rTMS Protocol Research Articles

A computational model elucidating mechanisms and variability in theta burst stimulation responses.

Theta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation (rTMS) with unknown underlying mechanisms and highly variable responses across subjects. To investigate these issues, we developed a simple computational model. Our model consisted of two neurons linked by an excitatory synapse that incorporates two mechanisms: short-term plasticity (STP) and spike-timing-dependent plasticity (STDP). We applied a variable-amplitude current through I-clamp with a TBS time pattern to the pre- and post-synaptic neurons, simulating synaptic plasticity. We analyzed the results and provided an explanation for the effects of TBS, as well as the variability of responses to it. Our findings suggest that the interplay of STP and STDP mechanisms determines the direction of plasticity, which selectively affects synapses in extended neurons and underlies functional effects. Our model describes how the timing, number, and intensity of pulses delivered to neurons during rTMS contribute to induced plasticity. This not only successfully explains the different effects of intermittent TBS (iTBS) and continuous TBS (cTBS), but also predicts the results of other protocols such as 10 Hz rTMS. We propose that the variability in responses to TBS can be attributed to the variable span of neuronal thresholds across individuals and sessions. Our model suggests a biologically plausible mechanism for the diverse responses to TBS protocols and aligns with experimental data on iTBS and cTBS outcomes. This model could potentially aid in improving TBS and rTMS protocols and customizing treatments for patients, brain areas, and brain disorders.

Multi-scale modelling of location- and frequency-dependent synaptic plasticity induced by transcranial magnetic stimulation in the dendrites of pyramidal neurons.

Repetitive transcranial magnetic stimulation (rTMS) induces long-term changes of synapses, but the mechanisms behind these modifications are not fully understood. Although there has been progress in the development of multi-scale modeling tools, no comprehensive module for simulating rTMS-induced synaptic plasticity in biophysically realistic neurons exists.. We developed a modelling framework that allows the replication and detailed prediction of long-term changes of excitatory synapses in neurons stimulated by rTMS. We implemented a voltage-dependent plasticity model that has been previously established for simulating frequency-, time-, and compartment-dependent spatio-temporal changes of excitatory synapses in neuronal dendrites. The plasticity model can be incorporated into biophysical neuronal models and coupled to electrical field simulations. We show that the plasticity modelling framework replicates long-term potentiation (LTP)-like plasticity in hippocampal CA1 pyramidal cells evoked by 10-Hz repetitive magnetic stimulation (rMS). This plasticity was strongly distance dependent and concentrated at the proximal synapses of the neuron. We predicted a decrease in the plasticity amplitude for 5 Hz and 1 Hz protocols with decreasing frequency. Finally, we successfully modelled plasticity in distal synapses upon local electrical theta-burst stimulation (TBS) and predicted proximal and distal plasticity for rMS TBS. Notably, the rMS TBS-evoked synaptic plasticity exhibited robust facilitation by dendritic spikes and low sensitivity to inhibitory suppression. The plasticity modelling framework enables precise simulations of LTP-like cellular effects with high spatio-temporal resolution, enhancing the efficiency of parameter screening and the development of plasticity-inducing rTMS protocols.

Efficacy of personalized rTMS to enhance upper limb function in subacute stroke patients: a protocol for a multi-center, randomized controlled study.

Repetitive transcranial magnetic stimulation (rTMS) is widely used therapy to enhance motor deficit in stroke patients. To date, rTMS protocols used in stroke patients are relatively unified. However, as the pathophysiology of stroke is diverse and individual functional deficits are distinctive, more precise application of rTMS is warranted. Therefore, the objective of this study was to determine the effects of personalized protocols of rTMS therapy based on the functional reserve of each stroke patient in subacute phase. This study will recruit 120 patients with stroke in subacute phase suffering from the upper extremity motor impairment, from five different hospitals in Korea. The participants will be allocated into three different study conditions based on the functional reserve of each participant, measured by the results of TMS-induced motor evoked potentials (MEPs), and brain MRI with diffusion tensor imaging (DTI) evaluations. The participants of the intervention-group in the three study conditions will receive different protocols of rTMS intervention, a total of 10 sessions for 2 weeks: high-frequency rTMS on ipsilesional primary motor cortex (M1), high-frequency rTMS on ipsilesional ventral premotor cortex, and high-frequency rTMS on contralesional M1. The participants of the control-group in all three study conditions will receive the same rTMS protocol: low-frequency rTMS on contralesional M1. For outcome measures, the following assessments will be performed at baseline (T0), during-intervention (T1), post-intervention (T2), and follow-up (T3) periods: Fugl-Meyer Assessment (FMA), Box-and-block test, Action Research Arm Test, Jebsen-Taylor hand function test, hand grip strength, Functional Ambulatory Category, fractional anisotropy measured by the DTI, and brain network connectivity obtained from MRI. The primary outcome will be the difference of upper limb function, as measured by FMA from T0 to T2. The secondary outcomes will be the differences of other assessments. This study will determine the effects of applying different protocols of rTMS therapy based on the functional reserve of each patient. In addition, this methodology may prove to be more efficient than conventional rTMS protocols. Therefore, effective personalized application of rTMS to stroke patients can be achieved based on their severity, predicted mechanism of motor recovery, or functional reserves. https://clinicaltrials.gov/, identifier NCT06270238.

Transcranial Magnetic Stimulation–Induced Plasticity Improving Cognitive Control in Obsessive-Compulsive Disorder, Part I: Clinical and Neuroimaging Outcomes From a Randomized Trial

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for obsessive-compulsive disorder (OCD). The neurobiological mechanisms of rTMS in OCD have been incompletely characterized. We compared clinical outcomes and changes in task-based brain activation following 3 different rTMS protocols, all combined with exposure and response prevention. MethodsIn this 3-arm proof-of-concept randomized trial, 61 treatment-refractory adult patients with OCD received 16 sessions of rTMS immediately before exposure and response prevention over 8 weeks, with task-based functional magnetic resonance imaging scans and clinical assessments before and after treatment. Patients received high-frequency rTMS to the left dorsolateral prefrontal cortex (n = 19 [13 women/6 men]), high-frequency rTMS to the left pre-supplementary motor area (preSMA) (n = 23 [13 women/10 men]), or control rTMS to the vertex (n = 19 [13 women/6 men]). Changes in task-based functional magnetic resonance imaging activation before/after treatment were compared using both a Bayesian region of interest and a general linear model whole-brain approach. ResultsMean OCD symptom severity decreased significantly in all treatment groups (Δ = −10.836, p < .001, 95% CI −12.504 to −9.168), with no differences between groups. Response rate in the entire sample was 57.4%. The dorsolateral prefrontal cortex rTMS group showed decreased planning-related activation after treatment that was associated with greater symptom improvement. No group-level activation changes were observed for the preSMA and vertex rTMS groups. Participants in the preSMA group with greater symptom improvement showed decreased error-related activation, and symptom improvement in the vertex group was associated with increased inhibition-related activation. ConclusionsrTMS to preSMA and dorsolateral prefrontal cortex combined with exposure and response prevention led to activation decreases in targeted task networks in individuals showing greater symptom improvement, although we observed no differences in symptom reduction between groups.

Comparison of Bilateral Versus Unilateral 5 Hz or 1 Hz Repetitive Transcranial Magnetic Stimulation in Subacute Stroke: Assessment of Motor Function in a Randomized Controlled Study.

Repetitive transcranial magnetic stimulation (rTMS) can enhance brain plasticity after stroke. At low frequencies, rTMS has an inhibitory effect, whereas at high frequencies, it has an excitatory effect. Combining both frequencies in bilateral stimulation is a new rTMS protocol under investigation, especially in the subacute stage. Fifty-five patients with subacute stroke were divided into four groups according to the rTMS protocol delivered: bilateral, inhibitory, excitatory, and control groups. All groups received concomitant task-oriented physiotherapy. Pretreatment to posttreatment assessment was performed twice, immediately after sessions and 1 month later. Volitional motor control was evaluated by Fugl-Meyer and Wolf motor function tests, and for spasticity, the Ashworth scale was used. All groups showed significant improvement. Bilateral, inhibitory, and excitatory groups showed same efficacy, but the bilateral protocol was superior in spasticity. No correlations were found between improvement and stroke duration and site except for spasticity. Bilateral rTMS shows a comparable effect to inhibitory and excitatory rTMS in improving motor disability in subacute stroke. However, it is superior for spasticity.

The protective effects of repetitive transcranial magnetic stimulation with different high frequencies on motor functions in MPTP/probenecid induced Parkinsonism mouse models.

High-frequency repeated transcranial magnetic stimulation (rTMS) stimulating the primary motor cortex (M1) is an alternative, adjunctive therapy for improving the motor symptoms of Parkinson's disease (PD). However, whether the high frequency of rTMS positively correlates to the improvement of motor symptoms of PD is still undecided. By controlling for other parameters, a disease animal model may be useful to compare the neuroprotective effects of different high frequencies of rTMS. The current exploratory study was designed to compare the protective effects of four common high frequencies of rTMS (5, 10, 15, and 20Hz) and iTBS (a special form of high-frequency rTMS) and explore the optimal high-frequency rTMS on an animal PD model. Following high frequencies of rTMS application (twice a week for 5weeks) in a MPTP/probenecid-induced chronic PD model, the effects of the five protocols on motor behavior as well as dopaminergic neuron degeneration levels were identified. The underlying molecular mechanisms were further explored. We found that all the high frequencies of rTMS had protective effects on the motor functions of PD models to varying degrees. Among them, the 10, 15, and 20Hz rTMS interventions induced comparable preservation of motor function through the protection of nigrostriatal dopamine neurons. The enhancement of brain-derived neurotrophic factor (BDNF), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT-2)and the suppression of TNF-α and IL-1β in the nigrostriatum were involved in the process. The efficacy of iTBS was inferior to that of the above three protocols. The effect of 5Hz rTMS protocol was weakest. Combined with the results of the present study and the possible side effects induced by rTMS, we concluded that 10Hz might be the optimal stimulation frequency for preserving the motor functions of PD models using rTMS treatment.

Treatment expectations and clinical outcomes following repetitive transcranial magnetic stimulation for treatment-resistant depression

BackgroundPatient expectations, including both positive (placebo) and negative (nocebo) effects, influence treatment outcomes, yet their impact on acute repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) is unclear. MethodsIn this single-center retrospective chart review, 208 TRD patients completed the Stanford Expectation of Treatment Scale (SETS) before starting open-label rTMS treatment. Patients were offered two excitatory rTMS protocols (deep TMS or intermittent theta-burst stimulation), which stimulated the left dorsolateral prefrontal cortex. A minimum of 20 once daily treatments were provided, delivered over 4–6 weeks. Primary outcomes were 1) remission, measured by a post-treatment score of <8 on the Hamilton Depression Rating Scale (HAMD-17), and 2) premature discontinuation. The change in HAMD-17 scores over time was used as a secondary outcome. Physicians were blinded to SETS scores. Logistic and linear regression, adjusting for covariates, assessed SETS and HAMD-17 relationships. ResultsOf 208 patients, 177 had baseline and covariate data available. The mean positivity bias score (positive expectancy minus negative expectancy subscale averages) was 0.48 ± 2.21, indicating the cohort was neutral regarding the expectations of their treatment on average. Higher positive expectancy scores were significantly associated with greater odds of remission (OR = 1.90, p = 0.003) and greater reduction in HAMD-17 scores (β = 1.30, p = 0.005) at the end of acute treatment, after adjusting for covariates. Negative expectancy was not associated with decreased odds of remission (p = 0.2) or treatment discontinuation (p = 0.8). ConclusionsHigher pre-treatment positive expectations were associated with greater remission rates with open-label rTMS in a naturalistic cohort of patients with TRD.

RTMS of the Cerebellum Using an Accelerated Stimulation Protocol Improved Gait in Parkinson’s Disease

Background Repetitive transcranial magnetic stimulation (rTMS) is a nonpharmacological and noninvasive brain stimulation technique that has been proven to be effective in Parkinson’s disease (PD). The combination of rTMS and treadmill training improved gait function in PD greater than treadmill training alone. Objective The aim of our study was to evaluate the combination of a novel high-intensity, short intervention rTMS treatment and a multimodal treatment protocol including of physiotherapy, occupational therapy and language therapy, the so-called Parkinson’s Disease Multimodal Complex Treatment (PD-MCT), to improve motor function. Methods In this randomized double-blind sham-controlled trial rTMS with 48 Hz or sham was applied over the cerebellum 3 times a day for 5 consecutive days. Patients were assessed at baseline (V0), after 5 days of treatment (V1), and 4 weeks later (V2). The primary clinical outcome measure was the motor sum-score of the Unified PD Rating Scale (UPDRSIII), secondary clinical outcomes were quantitative motor tasks. Results A total of 36 PD patients were randomly allocated either to rTMS (n = 20) or sham (n = 16), both combined with PD-MCT. rTMS improved the UDPRSIII score comparing baseline and V1 in the treatment group by −8.2 points (P = .004). The 8MW and dynamic posturography remained unchanged in both groups after intervention. Conclusion. Compressing weeks of canonical rTMS protocols into 5 days was effective and well tolerated. rTMS may serve as an add-on therapy for augmenting the multimodal complex treatment of motor symptoms, but seems to be ineffective to treat postural instability.

Placebo effects of repetitive transcranial magnetic stimulation on negative symptoms and cognition in patients with schizophrenia spectrum disorders: a systematic review and meta-analysis.

Negative symptoms and cognitive impairments are highly frequent in schizophrenia spectrum disorders (SSD), associated with adverse functional outcomes and quality of life. Repetitive transcranial magnetic stimulation (rTMS) has been considered a promising therapeutic option in SSD. However, placebo effects of rTMS on these symptoms remained unclear. To investigate placebo effects of rTMS on alleviating negative symptoms and cognitive impairment in patients with SSD and to explore potential moderators. We systematically searched five electronic databases up to 15 July 2023. Randomized, double-blind, sham-controlled trials investigating effects of rTMS on negative symptoms or cognition in patients with SSD were included. The pooled placebo effect sizes, represented by Hedges' g, were estimated using the random-effects model. Potential moderators were explored through subgroup analysis and meta-regression. Forty-four randomized controlled trials with 961 patients (mean age 37.53 years; 28.1% female) in the sham group were included. Significant low-to-moderate pooled placebo effect sizes were observed for negative symptoms (g=0.44, p<0.001), memory (g=0.31, p=0.010), executive function (g=0.35, p<0.001), working memory (g=0.26, p=0.004), and processing speed (g=0.36, p=0.004). Subgroup analysis indicated that placebo effects were affected by sham stimulation methods, rTMS targeting approaches, and stimulation frequency. Placebo effects of rTMS on negative symptoms and cognition in patients with SSD are significant in a small-to-moderate magnitude, which might be mediated by rTMS parameters. Our findings will provide new insights for practitioners to further optimize and establish standardized rTMS protocols for future RCTs tackling cardinal symptoms in SSD. https://www.crd.york.ac.uk/prospero/, identifier CRD42023390138.

Repetitive transcranial magnetic stimulation focusing on patients with neuropathic pain in the upper limb: a randomized sham-controlled parallel trial

This study aimed to evaluate the efficacy and safety of navigation-guided repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex in patients with neuropathic pain in the upper limb. This randomized, blinded, sham-controlled, parallel trial included a rTMS protocol (10-Hz, 2000 pulses/session) consisting of five daily sessions, followed by one session per week for the next seven weeks. Pain intensity, as well as pain-related disability, quality of life, and psychological status, were assessed. For the primary outcome, pain intensity was measured daily using a numerical rating scale as a pain diary. Thirty patients were randomly assigned to the active rTMS or sham-stimulation groups. In the primary outcome, the decrease (least square [LS] mean ± standard error) in the weekly average of a pain diary at week 9 compared to the baseline was 0.84 ± 0.31 in the active rTMS group and 0.58 ± 0.29 in the sham group (LS mean difference, 0.26; 95% confidence interval, − 0.60 to 1.13). There was no significant effect on the interaction between the treatment group and time point. Pain-related disability score improved, but other assessments showed no differences. No serious adverse events were observed. This study did not show significant pain relief; however, active rTMS tended to provide better results than sham. rTMS has the potential to improve pain-related disability in addition to pain relief.Clinical Trial Registration number: jRCTs052190110 (20/02/2020).

Axon morphology and intrinsic cellular properties determine repetitive transcranial magnetic stimulation threshold for plasticity.

Repetitive transcranial magnetic stimulation (rTMS) is a widely used therapeutic tool in neurology and psychiatry, but its cellular and molecular mechanisms are not fully understood. Standardizing stimulus parameters, specifically electric field strength, is crucial in experimental and clinical settings. It enables meaningful comparisons across studies and facilitates the translation of findings into clinical practice. However, the impact of biophysical properties inherent to the stimulated neurons and networks on the outcome of rTMS protocols remains not well understood. Consequently, achieving standardization of biological effects across different brain regions and subjects poses a significant challenge. This study compared the effects of 10 Hz repetitive magnetic stimulation (rMS) in entorhino-hippocampal tissue cultures from mice and rats, providing insights into the impact of the same stimulation protocol on similar neuronal networks under standardized conditions. We observed the previously described plastic changes in excitatory and inhibitory synaptic strength of CA1 pyramidal neurons in both mouse and rat tissue cultures, but a higher stimulation intensity was required for the induction of rMS-induced synaptic plasticity in rat tissue cultures. Through systematic comparison of neuronal structural and functional properties and computational modeling, we found that morphological parameters of CA1 pyramidal neurons alone are insufficient to explain the observed differences between the groups. Although morphologies of mouse and rat CA1 neurons showed no significant differences, simulations confirmed that axon morphologies significantly influence individual cell activation thresholds. Notably, differences in intrinsic cellular properties were sufficient to account for the 10% higher intensity required for the induction of synaptic plasticity in the rat tissue cultures. These findings demonstrate the critical importance of axon morphology and intrinsic cellular properties in predicting the plasticity effects of rTMS, carrying valuable implications for the development of computer models aimed at predicting and standardizing the biological effects of rTMS.

The Effectiveness of High-frequency Repetitive Transcranial Magnetic Stimulation in Persistent Somatic symptoms Disorder: A Case report study

IntroductionBackground:Somatic symptoms disorders are usually comorbid with depressive disorders despite that there is little evidence for effective treatment for it. Repetitive transcranial magnetic stimulation (rTMS) have been approved by FDA for mildly resistance depression. From this point we hypothesized that rTMS delivered over the prefrontal cortex (PFC) may be useful in somatic symptoms disorder. Therefore, in our case report we want to shed light on the potential effectiveness of rTMS in somatic symptoms disorder.Objectivescase reportMethodscase reportResultsCase Report: A 65-year-old Omani female with multiple medical comorbidities on multiple medications. She presented complaining of multiple somatic complains in the last 2 years after visiting multiple clinics and underwent several specialists’ examinations, investigations and procedure for somatic treatments, all of them where normal.Then patient was seen by different psychiatric clinic multiple anti-depressant and adjuvant anti-psychotic medication were try, patient still not improve.Patient get admitted to hospital for observation and management. Initially she was preoccupying by her somatic complain kept on Fluoxetine and Olanzapine along with that topiramate was added, but still with minimal improvement. Then rTMS was added to her management plan following Intermittent theta burst (iTBS) rTMS protocol. After complete all sessions of rTMS patient was recovering from her all symptoms, no complain report from her.ConclusionsConclusion: our case highlights the important of investigated more thoroughly in rTMS as treatment option for Persistent Somatic symptoms Disorder.Disclosure of InterestNone Declared

Low-intensity repetitive transcranial magnetic stimulation is safe and well tolerated by people living with MS - outcomes of the phase I randomised controlled trial (TAURUS).

Low-intensity repetitive transcranial magnetic stimulation (rTMS), delivered as a daily intermittent theta burst stimulation (iTBS) for four consecutive weeks, increased the number of new oligodendrocytes in the adult mouse brain. Therefore, rTMS holds potential as a remyelinating intervention for people with multiple sclerosis (MS). Primarily to determine the safety and tolerability of our rTMS protocol in people with MS. Secondary objectives include feasibility, blinding and an exploration of changes in magnetic resonance imaging (MRI) metrics, patient-reported outcome measures (PROMs) and cognitive or motor performance. A randomised (2:1), placebo controlled, single blind, parallel group, phase 1 trial of 20 rTMS sessions (600 iTBS pulses per hemisphere; 25% maximum stimulator output), delivered over 4-5 weeks. Twenty participants were randomly assigned to 'sham' (n = 7) or active rTMS (n = 13), with the coil positioned at 90° or 0°, respectively. Five adverse events (AEs) including one serious AE reported. None were related to treatment. Protocol compliance was high (85%) and blinding successful. Within participant MRI metrics, PROMs and cognitive or motor performance were unchanged over time. Twenty sessions of rTMS is safe and well tolerated in a small group of people with MS. The study protocol and procedures are feasible. Improvement of sham is warranted before further investigating safety and efficacy.

The Effectiveness of High-frequency Repetitive Transcranial Magnetic Stimulation in Persistent Somatic symptoms Disorder: A Case report study

IntroductionBackground:Somatic symptoms disorders are usually comorbid with depressive disorders despite that there is little evidence for effective treatment for it. Repetitive transcranial magnetic stimulation (rTMS) have been approved by FDA for mildly resistance depression. From this point we hypothesized that rTMS delivered over the prefrontal cortex (PFC) may be useful in somatic symptoms disorder. Therefore, in our case report we want to shed light on the potential effectiveness of rTMS in somatic symptoms disorder.Objectivescase reportMethodscase reportResultsCase Report: A 65-year-old Omani female with multiple medical comorbidities on multiple medications. She presented complaining of multiple somatic complains in the last 2 years after visiting multiple clinics and underwent several specialists’ examinations, investigations and procedure for somatic treatments, all of them where normal.Then patient was seen by different psychiatric clinic multiple anti-depressant and adjuvant anti-psychotic medication were try, patient still not improve.Patient get admitted to hospital for observation and management. Initially she was preoccupying by her somatic complain kept on Fluoxetine and Olanzapine along with that topiramate was added, but still with minimal improvement. Then rTMS was added to her management plan following Intermittent theta burst (iTBS) rTMS protocol. After complete all sessions of rTMS patient was recovering from her all symptoms, no complain report from her.ConclusionsConclusion: our case highlights the important of investigated more thoroughly in rTMS as treatment option for Persistent Somatic symptoms Disorder.Disclosure of InterestNone Declared

Transcranial Magnetic Stimulation and Dual Pathology: An Integrative Protocol

IntroductionDual pathology, characterized by the simultaneous presence of substance use disorders and psychiatric disorders, is a topic of growing interest in the scientific community. In particular, obsessive-compulsive disorder (OCD) is a common comorbid psychiatric condition in patients with substance use disorders.ObjectivesTo evaluate the efficacy of rTMS on comorbid disorder symptoms by applying specific protocols for OCD and substance use disorder in a clinical case of dual pathology.MethodsCase Description: A 36-year-old male diagnosed with OCD and habitual cocaine use (an average of 6 times per month). Previous unsuccessful attempts to quit substance use. Undergoing psychotherapy and psychopharmacological treatment for OCD since the age of 22 with no significant clinical improvement.Methodology: The severity of OCD was quantified before and after the intervention using the Yale-Brown Obsessive Compulsive Scale (YBOCS). To assess addictive behavior, the Maudsley Addiction Profile (MAP) was used. During the intervention period, the occurrence of substance use was recorded based on the patient’s and family members’ reports. The intervention involved the administration of an rTMS protocol tailored to the specific case, consisting of the simultaneous application, using a double-cone coil, of rTMS at 20Hz over the right dorsomedial prefrontal cortex (DMPFC) at an intensity of 100% of the resting motor threshold (RMT) to treat OCD symptoms, followed by intermittent theta burst stimulation (TBS) over the left DMPFC at an intensity of 120% of the RMT to address substance addiction. The patient received a total of 30 sessions at a rate of one session per day, five days a week, for six weeks.ResultsResults: The results showed an improvement in the total score on the YBOCS scale, decreasing from a value of 26 in the pre-intervention assessment to 16 in the post-intervention assessment, representing a reduction of more than 35% from pre- to post-intervention, meeting response criteria. Thus, there was a decrease in both obsessive and compulsive symptoms, with reduced associated distress and increased control. Additionally, throughout the intervention, there was a gradual decrease in substance use, decreasing from an average of 6 monthly instances before treatment initiation to a total of 1 in the month the treatment ended.ConclusionsConclusions: This unique case study represents a therapeutic window for the treatment of patients with comorbid disorders, demonstrating promising preliminary benefits of the combined rTMS intervention for both conditions, especially in the field of addictions.Keywords: rTMS, neuromodulation, obsessive-compulsive disorder, addictionsDisclosure of InterestNone Declared

Monitoring Changes in TMS-Evoked EEG and EMG Activity During 1 Hz rTMS of the Healthy Motor Cortex.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique capable of inducing neuroplasticity as measured by changes in peripheral muscle electromyography (EMG) or electroencephalography (EEG) from pre-to-post stimulation. However, temporal courses of neuromodulation during ongoing rTMS are unclear. Monitoring cortical dynamics via TMS-evoked responses using EMG (motor-evoked potentials; MEPs) and EEG (transcranial-evoked potentials; TEPs) during rTMS might provide further essential insights into its mode of action - temporal course of potential modulations. The objective of this study was to first evaluate the validity of online rTMS-EEG and rTMS-EMG analyses, and second to scrutinize the temporal changes of TEPs and MEPs during rTMS. As rTMS is subject to high inter-individual effect variability, we aimed for single-subject analyses of EEG changes during rTMS. Ten healthy human participants were stimulated with 1,000 pulses of 1 Hz rTMS over the motor cortex, while EEG and EMG were recorded continuously. Validity of MEPs and TEPs measured during rTMS was assessed in sensor and source space. Electrophysiological changes during rTMS were evaluated with model fitting approaches on a group- and single-subject level. TEPs and MEPs appearance during rTMS was consistent with past findings of single pulse experiments. Heterogeneous temporal progressions, fluctuations or saturation effects of brain activity were observed during rTMS depending on the TEP component. Overall, global brain activity increased over the course of stimulation. Single-subject analysis revealed inter-individual temporal courses of global brain activity. The present findings are in favor of dose-response considerations and attempts in personalization of rTMS protocols.

A real-world retrospective cohort study comparing two bilateral stimulation protocols of add-on rTMS in patients with treatment resistant depression and severe anxiety

BackgroundTranscranial magnetic stimulation (TMS) has been shown to improve response and remission in patients with treatment resistant depression. The objective of this study was to compare the efficacy of two bilateral rTMS protocols with different protocols in patients with treatment resistant depression and comorbid severe anxiety. MethodsA retrospective cohort study involving 67 patients who underwent two different bilateral TMS protocols and who met the specified eligibility criteria was conducted. Group 1 received stimulation with 85% RMT intermittent theta burst (iTBS) in the left DLPFC + 120% RMT (1 Hz) in the right DLPFC. Group 2 received stimulation with 100% RMT (iTBS) in the left DLPFC + 110% RMT (1 Hz) in the left DLPFC. ResultsAfter the magnetic stimulation treatment, 55% (n=22) achieved response to depression symptoms in group 1 and 62% (n=18) in group 2. Remission of depression symptoms was achieved in 13% in group 1 (n=5) and 24% in group 2 (n=7). There were no significant differences between the two protocols after TMS ConclusionsDifferent bilateral protocol parameters in individuals undergoing TMS may have an impact on symptom response and remission. Further studies with larger sample sizes are needed.

Role of Repetitive Transcranial Magnetic Stimulation in Treatment of Fibromyalgia: A Randomized Controlled Trial.

Fibromyalgia syndrome (FMS) is a chronic disease characterized by widespread, persistent musculoskeletal pain in association with impaired health-related quality of life. Repetitive transcranial magnetic stimulation (rTMS) is an emerging tool for the management of fibromyalgia. There is no standardized protocol of rTMS for the treatment of FMS, and both low- and high-frequency stimulation of the dorsolateral prefrontal cortex (DLPFC) are described in the literature with variable efficacy. The objective of this study was to determine the effectiveness of rTMS in people with fibromyalgia and compare the response of low- and high-frequency stimulation with sham stimulation. This study was a single-blinded, randomized, placebo-controlled trial. Ninety patients with the diagnosis of FMS were randomly allocated into one of the following three groups: low-frequency (1 Hz) group, high-frequency (10 Hz) group, and sham group. Pain, depression, anxiety, and quality of life were measured using the Numerical Pain Rating Scale (NPRS), Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HDRS), and Revised Fibromyalgia Impact Questionnaire (FIQR) immediately following treatment as well as at 1 and 3 months after treatment. The data was statistically analyzed using Statistical Package for the Social Sciences version 23 software. P value < 0.05 was considered statistically significant. Intergroup analysis revealed a significant improvement in NPRS, HAM-A, HDRS, and FIQR scores in both low- and high- frequency groups immediately following treatment and for 3 months after treatment. No significant difference in the efficacy of low- and high-frequency stimulation was noticed. rTMS is an effective mode of treatment in people with FMS. Both low and high frequencies of stimulation at DLPFC are equally effective in reducing pain and associated symptoms.

Transcranial Magnetic Stimulation of Dorsolateral Prefrontal Cortex in Treatment-Resistant Obsessive Compulsive Disorder: A Mini-Review

Introduction: Approximately two-thirds of patients with Obsessive-Compulsive Disorder (OCD) exhibit inadequate responses to current standard therapies. A previous meta-analysis has shown the potential benefit of repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (dlPFC) area in patients with OCD. However, the analysis also included patients who had not previously failed first-line treatments. This mini-review aims to explore the therapeutic effects of rTMS applied to the dlPFC area in patients with treatment-resistant OCD. Methods: We conducted a comprehensive search for randomized controlled trials (RCTs) and observational studies across various databases (PubMed, EMBASE, Ebsco, Web of Science, and Cochrane Central). Eligible studies encompassed rTMS administered to the dlPFC area in cases of treatment-resistant OCD. Studies that did not focus on using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) to assess the efficacy of rTMS were excluded. Quality assessments were conducted based on the Cochrane risk-of-bias tool. Results: Our review identified five RCTs involving 132 patients that met the established criteria. The application of high-frequency (HF) and low-frequency (LF) rTMS to the dlPFC region yielded controversial post-treatment Y-BOCS findings due to factors such as small sample sizes, short-term study durations, variations in rTMS protocols, and four studies exhibiting a high risk of bias. Discussion: The available data is constrained by a scarcity of high-quality, large-scale trials with extended follow-up periods and optimized protocols. Further research is warranted to establish the efficacy of rTMS administered to the dlPFC in this patient population.

Utility of Repetitive Transcranial Magnetic Stimulation for Chronic Daily Headache Prophylaxis: A Systematic Review and Meta-Analysis.

Management of chronic daily headaches (CDH) remains challenging due to the limited efficacy of standard prophylactic pharmacological measures. Several studies have reported that repetitive transcranial magnetic stimulation (rTMS) can effectively treat chronic headaches. The objective was to determine the utility of rTMS for immediate post-treatment and sustained CDH prophylaxis. All procedures were conducted per PRISMA guidelines. PubMed, Scopus, Web of Science, and ProQuest databases were searched for controlled clinical trials that have tested the efficacy of rTMS on populations with CDH. DerSimonian-Laird random-effects meta-analyses were performed using the 'meta' package in R to examine the post- vs. pre-rTMS changes in standardized headache intensity and frequency compared to sham-control conditions. Thirteen trials were included with a combined study population of N = 538 patients with CDH (rTMS, N = 284; Sham, N = 254). Patients exposed to rTMS had significantly reduced standardized CDH intensity and frequency in the immediate post-treatment period (Hedges' g = -1.16 [-1.89, -0.43], p = 0.002 and Δ = -5.07 [-10.05, -0.11], p = 0.045 respectively). However, these effects were sustained marginally in the follow-up period (Hedges' g = -0.43 [-0.76, -0.09], p = 0.012 and Δ = -3.33 [-5.52, -1.14], p = 0.003). Significant between-study heterogeneity was observed, at least partially driven by variations in rTMS protocols. Despite the observed clinically meaningful and statistically significant benefits in the immediate post-treatment period, the prophylactic effects of rTMS on CDH do not seem to sustain with discontinuation. Thus, the cost-effectiveness of the routine use of rTMS for CDH prophylaxis remains questionable. Protocol preregistered in PROSPERO International Prospective Register of Systematic Reviews (CRD42021250100).