Repetitive Transcranial Magnetic Stimulation Protocols Research Articles

Exploring the Therapeutic Potential of Quadripulse rTMS over the Visual Cortex: A Proof-of-Concept Study in Healthy Volunteers and Chronic Migraine Patients with Medication Overuse Headache.

In chronic migraine with medication overuse (CM-MOH), sensitization of visual cortices is reflected by (i) increased amplitude of stimulus-evoked responses and (ii) habituation deficit during repetitive stimulation. Both abnormalities might be mitigated by inhibitory transcranial neurostimulation. Here, we tested an inhibitory quadripulse repetitive transcranial magnetic stimulation (rTMS-QPI) protocol to decrease durably visual cortex excitability in healthy subjects (HS) and explored its therapeutic potential in CM-MOH patients. Pattern-reversal visual evoked potentials (VEP) were used as biomarkers of effect and recorded before (T1), immediately after (T2), and 3 h after stimulation (T3). In HS, rTMS-QPI durably decreased the VEP 1st block amplitude (p < 0.05) and its habituation (p < 0.05). These changes were more pronounced for the P1N2 component that was modified already at T2 up to T3, while for N1P1 they were significant only at T3. An excitatory stimulation protocol (rTMS-QPE) tended to have an opposite effect, restricted to P1N2. In 12 CM-MOH patients, during a four-week treatment (2 sessions/week), rTMS-QPI significantly reduced monthly headache days (p < 0.01). In patients reversing from CM-MOH to episodic migraine (n = 6), VEP habituation significantly improved after treatment (p = 0.005). rTMS-QPI durably decreases visual cortex responsivity in healthy subjects. In a proof-of-concept study of CM-MOH patients, rTMS-QPI also has beneficial clinical and electrophysiological effects, but sham-controlled trials are needed.

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

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

A randomized trial comparing beam F3 and 5.5 cm targeting in rTMS treatment of depression demonstrates similar effectiveness

BackgroundThe Beam F3 and 5.5 cm methods are the two most common targeting strategies for localizing the left dorsolateral prefrontal cortex (DLPFC) treatment site in repetitive transcranial magnetic stimulation (rTMS) protocols. This prospective, randomized, double-blind comparative effectiveness trial assesses the clinical outcomes for these two methods in a naturalistic sample of patients with major depressive disorder (MDD) undergoing clinical rTMS treatment. Methods105 adult patients with MDD (mean age = 43.2; range = 18–73; 66% female) were randomized to receive rTMS to the Beam F3 (n = 58) or 5.5 cm (n = 47) target. Between group differences from pre-to post-treatment were evaluated with the Patient Health Questionnaire-9 (PHQ-9) [primary outcome measure], Generalized Anxiety Disorder-7 (GAD-7), and clinician-administered Montgomery-Åsberg Depression Scale (MADRS). Primary treatment endpoint was completion of daily treatment series. ResultsPer-protocol analyses showed no statistically significant differences on any measure between the 5.5 cm and F3 groups (all p ≥ 0.50), including percent improvement (PHQ-9: 39% vs. 39%; GAD-7: 34% vs. 27%; MADRS: 40% vs. 38%), response rate (PHQ-9: 37% vs. 43%; GAD-7: 27% vs. 30%; MADRS: 43% vs. 43%), and remission rate (PHQ-9: 22% vs. 21%; MADRS: 20% vs. 19%). Post hoc analysis of anxiety symptom change while controlling for depression severity suggested more favorable anxiolytic effects with 5.5 cm targeting (p = 0.03). ConclusionsSimilar antidepressant effects were observed with DLFPC rTMS using either the Beam F3 or 5.5 cm targeting method, supporting clinical equipoise in MDD patients with head circumference ≤ 60 cm. Comparison to MRI-based targeting and differential effects on anxiety symptoms require further investigation. Trial registrationClinicalTrials.gov identifier: NCT03378570.

Pattern of Compliance and Efficacy of Repetitive Transcranial Magnetic Stimulation Protocol for Treating Major Depressive Disorder Among Treatment Participants and Completers: A Report From Iran.

Since the introduction of the Food and Drug Administration (FDA)-approved repetitive transcranial magnetic stimulation (rTMS) intervention in 2008, a breakthrough has been made in treating major depressive disorder (MDD). However, many sessions of treatment and its cost make it inconvenient for those who seek treatment, especially in large cities as well as in developing countries. A total of 22 patients (out of initial 24 referrals) who met diagnostic and statistical manual of mental disorders, 4th edition (DSM IV) criteria for MDD were enrolled in the study. All subjects had to fail at least one prior treatment for depression. The patients received the FDA-approved protocol of high-frequency (10 Hz) rTMS over the left dorsolateral prefrontal cortex. Seventeen out of twenty-two cases showed significant improvements after two weeks of treatment. Only six patients continued their treatments for the next two to four weeks. We have replicated other studies showing that the use of rTMS is effective for many patients with MDD without major side effects and their improvements are measurable mostly after two weeks. Our data highlight the importance of the application of more convenient protocols that require fewer sessions on fewer days to help with compliance and outcome, particularly in large populated cities and countries, such as Iran going through economic hardship. Repetitive transcranial magnetic stimulation (rTMS) is effective for treating major depresion.Improvemens are measurable after 2 weeks of treating with rTMS.Compliance is a major factorto for completing rTMS protocols. Major depression is one of the most common psychiatric disorders leading to debilitating course causing significant burden for the society. Many cases with major depression are resistent to treatment as they try multiple interventions with no success. This condition is also called refractory depression. rTMS is a novel intervention introduced first almost two decades ago to treat refractory depression among some other psychiatric disorders. In this intervention pulses generated by magnetic stimulation over the brain leads to improvement is depression. As this treatment is safe with no pain and discomfort there have been much interest in the field to use it more frequently. rTMS is usually done over 15-30 sessions with its maximum effects appearing within the first two weeks of treatment. The number of sessions is a potential factor contributing to poor compliance in some cases especially those living in large metropolitan areas. In this paper we explored compliance and effect of treatment within the first two weeks among a group of patients in a private outpatient clinic of a large metropolitan area.

Will Transcranial Magnetic Stimulation Improve the Treatment of Obsessive-Compulsive Disorder? A Systematic Review and Meta-Analysis of Current Targets and Clinical Evidence.

Although in 2017 a repetitive transcranial magnetic stimulation (rTMS) protocol received Food and Drug Administration approval for the first time for the treatment of obsessive-compulsive disorder (OCD), which neural target and which protocol should be used for OCD are still debated. The aim of the present study was to perform a systematic review and meta-analysis of the available open and sham-controlled trials. The primary analysis included a pairwise meta-analysis (over 31 trials), and then subgroup analyses were performed for each targeted brain area. Meta-regression analyses explored the possible moderators of effect size. The pairwise meta-analysis showed a significant reduction in OCD symptoms following active rTMS (g = -0.45 [95%CI: -0.62, -0.29]) with moderate heterogeneity (I2 = 34.9%). Subgroup analyses showed a significant effect of rTMS over the bilateral pre-SMA (supplementary motor area), the DLPFC (dorsolateral prefrontal cortex), the ACC/mPFC (anterior cingulate cortex and medial prefrontal cortex), and the OFC (orbitofrontal cortex). No moderators of the effect size emerged. TMS of several brain targets represents a safe and effective treatment option for OCD patients. Further studies are needed to help clinicians to individualize TMS protocols and targets for each patient.

Neuromodulatory effects and reproducibility of the most widely used repetitive transcranial magnetic stimulation protocols.

Repetitive transcranial magnetic stimulation (rTMS) is widely used in both research and clinical settings to modulate human brain function and behavior through the engagement of the mechanisms of plasticity. Based upon experiments using single-pulse TMS as a probe, the physiologic mechanism of these effects is often assumed to be via changes in cortical excitability, with 10 Hz rTMS increasing and 1 Hz rTMS decreasing the excitability of the stimulated region. However, the reliability and reproducibility of these rTMS protocols on cortical excitability across and within individual subjects, particularly in comparison to robust sham stimulation, have not been systematically examined. In a cohort of 28 subjects (39 ± 16 years), we report the first comprehensive study to (1) assess the neuromodulatory effects of traditional 1 Hz and 10 Hz rTMS on corticospinal excitability against both a robust sham control, and two other widely used patterned rTMS protocols (intermittent theta burst stimulation, iTBS; and continuous theta burst stimulation, cTBS), and (2) determine the reproducibility of all rTMS protocols across identical repeat sessions. At the group level, neither 1 Hz nor 10 Hz rTMS significantly modulated corticospinal excitability. 1 Hz and 10 Hz rTMS were also not significantly different from sham and both TBS protocols. Reproducibility was poor for all rTMS protocols except for sham. Importantly, none of the real rTMS and TBS protocols demonstrated greater neuromodulatory effects or reproducibility after controlling for potential experimental factors including baseline corticospinal excitability, TMS coil deviation and the number of individual MEP trials. These results call into question the effectiveness and reproducibility of widely used rTMS techniques for modulating corticospinal excitability, and suggest the need for a fundamental rethinking regarding the potential mechanisms by which rTMS affects brain function and behavior in humans.

Functional Connectivity Mapping for rTMS Target Selection in Depression.

Repetitive transcranial magnetic stimulation (rTMS) protocols increasingly use subgenual anterior cingulate cortex (sgACC) functional connectivity to individualize treatment targets. However, the efficacy of this approach is unclear, with conflicting findings and varying effect sizes across studies. Here, the authors investigated the effect of the stimulation site's functional connectivity with the sgACC (sgACC-StimFC) on treatment outcome to rTMS in 295 patients with major depression. The reliability and accuracy of estimating sgACC functional connectivity were validated with data from individuals who underwent extensive functional MRI testing. Electric field modeling was used to analyze associations between sgACC-StimFC and clinical improvement using standardized assessments and to evaluate sources of heterogeneity. An imputation-based method provided reliable and accurate sgACC functional connectivity estimates. Treatment responses weakly but robustly correlated with sgACC-StimFC (r=-0.16), but only when the stimulated cortex was identified using electric field modeling. Surprisingly, this association was driven by patients with strong global signal fluctuations stemming from a specific periodic respiratory pattern (r=-0.49). Functional connectivity between the sgACC and the stimulated cortex was correlated with individual differences in treatment outcomes, but the association was weaker than those observed in previous studies and was accentuated in a subgroup of patients with distinct, respiration-related signal patterns in their scans. These findings indicate that in a large representative sample of patients with major depressive disorder, individual differences in sgACC-StimFC explained only ∼3% of the variance in outcomes, which may limit the utility of existing sgACC-based targeting protocols. However, these data also provide strong evidence for a true-albeit small-effect and highlight opportunities for incorporating additional functional connectivity measures to generate models of rTMS response with enhanced predictive power.

Accelerated repetitive transcranial magnetic stimulation protocol: a 3-month follow-up study of treatment-resistant depressed patients

Accelerated repetitive transcranial magnetic stimulation protocol: a 3-month follow-up study of treatment-resistant depressed patients

Safety and effects of a therapeutic 15 Hz rTMS protocol administered at different suprathreshold intensities in able-bodied individuals.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) remains a promising strategy for neurorehabilitation. The stimulation intensity (SI) influences the aftereffects observed. Here, we examined whether single sessions of a 15 Hz rTMS protocol, administered at suprathreshold SI, can be safely administered to able-bodied (AB) individuals. Six right-handed men were included in this pilot study. HF-rTMS was delivered over the right M1, in 10 trains of 75 biphasic stimuli at 15 Hz, at 105-120% of the individual resting motor threshold (RMT). To assess safety, electromyography (EMG) was monitored to control for signs of spread of excitation and brief EMG burst (BEB) after stimulation. Additionally, TMS side effects questionnaires and the numeric rating scale (NRS) were administered during each session. We assessed corticospinal excitability (CSE) and motor performance changes with measures of resting (rMEP) and active (aMEP) motor evoked potential and grip strength and box and blocks test (BBT) scores, respectively. Overall, the sessions were tolerated and feasible without any pain development. However, EMG analysis during 15 Hz rTMS administration revealed increased BEB frequency with SI. Statistical models revealed an increase of CSE at rest (rMEP) but not during active muscle contraction (aMEP). No linear relationship was observed between 15 Hz rTMS SI and rMEP increase. No significant changes were highlighted for motor performance measures. Although feasible and tolerable by the AB individuals tested, the results demonstrate that when administered at suprathreshold intensities (≥ 105% RMT) the 15 Hz rTMS protocol reveals signs of persistent excitation, suggesting that safety precautions and close monitoring of participants should be performed when testing such combinations of high-intensity and high-frequency stimulation protocols. The results also give insight into the nonlinear existent relationship between the SI and HF-rTMS effects on CSE.NEW & NOTEWORTHY The results of this pilot study show the effects of a therapeutically promising 15 Hz repetitive transcranial magnetic stimulation (rTMS) protocol, administered at different suprathreshold intensities in able-bodied individuals. Although tolerable and feasible with a neuromodulatory potential, 15 Hz rTMS might result in persistent excitability that needs to be closely monitored if administered at suprathreshold stimulation intensity. These results reaffirm the importance of feasibility studies, especially in translational animal-to-human research.

Evaluation of the effect of low-intensity rhythmic transcranial magnetic stimulation on motor and non-motor manifestations of Parkinson's disease

BACKGROUND: The use of repetitive transcranial magnetic stimulation as a method of non-drug therapy of Parkinson's disease has been actively studied over the past decades. The prevailing number of repetitive transcranial magnetic stimulation protocols in Parkinson's disease use a high intensity of stimulation (80120% of the value of the threshold of the evoked motor threshold from the muscles of the hand), while the choice of the stimulation intensity parameter was carried out empirically.&#x0D; AIM: to study the effectiveness of low-intensity unilateral repetitive transcranial magnetic stimulation on motor and non-motor symptoms of Parkinson's disease.&#x0D; MATERIAL AND METHODS:An open prospective non-randomized clinical trial included 37 patients with stage IIII Parkinson's disease according to HoehnYahr (1967), akinetic-rigid and mixed (akinetic-rigid-tremor) forms. All patients underwent repetitive transcranial magnetic stimulation according to the protocol: M1 stimulation zone, frequency 5 Hz, intensity 40% of the cortical motor threshold, on 6s, off 8s, total number of pulses per session 3000. The course of treatment is 10 procedures with 2 days (weekend) off.&#x0D; RESULTS: All patients completed the study in accordance with the protocol. When analyzing the results of the UPDRS scale (Unified Parkinson's disease rating scale), positive dynamics was noted in all parts of the questionnaire: part I ― from 2 (0; 3) to 0 (0; 1) points, p 0.05; part II ― from 9 (5.5; 12.5) to 4 (2; 6.5) points, p 0.05; part III ― with 11 (7; 14.5) to 6 (2; 7.5) points, p 0.05; part IV (Schwab and England scale) ― from 80% (70; 95) to 90% (85; 100), p 0.05. There was also a selective effect on non-motor symptoms.&#x0D; CONCLUSION: Low-intensity exposure (40% of the motor threshold) has a significant clinical effect on motor and non-motor symptoms of Parkinson's disease; stimulation of the primary motor cortex can have an antidepressant effect; repetitive transcranial magnetic stimulation has a selective effect on non-motor symptoms of Parkinson's disease: a predominant effect has been demonstrated with respect to olfactory, emotional, cognitive disorders, sleep disorders and hypersalivation; when assessing the dynamics of motor disorders, a more pronounced effect was noted with respect to rigidity, postural disorders, walking speed, and to a lesser extent, the effect on tremor was noted.

Short- and Long-Term Effects of Repetitive Transcranial Magnetic Stimulation on Poststroke Visuospatial Neglect: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

This systematic review and meta-analysis aimed to assess the effects of repetitive transcranial magnetic stimulation and select a suitable protocol for poststroke visuospatial neglect. PubMed, Cochrane Library, and Embase databases were searched for relevant studies from the inception date to October 31, 2021. The inclusion criteria were (1) randomized controlled trials, (2) people with visuospatial neglect, (3) treatment with different repetitive transcranial magnetic stimulation protocols, (4) comparison with sham or blank control, and (5) reports of performance measurements. Data were obtained from 11 randomized controlled trials. The effects of immediate and 1-mo postintervention were measured using line bisection test, cancellation test, and Catherine Bergego Scale. Results showed statistically significant improvement when applying low-frequency (0.5-1 Hz) repetitive transcranial magnetic stimulation or continuous theta burst stimulation to the left hemisphere on short- and long-term line bisection test (standardized mean difference = -1.10, 95% confidence interval = -1.84 to -0.37; standardized mean difference = -1.25, 95% confidence interval = -2.11 to -0.39) and cancellation test (standardized mean difference = 1.08, 95% confidence interval = 0.45 to 1.71; standardized mean difference = 1.45, 95% confidence interval = 0.42, 2.47). Repetitive transcranial magnetic stimulation may be considered a treatment option for poststroke visuospatial neglect. This review proves that a decrease in neuronal excitation in the left hemisphere, which restores the interhemispheric balance, benefits poststroke visuospatial neglect.

Role of maintenance treatment on long-term efficacy of bilateral iTBS of the prefrontal cortex in treatment-seeking cocaine addicts: A retrospective analysis.

CUD, like other addictions, is a chronic disease characterized by a high rate of relapse and drop-out (DO) from medical and behavioral treatment programs, which is positively correlated with relapse. Repetitive transcranial Magnetic Stimulation (rTMS) protocols have shown therapeutic potential in addiction in the short term, but only a few studies have explored their long-term efficacy, so far. This study explores the long-term outcome of bilateral intermittent theta-burst stimulation (iTBS) of the prefrontal cortex (PFC) in cocaine use disorder (CUD) and the possible influence of maintenance treatment in improving abstinence and decreasing DO rates. Eighty-nine treatment-seeking CUD patients were exposed to 20 sessions of iTBS. At the end of the treatment 61 (81%) abstinent patients underwent a 12 months follow-up. Among these, 27 patients chose to follow a maintenance treatment (M), whereas 34 patients chose not to adhere to a maintenance treatment (NM). Overall, among patients reaching the 12 months follow-up endpoint, 69.7% were still abstinent and 30.3% relapsed. In NM-patients the DO rate was significantly higher than in M-ones (58.82 vs. 29.63%). The present observations show the long-term therapeutic effect of bilateral PFC iTBS to decrease cocaine consumption. Moreover, they underline the importance to perform a maintenance protocol to consolidate abstinence and decrease DO rates over time.

A Different rTMS Protocol for a Different Type of Depression: 20.000 rTMS Pulses for the Treatment of Bipolar Depression Type II

In this open-label naturalistic study, we assess the feasibility, tolerability, and effectiveness of a repetitive transcranial magnetic stimulation protocol with a reduced total pulse number for treating patients suffering from bipolar disorder type II. All patients received one rTMS treatment session of 1000 pulses for 20 consecutive working days, accumulating to 20.000 rTMS pulses applied over 4 weeks. We measured the patients’ symptoms before the start, halfway through, directly after, and one month after treatment. We quantified the depression symptoms using both the Beck depression inventory scale and the symptom checklist-90 depression subscale. Patients showed a significant reduction in depression symptoms directly after treatment and an even further reduction one month after treatment. The remission rates were at 26% halfway through treatment (after the 10th session), 61% directly after treatment (after the 20th session), and increased to 78% at the 1-month follow-up. Importantly, the protocol proved to be feasible and highly tolerable in this patient population, with no adverse effects being reported. Considering these positive results, further research should focus on replicating these findings in larger clinical samples with control groups and longer follow-up periods, while potentially adding maintenance sessions to optimize the treatment effect and stability for bipolar disorder type II patients.

Intensive rTMS for treatment-resistant depression patients with suicidal ideation: An open-label study.

The advantages of intensive repetitive transcranial magnetic stimulation (rTMS) protocol are in the possible acute effect of the stimulation and in the possible reduction in the time required to achieve remission in depression. Here, we investigated the antidepressant effects and antisuicidal effects of a more intensive rTMS protocol for treatment-resistant depression (TRD) patients with suicidal ideation. Thirty-one outpatients were included in this study, including 22 military veterans and 9 non- militaries. The rTMS treatment consisted of 25 sessions, each session lasting 30min (60 trains of 50 pulsations, 110 % resting motor threshold intensity) for a total of 3000 pulse. The total amount of stimulation (750,000 pulses) applied by our rTMS protocol was equivalent to that of a 5-week standard rTMS protocol. We found a significant effect of time on the 17-item Hamilton Depression Rating Scale (HAMD-17) scores and the Sheehan Disability Scale (SDS) scores. There was no difference in change in the HAMD-17 scores and SDS scores between the military veteran group and the non-military group between baseline and the week 4 assessment time point. The response rate of depression was 64.52 %, and the remission rate of depression was 51.61 % at day 5. 48.39 % and 35.48 % at week 4, respectively. All patients (100 %) met response criteria of suicidal ideation, and the remission rate was 87.09 % at day 5. The response rate was 83.87 % %, and the remission rate was 77.42 % at week 4. The accelerated high-dose rTMS treatment was well tolerated by all patients. Our intensive rTMS protocol is preliminarily safe and feasible. The TRD patients with suicidal ideation could benefit from much shorter exposure to this protocol with more efficacy in comparison with conventional rTMS protocol. In addition, intensive rTMS offers a promising treatment for military veteran populations.

Personalizing repetitive transcranial magnetic stimulation for precision depression treatment based on functional brain network controllability and optimal control analysis

Brain neuromodulation effectively treats neurological diseases and psychiatric disorders such as Depression. However, due to patient heterogeneity, neuromodulation treatment outcomes are often highly variable, requiring patient-specific stimulation protocols throughout the recovery stages to optimize treatment outcomes. Therefore, it is critical to personalize neuromodulation protocol to optimize the patient-specific stimulation targets and parameters by accommodating inherent interpatient variability and intersession alteration during treatments. The study aims to develop a personalized repetitive transcranial magnetic stimulation (rTMS) protocol and evaluate its feasibility in optimizing the treatment efficiency using an existing dataset from an antidepressant experimental imaging study in depression. The personalization of the rTMS treatment protocol was achieved by personalizing both stimulation targets and parameters via a novel approach integrating the functional brain network controllability analysis and optimal control analysis. First, the functional brain network controllability analysis was performed to identify the optimal rTMS stimulation target from the effective connectivity network constructed from patient-specific resting-state functional magnetic resonance imaging data. The optimal control algorithm was then applied to optimize the rTMS stimulation parameters based on the optimized target. The performance of the proposed personalized rTMS technique was evaluated using datasets collected from a longitudinal antidepressant experimental imaging study in depression (n = 20). Simulation models demonstrated that the proposed personalized rTMS protocol outperformed the standard rTMS treatment by efficiently steering a depressive resting brain state to a healthy resting brain state, indicated by the significantly less control energy needed and higher model fitting accuracy achieved. The node with the maximum average controllability of each patient was designated as the optimal target region for the personalized rTMS protocol. Our results also demonstrated the theoretical feasibility of achieving comparable neuromodulation efficacy by stimulating a single node compared to stimulating multiple driver nodes. The findings support the feasibility of developing personalized neuromodulation protocols to more efficiently treat depression and other neurological diseases.

Accelerated low-intensity rTMS does not rescue anxiety behaviour or abnormal connectivity in young adult rats following chronic restraint stress

Currently approved repetitive transcranial magnetic stimulation (rTMS) protocols for the treatment of major depressive disorder (MDD) involve once-daily (weekday) stimulation sessions, with 10 Hz or intermittent theta burst stimulation (iTBS) frequencies, over 4–6 weeks. Recently, accelerated treatment protocols (multiple daily stimulation sessions for 1–2 weeks) have been increasingly studied to optimize rTMS treatments. Accelerated protocols might confer unique advantages for adolescents and young adults but there are many knowledge gaps related to dosing in this age group. Off-label, clinical practice frequently outpaces solid evidence as rigorous clinical trials require substantial time and resources. Murine models present an opportunity for high throughput dose finding studies to focus subsequent clinical trials in humans. This project investigated the brain and behavioural effects of an accelerated low-intensity rTMS (LI-rTMS) protocol in a young adult rodent model of chronic restraint stress (CRS). Depression and anxiety-related behaviours were induced in young adult male Sprague Dawley rats using the CRS model, followed by the 3-times-daily delivery of 10 Hz LI-rTMS, for two weeks. Behaviour was assessed using the Elevated Plus Maze and Forced Swim Test, and functional, chemical, and structural brain changes measured using magnetic resonance imaging techniques. CRS induced an agitated depression-like phenotype but therapeutic effects from the accelerated protocol were not detected. Our findings suggest that the age of rodents may impact response to CRS and LI-rTMS. Future studies should also examine higher intensities of rTMS and accelerated theta burst protocols.

Transcranial Magnetic Stimulation in the Treatment of Neurological Diseases.

Transcranial Magnetic Stimulation (TMS) has widespread use in research and clinical application. For psychiatric applications, such as depression or OCD, repetitive TMS protocols (rTMS) are an established and globally applied treatment option. While promising, rTMS is not yet as common in treating neurological diseases, except for neurorehabilitation after (motor) stroke and neuropathic pain treatment. This may soon change. New clinical studies testing the potential of rTMS in various other neurological conditions appear at a rapid pace. This can prove challenging for both practitioners and clinical researchers. Although most of these neurological applications have not yet received the same level of scientific/empirical scrutiny as motor stroke and neuropathic pain, the results are encouraging, opening new doors for TMS in neurology. We here review the latest clinical evidence for rTMS in pioneering neurological applications including movement disorders, Alzheimer's disease/mild cognitive impairment, epilepsy, multiple sclerosis, and disorders of consciousness.

Improved Interhemispheric Functional Connectivity in Postpartum Depression Disorder: Associations With Individual Target-Transcranial Magnetic Stimulation Treatment Effects.

Postpartum depression (PPD) is a depressive condition that is associated with a high risk of stressful life events, poor marital relationships, and even suicide. Neuroimaging techniques have enriched our understanding of cerebral mechanisms underlying PPD; namely, abnormalities in the amygdala-insula-frontal circuit might contribute to the pathogenesis of PPD. Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) is a recently validated neuroscience-informed accelerated intermittent theta-burst stimulation repetitive transcranial magnetic stimulation (rTMS) protocol. It has been shown to be effective, safe, tolerable, and rapid acting for treating treatment-resistant depression, and may be a valuable tool in the treatment of PPD. The purpose of the current study was to detect inter-hemispheric connectivity changes and their relationship with the clinical treatment effects of rTMS. Resting-state fMRI data from 32 patients with PPD treated with SAINT were collected and compared with findings from 32 age matched healthy controls. Voxel-mirrored homotopic connectivity (VMHC) was used to analyze the patterns of interhemispheric intrinsic functional connectivity in patients with PPD. Scores on the 17-item Hamilton Depression Rating Scale, Edinburgh Postnatal Depression Scale (EPDS) scores, and the relationships between these clinical characteristics and VMHC were the primary outcomes. Patients with PPD at baseline showed reduced VMHC in the amygdala, insula, and medial frontal gyrus compared with the HCs. These properties showed a renormalization after individualized rTMS treatment. Furthermore, increased connectivity between the left and right insula after SAINT was significantly correlated with the improvement of EPDS scores. Our results reveal the disruptions in the intrinsic functional architecture of interhemispheric communication in patients with PPD, and provide evidence for the pathophysiological mechanisms and the effects of rTMS.

Modulating intrinsic functional connectivity with visual cortex using low-frequency repetitive transcranial magnetic stimulation.

IntroductionIntrinsic network connectivity becomes altered in pathophysiology. Noninvasive brain stimulation can modulate pathological functional networks in an attempt to restore the inherent response. To determine its usefulness for visual‐related disorders, we developed procedures investigating repetitive transcranial magnetic stimulation (rTMS) protocols targeting the visual cortex on modulating connectivity associated with the visual network and default mode network (DMN).MethodsWe compared two low‐frequency (1 Hz) rTMS protocols to the visual cortex (V1)—a single 20 min session and five successive 20 min sessions (accelerated/within‐session rTMS)—using multi‐echo resting‐state functional magnetic resonance whole‐brain imaging and resting‐state functional connectivity (rsFC). We also explored the relationship between rsFC and rTMS‐induced changes in key inhibitory and excitatory neurotransmitters, γ‐aminobutyric acid (GABA) and glutamate. GABA (GABA+) and glutamate (Glx) concentrations were measured in vivo using magnetic resonance spectroscopy.ResultsAcute disruption with a single rTMS session caused widespread connectivity reconfiguration with nodes of interest. Changes were not evident immediately post‐rTMS but were observed at 1 h post‐rTMS. Accelerated sessions resulted in weak alterations in connectivity, producing a relatively homeostatic response. Changes in GABA+ and Glx concentrations with network connectivity were dependent on the rTMS protocol.ConclusionsThis proof‐of‐concept study offers new perspectives to assess stimulation‐induced neural processes involved in intrinsic functional connectivity and the potential for rTMS to modulate nodes interconnected with the visual cortex. The differential effects of single‐session and accelerated rTMS on physiological markers are crucial for furthering the advancement of treatment modalities in visual cortex related disorders.

Effects of non-invasive brain stimulation in multiple sclerosis: systematic review and meta-analysis.

Objective:The objective of this meta-analysis was to summarize evidence on the therapeutic effects of non-invasive brain stimulation (NIBS) on core symptoms of multiple sclerosis (MS). Specifically, findings from studies deploying transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) protocols were summarized in this review.Methods:We systematically searched articles published in four databases, until 31 May 2021, which compared the effects of active tDCS or rTMS with sham intervention in MS patients. We used a random-effects model for this meta-analysis. Meta-regression and subgroup meta-analysis were used to examine the effects of stimulation dose and different stimulation protocols, respectively.Results:Twenty-five randomized controlled trials (RCTs) were included in this review, consisting of 19 tDCS and 6 rTMS studies. tDCS led to a significant and immediate reduction of fatigue with a large effect size (Hedges’s g = −0.870, 95% confidence intervals (CI) = [−1.225 to −0.458], number needed to treat (NNT) = 2). Particularly, a subgroup analysis showed that applying tDCS over the left DLPFC and bilateral S1 led to fatigue reductions compared to sham stimulation. Furthermore, tDCS had favorable effects on fatigue in MS patients with low physical disability but not those with high physical disability, and additionally improved cognitive function. Finally, whereas rTMS was observed to reduce muscle spasticity, these NIBS protocols showed no further effect on MS-associated pain and mood symptoms.Conclusion:tDCS in MS alleviates fatigue and improves cognitive function whereas rTMS reduces muscle spasticity. More high-quality studies are needed to substantiate the therapeutic effects of different NIBS protocols in MS.