Effects of a high-frequency,low-intensity,biphasic conditioning train of TMS pulses on the human motor cortex

Intracortical circuit excitability of the human motor cortex has been studied by measuring effects of some conditioning TMS stimulus on the succeeding test TMS stimulus in the motor cortex, such as short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). A single-pulse TMS was used as a conditioning stimulus (CS) in these techniques, but a train of several TMS pulses might induce some intracortical changes in the motor cortex more effectively. For nine healthy volunteers, we compared the SICI and ICF induced by a single conditioning biphasic TMS pulse with those induced by a train of 10 biphasic TMS pulses of the same intensity. As a conditioning stimulus, we delivered a subthreshold single biphasic pulse (CS1) or 10, 10-Hz biphasic pulses (CS10) before a suprathreshold monophasic test stimulus at several interstimulus intervals (ISIs) of 3–40 ms over the hand motor area. The CS intensity was 50–100% of the active motor threshold (AMT). We compared the motor cortical excitability after the conditioning stimulus (single pulse or a train of ten pulses) at the intervals for SICI and ICF. A train of ten 10-Hz pulses elicited greater inhibition at short ISIs than a single conditioning pulse did. The facilitation at ISIs around 10 ms corresponding to the ICF was evoked by CS1 only at an intensity of 80% AMT; CS10 evoked no ICF. Furthermore, CS10 evoked MEP inhibition at longer intervals. Results show that a train of high-frequency, low-intensity, biphasic TMS pulses can have a strong inhibitory effect on the motor cortex.     

Two phases of short-interval intracortical inhibition

Short-interval intracortical inhibition (SICI) is a widely used method to study cortical inhibition, and abnormalities have been found in several neurological and psychiatric disorders. Previous studies suggested that SICI involves two phases and the first phase may be explained by axonal refractoriness. Our objectives are to further investigate the mechanisms of the two phases of SICI. SICI was studied in 11 normal volunteers by a paired transcranial magnetic stimulation (TMS) paradigm applied to the left motor cortex with a subthreshold conditioning stimulus (80% resting motor threshold for rest condition and 95% active motor threshold for active condition) followed by a suprathreshold test stimulus at interstimulus intervals (ISIs) of 1–4.5 ms in steps of 0.5 ms. Motor-evoked potentials (MEPs) were recorded from the right first dorsal interosseous muscle. Three different test stimulus intensities adjusted to produce 0.2, 1 and 4 mV MEPs at rest were studied with the target muscle relaxed and during 20% maximum contraction. Maximum inhibition was observed at ISIs of 1 ms and 2.5 ms for the rest condition and the difference among ISIs was reduced with voluntary contraction. SICI increased with larger test MEP amplitude and decreased with voluntary contraction. At test MEP of 0.2 mV, some subjects showed facilitation and this is likely related to short-interval intracortical facilitation. For rest SICI, the correlation between adjacent ISIs was much higher from 3 to 4.5 ms than from 1 to 2.5 ms or between 1 and 2.5 ms. There was no correlation between SICI at different test MEP amplitudes. We conclude that maximum SICI at ISIs of 1 and 2.5 ms are mediated by different mechanisms. SICI at 1 ms cannot be fully explained by axonal refractoriness and synaptic inhibition may be involved. SICI is a complex phenomenon and inhibition at different ISIs may be mediated by different inhibitory circuits.     

Effects of paired pulse TMS of primary somatosensory cortex on perception of a peripheral electrical stimulus

Paired pulse transcranial magnetic stimulation (paired TMS) was introduced to study local inhibitory or facilitatory intracortical circuits of the primary motor cortex. However, similar interactions can be shown in other areas of cortex. The current study tests the effects of paired pulse TMS of the right primary somatosensory cortex (S1) on the sensory perception of electrical stimuli applied on the contralateral thumb finger. In the main experiment a subthreshold conditioning stimulus (CS) preceded a suprathreshold test stimulus (TS) at different inter-stimulus intervals. We found that perception of a peripheral electrical stimulus was markedly attenuated by paired TMS in comparison to single pulse TMS when the ISIs was 10 or 15 ms, while there was no effect at shorter ISIs. There was no additional effect of the CS pulse if the intensity of the TS was subthreshold. In control experiments we observed that the effect vanished when the delay between the peripheral stimulus and the TS was10 or 30 ms rather than 20 ms or if the pairs of pulses were applied over the vertex rather than the hand area. Furthermore, there was no change at longer ISIs when paired TMS was applied over the posterior parietal cortex of the same hemisphere. These results demonstrate that paired pulse TMS is able to probe intracortical circuits in S1 and that the intrinsic properties of these circuits differ even between closely adjacent areas of the cortex.     

Reduced intracortical inhibition during the foreperiod of a warned reaction time task

Reaction time (RT) is shortened when the response signal is preceded by a warning signal, a finding that has been attributed to response preparation during the foreperiod between the warning and response signals. Research suggests an increased excitability of cortical movement representations associated with response preparation during the foreperiod of a warned RT task (Davranche et al. in Eur J Neurosci 25:3766–3774, 2007). However when the foreperiod duration is short and constant, the motor evoked potential (MEP) amplitude elicited by transcranial magnetic stimulation (TMS) during the foreperiod is suppressed (Touge et al. in Clin Neurophysiol 111:1216–1226, 1998), suggesting a competing inhibitory process. Three experiments measured MEP amplitude and intracortical inhibition during the foreperiod of a warned RT task in which the response was a flexion of the right index finger. Experiments 1 and 2 measured short-interval intracortical inhibition (SICI) with paired TMS pulses separated by inter-stimulus intervals (ISIs) of 3 (SICI₃) and 1.5 ms (SICI_1.5), respectively. Experiment 3 measured long-interval intracortical inhibition (LICI) with paired TMS pulses with an ISI of 100 ms (LICI₁₀₀). In all experiments MEP amplitude was smaller in the warned condition than in the unwarned condition. There was less SICI₃ in the warned condition than in the unwarned condition (Experiment 1) whereas SICI_1.5 was similar in both conditions (Experiment 2). There was less LICI₁₀₀ in the warned condition than in the unwarned condition (Experiment 3). The intracortical inhibitory processes measured here cannot explain the suppression of MEP amplitude in the warned condition. We propose that the suppression of MEP amplitude is the result of an inhibitory mechanism, which acts on primary motor cortex to prevent premature response during the foreperiod.     

Task-dependent changes of intracortical inhibition

 The motor-evoked potential (MEP) to transcranial magnetic stimulation (TMS) is inhibited when preceded by a subthreshold TMS stimulus at short intervals (1–6 ms; intracortical inhibition, ICI) and is facilitated when preceded by a subthreshold TMS at longer intervals (10–15 ms; intracortical facilitation, ICF). We studied changes in ICI and ICF associated with two motor tasks requiring a different selectivity in fine motor control of small hand muscles (abductor pollicis brevis muscle, APB, and fourth dorsal interosseous muscle, 4DIO). In experiment 1 (exp. 1), nine healthy subjects completed four sets (5 min duration each) of repetitive (1 Hz) thumb movements. In experiment 2 (exp. 2), the subjects produced the same number of thumb movements, but complete relaxation of 4DIO was demanded. Following free thumb movements (exp. 1), amplitudes of MEPs in response to both single and paired TMS showed a trend to increase with the number of exercise sets in both APB and 4DIO. By contrast, more focal, selective thumb movementsinvolving APB with relaxation of 4DIO (exp. 2) caused an increase in MEP amplitudes after single and paired pulses only in APB, while a marked decrease in MEPs after paired pulses, but not after single TMS, in the actively relaxed 4DIO. This effect was more prominent for the interstimulus interval (ISI) of 1–3 ms than for longer ISIs (8 ms, 10 ms, and 15 ms). F-wave amplitudes reflecting excitability of the alpha motoneuron pool were unaltered in APB and 4DIO, suggesting a supraspinal origin for the observed changes. We conclude that plastic changes of ICI and ICF within the hand representation vary according to the selective requirements of the motor program. Performance of more focal tasks may be associated with a decrease in ICI in muscles engaged in the training task, while at the same time ICI may be increased in an actively relaxed muscle, also required for a focal performance. Additionally, our data further supports the idea that ICI and ICF may be controlled independently. Received: 20 September 1996 / Accepted: 1 October 1997     

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     

Intracortical inhibition of lower limb motor-evoked potentials after paired transcranial magnetic stimulation

The aim of the present study was to determine the characteristics of intracortical inhibition in the motor cortex areas representing lower limb muscles using paired transcranial magnetic (TMS) and transcranial electrical stimulation (TES) in healthy subjects. In the first paradigm (n=8), paired magnetic stimuli were delivered through a double cone coil and motor evoked potentials (MEPs) were recorded from quadriceps (Q) and tibialis anterior (TA) muscles during relaxation. The conditioning stimulus strength was 5% of the maximum stimulator output below the threshold MEP evoked during weak voluntary contraction of TA (33±5%). The test stimulus (67±2%) was 10% of the stimulator output above the MEP threshold in the relaxed TA. Interstimulus intervals (ISIs) from 1–15 ms were examined. Conditioned TA MEPs were significantly suppressed (P<0.01) at ISIs of less than 5 ms (relative amplitude from 20–50% of the control). TA MEPs tended to be only slightly facilitated at 9-ms and 10-ms ISIs. The degree of MEP suppression was not different between right and left TA muscles despite the significant difference in size of the control responses (P<0.001). Also, conditioned MEPs were not significantly different between Q and TA. The time course of TA MEP suppression, using electrical test stimuli, was similar to that found using TMS. In the second paradigm (n=2), the suppression of TA MEPs at 2, 3, and 4 ms ISIs was examined at three conditioning intensities with the test stimulation kept constant. For the pooled 2- to 4-ms ISI data, relative amplitudes were 34±6%, 61±5%, and 98±9% for conditioning intensities of 0.95, 0.90, and 0.85× active threshold, respectively (P<0.01). In conclusion, the suppression of lower limb MEPs following paired TMS showed similar characteristics to the intracortical inhibition previously described for the hand motor area. Received: 21 June 1996 / Accepted: 23 May 1997     

Different modulation of the cortical silent period by two phases of short interval intracortical inhibition

PURPOSE: To investigate the influence of 2 phases of short interval intracortical inhibition (SICI) on the cortical silent period (SP). MATERIALS AND METHODS: Single- and paired-pulse transcranial magnetic stimulations (TMSs) at 1 and 2.5ms interstimulus intervals (ISIs) were applied to the left motor cortex in 12 healthy subjects while their right hand muscles were moderately activated. Conditioning stimulation intensity was 90% of the active motor threshold (AMT). Test stimulation intensities were 120, 140, 160, 180, 200, 220, 240, 260% of the AMT and at 100% of the maximal stimulator output, the order of which was arranged randomly. The rectified electromyography area of motor evoked potential (MEP) and duration of the SP were measured off-line using a computerized program. RESULTS: At high-test stimulation intensities, MEP areas were saturated in both single- and paired-pulse stimulations, except that saturated MEPs were smaller for the paired-pulse TMS at 1ms ISI than for the other conditions. As the test stimulation intensity increased, SP was progressively prolonged in both single- and paired-pulse stimulations but was shorter in paired-pulse than single-pulse TMS. Overall, the ratio of SP duration/MEP area was comparable between single- and paired-pulse TMS except for the paired-pulse TMS at 1 ms ISI with a test stimulation intensity at 140-180% of the AMT, in which the ratio was significantly higher than in the single pulse TMS. CONCLUSION: These results suggest that 2 phases of SICI modulate MEP saturation and SP duration differently and provide additional evidence supporting the view that 2 phases of SICI are mediated by different inhibitory mechanisms.     

Responses to paired transcranial magnetic stimuli in resting, active, and recently activated muscles

Transcranial magnetic stimulation (TMS) causes the corticospinal system to become refractory to subsequent stimuli for up to 200 ms. We examined the phenomenon of paired pulse inhibition with TMS under conditions of rest, ongoing voluntary activation (isometric force generation), and at variable delays following activation (postactivation) of the wrist extensors of seven normal subjects. Paired stimuli were delivered to the motor cortex with a circular coil at 1.1 times motor evoked potential (MEP) threshold, with various interstimulus intervals. Voluntary activation caused a marked decrease in the variability of the ratio of the amplitude of the MEP evoked by the test pulse to that of the MEP evoked by the conditioning pulse. Marked inhibition of the MEP evoked by the test pulse was still present. Postactivation, however, caused a dramatic reversal of the inhibitory effect of the conditioning pulse in all subjects at interstimulus intervals ranging from 40 to 120 ms. This effect lasted for up to 10 s following the cessation of activation. MEPs to transcranial electrical stimulation were also inhibited by conditioning TMS, but postactivation did not reverse this inhibition, indicating that the reversal of paired pulse inhibition is intracortical. We conjecture that paired pulse inhibition reflects activity of inhibitory interneurons or inhibitory connections between cortical output cells that are inactivated in the postactivation state.     

Effects of low-frequency whole-body vibration on motor-evoked potentials in healthy men

The aim of this study was to determine whether low-frequency whole-body vibration (WBV) modulates the excitability of the corticospinal and intracortical pathways related to tibialis anterior (TA) muscle activity, thus contributing to the observed changes in neuromuscular function during and after WBV exercise. Motor-evoked potentials (MEPs) elicited in response to transcranial magnetic stimulation (TMS) of the leg area of the motor cortex were recorded in TA and soleus (SOL) muscles of seven healthy male subjects whilst performing 330 s continuous static squat exercise. Each subject completed two conditions: control (no WBV) and WBV (30 Hz, 1.5 mm vibration applied from 111 to 220 s). Five single suprathreshold and five paired TMS were delivered during each squat period lasting 110 s (pre-, during and post-WBV). Two interstimulus intervals (ISIs) between the conditioning and the testing stimuli were employed in order to study the effects of WBV on short-interval intracortical inhibition (SICI, ISI = 3 ms) and intracortical facilitation (ICF, ISI = 13 ms). During vibration relative to squat exercise alone, single-pulse TMS provoked significantly higher TA MEP amplitude (56 ± 14%, P = 0.003) and total area (71 ± 19%, P = 0.04), and paired TMS with ISI = 13 ms provoked smaller MEP amplitude (−21 ± 4%, P = 0.01) but not in SOL. Paired-pulse TMS with ISI = 3 ms elicited significantly lower MEP amplitude (TA, −19 ± 4%, P = 0.009; and SOL, −13 ± 4%, P = 0.03) and total area (SOL, −17 ± 6%, P = 0.02) during vibration relative to squat exercise alone in both muscles. Tibialis anterior MEP facilitation in response to single-pulse TMS suggests that WBV increased corticospinal pathway excitability. Increased TA and SOL SICI and decreased TA ICF in response to paired-pulse TMS during WBV indicate vibration-induced alteration of the intracortical processes as well.     

Modulatory effects of 1 Hz rTMS over the cerebellum on motor cortex excitability

Clinical observations and data from animal experiments point to a physiological facilitatory influence of the deep cerebellar structures on the motor system through the cerebello-thalamo-cortical pathways. The aim of the present study was to explore the long-term effects of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) over the cerebellum on short intracortical inhibition (SICI) and facilitation (ICF) of the motor cortex in normal subjects. Eight healthy subjects (mean age 26.9 ± 3.1) underwent 1 Hz frequency rTMS delivered on the right cerebellar hemisphere. Before and after cerebellar rTMS, SICI and ICF were assessed in the motor cortex contralateral to the stimulated cerebellar hemisphere by means of a paired pulse paradigm with a conditioning subthreshold stimulus set to 80% of the motor threshold (MT) followed by a testing stimulus at 120% of MT intensity. Five different interstimulus intervals (ISIs) were used to assess SICI (2 and 4 ms) and ICF (7, 10 and 15 ms). Amplitude of the responses was expressed as the percentage of motor evoked potential (MEP) to test stimulus alone. Results showed a significant decrease of ICF at 10 ms ISI that persisted up to 20 min after cerebellar rTMS. This was the only significant modulatory effect of cerebellar stimulation on intracortical motor excitability A suppressive effect of the low-frequency TMS on Purkinje cells could be supposed, even if, the lack of effects on other facilitatory ISIs, stands for more complex modulatory effects of rTMS over cerebellum. The study is a further demonstration that rTMS over the cerebellum induces a long-lasting modulatory effect on the excitability of the interconnected motor area.     

Effects of motor cortical stimulation on the excitability of contralateral motor and sensory cortices

Single pulses of transcranial magnetic stimulation (TMS) were applied to the right hemisphere over either the hand sensory area, the hand motor area (M1), ventral premotor area (vPM), dorsolateral prefrontal cortex, or 10 cm away from head (sham stimulation) in order to test the effect on motor evoked potentials (MEPs) elicited by single pulse TMS or transcranial electrical stimulus (TES) over the left M1 or the somatosensory evoked potential (SEP) elicited by an electrical stimulus to the right median nerve. The interstimulus intervals (ISIs) for MEP experiments were 50, 100, 150, 200, 300 and 400 ms, with those for SEP experiments being adjusted for the impulse conduction time from the wrist to the cortex. TMS over the right M1 reduced MEPs elicited by TMS of the left motor cortex at ISIs of 50–150 ms, whereas MEPs produced by TES were unaffected. TMS over M1 and vPM facilitated the contralateral cortical median nerve SEPs at an ISI of 100–200 ms, whereas it had no effect on tibial nerve SEPs or paired median nerve stimulation SEP. Based on these results, we conclude that at around 150-ms intervals, TMS over the motor areas (M1 and vPM) reduces the excitability of the contralateral motor area. This has a secondary effect of enhancing the responsiveness of the sensory cortex through cortico-cortical connections.     

Relaxation from a voluntary contraction is preceded by increased excitability of motor cortical inhibitory circuits

Termination of a muscle contraction is as important a part of movement as muscle activation yet the mechanisms responsible are less well understood. In the present experiments we examined the possible role of intracortical inhibitory circuits in terminating a 20% maximum isometric contraction of the first dorsal interosseous muscle (FDI) in eight healthy subjects. Subjects performed the task simultaneously with both hands and received single or pairs (at an interstimulus interval of 3 ms to evaluate short interval intracortical inhibition, SICI) of transcranial magnetic stimuli (TMS) via a focal coil over the motor hand area of the left hemisphere at different times before and after the onset of relaxation. The amplitude of the motor-evoked potential (MEP) following a single or a pair of TMS pulses was measured in the right FDI and plotted relative to the onset of relaxation as estimated from the surface electromyogram (EMG) of the left FDI. MEPs were larger during contraction than after relaxation whereas SICI was absent during contraction and reappeared after relaxation. We found that in all subjects, the time course of MEP changes during relaxation was closely fitted by a Boltzmann sigmoidal curve which allowed us to estimate the mean MEP amplitudes as well as the ratio of the amplitudes after single or pairs of TMS pulses (i.e.%SICI) at any time in the task. The data showed that the amplitude of MEPs to single pulse TMS had started to decline at about the same time as the onset of EMG silence. Furthermore, the size of the MEPs evoked by paired pulses decreased up to 30 ms beforehand. The latter suggests that an increase in SICI occurs prior to the onset of MEP changes, and hence that increased cortical inhibition may play a role in suppressing corticospinal excitability during relaxation. A subsidiary experiment showed that the time relations of changes in SICI and MEP were unchanged by a period of 10 min training on the task.     

Further evidence to support different mechanisms underlying intracortical inhibition of the motor cortex

Paired-pulse magnetic stimulation has been widely used to study intracortical inhibition of the motor cortex. Inhibition at interstimulus intervals (ISIs) of 1–5 ms is ascribed to a GABAergic inhibitory system in the motor cortex. However, Fisher et al. have proposed that different mechanisms are operating at an ISI of 1 ms and 2.5 ms. In order to confirm their concept and clarify whether inhibition at all these intervals is produced by a single mechanism, we compared effects of paired-pulse stimulation at ISIs of 1 ms, 2 ms, and 3–5 ms. We evaluated how intracortical inhibition affected the I3-wave, I1-wave, magnetic D-wave, and anodal D-wave components of electromyographic (EMG) responses using previously reported methods. The data suggest that three separate effects occur within these ISIs. At ISIs of 3–5 ms, inhibition was evoked only in responses to I3-waves, whereas no inhibition was elicited in responses to I1-waves or magnetic D-waves. In contrast, at an ISI of 1 ms, responses to I3-waves and I1-waves were moderately suppressed. Moreover, even magnetic D-waves were slightly suppressed, whereas anodal D-waves were unaffected. At an ISI of 2 ms, none of the descending volleys were inhibited. We propose that we should use ISIs of 3–5 ms for estimating function of the GABAergic inhibitory system of the motor cortex by paired-pulse transcranial magnetic stimulation (TMS). Our results support the idea of Fisher et al. that the mechanism responsible for the inhibition at an ISI of 1 ms is not the same as that responsible for suppression at ISIs of 3–5 ms (GABAergic inhibitory circuits in the motor cortex). At an ISI of 2 ms, we suggest that the inhibitory influence evoked by the first stimulus (S1) should collide with or be occluded by the second stimulus (S2), which leads to the lack of inhibition when the subjects make a voluntary contraction of the target muscle.     

Decision making and action implementation: Evidence for an early visually triggered motor activation specific to potential actions

To make a decision may rely on accumulating evidence in favor of one alternative until a threshold is reached. Sequential‐sampling models differ by the way of accumulating evidence and the link with action implementation. Here, we tested a model's prediction of an early action implementation specific to potential actions. We assessed the dynamics of action implementation in go/no‐go and between‐hand choice tasks by transcranial magnetic stimulation of the motor cortex (single‐ or paired‐pulse TMS; 3‐ms interstimulus interval). Prior to implementation of the selected action, the amplitude of the motor evoked potential first increased whatever the visual stimulus but only for the hand potentially involved in the to‐be‐produced action. These findings suggest that visual stimuli can trigger an early motor activation specific to potential actions, consistent with race‐like models with continuous transmission between decision making and action implementation.     

How does temporal preparation speed up response implementation in choice tasks? Evidence for an early cortical activation

We investigated the influence of temporal preparation on information processing. Single‐pulse transcranial magnetic stimulation (TMS) of the primary motor cortex was delivered during a between‐hand choice task. The time interval between the warning and the imperative stimulus varied across blocks of trials was either optimal (500 ms) or nonoptimal (2500 ms) for participants' performance. Silent period duration was shorter prior to the first evidence of response selection for the optimal condition. Amplitude of the motor evoked potential specific to the responding hand increased earlier for the optimal condition. These results revealed an early release of cortical inhibition and a faster integration of the response selection‐related inputs to the corticospinal pathway when temporal preparation is better. Temporal preparation may induce cortical activation prior to response selection that speeds up the implementation of the selected response.     

Transcranial magnetic stimulation reveals asymmetrical efficacy of intracortical circuits in primary motor cortex

The efficacy of inhibitory and excitatory intracortical circuits acting on the representation of an intrinsic hand muscle in the primary motor cortex of both hemispheres was measured with paired transcranial magnetic stimuli in right-handed subjects. Both intracortical inhibition (measured with an interstimulus interval of 3 ms) and intracortical facilitation (measured with an interstimulus interval of 16 ms) developed more rapidly with increasing conditioning stimulus intensity in the dominant than the non-dominant hand. We conclude that the intracortical circuits in the primary motor cortex are more potent in the dominant than the non-dominant hemisphere, and hypothesize that this difference is a factor in the asymmetrical dexterity associated with hand preference.     

Fatigue suppresses ipsilateral intracortical facilitation

Experimental data in animals and humans have demonstrated connections between right and left motor cortices. Interactions between these cortical areas can be explored with electrical or magnetic stimulation. In the present study we examined the interhemispheric effect of fatigue on intracortical facilitation (ICF) and inhibition (ICI) using a paired-pulse transcranial magnetic stimulation (TMS) paradigm. Ten healthy subjects performed pinch grips with their left hand with 50% maximum voluntary contraction (MVC) until fatigue occurred. In the control experiment, the same number of pinch grips was performed with 5% MVC without inducing fatigue. Motor evoked potentials (MEP) produced by single and paired pulse TMS over the left motor cortex were recorded from right first dorsal interosseous muscle (FDI) and right abductor digiti minimi muscle (ADM) before and after the tasks. ICF of the right FDI was significantly reduced after fatigue ( P=0.0008). Fifteen minutes after finishing the task ICF had returned to baseline values. There was no change of ICF of right FDI in the control experiment without inducing fatigue. In both experiments the right ADM did not show significant MEP changes. Additional control experiments showed that M-responses and F-waves were unchanged in right FDI after performing the fatigue task with left FDI, and TMS test pulse amplitudes were significantly reduced in left FDI after fatigue. Fatigue caused by pinch grips induces a short-lasting and task-specific suppression of intracortical facilitation in the motor cortex of an homologous contralateral hand muscle. These results indicate interhemispheric interactions between the two motor cortices that are still effective after cessation of movements.     

Origin of facilitation of motor-evoked potentials after paired magnetic stimulation: direct recording of epidural activity in conscious humans

A magnetic transcranial conditioning stimulus given over the motor cortex at intensities below active threshold for obtaining motor-evoked potentials (MEPs) facilitates EMG responses evoked at rest in hand muscles by a suprathreshold magnetic stimulus given 10-25 ms later. This is known as intracortical facilitation (ICF). We recorded descending volleys produced by single and paired magnetic motor cortex stimulation through high cervical epidural electrodes implanted for pain relief in six conscious patients. At interstimulus intervals (ISIs) of 10 and 15 ms, although MEP was facilitated, there was no change in the amplitude or number of descending volleys. An additional I wave sometimes was observed at 25 ms ISI. In one subject, we also evaluated the effects of reversing the direction of the induced current in the brain. At 10 ms ISI, the facilitation of the MEPs disappeared and was replaced by slight suppression; at 2 ms ISI, there was a pronounced facilitation of epidural volleys. Subsequent experiments on healthy subjects showed that a conditioning stimulus capable of producing ICF of MEPs had no effect on the EMG response evoked by transmastoidal electrical stimulation of corticospinal tract. We conclude that ICF occurs because either 1) the conditioning stimulus has a (thus far undetected) effect on spinal cord excitability that increases its response to the same amplitude test volley or 2) that it can alter the composition (but not the amplitude) of the descending volleys set up by the test stimulus such that a larger proportion of the activity is destined for the target muscle.