Effects Of Transcranial Magnetic Stimulation Research Articles

Neuromodulation in Behavioral and Psychological Symptoms of Dementia (BPSD)

Behavioral and psychological symptoms of dementia (BPSD) affect up to 90% of people living with dementia and include agitation, hallucinations, delusions, sleep or mood changes. BPSD are challenging to treat and there are limited safe and effective pharmacologic treatments. Electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), Deep Brain Stimulation (DBS), Vagal nerve stimulation (VNS), ketamine, and cannabinoids are interventions that have proven effectiveness for other psychiatric conditions including depression and psychosis. More recently, many of these have also been investigated for the treatment of BPSD.This presentation will review the current evidence for using ECT, TMS, ketamine, DBS, VNS, and cannabinoids for the treatment of BPSD. Out of these techniques, ECT has been the most studied and shows some benefit for the treatment of BPSD. TMS has also been studied in over 10 trials and most of these studies show an improvement in BPSD. The effect of TMS on apathy in dementia has been examined in multiple studies, the majority of which have shown benefit. DBS has shown some benefit for improving hallucinations in Parkinson disease dementia in one small RCT of six patients, and the procedure was well tolerated. VNS for BPSD has not been studied. Ketamine, in evidence from heterogeneous case reports, has shown to target three distinct behavioral disturbances, agitation, catatonia and depression, in dementia.Cannabinoids, particularly dronabinol and nabilone, have also been investigated in a number of RCTs and show mixed results for treating agitation in dementia. Sedation was the most common side effect reported but often did not result in discontinuation of therapy.In conclusion, neuromodulation has increasing evidence for the treatment of BPSD and most studies show good safety profiles. Larger and more rigorous trials are needed to further investigate the effectiveness, safety, and practicality of these interventions in this population. This presentation will summarize the effects of these various interventions, their side effects, doses used, and durations of treatment.

Chronometric TMS-fMRI of personalized left dorsolateral prefrontal target reveals state-dependency of subgenual anterior cingulate cortex effects.

Transcranial magnetic stimulation (TMS) applied to a left dorsolateral prefrontal cortex (DLPFC) area with a specific connectivity profile to the subgenual anterior cingulate cortex (sgACC) has emerged as a highly effective non-invasive treatment option for depression. However, antidepressant outcomes demonstrate significant variability among therapy plans and individuals. One overlooked contributing factor is the individual brain state at the time of treatment. In this study we used interleaved TMS-fMRI to investigate the influence of brain state on acute TMS effects, both locally and remotely. TMS was performed during rest and during different phases of cognitive task processing. Twenty healthy participants were included in this study. In the first session, imaging data for TMS targeting were acquired, allowing for identification of individualized targets in the left DLPFC based on highest anti-correlation with the sgACC. The second session involved chronometric interleaved TMS-fMRI measurements, with 10 Hz triplets of TMS administered during rest and at distinct timings during an N-back task. Consistent with prior findings, interleaved TMS-fMRI revealed significant BOLD activation changes in the targeted network. The precise timing of TMS relative to the cognitive states during the task demonstrated distinct BOLD response in clinically relevant brain regions, including the sgACC. Employing a standardized timing approach for TMS using a task revealed more consistent modulation of the sgACC at the group level compared to stimulation during rest. In conclusion, our findings strongly suggest that acute local and remote effects of TMS are influenced by brain state during stimulation. This study establishes a basis for considering brain state as a significant factor in designing treatment protocols, possibly improving TMS treatment outcomes.

The Use of Cognitive Paired Associative Stimulation (C-PAS) in Investigating and Remediating the Effects of Sleep Deprivation on Working Memory in Humans: The Importance of State-Dependency

Abstract Purpose of Review Sleep deprivation is a global health issue, and the resultant cognitive deficits can be debilitating. A series of studies reported success with individually neuronavigated transcranial magnetic stimulation (TMS), coupled with online task performance, in substantially reducing performance deficits in working memory in healthy adults caused by 2 days of total sleep depression. This paradigm of coupling TMS with online task performance has been referred to as Cognitive Paired Associative Stimulation (C-PAS). This review describes those studies and the research since using various TMS paradigms to remediate working memory deficits in sleep deprivation. Recent Findings Three such studies were found, but none replicated the earlier findings. However, in each case, there were differences in study design that might explain the negative findings and inform future methodological choices and to underline the need to combine TMS with brain imaging guidance. Summary Online task performance during TMS, as done in the C-PAS paradigm, appears to be essential to demonstrating lasting remediation of working memory deficits induced by sleep deprivation. This observation highlights the importance of state-dependency in determining the effects of TMS. Further work needs to be done to clarify the potential role of C-PAS in alleviating the effects of sleep deprivation and studying cognitive processes affected by sleep.

A meta-analysis of transcranial magnetic stimulation in Tourette syndrome

There is growing enthusiasm for the treatment of neuropsychiatric disorders using neuromodulation. While some reports claim that transcranial magnetic stimulation (TMS) can be used to treat Tourette Syndrome (TS), little research exists to support this assertion. This meta-analysis examined the efficacy of TMS to reduce tic severity in patients with TS. Additionally, it explored the effect of TMS to reduce premonitory urge severity—the primary mechanism implicated in the frontline evidence-based treatment of TS. Five treatment comparisons were selected using PRISMA guidelines. All studies included were required to be (1) a randomized controlled trial, (2) compare TMS to a sham condition, and (3) have all participants meet diagnostic criteria for a persistent tic disorder and/or TS. A random effects model meta-analysis examined the efficacy of using TMS to reduce tic severity and explored the effect of TMS to reduce premonitory urge severity. TMS did not significantly reduce tic severity (g = 0.44; 95% CI = −0.17, 1.05; z = 1.40; p = 0.16), but a moderate reduction in premonitory urge severity was found (g = 0.63; 95% CI = 0.9, 1.17; z = 2.27; p < 0.02). Trials with larger sample sizes and a preponderance of women were found to have greater therapeutic effects of TMS for tic severity. There is limited support for the use of TMS to reduce tic severity, though reductions in premonitory urge severity were observed. Major limitations of the existing literature are examined, with a call for research investigating newer TMS protocols and their use as a treatment augmentation strategy.

Computational simulation of transcranial magnetic stimulation-induced electric fields in the dorsolateral prefrontal cortex of heavy cannabis using individuals

We aimed to investigate the influence of demographic and clinical modulators on the strength of transcranial magnetic stimulation (TMS)-induced electric fields (EFs) in the left dorsolateral prefrontal cortex (lDLPFC) in heavy cannabis using individuals. Structural T1-weighted magnetic resonance imaging scans of 20 heavy cannabis using individuals and 22 non-cannabis users (the controls) in the age range of 18–25 were retrieved. Computational simulations of TMS-induced EFs in the lDLPFC were performed. No significant difference in the strength of TMS-induced EFs was observed between heavy cannabis using individuals and the controls. A negative correlation between the scalp-to-cortex distance demonstrated and the strength of the induced EFs. The severity of cannabis use related problems did not correlate with the induced EFs in the lDLPFC of heavy cannabis using individuals. However, the severity of alcohol use related problems was negatively correlated with the induced EF in the lDLPFC localized by the 5-cm method in the whole sample. Early adulthood seems related to an increase in the induced EFs in the lDLPFC. In conclusion, the dominant factor influencing TMS-induced EFs was the scalp-to-cortex distance. In early adulthood, the interaction between age and comorbid substance use may influence with the magnitude of TMS-induced EFs, thereby complicating the treatment effect of TMS in young people with substance use disorders.

Effects of transcranial magnetic stimulation on the human brain recorded with intracranial electrocorticography.

Transcranial magnetic stimulation (TMS) is increasingly used as a noninvasive technique for neuromodulation in research and clinical applications, yet its mechanisms are not well understood. Here, we present the neurophysiological effects of TMS using intracranial electrocorticography (iEEG) in neurosurgical patients. We first evaluated safety in a gel-based phantom. We then performed TMS-iEEG in 22 neurosurgical participants with no adverse events. We next evaluated intracranial responses to single pulses of TMS to the dorsolateral prefrontal cortex (dlPFC) (N = 10,1414 electrodes). We demonstrate that TMS is capable of inducing evoked potentials both locally within the dlPFC and in downstream regions functionally connected to the dlPFC, including the anterior cingulate and insular cortex. These downstream effects were not observed when stimulating other distant brain regions. Intracranial dlPFC electrical stimulation had similar timing and downstream effects as TMS. These findings support the safety and promise of TMS-iEEG in humans to examine local and network-level effects of TMS with higher spatiotemporal resolution than currently available methods.

Efficacy of Cerebellar Transcranial Magnetic Stimulation for Post-stroke Balance and Limb Motor Function Impairments: Meta-analyses of Random Controlled Trials and Resting-State fMRI Studies.

This study aimed to investigate the potential therapeutic effects of cerebellar transcranial magnetic stimulation (TMS) on balance and limb motor impairments in stroke patients. A meta-analysis of randomized controlled trials was conducted to assess the effects of cerebellar TMS on balance and motor impairments in stroke patients. Additionally, an activation likelihood estimation (ALE) meta-analysis was performed on resting-state functional magnetic resonance imaging (fMRI) studies to compare spontaneous neural activity differences between stroke patients and healthy controls using measures including the amplitude of low frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo). The analysis included 10 cerebellar TMS studies and 18 fMRI studies. Cerebellar TMS treatment demonstrated significant improvements in the Berg Balance Scale score (p < 0.0001) and the Fugl-Meyer Assessment lower extremity score (p < 0.0001) compared to the control group in stroke patients. Additionally, spontaneous neural activity alterations were identified in motor-related regions after stroke, including the precentral gyrus, putamen, thalamus, and paracentral lobule. Cerebellar TMS shows promise as a therapeutic intervention to enhance balance and lower limb motor function in stroke patients. It is easy for clinical application and addresses the limitations of insufficient direct stimulation depth on the leg area of the cortex. However, further research combining neuroimaging outcomes with clinical measurements is necessary to validate these findings.

A Generalized Cortico-Muscular-Cortical Network to Evaluate the Effects of Three-Week Brain Stimulation.

Post-stroke transcranial magnetic stimulation (TMS) has gradually become a brain intervention to assist patients in the recovery of motor function. The long lasting regulatory of TMS may involve the coupling changes between cortex and muscles. However, the effects of multi-day TMS on motor recovery after stroke is unclear. This study proposed to quantify the effects of three-week TMS on brain activity and muscles movement performance based on a generalized cortico-muscular-cortical network (gCMCN). The gCMCN-based features were further extracted and combined with the partial least squares (PLS) method to predict the Fugl-Meyer of upper extremity (FMUE) in stroke patients, thereby establishing an objective rehabilitation method that can evaluate the positive effects of continuous TMS on motor function. We found that the improvement of motor function after three-week TMS was significantly correlated with the complexity trend of information interaction between hemispheres and the intensity of corticomuscular coupling. In addition, the fitting coefficient ([Formula: see text]) for predicted and actual FMUE before and after TMS were 0.856 and 0.963, respectively, suggesting that the gCMCN-based measurement may be a promising method for evaluating the therapeutic effect of TMS. From the perspective of a novel brain-muscles network with dynamic contraction as the entry point, this work quantified TMS-induced connectivity differences while evaluating the potential efficacy of multi-day TMS. It provides a unique insight for the further application of intervention therapy in the field of brain diseases.

Novel multi-magnetic material transcranial magnetic stimulation coils for small animals application

Transcranial magnetic stimulation (TMS) is a non-invasive therapeutic approach with proven efficacy in treating certain psychiatric and neurological disorders. To broaden the application of TMS to a wider range of neurological disorders, the induced electric field (e-field) must be able to more focally target specific regions of the brain. Animal coil designs are promising for studying TMS effects and developing new procedures for treating various neurological and psychiatric disorders. However, investigations have mostly used coil designs intended for humans, and, as such, have failed to scale down for small animal sizes. Currently available coil systems have been limited by not adequately incorporating ideal soft magnetic materials as coil cores and not advancing the coil shapes for small animals as is necessary to achieve highly focused e-field concentration. In this study, we used multi-magnetic materials in TMS coils for the first time to our knowledge. We also considered the non-linear, hysteretic behavior of the cores in our FEM simulations of induced e-field and magnetic field in the brain models of the rat. Our study involved a comprehensive assessment of the distribution and intensity of the e-field across various coil configurations using our customized anatomically accurate rat head model. Iron-cobalt-vanadium (Permendur) alloy known for its high relative permeability, high saturation magnetization and low coercivity was used as the core material for all simulations. To enhance coil focality and concentration of the e-field, while avoiding stimulation of adjacent regions, we introduced a shape-conforming, flexible, diamagnetic pyrolytic graphite with susceptibility of -4.5×10-4 for our top performing coil. Simulation results were validated by comparing the simulated magnetic field results with experimental measurements obtained from the v-tip coil with a carbon steel AISI-1010 core at varying tip distances. This thorough study advances our knowledge of TMS coil designs and their optimization, particularly for small animal applications.

A Meta-Analysis of the Effectiveness of Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation as Therapy of Insomnia

Objective: Insomnia serves as the most common sleep disorder. Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are amongst most popular treatment for insomnia. This research aimed to determine the comparative effectiveness of TMS and tDCS as therapies for insomnia.Methods: PubMed/MEDLINE, ScienceDirect, Google Scholar, ResearchGate, Wiley Library Online, and Neurona were used to search for randomized controlled trials (RCTs) comparing TMS/tDCS with sham group in insomnia. Meta-analysis was done to determine the effectiveness of TMS and tDCS as a therapy for insomnia. Weighted mean difference were computed and reported with its 95% CI. Heterogeneity was reported with I&lt;sup&gt;2&lt;/sup&gt;. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Subjective pooled-analysis was done using Mann-Whitney U test with p&lt;0.05.Results: From a total 1,000 publications, 15 studies were included, revealing varying types of insomnia as follows: 26.7% comorbid depression, 13.3% comorbid pain, 13.3% involving athletes, 13.3% primary insomnia, 6.7% due to medication, 6.7% comorbid polio, 6.7% comorbid Sjogren’s syndrome, 6.7% comorbid stroke, and 6.7% comorbid Parkinson’s disease. From 15 studies, four homogenous articles were made for pooled-analyses, which included two studies on TMS and two studies on tDCS in insomnia comorbid depression. tDCS improved sleep onset latency, N2, and REM latency better than sham. TMS (2.29, 95% CI: 1.82–2.76) was superior to sham in improving the subjective quality of sleep, and tDCS (1.05, 0.68–1.43) with p=0.121.Conclusion: No significant differences were found between TMS and tDCS as therapies for insomnia. Most RCTs studying TMS/tDCS in insomnia reported high comorbidity with depression.

Effectiveness of Transcranial Magnetic Stimulation in Patients after Ischemic Stroke: a Prospective Study

INTRODUCTION. Despite the fact that a large number of studies are focused on the rehabilitation of patients with ischemic stroke in the early recovery period, currently, much attention is paid to improving existing and developing new technologies in neurorehabilitation at the early stages of the disease. Transcranial magnetic stimulation (TMS) is a promising technology for the rehabilitation and recovery of patients with movement disorders after a stroke, which has a direct effect on the premotor cortex of the brain.&#x0D; AIM. To assess the effectiveness of TMS in relation to daily activity in a comprehensive medical rehabilitation program in patients with ischemic stroke in the early recovery period.&#x0D; MATERIALS AND METHODS. The study included 124 patients aged 55–75 years (53.2 % men and 46.8 % women). The main group included 64 people who received the TMS procedure. The comparison group included 60 patients who received an identical course of treatment, but instead of TMS, they underwent a low-intensity headband magnetic therapy. Treatment effectiveness was assessed using the Rivermead Mobility Index, Rehabilitation Routing Scales, and NIHSS. The severity of anxiety and depressive symptoms was assessed using the HADS scale. The total duration of treatment was 21 days. The dynamics of the patients’ condition was assessed before the start of treatment, 21 days after the course of rehabilitation and 3 months after the start of treatment.&#x0D; RESULTS. The main group showed a significant decrease in neurological deficit according to the NIHSS scale from 15.3 ± 3.6 to 10.1 ± 1.7 (p 0.05), Rivermead Mobility Index decreased from 5.6 ± 1.9 to 10.5 ± 2.4 (p 0.05) and Rehabilitation Routing Scale decreased from 4.3 ± 0.8 to 2.5 ± 0.5 points (p 0.05) since the start of rehabilitation and 3 months after its start. After 3 months, the neurological deficit in the main group was statistically significantly less compared to patients in the comparison group (p 0.5). A significant decrease in depressive symptoms was found in the main group (χ2 = 28.641; p 0.001), while in the control group the dynamics was not significant (χ2 = 7.140; p = 0.129); in addition, there was a regression of the anxiety component both in the main (χ2 = 47.949; p 0.001) and control (χ2 = 12.483; p = 0.015) groups.&#x0D; CONCLUSION. The use of the TMS device at the second stage of rehabilitation significantly reduces the neurological deficit, increases the mobility of patients, and reduces the severity of anxiety and depressive symptoms.

Effects of transcranial magnetic stimulation on cortical structures during motor imagination performance in the brain-computer interface

The aftermath of a stroke can frequently result in impaired motor functions causing problems performing habitual limb movements. These movement disorders stem from damage to the cerebral cortex and disruptions to neuronal connections in the central pyramidal pathways [1]. Restoring motor skills following a stroke is a time-consuming and challenging process, requiring resources from both external medical sources and the patient. Despite these challenges, it is still feasible for patients to regain control over their limb movements. The common approach for stroke neurorehabilitation consists of therapeutic physical activities and kinesiotherapy. These methods rely on afferent information during motor tasks to repair connections between intact brain areas [2]. Through exercising the impacted limbs, synaptic rearrangement happens in the cortex, awakening dormant neurons and increasing cortical areas adjacent to inactive regions. Although these techniques can partially restore movement, a significant number of stroke patients still face impairments. It is crucial to acknowledge the limitations of the current interventions and explore new approaches for better outcomes. Traditional rehabilitation methods often do not fully restore movement control, prompting researchers to explore alternative approaches. Motor-imagery-based brain-computer interfaces (BCIs) have gained attention recently [3, 4]. They allow for integrating various feedback mechanisms, which can be combined with upper and lower limb exoskeletons. The level of control a subject has over a BCI system directly affects the recovery process [5]. Introducing transcranial magnetic stimulation (TMS) into motor-imagery BCIs shows promise for developing a unified and highly efficient approach to post-stroke rehabilitation. Twenty-nine healthy adult participants (21 females) with a mean age of 20.93±2.14 years were recruited for this experiment. All participants were right-handed and had no prior experience with brain-computer interfaces. Ethical approval was obtained from the local ethics committee of Lobachevsky State University of Nizhny Novgorod (ethical approval No. 2, dated 03/19/2021), and written informed consent was obtained from all participants. Subjects were randomly assigned to receive either a sham intervention (n=15) or active TMS (n=14). The experiment displayed tasks on a 24-inch LCD screen placed 2 meters away. Participants sat in a reclining chair with hands on adjustable armrests for EEG signal recording. Motor-imagery-based BCI training took place over two days with four daily tasks: motor performance, quasi-motor, and two motor imaginations of the dominant hand. EEG activity was recorded prior to and after completing the tasks. Each task comprised of 20 trials, each lasting 10 seconds. TMS was administered in between two motor imagination tasks, and a rest period of 2 minutes followed the stimulation. The researcher objectively monitored electromyography (EMG) in real-time during motor tasks. Certified NVX 52 amplifiers with 32 Cl/Ag electrodes positioned according to the international 10-10 system recorded electroencephalography (EEG) signals. The EEG was digitized at a sampling rate of 1000 Hz and filtered with a 50 Hz Notch filter. Disposable electrodes were used to record EMG data from musculus flexor digitorum superficialis on the right hand. EMG signals were digitized at 1000 Hz and filtered using a 50 Hz Notch filter. TMS was applied to the dorsolateral prefrontal cortex (dlPFC) using a figure-8 coil connected to a Neuro MS/D magnetic stimulator. Sham stimulation was performed with the same parameters, except the coil was tilted 90 degrees to simulate the sound of real stimulation. A nonparametric permutation test was conducted to assess the statistically significant dissimilarities between rest periods and periods subsequent to conducting motor imagery after TMS. Significant clusters of the highest event-related desynchronization (ERD) were observed. The analysis demonstrated a significant negative cluster in the theta rhythm (0–6 Hz) that was distinct from the magnetic stimulation site. Similar significant ERD clusters were identified during the first and second series of imaginary movements. The study examined alterations in motor cortex function following targeted rTMS. The results demonstrated that TMS using particular parameters resulted in the pre-activation of brain regions comparable to those stimulated during motor imagery. The implementation of this stimulation protocol increased activity in cortical regions related to motor imagery. The outcomes propose the probable effectiveness of TMS in elevating motor cortex activation during the rehabilitation process.

FC24: Transcranial Magnetic Stimulation (TMS) as a Treatment for Dementia due to non-Alzheimer’s disease (non-AD): What is the Evidence?

Objective:There is no cure for dementia due to non-Alzheimer’s disease (non-AD), and current treatments are symptomatic. Noninvasive brain stimulation therapies such as transcranial magnetic stimulation (TMS) are increasingly being investigated to improve cognitive function in dementia. We conducted a systematic review to investigate the effectiveness of TMS on cognition in non-AD dementia.Methods:Comprehensive search of databases (Medline, Embase, Cochrane, APA PsycINFO, Web of Science, and Scopus) from 2000 to February 2023 using keywords related to TMS and dementia (PROSPERO, CRD42022326423). Here we report outcomes from randomized controlled trials (RCTs) of TMS on non-AD dementia populations.Results:In total, 20 RCTs comprised of 660 patients, mean age 62 years (range 46-71). Diagnostic groups include stroke (n=8), Parkinson’s disease (n=6), Frontotemporal dementia (n=3), Huntington’s disease (n=2) and Progressive non-fluent aphasia (n=1). The most common site of stimulation was left (L) dorsolateral prefrontal cortex (DLPFC, n=13); other sites were primary motor cortex (n=2); Right (R) Broca's area, Brodmann area, Contralesional pars triangularis, R Inferior Frontal Gyrus (IFG) (all n=1); and multiple sites in 1 RCT (L and R IFG, L superior frontal gyrus, L DLPFC, L and R right anterior temporal lobe, supplementary motor area, anterior cingulate, and vertex). Studies used both low (1Hz, n=5) and high (50Hz, n=5) frequencies, or other high (5Hz, 10Hz, 20Hz) or combination low/high frequencies. Frequent duration of treatment was 10 days (n=7), range 1-40. Of 20 studies, 19 (95%) demonstrated improvement of global cognition (on MoCA, MMSE) and specific cognitive domains (learning and memory, language, executive function, problem-solving, attention, reaction time). The only RCT with no effect utilized a single session intermittent theta burst stimulation on the LDLPFC on PD patients. Adverse events in 7 studies included headaches (most common), dull skull pain, dizziness, insomnia, fatigue, anxiety, temporary decrease in hearing, and temporary decreased mental clarity.Conclusion:There is favorable evidence that rTMS improves global and specific cognitive domains in non-AD dementia. Left DLPFC is the most common stimulation site, both low- and high-frequency are utilized, and 10 sessions is frequently used. Further studies are needed to determine optimal TMS treatments in cognitively impaired populations

High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke.

JOURNAL/nrgr/04.03/01300535-202408000-00031/figure1/v/2023-12-16T180322Z/r/image-tiff Proliferation of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage. Transcranial magnetic stimulation (TMS) has recently emerged as a tool for inducing endogenous neural stem cell regeneration, but its underlying mechanisms remain unclear. In this study, we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells. Additionally, repetitive TMS reduced the volume of cerebral infarction in a rat model of ischemic stroke caused by middle cerebral artery occlusion, improved rat cognitive function, and promoted the proliferation of neural stem cells in the ischemic penumbra. RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia. Furthermore, PCR analysis revealed that repetitive TMS promoted AKT phosphorylation, leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4. This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway, which ultimately promotes the proliferation of neural stem cells. Subsequently, we validated the effect of repetitive TMS on AKT phosphorylation. We found that repetitive TMS promoted Ca2+ influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway, thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway. These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+ influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway. This study has produced pioneering results on the intrinsic mechanism of repetitive TMS to promote neural function recovery after ischemic stroke. These results provide a strong scientific foundation for the clinical application of repetitive TMS. Moreover, repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications, but also provide an effective platform for the expansion of neural stem cells.

EEG synchronized left prefrontal transcranial magnetic stimulation (TMS) for treatment resistant depression is feasible and produces an entrainment dependent clinical response: A randomized controlled double blind clinical trial

BackgroundSynchronizing a TMS pulse with a person's underlying EEG rhythm can modify the brain's response. It is unclear if synchronizing rTMS trains might boost the antidepressant effect of TMS. In this first-in-human trial, we demonstrated that a single TMS pulse over the prefrontal cortex produces larger effects in the anterior cingulate depending on when it is fired relative to the individual's EEG alpha phase. Objective/hypothesesWe had three hypotheses. 1) It is feasible to synchronize repetitive TMS (rTMS) delivery to a person's preferred prefrontal alpha phase in each train of every session during a 30-visit TMS depression treatment course. 2) EEG-synchronized rTMS would produce progressive entrainment greater than unsynchronized (UNSYNC) rTMS. And 3) SYNC TMS would have better antidepressant effects than UNSYNC (remission, final Hamilton Depression Rating <10). MethodsWe enrolled (n = 34) and treated (n = 28) adults with treatment resistant depression (TRD) and randomized them to receive six weeks (30 treatments) of left prefrontal rTMS at their individual alpha frequency (IAF) (range 6–13 Hz). Prior to starting the clinical trial, all patients had an interleaved fMRI-EEG-TMS (fET) scan to determine which phase of their alpha rhythm would produce the largest BOLD response in their dorsal anterior cingulate. Our clinical EEG-rTMS system then delivered the first TMS pulse in each train time-locked to this patient-specific ‘preferred phase’ of each patient's left prefrontal alpha oscillation. We randomized patients (1:1) to SYNC or UNSYNC, and all were treated at their IAF. Only the SYNC patients had the first pulse of each train for all sessions synchronized to their individualized preferred alpha phase (75 trains/session ×30 sessions, 2250 synchronizations per patient over six weeks). The UNSYNC group used a random firing with respect to the alpha wave. All other TMS parameters were balanced between the two groups.The system interfaced with a MagStim Horizon air-cooled Fig. 8 TMS coil. All patients were treated at their IAF, coil in the F3 position, 120 % MT, frequency 6–13 Hz, 40 pulses per train, average 15-s inter-train interval, 3000 pulses per session. All patients, raters, and treaters were blinded. ResultsIn the intent to treat (ITT) sample, both groups had significant clinical improvement from baseline with no significant between-group differences, with the USYNC group having mathematically more remitters but fewer responders. (ITT -15 SYNC; 13 UNSYNC, response 5 (33 %), 1 (7 %), remission 2 (13 %), 6 (46 %). The same was true with the completer sample - 12 SYNC; 12 UNSYNC, response 4, 4 (both 30 %), remission 2 (17 %), 3 (25 %)). The clinical EEG phase synchronization system performed well with no failures. The average treatment session was approximately 90 min, with 30 min for placing the EEG cap and the actual TMS treatment for 45 min (which included gathering 10 min of resting EEG). Four subjects (1 SYNC) withdrew before six weeks of treatment. All 24 completer patients were treated for six weeks despite the trial occurring during the COVID pandemic. SYNC patients exhibited increased post-stimulation EEG entrainment over the six weeks. A detailed secondary analysis of entrainment data in the SYNC group showed that responders and non-responders in this group could be cleanly separated based on the total number of sessions with entrainment and the session-to-session precision of the entrained phase. For the SYNC group only, depression improvement was greater when more sessions were entrained at similar phases. ConclusionsSynchronizing prefrontal TMS with a patient's prefrontal alpha frequency in a blinded clinical trial is possible and produces progressive EEG entrainment in synchronized patients only. There was no difference in overall clinical response in this small clinical trial. A secondary analysis showed that the consistency of the entrained phase across sessions was significantly associated with response outcome only in the SYNC group. These effects may not simply be due to how the stimulation is delivered but also whether the patient's brain can reliably entrain to a precise phase. EEG-synchronized clinical delivery of TMS is feasible and requires further study to determine the best method for determining the phase for synchronization.

The behavioral and neural effects of parietal theta burst stimulation on the grasp network are stronger during a grasping task than at rest

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

Modeling the effects of transcranial magnetic stimulation on spatial attention

Objectives. Transcranial magnetic stimulation (TMS) has been widely used to modulate brain activity in healthy and diseased brains, but the underlying mechanisms are not fully understood. Previous research leveraged biophysical modeling of the induced electric field (E-field) to map causal structure–function relationships in the primary motor cortex. This study aims at transferring this localization approach to spatial attention, which helps to understand the TMS effects on cognitive functions, and may ultimately optimize stimulation schemes. Approach. Thirty right-handed healthy participants underwent a functional magnetic imaging (fMRI) experiment, and seventeen of them participated in a TMS experiment. The individual fMRI activation peak within the right inferior parietal lobule (rIPL) during a Posner-like attention task defined the center target for TMS. Thereafter, participants underwent 500 Posner task trials. During each trial, a 5-pulse burst of 10 Hz repetitive TMS (rTMS) was given over the rIPL to modulate attentional processing. The TMS-induced E-fields for every cortical target were correlated with the behavioral modulation to identify relevant cortical regions for attentional orientation and reorientation. Main results. We did not observe a robust correlation between E-field strength and behavioral outcomes, highlighting the challenges of transferring the localization method to cognitive functions with high neural response variability and complex network interactions. Nevertheless, TMS selectively inhibited attentional reorienting in five out of seventeen subjects, resulting in task-specific behavioral impairments. The BOLD-measured neuronal activity and TMS-evoked neuronal effects showed different patterns, which emphasizes the principal distinction between the neural activity being correlated with (or maybe even caused by) particular paradigms, and the activity of neural populations exerting a causal influence on the behavioral outcome. Significance. This study is the first to explore the mechanisms of TMS-induced attentional modulation through electrical field modeling. Our findings highlight the complexity of cognitive functions and provide a basis for optimizing attentional stimulation protocols.

Exploring research trends and focal points in the application of transcranial magnetic stimulation for enhancing motor function in post-stroke patients: A bibliometric and content analytical approach

BackgroundMotor impairment is a significant health concern among post-stroke patients. Transcranial magnetic stimulation (TMS) is considered as an emerging rehabilitation therapy for various neurological conditions, and the effects of excitatory TMS on post-stroke have received much attention in past decade. However, the future hotspots and content analysis on the growth trends have not been studied. This bibliometric and content analysis aimed to study the global developmental history and current status of TMS for motor function of post-stroke from January 2004 to July 2023. MethodsLiterature published on Scopus database from January 2004 to July 2023 were searched. Extracted data was analysed using the R studio and VOS viewer for author's publication, institutions, sources, keyword co-occurrence and world network analysis. Keyword cluster analysis, co-citation analysis for references and content analysis were also performed. We screened top 10 most cited or collaborative areas for publications, institutions and sources in the field of TMS associated with motor function of post-stroke. ResultsIn this study, a comprehensive analysis of 267 publications was conducted, revealing a substantial surge in research output throughout 2022. China emerged as the leading contributor, with 409 publications, followed by the United States with 211 publications. Notably, Harvard Medical School stood out as one of the most prolific institutions, accounting for 34 publications (13.12 %). Among researchers, Abo M garnered the highest publication count, with 9 articles (14.5 %). The Word cloud showed that motor function, repetitive transcranial magnetic stimulation (rTMS) and upper limb have been the focus of recent attention. Burst keywords on thematic evolution and topic trend shows that quality of life scale, network parameters, cognition, lower limb motor function are the future trends. ConclusionThis bibliometric study describes that TMS has shown promising results in improving motor function of upper extremity in stroke patients, the long-term effects and durability of these improvements are still being investigated. Future research might focus on understanding the optimal duration and frequency of TMS sessions for sustained motor recovery and exploring strategies to maintain gains achieved through TMS over extended periods of time. Future studies can investigate the changes in the lower limb motor function.

Non-invasive brain stimulation on clinical symptoms in multiple sclerosis patients: A systematic review and meta-analysis.

Non-invasive brain stimulation (NIBS) has demonstrated mixed effects on the clinical symptoms of multiple sclerosis. This systematic review and meta-analysis aimed to evaluate the effects of NIBS techniques on the most common symptoms of MS. A literature search was performed until October 2022 which included randomized controlled trials and quasi-experimental studies that used sham-controlled NIBS in patients with MS. We calculated the Hedge's effect sizes of each domain of interest and their 95% confidence intervals (95% CIs) and performed random effects meta-analyses. A total of 49 studies were included in the systematic review (944 participants). Forty-four eligible studies were included for quantitative analysis, of which 33 applied transcranial direct current stimulation (tDCS), 9 transcranial magnetic stimulation (TMS), and 2 transcranial random noise stimulation (tRNS). We found a significant decrease in fatigue (ES: -0.86, 95% CI: -1.22 to-0.51, p<0.0001), pain (ES:-1.91, 95% CI,-3.64 to-0.19, p=0.03) and psychiatric symptoms (ES:-1.44, 95% CI-2.56 to-0.32, p=0.01) in favor of tDCS compared with the sham. On the other hand, there was no strong evidence showing tDCS effectiveness on motor performance and cognition (ES:-0.03, 95% CI-0.35 to 0.28, p=0.83 and ES: 0.71, 95% CI,-0.09 to 1.52, p=0.08, respectively). Regarding TMS, we found a significant decrease in fatigue (ES:-0.45, 95% CI:-0.84 to -0.07, p=0.02) and spasticity levels (ES:-1.11, 95% CI:-1.48 to-0.75, p<0.00001) compared to the sham. However, there was no strong evidence of the effectiveness of TMS on motor performance (ES:-0.39, 95% CI-0.95 to 0.16, p=0.16). Finally, there was no significant evidence showing the effectiveness of tRNS on fatigue levels (ES:-0.28, 95% CI:-1.02 to 0.47, p=0.46) and cognitive improvement (ES:-0.04, 95% CI:-0.6, 0.52, p=0.88) compared with the sham. Overall, most studies have investigated the effects of tDCS on MS symptoms, particularly fatigue. The symptom that most benefited from NIBS was fatigue, while the least to benefit was motor performance. In addition, we found that disability score was associated with fatigue improvement. Thus, these findings support the idea that NIBS could have some promising effects on specific MS symptoms. It is also important to underscore that studies are very heterogeneous regarding the parameters of stimulation, and this may also have influenced the effects on some specific behavioral domains.

TMS must not harm participants: guidelines for evaluating TMS protocol safety

ABSTRACT Transcranial magnetic stimulation (TMS) can modulate a targeted brain region to assess whether that region is involved in a cognitive process. When TMS is employed in cognitive neuroscience, participants are typically healthy volunteers, and the technique is described as noninvasive. However, TMS parameters can be set such that stimulation produces long-lasting effects. Critically, TMS effects that have any possibility of lasting beyond a participant’s time in the lab are potentially harmful. In this editorial, evidence is considered that indicates a 20-Hz multi-day TMS protocol has long-lasting effects, and a continuous theta-burst stimulation protocol needs further testing before it is deemed noninvasive. The following guidelines are provided for TMS protocol evaluation: 1) Effects must be shown to completely dissipate before participants leave the lab by testing well beyond the expected duration. 2) Participants should complete a cognitive test battery before TMS and after the effects are expected to dissipate. 3) Protocols should not be employed that produce effects lasting longer than the time in the lab. 4) The number of participants should ensure error bars are small, and results generalize to the population. 5) Results should be assessed at the group and individual-participant level, and effects should dissipate for every participant. 6) Bayesian analysis should be conducted to evaluate evidence in favor of the null hypothesis. 7) Effects should be assessed in multiple cortical regions. It is hoped that these guidelines will be employed to ensure the continued use of TMS as a valuable tool in the field of cognitive neuroscience.