Neuromodulatory Approaches Research Articles

Differential impact of unilateral stroke on the bihemispheric motor cortex representation of the jaw and tongue muscles in young and aged rats.

Dysphagia commonly occurs after stroke, yet the mechanisms of post-stroke corticobulbar plasticity are not well understood. While cortical activity associated with swallowing actions is bihemispheric, prior research has suggested that plasticity of the intact cortex may drive recovery of swallowing after unilateral stroke. Age may be an important factor as it is an independent predictor of dysphagia after stroke and neuroplasticity may be reduced with age. Based on previous clinical studies, we hypothesized that cranial muscle activating volumes may be expanded in the intact hemisphere and would contribute to swallowing function. We also hypothesized that older age would be associated with limited map expansion and reduced function. As such, our goal was to determine the impact of stroke and age on corticobulbar plasticity by examining the jaw and tongue muscle activating volumes within the bilateral sensorimotor cortices. Using the middle cerebral artery occlusion rat stroke model, intracortical microstimulation (ICMS) was used to map regions of sensorimotor cortex that activate tongue and jaw muscles in both hemispheres. Young adult (7 months) and aged (30 months) male F344 × BN rats underwent a stroke or sham-control surgery, followed by ICMS mapping 8 weeks later. Videofluoroscopy was used to assess oral-motor functions. Increased activating volume of the sensorimotor cortex within the intact hemisphere was found only for jaw muscles, whereas significant stroke-related differences in tongue activating cortical volume were limited to the infarcted hemisphere. These stroke-related differences were correlated with infarct size, such that larger infarcts were associated with increased jaw representation in the intact hemisphere and decreased tongue representation in the infarcted hemisphere. We found that both age and stroke were independently associated with swallowing differences, weight loss, and increased corticomotor thresholds. Laterality of tongue and jaw representations in the sham-control group revealed variability between individuals and between muscles within individuals. Our findings suggest the role of the intact and infarcted hemispheres in the recovery of oral motor function may differ between the tongue and jaw muscles, which may have important implications for rehabilitation, especially hemisphere-specific neuromodulatory approaches. This study addressed the natural course of recovery after stroke; future work should expand to focus on rehabilitation.

Multisensory mechanisms of gait and balance in Parkinson's disease: an integrative review.

Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging population. Posture and gait control does not happen automatically, as previously believed, but rather requires continuous involvement of central nervous mechanisms. To effectively exert control over the body, the brain must integrate multiple streams of sensory information, including visual, vestibular, and somatosensory signals. The mechanisms which underpin the integration of these multisensory signals are the principal topic of the present work. Existing multisensory integration theories focus on how failure of cognitive processes thought to be involved in multisensory integration leads to falls in older adults. Insufficient emphasis, however, has been placed on specific contributions of individual sensory modalities to multisensory integration processes and cross-modal interactions that occur between the sensory modalities in relation to gait and balance. In the present work, we review the contributions of somatosensory, visual, and vestibular modalities, along with their multisensory intersections to gait and balance in older adults and patients with Parkinson's disease. We also review evidence of vestibular contributions to multisensory temporal binding windows, previously shown to be highly pertinent to fall risk in older adults. Lastly, we relate multisensory vestibular mechanisms to potential neural substrates, both at the level of neurobiology (concerning positron emission tomography imaging) and at the level of electrophysiology (concerning electroencephalography). We hope that this integrative review, drawing influence across multiple subdisciplines of neuroscience, paves the way for novel research directions and therapeutic neuromodulatory approaches, to improve the lives of older adults and patients with neurodegenerative diseases.

Tetherless Optical Neuromodulation: Wavelength from Orange-red to Mid-infrared.

Optogenetics, a technique that employs light for neuromodulation, has revolutionized the study of neural mechanisms and the treatment of neurological disorders due to its high spatiotemporal resolution and cell-type specificity. However, visible light, particularly blue and green light, commonly used in conventional optogenetics, has limited penetration in biological tissue. This limitation necessitates the implantation of optical fibers for light delivery, especially in deep brain regions, leading to tissue damage and experimental constraints. To overcome these challenges, the use of orange-red and infrared light with greater tissue penetration has emerged as a promising approach for tetherless optical neuromodulation. In this review, we provide an overview of the development and applications of tetherless optical neuromodulation methods with long wavelengths. We first discuss the exploration of orange-red wavelength-responsive rhodopsins and their performance in tetherless optical neuromodulation. Then, we summarize two novel tetherless neuromodulation methods using near-infrared light: upconversion nanoparticle-mediated optogenetics and photothermal neuromodulation. In addition, we discuss recent advances in mid-infrared optical neuromodulation.

Disparities in the treatment of movement disorders using deep brain stimulation.

Deep brain stimulation (DBS) is a well-established treatment for Parkinson's disease (PD) and essential tremor (ET). Although the prevalence of PD and ET can vary by sex and race, little is known about the accessibility of neurosurgical treatments for these conditions. In this nationwide study, the authors aimed to characterize trends in the use of DBS for the treatment of PD and ET and to identify disparities in the neurosurgical treatment of these diseases based on ethnic, racial, sex, insurance, income, hospital, and geographic factors. Using the dates January 1, 2012, to December 31, 2019, the authors queried the National Inpatient Sample database for all discharges with an ICD-9 or ICD-10 diagnosis of PD or ET. Among these discharges, the DBS rates were reported for each subgroup of race, ethnicity, and sex. To develop national estimates, all analyses were weighted. Among 2,517,639 discharges with PD, 29,820 (1.2%) received DBS, and among 652,935 discharges with ET, 11,885 (1.8%) received DBS. Amid the PD cases, Black patients (n = 405 [0.2%], OR 0.16, 95% CI 0.12-0.20) were less likely than White patients (n = 23,975 [1.2%]) to receive DBS treatment, as were Hispanic patients (n = 1965 [1.1%], OR 0.76, 95% CI 0.65-0.88), whereas Asian/Pacific Islander patients (n = 855 [1.5%]) did not statistically differ from White patients. Amid the ET cases, Black (n = 230 [0.8%], OR 0.39, 95% CI 0.27-0.56), Hispanic (n = 215 [1.0%], OR 0.39, 95% CI 0.28-0.55), and Asian/Pacific Islander (n = 55 [1.0%], OR 0.51, 95% CI 0.28-0.93) patients were less likely than White patients (n = 10,440 [1.9%]) to receive DBS. Females were less likely than males to receive DBS for PD (OR 0.69, p < 0.0001) or ET (OR 0.70, p < 0.0001). The authors describe significant racial and sex-based differences in the utilization of DBS for the treatment of PD and ET. Further research is required to ascertain the causes of these disparities, as well as any differences in access to specialty neurosurgical care and referral for neuromodulation approaches.

Evaluating noninvasive brain stimulation to treat overactive bladder in individuals with multiple sclerosis: a randomized controlled trial protocol

BackgroundMultiple Sclerosis (MS) is an often debilitating disease affecting the myelin sheath that encompasses neurons. It can be accompanied by a myriad of pathologies and adverse effects such as neurogenic lower urinary tract dysfunction (NLUTD). Current treatment modalities for resolving NLUTD focus mainly on alleviating symptoms while the source of the discomfort emanates from a disruption in brain to bladder neural circuitry. Here, we leverage functional magnetic resonance imaging (fMRI), repetitive transcranial magnetic stimulation (rTMS) protocols and the brains innate neural plasticity to aid in resolving overactive bladder (OAB) symptoms associated with NLUTD.MethodsBy employing an advanced neuro-navigation technique along with processed fMRI and diffusion tensor imaging data to help locate specific targets in each participant brain, we are able to deliver tailored neuromodulation protocols and affect either an excitatory (20 min @ 10 Hz, applied to the lateral and medial pre-frontal cortex) or inhibitory (20 min @ 1 Hz, applied to the pelvic supplemental motor area) signal on neural circuitry fundamental to the micturition cycle in humans to restore or reroute autonomic and sensorimotor activity between the brain and bladder. Through a regimen of questionnaires, bladder diaries, stimulation sessions and analysis, we aim to gauge rTMS effectiveness in women with clinically stable MS.DiscussionSome limitations do exist with this study. In targeting the MS population, the stochastic nature of MS in general highlights difficulties in recruiting enough participants with similar symptomology to make meaningful comparisons. As well, for this neuromodulatory approach to achieve some rate of success, there must be enough intact white matter in specific brain regions to receive effective stimulation. While we understand that our results will represent only a subset of the MS community, we are confident that we will accomplish our goal of increasing the quality of life for those burdened with MS and NLUTD.Trial registrationThis trial is registered at ClinicalTrials.gov (NCT06072703), posted on Oct 10, 2023.

REPRINTED WITH PERMISSION OF IASP – PAIN 164 (2023) 2425–2434: Pain in Parkinson disease: mechanistic substrates, mainclassification systems, and how to make sense out of them

Parkinson disease (PD) affects up to 2% of the general population older than 65 years and is a major cause offunctional loss. Chronic pain is a common nonmotor symptom that affects up to 80% of patients with (Pw) PD bothin prodromal phases and during the subsequent stages of the disease, negatively affecting patient’s quality of lifeand function. Pain in PwPD is rather heterogeneous and may occur because of different mechanisms. Targetingmotor symptoms by dopamine replacement or with neuromodulatory approaches may only partially control PD---related pain. Pain in general has been classified in PwPD according to the motor signs, pain dimensions, or painsubtypes. Recently, a new classification framework focusing on chronic pain was introduced to group different typesof PD pains according to mechanistic descriptors: nociceptive, neuropathic, or neither nociceptive nor neuropathic.This is also in line with the International Classification of Disease-11, which acknowledges the possibility of chronicsecondary musculoskeletal or nociceptive pain due to disease of the CNS. In this narrative review and opinionarticle, a group of basic and clinical scientists revise the mechanism of pain in PD and the challenges faced whenclassifying it as a stepping stone to discuss an integrative view of the current classification approaches and howclinical practice can be influenced by them. Knowledge gaps to be tackled by coming classification and therapeuticefforts are presented, as well as a potential framework to address them in a patient oriented manner.

Repetitive transcranial magnetic stimulation via the hippocampal brain-derived neurotrophic factor-tyrosine kinase receptor B pathway to affect sexual behavior and neuroplasticity in rapid ejaculation rats.

Premature ejaculation (PE) is the most prevalent sexual dysfunction among men. Eejaculation involves a complex nervous mechanism in which the ejaculatory centers play a key role in modulating sperm emission. Although treatment possibilities span from psychotherapy to pharmacological approaches, results show inconsistent efficacy. In this context, the emergence of repetitive transcranial magnetic stimulation (rTMS) as a non-invasive neuromodulatory approach represents a compelling avenue for potential therapeutic exploration. To investigate whether high-frequency transcranial magnetic stimulation can modulate the ejaculatory behavior of rats with rapid ejaculation by altering neurotransmitter levels and neuroplasticity in the hippocampus. Rats have been screened for rapid ejaculation by observing behavioral indices of mating, and subsequently divided into two groups. The intervention group was administered with a 10Hz rTMS stimulation, whereas the control group received a sham procedure. Upon the delivery of rTMS, we investigated ejaculation latency (EL), the hippocampal 5-hydroxytryptamine (5-HT) concentration, brain-derived neurotrophic factor (BDNF), synaptophysin (SYN), and postsynaptic density protein 95 (PSD95) expressions, as well as BDNF-receptor tyrosine kinase receptor B (TrkB) pathway upregulation. After 14 days, EL was increased in the intervention group compared with the control group. 5-HT concentration in the hippocampal region was increased, and high-frequency rTMS activated the BDNF and TrkB pathways, including phosphorylation of cAMP response element-binding protein (CREB), and upregulated the transcription and protein expression of SYN, and PSD95. RTMS upregulates BDNF, SYN, and PSD95 expression through activation of the BDNF-TrkB pathway and increases brain 5-hydroxytryptamine thereby regulating neuroplasticity and improving ejaculation.

Exploring the synergy of the eye-brain connection: neuromodulation approaches for neurodegenerative disorders through transcorneal electrical stimulation.

Exploring the synergy of the eye-brain connection: neuromodulation approaches for neurodegenerative disorders through transcorneal electrical stimulation.

Combinatorial strategies for cell transplantation in traumatic spinal cord injury.

Spinal cord injury (SCI) substantially reduces the quality of life of affected individuals. Recovery of function is therefore a primary concern of the patient population and a primary goal for therapeutic interventions. Currently, even with growing numbers of clinical trials, there are still no effective treatments that can improve neurological outcomes after SCI. A large body of work has demonstrated that transplantation of neural stem/progenitor cells (NSPCs) can promote regeneration of the injured spinal cord by providing new neurons that can integrate into injured host neural circuitry. Despite these promising findings, the degree of functional recovery observed after NSPC transplantation remains modest. It is evident that treatment of such a complex injury cannot be addressed with a single therapeutic approach. In this mini-review, we discuss combinatorial strategies that can be used along with NSPC transplantation to promote spinal cord regeneration. We begin by introducing bioengineering and neuromodulatory approaches, and highlight promising work using these strategies in integration with NSPCs transplantation. The future of NSPC transplantation will likely include a multi-factorial approach, combining stem cells with biomaterials and/or neuromodulation as a promising treatment for SCI.

Research on feeding and eating disorders in India: A narrative review.

Despite growing evidence of their prevalence, research on feeding and eating disorders (FEDs) in India has been sporadic. This narrative review aimed to summarize the research on FED in India and set priorities for future research and translation of evidence. An electronic search was conducted in the MEDLINE, PsycINFO, and Google Scholar databases to identify relevant English peer-reviewed articles from April 1967 to July 2023. The extracted data from these studies included author names, publication year, research location, type of intervention (for interventional studies), nature of comparator treatments, and main outcomes or findings. We found a rising trend in the prevalence of EDs in India. Adolescent age group, female sex, higher socioeconomic status, family history of mental illness or disordered eating, and borderline personality pattern were risk factors for EDs. For feeding disorders (FDs), childhood age group, malnutrition, pregnancy, psychosis, intellectual disability (ID), and obsessive-compulsive disorder (OCD) were putative risk factors. Both physical and psychiatric comorbidities were common in FEDs. Culture appears to exert a pathoplastic effect on symptom presentation in FEDs; an illustrative example is the documented nonfat phobic variant of anorexia nervosa (AN) in India. Research on management has focused on using assessment tools, investigations to rule out medical comorbidities, psychosocial and family-based psychotherapies, nutritional rehabilitation, pharmacotherapy, and neuromodulation approaches. Whereas the publication output on FEDs in India has increased over the last decade, it remains an under-researched area, with a striking paucity of original research. Future research priorities in FEDs include conducting country-wide registry-based studies to offer real-world insights, longitudinal research to identify culturally relevant risk factors, and developing brief, culturally sensitive diagnostic instruments for FEDs in the Indian context. This will help generate locally relevant epidemiological data on FEDs and inform treatment and prevention strategies.

Amplitude Adaptive Modulation of Neural Oscillations Over Long-Term Dynamic Conditions: A Computational Study.

Closed-loop deep brain stimulation (DBS) shows great potential for precise neuromodulation of various neurological disorders, particularly Parkinson's disease (PD). However, substantial challenges remain in clinical translation due to the complex programming procedure of closed-loop DBS parameters. In this study, we proposed an online optimized amplitude adaptive strategy based on the particle swarm optimization (PSO) and proportional-integral-differential (PID) controller for modulation of the beta oscillation in a PD mean field model over long-term dynamic conditions. The strategy aimed to calculate the stimulation amplitude adapting to the fluctuations caused by circadian rhythm, medication rhythm, and stochasticity in the basal ganglia-thalamus-cortical circuit. The PID gains were optimized online using PSO, based on modulation accuracy, mean stimulation amplitude, and stimulation variation. The results showed that the proposed strategy optimized the stimulation amplitude and achieved beta power modulation under the influence of circadian rhythm, medication rhythm, and stochasticity of beta oscillations. This work offers a novel approach for precise neuromodulation with the potential for clinical translation.

Exploring the therapeutic potential of tDCS, TMS and DBS in overcoming tobacco use disorder: an umbrella review

&lt;p&gt;The purpose of the present study was to investigate the effects of neuromodulation techniques, including transcranial direct current stimulation, transcranial magnetic stimulation, and deep brain stimulation, on the treatments of nicotine dependence. Specifically, our objective was to assess the existing evidence by conducting an umbrella review of systematic reviews. The quality of the included studies was evaluated using the standardized tools designed to evaluate systematic reviews. The PubMed/MEDLINE database was queried for systematic reviews, and yielded 7 systematic reviews with a substantial sample size (N = 4,252), some of which included meta-analyses. A significant finding across these studies was the effectiveness of neuromodulation techniques to reduce nicotine cravings and consumption, through the evidence remains not yet conclusive. A significant efficacy of transcranial direct current stimulation and repetitive transcranial magnetic stimulation that targeted the dorsolateral prefrontal cortex was found, as well as the lateral prefrontal cortex and insula bilaterally, on smoking frequency and craving. Moreover, smoking behaviors may also be positively affected by the use of deep brain stimulation (DBS) targeting the nucleus accumbens. In conclusion, neuromodulation approaches hold promise as effective treatments for tobacco use disorder. Nonetheless, further research is required to comprehensively understand their effectiveness and to determine if combining them with other treatments can aid individuals to successfully quit smoking.&lt;/p&gt;

Feasibility of deep learning to predict tinnitus patient outcomes

Advances in machine and deep learning techniques provide a novel approach in understanding complex patterns within large datasets, leading to an implementation of personalized medicine approaches to support clinical decision making. Results from recent clinical trials (TENT-A1 and TENT-A2 studies; clinicaltrials.gov: NCT02669069 and NCT03530306) support that a novel bimodal neuromodulation approach could be a breakthrough treatment for patients with tinnitus, which adversely affects 10–15 % of the population. Given the heterogeneity of symptoms, it is important to identify whether treatment has an optimal effect on specific subgroups of tinnitus patients. The current study is a first look at the feasibility of using deep learning modelling on patient reported data to predict treatment outcomes in individuals with tinnitus, and highlights what features are most beneficial for clinical decision making.

Modulation of the autonomic nervous system for preventing perioperative atrial fibrillation: a review of literature

Introduction: Autonomic control of the heart is exerted by the neurocardiac axis, which comprises reflexes at three levels of cardiac activity: central (higher structures of the forebrain, brainstem, and spinal cord), intrathoracic extracardiac (stellate and dorsal root ganglia), and intracardiac. Neuromodulation of the autonomic nervous system (ANS) (ganglion plexus ablation, epicardial drug infusion for temporary neurotoxicity, low-level vagus nerve stimulation, stellate ganglion blockade, baroreceptor stimulation, spinal cord stimulation, renal and pulmonary artery nerve fiber denervation) is a new therapeutic approach for managing heart rhythm disorders and cardiovascular pathologies. Atrial fibrillation (AF) occurs in up to 30% of patients after open cardiac surgery and is associated with increased morbidity and mortality in the long-term follow-up. Objective: To evaluate the safety and efficacy of the different neuromodulation approaches for preventing postoperative atrial fibrillation (POAF) in clinical and experimental settings.Conclusion: ANS neuromodulation techniques have demonstrated high efficacy and safety for preventing POAF. Received 21 August 2023. Revised 16 October 2023. Accepted 31 October 2023. Funding: The study was supported by Russian Science Foundation (project No. 22-25-00672). Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: V.V. Shabanov, A.G. Filippenko, V.V. BeloborodovDrafting the article: V.V. Shabanov, A.G. Filippenko, T.U. Khalkhoghaev, V.I. MurtazinCritical revision of the article: V.V. ShabanovFinal approval of the version to be published: V.V. Shabanov, V.V. Beloborodov, T.U. Khalkhoghaev, V.I. Murtazin, A.G. Filippenko

Patient-specific modeling for guided rehabilitation of stroke patients: the BrainX3 use-case

BrainX3 is an interactive neuroinformatics platform that has been thoughtfully designed to support neuroscientists and clinicians with the visualization, analysis, and simulation of human neuroimaging, electrophysiological data, and brain models. The platform is intended to facilitate research and clinical use cases, with a focus on personalized medicine diagnostics, prognostics, and intervention decisions. BrainX3 is designed to provide an intuitive user experience and is equipped to handle different data types and 3D visualizations. To enhance patient-based analysis, and in keeping with the principles of personalized medicine, we propose a framework that can assist clinicians in identifying lesions and making patient-specific intervention decisions. To this end, we are developing an AI-based model for lesion identification, along with a mapping of tract information. By leveraging the patient's lesion information, we can gain valuable insights into the structural damage caused by the lesion. Furthermore, constraining whole-brain models with patient-specific disconnection masks can allow for the detection of mesoscale excitatory-inhibitory imbalances that cause disruptions in macroscale network properties. Finally, such information has the potential to guide neuromodulation approaches, assisting in the choice of candidate targets for stimulation techniques such as Transcranial Ultrasound Stimulation (TUS), which modulate E-I balance, potentiating cortical reorganization and the restoration of the dynamics and functionality disrupted due to the lesion.

Black Phosphorus Flake-Enabled Wireless Neuromodulation for Epilepsy Treatment.

Epilepsy is a prevalent and severe neurological disorder and generally requires prolonged electrode implantation and tether brain stimulation in refractory cases. However, implants may cause potential chronic immune inflammation and permanent tissue damage due to material property mismatches with soft brain tissue. Here, we demonstrated a nanomaterial-enabled near-infrared (NIR) neuromodulation approach to provide nongenetic and nonimplantable therapeutic benefits in epilepsy mouse models. Our study showed that crystal-exfoliated photothermal black phosphorus (BP) flakes could enhance neural activity by altering the membrane capacitive currents in hippocampus neurons through NIR photothermal neuromodulation. Optical stimulation facilitated by BP flakes in hippocampal slices evoked action potentials with a high spatiotemporal resolution. Furthermore, BP flake-enabled NIR neuromodulation of hippocampus neural circuits can suppress epileptic signals in epilepsy model mice with minimal invasiveness and high biocompatibility. Consequently, nanomaterial-enabled NIR neuromodulation may open up opportunities for nonimplantable optical therapy of epilepsy in nontransgenic organisms.

Abstract 17051: Oxytocin Receptor in the Spinal Neuraxial Modulation of Ventricular Excitability

Introduction: Cardiac sympathoexcitation is a major contributor to the pathogenesis of ventricular tachyarrhymias (VTs) during ischemia reperfusion (I/R) and chronic myocardial infarction (MI). Afferent network connections in the intermediolateral cell column (IML) and dorsal horn (DH) control sympathetic output to the heart. Our team reported spinal cord stimulation (SCS), decreased cardiac sympathoexcitation and reduced VTs during ischemia. Oxytocin (OXT) is a known neuromodulator; however, whether OXT signaling can modulate the cardiospinal neural network is unknown. Hypothesis: SCS neuromodulation is reducing sympathoexcitation and VTs through OXT signaling pathways. Methods: Two models of cardiac ischemia were used in Yorkshire domestic swine. In acute I/R, a suture was placed around the left anterior descending (LAD) coronary artery, after sternotomy. Chronic infarction (MI) was created by accessing the femoral with fluoroscopy guidance. Polystyrene microspheres (1ml) were injected via a 3mm angioplasty balloon catheter to the LAD. Animals then recovered post-MI for 6-8wk. SCS treatment was delivered through a four-pole lead which was inserted in the epidural space (T1-T4)(50Hz, 0.4ms pulse duration). T2-T4 spinal cord was collected postmortem for molecular analysis. Fluorescence in situ hybridization (FISH) protocol for RNAscope Fluorescent v2 Assay (ACD) was followed. Cell counts represented as 3 puncta or more centered around DAPI. Results: We report that OXT receptor positive cells significantly decreased as a result of I/R and MI (p&lt;0.001, two-way ANOVA n=4-5 animals, average of 2-3 slices per animal). Within the DH the majority of OXT positive cells were inhibitory GABAergic neurons. Within the IML, a majority of the cells regulated by I/R and MI were microglia, and both an inhibitory and excitatory population contributed to the onset of ischemia. SCS treatment after I/R and MI resulted in the recovery of this OXT receptor cell population. Conclusions: By evaluating the role of OXT in reducing cardiac sympathoexcitation at the level of the spinal cord, we provide new insights into optimizing current neuromodulation approaches and developing new pharmacologic therapies.

Enhanced and spatially controllable neuronal activity induced by transcranial focused ultrasound stimulation combined with phase-change nanodroplets

Non-invasive ultrasound neuromodulation (USNM) is a powerful tool to explore neural circuits and treat neurological disorders. Due to the heterogeneity of the skull and regional variations in modulation and treatment objectives, it is necessary to develop an efficient and spatially controllable neuromodulation approach. Recently, transcranial focused ultrasound (tFUS) combined with external biomicro/nanomaterials for brain stimulation has garnered significant attention. This study focused on tFUS combined with perfluoropentane (PFP) nanodroplets (NDs) to improve the efficacy and spatial controllability of USNM. The developed two-stage variable pulse tFUS sequence that include the acoustic droplet vaporization (ADV) pulse for vaporizing PFP NDs into microbubbles (MBs) and the USNM sequence for inducing mechanical oscillations of the formed MBs to enhance neuronal activity. Further, adjusting the acoustic pressure of the ADV pulse generated the controllable vaporization regions, thereby achieving spatially controllable neuromodulation. The results showed that the mean densities of c-fos+ cells expression in the group of PFP NDs with ADV (109 ± 19 cells/mm2) were significantly higher compared to the group without ADV (37.34 ± 8.24 cells/mm2). The acoustic pressure of the ADV pulse with 1.98 MPa and 2.81 MPa in vitro generated the vaporization regions of 0.146 ± 0.032 cm2 and 0.349 ± 0.056 cm2, respectively. Under the same stimulation conditions, a larger vaporization region was also obtained with higher acoustic pressure in vivo, inducing a broader region of neuronal activation. Therefore, this study will serve as a valuable reference for developing the efficient and spatially controllable tFUS neuromodulation strategy.

Research trends on the use of ultrasound as neuromodulation-based therapy, based on bibliometric analysis

Link of Video Abstract: https://youtu.be/3g92-Hr_5c0 Introduction: Ultrasound has seen a significant increase in use in neuromodulation-based therapy over the past decade due to technological advancements, enabling precise tissue ablation, clinical neuromodulatory brain stimulation, and targeted blood-brain barrier permeabilization. The bibliometric analysis reveals a growing body of literature focused on the utilization of low-intensity ultrasound (LI-US) and high-intensity focused ultrasound (HIFUS) in the field of neuromodulation. Ultrasonography has potential applications in treating neurological and psychiatric illnesses like neuropathic pain, epilepsy, and treatment-resistant mental illness, but further investigation is needed to understand mechanisms and safety considerations. The use of bibliometric analysis can effectively identify common research patterns and highlight advancements in this specific academic field. Research indicates that ultrasound-based neuromodulation approaches may offer novel therapeutic interventions with enhanced efficacy and safety in treating various neurological and mental illnesses. Methods: The process of data collection involved conducting a search on the Scopus website using specific keywords. Subsequently, the collected data is stored in the file formats of .bib and .csv. These files are then subjected to analysis using the biblioshiny and Vosviewer software tools. The research not only use quantitative analysis but also incorporates qualitative investigations. Results: The trend of the most significant affiliations, authors, documents with the highest number of citations, relevant sources, cited nations, and annual scientific production was determined. This academic study employs many visualization techniques, including overlay visualization of the Scopus database, utilization of VOSviewer for database analysis, network visualization, density visualization, and thematic mapping. Conclusions: The use of ultrasound as a neuromodulation therapy offers numerous opportunities and potential across various sub-topics, despite a limited literature corpus compared to other academic disciplines. The use of this discipline in human subjects is limited, requiring extensive clinical studies and cross-national collaboration for the advancement of therapeutic interventions.

Safety and Feasibility of Functional Repetitive Neuromuscular Magnetic Stimulation of the Gluteal Muscles in Children and Adolescents with Bilateral Spastic Cerebral Palsy.

Background: For children and adolescents affected by bilateral spastic cerebral palsy (BSCP), non-invasive neurostimulation with repetitive neuromuscular magnetic stimulation (rNMS) combined with physical exercises, conceptualized as functional rNMS (frNMS), represents a novel treatment approach. Methods: In this open-label study, six children and two adolescents (10.4 ± 2.5 years) with BSCP received a frNMS intervention targeting the gluteal muscles (12 sessions within 3 weeks). Results: In 77.1% of the sessions, no side effects were reported. In 16.7%, 6.3% and 5.2% of the sessions, a tingling sensation, feelings of pressure/warmth/cold or very shortly lasting pain appeared, respectively. frNMS was highly accepted by families (100% adherence) and highly feasible (97.9% of treatment per training protocol). A total of 100% of participants would repeat frNMS, and 87.5% would recommend it. The Canadian Occupational Performance Measure demonstrated clinically important benefits for performance in 28% and satisfaction in 42% of mobility-related tasks evaluated by caregivers for at least one follow-up time point (6 days and 6 weeks post intervention). Two patients accomplished goal attainment for one mobility-related goal each. One patient experienced improvement for both predefined goals, and another participant experienced improvement in one and outreach of the other goal as assessed with the goal attainment scale. Conclusions: frNMS is a safe and well-accepted neuromodulatory approach that could improve the quality of life, especially in regard to activity and participation, of children and adolescents with BSCP. Larger-scaled studies are needed to further explore the effects of frNMS in this setting.