Age-related decline in GABAergic intracortical inhibition can be counteracted by long-term learning of balance skills.

Ageing induces a decline in GABAergic intracortical inhibition, which seems to be associated not only with decremental changes in well-being, sleep quality, cognition and pain management but also with impaired motor control. So far, little is known regarding whether targeted interventions can prevent the decline of intracortical inhibition in the primary motor cortex in the elderly. Therefore, the present study investigated whether age-related cortical dis-inhibition could be reversed after 6 months of balance learning and whether improvements in postural control correlated with the extent of reversed dis-inhibition. The results demonstrated that intracortical inhibition can be upregulated in elderly subjects after long-term balance learning and revealed a correlation between changes in balance performance and intracortical inhibition. This is the first study to show physical activity-related upregulation of GABAergic inhibition in a population with chronic dis-inhibition and may therefore be seminal for many pathologies in which the equilibrium between inhibitory and excitatory neurotransmitters is disturbed. KEY POINTS: Ageing induces a decline in GABAergic intracortical inhibition. So far, little is known regarding whether targeted interventions can prevent the decline of intracortical inhibition in the primary motor cortex in the elderly. After 6 months of balance learning, intracortical inhibition can be upregulated in elderly subjects. The results of this study also revealed a correlation between changes in balance performance and intracortical inhibition. This is the first study to show physical activity-related upregulation of GABAergic inhibition in a population with chronic dis-inhibition.

The protective effects of repetitive transcranial magnetic stimulation with different high frequencies on motor functions in MPTP/probenecid induced Parkinsonism mouse models.

BACKGROUND: High-frequency repeated transcranial magnetic stimulation (rTMS) stimulating the primary motor cortex (M1) is an alternative, adjunctive therapy for improving the motor symptoms of Parkinson's disease (PD). However, whether the high frequency of rTMS positively correlates to the improvement of motor symptoms of PD is still undecided. By controlling for other parameters, a disease animal model may be useful to compare the neuroprotective effects of different high frequencies of rTMS. OBJECTIVE: The current exploratory study was designed to compare the protective effects of four common high frequencies of rTMS (5, 10, 15, and 20 Hz) and iTBS (a special form of high-frequency rTMS) and explore the optimal high-frequency rTMS on an animal PD model. METHODS: Following high frequencies of rTMS application (twice a week for 5 weeks) in a MPTP/probenecid-induced chronic PD model, the effects of the five protocols on motor behavior as well as dopaminergic neuron degeneration levels were identified. The underlying molecular mechanisms were further explored. RESULTS: We found that all the high frequencies of rTMS had protective effects on the motor functions of PD models to varying degrees. Among them, the 10, 15, and 20 Hz rTMS interventions induced comparable preservation of motor function through the protection of nigrostriatal dopamine neurons. The enhancement of brain-derived neurotrophic factor (BDNF), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT-2) and the suppression of TNF-α and IL-1ß in the nigrostriatum were involved in the process. The efficacy of iTBS was inferior to that of the above three protocols. The effect of 5 Hz rTMS protocol was weakest. CONCLUSIONS: Combined with the results of the present study and the possible side effects induced by rTMS, we concluded that 10 Hz might be the optimal stimulation frequency for preserving the motor functions of PD models using rTMS treatment.

Repetitive transcranial magnetic stimulation impacts the executive function of patients with vascular cognitive impairment: a systematic review and meta-analysis.

Objective: Executive dysfunction is a core symptom of vascular cognitive impairment (VCI), which seriously affects patients' prognosis. This paper aims to investigate the effectiveness of rTMS on executive function in VCI. Methods: The databases selected for this study included Pubmed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, China Science and Technology Journal Database (VIP), and China Biology Medicine Disc (CBM). The screening times were conducted from the time of library construction until August 23, 2023. The inclusion criteria for this meta-analysis were randomized controlled trials (RCTs) on rTMS for VCI, which include executive function scores. The primary metrics were executive subscale scores of the Cognitive Comprehensive Scale and total scores of the Executive Specificity Scale. The secondary metrics were subscale scores of the Executive Specificity Scale. The quality of each eligible study was assessed using the Cochrane Risk of Bias tool. Meta-analysis and bias analysis were performed using Stata (version 16.0) and RevMan (version 5.3). Results: A total of 20 high-quality clinical RCTs with 1,049 samples were included in this paper. The findings from the primary outcomes revealed that within the rTMS group, there were significantly higher scores observed for the executive sub-item on the cognitive composite scale (SMD = 0.93, 95% CI = 0.77-1.08, p < 0.00001, I 2 = 14%) and the total score on the executive specific scale (SMD = 0.69, 95% CI = 0.44-0.94, p < 0.00001, I 2 = 0%) compared to the control group. As for the secondary outcome measures, as shown by the Trail Making Test-A (time) (MD = -35.75, 95% CI = -68.37 to -3.12, p = 0.03, I 2 = 55%), the Stroop-C card (time) (SMD = -0.46, 95% CI = -0.86 to -0.06, p = 0.02, I 2 = 0%) and the Stroop-C card (correct number) (SMD = 0.49, 95% CI = 0.04-0.94, p = 0.03, I 2 = 0%), the experimental group shorts time and enhances accuracy of executive task in comparison to the control group. Subgroup analysis of the main outcome demonstrated that intermittent theta burst stimulation (iTBS), higher frequency, lower intensity, longer duration, and combined comprehensive therapy exhibited superior efficacy. Conclusion: rTMS is effective in the treatment of the executive function of VCI. The present study has some limitations, so multi-center, large-sample, objective indicators and parameters are needed to further explore in the future.Systematic review registration:https://www.crd.york.ac.uk/prospero/, CRD42023459669.

Macro and micro structural preservation of grey matter integrity after 24 weeks of rTMS in Alzheimer's disease patients: a pilot study.

Alzheimer's Disease (AD) is characterized by structural and functional dysfunction involving the Default Mode Network (DMN), for which the Precuneus (PC) is a key node. We proposed a randomized double-blind pilot study to determine neurobiological changes after 24 weeks of PC-rTMS in patients with mild-to-moderate AD. Sixteen patients were randomly assigned to SHAM or PC-rTMS, and received an intensive 2-weeks course with daily rTMS sessions, followed by a maintenance phase in which rTMS has been applied once a week. Before and after the treatment structural and functional MRIs were collected. Our results showed macro- and micro-structural preservation in PC-rTMS compared to SHAM-rTMS group after 24 weeks of treatment, correlated to an increase of functional connectivity (FC) within the PC in the PC-rTMS group. Even if preliminary, these results trigger the possibility of using PC-rTMS to arrest atrophy progression by manipulating distributed network connectivity patterns.

Effects of repetitive transcranial magnetic stimulation of the right inferior parietal lobe on the body image perception in anorexia nervosa: A pilot randomized controlled study.

INTRODUCTION: Restrictive anorexia nervosa (AN) is associated with distorted perception of body shape, previously linked to hypoactivity and reduced excitability of the right inferior parietal lobe (rIPL). Here, we investigated the impact of high-frequency repetitive transcranial magnetic stimulation (HF rTMS) of the rIPL on body shape perception in patients with AN. METHODS: Seventeen patients with AN (median [Q1_Q3] age, 35 [27_39] years; disease duration, 12 [6_18] years) were randomly assigned to receive real or sham HF (10 Hz) rTMS of the rIPL over a period of 2 weeks, comprising 10 sessions. The primary outcome measure was the Body Shape Questionnaire (BSQ). Secondary outcomes included eating disorder symptoms, body mass index, mood, anxiety, and safety. Data collection were done at baseline, post-rTMS, and at 2 weeks and 3 months post-rTMS. RESULTS: Following both real and sham rTMS of the rIPL, no significant differences were observed in body shape perception or other parameters. Both real and sham rTMS interventions were deemed safe and well tolerated. Notably, serious adverse events were associated with the underlying eating and mood disorders, resulting in hospitalization for undernutrition (five patients) or suicidal attempts (two patients). CONCLUSION: This pilot study does not support the use of rTMS of the rIPL as an effective method for improving body shape perception in individuals with the restrictive form of AN. Further research is warranted to comprehensively explore both the clinical and neurophysiological effects of HF rTMS in this population.

Modern neurophysiological techniques indexing normal or abnormal brain aging.

Brain aging is associated with a decline in cognitive performance, motor function and sensory perception, even in the absence of neurodegeneration. The underlying pathophysiological mechanisms remain incompletely understood, though alterations in neurogenesis, neuronal senescence and synaptic plasticity are implicated. Recent years have seen advancements in neurophysiological techniques such as electroencephalography (EEG), magnetoencephalography (MEG), event-related potentials (ERP) and transcranial magnetic stimulation (TMS), offering insights into physiological and pathological brain aging. These methods provide real-time information on brain activity, connectivity and network dynamics. Integration of Artificial Intelligence (AI) techniques promise as a tool enhancing the diagnosis and prognosis of age-related cognitive decline. Our review highlights recent advances in these electrophysiological techniques (focusing on EEG, ERP, TMS and TMS-EEG methodologies) and their application in physiological and pathological brain aging. Physiological aging is characterized by changes in EEG spectral power and connectivity, ERP and TMS parameters, indicating alterations in neural activity and network function. Pathological aging, such as in Alzheimer's disease, is associated with further disruptions in EEG rhythms, ERP components and TMS measures, reflecting underlying neurodegenerative processes. Machine learning approaches show promise in classifying cognitive impairment and predicting disease progression. Standardization of neurophysiological methods and integration with other modalities are crucial for a comprehensive understanding of brain aging and neurodegenerative disorders. Advanced network analysis techniques and AI methods hold potential for enhancing diagnostic accuracy and deepening insights into age-related brain changes.

Should rTMS be considered a first-line treatment for major depressive episodes in adults?

Treatment-resistant depression (TRD) is an epidemic with rising social, economic, and political costs. In a patient whose major depressive episode (MDE) persists through an adequate antidepressant trial, insurance companies often cover alternative treatments which may include repetitive transcranial magnetic stimulation (rTMS). RTMS is an FDA-cleared neuromodulation technique for TRD which is safe, efficacious, noninvasive, and well-tolerated. Recent developments in the optimization of rTMS algorithms and targeting have increased the efficacy of rTMS in treating depression, improved the clinical convenience of these treatments, and decreased the cost of a course of rTMS. In this opinion paper, we make a case for why conventional FDA-cleared rTMS should be considered as a first-line treatment for all adult MDEs. RTMS is compared to other first-line treatments including psychotherapy and SSRIs. These observations suggest that rTMS has similar efficacy, fewer side-effects, lower risk of serious adverse events, comparable compliance, the potential for more rapid relief, and cost-effectiveness. This suggestion, however, would be strengthened by further research with an emphasis on treatment-naive subjects in their first depressive episode, and trials directly contrasting rTMS with SSRIs or psychotherapy.

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

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

Identifying functional cortical plasticity after spinal tumour resection using navigated transcranial magnetic stimulation.

Our aim was to investigate the effectiveness of navigated transcranial magnetic stimulation (nTMS) brain mapping to characterise preoperative motor impairment caused by an intradural extramedullary (IDEM) tumour and postoperative cortical functional reorganisation. Preoperative and 1-year follow-up clinical, radiological and nTMS data from a case of thoracic spinal meningioma that underwent surgical resection of the lesion were collected and compared. A 67-year-old patient presented with severe progressive thoracic myelopathy (hypertonic paraparesis, clonus, insensate urinary retention) secondary to an IDEM tumour. Initial nTMS assessment showed bilateral upper limb representation with no positive responses for both lower limbs. He underwent successful surgical resection for his IDEM (meningioma WHO grade 1). At 1-year follow-up, the patient's gait was improved and his bladder function normalised. nTMS documented positive responses for both upper and lower limbs and a decrease in the area (right side: 1.01 vs 0.39cm2; left side: 1.92 vs 0.81cm2) and volume (right side: 344.2 vs 42.4uVcm2; left side: 467.1 vs 119uVcm2) of cortical activation for both upper limbs, suggesting a functional reorganisation of the motor areas after tumour resection. nTMS motor mapping and derived metrics can characterise preoperative motor deficit and cortical plasticity during follow-up after IDEM resection.

A comparison of techniques to determine active motor threshold for transcranial magnetic stimulation research.

The determination of active motor threshold (AMT) is a critical step in transcranial magnetic stimulation (TMS) research. As AMT is frequently determined using an absolute electromyographic (EMG) threshold (e.g., 200 µV peak-to-peak amplitude), wide variation in EMG recordings across participants has given reason to consider relative thresholds (e.g., = 2 × background sEMG) for AMT determination. However, these approaches have not been systemically compared. Our purpose was to compare AMT estimations derived from absolute and relative criteria commonly used in the quadriceps, and assess the test-retest reliability of each approach. We used a repeated measures design to assess AMT estimations in the vastus lateralis (VL) from eighteen young adults (9 males and 9 females; mean ± SD age = 23 ± 2 years) across two laboratory visits. AMT was determined for each criterion, at each lab visit. A paired samples t-test was used to compare mean differences in AMT estimations during the second laboratory visit. Paired samples t-tests and intraclass correlation coefficients (ICC2,1) were calculated to assess test-retest reliability of each criterion. Differences between the criteria were small and not statistically significant (p = 0.309). The absolute criterion demonstrated moderate to excellent reliability (ICC2,1 = 0.866 [0.648-0.950]), but higher AMTs were observed in the second visit (p = 0.043). The relative criteria demonstrated good-to-excellent test-retest reliability (ICC2,1 = 0.894 [0.746-0.959]) and AMTs were not different between visits (p = 0.420). TMS researchers aiming to track corticospinal characteristics across visits should consider implementing relative criterion approaches during their AMT determination protocol.

A neural signature for brain compensation in stroke with EEG and TMS: Insights from the DEFINE cohort study.

OBJECTIVE: This study aimed to explore the relationships between potential neurophysiological biomarkers and upper limb motor function recovery in stroke patients, specifically focusing on combining two neurophysiological markers: electroencephalography (EEG) and transcranial magnetic stimulation (TMS). METHODS: This cross-sectional study analyzed neurophysiological, clinical, and demographical data from 102 stroke patients from the DEFINE cohort. We searched for correlations of EEG and TMS measurements combined to build a prediction model for upper limb motor functionality, assessed by five outcomes, across five assessments: Fugl-Meyer Assessment (FMA), Handgrip Strength Test (HST), Finger Tapping Test (FTT), Nine-Hole Peg Test (9HPT), and Pinch Strength Test (PST). RESULTS: Our multivariate models agreed on a specific neural signature: higher EEG Theta/Alpha ratio in the frontal region of the lesioned hemisphere is associated with poorer motor outcomes, while increased MEP amplitude in the non-lesioned hemisphere correlates with improved motor function. These relationships are held across all five motor assessments, suggesting the potential of these neurophysiological measures as recovery biomarkers. CONCLUSION: Our findings indicate a potential neural signature of brain compensation in which lower frequencies of EEG power are increased in the lesioned hemisphere, and lower corticospinal excitability is also increased in the non-lesioned hemisphere. We discuss the meaning of these findings in the context of motor recovery in stroke.

Efficacy of MRI-guided rTMS for post-traumatic stress disorder by modulating amygdala activity: study protocol for a randomised controlled trial.

INTRODUCTION: Post-traumatic stress disorder (PTSD) is a prevalent and severe psychiatric disorder. Repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex provides limited relief for symptoms of PTSD. This study will be conducted to validate the efficacy of MRI-guided rTMS in targeting the sites most closely associated with the amygdala for patients with PTSD. We hypothesise that the intervention will improve clinical symptoms by decreasing amygdala activity in patients. METHODS AND ANALYSIS: A randomised, double-blind, sham-controlled trial will be conducted. Forty-eight eligible patients with PTSD will be randomly assigned to receive either active or sham MRI-guided rTMS for 10 consecutive days after the initial MRI scans. MRI scans will be recollected at the end of the intervention. Clinical assessments will be performed at baseline, treatment day 5, treatment day 10, and 2 weeks, 4 weeks, 8 weeks after completion of the intervention to monitor changes in clinical symptoms. The primary assessment outcome is the change in PTSD symptoms between baseline and treatment day 10, as measured by the PTSD Checklist for DSM-5. Repeated measures analysis of variance will be performed using statistical software SPSS V.26.0. The significance level will be set at 0.05. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of Xijing Hospital in Xi'an, China (KY20222176-X-1), and the trial has been registered on ClinicalTrials.gov. The findings of this trial will be disseminated at academic conferences or published in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT05544110.

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

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

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

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

Resection of meningiomas located in motor eloquent areas - comparative analysis of navigated transcranial magnetic stimulation and conventional neuronavigation.

BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) has been established as a preoperative diagnostic procedure in glioma surgery, increasing the extent of resection and preserving functional outcome. nTMS motor mapping for the resection of motor eloquent meningiomas has not been evaluated in a comparative analysis, yet. METHODS: We conducted a retrospective matched-pair analysis for tumor location and size in meningioma patients with tumors located over or close to the primary motor cortex. Half of the study population received nTMS motor mapping preoperatively (nTMS-group). The primary endpoint were permanent surgery-related motor deficits. Additional factors associated with new motor deficits were evaluated apart from nTMS. RESULTS: 62 patients (mean age 62 ± 15.8 years) were evaluated. 31 patients received preoperative nTMS motor mapping. In this group, motor thresholds (rMT) corresponded with tumor location and preoperative motor status, but could not predict motor outcome. No patient with preoperative intact motor function had a surgery-related permanent deficit in the nTMS group whereas four patients in the non-TMS group with preoperative intact motor status harbored from permanent deficits. 13 patients (21.3%) had a permanent motor deficit postoperatively with no difference between the nTMS and the non-TMS-group. Worsening in motor function was associated with higher patient age (p = 0.01) and contact to the superior sagittal sinus (p = 0.027). CONCLUSION: nTMSmotor mapping did not lead to postoperative preservation in motorfunction. nTMS data corresponded well with the preoperative motorstatus and were associated with postoperative permanent deficits if tumors were located over the motor hotspot according to nTMS.

Noninvasive transcranial brain stimulation in central post-stroke pain: A systematic review.

BACKGROUND: The aim of this systematic review is to analyze the efficacy of noninvasive brain stimulation (NBS) in the treatment of central post-stroke pain (CPSP). METHODS: We included randomized controlled trials testing the efficacy of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation versus placebo or other usual therapy in patients with CPSP. Articles in English, Portuguese, Spanish, Italian, and French were included. A bibliographic search was independently conducted on June 1, 2022, by two authors, using the databases MEDLINE (PubMed), Embase (Elsevier), Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science Core Collection. The risk of bias was assessed using the second version of the Cochrane risk of bias (RoB 2) tool and the certainty of the evidence was evaluated through Grading of Recommendations Assessment, Development and Evaluation. RESULTS: A total of 2,674 records were identified after removing duplicates, of which 5 eligible studies were included, involving a total of 119 patients. All five studies evaluated repetitive TMS, four of which stimulated the primary motor cortex (M1) and one stimulated the premotor/dorsolateral prefrontal cortex. Only the former one reported a significant pain reduction in the short term, while the latter one was interrupted due to a consistent lack of analgesic effect. CONCLUSION: NBS in the M1 area seems to be effective in reducing short-term pain; however, more high-quality homogeneous studies, with long-term follow-up, are required to determine the efficacy of this treatment in CSPS.

Efficacy of Cerebellar Transcranial Magnetic Stimulation in Treating Essential Tremor: A Randomized, Sham-Controlled Trial.

BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) of the cerebellar hemisphere represents a new option in treating essential tremor (ET) patients. We aimed to determine the efficacy of cerebellar rTMS in treating ET using different protocols regarding the number of sessions, exposure duration, and follow-up duration. METHODS: A randomized sham-controlled trial was conducted, in which 45 recruit patients were randomly allocated to 2 groups. The first (active group) comprised 23 patients who were exposed to 12 sessions of active rTMS with 900 pulses of 1-Hz rTMS at 90% of the resting motor threshold daily on each side of the cerebellar hemispheres over 4 weeks. The second group (sham group) comprised 22 patients who were exposed to 12 sessions of sham rTMS. Both groups were reassessed at baseline and after 1 day, 1 month, 2 months, and 3 months using the Fahn-Tolosa-Marin tremor-rating scale (FTM). RESULTS: Demographic characteristics did no differ between the two groups. There were significant reductions both in FTM subscores A and B and in the FTM total score in the active-rTMS group during the period of assessment and after 3 months (p=0.031 and 0.011, respectively). However, subscore C did not change significantly from baseline when assessed at 2 and 3 months (p=0.073 and 0.236, respectively). Furthermore, the global assessment score was significantly higher in the active-rTMS group (p>0.001). CONCLUSIONS: Low-frequency rTMS over the cerebellar cortex for 1 month showed relative safety and long-lasting efficacy in patients with ET. Further large-sample clinical trials are needed that include different sites of stimulation and longer follow-ups.

Objective sleep enhancement in Parkinson's disease: A sham-controlled trial of low-frequency repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex.

INTRODUCTION: Parkinson's disease (PD) is often accompanied by sleep disturbances, impacting patients' quality of life. While repetitive transcranial magnetic stimulation (rTMS) shows promise in improving self-reported sleep quality, its effects on objective sleep architecture in PD remain understudied. Sleep disturbances, including rapid eye movement (REM) and slow-wave sleep disturbances, correlate with cognitive decline and motor symptoms. This study investigated the effect of low-frequency rTMS targeting the right dorsolateral prefrontal cortex (DLPFC) modifying objective sleep architecture and explored symptom improvement mechanisms in PD patients. METHODS: In this randomized, double-blind, sham-controlled trial, 67 PD patients received 10 consecutive days of 1-Hz rTMS over the right DLPFC. Polysomnography assessed sleep microstructure, while electroencephalogram recordings evaluated power spectral density and sleep spindle activity. Clinical scales measured sleep quality, motor symptoms, and cognition at baseline, post-treatment, and 3 months post-rTMS. RESULTS: The rTMS group exhibited improvements in sleep quality, motor symptoms, and cognition post-treatment, persisting at the 3-month follow-up. There was a notable increase in the REM sleep proportion post-rTMS. The rTMS group exhibited elevated low-frequency (0.5-2 Hz) slow-wave electroencephalogram spectral density during non-REM sleep. Cognitive enhancement correlated with increased lower delta power, while motor symptom progression correlated with spindle frequency and slow-wave sleep percentage changes. CONCLUSION: Low-frequency rTMS targeting the right DLPFC holds promise for improving clinical symptoms and modulating sleep architecture in PD. These findings suggest a link between symptom improvement and sleep structure enhancement, highlighting the need for further investigation into the therapeutic potential of rTMS in PD management.

Permutation conditional mutual information to quantify TMS-evoked cortical connectivity in disorders of consciousness.

OBJECTIVE: To improve the understanding and diagnostic accuracy of disorders of consciousness (DOC) by quantifying transcranial magnetic stimulation evoked electroencephalography (TMS-EEG) connectivity using Permutation Conditional Mutual Information (PCMI). Approach: PCMI can characterize the functional connectivity between different brain regions. This study employed PCMI to analyze TMS-evoked cortical connectivity (TEC) in 154 DOC patients and 16 normal controls, focusing on optimizing parameter selection for PCMI (Data length, Order length, Time delay). We compared short-range and long-range PCMI values across different consciousness states-unresponsive wakefulness syndrome (UWS), minimally conscious state (MCS), and normal (NOR)-and assessed various feature selection and classification techniques to distinguish these states. Main Results: 1) PCMI can quantify TEC. We found optimal parameters to be Data length: 500ms; Order: 3; Time delay: 6ms. 2) TMS evoked potentials (TEP) for NOR showed a rich response, while MCS patients showed only a few components, and UWS patients had almost no significant components. The values of PCMI connectivity metrics demonstrated its usefulness for measuring cortical connectivity evoked by TMS. From NOR to MCS to UWS, the number and strength of TEC decreased. Quantitative analysis revealed significant differences in the strength and number of TEC in the entire brain, local regions and inter-regions among different consciousness states. 3) A decision tree with feature selection by mutual information performed the best (balanced accuracy: 87.0% and accuracy: 83.5%). This model could accurately identify NOR (100.0%), but had lower identification accuracy for UWS (86.5%) and MCS (74.1%). Significance: The application of PCMI in measuring TMS-evoked connectivity provides a robust metric that enhances our ability to differentiate between various states of consciousness in DOC patients. This approach not only aids in clinical diagnosis but also contributes to the broader understanding of cortical connectivity and consciousness. .

[Acupuncture combined with repeated transcranial magnetic stimulation for mild to moderate post-stroke depression: a randomized controlled trial].

OBJECTIVE: To explore the clinical effect of acupuncture combined with repeated transcranial magnetic stimulation (rTMS) for mild to moderate post-stroke depression. METHODS: Ninety patients with mild to moderate post-stroke depression were randomly divided into a combination group (30 cases, 4 cases dropped out), an acupuncture group (30 cases, 3 cases dropped out) and a rTMS group (30 cases, 5 cases dropped out). All the three groups received basic treatment, the combination group was treated with acupuncture combined with rTMS, the acupuncture group was treated with acupuncture, and the rTMS group was treated with rTMS. The acupuncture was applied at Baihui (GV 20), Yintang (GV 24+) , Danzhong (CV 17) and bilateral Shenmen (HT 7), Taichong (LR 3), Neiguan (PC 6). All the three groups were treated once a day, 5 times a week for 4 weeks. The Hamilton depression scale (HAMD-17) score, Pittsburgh sleep quality index (PSQI) score and event-related potential were compared among the three groups before and after treatment. RESULTS: After treatment, the HAMD-17 scores and PSQI scores in the three groups were reduced compared with those before treatment (P<0.01) , and the HAMD-17 score and PSQI score in the combination group were lower than those in the acupuncture group and the rTMS group (P<0.05). After treatment, the latency of event-related potential (P300, mismatch negativityï¼»MMNï¼½) in the three groups was shortened compared with that before treatment (P<0.05), and the latency of event-related potential in the combination group was shorter than that in the acupuncture group and the rTMS group (P<0.05). CONCLUSION: Acupuncture combined with rTMS can effectively alleviate the depressive state of patients with mild to moderate post-stroke depression, improve the sleep quality and the latency of event-related potential P300 and MMN.