A Randomised Controlled Trial of Neuronavigated Repetitive Transcranial Magnetic Stimulation (rTMS) in Anorexia Nervosa

Background

Anorexia nervosa (AN) is associated with morbid fear of fatness, extreme food restriction and altered self-regulation. Neuroimaging data implicate fronto-striatal circuitry, including the dorsolateral prefrontal cortex (DLPFC).

Methods

In this double-blind parallel group study, we investigated the effects of one session of sham-controlled high-frequency repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC (l-DLPFC) in 60 individuals with AN. A food exposure task was administered before and after the procedure to elicit AN-related symptoms.

Outcomes

The primary outcome measure was ‘core AN symptoms’, a variable which combined several subjective AN-related experiences. The effects of rTMS on other measures of psychopathology (e.g. mood), temporal discounting (TD; intertemporal choice behaviour) and on salivary cortisol concentrations were also investigated. Safety, tolerability and acceptability were assessed.

Results

Fourty-nine participants completed the study. Whilst there were no interaction effects of rTMS on core AN symptoms, there was a trend for group differences (p = 0.056): after controlling for pre-rTMS scores, individuals who received real rTMS had reduced symptoms post-rTMS and at 24-hour follow-up, relative to those who received sham stimulation. Other psychopathology was not altered differentially following real/sham rTMS. In relation to TD, there was an interaction trend (p = 0.060): real versus sham rTMS resulted in reduced rates of TD (more reflective choice behaviour). Salivary cortisol concentrations were unchanged by stimulation. rTMS was safe, well–tolerated and was considered an acceptable intervention.

Conclusions

This study provides modest evidence that rTMS to the l-DLPFC transiently reduces core symptoms of AN and encourages prudent decision making. Importantly, individuals with AN considered rTMS to be a viable treatment option. These findings require replication in multiple-session studies to evaluate therapeutic efficacy.

Trial Registration

www.Controlled-Trials.com ISRCTN22851337     

Task Type Affects Location of Language-Positive Cortical Regions by Repetitive Navigated Transcranial Magnetic Stimulation Mapping

Objectives

Recent repetitive TMS (rTMS) mapping protocols for language mapping revealed deficits of this method, mainly in posterior brain regions. Therefore this study analyzed the impact of different language tasks on the localization of language-positive brain regions and compared their effectiveness, especially with regard to posterior brain regions.

Methods

Nineteen healthy, right-handed subjects performed object naming, pseudoword reading, verb generation, and action naming during rTMS language mapping of the left hemisphere. Synchronically, 5 Hz/10 pulses were applied with a 0 ms delay

Results

The object naming task evoked the highest error rate (14%), followed by verb generation (13%) and action naming (11%). The latter revealed more errors in posterior than in anterior areas. Pseudoword reading barely generated errors, except for phonological paraphasias.

Conclusions

In general, among the evaluated language tasks, object naming is the most discriminative task to detect language-positive regions via rTMS. However, other tasks might be used for more specific questions.     

Event-related Potential Study of Novelty Processing Abnormalities in Autism

To better understand visual processing abnormalities in autism we studied the attention orienting related frontal event potentials (ERP) and the sustained attention related centro-parietal ERPs in a three stimulus oddball experiment. The three stimulus oddball paradigm was aimed to test the hypothesis that individuals with autism abnormally orient their attention to novel distracters as compared to controls. A dense-array 128 channel EGI electroencephalographic (EEG) system was used on 11 high-functioning children and young adults with autism spectrum disorder (ASD) and 11 age-matched, typically developing control subjects. Patients with ASD showed slower reaction times but did not differ in response accuracy. At the anterior (frontal) topography the ASD group showed significantly higher amplitudes and longer latencies of early ERP components (e.g., P100, N100) to novel distracter stimuli in both hemispheres. The ASD group also showed prolonged latencies of late ERP components (e.g., P2a, N200, P3a) to novel distracter stimuli in both hemispheres. However, differences were more profound in the right hemisphere for both early and late ERP components. Our results indicate augmented and prolonged early frontal potentials and a delayed P3a component to novel stimuli, which suggest low selectivity in pre-processing and later-stage under-activation of integrative regions in the prefrontal cortices. Also, at the posterior (centro-parietal) topography the ASD group showed significantly prolonged N100 latencies and reduced amplitudes of the N2b component to target stimuli. In addition, the latency of the P3b component was prolonged to novel distracters in the ASD group. In general, the autistic group showed prolonged latencies to novel stimuli especially in the right hemisphere. These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli. We propose the potential application of ERP evaluations in a novelty task as outcome measurements in the biobehavioral treatment (e.g., EEG biofeedback, TMS) of autism.     

The Effects of Different Repetitive Transcranial Magnetic Stimulation (rTMS) Protocols on Cortical Gene Expression in a Rat Model of Cerebral Ischemic-Reperfusion Injury

Although repetitive Transcranial Magnetic Stimulation (rTMS) in treatment of stroke in humans has been explored over the past decade the data remain controversial in terms of optimal stimulation parameters and the mechanisms of rTMS long-term effects. This study aimed to explore the potential of different rTMS protocols to induce changes in gene expression in rat cortices after acute ischemic-reperfusion brain injury. The stroke was induced by middle cerebral artery occlusion (MCAO) with subsequent reperfusion. Changes in the expression of 96 genes were examined using low-density expression arrays after MCAO alone and after MCAO combined with 1Hz, 5Hz, continuous (cTBS) and intermittent (iTBS) theta-burst rTMS. rTMS over the lesioned hemisphere was given for two weeks (with a 2-day pause) in a single daily session and a total of 2400 pulses. MCAO alone induced significant upregulation in the expression of 44 genes and downregulation in 10. Two weeks of iTBS induced significant increase in the expression of 52 genes. There were no downregulated genes. 1Hz and 5Hz had no significant effects on gene expression, while cTBS effects were negligible. Upregulated genes included those involved in angiogenesis, inflammation, injury response and cellular repair, structural remodeling, neuroprotection, neurotransmission and neuronal plasticity. The results show that long-term rTMS in acute ischemic-reperfusion brain injury induces complex changes in gene expression that span multiple pathways, which generally promote the recovery. They also demonstrate that induced changes primarily depend on the rTMS frequency (1Hz and 5Hz vs. iTBS) and pattern (cTBS vs. iTBS). The results further underlines the premise that one of the benefits of rTMS application in stroke may be to prime the brain, enhancing its potential to cope with the injury and to rewire. This could further augment its potential to favorably respond to rehabilitation, and to restore some of the loss functions.     

Improved Discrimination of Visual Stimuli Following Repetitive Transcranial Magnetic Stimulation

Background

Repetitive transcranial magnetic stimulation (rTMS) at certain frequencies increases thresholds for motor-evoked potentials and phosphenes following stimulation of cortex. Consequently rTMS is often assumed to introduce a “virtual lesion” in stimulated brain regions, with correspondingly diminished behavioral performance.

Methodology/Principal Findings

Here we investigated the effects of rTMS to visual cortex on subjects'' ability to perform visual psychophysical tasks. Contrary to expectations of a visual deficit, we find that rTMS often improves the discrimination of visual features. For coarse orientation tasks, discrimination of a static stimulus improved consistently following theta-burst stimulation of the occipital lobe. Using a reaction-time task, we found that these improvements occurred throughout the visual field and lasted beyond one hour post-rTMS. Low-frequency (1 Hz) stimulation yielded similar improvements. In contrast, we did not find consistent effects of rTMS on performance in a fine orientation discrimination task.

Conclusions/Significance

Overall our results suggest that rTMS generally improves or has no effect on visual acuity, with the nature of the effect depending on the type of stimulation and the task. We interpret our results in the context of an ideal-observer model of visual perception.     

低频重复经颅磁刺激联合艾司西酞普兰对广泛性焦虑障碍患者生活质量及事件相关电位P300的影响

摘要 目的：观察低频重复经颅磁刺激（rTMS）联合艾司西酞普兰对广泛性焦虑障碍（GAD）患者生活质量及事件相关电位P300的影响。方法：采用随机数字表法,将2019年2月~2021年1月期间我院收治的120例GAD患者分为对照组（艾司西酞普兰治疗）和研究组（对照组的基础上接受低频rTMS治疗）,各为60例。观察并对比两组疗效和不良反应,记录两组生活质量及事件相关电位P300的变化。结果：研究组的临床总有效率高于对照组（P<0.05）。研究组治疗2个月后P300潜伏期短于对照组,P300波幅长于对照组（P<0.05）。研究组治疗2个月后疼痛、生理职能、精神健康、生理功能、躯体精力、情感职能、社会功能、总体健康各维度评分高于对照组（P<0.05）。两组治疗2个月后汉密尔顿焦虑量表（HAMA）评分较治疗前下降,且研究组低于对照组（P<0.05）。两组不良反应发生率对比无统计学差异（P>0.05）。结论：低频rTMS联合艾司西酞普兰治疗GAD患者,可有效改善其焦虑症状,提高生活质量,促进认知功能恢复,具有显著的临床疗效。     

A Neuronal Network Model for Simulating the Effects of Repetitive Transcranial Magnetic Stimulation on Local Field Potential Power Spectra

Repetitive transcranial magnetic stimulation (rTMS) holds promise as a non-invasive therapy for the treatment of neurological disorders such as depression, schizophrenia, tinnitus, and epilepsy. Complex interdependencies between stimulus duration, frequency and intensity obscure the exact effects of rTMS stimulation on neural activity in the cortex, making evaluation of and comparison between rTMS studies difficult. To explain the influence of rTMS on neural activity (e.g. in the motor cortex), we use a neuronal network model. The results demonstrate that the model adequately explains experimentally observed short term effects of rTMS on the band power in common frequency bands used in electroencephalography (EEG). We show that the equivalent local field potential (eLFP) band power depends on stimulation intensity rather than on stimulation frequency. Additionally, our model resolves contradictions in experiments.     

Efficacy of Repetitive Transcranial Magnetic Stimulation in the Treatment of Patients with Chronic Primary Insomnia

This study assessed the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of patients with chronic primary insomnia. Hundred and twenty patients with chronic primary insomnia were randomly assigned to three study groups (n = 40 per group): rTMS, medication, or psychotherapy treatment (both latter as controls). The treatments proceeded for 2 weeks, after which treatment efficacies were assessed in each study group based on changes in polysomnography parameters, Pittsburgh sleep quality index, and indices of HPA and HPT axes (serum cortisol, adrenocorticotropic hormone, highly sensitive thyrotropin, free T3, and free T4). Further, the relapse and recurrence rates within 3 months after respective treatments were also measured. rTMS treatment significantly better (p < 0.05) improved stage III sleep and REM sleep cycle compared with both control groups. Further, rTMS treatment group was more advantageous in improving the indices of HPA and HPT axes (p < 0.05 vs. both control groups). In addition, the relapse and recurrence rates were also the lowest in rTMS treatment group. In conclusion, rTMS treatment is more advantageous than both medication and psychotherapy treatments in improving the sleep architecture. Further, rTMS significantly decreases the body awakening level and provides a better long-term treatment effect.     

Ringing Decay of Gamma Oscillations and Transcranial Magnetic Stimulation Therapy in Autism Spectrum Disorder

Applied Psychophysiology and Biofeedback - Research suggest that in autism spectrum disorder (ASD) a disturbance in the coordinated interactions of neurons within local networks gives rise to...     

重复经颅磁刺激对脑卒中后患者神经功能缺损的改善

目的:探讨重复经颅磁刺激在脑卒中康复的应用及效果.方法:选择2010年9月至2012年9月在我院神经内科收治的58例脑卒中患者分为两组,即A组和B组,A组患者给予常规药物治疗和康复训练,B组患者在上述治疗的基础上加用低频重复经颅磁刺激治疗,比较两组患者美国国立卫生院神经功能缺损评分情况、日常生活活动(ADL)评分和不良反应发生情况.结果:治疗后,随着时间的推移,两组患者美国国立卫生院神经功能缺损评分得分逐渐下降(P＜0.05).B组患者2周后和6周后两个时点美国国立卫生院神经功能缺损评分得分明显低于A组患者的,差异有显著性(P＜0.05),而随着时间的推移,两组患者日常生活活动(ADL)评分得分逐渐上升(P＜0.05).B组患者2周后和6周后两个时点日常生活活动(ADL)评分得分明显高于A组患者的,差异有显著性(P＜0.05).两组患者在不良反应发生方面差异无显著性(P＞0.05).结论:低频重复经颅磁刺激治疗脑卒中单侧肢体功能障碍患者临床疗效确切,安全可靠,不良反应少.     

Repetitive Transcranial Magnetic Stimulation Applications Normalized Prefrontal Dysfunctions and Cognitive-Related Metabolic Profiling in Aged Mice

Chronic high-frequency repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique that has recently received increasing interests as a therapeutic procedure for neurodegenerative diseases. To identify the metabolism mechanism underlying the improving effects of rTMS, we observed that high frequency (25Hz) rTMS for 14 days could reverse the decline of the performance of the passive avoidance task in aged mice. We further investigated the metabolite profiles in the prefrontal cortex (PFC) in those mice and found that rTMS could also reverse the metabolic abnormalities of gamma-aminobutyric acid, N-acetyl aspartic, and cholesterol levels to the degree similar to the young mice. These data suggested that the rTMS could ameliorate the age-related cognitive impairment and improving the metabolic profiles in PFC, and potentially can be used to improve cognitive decline in the elderly.     

Utilizing Repetitive Transcranial Magnetic Stimulation to Improve Language Function in Stroke Patients with Chronic Non-fluent Aphasia

Transcranial magnetic stimulation (TMS) has been shown to significantly improve language function in patients with non-fluent aphasia¹. In this experiment, we demonstrate the administration of low-frequency repetitive TMS (rTMS) to an optimal stimulation site in the right hemisphere in patients with chronic non-fluent aphasia. A battery of standardized language measures is administered in order to assess baseline performance. Patients are subsequently randomized to either receive real rTMS or initial sham stimulation. Patients in the real stimulation undergo a site-finding phase, comprised of a series of six rTMS sessions administered over five days; stimulation is delivered to a different site in the right frontal lobe during each of these sessions. Each site-finding session consists of 600 pulses of 1 Hz rTMS, preceded and followed by a picture-naming task. By comparing the degree of transient change in naming ability elicited by stimulation of candidate sites, we are able to locate the area of optimal response for each individual patient. We then administer rTMS to this site during the treatment phase. During treatment, patients undergo a total of ten days of stimulation over the span of two weeks; each session is comprised of 20 min of 1 Hz rTMS delivered at 90% resting motor threshold. Stimulation is paired with an fMRI-naming task on the first and last days of treatment. After the treatment phase is complete, the language battery obtained at baseline is repeated two and six months following stimulation in order to identify rTMS-induced changes in performance. The fMRI-naming task is also repeated two and six months following treatment. Patients who are randomized to the sham arm of the study undergo sham site-finding, sham treatment, fMRI-naming studies, and repeat language testing two months after completing sham treatment. Sham patients then cross over into the real stimulation arm, completing real site-finding, real treatment, fMRI, and two- and six-month post-stimulation language testing.     

低频重复经颅磁刺激联合Bobath疗法对脑卒中偏瘫患者神经功能、运动功能及平衡能力的影响

摘要 目的：观察Bobath疗法联合低频重复经颅磁刺激对脑卒中偏瘫患者运动功能、神经功能、平衡能力的影响。方法：研究对象为我院2020年05月-2022年05月期间收治的脑卒中偏瘫患者148例。按照随机数字表法分为对照组（Bobath疗法,74例）和研究组（低频重复经颅磁刺激联合Bobath疗法,74例）。观察两组平衡能力[Berg平衡量表（BBS）]、神经功能[美国国立卫生研究院卒中量表（NIHSS）]、日常生活自理能力[改良Barthel指数（mBI）]、运动功能[Fugl-Meyer上肢运动功能评定量表（FMA-UE）、Fugl-Meyer下肢运动功能评定量表（FMA-LE）]、凝血功能[凝血酶原时间（PT）、纤维蛋白原（FIB）、D- 二聚体（D-D）、活化部分凝血活酶时间（APTT）]的变化情况。结果：两组治疗20 d后NIHSS评分下降, mBI评分升高,且研究组变化程度大于对照组（P<0.05）。两组治疗20 d后FMA-UE、FMA-LE评分升高,且研究组高于对照组（P<0.05）。两组治疗20 d后BBS评分升高,且研究组高于对照组（P<0.05）。两组治疗20 d后FIB、APTT、D-D、PT均下降,且研究组低于对照组（P<0.05）。结论：低频重复经颅磁刺激联合Bobath疗法用于脑卒中偏瘫患者,可改善其凝血功能,恢复神经功能,进而改善运动功能,提高其日常生活活动能力。     

The Effect of 10 Hz Repetitive Transcranial Magnetic Stimulation of Posterior Parietal Cortex on Visual Attention

Repetitive transcranial magnetic stimulation (rTMS) of the posterior parietal cortex (PPC) at frequencies lower than 5 Hz transiently inhibits the stimulated area. In healthy participants, such a protocol can induce a transient attentional bias to the visual hemifield ipsilateral to the stimulated hemisphere. This bias might be due to a relatively less active stimulated hemisphere and a relatively more active unstimulated hemisphere. In a previous study, Jin and Hilgetag (2008) tried to switch the attention bias from the hemifield ipsilateral to the hemifield contralateral to the stimulated hemisphere by applying high frequency rTMS. High frequency rTMS has been shown to excite, rather than inhibit, the stimulated brain area. However, the bias to the ipsilateral hemifield was still present. The participants’ performance decreased when stimuli were presented in the hemifield contralateral to the stimulation site. In the present study we tested if this unexpected result was related to the fact that participants were passively resting during stimulation rather than performing a task. Using a fully crossed factorial design, we compared the effects of high frequency rTMS applied during a visual detection task and high frequency rTMS during passive rest on the subsequent offline performance in the same detection task. Our results were mixed. After sham stimulation, performance was better after rest than after task. After active 10 Hz rTMS, participants’ performance was overall better after task than after rest. However, this effect did not reach statistical significance. The comparison of performance after rTMS with task and performance after sham stimulation with task showed that 10 Hz stimulation significantly improved performance in the whole visual field. Thus, although we found a trend to better performance after rTMS with task than after rTMS during rest, we could not reject the hypothesis that high frequency rTMS with task and high frequency rTMS during rest equally affect performance.     

奥氮平联合重复经颅磁刺激或改良电休克治疗精神分裂症的疗效分析

目的:比较抗精神病药物奥氮平联合复经颅磁刺激(rTMS)或改良电休克(MECT)治疗精神分裂症的疗效。方法:将84例精神分裂症患者随机分为rTMS组(42例)与MECT组(42例),两组分别在奥氮平的基础上联合MECT或rTMS进行治疗。在治疗2、4、8周末后,采用阳性症状和阴性症状量表PANSS、治疗时出现症状量表TESS评估临床治疗效果及不良反应,同时采用修订韦氏记忆量表(WMS-RC)和威斯康星卡片分类测验(WCST)评定认知功能。结果:治疗后,两组总有效率比较无统计学差异(P0.05)。两组治疗后PANSS总分、阳性症状、阴性症状和一般病理分值均显著低于治疗前(P0.05,P0.01),但组间比较无统计学差异(P0.05)。两组TESS评分及不良反应的发生情况比较无统计学差异(P0.05)。与治疗前相比,两组患者治疗后认知功能均显著改善(P0.05,P0.01),且rTMS联合组在改善患者记忆功能、执行能力方面效果优于MTCT组(P0.05)。结论:奥氮平联合MECT或rTMS对精神分裂症状的疗效相当,但联合rTMS可更显著改善患者的认知功能。     

重复经颅磁刺激对卒中后抑郁的治疗效果及机制

卒中后抑郁（post-stroke depression,PSD）是并发于脑血管病的一种情感障碍疾病,发病率高,预后差。重复经颅磁刺激（repetitive transcranial magnetic stimulation,r TMS）是通过磁场变化在大脑中产生感应电流来刺激皮层的非创伤性脑刺激技术,是临床上治疗PSD的一种重要非药物治疗方法,可以显著改善PSD患者的抑郁症状。但目前rTMS的作用机制不明确。本文总结了PSD治疗中有效的rTMS刺激方案,并结合PSD的单胺类神经递质相关致病假说及PSD的临床治疗手段,探索了rTMS通过对单胺类神经递质的调控参与PSD治疗的可能机制。rTMS刺激诱导的皮层单胺类递质释放增加、葡萄糖代谢上升、皮层兴奋性增加,提高了单胺类神经递质和脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）水平,进而引发前额叶抑制功能上升、与下游脑区连接改变、脑网络功能的调整,可能是rTMS治疗PSD的重要机制之一。     

Repetitive Transcranial Magnetic Stimulation in Cervical Dystonia: Effect of Site and Repetition in a Randomized Pilot Trial

Dystonia is characterized by abnormal posturing due to sustained muscle contraction, which leads to pain and significant disability. New therapeutic targets are needed in this disorder. The objective of this randomized, sham-controlled, blinded exploratory study is to identify a specific motor system target for non-invasive neuromodulation and to evaluate this target in terms of safety and tolerability in the cervical dystonia (CD) population. Eight CD subjects were given 15-minute sessions of low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (MC), dorsal premotor cortex (dPM), supplementary motor area (SMA), anterior cingulate cortex (ACC) and a sham condition with each session separated by at least two days. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score was rated in a blinded fashion immediately pre- and post-intervention. Secondary outcomes included physiology and tolerability ratings. The mean change in TWSTRS severity score by site was 0.25 ± 1.7 (ACC), -2.9 ± 3.4 (dPM), -3.0 ± 4.8 (MC), -0.5 ± 1.1 (SHAM), and -1.5 ± 3.2 (SMA) with negative numbers indicating improvement in symptom control. TWSTRS scores decreased from Session 1 (15.1 ± 5.1) to Session 5 (11.0 ± 7.6). The treatment was tolerable and safe. Physiology data were acquired on 6 of 8 subjects and showed no change over time. These results suggest rTMS can modulate CD symptoms. Both dPM and MC are areas to be targeted in further rTMS studies. The improvement in TWSTRS scores over time with multiple rTMS sessions deserves further evaluation.

Trial Registration

ClinicalTrials.gov NCT01859247     

经颅磁刺激和经颅直流电刺激在调控大脑共情功能中的应用

共情可以帮助人们建立和谐的人际关系，更好地适应现实社会，是一种重要的社会认知功能。已有研究表明，诸多神经和精神类疾病的发生发展和复发与共情缺陷有关。非侵入性脑刺激技术（经颅磁刺激和经颅直流电刺激）可以通过调节大脑皮层兴奋性来调控个体的共情水平，缓解共情缺陷症状。针对健康群体使用该技术的现有证据显示：内侧前额叶、初级运动皮层、额下回、背外侧前额叶和颞顶交界处的活动有助于提升个体的认知共情水平，其中双侧背外侧前额叶的活动还有助于下调个体的情感共情水平，而右侧颞顶交界处的活动则可以增强自我表征从而支持个体在共情时进行自我和他人的区分。少数针对共情缺陷群体使用该技术的临床证据提示，增强左侧背外侧前额叶和内侧前额叶的活动可以分别提升精神疾病和神经退行性疾病患者的认知共情水平。未来的研究应探讨在统一的行为测量范式下针对不同刺激参数和刺激位点进行共情干预研究，通过融合其他神经生理技术进一步考察非侵入性脑刺激技术改善共情功能的作用机制，并考虑个体差异性对大脑共情功能干预效果的影响。     

Effects of Low Frequency Prefrontal Repetitive Transcranial Magnetic Stimulation on the N2 Amplitude in a GoNogo Task

During the last decade, repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex has become established as a treatment for various mental diseases. The rational of prefrontal stimulation has been adapted from the mode of action known from rTMS using motor-evoked potentials though little is known about the precise effect of rTMS at prefrontal sites. The objective of the current study is to investigate the inhibitory effect of prefrontal 1 Hz rTMS by stimulating the generators of event-related potentials (ERP) which are located in the prefrontal cortex. Thus, 1 Hz rTMS was applied offline over the left dorsolateral prefrontal cortex (DLPFC) and the medial prefrontal cortex (MPFC) in 18 healthy subjects who subsequently underwent a GoNogo task. Both active conditions were compared to sham rTMS within a randomized and counterbalanced cross-over design in one day. ERPs were recorded during task performance and the N2 and the P3 were analysed. After 1 Hz rTMS of the left DLPFC (but not of the MPFC), an inhibitory effect on the N2 amplitude was observed, which was related to inhibitory control. In contrast, after 1 Hz rTMS of the MPFC (but not at the left DLPFC) a trend towards an increased P3 amplitude was found. There was no significant modulation of latencies and behavioural data. The results argue in favour of an inhibitory effect of 1 Hz rTMS on N2 amplitudes in a GoNogo task. Our findings suggest that rTMS may mildly modulate prefrontally generated ERP immediately after stimulation, even where behavioural effects are not measurable. Thus, combined rTMS-ERP approaches need to be further established in order to serve as paradigms in experimental neuroscience and clinical research.     

A Pilot Study of EEG Source Analysis Based Repetitive Transcranial Magnetic Stimulation for the Treatment of Tinnitus

Objective

Repetitive Transcranial Magnetic Stimulation (rTMS) is a novel therapeutic tool to induce a suppression of tinnitus. However, the optimal target sites are unknown. We aimed to determine whether low-frequency rTMS induced lasting suppression of tinnitus by decreasing neural activity in the cortex, navigated by high-density electroencephalogram (EEG) source analysis, and the utility of EEG for targeting treatment.

Methods

In this controlled three-armed trial, seven normal hearing patients with tonal tinnitus received a 10-day course of 1-Hz rTMS to the cortex, navigated by high-density EEG source analysis, to the left temporoparietal cortex region, and to the left temporoparietal with sham stimulation. The Tinnitus handicap inventory (THI) and a visual analog scale (VAS) were used to assess tinnitus severity and loudness. Measurements were taken before, and immediately, 2 weeks, and 4 weeks after the end of the interventions.

Results

Low-frequency rTMS decreased tinnitus significantly after active, but not sham, treatment. Responders in the EEG source analysis-based rTMS group, 71.4% (5/7) patients, experienced a significant reduction in tinnitus loudness, as evidenced by VAS scores. The target site of neuronal generators most consistently associated with a positive response was the frontal lobe in the right hemisphere, sourced using high-density EEG equipment, in the tinnitus patients. After left temporoparietal rTMS stimulation, 42.8% (3/7) patients experienced a decrease in tinnitus loudness.

Conclusions

Active EEG source analysis based rTMS resulted in significant suppression in tinnitus loudness, showing the superiority of neuronavigation-guided coil positioning in dealing with tinnitus. Non-auditory areas should be considered in the pathophysiology of tinnitus. This knowledge in turn can contribute to investigate the pathophysiology of tinnitus.