Modulation of High-Frequency rTMS on Reward Circuitry in Individuals with Nicotine Dependence: A Preliminary fMRI Study.

Although previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) can ameliorate addictive behaviors and cravings, the underlying neural mechanisms remain unclear. This study aimed to investigate the effect of high-frequency rTMS with the left dorsolateral prefrontal cortex (L-DLPFC) as a target region on smoking addiction in nicotine-dependent individuals by detecting the change of spontaneous brain activity in the reward circuitry. We recruited 17 nicotine-dependence participants, who completed 10 sessions of 10 Hz rTMS over a 2-week period and underwent evaluation of several dependence-related scales, and resting-state fMRI scan before and after the treatment. Functional connectivity (FC) analysis was conducted with reward-related brain regions as seeds, including ventral tegmental area, bilateral nucleus accumbens (NAc), bilateral DLPFC, and bilateral amygdala. We found that, after the treatment, individuals showed reduced nicotine dependence, alleviated tobacco withdrawal symptoms, and diminished smoking cravings. The right NAc showed increased FC with right fusiform gyrus, inferior temporal gyrus (ITG), calcarine fissure and surrounding cortex, superior occipital gyrus (SOG), lingual gyrus, and bilateral cuneus. No significant FC changes were observed in other seed regions. Moreover, the changes in FC between the right NAc and the right ITG as well as SOG before and after rTMS were negatively correlated with changes in smoking scale scores. Our findings suggest that high-frequency L-DLPFC-rTMS reduces nicotine dependence and improves tobacco withdrawal symptoms, and the dysfunctional connectivity in reward circuitry may be the underlying neural mechanism for nicotine addiction and its therapeutic target.

Reducing pain by improving brain and muscle activity with motor cortical neuromodulation in women with interstitial cystitis/bladder pain syndrome: a study protocol for a randomized controlled trial.

INTRODUCTION: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain condition creating a wide range of urologic and pain symptoms. There is currently limited evidence to understand the mechanisms of IC/BPS. There have been recent studies suggesting that altered function in brain motor areas, particularly the supplementary motor cortex (SMA), relates to altered bladder sensorimotor control and may play an important role in IC/BPS. This study aims to provide evidence that non-invasive stimulation targeting the motor cortex may help reduce IC/BPS pain, as well as better understand the neural mechanism by which this stimulation targets neuromuscular dysfunction. This study is a two-group quadruple-blinded randomized controlled trial (RCT) of active vs. sham repetitive transmagnetic stimulation (rTMS). In addition, our study will also include functional magnetic resonance imaging (fMRI), pelvic floor electromyography (EMG), pelvic exam, and outcome measures and questionnaires to further study outcomes. ETHICS AND DISSEMINATION: All aspects of the study were approved by the Institutional Review Board of the University of Southern California (protocol HS-20-01021). All participants provided informed consent by the research coordinator/assistants. The results will be submitted for publication in peer-reviewed journals and disseminated at scientific conferences. TRIAL REGISTRATION: ClinicalTrials.gov NCT04734847. Registered on February 1, 2021.

Multimodal smoking cessation treatment combining repetitive transcranial magnetic stimulation, cognitive behavioral therapy, and nicotine replacement in veterans with posttraumatic stress disorder: A feasibility randomized controlled trial protocol.

Tobacco-related deaths remain the leading cause of preventable death in the United States. Veterans suffering from posttraumatic stress disorder (PTSD)-about 11% of those receiving care from the Department of Veterans Affairs (VA)-have triple the risk of developing tobacco use disorder (TUD). The most efficacious strategies being used at the VA for smoking cessation only result in a 23% abstinence rate, and veterans with PTSD only achieve a 4.5% abstinence rate. Therefore, there is a critical need to develop more effective treatments for smoking cessation. Recent studies suggest the insula is integrally involved in the neurocircuitry of TUD. Thus, we propose a feasibility phase II randomized controlled trial (RCT) to study a form of repetitive transcranial magnetic stimulation (rTMS) called intermittent theta burst stimulation (iTBS). iTBS has the advantage of allowing for a patterned form of stimulation delivery that we will administer at 90% of the subject's resting motor threshold (rMT) applied over a region in the right post-central gyrus most functionally connected to the right posterior insula. We hypothesize that by increasing functional connectivity between the right post-central gyrus and the right posterior insula, withdrawal symptoms and short-term smoking cessation outcomes will improve. Fifty eligible veterans with comorbid TUD and PTSD will be randomly assigned to active-iTBS + cognitive behavioral therapy (CBT) + nicotine replacement therapy (NRT) (n = 25) or sham-iTBS + CBT + NRT (n = 25). The primary outcome, feasibility, will be determined by achieving a recruitment of 50 participants and retention rate of 80%. The success of iTBS will be evaluated through self-reported nicotine use, cravings, withdrawal symptoms, and abstinence following quit date (confirmed by bioverification) along with evaluation for target engagement through neuroimaging changes, specifically connectivity differences between the insula and other regions of interest.

Real-time estimation of the optimal coil placement in transcranial magnetic stimulation using multi-task deep learning.

Transcranial magnetic stimulation (TMS) has emerged as a promising neuromodulation technique with both therapeutic and diagnostic applications. As accurate coil placement is known to be essential for focal stimulation, computational models have been established to help find the optimal coil positioning by maximizing electric fields at the cortical target. While these numerical simulations provide realistic and subject-specific field distributions, they are computationally demanding, precluding their use in real-time applications. In this paper, we developed a novel multi-task deep neural network which simultaneously predicts the optimal coil placement for a given cortical target as well as the associated TMS-induced electric field. Trained on large amounts of preceding numerical optimizations, the Attention U-Net-based neural surrogate provided accurate coil optimizations in only 35 ms, a fraction of time compared to the state-of-the-art numerical framework. The mean errors on the position estimates were below 2 mm, i.e., smaller than previously reported manual coil positioning errors. The predicted electric fields were also highly correlated (r> 0.97) with their numerical references. In addition to healthy subjects, we validated our approach also in glioblastoma patients. We first statistically underlined the importance of using realistic heterogeneous tumor conductivities instead of simply adopting values from the surrounding healthy tissue. Second, applying the trained neural surrogate to tumor patients yielded similar accurate positioning and electric field estimates as in healthy subjects. Our findings provide a promising framework for future real-time electric field-optimized TMS applications.

A randomized controlled trial of low-frequency repeated transcranial magnetic stimulation in patients with poststroke neurogenic bladder.

Urinary incontinence is a common complication in stroke survivors for whom new interventions are needed. This study investigated the therapeutic effect of low-frequency (LF) repeated transcranial magnetic stimulation (rTMS) on the contralesional primary motor cortex (M1) in patients with poststroke urinary incontinence (PSI). A total of 100 patients were randomly assigned to the rTMS group or sham-rTMS group on basis of the intervention they received. Both groups underwent five treatment sessions per week for 4 weeks. Data from the urodynamic examination were used as the primary outcome. The secondary outcome measures were questionnaires and pelvic floor surface electromyography. After 4 weeks of intervention, the maximum cystometric capacity (MCC), maximum detrusor pressure (Pdet.max), residual urine output, overactive bladder score (OABSS) (including frequency, urgency, and urgency urinary incontinence), and the ICIQ-UI SF improved significantly in the rTMS group compared with those in the sham-rTMS group (P < 0.05). However, no changes in pelvic floor muscle EMG were detected in patients with PSI (both P > 0.05). Our data confirmed that 4 weeks of LF-rTMS stimulation on the contralateral M1 positively affects poststroke urinary incontinence in several aspects, such as frequency, urgency urinary incontinence, MCC, end-filling Pdet, OABSS, and ICIQ-UI SF scores.

Repetitive transcranial magnetic stimulation reshaped the dynamic reconfiguration of the executive and reward networks in individuals with tobacco use disorder.

BACKGROUND: Studies have demonstrated the potential of repetitive transcranial magnetic stimulation (rTMS) to decrease smoking cravings in individuals with tobacco use disorder (TUD). However, the neural features underlying the effects of rTMS treatment, especially the dynamic attributes of brain networks associated with the treatment, remain unclear. METHODS: Using dynamic functional connectivity analysis, this study first explored the differences in dynamic functional network features between 60 subjects with TUD and 64 nonsmoking healthy controls (HCs). Then, the left dorsolateral prefrontal cortex (DLPFC) was targeted for a five-day course of rTMS treatment in the 60 subjects with TUD (active rTMS in 42 subjects and sham treatment in 18 subjects). We explored the effect of rTMS on the dynamic network features associated with rTMS by comparing the actively treated group and the sham group. RESULTS: Compared to nonsmokers, TUD subjects exhibited an increased integration coefficient between the frontoparietal network (FPN) and the basal ganglia network (BGN) and a reduced integration coefficient between the medial frontal network (MFN) and the FPN. Analysis of variance revealed that rTMS treatment reduced the integration coefficient between the FPN and BGN and improved the recruitment coefficient of the FPN. LIMITATIONS: This study involved a limited sample of young male smokers, and the findings may not generalize to older smokers or female smokers with an extensive history of smoking. CONCLUSION: rTMS treatment of the left DLPFC exhibited significant effectiveness in restructuring the neural circuits associated with TUD while significantly mitigating smoking cravings.

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.

Repetitive transcranial magnetic stimulation promotes motor function recovery in mice after spinal cord injury via regulation of the Cx43-autophagy loop.

Spinal cord injury (SCI) is a severe condition with an extremely high disability rate. It is mainly manifested as the loss of motor, sensory and autonomic nerve functions below the injury site. High-frequency transcranial magnetic stimulation, a recently developed neuromodulation method, can increase motor function in mice with spinal cord injury. This study aimed to explore the possible mechanism by which transcranial magnetic stimulation (TMS) restores motor function after SCI. A complete T8 transection model of the spinal cord was established in mice, and the mice were treated daily with 15 Hz high-frequency transcranial magnetic stimulation. The BMS was used to evaluate the motor function of the mice after SCI. Western blotting and immunofluorescence were used to detect the expression of Connexin43 (CX43) and autophagy-related proteins in vivo and in vitro, and correlation analysis was performed to study the relationships among autophagy, CX43 and motor function recovery after SCI in mice. Western blotting was used to observe the effect of magnetic stimulation on the expression of mTOR pathway members. In the control group, the expression of CX43 was significantly decreased, and the expression of microtubule-associated protein 1 A/1b light chain 3 (LC3II) and P62 was significantly increased after 4 weeks of spinal cord transection. After high-frequency magnetic stimulation, the level of CX43 decreased, and the levels of LC3II and P62 increased in primary astrocytes. The BMS of the magnetic stimulation group was greater than that of the control group. High-frequency magnetic stimulation can inhibit the expression of CX43, which negatively regulates autophagic flux. HF-rTMS increased the expression levels of mTOR, p-mTOR and p-S6. Our experiments showed that rTMS can restore hindlimb motor function in mice after spinal cord injury via regulation of the Cx43-autophagy loop and activation of the mTOR signalling pathway.

High-frequency repetitive transcranial magnetic stimulation ameliorates memory impairment by inhibiting neuroinflammation in the chronic cerebral hypoperfusion mice.

BACKGROUND: High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been found to ameliorate cognitive impairment. However, the effects of HF-rTMS remain unknown in chronic cerebral hypoperfusion (CCH). AIM: To investigate the effects of HF-rTMS on cognitive improvement and its potential mechanisms in CCH mice. MATERIALS AND METHODS: Daily HF-rTMS therapy was delivered after bilateral carotid stenosis (BCAS) and continued for 14 days. The mice were randomly assigned to three groups: the sham group, the model group, and the HF-rTMS group. The Y maze and the new object recognition test were used to assess cognitive function. The expressions of MAP-2, synapsis, Myelin basic protein(MBP), and brain-derived growth factors (BDNF) were analyzed by immunofluorescence staining and western blot to evaluate neuronal plasticity and white matter myelin regeneration. Nissl staining and the expression of caspase-3, Bax, and Bcl-2 were used to observe neuronal apoptosis. In addition, the activation of microglia and astrocytes were evaluated by fluorescence staining. The inflammation levels of IL-1ß, IL-6, and Tumor Necrosis Factor(TNF)-α were detected by qPCR in the hippocampus of mice in each group. RESULTS: Via behavioral tests, the BCAS mice showed reduced a rate of new object preference and decreased a rate of spontaneous alternations, while HF-rTMS significantly improved hippocampal learning and memory deficits. In addition, the mice in the model group showed decreased levels of MAP-2, synapsis, MBP, and BDNF, while HF-rTMS treatment reversed these effects. As expected, activated microglia and astrocytes increased in the model group, but HF-rTMS treatment suppressed these changes. HF-rTMS decreased BCAS-induced neuronal apoptosis and the expression of pro-apoptotic protein (Caspase-3 and Bax) and increased the expression of anti-apoptotic protein (Bcl-2). In addition, HF-rTMS inhibited the expression of inflammatory cytokines (IL-1ß, IL-6, and TNF-α). CONCLUSIONS: HF-rTMS alleviates cognitive impairment in CCH mice by enhancing neuronal plasticity and inhibiting inflammation, thus serving as a potential method for vascular cognitive impairment.

A simulation study of transcranial magnetoacoustic stimulation of the basal ganglia thalamic neural network to improve pathological beta oscillations in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease. Transcranial magnetoacoustic stimulation (TMAS) is a new therapy that combines a transcranial focused acoustic pressure field with a magnetic field to excite or inhibit neurons in targeted area, which suppresses the abnormally elevated beta band amplitude in PD states, with high spatial resolution and non-invasively. OBJECTIVE: To study the effective stimulation parameters of TMAS mononuclear and multinuclear stimulation for the treatment of PD with reduced beta band energy, improved abnormal synchronization, and no thermal damage. METHODS: The TMAS model is constructed based on the volunteer's computed tomography, 128 arrays of phase-controlled transducers, and permanent magnets. A basal ganglia-thalamic (BG-Th) neural network model of the PD state was constructed on the basis of the Izhikevich model and the acoustic model. An ultrasound stimulation neuron model is constructed based on the Hodgkin-Huxley model. Numerical simulations of transcranial focused acoustic pressure field, temperature field and induced electric field at single and dual targets were performed using the locations of STN, GPi, and GPe in the human brain as the main stimulation target areas. And the acoustic and electric parameters at the focus were extracted to stimulate mononuclear and multinuclear in the BG-Th neural network. RESULTS: When the stimulating effect of ultrasound is ignored, TMAS-STN simultaneously inhibits the beta-band amplitude of the GPi nucleus, whereas TMAS-GPi fails to simultaneously have an inhibitory effect on the STN. TMAS-STN&GPi can reduce the beta band amplitude. TMAS-STN&GPi&GPe suppressed the PD pathologic beta band amplitude of each nucleus to a greater extent. When considering the stimulatory effect of ultrasound, lower sound pressures of ultrasound do not affect the neuronal firing state, but higher sound pressures may promote or inhibit the stimulatory effect of induced currents. CONCLUSIONS: At 9 T static magnetic field, 0.5-1.5 MPa and 1.5-2.0 MPa ultrasound had synergistic effects on individual STN and GPi neurons. TMAS multinuclear stimulation with appropriate ultrasound intensity was the most effective in suppressing the amplitude of pathological beta oscillations in PD and may be clinically useful.

Neuromodulatory Responses Elicited by Intermittent versus Continuous Transcranial Focused Ultrasound Stimulation of the Motor Cortex in Rats.

Transcranial focused ultrasound stimulation (tFUS) has emerged as a promising neuromodulation technique that delivers acoustic energy with high spatial resolution for inducing long-term potentiation (LTP)- or depression (LTD)-like plasticity. The variability in the primary effects of tFUS-induced plasticity could be due to different stimulation patterns, such as intermittent versus continuous, and is an aspect that requires further detailed exploration. In this study, we developed a platform to evaluate the neuromodulatory effects of intermittent and continuous tFUS on motor cortical plasticity before and after tFUS application. Three groups of rats were exposed to either intermittent, continuous, or sham tFUS. We analyzed the neuromodulatory effects on motor cortical excitability by examining changes in motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS). We also investigated the effects of different stimulation patterns on excitatory and inhibitory neural biomarkers, examining c-Fos and glutamic acid decarboxylase (GAD-65) expression using immunohistochemistry staining. Additionally, we evaluated the safety of tFUS by analyzing glial fibrillary acidic protein (GFAP) expression. The current results indicated that intermittent tFUS produced a facilitation effect on motor excitability, while continuous tFUS significantly inhibited motor excitability. Furthermore, neither tFUS approach caused injury to the stimulation sites in rats. Immunohistochemistry staining revealed increased c-Fos and decreased GAD-65 expression following intermittent tFUS. Conversely, continuous tFUS downregulated c-Fos and upregulated GAD-65 expression. In conclusion, our findings demonstrate that both intermittent and continuous tFUS effectively modulate cortical excitability. The neuromodulatory effects may result from the activation or deactivation of cortical neurons following tFUS intervention. These effects are considered safe and well-tolerated, highlighting the potential for using different patterns of tFUS in future clinical neuromodulatory applications.

Does SLT combined with NIBS enhance naming recovery in post-stroke aphasia? A meta-analysis and systematic review.

BACKGROUND: Non-invasive brain stimulation has been widely used as an adjunctive treatment for aphasia following stroke. OBJECTIVE: The aim of this study was to investigate the effect of non-invasive brain stimulation as an adjunctive treatment on naming function in aphasia following stroke. METHODS: This review included randomized controlled trials (RCTs) involving 5 databases (Web of Science, Embase, Cochrane Library, OVID and PubMed) that investigated the effects of electrical stimulation on stroke patients. The search included literature published up to November 2023. RESULTS: We identified 18 studies, and the standardized mean differences (SMDs) showed that the effect sizes of TMS and tDCS were small to medium. Moreover, the treatment effects persisted over time, indicating long-term efficacy. CONCLUSION: This study suggested that NIBS combined with speech and language therapy can effectively promote the recovery of naming function in patients with post-stroke aphasia (PSA) and that the effects are long lasting.

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).

Assessing the effectiveness of high frequency repetitive transcranial magnetic stimulation for post-mastectomy pain in breast cancer patients: A randomized controlled trial.

BACKGROUND: Post-mastectomy pain Syndrome (PMPS), characterized by chronic neuropathic pain stemming from intercostobrachial nerve lesions, presents a formidable clinical challenge. With the incidence of breast cancer surging, effective interventions for PMPS are urgently needed. To address this, we conducted this double-blind, placebo-controlled, randomized clinical trial to study the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) therapy over the motor cortex on pain, quality of life and thermal sensitivity in PMPS patients. METHODS: We delivered 15 rTMS sessions over three weeks in a cohort of 34 PMPS patients. These patients were allocated randomly to either rTMS therapy or sham therapy groups. Pain assessments, utilizing the Visual Analogue Scale (VAS) and Short Form McGill Pain Questionnaire (SF-MPQ), alongside quality-of-life evaluations through the Functional Assessment of Cancer Therapy-Breast (FACT-B), were recorded before and after the 15 sessions. Additionally, we assessed thermal sensitivity using Quantitative Sensory Testing (QST). RESULTS: Our findings demonstrate the superior efficacy of rTMS therapy (over sham therapy) in reducing VAS and SF-MPQ scores (p < 0.0001), improving physical (p = 0.037), emotional (p = 0.033), and functional well-being (p = 0.020) components of quality of life, as quantified by FACT-B. Our investigation also unveiled marked enhancements in thermal sensitivity within the rTMS therapy group, with statistically significant improvements in cold detection threshold (p = 0.0001), warm detection threshold (p = 0.0033), cold pain threshold (p = 0.0078), and hot pain tolerance threshold (p = 0.0078). CONCLUSION: The study underscores the profound positive impact of rTMS therapy on pain, quality of life, and thermal sensitivity in patients having PMPS, opening new avenues for pain management strategies.

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

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

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.

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.