Repetitive transcranial magnetic stimulation in psychiatry

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and relatively painless tool that has been used to study various cognitive functions as well as to understand the brain–behavior relationship in normal individuals as well as in those with various neuropsychiatric disorders. It has also been used as a therapeutic tool in various neuropsychiatric disorders because of its ability to specifically modulate distinct brain areas. Studies have shown that repeated stimulation at low frequency produces long-lasting inhibition, which is called as long-term depression, whereas repeated high-frequency stimulation can produce excitation through long-term potentiation. This paper reviews the current status of rTMS as an investigative and therapeutic modality in various neuropsychiatric disorders. It has been used to study the cortical and subcortical functions, neural plasticity and brain mapping in normal individuals and in various neuropsychiatric disorders. rTMS has been most promising in the treatment of depression, with an overall milder adverse effect profile compared with electroconvulsive therapy. In other neuropsychiatric disorders such as schizophrenia, mania, epilepsy and substance abuse, it has been found to be useful, although further studies are required to establish therapeutic efficacy. It appears to be ineffective in the treatment of obsessive compulsive disorder. There is a paucity of studies of efficacy and safety of rTMS in pediatric and geriatric population. Although it appears safe, further research is required to optimize its efficacy and reduce the side-effects. Magnetic seizure therapy, which involves producing seizures akin to electroconvulsive therapy, appears to be of comparable efficacy in the treatment of depression with less cognitive adverse effects.     

Motor cortex stimulation for Parkinson's disease and dystonia: lessons from transcranial magnetic stimulation? A review of the literature

INTRODUCTION: Over the last few years, deep brain stimulation techniques, with targets such as the subthalamic nucleus or the pallidum, have bee found to be beneficial in the treatment of Parkinson's disease and dystonia. Conversely, therapeutic strategies of cortical stimulation have not yet been validated in these diseases, although they are known to be associated with various cortical dysfunctions. Transcranial magnetic stimulation (TMS) is a valuable tool for non-invasive study of the role played by the motor cortex in the pathophysiology of movement disorders, in particular by assessing various cortical excitability determinants using single or paired pulse paradigms. In addition, repetitive TMS (rTMS) trains can be used to study the effects of transient activity changes of a targeted cortical area. BACKGROUND: Studies with TMS revealed significant motor cortex excitability changes, particularly regarding intracortical inhibitory pathways, both in Parkinson's disease and in dystonia, and these changes can be distinguished owing to the resting state or to the phases of movement preparation or execution. However, more specific correlation between electrophysiological features and clinical symptoms remains to be established. In addition, the stimulation of various cortical targets by rTMS protocols applied at low or high frequencies have induced some clear clinical effects. PERSPECTIVES: The TMS effects are and will remain applied in movement disorders to better understand the role played by the motor cortex, to assess various types of treatment and appraise the therapeutic potential of cortical stimulation. CONCLUSION: TMS provides evidence for motor cortex dysfunction in Parkinson's disease or dystonia. Moreover, rTMS results have opened new perspectives for therapeutic strategies of implanted cortical stimulation. By these both aspects, TMS techniques show their usefulness in the assessment of movement disorders.     

A role for TMS/EEG in neuropsychiatric disorders

A direct and non-invasive measure of cortical excitability and effective connectivity is now made possible by the recent introduction of a new technique based on the combination of transcranial magnetic stimulation (TMS) and high-density electroencephalography (hd-EEG). This technique allows to directly and non invasively perturb any given cortical area and to simultaneously record, with good spatial and temporal resolution, the excitability and the short and long-range connectivity of the stimulated neurons. Alterations of these parameters of cortical circuits’ functioning have been suggested to underlie the most common neurologic and psychiatric conditions. This review focuses on the advantages of the TMS/hd-EEG technique and its contribution to the evaluation of cortical excitability, effective connectivity changes under physiological and pathological conditions. Moreover, it discusses the main findings of TMS/hd-EEG on cortical oscillatory properties, providing new insights into the neurophysiological underpinnings of neuropsychiatric disorders.     

Therapeutic application of repetitive transcranial magnetic stimulation: a review.

Transcranial magnetic stimulation (TMS), a non-invasive means of electrically stimulating neurons in the human cerebral cortex, is able to modify neuronal activity locally and at distant sites when delivered in series or trains of pulses. Data from stimulation of the motor cortex suggest that the type of effect on the excitability of the cortical network depends on the frequency of stimulation. These data, as well as results from studies in rodents, have been generalized across brain areas and species to provide rationales for using repetitive TMS (rTMS) to treat various brain disorders, most notably depression. Research into clinical applications for TMS remains active and has the potential to provide useful data, but, to date, the results of blinded, sham-controlled trials do not provide clear evidence of beneficial effects that replace or even match the effectiveness of conventional treatments in any disorder. In this review, we discuss the clinical and scientific bases for using rTMS as treatment, and review the results of trials in psychiatric and neurological disorders to date.     

Transcranial magnetic stimulation: review of accidental seizures

Transcranial magnetic stimulation (TMS) is a new technique that has been used for the treatment of neuropsychiatric disorders, specially depression. It uses a magnetic stimulator that generates a magnetic field that is applied over the patient's skull with a coil. Possible seizures may be induced accidentally by TMS. TMS is usually used with sub threshold stimuli and seizures may occur by chance, especially when over the safety parameters. This article reviews the eight cases of undesirable seizures occurred with rTMS The possible mechanisms of seizure induction and the patients profile with a higher risk of convulsion are also described.     

The value of repetitive transcranial magnetic stimulation (rTMS) for the treatment of anxiety disorders: an integrative review

Unlike for depression, only few studies are available today investigating the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) for anxiety disorders. This review aims to provide information on the current research approaches and main findings regarding the therapeutic use of rTMS in the context of various anxiety disorders. Although positive results have frequently been reported in both open and randomized controlled studies, our review of all identified studies indicates that at present no conclusive evidence of the efficacy of rTMS for the treatment for anxiety disorders is provided. Several treatment parameters have been used, making the interpretation of the results difficult. Moreover, sham-controlled research has often been unable to distinguish between response to rTMS and sham treatment. However, there is a limitation in the rTMS methods that likely impacts only the superficial cortical layers. It is not possible to directly stimulate more distant cortical areas, and also subcortical areas, relevant to the pathogenesis of anxiety disorders, though such effects in subcortical areas are thought to be indirect, via trans-synaptic connections. We thus recommend further studies to clearly determine the role of rTMS in the treatment of anxiety disorders. Key advances in combining TMS with neuroimaging technology may aid in such future developments.     

Transcranial Magnetic Stimulation in Neurology: What We Have Learned From Randomized Controlled Studies

Background. Initially developed to excite peripheral nerves, magnetic stimulation was quickly recognized as a valuable tool to noninvasively activate the cerebral cortex. The subsequent discovery that repetitive transcranial magnetic stimulation (rTMS) could have long‐lasting effects on cortical excitability spawned a broad interest in the use of this technique as a new therapeutic method in a variety of neuropsychiatric disorders. Although the current outcomes from initial trials include some conflicting results, initial evidence supports that rTMS might have a therapeutic value in different neurologic conditions. Methods. We reviewed the results of clinical trials of rTMS on four different disorders: stroke, Parkinson's disease, chronic refractory pain, and epilepsy. We reviewed randomized, controlled studies only in order to obtain the strongest evidence for the clinical effects of rTMS. Results. An extensive literature review revealed 32 articles that met our criteria. From these studies, we found evidence for the therapeutic efficacy of rTMS, particularly in the relief of chronic pain and motor neurorehabilitation in single hemisphere stroke patients. Repetitive TMS also seems to have a therapeutic effect on motor function in Parkinson's disease, but the evidence is somewhat confounded by the uncontrolled variability of multiple factors. Lastly, only two randomized, sham‐controlled studies have been performed for epilepsy; although evidence indicates rTMS may reduce seizure frequency in patients with neocortical foci, more research is needed to confirm these initial findings. Conclusions. There is mounting evidence for the efficacy of rTMS in the short‐term treatment of certain neurologic conditions. More long‐term research is needed in order to properly evaluate the effects of this method in a clinical setting.     

Preconditioning with transcranial direct current stimulation sensitizes the motor cortex to rapid-rate transcranial magnetic stimulation and controls the direction of after-effects.

BACKGROUND: Rapid-rate repetitive transcranial magnetic stimulation (rTMS) can produce a lasting increase in cortical excitability in healthy subjects or induce beneficial effects in patients with neuropsychiatric disorders; however, the conditioning effects of rTMS are often subtle and variable, limiting therapeutic applications. Here we show that magnitude and direction of after-effects induced by rapid-rate rTMS depend on the state of cortical excitability before stimulation and can be tuned by preconditioning with transcranial direct current stimulation (tDCS). METHODS: Ten healthy volunteers received a 20-sec train of 5-Hz rTMS given at an intensity of individual active motor threshold to the left primary motor hand area. This interventional protocol was preconditioned by 10 min of anodal, cathodal, or sham tDCS. We used single-pulse TMS to assess corticospinal excitability at rest before, between, and after the two interventions. RESULTS: The 5-Hz rTMS given after sham tDCS failed to produce any after-effect, whereas 5-Hz rTMS led to a marked shift in corticospinal excitability when given after effective tDCS. The direction of rTMS-induced plasticity critically depended on the polarity of tDCS conditioning. CONCLUSIONS: Preconditioning with tDCS enhances cortical plasticity induced by rapid-rate rTMS and can shape the direction of rTMS-induced after-effects.     

La stimulation magnétique transcrânienne répétée : vers un nouvel outil thérapeutique en psychiatrie

Transcranial magnetic stimulation (TMS) is a technique used for investigation of the tics, when repeatedly applied, has a therapeutic potential, notably in psychiatry. The physiological and neuroendocrine effects induced by repeated TMS treatment in an animal model are similar to those caused by antidepressants in man. In particular, TMS appears to modify the release of neuromediators (serotonin, dopamine) involved in depressive states. Because of these properties, repeated TMS has been proposed as a potential treatment for depression. Several randomized studies have now evaluated its effects in this regard and for the most part show statistically significant results, although the findings are sometimes modest at the clinical level. However, the therapeutic effects depend on various parameters which are generally not taken into account, such as cortical excitability and regional cerebral metabolism, Apart from depression, the trials focus on a limited number of disorders. In schizophrenia, the use of TMS has permitted abnormalities in cortical excitability to be demonstated and an improvement of the symptomatology, e.g. by suppressing the perception of auditory hallucinations. Parkinson?s disease, nervous twitch and Gilles de la Tourette syndome, obsessive-compulsive disorders and mania have also been the focus of promising albeit preliminary trials. Wider randomized studies should now assess the different parameters involved in the therapeutic effects, so that the treatment procedure can be optimized and the physiopathology of various neuropsychiatric disorders better understood.     

Enhancing plasticity through repeated rTMS sessions: The benefits of a night of sleep

Objective

Previous work has demonstrated that corticospinal facilitation from 20 Hz repetitive transcranial magnetic stimulation (rTMS) was greater during a second rTMS session 24 h after the first. We sought to determine whether such metaplasticity is dependent on a particular phase of the normal sleep–wake/circadian cycle.

Methods

Twenty healthy participants received two sessions of 20 Hz rTMS over the hand motor cortex (M1) spaced 12 h apart, either over-day or overnight.

Results

Baseline corticospinal excitability did not differ by group or session. The time-of-day of Session 1 did not influence the relative increase in excitability following rTMS. However, the increase in excitability from the second rTMS session was 2-fold greater in the overnight group.

Conclusions

When a night with sleep follows rTMS to M1, the capacity to induce subsequent plasticity in M1 is enhanced, suggesting sleep–wake and/or circadian-dependent modulation of processes of metaplasticity.

Significance

TMS treatment of neuropsychiatric disorders entails repeated sessions of rTMS. Our findings suggest that the timing of sessions relative to the sleep–wake/circadian cycle may be a critical factor in the cumulative effect of treatment. Future studies using this paradigm may provide mechanistic insights into human metaplasticity, leading to refined strategies to enhance non-invasive stimulation therapies.     

重复经颅磁刺激治疗药物难治性癫痫的临床研究进展

经颅磁刺激(TMS)可导致细胞膜去极化并激活神经元,能够短暂地兴奋或抑制特定脑区.重复TMS(rTMS)指具有不同频率或强度的重复脉冲刺激,其作用效果在刺激结束后依然持续,已经广泛用于治疗多种神经精神疾病.目前认为低频rTMS能够抑制癫痫活动从而导致局灶性癫痫发作频率降低,但多项rTMS治疗药物难治性癫痫的临床研究结果...     

Impairment of executive performance after transcranial magnetic modulation of the left dorsal frontal‐striatal circuit

The dorsal frontal‐striatal circuit is implicated in executive functions, such as planning. The Tower of London task, a planning task, in combination with off‐line low‐frequency repetitive transcranial magnetic stimulation (rTMS), was used to investigate whether interfering with dorsolateral prefrontal function would modulate executive performance, mimicking dorsal frontal‐striatal dysfunction as found in neuropsychiatric disorders. Eleven healthy controls (seven females; mean age 25.5 years) were entered in a cross‐over design: two single‐session treatments of low‐frequency (1 Hz) rTMS (vs. sham rTMS) for 20 min on the left dorsolateral prefrontal cortex (DLPFC). Directly following the off‐line rTMS treatment, the Tower of London task was performed during MRI measurements. The low‐frequency rTMS treatment impaired performance, but only when the subjects had not performed the task before: we found a TMS condition‐by‐order effect, such that real TMS treatment in the first session led to significantly more errors (P = 0.032), whereas this TMS effect was not present in subjects who received real TMS in the second session. At the neural level, rTMS resulted in decreased activation during the rTMS versus sham condition in prefrontal brain regions (i.e., premotor, dorsolateral prefrontal and anterior prefrontal cortices) and visuospatial brain regions (i.e., precuneus/cuneus and inferior parietal cortex). The results show that low‐frequency off‐line rTMS on the DLPFC resulted in decreased task‐related activations in the frontal and visuospatial regions during the performance of the Tower of London task, with a behavioral effect only when task experience is limited. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Transcranial magnetic stimulation: a new tool in the fight against depression

Since its introduction to the clinical realm in 1985, transcranial magnetic stimulation (TMS) has rapidly developed into a tool for exploring central nervous system function in both health and disease. The antidepressant effects of TMS were initially observed in 1993. Since then, a solid body of evidence has accumulated suggesting antidepressant effects for both slow TMS (sTMS) and repetitive TMS (rTMS). This review is divided into four parts. First, it addresses the basic concepts governing TMS, and then, second, it discusses the technical parameters involved in administering TMS. Knowledge of these parameters is necessary for understanding how TMS is administered, and how manipulation of the technique impacts on the results obtained. Third, we review the most relevant studies on the antidepressant effects of sTMS and rTMS published to date. Finally, we discuss cortical excitability and how the understanding of this basic neurophysiological function of cortical neurons can be used for monitoring the effects of TMS. In our discussion, we conclude that the time has arrived for TMS to be offered to depressed patients as a treatment.     

Safety aspects of chronic low-frequency transcranial magnetic stimulation based on localized proton magnetic resonance spectroscopy and histology of the rat brain

Because repetitive transcranial magnetic stimulation (rTMS) is capable of inducing lasting alterations of cortical excitability, it represents a promising therapeutic tool in several neuropsychiatric disorders. However, rTMS, especially when applied chronically, may cause harmful effects in the stimulated tissue. To study the safety of chronic rTMS we used a novel small stimulation coil, which was specially designed to treat rats, and investigated brain tissue using in vivo localized proton magnetic resonance spectroscopy (MRS) and post mortem histological analysis. Histology was based on a modified stereology method in combination with immunohistochemistry applying antibodies against OX-6, OX-42, ED, and GFAP to detect any microglial and/or astrocytic activation 48 h after the last TMS session. Conscious rats were treated with a daily suprathreshold rTMS regimen of 1000 stimuli applied on 5 consecutive days at a frequency of 1 Hz. In comparison with control animals receiving magnetic stimulation over the lumbar spine, quantitative evaluations of cerebral metabolite concentrations by proton MRS revealed no significant alterations of N-acetyl-aspartate, creatine and phosphocreatine, choline-containing compounds, myo-inositol, glucose and lactate after chronic rTMS. Similarly to the in vivo results, post mortem histology revealed no changes in microglial and astrocytic activation after rTMS. In conclusion, these data provide support for the safety of chronic rTMS. However, they do not exclude acute changes on neurotransmitters systems or other physiologic responses during or directly after the rTMS treatment.     

Electroconvulsive therapy in the treatment of neuropsychiatric conditions and transcranial magnetic stimulation as a pathophysiological probe in neuropsychiatry

It is a challenging task to review transcranial magnetic stimulation (TMS) studies in neuropsychiatric disorders alongside assessments of longstanding clinical applications of ECT as an empirical treatment. The task is challenging because TMS was developed as a probe of neural mechanisms, whereas, in marked contrast, ECT has been a clinical technique from its inception. Since the onset of modern psychopharmacology, the understanding of the potential applications of ECT to neuropsychiatric disorders is generally restricted to case reports of patients with intractable disease that have had at least a partial response to ECT. Studies of the possible efficacy of TMS in neuropsychiatric conditions have a significant advantage over ECT as the treatments are associated with less morbidity. The only serious known complication in TMS is a risk of seizures that may increase in patients with neuropsychiatric conditions such as course brain disease. Only cortical structures are themselves accessible to TMS using current technology. Present TMS techniques, however, seem capable of affecting activity in deeper brain structures that are functionally linked to cortical brain regions. TMS permits novel explorations of relationships between regional brain activity and symptoms of a number of neuropsychiatric disorders, as well as in research relating activity in functionally related brain regions to modulation of cognition and affective states in healthy individuals. This is particularly true at present because TMS and powerful neuroimaging and neuropsychological tools are all making rapid advances simultaneously.     

French guidelines on the use of repetitive transcranial magnetic stimulation (rTMS): safety and therapeutic indications

During the past decade, a large amount of work on transcranial magnetic stimulation (TMS) has been performed, including the development of new paradigms of stimulation, the integration of imaging data, and the coupling of TMS techniques with electroencephalography or neuroimaging. These accumulating data being difficult to synthesize, several French scientific societies commissioned a group of experts to conduct a comprehensive review of the literature on TMS. This text contains all the consensual findings of the expert group on the mechanisms of action, safety rules and indications of TMS, including repetitive TMS (rTMS). TMS sessions have been conducted in thousands of healthy subjects or patients with various neurological or psychiatric diseases, allowing a better assessment of risks associated with this technique. The number of reported side effects is extremely low, the most serious complication being the occurrence of seizures. In most reported seizures, the stimulation parameters did not follow the previously published recommendations (Wassermann, 1998) [430] and rTMS was associated to medication that could lower the seizure threshold. Recommendations on the safe use of TMS / rTMS were recently updated (Rossi et al., 2009) [348], establishing new limits for stimulation parameters and fixing the contraindications. The recommendations we propose regarding safety are largely based on this previous report with some modifications. By contrast, the issue of therapeutic indications of rTMS has never been addressed before, the present work being the first attempt of a synthesis and expert consensus on this topic. The use of TMS/rTMS is discussed in the context of chronic pain, movement disorders, stroke, epilepsy, tinnitus and psychiatric disorders. There is already a sufficient level of evidence of published data to retain a therapeutic indication of rTMS in clinical practice (grade A) in chronic neuropathic pain, major depressive episodes, and auditory hallucinations. The number of therapeutic indications of rTMS is expected to increase in coming years, in parallel with the optimisation of stimulation parameters.     

Applications of transcranial magnetic stimulation (TMS) in child and adolescent psychiatry

Transcranial magnetic stimulation (TMS) is emerging as a new treatment and neurophysiological research tool for psychiatric disorders. Recent publications suggest that this modality will also serve as a treatment and research tool in child and adolescent psychiatry. Current reports on therapeutic trials of repetitive transcranial magnetic stimulation (rTMS) in adolescents have primarily focused on depression. However, other pilot work involves the treatment of attention-deficit/hyperactivity disorder (ADHD), autism and schizophrenia. Neurophysiological studies typically utilize single and paired-pulse TMS paradigms which index cortical excitability and inhibition. Initial studies have focused on ADHD, autism, and depression. General knowledge regarding TMS among child and adolescent psychiatrists is lacking. The aim of this review is to provide an overview of TMS in the context of child and adolescent psychiatry, discuss recent therapeutic and neurophysiological studies, and examine relevant ethical considerations.     

Transcranial magnetic simulation in the treatment of migraine

Transcranial magnetic stimulation (TMS) is a diagnostic and therapeutic modality that is being developed as both an acute and preventive treatment for migraine. TMS delivers a fluctuating magnetic field from the scalp surface to induce current in the subjacent cortex. Magnetic pulses are delivered one at a time in single-pulse TMS (sTMS) or as a train of pulses in repetitive TMS (rTMS). For most of its 30-year history, TMS has been delivered in clinical and research settings using large tabletop devices. Based on the theory that sTMS may disrupt cortical spreading depression, sTMS has been studied and shown to be effective as an acute treatment for migraine with aura. Subsequent work in animal models confirms that sTMS disrupts cortical spreading depression. To make outpatient self-treatment possible, a portable device has been developed for acute treatment of migraine with aura. Based on the theory that rTMS alters brain excitability and neurotransmitter activity, rTMS has been studied as a preventive migraine treatment. A small body of evidence suggests that rTMS may have a role, but further studies are needed. In this review, we summarize the data on TMS as a treatment of migraine, and we suggest directions for future research.