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Introduction: Substance use disorders (SUDs) are severe conditions that remain extremely challenging to treat in clinical practice. With high rates of non-response to current treatment options and several SUDs with no approved interventions, novel therapies are needed. Repetitive transcranial magnetic stimulation (rTMS) can non-invasively modulate the neurocircuitry of brain-based disorders, and investigation into its therapeutic potential for SUDs is growing rapidly. Areas covered: In this review, we summarize the clinical research to date evaluating its safety and efficacy for various SUDs. We highlight the investigations comparing different stimulation parameters to present our current understanding on optimal stimulation parameters. Additionally, we cover key research avenues in the use of neuroimaging to guide treatment, cue-induction paradigms, and adjunctive or combination treatments that may optimize outcomes. Expert opinion: Evidence of rTMS as an effective treatment for certain SUDs has emerged and is preliminary for others. There are a growing number of studies showing benefit and meta-analyses suggesting that rTMS can significantly reduce substance craving and consumption. However, the optimal approach has not been determined, and there is a great deal of heterogeneity in rTMS protocols and mixed outcomes. Further research into strategies for enhancing precision will be crucial in moving the field forward. [ABSTRACT FROM AUTHOR]

• TMS changes resting state functional connectivity proportional to the electric field distribution of the TMS pulse. • Results offer critical insight into the mechanism underlying TMS modulation of brain connectivity. • They also show that a generalized connectivity mapping approach may inform precision targeting efforts. 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). 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). 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. 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. This finding lays the groundwork for future studies to individualize TMS targeting based on how predicted rs-fMRI changes might impact psychiatric symptoms. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to evaluate, using a network meta-analysis, the effects of different transcranial magnetic stimulation (TMS) modalities on improving cognitive function after stroke. Methods: Computer searches of the Cochrane Library, PubMed, Web of Science, Embass, Google Scholar, CNKI, and Wanfang databases were conducted to collect randomized controlled clinical studies on the use of TMS to improve cognitive function in stroke patients, published from the time of database construction to November 2023. Results: A total of 29 studies and 2123 patients were included, comprising five interventions: high-frequency rTMS (HF-rTMS), low-frequency rTMS (LF-rTMS), intermittent theta rhythm stimulation (iTBS), sham stimulation (SS), and conventional rehabilitation therapy (CRT). A reticulated meta-analysis showed that the rankings of different TMS intervention modalities in terms of the Montreal Cognitive Assessment (MoCA) scores, Mini-Mental State Examination scores (MMSE), and Modified Barthel Index (MBI) scores were: HF-rTMS > LF-rTMS > iTBS > SS > CRT; the rankings of different TMS intervention modalities in terms of the event-related potential P300. amplitude scores were HF-rTMS > LF-rTMS > iTBS > CRT > SS; the rankings of different TMS intervention modalities in terms of the P300 latency scores were: iTBS > HF-rTMS > LF-rTMS > SS > CRT. Subgroup analyses of secondary outcome indicators showed that HF-rTMS significantly improved Rivermead Behavior Memory Test scores and Functional Independence Measurement-Cognitive scores. Conclusions: High-frequency TMS stimulation has a better overall effect on improving cognitive functions and activities of daily living, such as attention and memory in stroke patients. [ABSTRACT FROM AUTHOR]

Xuan Li,1,2,* Qiong Xiang,1,2,* Haixin Cen,1,2 Zhaolin Zhai,1– 3 Tianhao Gao,1– 3 Chang Lu,1– 3 Yuke Dong,1– 3 Yujian Ye,1,2 Chenxi Zhang,4 Kaiming Zhuo,1,2 Yan Wang,5 Dengtang Liu1– 3,6,7,* 1Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Clinical Center for Psychotic Disorders, National Center for Mental Disorders, Shanghai, People’s Republic of China; 3Department of Psychiatry, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 4Department of Psychiatry, Feng Xian Mental Health Center, Shanghai, People’s Republic of China; 5School of Psychology and Cognitive Science, East China Normal University, Shanghai, People’s Republic of China; 6Institute of Mental Health, Fudan University, Shanghai, People’s Republic of China; 7Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dengtang Liu, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Email liudengtang@smhc.org.cn Yan Wang, School of Psychology and Cognitive Science, East China Normal University, Shanghai, People’s Republic of China, Email wangyan@psy.ecnu.edu.cnObjective: The objective of our study was to evaluate whether intermittent theta burst stimulation(iTBS) applied to the regions with the strongest cortico-hippocampal connectivity within the lateral parietal cortical (LPC) or dorsolateral prefrontal cortical (DLPFC) areas in individuals with schizophrenia could enhance associative memory.Methods: We randomized 96 participants with schizophrenia to receive either active iTBS applied to the right DLPFC, left LPC or sham iTBS for 20 days. Clinical and cognitive assessments were performed at baseline and at the end of treatment. The primary outcome was change in associative memory. The secondary outcome was change in other cognitive functions and psychiatric symptoms.Results: In comparison to the sham group, iTBS targeting the right DLPFC or left LPC in schizophrenia did not yield significant improvements in auditory-auditory associative memory (F=1.27, p=0.294), auditory-visual associative memory (F=0.49, p=0.617), or visual-visual associative memory (F=1.094, p=0.347). Furthermore, after adjusting for variables such as education, disease duration, and negative symptoms, no significant changes were observed in any of these three memory domains.Conclusion: Although our study suggests that iTBS applied to the cortical-hippocampal did not lead to a significant change in associative memory. However, further investigation combining hippocampal-targeted iTBS with functional magnetic resonance imaging (fMRI) is warranted to elucidate the regulatory effects of iTBS on hippocampal function.Trial Registration: clinicaltrials.gov NCT03608462.Keywords: theta burst stimulation, associative memory, schizophrenia, cortical-hippocampal network

Sex- and age-dependent outcome differences have been observed in treatment of Major Depressive Disorder (MDD), including 10 Hz repetitive Transcranial Magnetic Stimulation (rTMS). We examined whether there are sex- and age-dependent differences in outcome with intermittent Theta Burst Stimulation (iTBS), another rTMS protocol. The relationship between biological sex, age, and treatment outcome was retrospectively examined among 414 patients with MDD treated with 10 Hz or iTBS rTMS. Linear mixed-effects modeling was used to examine the association between treatment and change in the 30-item Inventory of Depressive Symptomatology Self-Report (IDS-SR30) score from baseline to treatments 10 and 30, with biological sex (M/F), protocol (iTBS/10 Hz), age (≥/<50 years old), and time (treatment 1/10/30) included as fixed effects. The three-way sex-protocol-time and age-protocol-time interactions were used to determine any differential relationships between protocol and outcome dependent on sex and age. Post-hoc t -tests were conducted to examine differences in improvement. There was a significant three-way sex-protocol-time interaction at treatments 10 (p = 0.016) and 30 (p = 0.031). Males showed significantly greater improvement with iTBS than females at treatments 10 (p = 0.041) and 30 (p = 0.035), while females showed numerically greater improvement with 10 Hz treatment. While there was not a significant three-way age-protocol-time interaction, there was a significant interaction between age (≥50 years old) and time at treatments 10 (p = 0.007) and 30 (p = 0.042), and among age, sex, and time at treatment 30 (p = 0.028). Retrospective naturalistic treatment protocol. iTBS appeared less efficacious in females than in males, and rTMS overall was more efficacious in patients over fifty, particularly females. • rTMS is an FDA-approved treatment for depression. • Two commonly used rTMS protocols for depression are 10 Hz and iTBS. • 10 Hz appears more efficacious in females than in males. • iTBS appears less efficacious in females than in males. • Overall, rTMS appears more efficacious in patients ≥50, particularly females ≥50. [ABSTRACT FROM AUTHOR]

Background: Previous studies have found that inhibitory priming with continuous theta burst stimulation (cTBS) can enhance the effect of subsequent excitatory conditioning stimuli with intermittent theta burst stimulation (iTBS) in the upper limbs. However, whether this combined stimulation approach elicits a comparable compensatory response in the lower extremities remains unclear. This study aimed to investigate how cTBS preconditioning modulated the effect of iTBS on motor cortex excitability related to the lower limb in healthy individuals. Methods: Using a randomised cross-over design, a total of 25 healthy participants (19 females, mean age = 24.80 yr) were recruited to undergo three different TBS protocols (cTBS + iTBS, sham cTBS + iTBS, sham cTBS + sham iTBS) in a random order. Each TBS intervention was administered with one-week intervals. cTBS and iTBS were administered at an intensity of 80% active motor threshold (AMT) delivering a total of 600 pulses. Before intervention (T0), immediately following intervention (T1), and 20 min after intervention (T2), the corticomotor excitability was measured for the tibialis anterior muscle of participants' non-dominant leg using a Magneuro100 stimulator and matched double-cone coil. The average amplitude of the motor-evoked potential (MEP) induced by applying 20 consecutive monopulse stimuli at an intensity of 130% resting motor threshold (RMT) was collected and analysed. Results: Compare with T0 time, the MEP amplitude (raw and normalised) at T1 and T2 showed a statistically significant increase following the cTBS + iTBS protocol (p < 0.01), but no significant differences were observed in amplitude changes following other protocols (sham cTBS + iTBS and sham cTBS + sham iTBS) (p > 0.05). Furthermore, no statistically significant difference was found among the three protocols at any given time point (p > 0.05). Conclusions: Preconditioning the lower extremity motor cortex with cTBS prior to iTBS intervention can promptly enhance its excitability in healthy participants. This effect persists for a minimum duration of 20 min. [ABSTRACT FROM AUTHOR]

Abstract Transcranial temporal interference stimulation (tTIS) is a promising brain stimulation method that can target deep brain regions by delivering an interfering current from surface electrodes. Most instances of tTIS stimulate the brain with a single-frequency sinusoidal waveform generated by wave interference. Theta burst stimulation is an effective stimulation scheme that can modulate neuroplasticity by generating long-term potentiation- or depression-like effects. To broaden tTIS application, we developed a theta burst protocol using tTIS technique to modulate neuroplasticity in rats. Two cannula electrodes were unilaterally implanted into the intact skull over the primary motor cortex. Electrical field of temporal interference envelopes generated by tTIS through cannula electrodes were recorded from primary motor cortex. Theta burst schemes were characterized, and motor activation induced by the stimulation was also evaluated simultaneously by observing electromyographic signals from the corresponding brachioradialis muscle. After validating the stimulation scheme, we further tested the modulatory effects of theta burst stimulation delivered by tTIS and by conventional transcranial electrical stimulation on primary motor cortex excitability. Changes in the amplitude of motor evoked potentials, elicited when the primary motor cortex was activated by electrical pulses, were measured before and after theta burst stimulation by both techniques. Significant potentiation and suppression were found at 15 to 30 min after the intermittent and continuous theta burst stimulation delivered using tTIS, respectively. However, comparing to theta burst stimulations delivered using conventional form of transcranial electrical stimulation, using tTIS expressed no significant difference in modulating motor evoked potential amplitudes. Sham treatment from both methods had no effect on changing the motor evoked potential amplitude. The present study demonstrated the feasibility of using tTIS to achieve a theta burst stimulation scheme for motor cortical neuromodulation. These findings also indicated the future potential of using tTIS to carry out theta burst stimulation protocols in deep-brain networks for modulating neuroplasticity.

This systematic review aimed to evaluate the effects of different theta burst stimulation (TBS) protocols on improving upper extremity motor functions in patients with stroke, their associated modulators of efficacy, and the underlying neural mechanisms. We conducted a meta-analytic review of 29 controlled trials published from January 1, 2000, to August 29, 2023, which investigated the effects of TBS on upper extremity motor, neurophysiological, and neuroimaging outcomes in poststroke patients. TBS significantly improved upper extremity motor impairment (Hedge's g = 0.646, p = 0.003) and functional activity (Hedge's g = 0.500, p < 0.001) compared to controls. Meta-regression revealed a significant relationship between the percentage of patients with subcortical stroke and the effect sizes of motor impairment (p = 0.015) and functional activity (p = 0.018). Subgroup analysis revealed a significant difference in the improvement of upper extremity motor impairment between studies using 600-pulse and 1200-pulse TBS (p = 0.002). Neurophysiological studies have consistently found that intermittent TBS increases ipsilesional corticomotor excitability. However, evidence to support the regional effects of continuous TBS, as well as the remote and network effects of TBS, is still mixed and relatively insufficient. In conclusion, TBS is effective in enhancing poststroke upper extremity motor function. Patients with preserved cortices may respond better to TBS. Novel TBS protocols with a higher dose may lead to superior efficacy compared with the conventional 600-pulse protocol. The mechanisms of poststroke recovery facilitated by TBS can be primarily attributed to the modulation of corticomotor excitability and is possibly caused by the recruitment of corticomotor networks connected to the ipsilesional motor cortex. [ABSTRACT FROM AUTHOR]

Whether brain stimulation could modulate brain structure in autism remains unknown. This study explored the impact of continuous theta burst stimulation (cTBS) over the left dorsolateral prefrontal cortex (DLPFC) on white matter macro/microstructure in intellectually able children and emerging adults with autism. Sixty autistic participants were randomized (30 active) and received active or sham cTBS for eight weeks twice per week, 16 total sessions using a double-blind (participant-, rater-, analyst-blinded) design. All participants received high-angular resolution diffusion MR imaging at baseline and week 8. Twenty-eight participants in the active group and twenty-seven in the sham group with good imaging quality entered the final analysis. With longitudinal fixel-based analysis and network-based statistics, we found no significant difference between the active and sham groups in changes of white matter macro/microstructure and connections following cTBS. In addition, we found no association between baseline white matter macro/microstructure and autistic symptom changes from baseline to week 8 in the active group. In conclusion, we did not find a significant impact of left DLPFC cTBS on white matter macro/microstructure and connections in children and emerging adults with autism. These findings need to be interpreted in the context that the current intellectually able cohort in a single university hospital site limits the generalizability. Future studies are required to investigate if higher stimulation intensities and/or doses, other personal factors, or rTMS parameters might confer significant brain structural changes visible on MRI in ASD. [ABSTRACT FROM AUTHOR]

Schizophrenia is a chronic psychiatric disorder severely affecting patients' functioning and quality of life. Unlike positive symptoms, cognitive impairment and negative symptoms cannot be treated pharmacologically and represent consistent predictors of the illness's prognosis. Cognitive remediation (CR) interventions have been applied to target these symptoms. Brain stimulation also provides promising yet preliminary results in reducing negative symptoms, whereas its effect on cognitive impairment remains heterogeneous. Here, we combined intermittent theta burst stimulation (iTBS) with CR to improve negative symptoms and cognitive impairment in schizophrenia spectrum patients. One hundred eligible patients were invited, and twenty-one participated. We randomized them into four groups, manipulating the stimulation condition (real vs. sham) and CR (no training vs. training). We delivered fifteen iTBS sessions over the left dorsolateral prefrontal cortex for three weeks, followed (or not) by 50 min of training. Consensus-based clinical and cognitive assessment was administered at baseline and after the treatment, plus at three follow-ups occurring one, three, and six months after the intervention. Mixed-model analyses were run on cognitive and negative symptom scores. The preliminary findings highlighted a marginal modulation of iTBS on negative symptoms, whereas CR improved isolated cognitive functions. We herein discuss the limitations and strengths of the methodological approach. [ABSTRACT FROM AUTHOR]

Suicidal ideation is a substantial clinical challenge in treatment-resistant depression (TRD). Recent work demonstrated promising antidepressant effects in TRD patients with no or mild suicidal ideation using a specific protocol termed intermittent theta burst stimulation (iTBS). Here, we examined the clinical effects of accelerated schedules of iTBS and continuous TBS (cTBS) in patients with moderate to severe suicidal ideation. Patients with TRD and moderate to severe suicidal ideation (n = 44) were randomly assigned to receive accelerated iTBS or cTBS treatment. Treatments were delivered in 10 daily TBS sessions (1800 pulses/session) for 5 consecutive days (total of 90,000 pulses). Neuronavigation was employed to target accelerated iTBS and cTBS to the left and right dorsolateral prefrontal cortex (DLPFC), respectively. Clinical outcomes were evaluated in a 4-week follow-up period. Accelerated cTBS was superior to iTBS in the management of suicidal ideation (p week 1 =.027) and anxiety symptoms (p week 1 =.01). Accelerated iTBS and cTBS were comparable in antidepressant effects (p <.001; accelerated cTBS: mean change at weeks 1, 3, 5 = 49.55%, 54.99%, 53.11%; accelerated iTBS: mean change at weeks 1, 3, 5 = 44.52%, 48.04%, 51.74%). No serious adverse events occurred during the trial. One patient withdrew due to hypomania. The most common adverse event was discomfort at the treatment site (22.73% in both groups). These findings provide the first evidence that accelerated schedules of left DLPFC iTBS and right DLPFC cTBS are comparably effective in managing antidepressant symptoms and indicate that right DLPFC cTBS is potentially superior in reducing suicidal ideation and anxiety symptoms. [ABSTRACT FROM AUTHOR]

IntroductionDespite the high hopes for the use of transcranial magnetic stimulation (TMS) in the treatment of depression, between 30% and 60.5% of patients do not respond to stimulation. The factors contributing to non-response, especially those related to personality, remain insufficiently investigated. The main aim of our study was to compare the efficacy of active TMS and sham–placebo protocols in combined therapy of treatment-resistant depression with evaluation of possible personality disorders comorbidity.MethodsThe study was conducted between December 2019 and December 2022, as a randomized, double-blind, active comparator-controlled and sham-controlled parallel trial. Patients (n = 41) were randomized into one of two experimental conditions (active TMS vs. placebo) and screened before and after stimulation as well as at a 3-month follow-up. Personality disorders were assessed with The Structured Clinical Interview for DSM-5 Personality Disorders.ResultsThere were no significant differences between the TMS active and sham groups in terms of general characteristics, coexisting personality disorders, and Montgomery–Åsberg Depression Rating Scale scores before stimulation, at the end of stimulation, and after 3 months of stimulation. However, linear regression analysis revealed significant negative associations between the coexistence of personality disorders and the reduction of depressive symptoms from baseline to the end of stimulation. The post-hoc exploratory analysis on the first phase of the RCT confirmed the presence of personality disorders to be a consistent negative influence on the reduction of depressive symptoms post-stimulation, regardless of protocol and experimental condition and demonstrated a smaller percentage reduction in depressive symptoms after stimulation in patients with personality disorders.DiscussionA central conclusion, based on our study, is that transcranial magnetic stimulation for treatment-resistant depression cannot be considered as a method independent of co-occurring personality disorders.

Abstract 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.

Abstract 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

What is the relationship between language and complex thought? In the context of deductive reasoning there are two main views. Under the first, which we label here the language-centric view, language is central to the syntax-like combinatorial operations of complex reasoning. Under the second, which we label here the language-independent view, these operations are dissociable from the mechanisms of natural language. We applied continuous theta burst stimulation (cTBS), a form of noninvasive neuromodulation, to healthy adult participants to transiently inhibit a subregion of Broca's area (left BA44) associated in prior work with parsing the syntactic relations of natural language. We similarly inhibited a subregion of dorsomedial frontal cortex (left medial BA8) which has been associated with core features of logical reasoning. There was a significant interaction between task and stimulation site. Post hoc tests revealed that performance on a linguistic reasoning task, but not deductive reasoning task, was significantly impaired after inhibition of left BA44, and performance on a deductive reasoning task, but not linguistic reasoning task, was decreased after inhibition of left medial BA8 (however not significantly). Subsequent linear contrasts supported this pattern. These novel results suggest that deductive reasoning may be dissociable from linguistic processes in the adult human brain, consistent with the language-independent view.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Continuous theta burst stimulation may be an important tool in the therapeutic management of amblyopia, when trying to correct the established neuronal imbalance. It is important to understand whether two sessions of continuous theta burst stimulation produce greater and longstanding changes in visual acuity and suppressive imbalance than one session of continuous theta burst stimulation We hypothesise that through the usage of continuous theta burst stimulation (cTBS) it is possible to change cortical excitability in a situation where visual impairment is present. We selected 22 adult amblyopes, 18 females and 4 males, with an age range of 20–59 years. They were randomised into two groups: group A with 10 amblyopes was submitted to one session of cTBS and group B with 12 amblyopes submitted to two sessions of cTBS. Visual acuity (VA) and suppressive imbalance (SI) were evaluated immediately before and after stimulation in both groups A and B. A follow-up was done in both groups. For both group A and B, the VA improvements were significant after cTBS (p = 0.005 and p = 0.003, respectively). Regarding SI, both group A and B had significant improvements after cTBS (p = 0.03 and p = 0.005, respectively). Comparing groups, A and B no significant differences were found with regard to the results obtained both for VA (p = 0.72) and SI (p = 0.24). However, significant differences were found between group A and B with regard to the duration of stimulation effect for VA (p = 0.049) and SI (p = 0.03). We conclude that two sessions of cTBS do not produce better results than one session of stimulation. However, it seems that two sessions of cTBS produce longstanding effects in VA and SI. [ABSTRACT FROM AUTHOR]

Introduction: Mal de Debarquement Syndrome (MdDS) is a rare central vestibular disorder characterised by a constant sensation of motion (rocking, swaying, bobbing), which typically arises after motion experiences (e.g. sea, air, and road travel), though can be triggered by non-motion events. The current standard of care is non-specific medications and interventions that only result in mild-to-moderate improvements. The vestibular ocular reflex (VOR) rehabilitation protocol, a specialised form of rehabilitation, has shown promising results in reducing symptoms amongst people with MdDS. Accumulating evidence suggests that it may be possible to augment the effects of VOR rehabilitation via non-invasive brain stimulation protocols, such as theta burst stimulation (TBS). Methods: The aim of this randomised controlled trial was to evaluate the effectiveness of intermittent TBS (iTBS) over the dorsolateral prefrontal cortex in enhancing the effectiveness of a subsequently delivered VOR rehabilitation protocol in people with MdDS. Participants were allocated randomly to receive either Sham (n = 10) or Active (n = 10) iTBS, followed by the VOR rehabilitation protocol. Subjective outcome measures (symptom ratings and mental health scores) were collected 1 week pre-treatment and for 16 weeks post-treatment. Posturography (objective outcome) was recorded each day of the treatment week. Results: Significant improvements in subjective and objective outcomes were reported across both treatment groups over time, but no between-group differences were observed. Discussion: These findings support the effectiveness of the VOR rehabilitation protocol in reducing MdDS symptoms. Further research into iTBS is required to elucidate whether the treatment has a role in the management of MdDS. TRN: ACTRN12619001519145 (Date registered: 04 November 2019). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Theta burst stimulation (TBS) is approved and widely used in the treatment of treatment resistant-major depression. More recently, accelerated protocols delivering multiple treatments per day have been shown to be efficacious and potentially enhance outcomes compared to once daily protocols. Meanwhile, bilateral treatment protocols have also been increasingly tested to enhance outcomes. Here, we examined the efficacy and safety of accelerated bilateral TBS in major depressive disorder (MDD). In this open label pilot study, 25 patients with MDD (60%: women; mean age (SD): 45.24 (12.22)) resistant to at least one antidepressant, received bilateral TBS, consisting of 5 sequential bilateral intermittent TBS (iTBS) (600 pulses) and continuous TBS (cTBS) (600 pulses) treatments delivered to the left and right dorsolateral prefrontal cortex (DLPFC), respectively, daily for 5 days at 120% resting motor threshold. Outcome measures were post-treat treatment changes at day 5 and 2-weeks in Hamilton Depression Rating Scale (HDRS-17) scores and response (≥ 50% reduction from the baseline scores) and remission (≤ 7) rates. There was a significant reduction in HDRS scores at day 5 (p < 0.001) and 2-weeks post treatment (p < 0.001). The response rates increased from 20% at day 5 to 32% at 2-weeks post treatment suggesting delayed clinical effects. However, reduction in symptom scores between two post treatment endpoints was non-significant. 60% of patients could not tolerate the high intensity stimulation. No major adverse events occurred. Open label uncontrolled study with small sample size. These preliminary findings suggest that accelerated bilateral TBS may be clinically effective and safe for treatment resistant depression. Randomized sham-controlled trials are needed to establish the therapeutic role of accelerated bilateral TBS in depression. Trial registration: ClinicalTrials.gov, NCT10001858. [ABSTRACT FROM AUTHOR]

To determine if theta burst stimulation (TBS) is of preferential benefit to those with melancholic or non-melancholic depression as an adjunctive treatment for treatment resistant depression (TRD). Fifty-two patients receiving TBS at a private psychiatric hospital participated in a naturalistic study. Four diagnostic strategies were used to assign melancholic versus non-melancholic depression subtype status. Depression symptoms were assessed at baseline, mid-treatment, and end of treatment using the Montgomery-Ǻsberg Depression Rating Scale – Self-Assessment (MADRS-S). Forty-one participants also completed the MADR-S at a six-week follow-up assessment. We quantified poor correlations between the four study measures of melancholia; a finding suggesting that valid measurement of melancholia is likely to remain problematic. TBS led to significant reductions in depression symptoms from baseline to end of treatment, with this effect maintained at follow up. Response rates for the whole sample were 61.5 % at end of treatment and 53.7 % at follow-up, while remission rates were 34.6 % at end of treatment and 31.7 % at follow-up. Improvement rates as well as responder and remission rates were comparable for the melancholic and non-melancholic groups, irrespective of the diagnostic strategy used. The study was naturalistic (i.e., there being no control group, and concomitant medication changes were allowed), depression severity was assessed only by use of self-report measures, and the sample size was relatively small. TBS appears to be non-specific, in that we failed to quantify any statistically significant differential benefit for those with melancholic compared to those with non-melancholic depression. • TBS appeared equally effective for melancholic and non-melancholic depression. • Comparable effectiveness was evident irrespective of diagnostic strategy. • More than half of patients responded to treatment, while around a third remitted. [ABSTRACT FROM AUTHOR]

Theta burst stimulation (TBS) is a noninvasive brain stimulation technique that can be used to modulate neural networks underlying psychiatric and neurological disorders. TBS can be delivered intermittently or continuously. The conventional intermittent TBS protocol is approved by the U.S. Food and Drug Administration to treat otherwise treatment-resistant depression, but the 6-week duration limits the applicability of this therapy. Accelerated TBS protocols present an opportunity to deliver higher pulse doses in shorter periods of time, thus resulting in faster and potentially more clinically effective treatment. However, the acceleration of TBS delivery raises questions regarding the relative safety, efficacy, and durability compared with conventional TBS protocols. In this review paper, we present the data from accelerated TBS trials to date that support the safety and effectiveness of accelerated protocols while acknowledging the need for more durability data. We discuss the stimulation parameters that seem to be important for the efficacy of accelerated TBS protocols and possible avenues for further optimization. [ABSTRACT FROM AUTHOR]

Objective: This study used network Meta-analysis to compare the effects of different transcranial magnetic stimulation (TMS) modalities on the effectiveness and long-term validity of improving cognitive function in Parkinson's patients. Methods: Computer searches of the Cochrane Library, PubMed, Web of Science, Embass, CNKI and Wanfang Data were conducted to collect randomized controlled clinical studies on TMS to improve cognitive function in Parkinson's patients published from the time of library construction to December 2023. Results: A total of 22 studies and 1,473 patients were included, comprising 5 interventions: high frequency repetitive transcranial magnetic stimulation (HFrTMS), low frequency repetitive transcranial magnetic stimulation (LF-rTMS), intermittent theta burst stimulation (iTBS), sham stimulation and conventional rehabilitation therapy (CRT). Network Meta-analysis showed that the ranking results of different TMS intervention modalities in terms of MoCA scores were: HF-rTMS > LF-rTMS > iTBS > sham > CRT, the ranking results of different TMS intervention modalities in terms of MMSE scores were: HF-rTMS > LF-rTMS > sham > CRT. The effect of TMS on improving Parkinsonian cognitive function lasted for 1 month compared to the no-stimulation group. Conclusion: TMS has some long-term sustained effects on improving cognitive function in Parkinson's patients. HF-rTMS is more effective in improving cognitive function in Parkinson's patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42023463958. [ABSTRACT FROM AUTHOR]

Specialized psychotherapeutic treatments like dialectical behavioral therapy (DBT) are recommended as first treatment for borderline personality disorder (BPD). In recent years, studies have emerged that focus on repetitive transcranial magnetic stimulation (rTMS) in BPD. Both have independently demonstrated efficacy in the treatment of BPD. Intermitted theta burst stimulation (iTBS), a modified design of rTMS, is thought to increase the excitability of neurons and could be a supplement to psychotherapy in addition to being a standalone treatment. However, no studies to date have investigated the combination of DBT and rTMS/iTBS. This study protocol describes the methods and design of a randomized, single-blinded, sham-controlled clinical pilot study in which BPD patients will be randomly assigned to either iTBS or sham during four consecutive weeks (20 sessions in total) in addition to standardized DBT treatment. The stimulation will focus on the unilateral stimulation of the left dorsolateral prefrontal cortex (DLPFC), which plays an important role in the control of impulsivity and risk-taking. Primary outcome is the difference in borderline symptomatology, while secondary target criteria are depressive symptoms, general functional level, impulsivity and self-compassion. Statistical analysis of therapy response will be conducted by Mixed Model Repeated Measurement using a 2 × 2-factorial between-subjects design with the between-subject factor stimulation (TMS vs. Sham) and the within-subject factor time (T0 vs. T1). Furthermore, structural magnetic resonance imaging (MRI) will be conducted and analyzed. The study will provide evidence and insight on whether iTBS has an enhancing effect as add-on to DBT in BPD. Trial registration: drks.de (DRKS00020413) registered 13/01/2020. [ABSTRACT FROM AUTHOR]

10-Hz repetitive transcranial magnetic stimulation(rTMS) and intermittent theta-burst stimulation(iTBS) over left prefrontal cortex are FDA-approved, effective options for treatment-resistant depression (TRD). Optimal prediction models for iTBS and rTMS remain elusive. Therefore, our primary objective was to compare prediction accuracy between classification by frontal theta activity alone and machine learning(ML) models by linear and non-linear frontal signals. The second objective was to study an optimal ML model for predicting responses to rTMS and iTBS. Two rTMS and iTBS datasets (n = 163) were used: one randomized controlled trial dataset (RCTD; n = 96) and one outpatient dataset (OPD; n = 67). Frontal theta and non-linear EEG features that reflect trend, stability, and complexity were extracted. Pretreatment frontal EEG and ML algorithms, including classical support vector machine(SVM), random forest(RF), XGBoost, and CatBoost, were analyzed. Responses were defined as ≥50 % depression improvement after treatment. Response rates between those with and without pretreatment prediction in another independent outpatient cohort (n = 208) were compared. Prediction accuracy using combined EEG features by SVM was better than frontal theta by logistic regression. The accuracy for OPD patients significantly dropped using the RCTD-trained SVM model. Modern ML models, especially RF (rTMS = 83.3 %, iTBS = 88.9 %, p -value(ACC > NIR) < 0.05 for iTBS), performed significantly above chance and had higher accuracy than SVM using both selected features (p < 0.05, FDR corrected for multiple comparisons) or all EEG features. Response rates among those receiving prediction before treatment were significantly higher than those without prediction (p = 0.035). The first study combining linear and non-linear EEG features could accurately predict responses to left PFC iTBS. The bootstraps-based ML model (i.e., RF) had the best predictive accuracy for rTMS and iTBS. • Frontal EEG activity may predict antidepressant responses to prefrontal rTMS or iTBS. • We compared prediction accuracy between different machine learning (ML) models and between different datasets. • Modern ML models, especially random forest, performed significantly above change. • Combing linear and non-linear EEG features accurately predict responses to rTMS and iTBS. [ABSTRACT FROM AUTHOR]

We investigated the influences of sepsis on central synaptic plasticity in vitro. Cecal ligation and puncture (CLP) was performed by creating rat sepsis models, which were divided into early and late sepsis groups (8 and 16 h after CLP, respectively). In the CA1 of the rat hippocampal slices, orthodromically elicited population spikes (PSs) and field excitatory postsynaptic potentials (fEPSPs) were simultaneously recorded, and their long-term potentiation (LTP) was induced by theta burst stimulation (TBS). TBS induced LTPs of PSs and fEPSPs in all groups. In the sham and early sepsis groups, there was no significant difference in LTPs between PSs and fEPSPs. However, in the late sepsis group, the LTP of PSs was greater than that of fEPSPs (p < 0.05) and was greater than the LTPs of PSs in the sham and early sepsis groups (p < 0.05). Superoxide dismutase, administered immediately before CLP, inhibited the enhancement of LTP in PS, as observed in the late sepsis group. The initial rapid potentiation component of LTP in fEPSPs was suppressed or reduced in all groups that underwent CLP. The results indicate that CLP-induced sepsis modulates hippocampal synaptic plasticity, depressing excitatory synaptic transmissions and facilitating somatic excitability, which is induced by septic oxygen superoxide. [ABSTRACT FROM AUTHOR]

Background: Continuous theta burst stimulation and intermittent theta burst stimulation are clinically popular models of repetitive transcranial magnetic stimulation. However, they are limited by high variability between individuals in cortical excitability changes following stimulation. Although electroencephalography oscillations have been reported to modulate the cortical response to transcranial magnetic stimulation, their association remains unclear. This study aims to explore whether machine learning models based on EEG oscillation features can predict the cortical response to transcranial magnetic stimulation. Method: Twenty-three young, healthy adults attended two randomly assigned sessions for continuous and intermittent theta burst stimulation. In each session, ten minutes of resting-state electroencephalography were recorded before delivering brain stimulation. Participants were classified as responders or non-responders based on changes in resting motor thresholds. Support vector machines and multi-layer perceptrons were used to establish predictive models of individual responses to transcranial magnetic stimulation. Result: Among the evaluated algorithms, support vector machines achieved the best performance in discriminating responders from non-responders for intermittent theta burst stimulation (accuracy: 91.30%) and continuous theta burst stimulation (accuracy: 95.66%). The global clustering coefficient and global characteristic path length in the beta band had the greatest impact on model output. Conclusion: These findings suggest that EEG features can serve as markers of cortical response to transcranial magnetic stimulation. They offer insights into the association between neural oscillations and variability in individuals' responses to transcranial magnetic stimulation, aiding in the optimization of individualized protocols.

The crucial role of the parietal cortex in working memory (WM) storage has been identified by fMRI studies. However, it remains unknown whether repeated parietal intermittent theta-burst stimulation (iTBS) can improve WM. In this within-subject randomized controlled study, under the guidance of fMRI-identified parietal activation in the left hemisphere, 22 healthy adults received real and sham iTBS sessions (five consecutive days, 600 pulses per day for each session) with an interval of 9 months between the two sessions. Electroencephalography signals of each subject before and after both iTBS sessions were collected during a change detection task. Changes in contralateral delay activity (CDA) and K-score were then calculated to reflect neural and behavioral WM improvement. Repeated-measures ANOVA suggested that real iTBS increased CDA more than the sham one (p = .011 for iTBS effect). Further analysis showed that this effect was more significant in the left hemisphere than in the right hemisphere (p = .029 for the hemisphere-by-iTBS interaction effect). Pearson correlation analyses showed significant correlations for two conditions between CDA changes in the left hemisphere and K score changes (ps

Recently, we have approached the recent systematic review conducted by Qin et al. (2023) (doi:10.1016/j.jad.2023.08.065) on the efficacy and safety of bilateral theta burst stimulation (TBS) for patients experiencing acute unipolar or bipolar depressive episodes with great interest. This meta-analysis is both timely and well-organized; however, we harbor reservations regarding the methodological rigor employed. In this critique, we have identified four concerns pertaining to the content of this article. We anticipate that the authors will acknowledge our remarks and provide a response, thereby enhancing the scholarly rigor and comprehensiveness of this meta-analysis. Furthermore, addressing these concerns will facilitate a better comprehension of the application bottleneck of transcranial magnetic stimulation (TMS) in depression, while also stimulating further contemplation and inspiration among readers.

Repetitive transcranial magnetic stimulation (TMS) is widely used in neuroscience and clinical settings to modulate human cortical activity. The effects of TMS on neural activity depend on the excitability of specific neural populations at the time of stimulation. Accordingly, the brain state at the time of stimulation may influence the persistent effects of repetitive TMS on distal brain activity and associated behaviors. We applied intermittent theta burst stimulation (iTBS) to a region in the posterior parietal cortex (PPC) associated with grasp control to evaluate the interaction between stimulation and brain state. Across two experiments, we demonstrate the immediate responses of motor cortex activity and motor performance to state-dependent parietal stimulation. We randomly assigned 72 healthy adult participants to one of three TMS intervention groups, followed by electrophysiological measures with TMS and behavioral measures. Participants in the first group received iTBS to PPC while performing a grasping task concurrently. Participants in the second group received iTBS to PPC while in a task-free, resting state. A third group of participants received iTBS to a parietal region outside the cortical grasping network while performing a grasping task concurrently. We compared changes in motor cortical excitability and motor performance in the three stimulation groups within an hour of each intervention. We found that parietal stimulation during a behavioral manipulation that activates the cortical grasping network increased downstream motor cortical excitability and improved motor performance relative to stimulation during rest. We conclude that constraining the brain state with a behavioral task during brain stimulation has the potential to optimize plasticity induction in cortical circuit mechanisms that mediate movement processes. [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorder (AUD) is associated with elevated brain response to cues. Recent studies have suggested that theta burst stimulation (TBS) to the medial prefrontal cortex (MPFC) can decrease reactivity to cues in a transdiagnostic manner. The goal of this clinical trial was to evaluate the effect of continuous TBS as a tool to decrease drinking behavior and brain reactivity to alcohol cues among individuals with AUD. Methods: A total of 50 individuals with AUD were recruited from an intensive outpatient treatment program. Using a randomized, double-blind, sham-controlled design, participants received 10 sessions of continuous TBS (left frontal pole, 1 session/10 days, 110% resting motor threshold, 3600 pulse/session, cue provocation before and during session). Brain reactivity to alcohol cues was acquired at four time points: at baseline and after all TBS sessions (1 month, 2 months, and 3 months). Results: Overall, 80% of the participants completed all TBS sessions. Individuals who received real TBS were 2.71 times more likely to remain enrolled in the study after 3 months and 3.09 times more likely to remain sober 3 months after treatment initiation. Real TBS also led to a significantly greater reduction in brain reactivity to alcohol cues, specifically a reduction in MPFC-striatum and MPFC-insula connectivity 2 and 3 months after TBS treatment. Conclusions: Ten days of MPFC TBS is well tolerated, reduces drinking, and decreases brain reactivity to alcohol cues for up to 3 months after treatment initiation. These results pave a critical next step in the path toward developing transcranial magnetic stimulation as an intervention for AUD and disorders associated with elevated cue reactivity.

Background Upper limb motor dysfunction is a common complication after stroke that seriously affects daily living skills of patients. As a common neuroelectrohysiological technique, repetitive transcranial magnetic stimulation (rTMS) has a good effect on post-stroke upper limb motor dysfunction. However, there is still no practice-based evidence on the selection of modalities of rTMS. Objective To evaluate the clinical efficacy of four rTMS modalities in post-stroke upper limb motor dysfunction by a network meta-analysis. Methods Randomized controlled trials (RCTs) about rTMS for treating upper limb motor dysfunction after stroke were searched with subject words combined with free words as searching terms in PubMed, Embase, Cochrane Library, Web of Science, CBM, CNKI, Wanfang Data, and VIP from inception to February 2022, supplemented by references from retrospective meta-analysis. Two researchers performed literature screening, data extraction, and quality evaluation separately. RevMan 5.0 and Stata 16.0 were used for statistical analysis. Results A total of 17 RCTs with 790 cases were included. Six interventions were involved: high frequency-rTMS (HF-rTMS), low frequency-rTMS (LF-rTMS), intermittent theta burst stimulation (iTBS), continuous theta burst stimulation (cTBS), sham stimulation and conventional therapy. Network meta-analysis results showed that HF-rTMS and LF-rTMS had better effects on increasing the FMA-UE score than sham stimulation and conventional therapy (PcTBS (75.3%) >HF-rTMS (71.1%) >iTBS (45.8%) >sham stimulation (20.2%) >conventional therapy (7.7%). The SUCRA ranking of decreasing the MAS score revealed the following: iTBS (77.0%) >LF-rTMS (64.1%) >cTBS (61.0%) >HF-rTMS (38.0%) >sham stimulation (30.6%) >conventional therapy (29.2%). The SUCRA ranking of increasing the MBI and BI scores showed the following: LF-rTMS (96.4%) >iTBS (74.9%) >HF-rTMS (38.6%) >sham stimulation (30.7%) >conventional therapy (9.4%). The SUCRA ranking of reducing the MEP latency showed the following: HF-rTMS (80.0%) >LF-rTMS (78.9%) >conventional therapy (58.8%) >iTBS (24.9%) >sham stimulation (7.5%) . Conclusion The available evidence indicates that, among four modalities producing better effects than sham stimulation and conventional therapy, namely LF-rTMS, HF-rTMS, iTBS, and cTBS, LF-rTMS was superior to the other three in improving upper limb motor function and daily living skills of stroke patients, iTBS performed best in decreasing upper limb muscle tension, and HF-rTMS did best in intervening the corticospinal excitability.

BackgroundRepetitive Transcranial Magnetic Stimulation (rTMS) is an effective intervention for treatment-resistant Major Depressive Disorder (MDD). Early improvement during high-frequency left-sided (HFL) stimulation of the dorsolateral prefrontal cortex (DLPFC) is an important predictor of longer-term outcome, but most patients benefit later in their treatment course. We examined patients without early improvement with HFL to determine whether augmentation with additional stimulation approaches improved treatment outcome.Methods139 participants received HFL in a measurement-based care paradigm. Participants who achieved < 20% improvement by treatment 10 could continue with HFL (N = 17) or receive one of two augmentation strategies: bilateral stimulation (BL; HFL followed by low-frequency stimulation of right DLPFC) (N = 69) or intermittent theta-burst priming of left DLPFC (iTBS-P) (N = 17) for their remaining treatment sessions. The primary outcome was the percent reduction in depressive symptoms at treatment 30.ResultsParticipants who achieved < 20% improvement by treatment 10 and continued with HFL showed limited benefit. iTBS-P participants had significantly greater improvement, while those receiving BL trended toward improved outcomes. Ten sessions of either augmentation strategy appeared necessary to determine the likelihood of benefit.ConclusionsAugmentation of early non-response to HFL appears to improve rTMS outcomes, with a novel iTBS-P strategy surpassing both continued HFL or BL treatment in participants with < 20% improvement after 10 treatments. These findings suggest that measurement-based care with addition of augmented stimulation for those not showing early improvement may yield superior rTMS treatment outcomes.

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.

Repetitive transcranial magnetic stimulation (TMS) is widely used in neuroscience and clinical settings to modulate human cortical activity. The effects of TMS on neural activity depend on the excitability of specific neural populations at the time of stimulation. Accordingly, the brain state at the time of stimulation may influence the persistent effects of repetitive TMS on distal brain activity and associated behaviors. We applied intermittent theta burst stimulation (iTBS) to a region in the posterior parietal cortex (PPC) associated with grasp control to evaluate the interaction between stimulation and brain state. Across two experiments, we demonstrate the immediate responses of motor cortex activity and motor performance to state-dependent parietal stimulation. We randomly assigned 72 healthy adult participants to one of three TMS intervention groups, followed by electrophysiological measures with TMS and behavioral measures. Participants in the first group received iTBS to PPC while performing a grasping task concurrently. Participants in the second group received iTBS to PPC while in a task-free, resting state. A third group of participants received iTBS to a parietal region outside the cortical grasping network while performing a grasping task concurrently. We compared changes in motor cortical excitability and motor performance in the three stimulation groups within an hour of each intervention. We found that parietal stimulation during a behavioral manipulation that activates the cortical grasping network increased downstream motor cortical excitability and improved motor performance relative to stimulation during rest. We conclude that constraining the brain state with a behavioral task during brain stimulation has the potential to optimize plasticity induction in cortical circuit mechanisms that mediate movement processes.

Objective: To investigate the clinical efficacy of intermittent theta burst stimulation(iTBS) and high frequency repetitive transcranial magnetic stimulation (rTMS) on post-stroke executive impairment(PSEI). Methods: Ninety patients with PSEI who were hospitalized in the rehabilitation department of Xuzhou Central Hospital and Xuzhou Rehabilitation Hospital from April 2021 to June 2022 were selected and divided into iTBS group, high-frequency group and control group. All three groups of patients received routine rehabilitation training, given rTMS treatment with iTBS, 10 Hz and shame stimulation for 4 weeks. Before and after treatment, all the patients were evaluated with the Montreal cognitive assessment (MoCA), the frontal assessment battery (FAB), troop color-word test (SCWT), shape trails test (STT), digit span test (DST) and event related potential P300. Results: After treatment, MoCA, FAB, SCWT, STT, DST scores, P300 latency and amplitude were significantly better in the three groups than before treatment (P<0.05). MoCA, FAB, SCWT, STT-B, DST scores, P300 latency and amplitude in the iTBS group and high-frequency group were better than in the control group, with significant differences (P<0.05). The difference between iTBS group and high-frequency group was not statistically significant(P>0.05). Conclusion: iTBS can improve PSEI, and the efficacy is comparable to 10Hz rTMS. iTBS takes less time with better efficiency, and it is worth popularizing and applying in clinic. [ABSTRACT FROM AUTHOR]

Although previous open‐label trials suggest the therapeutic potential of inhibitory repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) in autism spectrum disorder (ASD), methodological caveats exist. We conducted an 8‐week randomized, double‐blind sham‐controlled trial to investigate the efficacy of inhibitory continuous theta burst stimulation (cTBS, a variant of rTMS) over the left DLPFC in individuals with ASD. Sixty children, adolescents and young adults (aged 8–30 years) with ASD without co‐occurring intellectual disabilities were randomized to a 16‐session 8‐week cTBS versus sham stimulation course, with a follow‐up 4 weeks after the trial. The Active group was not superior to the Sham group in any clinical or neuropsychological metrics at Week 8 or Week 12. Time effects of 8‐week cTBS on symptoms and executive function were remarkable in both Active and Sham groups, with comparable response rates and effect sizes of changes in symptoms/cognition between groups. Our results from a sufficiently powered sample do not endorse the superior efficacy of cTBS over the left DLPFC to the shamed stimulation for children, adolescents and adults with ASD. These findings suggest that earlier positive open‐label trial findings may be generalized by generalized/placebo effects. This highlights the urgent need for more rTMS/TBS studies with rigorous trial designs in ASD. Lay Summary: Although previous open‐label studies demonstrated the therapeutic effects of inhibitory repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) in autism spectrum disorder (ASD), the results should be taken conservatively because of several methodological caveats. In our double‐blinded, sham‐controlled and randomized trial, we found 8‐week inhibitory theta burst stimulation (TBS) over the DLPFC is safe and feasible in children, adolescents, and adults with ASD without co‐occurring intellectual disabilities. We did not find that active stimulation was superior to the sham condition on clinical or neuropsychological measurements. Our study suggests that previous positive findings in open‐label rTMS trials may be driven by generalized/placebo effects, highlighting the urgent need for more rTMS/TBS studies with rigorous trial designs in ASD. [ABSTRACT FROM AUTHOR]

The neurophysiological effect of intermittent theta burst stimulation (iTBS) has been examined with TMS-electromyography (EMG)-based outcomes in healthy people; however, its effects in intracortical excitability and inhibition are largely unknown in patients with stroke. Concurrent transcranial magnetic stimulation and electroencephalogram (TMS-EEG) recording can be used to investigate both intracortical excitatory and inhibitory circuits of the primary motor cortex (M1) instantly and the property of brain networks at once. This study was to investigate the immediate effects of iTBS on intracortical excitatory and inhibitory circuits, neural connectivity, and network properties in patients with chronic stroke, using TMS-EEG and TMS-EMG approaches. In this randomized, sham-controlled, crossover study, 20 patients with chronic stroke received two separate stimulation conditions: a single-session iTBS or sham stimulation applied to the ipsilesional M1, in two separate visits, with a washout period of five to seven days between the two visits. A battery of TMS-EMG and TMS-EEG measurements were taken before and immediately after stimulation during the visit. Compared with sham stimulation, iTBS was effective in enhancing the amplitude of ipsilesional MEPs (p = 0.015) and P30 of TMS-evoked potentials located at the ipsilesional M1 (p = 0.037). However, iTBS did not show superior effects on ipsilesional intracortical facilitation, cortical silent period, or short-interval intracortical inhibition. Regarding the effects on TMS-related oscillations, and neural connectivity, comparisons of iTBS and sham did not yield any significant differences. iTBS facilitates intracortical excitability in patients with chronic stroke, but it does not show modulatory effects in intracortical inhibition.

Abstract Background Low frequency repetitive transcranial magnetic stimulation (rTMS) is commonly used to inhibit pathological hyperactivity of the auditory cortex in tinnitus. Novel and supposedly superior and faster inhibitory protocols such as continuous theta burst stimulation (cTBS) were examined as well, but so far there is not sufficient evidence for a treatment application in chronic tinnitus. rTMS effects in general are dependent on the brain state immediate before stimulation. This feasibility study was designed based on the concept to shift the pathological intrinsic brain state of tinnitus patients via acoustic stimulation (“activate”) and induce inhibitory effects via cTBS (“fire”). Methods Seven tinnitus patients with response in residual inhibition received 10 consecutive daily sessions of a combinatory treatment comprised of 3-minute acoustic stimulation with white noise followed by 600 pulses of cTBS over the left temporo-parietal cortex (activate & fire). A control group of 5 patients was treated parallel to the activate & fire data collection with 10 sessions á 3000 pulses of 1 Hz rTMS over the left temporo-parietal cortex. Results The activate & fire protocol was well tolerated except in one patient with tinnitus loudness increase. This patient was excluded from analyses. No statistical superiority of the activate & fire treatment approach in alleviating tinnitus-related symptoms was evident. Power calculations showed an effect size of 0.706 and a needed sample size of 66 for statistical significant group differences. On a descriptive level the activate & fire group demonstrated a stronger decrease in tinnitus-related symptoms. Conclusion The present feasibility study showed that combining acoustic stimulation with magnetic brain stimulation may be well-tolerable in the majority of patients and represents a promising treatment approach for tinnitus by hypothetically alter the intrinsic state prior to brain stimulation.

Autism spectrum disorder is classified as a spectrum of neurodevelopmental disorders with an unknown definitive etiology. Individuals with autism spectrum disorder show deficits in a variety of areas including cognition, memory, attention, emotion recognition, and social skills. With no definitive treatment or cure, the main interventions for individuals with autism spectrum disorder are based on behavioral modulations. Recently, noninvasive brain modulation techniques including repetitive transcranial magnetic stimulation, intermittent theta burst stimulation, continuous theta burst stimulation, and transcranial direct current stimulation have been studied for their therapeutic properties of modifying neuroplasticity, particularly in individuals with autism spectrum disorder. Preliminary evidence from small cohort studies, pilot studies, and clinical trials suggests that the various noninvasive brain stimulation techniques have therapeutic benefits for treating both behavioral and cognitive manifestations of autism spectrum disorder. However, little data is available for quantifying the clinical significance of these findings as well as the long-term outcomes of individuals with autism spectrum disorder who underwent transcranial stimulation. The objective of this review is to highlight the most recent advancements in the application of noninvasive brain modulation technology in individuals with autism spectrum disorder.

Theta burst stimulation (TBS) has been widely used in the treatment of mental disorders, but the cerebral functional difference between intermittent TBS (iTBS) and continuous TBS (cTBS) after one single session of stimulation is not clear. Here we applied resting‐state functional magnetic resonance imaging (RS‐FMRI) to evaluate the alterations in intrinsic brain activity after iTBS and cTBS in the precuneus. We recruited 32 healthy young adults and performed a single session each of iTBS and cTBS at a 1‐week interval. RS‐fMRI was collected at baseline before and immediately after the stimulation. Parameters for regional brain activity (ALFF/fALFF/ReHo) and functional connectivity (FC) with the stimulated site of the precuneus after iTBS and cTBS were calculated and compared between each stimulation using a paired t‐test. Correlation analysis among those parameters was calculated to explore whether changes in functional connectivity were associated with local spontaneous activity. After iTBS stimulation, fALFF increased in the bilateral precuneus, while fALFF decreased in the bilateral middle temporal gyrus. Reductions in precuneus FC were found in the bilateral cuneus, superior occipital gyrus, superior temporal gyrus, precentral gyrus, and postcentral gyrus, which correlated with regional activity. After cTBS, fALFF decreased in the bilateral insula, and precuneus FC was decreased in the bilateral inferior occipital gyrus and increased in the thalamus. In the current study, we observed that one session of iTBS or cTBS could cause inhibitory effects in remote brain regions, but only iTBS caused significant local activation in the target region. [ABSTRACT FROM AUTHOR]