Modulation of preparatory volitional motor cortical activity by paired associative transcranial magnetic stimulation

Paired associative transcranial magnetic stimulation (PAS) has been shown to induce long‐term potentiation (LTP)‐like or long‐term depression (LTD)‐like change in excitability of human primary motor cortex (M1), as probed by motor evoked potential (MEP) amplitude. In contrast, little is known about PAS effects on volitional motor cortical activity. In 10 healthy subjects, movement related cortical potentials (MRCP) were recorded to index volitional motor cortical activity during preparation of simple thumb abduction (prime mover: abductor pollicis brevis, APB) or wrist extension movements (prime mover: extensor carpi radialis, ECR). PAS_LTP increased, PAS_LTD decreased, and PAS_control did not change MEP_APB, while MEP_ECR, not targeted by PAS, remained unchanged in all PAS conditions. PAS_LTP decreased MRCP negativity during the late Bereitschaftspotential (?500 to 0 ms before movement onset), only in the APB task, and predominantly over central scalp electrodes contralateral to the thumb movements. This effect correlated negatively with the PAS_LTP induced increase in MEP_APB. PAS_LTD and PAS_control did not affect MRCP amplitude. Findings indicate a specific interference of PAS with preparatory volitional motor cortical activity, suggestive of a net result caused by increased M1 excitability and disrupted effective connectivity between premotor areas and M1. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Modulation of cortical excitability during action observation: a transcranial magnetic stimulation study

Paired-pulse transcranial magnetic stimulation (TMS) was used to examine changes in cortical excitability during action observation. We stimulated the left primary motor cortex (M1) of eight healthy volunteers during rest, observation of handwriting and observation of arm movements. Motor evoked potentials (MEP) were recorded from the first dorsal intereosseous (FDI) and biceps (BIC) muscles. Our results showed that action observation induced a facilitation of the MEP amplitude evoked by the single test stimulus and reduced intracortical inhibition and facilitation at 3 ms and 12 ms interstimulus intervals (ISIs), respectively, during paired-pulse stimulation. These changes were specific for the muscle involved in the observed action. Our study presents further evidence that motor excitability is significantly modified when the subject observes an action performed by another individual.     

Bihemispheric sensorimotor oscillatory network states determine cortical responses to transcranial magnetic stimulation

BackgroundBrain responses to external stimuli vary with fluctuating states of neuronal activity. Previous work has demonstrated effects of phase and power of the ongoing local sensorimotor μ-alpha-oscillation on responses to transcranial magnetic stimulation (TMS) of motor cortex (M1). However, M1 is part of a distributed network, and the effects of oscillatory activity in this network on TMS-evoked EEG responses (TEPs) have not been explored.ObjectivesTo determine the effects of oscillatory activity in the bihemispheric sensorimotor network on TEPs.Methods31 healthy subjects received single-pulse TMS of the left M1 hand area during EEG recording. Ongoing bihemispheric sensorimotor cortex oscillatory states were reconstructed from the EEG directly preceding TMS, and inferred by a data-driven method combining a multivariate autoregressive model and a Hidden Markov model. TEP amplitudes (P25, N45, P70, N100 and P180) were then compared between different bihemispheric sensorimotor cortex oscillatory states.ResultsFour bihemispheric sensorimotor cortex oscillatory states were identified, with different interhemispheric expressions of theta and alpha oscillations. High alpha-power states in the stimulated sensorimotor cortex increased P25 amplitude. Alpha power in the alpha-alpha state (stimulated - non-stimulated hemisphere) correlated in both hemispheres with N45 amplitude. Theta power in the alpha-theta state correlated in the non-stimulated hemisphere with P70 amplitude.ConclusionsBihemispheric sensorimotor cortex oscillatory states contribute to TEPs, with a relevance shift from stimulated to non-stimulated M1 from P25 over N45 to P70. This significantly extends previous findings: not only ongoing local oscillations but distributed network oscillatory states determine cortical responsiveness to external stimuli.     

Modulation of motor cortical excitability following rapid-rate transcranial magnetic stimulation.

OBJECTIVE: To investigate the effect of high frequency rTMS (25 Hz at 90-100% of resting motor threshold) on the excitability of the motor cortex of healthy human subjects. METHODS: Resting and active motor threshold, MEP recruitment curve (I/O curve), short interval intracortical inhibition (SICI) and facilitation (ICF), and the duration of the silent period (SP) were tested in the right first dorsal interosseous muscle (FDI) before and twice after the end of 1500 pulses in 16 normal young adult male volunteers. RESULTS: Twenty-five Hertz rTMS decreased motor thresholds, reduced the duration of the silent period and had a tendency to increase the slope of the I/O curve. Most of these effects lasted for the duration of the two post-testing sessions (at least 30 min) and had returned to normal by 2h. There were no significant effects on SICI/ICF. CONCLUSION: Twenty-five Hertz rTMS can produce a long lasting increase in cortical excitability in healthy subjects. SIGNIFICANCE: This method may prove useful for the study of normal human physiology and for therapeutic manipulation of brain plasticity.     

Modulation of cortical excitability by transcranial direct current stimulation

Modulation of cerebral excitability is thought to be one mechanism underlying the pharmacological treatment of neuropsychiatric diseases such as epilepsy, depression, and dystonia. Repetitive transcranial magnetic stimulation (rTMS) has been tested for several years as a nonpharmacological, noninvasive method of directly influencing patients' cortical functions. We present an overview of the more easily performed transcranial direct current stimulation (tDCS) with weak current, which produces distinctly more pronounced changes in excitability than rTMS. The basic underlying mechanism is a shift in the resting membrane potential towards either hyper- or depolarisation, depending on stimulation polarity. This in turn leads to changes in the excitability of cortical neurons. Anodic stimulation increases cortical excitability, while cathodic stimulation decreases it. These changes persist after the end of stimulation if the stimulation lasts long enough, i.e., at least several minutes. The duration of this aftereffect can be controlled through the duration and intensity of the stimulation. Transcranial direct current stimulation essentially allows a focal, selective, reversible, pain-free, and noninvasive induction of changes in cortical excitability, the therapeutic potential of which must be evaluated in clinical studies, once possible risk factors have been assessed.     

Experience with transcranial magnetic stimulation in cortical mapping

Abstract

Seventeen subjects underwent transcranial magnetic stimulation (TMS) toward cortical mapping. Cortical mapping produced scalp representations of five upper extremity muscles and their spatial orientation tended to support an expected anatomic pattern. Muscle map locations and map areas showed trends across musical skill and hand dominance as well. No subject experienc.ed adverse effects during the study. TMS promises to be an effective tool for noninvasive cortical mapping. [Neural Res 1997; 19: 435-440]     

Induction of cortical swallowing activity by transcranial magnetic stimulation in the anaesthetized cat

Transcranial magnetic stimulation (TMS) over human fronto-central areas of scalp can activate short latency responses in the muscles of the face, pharynx and oesophagus. However, the physiological relationship between this early activity and the swallowing activity programmed by the brainstem central pattern generator (CPG) remains unclear. The aim of this study was to explore the relationship between TMS-induced early muscle and late swallowing activities in the feline model. Twelve adult cats were studied under light anaesthesia. Mylohyoid and oesophageal EMG, together with pharyngeal, upper oesophageal sphincter (UOS) and upper oesophageal manometry, were recorded to single-pulse TMS of cat cortex. TMS at low stimulation intensities evoked consistent short latency EMG responses in the mylohyoid and oesophageal muscles (6.1 +/- 1.2 ms and 12.7 +/- 0.7 ms, respectively), and early contractile activity in the UOS (latency 31.8 +/- 3.6 ms). By contrast, TMS at high intensities induced swallowing activity as indicated by mylohyoid EMG, and UOS relaxation (latencies 1.1 +/- 0.4 s and 0.8 +/- 0.1 s, respectively). Both the early muscle and late swallowing activities were intensity-dependent, increasing stimulus strength producing a reduction in latency and greater number of swallows. The characteristics of the early response suggest an oligosynaptic projection from cortex to swallowing muscles. The induction of swallows at high intensities suggests a requisite for greater recruitment of cortical motoneurones, or associated swallowing regions.     

Modulation of large-scale cortical coupling by transcranial alternating current stimulation

BackgroundLong-range functional connectivity in the brain is considered fundamental for cognition and is known to be altered in many neuropsychiatric disorders. To modify such coupling independent of sensory input, noninvasive brain stimulation could be of utmost value.ObjectiveFirst, we tested if transcranial alternating current stimulation (tACS) is able to influence functional connectivity in the human brain. Second, we investigated the specificity of effects in frequency and space.MethodsParticipants were stimulated bifocally with high-definition tACS in counterbalanced order (1) in-phase, with identical electric fields in both hemispheres, (2) anti-phase, with phase-reversed electric fields in the two hemispheres, and (3) jittered-phase, generated by subtle frequency shifts continuously changing the phase relation between the two fields. EEG aftereffects were analyzed systematically in sensor and source space.ResultsWhile total power and spatial distribution of the fields were comparable between conditions, global pre-post stimulation changes in EEG connectivity were larger after in-phase stimulation than after anti-phase or jittered-phase stimulation. Those differences in connectivity were restricted to the stimulated frequency band and decayed within the first 120 s after stimulation offset. Source reconstruction localized the maximum effect between the stimulated occipito-parietal areas.ConclusionThe relative phase of bifocal alpha-tACS modulated alpha-band connectivity between the targeted regions. As side effects are not expected to differ between the stimulation conditions, we conclude that neural activity was phase-specifically influenced by the electric fields. We thus suggest bifocal high-definition tACS as a tool to manipulate long-range cortico-cortical coupling which outlasts the stimulation period.     

Modulation of movement-associated cortical activation by transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) is currently attracting increasing interest as a tool for neurorehabilitation. However, local and distant effects of tDCS on motor-related cortical activation patterns remain poorly defined, limiting the rationale for its use. Here we describe the results of a functional magnetic resonance imaging (MRI) experiment designed to characterize local and distant effects on cortical motor activity following excitatory anodal stimulation and inhibitory cathodal stimulation. Fifteen right-handed subjects performed a visually cued serial reaction time task with their right hand in a 3-T MRI scanner both before and after 10 min of 1-mA tDCS applied to the left primary motor cortex (M1). Relative to sham stimulation, anodal tDCS led to short-lived activation increases in the M1 and the supplementary motor area (SMA) within the stimulated hemisphere. The increase in activation in the SMA with anodal stimulation was found also when directly comparing anodal with cathodal stimulation. Relative to sham stimulation, cathodal tDCS led to an increase in activation in the contralateral M1 and dorsal premotor cortex (PMd), as well as an increase in functional connectivity between these areas and the stimulated left M1. These increases were also found when directly comparing cathodal with anodal stimulation. Significant within-session linear decreases in activation occurred in all scan sessions. The after-effects of anodal tDCS arose primarily from a change in the slope of these decreases. In addition, following sham stimulation compared with baseline, a between-session decrease in task-related activity was found. The effects of cathodal tDCS arose primarily from a reduction of this normal decrease.     

Early visual cortical processing suggested by transcranial magnetic stimulation

Single-pulse transcranial magnetic stimulation (TMS) was applied to the occipital pole of healthy subjects while they performed a forced-choice visual letter-identification task. Pulses were applied on the midline but with a left-right asymmetric polarity; pulse application occurred at a variable delay after letter presentation onset; letters were presented in left or right hemifield. Averaging data over subjects and hemifields showed that performance attained local minima at 20 ms and 100 ms; averaging data over subjects and delays showed that performance was biased towards the same hemifield during both delay intervals; averaging data over subjects showed that the hemifield bias progressively decreased from 20 ms to 50 ms. The data are consistent with the possibility that also the earlier delay interval reflects visual cortical processing.     

Modulation of corticospinal excitability by repetitive transcranial magnetic stimulation.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is able to modulate the corticospinal excitability and the effects appear to last beyond the duration of the rTMS itself. Different studies, employing different rTMS parameters, report different modulation of corticospinal excitability ranging from inhibition to facilitation. Intraindividual variability of these effects and their reproducibility are unclear. METHODS: We examined the modulatory effects of rTMS to the motor cortex at various frequencies (1, 10, 20 Hz) and at different time-points in twenty healthy volunteers. RESULTS: We observed significant inhibition of MEPs following 1 Hz rTMS and significant facilitation of MEPs following 20 Hz rTMS for both day1 and day 2. Interestingly, at 1 Hz and 20 Hz rTMS, the modulatory effect produced by rTMS was greater on day 2. However, there was no significant change in corticospinal excitability following 10 Hz rTMS neither on day 1 nor day 2. CONCLUSION: Our findings raise questions as to how stimulation parameters should be determined when conducting studies applying rTMS on multiple days, and in particular, studies exploring rTMS as a treatment modality in neuropsychiatric disorders.     

Human cortical theta reactivity to high-frequency repetitive transcranial magnetic stimulation

Electroencephalography (EEG) can directly monitor the temporal progression of cortical changes induced by repetitive Transcranial Magnetic Stimulation (rTMS) and facilitate the understanding of cortical and subcortical influences in the genesis of oscillations. In this combined rTMS/EEG study, we aimed to investigate changes in oscillatory activity after high-frequency (～11 Hz) rTMS relative to the number of applied pulses. Twenty intermittent trains of 20 or 60 rTMS pulses were delivered over the human primary motor cortex at rest and tuned to individual mu frequency. The regional and interregional oscillatory neural activity after stimulation were evaluated using event-related power (ERPow) and event-related coherence (ERCoh) transformations. The most prominent changes for ERPow were observed in the theta band (4-7 Hz), as an increase in ERPow up to 20 s following 60 rTMS pulses, whereas ERPow increases were smaller in mu (10-12 Hz) and beta (13-30 Hz). ERCoh revealed that rTMS 60 modulated the connectivity in the theta band for up to 20 s. The topography of mu and theta changes were not identical; mu was more focal and theta was more global. Our data suggested the presence of independent cortical theta and mu generators with different reactivity to rTMS but could not rule out possible thalamocortical contributions in generating theta and mu over the motor network.     

Modulation of electroencephalographic responses to transcranial magnetic stimulation: evidence for changes in cortical excitability related to movement

Transcranial magnetic stimulation (TMS) and multichannel electroencephalography (EEG) were used for the investigation of cortical excitability preceding voluntary movement in human subjects. The study showed the practical value of the combined TMS-EEG approach in differentiating between cortical and spinal-cord mechanisms, which is difficult with conventional electromyographic measures alone. TMS induced a pronounced negativity (N100) lasting for 150-200 ms, with the amplitude maximum in the stimulated hemisphere. When TMS was applied just before the onset of the visually triggered movement, N100 was markedly attenuated, although motor evoked potentials (MEPs) became larger. We suggest that the N100 component represents an inhibitory response following TMS. This interpretation is in agreement with intracellular recordings in animals, paired-pulse TMS studies and experiments showing increased premovement excitability on the basis of MEPs. N100 was not affected only by the subsequent movement, but also by the switching from rest to the motor-task condition, which caused a slight attenuation of the N100 component; no changes, however, were found in the amplitude of MEPs, suggesting that modified excitability did not affect the output of the corticospinal pyramidal cells. By contrast to MEPs, N100 was modulated also by the presentation of the visual stimulus alone, i.e. when no movement was required. This attenuation suggests that even in a rest condition visual stimuli have an access to the sensorimotor regions of the cortex, most probably through ascending arousal brain systems.     

Hand preference and transcranial magnetic stimulation asymmetry of cortical motor representation

Human handedness may be associated with asymmetry in the corticospinal motor system. Previous studies measuring the threshold for eliciting motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) have provided evidence consistent with this hypothesis. However, TMS asymmetry observed in previous studies may have reflected cortical or spinal differences. We therefore undertook this investigation to test the hypothesis that handedness is associated with asymmetry in cortical motor representations. We used TMS to map contralateral cortical motor representations of the right and left abductor pollicis brevis (APB) and flexor carpi radialis (FCR) muscles in nine normal subjects (three left-handed). Using focal stimulation with a figure-of-8 shaped magnetic coil, we found no differences in MEP threshold or MEP size between the preferred and the nonpreferred hand. However, we observed that the number of scalp stimulation sites eliciting MEPs was statistically greater for APB and FCR muscles of the preferred limb. We found significant asymmetry between right-handed and left-handed subjects, such that in right-handers, the representation of the right APB was larger than that of the left APB, but in left-handers the representation of right APB was smaller than that of the left APB. These results suggest that handedness is associated with asymmetry in cortical motor representation.     

A transcranial magnetic stimulation study of abnormal cortical inhibition in schizophrenia

Previous research suggests that patients with schizophrenia demonstrate deficits in a range of parameters of motor cortical and cognitive inhibition. I-wave facilitation and long-interval cortical inhibition (LICI) are two paired pulse transcranial magnetic stimulation paradigms that appear to assess aspects of cortical inhibitory function that have not previously been assessed in this patient group. Eighteen patients with schizophrenia (nine medication-free) were compared with eight control subjects. We assessed resting motor threshold (RMT) levels, LICI and I-wave facilitation. RMT levels did not differ between the three groups. There was a significant overall difference in I-wave facilitation levels. Both patient groups as compared with the control group showed increased facilitation. There were no differences between the groups in the measure of LICI. Patients with schizophrenia appear to have increased I-wave facilitation. Increased I-wave facilitation suggests deficient function of cortical inhibitory GABAergic activity. This is consistent with previous research that has found deficient cortical inhibition in patients with schizophrenia.     

Effect of paired transcranial magnetic stimulation on the cortical silent period

Objective. To investigate the behaviour of silent period (SP) during paired magnetic cortical stimulation. Background. Paired cortical magnetic stimulation is known to inhibit or facilitate motor evoked potentials (MEPs), but no attention has been paid to its effect on SP. Methods. SP was measured in the contracted first dorsal interosseus muscle after paired cortical stimuli at given interstimulus intervals (ISIs) in eight healthy subjects. Test stimulus intensity was fixed at 110% of resting threshold (RT), while three levels of conditioning stimulus intensities at 40%, 65% and 90% RT were separately employed. We also examined the effect of progressively increasing the test stimulus intensity (120–150 RT) on SP while maintaining stable conditioning stimulus intensity. Results. 65% RT conditioning stimulus shortened the SP at 1–3 ms ISIs with MEP size reduction, and prolonged the SP at 15–20 ms ISIs without affecting MEP size. 90% RT conditioning stimulus showed only SP prolongation, while 40% RT showed only SP shortening at 1 ms ISI. The SP shortening at 2 ms ISI was the most evident with 120% RT test stimulus, but without correlation with the MEP size. The SP prolongation at 15 ms ISI was maximal with 110% RT test stimulus and then almost abolished with 150% RT. The SP shortening at short intervals might be due not only to spinal but also to suprasegmental mechanisms, conceivably mediating cortical excitatory drive to the corticospinal tract. The SP prolongation at intermediate intervals might be due to activation of slowly conducting, intra- or sub-cortical polysynaptic pathways exerting a facilitatory drive on the cortical inhibitory interneurons.