Search Results (220)

Background: Functional dizziness and persistent postural-perceptual dizziness (PPPD) involve mutually reinforcing vestibular symptoms and anxiety. Non-pharmacological interventions, such as vestibular rehabilitation therapy (VRT) and cognitive behavioral therapy (CBT), aim to address both mechanisms, yet their overall effectiveness remains unclear. Methods: We systematically examined randomized controlled trials (RCTs) published between 2000 and 2025 that evaluated VRT, CBT, or multimodal approaches for adults with functional or chronic dizziness (including PPPD and related functional dizziness constructs) accompanied by significant anxiety. Twelve RCTs (513 participants) met the criteria, involving individuals with PPPD, chronic subjective dizziness, chronic vestibular disorders with prominent anxiety, and residual dizziness after benign paroxysmal positional vertigo. Results: Conventional VRT delivered in clinic or as structured home-based programs produced small-to-moderate improvements in dizziness-related disability versus usual care. Combining VRT with CBT or psychologically informed components yielded larger and more consistent reductions in disability and maladaptive dizziness-related beliefs. CBT-based interventions reduced anxiety and dizziness-related distress compared with supportive controls. Emerging modalities, including virtual-reality-based VRT, non-invasive neuromodulation, and heart-rate-variability biofeedback, showed potential, although they were limited by small samples and methodological issues. Most trials had some risk-of-bias concerns and evidence certainty ranged from very low to moderate. Conclusions: Integrated multimodal rehabilitation shows promise, although larger, high-quality RCTs using standardized procedures and outcome measures are required. Full article

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that utilizes magnetic fields to induce cortical electric currents, enabling both the measurement and modulation of neuronal activity. Initially developed as a diagnostic tool, TMS now serves dual roles in clinical neurology, offering insight into neurophysiological dysfunctions and the therapeutic modulation of abnormal cortical excitability. This review examines key TMS outcome measures, including motor thresholds (MT), input–output (I/O) curves, cortical silent periods (CSP), and paired-pulse paradigms such as short-interval intracortical inhibition (SICI), short-interval intracortical facilitation (SICF), intracortical facilitation (ICF), long interval cortical inhibition (LICI), interhemispheric inhibition (IHI), and short-latency afferent inhibition (SAI). These biomarkers reflect underlying neurotransmitter systems and can aid in differentiating neurological conditions. Diagnostic applications of TMS are explored in Parkinson’s disease (PD), dystonia, essential tremor (ET), Alzheimer’s disease (AD), and mild cognitive impairment (MCI). Each condition displays characteristic neurophysiological profiles, highlighting the potential for TMS-derived biomarkers in early or differential diagnosis. Therapeutically, repetitive TMS (rTMS) has shown promise in modulating cortical circuits and improving motor and cognitive symptoms. High- and low-frequency stimulation protocols have demonstrated efficacy in PD, dystonia, ET, AD, and MCI, targeting the specific cortical regions implicated in each disorder. Moreover, the successful application of TMS in differentiating and treating AD and MCI underscores its clinical utility and translational potential across all neurodegenerative conditions. As research advances, increased attention and investment in TMS could facilitate similar diagnostic and therapeutic breakthroughs for other neurological disorders that currently lack robust tools for early detection and effective intervention. Moreover, this review also aims to underscore the importance of maintaining standardized TMS protocols. By highlighting inconsistencies and variability in outcomes across studies, we emphasize that careful methodological design is critical for ensuring the reproducibility, comparability, and reliable interpretation of TMS findings. In summary, this review emphasizes the value of TMS as a distinctive, non-invasive approach to probing brain function and highlights its considerable promise as both a diagnostic and therapeutic modality in neurology—roles that are often considered separately. Full article

Pain in children and adolescents remains an underestimated and undertreated condition, with long-term physical and psychosocial consequences. Non-invasive neuromodulation has emerged as a promising, low-risk approach for managing acute and chronic pain by modulating central and peripheral neural pathways. This systematic review followed PRISMA 2020 guidelines to evaluate the efficacy, safety, and clinical applicability of non-invasive neuromodulation techniques in pediatric pain. Searches were conducted in PubMed, Embase, Scopus, Web of Science, Cochrane CENTRAL, and ScienceDirect for randomized controlled trials (RCTs) published between 2015 and 2025. Six RCTs met the inclusion criteria, encompassing percutaneous electrical nerve field stimulation (PENFS), transcutaneous auricular vagus nerve stimulation (taVNS), transcutaneous electrical acupoint stimulation (TEAS), and transcutaneous electrical nerve stimulation (TENS). Four trials reported significant reductions in pain intensity alongside improvements in functional outcomes and quality of life, particularly in functional abdominal pain and postoperative contexts. Most studies showed low or moderate risk across domains, with appropriate randomization and blinded assessment. No serious adverse events were reported, confirming an excellent safety profile. These findings support non-invasive neuromodulation as a feasible and well-tolerated adjunct to conventional pediatric pain management. Further high-quality trials are warranted to standardize protocols and explore mechanisms of neuroplasticity in the developing nervous system. PROSPERO (CRD420251170866). Full article

Background/Objectives: Traumatic spinal cord (SC) injury (SCI) is a debilitating neurological condition. Minimally invasive approaches to monitor in real time the functional state of the neuromotor apparatus in animal models of SCI (at rest and movement) to assess effectiveness of therapy are needed in preclinical studies. We aimed to develop such a bioethically acceptable platform for SCI studies on non-human primates (Rhesus macaques). Methods: Epidural and myographic electrode implantation (EI) (wireless and wired, connected via a head plug) was performed. After EI, motor responses caused by electrical stimulation of the SC at the level of the cervical and lumbar thickening were recorded; electromyography of the limb muscles was recorded during quadrupedal movement of the animal on a treadmill with simultaneous assessment of movements’ kinematic parameters. Five weeks after EI, three animals underwent lateral hemisection of the SC in the C4–C5 segment under the control of a surgical microscope and intraoperative recording of motor- and sensory-evoked potentials. Results: Within 30 days after SCI, during treadmill testing, a decrease in electromyographic activity of the limb muscles and the volume of angular movement in the joints on the side of the injury was detected. Electrical stimulation at the L2–S1 segments of the SC at a frequency of 30 Hz led to the appearance of a locomotor pattern in the muscles of the hind limbs and an increase in the range of motion. Conclusions: Our platform can be used for pathophysiological studies of various neuromodulation modes and as a basis for the development of control neurointerfaces. Full article

For decades, researchers have explored the therapeutic potential of the vagus nerve through vagus nerve stimulation (VNS). Initially developed for epilepsy, VNS has since been applied to treat resistant depression, stroke recovery, and inflammatory conditions. Transcutaneous VNS (tVNS) now offers a noninvasive alternative, fueling clinical trials in disorders ranging from rheumatoid arthritis and migraines to long COVID-19. Mechanistic studies suggest that afferent and efferent vagal fibers modulate immune responses, mood regulation, and neurotransmitter systems. The SPARC initiative has accelerated mapping of vagal circuits, enabling more precise approaches to stimulation. Despite progress, the results remain mixed: while some patients experience lasting symptom relief, others respond no better than to placebo. Depression studies, in particular, highlight both the promise and the complexity of VNS, as inflammation, motivation circuits, and gut–brain signaling emerge as key modulators. Next-generation closed-loop devices and circuit-specific targeting may improve efficacy and reduce adverse effects. VNS research thus lies at the intersection of neuromodulation, psychiatry, and immunology—offering hope for hard-to-treat conditions, yet demanding rigorous trials to separate myths from medicine. In this article, we review the current clinical and experimental applications of tVNS, analyze its mixed efficacy across psychiatric, immunological, and neurological disorders, and highlight the mechanistic insights, stimulation parameters, and emerging technologies that may shape next-generation therapies. 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

Development of new therapeutic approaches and strategies for common neuropsychiatric disorders, including Major Depressive Disorder, anxiety disorders, and Post-Traumatic Stress Disorder, represent a significant global health challenge. Recent research indicates that emotional dysregulation and persistent inflammation are closely linked and serve as key pathophysiological features of these conditions. Emotional dysregulation is mechanistically coupled to locus coeruleus and norepinephrine (LC-NE) or noradrenergic system activity. Stemming from chronic stress, persistently elevated activity of the LC-NE system leads to hypervigilance, anxious states, and depressed mood. Concurrently, these symptoms are marked by systemic inflammation as indicated by elevated pro-inflammatory cytokines, and central neuroinflammation indicated by microglial activation in brain regions and networks involved in mood regulation and emotional control. In turn, chronic inflammation increases sympathetic tone and LC-NE activity resulting in a vortex of psychoneuroimmunological dysfunction that worsens mental health. Transcutaneous auricular vagus nerve stimulation (taVNS) in a non-invasive neuromodulation method uniquely positioned to address both noradrenergic dysfunction and chronic inflammation in neuropsychiatric applications. Evidence spanning the past decade demonstrates taVNS works via two complementary mechanisms. An ascending pathway engages vagal afferents projecting to the LC-NE system in the brain stem, which has been shown to modulate cortical arousal, cognitive function, mood, and stress responses. Through descending circuits, taVNS also modulates the cholinergic anti-inflammatory pathway to suppress the production of pro-inflammatory cytokines like TNF-α and IL-6 mitigating poor health outcomes caused by inflammation. By enhancing both central brain function and peripheral immune responses, taVNS has shown significant potential for recalibrating perturbed affective-cognitive processing. The present article describes and discusses recent evidence suggesting that taVNS offers a promising network-based paradigm for restoring psychoneuroimmunological homeostasis in common neuropsychiatric conditions. Full article

Objectives: We aimed to evaluate the effect of non-invasive NESA neuromodulation compared to posterior tibial nerve stimulation (PTNS) in patients with an overactive bladder (OAB), also given the same exercises and patient education, on quality of life, symptoms, discomfort and sleep quality. Method: Twenty-four women, aged 38–85 years with OAB, were included in this preliminary randomized controlled trial. Each patient attended ten sessions, twice a week. Patient pelvic floor function and urinary incontinence symptoms were collected throughout ICIQ-SF and B-SAQ questionnaires. Patient QoL and sleep quality were reported using SF-36 and PSQI, respectively. All outcomes were measured using three assessments: previous treatment (T1), immediately after treatment (T2) and two-month follow-up (T3). Results: Both groups showed significant improvements in pelvic floor function and urinary incontinence symptoms, as well as in sleep quality (p < 0.05). Although no significant differences between the groups were observed for any of the variables (p > 0.05), only the NESA group showed compelling improvements in quality of life (p < 0.05). Conclusions: The two treatments improved OAB symptoms, discomfort, and sleep quality in the short term yet only the non-invasive NESA group improved quality of life in women with OAB. These findings warrant further investigation in larger trials. Full article

Major depressive disorder (MDD) continues to be a primary cause of disability globally, with a significant number of patients exhibiting resistance to standard pharmacological and psychotherapeutic interventions. In recent years, non-invasive brain stimulation techniques, especially transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have emerged as promising therapies for treatment-resistant MDD. A comprehensive search was performed in PubMed, which included all studies published over the last ten years. Eligible studies encompassed both animal models and clinical investigations. This review provides a comparative overview of transcranial electrical stimulation modalities, with a focus on their mechanisms of action, clinical efficacy, and underlying neurobiological mechanisms. We pay particular attention to the role of the neurotrophin system, specifically brain-derived neurotrophic factor (BDNF), in mediating the treatment effects of transcranial stimulation. Recent findings indicate that neuromodulation could improve neuroplasticity by increasing BDNF levels and associated signaling pathways, which may help stabilize mood and enhance the improvement of individuals with MDD. A more profound understanding of these mechanisms could lead to more precise, biomarker-driven interventions. Further research is essential to elucidating the long-term effects of brain stimulation on neurotrophin levels and to creating more individualized treatment strategies. Full article

Background: Alzheimer’s Disease (AD) is the most common form of dementia and is characterized by progressive cognitive decline and neurodegeneration. In Italy, AD represents a major public health and socio-economic challenge. This review aims to summarize current Italian research on pharmacological and non-pharmacological interventions, including preclinical studies, clinical trials, rehabilitative approaches, and emerging neuromodulation techniques, highlighting contributions and future directions. Methods: A narrative review of the literature was conducted, focusing on Italian preclinical and clinical studies, observational and real-world evidence, cognitive and physical interventions, music therapy, non-invasive brain stimulation (rTMS, tDCS, tACS), and digital or home-based rehabilitation programs. Results: Italian research has explored different pharmacological strategies, including multitarget compounds, eptastigmine, rotigotine, and combinatorial therapies (donepezil-memantine, citicoline addition). Non-pharmacological interventions, such as cognitive stimulation, motor rehabilitation, music therapy, and multidimensional programs, demonstrated benefits on cognition, behavior, daily functioning, and caregiver well-being. Non-invasive neuromodulation techniques, targeting the dorsolateral prefrontal cortex and precuneus, showed promising effects on memory, attention, and executive functions, especially when combined with cognitive training. Digital health technologies, including telerehabilitation and home-based brain stimulation programs, further enhanced accessibility and adherence. Challenges remain due to fragmented research, small sample sizes, and limited standardization. Conclusions: Italian research on AD reflects a growing emphasis on integrated, multidimensional, and technologically advanced approaches. Strengthening preclinical studies, promoting multicenter collaborations, and combining pharmacological, cognitive, and neuromodulatory strategies may enhance therapeutic efficacy and patient quality of life. Continued investment in innovation and multidisciplinary research positions Italy to contribute meaningfully to global AD management and prevention. Full article

Background/Objectives: Autism spectrum disorder is a neurodevelopmental condition affecting up to 1.7% of the global population. Current interventions do not treat the root cause, prompting research into novel treatments like non-invasive neuromodulation. The objective of this study is to examine the use of NESA technology in children with ASD, to determine if it generates changes in their conduct and their central symptoms related to the spectrum. Methods: In this study, twelve children with ASD underwent NESA neuromodulation therapy. We assessed the children’s (CSHQ) and parents’ sleep quality (Pittsburg scale), aberrant behavior (ABC-C), and sensory profile (SP-2). Results: In most cases (66.7%), we observed an improvement in the test results. A comparative analysis of NESA protocols revealed that the optimal programming strategy involves a longer duration of programs 7 and 8 of NESA microcurrents. Conclusions: Given the limited number of patients included in the data set, further investigations are necessary to draw more robust conclusions. This novel form of treatment offers the potential to address autism spectrum disorder by targeting the autonomic nervous system. This approach may influence underlying mechanisms of the autonomic nervous system. The pilot study has opened a new avenue for future research. Full article

Introduction: Persistent Spinal Pain Syndrome Type 2 (PSPS-T2) is associated with changes in the brain’s pain processing. This is often due to problems with the body’s natural way of handling the pain management system. Exercise therapy, such as motor control and spinal stabilization, can help reduce pain and disability. However, exercise alone may not be sufficient. Approaches that consider both body mechanics and brain function are gaining popularity. Since brain changes play a role in muscle and bone problems, noninvasive brain stimulation (NIBS) is considered a helpful adjunctive treatment. Studies have shown that NIBS may help people with spinal pain and mood disorders. The aim of this study is to assess the impact of combining tDCS targeting the dorsolateral prefrontal cortex with spinal motor control exercises in patients diagnosed with PSPS-T2. This investigation is based on the hypothesis that such a combined intervention could result in a more significant reduction in disability. Methods/Materials: This randomized controlled trial (RCT) is structured as a double-blind, comparative, longitudinal design in accordance with the CONSORT guidelines. This RCT has been registered at ClinicalTrials.gov (NCT06969456). Forty-two participants diagnosed with PSPS-T2 will be randomized in a 1:1 ratio into two groups: tDCS + rehabilitation (E_tDCS) or sham tDCS + rehabilitation (E_SHAM). The intervention will use tDCS to deliver low-intensity direct current to modulate cortical excitability. The intervention will consist of 24 supervised sessions (2 per week, 60 min each) over 12 weeks. Neuromodulation and exercise protocols will be adapted to the intervention phases based on previous research. The sample size has been calculated using GPower^®, assuming an effect size of 0.81, α = 0.05, power = 0.95, and a 40% dropout rate. Data will be collected from October 2025 to January 2027. Impact Statement: This study integrates neurophysiological modulation via tDCS with targeted exercise therapy, presenting an innovative approach to enhance pain modulation, functional recovery, and cortical reorganization in patients with PSPT-2. This approach has the potential to inform future evidence-based strategies for neurorehabilitation and pain management. Full article

Background/Objectives: Sacroiliitis is a painful inflammatory disorder of the sacroiliac joint, estimated to account for up to 25% of chronic low back pain. Treatment options are often limited, and many patients continue to experience symptoms despite conservative or interventional management. High-Intensity Focused ultrasound (HIFU) has emerged as a novel noninvasive neuromodulation technique. However, the contribution of individual lumbosacral nerve branches (L5–S3) to pain generation during such interventions remains unclear. This study aimed to characterize the distribution of pain-related interruptions during HIFU procedures, with a particular focus on identifying the most pain-sensitive targets. Methods: Eight patients with clinically confirmed sacroiliitis underwent HIFU ablation targeting the L5–S3 branches. Procedural data, including the total number of sonications and interruptions due to pain, were prospectively recorded. Statistical analyses were performed using chi-square tests, including overall distribution testing, pairwise branch comparisons, and an aggregated comparison of S3 versus all other branches combined. Effect sizes were calculated using Cohen’s w. Results: Across 243 sonications, 162 interruptions (66.7%) occurred due to pain. Interruptions were unevenly distributed: 81% occurred at S2 and S3, with S3 alone accounting for 42%. S3 showed significantly more interruptions than L5 (p = 0.0022), S1 (p = 0.0150), S2 (p = 0.0055), and all other branches combined (p < 0.001; w = 0.58, large effect). S2 also demonstrated greater sensitivity than L5 (p = 0.003) and S1 (p = 0.001). Subdivision analysis revealed uniformly high sensitivity across S3, whereas S1 and S2 displayed heterogeneous patterns. Conclusions: HIFU stimulation revealed disproportionate pain sensitivity in sacral branches, with S3—and to a lesser extent S2—emerging as dominant contributors. These findings provide new insight into sacroiliitis pathophysiology and suggest prioritization of S3 in targeted interventional management. Full article

Introduction: Stroke remains one of the leading causes of long-term disability worldwide. Post-stroke motor recovery depends on neuroplasticity, which is stimulated by intensive, repetitive, and task-specific training. Modern technologies such as robotic rehabilitation (RR), virtual reality (VR), functional electrical stimulation (FES), brain–computer interfaces (BCIs), and non-invasive brain stimulation (NIBS) offer novel opportunities to enhance rehabilitation. They operate through sensory feedback, neuromodulation, and robotic assistance which promote neural reorganization and motor relearning. Neurobiological Basis of Motor Recovery: Mechanisms such as long-term potentiation, mirror neuron activation, and cerebellar modulation underpin functional reorganization after stroke. Literature Review Methodology: A narrative review was conducted of studies published between 2005 and 2025 using PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar. Randomized controlled trials, cohort studies, and systematic reviews assessing the efficacy of these modern technologies were analyzed. Literature Review: Evidence indicates that RR, VR, FES, BCIs, and NIBS improve upper and lower limb motor function and strength, and enhance activities of daily living, particularly when combined with conventional physiotherapy (CP). Furthermore, integrated rehabilitation technologies (IRT) demonstrate synergistic neuroplastic effects. Discussion: Modern technologies enhance therapy precision, intensity, and motivation but face challenges related to cost, standardization, and methodological heterogeneity. Conclusions: RR, VR, FES, BCIs, NIBS, and IRT are effective complements to CP. Early, individualized, and standardized implementation can optimize neuroplasticity and functional recovery. Full article