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.     

Modulatory effects of 1 Hz rTMS over the cerebellum on motor cortex excitability

Clinical observations and data from animal experiments point to a physiological facilitatory influence of the deep cerebellar structures on the motor system through the cerebello-thalamo-cortical pathways. The aim of the present study was to explore the long-term effects of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) over the cerebellum on short intracortical inhibition (SICI) and facilitation (ICF) of the motor cortex in normal subjects. Eight healthy subjects (mean age 26.9 ± 3.1) underwent 1 Hz frequency rTMS delivered on the right cerebellar hemisphere. Before and after cerebellar rTMS, SICI and ICF were assessed in the motor cortex contralateral to the stimulated cerebellar hemisphere by means of a paired pulse paradigm with a conditioning subthreshold stimulus set to 80% of the motor threshold (MT) followed by a testing stimulus at 120% of MT intensity. Five different interstimulus intervals (ISIs) were used to assess SICI (2 and 4 ms) and ICF (7, 10 and 15 ms). Amplitude of the responses was expressed as the percentage of motor evoked potential (MEP) to test stimulus alone. Results showed a significant decrease of ICF at 10 ms ISI that persisted up to 20 min after cerebellar rTMS. This was the only significant modulatory effect of cerebellar stimulation on intracortical motor excitability A suppressive effect of the low-frequency TMS on Purkinje cells could be supposed, even if, the lack of effects on other facilitatory ISIs, stands for more complex modulatory effects of rTMS over cerebellum. The study is a further demonstration that rTMS over the cerebellum induces a long-lasting modulatory effect on the excitability of the interconnected motor area.     

Hemispheric cerebellar rTMS to treat drug-resistant epilepsy: case reports

Electrical stimulation of the cerebellar cortex by implanted electrodes has been shown to ameliorate refractory epilepsy. We investigated the potential therapeutic role of high-frequency cerebellar rTMS in patients affected by refractory epilepsy due to single or multiple foci. Six patients, three with single and three with multiple epileptic foci, underwent 20 rTMS sessions. Each session was given daily, excluding weekends, and consisted of two trains of 50 stimuli (5 Hz frequency and 90% motor threshold intensity), separated by 50s interval. rTMS was delivered through a focal coil (2 cm below and lateral to the inion) bilaterally in patients with multiple foci (two trains for hemisphere: 100 stimuli each side) and contralaterally to the epileptic focus in the others. Seizure frequency was monitored four weeks before stimulation (pre-rTMS), during the four-week treatment (rTMS) and four weeks after the treatment (post-rTMS). The rTMS over the cerebellar cortex was associated with a significant decrease of rTMS versus pre-rTMS seizure frequency both in patients with single and multiple epileptic foci. However, during the post-rTMS period seizure frequency was back to the pre-rTMS frequency. Although the results are still preliminary, they encourage further studies on larger series of patients. In particular, this rTMS approach, as compared with others, might be more useful in patients with multiple epileptic foci.     

Multimodal transcranial magnetic stimulation: using concurrent neuroimaging to reveal the neural network dynamics of noninvasive brain stimulation

Since its introduction in the 1980s, Transcranial Magnetic Stimulation (TMS) has proven to be a versatile method to non-invasively study human brain function by reversibly altering ongoing neural processing. In addition, TMS has been explored as a therapeutic intervention in a number of neurological and neuropsychiatric conditions. However, our understanding of TMS-induced changes in neural activity patterns is still rather limited, particularly when it comes to changes in neural network dynamics beyond the cortical site directly targeted by TMS. In order to monitor both its local and remote neurophysiological effects, TMS has been combined with complementary neuroimaging methods that allow additional insights into how observed TMS effects at the behavioral level can be interpreted by taking into account the full scale of its impact throughout the brain. The current review provides a comprehensive overview of the existing multimodal TMS literature, covering studies in which TMS was combined with one of the three main neuroimaging modalities, namely Electroencephalography, Positron Emission Tomography, and functional Magnetic Resonance Imaging. Besides constituting a reflection of the status quo in this exciting multidisciplinary research field, this review additionally reveals both convergent and divergent observations across modalities that await corroboration or resolution, thereby further guiding ongoing basic research and providing useful constraints to optimize future clinical applications.     

靳三针联合重复经颅磁治疗心脾两虚型失眠的临床研究

[目的]观察靳三针联合重复经颅磁(repetitive transcranial magnetic stimulation, rTMS)治疗心脾两虚型失眠的临床疗效。[方法]将符合纳入标准的60例失眠患者,依照随机数字表法随机分为A、B两组。B组予重复经颅磁治疗,A组在B组基础上增加针刺治疗,一天一次,以6天为一个疗程,共治疗4个疗程,治疗前后进行匹兹堡睡眠质量指数(Pittsburgh sleep quality index,PSQI)评分。[结果]组内比较:与治疗前对比,两组治疗后PSQI评分均有显著下降,且差异均具有统计学意义(P0.01);组间比较:①两组治疗后PSQI评分对比,A组小于B组,差异具有统计学意义(P0.05);②两组患者治疗后总有效率比较,A组高于B组,且差异具有统计学意义(P0.05)。[结论]靳三针联合重复经颅磁刺激能明显改善心脾两虚型失眠患者的睡眠质量,且疗效优于单用重复经颅磁治疗。     

低频rTMS联合奥拉西坦注射液治疗脑梗死恢复期轻度认知功能障碍患者的临床研究

目的探讨低频重复经颅磁刺激(rTMS)联合奥拉西坦注射液治疗脑梗死恢复期轻度认知功能障碍患者的临床效果。方法选取2016年2月至2018年1月我院收治的脑梗死恢复期轻度认知功能障碍患者83例,随机分为实验组(n=42)和对照组(n=41)。对照组采用奥拉西坦注射液治疗,实验组在对照组基础上采用低频rTMS治疗。观察两组的临床效果及治疗前后认知功能与日常生活能力。结果实验组的治疗总有效率为95.24%,明显高于对照组的73.17%(P<0.05)。治疗前,两组的MoCA、BI评分比较无统计学差异(P>0.05);治疗后,实验组的MoCA、BI评分均明显高于对照组(P<0.05)。结论采用低频rTMS联合奥拉西坦注射液治疗脑梗死恢复期轻度认知功能障碍患者效果显著,可有效改善患者的认知功能,提高其日常生活能力,值得临床推广。     

Seeing touch in the somatosensory cortex: a TMS study of the visual perception of touch

Recent studies suggest the existence of a visuo-tactile mirror system, comprising the primary (SI) and secondary (SII) somatosensory cortices, which matches observed touch with felt touch. Here, repetitive transcranial magnetic stimulation (rTMS) was used to determine whether SI or SII play a functional role in the visual processing of tactile events. Healthy participants performed a visual discrimination task with tactile stimuli (a finger touching a hand) and a control task (a finger moving without touching). During both tasks, rTMS was applied over either SI or SII, and to the occipital cortex. rTMS over SI selectively reduced subject performance for interpreting whether a contralateral visual tactile stimulus contains a tactile event, whereas SII stimulation impaired visual processing regardless of the tactile component. These findings provide evidence for a multimodal sensory-motor system with mirror properties, where somatic and visual properties of action converge. SI, a cortical area traditionally viewed as modality-specific, is selectively implicated in the visual processing of touch. These results are in line with the existence of a sensory mirror system mediating the embodied simulation concept.     

Contribution of the primary motor cortex to motor imagery: a subthreshold TMS study

Motor imagery (MI) mostly activates the same brain regions as movement execution (ME) including the primary motor cortex (Brodmann area 4, BA4). However, whether BA4 is functionally relevant for MI remains controversial. The finding that MI tasks are impaired by BA4 virtual lesions induced by transcranial magnetic stimulation (TMS) supports this view, though previous studies do not permit to exclude that BA4 is also involved in other processes such as hand recognition. Additionally, previous works largely underestimated the possible negative consequences of TMS-induced muscle twitches on MI task performance. Here we investigated the role of BA4 in MI by interfering with the function of the left or right BA4 in healthy subjects performing a MI task in which they had to make laterality judgements on rotated hand drawings. We used a subthreshold repetitive TMS protocol and monitored electromyographic activity to exclude undesirable effects of hand muscle twitches. We found that BA4 virtual lesions selectively increased reaction times in laterality judgments on hand drawings, leaving unaffected a task of equal difficulty, involving judgments on letters. Interestingly, the effects of virtual lesions of left and right BA4 on MI task performance were the same irrespective of the laterality (left/right) of hand drawings. A second experiment allowed us to rule out the possibility that BA4 lesions affect visual or semantic processing of hand drawings. Altogether, these results indicate that BA4 contribution to MI tasks is specifically related to the mental simulation process and further emphasize the functional coupling between ME and MI.     

Neurobiological mechanisms of repetitive transcranial magnetic stimulation on the underlying neurocircuitry in unipolar depression

For nearly two decades now, transcranial magnetic stimulation (TMS) has been available as a noninvasive clinical tool to treat patients suffering from major depression. In this period, a bulk of animal and human studies examined TMS parameters to improve clinical outcome. However, the neurobiological mechanisms underlying mood changes remain an important focus of research. In addition to having an effect on neuroendocrinological processes, neurotransmitter systems, and neurotrophic factors, TMS may not only affect the stimulated cortical regions, but also those connected to them. Therefore, we will review current human data on possible neurobiological mechanisms of repetitive (r) TMS implicated in the deregulated neurocircuitry present in unipolar depression. Furthermore, as the rTMS application can be considered as a "top-down" neuronal intervention, we will focus on the neuronal pathways linked with the stimulated area and we will present an integrative model of action.     

Early glycinergic axon contact with the Mauthner neuron during zebrafish development

One important aspect of empathy is a “resonance mechanism”, which includes emotional cue detection, facial mimicry (measured by electromyography, EMG) and a specific cortical response. This study explored the convergence of these three measures of affective empathy. The twenty students who took part in the study were required to empathise with the situation by entering into the other person's situation. The four emotions portrayed were anger, fear, happiness, and neutral, and the subjects were instructed to make a two-alternative response (emotion or no emotion) to each emotion. A repeated transcranial magnetic stimulation was used to produce a temporary inhibition of the medial prefrontal cortex (MPFC). The results support the hypothesis that there is a direct relationship between emotional cue recognition, EMG-measured facial response and prefrontal activity. First, both facial expression detection and autonomic mimicry in reaction to emotional faces were systematically modulated in response to inhibition of the MPFC. Second, the MPFC was implicated in facial cue detection and the subsequent autonomic response because an impaired performance on both measures was observed when this brain area was inhibited. Third, this effect increased when negative-valenced stimuli (angry and fearful faces) were presented to the subjects. These results revealed a significant effect of the MPFC on both cue detection and facial mimicry that was distinctly related to different types of emotions.