Neurosurgical treatment of spasticity: a potential return to the cerebellum.

OBJECTIVE: Neurosurgical targeting of the cerebellar dentate nucleus via ablative dentatotomy and stimulation of the dentate nucleus was historically used for effective treatment of spasticity. Yet for decades, neurosurgical treatment of spasticity targeting the cerebellum was bypassed in favor of alternative treatments such as intrathecal baclofen pumps and selective dorsal rhizotomies. Cerebellar neuromodulation has recently reemerged as a promising and effective therapy for spasticity and related movement disorders. METHODS: In this narrative review, the authors contextualize the historical literature of cerebellar neuromodulation, comparing it with modern approaches and exploring future directions with regard to cerebellar neuromodulation for spasticity. RESULTS: Neurosurgical intervention on the cerebellum dates to the use of dentatotomy in the 1960s, which had progressed to electrical stimulation of the cerebellar cortex and dentate nucleus by the 1980s. By 2024, modern neurosurgical approaches such as tractography-based targeting of the dentate nucleus and transcranial magnetic stimulation of cerebellar cortex have demonstrated promise for treating spasticity. CONCLUSIONS: Cerebellar neuromodulation of the dentate nucleus and cerebellar cortex are promising therapies for severe cases of spasticity. Open areas for exploration in the field include the following: tractography-based targeting, adaptive cerebellar stimulation, and investigations into the network dynamics between the cerebellar cortex, deep cerebellar nuclei, and the subcortical and cortical structures of the cerebrum.

Effects of repetitive transcranial magnetic stimulation on individual variability of resting-state functional connectivity in major depressive disorder.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), but substantial heterogeneity in outcomes remains. We examined a potential mechanism of action of rTMS to normalize individual variability in resting-state functional connectivity (rs-fc) before and after a course of treatment. METHODS: Variability in rs-fc was examined in healthy controls (baseline) and individuals with MDD (baseline and after 4-6 weeks of rTMS). Seed-based connectivity was calculated to 4 regions associated with MDD: left dorsolateral prefrontal cortex (DLPFC), right subgenual anterior cingulate cortex (sgACC), bilateral insula, and bilateral precuneus. Individual variability was quantified for each region by calculating the mean correlational distance of connectivity maps relative to the healthy controls; a higher variability score indicated a more atypical/idiosyncratic connectivity pattern. RESULTS: We included data from 66 healthy controls and 252 individuals with MDD in our analyses. Patients with MDD did not show significant differences in baseline variability of rs-fc compared with controls. Treatment with rTMS increased rs-fc variability from the right sgACC and precuneus, but the increased variability was not associated with clinical outcomes. Interestingly, higher baseline variability of the right sgACC was significantly associated with less clinical improvement (p = 0.037, uncorrected; did not survive false discovery rate correction).Limitations: The linear model was constructed separately for each region of interest. CONCLUSION: This was, to our knowledge, the first study to examine individual variability of rs-fc related to rTMS in individuals with MDD. In contrast to our hypotheses, we found that rTMS increased the individual variability of rs-fc. Our results suggest that individual variability of the right sgACC and bilateral precuneus connectivity may be a potential mechanism of rTMS.

Transcranial Magneto-Acoustic Stimulation Protects Synaptic Rehabilitation from Amyloid-Beta Plaques via Regulation of Microglial Functions.

Transcranial magneto-acoustic stimulation (TMAS), which is characterized by high spatiotemporal resolution and high penetrability, is a non-invasive neuromodulation technology based on the magnetic-acoustic coupling effect. To reveal the effects of TMAS treatment on amyloid-beta (Aß) plaque and synaptic plasticity in Alzheimer's disease, we conducted a comparative analysis of TMAS and transcranial ultrasound stimulation (TUS) based on acoustic effects in 5xFAD mice and BV2 microglia cells. We found that the TMAS-TUS treatment effectively reduced amyloid plaque loads and plaque-associated neurotoxicity. Additionally, TMAS-TUS treatment ameliorated impairments in long-term memory formation and long-term potentiation. Moreover, TMAS-TUS treatment stimulated microglial proliferation and migration while enhancing the phagocytosis and clearance of Aß. In 5xFAD mice with induced microglial exhaustion, TMAS-TUS treatment-mediated Aß plaque reduction, synaptic rehabilitation improvement, and the increase in phospho-AKT levels were diminished. Overall, our study highlights that stimulation of hippocampal microglia by TMAS treatment can induce anti-cognitive impairment effects via PI3K-AKT signaling, providing hope for the development of new strategies for an adjuvant therapy for Alzheimer's disease.

Study on Improving the Modulatory Effect of Rhythmic Oscillations by Transcranial Magneto-Acoustic Stimulation.

In hippocampus, synaptic plasticity and rhythmic oscillations reflect the cytological basis and the intermediate level of cognition, respectively. Transcranial ultrasound stimulation (TUS) has demonstrated the ability to elicit changes in neural response. However, the modulatory effect of TUS on synaptic plasticity and rhythmic oscillations was insufficient in the present studies, which may be attributed to the fact that TUS acts mainly through mechanical forces. To enhance the modulatory effect on synaptic plasticity and rhythmic oscillations, transcranial magneto-acoustic stimulation (TMAS) which induced a coupled electric field together with TUS's ultrasound field was applied. The modulatory effect of TMAS and TUS with a pulse repetition frequency of 100 Hz were compared. TMAS/TUS were performed on C57 mice for 7 days at two different ultrasound intensities (3 W/cm2 and 5 W/cm [Formula: see text]. Behavioral tests, long-term potential (LTP) and local field potentials in vivo were performed to evaluate TUS/TMAS modulatory effect on cognition, synaptic plasticity and rhythmic oscillations. Protein expression based on western blotting were used to investigate the under- lying mechanisms of these beneficial effects. At 5 W/cm2, TMAS-induced LTP were 113.4% compared to the sham group and 110.5% compared to TUS. Moreover, the relative power of high gamma oscillations (50-100Hz) in the TMAS group ( 1.060±0.155 %) was markedly higher than that in the TUS group ( 0.560±0.114 %) and sham group ( 0.570±0.088 %). TMAS significantly enhanced the synchronization of theta and gamma oscillations as well as theta-gamma cross-frequency coupling. Whereas, TUS did not show relative enhancements. TMAS provides enhanced effect for modulating the synaptic plasticity and rhythmic oscillations in hippocampus.

Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Across Mental Disorders: A Systematic Review and Dose-Response Meta-Analysis.

Importance: Noninvasive brain stimulation (NIBS) interventions have been shown to be efficacious in several mental disorders, but the optimal dose stimulation parameters for each disorder are unknown. Objective: To define NIBS dose stimulation parameters associated with the greatest efficacy in symptom improvement across mental disorders. Data Sources: Studies were drawn from an updated (to April 30, 2023) previous systematic review based on a search of PubMed, OVID, and Web of Knowledge. Study Selection: Randomized clinical trials were selected that tested transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) for any mental disorder in adults aged 18 years or older. Data Extraction and Synthesis: Two authors independently extracted the data. A 1-stage dose-response meta-analysis using a random-effects model was performed. Sensitivity analyses were conducted to test robustness of the findings. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: The main outcome was the near-maximal effective doses of total pulses received for TMS and total current dose in coulombs for tDCS. Results: A total of 110 studies with 4820 participants (2659 men [61.4%]; mean [SD] age, 42.3 [8.8] years) were included. The following significant dose-response associations emerged with bell-shaped curves: (1) in schizophrenia, high-frequency (HF) TMS on the left dorsolateral prefrontal cortex (LDLPFC) for negative symptoms (χ2 = 9.35; df = 2; P = .009) and TMS on the left temporoparietal junction for resistant hallucinations (χ2 = 36.52; df = 2; P < .001); (2) in depression, HF-DLPFC TMS (χ2 = 14.49; df = 2; P < .001); (3) in treatment-resistant depression, LDLPFC tDCS (χ2 = 14.56; df = 2; P < .001); and (4) in substance use disorder, LDLPFC tDCS (χ2 = 33.63; df = 2; P < .001). The following significant dose-response associations emerged with plateaued or ascending curves: (1) in depression, low-frequency (LF) TMS on the right DLPFC (RDLPFC) with ascending curve (χ2 = 25.67; df = 2; P = .001); (2) for treatment-resistant depression, LF TMS on the bilateral DLPFC with ascending curve (χ2 = 5.86; df = 2; P = .004); (3) in obsessive-compulsive disorder, LF-RDLPFC TMS with ascending curve (χ2 = 20.65; df = 2; P < .001) and LF TMS on the orbitofrontal cortex with a plateaued curve (χ2 = 15.19; df = 2; P < .001); and (4) in posttraumatic stress disorder, LF-RDLPFC TMS with ascending curve (χ2 = 54.15; df = 2; P < .001). Sensitivity analyses confirmed the main findings. Conclusions and Relevance: The study findings suggest that NIBS yields specific outcomes based on dose parameters across various mental disorders and brain regions. Clinicians should consider these dose parameters when prescribing NIBS. Additional research is needed to prospectively validate the findings in randomized, sham-controlled trials and explore how other parameters contribute to the observed dose-response association.

The Relationship of Anxious Arousal With Treatment of Dysphoria Using Virtual Reality Mindfulness and 2 Accelerated Transcranial Magnetic Stimulation Protocols.

Objective: This secondary analysis investigated the relationship of anxious arousal, as measured by the Tension Anxiety subscale of the Profile of Mood States (TA-POMS), to treatment outcome across diagnoses for each phase of the study. Sequential treatment phases of virtual reality (VR) mindfulness followed by left dorsolateral prefrontal cortex (dlPFC) accelerated transcranial magnetic stimulation (accel-TMS) and then dorsomedial prefrontal cortex (dmPFC) accel-TMS were used to treat dysphoria across diagnoses in an open trial from September 2021 to August 2023.Methods: The change in the TA-POMS subscale was compared to the percent change in primary clinician scale scores using a bivariate analysis. Baseline TA-POMS subscales were compared to treatment response using linear regression models to assess anxious arousal's impact on treatment outcome for the 3 phases. Significance was defined as P < .05, 2-tailed.Results: Twenty-three participants were enrolled in VR mindfulness, 19 in left dlPFC accel-TMS, and 12 in dmPFC accel TMS. Although the change in TA-POMS scores did not significantly correlate with the percent change in primary clinician scale ratings for the VR phase, they did for both the dlPFC (P = .041) and the dmPFC (P = .003) accel-TMS treatment phases. Importantly, baseline anxious arousal levels as measured by TA-POMS were not predictive of treatment outcome in any treatment phase.Conclusion: The outcome of accel-TMS treatment was not adversely affected by anxious arousal and similarly improved along with primary rating scales.Trial Registration: ClinicalTrials.gov identifier: NCT05061745.

A Pilot Study of High-Frequency Transcranial Magnetic Stimulation for Bipolar Depression.

Objective: Repetitive transcranial magnetic stimulation (rTMS) is a standard treatment approach for major depressive disorder. There is growing clinical experience to support the use of high-frequency left-sided rTMS in bipolar depression. This study collected open-label safety and effectiveness data in a sample of patients with bipolar depression.Methods: Thirty-one adults (13 male/ 18 female; mean age: 42.2 [14.3] years) with bipolar (I or II) depression verified by DSM-5 criteria were recruited at Sheppard Pratt and Mayo Clinic between August 2017 and February 2020 for rTMS. Standardized treatment protocols employed 6 weeks of 10-Hz rTMS to the left dorsolateral prefrontal cortex at 120% of motor threshold with 3,000 pulses per session in 4-second trains with intertrain intervals of 26 seconds. All patients were treated concurrently with a mood stabilizer. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS). Response and remission were defined as MADRS score reductions of ≥50% or score <10, respectively. We examined response, remission, and potential contributing factors with multivariate and logistic regression models.Results: The majority of patients with bipolar depression reached response (n = 27; 87.1%) and remission (n = 23; 74.2%). Older age and concurrent treatment with lithium were associated with higher MADRS scores throughout the treatment course (0.1 ± 0.05, P =.05; 4.05 ± 1.27, P = .003, respectively). Concurrent treatment with lamotrigine was associated with lower MADRS scores (-3.48 ± 1.26, P = .01). Treatment with rTMS was safe and well tolerated. There were no completed suicides, induced manic episodes, or other serious adverse events.Conclusion: Although preliminary, the present findings are encouraging regarding the safety and effectiveness of 10-Hz rTMS for bipolar depression.Trial Registration: ClinicalTrials.gov identifier: NCT02640950.

Ferroptosis and its implications in treating cognitive impairment caused by aging: A study on the mechanism of repetitive transcranial magnetic stimulation.

OBJECTIVE: Ferroptosis has been recognized as being closely associated with cognitive impairment. Research has established that Alzheimer's disease (AD)-associated proteins, such as amyloid precursor protein (APP) and phosphorylated tau, are involved in brain iron metabolism. These proteins are found in high concentrations within senile plaques and neurofibrillary tangles. Repetitive transcranial magnetic stimulation (rTMS) offers a non-pharmacological approach to AD treatment. This study aims to explore the potential therapeutic effects of rTMS on cognitive impairment through the modulation of the ferroptosis pathway, thereby laying both a theoretical and experimental groundwork for the application of rTMS in treating Alzheimer's disease. METHODS: The study utilized senescence-accelerated mouse prone 8 (SAMP8) mice to model brain aging-related cognitive impairment, with senescence-accelerated-mouse resistant 1 (SAMR1) mice acting as controls. The SAMP8 mice were subjected to high-frequency rTMS at 25 Hz for durations of 14 and 28 days. Cognitive function was evaluated using behavioral tests. Resting-state functional magnetic resonance imaging (rs-fMRI) assessed alterations in cerebral activity by measuring the fractional amplitude of low-frequency fluctuations (fALFF) of the blood oxygen level-dependent signal. Neuronal recovery post-rTMS in the SAMP8 model was examined via HE and Nissl staining. Immunohistochemistry was employed to detect the expression of APP and Phospho-Tau (Thr231). Oxidative stress markers were quantified using biochemical assay kits. ELISA methods were utilized to measure hippocampal levels of Fe2+ and Aß1-42. Finally, the expression of proteins related to the ferroptosis pathway was determined through western blot analysis. RESULTS: The findings indicate that 25 Hz rTMS enhances cognitive function and augments cerebral activity in SAMP8 model mice. Treatment with rTMS in these mice resulted in diminished oxidative stress and safeguarded neurons against damage. Additionally, iron accumulation was mitigated, and the expression of ferroptosis pathway proteins Gpx4, system Xc-, and Nrf2 was elevated. CONCLUSIONS: The Tau/APP-Fe-GPX4/system Xc-/Nrf2 pathway is implicated in the remedial effects of rTMS on cognitive dysfunction, offering a theoretical and experimental basis for employing rTMS in AD treatment.

Noninvasive brain stimulation in autism: review and outlook for personalized interventions in adult patients.

Noninvasive brain stimulation (NIBS) has been increasingly investigated during the last decade as a treatment option for persons with autism spectrum disorder (ASD). Yet, previous studies did not reach a consensus on a superior treatment protocol or stimulation target. Persons with ASD often suffer from social isolation and high rates of unemployment, arising from difficulties in social interaction. ASD involves multiple neural systems involved in perception, language, and cognition, and the underlying brain networks of these functional domains have been well documented. Aiming to provide an overview of NIBS effects when targeting these neural systems in late adolescent and adult ASD, we conducted a systematic search of the literature starting at 631 non-duplicate publications, leading to six studies corresponding with inclusion and exclusion criteria. We discuss these studies regarding their treatment rationale and the accordingly chosen methodological setup. The results of these studies vary, while methodological advances may allow to explain some of the variability. Based on these insights, we discuss strategies for future clinical trials to personalize the selection of brain stimulation targets taking into account intersubject variability of brain anatomy as well as function.

Retinal Tear Following Low-Frequency Repetitive Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive form of brain stimulation that uses magnetic pulses to stimulate specific brain regions. Retina is being investigated whether the retina, which is also known as the brain's window to the outside world, is affected by the treatment. METHODS: Magventure X100 device was used for the procedure. The bilateral supplementary motor area was targeted. Procedure protocol: power: 47%, repetitive rate (frequency): 1 Hz, pulses in train duration: 300, intertrain interval (waiting time): 120 seconds, number of trains: 4, total pulses: 1200. Twenty sessions of rTMS were planned for the patient. The patient was informed about the procedure, and her consent was obtained. RESULTS: The Yale-Brown Obsessive-Compulsive Disorder Scale (YBOCS) score before the first session was 31, and the Brown Assessment Beliefs Scale (BABS) score was 5. The patient's YBOCS score after the 15th session was 14, and the BABS score was 0. After the implementation of the 15th session of the patient's treatment, retinal detachment developed in the right eye, and the treatment was terminated. As a result of the eye examination of the patient, it was determined that there was 1 horseshoe rupture and 2 hole-shaped ruptures in the lower half of the left eye. CONCLUSIONS: Patients at risk for retinal detachment may require specialized treatment and close monitoring to prevent the condition from worsening. It is important to consult with an ophthalmologist for patients at risk for retinal detachment before TMS application.

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.

An update on noninvasive neuromodulation in the treatment of patients with prolonged disorders of consciousness.

BACKGROUND: With the improvement of emergency techniques, the survival rate of patients with severe brain injury has increased. However, this has also led to an annual increase in the number of patients with prolonged disorders of consciousness (pDoC). Hence, recovery of consciousness is an important part of treatment. With advancing techniques, noninvasive neuromodulation seems a promising intervention. The objective of this review was to summarize the latest techniques and provide the basis for protocols of noninvasive neuromodulations in pDoC. METHODS: This review summarized the advances in noninvasive neuromodulation in the treatment of pDoC in the last 5 years. RESULTS: Variable techniques of neuromodulation are used in pDoC. Transcranial ultrasonic stimulation (TUS) and transcutaneous auricular vagus nerve stimulation (taVNS) are very new techniques, while transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) are still the hotspots in pDoC. Median nerve electrical stimulation (MNS) has received little attention in the last 5 years. CONCLUSIONS: Noninvasive neuromodulation is a valuable and promising technique to treat pDoC. Further studies are needed to determine a unified stimulus protocol to achieve optimal effects as well as safety.

The effects of verbal and spatial working memory on short- and long-latency sensorimotor circuits in the motor cortex.

Multiple sensorimotor loops converge in the motor cortex to create an adaptable system capable of context-specific sensorimotor control. Afferent inhibition provides a non-invasive tool to investigate the substrates by which procedural and cognitive control processes interact to shape motor corticospinal projections. Varying the transcranial magnetic stimulation properties during afferent inhibition can probe specific sensorimotor circuits that contribute to short- and long-latency periods of inhibition in response to the peripheral stimulation. The current study used short- (SAI) and long-latency (LAI) afferent inhibition to probe the influence of verbal and spatial working memory load on the specific sensorimotor circuits recruited by posterior-anterior (PA) and anterior-posterior (AP) TMS-induced current. Participants completed two sessions where SAI and LAI were assessed during the short-term maintenance of two- or six-item sets of letters (verbal) or stimulus locations (spatial). The only difference between the sessions was the direction of the induced current. PA SAI decreased as the verbal working memory load increased. In contrast, AP SAI was not modulated by verbal working memory load. Visuospatial working memory load did not affect PA or AP SAI. Neither PA LAI nor AP LAI were sensitive to verbal or spatial working memory load. The dissociation of short-latency PA and AP sensorimotor circuits and short- and long-latency PA sensorimotor circuits with increasing verbal working memory load support multiple convergent sensorimotor loops that provide distinct functional information to facilitate context-specific supraspinal control.

Personalised functional imaging-guided multitarget continuous theta burst stimulation for post-stroke aphasia: study protocol for a randomised controlled trial.

INTRODUCTION: Continuous theta burst stimulation (cTBS), a form of repetitive transcranial magnetic stimulation (rTMS), targeting the language network in the right hemisphere of post-stroke aphasia (PSA) patients shows promising results in clinical trials. However, existing PSA studies have focused on single-target rTMS, leaving unexplored the potential benefits of multitarget brain stimulation. Consequently, there is a need for a randomised clinical trial aimed to evaluate the efficacy and safety of cTBS targeting on multiple critical nodes in the language network for PSA. METHODS AND ANALYSIS: This is a prospective, multicentre, double-blind, two-arm parallel-group, sham-controlled randomised trial. The study will include a total of 60 participants who will be randomly assigned in a 1:1 ratio to either the active cTBS group or the sham cTBS group. Using precision resting-state functional MRI for each participant, we will map personalised language networks and design personalised targets in the inferior frontal gyrus, superior temporal gyrus and superior frontal gyrus. Participants will undergo a 3-week cTBS intervention targeting the three personalised targets, coupled with speech and language therapy. The primary outcome is the change in the Western Aphasia Battery-Revised aphasia quotient score among participants after a 3-week treatment. Secondary outcomes include Boston Diagnostic Aphasia Examination severity ratings, Token Test and the Chinese-version of the Stroke and Aphasia Quality of Life Scale 39-generic version. ETHICS AND DISSEMINATION: The study has been approved by the ethics committees of Affiliated Hospital of Hebei University, Hebei General Hospital and Affiliated Hospital of Chengde Medical University. The findings of this study will be reported in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: The study has been registered on ClinicalTrials.gov (NCT05957445).

Clinical Effect Analysis of Wearable Sensor Technology-Based Gait Function Analysis in Post-Transcranial Magnetic Stimulation Stroke Patients.

(1) Background: This study evaluates the effectiveness of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) in improving gait in post-stroke hemiplegic patients, using wearable sensor technology for objective gait analysis. (2) Methods: A total of 72 stroke patients were randomized into control, sham stimulation, and LF-rTMS groups, with all receiving standard medical treatment. The LF-rTMS group underwent stimulation on the unaffected hemisphere for 6 weeks. Key metrics including the Fugl-Meyer Assessment Lower Extremity (FMA-LE), Berg Balance Scale (BBS), Modified Barthel Index (MBI), and gait parameters were measured before and after treatment. (3) Results: The LF-rTMS group showed significant improvements in the FMA-LE, BBS, MBI, and various gait parameters compared to the control and sham groups (p < 0.05). Specifically, the FMA-LE scores improved by an average of 5 points (from 15 ± 3 to 20 ± 2), the BBS scores increased by 8 points (from 35 ± 5 to 43 ± 4), the MBI scores rose by 10 points (from 50 ± 8 to 60 ± 7), and notable enhancements in gait parameters were observed: the gait cycle time was reduced from 2.05 ± 0.51 s to 1.02 ± 0.11 s, the stride length increased from 0.56 ± 0.04 m to 0.97 ± 0.08 m, and the walking speed improved from 35.95 ± 7.14 cm/s to 75.03 ± 11.36 cm/s (all p < 0.001). No adverse events were reported. The control and sham groups exhibited improvements but were not as significant. (4) Conclusions: LF-rTMS on the unaffected hemisphere significantly enhances lower-limb function, balance, and daily living activities in subacute stroke patients, with the gait parameters showing a notable improvement. Wearable sensor technology proves effective in providing detailed, objective gait analysis, offering valuable insights for clinical applications in stroke rehabilitation.

Prolonged intermittent theta burst stimulation targeting the left prefrontal cortex and cerebellum does not affect executive functions in healthy individuals.

Repetitive transcranial magnetic stimulation (rTMS) for alleviating negative symptoms and cognitive dysfunction in schizophrenia commonly targets the left dorsolateral prefrontal cortex (LDLPFC). However, the therapeutic effectiveness of rTMS at this site remains inconclusive and increasingly, studies are focusing on cerebellar rTMS. Recently, prolonged intermittent theta-burst stimulation (iTBS) has emerged as a rapid-acting form of rTMS with promising clinical benefits. This study explored the cognitive and neurophysiological effects of prolonged iTBS administered to the LDLPFC and cerebellum in a healthy cohort. 50 healthy participants took part in a cross-over study and received prolonged (1800 pulses) iTBS targeting the LDLPFC, cerebellar vermis, and sham iTBS. Mixed effects repeated measures models examined cognitive and event-related potentials (ERPs) from 2-back (P300, N200) and Stroop (N200, N450) tasks after stimulation. Exploratory non-parametric cluster-based permutation tests compared ERPs between conditions. There were no significant differences between conditions for behavioural and ERP outcomes on the 2-back and Stroop tasks. Exploratory cluster-based permutation tests of ERPs did not identify any significant differences between conditions. We did not find evidence that a single session of prolonged iTBS administered to either the LDLPFC or cerebellum could cause any cognitive or ERP changes compared to sham in a healthy sample.

Repetitive transcranial magnetic stimulation focusing on patients with neuropathic pain in the upper limb: a randomized sham-controlled parallel trial.

This study aimed to evaluate the efficacy and safety of navigation-guided repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex in patients with neuropathic pain in the upper limb. This randomized, blinded, sham-controlled, parallel trial included a rTMS protocol (10-Hz, 2000 pulses/session) consisting of five daily sessions, followed by one session per week for the next seven weeks. Pain intensity, as well as pain-related disability, quality of life, and psychological status, were assessed. For the primary outcome, pain intensity was measured daily using a numerical rating scale as a pain diary. Thirty patients were randomly assigned to the active rTMS or sham-stimulation groups. In the primary outcome, the decrease (least square [LS] mean ± standard error) in the weekly average of a pain diary at week 9 compared to the baseline was 0.84 ± 0.31 in the active rTMS group and 0.58 ± 0.29 in the sham group (LS mean difference, 0.26; 95% confidence interval, - 0.60 to 1.13). There was no significant effect on the interaction between the treatment group and time point. Pain-related disability score improved, but other assessments showed no differences. No serious adverse events were observed. This study did not show significant pain relief; however, active rTMS tended to provide better results than sham. rTMS has the potential to improve pain-related disability in addition to pain relief.Clinical Trial Registration number: jRCTs052190110 (20/02/2020).

Efficacy of different rehabilitation therapies on post-stroke aphasia patients: A network meta-analysis.

BACKGROUND: Although several rehabilitation interventions are effective in post-stroke aphasia (PSA), the efficacy of different rehabilitation interventions compared to each other remains controversial. Here, we aimed to compare the effectiveness of varying rehabilitation interventions in PSA. METHODS: Randomized controlled trials on 8 kinds of rehabilitation interventions to improve speech function in patients with PSA were searched by computer from 10 databases, including PubMed, Web of Science, Cochrane, OVID, CINAHL, Embase, CNKI, WanFang, CBM, and VIP. The search scope was from the establishment of the database to August 2023. The literature screening, extraction of basic information, and quality assessment of the literature were conducted independently by 2 researchers. Network meta-analysis (NMA) was performed using Stata 17.0 software. RESULTS: Fifty-four studies involving 2688 patients with PSA were included. The results of NMA showed that: ① in terms of improving the severity of aphasia, the therapeutic effects of repetitive transcranial magnetic stimulation were the most significant; ② motor imagery therapy was the most effective in improving spontaneous speech, repetition, and naming ability; ③ in terms of improving listening comprehension ability, the therapeutic effects of mirror neuron therapy was the most significant. CONCLUSION: The 8 rehabilitation interventions have different focuses in improving the speech function of PSA patients, and the clinical therapists can select the optimal rehabilitation interventions in a targeted manner according to the results of this NMA and the patients' conditions and other relevant factors.

Non-pharmacological interventions for improving language and communication in people with primary progressive aphasia.

BACKGROUND: Primary progressive aphasia (PPA) accounts for approximately 43% of frontotemporal dementias and is mainly characterised by a progressive impairment of speech and communication abilities. Three clinical variants have been identified: (a) non-fluent/agrammatic, (b) semantic, and (c) logopenic/phonological PPA variants. There is currently no curative treatment for PPA, and the disease progresses inexorably over time, with devastating effects on speech and communication ability, functional status, and quality of life. Several non-pharmacological interventions that may improve symptoms (e.g. different forms of language training and non-invasive brain stimulation) have been investigated in people with PPA. OBJECTIVES: To assess the effects of non-pharmacological interventions for people with PPA on word retrieval (our primary outcome), global language functions, cognition, quality of life, and adverse events. SEARCH METHODS: We searched the Cochrane Dementia and Cognitive Improvement Group's trial register, MEDLINE (Ovid SP), Embase (Ovid SP), four other databases and two other trial registers. The latest searches were run on 26 January 2024. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating the effects of non-pharmacological interventions in people with PPA. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: There were insufficient data available to conduct the network meta-analyses that we had originally planned (due to trial data being insufficiently reported or not reported at all, as well as the heterogeneous content of the included interventions). Therefore, we provide a descriptive summary of the included studies and results. We included 10 studies, with a total of 132 participants, evaluating non-pharmacological interventions. These were: transcranial direct current stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS) as stand-alone treatments (used by two and one studies, respectively); tDCS combined with semantic and phonological word-retrieval training (five studies); tDCS combined with semantic word-retrieval training (one study); and tDCS combined with phonological word-retrieval training (one study). Results for our primary outcome of word retrieval were mixed. For the two studies that investigated the effects of tDCS as stand-alone treatment compared to placebo ("sham") tDCS, we rated the results as having very low-certainty evidence. One study found a significant beneficial effect on word retrieval after active tDCS; one study did not report any significant effects in favour of the active tDCS group. Five studies investigated tDCS administered to the dorsolateral prefrontal cortex, inferior frontal cortex, left frontotemporal region, or the temporoparietal cortex, combined with semantic and phonological word-retrieval training. The most consistent finding was enhancement of word-retrieval ability for trained items immediately after the intervention, when behavioural training was combined with active tDCS compared to behavioural training plus sham tDCS. We found mixed effects for untrained items and maintenance of treatment effects during follow-up assessments. We rated the certainty of the evidence as very low in all studies. One study investigated tDCS combined with semantic word-retrieval training. Training was provided across 15 sessions with a frequency of three to five sessions per week, depending on the personal preferences of the participants. tDCS targeted the left frontotemporal region. The study included three participants: two received 1 mA stimulation and one received 2 mA stimulation. The study showed mixed results. We rated it as very low-certainty evidence. One study investigated tDCS combined with phonological word-retrieval training. Training was again provided across 15 sessions over a period of three weeks. tDCS targeted the left inferior frontal gyrus. This study showed a significantly more pronounced improvement for trained and untrained words in favour of the group that had received active tDCS, but we rated the certainty of the evidence as very low. One study compared active rTMS applied to an individually determined target site to active rTMS applied to a control site (vertex) for effects on participants' word retrieval. This study demonstrated better word retrieval for active rTMS administered to individually determined target brain regions than in the control intervention, but we rated the results as having a very low certainty of evidence. Four studies assessed overall language ability, three studies assessed cognition, five studies assessed potential adverse effects of brain stimulation, and one study investigated quality of life. AUTHORS' CONCLUSIONS: There is currently no high-certainty evidence to inform clinical decision-making regarding non-pharmacological treatment selection for people with PPA. Preliminary evidence suggests that the combination of active tDCS with specific language therapy may improve impaired word retrieval for specifically trained items beyond the effects of behavioural treatment alone. However, more research is needed, including high-quality RCTs with detailed descriptions of participants and methods, and consideration of outcomes such as quality of life, depressive symptoms, and overall cognitive functioning. Moreover, studies assessing optimal treatments (i.e. behavioural interventions, brain stimulation interventions, and their combinations) for individual patients and PPA subtypes are needed. We were not able to conduct the planned (network) meta-analyses due to missing data that could not be obtained from most of the authors, a general lack of RCTs in the field, and heterogeneous interventions in eligible trials. Journals should implement a mandatory data-sharing requirement to assure transparency and accessibility of data from clinical trials.