rTMS concurrent with cognitive training rewires AD brain by enhancing GM-WM functional connectivity: a preliminary study.

Repetitive transcranial magnetic stimulation (rTMS) and cognitive training for patients with Alzheimer's disease (AD) can change functional connectivity (FC) within gray matter (GM). However, the role of white matter (WM) and changes of GM-WM FC under these therapies are still unclear. To clarify this problem, we applied 40 Hz rTMS over angular gyrus (AG) concurrent with cognitive training to 15 mild-moderate AD patients and analyzed the resting-state functional magnetic resonance imaging before and after treatment. Through AG-based FC analysis, corona radiata and superior longitudinal fasciculus (SLF) were identified as activated WM tracts. Compared with the GM results with AG as seed, more GM regions were found with activated WM tracts as seeds. The averaged FC, fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo) of the above GM regions had stronger clinical correlations (r/P = 0.363/0.048 vs 0.299/0.108, 0.351/0.057 vs 0.267/0.153, 0.420/0.021 vs 0.408/0.025, for FC/fALFF/ReHo, respectively) and better classification performance to distinguish pre-/post-treatment groups (AUC = 0.91 vs 0.88, 0.65 vs 0.63, 0.87 vs 0.82, for FC/fALFF/ReHo, respectively). Our results indicated that rTMS concurrent with cognitive training could rewire brain network by enhancing GM-WM FC in AD, and corona radiata and SLF played an important role in this process.

Distinguishable neural circuit mechanisms associated with the clinical efficacy of rTMS in aMCI patients.

Repetitive transcranial magnetic stimulation is used in early-stage Alzheimer's disease to slow progression, but heterogeneity in response results in different treatment outcomes. The mechanisms underlying this heterogeneity are unclear. This study used resting-state neuroimaging to investigate the variability in episodic memory improvement from angular gyrus repetitive transcranial magnetic stimulation and tracked the neural circuits involved. Thirty-four amnestic mild cognitive impairment patients underwent angular gyrus repetitive transcranial magnetic stimulation (4 weeks, 20 Hz, 100% resting motor threshold) and were divided into high-response and low-response groups based on minimal clinically important differences in auditory verbal learning test scores. Baseline and pre/post-treatment neural circuit activities were compared. Results indicated that the orbital middle frontal gyrus in the orbitofrontal cortex network and the precuneus in the default mode network had higher local activity in the low-response group. After treatment, changes in local and remote connectivity within brain regions of the orbitofrontal cortex, default mode network, visual network, and sensorimotor network showed opposite trends and were related to treatment effects. This suggests that the activity states of brain regions within the orbitofrontal cortex and default mode network could serve as imaging markers for early cognitive compensation in amnestic mild cognitive impairment patients and predict the aftereffects of repetitive transcranial magnetic stimulation response.

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.

Effects of rTMS to primary motor cortex and cerebellum on balance control in healthy adults.

Both the primary motor cortex (M1) and the cerebellum are crucial for postural stability and deemed as potential targets for non-invasive brain stimulation (NIBS) to enhance balance performance. However, the optimal target remains unknown. The purpose of this study was to compare the role of M1 and the cerebellum in modulating balance performance in young healthy adults using facilitatory 5 Hz repetitive transcranial magnetic stimulation (rTMS). Twenty-one healthy young adults (mean age = 27.95 ± 1.15 years) received a single session of 5 Hz rTMS on M1 and the cerebellum in a cross-over order with a 7-day washout period between the two sessions. Three balance assessments were performed on the Biodex Balance system SD: Limits of Stability (LOS), modified Clinical Test of Sensory Interaction on Balance (mCTSIB), and Balance Error Scoring System (BESS). No significant effect of rTMS was found on the LOS. The effect of rTMS on the mCTSIB was mediated by stimulation target, proprioception, and vision (p = .003, ηp 2 = 0.37). Cerebellar rTMS improved the mCTSIB sway index under eyes closed-foam surface condition (p = .02), whereas M1 rTMS did not result in improvement on the mCTSIB. The effect of rTMS on the BESS was mediated by stimulation target, posture, and proprioception (p = .049, ηp 2 = 0.14). Cerebellar rTMS enhanced reactive balance performance during most sensory deprived conditions.

Low-frequency rTMS induces modifications in cortical structural connectivity - functional connectivity coupling in schizophrenia patients with auditory verbal hallucinations.

Auditory verbal hallucinations (AVH) are distinctive clinical manifestations of schizophrenia. While low-frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated potential in mitigating AVH, the precise mechanisms by which it operates remain obscure. This study aimed to investigate alternations in structural connectivity and functional connectivity (SC-FC) coupling among schizophrenia patients with AVH prior to and following treatment with 1 Hz rTMS that specifically targets the left temporoparietal junction. Initially, patients exhibited significantly reduced macroscopic whole brain level SC-FC coupling compared to healthy controls. Notably, SC-FC coupling increased significantly across multiple networks, including the somatomotor, dorsal attention, ventral attention, frontoparietal control, and default mode networks, following rTMS treatment. Significant alternations in SC-FC coupling were noted in critical nodes comprising the somatomotor network and the default mode network, such as the precentral gyrus and the ventromedial prefrontal cortex, respectively. The alternations in SC-FC coupling exhibited a correlation with the amelioration of clinical symptom. The results of our study illuminate the intricate relationship between white matter structures and neuronal activity in patients who are receiving low-frequency rTMS. This advances our understanding of the foundational mechanisms underlying rTMS treatment for AVH.

Online and offline effects of parietal 10 Hz repetitive transcranial magnetic stimulation on working memory in healthy controls.

Parietal alpha activity shows a specific pattern of phasic changes during working memory. It decreases during the encoding and recall phases but increases during the maintenance phase. This study tested whether online rTMS delivered to the parietal cortex during the maintenance phase of a working memory task would increase alpha activity and hence improve working memory. Then, 46 healthy volunteers were randomly assigned to two groups to receive 3-day parietal 10 Hz online rTMS (either real or sham, 3600 pulses in total) that were time-locked to the maintenance phase of a spatial span task (180 trials in total). Behavioral performance on another spatial span task and EEG signals during a change detection task were recorded on the day before the first rTMS (pretest) and the day after the last rTMS (posttest). We found that rTMS improved performance on both online and offline spatial span tasks. For the offline change detection task, rTMS enhanced alpha activity within the maintenance phase and improved interference control of working memory at both behavioral (K score) and neural (contralateral delay activity) levels. These results suggested that rTMS with alpha frequency time-locked to the maintenance phase is a promising way to boost working memory.

Cognitive Effects Following Offline High-Frequency Repetitive Transcranial Magnetic Stimulation (HF-rTMS) in Healthy Populations: A Systematic Review and Meta-Analysis.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) is a commonly used form of rTMS to treat neuropsychiatric disorders. Emerging evidence suggests that 'offline' HF-rTMS may have cognitive enhancing effects, although the magnitude and moderators of these effects remain unclear. We conducted a systematic review and meta-analysis to clarify the cognitive effects of offline HF-rTMS in healthy individuals. A literature search for randomised controlled trials with cognitive outcomes for pre and post offline HF-rTMS was performed across five databases up until March 2022. This study was registered on the PROSPERO international prospective protocol for systematic reviews (PROSPERO 2020 CRD 42,020,191,269). The Risk of Bias 2 tool was used to assess the risk of bias in randomised trials. Separate analyses examined the cognitive effects of excitatory and inhibitory forms of offline HF-rTMS on accuracy and reaction times across six cognitive domains. Fifty-three studies (N = 1507) met inclusion criteria. Excitatory offline HF-rTMS showed significant small sized effects for improving accuracy (k = 46, g = 0.12) and reaction time (k = 44, g = -0.13) across all cognitive domains collapsed. Excitatory offline HF-rTMS demonstrated a relatively greater effect for executive functioning in accuracy (k = 24, g = 0.14). Reaction times were also improved for the executive function (k = 21, g = -0.11) and motor (k = 3, g = -0.22) domains following excitatory offline HF-rTMS. The current review was restricted to healthy individuals and future research is required to examine cognitive enhancement from offline HF-rTMS in clinical cohorts.

Reduced dorsal fronto-striatal connectivity at rest in anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a serious psychiatric illness that remains difficult to treat. Elucidating the neural mechanisms of AN is necessary to identify novel treatment targets and improve outcomes. A growing body of literature points to a role for dorsal fronto-striatal circuitry in the pathophysiology of AN, with increasing evidence of abnormal task-based fMRI activation within this network among patients with AN. Whether these abnormalities are present at rest and reflect fundamental differences in brain organization is unclear. METHODS: The current study combined resting-state fMRI data from patients with AN (n = 89) and healthy controls (HC; n = 92) across four studies, removing site effects using ComBat harmonization. First, the a priori hypothesis that dorsal fronto-striatal connectivity strength - specifically between the anterior caudate and dlPFC - differed between patients and HC was tested using seed-based functional connectivity analysis with small-volume correction. To assess specificity of effects, exploratory analyses examined anterior caudate whole-brain connectivity, amplitude of low-frequency fluctuations (ALFF), and node centrality. RESULTS: Compared to HC, patients showed significantly reduced right, but not left, anterior caudate-dlPFC connectivity (p = 0.002) in small-volume corrected analyses. Whole-brain analyses also identified reduced connectivity between the right anterior caudate and left superior frontal and middle frontal gyri (p = 0.028) and increased connectivity between the right anterior caudate and right occipital cortex (p = 0.038). No group differences were found in analyses of anterior caudate ALFF and node centrality. CONCLUSIONS: Decreased coupling of dorsal fronto-striatal regions indicates that circuit-based abnormalities persist at rest and suggests this network may be a potential treatment target.

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.

Effect of Regional Brain Activity Following Repeat Transcranial Magnetic Stimulation in SCA3: A Secondary Analysis of a Randomized Clinical Trial.

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuroregulatory technique used to treat neurodegenerative diseases, holds promise for spinocerebellar ataxia type 3 (SCA3) treatment, although its efficacy and mechanisms remain unclear. This study aims to observe the short-term impact of cerebellar rTMS on motor function in SCA3 patients and utilize resting-state functional magnetic resonance imaging (RS-fMRI) to assess potential therapeutic mechanisms. Twenty-two SCA3 patients were randomly assigned to receive actual rTMS (AC group, n = 11, three men and eight women; age 32-55 years) or sham rTMS (SH group, n = 11, three men and eight women; age 26-58 years). Both groups underwent cerebellar rTMS or sham rTMS daily for 15 days. The primary outcome measured was the ICARS scores and parameters for regional brain activity. Compared to baseline, ICARS scores decreased more significantly in the AC group than in the SH group after the 15-day intervention. Imaging indicators revealed increased Amplitude of Low Frequency Fluctuation (ALFF) values in the posterior cerebellar lobe and cerebellar tonsil following AC stimulation. This study suggests that rTMS enhances motor functions in SCA3 patients by modulating the excitability of specific brain regions and associated pathways, reinforcing the potential clinical utility of rTMS in SCA3 treatment. The Chinese Clinical Trial Registry identifier is ChiCTR1800020133.

Microglia and Astrocytes Responses Contribute to Alleviating Inflammatory Damage by Repetitive Transcranial Magnetic Stimulation in Rats with Traumatic Brain Injury.

Repetitive transcranial magnetic stimulation (rTMS) is a therapeutic strategy that shows promise in ameliorating the clinical sequelae following traumatic brain injury (TBI). These improvements are associated with neuroplastic changes in neurons and their synaptic connections. However, it has been hypothesized that rTMS may also modulate microglia and astrocytes, potentially potentiating their neuroprotective capabilities. This study aims to investigate the effects of high-frequency rTMS on microglia and astrocytes that may contribute to its neuroprotective effects. Feeney's weight-dropping method was used to establish rat models of moderate TBI. To evaluate the neuroprotective effect of high frequency rTMS on rats by observing the synaptic ultrastructure and the level of neuron apoptosis. The levels of several important inflammation-related proteins within microglia and astrocytes were assessed through immunofluorescence staining and western blot. Our findings demonstrate that injured neurons can be rescued through the modulation of microglia and astrocytes by rTMS. This modulation plays a key role in preserving the synaptic ultrastructure and inhibiting neuronal apoptosis. Among microglia, we observed that rTMS inhibited the levels of proinflammatory factors (CD16, IL-6 and TNF-α) and promoted the levels of anti-inflammatory factors (CD206, IL-10 and TNF-ß). rTMS also reduced the levels of pyroptosis within microglia and pyroptosis-related proteins (NLRP3, Caspase-1, GSDMD, IL-1ß and IL-18). Moreover, rTMS downregulated P75NTR expression and up-regulated IL33 expression in astrocytes. These findings suggest that regulation of microglia and astrocytes is the mechanism through which rTMS attenuates neuronal inflammatory damage after moderate TBI.

Targeting Method for rTMS for Treating Depression in Japanese Patients: A Comparison of the Standard, F3, and Neuronavigation Approaches.

INTRODUCTION: The left dorsolateral prefrontal cortex (lDLPFC) is a commonly targeted brain region for repetitive transcranial magnetic stimulation (rTMS) for depression. The lDLPFC has been identified using the "5-cm rule." However, identification of the lDLPFC may deviate from the ideal stimulation site localized by neuronavigation. Therefore, we aimed to compare this method with other methods and examine the relationship between deviation from the ideal stimulation site and treatment effects. While most existing studies have focused on participants of European descent, this study focused on Japanese participants. METHODS: The study participants were 16 patients who underwent rTMS and had the stimulus location identified using the 5-cm method. The lDLPFC was identified by the F3 electrode position and neuronavigation in addition to the 5-cm rule, and these locations were compared. We then performed a correlation analysis of the distance between the sites identified by the 5-cm method and by neuronavigation, as well as changes in scores on the 17-item Hamilton Depression Scale (HAMD-17). RESULTS: The lDLPFC identified by the F3 site and neuronavigation was approximately 3 cm more anterolateral than that identified by the 5-cm method. A significant correlation was found between the distance between the sites identified by the 5-cm method and neuronavigation and the rate of change in HAMD-17 scores. CONCLUSION: The ideal stimulation site may be approximately 3 cm anterior to the site identified by the 5-cm method, and stimulation of the F3 site may be a valid alternative to the 5-cm method.

Association between Stimulation-Site Pain and Clinical Improvement during Repetitive Transcranial Magnetic Stimulation for Patients with Major Depressive Disorders: A Prospective Observational Study at Two Sites.

INTRODUCTION: The clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) in Japan has not been adequately investigated. Furthermore, the relationship between stimulation-site pain and the antidepressant effects of rTMS has not been thoroughly examined. Therefore, this study aimed to clarify (1) the real-world efficacy and safety of rTMS for TRD in Japan and (2) the relationship between stimulation-site pain and clinical improvement of depressive symptoms. METHODS: We conducted a retrospective observational study involving 50 right-handed patients with TRD. All patients received high-frequency rTMS for up to 6 weeks. Depressive symptoms were assessed using the Montgomery-Åsberg depression rating scale (MADRS). Pain at the stimulation site was reported by the patients using a visual analog scale (VAS) after each session. Remission and response rates at 3 and 6 weeks were calculated based on the MADRS scores. The correlation between changes in the MADRS and VAS scores was examined. RESULTS: Remission and response rates were 36% and 46%, respectively, at the end of 3 weeks, and 60% and 70%, respectively, at 6 weeks. At the end of the treatment, there was significant correlation between the reduction of MADRS and VAS scores (r = 0.42, p = 0.003). CONCLUSION: This study demonstrates the clinical efficacy of rTMS in Japan and the correlation between its antidepressant effects and stimulation-site pain.

Efficacy of rTMS for poststroke epilepsy and its effects on patients' cognitive function and depressive status.

OBJECTIVE: This study aimed to investigate the efficacy of rTMS in the treatment of poststroke epilepsy and the effect of rTMS on patients' cognitive function and depressive status. METHODS: One hundred and twenty-one poststroke epilepsy patients with mild cognitive impairment and depressive status admitted to the Department of Neurology of the Second People's Hospital of Nanning from January 1, 2017, to April 31, 2023, were selected and divided into the rTMS treatment group (treated group) and the control group. MMSE scores and HAMD scores were recorded before and after treatment. The frequency of EEG spiky waves recorded before and after treatment within 24 h and the frequency of any clinical seizure form (the number of clinical seizures within 1 month after treatment) and changes in observed indices before and after treatment were calculated. The differences between the data of the two groups were analyzed, to further assess the efficacy of rTMS in the treatment of poststroke epilepsy and the rTMS' effects on cognition and depression. RESULTS: Compared with drug treatment alone, rTMS significantly decreased clinical seizures and epileptiform discharges after stroke, especially in patients with lesions in the frontal, temporal, and parietal lobes. Compared with drug treatment alone, rTMS treatment can effectively reduce cognitive impairment and mood disorders, such as depression, especially for patients with lesions in the frontal and temporal lobes. The results of this experiment suggest that rTMS treatment does not increase adverse effects. CONCLUSION: rTMS reduces clinical seizures while improving cognitive impairment and depression in patients with epilepsy. Therefore, we suggest that low-frequency rTMS can be used as an adjunctive treatment for patients with epilepsy and provide some ideas and references for the treatment of epilepsy with cognitive impairment and depression.

Repetitive Transcranial Magnetic Stimulation with Body Weight-supported Treadmill Training Enhances Independent Walking of Individuals with Chronic Incomplete Spinal Cord Injury: A Pilot Randomized Clinical Trial.

The purpose of this study is to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with body weight-support treadmill training (BWSTT) for improving walking function of individuals with chronic incomplete spinal cord injury (iSCI). A 4-week, double-blinded, randomized, sham-controlled pilot study involved 12 sessions of real (10 Hz, 1800 pulses) or sham rTMS combined with BWSTT (15-20 min, moderate intensity). Walking independence was assessed using the Walking Index for Spinal Cord Injury II (WISCI-II). Lower extremity motor function (lower extremity motor score [LEMS]) and spasticity, sensory function, functional independence (Spinal Cord Injury Measure III [SCIM-III]), and quality of life were also assessed. Walking independence (WISCI-II) after the 6th session was higher in the BWSTT/rTMS real (n = 7) (median change (IQR): 3 (1.5 to 3.5)) than in the sham group (n = 8) (median change (IQR): 0 (0 to 0.25), but there was no difference between groups after 12th session (BWSTT/rTMS real median change (IQR): 4 (2 to 5); BWSSTT/rTMS sham median change (IQR): 0 (0 to 3.25). Compared to baseline, LEMS and SCIM-III mobility scores were increased after 12 sessions in the BWSTT/rTMS real but not in the sham group. Within- and between-group sensory function, functional independence, and quality of life remained similar. This preliminary result suggests that combining BWSTT with rTMS could lead to earlier gait improvement in patients with chronic iSCI.

Predictors of response to accelerated rTMS in the treatment of treatment-resistant depression.

Accelerated repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for treatment-resistant depression (TRD). We aimed to investigate the existence of clinical predictive factors in response to accelerated rTMS in the treatment of TRD. In total, 119 TRD patients who received accelerated rTMS were included in this study. The stimulation protocol was 15 Hz stimulation over the the left dorsolateral prefrontal cortex. The protocol consisted of 25 sessions, each session lasting 30 min for a total of 3000 pulses. Five sessions were applied per day for 5 consecutive days. At baseline (T0), day 5 (immediately after treatment) (T1), 4 weeks after treatment (T2), depression severity was evaluated using the 17-item Hamilton Depression Rating Scale (HAMD-17), cognitive function was evaluated using Wisconsin Card Sorting Test (WCST), the intensity of suicidal ideation was evaluated using the Columbia-Suicide Severity Rating Scale (C-SSRS). Systemic immune-inflammation index (SII) was calculated at T0 and T2. The HAMD-17 scores, WCST performance, the C-SSRS scores at T1 and T2 were improved from T0 (P < 0.01). The SII at T2 was lower than at T0 (P < 0.01). The response rates at T1 and T2 were 57.98% (69/119) and 48.74% (58/119), respectively. The results of binary logistic analysis showed that shorter course of depression, two failed antidepressant trials, no history of ECT treatment, and lower levels of SII were predictive factors for accelerated rTMS treatment response at T1 and T2 (P < 0.05), while not having a history of hospitalization was a predictive factor for response at T2 (P < 0.05) but not at T1 (P > 0.05). Based on ROC curve analysis, the optimal cut-off values of SII for discriminating responders from non-responders at T1 and T2 were < 478.56 and < 485.03, respectively. The AUC of SII at T0 predicting response for T1 and T2 were 0.729 and 0.797. We found several clinical predictors of better responses to the accelerated rTMS. Identifying clinical predictors of response is relevant to personalize and adapt rTMS protocols in TRD patients.

Repetitive transcranial magnetic stimulation rescues simulated space complex environment-induced emotional and social impairments by enhancing neuronal excitability in the medial prefrontal cortex.

Studies have shown that spaceflight affects the emotional and social performance of astronauts. Identifying the neural mechanisms underlying the emotional and social effects of spacefaring-specific environments is essential to specify targeted treatment and prevention interventions. Repetitive transcranial magnetic stimulation (rTMS) has been shown to improve the neuronal excitability and is used to treat psychiatric disorders such as depression. To study the changes of excitatory neuron activity in medial prefrontal cortex (mPFC) in simulated space complex environment (SSCE), and to explore the role of rTMS in behavioral disorders caused by SSCE and the neural mechanism. We found that rTMS effectively ameliorated the emotional and social impairments of mice in SSCE, and acute rTMS could instantaneously enhance the excitability of mPFC neurons. During depression-like and social novelty behaviors, chronic rTMS enhanced the mPFC excitatory neuronal activity that was inhibited by SSCE. Above results suggested that rTMS can completely reverse the SSCE-induced mood and social impairment by enhancing the suppressed mPFC excitatory neuronal activity. It was further found that rTMS suppressed the SSCE-induced excessive dopamine D2 receptor expression, which may be the cellular mechanism by which rTMS potentiates the SSCE-evoked hypoactive mPFC excitatory neurons. Our current results raise the possibility of rTMS being applied as a novel neuromodulation for mental health protection in spaceflight.

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.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on global cognitive function of elderly in mild to moderate Alzheimer's disease: a systematic review and meta-analysis.

OBJECTIVE: High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) is a non-invasive brain stimulation technique used to improve cognitive deficits in patients with Alzheimer's disease (AD). This systematic review and meta-analysis aimed to evaluate the efficacy of HF-rTMS in improving global cognitive function rehabilitation in elderly patients with mild to moderate AD. METHODS: A detailed literature search of publications using ten databases (Chinese: Wanfang, VIP Periodical, SinoMed, the Chinese National Knowledge Infrastructure; English: PubMed, Embase, OVID, Web of Science, Cochrane Library, and EBSCOhost) was performed to identify English and Chinese language articles published up to December 2022. We only included randomized controlled trials (RCTs) that evaluate the effect of HF-rTMS on elderly patients with mild to moderate AD. The retrieved studies were carefully reviewed, extracted data, and assessed quality. RESULTS: Seventeen studies, including 1161 elderly patients with mild to moderate AD, were included in this meta-analysis. Compared to the control group, HF-rTMS could increase MMSE (mean difference [MD] = 3.64; 95%CI 1.86-5.42; P < 0.0001), MoCA (MD = 3.69; 95%CI 1.84-5.54; P < 0.0001), P300 amplitude (MD = 1.09; 95%CI 0.45-1.72; P = 0.0008), and total effective rate scores (MD = 3.64; 95% CI 2.14-6.18; P < 0.00001) while decreasing ADAS-Cog (MD = - 3.53; 95%CI - 4.91- - 2.15; P < 0.00001) and P300 latency scores (MD = - 38.32; 95%CI - 72.40- - 4.24; P = 0.03). Our study showed that HF-rTMS could improve the global cognitive function of elderly patients with mild to moderate AD. CONCLUSION: HF-rTMS can improve global cognitive function in elderly patients with mild to moderate AD, which is an effective and safe rehabilitation treatment tool for AD patients.

Therapeutic effects of repetitive transcranial magnetic stimulation in patients with cerebral palsy: a systematic review and network meta-analysis.

The purpose of this study was to systematically evaluate the efficacy of repetitive transcranial magnetic stimulation in children with cerebral palsy and to compare the differences in efficacy of different treatment parameters. Computer searches of PubMed, Embase, Cochrane Library, Scopus, Web of Science, China Knowledge Network, Wanfang Data Knowledge Service Platform, Vipshop and China Biomedical Literature Database were conducted to collect randomized controlled trials (RCTs) of TMS to improve function in children with cerebral palsy. The search period was from the establishment of the database to April 2023. Two researchers independently screened the literature and extracted data information, and the risk of bias was assessed for the included studies using the Cochrane Systematic Evaluation Manual 5.1.0. Statistical analysis was performed using RevMan 5.4 and Stata software. A total of 18 studies containing 1675 patients with cerebral palsy were included, and r-TMS did not differ significantly from other treatments in improving language function [MD = 2.80, 95% CI (-1.51, 7.11), Z = 1.27, P = 0.20] after treatment. The results of the reticulated meta-analysis showed the best probability ranking of the effect of three different frequencies of r-TMS on motor function scores in children with cerebral palsy: combined LF-rTMS + HF-rTMS (49.8%) > LF-rTMS (45.6%) > HF-rTMS (4.6%) > conventional rehabilitation (0%). Publication bias showed no significant asymmetry in the inverted funnel plot, but the possibility of publication bias could not be excluded. The results of this study showed that r-TMS was not statistically significant in improving language function in children with cerebral palsy compared to conventional treatment. r-TMS was almost unanimously significantly effective in motor function in children with cerebral palsy according to current literature data, and the combined high- and low-frequency transcranial magnetic therapy was better than low-frequency transcranial magnetic therapy.