Intermittent Theta Burst Stimulation Research Articles

Intermittent theta-burst stimulation improves motor function by inhibiting neuronal pyroptosis and regulating microglial polarization via TLR4/NFκB/NLRP3 signaling pathway in cerebral ischemic mice

BackgroundNeuronal pyroptosis and neuroinflammation with excess microglial activation are widely involved in the early pathological process of ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive neuromodulatory technique, has recently been reported to be anti-inflammatory and regulate microglial function. However, few studies have elucidated the role and mechanism of rTMS underlying regulating neuronal pyroptosis and microglial polarization.MethodsWe evaluated the motor function in middle cerebral artery occlusion/reperfusion (MCAO/r) injury mice after 1-week intermittent theta-burst rTMS (iTBS) treatment in the early phase with or without depletion of microglia by colony-stimulating factor 1 receptor (CSF1R) inhibitor treatment, respectively. We further explored the morphological and molecular biological alterations associated with neuronal pyroptosis and microglial polarization via Nissl, EdU, TTC, TUNEL staining, electron microscopy, multiplex cytokine bioassays, western blot assays, immunofluorescence staining and RNA sequencing.ResultsITBS significantly protected against cerebral ischemia/reperfusion (I/R) injury-induced locomotor deficits and neuronal damage, which probably relied on the regulation of innate immune and inflammatory responses, as evidenced by RNA sequencing analysis. The peak of pyroptosis was confirmed to be later than that of apoptosis during the early phase of stroke, and pyroptosis was mainly located and more severe in the peri-infarcted area compared with apoptosis. Multiplex cytokine bioassays showed that iTBS significantly ameliorated the high levels of IL-1β, IL-17A, TNF-α, IFN-γ in MCAO/r group and elevated the level of IL-10. ITBS inhibited the expression of neuronal pyroptosis-associated proteins (i.e., Caspase1, IL-1β, IL-18, ASC, GSDMD, NLRP1) in the peri-infarcted area rather than at the border of infarcted core. KEGG enrichment analysis and further studies demonstrated that iTBS significantly shifted the microglial M1/M2 phenotype balance by curbing proinflammatory M1 activation (Iba1+/CD86+) and enhancing the anti-inflammatory M2 activation (Iba1+/CD206+) in peri-infarcted area via inhibiting TLR4/NFκB/NLRP3 signaling pathway. Depletion of microglia using CSF1R inhibitor (PLX3397) eliminated the motor functional improvements after iTBS treatment.ConclusionsrTMS could alleviate cerebral I/R injury induced locomotor deficits and neuronal pyroptosis by modulating the microglial polarization. It is expected that these data will provide novel insights into the mechanisms of rTMS protecting against cerebral I/R injury and potential targets underlying neuronal pyroptosis in the early phase of stroke.

Effect of neuroanatomy on corticomotor excitability during and after transcranial magnetic stimulation and intermittent theta burst stimulation.

Individual neuroanatomy can influence motor responses to transcranial magnetic stimulation (TMS) and corticomotor excitability after intermittent theta burst stimulation (iTBS). The purpose of this study was to examine the relationship between individual neuroanatomy and both TMS response measured using resting motor threshold (RMT) and iTBS measured using motor evoked potentials (MEPs) targeting the biceps brachii and first dorsal interosseus (FDI). Ten nonimpaired individuals completed sham‐controlled iTBS sessions and underwent MRI, from which anatomically accurate head models were generated. Neuroanatomical parameters established through fiber tractography were fiber tract surface area (FTSA), tract fiber count (TFC), and brain scalp distance (BSD) at the point of stimulation. Cortical magnetic field induced electric field strength (EFS) was obtained using finite element simulations. A linear mixed effects model was used to assess effects of these parameters on RMT and iTBS (post‐iTBS MEPs). FDI RMT was dependent on interactions between EFS and both FTSA and TFC. Biceps RMT was dependent on interactions between EFS and and both FTSA and BSD. There was no groupwide effect of iTBS on the FDI but individual changes in corticomotor excitability scaled with RMT, EFS, BSD, and FTSA. iTBS targeting the biceps was facilitatory, and dependent on FTSA and TFC. MRI‐based measures of neuroanatomy highlight how individual anatomy affects motor system responses to different TMS paradigms and may be useful for selecting appropriate motor targets when designing TMS based therapies.

Efficacy of mechanisms of neuroplasticity after a stroke.

The sequelae of stoke, including the loss and recovery of function, are strongly linked to the mechanisms of neuroplasticity. Rehabilitation and non-invasive brain stimulation (NIBS) paradigms have shown promise in modulating corticomotor neuroplasticity to promote functional recovery in individuals post-stroke. However, an important limitation to these approaches is that while stroke recovery depends on the mechanisms of neuroplasticity, those mechanisms may themselves be altered by a stroke. Compare Transcranial Magnetic Stimulation (TMS)-based assessments of efficacy of mechanism of neuroplasticity between individuals post-stroke and age-matched controls. Thirty-two participants (16 post-stroke, 16 control) underwent an assessment of mechanisms of neuroplasticity, measured by the change in amplitude of motor evoked potentials elicited by single-pulse TMS 10-20 minutes following intermittent theta-burst stimulation (iTBS), and dual-task effect (DTE) reflecting cognitive-motor interference (CMI). In stroke participants, we further collected: time since stroke, stroke type, location, and Stroke Impact Scale 16 (SIS-16). Although there was no between-group difference in the efficacy of TMS-iTBS neuroplasticity mechanism (p = 0.61, η2 = 0.01), the stroke group did not exhibit the expected facilitation to TMS-iTBS (p = 0.60, η2 = 0.04) that was shown in the control group (p = 0.016, η2 = 0.18). Sub-cohort analysis showed a trend toward a difference between those in the late-stage post-stroke and the control group (p = 0.07, η2 = 0.12). Within the post-stroke group, we found significant relationships between TMS-iTBS neuroplasticity and time since stroke onset, physical function (SIS-16), and CMI (all rs > |0.53| and p-values < 0.05). In this proof-of-principle study, our findings suggested altered mechanisms of neuroplasticity in post-stroke patients which were dependent on time since stroke and related to motor function. TMS-iTBS neuroplasticity assessment and its relationship with clinical functional measures suggest that TMS may be a useful tool to study post-stroke recovery. Due to insufficient statistical power and high variability of the data, generalization of the findings will require replication of the results in a larger, better-characterized cohort.

Efficacy and safety of intermittent theta burst stimulation (iTBS) in treatment resistant depression

IntroductionRepetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulatory treatment option, which is used in a variety of neurological and psychiatric diseases. It is approved for depression treatment and recommended in international guidelines. A significant reduction in treatment duration was achieved by using theta burst stimulation (TBS) protocols, which are practicable and non-inferior to conventional TMS.ObjectivesTo analyse the efficacy and safety of intermittent theta burst stimulation (iTBS) of left DLPFC in inpatients with treatment-resistant depression.MethodsWe evaluated n=44 inpatients with treatment resistant major depressive disorder (n=37) and bipolar depression (n=7), who were treated with the 5 Hz intermittent TBS once daily for 3-6 weeks according to clinical decision. A total of 600 pulses and 200 bursts were applied in each treatment session. Clinical and response data were obtained by chart review.ResultsMean age at time of first stimulation was 54 years. 61,3 % of patients were female. On average, the current episode started 21 months before the first stimulation. In total, 924 treatment sessions were performed. On average, patients received 21 sessions. The mean MADRS Score pre-treatment was 27.2. Post-treatment, there was a clear reduction in depression severity (MADRS 18.3). No severe adverse events and no seizures occurred in this clinical observational analysis.ConclusionsIntermittent TBS is efficacious and safe in patients with chronic and refractory depression.DisclosureNo significant relationships.

P.054 Effects of cerebellar Theta Burst Stimulation (TBS) on working memory

Background: Recent evidence suggests that the cerebellum is involved in cognitive functions. Theta burst stimulation (TBS), a modality of transcranial magnetic stimulation (TMS), on the cerebellum can change its contribution to working memory. Therefore, we hypothesize that excitatory intermittent TBS (iTBS) on the cerebellum would improve performance on working memory tasks, whereas inhibitory continuous TBS (cTBS) would disrupt it. Methods: As this is an ongoing study, nine participants (6 women) took part in this study so far. TBS was applied on the cerebellum bilaterally. All subjects received iTBS, cTBS, and sham iTBS in three sessions in random order. After TBS in each session, participants performed three types of working memory tasks: letter 2-back, digit span forward (DSF), and digit span backward (DSB). Results: The preliminary results suggest that participants performed better in the sham condition in the letter 2-back and the DSB tasks compared to the iTBS and cTBS conditions, but the results did not reach statistical significance due to the small sample size. Conclusions: The preliminary results show that the cerebellar contribution to working memory may be disrupted by TBS. As we gain more statistical power by recruiting more participants, we hope to further demonstrate the effects of cerebellar TBS on working memory.

Efficacy of Repetitive Transcranial Magnetic Stimulation in Patients With Methamphetamine Use Disorder: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has demonstrated therapeutic potential for treating patients with methamphetamine use disorder (MUD). However, the most effective target and stimulation frequency of rTMS for treating MUD remains unclear. This meta-analysis explored the effect of rTMS on MUD.MethodsIn this study, PubMed, Cochrane Systematic Reviews, and the Cochrane Collaboration Central Register of Controlled Clinical Trials were searched electronically for double-blind randomized controlled trials that used rTMS for treating MUD. We used published trials to investigate the efficacy of rTMS in MUD up to March 5, 2022, and pooled studies using a random-effect model to compare rTMS treatment effects. Patients who were diagnosed with MUD according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders were recruited. Clinical craving scores between baseline and after rTMS were compared using the standardized mean difference (SMD) with 95% confidence intervals (CIs). The heterogeneity of the included trials was evaluated through a visual inspection of funnel plots and the I2 statistic.ResultsWe identified seven trials with 462 participants with MUD that met the inclusion criteria. All the studies evaluated craving scores, with rTMS demonstrating a more significant effect than the sham treatment on reducing craving scores (SMD = 0.983, CI = 0.620–1.345, p ≤ 0.001). A subgroup meta-analysis revealed that intermittent theta-burst stimulation (iTBS) had a greater positive effect than 10-Hz rTMS. A metaregression revealed that the SMDs increased with the increase in baseline craving scores, whereas they decreased with the increase in the proportion of men and duration of abstinence.ConclusionThe meta-analysis suggests that rTMS may be associated with treatment effect on craving symptoms in patients with MUD. iTBS may have a greater positive effect on craving reduction than 10-z rTMS.

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.

Accelerated Intermittent Theta Burst Stimulation in Smoking Cessation: Placebo Effects Equal to Active Stimulation When Using Advanced Placebo Coil Technology

Smoking is currently one of the main public health problems. Smoking cessation is known to be difficult for most smokers because of nicotine dependence. Repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) has been shown to be effective in the reduction of nicotine craving and cigarette consumption. Here, we evaluated the efficacy of accelerated intermittent theta burst stimulation (aiTBS; four sessions per day for 5 consecutive days) over the left DLPFC in smoking cessation, and we investigated whether the exposure to smoking-related cues compared to neutral cues during transcranial magnetic stimulation (TMS) impacts treatment outcome. A double-blind, randomized, controlled study was conducted in which 89 participants (60 males and 29 females; age 45.62 ± 13.42 years) were randomly divided into three groups: the first group received active aiTBS stimulation while watching neutral videos, the second group received active aiTBS stimulation while watching smoking-related videos and the last group received sham stimulation while watching smoking-related videos. Our results suggest that aiTBS is a tolerable treatment. All treatment groups equally reduced cigarette consumption, nicotine dependence, craving and perceived stress. The effect on nicotine dependence, general craving and perceived stress lasted for at least 1 week after the end of treatment. Active aiTBS over the left DLPFC, combined with smoking related cues, is as effective as active aiTBS combined with neutral cues as well as placebo aiTBS in smoking cessation. These findings extend the results of previous studies indicating that TMS therapy is associated with considerably large placebo effects and that these placebo effects may be further increased when using advanced placebo coil technology.Clinical Trial Registrationwww.clinicaltrials.gov, identifier NCT05271175.

Cortical excitatory and inhibitory correlates of the fronto-limbic circuit in major depression and differential effects of left frontal brain stimulation in a randomized sham-controlled trial

BackgroundMajor depressive disorder (MDD), particularly treatment-resistant ones, is associated with abnormal fronto-limbic glucose metabolism. 10-Hz repetitive transcranial magnetic stimulation (rTMS) over left prefrontal cortex (PFC) is believed to normalize the abnormal metabolism to treat depression. However, the exact molecular mechanisms underlying the mood circuit of depressed brains and whether brain stimulation techniques regulate the underlying molecules remain elusive. MethodsWhole-brain glucose metabolism and cortical excitatory and inhibitory markers including P30, N45, P60, N100, and LICI (long-interval cortical inhibition) of TMS-evoked potentials from left DLPFC were measured in 40 subjects with MDD patients. The neurophysiological markers were repeated immediately after 1st session of left PFC rTMS, intermittent theta-burst stimulation (iTBS), and sham (randomly assigned). ResultsBrain glucose metabolism in the limbic structures significantly correlated with left PFC P30 (mainly GABA-A and glutamate receptor mediated) and with LICI (mainly GABA-B receptor mediated inhibition) (FWE-corrected p < 0.001). Correlations between other neurophysiological markers (left PFC N45, P60, and N100) and posterior cingulate cortex, a key region in the default mode network, were also noted. One session of rTMS significantly decreased left PFC P60 (mainly glutamate receptor mediated), while a significant group effect was found for LICI (iTBS < sham). ConclusionThe first study showed that the underlying molecular mechanisms of fronto-limbic circuit of MDD brains involved glutamatergic excitation and GABAergic inhibition at specific time points. In addition, one session of rTMS mainly modulated glutamatergic neurotransmission at left PFC, while the mechanisms of iTBS might involve GABA-B receptor mediated inhibition. Clinical trials registry numberUMIN000044951.

Intermittent Theta Burst Stimulation Ameliorates Cognitive Deficit and Attenuates Neuroinflammation via PI3K/Akt/mTOR Signaling Pathway in Alzheimer's-Like Disease Model.

Neurodegeneration implies progressive neuronal loss and neuroinflammation further contributing to pathology progression. It is a feature of many neurological disorders, most common being Alzheimer’s disease (AD). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive stimulation which modulates excitability of stimulated brain areas through magnetic pulses. Numerous studies indicated beneficial effect of rTMS in several neurological diseases, including AD, however, exact mechanism are yet to be elucidated. We aimed to evaluate the effect of intermittent theta burst stimulation (iTBS), an rTMS paradigm, on behavioral, neurochemical and molecular level in trimethyltin (TMT)-induced Alzheimer’s-like disease model. TMT acts as a neurotoxic agent targeting hippocampus causing cognitive impairment and neuroinflammation, replicating behavioral and molecular aspects of AD. Male Wistar rats were divided into four experimental groups–controls, rats subjected to a single dose of TMT (8 mg/kg), TMT rats subjected to iTBS two times per day for 15 days and TMT sham group. After 3 weeks, we examined exploratory behavior and memory, histopathological and changes on molecular level. TMT-treated rats exhibited severe and cognitive deficit. iTBS-treated animals showed improved cognition. iTBS reduced TMT-induced inflammation and increased anti-inflammatory molecules. We examined PI3K/Akt/mTOR signaling pathway which is involved in regulation of apoptosis, cell growth and learning and memory. We found significant downregulation of phosphorylated forms of Akt and mTOR in TMT-intoxicated animals, which were reverted following iTBS stimulation. Application of iTBS produces beneficial effects on cognition in of rats with TMT-induced hippocampal neurodegeneration and that effect could be mediated via PI3K/Akt/mTOR signaling pathway, which could candidate this protocol as a potential therapeutic approach in neurodegenerative diseases such as AD.

Bilateral Cerebellar Intermittent Theta Burst Stimulation Combined With Swallowing Speech Therapy for Dysphagia After Stroke: A Randomized, Double-Blind, Sham-Controlled, Clinical Trial

Background: Previous studies have found that high-frequency repetitive transcranial magnetic stimulation (rTMS) of the cerebellar hemisphere could improve swallowing function, but whether intermittent theta burst stimulation (iTBS), which has similar excitatory effect and higher efficiency, can also improve swallowing function for dysphagia after stroke remains unclear. Objective: This trial aimed to explore the efficacy and safety of bilateral cerebellar transcranial magnetic stimulation with iTBS for dysphagia after stroke. Methods: Seventy patients with dysphagia after stroke were divided into 2 treatment groups: true bilateral cerebellar iTBS and sham bilateral cerebellar iTBS. The true iTBS group underwent ten 100% resting motor threshold (RMT) iTBS sessions for 2 weeks. In the sham iTBS group, the parameters were the same except that the figure-eight coil was perpendicular to the skull. Both groups received traditional swallowing rehabilitation treatment 5 times a week for 2 weeks. Swallowing function was assessed with the Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS), Penetration/Aspiration Scale (PAS), Standardized Swallowing Assessment (SSA), and Functional Oral Intake Scale (FOIS) at baseline, 2 weeks after the intervention, and at 4 weeks of follow-up. Results: There were significant time and group interaction effects in both multi-factorial adjusted and unadjusted FEDSS, PAS, SSA, and FOIS score (P < .001). In the pairwise comparison of the swallowing parameters among the 2 groups, the FEDSS, PAS, SSA, and FOIS scores at 2 weeks and 4 weeks showed a significantly higher improvement in the iTBS simulation group than sham group (P < .05). In both the true iTBS and sham iTBS stimulation groups, all FEDSS, PAS, SSA, and FOIS scores were significantly improved over time (P < .001). Conclusions: The present study suggested that as a more efficient TMS stimulation mode, iTBS could efficiently improve swallowing function by stimulating the bilateral cerebellar hemisphere. In addition, 100% resting motor threshold bilateral cerebellar iTBS is a relatively safe treatment. Clinical Trial Registration: Effect analysis of repeated transcranial magnetic stimulation of cerebellar on dysphagia after stroke. www.chictr.org.cn. Identifier: ChiCTR2100042092.

Early Improvement Predicts Clinical Outcomes Similarly in 10 Hz rTMS and iTBS Therapy for Depression.

BackgroundPrior studies have demonstrated that early treatment response with transcranial magnetic stimulation (TMS) can predict overall response, yet none have directly compared that predictive capacity between intermittent theta-burst stimulation (iTBS) and 10 Hz repetitive transcranial magnetic stimulation (rTMS) for depression. Our study sought to test the hypothesis that early clinical improvement could predict ultimate treatment response in both iTBS and 10 Hz rTMS patient groups and that there would not be significant differences between the modalities.MethodsWe retrospectively evaluated response to treatment in 105 participants with depression that received 10 Hz rTMS (n = 68) and iTBS (n = 37) to the dorsolateral prefrontal cortex (DLPFC). Percent changes from baseline to treatment 10 (t10), and to final treatment (tf), were used to calculate confusion matrices including negative predictive value (NPV). Treatment non-response was defined as <50% reduction in PHQ-9 scores according to literature, and population, data-driven non-response was defined as <40% for 10 Hz and <45% for iTBS.ResultsFor both modalities, the NPV related to degree of improvement at t10. NPV for 10 Hz was 80%, 63% and 46% at t10 in those who failed to improve >20, >10, and >0% respectively; while iTBS NPV rates were 65, 50, and 35%. There were not significant differences between protocols at any t10 cut-off assessed, whether research defined 50% improvement as response or data driven kernel density estimates (p = 0.22–0.44).ConclusionPatients who fail to achieve >20% improvement by t10 with both 10 Hz rTMS and iTBS therapies have ~70% chance of non-response to treatment. With no significant differences between predictive capacities, identifying patients at-risk for non-response affords psychiatrists greater opportunity to adapt treatment strategies.

Continuous but not intermittent theta burst stimulation decreases striatal dopamine release and cortical excitability

Dopamine modulation is thought to underpin some of the therapeutic effects associated with repetitive transcranial magnetic stimulation (rTMS). However, patient studies have failed to demonstrate consistent changes in the dopamine system in vivo after a therapeutic course of rTMS. Here, we evaluated acute and chronic changes in striatal dopamine release elicited by a clinically relevant course of theta burst (TBS) or sham stimulation using [11C]raclopride in healthy non-human primates (n = 11). Subjects were scanned immediately after the first session of TBS and the day after a 3 week course of daily TBS delivery. After experiment completion, animals were euthanized, and immunofluorescence staining was carried out using antibodies targeting D2 receptors (D2R).Continuous TBS (cTBS, an inhibitory form of rTMS) over the left primary motor cortex acutely decreased dopamine release bilaterally in the putamen. However, no significant changes in dopamine receptors nor D2R immunoreactivity were noted 24 h after the last stimulation, while a decrease in cortical excitability, as measured by an increase in resting motor threshold, could still be quantified. On the opposite, intermittent TBS (iTBS, an excitatory form of rTMS) did not affect dopamine release, acutely or chronically, D2R immunoreactivity or cortical excitability. These findings suggest that the long-term therapeutic effects of TBS might be facilitated through the modulation of different neurotransmission systems beyond the dopamine system. However, given the small sample size, these results should be interpreted with caution.

Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP)

BackgroundRecently intermittent theta burst stimulation (iTBS) proved to be non-inferior to conventional repetitive transcranial magnetic stimulation (10 Hz rTMS) in unipolar depression after failure of one antidepressant trial, but to date no randomized control trial assessed the ability of iTBS to improve depression level and quality of life in more resistant features of depression with a long-term (6 month) follow-up in comparison to 10 Hz rTMS. Objectives/HypothesisThe aim of our study was to compare the efficacy of 10 Hz rTMS and iTBS in treatment-resistant unipolar depression on response rates (50% decrease of MADRS scores at one month from baseline) and change in quality of life during a 6-month follow-up. In addition, we investigated whether some clinical features at baseline were associated with the response in the different groups. MethodSixty patients were randomized in a double-blind, controlled study at the University Hospital Center of Nantes, and received 20 sessions of either rTMS or iTBS applied to the left dorsolateral prefrontal cortex targeted by neuronavigation. Statistical analysis used Fischer's exact test and Chi-square test as appropriate, linear mixed model, and logistic regression (occurrence of depressive relapse and factors associated with the therapeutic response). ResultsIncluded patients showed in mean more than 3 antidepressants trials. Response rates were 36.7% and 33.3%, and remission rates were 18.5% and 14.8%, in the iTBS and 10 Hz rTMS groups respectively. Both groups showed a similar significant reduction in depression scores and quality of life improvement at 6 months. We did not find any clinical predictive factor of therapeutic response in this sample. ConclusionOur study suggests the clinical interest of iTBS stimulation (which is more time saving and cost-effective as conventional rTMS) to provide long-lasting improvement of depression and quality of life in highly resistant unipolar depression.

Effects of the Intermittent Theta Burst Stimulation of the Cerebellar Vermis on Balance Recovery After Stroke: A Study Protocol for a Randomized Controlled Trial.

BackgroundThe recovery of balance function is a critical segment in the rehabilitation treatment of stroke. The cerebellum is considered as the key structure involved in balance and motor control. The cerebellar vermis plays an important role in integrating vision, proprioception, and sensory skin input and may be a candidate stimulation target for regulating the motor network related with balance. However, evidence that the intermittent theta burst stimulation (iTBS) of cerebellar vermis can promote the recovery of balance function after stroke remains insufficient. Therefore, this study aims to explore the efficacy of the cerebellar vermis iTBS for the treatment of balance function in patients with stroke.Methods and AnalysisForty patients with stroke will be recruited in this prospective, randomized, sham-controlled trial. Participants will be randomized in a 1:1 ratio to receive either 15 sessions of cerebellar vermis iTBS (600 pulses) or sham stimulation. Additionally, a routine rehabilitation therapy follows the intervention. The primary outcome is the Berg Balance Scale, and the secondary outcomes are the Fugl–Meyer assessment of the lower extremity and modified Barthel index. The above outcomes will be assessed before intervention and at the end of each week. Pre- and post-iTBS resting-state functional magnetic resonance imaging (rs-fMRI) will be acquired, and the regional homogeneity, fractional amplitude of low-frequency fluctuation and functional connectivity will be calculated and analyzed.DiscussionThis protocol holds promise as a potential method to improve balance function in patients with stroke. If the outcomes of patients improve after the intervention, the study will provide new insights into improving balance function.Ethics and DisseminationThis study has been approved by the Medical Research Ethics Committee of Wuxi Mental Health Center (Wuxi Tongren Rehabilitation Hospital). Results will be disseminated through (open-access) peer-reviewed publications, networks of scientists, professionals, and the public and presented at conferences.Clinical Trial Registration Numberwww.chictr.org.cn, identifier ChiCTR2100052590.

Improvement of poststroke cognitive impairment by intermittent theta bursts: A double-blind randomized controlled trial.

BackgroundIntermittent theta burst stimulation (iTBS) is known to improve cognitive impairment caused by Alzheimer's disease and Parkinson's disease, but studies are lacking with respect to the efficacy of iTBS on poststroke cognitive impairment (PSCI).ObjectiveThis study was conducted to investigate the effect of left dorsolateral prefrontal cortex (DLPFC) iTBS on improving cognitive function in stroke patients.MethodsFifty‐eight patients with PSCI are randomly divided into iTBS (n = 28) and sham stimulation groups (n = 30). Both groups receive routine cognitive‐related rehabilitation. The iTBS group is treated with iTBS intervention of the left DLPFC, and the sham stimulation group is treated with the same parameters at the same site for 2 weeks. Outcome measures are assessed at baseline (T0) and immediately after the last intervention (T1) by mini‐mental state examination (MMSE), Oxford cognitive screen, and event‐related potential P300.ResultsThere are no differences in baseline clinical characteristics between the two groups. After intervention, the MMSE scores and P300 amplitude increase significantly for both groups, and the P300 incubation period reduces significantly. The change value of the iTBS group is significantly higher than that of sham stimulation group (p < .05). Compared with the sham stimulation group, the iTBS group has more significant changes in semantic comprehension and executive function (p < .05).ConclusioniTBS can effectively and safely improve overall cognitive impairment in stroke patients, including semantic understanding and executive function, and it also has a positive impact on memory function. Future randomized controlled studies with large samples and long‐term follow‐up should be conducted to further validate the results of the present study

Modulation of Interhemispheric Synchronization and Cortical Activity in Healthy Subjects by High-Definition Theta-Burst Electrical Stimulation.

Background Various forms of theta-burst stimulation (TBS) such as intermittent TBS (iTBS) and continuous TBS (cTBS) have been introduced as novel facilitation/suppression schemes during repetitive transcranial magnetic stimulation (rTMS), demonstrating a better efficacy than conventional paradigms. Herein, we extended the rTMS-TBS schemes to electrical stimulation of high-definition montage (HD-TBS) and investigated its neural effects on the human brain. Methods In a within-subject design, fifteen right-handed healthy adults randomly participated in 10 min and 2 mA HD-TBS sessions: unilateral (Uni)-iTBS, bilateral (Bi)-cTBS/iTBS, and sham stimulation over primary motor cortex regions. A 20-channel near-infrared spectroscopy (NIRS) system was covered on the bilateral prefrontal cortex (PFC), sensory motor cortex (SMC), and parietal lobe (PL) for observing cerebral hemodynamic responses in the resting-state and during fast finger-tapping tasks at pre-, during, and poststimulation. Interhemispheric correlation coefficient (IHCC) and wavelet phase coherence (WPCO) from resting-state NIRS and concentration of oxyhemoglobin during fast finger-tapping tasks were explored to reflect the symmetry between the two hemispheres and cortical activity, respectively. Results The IHCC and WPCO of NIRS data in the SMC region under Bi-cTBS/iTBS showed relatively small values at low-frequency bands III (0.06–0.15 Hz) and IV (0.02–0.06), indicating a significant desynchronization in both time and frequency domains. In addition, the SMC activation induced by fast finger-tapping exercise was significantly greater during Uni-iTBS as well as during and post Bi-cTBS/iTBS sessions. Conclusions It appears that a 10 min and 2 mA Bi-cTBS/iTBS applied over two hemispheres within the primary motor cortex region could effectively modulate the interhemispheric synchronization and cortical activation in the SMC of healthy subjects. Our study demonstrated that bilateral HD-TBS approaches is an effective noninvasive brain stimulation scheme which could be a novel therapeutic for inducing effects of neuromodulation on various neurological disorders caused by ischemic stroke or traumatic brain injuries.

Predicting Symptom-Specific Antidepressant Response to 10 Hz TMS and iTBS With Resting-State Functional Connectivity

Intermittent theta burst stimulation (iTBS) is increasingly being used as a cost-effective alternative to 10 Hz repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) for treatment resistant depression (TRD). However, the biological mechanisms and predictors of these two stimulatory regimens are not yet fully understood. Therefore, we aimed to compare resting-state functional neuroimaging (fMRI) markers of antidepressant response to these two interventions.

P275. Accelerated Theta Burst Stimulation in the Treatment of Major Depression

Theta burst stimulation (TBS) is a newer form of repetitive transcranial magnetic stimulation (rTMS) with proven efficacy and safety in the treatment of major depressive disorder (MDD). Recently the use of accelerated rTMS and intermittent TBS (iTBS) protocols to speed the treatment response have been investigated. Here, we examined the efficacy and safety of accelerated bilateral TBS in MDD

Adjunctive D-Cycloserine with Intermittent Theta-Burst Stimulation: A Randomized Placebo-Controlled Trial in Major Depressive Disorder

Intermittent theta-bust stimulation (iTBS) is emerging as a first-choice transcranial magnetic stimulation (TMS) protocol in the treatment of refractory Major Depressive Disorder (MDD). While the mechanisms for antidepressant efficacy remain unclear, physiological studies suggest that N-Methyl-D-Aspartate (NMDA) receptor activation is required for iTBS related synaptic plasticity. No study to date has directly targeted the NMDA receptor as a means of enhancing clinical efficacy in MDD.