Modulation of corticospinal excitability and intracortical inhibition during motor imagery is task-dependent

Previous studies have clearly shown that motor imagery modulates corticospinal excitability. However, there is no clear evidence for the modulation of intracortical inhibition (ICI) during imagined task performance. The aim of this study was to use transcranial magnetic stimulation (TMS) to assess changes in corticospinal excitability and ICI during the imagined performance of two types of task. In Experiment 1, eight subjects performed phasic depression of a computer mouse button using the dominant index finger in time with a 1 Hz auditory metronome. Single and paired pulse magnetic stimuli were delivered at rest, and during the on and off phases of actual and imagined task performance. Motor evoked potentials (MEPs) were recorded from FDI and APB. In Experiment 2, eight subjects performed phasic isometric abduction of the dominant thumb in time with a 1 Hz auditory metronome. As before, single and paired pulse magnetic stimuli were delivered at rest, and during the on and off phases of actual and imagined task performance. In both experiments, the conditioning stimulus intensity was set to produce 50% inhibition at rest, to enable both increases and decreases in ICI during task performance to be detected. No significant temporal or spatial modulation of MEP amplitude or ICI was observed in Experiment 1. In contrast, MEP amplitude was significantly greater, and ICI significantly lower during the on phase of imagined task performance in Experiment 2. These results are most likely related to the higher levels of target muscle activation required during actual task performance and the greater anatomical distance between target and control muscles in Experiment 2. These task characteristics may influence the observed degree of corticospinal excitability and ICI modulation.     

Rapid changes in corticospinal excitability during force field adaptation of human walking

Force field adaptation of locomotor muscle activity is one way of studying the ability of the motor control networks in the brain and spinal cord to adapt in a flexible way to changes in the environment. Here, we investigate whether the corticospinal tract is involved in this adaptation. We measured changes in motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in the tibialis anterior (TA) muscle before, during, and after subjects adapted to a force field applied to the ankle joint during treadmill walking. When the force field assisted dorsiflexion during the swing phase of the step cycle, subjects adapted by decreasing TA EMG activity. In contrast, when the force field resisted dorsiflexion, they increased TA EMG activity. After the force field was removed, normal EMG activity gradually returned over the next 5 min of walking. TA MEPs elicited in the early swing phase of the step cycle were smaller during adaptation to the assistive force field and larger during adaptation to the resistive force field. When elicited 5 min after the force field was removed, MEPs returned to their original values. The changes in TA MEPs were larger than what could be explained by changes in background TA EMG activity. These effects seemed specific to walking, as similar changes in TA MEP were not seen when seated subjects were tested during static dorsiflexion. These observations suggest that the corticospinal tract contributes to the adaptation of walking to an external force field.     

Modulation of corticospinal excitability during lengthening and shortening contractions in the first dorsal interosseus muscle of humans

Lengthening and shortening contractions are the fundamental patterns of muscle activation underlying various movements. It is still unknown whether or not there is a muscle-specific difference in such a fundamental pattern of muscle activation. The purpose of this study was, therefore, to investigate whether or not the relationship between lengthening and shortening contractions in the modulation of corticospinal excitability in the first dorsal interosseus (FDI) muscle is the same as that of previously tested muscles because the hand muscles are anatomically and functionally different from the other muscles. To this end, we investigated the relationship between the input-output curves of the corticospinal pathway (i.e., the relationship between the stimulus intensities vs. the area of motor-evoked potentials) during lengthening and shortening contractions in 17 healthy subjects. The shape of this relationship was sigmoidal and characterized by a plateau value, maximum slope, and threshold. The plateau value was at the same level between lengthening and shortening contractions. However, the maximum slope (P < 0.01) and threshold (P < 0.01) were significantly higher during lengthening contractions than during shortening contractions. These findings were different from the results of other muscles tested in previous studies (i.e., the soleus muscle and the elbow flexors). That is to say, the plateau value and the maximum slope during lengthening contractions were significantly lower than those during shortening contractions in previous studies. This study provides tentative evidence that the relationship between lengthening and shortening contractions in the modulation of corticospinal excitability differs between muscles, indicating that the underlying neural control is not necessarily the same even though the fundamental patterns of muscle activation are carried out.     

Suppression of corticospinal excitability during negative motor imagery

To investigate the effect of negative motor imagery on corticospinal excitability, we performed transcranial magnetic stimulation (TMS) studies in seven healthy subjects during imagination of suppressing movements. Subjects were asked to imagine suppression of TMS-induced twitching movement of their nondominant left hands by attempting to increase the amount of relaxation after receiving an auditory NoGo cue (negative motor imagery), but to imagine squeezing hands after a Go cue (positive motor imagery). Single- and paired-pulse TMS were triggered at 2 s after Go or NoGo cues. Motor-evoked potentials (MEPs) were recorded in the first dorsal interosseus (FDI), abductor pollicis brevis (APB), and abductor digiti minimi (ADM) muscles of the left hand. Paired-pulse TMS with subthreshold conditioning stimuli at interstimulus intervals of 2 (short intracortical inhibition) and 15 ms (intracortical facilitation) and that with suprathreshold conditioning stimuli at interstimulus interval of 80 ms (long intracortical inhibition) were performed in both negative motor imagery and control conditions. Compared with the control state (no imagination), MEP amplitudes of FDI (but not APB and ADM) were significantly suppressed in negative motor imagery, but those from all three muscles were unchanged during positive motor imagery. F-wave responses (amplitudes and persistence) were unchanged during both negative and positive motor imagery. During negative motor imagery, resting motor threshold was significantly increased, but short and long intracortical inhibition and intracortical facilitation were unchanged. The present results demonstrate that excitatory corticospinal drive is suppressed during imagination of suppressing movements.     

Execution-dependent modulation of corticospinal excitability during action observation

Excitability of the corticospinal pathway increased during observation of an action. The present study investigated whether corticospinal excitability during an action observation is modulated by physical movement executed by the observers themselves. Participants alternately repeated the observation of a pinching action with the thumb and index finger and execution (30 times) of the same action. Motor-evoked potentials (MEPs) induced by transcranial magnetic stimulation were recorded from the first dorsal interosseous muscle during observation of the action. MEP amplitude gradually increased with the number of executions of the same action. However, MEP amplitude did not change when the participants only repeated observation of the pinching action or when the participants alternately repeated observation of the pinching action and execution of the isometric abduction of the index finger. These findings suggest that enhancement of cotricospinal excitability is dependent on the execution of a particular action that is very similar to the observed action.     

Dynamic changes in corticospinal excitability during motor imagery

 We investigated temporal changes in the amplitudes of motor-evoked potentials (MEPs) induced by transcranial magnetic stimulation over the left motor cortex during motor imagery. Nine subjects were instructed to imagine repetitive wrist flexion and extension movements at 1 Hz, in which the flexion timing was cued by a tone signal. Electromyographs (EMGs) were recorded from the first dorsal interosseous, flexor carpi radialis and extensor carpi radialis muscles of the right hand, and magnetic stimulation was delivered at 0, 250, 500 and 750 ms after the auditory cue. On average, the evoked EMG responses were larger in the flexor muscle during the phase of imagined flexion than during extension, whilst the opposite was true for the extensor muscle. There were no consistent changes in the amplitudes of MEPs in the intrinsic hand muscle (first dorsal interosseous). The EMG remained relaxed in all muscles and did not show any significant temporal changes during the test. The H-reflex in the flexor muscle was obtained in four subjects. There was no change in its amplitude during motor imagery. These observations lead us to suggest that motor imagery can have dynamic effects on the excitability of motor cortex similar to those seen during actual motor performance. Received: 23 July 1998 / Accepted: 26 October 1998     

Increased corticospinal excitability induced by unpleasant visual stimuli

Pleasant and unpleasant emotional stimuli are frequently conceptualized as motivators for action. This notion was examined using focal transcranial magnetic stimulation (TMS). Ten healthy participants viewed pleasant, neutral, and unpleasant pictures from the International Affective Picture System (IAPS). During picture viewing, focal TMS was applied to the right motor cortex over the area innervating the first dorsal interosseous muscle of the left hand. Corticomotor excitability was larger while viewing negative pictures than while viewing neutral or positive images, as evidenced by greater motor evoked potentials. No difference was found between pleasant and neutral pictures. These results are consistent with models of emotion in which the neural networks underlying negative emotions have selective, direct connections to brain structures that mediate motor responses.     

Stability of corticospinal excitability and grip force in intrinsic hand muscles in man over a 24-h period

The maximum voluntary muscle force can vary throughout the day; typically being low in the morning and high in the evening. The nature of this possible variation has been investigated with respect to corticospinal excitability. Six healthy subjects were studied. Maximum voluntary contraction (MVC) in the thenar muscles was measured. In addition, we monitored several indices of corticospinal excitability using electromyographic (EMG) recording and transcranial magnetic stimulation (TMS) of the motor cortex. Motor evoked potentials (MEPs) were recorded while relaxed and at 10% MVC when the silent period was assessed as an index of corticospinal inhibition. Readings were taken every 3 h for 24 h. MVC of the thenar muscles did not change significantly over the 24 h. The mean areas, latencies and durations of MEPs did not show significant changes over the 24-h test period with the muscle relaxed or contracted; however, MEP area did vary between sessions at all stimulus intensities suggesting non-time-of-day-dependent changes in corticospinal excitability. Furthermore, the extent and duration of the silent period seen after the MEP in the contracted muscle did not change significantly over the 24 h of the experiment at any stimulus intensity. These results provide evidence that the MVC force of the thenar muscles and their responses to TMS are stable throughout the course of the day and suggest that, in hand muscles, corticospinal excitability may not be subject to circadian variation.     

Experience-dependent modulation of motor corticospinal excitability during action observation

The primate premotor cortex is endowed with an "action observation/execution matching system", that is, the same premotor neurons discharge when actions are performed and when actions are observed. Hence, this system predicts a strong visual input to the motor system. Whether this input is dependent on visual experience or not has not been previously investigated. To address this issue we compared corticospinal excitability while subjects viewed frequently observed and less frequently observed hand actions of others and of themselves. Motor corticospinal excitability was larger when the action orientations were as they are frequently observed (Self-away, subject's own hand facing out from the subject, or Other-toward, an unknown hand facing toward the subject) compared with less frequently observed actions (Self-toward, subject's own hand facing "toward" the subject, or Other-away, an unknown hand facing out from the subject). This finding suggests that the modulation of motor corticospinal excitability during action observation and hence the "action observation/execution matching system" is largely dependent upon visual experience. Electronic Publication     

Voluntary breathing influences corticospinal excitability of nonrespiratory finger muscles

The present study aimed to investigate neurophysiologic mechanisms mediating the newly discovered phenomenon of respiratory-motor interactions and to explore its potential clinical application for motor recovery. First, young and healthy subjects were instructed to breathe normally (NORM); to exhale (OUT) or inhale (IN) as fast as possible in a self-paced manner; or to voluntarily hold breath (HOLD). In experiment 1 (n = 14), transcranial magnetic stimulation (TMS) was applied during 10% maximal voluntary contraction (MVC) finger flexion force production or at rest. The motor-evoked potentials (MEPs) were recorded from flexor digitorum superficialis (FDS), extensor digitorum communis (EDC), and abductor digiti minimi (ADM) muscles. Similarly, in experiment 2 (n = 11), electrical stimulation (ES) was applied to FDS or EDC during the described four breathing conditions while subjects maintained 10%MVC of finger flexion or extension and at rest. In the exploratory clinical experiments (experiment 3), four patients with chronic neurological disorders (three strokes, one traumatic brain injury) received a 30-min session of breathing-controlled ES to the impaired EDC. In experiment 1, the EDC MEP magnitudes increased significantly during IN and OUT at both 10%MVC and rest; the FDS MEPs were enhanced only at 10%MVC, whereas the ADM MEP increased only during OUT, compared with NORM for both at rest and 10%MVC. No difference was found between NORM and HOLD for all three muscles. In experiment 2, when FDS was stimulated, force response was enhanced during both IN and OUT, but only at 10%MVC. When EDC was stimulated, force response increased at both 10%MVC and rest, only during IN, but not OUT. The averaged response latency was 83 ms for the finger extensors and 79 ms for the finger flexors. After a 30-min intervention of ES to EDC triggered by forced inspiration in experiment 3, we observed a significant reduction in finger flexor spasticity. The spasticity reduction lasted for ≥ 4 wk in all four patients. TMS and ES data, collectively, support the phenomenon that there is an overall respiration-related enhancement on the motor system, with a strong inspiration-finger extension coupling during voluntary breathing. As such, breathing-controlled electrical stimulation (i.e., stimulation to finger extensors delivered during the voluntary inspiratory phase) could be applied for enhancing finger extension strength and finger flexor spasticity reduction in poststroke patients.     

Human corticospinal excitability during a precued reaction time paradigm

The purpose of this study was to investigate the time-course of corticospinal excitability during reaction time (RT), and compare the excitability when a precue provided information regarding both the direction and extent of the upcoming movement (Full condition), specified the direction of the upcoming movement only (Direction condition), or provided no information at all (None condition). Ten healthy, right-handed subjects performed a four-choice RT task that involved flexion and extension of dominant wrist. Transcranial magnetic stimulation (TMS) was presented at random intervals over a period of 120 ms prior to the subjects average non-stimulated voluntary electromyography (EMG) activity onset. We found that there was a significant relationship between motor-evoked potential (MEP) amplitude and TMS onset when both the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) acted as an agonist. This relationship could be explained using the sigmoidal Boltzmann equation. The slope for the relationship did not differ between the Full and Direction conditions, suggesting that corticospinal excitability is not altered in the specification of movement extent. Both these conditions differed significantly from the None condition. The modulation of corticospinal excitability appeared greater in the FCR than in the ECR. There was a significant delay in RT the closer in time TMS was presented with respect to EMG onset. During extension, there was no difference in slope between the three conditions, whereas during flexion the slope was greater in the None condition than in the Direction condition, which was in turn greater than in the Full condition. This was mirrored in the relationship between agonist MEP amplitude and TMS onset for both muscles. It is possible that the gain of the corticospinal tract is increased in the conditions in which less information is provided in the precue to partly compensate for the increase in RT, which comes as a result of the additional processing required in those conditions.     

Lower limb immobilization is associated with increased corticospinal excitability

Temporary immobilization of the leg serves as a useful model for the brain’s adaptive responses to casting, long-term confinement to bed rest and possibly to trauma. As part of a larger program using TMS to investigate changes associated with bed rest, we sought to determine whether casting of the leg causes brain excitability changes measurable with TMS, and the time course of resolution of these changes. In this study, eight adults wore a full leg cast for 10 days. TMS measures of motor cortex excitability were gathered before the cast was placed, and then immediately after cast removal, and 24 and 48 h later. A control group did not wear a cast and underwent the same TMS sessions. Significant excitability changes occurred and peaked at 24 h post cast removal in the TMS experimental group but not the non-casted group.     

Influence of somatosensory input on corticospinal excitability during motor imagery

Our previous studies showed that corticospinal excitability during imagery of squeezing a foam ball was enhanced by somatosensory input generated by passively holding the ball. In the present study, using the same experimental model, we investigated whether corticospinal excitability was influenced by holding the object with the hand opposite to the imagined hand. Corticospinal excitability was assessed by monitoring motor evoked potentials (MEPs) in the first dorsal interosseous muscle following transcranial magnetic stimulation over the motor cortex during motor imagery. Subjects were asked to imagine squeezing a foam ball with the right hand (experiment 1) or the left hand (experiment 2), while either holding nothing (Null condition), a ball in the right hand (Right condition) or a ball in the left hand (Left condition). The MEPs amplitude during motor imagery was increased, only when the holding hand and the imagined hand were on the same side. These results suggest that performance improvement and rehabilitation exercises will be more effective when somatosensory stimulation and motor imagery are done on the same side.     

Differential modulation of spinal and corticospinal excitability during drop jumps

Previously it was shown that spinal excitability during hopping and drop jumping is high in the initial phase of ground contact when the muscle is stretched but decreases toward takeoff. To further understand motor control of stretch-shortening cycle, this study aimed to compare modulation of spinal and corticospinal excitability at distinct phases following ground contact in drop jump. Motor-evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) and H-reflexes were elicited at the time of the short (SLR)-, medium (MLR)-, and long (LLR, LLR₂)-latency responses of the soleus muscle (SOL) after jumps from 31 cm height. MEPs and H-reflexes were expressed relative to the background electromyographic (EMG) activity. H-reflexes were highly facilitated at SLR (172%) and then progressively decreased (MLR = 133%; LLR = 123%; LLR₂ = 110%). TMS showed no effect at SLR, MLR, and LLR, whereas MEPs were significantly facilitated at the LLR₂ (122%; P = 0.003). Background EMG was highest at LLR and lowest at LLR₂. Strong H-reflex facilitation at the beginning of the stance phase indicated significant contribution of Ia-afferent input to the -motoneurons during this phase that then progressively declined toward takeoff. Conversely, corticospinal excitability was exclusively increased at the phase of push off (LLR₂, 120 ms). It is argued that corticomotoneurons increased their excitability at LLR₂. At LLR (90 ms), Ia-afferent transmission as well as corticospinal excitability was low, whereas background EMG was high. Therefore it is speculated that other sources, presumably subcortical in origin, contributed to the EMG activity at LLR in drop jumps.     

Changes in corticospinal motor excitability induced by non-motor linguistic tasks

The excitability of the corticospinal motor pathways to transcranial magnetic stimulation (TMS) can be differentially modulated by a variety of motor tasks. However, there is emerging evidence that linguistic tasks may alter excitability of the corticospinal motor pathways also. In this study we evaluated the effect of several movement-free, low-level linguistic processes involved in reading and writing on the excitability of the bilateral corticospinal motor pathways in a group of right-handed subjects. The study included two series of tasks, visual searching/matching and imaginal writing/drawing. The tasks were designed to roughly correspond with elemental aspects of the reading and writing, grapheme recognition and grapheme generation, respectively. Each task series included separate blocks with different task targets: letters, digits, semantically easy-to-code (i.e. geometric) shapes, and semantically hard-to-code shapes, as well as control blocks with no task. During task performance, TMS was delivered randomly over the hand area of either the left or right motor cortex and the modulation of the excitability of the corticospinal motor pathways was measured bilaterally through changes of the size of the motor-evoked potential (MEP) induced in the relaxed right and left first dorsal interosseous (FDI) muscles. We found that the size of the MEP in hand muscles increased during visual searching/matching tasks, particularly when targets were letters or geometric shapes, and the increase was significant for the dominant hand (left hemisphere) only. No such consistent effects were seen across subjects during imaginal tasks. This study provides evidence that even the performance of certain low-level linguistic tasks can modulate the excitability of the corticospinal motor pathways, particularly those originating from the left (dominant) hemisphere, despite the absence of overt motor activity. Moreover, in the light of the recently increased awareness of the role of "mirror neurons" in perception, the results suggest that activation of motor circuits used in generation of the written output may be an essential part of the perception of the written material as well. Understanding the patterns of task-dependent changes in excitability of the corticospinal motor pathways will provide insights into the organisation of central nervous system functional networks involved in linguistic processes, and may also be useful for future development of novel approaches to rehabilitation therapy of linguistic and motor functions.     

Changes in corticospinal excitability following adaptive modification to human walking

Locomotor adaptations to a novel environment can be measured through changes in muscle activity patterns and lower limb kinematics. The location and mechanisms underlying these adaptive changes are unknown. The purposes of the current study were (1) to determine whether corticospinal tract (CST) excitability is altered by resisted walking and (2) to ascertain whether changes in cortical excitability are muscle specific. Forty healthy participants walked with a robotic gait device (Lokomat) that applied a velocity-dependent resistance against hip and knee movements during walking. CST excitability was assessed by quantifying motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation immediately before and after baseline and resisted walking. MEPs were measured in either the biceps femoris (BF) or the rectus femoris (RF). Recruitment curves were collected by stimulating in 5 % increments from 105 to 145 % of active motor threshold. Results demonstrated a significant increase in MEP amplitude in the BF following baseline walking in the Lokomat. The RF did not demonstrate these changes. There was no further change in MEP size following resisted walking in either muscle group. These results suggest that locomotion increases CST excitability in a muscle-specific fashion. As such, it may be important for determining how to enhance the central nervous system’s ability to integrate adaptive strategies during walking.     

Interhemispheric coupling of corticospinal excitability is suppressed during voluntary muscle activation

Motor-evoked potentials (MEPs) after transcranial magnetic stimulation (TMS) show a trial-to-trial variation in size at rest that is positively correlated for muscles of the same, and opposite, upper limbs. To investigate the mechanisms responsible for this we have examined the effect of voluntary activation on the correlated fluctuations of MEP size. In 8 subjects TMS was concurrently applied to the motor cortex of each hemisphere using 2 figure-8 coils. MEPs (n = 50) were recorded from left and right first dorsal interosseous (FDI), abductor digiti minimi (ADM), and extensor digitorum communis. At rest, MEPs were significantly positively correlated for pairs of muscles of the same (75% of comparisons) and opposite limb (56% of comparisons). The correlation for within-limb muscle pairs was strongest for FDI and ADM. In contrast, between-limb MEP correlations showed no somatotopic organization. Voluntary activation reduced the strength of MEP correlations between limbs, even for muscle pairs that remained at rest while a remote upper limb muscle was active. In contrast, activation of a remote muscle did not affect the strength of MEP correlation for muscle pairs within the same limb that remained at rest. For within-limb comparisons, activation of one or both muscles of a pair reduced the strength of the MEP correlation, but to a lesser extent than for between-limb pairs. It is concluded that the process linking corticospinal excitability in the two hemispheres is suppressed during voluntary activation, and that different processes contribute to common fluctuations in MEP size for muscles within the same limb.