Repetitive transcranial magnetic stimulation as a neuropsychiatric tool: present status and future potential

Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising therapeutic intervention in the treatment of affective disorders. The differences in the type of electrical stimulation required for therapeutic efficacy by rTMS and electroconvulsive therapy (ECT) are discussed. In contrast to ECT, rTMS would not appear to require the generation of a major motor seizure to achieve therapeutic efficacy. Accordingly, it carries the potentially important clinical advantages of not requiring anesthesia and of avoiding side effects such as transient memory loss. Preclinical studies on long-term potentiation (LTP) and long-term depression (LTD) in hippocampal and amygdala slices, as well as clinical data from neuroimaging studies, have provided encouraging clues for potential frequency-dependent effects of rTMS. Preliminary evidence from position emission tomography (PET) scans suggests that higher frequency (20 Hz) stimulation may increase brain glucose metabolism in a transsynaptic fashion, whereas lower frequency (1 Hz) stimulation may decrease it. Therefore, the ability of rTMS to control the frequency as well as the location of stimulation, in addition to its other advantages, has opened up new possibilities for clinical explorations and treatments of neuropsychiatric conditions.     

Repetitive transcranial magnetic stimulation as treatment for anxiety disorders

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive and generally well-tolerated method of focally stimulating brain regions. It has been shown to be efficacious in the treatment for depression, but only to a limited degree. It has also been investigated for the treatment of some anxiety disorders, particularly obsessive-compulsive disorder, post-traumatic stress disorder and panic disorder. While anecdotal reports and open studies have suggested a therapeutic role for rTMS in anxiety disorders, controlled studies, which have varied greatly in terms of rTMS administration, have not shown it to be superior to placebo. Furthermore, reports in animal models of anxiety have not been consistent. Therefore, to date, there is no convincing evidence for the clinical role of rTMS in anxiety disorders. Further research is needed, drawing on advances in our understanding of pathological neurocircuitry in anxiety disorders and the mechanisms of action by which rTMS may alter that neurocircuitry. With advances in neuroimaging technology, this understanding is likely to be more accessible than it has been in the past.     

Connectome-guided transcranial magnetic stimulation treatment in depression

European Child & Adolescent Psychiatry -     

Electroconvulsive therapy and repetitive transcranial magnetic stimulation in children and adolescents: a review and report of two cases of epilepsia partialis continua

Brain stimulation for the treatment of psychiatric disorders has received increasing attention over the past decade. The introduction of experimental means to stimulate the brain noninvasively with magnetic fields not only has raised interest in these novel means of modulating brain activity but also has refocused attention on a mainstay in the treatment of severe major depression and other disorders (electroconvulsive therapy). This article reviews the current state of knowledge concerning the use electroconvulsive therapy, repetitive transcranial magnetic stimulation, and magnetic seizure therapy in children and adolescents. Two cases of medically intractable epilepsia partialis continua are presented to add to the limited literature on the use of repetitive transcranial magnetic stimulation in children and adolescents and illustrate the concept of using functional neuroimaging results to target the application of a focal intervention in an attempt to dampen hyperactive regions of the cortex.     

Prefrontal repetitive transcranial magnetic stimulation as add on treatment in depression

A growing number of studies report antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) in patients with major depression. The hypothesis that high frequency (20 Hz) rTMS (HF-rTMS) may speed up and strengthen the therapeutic response to sertraline in MD was tested. Twenty eight patients who had not yet received medication for the present depressive episode (n=12) or had failed a single trial of an antidepressant medication (n=16) were started on sertraline and randomised to receive either real of sham HF-rTMS. HF-rTMS was applied to the left dorsolateral prefrontal area in daily sessions (30 trains of 2 s, 20-40 s intertrain interval, at 90% motor threshold) on 10 consecutive working days. The results suggest that in this patient population, HF-rTMS does not add efficacy over the use of standard antidepressant medication.     

Repetitive transcranial magnetic stimulation as an add-on therapy in the treatment of mania: a case series of eight patients

The aim of this study is to assess the efficacy of repetitive transcranial magnetic stimulation (rTMS) as an add-on therapy in the treatment of manic bipolar patients. Eight patients were enrolled in an open trial. They received fast rTMS (five trains of 15 s, 80% of the motor threshold, 10 Hz) over the right dorsolateral prefrontal cortex (DLPFC). They were evaluated using the Mania Assessment Scale (MAS) and the Clinical Global Impression (CGI) at baseline and at day 14. All patients were taking medication during the treatment trial. There was a significant improvement of manic symptoms at the end of the trial. No side effects were reported. The results show a significant improvement of mania when patients are treated with fast rTMS over the right DLPFC. However, these results have to be interpreted with caution since they derive from an open case series and all the subjects were taking psychotropic medication during rTMS treatment. Double-blind controlled studies with a sham comparison condition should be conducted to investigate the efficiency of this treatment in manic bipolar disorders.     

A controlled study of repetitive transcranial magnetic stimulation as a treatment of depression in the elderly

Rapid transcranial magnetic stimulation (rTMS) applied to the left dorsal lateral frontal cortex has been shown to produce antidepressant effects. Older depressed patients, however, in one study showed a lower response rate than younger patients. The current study examined treatment response in 20 depressed, treatment-refractory patients (mean age 60.7 +/- 9.8 years) given five sessions of rTMS at 20 Hz for 2 seconds over 20 trains at 80% of motor threshold or identical placebo stimulation, after patients had been withdrawn from their antidepressants. There were no significant differences in Hamilton Depression Scale scores either before or after treatment at 7 days' follow-up. There were three responders to active treatment and three to sham treatment and responders had significantly greater frontal lobe volume than nonresponders (p = .03). These findings suggest that the stimulation parameters used in this study were probably insufficient to produce treatment response and that frontal atrophy may interfere with the effectiveness of rTMS.     

Contribution of transcranial magnetic stimulation in restless legs syndrome: pathophysiological insights and therapeutical approaches

Transcranial magnetic stimulation (TMS) may offer a reliable means to characterize significant pathophysiologic and neurochemical aspects of restless legs syndrome (RLS). Namely, TMS has revealed specific patterns of changes in cortical excitability and plasticity, in particular dysfunctional inhibitory mechanisms and sensorimotor integration, which are thought to be part of the pathophysiological mechanisms of RLS rather than reflect a non-specific consequence of sleep architecture alteration.If delivered repetitively, TMS is able to transiently modulate the neural activity of the stimulated and connected areas. Some studies have begun to therapeutically use repetitive TMS (rTMS) to improve sensory and motor disturbances in RLS. High-frequency rTMS applied over the primary motor cortex or the supplementary motor cortex, as well as low-frequency rTMS over the primary somatosensory cortex, seem to have transient beneficial effects. However, further studies with larger patient samples, repeated sessions, an optimized rTMS setup, and clinical follow-up are needed in order to corroborate preliminary results.Thus, we performed a systematic search of all the studies that have used TMS and rTMS techniques in patients with RLS.     

Functional neuroimaging and the treatment of aphasia: speech therapy and repetitive transcranial magnetic stimulation

Functional imaging has provided new evidence of the neurobiological impact of the treatment of aphasia, including speech therapy, through the alteration of the activated language neural network. In such a way, speech therapy has proved its impact. The role of each hemisphere is still very unclear. Some of the authors link the left-lateralisation of activations to the therapeutic improvement of language and the right-activated network to a maladaptative strategy, whereas others consider the latter as a useful compensatory network for speech disorders. Repetitive trans-cranial magnetic stimulation (rTMS), first used to determine cortical activity, is now used to directly interfere with cerebral activity. In the years to come, rTMS should be developed as an adjuvant therapy for aphasia.     

Repetitive transcranial magnetic stimulation as treatment of poststroke depression: a preliminary study.

BACKGROUND: Depression has a significant impact on poststroke recovery and mortality. There are a proportion of patients with poststroke depression (PSD) who do not respond to antidepressants. Repetitive Transcranial Magnetic Stimulation (rTMS) might be a safe and effective alternative in these refractory cases. METHODS: We conducted a randomized, parallel, double-blind study of active versus sham left prefrontal rTMS in patients with refractory PSD. After discontinuing antidepressants, patients were randomly assigned to receive 10 sessions of active (10 Hz, 110% of the motor threshold, 20 trains of 5 seconds duration) or sham left prefrontal rTMS. Efficacy measures included HAM-D scores, response and remission rates. Patients completed a neuropsychological battery at baseline and after completing the protocol. RESULTS: When compared with sham stimulation, 10 sessions of active rTMS of the left dorsolateral prefrontal cortex were associated with a significant reduction of depressive symptoms. This reduction was not influenced by patient's age, type or location of stroke, volume of left frontal leukoaraiosis or by the distance of the stimulating coil to the prefrontal cortex. However, there was a significant positive correlation between the percentage of reduction of Ham-D scores and frontal gray and white matter volumes. There were no significant changes in cognitive functioning between the active and the sham stimulation groups. In addition, there were few and mild adverse effects that were equally distributed among groups. CONCLUSIONS: Taken together, these preliminary findings suggest that rTMS may be an effective and safe treatment alternative for patients with refractory depression and stroke.     

Usefulness of repetitive transcranial magnetic stimulation as a maintenance treatment in patients with major depression

Objectives: To investigate the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS), venlafaxine or a combination of both treatments as a maintenance treatment in patients with treatment-resistant depression (TRD).

Methods: In a three-arm open-label study, 66 patients, including 45 remitters, who responded to rTMS (n?=?25), venlafaxine (n?=?22), or a combination of both treatments (n?=?19) continued to receive the treatment that led to a response as a maintenance treatment over 12 months. Maintenance rTMS was administered twice per week for 1 month, once per week for 2 months, and once every 2 weeks for 9 months. Venlafaxine was maintained at the dose that induced a clinical response (150 or 225?mg/day).

Results: After the 12-month follow-up, the rates of remitters (HDRS?2?=^?1.25; P?=?.3). The rates of patients who not relapsed (HDRS?2?=^?0.33; P?=?.8): 40.0% in the rTMS group, 45.1% in the venlafaxine group and 36.9% in the combination group.

Conclusions: The three maintenance approaches exhibited similar efficacies in relapse prevention and the maintenance of remission in patients with TRD.     

高频重复经颅磁刺激联合文拉法辛治疗抑郁症的早期疗效

目的:探讨高频重复经颅磁刺激(20HzrTMS)联合文拉法辛治疗抑郁症的早期疗效与安全性。方法:将40例抑郁症患者随机分为研究组(n=20例)和对照组(n=20例)。研究组给予20HzrTMS联合文拉法辛治疗,对照组单用文拉法辛联合假rTMS治疗。观察6周。两组分别于治疗前和治疗2、4、6周采用汉密尔顿抑郁量表(HAMD)评定疗效;采用治疗中出现的症状量表(TESS)评定不良反应。结果:两组治疗后HAMD评分均有显著下降(P<0.05);以研究组在治疗2、4周时降分显著(P<0.05)。两组间部分不良反应发生率存在统计学意义(P<0.05)。结论:高频重复经颅磁刺激联合文拉法辛治疗抑郁症早期疗效优于单一用药,不良反应发生率较低。     

Research with transcranial magnetic stimulation in the treatment of aphasia

Repetitive transcranial magnetic stimulation (rTMS) has been used to improve language behavior, including naming, in stroke patients with chronic, nonfluent aphasia. Part 1 of this article reviews functional imaging studies related to language recovery in aphasia. Part 2 reviews the rationale for using rTMS to treat nonfluent aphasia (based on functional imaging) and presents our current rTMS protocol. We present language results from our rTMS studies as well as imaging results from overt naming functional MRI scans obtained before and after a series of rTMS treatments. Part 3 presents results from a pilot study in which rTMS treatments were followed immediately by constraint-induced language therapy. Part 4 reviews our diffusion tensor imaging study examining the possible connectivity of the arcuate fasciculus to different parts of Broca’s area (pars triangularis, pars opercularis) and to the ventral premotor cortex. The potential role of mirror neurons in the right pars opercularis and ventral premotor cortex in aphasia recovery is discussed.     

Deep transcranial magnetic stimulation as a treatment for psychiatric disorders: A comprehensive review

Deep transcranial magnetic stimulation (TMS) is a technique of neuromodulation and neurostimulation based on the principle of electromagnetic induction of an electric field in the brain. The coil (H-coil) used in deep TMS is able to modulate cortical excitability up to a maximum depth of 6 cm and is therefore able not only to modulate the activity of the cerebral cortex but also the activity of deeper neural circuits. Deep TMS is largely used for the treatment of drug-resistant major depressive disorder (MDD) and is being tested to treat a very wide range of neurological, psychiatric and medical conditions. The aim of this review is to illustrate the biophysical principles of deep TMS, to explain the pathophysiological basis for its utilization in each psychiatric disorder (major depression, autism, bipolar depression, auditory hallucinations, negative symptoms of schizophrenia), to summarize the results presented thus far in the international scientific literature regarding the use of deep TMS in psychiatry, its side effects and its effects on cognitive functions.     

Electroconvulsive treatment and new techniques of electrical and magnetic stimulation in treatment of depression--question of placebo and warranting of blind conditions, as well as other methodological problems

Testing new therapeutic methods requires the confirmation so their efficacy, application and their safety. So that the specific and subjective factors do not influence the evaluation, it is necessary to assure suitable conditions--enclosing carrying out of the investigations in control to placebo and providing blinding conditions. In the case of pharmacological investigations it is possible and necessary to fulfill the most raw investigation criteria. Examinations of physical methods meet essential obstacles by granting of these criteria. The paper describes these impediments and methodological difficulties which accompany investigations on the following techniques: electroconvulsive treatment ECT, nerve vagus stimulation NVS, magnetic seizure therapy MST/magnetoconvulsive therapy MCT, the deep brain stimulation DBS and trancranial direct current stimulation tDCS.