BOLD fMRI response to direct stimulation (transcranial magnetic stimulation) of the motor cortex shows no decline with age

Previous studies using BOLD fMRI to examine age-related changes in cortical activation used tasks that relied on peripheral systems to activate the brain. They were unable to distinguish between alterations due to age-related changes in the periphery and actual changes in cortical physiology. Transcranial magnetic stimulation (TMS), which allows direct, noninvasive stimulation of cortical neurons, was interleaved with BOLD fMRI to study 6 young and 5 old subjects. Three different tasks were compared: direct stimulation by TMS, indirect active stimulation produced by a motor task, and indirect passive stimulation produced by hearing the TMS coil discharge.Direct neuronal stimulation by TMS produced similar fMRI signal increases in both groups, suggesting that cortical physiology itself may not necessarily decline with age.     

Multi-modality mapping of motor cortex: comparing echoplanar BOLD fMRI and transcranial magnetic stimulation

Summary Multiple non-invasive methods of imaging brain function are now available for presurgical planning and neurobiological research. As these new methods become available, it is important to understand their relative advantages and liabilities, as well as how the information gained compares across different methods. A current and future trend in neurobiological studies as well as presurgical planning is to combine information from different imaging techniques. Multi-modal integration may perhaps give more powerful information than each modality alone, especially when one of the methods is transcranial magnetic stimulation (TMS), with its ability to non-invasively activate the brain. As an initial venture in cross comparing new imaging methods, we performed the following 2 studies, locating motor cortex with echoplanar BOLD fMRI and TMS. The two methods can be readily integrated, with concurring results, although each have important limitations.     

Cortical and subcortical brain effects of transcranial magnetic stimulation (TMS)-induced movement: an interleaved TMS/functional magnetic resonance imaging study.

BACKGROUND: To date, interleaved transcranial magnetic stimulation and functional magnetic resonance imaging (TMS/fMRI) studies of motor activation have not recorded whole brain patterns. We hypothesized that TMS would activate known motor circuitry with some additional regions plus some areas dropping out. METHODS: We used interleaved TMS/fMRI (11 subjects, three scans each) to elucidate whole brain activation patterns from 1-Hz TMS over left primary motor cortex. RESULTS: Both TMS (110% motor threshold) and volitional movement of the same muscles excited by TMS caused blood oxygen level-dependent (BOLD) patterns encompassing known motor circuitry. Additional activation was observed bilaterally in superior temporal auditory areas. Decreases in BOLD signal with unexpected post-task "rebounds" were observed for both tasks in the right motor area, right superior parietal lobe, and in occipital regions. Paired t test of parametric contrast maps failed to detect significant differences between TMS- and volition-induced effects. Differences were detectable, however, in primary data time-intensity profiles. CONCLUSIONS: Using this interleaved TMS/fMRI technique, TMS over primary motor cortex produces a whole brain pattern of BOLD activation similar to known motor circuitry, without detectable differences from mimicked volitional movement. Some differences may exist between time courses of BOLD intensity during TMS circuit activation and volitional circuit activation.     

诊断性经颅磁刺激研究进展

经颅磁刺激是一种无创性神经电生理学技术,经颅磁刺激运动诱发电位已广泛应用于运动皮质兴奋性与皮质延髓束、皮质脊髓束传导功能的评价。近年随着对磁刺激原理的深入了解和刺激线圈、刺激模式的不断多样化,经颅磁刺激在神经病学临床诊断中的应用不断拓展,逐渐形成更加科学和标准化的运动诱发电位操作流程。本文拟对诊断性经颅磁刺激常规刺激模式研究进展、特殊模式刺激方案,以及经颅磁刺激与脑电图、f MRI的联合应用进行综述。     

A lack of effect from transcranial magnetic stimulation (TMS) on the vagus nerve stimulator (VNS).

OBJECTIVE: The effects of transcranial magnetic stimulation (TMS) on vagus nerve stimulation (VNS) are unknown. Understanding these effects is important before exposing individuals with an implanted VNS to TMS, as could occur in epilepsy or depression TMS research. To explore this issue, the TMS-induced current in VNS leads and whether TMS has an effect on the VNS pulse generator was assessed. METHODS: Ex vivo measurement of current in VNS leads during single-pulse TMS and pulse generator function before, during, and after single-pulse TMS was assessed. RESULTS: At the highest intensity and with the TMS coil held approximately 5 mm from the VNS wires, a 200 nA, 1.0 ms current was induced by TMS. This translates to an induced charge density of 3.3 nC/cm2/phase. The function of the pulse generator was unaffected by single-pulse TMS, even when its case was directly stimulated by the coil. CONCLUSIONS: TMS-induced current in VNS electrodes was not only well outside of the range known to be injurious to peripheral nerve, but also below the activation threshold of nerve fibers. SIGNIFICANCE: Using single-pulse TMS in individuals with VNS should not result in nerve stimulation or damage. Furthermore, single-pulse TMS does not affect the VNS pulse generator's function.     

重复经颅磁刺激治疗慢性神经病理性疼痛

目的探讨重复经颅磁刺激（rTMS）对慢性神经病理性疼痛的疗效和安全性。方法回顾性分析4例慢性神经病理性疼痛病人的资料,其中丘脑痛3例,臂丛神经撕脱伤后疼痛1例,均经正规药物治疗效果欠佳,给予运动皮质10Hz的rTMS（1000次刺激）治疗,每个疗程5d,共3个疗程。分别于治疗前、每个疗程后以及全部疗程结束后1个月、6个月和1年采用视觉模拟疼痛评分（VAS）、汉密尔顿抑郁评分（HAMD）和汉密尔顿焦虑评分（HAMA）来评估疗效。结果全部疗程结束后,疗效满意3例,疗效差l例。疗效满意病人中,随访1年后复发2例。副作用为治疗期间头面部轻度疼痛1例。结论rTMS对部分慢性神经病理性疼痛安全有效．尤其是面部和肢体疼痛的病人。但其疗效不持久,可作为运动皮质电刺激的测试方法。     

Seizure incidence during single- and paired-pulse transcranial magnetic stimulation (TMS) in individuals with epilepsy

OBJECTIVE: We reviewed published data and our own data to determine a quantitative incidence of seizure in subjects with epilepsy undergoing single- and paired-pulse transcranial magnetic stimulation (spTMS and ppTMS) and to explore conditions that may increase this risk. METHODS: A PubMed literature search was performed, and articles from this search were reviewed. Subjects from our institution also were included. RESULTS: The crude risk of a TMS-associated seizure ranges from 0.0 to 2.8% for spTMS and 0.0-3.6% for ppTMS. Medically intractable epilepsy and lowering antiepileptic drugs were associated with increased incidence. There was significant center-to-center variability that could not be explained by differences in patient population or by differences in reported stimulation parameters. In all cases, seizures were similar to each subject's typical seizure and without long-term adverse outcome. In most cases, doubt was expressed in the original reports as to whether the seizures were induced by TMS or merely coincidental. CONCLUSIONS: The incidence of seizure in a subject with epilepsy during spTMS and ppTMS appears to be small and not associated with long-term adverse outcome. The incidence is higher under the specific conditions mentioned above. SIGNIFICANCE: These findings may enable researchers to more accurately inform subjects of seizure risk during TMS.     

Short-term reliability of transcranial magnetic stimulation motor maps in upper limb amputees

The aim of this study was to verify the short-term reliability of transcranial magnetic stimulation (TMS) parameters for a damaged stump muscle in upper-limb amputees (n = 6). The motor threshold, response latency and map center of gravity in the mediolateral plane showed good reliability, whereas the map volume measure was less stable. The stability of most TMS measures across time supports the use of TMS in studying cortical plasticity in amputees.     

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. © 2010 Movement Disorder Society     

Late EEG responses triggered by transcranial magnetic stimulation (TMS) in the evaluation of focal epilepsy

PURPOSE: To evaluate the use of EEG responses to transcranial magnetic stimulation (TMS-EEG responses) as a noninvasive tool for the diagnosis of focal epilepsy. METHODS: Fifteen patients and 15 healthy subjects were studied. TMS at an intensity set at resting corticomotor threshold were delivered at the standard EEG electrode positions. For each position, EEG responses to TMS were evaluated before and after averaging EEG recordings synchronized with the TMS pulse. RESULTS: Two types of TMS-EEG responses were seen: (A) early responses: consisting of a single slow wave seen after the TMS pulse; and (B) late TMS-EEG responses, which were subclassified into (b.1) delayed responses: waveforms resembling interictal epileptiform discharges induced by TMS; or (b.2) repetitive responses: onset of a new rhythym induced by TMS. Early responses were observed in patients and healthy subjects when stimulating at various sites and were considered normal responses to TMS. Late TMS-EEG responses were not seen in healthy subjects, whereas they were seen in 11 of the 15 epileptic patients. Late TMS-EEG responses occurred when stimulating the epileptogenic side in eight out of the nine patients who had lateralized late TMS-EEG responses. The combined use of late TMS-EEG responses and interictal scalp EEG would have suggested the diagnosis of focal epilepsy in all patients, despite the absence of late TMS-EEG responses in four patients and the presence of normal interictal scalp EEG in three. CONCLUSIONS: TMS-EEG responses can identify epileptogenic cortex and may substantially improve the diagnosis of focal epilepsy, particularly, if combined with standard EEG studies.     

Repetitive transcranial magnetic stimulation (rTMS) versus transcranial direct current stimulation (tDCS) in the management of patients with fibromyalgia: A randomized controlled trial

ObjectivesThe aim of this study was to compare the effects of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) on pain and quality of life in patients with fibromyalgia.MethodsThirty participants were randomized into two groups of 15 patients, to receive 3 sessions of either high-frequency (10 Hz) rTMS or 2 mA, 20 min anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex (DLPFC) over 1 week. Pain was assessed using a Visual Analog Scale (VAS) before treatment, immediately after treatment, 6 and 12 weeks later. Quality of life was evaluated using the Revised Fibromyalgia Impact Questionnaire (FIQR) and psychiatric symptoms were measured using the Depression Anxiety Stress Scale-21 Item (DASS-21) before treatment, and 6 and 12 weeks after treatment.ResultsFor the VAS there was a significant time-group interaction, showing that the behavior of two groups differed regarding changes of VAS in favor of the RTMS group (df = 1.73, F = 4.80, p = <0.016). Time-group interaction effect on DASS-21 and FIQR was not significant. 66.6% of patients in rTMS group and 26.6% of patients in tDCS group experienced at least a 30% reduction of VAS from baseline to last follow-up (p = 0.028).DiscussionWith the methodology used in this study, both rTMS and tDCS were safe modalities and three sessions of rTMS over DLPFC had greater and longer lasting analgesic effects compared to tDCS in patients with FM. However, considering the limitations of this study, further studies are needed to explore the most effective modality.     

Predominant activation of I1-waves from the leg motor area by transcranial magnetic stimulation

We performed transcranial magnetic stimulation (TMS) to elucidate the D- and I-wave components comprising the motor evoked potentials (MEPs) elicited from the leg motor area, especially at near-threshold intensity. Recordings were made from the tibialis anterior muscle using needle electrodes. A figure-of-eight coil was placed so as to induce current in the brain in eight different directions, starting from the posterior-to-anterior direction and rotating it in 45 degrees steps. The latencies were compared with those evoked by transcranial electrical stimulation (TES) and TMS using a double cone coil. Although the latencies of MEPs ranged from D to I3 waves, the most prominent component evoked by TMS at near-threshold intensity represented the I1 wave. With the double cone coil, the elicited peaks always represented I1 waves, and D waves were evoked only at very high stimulus intensities, suggesting a high effectiveness of this coil in inducing I1 waves. Using the figure-of-eight coil, current flowing anteriorly or toward the hemisphere contralateral to the recorded muscle was more effective in eliciting large responses than current flowing posteriorly or toward the ipsilateral hemisphere. The effective directions induced I1 waves with the lowest threshold, whereas the less effective directions elicited I1 and I2 waves with a similar frequency. Higher stimulus intensities resulted in concomitant activation of D through I3 waves with increasing amount of D waves, but still the predominance of I1 waves was apparent. The amount of I waves, especially of I1 waves, was greater than predicted by the hypothesis that TMS over the leg motor area activates the output cells directly, but rather suggests predominant transsynaptic activation. The results accord with those of recent human epidural recordings.     

Long-term follow-up study with repetitive transcranial magnetic stimulation (rTMS) in Parkinson's disease

Several studies have claimed the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in Parkinson's disease (PD). The rTMS therapy has to be repeated regularly to achieve a permanent effect but the side effects of long-term administration of low frequency rTMS are not known. Further, there is no information about its influence on the development of Parkinson's disease. Two different groups of patients with PD were compared in a retrospective study for 3 years. The first group (A) was treated with drugs, the second group (B) was treated with drugs + rTMS (1 Hz, 0.6 T, 100 stimuli per day for 7 days using a round coil). rTMS was repeated at least twice each year for 3 years. Symptoms of PD were assessed using the Graded Rating Scale. Although at the onset of the study group B patients had greater disease severity and were receiving higher doses of levodopa, this group (receiving rTMS) showed no deterioration in these parameters, whereas those in group A receiving drugs alone showed a marked deterioration. Hoehn–Yahr (H–Y) stages at the onset of the study and 3 years later were: group A: 1.93 ± 0.75, 3.03 ± 1.01; group B: 2.50 ± 0.83, 2.45 ± 0.62. The dose of levodopa (mg/day) was at the onset of trial and 3 years later was: group A: 124.4 ± 144.0, 555.5 ± 247.2; group B: 287.7 ± 217.1, 333.4 ± 181.0. The yearly increment in the scores was: group A: 1.308 ± 0.307 (P < 0.001), group B: 0.642 ± 0.389 (P < 0.1). Accordingly, this retrospective study using regularly repeated rTMS with 1 Hz for 7 days, at least twice yearly for 3 years, significantly slowed the development of Parkinson's disease. Unwanted side effects were not observed during the 3 years.     

Multi-locus transcranial magnetic stimulation system for electronically targeted brain stimulation

BackgroundTranscranial magnetic stimulation (TMS) allows non-invasive stimulation of the cortex. In multi-locus TMS (mTMS), the stimulating electric field (E-field) is controlled electronically without coil movement by adjusting currents in the coils of a transducer.ObjectiveTo develop an mTMS system that allows adjusting the location and orientation of the E-field maximum within a cortical region.MethodsWe designed and manufactured a planar 5-coil mTMS transducer to allow controlling the maximum of the induced E-field within a cortical region approximately 30 mm in diameter. We developed electronics with a design consisting of independently controlled H-bridge circuits to drive up to six TMS coils. To control the hardware, we programmed software that runs on a field-programmable gate array and a computer. To induce the desired E-field in the cortex, we developed an optimization method to calculate the currents needed in the coils. We characterized the mTMS system and conducted a proof-of-concept motor-mapping experiment on a healthy volunteer. In the motor mapping, we kept the transducer placement fixed while electronically shifting the E-field maximum on the precentral gyrus and measuring electromyography from the contralateral hand.ResultsThe transducer consists of an oval coil, two figure-of-eight coils, and two four-leaf-clover coils stacked on top of each other. The technical characterization indicated that the mTMS system performs as designed. The measured motor evoked potential amplitudes varied consistently as a function of the location of the E-field maximum.ConclusionThe developed mTMS system enables electronically targeted brain stimulation within a cortical region.     

Measuring latency distribution of transcallosal fibers using transcranial magnetic stimulation

BackgroundNeuroimaging technology is being developed to enable non-invasive mapping of the latency distribution of cortical projection pathways in white matter, and correlative clinical neurophysiological techniques would be valuable for mutual verification. Interhemispheric interaction through the corpus callosum can be measured with interhemispheric facilitation and inhibition using transcranial magnetic stimulation.ObjectiveTo develop a method for determining the latency distribution of the transcallosal fibers with transcranial magnetic stimulation.MethodsWe measured the precise time courses of interhemispheric facilitation and inhibition with a conditioning-test paired-pulse magnetic stimulation paradigm. The conditioning stimulus was applied to the right primary motor cortex and the test stimulus was applied to the left primary motor cortex. The interstimulus interval was set at 0.1 ms resolution. The proportions of transcallosal fibers with different conduction velocities were calculated by measuring the changes in magnitudes of interhemispheric facilitation and inhibition with interstimulus interval.ResultsBoth interhemispheric facilitation and inhibition increased with increment in interstimulus interval. The magnitude of interhemispheric facilitation was correlated with that of interhemispheric inhibition. The latency distribution of transcallosal fibers measured with interhemispheric facilitation was also correlated with that measured with interhemispheric inhibition.ConclusionsThe data can be interpreted as latency distribution of transcallosal fibers. Interhemispheric interaction measured with transcranial magnetic stimulation is a promising technique to determine the latency distribution of the transcallosal fibers. Similar techniques could be developed for other cortical pathways.     

Blood oxygenation changes resulting from suprathreshold transcranial magnetic stimulation

The hemodynamic response to low-intensity transcranial magnetic stimulation (TMS) has previously been demonstrated at motor cortex using near infrared spectroscopy (NIRS). To investigate the effect of TMS on oxy-hemoglobin (HbO) at prefrontal cortex, both subthreshold and suprathreshold TMS relative to resting motor threshold (rMT) were applied at typical intensities used in experimental settings. Although there was no significant change after 90% and 110% rMT TMS, there was a significant drop in HbO after 130% rMT TMS. This drop was maximal at approximately 8 seconds post-TMS. This study may have implications for determining appropriate TMS intensities when stimulating nonmotor areas.     

Navigated transcranial magnetic stimulation in amyotrophic lateral sclerosis

Introduction: Amyotrophic lateral sclerosis (ALS) is a set of disorders associated with preferential degeneration of both upper and lower motor neurons. Navigated transcranial magnetic stimulation (nTMS) is a tool used to perform noninvasive functional brain mapping. We aimed to assess function of upper motor neurons in ALS. Methods: nTMS was performed on 30 patients with ALS (mean age 54.4 ± 12.1 years) and 24 healthy volunteers (mean age 32.7 ± 13.3 years). Results: The resting motor threshold (MT) was significantly higher in ALS patients compared with controls (P < 0.001). The mean map areas were smaller in patients with ALS than in healthy individuals, although some patients with short disease duration had extended maps. Conclusions: Motor area maps serve as markers of upper motor neuron damage in ALS. Further research may elucidate the pathogenic mechanisms of the neurodegenerative process and aid in development of diagnostic and prognostic markers. Muscle Nerve 51 : 125–131, 2015     

Augmentative repetitive navigated transcranial magnetic stimulation (rTMS) in drug-resistant bipolar depression

Objectives:  The efficacy of transcranial magnetic stimulation (TMS) has been poorly investigated in bipolar depression. The present study aimed to assess the efficacy of low-frequency repetitive TMS (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) combined with brain navigation in a sample of bipolar depressed subjects.
Methods:  Eleven subjects with bipolar I or bipolar II disorder and major depressive episode who did not respond to previous pharmacological treatment were treated with three weeks of open-label rTMS at 1 Hz, 110% of motor threshold, 300 stimuli/day.
Results:  All subjects completed the trial showing a statistically significant improvement on the 21-item Hamilton Depression Rating Scale (HAM-D), Montgomery-Åsberg Depression Rating Scale, and Clinical Global Impression severity of illness scale (ANOVAs with repeated measures: F  =   22.36, p < 0.0001; F  =   12.66, p < 0.0001; and F  =   10.41, p < 0.0001, respectively). In addition, stimulation response, defined as an endpoint HAM-D score reduction of ≥50% compared to baseline, was achieved by 6 out of 11 subjects, 4 of whom were considered remitters (HAM-D endpoint score ≤ 8). Partial response (endpoint HAM-D score reduction between 25% and 50%) was achieved by 3/11 patients. No manic/hypomanic activation was detected during the treatment according to Young Mania Rating Scale scores (ANOVAs with repeated measures: F  =   0.62, p = 0.61). Side effects were slight and were limited to the first days of treatment.
Conclusions:  Augmentative low-frequency rTMS of the right DLPFC combined with brain navigation was effective and well tolerated in a small sample of drug-resistant bipolar depressive patients, even though the lack of a sham controlled group limits confidence in the results.