Effect of iTBS dual-target stimulation on lower limb function in patients with incomplete spinal cord injury:a randomized, single-blind,sham-controlled study.

OBJECTIVE: To explore the influence of intermittent theta burst stimulation (iTBS) dual-target stimulation on lower limb function in patients with incomplete spinal cord injury (iSCI). METHODS: A randomized, single -blind,sham-controlled trial was used in this study. Thirty iSCI patients with lower limb dysfunction meeting the inclusion criteria were randomly divided into a sham group and an iTBS group, with 15 cases in each group. The iTBS group received conventional rehabilitation therapy combined with iTBS dual-target stimulation on the central cerebral sulcus and the nerve root of the spinal cord injury segment. The sham group was treated with conventional rehabilitation therapy combined with iTBS dual-target sham stimulation therapy. Comprehensive functional assessment was performed on all patients before treatment, on the Day 3 and Day 21 of treatment.The main evaluation indicators were as follows: amplitude and latency of motor-evoked potential (MEP) in the anterior tibial muscles of both lower limbs,latency of sensory-evoked potential (SEP) of both lower limbs, knee flexor strength and knee extensor strength, lower extremity motor score (LEMS), lower extremity sensory score (LESS), spinal cord independence measure (SCIM) score and gait parameters (stride speed, stride frequency, stride length, ground reaction force). RESULTS: On day 21 of treatment, in the iTBS group, the MEP amplitude of the anterior tibial muscles increased, the latency of MEP shortened, knee flexor strength and knee extensor strength increased, and the lower extremity motor score and SCIM score of both lower limbs increased. In addition, there were statistically significant differences in the muscle strength of the knee flexion muscle, knee extensor muscle, MEP amplitude, LEMS and SCIM between the two groups (p<0.05). Among the 10 patients who could walk with an assisted walker, the step length and step frequency of the iTBS group were increased compared with the sham group after treatment (p<0.01), and the ground reaction force (GRF) was increased (p<0.05). There was no significant difference in the LESS of the lower limbs between the two groups (p > 0.05). CONCLUSIONS: ITBS dual-target stimulation can significantly improve the motor function of both lower limbs in patients with iSCI but does not significantly improve the sensory function of both lower limbs. Therefore, this treatment mode may participate in the reconstruction and repair of some nerve circuits in patients with iSCI. In addition, iTBS dual-target stimulation can improve the ability of iSCI patients to perform daily living.

A network meta-analysis of non-invasive brain stimulation interventions for autism spectrum disorder: evidence from randomized controlled trials.

The efficacy and acceptability of various non-invasive brain stimulation (NIBS) interventions for autism spectrum disorder remain unclear. We carried out a systematic review for randomized controlled trials (RCTs) regarding NIBS for reducing autistic symptoms (INPLASY202370003). Sixteen articles (N = 709) met the inclusion criteria for network meta-analysis. Effect sizes were reported as standardized mean differences (SMDs) or odds ratios with 95% confidence intervals (CIs). Fourteen active NIBS interventions, including transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation, and transcranial pulse stimulation were analyzed. Only anodal tDCS over the left dorsolateral prefrontal cortex paired with cathodal tDCS over an extracephalic location (atDCS_F3+ctDCS_E) significantly improved autistic symptoms compared to sham controls (SMD = -1.40, 95%CIs = -2.67 to -0.14). None of the NIBS interventions markedly improved social-communication symptoms or restricted/repetitive behaviors in autistic participants. Moreover, no active NIBS interventions exhibited significant dropout rate differences compared to sham controls, and no serious adverse events were reported for any intervention.

Theta-burst stimulation over primary somatosensory cortex modulates tactile acuity of tongue.

Background: Emerging studies in humans have established the modulatory effects of repetitive transcranial magnetic stimulation (rTMS) over primary somatosensory cortex (S1) on somatosensory cortex activity and perception. However, to date, research in this area has primarily focused on the hand and fingers, leaving a gap in our understanding of the modulatory effects of rTMS on somatosensory perception of the orofacial system and speech articulators. Objective: The present study aimed to examine the effects of different types of theta-burst stimulation-continuous TBS (cTBS), intermittent TBS (iTBS), or sham-over the tongue representation of left S1 on tactile acuity of the tongue. Methods: In a repeated-measures design, fifteen volunteers participated in four separate sessions, where cTBS, iTBS, sham, or no stimulation was applied over the tongue representation of left S1. Effects of TBS were measured on both temporal and spatial perceptual acuity of tongue using a custom vibrotactile stimulator. Results: CTBS significantly impaired spatial amplitude threshold at the time window of 16-30 minutes after stimulation, while iTBS improved it at the same time window. The effect of iTBS, however, was smaller than cTBS. In contrast, neither cTBS nor iTBS had any effect on the temporal discrimination threshold. Conclusions: The current study establishes the validity of using TBS to modulate somatosensory perception of the orofacial system. Directly modifying somatosensation in the orofacial system has the potential to benefit clinical populations with abnormal tactile acuity, improve our understanding of the role of sensory systems in speech production, and enhance speech motor learning and rehabilitation.

Neuromodulatory transcranial magnetic stimulation (TMS) changes functional connectivity proportional to the electric-field induced by the TMS pulse.

OBJECTIVE: Transcranial magnetic stimulation (TMS) can efficiently and robustly modulate synaptic plasticity, but little is known about how TMS affects functional connectivity (rs-fMRI). Accordingly, this project characterized TMS-induced rsFC changes in depressed patients who received 3 days of left prefrontal intermittent theta burst stimulation (iTBS). METHODS: rs-fMRI was collected from 16 subjects before and after iTBS. Correlation matrices were constructed from the cleaned rs-fMRI data. Electric-field models were conducted and used to predict pre-post changes in rs-fMRI. Site by orientation heatmaps were created for vectors centered on the stimulation site and a control site (contralateral motor cortex). RESULTS: For the stimulation site, there was a clear relationship between both site and coil orientation, and connectivity changes. As distance from the stimulation site increased, prediction accuracy decreased. Similarly, as eccentricity from the optimal orientation increased, prediction accuracy decreased. The systematic effects described above were not apparent in the heatmap centered on the control site. CONCLUSIONS: These results suggest that rs-fMRI following iTBS changes systematically as a function of the distribution of electrical energy delivered from the TMS pulse, as represented by the e-field model. SIGNIFICANCE: This finding lays the groundwork for future studies to individualize TMS targeting based on how predicted rs-fMRI changes might impact psychiatric symptoms.

Activation changes in patients with post-stroke cognitive impairment receiving intermittent theta burst stimulation: A functional near-infrared spectroscopy study.

BACKGROUND: Intermittent theta burst stimulation (iTBS) has demonstrated efficacy in patients with cognitive impairment. However, activation patterns and mechanisms of iTBS for post-stroke cognitive impairment (PSCI) remain insufficiently understood. OBJECTIVE: To investigate the activation patterns and potential benefits of using iTBS in patients with PSCI. METHODS: A total of forty-four patients with PSCI were enrolled and divided into an iTBS group (iTBS and cognitive training) or a control group (cognitive training alone). Outcomes were assessed based on the activation in functional near-infrared spectroscopy (fNIRS), as well as Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) and the modified Barthel Index (MBI). RESULTS: Thirty-eight patients completed the interventions and assessments. Increased cortical activation was observed in the iTBS group after the interventions, including the right superior temporal gyrus (STG), left frontopolar cortex (FPC) and left orbitofrontal cortex (OFC). Both groups showed significant improvements in LOTCA and MBI after the interventions (p < 0.05). Furthermore, the iTBS group augmented superior improvement in the total score of MBI and LOTCA compared to the control group, especially in visuomotor organization and thinking operations (p < 0.05). CONCLUSION: iTBS altered activation patterns and improved cognitive function in patients with PSCI. The activation induced by iTBS may contribute to the improvement of cognitive function.

Continuous Theta-Burst Stimulation on the Left Posterior Inferior Frontal Gyrus Perturbs Complex Syntactic Processing Stability in Mandarin Chinese.

The structure of human language is inherently hierarchical. The left posterior inferior frontal gyrus (LpIFG) is proposed to be a core region for constructing syntactic hierarchies. However, it remains unclear whether LpIFG plays a causal role in syntactic processing in Mandarin Chinese and whether its contribution depends on syntactic complexity, working memory, or both. We addressed these questions by applying inhibitory continuous theta-burst stimulation (cTBS) over LpIFG. Thirty-two participants processed sentences containing embedded relative clauses (i.e., complex syntactic processing), syntactically simpler coordinated sentences (i.e., simple syntactic processing), and non-hierarchical word lists (i.e., word list processing) after receiving real or sham cTBS. We found that cTBS significantly increased the coefficient of variation, a representative index of processing stability, in complex syntactic processing (esp., when subject relative clause was embedded) but not in the other two conditions. No significant changes in d' and reaction time were detected in these conditions. The findings suggest that (a) inhibitory effect of cTBS on the LpIFG might be prominent in perturbing the complex syntactic processing stability but subtle in altering the processing quality; and (b) the causal role of the LpIFG seems to be specific for syntactic processing rather than working memory capacity, further evidencing their separability in LpIFG. Collectively, these results support the notion of the LpIFG as a core region for complex syntactic processing across languages.

Continuous theta burst stimulation for bipolar depression: A multicenter, double-blind randomized controlled study exploring treatment efficacy and predictive potential of kynurenine metabolites.

BACKGROUND: While theta burst stimulation (TBS) shows promise in Major Depressive Disorder (MDD), its effectiveness in bipolar depression (BD-D) remains uncertain. Optimizing treatment parameters is crucial in the pursuit of rapid symptom relief. Moreover, aligning with personalized treatment strategies and increased interest in immunopsychiatry, biomarker-based stratification of patients most likely to benefit from TBS might improve remission rates. We investigated treatment effectiveness of continuous TBS (cTBS) compared to sham in BD-D, and assessed the capacity of plasma kynurenine pathway metabolites to predict treatment outcome. METHODS: Thirty-seven patients with BD-D underwent accelerated active or sham cTBS treatment in a multicenter, double-blind, randomized controlled trial. Depressive symptoms were measured with the 17-item Hamilton Depression Rating Scale (HDRS-17) before treatment (T0), 3-4 days posttreatment (T1) and 10-11 days posttreatment (T2). Plasma tryptophan, kynurenine, kynurenic acid and quinolinic acid concentrations were quantified with ELISA. Linear mixed models were used for statistical analyses. RESULTS: Although the total sample showed depressive symptom improvement, active cTBS did not demonstrate greater symptom alleviation compared to sham. However, higher baseline quinolinic acid significantly predicted symptom improvement in the active treatment group, not in sham-stimulated patients. LIMITATIONS: The modest sample size limited the power to detect significant differences with regard to treatment effect. Also, the follow-up period was 10-11 days, whereas similar studies usually follow up for at least one month. CONCLUSION: More research is required to optimize cTBS for BD-D and explore the involvement of quinolinic acid in treatment outcome.

Early symptom improvement and other clinical predictors of response to repetitive transcranial magnetic stimulation for depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a rapidly emerging treatment for depression, but outcome prediction is still a challenge. This study aimed to identify predictors of response to rTMS among baseline clinical factors and early symptomatic improvements. METHODS: This cohort study comprised 136 patients with a unipolar or bipolar depressive episode referred for clinical intermittent theta-burst stimulation or right-sided 1 Hz rTMS at the Uppsala Brain Stimulation Unit. The co-primary outcomes used for logistic regression were response, defined as ≥50 % reduction of Montgomery and Åsberg Depression Rating Scale Self-assessment (MADRS-S) total score, and 1-2 points on the Clinical Global Impression Improvement (CGI-I) scale. Early improvement was defined as ≥20 % reduction in the MADRS-S total score, or ≥ 1 point reduction in each MADRS-S item, after two weeks of treatment. RESULTS: The response rates were 21 % for MADRS-S and 45 % for CGI-I. A depressive episode >24 months had lower odds for MADRS-S response compared to ≤12 months. Early improvement of the MADRS-S total score predicted CGI-I response (95 % CI = 1.35-9.47, p = 0.011), Initiative6 predicted MADRS-S response (95 % CI = 1.08-9.05, p = 0.035), and Emotional involvement7 predicted CGI-I response (95 % CI = 1.03-8.66, p = 0.044). LIMITATIONS: No adjustment for concurrent medication. CONCLUSIONS: A depressive episode ≤12 months and early improvement in overall depressive symptoms, as well as the individual items, Initiative6 and Emotional involvement7, predicted subsequent rTMS response in a naturalistic sample of depressed patients. This could facilitate the early identification of patients who will benefit from further rTMS sessions.

Exploration of Theta Burst-Induced Modulation of Transcranial Magnetic Stimulation-Evoked Potentials Over the Motor Cortex.

OBJECTIVES: This study investigates the way theta burst stimulation (TBS) applied to the motor cortex (M1) affects TMS-evoked potentials (TEPs). There have been few direct comparisons of continuous TBS (cTBS) and intermittent TBS (iTBS), and there is a lack of consensus from existing literature on the induced effects. We performed an exploratory trial to assess the effect of M1-cTBS and M1-iTBS on TEP components. MATERIALS AND METHODS: In a cross-over design, 15 participants each completed three experimental sessions with ≥one week in between sessions. The effect of a single TBS train administered over M1 was investigated using TEPs recorded at the same location, 20 to 30 minutes before and in the first 10 minutes after the intervention. In each session, a different type of TBS (cTBS, iTBS, or active control cTBS) was administered in a single-blinded randomized order. For six different TEP components (N15, P30, N45, P60, N100, and P180), amplitude was compared before and after the intervention using cluster-based permutation (CBP) analysis. RESULTS: We were unable to identify a significant modulation of any of the six predefined M1 TEP components after a single train of TBS. When waiving statistical correction for multiple testing in view of the exploratory nature of the study, the CBP analysis supports a reduction of the P180 amplitude after iTBS (p = 0.015), whereas no effect was observed after cTBS or in the active control condition. The reduction occurred in ten of 15 subjects, showing intersubject variability. CONCLUSIONS: The observed decrease in the P180 amplitude after iTBS may suggest a neuromodulatory effect of iTBS. Despite methodologic issues related to our study and the potential sensory contamination within this latency range of the TEP, we believe that our finding deserves further investigation in hypothesis-driven trials of adequate power and proper design, focusing on disentanglement between TEPs and peripherally evoked potentials, in addition to indicating reproducibility across sessions and subjects. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT05206162.

Effects of continuous versus intermittent theta-burst TMS on fMRI connectivity.

Transcranial magnetic stimulation is a noninvasive technique that can be used to evoke distributed network-level effects. Previous work demonstrated that the Hippocampal-Cortical Network responds preferably (i.e., greater memory improvement and increases in hippocampal-network connectivity) to continuous theta-burst stimulation protocol relative to intermittent theta-burst and to 20-Hz rTMS. Here, these data were further analyzed to characterize effects of continuous versus intermittent theta-burst stimulation on network-level connectivity measures - as well as local connectedness - via resting-state fMRI. In contrast to theories that propose continuous and intermittent theta-burst cause local inhibitory versus excitatory effects, respectively, both protocols caused local decreases in fMRI connectivity around the stimulated parietal site. While iTBS caused decreases in connectivity across the hippocampal-cortical network, cTBS caused increases and decreases in connectivity across the network. cTBS had no effect on the parietal-cortical network, whereas iTBS caused decreases in the right parietal cortex (contralateral hemisphere to the stimulation target). These findings suggest that continuous theta-burst may have entrained the endogenous hippocampal-cortical network, whereas the intermittent train was unable to maintain entrainment that may have yielded the long-lasting effects measured in this study (i.e., within 20-min post-stimulation). Furthermore, these effects were specific to the hippocampal-cortical network, which has a putative endogenous functionally-relevant theta rhythm, and not to the parietal network. These results add to the growing body of evidence that suggests effects of theta-burst stimulation are not fully characterized by excitatory/inhibitory theories. Further work is required to understand local and network-level effects of noninvasive stimulation.

Neuronavigated Right Orbitofrontal 20 Hz Theta Burst Transcranial Magnetic Stimulation Augmentation for Obsessive-Compulsive Disorder with Comorbid Depression and Anxiety Disorders: An Open-Label Study.

BACKGROUND: Despite the availability of pharmacotherapy and psychotherapy for treating obsessive-compulsive disorder (OCD), alternative approaches need to be explored due to the high likelihood of treatment resistance. Neuronavigated 20 Hz theta burst stimulation (TBS-20 Hz), targeting the bilateral dorsolateral prefrontal cortex (DLPFC) augmented with the right orbitofrontal cortex (ROFC), was tested for treating OCD comorbid with depression and anxiety disorders. METHODS: A retrospective chart review was performed on fourteen patients treated for moderate-to-severe OCD in a private outpatient clinic. Twelve patients had comorbid major depressive disorder (MDD), and thirteen patients had either generalized anxiety disorder (GAD) or panic disorder (PD). Patients completed the Y-BOCS-SR, BDI-II, and BAI rating scales weekly, which were used to measure the changes in OCD, depression, and anxiety symptoms, respectively. RESULTS: Neuronavigated TBS-20 Hz was sequentially applied to the right DLPFC (RDLPFC), left DLPFC (LDLPFC), and ROFC. A total of 64% (9/14) of patients achieved remission from OCD (Y-BOCS-SR ≤ 14) in an average of 6.1 weeks of treatment (SD = 4.0). A total of 58% (7/12) of patients remitted from MDD (BDI < 13) in an average of 4.1 weeks (SD = 2.8), and 62% (8/13) of patients remitted from GAD/PD (BAI < 8) in an average of 4.3 weeks (SD = 2.5). CONCLUSIONS: The neuronavigated TBS-20 Hz sequential stimulation of RDLPFC and LDLPFC, followed by ROFC, significantly reduced OCD, MDD, and GAD/PD symptoms. Randomized sham controls are warranted to validate these results.

Switching off: disruptive TMS reveals distinct contributions of the posterior middle temporal gyrus and angular gyrus to bilingual speech production.

The role of the left temporoparietal cortex in speech production has been extensively studied during native language processing, proving crucial in controlled lexico-semantic retrieval under varying cognitive demands. Yet, its role in bilinguals, fluent in both native and second languages, remains poorly understood. Here, we employed continuous theta burst stimulation to disrupt neural activity in the left posterior middle-temporal gyrus (pMTG) and angular gyrus (AG) while Italian-Friulian bilinguals performed a cued picture-naming task. The task involved between-language (naming objects in Italian or Friulian) and within-language blocks (naming objects ["knife"] or associated actions ["cut"] in a single language) in which participants could either maintain (non-switch) or change (switch) instructions based on cues. During within-language blocks, cTBS over the pMTG entailed faster naming for high-demanding switch trials, while cTBS to the AG elicited slower latencies in low-demanding non-switch trials. No cTBS effects were observed in the between-language block. Our findings suggest a causal involvement of the left pMTG and AG in lexico-semantic processing across languages, with distinct contributions to controlled vs. "automatic" retrieval, respectively. However, they do not support the existence of shared control mechanisms within and between language(s) production. Altogether, these results inform neurobiological models of semantic control in bilinguals.

Intermittent theta-burst stimulation alleviates hypoxia-ischemia-caused myelin damage and neurologic disability.

Neonatal hypoxia-ischemia (HI) results in behavioral deficits, characterized by neuronal injury and retarded myelin formation. To date, limited treatment methods are available to prevent or alleviate neurologic sequelae of HI. Intermittent theta-burst stimulation (iTBS), a non-invasive therapeutic procedure, is considered a promising therapeutic tool for treating some neurocognitive disorders and neuropsychiatric diseases. Hence, this study aims to investigate whether iTBS can prevent the negative behavioral manifestations of HI and explore the mechanisms for associations. We exposed postnatal day 10 Sprague-Dawley male and female rats to 2 h of hypoxia (6% O2) following right common carotid artery ligation, resulting in oligodendrocyte (OL) dysfunction, including reduced proliferation and differentiation of oligodendrocyte precursor cells (OPCs), decreased OL survival, and compromised myelin in the corpus callosum (CC) and hippocampal dentate gyrus (DG). These alterations were concomitant with cognitive dysfunction and depression-like behaviors. Crucially, early iTBS treatment (15 G, 190 s, seven days, initiated one day post-HI) significantly alleviated HI-caused myelin damage and mitigated the neurologic sequelae both in male and female rats. However, the late iTBS treatment (initiated 18 days after HI insult) could not significantly impact these behavioral deficits. In summary, our findings support that early iTBS treatment may be a promising strategy to improve HI-induced neurologic disability. The underlying mechanisms of iTBS treatment are associated with promoting the differentiation of OPCs and alleviating myelin damage.

Pilot study with randomised control of dual site theta burst transcranial magnetic stimulation (TMS) for methamphetamine use disorder: a protocol for the TARTAN study.

BACKGROUND: Transcranial magnetic stimulation (TMS) (including the theta burst stimulation (TBS) form of TMS used in this study) is a non-invasive means to stimulate nerve cells in superficial areas of the brain. In recent years, there has been a growth in the application of TMS to investigate the modulation of neural networks involved in substance use disorders. This study examines the feasibility of novel TMS protocols for the treatment of methamphetamine (MA) use disorder in an ambulatory drug and alcohol treatment setting. METHODS: Thirty participants meeting the criteria for moderate to severe MA use disorder will be recruited in community drug and alcohol treatment settings and randomised to receive active TMS or sham (control) intervention. The treatment is intermittent TBS (iTBS) applied to the left dorsolateral prefrontal cortex (DLPFC), then continuous TBS (cTBS) to the left orbitofrontal cortex (OFC). Twelve sessions are administered over 4 weeks with opt-in weekly standardized cognitive behaviour therapy (CBT) counselling and a neuroimaging sub-study offered to participants. Primary outcomes are feasibility measures including recruitment, retention and acceptability of the intervention. Secondary outcomes include monitoring of safety and preliminary efficacy data including changes in substance use, cravings (cue reactivity) and cognition (response inhibition). DISCUSSION: This study examines shorter TBS protocols of TMS for MA use disorder in real-world drug and alcohol outpatient settings where withdrawal and abstinence from MA, or other substances, are not eligibility requirements. TMS is a relatively affordable treatment and staff of ambulatory health settings can be trained to administer TMS. It is a potentially scalable and translatable treatment for existing drug and alcohol clinical settings. TMS has the potential to provide a much-needed adjuvant treatment to existing psychosocial interventions for MA use disorder. A limitation of this protocol is that the feasibility of follow-up is only examined at the end of treatment (4 weeks). TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12622000762752. Registered on May 27, 2022, and retrospectively registered (first participant enrolled) on May 23, 2022, with protocol version 7 on February 24, 2023.

Prolonged intermittent theta burst stimulation for post-stroke aphasia: protocol of a randomized, double-blinded, sham-controlled trial.

Background: Post-stroke aphasia (PSA) is one of the most devastating symptoms after stroke, yet limited treatment options are available. Prolonged intermittent theta burst stimulation (piTBS) is a promising therapy for PSA. However, its efficacy remains unclear. Therefore, we aim to investigate the efficacy of piTBS over the left supplementary motor area (SMA) in improving language function for PSA patients and further explore the mechanism of language recovery. Methods: This is a randomized, double-blinded, sham-controlled trial. A total of 30 PSA patients will be randomly allocated to receive either piTBS stimulation or sham stimulation for 15 sessions over a period of 3 weeks. The primary outcome is the Western Aphasia Battery Revised (WAB-R) changes after treatment. The secondary outcomes include The Stroke and Aphasia Quality of Life Scale (SAQOL-39 g), resting-state electroencephalogram (resting-state EEG), Event-related potentials (ERP), brain derived neurotrophic factor (BDNF). These outcome measures are assessed before treatment, after treatment, and at 4-weeks follow up. This study was registered in Chinese Clinical Trial Registry (No. ChiCTR23000203238). Discussion: This study protocol is promising for improving language in PSA patients. Resting-state EEG, ERP, and blood examination can be used to explore the neural mechanisms of PSA treatment with piTBS. Clinical trial registration: https://www.chictr.org.cn/index.html, ChiCTR2300074533.

Real-world case series of maintenance theta burst stimulation therapy following response to acute theta burst stimulation therapy for difficult-to-treat depression.

OBJECTIVE: Treatment and management for difficult-to-treat depression are challenging, especially in a subset of patients who are at high risk for relapse and recurrence. The conditions that represent this subset are recurrent depressive disorder (RDD) and bipolar disorder (BD). In this context, we aimed to examine the effectiveness of maintenance transcranial magnetic stimulation (TMS) on a real-world clinical basis by retrospectively extracting data from the TMS registry data in Tokyo, Japan. METHODS: Data on patients diagnosed with treatment-resistant RDD and BD who received maintenance intermittent theta burst stimulation (iTBS) weekly after successful treatment with acute iTBS between March 2020 and October 2023 were extracted from the registry. RESULTS: All patients (21 cases: 10 cases with RDD and 11 cases with BD) could sustain response, and 19 of them further maintained remission. In this study, maintenance iTBS did not exacerbate depressive symptoms in any of the cases, but may rather have the effect of stabilizing the mental condition and preventing recurrence. CONCLUSIONS: This case series is of great clinical significance because it is the first study to report on the effectiveness of maintenance iTBS for RDD and BD, with a follow-up of more than 2 years. Further validation with a randomized controlled trial design with a larger sample size is warranted.

Sex differences in brain excitability revealed by concurrent iTBS/fNIRS.

Sex differences have been claimed an imperative factor in the optimization of psychiatric treatments. Intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation, is a promising non-invasive treatment option. Here, we investigated whether the real-time neural response to iTBS differs between men and women, and which mechanisms may mediate these differences. To this end, we capitalized on a concurrent iTBS/functional near-infrared spectroscopy setup over the left dorsolateral prefrontal cortex, a common clinical target, to test our assumptions. In a series of experiments, we show (1) a biological sex difference in absolute hemoglobin concentrations in the left dorsolateral prefrontal cortex in healthy participants; (2) that this sex difference is amplified by iTBS but not by cognitive tasks; and (3) that the sex difference amplified by iTBS is modulated by stimulation intensity. These results inform future stimulation treatment optimizations towards precision psychiatry.

The effect of intermittent theta burst stimulation for cognitive dysfunction: a meta-analysis.

BACKGROUND: Growing evidence suggests that cognitive dysfunction significantly impacts patients' quality of life. Intermittent theta burst stimulation (iTBS) has emerged as a potential intervention for cognitive dysfunction. However, consensus on the iTBS protocol for cognitive impairment is lacking. METHODS: We conducted searches in the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, Chinese National Knowledge Infrastructure, Wanfang Database and the Chongqing VIP Chinese Science and Technology Periodical Database from their inception to January 2024. Random-effects meta-analyzes were used to calculate standardized mean differences and 95% confidence intervals. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Twelve studies involving 506 participants were included in the meta-analysis. The analysis showed a trend toward improvement of total cognitive function, activities of daily living and P300 latency compared to sham stimulation in patients with cognitive dysfunction. Subgroup analysis demonstrated that these effects were restricted to patients with post-stroke cognitive impairment but not Alzheimer's disease or Parkinson's disease. Furthermore, subthreshold stimulation also exhibited a significant improvement. CONCLUSIONS: The results suggest that iTBS may improve cognitive function in patients with cognitive dysfunction, although the quality of evidence remains low. Further studies with better methodological quality should explore the effects of iTBS on cognitive function.

Single session of intermittent theta burst stimulation alters brain activity of patients in vegetative state.

BACKGROUND: Non-invasive brain stimulation is considered as a promising technology for treating patients with disorders of consciousness (DOC). Various approaches and protocols have been proposed; however, few of them have shown potential effects on patients with vegetative state (VS). This study aimed to explore the neuro-modulation effects of intermittent theta burst stimulation (iTBS) on the brains of patients with VS and to provide a pilot investigation into its possible role in treating such patients. METHODS: We conducted a sham-controlled crossover study, a real and a sham session of iTBS were delivered over the left dorsolateral prefrontal cortex of such patients. A measurement of an electroencephalography (EEG) and a behavioral assessment of the Coma Recovery Scale-Revised (CRS-R) were applied to evaluate the modulation effects of iTBS before and after stimulation. RESULTS: No meaningful changes of CRS-R were found. The iTBS altered the spectrum, complexity and functional connectivity of the patients. The real stimulation induced a trend of decreasing of delta power at T1 and T2 in the frontal region, significant increasing of permutation entropy at the T2 in the left frontal region. In addition, brain functional connectivity, particularly inter-hemispheric connectivity, was strengthened between the electrodes of the frontal region. The sham stimulation, however, did not induce any significant changes of the brain activity. CONCLUSIONS: One session of iTBS significantly altered the oscillation power, complexity and functional connectivity of brain activity of VS patients. It may be a valuable tool on modulating the brain activities of patients with VS.

Synergistic efficacy of repetitive peripheral magnetic stimulation on central intermittent theta burst stimulation for upper limb function in patients with stroke: a double-blinded, randomized controlled trial.

BACKGROUND: Non-invasive techniques such as central intermittent theta burst stimulation (iTBS) and repetitive peripheral magnetic stimulation (rPMS) have shown promise in improving motor function for patients with stroke. However, the combined efficacy of rPMS and central iTBS has not been extensively studied. This randomized controlled trial aimed to investigate the synergistic effects of rPMS and central iTBS in patients with stroke. METHOD: In this study, 28 stroke patients were randomly allocated to receive either 1200 pulses of real or sham rPMS on the radial nerve of the affected limb, followed by 1200 pulses of central iTBS on the ipsilesional hemisphere. The patients received the intervention for 10 sessions over two weeks. The primary outcome measures were the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and the Action Research Arm Test (ARAT). Secondary outcomes for activities and participation included the Functional Independence Measure-Selfcare (FIM-Selfcare) and the Stroke Impact Scale (SIS). The outcome measures were assessed before and after the intervention. RESULTS: Both groups showed significant improvement in FMA-UE and FIM-Selfcare after the intervention (p < 0.05). Only the rPMS + iTBS group had significant improvement in ARAT-Grasp and SIS-Strength and activity of daily living (p < 0.05). However, the change scores in all outcome measures did not differ between two groups. CONCLUSIONS: Overall, the study's findings suggest that rPMS may have a synergistic effect on central iTBS to improve grasp function and participation. In conclusion, these findings highlight the potential of rPMS as an adjuvant therapy for central iTBS in stroke rehabilitation. Further large-scale studies are needed to fully explore the synergistic effects of rPMS on central iTBS. TRIAL REGISTRATION: This trial was registered under ClinicalTrials.gov ID No.NCT04265365, retrospectively registered, on February 11, 2020.