Changes in the cortical silent period after repetitive magnetic stimulation of cortical motor areas

Behavioral experiments were conducted to examine the role of the cholinergic receptor-agonist muscarine or its antagonist homatropine on the mating behavior of sexually experienced male rats. Male copulatory behavior was recorded after intrathecally administered saline, muscarine (7.5 μg), or homatropine (25 μg). Changes in copulatory behavior were assessed by the following parameters: intromission latency, intromission frequency, intercopulatory interval, ejaculation latency, and postejaculatory interval. Intromission frequency, intercopulatory interval, and ejaculation latency were decreased significantly by muscarine. Intrathecal homatropine decreased the number of copulating animals (five out of 13). In the five animals that were able to ejaculate after homatropine, intromission latency, intercopulatory interval, and ejaculation latency increased significantly. The effects of both drugs on locomotion were also tested. Muscarine induced no significant changes in locomotion compared with saline. A significant increase in locomotion was found after homatropine treatment. These results suggest that acetylcholine, acting at spinal-cord muscarinic receptors, may be involved in ejaculation. Electronic Publication     

Function of scalene muscles under conditions of quiet breathing and inspiratory resistive load

Low-threshold slow motor units in feline scalene muscle generated spontaneous discharges (6–8 imp/sec) during resting ventilation, which were independent of the respiration cycle. Under conditions of resistive load, activity of these motor units and its electromyographic pattern changed from tonic towards phasic type, synchronized with the inspiration phase. Removal of the load restored the initial pattern of activity. Clear dependency of activity transformations on respiratory load implies a functional modulation of respiratory neural drive to the scalene muscles and the role of these muscles in compensation of inspiratory load. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 12, pp. 623–626, December 1999     

Effects of hand movement path on motor cortical activity in awake,behaving rhesus monkeys

Summary Neuronal activity was studied in the primary (M1), supplementary (M2), dorsal premotor (PMd), and ventral premotor (PMv) cortex of awake, behaving rhesus monkeys. The animals performed forelimb movements to three targets, each approached by three different types of trajectories. With one trajectory type, the monkey moved its hand straight to the target, with another, the path curved in a clockwise direction, and with a third, the path curved in a counter-clockwise direction. We examined whether neuronal activity in these areas exclusively reflects a hand movement's net distance and direction or, alternatively, whether other factors also influence cortical activity. It was found that neuronal activity during all phases of a trial reflects aspects of movement in addition to target location. Among these aspects may be selection of an integrated motor act from memory, perhaps specifying the entirety of a path by which the hand moves to a target.     

Excitability of the ipsilateral motor cortex during phasic voluntary hand movement

We investigated the influence of self-paced, phasic voluntary hand movement on the excitability of the ipsilateral motor cortex. Single- and paired-pulse transcranial magnetic stimulation (TMS) was applied to the right motor cortex triggered by EMG onset of self-paced movements of individual right hand fingers at intervals ranging from 13 to 2,000 ms. Motor evoked potentials (MEPs) were evaluated in several left arm muscles. Significant suppression of MEP amplitudes was observed when TMS was applied between 35 and 70 ms after EMG onset. This inhibition was diffuse, affecting "adjacent" muscles (those near the homologous muscle in the same extremity) as well as homologous muscles, but more inhibition was observed in adjacent and distal muscles than homologous and proximal muscles. Significant inhibition of ipsilateral motor cortex was produced by index finger movements (both the extensor indicis proprius and the first dorsal interosseus), but not by little finger movement (the abductor digiti minimi). Paired-pulse TMS (at 2- and 10-ms interstimulus intervals) showed a significant increase in intracortical facilitation (ICF) selectively in the homologous muscle when triggered by self-paced movement of the opposite hand, but no change was observed in intracortical inhibition. When stimulation was triggered by self-paced movements, the silent period of the homologous muscle was significantly shortened, but the F-wave and compound muscle action potential were unchanged. Our findings demonstrate that voluntary hand movement exerts an inhibitory influence on a diffuse area of the ipsilateral motor cortex. This inhibitory influence is both time and movement dependent. The inhibitory influence is nonselective, while the facilitatory influence (enhancing ICF) appears to act selectively on the homologous muscles. These effects are most likely mediated by a transcallosal pathway. Electronic Publication     

Comparison of motor effects following subcortical electrical stimulation through electrodes in the globus pallidus internus and cortical transcranial magnetic stimulation

Current concepts of transcranial magnetic stimulation (TMS) over the primary motor cortex are still under debate as to whether inhibitory motor effects are exclusively of cortical origin. To further elucidate a potential subcortical influence on motor effects, we combined TMS and unilateral subcortical electrical stimulation (SES) of the corticospinal tract. SES was performed through implanted depth electrodes in eight patients treated with deep brain stimulation (DBS) for severe dystonia. Chronaxie, conduction velocity (CV) of the stimulated fibres and poststimulus time histograms of single motor unit recordings were calculated to provide evidence of an activation of large diameter myelinated fibres by SES. Excitatory and inhibitory motor effects recorded bilaterally from the first dorsal interosseus muscle were measured after SES and focal TMS of the motor cortex. This allowed us to compare motor effects of subcortical (direct) and cortical (mainly indirect) activation of corticospinal neurons. SES activated a fast conducting monosynaptic pathway to the alpha motoneuron. Motor responses elicited by SES had significantly shorter onset latency and shorter duration of the contralateral silent period compared to TMS induced motor effects. Spinal excitability as assessed by H-reflex was significantly reduced during the silent period after SES. No ipsilateral motor effects could be elicited by SES while TMS was followed by an ipsilateral inhibition. The results suggest that SES activated the corticospinal neurons at the level of the internal capsule. Comparison of SES and TMS induced motor effects reveals that the first part of the TMS induced contralateral silent period should be of spinal origin while its later part is due to cortical inhibitory mechanisms. Furthermore, the present results suggest that the ipsilateral inhibition is predominantly mediated via transcallosal pathways.This paper is dedicated to Bernd-Ulrich Meyer, who died in a plane accident     

Unconscious modulation of motor cortex excitability revealed with transcranial magnetic stimulation

The neuronal effects of sensory events that do not enter conscious awareness have been reported in numerous pathological conditions and in normal subjects. In the present study, unconscious modulation of corticospinal excitability was probed in healthy volunteers with transcranial magnetic stimulation (TMS). TMS-induced motor evoked potentials (MEPs) were collected from the first dorsal interosseus muscle while subjects performed a masked semantic priming task that has been shown to elicit covert motor cortex activations. Our data show that the amplitude of the MEPs is modulated by an unseen prime, in line with temporal patterns revealed with event related potentials. These data confirm previous reports showing specific motor neural responses associated with an unseen visual stimulus and establish TMS as a valuable tool in the study of the neural correlates of consciousness.     

Control of human inspiratory motoneurones during voluntary and involuntary contractions

In this review, we consider the discharge of human respiratory motoneurones during involuntary and voluntary contractions and what this reveals about the neural control of respiratory muscles. Motoneurone discharge is the final output of neural drive and can be recorded in humans during a range of experimental protocols. However, human studies have limitations and recordings can only be made indirectly from motoneurones. Animal data allows us to hypothesise how neural drive to these motoneurones is organised in humans. We propose that premotoneuronal networks, perhaps in the spinal cord (i.e. 'spinal distribution networks'), sculpt descending drive from multiple sources. This would determine the differential pattern of activation across inspiratory muscles, preserve the neural and mechanical coupling when voluntary breaths are taken and allow for different patterns of activation in non-respiratory contractions.     

Fast increase of motor cortical inhibition following postural changes in healthy subjects

Background and aims

Postural reactions are associated with changes in the excitability of the motor system. In the present study we investigated the presence of neurophysiological changes of motor cortical areas targeting muscles of the inferior limbs following treatment with a physiotherapy technique aimed to treat postural dysfunctions by stretching postural muscles, global postural reeducation (GPR).

Methods

Twenty healthy subjects were evaluated with paired-transcranial magnetic stimulation (TMS) of the motor cortex and recording of motor evoked potentials (MEPs) from peripheral muscles of the inferior limb before and after two GPR manoeuvres applied in different experiments (1 and 2).

Results

The effects of GPR were posture- and task-specific: indeed, a GPR manoeuvre applied in standing subjects increased inhibition in cortical areas controlling flexor muscles (Biceps Femoris: p < 0.05) while increasing the excitation of cortical areas controlling extensor muscles (Tibialis Anterior: p < 0.05). On the other hand, following a GPR manoeuvre applied in subjects in supine position, increased inhibition in cortical areas controlling flexor muscles (Biceps Femoris and Soleus) was not paralleled by excitation of extensor ones (F = 12.2; p = 0.005).

Conclusions

These findings provide a neurophysiological basis to the clinical benefits associated to physiotherapy and suggest potential applications of treatments based on postural changes on motor cortical disorders.     

Effect of observation combined with motor imagery of a skilled hand-motor task on motor cortical excitability: Difference between novice and expert

We examined the effects of observation combined with motor imagery (MI) of a skilled hand-motor task on motor cortex excitability, which was assessed by transcranial magnetic stimulation (TMS). Novices and experts at 3-ball cascade juggling (3BCJ) participated in this study. In one trial, the subjects observed a video clip of 3BCJ while imagining performing it. In addition, the subjects also imagined performing 3BCJ without video clip observation. Motor evoked potentials (MEPs) were recorded from the hand muscles that were activated by the task during each trial. In the novices, the MEP amplitude was significantly increased by video clip observation combined with MI. In contrast, MI without video clip observation significantly increased the MEP amplitude of the experts. These results suggest that action observation of 3BCJ increases the ability of novices to make their MI performing the task. Meanwhile, experts use their own motor program to recall their MI of the task.     

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.     

The effects upon the activity of hand and forearm muscles of intracortical stimulation in the vicinity of corticomotor neurones in the conscious monkey

Summary Corticomotor (CM) neurones were identified in three conscious macaque monkeys by the presence of post-spike facilitation (PSF) in spike-triggered averages of e.m.g. recorded from intrinsic hand and forearm muscles during performance of a precision grip task. Post-spike effects were compared with those produced by single-pulse intracortical microstimulation (ICMS), with strengths of 4–20 A, delivered at the site of 47 CM cells. Most muscles facilitated by a CM cell were also facilitated by ICMS at the site of the cell. ICMS effects were stronger: at 10 A, the amplitude of ICMS-evoked facilitation was on average 2.8 times greater than PSF, and 6.9 times greater at 20 A. Onset latency of ICMS-evoked facilitation was consistently longer (by 1.7 and 1.3 ms at 10 and 20 A respectively) than PSF, and it is suggested that this results from the indirect, trans-synaptic excitation of CM cells by ICMS. Post-spike suppression was rarely seen (7/421 compared to 105/421 cases of PSF). In contrast, suppression and facilitation were equally common in response to ICMS. The synaptic mechanisms underlying these effects were explored in 5 anaesthetised macaque monkeys. ICMS facilitated a greater proportion of the tested muscles than did the CM cell recorded at the stimulus site. The results suggest the juxtaposition in the motor cortex of CM neurones with different muscle fields. The merits of STA and ICMS for exploring cortical organisation are discussed.     

Altered responses of human elbow flexors to peripheral-nerve and cortical stimulation during a sustained maximal voluntary contraction

 The short-latency electromyographic response evoked by transcranial magnetic stimulation (MEP) increases in size during fatigue, but the mechanisms are unclear. Because large changes occur in the muscle action potential, we tested whether changes in the response to stimulation of the peripheral motor nerve could fully account for the increase in the MEP. Subjects (n=8) performed sustained maximal voluntary contractions (MVCs) of the right elbow flexors for 2 min. During the contraction, the MEP and the response to supramaximal stimulation of motor-nerve fibres in the brachial plexus were alternately recorded. During the contraction, responses to motor-nerve stimulation increased in area by 87±35% (mean±SD) in the biceps brachii and 74±30% in the brachioradialis, but the area of the MEPs increased by 153±86% and 175±122%, respectively. Thus, the increase in the MEP was greater than the increase in the peripheral M-wave. The onset latency of the MEP in the biceps brachii increased by 0.7±0.6 ms (range: –0.2 to 1.9 ms) during the sustained contraction. A smaller increase occurred in response to peripheral nerve stimulation (0.3±0.3 ms; from –0.3 to 0.9 ms). In the contralateral elbow flexors, neither responses to transcranial magnetic stimulation nor responses to motor-nerve stimulation changed in size or latency. During the sustained contraction, the short silent period after stimulation of the peripheral nerve (48±5 ms in biceps brachii and 48±4 ms in brachioradialis) increased in duration by about 12 ms (to 61±12 ms and 60±9 ms, respectively), whereas the silent period following transcranial magnetic stimulation increased from 238±39 ms in biceps brachii and 243±34 ms in brachioradialis to 325±41 ms and 343±42 ms, respectively. During a sustained MVC, while the motor responses to peripheral and to cortical stimulation grow concurrently, growth of the MEP cannot be entirely accounted for by changes in the muscle action potential. Hence, some of the increase in MEP size during fatigue must reflect changes in the central nervous system. Increased latency of the MEPs and lengthening of the peripherally evoked silent period are consistent with decreased excitability of the alpha motoneurone pool. Thus, an increased response from the motor cortex to the magnetic stimulus remains a likely contributor to the increase in the size of the MEP in fatigue. Received: 11 September 1998 / Accepted: 28 January 1999     

Further evidence for excitability changes in human primary motor cortex during ipsilateral voluntary contractions

The present study aimed to further investigate whether the intracortical neural circuits within the primary motor cortex (M1) are modulated during ipsilateral voluntary finger movements. Single- and paired-pulse (interstimulus intervals, ISIs; 3 ms and 12 ms) transcranial magnetic stimulations of the left M1 were applied to elicit motor evoked potential (MEP) in the right first dorsal interosseous (Rt-FDI) muscle during voluntary contractions (10% and 30% maximum voluntary contraction) of the left FDI (Lt-FDI) muscle. F-waves of Rt-FDI muscle were recorded under these left index-finger conditions for ensuring that the excitability changes occur at the supraspinal level. MEPs were also recorded during motor imagery of the left index-finger abduction instead of overt movement. The results showed that, in single-pulse transcranial magnetic stimulation (TMS) paradigm, MEPs in Rt-FDI muscle were markedly enhanced during voluntary contractions of Lt-FDI muscle compared with the complete resting state. In paired-pulse TMS paradigm, the short intracortical inhibition was significantly reduced in proportion to increments of the ipsilateral muscle contraction, whereas the intracortical facilitation had no change. F-wave of Rt-FDI muscle was unchanged under these conditions, while MEP in Rt-FDI muscle was also enhanced during motor imagery of the left index-finger abduction. Based on the present results, it is suggested that the intracortical inhibitory neural circuits may be modulated in the transition from rest to activity of the ipsilateral homonymous muscle. The excitability changes in M1 might be induced by overflows of voluntary drive given to the ipsilateral limb, probably via the transcallosal pathway.     

Changes in muscle responses to stimulation of the motor cortex induced by peripheral nerve stimulation in human subjects

The aim of this study was to determine whether prolonged, repetitive mixed nerve stimulation (duty cycle 1 s, 500 ms on-500 ms off, 10 Hz) of the ulnar nerve leads to a change in excitability of primary motor cortex in normal human subjects. Motor-evoked potentials (MEPs) generated in three intrinsic hand muscles [abductor digiti minimi (ADM), first dorsal interosseous (FDI) and abductor pollicis brevis (APB)] by focal transcranial magnetic stimulation were recorded during complete relaxation before and after a period of prolonged repetitive ulnar nerve stimulation at the wrist. Transcranial magnetic stimuli were applied at seven scalp sites separated by 1 cm: the optimal scalp site for eliciting MEPs in the target muscle (FDI), three sites medial to the optimal site and three sites lateral to the optimal stimulation site. The area of the MEPs evoked in the ulnar-(FDI, ADM) but not the median-innervated (APB) muscles was increased after prolonged ulnar nerve stimulation. Centre of gravity measures demonstrated that there was no significant difference in the distribution of cortical excitability after the peripheral stimulation. F-wave responses in the intrinsic hand muscles were not altered after prolonged ulnar nerve stimulation, suggesting that the changes in MEP areas were not the result of stimulus-induced increases in the excitability of spinal motoneurones. Control experiments employing transcranial electric stimulation provided no evidence for a spinal origin for the excitability changes. These results demonstrate that in normal human subjects the excitability of the cortical projection to hand muscles can be altered in a manner determined by the peripheral stimulus applied.     

Excitability changes in human hand motor area induced by voluntary teeth clenching are dependent on muscle properties

To investigate whether the early effects of voluntary teeth clenching (VTC) among the first dorsal interosseous (FDI), abductor digiti minimi (ADM), and abductor pollicis brevis (APB) muscles are differently modulated depending on their muscle properties, we examined the responses of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation with selected current directions and by brainstem magnetic stimulation (BMS). Although MEP responses with anterior-medially current direction (preferentially elicited I1-waves) were facilitated in all three muscles, those responses with posterior-laterally current direction (preferentially elicited I3-waves) were different among FDI, ADM, and APB muscles. That is, MEP responses in FDI and APB muscles were significantly reduced, whereas those responses in ADM muscle were not significantly reduced. Further, inhibitory effects of VTC in FDI muscle were more potent than those in ADM or APB muscles. On the other hand, the responses to BMS were unchanged by VTC in all three muscles, suggesting that the modulations of MEP were attributed to the cortical origin. On the basis of our previous findings that the inhibitory connections in FDI muscle are more potent than those in ADM muscle (Takahashi et al. in Clin Neurophysiol 116:2757–2764, 2005), the cortical effects of VTC among three hand muscles are differently modulated, depending on muscle properties, presumably the extents of inhibitory connections to corticospinal tract neurons. Considering that the functional capacity in FDI muscle is higher than that in ADM or APB muscles, the cortical inhibitory effect of VTC might contribute to the sophisticated regulation of the motor outputs even during VTC.     

The excitability of human cortical inhibitory circuits responsible for the muscle silent period after transcranial brain stimulation

The silent period after transcranial magnetic brain stimulation mainly reflects the activity of inhibitory circuits in the human motor cortex. To assess the excitability of the cortical inhibitory mechanisms responsible for the silent period after transcranial stimulation, we studied, in 15 healthy human subjects, the recovery cycle of the silent period evoked by transcranial and mixed nerve stimulation delivered with a paired stimulation technique. The recovery cycle is defined as the time course of the changes in the size or duration of a conditioned test response when pairs of stimuli (conditioning and test) are used at different conditioning-test intervals. The recovery cycle of the duration of the silent period in the first dorsal interosseous (FDI) muscle during maximum voluntary contraction after transcranial magnetic stimulation was studied by delivering paired magnetic shocks (a conditioning shock and a test shock) at 120% motor-threshold intensity. Conditioning-test intervals ranged from 20-550 ms. The recovery cycle of the silent period in the FDI muscle during maximum voluntary contraction after nerve stimulation was evaluated by paired, supramaximum bipolar electrical stimulation of the ulnar nerve at the wrist (conditioning-test intervals ranging from 20 to 550 ms). Electromyographic activity was recorded by a pair of surface-disk electrodes over the FDI muscle. The recovery cycle of the silent period after transcranial magnetic stimulation delivered through the large round coil showed two phases of facilitation (lengthening of the silent period), one at 20-40 ms and the other at 180-350 ms conditioning-test intervals, with an interposed phase of inhibition (shortening of the silent period) at 80-160 ms. The conditioning magnetic shock left the size of the test motor-evoked potentials statistically unchanged during maximum voluntary contraction. Paired transcranial stimulation with a figure-of-eight coil increased the duration of the test silent period only at short conditioning-test intervals. Conditioning nerve stimulation left the silent period produced by test nerve stimulation unchanged. In conclusion, after a single transcranial magnetic shock, inhibitory circuits in the human motor cortex undergo distinctive short-term changes in their excitability, probably involving different mechanisms.     

Interindividual variability and age-dependency of motor cortical plasticity induced by paired associative stimulation

Paired associative stimulation (PAS) can increase motor cortical excitability, possibly by long-term potentiation (LTP)-like mechanisms. As the capability of the cortex for plasticity decreases with age, we were interested here in testing interindividual variability and age-dependency of the PAS effect. Motor-evoked potentials (MEPs) were recorded from the resting right abductor pollicis brevis muscle before and for 30 min after PAS in 27 healthy subjects (22–71 years of age). PAS consisted of 225 pairs (rate, 0.25 Hz) of right median nerve stimulation followed at an interval equaling the individual N20-latency of the median nerve somatosensory-evoked cortical potential plus 2 ms by transcranial magnetic stimulation of the hand area of left primary motor cortex (PAS_N20+2). The PAS_N20+2-induced changes in MEP amplitude (ratio post PAS/pre PAS) were highly variable (1.00 ± 0.07, range 0.36–1.68). Fourteen subjects showed the expected LTP-like MEP increase (responders) while 13 subjects showed a long-term depression (LTD)-like MEP decrease (non-responders). Responders had a significantly lower resting motor threshold (RMT) and minimum stimulus intensity to elicit MEPs of 1 mV (MEP_{1 mV}) than non-responders. RMT and MEP_{1 mV} correlated significantly negatively with the PAS_N20+2 effect. The absolute PAS_N20+2 effect size irrespective of its direction decreased with age (r = −0.57, P = 0.002), i.e., LTP-like and LTD-like plasticity were large in young subjects but substantially smaller in elderly subjects. In conclusion, measures of motor cortical excitability (RMT, MEP_{1 mV}) and age determine direction and magnitude of PAS effects in individual subjects.     

The influence of peripheral load on resetting voluntary movement by cortical stimulation: importance of the induced twitch

 We studied the effects of changes in loading torque on the effectiveness of magnetic cortical stimulation in evoking phase resetting of voluntary wrist movement. Nine normal subjects were studied (five on two occasions), while making rhythmical movements of the right wrist, at their preferred rate, against extension torque loads of 0.35 Nm, 0.26 Nm and 0.18 Nm, flexion torque loads of 0.09 Nm and 0.18 Nm and without external load. The position records of individual trials were used to measure the effectiveness of resetting (resetting index: the slope of the phase-response curve) and the ”null phase”, the phase to which the trials were being reset. The loading torque had a strong influence upon both the resetting index and the null phase, generated by a constant intensity of cortical stimulation such that the largest resetting indices were obtained for movements made against the largest extension torque load (mean resetting index 0.72). The degree of resetting and null phase were related to the mean amplitude and direction of the first poststimulus position peak, which in turn was largely determined by the twitch induced by the cortical shock. The timings of the averaged poststimulus position peaks following the first were simple multiples of the prestimulus movement period. Our results indicate that loading conditions profoundly influence the effectiveness of magnetic cortical stimulation in resetting a voluntary movement and that these effects appear to be largely explicable by the changes in the muscle twitch evoked by the stimulus with the different loads. We suggest that the magnetic shock is therefore unlikely to reset voluntary movement by an action directly upon the motor programme. We propose that the main method by which magnetic cortical stimulation resets repetitive wrist movement is indirect: normal generation of repetitive wrist flexion and extension is disrupted by the cortical shock, following which afferent information related to the twitch induced is able to reset the movement. Received: 2 September 1996 / Accepted: 3 April 1997     

Short and long duration transcranial direct current stimulation (tDCS) over the human hand motor area

The aim of the present paper is to study effects of short and long duration transcranial direct current stimulation (tDCS) on the human motor cortex. In eight normal volunteers, motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) were recorded from the right first dorsal interosseous muscle, and tDCS was given with electrodes over the left primary motor cortex (M1) and the contralateral orbit. We performed two experiments: one for short duration tDCS (100 ms, 1, 3 or 5 mA) and the other for long duration tDCS (10 min, 1 mA). The stimulus onset asynchrony (SOA) between the onset of tDCS and TMS were 1–7 and 10–120 ms for the former experiment. In the latter experiment, TMS was given 0–20 min after the end of 10 min tDCS. We evaluated the effect of tDCS on the motor cortex by comparing MEPs conditioned by tDCS with control MEPs. Cathodal short duration tDCS significantly reduced the size of responses to motor cortical stimulation at SOAs of 1–7 ms when the intensity was equal to or greater than 3 mA. Anodal short duration tDCS significantly increased MEPs when the intensity was 3 mA, but the enhancement did not occur when using 5 mA conditioning stimulus. Moreover, both anodal and cathodal short duration tDCS decreased responses to TMS significantly at SOAs of 20–50 ms and enhanced them at an SOA of 90 ms. Long duration cathodal tDCS decreased MEPs at 0 and 5 min after the offset of tDCS and anodal long duration tDCS increased them at 1 and 15 min. We conclude that the effect at SOAs less than 10 ms is mainly caused by acute changes in resting membrane potential induced by tDCS. The effect at SOAs of 20–100 ms is considered to be a nonspecific effect of a startle-like response produced by activation of skin sensation at the scalp. The effect provoked by long duration tDCS may be short-term potentiation or depression like effects.     

Two different effects of transcranial magnetic stimulation to the human motor cortex during the pre-movement period

A single-pulse TMS to the human motor cortex (M1) influences reaction time (RT). We may summarize from previous studies where different groups of subjects participated in various types of RT tasks that TMS above motor threshold (MT) delays RT, whereas TMS below MT shortens RT and that these RT changes depends on TMS timings during RT period. However, these effects have never been systematically investigated in a single study where an identical group of subjects participated. The purpose of this study is to test previous TMS effects in a study of simple RT task. Seven subjects isometrically abducted their right index fingers as quickly as possible when a visual stimulus appeared. A single-pulse TMS was randomly delivered over the left M1 at various timings during RT period in a single trial (at 0, 40, 60, 80 or 100 ms after the visual stimulus). Motor-evoked potential (MEP) and EMG activity for response were recorded from the right finger muscles. Only the TMS above MT delivered at 80 or 100 ms, which increased MEP amplitude, significantly delayed RT and increased the size of response EMG activities that may reflect contents of central motor commands. The TMS below MT at these timings, which occasionally evoked MEP, exclusively shortened RT despite the fact that the response EMG size was unchanged. A single-pulse TMS has different effects on the ongoing neuronal processes in M1 during the pre-movement period: TMS above MT may temporally retard the processes and also affect contents of central motor commands, whereas TMS below MT may simply facilitate its processes without affecting motor commands.