Repetitive transcranial magnetic stimulation of the primary motor cortex in the treatment of motor signs in Parkinson's disease: A quantitative review of the literature

Parkinson's disease (PD) is a progressive disorder characterized by the emergence of motor deficits. In light of the voluminous and conflicting findings in the literature, the aim of the present quantitative review was to examine the effects of repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (M1) in the treatment of motor signs in PD. Studies meeting inclusion criteria were analyzed using meta‐analytic techniques and the Unified Parkinson's Disease Rating Scale (UPDRS) sections II and III were used as outcome measures. In order to determine the treatment effects of rTMS, the UPDRS II and III scores obtained at baseline, same day, to 1 day post rTMS treatment (short‐term follow‐up) and 1‐month post stimulation (long‐term follow‐up) were compared between the active and sham rTMS groups. Additionally, the placebo effect was evaluated as the changes in UPDRS III scores in the sham rTMS groups. A placebo effect was not demonstrated, because sham rTMS did not improve motor signs as measured by UPDRS III. Compared with sham rTMS, active rTMS targeting the M1 significantly improved UPDRS III scores at the short‐term follow‐up (Cohen's d of 0.27, UPDRS III score improvement of 3.8 points). When the long‐term follow‐up UPDRS III scores were compared with baseline scores, the standardized effect size between active and sham rTMS did not reach significance. However, this translated into a significant nonstandardized 6.3‐point improvement on the UPDRS III. No significant improvement in the UPDRS II was found. rTMS over the M1 may improve motor signs. Further studies are needed to provide a definite conclusion. © 2015 International Parkinson and Movement Disorder Society     

Improved language performance subsequent to low‐frequency rTMS in patients with chronic non‐fluent aphasia post‐stroke

Background: Low‐frequency repetitive transcranial magnetic stimulation (rTMS) has emerged as a potential tool for neurorehabilitation and remediation of language in chronic non‐fluent aphasia post‐stroke. Inhibitory (1 Hz) rTMS has been applied to homologous language sites to facilitate behavioural language changes. Improvements in picture‐naming performance and speech output over time have been reported. Methods: Low‐frequency (1 Hz) rTMS was applied to six real stimulation and six sham placebo patients for 20 min per day, for 10 days, and behavioural language outcome measures were taken at baseline (pre‐stimulation) and 2 months post‐stimulation. Results: The findings demonstrate treatment‐related changes observed in the stimulation group when compared to the placebo control group at 2 months post‐stimulation on naming performance as well as other aspects of expressive language and auditory comprehension. Conclusions: These findings provide considerable evidence to support the theory of rTMS modulating mechanisms of transcallosal disinhibition in the aphasic brain and highlight the potential clinical applications for language rehabilitation post‐stroke.     

High‐frequency rTMS over the supplementary motor area for treatment of Parkinson's disease

Dysfunction of the basal ganglia‐thalamocortical motor circuit is a fundamental model to account for motor symptoms in Parkinson's disease (PD). Using high‐frequency repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA), we investigated whether modulation of SMA excitability engenders therapeutic effects on motor symptoms in PD. In this double‐blind placebo‐controlled study, 99 patients were enrolled and assigned randomly to SMA‐stimulation and sham‐stimulation groups. For SMA stimulation, 20 trains of 50 transcranial magnetic stimuli at 5 Hz were delivered at an intensity of 110% active motor threshold for leg muscles in one session. The sham stimulation was 20 trains of electric stimuli given through electrodes fixed on the head to mimic the cutaneous sensation during rTMS. Each session of intervention was carried out once a week for the first 8 weeks. The SMA stimulation, in contrast to the sham stimulation, engendered significant improvements in total scores and motor scores of the Unified Parkinson's Disease Rating Scale. Mean improvements in motor scores were 4.5 points in the SMA‐stimulation group and ?0.1 points in the sham‐stimulation group. Results indicate that 5 Hz rTMS over SMA modestly improves motor symptoms in PD patients; SMA is a potential stimulation site for PD treatment. © 2008 Movement Disorder Society     

rTMS as a treatment for neurogenic communication and swallowing disorders

Recent years have seen the introduction of non‐invasive brain stimulation techniques (e.g. transcranial direct current stimulation and transcranial magnetic stimulation) utilized to target neural‐based pathologies, for therapeutic gain. The direct manipulation of cortical brain activity by repetitive transcranial magnetic stimulation (rTMS) could potentially serve as an efficacious complimentary rehabilitatory treatment for speech, language and swallowing disorders of a neurological origin. The high prevalence of positive reports on communication and swallowing outcomes support these premises. Nonetheless, experimental evidence to date in some areas is considered rudimentary and is deficient in providing placebo‐controlled substantiation of longitudinal neuroplastic change subsequent to stimulation. The most affirmative therapeutic responses have arisen from small placebo‐controlled trials using low‐frequency rTMS for patients with non‐fluent aphasia and high‐frequency rTMS applied to individuals with Parkinson's disease to improve motor speech performance and outcomes. Preliminary studies applying rTMS to ameliorate dysphagic symptoms post‐stroke provide positive swallowing outcomes for patients. Further research into the optimization of rTMS protocols, including dosage, stimulation targets for maximal efficacy and placebo techniques, is critically needed to provide a fundamental basis for clinical interventions using this technique. rTMS represents a highly promising and clinically relevant technique, warranting the future development of clinical trials across a spectrum of communication and swallowing pathologies, to substantiate and expand on the methods outlined in published reports.     

Repetitive transcranial magnetic stimulation for levodopa‐induced dyskinesias in Parkinson's disease

In a placebo‐controlled, single‐blinded, crossover study, we assessed the effect of “real” repetitive transcranial magnetic stimulation (rTMS) versus “sham” rTMS (placebo) on peak dose dyskinesias in patients with Parkinson's disease (PD). Ten patients with PD and prominent dyskinesias had rTMS (1,800 pulses; 1 Hz rate) delivered over the motor cortex for 4 consecutive days twice, once real stimuli and once sham stimulation were used; evaluations were done at the baseline and 1 day after the end of each of the treatment series. Direct comparison between sham and real rTMS effects showed no significant difference in clinician‐assessed dyskinesia severity. However, comparison with the baseline showed small but significant reduction in dyskinesia severity following real rTMS but not placebo. The major effect was on dystonia subscore. Similarly, in patient diaries, although both treatments caused reduction in subjective dyskinesia scores during the days of intervention, the effect was sustained for 3 days after the intervention for the real rTMS only. Following rTMS, no side effects and no adverse effects on motor function and PD symptoms were noted. The results suggest the existence of residual beneficial clinical aftereffects of consecutive daily applications of low‐frequency rTMS on dyskinesias in PD. The effects may be further exploited for potential therapeutic uses. © 2008 Movement Disorder Society     

The impact of left prefrontal repetitive transcranial magnetic stimulation on depression in Parkinson's disease: A randomized,double‐blind,placebo‐controlled study

Based on several open‐label and case studies, repetitive transcranial magnetic stimulation (rTMS) seems to have an antidepressive effect on patients with Parkinson's disease (PD). However, this hypothesis requires further confirmation. We conducted a randomized, double‐blind placebo‐controlled study to evaluate the effect of rTMS over the left dorsolateral prefrontal cortex (DLPFC) on depression and various motor and nonmotor features of PD. Twenty‐two PD patients with mild or moderate depressive episodes were assigned into two groups, one receiving real‐rTMS (90% of resting motor threshold, 5 Hz, 600 pulses‐a‐day for 10 days) over the left DLPFC, and another group receiving sham‐rTMS. An investigator blinded to the treatment performed three video‐taped examinations on each patient: before stimulation (baseline), 1 day (short term), and 30 days after treatment session ended (long‐term effect). Mini‐Mental State Examination, Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn‐Yahr, Epworth Sleepiness, Visual Analog and Montgomery‐Asberg Depression Rating Scales (MADRS), Beck Depression Inventory (BDI), and Trail making and Stroop tests were applied. In the actively treated group, not only depression rating scales showed significant improvement 30 days after treatment ended (BDI by 44.4% and MADRS by 26.1%), but also the accuracy of Stroop test (by 16%). We could also demonstrate an insignificant improvement in UPDRS‐III by 7.5 points (31.9%, P = 0.06). In the sham‐treated group none of the examined tests and scales improved significantly after sham stimulation. Our study demonstrated the beneficial effect of the left DLPFC rTMS on depression in PD lasting at least 30 days after treatment. However, this result should be confirmed in patients with severe depression by further clinical trials. © 2010 Movement Disorder Society     

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.     

Prefrontal cortex rTMS enhances action naming in progressive non‐fluent aphasia

Background and purpose:  Progressive non‐fluent aphasia (PNFA) is a neurodegenerative disorder that is characterized by non‐fluent speech with naming impairment and grammatical errors. It has been recently demonstrated that repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) improves action naming in healthy subjects and in subjects with Alzheimer’s disease. Purpose:  To investigate whether the modulation of DLPFC circuits by rTMS modifies naming performance in patients with PNFA. Methods:  Ten patients with a diagnosis of PNFA were enrolled. High‐frequency rTMS was applied to the left and right DLPFC and the sham (i.e. placebo) condition during object and action naming. A subgroup of patients with semantic dementia was enrolled as a comparison group. Results:  A repeated‐measure anova with stimulus site (sham, left and right rTMS) showed significant effects. Action‐naming performances during stimulation of both the left and right DLPFC were better than during placebo stimulation. No facilitating effect of rTMS to the DLPFC on object naming was observed. In patients with a diagnosis of semantic dementia, no effect of stimulation was reported. Conclusions:  Our study demonstrated that rTMS improved action naming in subjects with PNFA, possibly due to the modulation of DLPFC pathways and a facilitation effect on lexical retrieval processes. Future studies on the potential of a rehabilitative protocol using rTMS applied to the DLPFC in this orphan disorder are required.     

Repetitive transcranial magnetic stimulation to SMA worsens complex movements in Parkinson's disease.

OBJECTIVES: To evaluate the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS) for Parkinson's disease (PD) by delivering stimulation at higher intensity and frequency over longer time than in previous research. Promising beneficial effects on movement during or after rTMS have been reported. METHODS: Ten patients with idiopathic PD were enrolled in a randomized crossover study comparing active versus sham rTMS to the supplementary motor area (SMA). Assessments included reaction and movement times (RT/MT), quantitative spiral analysis, timed motor performance tests, United Parkinson's Disease Rating Scale (UPDRS), patient self-report and guess as to stimulation condition. RESULTS: Two of 10 patients could not tolerate the protocol. Thirty to 45 min following stimulation, active rTMS as compared with sham stimulation worsened spiral drawing (P=0.001) and prolonged RT in the most affected limb (P=0.030). No other significant differences were detected. CONCLUSIONS: We sought clinically promising improvement in PD but found subclinical worsening of complex and preparatory movement following rTMS to SMA. These results raise safety concerns regarding the persistence of dysfunction induced by rTMS while supporting the value of rTMS as a research tool. Studies aimed at understanding basic mechanisms and timing of rTMS effects are needed.     

Clinical effects of repetitive transcranial magnetic stimulation versus acute levodopa challenge in Parkinson's disease

We studied the short-term clinical effects of 10-Hz repetitive transcranial magnetic stimulation (rTMS) of the motor hand area contralateral to the more affected limb in 12 non-fluctuating, for at least 12 hours drug free patients with Parkinson's disease (PD). We investigated the efficacy of rTMS in combination with a levodopa challenge test design under double-blind, placebo controlled conditions. Significant reductions of UPDRS III motor scores showed the treatment conditions: placebo/rTMS, levodopa/sham stimulation and levodopa/rTMS. A more detailed evaluation of arm symptoms contralateral to the stimulated brain region showed even more pronounced effects for the three conditions. There were significant differences between the mean response of the UPDRS III arm scores to the four test conditions. In conclusion our study demonstrates short-term beneficial effects of 10-Hz rTMS on motor symptoms in PD patients. A release of endogenous dopamine in subcortical structures, i.e. putamen, in response to rTMS is the most likely mechanism of action.     

Controlled trial on the effect of 10 days low‐frequency repetitive transcranial magnetic stimulation (rTMS) on motor signs in Parkinson's disease

We evaluated the effect of low‐frequency rTMS on motor signs in Parkinson's disease (PD), under a double‐blind placebo‐controlled trial design. PD patients were randomly assigned to received either real (n = 9) or sham (n = 9) rTMS for 10 days. Each session comprises two trains of 50 stimuli each delivered at 1 Hz and at 90% of daily rest motor threshold using a large circular coil over the vertex. The effect of the stimulation, delivered during the ON‐period, was evaluated during both ON and OFF periods. Tests were carried out before and after the stimulation period, and again 1 week after. The effect of the stimulation was evaluated through several gait variables (cadence, step amplitude, velocity, the CV_{stride‐time}, and the turn time), hand dexterity, and also the total and motor sections of the UPDRS. Only the total and motor section of the UPDRS and the turn time during gait were affected by the stimulation, the effect appearing during either ON or OFF evaluation, and most importantly, equally displayed in both real and sham group. The rest of the variables were not influenced. We conclude the protocol of stimulation used, different from most protocols that apply larger amount of stimuli, but very similar to some previously reported to have excellent results, has no therapeutic value and should be abandoned. This contrasts with the positive reported effects using higher frequency and focal coils. Our work also reinforces the need for sham stimulation when evaluating the therapeutic effect of rTMS. © 2010 Movement Disorder Society     

Effects of repetitive transcranial magnetic stimulation on voice and speech in Parkinson's disease

OBJECTIVE: To investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on vocal function in Parkinson's disease (PD). MATERIAL AND METHODS: Two different sets of rTMS parameters were investigated on 30 patients with PD: active or sham 15 Hz rTMS of the left dorsolateral prefrontal cortex (LDLPFC) (110% of motor threshold (MT), 3000 pulses per session) and active 5 Hz rTMS of the primary motor cortex (M1)-mouth area (90% MT, 2250 pulses per session). A blind rater evaluated speech characteristics (acoustic and perceptual analysis of voice) and voice-related quality of life (V-RQOL). RESULTS: rTMS of LDLPFC resulted in mood amelioration and subjective improvement of the V-RQOL only (71.9% improvement, P < 0.001), but not in objective measures such as fundamental frequency (P = 0.86) and voice intensity (P = 0.99). On the other hand, rTMS of M1-mouth induced a significant improvement of the fundamental frequency (12.9% for men and 7.6% for women, P < 0.0001) and voice intensity (20.6%, P < 0.0001). CONCLUSIONS: Our findings provide initial evidence that rTMS of the primary motor cortex might yield a beneficial effect on vocal function in PD.     

Repetitive transcranial magnetic stimulation at 1Hz and 5Hz produces sustained improvement in motor function and disability after ischaemic stroke

Background: Repetitive transcranial magnetic stimulation (rTMS) is a simple and non‐invasive method of augmenting motor recovery after stroke, probably mediated by restoring inter‐hemispheric activation balance. This placebo‐controlled pilot study examined the possible benefit of stimulating the lesioned hemisphere (5‐Hz rTMS) or inhibiting the contra‐lesional hemisphere (1‐Hz rTMS) on clinical recovery of motor function in patients with ischaemic stroke and assessed the sustainability of the response. Methods: Sixty patients with ischaemic stroke (>1 month from onset) with mild‐to‐moderate hemiparesis were randomized to receive 10 daily sessions of either sham rTMS, 5‐Hz ipsi‐lesional rTMS or 1‐Hz contra‐lesional rTMS, in addition to a standard physical therapy protocol. Serial assessments were made over a period of 12 weeks by the thumb‐index finger tapping test (FT), Activity Index (AI) score and the modified Rankin Scale (mRS). Results: In contrast to control patients, those receiving active rTMS as ipsi‐lesional 5‐Hz stimulation or 1‐Hz contra‐lesional stimulation showed statistically significant improvement on the FT test, AI scores and mRS score at 2 weeks, and the effect was sustained over the 12‐week observation period. No significant adverse events were observed during treatment in either group. Conclusions: Repetitive TMS has beneficial effects on motor recovery that can be translated to clinically meaningful improvement in disability in patients with post‐stroke hemiparesis, with a well‐sustained effect. The similarity of inhibitory and stimulatory rTMS in producing these effects supports the inter‐hemispheric balance hypothesis and encourages further research into their use in long‐term neurorehabilitation programmes of patients with stroke.     

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.     

1 Hz rTMS preconditioned by tDCS over the primary motor cortex in Parkinson’s disease: effects on bradykinesia of arm and hand

To investigate whether a period of 1 Hz repetitive transcranial magnetic stimulation (rTMS) over M1 preconditioned by tDCS improves bradykinesia of the upper limb in Parkinson’s disease (PD). Fifteen patients with PD performed index finger, hand tapping and horizontal pointing movements as well as reach-to-grasp movements with either hand before (baseline conditions) and after a period of 1 Hz rTMS preconditioned by (1) sham, (2) anodal or (3) cathodal tDCS over the primary motor cortex contralateral to the more affected body side. Movement kinematics was analysed using an ultrasound-based motion analyser at baseline, immediately after and 30 min after each stimulation session. Dopaminergic medication was continued. Compared to baseline, 1 Hz rTMS significantly increased the frequency of index finger and hand tapping as well as horizontal pointing movements performed with the contralateral hand. Movement frequency increased up to 40% over 30 min after cessation of the stimulation. Preconditioning with cathodal tDCS, but not with anodal tDCS, reduced the effectiveness of 1 Hz rTMS to improve tapping and pointing movements. There was no significant increase of movement frequencies of the ipsilateral hand induced by 1 Hz rTMS preconditioned by either tDCS session. Movement kinematics of reach-to-grasp movements were not significantly influenced by either stimulation session. In PD the beneficial effects of 1 Hz rTMS over the primary motor cortex on bradykinesia of simple finger, hand and pointing movements is reduced by preconditioning with cathodal tDCS, but not with anodal tDCS. Preconditioning with tDCS is a powerful tool to modulate the behavioural effect of 1 Hz rTMS over the primary motor cortex in PD.     

Effect of repetitive TMS and fluoxetine on cognitive function in patients with Parkinson's disease and concurrent depression.

Previous studies show that cognitive functions are more impaired in patients with Parkinson's disease (PD) and depression than in nondepressed PD patients. We compared the cognitive effects of two types of antidepressant treatments in PD patients: fluoxetine (20 mg/day) versus repetitive transcranial magnetic stimulation (rTMS, 15 Hz, 110% above motor threshold, 10 daily sessions) of the left dorsolateral prefrontal cortex. Twenty-five patients with PD and depression were randomly assigned either to Group 1 (active rTMS and placebo medication) or to Group 2 (sham rTMS and fluoxetine). A neuropsychological battery was assessed by a rater blind to treatment arm at baseline and 2 and 8 weeks after treatment. Patients in both groups had a significant improvement of Stroop (colored words and interference card) and Hooper and Wisconsin (perseverative errors) test performances after both treatments. Furthermore, there were no adverse effects after either rTMS or fluoxetine in any neuropsychological test of the cognitive test battery. The results show that rTMS could improve some aspects of cognition in PD patients similar to that of fluoxetine. The mechanisms for this cognitive improvement are unclear, but it is in the context of mood improvement.     

Acoustic evaluation of short-term effects of repetitive transcranial magnetic stimulation on motor aspects of speech in Parkinson’s disease

Hypokinetic dysarthria in Parkinson’s disease (PD) can be characterized by monotony of pitch and loudness, reduced stress, variable rate, imprecise consonants, and a breathy and harsh voice. Using acoustic analysis, we studied the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) applied over the primary orofacial sensorimotor area (SM1) and the left dorsolateral prefrontal cortex (DLPFC) on motor aspects of voiced speech in PD. Twelve non-depressed and non-demented men with PD (mean age 64.58 ± 8.04 years, mean PD duration 10.75 ± 7.48 years) and 21 healthy age-matched men (a control group, mean age 64 ± 8.55 years) participated in the speech study. The PD patients underwent two sessions of 10 Hz rTMS over the dominant hemisphere with 2,250 stimuli/day in a random order: (1) over the SM1; (2) over the left DLPFC in the “on” motor state. Speech examination comprised the perceptual rating of global speech performance and an acoustic analysis based upon a standardized speech task. The Mann–Whitney U test was used to compare acoustic speech variables between controls and PD patients. The Wilcoxon test was used to compare data prior to and after each stimulation in the PD group. rTMS applied over the left SM1 was associated with a significant increase in harmonic-to-noise ratio and net speech rate in the sentence tasks. With respect to the vowel task results, increased median values and range of Teager-Kaiser energy operator, increased vowel space area, and significant jitter decrease were observed after the left SM1 stimulation. rTMS over the left DLPFC did not induce any significant effects. The positive results of acoustic analysis were not reflected in a subjective rating of speech performance quality as assessed by a speech therapist. Our pilot results indicate that one session of rTMS applied over the SM1 may lead to measurable improvement in voice quality and intensity and an increase in speech rate and tongue movements. Nevertheless, these changes were not accompanied by changes in a perceptual evaluation of speech performance by a speech therapist. Future placebo-controlled studies in larger patient cohorts should verify if rTMS would be clinically useful for treating hypokinetic dysarthria in PD.     

Low-frequency repetitive transcranial magnetic stimulation for dyskinesia and motor performance in Parkinson’s disease

Dyskinesias are one of the most frequent and disabling complications of the long-term treatment of Parkinson’s disease (PD). Although the cause is not completely understood, it appears that an imbalance between excitatory and inhibitory inputs from the basal ganglia to the motor cortex leads to overactivation of motor and premotor areas. Overactivation of the supplementary motor area (SMA) has been observed in neuroimaging studies in dyskinetic PD patients. We investigated the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) of the SMA on levodopa-induced dyskinesias (LID) and motor performance in PD. We tested whether longer duration (10 days) and higher number of total pulses (1800 pulses) would enhance the beneficial effect. Seventeen dyskinetic PD patients were randomly assigned to real rTMS or sham (placebo) rTMS, and 1 Hz rTMS or sham rTMS was applied over the SMA for 10 consecutive days. Patients were assessed at baseline and 1 day after the last rTMS with a levodopa challenge test, and video recordings were taken. Dyskinesias and motor performance were rated off-line by two blinded raters using video recordings. After 10 days of treatment with rTMS, we observed that 1 Hz rTMS delivered over the SMA had decreased LID lasting for 24 hours without a change in motor performance, whereas sham rTMS induced no significant change in dyskinesia scores. These results support a possible therapeutic effect of low-frequency rTMS in LID. However, in order to suggest rTMS as an effective treatment, long-term observations and further investigations with a larger patient population are essential.     

Add-on rTMS for medication-resistant depression: a randomized, double-blind, sham-controlled trial in Chinese patients

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been developed as a novel tool for improving depression by delivering magnetic stimulation to the brain. However, the apparent effects of rTMS on depression have been varied in different studies. The aims of this study were to determine whether left dorsolateral prefrontal cortex rTMS can alleviate medication-resistant depression in Chinese patients and to investigate what demographic variables or clinical features may predict better response. METHOD: We designed a 2-week randomized, double-blind, sham-controlled study of add-on rTMS. A total of 30 medication-resistant patients with DSM-IV major depressive disorder or bipolar disorder, depressed episode completed 10 sessions of active or sham rTMS-10 patients at each of 2 frequencies, faster (20 Hz) or slower (5 Hz) at 100% motor threshold, and 10 patients at sham stimulation. RESULTS: Patients at both stimulation frequencies demonstrated a superior reduction of depression severity compared to sham stimulation (active = 55.7% vs. sham = 16.3%). The response rate for active rTMS was 60%, in contrast to 10% for the sham treatment. No difference in clinical response was observed between 5 Hz and 20 Hz active rTMS. Clinical variables showed that younger age and less severe depression at entry may predict the clinical response to rTMS. Except for 1 patient in which rTMS appeared to induce mania, this procedure posed no safety problem. CONCLUSIONS: To our knowledge, this is the first study to demonstrate the clinical efficacy and safety of rTMS in Chinese patients. Since not all the rTMS trials in previous reports had positive results, further larger trials are still warranted.