Active rTMS Research Articles

Transcranial Direct Current Stimulation Combined With Repetitive Transcranial Magnetic Stimulation for Depression: A Randomized Clinical Trial.

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are both recognized as effective treatments for depression when applied individually. However, it is unknown whether rTMS combined with tDCS has better efficacy in the treatment of major depressive disorder (MDD). To investigate the clinical effectiveness and safety of rTMS, tDCS, tDCS + rTMS, and sham tDCS + sham rTMS after 2 weeks of treatment in patients with MDD. This double-blind, sham-controlled randomized clinical trial was conducted from November 2021 to April 2023 at 3 hospitals in China (Kangning Hospital affiliated with Ningbo University, Lishui Second People's Hospital, and Taizhou Second People's Hospital). Adult patients (aged 18-65 years) who were diagnosed with major depressive disorder were recruited. Participants were randomly assigned to 1 of 4 interventions: active tDCS + active rTMS, sham tDCS + active rTMS, active tDCS + sham rTMS, and sham tDCS + sham rTMS. Data analysis followed an intention-to-treat approach. Patients received a 2-week course of treatment. The tDCS was administered using a 2-mA direct current stimulator with electrodes placed on the left and right dorsolateral prefrontal cortex (DLPFC). Each tDCS session lasted 20 minutes and was conducted 30 to 60 minutes prior to the rTMS session for a total of 10 sessions. The rTMS was delivered at a frequency of 10 Hz using a figure-8 coil placed on the left DLPFC, with each session consisting of 1600 pulses. Treatments were administered 5 times per week for 2 weeks. Sham treatments were performed with a pseudostimulation coil and emitted only sound. The primary outcome was the change in total score from baseline to week 2 on the 24-item Hamilton Depression Rating Scale (HDRS-24; score range: 0-52, with the highest score indicating more severe symptoms). A total of 240 participants (139 females [57.9%]; mean [SD] age, 32.50 [15.18] years) were included. As a primary outcome, patients who received active tDCS + active rTMS showed a significantly greater reduction in mean (SD) HDRS-24 total scores compared with patients in the other 3 groups (active tDCS + active rTMS: 18.33 [5.39], sham tDCS + active rTMS: 14.86 [5.59], active tDCS + sham rTMS: 9.21 [4.61], and sham tDCS + sham rTMS: 10.77 [5.67]; F3,236 = 35.79; η2 = 0.31 [95% CI, 0.21-0.39]; P < .001). This trial found that tDCS + rTMS was a more effective and safe treatment option than either the tDCS or rTMS intervention alone for patients with MDD. China Clinical Trial Registry Identifier ChiCTR2100052122.

Repetitive Transcranial Magnetic Stimulation for Auditory Verbal Hallucinations in Schizophrenia: A Randomized Clinical Trial.

Auditory verbal hallucinations (AVH) are a common symptom of schizophrenia, increasing the patient's risks of suicide and violence. Repetitive transcranial magnetic stimulation (rTMS) is a potential treatment for AVH. To investigate the effect of imaging-navigated rTMS on AVH in patients with schizophrenia. This 6-week, double-blind, sham-controlled, randomized clinical trial was performed at the Anhui Mental Health Center, Hefei, China, from September 1, 2016, to August 31, 2021. Participants included 66 patients with AVH and schizophrenia. Data were analyzed from May 1, 2022, to March 31, 2023. Participants were randomly assigned 1:1 to either imaging-navigated active or sham rTMS over the left temporoparietal junction for 2 weeks. The primary outcome measured improvements in AVH from baseline to week 2 and week 6 using the Auditory Hallucination Rating Scale (AHRS) scores. In addition, the TMS-induced electric field strength was used to estimate improvements in AVH as a secondary outcome. A total of 62 participants (33 women [53%]; mean [SD] age, 27.4 [9.2] years) completed the 2-week treatments. Of these, 32 were randomized to the active rTMS group (18 women [56%]; mean [SD] age, 26.9 [9.2] years) and 30 to the sham treatment group (15 women [50%]; mean [SD] age, 27.8 [9.4] years). In the intention-to-treat analyses, patients receiving active rTMS showed a significantly greater reduction in AHRS scores compared with those receiving sham treatment at week 2 (difference, 5.96 [95% CI, 3.42-8.50]; t = 4.61; P < .001; Cohen d, 1.17 [95% CI, 0.62-1.71]). These clinical effects were sustained at week 6. Additionally, a stronger TMS-induced electric field within a predefined AVH brain network was associated with greater reductions in AHRS scores (B = 3.12; t = 3.58; P = .002). No serious adverse event was observed. The findings of this randomized clinical trial suggest that imaging-navigated rTMS may effectively and safely alleviate AVH in patients with schizophrenia. Findings also suggest that the electric field strength in the individualized AVH network is a vital parameter for optimizing the efficacy of the rTMS protocol. ClinicalTrials.gov Identifier: NCT02863094.

Limited Potential of Repetitive Transcranial Magnetic Stimulation for Treatment of Essential Tremor: A Systematic Review

Essential tremor (ET) is a prevalent movement disorder characterized by action tremors, predominantly affecting the upper limbs. While various pharmacological and non-pharmacological interventions have shown efficacy in managing ET, the therapeutic role of repetitive transcranial magnetic stimulation (rTMS) remains uncertain. This systematic review synthesizes evidence from clinical trials investigating rTMS as a treatment for ET. Despite some open-label trials reporting reductions in tremor severity, double-blinded studies revealed no significant difference between active and sham rTMS, suggesting a strong placebo effect. The findings indicate that while rTMS can reduce tremor scores, its therapeutic efficacy in ET remains unproven. Future research should focus on improving sham designs and conducting larger, rigorously controlled trials to clarify rTMS’s role in ET management. Current evidence supports considering alternative treatments, such as deep brain stimulation, over rTMS for ET.

Efficacy and safety of low-frequency repetitive transcranial magnetic stimulation in adolescents with first-episode major depressive disorder: A randomized, double-blind, sham-controlled pilot trial

BackgroundA few sham-controlled studies have examined the efficacy, safety, and tolerability of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) in adolescents with first-episode major depressive disorder (FE-MDD). MethodsForty adolescents (aged 13–17 years) with FE-MDD were randomly assigned to receive active rTMS (n = 20) or sham rTMS (n = 20) for 10 sessions over two weeks. The severity of baseline depressive symptoms and their improvement on the day immediately after the second, fourth, sixth, eighth, and tenth sessions were assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17). Results: After completing 10 rTMS treatment sessions, there was no significant difference in antidepressant response (70.0 % vs. 60.0 %, p > 0.05) and antidepressant remission (55.0 % vs. 35.0 %, p > 0.05) between rTMS groups. The linear mixed model analysis did not show a significant group-by-time interaction (F = 1.26; p > 0.05) in the HAMD-17 scores. There was a significant time main effect on the speed of processing (F = 13.61; p < 0.05), but this did not differ significantly between groups (p > 0.05). There were no other main effects and group-by-time interactions in the other MATRICS Consensus Cognitive Battery domains (all p > 0.05). All adverse event categories, such as fatigue and headache, were similar in the two groups (all p > 0.05). ConclusionsIn this study that compared a combination of LF-rTMS + medication with sham + medication, LF-rTMS had higher response and remission rates than a sham procedure in adolescents with FE-MDD, but the change was not statistically significant. LF-rTMS is generally safe, with mild adverse effects and no negative impact on neurocognitive performance for adolescents with FE-MDD. Registration numberChiCTR2000037878.

Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment Reduces Variability in Brain Function in Schizophrenia: Data From a Double-Blind, Randomized, Sham-Controlled Trial.

There is increasing awareness of interindividual variability in brain function, with potentially major implications for repetitive transcranial magnetic stimulation (rTMS) efficacy. We perform a secondary analysis using data from a double-blind randomized controlled 4-week trial of 20 Hz active versus sham rTMS to dorsolateral prefrontal cortex (DLPFC) during a working memory task in participants with schizophrenia. We hypothesized that rTMS would change local functional activity and variability in the active group compared with sham. 83 participants were randomized in the original trial, and offered neuroimaging pre- and post-treatment. Of those who successfully completed both scans (n = 57), rigorous quality control left n = 42 (active/sham: n = 19/23), who were included in this analysis. Working memory-evoked activity during an N-Back (3-Back vs 1-Back) task was contrasted. Changes in local brain activity were examined from an 8mm ROI around the rTMS coordinates. Individual variability was examined as the mean correlational distance (MCD) in brain activity pattern from each participant to others within the same group. We observed an increase in task-evoked left DLPFC activity in the active group compared with sham (F1,36 = 5.83, False Discovery Rate (FDR))-corrected P = .04). Although whole-brain activation patterns were similar in both groups, active rTMS reduced the MCD in activation pattern compared with sham (F1,36 = 32.57, P < .0001). Reduction in MCD was associated with improvements in attention performance (F1,16 = 14.82, P = .0014, uncorrected). Active rTMS to DLPFC reduces individual variability of brain function in people with schizophrenia. Given that individual variability is typically higher in schizophrenia patients compared with controls, such reduction may "normalize" brain function during higher-order cognitive processing.

Neural Circuitry and Therapeutic Targeting of Depressive Symptoms in Schizophrenia Spectrum Disorders.

Conceptual similarities between depressive and negative symptoms complicate biomarker and intervention development. This study employed a data-driven approach to delineate the neural circuitry underlying depressive and negative symptoms in schizophrenia spectrum disorders (SSDs). Data from three studies were analyzed (157 participants with SSDs) to assess brain-behavior relationships: two neuroimaging studies and a randomized trial of repetitive transcranial magnetic stimulation (rTMS). Partial least squares correlation (PLSC) was used to investigate associations between resting-state functional connectivity and depressive and negative symptoms. Secondary analyses of rTMS trial data (active, N=37; sham, N=33) were used to assess relationships between PLSC-derived symptom profiles and treatment outcomes. PLSC identified three latent variables (LVs) relating functional brain circuitry with symptom profiles. LV1 related a general depressive symptom factor with positive associations between and within the default mode network (DMN), the frontoparietal network (FPN), and the cingulo-opercular network (CON). LV2 related negative symptoms (no depressive symptoms) via negative associations, especially between the FPN and the CON, but also between the DMN and the FPN and the CON. LV3 related a guilt and early wakening depression factor via negative rather than positive associations with the DMN, FPN, and CON. The secondary visual network had a positive association with general depressive symptoms and negative associations with guilt and negative symptoms. Active (but not sham) rTMS applied bilaterally to the dorsolateral prefrontal cortex (DLPFC) reduced general depressive but not guilt-related or negative symptoms. The results clearly differentiate the neural circuitry underlying depressive and negative symptoms, and segregated across the two-factor structure of depression in SSDs. These findings support divergent neurobiological pathways of depressive symptoms and negative symptoms in people with SSDs. As treatment options are currently limited, bilateral rTMS to the DLPFC is worth exploring further for general depressive symptoms in people with SSDs.

Safety of rTMS for Schizophrenia: A Systematic Review and Meta-analysis.

Current treatments for schizophrenia are only partially effective, and there are no medications for negative symptoms or cognitive impairment. Neuromodulation, such as repetitive transcranial magnetic stimulation (rTMS), has potential as a novel intervention for schizophrenia. Prior to clinical use, rTMS should have demonstrated safety in a large schizophrenia population. However, the safety profile of rTMS in schizophrenia is not well characterized, and regulatory agencies have expressed concern about safety in this population. We conducted a systematic review with meta-analysis of rTMS studies in schizophrenia. We searched PubMed, the Cochrane Library, PsycINFO, and Science Citation Index Expanded for rTMS studies in schizophrenia that reported adverse effects. We extracted the number of participants who experienced an adverse effect and calculated the prevalence of each adverse effect for active or sham rTMS. We tested the difference between the prevalence of events in the active and sham conditions. We assessed risk of bias using the Cochrane Handbook. The initial search identified 1472 studies. After screening, 261 full-text studies were assessed, and 126 met inclusion criteria (N = 4122 total subjects). The prevalence of headache or scalp pain, dizziness or syncope, facial twitching, and nausea was higher for active rTMS compared to sham (P < .05). The prevalence of all other adverse effects, including seizure, was not different between active and sham rTMS. rTMS is safe and well tolerated for people with schizophrenia. Individuals with schizophrenia are not at increased risk for adverse effects, including seizure, compared to the general population.

Metaanalysis of Repetitive Transcranial Magnetic Stimulation (rTMS) Efficacy for OCD Treatment: The Impact of Stimulation Parameters, Symptom Subtype and rTMS-Induced Electrical Field.

Background: Repetitive transcranial magnetic stimulation (rTMS) has recently demonstrated significant potential in treating obsessive-compulsive disorder (OCD). However, its effectiveness depends on various parameters, including stimulation parameters, OCD subtypes and electrical fields (EFs) induced by rTMS in targeted brain regions that are less studied. Methods: Using the PRISMA approach, we examined 27 randomized control trials (RCTs) conducted from 1985 to 2024 using rTMS for the treatment of OCD and conducted several meta-analyses to investigate the role of rTMS parameters, including the EFs induced by each rTMS protocol, and OCD subtypes on treatment efficacy. Results: A significant, medium effect size was found, favoring active rTMS (gPPC = 0.59, p < 0.0001), which was larger for the obsession subscale. Both supplementary motor area (SMA) rTMS (gPPC = 0.82, p = 0.048) and bilateral dorsolateral prefrontal cortex (DLPFC) rTMS (gPPC = 1.14, p = 0.04) demonstrated large effect sizes, while the right DLPFC showed a significant moderate effect size for reducing OCD severity (gPPC = 0.63, p = 0.012). These protocols induced the largest EFs in dorsal cognitive, ventral cognitive and sensorimotor circuits. rTMS protocols targeting DLPFC produced the strongest electrical fields in cognitive circuits, while pre-supplementary motor area (pre-SMA) and orbitofrontal cortex (OFC) rTMS protocols induced larger fields in regions linked to emotional and affective processing in addition to cognitive circuits. The pre-SMA rTMS modulated more circuits involved in OCD pathophysiology-sensorimotor, cognitive, affective, and frontolimbic-with larger electrical fields than the other protocols. Conclusions: While rTMS shows moderate overall clinical efficacy, protocols targeting ventral and dorsal cognitive and sensorimotor circuits demonstrate the highest potential. The pre-SMA rTMS appears to induce electrical fields in more circuits relevant to OCD pathophysiology.

Seizure Risk Associated With the Use of Transcranial Magnetic Stimulation for Coma Recovery in Individuals With Disordered Consciousness After Severe Traumatic Brain Injury.

Repetitive Transcranial Magnetic Stimulation (rTMS) is emerging as a promising treatment for persons with disorder of consciousness (DoC) following traumatic brain injury (TBI). Clinically, however, there are concerns about rTMS exacerbating baseline seizure risk. To advance understanding of risks, this article reports evidence of DoC-TBI rTMS-related seizure risk. Acute and sub-acute hospitals. Persons in states of DoC 6.5months to 15years after TBI (n=20) who received active rTMS (n=17) or placebo rTMS (n=3). After completing placebo procedures, placebo participants completed active rTMS procedures. These 3 participants are included in the active group. Meta-analysis of data from 3 clinical trials; 2 within-subject, 1 double blind randomized placebo-controlled. Each trial used the same rTMS protocol, provided at least 30 rTMS sessions, and delivered rTMS to the dorsolateral prefrontal cortex. During each study's rTMS treatment phase, seizure occurrences were compared between active and placebo groups using logistic regression. After stratifying active group by presence/absence of seizure occurrences, sub-groups were compared using contingency chi-square tests of independence and relative risk (RR) ratios. Two unique participants experienced seizures (1 active, 1 placebo). Post seizure, both participants returned to baseline neurobehavioral function. Both participants received antiepileptics during remaining rTMS sessions, which were completed without further seizures. rTMS-related seizure incidence rate is 59 per 1000 persons. Logistic regression revealed no difference in seizure occurrence by treatment condition (active vs placebo) or when examined with seizure risk factors (P >.1). Presence of ventriculoperitoneal shunt elevated seizure risk (RR=2.0). Collectively, findings indicate a low-likelihood that the specified rTMS protocol exacerbates baseline seizure rates in persons with DoC after TBI. In presence of VP shunts, however, rTMS likely elevates baseline seizure risk and mitigation of this increased risk with pharmacological seizure prophylaxis should be considered.

Repetitive Transcranial Magnetic Stimulation Modulates Brain Connectivity in Children with Self-limited Epilepsy with Centrotemporal Spikes.

Interictal epileptiform discharges (IEDs) alter brain connectivity in children with epilepsy; this connectivity change may be a mechanism by which epilepsy induces cognitive deficits. Here, we test whether repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, modulates connectivity and reduces IEDs in children with epilepsy. Nineteen children with self-limited epilepsy with centrotemporal spikes (SeLECTS) participated in a cross-over study comparing the impact of active vs. sham rTMS on IEDs and brain connectivity. SeLECTS is an epilepsy syndrome affecting the motor cortex, and prior studies show that motor cortices become pathologically hyper-connected to frontal and temporal language cortices. Using a crossover design, we compared the effect of single doses of active versus sham motor cortex rTMS. Connectivity, which was quantified by the weighted phase lag index (wPLI), was measured before and after rTMS using single pulses of TMS combined with EEG (spTMS-EEG). Analyses focused on six regions: bilateral motor cortices and bilateral inferior frontal and superior temporal regions. IEDs were counted in the five minutes before and after rTMS. Active, but not sham, rTMS significantly and globally decreased wPLI connectivity between multiple regions, with the greatest reductions seen in the superior temporal region connections in the stimulated hemisphere. Additionally, there was a trend suggesting that rTMS decreases IED frequency. These findings underscore the potential of low-frequency rTMS to target pathologic hyperconnectivity and reduce IEDs in children with SeLECTS and potentially other pediatric epilepsy syndromes, offering a promising avenue for therapeutic intervention.

Differential analgesic effects of high-frequency or accelerated intermittent theta burst stimulation of M1 on experimental tonic pain: Correlations with cortical activity changes assessed by TMS-EEG

Accelerated intermittent theta burst stimulation (AiTBS) has attracted much attention in the past few years as a new form of brain stimulation paradigm. However, it is unclear the relative efficacy of AiTBS on cortical excitability compared to conventional high-frequency rTMS. Using concurrent TMS and electroencephalogram (TMS-EEG), this study systematically compared the efficacy on cortical excitability and a typical clinical application (i.e. pain), between AiTBS with different intersession interval (ISIs) and 10-Hz rTMS. Participants received 10-Hz rTMS, AiTBS-15 (3 iTBS sessions with a 15-min ISI), AiTBS-50 (3 iTBS sessions with a 50-min ISI), or Sham stimulation over the primary motor cortex on four separate days. All four protocols included a total of 1800 pulses but with different session durations (10-Hz rTMS ​= ​18, AiTBS-15 ​= ​40, and AiTBS-50 ​= ​110 ​min). AiTBS-50 and 10-Hz rTMS were more effective in pain reduction compared to AiTBS-15. Using single-pulse TMS-induced oscillation, our data revealed low gamma oscillation as a shared cortical excitability change across all three active rTMS protocols but demonstrated completely opposite directions. Changes in low gamma oscillation were further associated with changes in pain perception across the three active conditions. In contrast, a distinct pattern of TMS-evoked potentials (TEPs) was revealed, with 10-Hz rTMS decreasing inhibitory N100 amplitude and AiTBS-15 reducing excitatory P60 amplitude. These changes in TEPs were also covarying with low gamma power changes. Sham stimulation indicated no significant effect on either cortical excitability or pain perception. These results are relevant only for provoked experimental pain, without being predictive for chronic pain, and revealed a change in low gamma oscillation, particularly around the very particular frequency of 40 ​Hz, shared between AiTBS and high-frequency rTMS. Conversely, cortical excitability (balance between excitation and inhibition) assessed by TEP recording was modulated differently by AiTBS and high-frequency rTMS paradigms.

Repetitive transcranial magnetic stimulation reshaped the dynamic reconfiguration of the executive and reward networks in individuals with tobacco use disorder

BackgroundStudies have demonstrated the potential of repetitive transcranial magnetic stimulation (rTMS) to decrease smoking cravings in individuals with tobacco use disorder (TUD). However, the neural features underlying the effects of rTMS treatment, especially the dynamic attributes of brain networks associated with the treatment, remain unclear. MethodsUsing dynamic functional connectivity analysis, this study first explored the differences in dynamic functional network features between 60 subjects with TUD and 64 nonsmoking healthy controls (HCs). Then, the left dorsolateral prefrontal cortex (DLPFC) was targeted for a five-day course of rTMS treatment in the 60 subjects with TUD (active rTMS in 42 subjects and sham treatment in 18 subjects). We explored the effect of rTMS on the dynamic network features associated with rTMS by comparing the actively treated group and the sham group. ResultsCompared to nonsmokers, TUD subjects exhibited an increased integration coefficient between the frontoparietal network (FPN) and the basal ganglia network (BGN) and a reduced integration coefficient between the medial frontal network (MFN) and the FPN. Analysis of variance revealed that rTMS treatment reduced the integration coefficient between the FPN and BGN and improved the recruitment coefficient of the FPN. LimitationsThis study involved a limited sample of young male smokers, and the findings may not generalize to older smokers or female smokers with an extensive history of smoking. ConclusionrTMS treatment of the left DLPFC exhibited significant effectiveness in restructuring the neural circuits associated with TUD while significantly mitigating smoking cravings.

H-coil repetitive transcranial magnetic stimulation does not improve executive function in patients with chronic peripheral neuropathic pain: a randomized sham-controlled crossover study.

Deep rTMS is an increasingly popular noninvasive brain stimulation technique which has shown promise for treating cognitive impairments. However, few studies have investigated the cognitive effects it could exert in patients with chronic peripheral neuropathic pain. Therefore, we aimed to assess the effects of deep rTMS on executive functioning in patients with peripheral neuropathic pain, in a randomized, double-blind crossover trial. In total, 17 patients were randomly assigned to receive both active and sham deep H-coil rTMS targeting the primary motor cortex. Each treatment period consisted of five daily rTMS sessions. Selected tests of executive functioning from the CANTAB test battery (paired associates learning, stop signal task, spatial working memory and multitasking test) were performed at baseline, and at 1 week and 3 weeks follow-ups. We did not find any significant interactions between time and treatment for the measures of executive functioning for the patient group, or for patients with reduced cognition compared to normative means. High-frequency deep H-coil rTMS targeting the hand area of the primary motor cortex and delivered over 5 consecutive days did not improve executive functioning in patients with chronic peripheral neuropathic pain. https://clinicaltrials.gov/, identifier NCT05488808.

Neural correlates of approach–avoidance behavior in healthy subjects: Effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the right dorsolateral prefrontal cortex

The dorsolateral prefrontal cortex (dlPFC) is implicated in top-down regulation of emotion, but the detailed network mechanisms require further elucidation. To investigate network-level functions of the dlPFC in emotion regulation, this study measured changes in task-based activation, resting-state and task-based functional connectivity (FC) patterns following suppression of dlPFC excitability by 1-Hz repetitive transcranial magnetic stimulation (rTMS). In a sham-controlled within-subject design, 1-Hz active or sham rTMS was applied to the right dlPFC of 19 healthy volunteers during two separate counterbalanced sessions. Following active and sham rTMS, functional magnetic resonance imaging (fMRI) was conducted in the resting state (rs-fMRI) and during approach–avoidance task responses to pictures with positive and negative emotional content (task-based fMRI). Activation and generalized psychophysiological interaction analyses were performed on task-based fMRI, and seed-based FC analysis was applied to rs-fMRI data. Task-based fMRI revealed greater and more lateralized activation in the right hemisphere during negative picture responses compared to positive picture responses. After active rTMS, greater activation was observed in the left middle prefrontal cortex compared to sham rTMS. Further, rTMS reduced response times and error rates in approach to positive pictures compared to negative pictures. Significant FC changes due to rTMS were observed predominantly in the frontoparietal network (FPN) and visual network (VN) during the task, and in the default mode network (DMN) and VN at rest. Suppression of right dlPFC activity by 1-Hz rTMS alters large-scale neural networks and modulates emotion, supporting potential applications for the treatment of mood disorders.

Efficacy of MRI-guided rTMS for post-traumatic stress disorder by modulating amygdala activity: study protocol for a randomised controlled trial

IntroductionPost-traumatic stress disorder (PTSD) is a prevalent and severe psychiatric disorder. Repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex provides limited relief for symptoms of PTSD. This study...

Early efficacy of rTMS intervention at week 2 predicts subsequent responses at week 24 in schizophrenia in a randomized controlled trial

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique for modulating cortical activities and improving neural plasticity. Several studies investigated the effects of rTMS, etc., but the results are inconsistent. This study was designed to examine whether rTMS applied on the left dorsolateral prefrontal cortex (l-DLPFC) showed an effect on improving cognitive deficits in SZ and whether the early efficacy could predict efficacy at subsequent follow-ups. Cognitive ability was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale at baseline, weeks 2, 6, and 24. We found a significant interaction between time (weeks 0, 2, 6, and 24) and intervention on immediate memory and RBANS total scores (p ​= ​0.02 and p ​= ​0.04), indicating that both 10-Hz and 20-Hz rTMS stimulations had a delayed beneficial effect on immediate memory in SZ. Moreover, we found that 20-Hz rTMS stimulation, but not 10-Hz rTMS improved immediate memory at week 6 compared to the sham group (p ​= ​0.029). More importantly, improvements in immediate memory at week 2 were positively correlated with improvements at week 24 (β ​= ​0.461, t ​= ​3.322, p ​= ​0.002). Our study suggests that active rTMS was beneficial for cognitive deficits in patients with SZ. Furthermore, efficacy at week 2 could predict the subsequent efficacy at 24-week follow-up.

Cortical intermittent theta burst stimulation on gait pathomechanics and urinary tract dysfunction in incomplete spinal cord injury patients: Protocol for a randomized controlled trial

Gait impairment and neurogenic bladder are co-existing common findings in incomplete spinal cord injury (iSCI). Repetitive transcranial magnetic stimulation (rTMS), evident to be a promising strategy adjunct to physical rehabilitation to regain normal ambulation in SCI. However, there is a need to evaluate the role of Intermittent theta burst stimulation (iTBS), a type of patterned rTMS in restoring gait and neurogenic bladder in SCI patients. The aim of the present study is to quantify the effect of iTBS on spatiotemporal, kinetic, and kinematic parameters of gait and neurogenic bladder dyssynergia in iSCI. After maturing all exclusion and inclusion criteria, thirty iSCI patients will be randomly divided into three groups: Group-A (sham), Group-B (active rTMS) and Group-C (active iTBS). Each group will receive stimulation adjunct to physical rehabilitation for 2 weeks. All patients will undergo gait analysis, as well assessment of bladder, electrophysiological, neurological, functional, and psychosocial parameters. All parameters will be assessed at baseline and 6th week (1st follow-up). Parameters except urodynamics and gait analysis will also be assessed after the end of the 2 weeks of the intervention (post-intervention) and at 12th week (2nd follow-up). Appropriate statistical analysis will be done using various parametric and non-parametric tests based on results.

Cognitive enhancing effect of rTMS combined with tDCS in patients with major depressive disorder: a double-blind, randomized, sham-controlled study

BackgroundCognitive dysfunction is one of the common symptoms in patients with major depressive disorder (MDD). Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been studied separately in the treatment of cognitive dysfunction in MDD patients. We aimed to investigate the effectiveness and safety of rTMS combined with tDCS as a new therapy to improve neurocognitive impairment in MDD patients.MethodsIn this brief 2-week, double-blind, randomized, and sham-controlled trial, a total of 550 patients were screened, and 240 MDD inpatients were randomized into four groups (active rTMS + active tDCS, active rTMS + sham tDCS, sham rTMS + active tDCS, sham rTMS + sham tDCS). Finally, 203 patients completed the study and received 10 treatment sessions over a 2-week period. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess patients’ cognitive function at baseline and week 2. Also, we applied the 24-item Hamilton Depression Rating Scale (HDRS-24) to assess patients’ depressive symptoms at baseline and week 2.ResultsAfter 10 sessions of treatment, the rTMS combined with the tDCS group showed more significant improvements in the RBANS total score, immediate memory, and visuospatial/constructional index score (all p < 0.05). Moreover, post hoc tests revealed a significant increase in the RBANS total score and Visuospatial/Constructional in the combined treatment group compared to the other three groups but in the immediate memory, the combined treatment group only showed a better improvement than the sham group. The results also showed the RBANS total score increased significantly higher in the active rTMS group compared with the sham group. However, rTMS or tDCS alone was not superior to the sham group in terms of other cognitive performance. In addition, the rTMS combined with the tDCS group showed a greater reduction in HDRS-24 total score and a better depression response rate than the other three groups.ConclusionsrTMS combined with tDCS treatment is more effective than any single intervention in treating cognitive dysfunction and depressive symptoms in MDD patients.Trial registrationChinese Clinical Trial Registry (ChiCTR2100052122).

Anterior–temporal hippocampal network mechanisms of left angular gyrus-navigated rTMS for memory improvement in aMCI: A sham-controlled study

IntroductionNeuro-navigated repetitive transcranial magnetic stimulation (rTMS) of the left angular gyrus has been broadly investigated for the treatment of amnestic mild cognitive impairment (aMCI). Although abnormalities in two hippocampal networks, the anterior–temporal (AT) and posterior–medial (PM) networks, are consistent with aMCI and are potential therapeutic targets for rTMS, the underlying mechanisms of the therapeutic effects of rTMS on hippocampal network connections remain unknown. Here, we assessed the impact of left angular gyrus rTMS on activity in these networks and explored whether the treatment response was due to the distance between the clinically applied target (the group average optimal site) and the personalized target in patients with aMCI. MethodsSixty subjects clinically diagnosed with aMCI participated in this study after 20 sessions of sham-controlled rTMS targeting the left angular gyrus. Resting-state functional magnetic resonance imaging and neuropsychological assessments were performed before and after rTMS. Functional connectivity alterations in the PM and AT networks were assessed using seed-based functional connectivity analysis and two-factor repeated measures analysis of variance (ANOVA). We then computed the correlations between the functional connectivity changes and clinical rating scales. Finally, we examined whether the Euclidean distance between the clinically applied and personalized targets predicted the subsequent treatment response. ResultsCompared with the sham group, the active rTMS group showed rTMS-induced deactivation of functional connectivity within the medial temporal lobe-AT network, with a negative correlation with episodic memory score changes. Moreover, the active rTMS lowers the interdependency of changes in the PM and AT networks. Finally, the Euclidean distance between the clinically applied and personalized target distances could predict subsequent network lever responses in the active rTMS group. ConclusionsNeuro-navigated rTMS selectively modulates widespread functional connectivity abnormalities in the PM and AT hippocampal networks in aMCI patients, and the modulation of hippocampal-AT network connectivity can efficiently reverse memory deficits. The results also highlight the necessity of personalized targets for fMRI.

A 5-day course of rTMS before pain onset ameliorates future pain and increases sensorimotor peak alpha frequency.

Repetitive transcranial magnetic stimulation (rTMS) has shown promise as an intervention for pain. An unexplored research question is whether the delivery of rTMS prior to pain onset might protect against a future episode of prolonged pain. The present study aimed to determine i) whether 5 consecutive days of rTMS delivered prior to experimentally-induced prolonged jaw pain could reduce future pain intensity and ii) whether any effects of rTMS on pain were mediated by changes in corticomotor excitability (CME) and/or sensorimotor peak alpha frequency (PAF). On each day from Day 0-4, forty healthy individuals received a single session of active (n = 21) or sham (n = 19) rTMS over the left primary motor cortex. PAF and CME were assessed on Day 0 (before rTMS) and Day 4 (after rTMS). Prolonged pain was induced via intramuscular injection of nerve growth factor (NGF) in the right masseter muscle after the final rTMS session. From Days 5-25, participants completed twice-daily electronic dairies including pain on chewing and yawning (primary outcomes), as well as pain during other activities (e.g. talking), functional limitation in jaw function and muscle soreness (secondary outcomes). Compared to sham, individuals who received active rTMS subsequently experienced lower pain on chewing and yawning. Although active rTMS increased PAF, the effects of rTMS on pain were not mediated by changes in PAF or CME. This study is the first to show that rTMS delivered prior to pain onset can protect against future pain and associated functional impairment. Thus, rTMS may hold promise as a prophylactic intervention for persistent pain.