Transcranial direct current stimulation modulates motor responses evoked by repetitive transcranial magnetic stimulation

Introduction

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive techniques able to induce changes in corticospinal excitability. In this study, we combined rTMS and tDCS to understand possible interactions between the two techniques, and investigate whether they are polarity dependent.

Materials and methods

Eleven healthy subjects participated in the study. Each patient underwent both anodal and cathodal conditioning tDCS in two separate sessions; brief 5 Hz-rTMS trains were delivered over the primary motor cortex at an intensity of 120% the resting motor threshold (RMT) before tDCS (T0), immediately after (T1) and 10 min after current offset (T2). We then analysed changes induced by cathodal and anodal tDCS on TMS variables.

Results

Our results showed that in both anodal and cathodal sessions, the motor evoked potential (MEP) amplitude increased significantly in size before stimulation (T0). Conversely, after anodal tDCS, the MEP facilitation measured at T1 and T2 was absent, whereas after cathodal tDCS it was preserved.

Conclusions

Our findings provide new direct neurophysiological evidence that tDCS influences primary motor cortex excitability.     

Short-term reduction of intracortical inhibition in the human motor cortex induced by repetitive transcranial magnetic stimulation

Ten healthy subjects and two patients who had an electrode implanted into the cervical epidural space underwent repetitive transcranial magnetic stimulation (rTMS; 50 stimuli at 5 Hz at active motor threshold intensity) of the hand motor area. We evaluated intracortical inhibition before and after rTMS. In healthy subjects, we also evaluated threshold and amplitude of motor evoked potentials (MEPs), duration of cortical silent period and short-latency intracortical facilitation. rTMS led to a short-lasting reduction in the amount of intracortical inhibition in control subjects with a high interindividual variability. There was no significant effect on other measures of motor cortex excitability. Direct recordings of descending corticospinal volleys from the patients were consistent with the idea that the effect of rTMS on intracortical inhibition occurred at the cortical level. Since the level of intracortical inhibition can be influenced by drugs that act on GABAergic systems, this may mean that low-intensity repetitive magnetic stimulation at 5 Hz can selectively modify the excitability of GABAergic networks in the human motor cortex. Electronic Publication     

Short-term effects of functional electrical stimulation on spinal excitatory and inhibitory reflexes in ankle extensor and flexor muscles

The purpose of this study was to investigate short-term effects of walking with functional electrical stimulation (FES) on inhibitory and excitatory spinal reflexes in healthy subjects. The FES was applied to the common peroneal (CP) nerve during the swing phase of the step cycle when the ankle flexors are active. We have previously shown that corticospinal excitability for the tibialis anterior (TA) muscle increased after 30 min of FES-assisted walking. An increase of corticospinal excitability could be due to the changes in spinal and/or cortical excitability. Thus, we wished to examine whether a short-term application of FES would increase spinal motoneuronal excitability. Changes could also result from effects on inhibitory as well as excitatory pathways, but to our knowledge no studies have investigated short-term effects of FES on spinal inhibitory pathways. Therefore, we measured reciprocal and presynaptic inhibition, as well as reflex excitability, before and after FES-assisted walking. As controls, effects of FES-like stimulation at rest and walking without stimulation were tested in separate sessions. The TA H-reflex amplitude did not increase after FES in any of the conditions tested, so we have no evidence that FES increases spinal excitability for the TA. The soleus H-reflex decreased slightly (10%) after FES-assisted walking, and remained decreased for at least 30 min. However, the control experiment indicated that this decrease was associated with walking and not with stimulation. Thirty minutes of FES did not produce any significant effects on spinal inhibitory pathways examined in the present study. In conclusion, the soleus H-reflex showed a small but consistent decrease and no spinal circuits examined showed an increase, as was observed in the corticospinal excitability. Thus, we suggest that a short-term application of FES increases the excitability of the cortex or its connections to the spinal cord more effectively than that of spinal pathways.     

Electrical and magnetic repetitive transcranial stimulation of the primary motor cortex in healthy subjects

Repetitive transcranial magnetic stimulation (rTMS) delivered in short trains at 5 Hz frequency and suprathreshold intensity over the primary motor cortex (M1) in healthy subjects facilitates the motor-evoked potential (MEP) amplitude by increasing cortical excitability through mechanisms resembling short-term synaptic plasticity. In this study, to investigate whether rTES acts through similar mechanisms we compared the effects of rTMS and repetitive transcranial electrical stimulation (rTES) (10 stimuli-trains, 5 Hz frequency, suprathreshold intensity) delivered over the M1 on the MEP amplitude. Four healthy subjects were studied in two separate sessions in a relaxed condition. rTMS and anodal rTES were delivered in trains to the left M1 over the motor area for evoking a MEP in the right first dorsal interosseous muscle. Changes in MEP size and latency during the course of the rTMS and rTES trains were compared. The possible effects of muscle activation on MEP amplitude were evaluated, and the possible effects of cutaneous trigeminal fibre activation on corticospinal excitability were excluded in a control experiment testing the MEP amplitude before and after supraorbital nerve repetitive electrical stimulation. Repeated measures analysis of variance (ANOVA) showed that rTES and rTMS trains elicited similar amplitude first MEPs and a similar magnitude MEP amplitude facilitation during the trains. rTES elicited a first MEP with a shorter latency than rTMS, without significant changes during the course of the train of stimuli. The MEP elicited by single-pulse TES delivered during muscle contraction had a smaller amplitude than the last MEP in the rTES trains. Repetitive supraorbital nerve stimulation left the conditioned MEP unchanged. Our results suggest that 5 Hz-rTES delivered in short trains increases cortical excitability and does so by acting on the excitatory interneurones probably through mechanisms similar to those underlying the rTMS-induced MEP facilitation.     

Treating anxious depression using repetitive transcranial magnetic stimulation

Background

A subset of patients given a clinical diagnosis of major depressive disorder (MDD) are described as having “anxious depression,” a presentation that, in some studies, has been an indicator of poor response to pharmacotherapy. The aim of this study was to determine if anxious depression is associated with attenuated response to repetitive transcranial magnetic stimulation (rTMS), an FDA-approved treatment for MDD.

Methods

Participants were 32 adult outpatients with treatment resistant MDD who were referred for rTMS. The Hamilton Rating Scale for Depression (HAMD) was administered to assess treatment response, and anxious depression was defined as a score of seven or above on the anxiety/somatization factor of the HAMD. A quarter of the sample met the anxious depression criterion at pretreatment.

Results

Both depression (total score) and anxiety symptoms improved from pre- to post-treatment with moderate to large treatment effects. Patients with and without anxious depression demonstrated similar rates of improvement in depression. Patients with versus without anxious depression demonstrated larger improvements in anxiety.

Limitations

The sample size was small, and assessments did not include structured diagnostic interview or independent measures of anxiety symptoms.

Conclusions

For the sample as a whole, there were significant improvements in both depression and anxiety. Anxious depression was not associated with attenuated treatment response to rTMS.     

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 5 Hz 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 5 Hz “real” rTMS at 90% of resting motor threshold to the motor hotspot of the abductor pollicis brevis (APB) muscle in 15 healthy subjects before 1 h of motor training. Furthermore, 15 subjects received 5 Hz “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 5 Hz 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.     

The effects of 10 Hz repetitive transcranial magnetic stimulation on resting EEG power spectrum in healthy subjects

10 Hz rTMS over the left prefrontal cortex may be useful in the treatment of depressive disorders. However, the effects of 10 Hz rTMS applied in potentially effective doses on electroencephalographic activity are not well studied. Using EEG, we aimed to investigate the neurobiological effects of the 10 Hz rTMS set of parameters currently used for depression treatment in a sample of healthy subjects. In 18 healthy subjects, either 10 Hz real rTMS or sham stimulation were given in a crossover design. Real rTMS stimulation was carried out with an intensity of 110% of motor threshold (MT) over the left dorsolateral prefrontal cortex. For the sham condition, the coil was angled over a parietotemporal position and the intensity was reduced to 90% of MT. EEG recordings were taken before and after a single rTMS session. EEG power spectrum was extracted using the complex demodulation method and changes in power were evaluated statistically. Real 10 Hz rTMS induced an overall increase in delta power. This increase prevailed throughout the sample, whereas effects on the power of the alpha, beta and theta EEG bands were highly variable. Sham stimulation had no substantial effects on the EEG power spectrum. Furthermore, no changes in EEG asymmetry were detected. Real 10 Hz rTMS applied at 2000 stimuli and 110% intensity may induce significant changes in resting EEG in healthy subjects.     

经颅磁刺激对部位相关癫癎患者运动皮质功能的评估

目的:采用经颅磁刺激技术(TMS)探讨症状性运动部位相关癫癎患者发作间期运动皮质的兴奋性.方法:对诊断明确的34例癫癎患者(分治疗组和未治疗组)及20例年龄、性别匹配的正常对照组进行单脉冲经颅磁刺激,刺激部位头颅相应的运动手区和颈7棘突外侧,并于对侧小指外展肌记录运动诱发电位(MEP),分析其阈强度(TI)、周围潜伏期(PL)及皮质潜伏期(CL)、中枢传导时间(CCT)和静息期(SP).结果:所有癫癎患者PL、CL及CCT均在正常范围内,但TI和SP明显低于正常对照组(P< 0.01).在癫癎患者中,未治疗组TI及SP明显低于治疗组(P< 0.01),致癎灶侧TI及SP低于非致癎灶侧(P< 0.05),但非致癎灶侧SP亦缩短.结论:单脉冲低频TMS能有效地反映中枢运动皮质的功能状态,用于症状性运动部位相关癫癎患者发作间期运动皮质兴奋性研究具有重要的实用价值.     

Modulatory effects of high-frequency repetitive transcranial magnetic stimulation on the ipsilateral silent period

In healthy subjects, suprathreshold repetitive transcranial magnetic stimulation (rTMS) at frequencies >2 Hz prolongs the cortical silent period (CSP) over the course of the train. This progressive lengthening probably reflects temporal summation of the inhibitory interneurons in the stimulated primary motor cortex (M1). In this study, we tested whether high-frequency rTMS also modulates the ipsilateral silent period (ISP). In nine normal subjects, suprathreshold 10-pulse rTMS trains were delivered to the right M1 at frequencies of 3, 5, and 10 Hz during maximal isometric contraction of both first dorsal interosseous muscles. At 10 Hz, the second pulse of the train increased the area of the ISP; the other stimuli did not increase it further. During rTMS at 3 and 5 Hz, the ISP remained significantly unchanged. Control experiments showed that 10-Hz rTMS delivered at subthreshold intensity also increased the ISP. rTMS over the hand motor area did not facilitate ISPs in the biceps muscles. Finally, rTMS-induced ISP facilitation did not outlast the 10-Hz rTMS train. These findings suggest that rTMS at a frequency of 10 Hz potentiates the interhemispheric inhibitory mechanisms responsible for the ISP, partly through temporal summation. The distinct changes in the ISP and CSP suggest that rTMS facilitates intrahemispheric and interhemispheric inhibitory phenomena through separate neural mechanisms. The ISP facilitation induced by high-frequency rTMS is a novel, promising tool to investigate pathophysiological abnormal interhemispheric inhibitory transfer in various neurological diseases.     

Transcranial magnetic stimulation: Cortical motor maps in acute spinal cord injury

Summary This investigation examined the motor pathways of four, C5-6 spinal cord injured (SCI) patients within 6–17 days of injury. Mapping of the motor cortex was achieved by transcranial magnetic stimulation (TMS) applied to the scalp. Motor evoked potentials were recorded from target muscle groups (Biceps brachii and Abductor pollicis brevis m.). Evidence of an expanded cortical map of the preserved contralateral biceps muscle was demonstrated in these patients as early as 6 days. These findings suggested that early motor re-organization may occur following acute cervical spinal cord injury in man.     

Laterality effects in selective attention to threat after repetitive transcranial magnetic stimulation at the prefrontal cortex in female subjects

Recently, several experiments have indicated that the left and right prefrontal cortex (PFC) are differently involved in emotional processing. The aim of this study was to investigate the role of the left and right PFC in selective attention to angry faces by using a pictorial emotional Stroop task. Slow repetitive transcranial magnetic stimulation (rTMS) was applied to the left and right PFC of 10 female subjects for 15 min on separate days. Results showed a significant effect of stimulation position: right PFC rTMS resulted in selective attention towards angry faces, whereas left PFC rTMS resulted in selective attention away from angry faces. This finding is in accordance with theoretical accounts of the neural implementation of approach and withdrawal systems.     

Manipulation of phosphene thresholds by transcranial direct current stimulation in man

Transcranial direct current stimulation (tDCS) can modulate the excitability of the human motor cortex, as revealed by the amplitude of the motor-evoked potentials (MEP). The aim of our study has been to produce localized changes of cerebral excitability of the visual cortex in the intact human by weak anodal and cathodal stimulation. For quantification of current-induced excitability changes, we measured phosphene threshold (PT) using short trains of 5-Hz transcranial magnetic stimulation (TMS) pulses in nine healthy subjects before, immediately after, 10 min, and 20 min after the end of tDCS. PTs are suggested as representative values of visual cortex excitability changes. Reduced PT was detected immediately and 10 min after the end of anodal stimulation, while cathodal stimulation resulted in an opposite effect. Our results show that tDCS elicits a transient, reversible excitability alteration of the visual cortex, thus representing a promising tool for neuroplasticity research. Electronic Publication     

Physiology of modulation of motor cortex excitability by low-frequency suprathreshold repetitive transcranial magnetic stimulation

Many studies show consistently that repetitive transcranial magnetic stimulation (rTMS) with a frequency of 1 Hz and an intensity above the resting motor threshold (RMT) performed for several minutes over the primary motor cortex (M1) leads to a depression of cortical excitability. Furthermore, most studies concur on a facilitation of the non-stimulated contralateral M1. Little is known, however, about the physiological mechanisms underlying these effects. In 11 healthy volunteers, we stimulated the left M1 for 15 min with 1 Hz-rTMS of 115% RMT. Before, immediately after, and 30 min after the rTMS train, we examined short-interval intracortical inhibition (SICI; interstimulus interval (ISI) of 2 and 4 ms), intracortical facilitation (ICF; ISI 10 ms), and short-interval intracortical facilitation (SICF; ISI 1.5 ms) with established paired-pulse protocols. Mean unconditioned motor evoked potential (MEP) amplitudes and RMT were also measured. Two sessions were run at least 1 week apart, in one excitability of the stimulated M1 was tested, in the other one excitability of the non-stimulated M1. rTMS led to the expected reduction of MEP amplitude of the stimulated M1, which was significant only immediately after the rTMS train. rTMS increased MEP amplitude of the non-stimulated M1, which lasted for at least 30 min. RMT, SICI, ICF and SICF did not show any significant change in either M1, except for a long lasting increase of SICF in the non-stimulated M1. In conclusion, the MEP increase in the non-stimulated M1 lasted longer than the MEP decrease in the stimulated M1. Only the long-lasting MEP increase was associated with a specific change in intracortical excitability (increase in SICF). Modulation of motor cortical inhibition did not play a role in explaining the rTMS induced changes in MEP amplitude.     

Short-latency subliminal effects of transcranial magnetic stimulation on forearm motoneurones

The H-reflex technique has been used to evaluate the time-course of the effects evoked by transcranial clockwise magnetic stimuli in flexor or extensor carpi radialis motoneurones. In six subjects, magnetic stimulation was applied over the scalp in the focus for the motor response of those muscles. At intensities below motor threshold, a facilitation of the H-reflex started at a conditioning-test interval of -4 ms (i.e. when the magnetic stimulus lagged the test stimulus by 4 ms), reached a peak at about -2 ms and rapidly decayed. At about -1 ms, the decay attained a local minimum, which in three subjects had values indicating the presence of an inhibition. Thereafter, a second facilitatory phase peaked at about +1 ms. By matching the time course with the latency of the cortical muscle action potential (CMAP) evoked by suprathreshold magnetic stimulation, it is inferred that the motoneuronal discharge coincides with the second peak of facilitation and is preceded by 3–4 ms of subliminal excitation. This early effect could be brought to threshold by convergence of a subliminal Ia EPSP, leading to a reduction of the CMAP latency. The early excitatory effects reported above are as fast as those described as following transcranial electrical stimulation, and should likewise be considered as monosynaptic.     

重复经颅磁刺激治疗脊髓损伤的临床疗效

目的：观察重复经颅磁刺激（rTMS）治疗对脊髓损伤（SCI）的临床疗效。方法：对26例SCI患者进行rTMS治疗,并与20例健康志愿者对照分析,观察治疗前后运动诱发电位（MEP）波幅及潜伏期的变化。结果：26例SCI患者治疗前MEP潜伏期延迟,波幅降低,治疗后均有明显变化,表现为MEP潜伏期明显缩短,波幅明显增高,治疗前后比较,差异有统计学意义。结论：rTMS治疗SCI具有一定疗效。     

1-Hz low frequency repetitive transcranial magnetic stimulation in children with Tourette's syndrome

The aim of the current study was to assess the efficacy of repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA) of the cortex to children with Tourette's syndrome (TS), if rTMS over the SMA had positive effects on ameliorating tics. We designed a pilot open label 12 weeks cohort study to assess the efficacy of rTMS with TS at specific regions. We administered rTMS over SMA with slow frequency to children with TS. We examined 10 male children (mean age 11.2 ± 2.0 years) diagnosed with TS according to the Diagnostic and Statistical Manual of Mental Disorders version IV and Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. Children with TS were treated with active rTMS to the SMA for 10 daily sessions (1 Hz, 100% of motor threshold, and 1200 stimuli/day). All subjects completed the study with no side effects and no worsening of ADHD or depressive and anxiety symptoms. Tic symptoms improved significantly over the 12 weeks of the study. Statistically significant reductions were seen in the Yale Global Tourette's Syndrome Severity Scale (YGTSS) and Clinical Global Impression (CGI). Low-frequency rTMS over the SMA appears to be effective in children with TS. Further studies using repetitive transcranial magnetic stimulation in TS are warranted, using blinded, balanced, and parallel designs. rTMS over the SMA to children with TS might result in a significant clinical improvement and a normalization of both the hemisphere hyperexcitability.     

A transcranial magnetic stimulation study of corticospinal excitability during the observation of meaningless,goal-directed,and social behaviour

The effects of action observation on cortical processes have typically been interpreted in the context of so-called “mirror systems” (i.e., brain regions active during both the experience and observation of behaviour, emotion, or sensation), and viewed as subserving social cognition via a self-other matching mechanism. If such cortical processes do indeed facilitate social understanding, then cortical activity during action observation might be further enhanced when observing behaviour embedded within a social, interactive context. Transcranial magnetic stimulation (TMS) was administered to 27 healthy adults, and corticospinal excitability (CSE), which is a putative measure of the mirror system, was examined during the observation of (1) meaningless behaviour, (2) goal-directed behaviour, and (3) social behaviour. Although CSE was enhanced during the observation of both goal-directed and social behaviour, there was no difference between the two. These findings suggest that while the putative human mirror system is responsive to goal-directed behaviour, it may not be more responsive to behaviour that occurs within a social context.     

Modulation of visual cortical excitability in migraine with aura: effects of 1 Hz repetitive transcranial magnetic stimulation

Recent studies showed hyperexcitability of the occipital cortex in subjects affected by migraine with aura. It has been shown that 1 Hz repetitive transcranial magnetic stimulation (rTMS) reduces excitability of visual cortex in normal subjects. The aim of the study was to investigate the effects of low frequency (1 Hz) rTMS on visual cortical excitability by measuring changes in phosphene threshold (PT) in subjects with migraine with aura. Thirteen patients with migraine with aura and 15 healthy controls were examined. Using a standardized transcranial magnetic stimulation protocol of the occipital cortex, we assessed the PT (the lowest magnetic stimulation intensity at which subjects just perceived phosphenes) before and after a 1-Hz rTMS train delivered at PT intensity for 15 min. The difference in the proportion of subjects reporting phosphenes in migrainer and control groups was significant (migrainers: 100% vs controls 47%; P<0.05), and 1 Hz rTMS over the occipital cortex led to a significantly increased visual cortex excitability expressed as a decrease in PT in subjects affected by migraine with aura. Conversely, after a 1-Hz TMS train normal subjects showed increased PT values, which suggests a decreased visual cortex excitability. Our findings confirm that the visual cortex is hyperexcitable in migrainers and suggest a failure of inhibitory circuits, which are unable to be upregulated by low frequency rTMS.     

Comparison of descending volleys evoked by monophasic and biphasic magnetic stimulation of the motor cortex in conscious humans

The descending spinal volleys evoked by monophasic and biphasic magnetic stimulation of the motor cortex were recorded from a bipolar electrode inserted into the cervical epidural space of four conscious human subjects. The results suggest that both phases of the biphasic pulse are capable of activating descending motor output. The pattern of recruitment of descending activity depends on the intensity of the stimulus and the relative threshold of each volley to each direction of current flow.     

The effects of repetitive transcranial magnetic stimulation on cortical inhibition in healthy human subjects

It has been suggested that the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) are mediated through changes in cortical inhibition (CI). However, in healthy human subjects the effects of rTMS on CI have been inconsistent. Therefore, this study sought to improve on the methodological limitations of previous studies by exploring several different rTMS-stimulus conditions on inhibition in the human motor cortex. In the first experiment, 12 healthy control subjects were randomly assigned to receive regular 1, 10 or 20 Hz rTMS in a counterbalanced order with sessions separated by at least 1 week. In the second experiment, 10 of these 12 subjects received priming rTMS (600 stimuli at 6 Hz followed by 600 stimuli at 1 Hz). Cortical inhibition was indexed using short-interval intracortical inhibition (SICI) and cortical silent period (CSP). Corticospinal excitability was indexed using motor threshold and MEP amplitude. We found no significant overall change in SICI, although there was a significant correlation between changes in SICI with baseline SICI. Subjects with greater SICI at baseline tended to have reduction in SICI post-rTMS, whereas subjects with less SICI tended to have increase in SICI post-rTMS. There was also a significant lengthening of the CSP with higher stimulation frequencies compared to lower stimulation frequencies. These findings suggest that rTMS increases CI, particularly in subjects with reduced baseline inhibition, a finding consistent with the concept of homeostatic plasticity. Baseline physiological characteristics may be further explored as a method to select patients who may benefit from rTMS treatment.