Neurostimulation Techniques Research Articles

Transcranial Magnetic Stimulation: A New Possibility in Obesity Treatment

Obesity is a major public health challenge and results from the complex interaction of many etiopathogenetic factors. However, food-related hedonic stimuli and poor inhibitory control often appear to be specific maintenance factors, and conventional treatments are sometimes ineffective. Transcranial magnetic stimulation is emerging as a promising treatment option. Targeting specific brain regions, such as the dorsolateral prefrontal cortex, was found to be effective in modulating acute food craving and improving cognitive control. This review traces the evolution and development of transcranial magnetic stimulation and presents the results of recent randomized clinical trials conducted in obese subjects. These suggest that repetitive transcranial magnetic stimulation and deep transcranial magnetic stimulation may be effective in reducing body weight, BMI and food cravings. The neural circuits involved and the underlying mechanisms of action of this neurostimulation technique are also reviewed. Finally, outstanding questions and future research directions are identified to further understand and develop this promising therapy.

The Role of Brain Plasticity in Neuromuscular Disorders: Current Knowledge and Future Prospects.

Background/Objectives: Increasing evidence shows an involvement of brain plasticity mechanisms in both motor and central manifestations of neuromuscular disorders (NMDs). These mechanisms could be specifically addressed with neuromodulation or rehabilitation protocols. The aim of this scoping review is to summarise the evidence on plasticity mechanisms' involvement in NMDs to encourage future research. Methods: A scoping review was conducted searching the PubMed and Scopus electronic databases. We selected papers addressing brain plasticity and central nervous system (CNS) studies through non-invasive brain stimulation techniques in myopathies, muscular dystrophies, myositis and spinal muscular atrophy. Results: A total of 49 papers were selected for full-text examination. Regardless of the variety of pathogenetic and clinical characteristics of NMDs, studies show widespread changes in intracortical inhibition mechanisms, as well as disruptions in glutamatergic and GABAergic transmission, resulting in altered brain plasticity. Therapeutic interventions with neurostimulation techniques, despite being conducted only anecdotally or on small samples, show promising results; Conclusions: despite challenges posed by the rarity and heterogeneity of NMDs, recent evidence suggests that synaptic plasticity may play a role in the pathogenesis of various muscular diseases, affecting not only central symptoms but also strength and fatigue. Key questions remain unanswered about the role of plasticity and its potential as a therapeutic target. As disease-modifying therapies advance, understanding CNS involvement in NMDs could lead to more tailored treatments.

Cell-specific effects of temporal interference stimulation on cortical function

Temporal interference (TI) stimulation is a popular non-invasive neurostimulation technique that utilizes the following salient neural behavior: pure sinusoid (generated in off-target brain regions) appears to cause no stimulation, whereas modulated sinusoid (generated in target brain regions) does. To understand its effects and mechanisms, we examine responses of different cell types, excitatory pyramidal (Pyr) and inhibitory parvalbumin-expressing (PV) neurons, to pure and modulated sinusoids, in intact network as well as in isolation. In intact network, we present data showing that PV neurons are much less likely than Pyr neurons to exhibit TI stimulation. Remarkably, in isolation, our data shows that almost all Pyr neurons stop exhibiting TI stimulation. We conclude that TI stimulation is largely a network phenomenon. Indeed, PV neurons actively inhibit Pyr neurons in the off-target regions due to pure sinusoids (in off-target regions) generating much higher PV firing rates than modulated sinusoids in the target regions. Additionally, we use computational studies to support and extend our experimental observations.

Transcranial alternating current stimulation can modulate the blink reflex excitability. Effects of a 10- and 20-Hz tACS session on the blink reflex recovery cycle in healthy subjects.

The blink reflex excitability, assessed through paired electrical stimuli responses, has been modulated using traditional non-invasive neurostimulation techniques. Recently, transcranial Alternating Current Stimulation (tACS) emerged as a tool to modulate brain oscillations implicated in various motor, perceptual, and cognitive functions. This study aims to investigate the influence of 20-Hz and 10-Hz tACS sessions on the primary motor cortex and their impact on blink reflex excitability. Fifteen healthy volunteers underwent 10-min tACS sessions (intensity 1mA) with active/reference electrodes placed over C4/Pz, delivering 20-Hz, 10-Hz, and sham stimulation. The blink reflex recovery cycle (BRrc) was assessed using the R2 amplitude ratio at various interstimulus intervals (ISIs) before (T0), immediately after (T1), and 30min post-tACS (T2). Both 10-Hz and 20-Hz tACS sessions significantly increased R2 ratio at T1 (10-Hz: p = 0.02; 20-Hz: p < 0.001) and T2 (10-Hz: p = 0.01; 20-Hz: p < 0.001) compared to baseline (T0). Notably, 20-Hz tACS induced a significantly greater increase in blink reflex excitability compared to sham at both T1 (p = 0.04) and T2 (p < 0.001). This study demonstrates the modulatory effect of tACS on trigemino-facial reflex circuits, with a lasting impact on BRrc. Beta-band frequency tACS exhibited a more pronounced effect than alpha-band frequency, highlighting the influential role of beta-band oscillations in the motor cortex on blink reflex excitability modulation.

Repetitive Transcranial Magnetic Stimulation (rTMS) Therapy in Mood Disorders and Generalized Anxiety Disorder (GAD)

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neurostimulation technique increasingly investigated for its therapeutic potential in mood disorders and related brain conditions. This paper using content analysis reviewed literatures and summarized current research on the efficacy and safety of rTMS in treating mood disorders, including major depressive disorder (MDD), bipolar disorder (BD), and Generalized Anxiety Disorders (GAD). Studies suggest that rTMS may offer significant improvements in depressive symptoms and mood regulation, particularly in individuals who have not responded to traditional treatments. Mechanisms of action involve modulation of cortical excitability and neural circuitry implicated in mood regulation. While rTMS demonstrates promise as a well-tolerated intervention with minimal side effects, further research is needed to optimize treatment protocols, identify patient-specific predictors of response, and elucidate long-term outcomes. Understanding the role of rTMS in mood disorder management holds potential for advancing personalized treatment approaches and improving overall patient outcomes. The paper concludes that rTMS is a promising intervention for individuals with major depressive disorder (MDD), and generalized anxiety disorder (GAD). Finally, it was recommended that further studies should be conducted on the efficacy or rTMS on mood disorders generally.

Evaluating the Efficacy of Transcranial Magnetic Stimulation in Symptom Relief and Cognitive Function in Obsessive–Compulsive Disorder, Substance Use Disorder, and Depression: An Insight from a Naturalistic Observational Study

The utilization of non-invasive neurostimulation techniques, such as transcranial magnetic stimulation (TMS), is increasingly prevalent in psychiatry due to their efficacy and safety. Although the precise therapeutic mechanisms remain partially unclear, repetitive TMS, particularly high-frequency stimulation, may enhance cognitive functions, contributing to therapeutic benefits. This within-subjects study examined the impact of TMS on cognitive and symptomatic outcomes in patients with obsessive–compulsive disorder (OCD), substance use disorder (SUD), and major depressive disorder (MDD). A total of 44 patients underwent cognitive tests and symptom assessments before and after an intensive four-week TMS treatment phase, followed by a four-week maintenance phase. Cognitive assessments included Raven’s matrices, verbal fluency, and digit span tests, while symptom severity was measured using the Italian version of the SCL-90-R. Decision-making performance was also evaluated by administering a delay discounting (DD) test. Principal component analysis was used to generate a dimensional characterization of subjects along cognitive and symptom-related axes before and after treatment. The results indicated that TMS significantly improved symptom scores, but no significant cognitive enhancement was observed. Statistical analysis based on linear mixed-effects models confirmed these findings, showing a significant fixed effect of TMS treatment on symptoms but not on cognitive performance. DD metrics remained unchanged. These findings suggest that while TMS effectively alleviates clinical symptoms, it does not produce consistent or appreciable enhancement of cognitive functions in these protocols. This study highlights the need for more personalized and combined therapeutic approaches to maximize the benefits of TMS, potentially incorporating cognitive enhancement strategies. Future studies will be useful to explore whether the results we obtained are valid for other pathologies, cognitive tests, and stimulation protocols.

Transcranial photobiomodulation for neurodevelopmental disorders: a narrative review.

Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Down syndrome (DS) significantly impact social, communicative, and behavioral functioning. Transcranial photobiomodulation (t-PBM) with near-infrared light is a promising non-invasive neurostimulation technique for neuropsychiatric disorders, including NDDs. This narrative review aimed to examine the preclinical and clinical evidence of photobiomodulation (PBM) in treating NDDs. A comprehensive search across six databases was conducted, using a combination of MeSH terms and title/abstract keywords: "photobiomodulation", "PBM", "neurodevelopmental disorders", "NDD", and others. Studies applying PBM to diagnosed NDD cases or animal models replicating NDDs were included. Protocols, reviews, studies published in languages other than English, and studies not evaluating clinical or cognitive outcomes were excluded. Nine studies were identified, including one preclinical and eight clinical studies (five on ASD, two on ADHD, and one on DS). The reviewed studies encompassed various t-PBM parameters (wavelengths: 635-905nm) and targeted primarily frontal cortex areas. t-PBM showed efficacy in improving disruptive behavior, social communication, cognitive rigidity, sleep quality, and attention in ASD; in enhancing attention in ADHD; and in improving motor skills and verbal fluency in DS. Minimal adverse effects were reported. Proposed mechanisms involve enhanced mitochondrial function, modulated oxidative stress, and reduced neuroinflammation. t-PBM emerges as a promising intervention for NDDs, with potential therapeutic effects across ASD, ADHD, and DS. These findings underscore the need for further research, including larger-scale, randomized sham-controlled clinical trials with comprehensive biomarker analyses, to optimize treatment parameters and understand the underlying mechanisms associated with the effects of t-PBM.

Neuroplasticity and Rehabilitation: Harnessing Brain Plasticity for Stroke Recovery and Functional Improvement

This paper provides a comprehensive review of the current understanding of neuroplasticity and its application in stroke rehabilitation. Stroke remains a leading cause of disability worldwide, often resulting in motor, sensory, and cognitive impairments. Neuroplasticity, the brain's ability to reorganize and adapt in response to experience and injury, offers promising avenues for recovery. This review discusses key principles of neuroplasticity and explores various rehabilitation strategies aimed at harnessing its potential for stroke recovery. Topics covered include early intervention, task-specific training, intensity and repetition, constraint-induced movement therapy, multimodal approaches, environmental enrichment, and neurostimulation techniques. Additionally, the paper discusses emerging research directions and challenges in optimizing neuroplasticity-based rehabilitation approaches. Understanding the role of neuroplasticity in stroke recovery can inform the development of more effective rehabilitation interventions and improve outcomes for individuals affected by stroke.

Revolutionizing Neurological Disorder Treatment: Integrating Innovations in Pharmaceutical Interventions and Advanced Therapeutic Technologies.

Neurological disorders impose a significant burden on individuals, leading to disabilities and a reduced quality of life. However, recent years have witnessed remarkable advancements in pharmaceutical interventions aimed at treating these disorders. This review article aims to provide an overview of the latest innovations and breakthroughs in neurological disorder treatment, with a specific focus on key therapeutic areas such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, and stroke. This review explores emerging trends in drug development, including the identification of novel therapeutic targets, the development of innovative drug delivery systems, and the application of personalized medicine approaches. Furthermore, it highlights the integration of advanced therapeutic technologies such as gene therapy, optogenetics, and neurostimulation techniques. These technologies hold promise for precise modulation of neural circuits, restoration of neuronal function, and even disease modification. While these advancements offer hopeful prospects for more effective and tailored treatments, challenges such as the need for improved diagnostic tools, identification of new targets for intervention, and optimization of drug delivery methods will remain. By addressing these challenges and continuing to invest in research and collaboration, we can revolutionize the treatment of neurological disorders and significantly enhance the lives of those affected by these conditions.

Efficacy of deep brain stimulation for Tourette syndrome and its comorbidities: A meta-analysis

Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by multiple motor and vocal tics, often accompanied by comorbid disorders. Optional treatments for patients with TS include behavioral therapy, pharmacotherapy, and neurostimulation techniques. Deep brain stimulation (DBS) has been considered a therapeutic approach for refractory TS and its comorbid symptoms. However, systematic comparison is necessary to understand the therapeutic effect of DBS among patients with TS with various comorbid symptoms, demographic characteristics, or stimulation targets. Consequently, our research aimed to assess the clinical efficacy of DBS in alleviating the symptoms of TS and its comorbidities. A systematic literature search was conducted across five databases: PubMed, Web of Science, MEDLINE, Embase, and PsycINFO. The primary outcome was the mean change in the global score of the Yale Global Tic Severity Scale (YGTSS), which assesses the severity of tics. The secondary outcomes included mean improvement of comorbid symptoms, such as obsessive-compulsive behaviors (OCB), depression symptoms and anxiety symptoms. In total, 51 studies with 673 participants were included in this meta-analysis. Overall, the DBS led to a significant improvement in tic symptoms (p ​< ​0.001), as well as the comorbid obsessive-compulsive, depression, and anxiety symptoms with effect sizes of 1.88, 0.88, 1.04, and 0.76 accordingly. In the subgroup analysis, we found that striatum stimulation led to a more significant improvement in OCB in patients with TS compared to that observed with thalamic stimulation (p ​= ​0.017). The relationship between sex, age, and target with the improvement of tics, depression, and anxiety was not statistically significant (p ​= ​0.923, 0.438, 0.591 for different male proportions; p ​= ​0.463, 0.425, 0.105 for different age groups; p ​= ​0.619, 0.113, 0.053 for different targets). In conclusion, DBS is an efficient treatment option for TS, as well as the comorbid OCB, depression symptoms, and anxiety symptoms. It is important to highlight that stimulating the striatum is more effective in managing obsessive-compulsive symptoms compared to stimulating the thalamus.

Neurostimulation for treatment of post-stroke impairments.

Neurostimulation, the use of electrical stimulation to modulate the activity of the nervous system, is now commonly used for the treatment of chronic pain, movement disorders and epilepsy. Many neurostimulation techniques have now shown promise for the treatment of physical impairments in people with stroke. In 2021, vagus nerve stimulation was approved by the FDA as an adjunct to intensive rehabilitation therapy for the treatment of chronic upper extremity deficits after ischaemic stroke. In 2024, pharyngeal electrical stimulation was conditionally approved by the UK National Institute for Health and Care Excellence for neurogenic dysphagia in people with stroke who have a tracheostomy. Many other approaches have also been tested in pivotal device trials and a number of approaches are in early-phase study. Typically, neurostimulation techniques aim to increase neuroplasticity in response to training and rehabilitation, although the putative mechanisms of action differ and are not fully understood. Neurostimulation techniques offer a number of practical advantages for use after stroke, such as precise dosing and timing, but can be invasive and costly to implement. This Review focuses on neurostimulation techniques that are now in clinical use or that have reached the stage of pivotal trials and show considerable promise for the treatment of post-stroke impairments.

The Safety of Peripheral Nerve Blocks: The Role of Triple Monitoring in Regional Anaesthesia, a Comprehensive Review.

Regional anaesthesia, referred to as regional blocks, is one of the most frequently used methods of anaesthesia for surgery and for pain management. Local anaesthetic drug should be administered as close to the nerve as possible. If administered too far away, this may result in insufficient block. If it is administrated too close, severe nerve damage can occur. Neurostimulation techniques and ultrasound imaging have improved the effectiveness and safety of blockade, but the risk of nerve injury with permanent nerve disfunction has not been eliminated. Intraneural administration of a local anaesthetic damages the nerve mechanically by the needle and the high pressure generated by the drug inside the nerve. In many studies, injection pressure is described as significantly higher for unintended intraneural injections than for perineural ones. In recent years, the concept of combining techniques (neurostimulation + USG imaging + injection pressure monitoring) has emerged as a method increasing safety and efficiency in regional anaesthesia. This study focuses on the contribution of nerve identification methods to improve the safety of peripheral nerve blocks by reducing the risk of neural damage.

Transcutaneous Auricular Vagus Nerve Stimulation to Improve Emotional State.

Emotional experiences are a part of our lives. The maladaptive functioning of an individual's emotional field can lead to emotional disturbances of various kinds, such as anxiety and depression. Currently, there is an increasing prevalence of emotional disorders that cause great human suffering and high socioeconomic costs. Emotional processing has a biological basis. The major neuroscientific theories of emotion are based on biological functioning, and all of them take into account the anatomy and function of the tenth cranial nerve: the vagus nerve. The vagus nerve connects the subdiaphragmatic and supradiaphragmatic areas and modulates emotional processing as the basis of interoceptive functioning. Auricular vagus nerve stimulation is a new and innovative neuromodulation technique based on the function of the vagus nerve. Several interventions have shown that this new neurostimulation technique is a very promising resource for treating emotional disorders. In this paper, we summarise three neuroscientific theories of emotion, explain what transcutaneous auricular nerve stimulation is, and present arguments for its use and continued research.

VGLUT2 and APP family: unraveling the neurobiochemical mechanisms of neurostimulation therapy to STZ-induced diabetes and neuropathy.

Diabetic Peripheral Neuropathy (DPN) poses an escalating threat to public health, profoundly impacting well-being and quality of life. Despite its rising prevalence, the pathogenesis of DPN remains enigmatic, and existing clinical interventions fall short of achieving meaningful reversals of the condition. Notably, neurostimulation techniques have shown promising efficacy in alleviating DPN symptoms, underscoring the imperative to elucidate the neurobiochemical mechanisms underlying DPN. This study employs an integrated multi-omics approach to explore DPN and its response to neurostimulation therapy. Our investigation unveiled a distinctive pattern of vesicular glutamate transporter 2 (VGLUT2) expression in DPN, rigorously confirmed through qPCR and Western blot analyses in DPN C57 mouse model induced by intraperitoneal Streptozotocin (STZ) injection. Additionally, combining microarray and qPCR methodologies, we revealed and substantiated variations in the expression of the Amyloid Precursor Protein (APP) family in STZ-induced DPN mice. Analyzing the transcriptomic dataset generated from neurostimulation therapy for DPN, we intricately explored the differential expression patterns of VGLUT2 and APPs. Through correlation analysis, protein-protein interaction predictions, and functional enrichment analyses, we predicted the key biological processes involving VGLUT2 and the APP family in the pathogenesis of DPN and during neurostimulation therapy. This comprehensive study not only advances our understanding of the pathogenesis of DPN but also provides a theoretical foundation for innovative strategies in neurostimulation therapy for DPN. The integration of multi-omics data facilitates a holistic view of the molecular intricacies of DPN, paving the way for more targeted and effective therapeutic interventions.

Abstract WP14: Photobiomodulation Treatment Enhancesand Sustains Neurogenesis Following Acute Ischemic Stroke

Rationale: Previous work has indicated that photobiomodulation (PBM), may provide neuroprotection and improve neurological function after acute ischemic stroke. However, the underlying mechanism remains unclear. The present study was performed to examine whether PBM, a noninvasive neurostimulation technique, promotes neurogenesis in a middle cerebral artery occlusion (MCAO) stroke rat model. Methods: Beginning 6 h after MCAO, once-daily 2-min PBM treatments(808 nm) were applied to the infarcted hemisphere for 7 consecutive days. Samples were collected 7 days and 14 days after MCAO stroke. Fluorescent labeling, Western blotting, and behavioral tests were performed accordingly. Results: We found that PBM-treated animals displayed improved motor and sensory functions. PBM treatment significantly expanded the pool of neural progenitor cell (NPC) and newly generated immature neurons in the cortical peri-infarct region after acute ischemic stroke. Application of PBM strikingly diminished the MCAO-induced loss of NPCs and newly-formed neurons. In addition, the amount of newly generated mature neurons in the peri-infarct zone was significantly promoted by PBM treatment. Intriguingly, PBM reduced reactive gliogenesis significantly while promoting oligodendrogenesis and preserving myelination. Mechanistic studies uncovered that PBM enhances the expression of brain-derived neurotrophic factor (BDNF) and initiates the activation of the BDNF/TrkB signaling pathway. Conclusions: Our findings indicate that PBM promotes neurogenesis and functional recovery through stimulating NPC proliferation, reducing NPC and immature neuron cell death, and tamping excessive gliogenesis. These effects were due, in part, to the upregulated release of trophic factors. These findings support PBM as an effective neuroregenerative treatment for acute ischemic stroke. Keywords: Ischemic stroke, Photobiomodulation (PBM), Neurogenesis, Functional recovery, Neurotrophic factors

Molecular Insights into Transcranial Direct Current Stimulation Effects: Metabolomics and Transcriptomics Analyses.

Transcranial direct current stimulation (tDCS) is an evolving non-invasive neurostimulation technique. Despite multiple studies, its underlying molecular mechanisms are still unclear. Several previous human studies of the effect of tDCS suggest that it generates metabolic effects. The induction of metabolic effects by tDCS could provide an explanation for how it generates its long-term beneficial clinical outcome. Given these hints of tDCS metabolic effects, we aimed to delineate the metabolic pathways involved in its mode of action. To accomplish this, we utilized a broad analytical approach of co-analyzing metabolomics and transcriptomic data generated from anodal tDCS in rat models. Since no metabolomic dataset was available, we performed a tDCS experiment of bilateral anodal stimulation of 200 µA for 20 min and for 5 consecutive days, followed by harvesting the brain tissue below the stimulating electrode and generating a metabolomics dataset using LC-MS/MS. The analysis of the transcriptomic dataset was based on a publicly available dataset. Our analyses revealed that tDCS alters the metabolic profile of brain tissue, affecting bioenergetic-related pathways, such as glycolysis and mitochondrial functioning. In addition, we found changes in calcium-related signaling. We conclude that tDCS affects metabolism by modulating energy production-related processes. Given our findings concerning calcium-related signaling, we suggest that the immediate effects of tDCS on calcium dynamics drive modifications in distinct metabolic pathways. A thorough understanding of the underlying molecular mechanisms of tDCS has the potential to revolutionize its applicability, enabling the generation of personalized medicine in the field of neurostimulation and thus contributing to its optimization.

New possibilities of overcoming pharmacoresistance in epilepsy

Despite the presence of antiepileptic drugs with different mechanisms of action and application points, almost a third of patients still remain resistant to drug therapy. In such patients, the risk of physical and mental injuries, depression, premature death increases, and the quality and standard of living decreases.Objective. To study the mechanisms of formation of pharmacoresistance in epilepsy and to evaluate possible ways to overcome it based on the analysis of current scientific publications containing information on this topic.Results. The proposed pathophysiological mechanisms of the formation of drug resistance reflect the target hypothesis, the carrier hypothesis, pharmacokinetic theory and neural network theory. However, they are based on preclinical studies and do not have a comprehensive explanation for the appearance of this phenomenon. Surgical treatment remains the most studied and most commonly used approach. Both the usual resection of the epileptogenic part of the brain and new less crippling interventions are used: laser ablation and stereotactic radiosurgery. As an alternative, polytherapy schemes, invasive and non-invasive neurostimulation techniques, and diet therapy can be considered.Conclusions. Insensitivity to antiepileptic drugs remains a major problem in epileptology, and to overcome it, new methods are being sought and developed to influence the presumed pathogenetic targets of pharmacoresistant epileptogenesis. Vagus, deep, transcranial neurostimulation, stereotactic surgery, and laser ablation should be considered as new safe and potentially effective techniques.

A review: flexible devices for nerve stimulation

Nerve stimulation technology utilizing electricity, magnetism, light, and ultrasound has found extensive applications in biotechnology and medical fields. Neurostimulation devices serve as the crucial interface between biological tissue and the external environment, posing a bottleneck in the advancement of neurostimulation technology. Ensuring safety and stability is essential for their future applications. Traditional rigid devices often elicit significant immune responses due to the mechanical mismatch between their materials and biological tissues. Consequently, there is a growing demand for flexible nerve stimulation devices that offer enhanced treatment efficacy while minimizing irritation to the human body. This review provides a comprehensive summary of the historical development and recent advancements in flexible devices utilizing four neurostimulation techniques: electrical stimulation, magnetic stimulation, optic stimulation, and ultrasonic stimulation. It highlights their potential for high biocompatibility, low power consumption, wireless operation, and superior stability. The aim is to offer valuable insights and guidance for the future development and application of flexible neurostimulation devices.

Are We Depleted of Research Questions in Regional Anaesthesia?

Regional anaesthesia has significantly evolved, shaping pain management in surgery. This article examines whether research question in this field are becoming exhausted, or if new avenues remain unexplored. Key trends include the integration of ultrasound guidance for precision, optimizing drug combinations for enhanced safety and efficacy, and focusing on patient-concerned outcomes to improve satisfaction and recovery. Tailored approaches for special populations and long-term safety studies are also crucial. Future research may explore innovations in drug delivery, novel local anaesthetic adjuncts, neurostimulation techniques, global access, interdisciplinary collaborations, and the application of artificial intelligence. Emphasizing simplicity, innovation, and patient centric care will ensure continued progress in regional anaesthesia, fostering advancement that enhance both scientific knowledge and clinical practices. Keywords: Pain management, Regional anaesthesia, Research trends

Targeted sonogenetic modulation of GABAergic interneurons in the hippocampal CA1 region in status epilepticus.

Rationale: Sonogenetics is an advanced ultrasound-based neurostimulation approach for targeting neurons in specific brain regions. However, the role of sonogenetics in treating status epilepticus (SE) remains unclear. Here, we aimed to investigate the effects of ultrasound neurostimulation and MscL-G22S (a mechanosensitive ion channel that mediates Ca2+ influx)-mediated sonogenetics (MG-SOG) in a mouse model of kainic acid (KA)-induced SE. Methods: For MG-SOG, a Cre-dependent AAV expressing MscL-G22S was injected into parvalbumin (PV)-cre and somatostatin (SST)-cre mice to induce the expression of MscL-G22S-EGFP in PV interneurons (PV-INs) and SST interneurons (SST-INs), respectively; mice were stimulated with continuous pulses of ultrasound stimulation during the latency of generalized seizures (GSs), the latency to SE, in SE model mice. We performed calcium fiber photometry, patch-clamp recording, local field potential recording, and SE monitoring to investigate the role of MG-SOG in treating SE. Results: First, we observed obvious neuronal activation in the hippocampal CA1 region in SE model mice. Both excitatory neurons (ENs) and GABAergic interneurons (GABA-INs) in the CA1 region were activated in SE model mice; however, the inhibitory effect of GABA-INs on ENs seemed to be insufficient to reduce EN excitability despite the increased activation of GABA-INs in SE model mice. Thus, we speculated that MG-SOG-induced activation of GABA-INs, mainly SST-INs and PV-INs, in the CA1 region may protect against SE. We found that MG-SOG-mediated PV-IN activation in the CA1 region ameliorated SE and changed SE-related electrophysiological abnormalities in the CA1 region; however, MG-SOG-induced SST-IN activation in the CA1 region did not ameliorate SE. Conclusions: MG-SOG-mediated activation of PV-INs had a positive effect on relieving SE. Our work may promote the development of sonogenetic neurostimulation techniques for treating SE.