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

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

Predictive values of pre-treatment brain age models to rTMS effects in neurocognitive disorder with depression: Secondary analysis of a randomised sham-controlled clinical trial.

INTRODUCTION: One major challenge in developing personalised repetitive transcranial magnetic stimulation (rTMS) is that the treatment responses exhibited high inter-individual variations. Brain morphometry might contribute to these variations. This study sought to determine whether individual's brain morphometry could predict the rTMS responders and remitters. METHODS: This was a secondary analysis of data from a randomised clinical trial that included fifty-five patients over the age of 60 with both comorbid depression and neurocognitive disorder. Based on magnetic resonance imaging scans, estimated brain age was calculated with morphometric features using a support vector machine. Brain-predicted age difference (brain-PAD) was computed as the difference between brain age and chronological age. RESULTS: The rTMS responders and remitters had younger brain age. Every additional year of brain-PAD decreased the odds of relieving depressive symptoms by ∼25.7% in responders (Odd ratio [OR] = 0.743, p = .045) and by ∼39.5% in remitters (OR = 0.605, p = .022) in active rTMS group. Using brain-PAD score as a feature, responder-nonresponder classification accuracies of 85% (3rd week) and 84% (12th week), respectively were achieved. CONCLUSION: In elderly patients, younger brain age appears to be associated with better treatment responses to active rTMS. Pre-treatment brain age models informed by morphometry might be used as an indicator to stratify suitable patients for rTMS treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ChiCTR-IOR-16008191.

Fluctuation of fine motor skills throughout the menstrual cycle in women.

The effect of the menstrual cycle on fine motor skills is unclear. This study determined whether the menstrual cycle affected fine motor skills and related neural activities. Nineteen women with regular menstrual cycles were tested for fine motor skills using two types of tasks: grooved pegboard task (GPT), which evaluates motor control with high freedom of movements, and force modulation task (FMT), which evaluates more complex and fine motor control with low freedom of movements. We also assessed primary motor cortex intracortical circuits and sensorimotor integration using paired-pulse transcranial magnetic stimulation to reveal why the menstrual cycle affects fine motor skills. The present study indicated that fine motor skills assessed by FMT varied throughout the menstrual cycle while those measured by GPT did not. These results suggest that fine motor skills requiring more complex and fine control may be affected by the menstrual cycle. Additionally, changes in fine motor skills throughout the menstrual cycle may be associated with the severity of menstruation-related symptoms.

[Thinking on the classification of non-invasive brain stimulation as neuromodulation technique].

Neuromodulation techniques have gradually evolved from electrical or chemical methods to various physical stimulation techniques including electricity, magnetism, sound, light, heat, and more. However, the clinical efficacy and mechanisms of each stimulation technique or paradigm vary greatly. To facilitate the understanding of the therapeutic effects and mechanisms of different neuromodulation techniques, combined with current clinical practice, the author takes the classification of non-invasive transcranial electrical stimulation as an example and proposes the idea of using energy magnitude as the primary classification and different media/stimulation routes as the secondary classification. This classification emphasizes the energy essence of various physical stimuli, followed by the transmission carriers of physical stimuli. This classification method helps to guide and design neuromodulation paradigms for different target symptoms in various brain disorders, which is beneficial for better serving clinical diagnosis and treatment. The Expert Forum also discusses the advantages and disadvantages of various neuromodulation technologies and their clinical applications.

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

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

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.

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

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

Efficacy of repetitive transcranial magnetic stimulation on post-stroke cognitive impairment: A systematic and a network meta-analysis.

OBJECTIVES: This study aimed to evaluate the efficacy of different repetitive transcranial magnetic stimulation (rTMS) modes in stroke patients with cognitive impairment, and to rank the best option according to the outcome measures. METHODS: Literature was searched in PubMed, Cochrane Library, Web of Science, Embase, SinoMed, China National Knowledge Infrastructure, Wanfang Database, and VIP Database, from database inception to September 2023. We included randomized controlled trials (RCTs) investigating the efficacy of all rTMS modes for post-stroke cognitive impairment. The selected studies assessed at least one of the following outcome measures: Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), P300 latency and amplitude, and modified Barthel Index (MBI) or BI. Two researchers independently conducted data extraction. Quality assessment was performed using RevMan 5.3 software based on the Cochrane Collaboration's tool, and statistical analysis was conducted by GeMTC 0.14.3 software and Stata 17.0 software. RESULTS: The network meta-analysis included 74 RCTs with a total of 5478 patients. The best probability ranking indicated that intermittent theta burst stimulation (iTBS) was the most effective in enhancing MoCA, MMSE and MBI scores (85%, 54%, 42%, respectively), followed by 10 Hz rTMS (79%, 50%, 39%, respectively), for P300 amplitude, ≤1 Hz rTMS was ranked first (52%). CONCLUSIONS: The current limited evidence suggests that iTBS may be the optimal approach for improving cognitive and daily life abilities of stroke patients, followed by 10 Hz rTMS, ≤1 Hz rTMS may be the preferred option for enhancing P300 amplitude. TRAIL REGISTRATION: PROSPERO 2023 CRD42023424771 available from: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=424771.

An Efficient Pulse Circuit Design for Magnetic Stimulation with Diversified Waveforms and Adjustable Parameters.

As a noninvasive neuromodulation technique, transcranial magnetic stimulation (TMS) has important applications both in the exploration of mental disorder causes and the treatment of mental disorders. During the stimulation, the TMS system generates the intracranial time-varying induced E-field (E-field), which alters the membrane potential of neurons and subsequently exerts neural regulatory effects. The temporal waveform of the induced E-fields is directly related to the stimulation effect. To meet the needs of scientific research on diversified stimulation waveforms and flexible adjustable stimulation parameters, a novel efficient pulse magnetic stimulation circuit (the EPMS circuit) design based on asymmetric cascaded multilevel technology is proposed in this paper. Based on the transient analysis of the discharge circuit, this circuit makes it possible to convert the physical quantity (the intracranial induced E-field) that needs to be measured after magnetic stimulation into easily analyzable electrical signals (the discharge voltage at both ends of the stimulation coil in the TMS circuit). This EPMS circuit can not only realize monophasic and biphasic cosine-shaped intracranial induced E-fields, which are widely used in the market, but also realize three types of new intracranial induced E-field stimulation waveform with optional amplitude and adjustable pulse width, including monophasic near-rectangular, biphasic near-rectangular and monophasic/biphasic ladder-shaped stimulation waveform, which breaks through the limitation of the stimulation waveform of traditional TMS systems. Among the new waveforms produced by the EPMS circuit, further research was conducted on the dynamic response characteristics of neurons under the stimulation of the biphasic four-level waveform (the BFL waveform) with controllable parameters. The relationship between TMS circuit parameters (discharge voltage level and duration) and corresponding neural response characteristics (neuron membrane potential change and neuronal polarizability ratio) was explained from a microscopic perspective. Accordingly, the biological physical quantities (neuronal membrane potential) that are difficult to measure can be transformed into easily analyzable electrical signals (the discharge voltage level and duration). Results showed that compared with monophasic and biphasic cosine induced E-fields with the same energy loss, the neuron polarization ratio is decreased by 54.5% and 87.5%, respectively, under the stimulation of BFL waveform, which could effectively enhance the neuromodulation effect and improve the stimulation selectivity.

Corpus Callosum-Mediated Interhemispheric Interactions in Cervical Spondylotic Myelopathy.

PURPOSE: The corpus callosum is crucial for interhemispheric interactions in the motor control of limb functions. Human and animal studies suggested spinal cord pathologies may induce cortical reorganization in sensorimotor areas. We investigate participation of the corpus callosum in executions of a simple motor task in patients with cervical spondylotic myelopathy (CSM) using transcranial magnetic stimulation. METHODS: Twenty patients with CSM with various MRI grades of severity of cord compression were compared with 19 normal controls. Ipsilateral silent period, contralateral silent period, central motor conduction time, and transcallosal conduction time (TCT) were determined. RESULTS: In both upper and lower limbs, TCTs were significantly increased for patients with CSM than normal controls ( p < 0.001 for all), without side-to-side differences. Ipsilateral silent period and contralateral silent period durations were significantly increased bilaterally for upper limbs in comparison to controls ( p < 0.01 for all), without side-to-side differences. There were no significant correlations of TCT with central motor conduction time nor severity of CSM for both upper and lower limbs ( p > 0.05 for all) bilaterally. CONCLUSIONS: Previous transcranial magnetic stimulation studies show increased motor cortex excitability in CSM; hence, increased TCTs observed bilaterally may be a compensatory mechanism for effective unidirectional and uniplanar execution of muscle activation in the distal limb muscles. Lack of correlation of TCTs with severity of CSM or central motor conduction time may be in keeping with a preexistent role of the corpus callosum as a predominantly inhibitory pathway for counteracting redundant movements resulting from increased motor cortex excitability occurring after spinal cord lesions.

Comparison of Bilateral Versus Unilateral 5 Hz or 1 Hz Repetitive Transcranial Magnetic Stimulation in Subacute Stroke: Assessment of Motor Function in a Randomized Controlled Study.

PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) can enhance brain plasticity after stroke. At low frequencies, rTMS has an inhibitory effect, whereas at high frequencies, it has an excitatory effect. Combining both frequencies in bilateral stimulation is a new rTMS protocol under investigation, especially in the subacute stage. METHODS: Fifty-five patients with subacute stroke were divided into four groups according to the rTMS protocol delivered: bilateral, inhibitory, excitatory, and control groups. All groups received concomitant task-oriented physiotherapy. Pretreatment to posttreatment assessment was performed twice, immediately after sessions and 1 month later. Volitional motor control was evaluated by Fugl-Meyer and Wolf motor function tests, and for spasticity, the Ashworth scale was used. RESULTS: All groups showed significant improvement. Bilateral, inhibitory, and excitatory groups showed same efficacy, but the bilateral protocol was superior in spasticity. No correlations were found between improvement and stroke duration and site except for spasticity. CONCLUSIONS: Bilateral rTMS shows a comparable effect to inhibitory and excitatory rTMS in improving motor disability in subacute stroke. However, it is superior for spasticity.

Role of Electroconvulsive Therapy, Ketamine Infusion, and Deep Repetitive Transcranial Magnetic Stimulation in Treatment-Resistant Bipolar Depression: A Case Report.

Background and Objectives: Options for treatment-resistant bipolar depression (TRBPD) are limited. Electroconvulsive therapy (ECT) has shown efficacy in TRBPD. However, the cognitive deficits and memory concerns associated with ECT are problematic for a significant number of patients. It remains unclear what the next step is for patients with TRBPD who fail ECT. Materials and Methods: In this case report, we present a patient with TRBPD who sequentially received 12 sessions of brief-pulse right unilateral ECT, 22 sessions of ketamine infusion at 0.5-0.75 mg/kg for 40 min, and 39 sessions of deep repetitive transcranial magnetic stimulation (dTMS). Results: The patient had some benefit from ECT, but declined continuation of ECT due to memory concerns. The patient tolerated ketamine infusion well but had limited benefit. However, the patient responded well to acute treatment with dTMS and maintained relative stability for more than 2 years. Conclusions: This case suggests that patients with TRBPD who fail ECT and/or ketamine infusion might benefit from dTMS.

Feasibility of a randomized, sham-controlled pilot study for accelerated rTMS-treatment of the cerebellum plus physiotherapy in CANVAS patients.

BACKGROUND: Cerebellar ataxia, neuropathy and bilateral vestibular areflexia (CANVAS) is a rare neurodegenerative disease affecting the cerebellum, the peripheral nervous system and the vestibular system. Due to the lack of approved drugs, therapy comprises physiotherapy and speech therapy. Transcranial magnetic stimulation is a promising non-invasive therapeutic option to complement classical symptomatic therapies. OBJECTIVE: To test feasibility of the combination of transcranial magnetic stimulation using an accelerated protocol and standard symptomatic therapy in patients with CANVAS. METHODS: Eight patients with genetically confirmed CANVAS were assigned to either verum or sham cerebellar transcranial magnetic stimulation using an accelerated protocol. Treatment duration was limited to 5 days. Additionally, patients in both groups received symptomatic therapy (speech and physiotherapy) for the duration of the study. RESULTS: All patients completed the stimulation protocol. Adverse events were rare. Ataxia severity improved in the verum group only. CONCLUSION: The combination of transcranial magnetic stimulation and classic symptomatic therapy is feasible in a neuro-rehabilitation setting and potentially ameliorates ataxia severity.

Activation changes in patients with post-stroke cognitive impairment receiving intermittent theta burst stimulation: A functional near-infrared spectroscopy study.

BACKGROUND: Intermittent theta burst stimulation (iTBS) has demonstrated efficacy in patients with cognitive impairment. However, activation patterns and mechanisms of iTBS for post-stroke cognitive impairment (PSCI) remain insufficiently understood. OBJECTIVE: To investigate the activation patterns and potential benefits of using iTBS in patients with PSCI. METHODS: A total of forty-four patients with PSCI were enrolled and divided into an iTBS group (iTBS and cognitive training) or a control group (cognitive training alone). Outcomes were assessed based on the activation in functional near-infrared spectroscopy (fNIRS), as well as Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) and the modified Barthel Index (MBI). RESULTS: Thirty-eight patients completed the interventions and assessments. Increased cortical activation was observed in the iTBS group after the interventions, including the right superior temporal gyrus (STG), left frontopolar cortex (FPC) and left orbitofrontal cortex (OFC). Both groups showed significant improvements in LOTCA and MBI after the interventions (p < 0.05). Furthermore, the iTBS group augmented superior improvement in the total score of MBI and LOTCA compared to the control group, especially in visuomotor organization and thinking operations (p < 0.05). CONCLUSION: iTBS altered activation patterns and improved cognitive function in patients with PSCI. The activation induced by iTBS may contribute to the improvement of cognitive function.

The effects of combining repetitive transcranial magnetic stimulation with task-specific training on gait performance in individuals with Parkinson's disease: A review article.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor impairments, especially in the area of gait disturbances. Physiotherapy, with a focus on task-specific training, has demonstrated a level of efficacy as regards alleviating symptoms and enhancing functional capabilities in individuals with PD. Repetitive Transcranial Magnetic Stimulation (rTMS) has emerged as a potential therapeutic intervention for improving motor functions in individuals with PD. AIMS: This review article aims to investigate the effects of combining rTMS with task-specific training on gait performance in individuals with PD. MATERIALS AND METHODS: PubMed, Physiotherapy Evidence Database (PEDro), and Scopus were all searched for relevant studies. The focus of the search was on studies that investigated the efficacy of combining rTMS with task-specific training to improve gait performance in individuals with PD. RESULTS: Four studies were identified as fulfilling the eligibility criteria and were included in the study. The combination of rTMS with specific treadmill training and weight-bearing exercises can significantly enhance walking efficiency, including improvements in walking speed, self-mobility, and step rate. In addition, the combination of rTMS and task-specific training, such as treadmill-based training, shows promise in enhancing gait performance in individuals with PD. DISCUSSION AND CONCLUSION: High-frequency rTMS targeting the primary motor cortex (or M1) can result in improved walking speed, self-mobility, and step rate. However, limited research exists regarding low-frequency stimulation of the supplementary motor area (SMA) in individuals with gait issues. Further research is required to determine the optimal parameters of rTMS, such as strength, frequency, and duration of stimulation and it is worth considering the incorporation of additional training modalities, including cognitive exercises.

Enhancement of Motor Learning and Corticospinal Excitability: The Role of Electroacupuncture and Motor Training in Healthy Volunteers.

BACKGROUND This study embarked on an innovative exploration to elucidate the effects of integrating electroacupuncture (EA) with motor training (MT) on enhancing corticospinal excitability and motor learning. Central to this investigation is the interplay between homeostatic and non-homeostatic metaplasticity processes, providing insights into how these combined interventions may influence neural plasticity and motor skill acquisition. MATERIAL AND METHODS The investigation enrolled 20 healthy volunteers, subjecting them to 4 distinct interventions to parse out the individual and combined effects of EA and MT. These interventions were EA alone, MT alone, EA-priming followed by MT, and MT-priming followed by EA. The assessment of changes in primary motor cortex (M1) excitability was conducted through motor-evoked potentials (MEPs), while the grooved pegboard test (GPT) was used to evaluate alterations in motor performance. RESULTS The findings revealed that EA and MT independently contributed to enhanced M1 excitability and motor performance. However, the additional priming with EA or MT did not yield further modulation in MEPs amplitudes. Notably, EA-priming was associated with improved GPT completion times, underscoring its potential in facilitating motor learning. CONCLUSIONS The study underscores that while EA and MT individually augment motor cortex excitability and performance, their synergistic application does not further enhance or inhibit cortical excitability. This points to the involvement of non-homeostatic metaplasticity mechanisms. Nonetheless, EA emerges as a critical tool in preventing M1 overstimulation, thereby continuously fostering motor learning. The findings call for further research into the strategic application of EA, whether in isolation or with MT, within clinical settings to optimize rehabilitation outcomes.

Hebbian priming of human motor learning.

Motor learning relies on experience-dependent plasticity in relevant neural circuits. In four experiments, we provide initial evidence and a double-blinded, sham-controlled replication (Experiment I-II) demonstrating that motor learning involving ballistic index finger movements is improved by preceding paired corticospinal-motoneuronal stimulation (PCMS), a human model for exogenous induction of spike-timing-dependent plasticity. Behavioral effects of PCMS targeting corticomotoneuronal (CM) synapses are order- and timing-specific and partially bidirectional (Experiment III). PCMS with a 2 ms inter-arrival interval at CM-synapses enhances learning and increases corticospinal excitability compared to control protocols. Unpaired stimulations did not increase corticospinal excitability (Experiment IV). Our findings demonstrate that non-invasively induced plasticity interacts positively with experience-dependent plasticity to promote motor learning. The effects of PCMS on motor learning approximate Hebbian learning rules, while the effects on corticospinal excitability demonstrate timing-specificity but not bidirectionality. These findings offer a mechanistic rationale to enhance motor practice effects by priming sensorimotor training with individualized PCMS.

A dual-brain therapeutic approach using noninvasive brain stimulation based on two-person neuroscience: A perspective review.

Our actions and decisions in everyday life are heavily influenced by social interactions, which are dynamic feedback loops involving actions, reactions, and internal cognitive processes between individual agents. Social interactions induce interpersonal synchrony, which occurs at different biobehavioral levels and comprises behavioral, physiological, and neurological activities. Hyperscanning-a neuroimaging technique that simultaneously measures the activity of multiple brain regions-has provided a powerful second-person neuroscience tool for investigating the phase alignment of neural processes during interactive social behavior. Neural synchronization, revealed by hyperscanning, is a phenomenon called inter-brain synchrony- a process that purportedly facilitates social interactions by prompting appropriate anticipation of and responses to each other's social behaviors during ongoing shared interactions. In this review, I explored the therapeutic dual-brain approach using noninvasive brain stimulation to target inter-brain synchrony based on second-person neuroscience to modulate social interaction. Artificially inducing synchrony between the brains is a potential adjunct technique to physiotherapy, psychotherapy, and pain treatment- which are strongly influenced by the social interaction between the therapist and patient. Dual-brain approaches to personalize stimulation parameters must consider temporal, spatial, and oscillatory factors. Multiple data fusion analysis, the assessment of inter-brain plasticity, a closed-loop system, and a brain-to-brain interface can support personalized stimulation.

Effectiveness of repetitive transcranial magnetic stimulation for insomnia disorder on fear memory extinction: study protocol for a randomised controlled trial.

BACKGROUND: Fear memory extinction is closely related to insomnia. Repetitive transcranial magnetic stimulation (rTMS) is safe and effective for treating insomnia disorder (ID), and it has been shown to be an efficient method for modulating fear extinction. However, whether rTMS can improve fear extinction memory in ID patients remains to be studied. In this study, we specifically aim to (1) show that 1 Hz rTMS stimulation could improve fear extinction memory in ID patients and (2) examine whether changes in sleep mediate this impact. METHODS AND DESIGN: We propose a parallel group randomised controlled trial of 62 ID participants who meet the inclusion criteria. Participants will be assigned to a real rTMS group or a sham rTMS group. The allocation ratio will be 1:1, with 31 subjects in each group. Interventions will be administered five times per week over a 4-week period. The assessments will take place at baseline (week 0), post-intervention (week 4), and 8-week follow-up (week 8). The primary outcome measure of this study will be the mean change in the Pittsburgh Sleep Quality Index (PSQI) scores from baseline to post-intervention at week 4. The secondary outcome measures include the mean change in skin conductance response (SCR), fear expectation during fear extinction, Insomnia Severity Index (ISI), Zung Self-Rating Anxiety Scale (SAS), and the Zung Self-Rating Depression Scale (SDS). DISCUSSION: This study will be the first examination of the impact of rTMS on fear memory extinction in ID patients. TRIAL REGISTRATION: Chinese Clinical Trials Register ChiCTR2300076097. Registered on 25 September 2021.