals

We aimed to determine, using transcranial magnetic stimulation (TMS), the number of elicited motor evoked potentials (MEPs) that induces the highest intra- and inter-sessions reliability for the extensor carpi radialis (ECR) and first dorsal interosseus (FDI) muscles. Twelve healthy subjects participated in this study on two separate days. Single pulse magnetic stimuli were triggered with Magstim 200² to obtain MEPs from the muscles of interest, with the subjects in a relaxed position. Reliability of MEP responses was investigated in three blocks of 5, 10 and 15 trials. The intra- and inter-session reliability of the MEPs'' amplitudes and latencies were assessed using intraclass correlation coefficients (ICCs). Repeated measures ANOVA and paired t-tests revealed no significant time effect in the MEP amplitude and latency measurements (P>0.05). The ICCs indicated high intra-session reliability in the MEPs'' amplitudes for the ECR and FDI muscles (0.77 to 0.99, 0.90 to 0.99, respectively) and latency (0.80 to 1.00, 0.75 to 0.97, respectively). The MEPs'' amplitudes also had high inter-session reliability (0.84 to 0.97, 0.88 to 0.93, respectively), as did their latency (0.80 to 0.90, 0.75 to 0.97, respectively). Highest intra- and inter-session reliability was achieved for blocks of 10 and 15 trials. Our data suggest that intra- and inter-session comparisons should be performed using at least 10 MEPs in “combined hotspot” stimulation technique to ensure highest reliability.     

Stimulus–response characteristics of motor evoked potentials and silent periods in proximal and distal upper-extremity muscles

ObjectiveTo compare stimulus–response characteristics of both motor evoked potentials (MEP) and silent periods (SP) induced by transcranial magnetic stimulation (TMS) in proximal and distal upper-extremity muscles.MethodsStimulus–response curves of MEPs and SPs were obtained from the biceps brachii (BB) and abductor digiti minimi (ADM) muscles in 15 healthy participants. A nonlinear mixed model was used to fit the stimulus–response curves to a sigmoid Boltzmann function.ResultsSmall residuals of the function were found for MEPs and SPs in both muscles. Higher maximal MEP amplitudes were found for the BB compared to the ADM (p < 0.01). The active motor threshold to obtain a SP was less for the ADM compared to the BB (p < 0.01). The slope parameter of the function of the SP duration was steeper and more variable in the ADM than in the BB (p < 0.01). For the MEP amplitude no difference in active motor threshold and slope of the function was found between both muscles.ConclusionsExcitatory (MEP) and inhibitory (SP) effects of TMS differ between proximal arm and distal hand muscles in healthy participants. The adequate fit of our model suggests that this model can be used to study between and within subject changes in future studies.     

Modulation of Short-Latency Afferent Inhibition Depends on Digit and Task-Relevance

Short-latency afferent inhibition (SAI) occurs when a single transcranial magnetic stimulation (TMS) pulse delivered over the primary motor cortex is preceded by peripheral electrical nerve stimulation at a short inter-stimulus interval (∼20–28 ms). SAI has been extensively examined at rest, but few studies have examined how this circuit functions in the context of performing a motor task and if this circuit may contribute to surround inhibition. The present study investigated SAI in a muscle involved versus uninvolved in a motor task and specifically during three pre-movement phases; two movement preparation phases between a “warning” and “go” cue and one movement initiation phase between a “go” cue and EMG onset. SAI was tested in the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles in twelve individuals. In a second experiment, the origin of SAI modulation was investigated by measuring H-reflex amplitudes from FDI and ADM during the motor task. The data indicate that changes in SAI occurred predominantly in the movement initiation phase during which SAI modulation depended on the specific digit involved. Specifically, the greatest reduction in SAI occurred when FDI was involved in the task. In contrast, these effects were not present in ADM. Changes in SAI were primarily mediated via supraspinal mechanisms during movement preparation, while both supraspinal and spinal mechanisms contributed to SAI reduction during movement initiation.     

Influence of Vibration on Motor Responses in the Upper Arm Muscles under Stationary Conditions and during Voluntary and Evoked Arm Movements under Limb Unloading Conditions

Locomotion of mammals, including humans, is based on the rhythmic activity of spinal cord circuitries. The functioning of these circuitries depends on multimodal afferent information and on supraspinal influences from the motor cortex. Using the method of transcranial magnetic stimulation (TMS) of arm muscle areas in the motor cortex, we studied the motor evoked potentials (MEP) in the upper arm muscles in stationary conditions and during voluntary and vibration-evoked arm movements. The study included 13 healthy subjects under arm and leg unloading conditions. In the first series of experiments, with motionless limbs, the effect of vibration of left upper arm muscles on motor responses in these muscles was evaluated. In the second series of experiments, MEP were compared in the same muscles during voluntary and rhythmic movements generated by left arm m. triceps brachii vibration (the right arm was stationary). Motionless left arm vibration led to an increase in MEP values in both vibrated muscle and in most of the non-vibrated muscles. For most target muscles, MEP was greater with voluntary arm movements than with vibration-evoked movements. At the same time, a similar MEP modulation in the cycle of arm movements was observed in the same upper arm muscles during both types of arm movements. TMS of the motor cortex significantly potentiated arm movements generated by vibration, but its effect on voluntary movements was weaker. These results indicate significant differences in the degree of motor cortex involvement in voluntary and evoked arm movements. We suppose that evoked arm movements are largely due to spinal rather than central mechanisms of generation of rhythmic movements.     

Primary Motor Cortex Representation of Handgrip Muscles in Patients with Leprosy

Background

Leprosy is an endemic infectious disease caused by Mycobacterium leprae that predominantly attacks the skin and peripheral nerves, leading to progressive impairment of motor, sensory and autonomic function. Little is known about how this peripheral neuropathy affects corticospinal excitability of handgrip muscles. Our purpose was to explore the motor cortex organization after progressive peripheral nerve injury and upper-limb dysfunction induced by leprosy using noninvasive transcranial magnetic stimulation (TMS).

Methods

In a cross-sectional study design, we mapped bilaterally in the primary motor cortex (M1) the representations of the hand flexor digitorum superficialis (FDS), as well as of the intrinsic hand muscles abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor digiti minimi (ADM). All participants underwent clinical assessment, handgrip dynamometry and motor and sensory nerve conduction exams 30 days before mapping. Wilcoxon signed rank and Mann-Whitney tests were performed with an alpha-value of p<0.05.

Findings

Dynamometry performance of the patients’ most affected hand (MAH), was worse than that of the less affected hand (LAH) and of healthy controls participants (p = 0.031), confirming handgrip impairment. Motor threshold (MT) of the FDS muscle was higher in both hemispheres in patients as compared to controls, and lower in the hemisphere contralateral to the MAH when compared to that of the LAH. Moreover, motor evoked potential (MEP) amplitudes collected in the FDS of the MAH were higher in comparison to those of controls. Strikingly, MEPs in the intrinsic hand muscle FDI had lower amplitudes in the hemisphere contralateral to MAH as compared to those of the LAH and the control group. Taken together, these results are suggestive of a more robust representation of an extrinsic hand flexor and impaired intrinsic hand muscle function in the hemisphere contralateral to the MAH due to leprosy.

Conclusion

Decreased sensory-motor function induced by leprosy affects handgrip muscle representation in M1.     

Different motor learning effects on excitability changes of motor cortex in muscle contraction state

Abstract

We aimed to investigate whether motor learning induces different excitability changes in the human motor cortex (M1) between two different muscle contraction states (before voluntary contraction [static] or during voluntary contraction [dynamic]). For the same, using motor evoked potentials (MEPs) obtained by transcranial magnetic stimulation (TMS), we compared excitability changes during these two states after pinch-grip motor skill learning. The participants performed a force output tracking task by pinch grip on a computer screen. TMS was applied prior to the pinch grip (static) and after initiation of voluntary contraction (dynamic). MEPs of the following muscles were recorded: first dorsal interosseous (FDI), thenar muscle (Thenar), flexor carpi radialis (FCR), and extensor carpi radialis (ECR) muscles. During both the states, motor skill training led to significant improvement of motor performance. During the static state, MEPs of the FDI muscle were significantly facilitated after motor learning; however, during the dynamic state, MEPs of the FDI, Thenar, and FCR muscles were significantly decreased. Based on the results of this study, we concluded that excitability changes in the human M1 are differentially influenced during different voluntary contraction states (static and dynamic) after motor learning.     

Participation of primary motor cortex in the programming of muscle activity during catching of a falling object

A sitting person has been exposed to transcranial magnetic stimulation (TMS) of the primary motor cortex shortly before and during increasing anticipatory grip force, while an object was falling into a cup held between the thumb and index finger of the subject. Comparison of the changes in the electrical activity of adductor pollicis brevis and the first dorsal interosseous muscles and of TMS response in these muscles revealed, on the one hand, a strong increase in TMS response not long before enhancement of muscle activity and, on the other hand, an insignificant increase in the response amplitude during substantial increase in muscle activity. An increase in the TMS response prior to initiation of motor activity suggests that the excitability of the primary motor cortex is enhanced due to specific processes caused by the direct involvement of the cortex in the programming of motor activity.     

Corticospinal Facilitation during Observation of Graspable Objects: A Transcranial Magnetic Stimulation Study

In 1979, Gibson first advanced the idea that the sight of graspable objects automatically activates in the observer the repertoire of actions necessary to interact with them, even in the absence of any intention to act (“affordance effect”). The neurophysiological substrate of this effect was later identified in a class of bimodal neurons, the so-called "canonical" neurons, located within monkey premotor cortex. In humans, even if different behavioral studies supported the existence of affordance effect, neurophysiological investigations exploring its neural substrates showed contradictory results. Here, by means of Transcranial Magnetic Stimulation (TMS), we explored the time-course of the “affordance effect” elicited by the observation of everyday-life graspable objects on motor cortex of resting observers. We recorded motor evoked potentials (MEP) from three intrinsic hand muscles (two "synergic" for grasping, OP and FDI and one "neutral", ADM). We found that objects’ vision determined an increased excitability at 120 milliseconds after their presentation. Moreover, this modulation was proved to be specific to the cortical representations of synergic muscles. From an evolutionary perspective, this timing perfectly fits with a fast recruitment of the motor system aimed at rapidly and accurately choosing the appropriate motor plans in a competitive environment filled with different opportunities.     

Startle stimuli exert opposite effects on human cortical and spinal motor system excitability in leg muscles

Increased excitability of the spinal motor system has been observed after loud and unexpected acoustic stimuli (AS) preceding H-reflexes. The paradigm has been proposed as an electrophysiological marker of reticulospinal tract activity in humans. The brainstem reticular formation also maintains dense anatomical interconnections with the cortical motor system. When a startling AS is delivered, prior to transcranial magnetic stimulation (TMS), the AS produces a suppression of motor evoked potential (MEP) amplitude in hand and arm muscles of healthy subjects. Here we analyzed the conditioning effect of a startling AS on MEP amplitude evoked by TMS to the primary motor leg area. Ten healthy volunteers participated in two experiments that used a conditioning-test paradigm. In the first experiment, a startling AS preceded a suprathreshold transcranial test stimulus. The interstimulus interval (ISI) varied between 20 to 160 ms. When given alone, the test stimulus evoked a MEP amplitude of approximately 0.5 mV in the slightly preinervated soleus muscle (SOL). In the second experiment, the startling AS was used to condition the size of the H-reflex in SOL muscle. Mean MEP amplitude was calculated for each ISI. The conditioning AS suppressed MEP amplitude at ISIs of 30-80 ms. By contrast, H-reflex amplitude was augmented at ISIs of 100-200 ms. In conclusions, acoustic stimulation exerts opposite and ISI-specific effects on the amplitude of MEPs and H-reflex in the SOL muscle, indicating different mechanism of auditory-to-motor interactions at cortical and spinal level of motor system.     

Motor cortex excitability during unilateral muscle activity.

The effect of unilateral tonic muscle activity with and without co-activation of the antagonists on motor cortex excitability has been studied. Motor evoked potentials (MEPs) were recorded from the first dorsal interosseus muscles of both hands in response to transcranial magnetic stimulation (TMS) during relax, isometric index finger abduction and antagonistic co-activation. The intracortical inhibition (ICI) and intracortical facilitation (ICF) were investigated by paired-pulse TMS with interstimulus intervals of 3 and 13 ms. The unilateral tonic activation of the right hand facilitated contralateral and ipsilateral responses (cMEP and iMEP) recorded from both hands with an exception of iMEPs recorded from the left hand. During paired-pulse TMS ICI for cMEPs was not influenced by the unilateral tonic activity in both hands, while ICF was suppressed when MEPs were recorded from the active right hand. The effect of unilateral tonic activity on iMEP in response to paired-pulse TMS was essentially different: generally, ICI was greater for iMEPs and ICF was completely abolished with an exception of iMEPs recorded from the left hand during right finger isometric abduction when a strong ICF was evident. The decreased ICF and/or increased ICI are assumed to reflect mechanisms underlying the co-activation of antagonists.     

Hasty sensorimotor decisions rely on an overlap of broad and selective changes in motor activity

Humans and other animals are able to adjust their speed–accuracy trade-off (SAT) at will depending on the urge to act, favoring either cautious or hasty decision policies in different contexts. An emerging view is that SAT regulation relies on influences exerting broad changes on the motor system, tuning its activity up globally when hastiness is at premium. The present study aimed to test this hypothesis. A total of 50 participants performed a task involving choices between left and right index fingers, in which incorrect choices led either to a high or to a low penalty in 2 contexts, inciting them to emphasize either cautious or hasty policies. We applied transcranial magnetic stimulation (TMS) on multiple motor representations, eliciting motor-evoked potentials (MEPs) in 9 finger and leg muscles. MEP amplitudes allowed us to probe activity changes in the corresponding finger and leg representations, while participants were deliberating about which index to choose. Our data indicate that hastiness entails a broad amplification of motor activity, although this amplification was limited to the chosen side. On top of this effect, we identified a local suppression of motor activity, surrounding the chosen index representation. Hence, a decision policy favoring speed over accuracy appears to rely on overlapping processes producing a broad (but not global) amplification and a surround suppression of motor activity. The latter effect may help to increase the signal-to-noise ratio of the chosen representation, as supported by single-trial correlation analyses indicating a stronger differentiation of activity changes in finger representations in the hasty context.

Many have argued that the regulation of the speed-accuracy tradeoff relies on an urgency signal, which implements "collapsing decision thresholds" by tuning neural activity in a global manner in decision-related structures. This study indicates that the reality is more subtle, with several aspects of "urgency" being specifically targeted to particular corticospinal populations within the motor system.     

Contralateral muscle activity and fatigue in the human first dorsal interosseous muscle.

During effortful unilateral contractions, muscle activation is not limited to the target muscles but activity is also observed in contralateral muscles. The amount of this associated activity is depressed in a fatigued muscle, even after correction for fatigue-related changes in maximal force. In the present experiments, we aimed to compare fatigue-related changes in associated activity vs. parameters that are used as markers for changes in central nervous system (CNS) excitability. Subjects performed brief maximal voluntary contractions (MVCs) with the index finger in abduction direction before and after fatiguing protocols. We followed changes in MVCs, associated activity, motor-evoked potentials (MEP; transcranial magnetic stimulation), maximal compound muscle potentials (M waves), and superimposed twitches (double pulse) for 20 min after the fatiguing protocols. During the fatiguing protocols, associated activity increased in contralateral muscles, whereas afterwards the associated force was reduced in the fatigued muscle. This force reduction was significantly larger than the decline in MVC. However, associated activity (force and electromyography) remained depressed for only 5-10 min, whereas the MVCs stayed depressed for over 20 min. These decreases were accompanied by a reduction in MEP, MVC electromyography activity, and voluntary activation in the fatigued muscle. According to these latter markers, the decrease in CNS motor excitability lasted much longer than the depression in associated activity. Differential effects of fatigue on (associated) submaximal vs. maximal contractions might contribute to these differences in postfatigue behavior. However, we cannot exclude differences in processes that are specific to either voluntary or to associated contractions.     

Selective increase in corticospinal excitability in the context of tactile exploration

In this study, we compared changes in corticomotor excitability under various task conditions engaging the index finger of each hand. Functional demands were varied, from simple execution to demanding sensory exploration. In a first experiment, we contrasted facilitation in the first dorsal interosseus (FDI) by monitoring changes in motor evoked potentials (MEPs) when participants (young adults, n = 18) performed either a simple button pressing (BP) task or a more demanding tactile exploration (TE) task (i.e., discrimination of raised letters). This experiment showed a large effect of task conditions (p < 0.01) on MEP amplitude but no effect of “Hand”, while latency measurements were unchanged. In fact, MEPs were on average 40% larger during TE (2410 ± 1358 µV) than during BP (1670 ± 1477 µV). The two tasks produced, however, different patterns of electromyographic (EMG) activity, which could have accounted for some of the differences observed. A second experimental session involved a subset of participants (10/18) tested in third task condition: finger movement (FM). The latter task consisted of scanning a smooth surface with the tip of the index finger to reproduce the movements seen with the TE task. The addition of this third condition task confirmed that MEP facilitation seen during TE reflected task-specific influences and not differences in background EMG activity. These results, altogether, provide further insights into the effect of task conditions on corticomotor excitability. Our findings, in particular, stress the importance of behavioural context and tactile exploration in leading to selective increase in corticomotor excitability during finger movements.     

Prognostic value of cortically induced motor evoked activity by TMS in chronic stroke: Caveats from a revealing single clinical case

Background

We report the case of a chronic stroke patient (62?months after injury) showing total absence of motor activity evoked by transcranial magnetic stimulation (TMS) of spared regions of the left motor cortex, but near-to-complete recovery of motor abilities in the affected hand.

Case presentation

Multimodal investigations included detailed TMS based motor mapping, motor evoked potentials (MEP), and Cortical Silent period (CSP) as well as functional magnetic resonance imaging (fMRI) of motor activity, MRI based lesion analysis and Diffusion Tensor Imaging (DTI) Tractography of corticospinal tract (CST). Anatomical analysis revealed a left hemisphere subinsular lesion interrupting the descending left CST at the level of the internal capsule. The absence of MEPs after intense TMS pulses to the ipsilesional M1, and the reversible suppression of ongoing electromyographic (EMG) activity (indexed by CSP) demonstrate a weak modulation of subcortical systems by the ipsilesional left frontal cortex, but an inability to induce efficient descending volleys from those cortical locations to right hand and forearm muscles. Functional MRI recordings under grasping and finger tapping patterns involving the affected hand showed slight signs of subcortical recruitment, as compared to the unaffected hand and hemisphere, as well as the expected cortical activations.

Conclusions

The potential sources of motor voluntary activity for the affected hand in absence of MEPs are discussed. We conclude that multimodal analysis may contribute to a more accurate prognosis of stroke patients.     

Participation of the primary motor cortex in programming of muscle activity during catching of falling object

Object fell into the cup that sitting subject held between thumb and index fingers. Transcranial magnetic stimulation (TMS) of the primary motor cortex was performed early before and during anticipatory grip force increasing. Comparison of current EMG activity of adductor pollicis brevis and first dorsal interosseous muscles and responses of these muscles on TMS showed that responses were increased before the raising of muscle activity. From the other side only slight augmentation of responses was observed during subsequent strong muscle activation. It is assumed that the increasing of the TMS responses that occurred before the initiation of muscle activity reflects the enhancement ofthe motor cortex excitability associated to specific processes related to the motor cortex participation in programming of the muscles activities.     

Motor unit number estimation as a complementary test to routine electromyography in the diagnosis of amyotrophic lateral sclerosis

Electromyographic (EMG) abnormalities that reveal denervation and reinnervation caused by lower motor neuron degeneration do not reflect the number of motor units that determines muscle strength. Consequently, motor unit activity potential (MUAP) parameters do not reflect muscle dysfunction.The aim of the study was to compare the value of motor unit number estimation (MUNE) and MUAP parameters as indicators of clinical muscle dysfunction in patients with amyotrophic lateral sclerosis (ALS), and to analyze the role of MUNE as a supplement to the EMG criteria for the diagnosis of ALS.In 25 patients with ALS, MUNE by the multipoint incremental method in the abductor digiti minimi (ADM) and quantitative EMG in the first dorsal interosseous (FDI) were obtained. The Medical Research Council (MRC) scale was used to evaluate clinical muscle dysfunction. A strong correlation between the number of motor units evaluated by MUNE and ADM clinical function by the MRC scale was found (P < 0.001). An increased value of surface-detected single motor action potential was associated with a decreased MRC score for ADM (P < 0.1). No relation was found between MUAP parameters in FDI and MRC scores. Our data support the value of the MUNE method for the detection of motor unit loss in ALS, and it could be postulated that MUNE studies may be considered complementary tests for ALS in a future revision of ALS criteria.     

Alterations in corticospinal excitability with imposed vs. voluntary fatigue in human hand muscles.

We aimed to determine whether postexercise depression of motor-evoked potentials (MEPs) could be demonstrated without voluntary muscle activation in humans. Voluntary fatigue was induced with a 2-min maximal voluntary contraction (MVC) of the first dorsal interosseous (FDI) muscle. On another occasion, "electrical fatigue" was induced with trains of shocks delivered for 2 min over the FDI motor point. Five of the twelve subjects also underwent "sequential fatigue" consisting of a 2-min MVC of FDI followed by 20 min of rest and then 2 min of motor point stimulation. Voluntary fatigue induced MEP depression that persisted for at least 20 min. Electrical fatigue induced a transient MEP facilitation that subsided 20 min after the stimulation and became depressed within 30 min. Thus MEP depression can be induced by both voluntary and electrical fatigue. With electrical fatigue, the initial depression is "masked" by transient MEP facilitation, reflecting cortical plasticity induced by the prolonged electrical stimulation. MEP depression probably reflects tonic afferent input from the exercising muscle that alters cortical excitability without altering spinal excitability.     

Transpinal and Transcortical Stimulation Alter Corticospinal Excitability and Increase Spinal Output

The objective of this study was to assess changes in corticospinal excitability and spinal output following noninvasive transpinal and transcortical stimulation in humans. The size of the motor evoked potentials (MEPs), induced by transcranial magnetic stimulation (TMS) and recorded from the right plantar flexor and extensor muscles, was assessed following transcutaneous electric stimulation of the spine (tsESS) over the thoracolumbar region at conditioning-test (C-T) intervals that ranged from negative 50 to positive 50 ms. The size of the transpinal evoked potentials (TEPs), induced by tsESS and recorded from the right and left plantar flexor and extensor muscles, was assessed following TMS over the left primary motor cortex at 0.7 and at 1.1× MEP resting threshold at C-T intervals that ranged from negative 50 to positive 50 ms. The recruitment curves of MEPs and TEPs had a similar shape, and statistically significant differences between the sigmoid function parameters of MEPs and TEPs were not found. Anodal tsESS resulted in early MEP depression followed by long-latency MEP facilitation of both ankle plantar flexors and extensors. TEPs of ankle plantar flexors and extensors were increased regardless TMS intensity level. Subthreshold and suprathreshold TMS induced short-latency TEP facilitation that was larger in the TEPs ipsilateral to TMS. Noninvasive transpinal stimulation affected ipsilateral and contralateral actions of corticospinal neurons, while corticocortical and corticospinal descending volleys increased TEPs in both limbs. Transpinal and transcortical stimulation is a noninvasive neuromodulation method that alters corticospinal excitability and increases motor output of multiple spinal segments in humans.