Sessions Of High-frequency rTMS Research Articles

The effect of repetitive transcranial magnetic stimulation on social cognition in autism spectrum disorder: preliminary analysis of a pilot clinical trial

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a promising tool for modulating the cortical activity in individuals with autism spectrum disorder (ASD), however there is currently no consensus regarding the optimal cortical targets or stimulation paradigms. One prevailing theory in ASD attributes the core social deficits to dysfunction of the mirror neurons located in the inferior parietal lobule (IPL) and inferior frontal gyrus. This is an ongoing pilot clinical trial which aims to explore the effects of excitatory modulation of the IPL via rTMS on social cognition in ASD. At the time of drafting this manuscript, 11 subjects with ASD, 10 boys and 1 girl with the mean age of 13.27 years had completed the study, receiving 10 sessions of high frequency rTMS on the left or right IPL and sham stimulation on the contralateral IPL. None of the 11 subjects experienced any adverse effects. This preliminary analysis on the 11 subjects shows a favorable response to high frequency rTMS modulation of the mirror neurons at IPL on measures of social awareness. Our observations indicate that subjects with ASD levels I and II are more likely to have a favorable response to this intervention.

Effects of repetitive transcranial magnetic stimulation combined with action-observation-execution on social interaction and communication in autism spectrum disorder: Feasibility study

ObjectiveTo investigate the feasibility of a combined high-frequency rTMS (HF-rTMS) with action observation and execution (AOE) on social interaction and communication in children with Autistic Spectrum Disorder (ASD). Materials and methodsFifteen children underwent 10 sessions of 5-Hz HF-rTMS on the right inferior frontal gyrus combined with AOE. An experimental group received the real HF-rTMS while the control group received the sham one. For the AOE protocol, they were instructed to watch and imitate a video showing the procedure, including reaching and grasping tasks, gustatory tasks, and facial expressions. Their behavioural outcomes were evaluated using the Vineland Adaptive Behaviour Scale (VABS) and electroencephalograms (EEGs) recorded at three time points: baseline, immediately after each treatment, and at the 1-week follow-up after the 10th treatment. ResultsThere were increased VABS subitem scores in the experimental group, including the receptive, expressive, domestic, and community scores but no such increase was observed in the control group. For the EEG, the beta rhythm at C3 and C4 increased in the experimental group. Additionally, positive correlations were observed between changes in the scores for the expressive subitem and changes in the beta rhythm on the C4 electrode at baseline and immediately after treatment in the experimental group. The control group showed no significant differences in any items for both observation and imitation times. ConclusionTen sessions of HF-rTMS combined with AOE could improve both the subitems of communication and daily living skills domain in children aged 7–12 years with ASD. Although it is still inconclusive, this behavioural improvement may be partly attributable to increased cortical activity, as evidenced by beta rhythms.

Repetitive Transcranial Magnetic Stimulation With H-Coil Coupled With Cycling for Improving Lower Limb Motor Function After Stroke: An Exploratory Study

Repetitive transcranial magnetic stimulation (rTMS) has been recognized as a promising intervention for the treatment of post-stroke motor deficits. Here, we explore safety, feasibility, and potential effectiveness of high-frequency rTMS (HF-rTMS) delivered with the Hesed coil (H-coil) during active cycling on paretic lower extremity (LE) motor function in chronic stroke. Twelve subjects with a first-ever stroke were recruited in this double-blind, placebo controlled, crossover study. Eleven sessions of HF-rTMS (40 2s-trains of 20Hz at 90% resting leg motor threshold) were delivered over the LE motor areas using the H-coil during active cycling for three weeks. Each subject underwent both real and sham rTMS treatments separated by a four-week washout period, in a random sequence. Vital signs were recorded before and after each rTMS session. Any discomfort related to stimulation and side effects were recorded. LE function was also evaluated with Fugl-Meyer assessment (FMA-LE), spasticity was assessed with modified-Ashworth scale and measures of gait speed and endurance (10-meter and 6-min walk tests, respectively) were recorded. No participant reported serious adverse effects. During real rTMS, 4 of 12 subjects reported mild side effects including transitory dizziness and muscle twitches on shoulder, so that intensity of stimulation initially set at 90% of RMT was reduced to 80% of RMT on average in these four subjects. Only real treatment was associated with a significant and sustained improvement in FMA-LL (67% responders vs. 9% of the sham). Spasticity significantly ameliorated only after the real rTMS. Real treatment did not offer advantages on walking timed measures when compared with sham. This exploratory study suggests that bilateral HF-rTMS combined with cycling is safe and potentially effective in ameliorating paretic LE motor function and spasticity, rather than gait speed or endurance, in chronic stroke.

P30 The effect of a single session of high frequency rTMS on heart rate variability; an investigation of the role of RDLPFC in emotional appraisal and regulation

P30 The effect of a single session of high frequency rTMS on heart rate variability; an investigation of the role of RDLPFC in emotional appraisal and regulation

O-14 Does rTMS targeting with individual functional connectivity analysis improve the efficacy in recurrent depression?

Background Clinical efficacy of rTMS in recurrent depression (RD) is highly variable. It is important to search for approaches improving the efficacy, and choosing the target based on functional connectivity (FC) is promising. We aimed to compare the effects of the standard and FC-based rTMS targeting in RD patients. Methods 30 pharmacoresistant RD patients (17 women, age median 40, quartiles 28, 44) were divided into two groups comparable in age, sex and RD severity. All patients received 20 sessions of high frequency rTMS of lDLPFC (20 Hz, 100% RMT, 3200 stimuli/session). In the standard targeting group, the stimulation points were 5 cm anterior to the individual APB muscle hotspots. In the FC-based targeting group, rTMS was targeted to the individual points in the left DLPFC with maximum negative correlation to subgenual cingulate (10 mm radius sphere at MNI coordinates (6,16,−10)). We used Beck depression inventory (BDI) and SF-36 questionnaires before rTMS, after 10 and 20 sessions of rTMS for clinical evaluation. Results In the FC-based targeting group, significant decreases in both BDI and SF-36 scores were observed after 10 rTMS sessions (Wilcoxon, p 0.05). Conclusions Both methods of rTMS targeting are effective in depression, but the use of FC analysis allows accelerating the onset of the effect.

Peripheral plus central repetitive transcranial magnetic stimulation (rTMS) for upper limb motor rehabilitation in chronic stroke - A case report

Motor dysfunction of the hand and upper limb is a major cause of physical disability for patients with chronic stroke. Our aim was to investigate the effectiveness of a peripheral plus central repetitive transcranial magnetic stimulation (rTMS) treatment for upper limb motor rehabilitation in chronic stroke patients. We reported the case of a patient WLX, who had one ischemic stroke more than 3 years ago, and had underwent intermittent rehabilitation since then. He still had profound right upper limb paralysis and moderate spasm, accompanied with non-fluent aphasia when came to our department; and complained that his recovery had been rather slow for about two years. In addition to the custom rehabilitation, we applied a peripheral plus central rTMS paradigm to him, which included 3 sessions of peripheral magnetic stimulation to his paralyzed right forearm, followed by a session of high frequency rTMS to the bilateral sensorimotor cortex region. The total magnetic stimulation therapy lasted about 30 min a day, and was applied 5 days/week for 4 weeks. After 4 weeks’ treatment, the patient's Fulg–Meyer upper limb assessment (FMA) score was obviously improved (from 27 to 37 points), and the spasm was largely relieved in his right hand and arm. Peripheral plus central rTMS might be an effective treatment for motor dysfunction of chronic stroke patients.

Changes in brain connectivity during a sham-controlled, transcranial magnetic stimulation trial for depression

BackgroundThe subgenual anterior cingulate cortex (sgACC) has been implicated in major depressive disorder (MDD), and this study evaluated sgACC connectivity before and after repetitive transcranial magnetic stimulation (rTMS) treatment. MethodsThirty-two MDD patients entered a sham-controlled, double-blinded, randomized trial of rTMS to the left dorsolateral prefrontal cortex (dlFPC). Subjects underwent resting state functional magnetic resonance imaging before and after 20 sessions of high frequency rTMS. Seed voxels identified the affective network (AN; sgACC, amygdala), default mode network (DMN; posterior cingulate cortex [PCC]), and fronto-parietal network (FPN; dlPFC stimulation site). ResultsThere was no significant effect of active rTMS over sham on the primary outcome measure (Montgomery-Asberg Depression Scale rating), with both groups improving over time, and no specific effect of rTMS (sham vs active) on connectivity. However, among patients who showed significant improvement, sgACC connectivity decreased for sham (to AN, trend to DMN) and active rTMS responders (to AN, DMN, FPN), but not in non-responders, who tended to maintain connectivity. Including subjects who started with sham but then received open-label active treatment, baseline connectivity from the PCC to the anterior insula was greater in non-responders compared to responders (n = 27, excluding 5 sham responders). LimitationsThe sample size was small; the stimulation target was non-standard, and the lack of a significant clinical effect of rTMS limits conclusions about negative findings. ConclusionssgACC connectivity reduces along with depressive symptoms, not specific to rTMS therapy. Altered connectivity of DMN with anterior insula may reflect a type of patient less likely to respond to an intervention.

O204 Simultaneous bi-hemispheric repetitive transcranial magnetic stimulation for upper limb motor recovery in chronic stroke: A double blind placebo controlled study

Objective repetitive transcranial magnetic stimulation (rTMS) is a promising intervention for the treatment of post-stroke motor deficits. Since the crucial role of non-primary motor cortices and contralesional brain areas is emerging for motor recovery in chronic stroke; we assessed safety and efficacy of bilateral rTMS over the motor areas associated to physical training (PT) on upper extremity (UE) motor function. Methods double-blind, placebo-controlled trial on 20 patients with chronic stroke conditioning moderate to mild upper limb motor impairment. Eleven sessions of high frequency rTMS were delivered with the H-coil over the motor areas bilaterally. Subjects were randomly allocated to the real rTMS plus PT or the placebo (sham) rTMS plus PT. UE impairment was evaluated by the Fugl-Meyer assessment for UE (FM-UE), Modified Ashworth Scale (MAS) and hand grip strength at baseline (T0), after treatment (T1) and one-month follow-up (T2). Results no serious adverse events were reported. At T1 FM-UE significantly improved in both groups, while at T2 the improvement was significant only for the real group. The improvement was significantly higher in the real compared with the sham group. In the real group, greater improvement in FM-UE was found in patients moderately impaired compared with less impaired at baseline. Spasticity and hand grip strength also significantly improved in the real group at T1 and amelioration of spasticity persisted also at T2. Conclusion bilateral high-frequency rTMS with H-coil associated with PT is safe and enhances the effect of PT alone. Although plegic patients were not included, subjects with moderate rather than mild motor impairment may mainly benefit from this stimulation protocol.

A single session of repetitive transcranial magnetic stimulation of the prefrontal cortex reduces cue-induced craving in patients with gambling disorder

BackgroundGambling disorder (GD) is common and disabling addictive disorder. In patients with substance use disorders, the application of repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers promise to alleviate craving. We hypothesized that applying real compared to sham rTMS over the left DLPFC would reduce gambling craving in patients with GD. MethodsIn a randomized sham-controlled crossover design, 22 treatment-seeking patients with GD received real or sham treatment with high frequency rTMS over the left DLPFC followed a week later by the other type of treatment. Before and after each rTMS session, participants rated their gambling craving (from 0 to 100) before and after viewing a gambling video used as a cue. We used the Yale-Brown Obsessive Compulsive Scale adapted for Pathological Gambling to assess gambling behavior before and 7 days after each rTMS session. ResultsAs compared to sham (mean +0.74; standard deviation±3.03), real rTMS significantly decreased cue-induced craving (−2.12±3.39; F(1,19)=4.87; P=0.04; partial η2=0.05; 95% CI: 0.00–0.21). No significant effect of rTMS was observed on gambling behavior. ConclusionsPatients with GD reported decreased cue-induced craving following a single session of high frequency rTMS applied over the left DLPFC. Further large randomized controlled studies are needed to determine the usefulness of rTMS in GD.

Brain SPECT guided repetitive transcranial magnetic stimulation (rTMS) in treatment resistant major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) has emerged as a potential treatment in treatment resistant major depressive disorder (MDD). However, there is no consensus about the exact site of stimulation for rTMS. Single-photon emission computed tomography (SPECT) offers a potential technique in deciding the site of stimulation. The present study was conducted to assess the difference in outcome of brain SPECT assisted rTMS versus standard protocol of twenty sessions of high frequency rTMS as add on treatment in 20 patients with treatment resistant MDD, given over a period of 4 weeks. Thirteen subjects (group I) received high frequency rTMS over an area of hypoperfusion in the prefrontal cortex, as identified on SPECT, whereas 7 subjects (group II) were administered rTMS in the left dorsoslateral prefrontal cortex (DLPFC) area. Improvement was monitored using standardized instruments. Patients in the group I showed a significantly better response compared to those in the group II. In group I, 46% of the subjects were responders on MADRS, 38% on BDI and 77% on CGI. The parallel figures of responders in Group II were 0% on MADRS, 14% on BDI and 43% on CGI. There were no remitters in the study. No significant untoward side effects were noticed. The study had limitations of a small sample size and non-controlled design, and all the subjects were also receiving the standard antidepressant therapy. Administration of rTMS over brain SPECT specified area of hypoperfusion may have a better clinical outcome compared to the standard protocol.

Effects of prefrontal rTMS on autonomic reactions to affective pictures.

Repetitive transcranial magnetic stimulation (rTMS) can modulate the excitability of stimulated cortical areas, such as prefrontal areas involved in emotion regulation. Low frequency (LF) rTMS is expected to have inhibitory effects on prefrontal regions, and thereby should disinhibit limbic activity, resulting in enhanced emotional and autonomic reactions. For high frequency (HF) rTMS, the opposite pattern might be assumed. The objective of this study was to determine the effects of different rTMS frequencies applied to the right dlPFC on autonomic functions and on emotional perception. In a crossover design, two groups of 20 healthy young women were either stimulated with one session of LF rTMS (1Hz) or one session of HF rTMS (10Hz), compared to sham stimulation. We assessed phasic cardiac responses (PCR), skin conductance reactions (SCR), and emotional appraisal of emotional pictures as well as recognition memory after each rTMS application. After LF rTMS, PCR (heart rate deceleration) during presentation of pictures with negative and neutral valence was significantly increased compared to the presentation of positive pictures. In contrast, the modulatory effect of picture valence and arousal on the cardiac orienting response was absent after HF rTMS. Our results suggest that frontal LF rTMS indirectly activates the ANS via inhibition of the right dlPFC activity, likely by enhancing the sensory processing or attention to aversive and neutral stimuli.

Localized Potentiation of Sleep Slow-Wave Activity Induced by Prefrontal Repetitive Transcranial Magnetic Stimulation in Patients with a Major Depressive Episode

BackgroundThe effects of repetitive transcranial magnetic stimulation (rTMS) on sleep structure in major depression are currently unknown. ObjectiveTo determine the effects of prefrontal rTMS on sleep electroencephalography (EEG) in major depression. MethodsIn this open-label pilot study, twelve male patients with relatively mild depression, who had been medication-resistant, underwent 10 daily rTMS sessions over the left dorsolateral prefrontal cortex (DLPFC). Polysomnographic (PSG) data were recorded over four nights: Adaptation, Baseline, Post-1 (after the fifth rTMS session), and Post-2 (after the tenth rTMS session). Discrete Fourier Transform (DFT) band power analyses were performed to quantify delta and sigma band activities during Stages II–IV, and determine time courses of these activities between Baseline and Post-1 (first five sessions) and between Post-1 and Post-2 (last five sessions). ResultsPost-hoc tests based on a three-way ANOVA model indicated significant delta power increase at F3 (t11 = −2.762, P = 0.018) during the first five sessions; however, sigma power was unchanged. No significant band power changes were observed during the second half. Stages II–IV (percent total sleep time) increased significantly during the first half (t12 = −2.43, P = 0.033). No other significant changes in sleep parameters or clinical correlations were observed. ConclusionsThe first five sessions of high frequency rTMS to the left DLPFC increase slow-wave activity (SWA) at F3, possibly reflecting locally enhanced synaptic plasticity induced by rTMS. This increased activity was not observed during the last half, possibly due to a homeostatic regulation mechanism intrinsic to SWA.

Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer’s dementia

The aim of the study was to compare the long-term efficacy of high versus low frequency repetitive transcranial magnetic stimulation (rTMS), applied bilaterally over the dorsolateral prefrontal cortex (DLPFC), on cognitive function and cortical excitability of patients with Alzheimer's disease (AD). Forty-five AD patients were randomly classified into three groups. The first two groups received real rTMS over the DLPFC (20 and 1 Hz, respectively) while the third group received sham stimulation. All patients received one session daily for five consecutive days. In each session, rTMS was applied first over the right DLPFC, immediately followed by rTMS over the left DLPFC. Mini Mental State Examination (MMSE), Instrumental Daily Living Activity (IADL) scale and the Geriatric Depression Scale (GDS) were assessed before, after the last (fifth) session, and then followed up at 1 and 3 months. Neurophysiological evaluations included resting and active motor threshold (rMT and aMT), and the duration of transcallosal inhibition (TI) before and after the end of the treatment sessions. At base line assessment there were no significant differences between groups in any of the rating scales. The high frequency rTMS group improved significantly more than the low frequency and sham groups in all rating scales (MMSE, IADL, and GDS) and at all time points after treatment. Measures of cortical excitability immediately after the last treatment session showed that treatment with 20 Hz rTMS reduced TI duration. These results confirm that five daily sessions of high frequency rTMS over the left and then the right DLPFC improves cognitive function in patients with mild to moderate degree of AD. This improvement was maintained for 3 months. High frequency rTMS may be a useful addition to therapy for the treatment of AD.

Effect of high frequency repetitive transcranial magnetic stimulation on reaction time, clinical features and cognitive functions in patients with Parkinson’s disease

The aim of the present study was to investigate the effects of one session of high-frequency repetitive transcranial magnetic stimulation (rTMS) applied over the left dorsal premotor cortex (PMd) and left dorsolateral prefrontal cortex (DLPFC) on choice reaction time in a noise-compatibility task, and cognitive functions in patients with Parkinson's disease (PD). Clinical motor symptoms of PD were assessed as well. Ten patients with PD entered a randomized, placebo-controlled study with a crossover design. Each patient received 10 Hz stimulation over the left PMd and DLPFC (active stimulation sites) and the occipital cortex (OCC; a control stimulation site) in the OFF motor state, i.e. at least after 12 h of dopaminergic drugs withdrawal. Frameless stereotaxy was used to target the optimal position of the coil. For the evaluation of reaction time, we used a noise-compatibility paradigm. A short battery of neuropsychological tests was performed to evaluate executive functions, working memory, and psychomotor speed. Clinical assessment included a clinical motor evaluation using part III of the Unified Parkinson's Disease Rating Scale. Statistical analysis revealed no significant effect of rTMS applied over the left PMd and/or DLPFC in patients with PD in any of the measured parameters. In this study, we did not observe any effect of one session of high frequency rTMS applied over the left PMd and/or DLPFC on choice reaction time in a noise-compatibility task, cognitive functions, or motor features in patients with PD. rTMS applied over all three stimulated areas was well tolerated and safe in terms of the cognitive and motor effects.

Neurocognitive Effects of Repetitive Transcranial Magnetic Stimulation in Patients with Cerebrovascular Disease Without Dementia

Aims: The results of our pilot study suggested that one session of high frequency rTMS applied over the left dorsolateral prefrontal cortex (DLPFC) might induce measurable positive effects on executive functioning in patients with mild cognitive impairment of the vascular type without dementia (MCI-V). The aims of the current study were to replicate the results of our pilot study using a frameless stereotaxy as opposed to the standard and routinely used procedure. We also studied the effects of low frequency rTMS. Patients and method: Seven patients with MCI-V participated in a randomized, controlled, blind study with a crossover design. Each patient received 10 Hz and 1 Hz stimulation over the left DLPFC (an active stimulation site) or the motor cortex (MC; a control stimulation site). Frameless stereotaxy was used to target the DLPFC. The order of sites and frequencies was randomized. A short battery of neuropsychological tests was performed to evaluate executive function, working memory, and psychomotor speed. Results: One session of both high and low frequency rTMS was well tolerated and safe in terms of the cognitive after-effects in patients with MCI-V. We did not observe any significant frequency dependent or stimulation site-dependent cognitive effects of rTMS. Conclusion: We found neither positive nor negative significant effect of either low or high frequency rTMS applied over the DLPFC or the MC, while a mild positive site-specific effect of 10 Hz rTMS was observed in our pilot study on the Stroop interference results. These results suggested that MCI-V is a heterogeneous and poorly defined entity and, thus, rTMS might be useful in a subpopulation of this group of patients.