Real rTMS Group Research Articles

Modulation of electroencephalogram brain activity dynamics by 10 Hz parietal repetitive transcranial magnetic stimulation: Implications for recovery of the minimally conscious state

Background and objectivesDespite the fact that the parietal cortex is associated with consciousness, the underlying mechanisms of parietal repetitive transcranial magnetic stimulation (rTMS) have not yet been specifically investigated. The present study aims to examine the effects of parietal rTMS on patients with disorders of consciousness (DoC) and identify a novel potential target. MethodsTwenty minimally conscious state (MCS) patients were stochastically assigned to a real or sham rTMS group in a controlled trial. The real rTMS group was administered over the parietal cortex, with a frequency of 10 Hz and a rest motor threshold of 90 %. The sham rTMS group was identical to the real rTMS group without magnetic stimulation over the cortex. Pre- and post-treatment resting-state electrophysiological (EEG) data and coma recovery scale-revised (CRS-R) score were gathered. Microstate analyses were calculated to evaluate the brain activity dynamics. ResultsThe real rTMS treatment improved the CRS-R scores. There were notable alterations in the mean microstate duration (MMD) of microstate B in the real rTMS group. The sham rTMS group did not exhibit such changes in CRS-R score or EEG results, which were not statistically significant. Furthermore, the MMD and RTC of microstate E were found to be negatively correlated with baseline CRS-R scores. ConclusionParietal rTMS can induce behavioral improvement and brain activity dynamics in patients with MCS. EEG microstates can be used as a valuable method to study neurophysiological mechanisms behind MCS. And the parietal cortex represents an alternative for rTMS therapy protocols.

Comparison of intermittent theta burst stimulation and high-frequency repetitive transcranial magnetic stimulation on spinal cord injury-related neuropathic pain: A sham-controlled study

Objective To compare the effects of intermittent theta burst stimulation (iTBS) and high-frequency repetitive transcranial magnetic stimulation (rTMS) on spinal cord injury-related neuropathic pain with sham controls, using neuropathic pain-specific evaluation tools. Design A randomized, double-blind, sham-controlled trial. Setting Rehabilitation medicine department of a university hospital. Participants Thirty-three patients with spinal cord injury-related neuropathic pain. Interventions Patients were randomly allocated to one of three groups (real iTBS, real rTMS, and sham rTMS). Each patient underwent five sessions of assigned stimulation. Outcome Measures Before and after completion of the five sessions, patients were evaluated using the self-completed Leeds Assessment of Neuropathic Symptoms and Signs, Numeric Rating Scale, Neuropathic Pain Symptom Inventory, and Neuropathic Pain Scale. Results Real iTBS and real rTMS reduced pain levels after stimulation according to all the evaluation tools, and the changes were significant when compared to the values of the sham rTMS group. No significant differences were found between the real iTBS and real rTMS groups. Conclusion Both iTBS and rTMS were effective in reducing spinal cord injury-related neuropathic pain. When safety, convenience, and compliance are considered, iTBS would have an advantage over rTMS in clinical situations with spinal cord injury-related neuropathic pain. Trial Registration: This trial was registered with the Clinical Research Information Service (registration no. KCT0004976).

Somatosensory evoked potentials amplitude is enhanced after non-invasive brain stimulation in chronic ischemic stroke: Preliminary results from a randomised control trial

ObjectiveTo investigate the effects of transcranial electrical and magnetic non-invasive brain stimulation (NIBS) protocols on somatosensory evoked potential (SEP) in chronic ischemic stroke. Methods33 patients were randomly assigned to one of the four treatment groups of the transcranial direct current stimulation (tDCS) and/or repetitive transcranial magnetic stimulation (rTMS) protocol. SEP parameters were recorded before and after ten days of the treatment session. All the statistical analyses were carried out using SPSS version 19. ResultsIt was found that there is a statistically significant improvement in the N20-P22 mean amplitude after treatment sessions in all groups except the group where tDCS and rTMS groups were sham. On paired t-tests, the difference betweeen post and pre-stimulation SEP amplitudes for the real tDCS and real rTMS coupled group was 1.045 ± 0.732 (p value = 0.005). For sham tDCS+real rTMS group, 1.05 ± 0.96 (P = 0.04); for real tDCS+sham rTMS 0.543 ± 0.332 (P = 0.01) and for double sham stimulation, 0.204 ± 0.648 (P = 0.4) respectively ConclusionIn ischemic stroke patients, either or coupled true transcranial tDCS and rTMS was found to be safe and significantly enhanced the amplitude of cortical somatosensory potentials when combined with standard physiotherapy, in the interim analysis of an ongoing randomised controlled trial. Clinical Trial Registry of IndiaCTRI/2019/11/022009 SignificanceThe results of this research indicates the importance of RCTs in developing robust improved NIBS protocols coupled to physiotherapy to enhance the sensory-motor functional recovery following ischemic stroke.

The effect of high-frequency repetitive transcranial magnetic stimulation on motor recovery and gait parameters in chronic incomplete spinal cord injury: A randomized-controlled study.

This study aims to examine the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) on gait parameters and lower extremity motor recovery in a more specific sample of individuals with chronic and traumatic incomplete spinal cord injury (iSCI). This double-blind, sham-controlled, randomized study included a total of 28 individuals (20 males, 8 females; mean age: 35.7±12.1 years; range, 18 to 45 years) with chronic (>1 year) traumatic iSCI. The participants were randomly allocated to either sham rTMS group (n=14) or real rTMS group (n=14). We compared the groups based on the lower extremity motor scores (LEMS), the temporal-spatial gait measurements using three-dimensional gait analysis, the Walking Index for SCI-II (WISCI-II), and 10-m walking test at baseline, three weeks (post-treatment) and five weeks (follow-up) after the treatment. The real rTMS group revealed a significant improvement in walking speed, LEMS score, and 10-m walking test after the treatment compared to baseline (p=0.001, p=0.002, and p=0.023, respectively). Changes in the LEMS score were significantly increased in the real rTMS group compared to the sham group at both three and five weeks (p=0.001 and p=0.001, respectively). No significant difference was observed in the other variables between the groups (p>0.05). Our study findings support the therapeutic effectiveness of rTMS on motor recovery in chronic iSCI. The rTMS can be used as an adjuvant therapy to conventional physiotherapy in the rehabilitation of patients with iSCI.

Cerebral blood flow changes induced by high-frequency repetitive transcranial magnetic stimulation combined with cognitive training in Alzheimer's disease.

Hypoperfusion of the posterior cingulate cortex (PCC) and precuneus has consistently been reported in patients with Alzheimer's disease (AD). Repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training (COG) is effective in alleviating the symptoms of patients with mild AD. This study investigated the effects of rTMS-COG therapy on cerebral blood flow (CBF), with a special interest in the PCC/precuneus, and whether observed CBF changes are associated with changes in neuropsychological assessments in AD. Twenty-one patients with mild or moderate AD were randomly divided into real rTMS (n = 11) and sham treatment (n = 10) groups, both combined with COG. Neuro-navigated 10 Hz rTMS was used to stimulate the left dorsolateral prefrontal cortex (DLPFC) and then the left lateral temporal lobe (LTL) for 20 min each day for 4 weeks in the real rTMS group. All patients with AD underwent neuropsychological assessment, pseudo-continuous arterial spin labeling, and structural 3D T1-weighted MRI before treatment (T0), immediately after treatment (T1), and 4 weeks after treatment (T2). CBF in the precuneus, PCC, and stimulation targets at the region-of-interest (ROI) level, as well as whole-brain CBF changes at the voxel level, were compared between the two groups at three timepoints. rTMS-COG therapy revealed significant group × time interactions for the Mini-Mental State Examination (F = 5.339, p = 0.023, η2 = 0.433) and activities of daily living (F = 5.409, p = 0.039, η2 = 0.436) scores. The regional CBF in the precuneus showed a significant group × time interaction (F = 5.833, p = 0.027, η2 = 0.593). For voxel-level analysis, a significant group main effect was found in the left limbic lobe cluster, with the maximal peak in the left parahippocampus (p < 0.001, uncorrected, peak at [-16 -8 -24]). Simple effects analysis indicated that rTMS-COG therapy induced a decrease in CBF in the precuneus at T1 (p = 0.007) and an increase in the left parahippocampus at T2 (p=0.008). CBF decrease in the precuneus was correlated with better cognitive function immediately after treatment (T1) (r =-0.732, p=0.025). Neuropsychological assessments showed immediate and long-term effects on cognitive function and activities of daily living after rTMS-COG therapy. CBF changes induced by high-frequency rTMS-COG therapy are region-dependent, showing immediate effects in the precuneus and long-term effects in the left parahippocampus. These results provide imaging evidence to understand the underlying neurobiological mechanism for the application of rTMS-COG in AD.

Repetitive transcranial magnetic stimulation for psychiatric symptoms in long-term hospitalized veterans with schizophrenia: A randomized double-blind controlled trial.

Multiple lines of evidence demonstrate that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may improve clinical outcomes in patients with schizophrenia (SCZ). However, the efficacy of HF-rTMS on psychiatric symptoms remains unknown in veterans with SCZ. This study aimed to investigate whether HF-rTMS was beneficial in alleviating the clinical symptoms in veterans with SCZ. Forty-seven long-term hospitalized veterans with SCZ were randomly allocated to receive neuronavigated 10 Hz rTMS or sham stimulation over the left dorsolateral prefrontal cortex once daily for four consecutive weeks. Symptoms were assessed by using the Positive and Negative Syndrome Scale at baseline and at the end of week 4. We also collected easily available routine biochemical markers including blood sugar, lipid profiles, hormone, and blood cell counts, considering that these markers may potentially be used to predict the outcomes of rTMS treatment. We found that there was a significant interaction effect of time and group on the positive symptoms. Compared with the sham group, the positive factor score of veterans with SCZ was significantly decreased after treatment in the real rTMS group. Interestingly, the improvement of positive symptoms from baseline to 4-week follow-up was significantly associated with the whole white blood cells (WBC) counts at baseline in the real rTMS group, and baseline WBC counts were predictive of the symptom improvement after rTMS treatment. Our findings indicate that add-on 10 Hz rTMS is beneficial for clinical symptoms in veterans with SCZ. In addition, the baseline WBC counts were predictive of the outcomes after treatment.Clinical trial registrationclinicaltrials.gov, identifier NCT03774927.

Effect of cerebellum stimulation on cognitive recovery in patients with Alzheimer disease: A randomized clinical trial

IntroductionEvidence indicates that the cerebellum is involved in cognitive processing. However, the specific mechanisms through which the cerebellum repetitive transcranial magnetic stimulation (rTMS) contributes to the cognitive state are unclear. MethodsIn the current randomized, double-blind, sham-controlled trial, 27 patients with Alzheimer's disease (AD) were randomly allotted to one of the two groups: rTMS-real or rTMS-sham. We investigated the efficacy of a four-week treatment of bilateral cerebellum rTMS to promote cognitive recovery and alter specific cerebello-cerebral functional connectivity. ResultsThe cerebellum rTMS significantly improves multi-domain cognitive functions, directly associated with the observed intrinsic functional connectivity between the cerebellum nodes and the dorsolateral prefrontal cortex (DLPFC), medial frontal cortex, and the cingulate cortex in the real rTMS group. In contrast, the sham stimulation showed no significant impact on the clinical improvements and the cerebello-cerebral connectivity. ConclusionOur results depict that 5 Hz rTMS of the bilateral cerebellum is a promising, non-invasive treatment of cognitive dysfunction in AD patients. This cognitive improvement is accompanied by brain connectivity modulation and is consistent with the pathophysiological brain disconnection model in AD patients.

The Effect of Cerebellar Repetitive Transcranial Magnetic Stimulation on Dysphagia due to Posterior Circulation Stroke, a Randomized Controlled Trial Protocol

Introduction: Cerebellum might be active during the task of swallowing. Little is known whether cerebellar repetitive transcranial magnetic stimulation (rTMS) could improve post-stroke dysphagia (PSD) due to occlusion in the posterior circulation. This paper describes the rationale and design of a randomized controlled trial that aims to determine the effect of cerebellar rTMS on dysphagia due to posterior circulation stroke. Methods and Analysis: Thirty patients with PSD due to occlusion in the posterior circulation will be randomly divided to receive real (n = 20) or sham (n = 10) cerebellar rTMS. Patients in the real rTMS group will receive 250 pulses rTMS at a low intensity with 10 Hz frequency for 10 days (five consecutive days per week). The severity of dysphagia will be assessed with videofluoroscopic swallowing study (VFSS) using the Rosenbek penetration aspiration scale (PAS), the pharyngeal constriction ratio (PCR), and the dysphagia outcome and severity scale (DOSS) before and immediately after the last session and then again after 1 and 3 months. The functional magnetic resonance imaging (fMRI) will be assessed before and after the last session and then again after 1 month and 3 months. The primary outcome is the improvement of swallowing function determined by PAS, PCR, and DOSS. The secondary outcomes include changes in brain connectivity network detected using fMRI. Discussion: This study will determine whether cerebellar rTMS improves dysphagia due to posterior circulation stroke in Chinese patients. Our findings will contribute to a new approach for swallowing function recovery after posterior circulation stroke.

The Effect of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cognition in Patients With Traumatic Brain Injury: A Protocol for a Randomized Controlled Trial.

Cognitive impairment, defined as a decline in memory and executive function, is one of the most severe complications of traumatic brain injury (TBI). Patients with TBI are often unable to return to work due to cognitive impairment and their overall quality of life is reduced. TBI can bring a serious economic burden to patient's families and to society. Reported findings on the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving cognitive impairment following TBI are inconsistent. The purpose of the proposed study is to investigate whether rTMS can improve memory and executive function in patients with TBI. Herein, we propose a prospective randomized placebo-controlled (rTMS, sham rTMS, cognitive training), parallel-group, single-center trial. 36 participants with a TBI occurring at least 6 months prior will be recruited from an inpatient rehabilitation center. Participants will be randomly assigned to the real rTMS, sham rTMS, or cognitive training groups with a ratio of 1:1:1. A 20-session transcranial magnetic stimulation protocol will be applied to the left and right dorsolateral prefrontal cortices (DLPFC) at frequencies of 10 Hz and 1 Hz, respectively. Neuropsychological assessments will be performed at four time points: baseline, after the 10th rTMS session, after the 20th rTMS session, and 30 days post-intervention. The primary outcome is change in executive function assessed using the Shape Trail Test (STT). The secondary outcome measures are measures from neuropsychological tests: the Hopkins Verbal Learning Test (HVLT), the Brief Visuospatial Memory Test (BVMT), the Digit Span Test (DST). We report on positive preliminary results in terms of improving memory and executive function as well as beneficial changes in brain connectivity among TBI patients undergoing rTMS and hypothesize that we will obtain similar results in the proposed study.

Alteration of gamma-aminobutyric acid in the left dorsolateral prefrontal cortex of individuals with chronic insomnia: a combined transcranial magnetic stimulation-magnetic resonance spectroscopy study

ObjectiveTo investigate changes in the level of gamma-aminobutyric acid (GABA) in the left dorsolateral prefrontal cortex (DLPFC) of patients with chronic insomnia treated with real repetitive transcranial magnetic stimulation (rTMS) as compared to sham-rTMS, as measured with 1H-Magnetic Resonance Spectroscopy (1H-MRS). MethodsForty chronic insomnia participants were randomized to either real or sham rTMS group. The rTMS was administered once per day Continuously for 14 days with the stimulation over the left DLPFC. Left DLPFC GABA level relative to creatine (Cr) was measured by 1H-MRS. Insomnia symptom was evaluated by Insomnia Severity Index (ISI). MRS and ISI were assessed among all participants before and after treatment. This study was registered in the Chinese Clinical Trial Registry (No. ChiCTR2100047255). ResultsAfter treatment, the ISI score in real rTMS group was markedly decreased as compared to pre-rTMS (t = −4.25, p < 0.001, Cohen's d = 0.90), whereas no significant change in ISI was observed in the group of sham rTMS. In addition, we observed a significant increase of GABA+/Cr concentration in the real rTMS group after stimulation (0.37 ± 0.11 to 0.40 ± 0.11, p = 0.039), but that of sham did not (0.38 ± 0.10 to 0.39 ± 0.11, p = 0.151). However, there was no significant association between the change of GABA+/Cr in left DLPFC and the changes of ISI scores in the two groups. Conclusion1 Hz rTMS has the potential to increase GABA + level in left DLPFC of patients with chronic insomnia, and warrants further investigation.

A Randomized Controlled Trial of the Effect of Repetitive Transcranial Magnetic Stimulation of the Motor Cortex on Lower Extremity Spasticity in Hereditary Spastic Paraplegia.

Hereditary spastic paraplegia refers to a group of conditions characterized by a slow progression of spasticity in lower limbs resulting in gait abnormalities. Current treatment options have proven to be insufficient in terms of symptom alleviation. In this study, we tested the effectiveness of repetitive transcranial magnetic stimulation (rTMS) on lower limb spasticity in patients with hereditary spastic paraplegia. Eight patients were randomly assigned to receive either five sessions of active 5 Hz-rTMS ( n = 4) or sham rTMS ( n = 4). The primary outcome was a change in spasticity assessed by the modified Ashworth scale. Secondary outcomes were change in 10 m walking test, Fugl-Meyer assessment of lower extremity motor function, and quality-of-life short-form survey scores. Assessment of the outcomes was done before, upon completion, and 1 month after the intervention. We analyzed the data using repeated-measure analysis of variance. Mean age of the participants was 38.5 (SD = 5.4) years, and 50% were women. Compared with sham rTMS, real rTMS was effective in decreasing modified Ashworth scale (rTMS × time: F [df = 2] = 7.44; P = 0.008). Real rTMS group had lower modified Ashworth scale scores at the end of rTMS sessions (estimate = -0.938; SE = 0.295; P = 0.019) and at the end of follow-up (estimate = -0.688; SE = 0.277; P = 0.048) compared with the sham rTMS group. Real and sham rTMS groups were not different in the secondary outcomes. Repetitive transcranial magnetic stimulation is an effective method in reducing lower limb spasticity of patients with hereditary spastic paraplegia.

Motor Network Reorganization After Repetitive Transcranial Magnetic Stimulation in Early Stroke Patients: A Resting State fMRI Study

Objective To compare the effects of high-frequency (10 Hz) versus low-frequency (1 Hz) repetitive Transcranial Magnetic Stimulation (rTMS) on motor recovery and functional reorganization of the cortical motor network during the early phase of stroke. Methods Forty-six hospitalized, first-ever ischemic stroke patients in early stage (within two weeks) with upper limb motor deficits were recruited. They were randomly allocated to three groups with 10 Hz ipsilesional rTMS, 1 Hz contralesional rTMS, and sham rTMS of five daily session. All patients underwent motor function (Upper Extremity Fugl–Meyer), neurophysiological and resting-state functional Magnetic Resonance Imaging (fMRI) (rs-fMRI) assessments before and after rTMS intervention. Motor recovery (△Fugl–Meyer Assessment) was defined as motor function changes before and after rTMS intervention. Motor function assessment was reevaluated at time point of three month follow-up. Results The two real rTMS groups manifested greater motor improvements than the sham group. The effect sustained for at least 3 months after the end of the treatment sessions. Compared with the sham group, 10 Hz ipsilesional rTMS group presented increased resting-state functional connectivity (FC) between ipsilesional primary motor cortex (M1) and contralesional M1 (P = .007), whereas 1 Hz contralesional rTMS group presented increased FC between contralesional M1 and ipsilesional supplementary motor area (P = .010), which were positively correlated with motor recovery (P < .05). Conclusion Beneficial effect of rTMS on motor recovery might be underlaid by increased FC between stimulating site and the remote motor areas, highlighting the motor network reorganization mechanism of rTMS in early post-stroke phase.

Increased migraine-free intervals with multifocal repetitive transcranial magnetic stimulation

IntroductionEpisodic migraine is a debilitating condition associated with vast impairments of health, daily living, and life quality. Several prophylactic treatments exist, having a moderate ratio of action related to side effects and therapy costs. Repetitive transcranial magnetic stimulation (rTMS) is an evidence based therapy in several neuropsychiatric conditions, showing robust efficacy in alleviating specific symptoms. However, its efficacy in migraine disorders is unequivocal and might be tightly linked to the applied rTMS protocol. We hypothesized that multifocal rTMS paradigm could improve clinical outcomes in patients with episodic migraine by reducing the number of migraine days, frequency and intensity of migraine attacks, and improve the quality of life. MethodsWe conducted an experimental, double-blind, randomized controlled study by applying a multifocal rTMS paradigm. Patients with episodic migraine with or without aura were enrolled in two centers from August 2018, to December 2019, and randomized to receive either real (n = 37) or sham (sham coil stimulation, n = 28) multifocal rTMS for six sessions over two weeks. Patients, physicians, and raters were blinded to the applied protocol. The experimental multifocal rTMS protocol included two components; first, swipe stimulation of 13 trains of 140 pulses/train, 67 Hz, 60% of RMT, and 2s intertrain interval and second, spot burst stimulation of 33 trains of 15 pulses/train, 67 Hz, 85% of RMT, and 8s intertrain interval. Reduction >50% from the baseline in migraine days (as primary outcome) and frequency and intensity of migraine attacks (as key secondary outcomes) over a 12-week period were assessed. To balance the baseline variables between the treatment arms, we applied the propensity score matching through the logistic regression. ResultsAmong 65 randomized patients, sixty (age 39.7 ± 11.6; 52 females; real rTMS n = 33 and sham rTMS n = 27) completed the trial and five patients dropped out. Over 12 weeks, the responder's rate in the number of migraine days was significantly higher in the real rTMS compared to the sham group (42% vs. 26%, p < 0.05). The mean migraine days per month decreased from 7.6 to 4.3 days in the real rTMS group and from 6.2 to 4.3 days in the sham rTMS group, resulting in a difference with real vs. sham rTMS of −3.2 days (p < 0.05). Similarly, over the 12-week period, the responder's rate in the reduction of migraine attacks frequency was higher in the real rTMS compared to the sham group (42% vs 33%, p < 0.05). No serious adverse events were observed. ConclusionOur pilot study shows compelling evidence in a double placebo-controlled trial that multifocal rTMS is an effective and well-tolerated preventive treatment in patients with episodic migraine.

The Effect of Sham Controlled Continuous Theta Burst Stimulation and Low Frequency Repetitive Transcranial Magnetic Stimulation on Upper Extremity Spasticity and Functional Recovery in Chronic Ischemic Stroke Patients

ObjectiveThis randomized controlled study examined the effect of continuous theta burst stimulation (cTBS) and low frequency repetitive transcranial magnetic stimulation (rTMS) on upper extremity spasticity and functional recovery in chronic ischemic stroke patients. Materials and MethodsTwenty chronic ischemic stroke patients were randomized into three groups as real rTMS group (n = 7), real cTBS group (n = 7) and sham cTBS group (n = 6), in which real rTMS with physical therapy (PT), real cTBS with PT and sham cTBS with PT were applied in 10 sessions, respectively. The evaluation parameters were assessed at pre-treatment, post-treatment and follow up at 4 weeks. ResultsTen sessions of real rTMS or real cTBS combined with PT were found beneficial in motor functional recovery and daily living activities both at post-treatment and follow up at 4 weeks (p ˂ 0.05). In the sham cTBS group, functional improvement was not significant (p > 0.05). In addition, in the real rTMS group, elbow flexor, pronator, wrist flexor and finger flexor spasticity were significantly decreased; in the real cTBS group, significant decrease was observed in the elbow flexor and wrist flexor spasticity (p ˂ 0.05). In comparison with sham cTBS group, only in the real cTBS group, significant improvement was observed in the level of wrist flexor spasticity at follow up at 4 weeks (p ˂ 0.017). ConclusionsIn this study, it was observed that real cTBS or real rTMS combined with PT provided improvement on upper extremity motor functions and daily living activities in chronic ischemic stroke patients, but improvement in spasticity was limited.

Bilateral Repetitive Transcranial Magnetic Stimulation With the H-Coil in Parkinson's Disease: A Randomized, Sham-Controlled Study.

Background: Pilot open-label application of high-frequency repetitive transcranial magnetic stimulation (rTMS) with H-coil in Parkinson's Disease (PD) have shown promising results.Objective: To evaluate safety and efficacy of high-frequency rTMS with H-coil in PD in a double-blind, placebo-controlled, randomized study.Methods: Sixty patients with PD were randomized into 3 groups: M1-PFC (real stimulation on primary motor-M1 and pre-frontal cortices-PFC), M1 (real rTMS on M1, sham on PFC), Sham (apparent stimulation). Primary outcome was baseline-normalized percent improvement in UPDRS part III OFF-therapy at the end of treatment (12 rTMS sessions, 4 weeks). Secondary outcomes were improvement in UPDRS part III sub-scores, timed tests, and neuropsychological tests. Statistical analysis compared improvement following real and sham stimulation at the end of the protocol using either a t-test or a Mann-Whitney test.Results: All patients tolerated the treatment and concluded the study. One patient from M1-PFC group was excluded from the analysis due to newly discovered uncontrolled diabetes mellitus. No serious adverse effect was recorded. At the end of treatment, patients receiving real rTMS (M1-PFC and M1 combined) showed significantly greater improvement compared to sham in UPDRS part III total score (p = 0.007), tremor subscore (p = 0.011), and lateralized sub-scores (p = 0.042 for the more affected side; p = 0.012 for the less affected side). No significant differences have been oserved in safety and efficacy outcomes between the two real rTMS groups. Notably, mild, not-distressing and transient dyskinesias occurred in 3 patients after real rTMS in OFF state.Conclusions: The present findings suggest that high-frequency rTMS with H-coil is a safe and potentially effective procedure and prompt larger studies for validation as add-on treatment in PD.

Repetitive transcranial magnetic stimulation treatment in severe, enduring anorexia nervosa: An open longer-term follow-up.

This study assessed longer-term outcomes from a randomised controlled feasibility trial of 20 sessions of real versus sham high-frequency repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex in adults with severe, enduring anorexia nervosa (SE-AN). Thirty participants who completed the original study protocol were invited to take part in an open follow-up (18-months post-randomisation), assessing body mass index (BMI), eating disorder (ED) symptoms and other psychopathology. Twenty-four participants (12 each originally allocated to real/sham) completed the 18-month follow-up. Ten of 12 participants who originally received sham treatment had real rTMS at some stage during the follow-up. A medium between-group effect size was seen for BMI change from baseline to 18-months, favouring those originally allocated to real rTMS. In this group at 18-months, five participants were weight recovered (BMI ≥18.5 kg/m2 ), compared with one participant in the original sham group. Both groups showed further improvement in ED symptoms during the follow-up. Effects on mood were largely maintained at follow-up, with catch-up effects in the original sham group. Findings suggest that rTMS treatment effects on mood are durable and that BMI and ED symptom improvements need time to emerge. Large-scale trials are needed.

Neuronavigation based 10 sessions of repetitive transcranial magnetic stimulation therapy in chronic migraine: an exploratory study.

Chronic migraine is a disease of altered cortical excitability. Repetitive transcranial magnetic stimulation provides a novel non-invasive method to target the nociceptive circuits in the cortex. Motor cortex is one such potential target. In this study, we targeted the left motor cortex using fMRI-guided neuronavigation. Twenty right-handed patients were randomized into real and sham rTMS group. Baseline subjective pain assessments were done using visual analog scale (VAS) and questionnaires: State-Trait Anxiety Inventory, Becks Depression Inventory, and Migraine Disability Assessment (MIDAS) questionnaire. Objectively, pain was assessed by means of thermal pain thresholds using quantitative sensory testing. For corticomotor excitability parameters, resting motor thresholds and motor-evoked potentials were mapped. For rTMS total, 600 pulses in 10 trains at 10Hz with an intertrain interval of 60s were delivered in each session. Ten such sessions were given 5days per week over 2 consecutive weeks. The duration of each session was 10min. Real rTMS was administered at 70% of Resting MT. All the tests were repeated post-intervention and after 1month of follow-up. There are no studies reporting the use of fMRI-based TMS for targeting the motor cortex in CM patients. We observed a significant reduction in the mean VAS rating, headache frequency, and MIDAS questionnaire in real rTMS group which was maintained after 1month of follow-up. Ten sessions of fMRI-based rTMS over the left motor cortex may provide long-term pain relief in CM, but further studies are warranted to confirm our preliminary findings.

Cognitive and emotional predictors of real versus sham repetitive transcranial magnetic stimulation treatment response in methamphetamine use disorder

Background and aimsRepetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) can effectively reduce cravings in methamphetamine use disorder (MUD). However, a considerable group still fails to respond. Cognitive and emotional disturbance, as well as impulsive features, are widespread in patients with MUD and might mediate the treatment response of rTMS. The purpose of this study is to figure out whether these variables can help predicting patients' responses to rTMS treatment. MethodsNinety-seven patients with severe MUD and thirty-one gender- and age-matched healthy subjects were included. Patients were randomized to receive 20 sessions of real or sham rTMS. Intermittent theta burst protocols (iTBS) or sham iTBS were applied every weekday over the DLPFC for 20 daily sessions. Both groups received regular treatment. Craving induced by drug-related cue was measured before and after stimulation. Cognition was evaluated by using the CogState Battery. Baseline characteristics were collected through the Addiction Severity Index, Patient Health Questionnaire-9, General Anxiety Disorder Scale-7, and Barrett Impulsivity Scale-11. ResultsResults showed that patients with MUD have worse spatial working memory, problem-solving ability, as well as depression and anxiety symptoms compared with healthy controls. Cognition and emotion differed between responders (craving decrease ≥60%) and non-responders in real rTMS group but not in the sham group. Better cognitive and emotional functions means that patients have higher possibility for better response to real rTMS treatment. ConclusionsThis study suggests that cognitive, emotional and impulsive features could be used to predict the prospective treatment responses of rTMS in patients with MUD.

Efficacy of Low-Frequency Repetitive Transcranial Magnetic Stimulation in Ischemic Stroke: A Double-Blind Randomized Controlled Trial

ObjectiveTo investigate the role of low-frequency repetitive transcranial magnetic stimulation (rTMS) along with conventional physiotherapy in the functional recovery of patients with subacute ischemic stroke. DesignDouble-blind, parallel group, randomized controlled trial. SettingThe outpatient department of a tertiary hospital participants: first ever ischemic stroke patients (N=96) in the previous 15 days were recruited and were randomized after a run-in period of 75±7 days into real rTMS (n=47) and sham rTMS (n=49) groups. InterventionConventional physical therapy was given to both the groups for 90±7 days postrecruitment. Total 10 sessions of low-frequency rTMS on contralesional premotor cortex was administered to real rTMS group (n=47) over a period of 2 weeks followed by physiotherapy regime for 45-50 minutes. Main Outcome MeasuresThe primary efficacy outcomes were change in modified Barthel Index (mBI) score (pre- to postscore) and proportion of participants with mBI score more than 90, measured at 90±7 days postrecruitment. The secondary outcomes were change in Fugl-Meyer Assessment–upper extremity, Fugl-Meyer Assessment–lower extremity, Hamilton Depression Scale, modified Rankin Scale, and National Institute of Health and Stroke Scale (pre- to post-rTMS) scores at 90±7 days post recruitment. ResultsModified intention to treat analysis showed a significant increase in the mBI score from pre- to post-rTMS in real rTMS group (4.96±4.06) versus sham rTMS group (2.65±3.25). There was no significant difference in proportion of patients with mBI>90 (55% vs 59%; P=.86) at 3 months between the groups. ConclusionIn patients with subacute ischemic stroke, 1-Hz low-frequency rTMS on contralesional premotor cortex along with conventional physical therapy resulted in significant change in mBI score.

The safety and efficacy of adjunctive 20-Hz repetitive transcranial magnetic stimulation for treatment of negative symptoms in patients with schizophrenia: A double-blinded, randomized, sham-controlled study.

Background:Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment strategy for negative symptoms. However, the evidence for its efficacy is mixed, with contradictory results between studies due to lack of consensus about the optimal stimulation parameters.Aim:The present study was planned to assess the safety and efficacy of 20-Hz rTMS over left dorsolateral prefrontal cortex (Lt-DLPFC) with more robust stimulation parameters for adjunctive treatment of negative symptoms in patients with schizophrenia.Materials and Methods:Thirty patients with negative symptoms of schizophrenia (Positive and Negative Syndrome Scale [PANSS] negative subscore ≥15) were randomized to receive a 4-week treatment with either real-rTMS (n = 15) or sham-rTMS (n = 15). The study outcomes were assessed at baseline, after 5th and 20th rTMS sessions with PANSS, Scale for the Assessment of Negative Symptoms (SANS), Calgary Depression Scale for Schizophrenia, Clinical Global Impressions-Severity of illness scale, and rTMS side-effect checklist.Results:There was significantly greater reduction in negative symptoms assessed by SANS score in the real rTMS group, compared with the sham rTMS group. There was no significant difference in the rate of side-effects reported between the two groups. The rTMS treatment was well-tolerated by all the patients, except one seizure episode reported in the active group.Conclusion:The high-frequency rTMS protocol was safe and well-tolerated, provided patients prone to developing seizure were excluded by baseline electroencephalography prior to starting of the treatment. The 20-Hz rTMS over Lt-DLPFC with more robust stimulation parameters (100% motor threshold and 40,000 pulses) might be an effective augmentation strategy for the treatment of negative symptoms in schizophrenia.