TMS Pulses Research Articles

Relief of primary cervical dystonia symptoms by low frequency transcranial magnetic stimulation of the premotor cortex: case report

To evaluate the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on the symptoms of a patient with primary segmental dystonia (PSD). 1200 TMS pulses at a frequency of 1Hz, over the premotor cortex, with an intensity of 90% of the motor threshold (MT), using an eight-shaped coil; a total of 5 sessions were carried out. A reduction of 50 percent in the neck subset of the Burke, Fahn and Marsden torsion dystonia scale (BFM) was observed in our patient. The reduction in the BFM scale supports the concept that rTMS of the premotor cortex may reduce specific motor symptoms in PSD.

TMS Evidence for the Involvement of the Right Occipital Face Area in Early Face Processing

Extensive research has demonstrated that several specialized cortical regions respond preferentially to faces. One such region, located in the inferior occipital gyrus, has been dubbed the occipital face area (OFA). The OFA is the first stage in two influential face-processing models, both of which suggest that it constructs an initial representation of a face, but how and when it does so remains unclear. The present study revealed that repetitive transcranial magnetic stimulation (rTMS) targeted at the right OFA (rOFA) disrupted accurate discrimination of face parts but had no effect on the discrimination of spacing between these parts. rTMS to left OFA had no effect. A matched part and spacing discrimination task that used house stimuli showed no impairment. In a second experiment, rTMS to rOFA replicated the face-part impairment but did not produce the same effect in an adjacent area, the lateral occipital cortex. A third experiment delivered double pulses of TMS separated by 40 ms at six periods after stimulus presentation during face-part discrimination. Accuracy dropped when pulses were delivered at 60 and 100 ms only. These findings indicate that the rOFA processes face-part information at an early stage in the face-processing stream.

Interactions between pairs of transcranial magnetic stimuli over the human left dorsal premotor cortex differ from those seen in primary motor cortex

A single TMS pulse (110% resting motor threshold, RMT) to the left dorsal premotor cortex (PMd) (CS2) suppresses the amplitude of motor evoked potentials (MEPs) from a test pulse (TS) over the right motor cortex (M1), and facilitates MEPs from the left motor cortex. We probed how this interaction was changed by a prior conditioning pulse over PMd (CS1) using a paired pulse TMS design. In the main experiments, the intensity of CS1 was 80% RMT. Basal suppression of right M1 was removed when CS1-CS2 was 1 ms or 5 ms with a similar tendency at 15 ms. Basal facilitation of left M1 was suppressed at CS1-CS2 of 5 ms. A similar time course was seen if CS2 was increased to 100% RMT, but there was no significant effect if CS1 was 70% RMT. Preconditioning PMd with continuous or intermittent theta burst repetitive TMS (cTBS, iTBS) abolished the basal CS2-TS interaction between premotor and motor cortices. Finally, if very short interstimulus intervals between CS1 and CS2 were explored to detect interactions similar to I-wave facilitation in M1, we found that the basal suppression of right M1 was abolished at CS1-CS2 intervals of 1.8 and 2.8 ms. We suggest that paired pulse TMS may be capable of investigating properties of intrinsic circuits in PMd and that their properties differ from those in the nearby M1. Paired TMS may be a useful method of studying the excitability of intrinsic circuits in non-primary areas of the motor system.

Abnormal plasticity of the sensorimotor cortex to slow repetitive transcranial magnetic stimulation in patients with writer's cramp

Previous studies demonstrated functional abnormalities in the somatosensory system, including a distorted functional organization of the somatosensory cortex (S1) in patients with writer's cramp. We tested the hypothesis that these functional alterations render S1 of these patients more susceptible to the "inhibitory" effects of subthreshold 1 Hz repetitive transcranial magnetic stimulation (rTMS) given to S1. Seven patients with writer's cramp and eight healthy subjects were studied. Patients also received rTMS to the motor cortex hand area (M1). As an outcome measure, short-latency afferent inhibition (SAI) was tested. SAI was studied in the relaxed first dorsal interosseous muscle using conditioning electrical stimulation of the index finger and TMS pulses over the contralateral M1. Baseline SAI did not differ between groups. S1 but not M1 rTMS reduced SAI in patients. rTMS had no effects on SAI in healthy subjects. Because SAI is mediated predominantly at a cortical level in the sensorimotor cortex, we conclude that there is an abnormal responsiveness of this area to 1 Hz rTMS in writer's cramp, which may represent a trait toward maladaptive plasticity in the sensorimotor system in these patients.

Repetitive TMS over the human oculomotor cortex: Comparison of 1-Hz and theta burst stimulation

The aim of the study was to compare the effect duration of two different protocols of repetitive transcranial magnetic stimulation (rTMS) on saccade triggering. In four experiments, two regions (right frontal eye field (FEF) and vertex) were stimulated using a 1-Hz and a theta burst protocol (three 30 Hz pulses repeated at intervals of 100 ms). The same number of TMS pulses (600 pulses) was applied with stimulation strength of 80% of the resting motor threshold for hand muscles. Following stimulation the subjects repeatedly performed an oculomotor task using a modified overlap paradigm, and saccade latencies were measured over a period of 60 min. The results show that both 1-Hz and theta burst stimulation had inhibitory effects on saccade triggering when applied over the FEF, but not over the vertex. One-hertz rTMS significantly increased saccade latencies over a period of about 8 min. After theta burst rTMS, this effect lasted up to 30 min. Furthermore, the decay of rTMS effects was protocol-specific: After 1-Hz stimulation, saccade latencies returned to a baseline level much faster than after theta burst stimulation. We speculate that these time course differences represent distinct physiological mechanisms of how TMS interacts with brain function.

Repetitive Transcranial Magnetic Stimulation for Tinnitus: A Case Study

Correlate subjective improvements in tinnitus severity with restoration of cortical symmetry and sustained attention after neuronavigated low-frequency, repetitive transcranial magnetic stimulation (rTMS). Case study. Positron emission tomography and computed tomography imaging (PET-CT) guided rTMS was performed on a 43-year-old white male with more than a 30 year history of bilateral tinnitus. rTMS was administered to the area of increased cortical activation visualized on PET-CT at a rate of 1 Hz for 30 minutes (1,800 pulses/session) for each of 5 consecutive days, with optimization applied on day 5 using single pulses of TMS to temporarily alter tinnitus perception. Subjective tinnitus severity was rated before and after rTMS using the tinnitus severity index with analogue scale. Attention and vigilance were assessed before and after therapy using the psychomotor vigilance task (PVT), a simple reaction time test that is sensitive to thalamocortical contributions to sustained attention. Posttherapy PET-CT was used to evaluate any change in asymmetric cortical activation. The most marked reduction in tinnitus severity occurred after rTMS optimization; this persisted up to 4 weeks after rTMS. PVT testing showed the patient exhibited a statistically significant improvement in mean slowest 10% reaction times after rTMS (P = .004). PET-CT imaging 2 days after the cessation of rTMS showed no changes in cortical blood flow or metabolic asymmetries. Low-frequency rTMS applied to the primary auditory cortex can reduce tinnitus severity, with rTMS optimization yielding the most favorable results. Beneficial changes occurring in the patient's slowest reaction times suggest that attentional deficits associated with tinnitus may also respond to low-frequency rTMS.

Magnetic Stimulation of the Left Visual Cortex Impairs Expert Word Recognition

One of the hallmarks of expert reading is the ability to identify arrays of several letters quickly and in parallel. Such length-independent reading has only been found for word stimuli appearing in the right visual hemifield (RVF). With left hemifield presentation (LVF), response times increase as a function of word length. Here we investigated the comparative efficiency with which the two hemispheres are able to recognize visually presented words, as measured by word length effects. Repetitive transcranial magnetic stimulation (rTMS) of the left occipital cortex disrupted expert processing of the RVF such that a length effect was created (Experiment 1). Right occipital rTMS, on the other hand, had no such effect on RVF words and nor did it modulate the length effect already present in the LVF. Experiment 2 explored the time course of these TMS-induced effects by applying single pulses of TMS at various stimulus-onset asynchronies for the same task. We replicated the TMS-induced length effect for RVF words, but only when a single pulse was applied to the left visual cortex 80 msec after target presentation. This is the first demonstration of TMS-induced impairment producing a word length effect, and as such confirms the specialization of the left hemisphere in word recognition. It is likely that anatomical differences in the pathway linking retinal input to higher level cortical processing drive this effect.

Electroencephalographic recording during transcranial magnetic stimulation in humans and animals

Objective We report on the development of an EEG recording system, comprised of electrodes and amplifiers that are compatible with TMS (single and rapid-rate) in both human and animal studies. Methods We assembled a versatile multi-channel EEG recording system consisting of: (1) two types of electrodes that are safe during TMS or rTMS. (2) Low slew-rate EEG amplifiers that recover within a few milliseconds after the application of TMS pulses. Results The two electrode types: (a) a conductive-plastic surface electrode with a conductive-silver epoxy coat and (b) a subdermal silver wire electrode (SWE) are compatible to TMS pulses. The amplifiers recover within 30 ms, so that the EEG can be viewed online, essentially without interruption and/or blocking or excessive artifact. Conclusions Our TMS compatible electrode and EEG recording system allows safe and online viewing/recording of the subject's (human or animal) EEG/EP during experiments or studies involving TMS or rTMS applications. The TMS compatible electrode/amplifier system can be used with any EEG recording instrument. Significance A simple recording technique coupled with new electrodes permit safe and readable EEG records during TMS in humans and animals. Such online monitoring of the EEG would allow control of TMS/rTMS parameters based on EEG activity.

Effects of theta burst stimulation protocols on phosphene threshold

Objective We investigated the effects on occipital cortex, of two newly developed methods of repetitive transcranial magnetic stimulation (rTMS): continuous and intermittent theta burst stimulation (cTBS and iTBS), that lead to long lasting changes in excitability when applied over primary motor cortex. Methods Phosphene threshold to a single TMS pulse was measured before and after application of either continuous or intermittent theta burst stimulation (cTBS/iTBS; 600 total pulses at 80% phosphene threshold). Results In our cohort, cTBS increased phosphene threshold by an average of 10%. In contrast, iTBS, which transiently increases motor cortex excitability, had no effect on phosphene threshold. Conclusions cTBS can be applied successfully to non-motor areas of cortex, but iTBS may need modification to produce maximal effects. Significance cTBS maybe a new useful tool in disorders characterized by an abnormal state of activity of the visual cortex.

Associative Plasticity in Human Motor Cortex During Voluntary Muscle Contraction

TMS pulses over the hand area of motor cortex activate different subpopulations of synaptic connections if the direction of the induced current in the brain is reversed from posterior-anterior (PA) direction to anterior-posterior (AP). We tested whether this also made a difference to the after-effects of paired associative stimulation (PAS: ulnar nerve stimulation followed 25 ms later by a transcranial magnetic stimulation pulse). If 50 pairs of stimuli (0.1 Hz) were applied using conventional suprathreshold PA-PAS in resting subjects, there was no effect on motor-evoked potentials (MEPs) in the first dorsal interosseous muscle. In contrast if the same number of pulses were given while subjects made a small tonic (5% maximum) contraction, MEPs were facilitated and resting motor threshold reduced when AP but not PA pulses were used. Subsequent experiments employed subthreshold TMS (95% of the active motor threshold) during voluntary muscle contraction. MEP facilitation accompanied by reduced AP threshold occurred when PAS was given using AP pulses (AP-Sub-PAS), whereas PAS using PA pulses (PA-Sub-PAS) had no excitatory effect. There was no facilitation if the ulnar nerve stimulus was replaced by digital nerve stimulation. There was a tendency for short interval intracortical inhibition (SICI) to decrease and intracortical facilitation (ICF) to increase after AP-Sub-PAS. We propose that the increased effectiveness of AP-Sub-PAS over PA-Sub-PAS is due to the fact that AP TMS more readily activates I3 inputs to corticospinal neurons and hence that these are an important component of associative plasticity in the human motor cortex.

Action Understanding Requires the Left Inferior Frontal Cortex

Numerous studies have established that inferior frontal cortex is active when hand actions are planned, imagined, remembered, imitated, and even observed. Furthermore, it has been proposed that these activations reflect a process of simulating the observed action to allow it to be understood and thus fully perceived. However, direct evidence for a perceptual role for left inferior frontal cortex is rare, and linguistic or motor contributions to the reported activations have not been ruled out. We used repetitive transcranial magnetic stimulation (rTMS) over inferior frontal gyrus during a perceptual weight-judgement task to test the hypothesis that this region contributes to action understanding. rTMS at this site impaired judgments of the weight of a box lifted by a person, but not judgements of the weight of a bouncing ball or of stimulus duration, and rTMS at control sites had no impact. This demonstrates that the integrity of left inferior frontal gyrus is necessary to make accurate perceptual judgments about other people's actions.

Reduction of intractable deafferentation pain by navigation-guided repetitive transcranial magnetic stimulation of the primary motor cortex

The precentral gyrus (M1) is a representative target for electrical stimulation therapy of pain. To date, few researchers have investigated whether pain relief is possible by stimulation of cortical areas other than M1. According to recent reports, repetitive transcranial magnetic stimulation (rTMS) can provide an effect similar to that of electrical stimulation. With this in mind, we therefore examined several cortical areas as stimulation targets using a navigation-guided rTMS and compared the effects of the different targets on pain. Twenty patients with intractable deafferentation pain received rTMS of M1, the postcentral gyrus (S1), premotor area (preM), and supplementary motor area (SMA). Each target was stimulated with ten trains of 10-s 5-Hz TMS pulses, with 50-s intervals in between trains. Intensities were adjusted to 90% of resting motor thresholds. Thus, a total of 500 stimuli were applied. Sham stimulations were undertaken at random. The effect of rTMS on pain was rated by patients using a visual analogue scale (VAS) and the short form of the McGill Pain Questionnaire (SF-MPQ). Ten of the 20 patients (50%) indicated that stimulation of M1, but not other areas, provided significant and beneficial pain relief ( p < 0.01). Results indicated a statistically significant effect lasting for 3 hours after the stimulation of M1 ( p < 0.05). Stimulation of other targets was not effective. The M1 was the sole target for treating intractable pain with rTMS, in spite of the fact that M1, S1, preM, and SMA are located adjacently.

A direct demonstration of cortical LTP in humans: A combined TMS/EEG study

Repetitive transcranial magnetic stimulation (rTMS) is increasingly being used to promote cortical reorganization, under the assumption that it can induce long-term potentiation (LTP) of neural responses. This assumption is supported by several lines of indirect evidence. For example, rTMS of motor cortex can induce a potentiation of muscle motor evoked potentials that outlasts the stimulation by several minutes. In animal models, a direct demonstration of LTP is typically obtained by high-frequency electrical stimulation coupled with local field recordings of population responses. In this study, we exploited a new approach based on combined rTMS/high-density electroencephalography (hd-EEG) to obtain direct, noninvasive evidence for LTP in humans. Cortical responses to single TMS pulses were measured with hd-EEG before and after applying rTMS to motor cortex (5 Hz, 1500 pulses). The results demonstrate that, after rTMS, EEG responses at latencies of 15–55 ms were significantly potentiated. A topographic analysis revealed that this potentiation was significant at EEG electrodes located bilaterally over premotor cortex. Thus, these findings provide a direct demonstration in humans of LTP induced by rTMS.

Slow rTMS to the somatosensory cortex attenuates afferent inhibition in patients with writer's cramp

Previous studies have shown a number of functional abnormalities in the somatosensory system including a distorted functional organisation of the somatosensory cortex (S1) in patients with writer's cramp. Here we tested the hypothesis that these functional alterations render S1 more susceptible to the „inhibitory“ effects of low-frequency repetitive transcranial magnetic stimulation (rTMS). To this end, we explored the effects of subthreshold 1Hz rTMS (1200 stimuli) given to S1 on clinical symptoms (writing speed) and short latency afferent inhibition (SAI), a measure of sensorimotor integration, in seven writer's cramp patients and eight healthy subjects. In a control experiment, patients also received rTMS to the motor cortex hand area (M1). SAI was tested in the relaxed first dorsal interosseous muscle (FDI) of the dominant hand using conditioning electrical stimulation of the index finger and TMS pulses given over the contralateral M1 at interstimulus intervals (ISI) of 25, 30 and 40 ms. Baseline SAI did not differ between patients and healthy subjects. S1 but not M1 rTMS reduced SAI in patients with significant changes occurring at an ISI of 25 ms. There were no clinical changes. rTMS had no effects on SAI in healthy subjects.

Improvement of Tactile Discrimination Performance and Enlargement of Cortical Somatosensory Maps after 5 Hz rTMS

Repetitive transcranial magnetic stimulation (rTMS) is increasingly used to investigate mechanisms of brain functions and plasticity, but also as a promising new therapeutic tool. The effects of rTMS depend on the intensity and frequency of stimulation and consist of changes of cortical excitability, which often persists several minutes after termination of rTMS. While these findings imply that cortical processing can be altered by applying current pulses from outside the brain, little is known about how rTMS persistently affects learning and perception. Here we demonstrate in humans, through a combination of psychophysical assessment of two-point discrimination thresholds and functional magnetic resonance imaging (fMRI), that brief periods of 5 Hz rTMS evoke lasting perceptual and cortical changes. rTMS was applied over the cortical representation of the right index finger of primary somatosensory cortex, resulting in a lowering of discrimination thresholds of the right index finger. fMRI revealed an enlargement of the right index finger representation in primary somatosensory cortex that was linearly correlated with the individual rTMS-induced perceptual improvement indicative of a close link between cortical and perceptual changes. The results demonstrate that repetitive, unattended stimulation from outside the brain, combined with a lack of behavioral information, are effective in driving persistent improvement of the perception of touch. The underlying properties and processes that allow cortical networks, after being modified through TMS pulses, to reach new organized stable states that mediate better performance remain to be clarified.

Short-lasting impairment of tactile perception by 0.9Hz-rTMS of the sensorimotor cortex.

To test whether low-frequency repetitive transcranial magnetic stimulation (rTMS) of sensorimotor cortex (SM1) has prolonged effects on somatosensory function, eight subjects were given 900 TMS pulses over the left hand SM1 (0.9Hz, 90% of the resting motor threshold) or at sites 3 cm anterior or posterior to it. Tactile threshold of the right hand was increased for a short duration after rTMS over SM1, but two-point discrimination and median nerve SEPs were unaffected after rTMS at any sites.

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.

Motor cortex excitability following short trains of repetitive magnetic stimuli.

Trains of repetitive transcranial magnetic stimuli (rTMS) appear to have effects on corticospinal excitability that outlast the duration of the train. In order to investigate the mechanism of this effect in more detail we applied short periods of rTMS consisting of up to 20 stimuli at 5 Hz, 10 Hz or 20 Hz (rTMS) to the motor cortex at an intensity equal to resting threshold in 11 healthy, relaxed subjects. Spinal excitability, as judged by effects on the H-reflex or on transcranial anodal facilitation of the H-reflex, was not affected by the rTMS. However, cortical excitability, as judged by the effect on the size of EMG responses evoked by a suprathreshold TMS pulse, was decreased for up to 1 s after the end of rTMS. Post-train suppression was more powerful following longer trains or higher frequencies of rTMS. The predominant suppression contrasts with previous reports of facilitation, particularly after high-frequency rTMS. A second set of experiments, however, showed that this could be converted into facilitation if the intensity of rTMS was increased. We conclude that the after-effects of rTMS depend on its frequency, intensity and duration. The results are consistent with a model in which inhibition and facilitation build up gradually during the course of a conditioning train. Inhibition reaches its maximum effect after only a small number of stimuli, whereas facilitation takes longer. The threshold for evoking inhibition is lower than that for facilitation. Thus if moderate intensities of conditioning train are applied, inhibition is predominant after short trains, whereas facilitation dominates after long trains.

Early nuchal reflexes in man

Concurrent transcranial magnetic stimulation and electroencephalography (TMS–EEG) is an emerging method for studying cortical network properties. However, various artifacts affect measurement of TMS-evoked cortical potentials (TEPs), especially within 30 ms of stimulation.The aim of this study was to assess the origin and recovery of short-latency TMS–EEG artifacts (<30 ms) using different stimulators and under different experimental conditions.EEG was recorded during TMS delivered to a phantom head (melon) and 12 healthy volunteers with different TMS machines, at different scalp positions, at different TMS intensities, and following paired-pulse TMS. Recovery from the TMS artifact and other short-latency artifacts were compared between conditions.Following phantom stimulation, the artifact resulting from different TMS machines (Magstim 200, Magventure MagPro R30 and X100) and pulse shapes (monophasic and biphasic) resulted in different artifact profiles. After accounting for differences between machines, TMS artifacts recovered within ∼12 ms. This was replicated in human participants, however a large secondary artifact (peaks at 5 and 10 ms) became prominent following stimulation over lateral scalp positions, which only recovered after ∼25–40 ms. Increasing TMS intensity increased secondary artifact amplitude over both motor and prefrontal cortex. There was no consistent modulation of the secondary artifact following inhibitory paired-pulse TMS (interstimulus interval = 100 ms) over motor cortex.The secondary artifact observed in humans is consistent with activation of scalp muscles following TMS. TEPs can be recorded within a short period of time (10–12 ms) following TMS, however measures must be taken to avoid muscle stimulation.