Unimanual muscle activation increases interhemispheric inhibition from the active to the resting hemisphere

Interhemispheric inhibition (IHI) is an important mechanism to maximize the independent functioning of each hemisphere and is most likely mediated by transcallosal fibres. IHI can be investigated by paired pulse transcranial magnetic stimulation (TMS) whereby, in half of the trials, a test stimulus (TS) over one hemisphere is preceded by a conditioning stimulus (CS) over the other hemisphere. Whereas various studies have investigated IHI in rest, less is known about interhemispheric interactions during voluntary muscle activation. Here, we investigated the influence of tonic muscle activity (5% of the maximal voluntary contraction) in either the right wrist flexor or extensor versus rest on IHI from the active (left) to the resting (right) hemisphere. Our main finding was that tonic activation of the right wrist flexor, led to an increase in IHI from the active (dominant left) to the resting (non-dominant right) hemisphere as compared to rest. A control experiment employed the same design but CS intensity was lowered to match MEP amplitudes of the conditioning hand between active and rest conditions. This resulted in a relative decrease of IHI. It is hypothesized that functional regulation of IHI might prevent the occurrence of mirror activity in the primary motor cortex (M1) of the resting hemisphere and, thus, might play an important role in the execution of unimanual actions.     

Unilateral contractions modulate interhemispheric inhibition most strongly and most adaptively in the homologous muscle of the contralateral limb

We investigated how volitional contractions affect interhemispheric inhibition (IHI) from the active to the passive hemisphere. Younger and older adults isometrically contracted their dominant thumb (abductor pollicis brevis, APB) to various force targets. In ballistic contraction trials, transcranial magnetic stimulation (TMS) was administered very shortly after the onset of APB activity. In tonic contraction trials, TMS was delivered while the target force was maintained. In control trials both thumbs remained quiescent. In all trials, a test stimulus (TS) was directed to the APB hotspot in the non-dominant hemisphere (130% left APB resting motor threshold, RMT). In half the trials, a conditioning stimulus (130% right APB RMT) was applied to the APB hotspot in the dominant hemisphere 10 ms prior to the TS. Targeted ballistic contractions of the right APB were found to modulate (increase) IHI measured in the left APB, as previously reported for tonic contractions. Furthermore, the extent of the IHI increase was found to scale with the strength of the contralateral ballistic or tonic contraction. Less pronounced, but statistically significant, IHI increases were also observed in the left abductor digiti minimi and extensor carpi radialis during right APB contraction. For these muscles, however, the extent of the IHI modulation was independent of APB contraction strength. The capacity to modulate inhibition during contractions was unaffected by advancing age. During volitional actions, the ability to modulate IHI most adaptively in the homologous muscle of the resting limb may contribute to the prevention of mirror movements.     

Dynamical changes in corticospinal excitability during imagery of unimanual and bimanual wrist movements in humans: a transcranial magnetic stimulation study

This study explored the dynamical changes in corticospinal excitability during the imagination of cyclical unimanual and bimanual wrist flexion-extension movements. Transcranial magnetic stimulation was applied over the left motor cortex to evoke motor evoked potentials in the right wrist flexor and extensor muscles. Findings provided evidence for increased reciprocal excitability changes during imagery of symmetrical in-phase movements as compared to asymmetrical (anti-phase) or unimanual movements. This suggests that in-phase movements may reinforce whereas anti-phase movements may reduce the temporal representation of the task in the corticospinal motor networks of the brain.     

Physiological changes underlying bilateral isometric arm voluntary contractions in healthy humans

Many bilateral motor tasks engage simultaneous activation of distal and proximal arm muscles, but little is known about their physiological interactions. Here, we used transcranial magnetic stimulation to examine motor-evoked potentials (MEPs), interhemispheric inhibition at a conditioning-test interval of 10 (IHI(10)) and 40 ms (IHI(40)), and short-interval intracortical inhibition (SICI) in the left first dorsal interosseous (FDI) muscle during isometric index finger abduction. The right side remained at rest or performed isometric voluntary contraction with the FDI, biceps or triceps brachii, or the tibialis anterior. Left FDI MEPs were suppressed to a similar extent during contraction of the right FDI and biceps and triceps brachii but remained unchanged during contraction of the right tibialis anterior. IHI(10) and IHI(40) were decreased during contraction of the right biceps and triceps brachii compared with contraction of the right FDI. SICI was increased during activation of the right biceps and triceps brachii and decreased during activation of the right FDI. The present results indicate that an isometric voluntary contraction with either a distal or a proximal arm muscle, but not a foot dorsiflexor, decreases corticospinal output in a contralateral active finger muscle. Transcallosal inhibitory effects were strong during bilateral activation of distal hand muscles and weak during simultaneous activation of a distal and a proximal arm muscle, whereas GABAergic intracortical activity was modulated in the opposite manner. These findings suggest that in intact humans crossed interactions at the level of the motor cortex involved different physiological mechanisms when bilateral distal hand muscles are active and when a distal and a proximal arm muscle are simultaneously active.     

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     

Effect of transcranial magnetic stimulation on bimanual movements

Transcranial magnetic stimulation (TMS) of the motor cortex can interrupt voluntary contralateral rhythmic limb movements. Using the method of "resetting index" (RI), our study investigated the TMS effect on different types of bimanual movements. Six normal subjects participated. For unimanual movement, each subject tapped either the right or left index finger at a comfortable rate. For bimanual movement, index fingers of both hands tapped in the same (in-phase) direction or in the opposite (antiphase) direction. TMS was applied to each hemisphere separately at various intensities from 0.5 to 1.5 times motor threshold (MT). TMS interruption of rhythm was quantified by RI. For the unimanual movements, TMS disrupted both contralateral and ipsilateral rhythmic hand movements, although the effect was much less in the ipsilateral hand. For the bimanual in-phase task, TMS could simultaneously reset the rhythmic movements of both hands, but the effect on the contralateral hand was less and the effect on the ipsilateral hand was more compared with the unimanual tasks. Similar effects were seen from right and left hemisphere stimulation. TMS had little effect on the bimanual antiphase task. The equal effect of right and left hemisphere stimulation indicates that neither motor cortex is dominant for simple bimanual in-phase movement. The smaller influence of contralateral stimulation and the greater effect of ipsilateral stimulation during bimanual in-phase movement compared with unimanual movement suggest hemispheric coupling. The antiphase movements were resistant to TMS disruption, and this suggests that control of rhythm differs in the 2 tasks. TMS produced a transient asynchrony of movements on the 2 sides, indicating that both motor cortices might be downstream of the clocking command or that the clocking is a consequence of the 2 hemispheres communicating equally with each other.     

Effect of low-frequency repetitive transcranial magnetic stimulation on interhemispheric inhibition

We studied the effects of 1-Hz repetitive transcranial magnetic stimulation (rTMS) on the excitability of interhemispheric connections in 13 right-handed healthy volunteers. TMS was performed using figure-eight coils, and surface electromyography (EMG) was recorded from both first dorsal interosseous (FDI) muscles. A paired-pulse method with a conditioning stimulus (CS) to the motor cortex (M1) followed by a test stimulus to the opposite M1 was used to study the interhemispheric inhibition (ppIHI). Both CS and TS were adjusted to produce motor-evoked potentials of approximately 1 mV in the contralateral FDI muscles. After baseline measurement of right-to-left IHI (pre-RIHI) and left-to-right IHI (pre-LIHI), rTMS was applied over left M1 at 1 Hz with 900 stimuli at 115% of resting motor threshold. After rTMS, ppIHI was studied using both the pre-rTMS CS (post-RIHI and post-LIHI) and an adjusted post-rTMS CS set to produce 1-mV motor evoked potentials (MEPs; post-RIHI(adj) and post-LIHI(adj)). The TS was set to produce 1-mV MEPs. There was a significant reduction in post-LIHI (P = 0.0049) and post-LIHI(adj) (P = 0.0169) compared with pre-LIHI at both interstimulus intervals of 10 and 40 ms. Post-RIHI was significantly reduced compared with pre-RIHI (P = 0.0015) but pre-RIHI and post-RIHI(adj) were not significantly different. We conclude that 1-Hz rTMS reduces IHI in both directions but is predominantly from the stimulated to the unstimulated hemisphere. Low-frequency rTMS may be used to modulate the excitability of IHI circuits. Treatment protocols using low-frequency rTMS to reduce cortical excitability in neurological and psychiatric conditions need to take into account their effects on IHI.     

Speech-induced modulation of interhemispheric inhibition

This study aimed to determine the effects of speech and mastication on interhemispheric inhibition between the right and left primary motor areas (M1s) by using transcranial magnetic stimulation (TMS). Motor-evoked potentials (MEPs) were recorded from the first dorsal interossei (FDIs) of each hand of 10 healthy right-handed subjects under 3 conditions: at rest (control), during mastication (non-verbal oral movement), and during speech (reading aloud). Test TMS was delivered following conditioning TMS of the contralateral M1 at various interstimulus intervals. Under all conditions, the MEPs in the left FDIs were significantly inhibited after conditioning of the left M1 (i.e. inhibition of the right M1 by TMS of the left hemisphere). In contrast, the left M1 was significantly inhibited by the right hemisphere only during the control and mastication tasks, but not speech task. These results suggest that speech may facilitate the activity of the dominant M1 via functional connectivity between the speech area and the left M1, or may modify the balance of interhemispheric interactions, by suppressing inhibition of the dominant hemisphere by the non-dominant hemisphere. Our findings show a novel aspect of interhemispheric dominance and may improve therapeutic strategies for recovery from stroke.     

Organization of ipsilateral excitatory and inhibitory pathways in the human motor cortex

Motor cortex stimulation has both excitatory and inhibitory effects on ipsilateral muscles. Excitatory effects can be assessed by ipsilateral motor-evoked potentials (iMEPs). Inhibitory effects include an interruption of ipsilateral voluntary muscle activity known as the silent period (iSP) and a reduction in corticospinal excitability evoked by conditioning stimulation of the contralateral motor cortex (interhemispheric inhibition, IHI). Both iSP and IHI may be mediated by transcallosal pathways. Their relationship to the contralateral corticospinal projection and whether iSP and IHI represent the same phenomenon remain unclear. The neuronal population activated by transcranial magnetic stimulation (TMS) is highly dependent on the direction of the induced current in the brain. We examined the relationship among iMEP, iSP, IHI, and the contralateral corticospinal system by examining the effects of different stimulus intensities and current directions. Surface electromyography (EMG) was recorded from both first dorsal interosseous (FDI) muscles. The iSP in the right FDI muscle was obtained by right motor cortex stimulation during voluntary muscle contraction. IHI was examined by conditioning stimulation of the right motor cortex followed by test stimulation of the left motor cortex at interstimulus intervals (ISIs) of 2-80 ms. The induced current directions tested in the right motor cortex were anterior medial (AM), posterior medial (PM), posterior lateral, and anterior lateral (AL). Contralateral MEPs (cMEPs) had the lowest threshold with the AM direction and the shortest latency with the PM direction. iMEPs were present in 8 of 10 subjects. Both iMEP and IHI did not show significant directional preference. iSP was observed in all subjects with the highest threshold for the AL direction and the longest duration for the AM direction. cMEP, iSP, and IHI all increased with stimulus intensity up to approximately 75% stimulator output. Target muscle activation decreased IHI at 8-ms ISI but had little effect on IHI at 40-ms ISI. iSP and IHI at 8-ms ISI did not correlate at any stimulus intensities and current directions tested, and factor analysis showed that they are explained by different factors. However, active IHI at 40-ms ISI was explained by the same factor as iSP. The different directional preference for cMEP compared with iMEP and IHI suggests that these ipsilateral effects are mediated by populations of cortical neurons that are different from those activating the corticospinal neurons. iSP and IHI do not represent the same phenomenon and should be considered complementary measures of ipsilateral inhibition.     

Suppression of the non-dominant motor cortex during bimanual symmetric finger movement: a functional magnetic resonance imaging study

Patterns of bimanual coordination in which homologous muscles are simultaneously active are more stable than those in which homologous muscles are engaged in an alternating fashion. This may be attributable to the stronger involvement of the dominant motor cortex in ipsilateral hand movements via interaction with the non-dominant motor system, known as neural crosstalk. We used functional magnetic resonance imaging to investigate the neural representation of the interhemispheric interaction during bimanual mirror movements. Thirteen right-handed subjects completed four conditions: sequential finger tapping using the right and left index and middle fingers, bimanual mirror and parallel finger tapping. Auditory cues (3 Hz) were used to keep the tapping frequency constant. Task-related activation in the right primary motor cortex was significantly less prominent during mirror than unimanual left-handed movements. This was mirror- and non-dominant side-specific; parallel movements did not cause such a reduction, and the left primary motor cortex showed no such differential activation across the unimanual right, bimanual mirror, and bimanual parallel conditions. Reducing the contralateral innervation of the left hand may increase the fraction of the force command to the left hand coming from the left primary motor cortex, enhancing the neural crosstalk.     

Synaptic connections from large afferents of wrist flexor and extensor muscles to synergistic motoneurones in man

 Short-latency excitatory Ia reflex connections were determined between pairs of human wrist flexor and extensor muscles. Spindle Ia afferents were stimulated by either tendon tap or electrical stimulation. The activity of voluntarily activated single motor units was recorded intramuscularly from pairs of wrist flexor or extensor muscles. Cross-correlation between stimuli and the discharge of the motor units provided a measure of the homonymous or heteronymous excitatory input to a motoneurone. Homonymous motoneurone facilitation was generally stronger than that of the heteronymous motoneurones. The principal wrist flexors, flexor carpi radialis (FCR) and flexor carpi ulnaris (FCU), were tightly connected through a bidirectional short-latency reflex pathway. In contrast, the extensor carpi ulnaris (ECU) and the extensor carpi radialis (ECR) did not have similar connections. ECU motoneurones received no short-latency excitatory Ia input from the ECR. ECR motoneurones did receive excitatory Ia input from ECU Ia afferents; however, its latency was delayed by several milliseconds compared with other heteronymous Ia excitatory effects observed. The wrist and finger extensors were linked through heteronymous Ia excitatory reflexes. The reflex connections observed in humans are largely similar to those observed in the cat, with the exception of heteronymous effects from the ECU to the ECR and from the extensor digitorum communis (EDC) to the ECU, which are present only in humans. The differences in the reflex organization of the wrist flexors versus the extensors probably reflects the importance of grasping. Received: 19 August 1996 / Accepted: 6 March 1997     

The effect of age on task-related modulation of interhemispheric balance

Normal aging is associated with less lateralised task-related activation of the primary motor cortices. It has been hypothesized, but not tested, that this phenomenon is mediated transcallosaly. We have used Transcranial Magnetic Stimulation to look for age-related changes in interhemispheric inhibition (IHI). Thirty healthy individuals (aged 19–78 years) were studied using a paired-pulse protocol at rest and during a low-strength isometric contraction with the right hand. The IHI targeting the right motor cortex was assessed at two intervals, 10 ms (IHI10) and 40 ms (IHI40). The corticospinal excitability of the left hemisphere was assessed by means of input–output curves constructed during voluntary construction. Age was not correlated with IHI10 or IHI40 at rest. During muscle contraction IHI tended to increase at both intervals. However, this increase in IHI during the active condition (changeIHI) was less evident with advancing age for the 40 ms interval (r = 0.444, P = 0.02); in fact a degree of disinhibition was often present. There was no correlation between age and changeIHI10. Age was negatively correlated with the area under the recruitment curve (r = −0.585, P = 0.001) and the size of the maximum MEP collected (r = −0.485, P = 0.007). ChangeIHI and measures of corticospinal excitability were not intercorrelated. In conclusion, task-related increases in interhemispheric inhibition seem to diminish with advancing age. This phenomenon is specific for long-latency IHI and may underlie the age-related bihemispheric activation seen in functional imaging studies. The mechanism underlying changes in IHI with advancing age and the association with changes in corticospinal excitability need further investigation.     

Laterality of interhemispheric inhibition depends on handedness

There is some evidence that handedness is related to lateralisation of excitability in the motor system. We investigated lateralisation of interhemispheric inhibition (IHI), motor thresholds and short interval intracortical inhibition (SICI) and facilitation (SICF) in relation to handedness in 12 right (RH) and 13 left handed (LH) subjects. Because there is some controversy as to the optimal localisation to produce IHI we also compared IHI induced by conditioning the dorsal premotor cortex (dPM) versus primary motor cortex (M1) in ten RH. IHI was stronger following conditioning the motor dominant as compared to the motor non-dominant hemisphere in RH and LH. Motor thresholds were higher when elicited over the right hemisphere than over the left in both RH and LH, while SICI and SICF showed no differences between hemispheres or dependency from handedness. We hypothesize that IHI is a function of handedness perhaps reflecting predominant usage of the dominant hand, while lateralisation of thresholds and intracortical excitability are determined by other factors.     

Inability to activate muscles maximally during cocontraction and the effect on joint stiffness

In order to determine the maximum joint stiffness that could be produced by cocontraction of wrist flexor and extensor muscles, experiments were conducted in which healthy human subjects stabilized a wrist manipulandum that was made mechanically unstable by using positive position feedback to create a load with the characteristics of a negative spring. To determine a subject's limit of stability, the negative stiffness of the manipulandum was increased by increments until the subject could no longer reliably stabilize the manipulandum in a 1° target window. Static wrist stiffness was measured by applying a 3° rampand-hold displacement of the manipulandum, which stretched the wrist flexor muscles. As the load stiffness was made more and more negative, subjects responded by increasing the level of cocontraction of flexor and extensor muscles to increase the stiffness of the wrist. The stiffness measured at a subject's limit of stability was taken as the maximum stiffness that the subject could achieve by cocontraction of wrist flexor and extensor muscles. In almost all cases, this value was as large or larger than that measured when the subject was asked to cocontract maximally to stiffen the wrist in the absence of any load. Static wrist stiffness was also measured when subjects reciprocally activated flexor or extensor muscles to hold the manipulandum in the target window against a load generated by a stretched spring. We found a strong linear correlation between wrist stiffness and flexor torque over the range of torques used in this study (20–80% maximal voluntary contraction). The maximum stiffness achieved by cocontraction of wrist flexor and extensor muscles was less than 50% of the maximum value predicted from the joint stiffness measured during matched reciprocal activation of flexor and extensor muscles. EMG recorded from either wrist flexor or extensor muscles during maximal cocontraction confirmed that this reduced stiffness was due to lower levels of activation during cocontraction of flexor and extensor muscles than during reciprocal contraction.     

The effect of simultaneous contractions of ipsilateral muscles on changes in corticospinal excitability induced by paired associative stimulation (PAS)

Consideration was given to means of increasing the reliability and muscle specificity of paired associative stimulation (PAS) by utilising the phenomenon of crossed-facilitation. Eight participants completed three separate sessions: isometric flexor contractions of the left wrist at 20% of maximum voluntary contraction (MVC) simultaneously with PAS (20 s intervals; 14 min duration) delivered at the right median nerve and left primary motor cortex (M1); isometric contractions at 20% of MVC; and PAS only (14 min). Eight further participants completed two sessions of longer duration PAS (28 min): either alone or in conjunction with flexion contractions of the left wrist. Thirty motor potentials (MEPs) were evoked in the right flexor (rFCR) and extensor (rECR) carpi radialis muscles by magnetic stimulation of left M1 prior to the interventions, immediately post-intervention, and 10 min post-intervention. Both 14 and 28 min of combined PAS and (left wrist flexion) contractions resulted in reliable increases in rFCR MEP amplitude, which were not present in rECR. In the PAS only conditions, 14 min of stimulation gave rise to unreliable increases in MEP amplitudes in rFCR and rECR, whereas 28 min of PAS induced small (unreliable) changes only for rFCR. These results support the conclusion that changes in the excitability of the corticospinal pathway induced by PAS interact with those associated with contraction of the muscles ipsilateral to the site of cortical stimulation. Furthermore, focal contractions applied by the opposite limb increase the extent and muscle specificity of the induced changes in excitability associated with PAS.     

Effects on the right motor hand-area excitability produced by low-frequency rTMS over human contralateral homologous cortex

Repetitive transcranial magnetic stimulation (rTMS) has long lasting effects on cortical excitability at the site of stimulation, on interconnected sites at a distance and on the connections between them. In the present experiments we have used the technique of transcallosal inhibition between the motor cortices to examine all three effects in the same protocol. Ten healthy subjects received 900 rTMS stimuli at 1 Hz from a figure of eight coil over the left motor hand area. The intensity of rTMS was above the threshold for inducing short latency interhemispherical inhibition with a single stimulus (equivalent to 115–120 % resting motor threshold). Before and after the rTMS we evaluated: (1) in the left hemisphere, the amplitude of motor-evoked potentials (MEPs), and contralateral and ipsilateral cortical silent periods (CSP, ISP); (2) in the right hemisphere, MEP, CSP, ISP and short-interval intracortical inhibition and intracortical facilitation (SICI/ICF), and (3) interhemispherical inhibition (IHI) from the left-to-right hemisphere using a paired-pulse method. There were two main effects after rTMS to the left hemisphere: first, the amplitude of MEPs from the right hemisphere increased; second, there was a reduction in the IHI from the left-to-right hemisphere at interstimulus intervals of 7 and 10 ms but not at longer intervals (15–75 ms). Control experiments showed that these effects were not due to afferent inputs produced by the muscle twitches induced during the rTMS. The data are compatible with the notion that rTMS to the left hemisphere leads to reduced interhemispherical inhibition of the right hemisphere and a consequent increase in corticospinal excitability in that hemisphere.     

Different effects of fatiguing exercise on corticospinal and transcallosal excitability in human hand area motor cortex

Following forceful exercise that leads to muscle fatigue, the size of muscle evoked responses (MEPs) generated by transcranial magnetic stimulation (TMS) in the exercised muscle is depressed over a prolonged period. Strong evidence implicates intracortical mechanisms in this depression. As well as evoking MEPs in contralateral muscles, TMS also reduces MEPs evoked in ipsilateral muscles through interhemispheric inhibition mediated by a transcallosal pathway. Here we have sought to determine whether this effect is also depressed after exercise. Using two magnetic stimulators, the aftereffects of unilateral hand muscle exercise on the ability of TMS delivered to the hemisphere that generated the exercise were examined to i) generate MEPs in the exercised hand muscles, and ii) depress MEPs evoked by TMS pulses in contralateral (non-exercised) hand muscles. After exercise there was a significant reduction in the amplitudes of MEPs evoked by TMS in the exercised muscles (p<0.001). However, the same stimuli remained able to depress responses evoked by TMS to the contralateral hemisphere in the non-exercised muscles as effectively as before the exercise. We conclude that unlike the MEPs evoked by corticospinal output, interhemispheric inhibition evoked from the hemisphere that generated the exercise is not depressed after exercise. A similar differential effect on interhemispheric inhibition and corticospinal output has been reported recently for the effects of transcranial direct current (DC) stimulation of the motor cortex. Fatiguing exercise and transcranial DC stimulation may therefore engage similar intracortical mechanisms.     

Spread of electrical activity at cortical level after repetitive magnetic stimulation in normal subjects

In normal subjects, focal repetitive transcranial magnetic stimulation (rTMS) of the hand motor area evokes muscle potentials (MEPs) from muscles in the hand (target muscles) and the arm (non-target muscles). In this study we investigated the mechanisms underlying the spread of MEPs induced by focal rTMS in non-target muscles. rTMS was delivered with a Magstim stimulator and a figure-of-eight coil placed over the first dorsal interosseus (FDI) motor area of the left hemisphere. Trains of 10 stimuli were given at a suprathreshold intensity (120% of motor threshold) and at frequencies of 5, 10 and 20 Hz at rest. Electromyographic (EMG) activity was recorded simultaneously from the FDI (target muscle) and the contralateral biceps muscle and from the FDI muscle ipsilateral to the side of stimulation (non-target muscle). rTMS delivered in trains to the FDI motor area of the left hemisphere elicited MEPs in the contralateral FDI (target muscle) that gradually increased in amplitude over the course of the train. Focal rTMS trains also induced MEPs in the contralateral biceps (non-target muscle) but did so only after the second or third stimulus; like target-muscle MEPs, in non-target muscle MEPs progressively increased in amplitude during the train. At no frequency did rTMS elicit MEPs in the FDI muscle ipsilateral to the site of stimulation. rTMS left the latency of EMG responses in the FDI and biceps muscles unchanged during the trains of stimuli. The latency of biceps MEPs was longer after rTMS than after a single TMS pulse. In conditioning-test experiments designed to investigate the cortical origin of the spread, a single TMS pulse delivered over the left hemisphere at an interstimulus interval (ISI) of 50, 100 and 150 ms reduced the amplitude of the test MEP evoked by a single TMS pulse delivered over the right hemisphere; and a conditioning rTMS train delivered over the left hemisphere increased the amplitude of the test MEP evoked by a single TMS pulse over the right hemisphere. A conditioning rTMS train delivered over the left hemisphere and paired magnetic shocks (test stimulus) at 3 and 13 ms ISIs over the right hemisphere reduced MEP inhibition at the 3-ms ISI but left the MEP facilitation at 13 ms unchanged. Using a control MEP size matched with that observed after a conditioning contralateral rTMS, we found that paired-pulse inhibition remained unchanged. Yet a single TMS conditioning pulse sufficiently strong to evoke a MEP in the contralateral FDI and biceps muscles simultaneously (as rTMS did) left paired-pulse inhibition unchanged. We conclude that the spread of EMG activity to non-target muscles depends on cortical mechanisms, mainly including changes in the excitability of the interneurones mediating intracortical inhibition. Electronic Publication     

Impaired crossed facilitation of the corticospinal pathway after cervical spinal cord injury

In uninjured humans, it is well established that voluntary contraction of muscles on one side of the body can facilitate transmission in the contralateral corticospinal pathway. This crossed facilitatory effect may favor interlimb coordination and motor performance. Whether this aspect of corticospinal function is preserved after chronic spinal cord injury (SCI) is unknown. Here, using transcranial magnetic stimulation, we show in patients with chronic cervical SCI (C(5)-C(8)) that the size of motor evoked potentials (MEPs) in a resting intrinsic hand muscle remained unchanged during increasing levels of voluntary contraction with a contralateral distal or proximal arm muscle. In contrast, MEP size in a resting hand muscle was increased during the same motor tasks in healthy control subjects. The magnitude of voluntary electromyography was negatively correlated with MEP size after chronic cervical SCI and positively correlated in healthy control subjects. To examine the mechanisms contributing to MEP crossed facilitation we examined short-interval intracortical inhibition (SICI), interhemispheric inhibition (IHI), and motoneuronal behavior by testing F waves and cervicomedullary MEPs (CMEPs). During strong voluntary contractions SICI was unchanged after cervical SCI and decreased in healthy control subjects compared with rest. F-wave amplitude and persistence and CMEP size remained unchanged after cervical SCI and increased in healthy control subjects compared with rest. In addition, during strong voluntary contractions IHI was unchanged in cervical SCI compared with rest. Our results indicate that GABAergic intracortical circuits, interhemispheric glutamatergic projections between motor cortices, and excitability of index finger motoneurons are neural mechanisms underlying, at least in part, the lack of crossed corticospinal facilitation observed after SCI. Our data point to the spinal motoneurons as a critical site for modulating corticospinal transmission after chronic cervical SCI.     

The origin of activity in the biceps brachii muscle during voluntary contractions of the contralateral elbow flexor muscles

During strong voluntary contractions, activity is not restricted to the target muscles. Other muscles, including contralateral muscles, often contract. We used transcranial magnetic stimulation (TMS) to analyse the origin of these unintended contralateral contractions (termed “associated” contractions). Subjects (n = 9) performed maximal voluntary contractions (MVCs) with their right elbow-flexor muscles followed by submaximal contractions with their left elbow flexors. Electromyographic activity (EMG) during the submaximal contractions was matched to the associated EMG in the left biceps brachii during the right MVC. During contractions, TMS was delivered to the motor cortex of the right or left hemisphere and excitatory motor evoked potentials (MEPs) and inhibitory (silent period) responses recorded from left biceps. Changes at a spinal level were investigated using cervicomedullary stimulation to activate corticospinal paths (n = 5). Stimulation of the right hemisphere produced silent periods of comparable duration in associated and voluntary contractions (218 vs 217 ms, respectively), whereas left hemisphere stimulation caused a depression of EMG but no EMG silence in either contraction. Despite matched EMG, MEPs elicited by right hemisphere stimulation were ∼1.5–2.5 times larger during associated compared to voluntary contractions (P < 0.005). Similar inhibition of the associated and matched voluntary activity during the silent period suggests that associated activity comes from the contralateral hemisphere and that motor areas in this (right) hemisphere are activated concomitantly with the motor areas in the left hemisphere. Comparison of the MEPs and subcortically evoked potentials implies that cortical excitability was greater in associated contractions than in the matched voluntary efforts.