Search Results (47)

Background/Objectives: Alzheimer’s disease (AD) remains a significant global health challenge, characterised by a persistent resistance to traditional pharmacological interventions. While non-invasive brain stimulation (NIBS) techniques like transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) show therapeutic promise, their limited depth of penetration restricts their efficacy in targeting deep-brain AD pathology. Transcranial focused ultrasound stimulation (tFUS) has emerged as a novel, non-invasive neuromodulatory tool capable of precise deep-brain targeting. This scoping review aims to systematically map the current evidence base regarding the neuromodulatory application of tFUS in AD. Methods: Following PRISMA-ScR guidelines, a scoping search was conducted across four major databases (Ovid MEDLINE, Embase, Web of Science, and CENTRAL). Studies were included if they investigated focused ultrasound stimulation (FUS) as a neuromodulatory intervention for AD, excluding applications involving blood–brain-barrier disruption via microbubbles. Two independent reviewers performed screening and data extraction, with inter-rater reliability assessed via Cohen’s kappa. Results: Our analysis indicates that tFUS represents a safe and potent multi-modal intervention for AD that addresses both pathological protein aggregation and electrophysiological network failure. Its ability to modulate neuroplasticity and metabolic recovery suggests a promising therapeutic trajectory. Conclusions: Future research should prioritise the standardisation of acoustic protocols and the pursuit of longitudinal clinical cohorts to establish the long-term efficacy of this non-invasive technology. Full article

Background/Objectives: The growing aging population is susceptible to cognitive and memory impairment, most commonly due to Alzheimer’s disease, with no cures currently available. Noninvasive brain stimulation (NIBS) techniques may serve to improve cognition and delay catastrophic memory loss. Methods: A systematic review of NIBS research on cognitive impairment was carried out using PubMed, with additional backward citation searching. A total of 81 studies using NIBS were included. Conclusions: The reviewed studies show that NIBS holds promise in improving memory deficits in patients with cognitive impairment. While the longevity of benefits from transcranial electrical stimulation appears limited, its short-term effects may provide benefits when used consistently. Transcranial magnetic stimulation appears to provide longer-lasting benefits. Transcranial focused ultrasound stimulation may also provide further benefits through more precise targeting of deeper brain structures compared to other NIBS techniques. Together, these results suggest that NIBS shows promise for the treatment of symptoms related to cognitive and memory impairment, and may help to alleviate some of the growing issues associated with the increasing level of Alzheimer’s disease in an aging population. Full article

Transcranial acoustoelectric brain imaging (tABI) is a potential brain activity imaging technique with high spatiotemporal resolution. Precise focus of transcranial ultrasound is critical for realizing millimeter-level spatial resolution in tABI. In this study, a precise focusing simulation platform is proposed by constructing a high-precision 3D skull model from Bama pig computed tomography data and a mathematical model equation by considering the skull’s heterogeneous properties. Then, the delay parameters derived from the simulation platform improve the precision of transcranial ultrasound focusing, enabling precise localization of brain activation sources with tABI. Phantom experimental results demonstrate that the transcranial ultrasound field is precisely focused at the target with a 0.20 mm deviation when delay parameters are obtained from the proposed simulation platform, whereas it exhibits divergence when using delay parameters derived from pure water or homogeneous skull models. Furthermore, using the proposed simulation platform, tABI can accurately identify intracranial electrical signals of distinct frequencies and precisely locate the corresponding activation sources with a spatial deviation of 0.50 mm. These results demonstrate that the proposed simulation platform is a powerful tool for the precise focusing of tABI. Full article

Background: Glioblastoma (GBM) is a lethal, highly invasive, and recurrent brain tumor. Standard treatment combines maximal surgical resection, radiation, and chemotherapy; however, such approaches are often infeasible for tumors in eloquent brain regions. Objective: Histotripsy is a noninvasive, nonthermal ultrasound-based mechanical ablation modality that employs focused acoustic energy for targeted tissue destruction. This study aimed to investigate the feasibility, safety, and therapeutic effect of a one-time transcranial histotripsy treatment in a pre-clinical murine GBM model. Methods: GL261 GBM cells were orthotopically implanted into C56BL/6 mouse brains. Transcranial histotripsy was performed using a stereotactically guided 2 MHz transducer targeting either lower (25%) or higher (75%) tumor volume, with 5 or 10 pulses per location (PPL) administered. Tumor growth and cerebral injury were monitored with weekly magnetic resonance imaging (MRI) following treatment. At the study endpoint, hematoxylin and eosin (H&E) histology assessed residual tumor burden and histotripsy-induced tissue changes. Results: Mice receiving 5 PPL high-percent treatment (>30 sites) showed a statistically significant median survival extension of 5 days (18.5%) compared to untreated controls. MRI demonstrated marked tumor volume reduction in the high-percent treatment group at week 4, while H&E confirmed increased tumor necrosis and cellular damage in the treated cohort. Conclusions: Single-session, incisionless transcranial histotripsy was well tolerated and conferred mild yet meaningful survival advantages in this GBM model. These results support ongoing exploration of histotripsy, alone or in combination with existing therapies, for safe and effective treatment of challenging brain tumors. Full article

Transcranial focused ultrasound stimulation (tFUS), an emerging non-invasive neuromodulation technique, has garnered growing attention owing to its high spatial resolution and precise targeting capability for deep brain structures. A body of evidence demonstrates that tFUS can effectively modulate neural activity in specific brain regions, inducing excitatory or inhibitory effects, and it is an important means to reshape neural functions. Ultrasound parameters are crucial in determining the transcranial ultrasound modulation effects. However, there is still controversy over which parameters can regulate neural excitability or inhibition, and there are significant differences in the parameters used in previous studies, which have limited the clinical application of transcranial ultrasound to some extent. Therefore, a systematic clarification of parameter–effect relationships is urgently needed to enable qualitative and quantitative understanding of ultrasound-induced neuromodulation, which is essential for achieving reliable and reproducible outcomes. This paper intends to review the effects of different tFUS parameters and their combinations on the excitability and inhibition of brain neural activities as well as the possible mechanisms. By integrating recent findings from both animal models and human clinical studies, we also discuss critical safety issues related to tFUS, aiming to provide a theoretical basis for future transcranial focused ultrasound modulation treatments for various neurological diseases such as stroke, Parkinson’s disease, dementia, epilepsy, pain disorders, and disorders of consciousness while providing reference value for selecting tFUS treatment regimens. Full article

Background: Transcranial pulse stimulation (TPS) is an innovative non-invasive brain stimulation technique using ultrasonic waves. Despite its application in first clinical trials, so far, no systematic overview of its effects across different patient populations has been conducted. Objectives: This systematic review and meta-analysis examines the effects of TPS on cognitive, motor, and mental health outcomes as well as on patient safety in neurological and psychiatric disorders. Methods: We conducted a literature search in MEDLINE, PsycINFO & PsycArticles, CENTRAL, Web of Science, and Google Scholar, covering the period from January 2013 to December 2024. Two independent reviewers conducted the study selection, data extraction, and quality assessment. To evaluate the risk of bias, the RoB2 tool was used for randomized studies and the ROBINS-I tool for non-randomized studies. Results: A total of fifteen studies (five randomized controlled trials and ten non-blinded, single-arm trials) including both adolescent and adult and elderly patient populations (Alzheimer’s disease, mild cognitive impairment, Parkinson’s disease, major depressive disorder, autism spectrum disorder, attention-deficit hyperactivity disorder) were included. Positive effects of TPS intervention on cognitive, motor, and mental health outcomes, as well as a high safety profile, were demonstrated in a majority of the studies and outcome parameters. However, limitations of the included studies persist due to small sample sizes, lack of control groups, retrospective analyses, and heterogeneity of study protocols and measurements. Conclusions: TPS is a safe and promising method for treating neurological and psychiatric disorders. To better assess the potential of this innovative technique, standardized protocol procedures and larger, sham-controlled trials are needed. Full article

Transcranial focused ultrasound is a promising noninvasive technique for neuromodulation in neurological and psychiatric disorders, but accurate prediction of acoustic transmission through the skull remains a major challenge. In this study, we present a five-layer numerical human head model that integrates frequency-dependent acoustic parameters with nonlinear time-explicit dynamics to realistically capture ultrasound propagation. The model explicitly represents skin, trabecular bone, cortical bone, and brain, each assigned experimentally derived acoustic properties across a clinically relevant frequency range (0.5–5 MHz). Numerical simulations were performed in the frequency domain and time-explicit to quantify sound transmission loss and focal depth under high-intensity and high-frequency stimulation. The results show the effect of frequency, radius of curvature, and skull thickness on maximum pressure ratio, focal depth, and focus zone inside the brain tissue. Findings indicate that skull geometry, particularly radius of curvature and thickness, strongly influences the focal zone, with thinner skull regions allowing deeper penetration and reduced transmission loss. Comparison of the frequency-domain model with the time-explicit model demonstrated broadly similar trends; however, the frequency-domain approach consistently underestimated transmission loss and was unable to capture nonlinear effects such as frequency harmonics. These findings highlight the importance of nonlinear, time-explicit modeling for accurate transcranial ultrasound planning and suggest that the proposed framework provides a robust tool for optimizing stimulation parameters and identifying ideal target zones, supporting the development of safer and more effective neuromodulation strategies. Full article

Background: Depression and anxiety disorders impact millions globally. In recent years, low-intensity focused ultrasound (LIFU), characterized by its high precision, deep penetration, and non-invasive nature, has garnered significant interest in neuroscience and clinical practice. To enhance understanding of its effects on mood, therapeutic availability in treatment of depression/anxiety disorders, and potential mechanisms, a systematic review of studies investigating the emotional impact of LIFU on depressive/anxious-like animal models, healthy volunteers, and patients with depression or anxiety disorders has been undertaken. Methods: Relevant papers published before 15 July 2025 were searched across four databases: Web of Science, PubMed, Science Direct, and Embase. A total of 28 papers which met the inclusion and exclusion criteria are included in this review. Results: Our findings indicate that LIFU reversed the depressive/anxious-like behaviors in the animal models and showed antidepressant/anti-anxiety effects among the state-of-art clinical studies. For example, immobility time in FST or TST is reduced in depressive animal models, and HRSD/BAI scales are improved in human studies. Key molecules such as BDNF/5-HT are found restored in animal models, and FC between key brain areas related to depression/anxiety is modulated after LIFU treatment. Notably, no brain tissue damage was observed in animal studies, and only mild adverse effects (such as dizziness and vomiting) were noted in a few human studies. Conclusions: The studies using LIFU to treat depression and anxiety remain in the preliminary stage. The mechanisms underlying LIFU’s mood effects—such as activation or inhibition of specific brain regions or neural circuits, anti-inflammatory effects, alterations in functional connectivity, synaptic plasticity, neurotransmitter levels, and BDNF—remain incompletely understood and warrant further investigation. Nevertheless, the LIFU technique holds promise for regulating both cortical and subcortical brain areas implicated in depression/anxiety disorders as a precise neuromodulation tool. Full article

Objectives: Ketamine has demonstrated rapid and sustained antidepressant effects; however, its clinical utility is limited by the risk of addiction and systemic side effects. This study aimed to develop ketamine-loaded nanodroplets (Ket-NDs) with high encapsulation efficiency (EE) and stability for targeted low-dose intravenous (IV) administration in a mice model of depression. Low-intensity focused ultrasound (LIFU) was employed to induce transcranial, region-specific drug release in the lateral habenula (LHb). Methods: Ket-NDs were synthesized using a thin-film hydration method with sonication and emulsification, incorporating perfluoropentane as the core material. Characterization was performed using light microscopy, cryogenic scanning electron microscopy (cryo-SEM), transmission electron microscopy, and dynamic light scattering (DLS). Drug EE and loading efficiency (LE) were quantified by reversed-phase high-performance liquid chromatography. A chronic restraint stress model was established, and Ket-NDs were administered intravenously followed by LIFU targeting the LHb. Antidepressant efficacy and biosafety were systematically evaluated. Results: (1) Ket-NDs exhibited uniform spherical morphology and a narrow size distribution, as confirmed by DLS (particle size: 139.75 ± 9.43 nm; Polydispersity index: 0.225 ± 0.025) and cryo-SEM analysis (number-average diameter: 109.5 ± 10.4 nm). The zeta potential was −15.93 ± 5.906 mV, and the formulation remained stable under 4 °C storage. (2) Ket-NDs demonstrated high EE (78.25 ± 16.13%) and LE (15.55 ± 4.49%). (3) In depressive mice, IV administration of Ket-NDs followed by LIFU targeting the LHb significantly improved behavioral outcomes: increased locomotor activity in the open field test, elevated sucrose preference index, and reduced immobility time in the tail suspension test. (4) Safety assessments revealed no significant organ toxicity or brain tissue damage in ultrasound-exposed regions. Conclusions: In summary, this study developed stable Ket-NDs. When combined with LIFU, they enable precise regional drug delivery to the brain, showcasing a promising treatment strategy for depression with reduced systemic side effects. Full article

Background/Objectives: Essential tremor (ET) is the most common movement disorder worldwide. It negatively affects patients’ activities of daily living (ADL) and quality of life. Unilateral transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy has been proven as a highly effective and safe treatment option for patients with refractory ET. The aims of this study are to explore the effectiveness and safety of tcMRgFUS thalamotomy in patients with ET in a real-world setting. Methods: Patients who underwent tcMRgFUS thalamotomy at the University Hospital of Palermo were prospectively enrolled. Scores obtained by Quality of Life in Essential Tremor Questionnaire (QUEST) and The Essential Tremor Rating Assessment Scale (TETRAS) were compared before and after tcMRgFUS thalamotomy. Predictors of tcMRgFUS thalamotomy effectiveness were explored by multivariable Cox regression analyses. All the adverse events (AEs) during and after the procedure were collected. Results: Fifty patients were included (80% male; median age at tcMRgFUS 67.4 years). After procedure, the QUEST score decreased by 46.2%, while TETRAS-ADL and TETRAS Performance (TETRAS-PE) decreased by 52.2% and 51.8%, respectively. Temperature peak and longitudinal lesion diameter positively correlated with the magnitude of QUEST and TETRAS-PE reduction. A higher baseline TETRAS-PE score predicted a good prognosis (HR = HR 6.6 [95% CI: 2.1–21.3]; p = 0.001). AEs were mild to moderate and transient, while permanent AE was observed only in one case. Conclusions: This real-world study confirms the higher effectiveness and the favorable safety profile of tcMRgFUS thalamotomy in patients with ET by reducing the tremor-related interference in quality of life, disability in ADL, and tremor severity. Full article

A wide range of strategies have been developed to modulate dysfunctional brain activities. This narrative review provides a comparative analysis of biophysical, genetic, and biological neuromodulation approaches with an emphasis on their known or unknown molecular targets and translational potential. The review incorporates data from both preclinical and clinical studies covering deep brain stimulation, transcranial electrical and magnetic stimulation, focused ultrasound, chemogenetics, optogenetics, magnetogenetics, and toxin-based neuromodulation. Each method was assessed based on specificity, safety, reversibility, and mechanistic clarity. Biophysical methods are widely used in clinical practice but often rely on empirical outcomes due to undefined molecular targets. Genetic tools offer cell-type precision in experimental systems but face translational barriers related to delivery and safety. Biological agents, such as botulinum neurotoxins, provide long-lasting yet reversible inhibition via well-characterized molecular pathways. However, they require stereotaxic injections and remain invasive. To overcome individual limitations and improve targeting, delivery, and efficacy, there is a growing interest in the synthesis of multiple approaches. This review highlights a critical gap in the mechanistic understanding of commonly used methods. Addressing this gap by identifying molecular targets may help to improve therapeutic precision. This concise review could be valuable for researchers looking to enter the evolving field of the neuromodulation of brain function. Full article

Transcranial focused ultrasound (TcFUS) neuromodulation is hindered by skull-induced acoustic limitations. To enable synergistic multi-region brain stimulation, we designed non-coaxial multi-focal composite Fresnel acoustic lenses, including an overlapping Fresnel lens (OFL) and an alternating-segmented Fresnel lens (ASFL). These lenses convert planar ultrasound into multiple foci. Based on Fresnel theory, acoustic fields were analyzed via simulations and experiments, validating the generation of four non-coaxial foci (10/30 mm focal lengths) from a 1 MHz planar wave using both OFL and ASFL. The influence of lens parameters on focal pressure distribution was investigated, and morphology was quantified using a linear least-squares method. Significant differences in focal morphology and intensity between OFL and ASFL provide crucial guidance for optimizing multi-target TcFUS strategies. Full article

Despite the massive efforts of modern medicine to stop the evolution of Alzheimer’s disease (AD), it affects an increasing number of people, changing individual lives and imposing itself as a burden on families and the health systems. Considering that the vast majority of conventional drug therapies did not lead to the expected results, this review will discuss the newly developing therapies as an alternative in the effort to stop or slow AD. Focused Ultrasound (FUS) and its derived Transcranial Pulse Stimulation (TPS) are non-invasive therapeutic approaches. Singly or as an applied technique to change the permeability of the blood–brain–barrier (BBB), FUS and TPS have demonstrated the benefits of use in treating AD in animal and human studies. Adipose-derived stem Cells (ADSCs), gene therapy, and many other alternative methods (diet, sleep pattern, physical exercise, nanoparticle delivery) are also new potential treatments since multimodal approaches represent the modern trend in this disorder research therapies. Full article

Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterized by a range of motor and non-motor symptoms (NMSs) that significantly impact patients’ quality of life. This review aims to synthesize the current literature on the application of brain stimulation techniques, including non-invasive methods such as transcranial magnetic stimulation (TMS), transcranial electrical stimulation (tES), transcranial focused ultrasound stimulation (tFUS), and transcutaneous vagus nerve stimulation (tVNS), as well as invasive approaches like deep brain stimulation (DBS). We explore the efficacy and safety profiles of these techniques in alleviating both motor impairments, such as bradykinesia and rigidity, and non-motor symptoms, including cognitive decline, depression, and impulse control disorders. Current findings indicate that while non-invasive techniques present a favorable safety profile and are effective for milder symptoms, invasive methods like DBS provide significant relief for severe cases that are unresponsive to other treatments. Future research is needed to optimize stimulation parameters, establish robust clinical protocols, and expand the application of these technologies across various stages of PD. This review underscores the potential of brain stimulation as a vital therapeutic tool in managing PD, paving the way for enhanced treatment strategies and improved patient outcomes. Full article

This study explores the feasibility of using low-intensity focused ultrasound (LIFU) to induce rotational sensations in the human semicircular canal (SCC) through the acoustic streaming effect. Existing vestibular stimulation methods, such as galvanic vestibular stimulation (GVS), caloric vestibular stimulation (CVS), and magnetic vestibular stimulation (MVS), face limitations in spatial and temporal resolution, with unclear mechanisms. This study investigates whether LIFU can overcome these limitations by modulating endolymph motion within SCC. A 3D finite element model was constructed to simulate the effects of LIFU-induced acoustic streaming on SCC (particularly the endolymph), with thermal effects evaluated to ensure safety. Fluid–structure interaction (FSI) was used to analyze the relationship between endolymph flow and cupula deformation. By adjusting the focal point of the ultrasound transducer, we were able to alter fluid flow pattern, which resulted in variations in cupula displacement. The results demonstrated that LIFU successfully induces fluid motion in SCC without exceeding thermal safety limits (<1 °C), suggesting its potential for controlling rotational sensations, with cupula displacement exceeding 1 μm. This novel approach enhances the understanding of LIFU’s thermal and neuromodulatory effects on the vestibular system, and thereby offers promising implications for future therapeutic applications. Full article