Transcranial magnetic stimulation in neurorehabilitation.

In neurorehabilitation, transcranial magnetic stimulation (TMS) offers information regarding prognosis and pathophysiology and could also be useful for therapeutic purposes. Numerous studies have indicated that, after stroke, the absence of motor evoked potentials is associated with a poor motor recovery. In contrast, MEPs obtained in the paretic muscle with low stimulus intensities suggest a good restitution of motor function. TMS studies have shown that the location of a brain lesion determines motor cortex excitability changes: Patients with central somatosensory lesions show a disinhibition in the ipsilesional motor cortex. Lesions in the territory of the superior cerebellar artery are associated with a loss of motor cortex excitability. Stroke patients participating in a Constraint-induced movement therapy show an enlargement of the motor output area in the affected hemisphere after therapy. This enhancement of motor excitability is associated with an improvement of motor function. Some evidence is emerging that the application of low frequency repetitive TMS over the non-lesioned hemisphere improves neglect phenomena by down-regulation of the excitability of the non-lesioned hemisphere.

Temporoparietal transcranial magnetic stimulation for auditory hallucinations: safety, efficacy and moderators in a fifty patient sample.

BACKGROUND: Auditory hallucinations are often resistant to treatment and can produce significant distress and behavioral difficulties. A preliminary report based on 24 patients with schizophrenia or schizoaffective disorder indicated greater improvement in auditory hallucinations following 1-hertz left temporoparietal repetitive transcranial magnetic stimulation (rTMS) compared to sham stimulation. Data from the full 50-subject sample incorporating 26 new patients are now presented to more comprehensively assess safety/tolerability, efficacy and moderators of this intervention. METHODS: Right-handed patients experiencing auditory hallucinations at least 5 times per day were randomly allocated to receive either rTMS or sham stimulation. A total of 132 minutes of rTMS was administered over 9 days at 90% motor threshold using a double-masked, sham-controlled, parallel design. RESULTS: Hallucination Change Score was more improved for rTMS relative to sham stimulation (p = .008) as was the Clinical Global Impressions Scale (p = .0004). Hallucination frequency was significantly decreased during rTMS relative to sham stimulation (p = .0014) and was a moderator of rTMS effects (p = .008). There was no evidence of neurocognitive impairment associated with rTMS. CONCLUSIONS: Left temporoparietal 1-hertz rTMS warrants further study as an intervention for auditory hallucinations. Data suggest that this intervention selectively alters neurobiological factors determining frequency of these hallucinations.

Effect of transcranial magnetic stimulation on voluntary activation in patients with quadriceps weakness.

Joint disease causes weakness and wasting of adjacent muscles, in part because of inability to fully activate these muscles voluntarily. Previous findings suggest that transcranial magnetic stimulation (TMS) paired with muscle contractions enhances maximal voluntary contraction force (MVC) in healthy subjects by improving voluntary activation (VA). The aim of the present study was to evaluate whether such an effect is also present in subjects suffering from diminished muscle force due to decreased VA. Three single TMS over resting motor threshold were applied in 10 patients with a mean age of 62 years after total-knee arthroplasty either during MVC or during muscle relaxation (control experiment) in a blinded randomized crossover study. MVC and VA were determined using a twitch-interpolation technique at 1, 15, 30, and 60 min after stimulation. There was a significant effect of TMS on MVC if applied in synchrony with muscle contraction, and this persisted for at least 60 min beyond stimulation. In patients suffering from joint disease, TMS might make physiotherapy more effective.

[A new method for the treatment of depression: repetitive transcranial magnetic stimulation]. / Ein neues Behandlungsverfahren der Depression: Die repetitive transkranielle Magnetstimulation (rTMS).

Recent data suggest that repetitive transcranial magnetic stimulation (rTMS) is effective in treating depressive symptoms to a lesser extent compared with classical electroconvulsive therapy. However, rTMS represents an economical and well tolerable procedure in relation to the expenditure of electroconvulsive therapy with anaesthesia. Usually, rTMS is applicated as an add-on-therapy accompanying psychopharmacological treatment. So far, it has predominantly been used for patients with long-standing and so called treatment-refractory symptoms. However, even in the early phase of a depressive episode rTMS would be possibly more effective. In many cases, the standard procedure-application of up to 10 rTMS-sessions will not be enough to produce therapeutic benefit. Therefore rTMS series including up to 20 sessions are recommended. Long-term studies are needed to clarify the role of rTMS for relapse prevention and to determine the optimal frequency and duration of rTMS in such an indication. Although numerous results of newer studies suggest a moderate antidepressive effect of rTMS, its application in daily clinical routine practice cannot be recommended yet. Larger, accurate designed and controlled studies, especially involving patients of old age, are needed to evaluate the true tolerability and effectiveness of rTMS as a new treatment option for depressive symptoms.

Transcranial magnetic stimulation for central pain.

Transcranial magnetic stimulation recently has emerged as a therapeutic tool in neurology and psychiatry, with contradictory results. Central pain, a major chronic pain syndrome affecting millions of people worldwide, has been the focus of a few studies. Although transcranial magnetic stimulation has no role in the chronic management of such pain, it has potential as a screening procedure for the much more effective extradural cortical stimulation, a minimally invasive neurosurgical procedure that has emerged as the technique of choice in treating these patients.

[Vagus nerve stimulation, repetitive transcranial magnetic stimulation, and electroconvulsive therapy in the treatment of depressive disorders]. / Antidepressive Stimulationsverfahren Vagusnervstimulation, repetitive transkranielle Magnetstimulation und Elektrokonvulsionstherapie zur Behandlung depressiver Störungen.

Affective disorders, especially major depression, are the most common psychiatric disorders. Although well treatable, a number of patients do not or do not sufficiently respond to antidepressant pharmacotherapy. Therefore there is a need for safe and efficient alternative therapeutic strategies. Neurostimulatory therapies such as electroconvulsive therapy, repetitive transcranial magnetic stimulation, and vagus nerve stimulation belong to these alternatives. In this article we review their mechanisms of action and summarize efficacy and adverse effects.

Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: a double-blind placebo-controlled study.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a noninvasive method to stimulate the cortex, and the treatment of depression is one of its potential therapeutic applications. Three recent meta analyses strongly suggest its benefits in the treatment of depression. The present study investigates whether repetitive TMS (rTMS) accelerates the onset of action and increases the therapeutic effects of amitriptyline. METHODS: Forty-six outpatients meeting DSM-IV criteria for nonpsychotic depressive episode were randomly assigned to receive rTMS (n = 22) or sham repetitive TMS (sham) (n = 24) during 4 weeks over dorsolateral prefrontal cortex (DLPFC) in this double-blind controlled trial. All patients were concomitantly taking amitriptyline (mean dose 110 mg/d). The rTMS group received 20 sessions (5 sections per week) of 5 Hz rTMS (120% of motor threshold and 1250 pulses per session). Sham stimulation followed the same schedule, however, using a sham coil. The efficacy variables were the Hamilton Depression Rating Scale-17 items (HAM-D/17), the Montgomery-Asberg Depression Rating Scale (MADRS), a Visual Analogue Scale (VAS), and the Clinical Global Impression (CGI). Tolerability was assessed by clinical examination and a safety screening of TMS side effects. RESULTS: Repetitive TMS had a significantly faster response to amitriptyline. There was a significant decrease in HAM-D/17 scores, already after the first week of treatment (p < .001 compared with baseline and p < .001 compared with sham). The decrease in HAM-D/17 scores in the rTMS group was significantly superior compared with the sham group throughout the study (p < .001 at fourth week). CONCLUSIONS: Repetitive TMS at 5 Hz accelerated the onset of action and augmented the response to amitriptyline.

Slow transcranial magnetic stimulation can rapidly reduce resistant auditory hallucinations in schizophrenia.

BACKGROUND: Almost a quarter of patients with schizophrenia present with resistant auditory verbal hallucinations (AVH), a phenomenon that may relate to activation of brain areas underlying speech perception. Repetitive transcranial magnetic stimulation (rTMS) at 1 Hz reduces cortical activation, and recent results have shown that 1-Hz left temporoparietal rTMS may reduce AVH. The aim of this study was to replicate recent data and investigate whether low-frequency rTMS with a high total stimulation number delivered in a shorter 5-day block produces similar benefit. METHODS: Ten right-handed schizophrenia patients with resistant AVH received 5 days of active rTMS and 5 days of sham rTMS (2,000 stimulations per day at 90% of motor threshold) over the left temporoparietal cortex in a double-blind crossover design. The two weeks of stimulation were separated by a 1-week washout period. RESULTS: AVH were robustly improved (56%) by 5 days active rTMS, whereas no variation was observed after sham. Seven patients were responders to active treatment, five of whom maintained improvement for at least 2 months. CONCLUSIONS: These data confirm the efficiency of low-frequency rTMS applied to the left temporoparietal cortex, compared with sham stimulation, in reducing resistant AVH. This improvement can be obtained in only 5 days without serious initial adverse events.

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.

Three-dimensional head model simulation of transcranial magnetic stimulation.

This paper presents a finite element method used to evaluate the induced current density in a realistic model of the human head exposed to a time varying magnetic field. The tissue electric properties were varied to ascertain their influence on the induced currents. Current density magnitude and vector plots were generated throughout the tissue layers to determine the effects of tissue boundaries on the field. The current density magnitude correlated to the conductivity of the tissue in all the cases tested except where the tissue permittivity was raised to a level to allow for displacement currents. In this case, the permittivity of the tissue was the dominant factor. Current density components normal to the tissue interface were shown to exist in all solutions within the cortex contrary to the predictions of present models that rely on symmetrical geometries. Additionally, modifications in the cortical geometry were shown to perturb the field so that the site of activation could be altered in diseased patient populations. Finally, by varying the tissue permittivity values and the source frequency, we tested the effects of alpha dispersion theories on transcranial magnetic stimulation.

Transcranial magnetic stimulation: applications for neuropsychopharmacology.

Transcranial magnetic stimulation (TMS) provides new possibilities for studying localized changes in the electrical properties of the human cortex. TMS combined with electromyography (EMG) has revealed that drugs blocking Na(+) or Ca(2+) channels such as phenytoin, lamotrigin or carbamazepine change the motor threshold without affecting intracortical inhibition or facilitation. Gabaergic agents vigabatrin, lorazepam, diazepam, baclofen and ethanol do not affect the motor threshold, but increase intracortical inhibition and decrease facilitation. N-methyl-D-aspartate receptor antagonists riluzole, dextromethorphan and memantine have similar effects. Dopamine receptor antagonists such as haloperidol, but not sulpiride, decrease intracortical inhibition and increase intracortical facilitation. Other monoamines, such as serotonin and noradrenaline, may have some modulating effect on the cortical excitability. However, TMS combined with EMG gives only indirect evidence about the excitability of the motor cortex because spinal mechanisms may contribute to the results. Cortical excitability can be studied directly by combining TMS with brain imaging methods such as electroencephalography (EEG). Motor and non-motor areas can be stimulated and subsequent brain activity can be measured. Ethanol has been shown to modulate EEG responses evoked by motor-cortex TMS, the effects being largest at the right prefrontal cortex, meaning that ethanol would have changed the functional connectivity. Furthermore, alcohol decreases amplitudes of EEG responses after the left prefrontal stimulation mainly in anterior parts of the cortex, which may be associated with the decrease of the prefrontal cortical excitability. Taken together, TMS provides a new insight to the actions of central nervous system drugs at the cortical level.

Treatment of bipolar mania with right prefrontal rapid transcranial magnetic stimulation.

BACKGROUND: Transcranial magnetic stimulation (TMS) has been suggested for the treatment of a variety of CNS disorders including depression and mania. METHODS: Nine bipolar (I) in-patients diagnosed with mania were treated with right prefrontal rapid TMS in an open and prospective study. Eight of nine patients received TMS as add-on treatment to an insufficient or only partially effective drug therapy. RESULTS: During the 4 weeks of TMS treatment a sustained reduction of manic symptoms as measured by the Bech-Rafaelsen mania scale (BRMAS) was observed in all patients. LIMITATIONS: Due to the open and add-on design of the study, a clear causal relationship between TMS treatment and reduction of manic symptoms cannot be established. CONCLUSIONS: Our data suggest that right prefrontal rapid TMS is safe and efficacious in the add-on treatment of bipolar mania showing laterality opposed to the proposed effect of rapid TMS in depression.

[Repetitive transcranial magnetic stimulation in depression; stimulation of the brain in order to cure the psyche]. / Repetitieve transcraniële magnetische stimulatie bij depressie; stimulatie van het brein om de psyche te genezen.

Transcranial magnetic stimulation (TMS) is a non-invasive approach to briefly stimulate or inhibit cortical brain areas. A novel approach entails the delivery of repetitive TMS pulses (rTMS) at a fixed frequency. In rTMS cortical activity is altered beyond the period of actual stimulation. The changes occur locally as well as at a distance in functionally connected brain areas. These features render rTMS a suitable tool to study normal brain functions and the pathophysiology of brain diseases. Furthermore, it is expected that rTMS could be used as a novel therapy for neurological or psychiatric diseases characterised by abnormal cortical activation. This possibility has been studied mostly in patients suffering from depression, where rTMS has been used to restore normal activity in the hypoactive prefrontal cortex. Despite statistically significant therapeutic effects in small sized trials, the clinical implications are still limited.

Information for assistants of repeated transcranial magnetic stimulation.

Repeated transcranial magnetic stimulation (rTMS) is an exciting new technology being used in psychiatric and neurological research in many centres around the world. rTMS has been accepted as a routine treatment of depression in Canada and Israel. To this point, it has been exclusively conducted by medical officers. As knowledge and experience grows, it is probable that professionals with other backgrounds will have the opportunity to play a role. The aim of this paper is to provide information that will be valuable to assistants. Electromagnetic principles are harnessed to deliver electric currents to localized regions of the cortex. rTMS does not involve anaesthesia or seizure. Side-effects appear to be few. Much remains uncertain, however, even including the most appropriate treatment parameters.

Neuroprotection trek--the next generation: neuromodulation I. Techniques--deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation.

Neuromodulation denotes controlled electrical stimulation of the central or peripheral nervous system. The three forms of neuromodulation described in this paper-deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation-were chosen primarily for their demonstrated or potential clinical usefulness. Deep brain stimulation is a completely implanted technique for improving movement disorders, such as Parkinson's disease, by very focal electrical stimulation of the brain-a technique that employs well-established hardware (electrode and pulse generator/battery). Vagus nerve stimulation is similar to deep brain stimulation in being well-established (for the treatment of refractory epilepsy), completely implanted, and having hardware that can be considered standard at the present time. Vagus nerve stimulation differs from deep brain stimulation, however, in that afferent stimulation of the vagus nerve results in diffuse effects on many regions throughout the brain. Although use of deep brain stimulation for applications beyond movement disorders will no doubt involve placing the stimulating electrode(s) in regions other than the thalamus, subthalamus, or globus pallidus, the use of vagus nerve stimulation for applications beyond epilepsy-for example, depression and eating disorders-is unlikely to require altering the hardware significantly (although stimulation protocols may differ). Transcranial magnetic stimulation is an example of an external or non-implanted, intermittent (at least given the current state of the hardware) stimulation technique, the clinical value of which for neuromodulation and neuroprotection remains to be determined.

Prefrontal cortex transcranial magnetic stimulation does not change local diffusion: a magnetic resonance imaging study in patients with depression.

OBJECTIVE: To determine whether transcranial magnetic stimulation over the left dorsolateral prefrontal cortex produces pathologic changes or leakage of the blood-brain barrier in patients with depression by using apparent diffusion coefficient magnetic resonance imaging. BACKGROUND: Transcranial magnetic stimulation is a new technology for noninvasively stimulating the brain. It appears to be a relatively safe technique, with some important exceptions. Its neurobiologic mechanisms of action are poorly understood. One theory to explain its apparent antidepressant effects involves a potential change in local blood-brain barrier settings, allowing passage of peripheral substances directly into brain parenchyma. Knowing whether transcranial magnetic stimulation changes local brain diffusion is important as well from a safety perspective. To test whether transcranial magnetic stimulation changes local brain diffusion, we used apparent diffusion coefficient magnetic resonance imaging in depressed patients undergoing interleaved transcranial magnetic stimulation/functional magnetic resonance imaging over the left prefrontal cortex. METHODS: Within a 1.5 Tesla magnetic resonance imaging scanner, 14 depressed patients were stimulated with a figure-eight transcranial magnetic stimulation coil over the left prefrontal cortex. Apparent diffusion coefficient magnetic resonance imaging was acquired before, and immediately after, 1 Hertz transcranial magnetic stimulation (147 stimuli) intermittently delivered at a motor threshold of more than 7.35 minutes. Phase maps of the transcranial magnetic stimulation magnetic fields were used to guide region-of-interest placement. RESULTS: No significant qualitative apparent diffusion coefficient differences were observed before and after 1 Hertz transcranial magnetic stimulation underneath the coil. CONCLUSIONS: One Hertz transcranial magnetic stimulation over the left dorsolateral prefrontal cortex as applied in this study did not result in pathologic changes or leakage of the blood-brain barrier in patients with depression. If prefrontal transcranial magnetic stimulation at these usage parameters changes local diffusion, it is not an obvious or large effect.

Repetitive transcranial magnetic stimulation : does it have potential in the treatment of depression?

Transcranial magnetic stimulation (TMS) has become a major research tool in experimental clinical neurophysiology as a result of its potential to noninvasively and focally stimulate cortical brain regions. Currently, studies are being conducted to investigate whether repetitive TMS (rTMS)-mediated modulation of cortical function may also provide a therapeutic approach in neurological and psychiatric disorders. Preclinical findings have shown that prefrontal rTMS can modulate the function of fronto-limbic circuits, which is reversibly altered in major depression. rTMS has also been found to exert effects on neurotransmitter systems involved in the pathophysiology of major depression (e.g. stimulates subcortical dopamine release and acts on the hypothalamic pituitary adrenal axis, which is dysregulated in depression). To date, numerous open and controlled clinical trials with widely differing stimulation parameters have explored the antidepressant potential of rTMS. Though conducted with small sample sizes, the majority of the controlled trials demonstrated significant antidepressant effects of active rTMS compared with a sham condition. Effect sizes, however, varied from modest to substantial, and the patient selection focused on therapy-resistant cases. Moreover, the average treatment duration was approximately 2 weeks, which is short compared with other antidepressant interventions. Larger multicentre trials, which would be mandatory to demonstrate the antidepressant effectiveness of rTMS, have not been conducted to date.A putative future application of rTMS may be the treatment of patients who did not tolerate or did not respond to antidepressant pharmacotherapy before trying more invasive strategies such as electroconvulsive therapy and vagus nerve stimulation. Theoretically, rTMS may be also applied early in the course of disease in order to speed up and increase the effects of antidepressant pharmacotherapy. However, this application has not been a focus of clinical trials to date. Research efforts should be intensified to further investigate the effectiveness of rTMS as an antidepressant intervention and to test specific applications of the technique in the treatment of depressive episodes.

0.2-Hz repetitive transcranial magnetic stimulation has no add-on effects as compared to a realistic sham stimulation in Parkinson's disease.

To study the efficacy of 0.2-Hz repetitive transcranial magnetic stimulation (rTMS) on Parkinson's disease (PD), 85 patients with PD were enrolled into three groups: 1). motor cortical, 2). occipital, and 3). sham stimulation. A round coil was centered over the vertex in motor cortical stimulation, and over the inion in occipital stimulation. In one session, 100 stimuli of 0.2-Hz rTMS at an intensity of 1.1 times active motor threshold (AMT) were given. In sham stimulation, electric currents were given with electrodes fixed on the head to mimic the sensation in real stimulation. Each session was carried out once a week for the first 8 weeks. The Unified Parkinson Disease Rating Scale (UPDRS), Hamilton Rating Scale for Depression (HRSD) and subjective score (visual analogue scale) were assessed. There were no significant differences in clinical features among the three groups. Total and motor score of UPDRS were improved to the same extent by rTMS over Cz, inion, and sham stimulation. HRSD was improved by rTMS over Cz and sham stimulation in the same manner. Subjective score was not significantly improved by any methods of stimulation. 0.2-Hz rTMS at an intensity of 1.1 x AMT has only a placebo effect on PD. Our realistic sham stimulation maneuver must produce powerful placebo effects as a real stimulation.

Neuronal tissue polarization induced by repetitive transcranial magnetic stimulation?

In a blinded cross-over design, 10 healthy controls received 900 monophasic and biphasic repetitive transcranial magnetic stimuli over the primary motor cortex. Stimulation frequency was 1 Hz, and stimulation intensity 90% of the individual resting motor threshold. Suprathreshold stimuli applied at 0.1 Hz before and after repetitive stimulation controlled for changes in corticospinal excitability. We found a lasting corticospinal inhibition that was significantly more pronounced after monophasic than after biphasic repetitive transcranial magnetic stimulation (motor evoked potential amplitude reduced by 35 +/- 20% vs 12 +/- 37%, mean+/- s.d.). We propose that the current flow in the coil plays a significant role in optimising after effects, and asymmetric current flow may be particularly efficient in building up tissue polarization.

Modulation of slow cortical potentials by transcranial magnetic stimulation in humans.

We studied the effects of transcranial magnetic stimulation (TMS) on slow cortical potentials (SCPs) of the brain elicited during performance of a feedback and reward task. Ten healthy participants were trained to self-regulate their SCP amplitude using visual feedback and reward for increased or decreased amplitudes. Subjects participated in 27 runs (each comprising 70 trials) under three different conditions: single-pulse TMS delivered with the coil centered over Cz (vertex), over a lateral scalp position (LSP), which increased task difficulty, and in the absence of stimulation. Cz stimulation led to a non-significant enhancement of negative SCPs, while LSP stimulation led to a significant increase of positive SCPs. These results are consistent with the idea that enhanced task difficulty, as in LSP stimulation, enhances cognitive processing load leading to an increase of positive SCPs. Additionally, the data raise the hypothesis that TMS delivered to bilateral midcentral regions could modulate the amplitude of negative SCPs.