Targeting the adenosinergic system in restless legs syndrome: A pilot, "proof-of-concept" placebo-controlled TMS-based protocol.

Restless Legs Syndrome (RLS) is a common sleep disorder characterized by an urge to move the legs that is responsive to movement (particularly during rest), periodic leg movements during sleep, and hyperarousal. Recent evidence suggests that the involvement of the adenosine system may establish a connection between dopamine and glutamate dysfunction in RLS. Transcranial magnetic stimulation (TMS) is a non-invasive electrophysiological technique widely applied to explore brain electrophysiology and neurochemistry under different experimental conditions. In this pilot study protocol, we aim to investigate the effects of dipyridamole (a well-known enhancer of adenosinergic transmission) and caffeine (an adenosine receptor antagonist) on measures of cortical excitation and inhibition in response to TMS in patients with primary RLS. Initially, we will assess cortical excitability using both single- and paired-pulse TMS in patients with RLS. Then, based on the measures obtained, we will explore the effects of dipyridamole and caffeine, in comparison to placebo, on various TMS parameters related to cortical excitation and inhibition. Finally, we will evaluate the psycho-cognitive performance of RLS patients to screen them for cognitive impairment and/or mood-behavioral dysfunction, thus aiming to correlate psycho-cognitive findings with TMS data. Overall, this study protocol will be the first to shed lights on the neurophysiological mechanisms of RLS involving the modulation of the adenosine system, thus potentially providing a foundation for innovative "pharmaco-TMS"-based treatments. The distinctive TMS profile observed in RLS holds indeed the potential utility for both diagnosis and treatment, as well as for patient monitoring. As such, it can be considered a target for both novel pharmacological (i.e., drug) and non-pharmacological (e.g., neuromodulatory), "TMS-guided", interventions.

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.

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).

Repetitive transcranial magnetic stimulation ameliorates cognitive deficits in mice with radiation-induced brain injury by attenuating microglial pyroptosis and promoting neurogenesis via BDNF pathway.

BACKGROUND: Radiation-induced brain injury (RIBI) is a common and severe complication during radiotherapy for head and neck tumor. Repetitive transcranial magnetic stimulation (rTMS) is a novel and non-invasive method of brain stimulation, which has been applied in various neurological diseases. rTMS has been proved to be effective for treatment of RIBI, while its mechanisms have not been well understood. METHODS: RIBI mouse model was established by cranial irradiation, K252a was daily injected intraperitoneally to block BDNF pathway. Immunofluorescence staining, immunohistochemistry and western blotting were performed to examine the microglial pyroptosis and hippocampal neurogenesis. Behavioral tests were used to assess the cognitive function and emotionality of mice. Golgi staining was applied to observe the structure of dendritic spine in hippocampus. RESULTS: rTMS significantly promoted hippocampal neurogenesis and mitigated neuroinflammation, with ameliorating pyroptosis in microglia, as well as downregulation of the protein expression level of NLRP3 inflammasome and key pyroptosis factor Gasdermin D (GSDMD). BDNF signaling pathway might be involved in it. After blocking BDNF pathway by K252a, a specific BDNF pathway inhibitor, the neuroprotective effect of rTMS was markedly reversed. Evaluated by behavioral tests, the cognitive dysfunction and anxiety-like behavior were found aggravated with the comparison of mice in rTMS intervention group. Moreover, the level of hippocampal neurogenesis was found to be attenuated, the pyroptosis of microglia as well as the levels of GSDMD, NLRP3 inflammasome and IL-1ß were upregulated. CONCLUSION: Our study indicated that rTMS notably ameliorated RIBI-induced cognitive disorders, by mitigating pyroptosis in microglia and promoting hippocampal neurogenesis via mediating BDNF pathway.

A randomized controlled trial of intermittent theta burst stimulation to the medial prefrontal cortex for tobacco use disorder: Clinical efficacy and safety.

OBJECTIVE: This study aimed to evaluate the clinical efficacy and safety of administering intermittent theta burst stimulation (iTBS) to the medial prefrontal cortex for tobacco use disorder. METHODS: A randomized sham-controlled trial was conducted, with 38 participants receiving 28 sessions of active (n=25) or sham (n=13) iTBS (2 sessions/day, 600 pulses/session, 110% resting motor threshold, AFz target) along with smoking cessation education (Forever Free © booklets) over 14 visits. Primary outcomes included self-reported cigarette consumption and abstinence, verified by urinary cotinine tests. Secondary outcomes included symptoms of tobacco use disorder, negative mood, and safety/tolerability. RESULTS: Both active and sham groups reported reduced cigarette consumption (ß = -0.12, p = 0.015), cigarette craving (ß = -0.16, p = 0.002), and tobacco withdrawal symptoms (ß = -0.05, p < 0.001). However, there were no significant time x group interaction effects for any measure. Similarly, the two groups had no significant differences in urinary cotinine-verified abstinence. Adverse events occurred with similar frequency in both groups. CONCLUSION: There were no differences in cigarette consumption between the active and sham iTBS groups, both groups decreased cigarette consumption similarly. Further research is needed to compare iTBS to standard high-frequency rTMS and explore the potential differences in efficacy. Despite limitations, this study contributes to experimental design considerations for TMS as a novel intervention for tobacco and other substance use disorders, emphasizing the need for a more comprehensive understanding of the stimulation parameters and target sites.

Noninvasive- and invasive mapping reveals similar language network centralities - A function-based connectome analysis.

BACKGROUND: Former comparisons between direct cortical stimulation (DCS) and navigated transcranial magnetic stimulation (nTMS) only focused on cortical mapping. While both can be combined with diffusion tensor imaging, their differences in the visualization of subcortical and even network levels remain unclear. Network centrality is an essential parameter in network analysis to measure the importance of nodes identified by mapping. Those include Degree centrality, Eigenvector centrality, Closeness centrality, Betweenness centrality, and PageRank centrality. While DCS and nTMS have repeatedly been compared on the cortical level, the underlying network identified by both has not been investigated yet. METHOD: 27 patients with brain lesions necessitating preoperative nTMS and intraoperative DCS language mapping during awake craniotomy were enrolled. Function-based connectome analysis was performed based on the cortical nodes obtained through the two mapping methods, and language-related network centralities were compared. RESULTS: Compared with DCS language mapping, the positive predictive value of cortical nTMS language mapping is 74.1%, with good consistency of tractography for the arcuate fascicle and superior longitudinal fascicle. Moreover, network centralities did not differ between the two mapping methods. However, ventral stream tracts can be better traced based on nTMS mappings, demonstrating its strengths in acquiring language-related networks. In addition, it showed lower centralities than other brain areas, with decentralization as an indicator of language function loss. CONCLUSION: This study deepens the understanding of language-related functional anatomy and proves that non-invasive mapping-based network analysis is comparable to the language network identified via invasive cortical mapping.

Comprehensive assessment of HF-rTMS treatment mechanism for post-stroke dysphagia in rats by integration of fecal metabolomics and 16S rRNA sequencing.

Background: The mechanism by which high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) improves swallowing function by regulating intestinal flora remains unexplored. We aimed to evaluate this using fecal metabolomics and 16S rRNA sequencing. Methods: A Post-stroke dysphagia (PSD) rat model was established by middle cerebral artery occlusion. The magnetic stimulation group received HF-rTMS from the 7th day post-operation up to 14th day post-surgery. Swallowing function was assessed using a videofluoroscopic swallowing study (VFSS). Hematoxylin-eosin (H&E) staining was used to assess histopathological changes in the intestinal tissue. Intestinal flora levels were evaluated by sequencing the 16S rRNA V3-V4 region. Metabolite changes within the intestinal flora were evaluated by fecal metabolomics using liquid chromatography-tandem mass spectrometry. Results: VFSS showed that the bolus area and pharyngeal bolus speed were significantly decreased in PSD rats, while the bolus area increased and pharyngeal transit time decreased after HF-rTMS administration (p < 0.05). In the PSD groups, H&E staining revealed damaged surface epithelial cells and disrupted cryptal glands, whereas HF-rTMS reinforced the integrity of the intestinal epithelial cells. 16S rRNA sequencing indicated that PSD can disturb the intestinal flora and its associated metabolites, whereas HF-rTMS can significantly regulate the composition of the intestinal microflora. Firmicutes and Lactobacillus abundances were lower in the PSD group than in the baseline group at the phylum and genus levels, respectively; however, both increased after HF-rTMS administration. Levels of ceramides (Cer), free fatty acids (FA), phosphatidylethanolamine (PE), triacylglycerol (TAG), and sulfoquinovosyl diacylglycerol were increased in the PSD group. The Cer, FA, and DG levels decreased after HF-rTMS treatment, whereas the TAG levels increased. Peptococcaceae was negatively correlated with Cer, Streptococcus was negatively correlated with DG, and Acutalibacter was positively correlated with FA and Cer. However, these changes were effectively restored by HF-rTMS, resulting in recovery from dysphagia. Conclusion: These findings suggest a synergistic role for the gut microbiota and fecal metabolites in the development of PSD and the therapeutic mechanisms underlying HF-rTMS.

Does deep TMS really works for smoking cessation? A prospective, double blind, randomized, sham controlled study.

INTRODUCTION: A substantial proportion of smokers wishing to quit do not stop smoking when using current therapies to aid cessation. Magnetic pulses to specific brain areas designated as transcranial magnetic stimulation may modulate brain activity and thereby change chemical dependencies. Deep transcranial magnetic stimulation (dTMS) with the H4 coil stimulates neuronal pathways in the lateral prefrontal cortex and insula bilaterally, areas involved in tobacco addiction. OBJECTIVE: To evaluate the efficacy and safety of dTMS with T4 coil in smoking cessation. METHODS: In a double blind, controlled clinical trial, adult smokers of at least 10 cigarettes/day were randomized to active (n = 50) versus sham dTMS (n = 50). The protocol involved up to 21 sessions administered over up to 12 weeks. Tobacco use was monitored by self-report and confirmed by expired air monoximetry (at each dTMS visit) and blood cotinine (at the screening visit and at the end of sessions). Participants completed abstinence, mood and cognition scales at determined timepoints during follow-up. RESULTS: In the intention to-treat-analysis, the cessation rate of the intervention and control groups was 14.0%. The reported side effects were as expected for this procedure. Although there were no serious adverse events, three participants were withdrawn according to safety criteria. CONCLUSION: Active treatment with dTMS H4 coil was safe but not effective for smoking cessation.

Skeletal muscle fiber type and TMS-induced muscle relaxation in unfatigued and fatigued knee-extensor muscles.

The force drop after transcranial magnetic stimulation (TMS) delivered to the motor cortex during voluntary muscle contractions could inform about muscle relaxation properties. Because of the physiological relation between skeletal muscle fiber-type distribution and size and muscle relaxation, TMS could be a noninvasive index of muscle relaxation in humans. By combining a noninvasive technique to record muscle relaxation in vivo (TMS) with the gold standard technique for muscle tissue sampling (muscle biopsy), we investigated the relation between TMS-induced muscle relaxation in unfatigued and fatigued states, and muscle fiber-type distribution and size. Sixteen participants (7F/9M) volunteered to participate. Maximal knee-extensor voluntary isometric contractions were performed with TMS before and after a 2-min sustained maximal voluntary isometric contraction. Vastus lateralis muscle tissue was obtained separately from the participants' dominant limb. Fiber type I distribution and relative cross-sectional area of fiber type I correlated with TMS-induced muscle relaxation at baseline (r = 0.67, adjusted P = 0.01; r = 0.74, adjusted P = 0.004, respectively) and normalized TMS-induced muscle relaxation as a percentage of baseline (r = 0.50, adjusted P = 0.049; r = 0.56, adjusted P = 0.031, respectively). The variance in the normalized peak relaxation rate at baseline (59.8%, P < 0.001) and in the fatigue resistance (23.0%, P = 0.035) were explained by the relative cross-sectional area of fiber type I to total fiber area. Fiber type I proportional area influences TMS-induced muscle relaxation, suggesting TMS as an alternative method to noninvasively inform about skeletal muscle relaxation properties.NEW & NOTEWORTHY Transcranial magnetic stimulation (TMS)-induced muscle relaxation reflects intrinsic muscle contractile properties by interrupting the drive from the central nervous system during voluntary muscle contractions. We showed that fiber type I proportional area influences the TMS-induced muscle relaxation, suggesting that TMS could be used for the noninvasive estimation of muscle relaxation in unfatigued and fatigued human muscles when the feasibility of more direct method to study relaxation properties (i.e., muscle biopsy) is restricted.

Combining neuroimaging and brain stimulation to test alternative causal pathways for nicotine addiction in schizophrenia.

The smoking rate is high in patients with schizophrenia. Brain stimulation targeting conventional brain circuits associated with nicotine addiction has also yielded mixed results. We aimed to identify alternative circuitries associated with nicotine addiction in both the general population and schizophrenia, and then test whether modulation of such circuitries may alter nicotine addiction behaviors in schizophrenia. In Study I of 40 schizophrenia smokers and 51 non-psychiatric smokers, cross-sectional neuroimaging analysis identified resting state functional connectivity (rsFC) between the dorsomedial prefrontal cortex (dmPFC) and multiple extended amygdala regions to be most robustly associated with nicotine addiction severity in healthy controls and schizophrenia patients (p = 0.006 to 0.07). In Study II with another 30 patient smokers, a proof-of-concept, patient- and rater-blind, randomized, sham-controlled rTMS design was used to test whether targeting the newly identified dmPFC location may causally enhance the rsFC and reduce nicotine addiction in schizophrenia. Although significant interactions were not observed, exploratory analyses showed that this dmPFC-extended amygdala rsFC was enhanced by 4-week active 10Hz rTMS (p = 0.05) compared to baseline; the severity of nicotine addiction showed trends of reduction after 3 and 4 weeks (p ≤ 0.05) of active rTMS compared to sham; Increased rsFC by active rTMS predicted reduction of cigarettes/day (R = -0.56, p = 0.025 uncorrected) and morning smoking severity (R = -0.59, p = 0.016 uncorrected). These results suggest that the dmPFC-extended amygdala circuit may be linked to nicotine addiction in schizophrenia and healthy individuals, and future efforts targeting its underlying pathophysiological mechanisms may yield more effective treatment for nicotine addiction.

Effects of Transcranial Magnetic Stimulation Combined with Sertraline on Cognitive Level, Inflammatory Response and Neurological Function in Depressive Disorder Patients with Non-suicidal Self-injury Behavior.

BACKGROUND: Depressive disorder is a chronic mental illness characterized by persistent low mood as its primary clinical symptom. Currently, psychotherapy and drug therapy stand as the primary treatment modalities in clinical practice, offering a certain degree of relief from negative emotions for patients. Nevertheless, sole reliance on drug therapy exhibits a delayed impact on neurotransmitters, and long-term usage often results in adverse side effects such as nausea, drowsiness, and constipation, significantly impeding medication adherence. This study aims to investigate the impact of combining transcranial magnetic stimulation with sertraline on the cognitive level, inflammatory response, and neurological function in patients with depressive disorder who engage in non-suicidal self-injury (NSSI) behavior. METHODS: A total of 130 depressive patients NSSI behavior, who were admitted to our hospital from December 2020 to February 2023, were selected as the subjects for this research. The single-group (65 cases) received treatment with oral sertraline hydrochloride tablets, while the combination group (65 cases) underwent repetitive transcranial magnetic stimulation (rTMS) in conjunction with sertraline. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was utilized to assess the depression status and cognitive function levels of both groups. Additionally, the enzyme-linked immunosorbent assay (ELISA) was employed to measure serum levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). Furthermore, serum levels of neurotransmitters (norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT)) and neuro-cytokines (brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial fibrillary acidic protein (GFAP)) were assessed. The clinical effects of the interventions on both groups were then evaluated. RESULTS: Following the treatment, the combination group exhibited significantly higher levels of immediate memory, delayed memory, attention, visual function, and language function compared to the single group, with statistically significant differences (p < 0.05). Additionally, the serum levels of TNF-α, IL-1ß, IL-6, and GFAP in the combination group were lower than those in the single group, while the levels of BDNF and NGF were higher in the combination group compared to the single group. These differences were also statistically significant (p < 0.05). Simultaneously, the total clinical effective rate in the combination group reached 95.38%, surpassing the 84.61% observed in the single group, and the disparity between the two groups was statistically significant (p < 0.05). CONCLUSIONS: The combined use of rTMS and sertraline in treating patients with depressive disorder exhibiting NSSI behavior has proven to be effective in enhancing cognitive function, mitigating inflammatory responses, and elevating levels of neurotransmitters and nerve cytokines in the patients.

High-frequency repetitive transcranial magnetic stimulation promotes ipsilesional functional hyperemia and motor recovery in mice with ischemic stroke.

Neurovascular decoupling plays a significant role in dysfunction following an ischemic stroke. This study aimed to explore the effect of low- and high-frequency repetitive transcranial magnetic stimulation on neurovascular remodeling after ischemic stroke. To achieve this goal, we compared functional hyperemia, cerebral blood flow regulatory factors, and neurochemical transmitters in the peri-infract cortex 21 days after a photothrombotic stroke. Our findings revealed that low- and high-frequency repetitive transcranial magnetic stimulation increased the real-time cerebral blood flow in healthy mice and improved neurobehavioral outcomes after stroke. Furthermore, high-frequency (5-Hz) repetitive transcranial magnetic stimulation revealed stronger functional hyperemia recovery and increased the levels of post-synaptic density 95, neuronal nitric oxide synthase, phosphorylated-endothelial nitric oxide synthase, and vascular endothelial growth factor in the peri-infract cortex compared with low-frequency (1-Hz) repetitive transcranial magnetic stimulation. The magnetic resonance spectroscopy data showed that low- and high-frequency repetitive transcranial magnetic stimulation reduced neuronal injury and maintained excitation/inhibition balance. However, 5-Hz repetitive transcranial magnetic stimulation showed more significant regulation of excitatory and inhibitory neurotransmitters after stroke than 1-Hz repetitive transcranial magnetic stimulation. These results indicated that high-frequency repetitive transcranial magnetic stimulation could more effectively promote neurovascular remodeling after stroke, and specific repetitive transcranial magnetic stimulation frequencies might be used to selectively regulate the neurovascular unit.

Neuromodulation for Treatment of Tinnitus: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the treatment efficacy of neuromodulation versus sham for the treatment of tinnitus. DATA SOURCES: Cochrane Library, CINAHL, PubMed, Scopus. REVIEW METHODS: The Cochrane Library, CINAHL, PubMed, and Scopus were searched from inception through May 2023 for English language articles documenting "neuromodulation" and "tinnitus" stratified by sham-controlled randomized control trials with 40 or more patients. Data collected included Beck Anxiety Inventory, Beck Depression Inventory (BDI), Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire, and Visual Analog Scale. A Meta-analysis of continuous measures (mean) and proportions (%) were conducted. RESULTS: A total of 19 randomized control trials (N = 1186) were included. The mean age was 48.4 ± 5.3 (range: 19-74), mean duration of tinnitus was 3.8 ± 3.4 years, 61% [56.2-65.7] male, and 55.7% [46-65] with unilateral tinnitus. The short-term effect of transcutaneous electrical nerve stimulation and transcranial direct current stimulation on THI score is -16.2 [-23.1 to -9.3] and -19 [-30.1 to -7.8], respectively. The long-term effect of repetitive transcranial magnetic stimulation on THI score is -8.6 [-11.5 to -5.7]. Transcranial direct current stimulation decreases BDI score by -11.8 [-13.3 to -10.3]. CONCLUSION: As measured by the Tinnitus Handicap Index, our findings suggest the effects of transcutaneous electrical nerve stimulation and transcranial direct current stimulation reach significant benefit in the short term, whereas repetitive transcranial magnetic stimulation reaches significant benefit in the long term. Based on the BDI, transcranial direct current stimulation significantly reduces comorbid depression in patients with tinnitus.

Cortical stimulation depth of nTMS investigated in a cohort of convexity meningiomas above the primary motor cortex.

BACKGROUND: In clinical routine, navigated transcranial magnetic stimulation (nTMS) is usually applied down to 25 mm. Yet, besides clinical experience and mathematical models, the penetration depth remains unclear. This study aims to investigate the maximum cortical stimulation depth of nTMS in patients with meningioma above the primary motor cortex, causing a displacement of the primary motor cortex away from the skull. NEW METHOD: nTMS stimulation data was reviewed regarding the maximum depth of stimulations eliciting motor-evoked potentials (MEPs). Additionally, electric field values and stimulation intensity were analyzed. RESULTS: Out of a consecutive cohort of 17 meningioma cases, 3 cases of meningioma located in motor-eloquent regions of the upper extremity and 3 cases of the lower extremity were analyzed after fulfilling all inclusion criteria. Regarding the upper extremity motor representations, the MEP could be elicited at a stimulation depth of up to 44 mm, with an electric field of 69 V/m. These results were found in 1 case with the maximum potential distance to the cortex being higher than the maximum stimulation depth eliciting MEPs. For the lower extremities, a maximum depth of 40 mm was recorded (electric field 64 V/m). COMPARISON WITH EXISTING METHODS: None available CONCLUSIONS: The effect of nTMS is not limited to superficial cortical stimulation alone. Depending on electric-field intensity and focality, nTMS stimulation can be applied at a depth of 44 mm. In all cases, electric field strength was comparable and no superficial cortex with comparable electric field strength was observed to elicit MEPs.

A literature review and meta-analysis of the optimal factors study of repetitive transcranial magnetic stimulation in post-infarction aphasia.

BACKGROUND: The existing literature indicates that repetitive transcranial magnetic stimulation (rTMS) can potentially enhance the prognosis of poststroke aphasia (PSA). Nevertheless, these investigations did not identify the most effective parameters or settings for achieving optimal treatment outcomes. This study involved a meta-analysis aimed to identify the optimal variables for rTMS in treating post-infarction aphasia to guide the use of rTMS in rehabilitating PSA. METHODS: PubMed, Embase, and Cochrane Library databases were searched from inception to May 2023, and articles were reviewed manually using subject words and free words and supplemented with references from the included literature to obtain additional relevant literature. The search terms included "poststroke aphasia" and "repetitive transcranial magnetic stimulation (rTMS)" repetitive transcranial magnetic stimulation. Additionally, a review of the reference lists of previously published systematic reviews identified through the Cochrane Database of Systematic Reviews (search terms: poststroke aphasia, rTMS; restrictions: none) and PubMed (search terms: poststroke aphasia, rTMSs; restrictions: systematic review or meta-analysis) was performed. Information from studies involving different doses of rTMS in PSA was independently screened and extracted by 2 researchers. RESULTS: This meta-analysis included 387 participants with PSA across 18 randomized controlled trials. The results showed that the total pulse had a trend toward a significant correlation with the treatment effect (P = 0.088), while all other variables did not correlate significantly. When rTMS was not grouped by stimulus parameter and location, our nonlinear results showed that when the total pulses were 40,000 (standardized mean difference (SMD):1.86, 95% credible interval (CrI) 0.50 to 3.33), the pulse/session was 1000 (SMD:1.05, 95% CrI 0.55-1.57), and an RMT of 80% (SMD:1.08, 95% CrI 0.60-1.57) had the best treatment effect. When rTMS was grouped by stimulus parameters and location, our nonlinear results showed that when the total low-frequency (LF)-rTMS-right inferior frontal gyrus (RIFG) pulse was 40,000 (SMD:1.76, 95% CrI:0.36-3.29), the pulse/session was 1000 (SMD:1.06, 95% CrI:0.54-1.59). Optimal results were obtained with an RMT of 80% (SMD:1.14, 95% CrI 0.54 - 1.76). CONCLUSIONS: The optimal treatment effects of rTMS for PSA may be obtained with a total pulse of 40,000, a pulse/session of 1000, and an RMT of 80%. Further rigorous randomized controlled studies are required to substantiate the validity of these results.

rTMS effects on urges and severity of tobacco use disorder operate independently of a retrieval-extinction component and involve frontal-striatal pathways.

BACKGROUND: Although smoking remains a leading cause of preventable disease, the treatment options for smoking are limited. The present study evaluated the neural features underlying effects of repetitive transcranial magnetic stimulation (rTMS) for reducing smoking cravings. In addition, the efficacy of a simulated retrieval-extinction procedure to augment rTMS efficacy was examined. METHODS: Sixty-one individuals with tobacco use disorder (TUD) were randomized into three groups: classic rTMS, retrieval rTMS (viewed smoking videos before rTMS), and sham rTMS. rTMS was performed on the left dorsolateral prefrontal cortex (DLPFC) over 5 days using a standard figure-8 coil. Smoking cravings and brain responses to smoking cues were measured before and after rTMS treatment. Changes in functional connectivity (FC) among different brain regions were calculated. RESULTS: rTMS reduced smoking urges in TUD. Both active-rTMS groups demonstrated greater activations of the DLPFC, caudate, and bilateral insula relative to the sham group. Increased FC was observed between executive and reward network brain regions, and decreased FC was observed within reward network regions. Compared with standard rTMS, retrieval-extinction rTMS demonstrated similar outcomes and was associated with less activation of the medial frontal gyrus. CONCLUSIONS: rTMS increased activations in brain regions implicated in executive control and reward processing. Strengthened prefrontal-striatal pathway suggests that rTMS enhanced top-down control over smoking cravings. The retrieval-extinction process, although associated with some different and multiple similar neural correlates as the standard rTMS, did not enhance cessation outcomes.

Comparing the efficacy of awake and sedated MEG to TMS in mapping hand sensorimotor cortex in a clinical cohort.

Non-invasive methods such as Transcranial Magnetic Stimulation (TMS) and magnetoencephalography (MEG) aid in the pre-surgical evaluation of patients with epilepsy or brain tumor to identify sensorimotor cortices. MEG requires sedation in children or patients with developmental delay. However, TMS can be applied to awake patients of all ages with any cognitive abilities. In this study, we compared the efficacy of TMS with MEG (in awake and sedated states) in identifying the hand sensorimotor areas in patients with epilepsy or brain tumors. We identified 153 patients who underwent awake- (n = 98) or sedated-MEG (n = 55), along with awake TMS for hand sensorimotor mapping as part of their pre-surgical evaluation. TMS involved stimulating the precentral gyrus and recording electromyography responses, while MEG identified the somatosensory cortex during median nerve stimulation. Awake-MEG had a success rate of 92.35 % and TMS had 99.49 % (p-value = 0.5517). However, in the sedated-MEG cohort, TMS success rate of 95.61 % was significantly higher compared to MEG's 58.77 % (p-value = 0.0001). Factors affecting mapping success were analyzed. Logistic regression across the entire cohort identified patient sedation as the lone significant predictor, contrary to age, lesion, metal, and number of antiseizure medications (ASMs). A subsequent analysis replaced sedation with anesthetic drug dosage, revealing no significant predictors impacting somatosensory mapping success under sedation. This study yields insights into the utility of TMS and MEG in mapping hand sensorimotor cortices and underscores the importance of considering factors that influence eloquent cortex mapping limitations during sedation.

Evaluation of the Effect of Repetitive Transcranial Magnetic Stimulation of Motor Cortex on Failed Back Surgery Syndrome Pain Control in the Short Term.

BACKGROUND: This study aimed to evaluate the short-term efficacy of repetitive transcranial magnetic stimulation (rTMS) on the treatment of failed back surgery syndrome (FBSS). METHODS: In this prospective clinical trial study, 13 patients with FBSS were selected to undergo rTMS, including 5 sessions of stimulation of the primary motor cortex of 90 trains with a frequency of 10 Hz for 2 seconds and an intertrain interval of 20 seconds with a total pulse rate of 1800 per session. The time of each session was 30 minutes with an intensity of 80% of the motor threshold. The severity of pain before and after the intervention was measured by the short-form McGill Pain Questionnaire and visual analog scale (VAS). RESULTS: The mean of pain severity was 26.54 ± 6.78 and 14.92 ± 10.1 before and after rTMS, respectively. The severity of pain was significantly decreased after the intervention (p = 0.001). According to the McGill Pain Questionnaire, the severity of pain in the patients was decreased by 44.09 ± 27.32. The mean of the severity of pain according to VAS was 77.31 ± 16.66 before rTMS and 53.46 ± 22.49 after rTMS, which showed that pain intensity was significantly decreased after the intervention (p = 0.006). CONCLUSIONS: The use of rTMS of the primary motor cortex in patients who have undergone lumbosacral spine surgery and suffer from pain related to FBSS is associated with a significant reduction in the severity of pain. Because rTMS is a noninvasive treatment method, it can be used as a suitable treatment in these patients.

Association between the morphological features of the central sulcus and the somatomotory representation: anatomo-functional evaluation of neuroplasticity through nTMS.

In recent years navigated transcranial magnetic stimulation (nTMS) has emerged as a useful tool for the preoperative mapping of brain cortical areas surrounding neoplastic tissues allowing for maximal safe tumor resection and minimizing new postoperative permanent neurological deficits. Three patients presenting with an intrinsic brain tumor (one metastasis from mammary carcinoma, one high-grade glioma, and one low-grade glioma) located within or in close relationship to the central sulcus were enrolled for this study. The MRI-based morphological and nTMS mapping of the central sulcus of the intact hemisphere was complemented by the examination of the contralateral region harboring the lesion. The findings were independently compared, in search of evidence of tumor-induced neuroplasticity and/or signs of parenchymal dislocation/infiltration caused by the tumor. An individual description of each mapping session is provided. Significant discrepancies were observed between morphological MRI and functional nTMS mapping in two patients, demonstrating a tumor-induced shift of distinct cortical areas controlling hand and/or facial movements. In the cases of gliomas, a lower MT was detected in the lesioned hemisphere, possibly due to increased electrical excitability caused by the tumor itself. The integration of MRI-based morphological mapping of the central sulcus with the detection of its somatomotor representations through nTMS can assist neurosurgeons when planning the resection of a motor-eloquent tumor, stratifying the risks of secondary neurological deficits. The combination of the two preoperative techniques is able to disclose tumor-induced neural plasticity subsequently guiding a more precise resection.

Immune-inflammatory markers of response to repetitive transcranial magnetic stimulation in depression: A scoping review.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a safe, effective and non-invasive form of neuromodulatory therapy in patients with major depressive disorder (MDD). MDD is associated with increased peripheral and brain inflammation. The current paper aims to provide an overview of research examining the relationship between immune and inflammatory markers and response to rTMS in MDD. METHODS: A scoping review method was adopted in keeping with the PRISMA-ScR guidelines. Twelve relevant studies were retrieved from the PubMed and Scopus databases and rated for study quality using a modified version of the BIOCROSS tool. RESULTS: Response to rTMS in MDD was associated with basal and post-treatment levels of the inflammatory markers amyloid A, antithrombin III, oxidised phosphatidylcholine, and the microRNA miR-146a-5p. Inconsistent results were observed for the cytokines interleukin-1ß, interleukin-2 and tumour necrosis factor-α. Increased baseline levels of interleukin-6 and C-reactive protein were linked to a poorer response to rTMS. DISCUSSION: These results suggest that rTMS may have effects on immune-inflammatory pathways that are distinct from those of antidepressants and electroconvulsive therapy. Because of certain methodological limitations in the included studies, these results should be interpreted with caution.