rTMS Of Motor Cortex Research Articles

Movement related cortical potentials of cued versus self‐initiated movements: Double dissociated modulation by dorsal premotor cortex versus supplementary motor area rTMS

The dorsal premotor cortex (PMd) is thought to play a significant role in movement preparation cued by sensory information rather than in self-initiated movements. The evidence in humans for this contention is still circumstantial. Here we explored the effects of modulation of PMd by excitability decreasing 1 Hz repetitive transcranial magnetic stimulation (rTMS) versus excitability increasing 5 Hz rTMS on two forms of movement related cortical potentials: contingent negative variation (CNV) versus Bereitschaftspotential (BP) reflecting externally cued versus self-triggered movement preparation. Ten healthy right-handed subjects performed visually cued or self-triggered simple sequential finger movements with their right hand. CNV and BP were recorded by 25 EEG electrodes covering the fronto-centro-parietal cortex and divided into an early (1500-500 ms before a go-signal or movement onset) and a late potential (500-0 ms). MRI-navigated 1 Hz rTMS of the left PMd resulted in significant increase of the late CNV over the left central region predominantly contralateral to the prepared right hand movement, while 5 Hz rTMS had no effect on CNV. In contrast, 1 and 5 Hz rTMS did not modify BP. Control experiments of 1 Hz rTMS of the supplementary motor area (SMA) and of low-intensity 1 Hz rTMS of the left primary motor cortex did not change CNV, but 1 Hz SMA-rTMS increased late BP. This double dissociation of effects of PMd-rTMS versus SMA-rTMS on CNV versus BP provides direct evidence that the left PMd in humans is more involved in preparatory processes of externally cued rather than self-initiated movements, contrasting with an opposite role of the SMA.

Modulation of motor cortex neuronal networks by rTMS: comparison of local and remote effects of six different protocols of stimulation

Repetitive transcranial magnetic stimulation (rTMS) of human motor cortex can produce long-lasting changes in the excitability of excitatory and inhibitory neuronal networks. The effects of rTMS depend critically on stimulus frequency. The aim of our present study was to compare the effects of different rTMS protocols. We compared the aftereffects of 6 different rTMS protocols [paired associative stimulation at interstimulus intervals of 25 (PAS(25)) and 10 ms (PAS(10)); theta burst stimulation delivered as continuous (cTBS) or intermittent delivery pattern (iTBS); 1- and 5-Hz rTMS] on the excitability of stimulated and contralateral motor cortex in 10 healthy subjects. A pronounced increase of cortical excitability, evaluated by measuring the amplitude of motor evoked potentials (MEPs), was produced by iTBS (+56%) and PAS(25) (+45%). Five-hertz rTMS did not produce a significant increase of MEPs. A pronounced decrease of cortical excitability was produced by PAS(10) (-31%), cTBS (-29%), and 1-Hz rTMS (-20%). Short-interval intracortical inhibition was suppressed by PAS(10). Cortical silent period duration was increased by 1-Hz stimulation. No significant effect was observed in the contralateral hemisphere. Head-to-head comparison of the different protocols enabled us to identify the most effective paradigms for modulating the excitatory and inhibitory circuits activated by TMS.

RTMS over the cerebellum modulates temperature detection and pain thresholds through peripheral mechanisms

Repetitive transcranial magnetic stimulation (rTMS) of motor and prefrontal cortex has been shown to modulate pain perception. Even though evidence suggests an involvement of cerebellar structures in pain processing, the effect of rTMS over the cerebellum on pain perception has not yet been investigated. This study aimed to test the effects of rTMS over the cerebellum on sensory perception, particularly controlling for peripheral stimulation effects. Sensory perception was determined as temperature detection and temperature pain thresholds. Experiment one explored the effects of four different rTMS protocols (flat figure-of-eight coil; 120% motor resting threshold; 1000 stimuli; 1 Hz and 10 Hz; medial and right lateral cerebellum) on sensory thresholds in 10 healthy volunteers using pairwise comparisons. The most efficient protocol of experiment one was compared in a second experiment with two control conditions (rTMS with a sham coil over the cerebellum [sham] and repetitive magnetic stimulation [rMS] of the neck) by using robust statistics (MANOVA). The first experiment demonstrated pronounced effects on sensory perception for 1Hz rTMS over the lateral cerebellum. The second experiment confirmed this result in comparison to sham. However, rMS over the neck had a similar effect like rTMS over the cerebellum. Our findings suggest that changes in sensory perception after rTMS over the cerebellum are largely due to stimulation effects on peripheral structures and support recent reports of analgesic effects of neck rMS. They advocate the critical review of the proposed analgesic effects of rTMS and encourage the future use of proper control conditions in rTMS research.

Neuronavigation Increases the Physiologic and Behavioral Effects of Low-Frequency rTMS of Primary Motor Cortex in Healthy Subjects

Low-frequency repetitive transcranial magnetic stimulation (rTMS) can exert local and inter-hemispheric neuromodulatory effects on cortical excitability. These physiologic effects can translate into changes in motor behavior, and may offer valuable therapeutic interventions in recovery from stroke. Neuronavigated TMS can maximize accurate and consistent targeting of a given cortical region, but is a lot more involved that conventional TMS. We aimed to assess whether neuronavigation enhances the physiologic and behavioral effects of low-frequency rTMS. Ten healthy subjects underwent two experimental sessions during which they received 1600 pulses of either navigated or non-navigated 1 Hz rTMS at 90% of the resting motor threshold (RMT) intensity over the motor cortical representation for left first dorsal interosseous (FDI) muscle. We compared the effects of navigated and non-navigated rTMS on motor-evoked potentials (MEPs) to single-pulse TMS, intracortical inhibition (ICI) and intracortical facilitation (ICF) by paired-pulse TMS, and performance in various behavioral tasks (index finger tapping, simple reaction time and grip strength tasks). Following navigated rTMS, the amplitude of MEPs elicited from the contralateral (unstimulated) motor cortex was significantly increased, and was associated with an increase in ICF and a trend to decrease in ICI. In contrast, non-navigated rTMS elicited nonsignificant changes, most prominently ipsilateral to rTMS. Behaviorally, navigated rTMS significantly improved reaction time RT and pinch force with the hand ipsilateral to stimulation. Non-navigated rTMS lead to similar behavioral trends, although the effects did not reach significance. In summary, navigated rTMS leads to more robust modulation of the contralateral (unstimulated) hemisphere resulting in physiologic and behavioral effects. Our findings highlight the spatial specificity of inter-hemispheric TMS effects, illustrate the superiority of navigated rTMS for certain applications, and have implications for therapeutic applications of rTMS.

Effects of high-frequency repetitive transcranial magnetic stimulation of primary motor cortex on laser-evoked potentials in migraine.

The aim of this study was to examine the effects of high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex (M1) on subjective pain and evoked responses induced by laser stimulation (LEPs) of the contralateral hand and supraorbital zone in a cohort of migraine patients without aura during the inter-critical phase, and to compare the effects with those of non-migraine healthy controls. Thirteen migraine patients and 12 sex- and age-matched controls were evaluated. Each rTMS session consisted of 1,800 stimuli at a frequency of 5 Hz and 90% motor threshold intensity. Sham (control) rTMS was performed at the same stimulation position. The vertex LEP amplitude was reduced at the trigeminal and hand levels in the sham-placebo condition and after rTMS to a greater extent in the migraine patients than in healthy controls, while the laser pain rating was unaffected. These results suggest that HF rTMS of motor cortex and the sham procedure can both modulate pain-related evoked responses in migraine patients.

Psychogenic paralysis and recovery after motor cortex transcranial magnetic stimulation

Psychogenic paralysis presents a real treatment challenge. Despite psychotherapy, physiotherapy, antidepressants, acupuncture, or hypnosis, the outcome is not always satisfactory with persistent symptoms after long-term follow-up. We conducted a retrospective study to assess clinical features and to propose an alternative treatment based on repetitive transcranial magnetic stimulation (rTMS). Seventy patients (44 F/26 M, mean age: 24.7 +/- 16.6 years) experienced paraparesis (57%), monoparesis (37%), tetraparesis (3%), or hemiparesis (3%). A precipitating event was observed in 42 patients, primarily as a psychosocial event or a physical injury. An average of 30 stimuli over the motor cortex contralateral to the corresponding paralysis was delivered at low frequency with a circular coil. The rTMS was effective in 89% of cases, with a significantly better outcome for acute rather than chronic symptoms. In conclusion, motor cortex rTMS seem to be very effective in patients with psychogenic paralysis and could be considered a useful therapeutic option.

Motor cortex rTMS reduces acute pain provoked by laser stimulation in patients with chronic neuropathic pain

To assess the modulation of acute provoked pain by repetitive transcranial magnetic stimulation (rTMS) of the motor cortex in patients with chronic neuropathic pain. In 32 patients with chronic neuropathic pain affecting one upper limb, laser-evoked potentials (LEPs) (N2 and P2 components) were recorded in response to laser stimulation of the painful or painless hand, before and after active or sham rTMS applied at 10Hz over the motor cortex corresponding to the painful hand. Laser-induced pain was scored on a visual analogue scale. Both active and sham rTMS reduced N2-P2 amplitude of the LEPs in response to painful or painless hand stimulation, likely due to the decline of attention during the sessions. However, active rTMS, but not sham rTMS, specifically reduced N2 amplitude and N2/P2 amplitude ratio of the painful hand LEPs. Painful hand LEP attenuation correlated with the magnitude of pain relief produced by active rTMS. Motor cortex rTMS delivered at high frequency (10Hz) was able to reduce LEP amplitude in parallel with laser-induced pain scores in patients with chronic neuropathic pain. The preferential change in the N2 component suggested a modulation of the sensori-discriminative aspect of laser-induced pain. Previous studies have shown that rTMS delivered to various cortical targets by different protocols could modulate experimental pain, primarily in healthy subjects. The present results demonstrate the ability of motor cortex rTMS to interfere with the processing of acute provoked pain, even if there is an underlying chronic neuropathic pain.

The effects of motor cortex rTMS on corticospinal descending activity

Repetitive transcranial magnetic stimulation (rTMS) of the human motor cortex can produce long-lasting changes in the excitability of the motor cortex to single pulse transcranial magnetic stimulation (TMS). rTMS may increase or decrease motor cortical excitability depending critically on the characteristics of the stimulation protocol. However, it is still poorly defined which mechanisms and central motor circuits contribute to these rTMS induced long-lasting excitability changes. We have had the opportunity to perform a series of direct recordings of the corticospinal volley evoked by single pulse TMS from the epidural space of conscious patients with chronically implanted spinal electrodes before and after several protocols of rTMS that increase or decrease brain excitability. These recordings provided insight into the physiological basis of the effects of rTMS and the specific motor cortical circuits involved.

Therapeutic role of rTMS on recovery of dysphagia in patients with lateral medullary syndrome and brainstem infarction

BackgroundThere is some evidence for a therapeutic effect of repetitive transcranial magnetic stimulation (rTMS) on dysphagia in hemispheric stroke.AimTo compare the effect of active or sham rTMS applied to the...

Perceptual Encoding of Self‐Motion Duration in Human Posterior Parietal Cortex

It has been demonstrated previously that repetitive transcranial magnetic stimulation (rTMS) to right or left posterior parietal cortex (PPC) disrupts perceptual encoding of whole-body displacement during an angular path integration task using only vestibular cues for its completion. The effects of rTMS applied to right PPC (and left motor cortex as a control) during a vestibular-cued motion-reproduction task (i.e., not requiring path integration) were investigated in 5 subjects. Specifically, subjects were rotated in the dark on a motorized Bárány chair with raised cosine velocities of durations 1, 2, and 3 s and peak 30 degrees, 60 degrees, 90 degrees, and 120 degrees/s. Subjects were required to actively reproduce the motion profile after every rotation with a chair-bound joystick. It was found that rTMS applied to the right PPC during the passive (encoding) stimulus phase had no effect on angular velocity reproduction when compared to control (motor-cortex rTMS). In contrast, motion-duration reproduction was significantly worse with right PPC (versus control motor cortex) rTMS. The results imply that vestibular-derived cues of motion duration, but not velocity, are encoded in human PPC. It was inferred from these and previous data that human PPC is involved in human path integration and motion-duration perception, but not angular velocity self-motion perception.

Influence of 5 Hz repetitive transcranial magnetic stimulation on motor learning

The aim of our study was to assess a possible improvement in motor learning induced by 5Hz repetitive transcranial magnetic stimulation (rTMS) of human motor cortex. The same stimulation protocol previously enhanced perceptual learning as assessed by tactile discrimination performance when applied to the human primary somatosensory cortex. We applied 1250 pulses of 5Hz “real” rTMS at 90% of resting motor threshold to the motor hotspot of the abductor pollicis brevis (APB) muscle in 15 healthy subjects before 1h of motor training. Furthermore, 15 subjects received 5Hz “sham” rTMS and served as control group. The motor task consisted of a synchronized co-contraction of the right APB and deltoid muscle. The latency between the onsets of muscle contractions was measured during training and served as a parameter for motor learning. MEP amplitudes were assessed in a subgroup of 10 subjects before and after rTMS as a parameter of corticospinal excitability. We found a significant learning effect in both groups as indicated by a reduction of latencies between the onsets of muscle contractions in the course of the training. Corticospinal excitability increased after “real”, but not after “sham” rTMS. However, “real” rTMS did not significantly influence motor learning as compared to “sham” rTMS. We conclude that 5Hz rTMS of human primary motor cortex is not able to improve motor learning in healthy subjects, which might be due to the higher complexity of motor learning as compared to perceptual learning in the tactile domain.

Altered the timing of intension to move by repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex (M1)

Altered the timing of intension to move by repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex (M1)

<b>The mechanism of high-frequency rTMS </b><b>for intractable pain, a TMS study </b>

We have previously reported the efficacy of navigation-guided 5-Hz repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex in relief of intractable neuropathic pain. The objective of this study was to assess changes of cortical excitability induced by rTMS which might give an insight to the mechanism of pain relief with rTMS. In 14 patients with neuropathic pain in a hand and five healthy controls, the cortical excitability and visual analogue scale (VAS) were evaluated before and after 5Hz-rTMS of the primary motor cortex corresponding to the painful hand. Resting motor threshold, amplitude of motor evoked potential, cortical silent period, intracortical inhibition and intracortical facilitation (ICF) were measured as parameters of cortical excitability with single- or paired-pulse TMS method. The patients who showed ≥ 30% pain reduction in VAS after rTMS were classified as “good responders", the others were as “poor responders". Five of 14 patients were good responders,in whom ICF was significantly lower than that in controls at baseline (p=0.039). ICF increase induced by rTMS was significantly higher in good responders than in poor responders (p=0.046). There were no significant differences and changes in the other parameters. Our findings suggested that restoration of the abnormal cortical excitability was one of the mechanism underling the pain relief with rTMS in neuropathic pain.

Training Effects Outweigh Effects of Single-Session Conventional rTMS and Theta Burst Stimulation in PD Patients

Background. Focal single-session repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex has been claimed to be capable of improving motor function in Parkinson's disease. Objective. The authors sought to determine which type of rTMS protocol holds the highest potential for future therapeutic application. Methods. Twenty-two patients with Parkinson's disease received 5 different rTMS protocols on 5 consecutive days in a pseudorandomized and counterbalanced order either in the defined OFF condition or with their usual medication. The protocols tested in the present study included 2 conventional rTMS protocols (0.5 and 10 Hz) as well as the recently introduced theta burst stimulation (cTBS, iTBS) and a sham condition. Cortical excitability, motor performance (pointing movement, pronation-supination, Purdue Pegboard Test, walking), and mood were assessed before and after each session. Results . The authors observed motor training from days 1 to 4, particularly in the group on dopaminergic medication. None of the rTMS paradigms excelled placebo stimulation. The only exception was the Purdue Pegboard Test, in which all active stimulation paradigms yielded slightly stronger effects than sham stimulation. Conclusions. Within a single session, no clinically relevant difference in the rTMS protocols could be detected. Training effects outweigh and may have masked rTMS effects, particularly in the group on dopaminergic mediation.

Effect of slow rTMS of motor cortex on the excitability of the Blink Reflex: A study in healthy humans

Objective To evaluate the after-effects of low frequency, sub-threshold repetitive Transcranial Magnetic Stimulation (rTMS) of primary motor cortex, on the excitability of Blink Reflex (BR) in healthy subjects. Methods The BR recovery cycle was carried out in 10 healthy volunteers in basal conditions, immediately after rTMS (30 s), 15 and 60 min later. A paired electric supraorbital stimulus paradigm with inter-stimulus intervals (ISI) of 100–600–1000–1500 ms was used. The “real” rTMS consisted of a 200 stimuli long train delivered at 1 Hz and intensity 80% of rest Motor Threshold of the FDI muscle, using a focal coil applied over the primary motor cortex region. The basal BR recovery cycle was also compared with that obtained after a “sham” rTMS. Results The recovery of the R2 component of the BR was significantly suppressed 30 s after rTMS. This effect was also observed at 15 min, though of lower magnitude and only at long ISIs (1000-1500 ms). No significant effect on R2 recovery was observed 60 min after real rTMS as well as after sham rTMS. Conclusions rTMS of motor cortex modulates the excitability of BR through its action on cortical excitability and on the cortical facilitatory drive to the brainstem reflex pathways. Significance Slow (1 Hz), sub-threshold rTMS of motor cortex determines a long-lasting reduction of excitability of BR.

Chronic low-frequency rTMS of primary motor cortex diminishes exercise training-induced gains in maximal voluntary force in humans

Although there is consensus that the central nervous system mediates the increases in maximal voluntary force (maximal voluntary contraction, MVC) produced by resistance exercise, the involvement of the primary motor cortex (M1) in these processes remains controversial. We hypothesized that 1-Hz repetitive transcranial magnetic stimulation (rTMS) of M1 during resistance training would diminish strength gains. Forty subjects were divided equally into five groups. Subjects voluntarily (Vol) abducted the first dorsal interosseus (FDI) (5 bouts x 10 repetitions, 10 sessions, 4 wk) at 70-80% MVC. Another group also exercised but in the 1-min-long interbout rest intervals they received rTMS [Vol+rTMS, 1 Hz, FDI motor area, 300 pulses/session, 120% of the resting motor threshold (rMT)]. The third group also exercised and received sham rTMS (Vol+Sham). The fourth group received only rTMS (rTMS_only). The 37.5% and 33.3% gains in MVC in Vol and Vol+Sham groups, respectively, were greater (P = 0.001) than the 18.9% gain in Vol+rTMS, 1.9% in rTMS_only, and 2.6% in unexercised control subjects who received no stimulation. Acutely, within sessions 5 and 10, single-pulse TMS revealed that motor-evoked potential size and recruitment curve slopes were reduced in Vol+rTMS and rTMS_only groups and accumulated to chronic reductions by session 10. There were no changes in rMT, maximum compound action potential amplitude (M(max)), and peripherally evoked twitch forces in the trained FDI and the untrained abductor digiti minimi. Although contributions from spinal sources cannot be excluded, the data suggest that M1 may play a role in mediating neural adaptations to strength training.

Diffusion tensor fiber tracking in patients with central post-stroke pain; correlation with efficacy of repetitive transcranial magnetic stimulation

Central post-stroke pain (CPSP) is one of the most common types of intractable pain. We reported that repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex relieves pain for patients who were refractory to medical treatment. But the mechanism is unclear. In the present study, we investigated relations between the characteristics of CPSP and the results of fiber tracking, which is the only noninvasive method of evaluating the anatomical connectivity of white matter pathways. Fiber tracking of the corticospinal tract (CST) and thalamocortical tract (TCT) was investigated in 17 patients with CPSP. The stroke lesion was located in a supratentorial region in all cases (corona radiata, one case; thalamus, seven cases; putamen, nine cases). Relations between the delineation ratio (defined as the ratio of the cross section of the affected side to that of the unaffected side) of the CST and of the TCT, manual muscle test score, pain score, region of pain, and efficacy of rTMS were evaluated. Fiber tracking was successful in 13 patients with the stroke lesion involving the TCT. The rTMS-effective group had higher delineation ratio of the CST ( p = 0.02) and the TCT ( p = 0.005) than the rTMS-ineffective group. Previous studies suggested that an intact CST allows pain control but did not discuss the TCT. Our results suggest that the TCT also plays a role in pain reduction by rTMS of the primary motor cortex and that the efficacy of rTMS for patients with CPSP is predictable by fiber tracking.

Eye Position Representation in Human Anterior Parietal Cortex

Eye position helps locate visual targets relative to one's own body and modulates the distribution of attention in visual space. Whereas in the monkey, proprioceptive eye position signals have been recorded in the somatosensory cortex, in humans, no brain site has yet been associated with eye position. We aimed to disrupt the proprioceptive representation of the right eye in the left somatosensory cortex, presumably located near the representation of the right hand, using repetitive transcranial magnetic stimulation (rTMS). Head-fixed subjects reported their perceived visual straight-ahead position using both left and right eye monocular vision, before and after 15 min of 1 Hz rTMS. rTMS over left somatosensory but not over left motor cortex shifted the perceived visual straight ahead to the left, whereas nonvisual detection of body midline was unchanged for either brain area. These results can be explained by the underestimation of the angle of gaze of the right eye when fixating the target. To link this effect more tightly to an altered ocular proprioception, we applied a passive deviation to the right eye before the visual straight-ahead task. Passive eye displacement modulated the shift in the perceived straight ahead induced by somatosensory rTMS, without affecting the perceived straight ahead at baseline or after motor cortex rTMS. We conclude that the anterior parietal cortex in humans encodes eye position and that this signal has a proprioceptive component.

Multimodal approach for mapping effects of subthreshold motor cortex rTMS in parkinsonian patients

Multimodal approach for mapping effects of subthreshold motor cortex rTMS in parkinsonian patients

Improvement of hand dexterity following motor cortex rTMS in multiple sclerosis patients with cerebellar impairment

We tested the effects of 5-Hz repetitive transcranial magnetic stimulation (rTMS) over the motor cortex in multiple sclerosis (MS) subjects with cerebellar symptoms. rTMS improved hand dexterity in cerebellar patients (n = 8) but not in healthy subjects (n = 7), as detected by a significant transient reduction of the time required to complete the nine-hole pegboard task. rTMS of the motor cortex may be a useful approach to treat cerebellar impairment in MS patients.