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.

Effects of accelerated intermittent theta-burst stimulation in modulating brain of Alzheimer's disease.

Intermittent theta-burst stimulation (iTBS) is emerging as a noninvasive therapeutic strategy for Alzheimer's disease (AD). Recent advances highlighted a new accelerated iTBS (aiTBS) protocol, consisting of multiple sessions per day and higher overall pulse doses, in brain modulation. To examine the possibility of applying the aiTBS in treating AD patients, we enrolled 45 patients in AD at early clinical stages, and they were randomly assigned to either receive real or sham aiTBS. Neuropsychological scores were evaluated before and after treatment. Moreover, we detected cortical excitability and oscillatory activity changes in AD, by the single-pulse TMS in combination with EEG (TMS-EEG). Real stimulation showed markedly better performances in the group average of Auditory Verbal Learning Test scores compared to baseline. TMS-EEG revealed that aiTBS has reinforced this memory-related cortical mechanism by increasing cortical excitability and beta oscillatory activity underlying TMS target. We also found an enhancement of local natural frequency after aiTBS treatment. The novel findings implicated that high-dose aiTBS targeting left DLPFC is rapid-acting, safe, and tolerable in AD patients. Furthermore, TMS-related increase of specific neural oscillation elucidates the mechanisms of the AD cognitive impairment ameliorated by aiTBS.

Diffusion MRI-guided theta burst stimulation enhances memory and functional connectivity along the inferior longitudinal fasciculus in mild cognitive impairment.

Mild cognitive impairment (MCI) during aging is often a harbinger of Alzheimer's disease, and, therefore, early intervention to preserve cognitive abilities before the MCI symptoms become medically refractory is particularly critical. Functional MRI­guided transcranial magnetic stimulation is a promising approach for modulating hippocampal functional connectivity and enhancing memory in healthy adults. Here, we extend these previous findings to individuals with MCI and leverage theta burst stimulation (TBS) and white matter tractography derived from diffusion-weighted MRI to target the hippocampus. Our preliminary findings suggested that TBS could be used to improve associative memory performance and increase resting-state functional connectivity of the hippocampus and other brain regions, including the occipital fusiform, frontal orbital cortex, putamen, posterior parahippocampal gyrus, and temporal pole, along the inferior longitudinal fasciculus in MCI. Although the sample size is small, these results shed light on how TBS propagates from the superficial cortex around the parietal lobe to the hippocampus.

Personalized depth-specific neuromodulation of the human primary motor cortex via ultrasound.

Non-invasive brain stimulation has the potential to boost neuronal plasticity in the primary motor cortex (M1), but it remains unclear whether the stimulation of both superficial and deep layers of the human motor cortex can effectively promote M1 plasticity. Here, we leveraged transcranial ultrasound stimulation (TUS) to precisely target M1 circuits at depths of approximately 5 mm and 16 mm from the cortical surface. Initially, we generated computed tomography images from each participant's individual anatomical magnetic resonance images (MRI), which allowed for the generation of accurate acoustic simulations. This process ensured that personalized TUS was administered exactly to the targeted depths within M1 for each participant. Using long-term depression and long-term potentiation (LTD/LTP) theta-burst stimulation paradigms, we examined whether TUS over distinct depths of M1 could induce LTD/LTP plasticity. Our findings indicated that continuous theta-burst TUS-induced LTD-like plasticity with both superficial and deep M1 stimulation, persisting for at least 30 min. In comparison, sham TUS did not significantly alter M1 excitability. Moreover, intermittent theta-burst TUS did not result in the induction of LTP- or LTD-like plasticity with either superficial or deep M1 stimulation. These findings suggest that the induction of M1 plasticity can be achieved with ultrasound stimulation targeting distinct depths of M1, which is contingent on the characteristics of TUS. KEY POINTS: The study integrated personalized transcranial ultrasound stimulation (TUS) with electrophysiology to determine whether TUS targeting superficial and deep layers of the human motor cortex (M1) could elicit long-term depression (LTD) or long-term potentiation (LTP) plastic changes. Utilizing acoustic simulations derived from individualized pseudo-computed tomography scans, we ensured the precision of TUS delivery to the intended M1 depths for each participant. Continuous theta-burst TUS targeting both the superficial and deep layers of M1 resulted in the emergence of LTD-like plasticity, lasting for at least 30 min. Administering intermittent theta-burst TUS to both the superficial and deep layers of M1 did not lead to the induction of LTP- or LTD-like plastic changes. We suggest that theta-burst TUS targeting distinct depths of M1 can induce plasticity, but this effect is dependent on specific TUS parameters.

Improving social cognition following theta burst stimulation over the right inferior frontal gyrus in autism spectrum: an 8-week double-blind sham-controlled trial.

BACKGROUND: The right inferior frontal gyrus (RIFG) is a potential beneficial brain stimulation target for autism. This randomized, double-blind, two-arm, parallel-group, sham-controlled clinical trial assessed the efficacy of intermittent theta burst stimulation (iTBS) over the RIFG in reducing autistic symptoms (NCT04987749). METHODS: Conducted at a single medical center, the trial enrolled 60 intellectually able autistic individuals (aged 8-30 years; 30 active iTBS). The intervention comprised 16 sessions (two stimulations per week for eight weeks) of neuro-navigated iTBS or sham over the RIFG. Fifty-seven participants (28 active) completed the intervention and assessments at Week 8 (the primary endpoint) and follow-up at Week 12. RESULTS: Autistic symptoms (primary outcome) based on the Social Responsiveness Scale decreased in both groups (significant time effect), but there was no significant difference between groups (null time-by-treatment interaction). Likewise, there was no significant between-group difference in changes in repetitive behaviors and exploratory outcomes of adaptive function and emotion dysregulation. Changes in social cognition (secondary outcome) differed between groups in feeling scores on the Frith-Happe Animations (Week 8, p = 0.026; Week 12, p = 0.025). Post-hoc analysis showed that the active group improved better on this social cognition than the sham group. Dropout rates did not vary between groups; the most common adverse event in both groups was local pain. Notably, our findings would not survive stringent multiple comparison corrections. CONCLUSIONS: Our findings suggest that iTBS over the RIFG is not different from sham in reducing autistic symptoms and emotion dysregulation. Nonetheless, RIFG iTBS may improve social cognition of mentalizing others' feelings in autistic individuals.

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

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

Differential Effects of Continuous Theta Burst Stimulation over the Bilateral and Unilateral Cerebellum on Working Memory.

Recent functional MRI studies have implicated the cerebellum in working memory (WM) alongside the prefrontal cortex. Some findings indicate that the right cerebellum is activated during verbal tasks, while the left is engaged during visuospatial tasks, suggesting cerebellar lateralization in WM function. The cerebellum could be a potential target for non-invasive brain stimulation (NIBS) to enhance WM function in cognitive disorders. However, the comprehensive influence of cerebellar lateralization on different types of WM and the effect of stimulation over the unilateral or bilateral cerebellum remain uncertain. This study was to investigate the cerebellum's functional lateralization and its specific impact on various aspects of WM in a causal manner using unilateral or bilateral cerebellar continuous theta burst stimulation (cTBS), a form of inhibitroy NIBS. Twenty-four healthy participants underwent four sessions of cTBS targeting the left, right, or bilateral Crus I of the cerebellum, or a sham condition, in a controlled cross-over design. WM performance was assessed pre- and post-stimulation using neuropsychological tests, including the 3-back task, spatial WM task, and digit span task. Results indicated that cTBS over the bilateral and right cerebellum both led to a greater improvement in 3-back task performance compared to sham stimulation. Additionally, active cTBS over the bilateral cerebellum yielded better performance in the spatial WM task than sham stimulation. However, no significant differences were observed between stimulation conditions for the auditory digit span task. This study may provide novel causal evidence highlighting the specific involvement of the right and bilateral cerebellum in various types of WM. Specifically, the right cerebellum appears crucial for updating and tracking 3-back WM content, while spatial WM processes require the coordinated engagement of both cerebellar hemispheres.

Cerebellar Theta Burst Stimulation Impairs Working Memory.

Working memory refers to the process of temporarily storing and manipulating information. The role of the cerebellum in working memory is thought to be achieved through its connections with the prefrontal cortex. Previous studies showed that theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation, of the cerebellum changes its functional connectivity with the prefrontal cortex. Specifically, excitatory intermittent TBS (iTBS) increases, whereas inhibitory continuous TBS (cTBS) decreases this functional connectivity. We hypothesized that iTBS on the cerebellum will improve working memory, whereas cTBS will disrupt it. Sixteen healthy participants (10 women) participated in this study. Bilateral cerebellar stimulation was applied with a figure-of-eight coil at 3 cm lateral and 1 cm below the inion. The participants received iTBS, cTBS, and sham iTBS in three separate sessions in random order. Within 30 min after TBS, the participants performed four working memory tasks: letter 1-Back and 2-Back, digit span forward, and digit span backward. Repeated measures analysis of variance revealed a significant effect of the type of stimulation (iTBS/cTBS/Sham) on performance in the digit span backward task (p = 0.02). The planned comparison showed that the cTBS condition had significantly lower scores than the sham condition (p = 0.01). iTBS and cTBS did not affect performance in the 1- and 2-Back and the digit span forward tasks compared to sham stimulation. The findings support the hypothesis that the cerebellum is involved in working memory, and this contribution may be disrupted by cTBS.

Theta burst stimulation: what role does it play in stroke rehabilitation? A systematic review of the existing evidence.

Various post-stroke dysfunctions often result in poor long-term outcomes for stroke survivors, but the effect of conventional treatments is limited. In recent years, lots of studies have confirmed the effect of repetitive transcranial magnetic stimulation (rTMS) in stroke rehabilitation. As a new pattern of rTMS, theta burst stimulation (TBS) was proved recently to yield more pronounced and long-lasting after-effects than the conventional pattern at a shorter stimulation duration. To explore the role of TBS in stroke rehabilitation, this review summarizes the existing evidence from all the randomized controlled trials (RCTs) so far on the efficacy of TBS applied to different post-stroke dysfunctions, including cognitive impairment, visuospatial neglect, aphasia, dysphagia, spasticity, and motor dysfunction. Overall, TBS promotes the progress of stroke rehabilitation and may serve as a preferable alternative to traditional rTMS. However, it's hard to recommend a specific paradigm of TBS due to the limited number of current studies and their heterogeneity. Further high-quality clinical RCTs are needed to determine the optimal technical settings and intervention time in stroke survivors.

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.

Theta burst stimulation add on to dialectical behavioral therapy in borderline-personality-disorder: methods and design of a randomized, single-blind, placebo-controlled pilot trial.

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.

Accelerated sequential bilateral theta-burst stimulation in major depression: an open trial.

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.

A randomized sham-controlled trial of high-dosage accelerated intermittent theta burst rTMS in major depression: study protocol.

BACKGROUND: Intermittent theta burst stimulation (iTBS), a novel form of repetitive transcranial magnetic stimulation (rTMS), can be administered in 1/10th of the time of standard rTMS (~ 3 min vs. 37.5 min) yet achieves similar outcomes in depression. The brief nature of the iTBS protocol allows for the administration of multiple iTBS sessions per day, thus reducing the overall course length to days rather than weeks. This study aims to compare the efficacy and tolerability of active versus sham iTBS using an accelerated regimen in patients with treatment-resistant depression (TRD). As a secondary objective, we aim to assess the safety, tolerability, and treatment response to open-label low-frequency right-sided (1 Hz) stimulation using an accelerated regimen in those who do not respond to the initial week of treatment. METHODS: Over three years, approximately 230 outpatients at the Centre for Addiction and Mental Health and University of British Columbia Hospital, meeting diagnostic criteria for unipolar MDD, will be recruited and randomized to a triple blind sham-controlled trial. Patients will receive five consecutive days of active or sham iTBS, administered eight times daily at 1-hour intervals, with each session delivering 600 pulses of iTBS. Those who have not achieved response by the week four follow-up visit will be offered a second course of treatment, regardless of whether they initially received active or sham stimulation. DISCUSSION: Broader implementation of conventional iTBS is limited by the logistical demands of the current standard course consisting of 4-6 weeks of daily treatment. If our proposed accelerated iTBS protocol enables patients to achieve remission more rapidly, this would offer major benefits in terms of cost and capacity as well as the time required to achieve clinical response. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04255784.

Theta-burst stimulation as a therapeutic tool in neurological pathology: a systematic review.

TBS (theta-burst stimulation) is a novel therapeutic approach in a wide range of neurological diseases. The present systematic review aims to identify the various protocols used in the last years, to assess study quality and to offer a general overview of the current state of the literature. The systematic review was conducted according to the Preferred Reporting Item for Systematic Review and Meta-Analyses (PRISMA) guidelines. We applied the following inclusion criteria: (1) population over 18 years old with diagnosed neurological disorders, (2) patients treated with sessions of theta-burst stimulation, (3) randomized-controlled clinical trials, (4) articles in the English language, and (5) studies that report response and score reduction on a validated scale of the investigated disorder or remission rates. We included in the final analysis 56 randomized controlled trials focusing on different neurological pathologies (stroke, Parkinson`s disease, multiple sclerosis, tinnitus, dystonia, chronic pain, essential tremor and tic disorder), and we extracted data regarding study design, groups and comparators, sample sizes, type of coil, stimulation parameters (frequency, number of pulses, intensity, stimulation site etc.), number of sessions, follow-up, assessment through functional connectivity and neurological scales used. We observed a great interstudy heterogenicity that leads to a difficulty in drawing plain conclusions. TBS protocols have shown promising results in improving various symptoms in patients with neurological disorders, but larger and more coherent studies, using similar stimulation protocols and evaluation scales, are needed to establish guideline recommendations.

Efficacy of intermittent theta burst stimulation (iTBS) on post-stroke cognitive impairment (PSCI): a systematic review and meta-analysis.

BACKGROUND: Stroke is a significant global cause of mortality and morbidity, and post-stroke cognitive impairment (PSCI) affects up to half of stroke patients. Despite the availability of pharmacological and non-pharmacological interventions, there is a lack of definitive effective treatments for PSCI. Non-invasive brain stimulation, particularly intermittent theta burst stimulation (iTBS), has emerged as a promising therapy for the treatment of PSCI. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of iTBS in enhancing cognitive function among patients with PSCI. METHODS: A comprehensive search was conducted across multiple databases, including PubMed, Web of Science, Scopus, Cochrane Library, and CNKI, to identify relevant randomized controlled trials published before April 2023. The primary outcome measured changes in global cognitive scales, while the secondary outcomes focused on improvements in attention, orientation, visual-spatial perception, and activities of daily living. RESULTS: The meta-analysis encompassed six studies involving 325 patients. The results demonstrated that iTBS led to a significant improvement in global cognitive scales (SMD = 1.12, 95% CI = [0.59 to 1.65], P < 0.0001), attention (SMD = 0.48, 95% CI [0.13 to 0.82], P = 0.007), visual perception (SMD = 0.99, 95% CI [0.13 to 1.86], P = 0.02), and activities of daily living (SMD = 0.82, 95% CI [0.55 to 1.08], P < 0.00001). However, there was no significant effect on orientation (SMD = 0.36, 95% CI [- 0.04 to 0.76], P = 0.07). Subgroup analysis based on the number of sessions was conducted, revealing a significant improvement in global cognition among patients with PSCI across the three categories (10 sessions, 20 sessions, and 30 sessions) with no between-group difference (P = 0.28). None of the included studies reported any serious adverse effects. CONCLUSION: In conclusion, iTBS appears to be a safe and effective non-invasive treatment that can enhance the cognitive abilities and daily living skills of patients with post-stroke cognitive impairment. However, our conclusion is constrained by the limited number of studies. Further high-quality, large-sample RCTs with extended follow-up periods are necessary to validate these findings. Integrating iTBS with brain imaging techniques, such as functional near-infrared spectroscopy and functional magnetic resonance, could aid in understanding the mechanism of iTBS action.

Effects of different modalities of transcranial magnetic stimulation on post-stroke cognitive impairment: a network meta-analysis.

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.

Repetitive Transcranial Magnetic Stimulation (rTMS) in Major Depression.

Major depressive disorder (MDD) is a psychiatric disorder with several effective therapeutic approaches, being antidepressants and psychotherapies the first-line treatments. Nonetheless, due to side effects, limited efficacy, and contraindications for these treatments, alternative treatment options are required. Neurostimulation is a non-pharmacological and non-psychotherapeutic approach that has been under study for diverse neuropsychiatric conditions in the form of electrical or magnetic stimulation of the brain. Repetitive transcranial magnetic stimulation (rTMS) is a neurostimulation method designed to generate magnetic fields and deliver magnetic pulses to stimulate the brain cortex. The magnetic pulses produce electrical currents in the brain which are not intense enough to provoke seizures, differentiating this method from other forms of neurostimulation that produce seizures. Although the exact rTMS mechanisms of action are not completely understood, rTMS seems to cause its beneficial effects through changes in neuroplasticity. Devices and protocols for rTMS are still evolving, becoming more efficient over time. There are still some challenges to be addressed, including further refinement of parameters (coil/device type, location, intensity, frequency, number of sessions, and duration of treatment); treatment cost and burden for patients; and treatment resistance. However, the efficacy, tolerability, and safety of some rTMS protocols have been demonstrated in different double-blind sham-controlled randomized controlled trials and meta-analyses for treatment-resistant depression.

Spinal cord representation of motor cortex plasticity reflects corticospinal tract LTP.

Although it is well known that activity-dependent motor cortex (MCX) plasticity produces long-term potentiation (LTP) of local cortical circuits, leading to enhanced muscle function, the effects on the corticospinal projection to spinal neurons has not yet been thoroughly studied. Here, we investigate a spinal locus for corticospinal tract (CST) plasticity in anesthetized rats using multichannel recording of motor-evoked, intraspinal local field potentials (LFPs) at the sixth cervical spinal cord segment. We produced LTP by intermittent theta burst electrical stimulation (iTBS) of the wrist area of MCX. Approximately 3 min of MCX iTBS potentiated the monosynaptic excitatory LFP recorded within the CST termination field in the dorsal horn and intermediate zone for at least 15 min after stimulation. Ventrolaterally, in the spinal cord gray matter, which is outside the CST termination field in rats, iTBS potentiated an oligosynaptic negative LFP that was localized to the wrist muscle motor pool. Spinal LTP remained robust, despite pharmacological blockade of iTBS-induced LTP within MCX using MK801, showing that activity-dependent spinal plasticity can be induced without concurrent MCX LTP. Pyramidal tract iTBS, which preferentially activates the CST, also produced significant spinal LTP, indicating the capacity for plasticity at the CST-spinal interneuron synapse. Our findings show CST monosynaptic LTP in spinal interneurons and demonstrate that spinal premotor circuits are capable of further modifying descending MCX control signals in an activity-dependent manner.

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.

Immediate Effects of Preconditioning Intermittent Theta Burst Stimulation on Lower Extremity Motor Cortex Excitability in Healthy Participants.

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. CLINICAL TRIAL REGISTRATION: No: ChiCTR2300069315. Registered 13 March, 2023, https://www.chictr.org.cn.