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Search Results (1,450)

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Keywords = neuromodulation.

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24 pages, 1813 KB  
Review
Cerebral Venous Thrombosis: Pathophysiologic Insights, Clinical Evaluation Tools, and Novel Therapeutic Strategies
by Min Li, Qiqi Cui, Xiaogang Gao, Xuefan Yao, Ran Meng, Xunming Ji and Juexian Song
Diagnostics 2026, 16(9), 1308; https://doi.org/10.3390/diagnostics16091308 - 27 Apr 2026
Abstract
Cerebral venous thrombosis (CVT) is a rare but potentially life-threatening subtype of stroke, characterized by thrombus formation within the dural venous sinuses and cerebral veins. Recent advances have deepened our understanding of CVT pathophysiology, highlighting a multifactorial process that encompasses thrombus initiation, subsequent [...] Read more.
Cerebral venous thrombosis (CVT) is a rare but potentially life-threatening subtype of stroke, characterized by thrombus formation within the dural venous sinuses and cerebral veins. Recent advances have deepened our understanding of CVT pathophysiology, highlighting a multifactorial process that encompasses thrombus initiation, subsequent thrombus propagation, venous hypertension with blood–brain barrier disruption, and secondary parenchymal brain injury. Comprehensive clinical assessment, including diagnosis and differential diagnosis, disease severity scores, imaging-based metrics, and prognostic scoring systems, enables accurate evaluation and risk stratification. Emerging therapeutic strategies, including direct oral anticoagulants, corticosteroids for selected patients, natural-origin agents, immunomodulatory therapy, endovascular treatment, optic nerve sheath fenestration, and neuromodulation, provide novel and alternative options for the management of CVT. This review provides a comprehensive overview of CVT pathophysiology, clinical assessment tools, and novel therapeutic strategies to guide clinical decision-making and inform future research. Full article
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30 pages, 504 KB  
Review
Alterations in Cortical Oscillatory Dynamics Following SARS-CoV-2 Infection: QEEG Biomarkers of Vulnerability to Attention and Seizure-Related Symptoms
by Marta Kopańska, Julia Trojniak, Jolanta Góral-Półrola and Maria Pąchalska
Cells 2026, 15(9), 790; https://doi.org/10.3390/cells15090790 (registering DOI) - 27 Apr 2026
Abstract
SARS-CoV-2 infection is associated with not only acute respiratory symptoms but is also characterized by strong neurotropism which may contribute to the development of the multisystem post-COVID syndrome (PASC). Patients frequently report chronic neurocognitive disorders such as brain fog, significant attention deficits and [...] Read more.
SARS-CoV-2 infection is associated with not only acute respiratory symptoms but is also characterized by strong neurotropism which may contribute to the development of the multisystem post-COVID syndrome (PASC). Patients frequently report chronic neurocognitive disorders such as brain fog, significant attention deficits and increased susceptibility to epileptiform discharges. The aim of this review is to systematize the knowledge regarding deviations in quantitative electroencephalography (QEEG) recordings in convalescents and to evaluate the utility of this method as an objective biomarker. This work constitutes a comprehensive literature review integrating the latest data on neuroinflammation, blood-brain barrier damage and changes in cortical oscillatory dynamics induced by the infection. The literature analysis indicates that the virus may induce a pathological excitation and inhibition imbalance (E/I imbalance) in neuronal networks. In QEEG studies this manifests as excessive activity of slow bands (Theta, Delta), a deficit of rhythms responsible for attention and sensorimotor integration (SMR) and a pathologically elevated Theta to Beta ratio (TBR). In conclusion, QEEG can serve as an objective and highly sensitive tool supporting the diagnosis and stratification of patients with neurocognitive complications of Long COVID. The integration of precise electrophysiological phenotyping with targeted behavioral neuromodulation (e.g., EEG-Biofeedback) fits into the paradigm of personalized medicine and offers a prospective strategy for mitigating long-term neurological burdens. Full article
(This article belongs to the Special Issue Insights into the Pathophysiology of NeuroCOVID: Current Topics)
16 pages, 3557 KB  
Article
Breathing-Controlled Electrical Stimulation (BreEStim) Selectively Modulates Affective and Cognitive Components of Pain—An EEG Study
by Ahmad Z. Rao, Michael Houston, Hao Meng, Shengai Li, Yingchun Zhang and Sheng Li
Bioengineering 2026, 13(5), 501; https://doi.org/10.3390/bioengineering13050501 (registering DOI) - 25 Apr 2026
Abstract
Breathing-controlled electrical stimulation (BreEStim) is an innovative neuromodulation intervention that synchronizes deep voluntary breathing with peripheral electrical stimulation. Prior studies have shown its analgesic effects in healthy adults and spinal cord injury patients with neuropathic pain. The present study used EEG to examine [...] Read more.
Breathing-controlled electrical stimulation (BreEStim) is an innovative neuromodulation intervention that synchronizes deep voluntary breathing with peripheral electrical stimulation. Prior studies have shown its analgesic effects in healthy adults and spinal cord injury patients with neuropathic pain. The present study used EEG to examine BreEStim’s neural effects on sensory, affective, and cognitive components of pain. Fourteen healthy participants (7 M, 7 F) completed 30 min of BreEStim and conventional electrical stimulation (EStim) interventions in a randomized, crossover within-subject design. Electrical pain thresholds (EPT) and EEG were recorded pre- and post-intervention. Event-related potentials (ERPs) at pre-EPT-level stimuli before and immediately after each intervention were analyzed for early sensory (P30) and affective (P250) processing, while resting-state EEG assessed spectral power across delta, theta, alpha, and beta bands for cognitive processing. Both BreEStim and EStim increased EPT, indicating short-term habituation. There was no change in early ERP responses (P30) after each intervention, suggesting preserved sensory perception. BreEStim selectively reduced P250, reflective of the affective component of pain. BreEStim significantly increased delta and theta band power and reduced alpha band power on resting-state EEG analyses, whereas no significant changes after EStim were observed. Collectively, BreEStim preserves sensory encoding while selectively modulating affective and cognitive dimensions of pain, supporting its potential as a targeted, non-pharmacological neuromodulation strategy. Full article
(This article belongs to the Section Biosignal Processing)
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14 pages, 971 KB  
Article
Effectiveness of Spinal Cord Stimulation in the Treatment of Lumbar Spine Pain Syndromes
by Sebastian Podlewski, Rafał Morga, Jacek Antecki, Piotr Dubiński and Natalia Gołębiowska
Medicina 2026, 62(5), 816; https://doi.org/10.3390/medicina62050816 - 24 Apr 2026
Viewed by 73
Abstract
Background and Objectives: Functional neurosurgery encompasses surgical interventions aimed at modulating the function of the central and peripheral nervous systems. Spinal cord stimulation (SCS), as a form of neuromodulation, is an established treatment for chronic pain and is increasingly utilized by both anesthesiologists [...] Read more.
Background and Objectives: Functional neurosurgery encompasses surgical interventions aimed at modulating the function of the central and peripheral nervous systems. Spinal cord stimulation (SCS), as a form of neuromodulation, is an established treatment for chronic pain and is increasingly utilized by both anesthesiologists and neurosurgeons. The aim of this study was to evaluate the effectiveness of SCS in patients with chronic neuropathic spinal pain. Materials and Methods: This prospective study included 42 patients who demonstrated a positive response to trial stimulation. Only patients achieving a clinically meaningful response (≥50% pain reduction) during the trial phase were included in the final analysis. Pain intensity and functional disability were assessed using the Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI). All patients underwent a two-stage percutaneous implantation procedure using burst stimulation. A follow-up assessment was performed 3–6 months after implantation. Results: A statistically significant reduction in pain intensity was observed (p < 0.0001), with median VAS scores decreasing from 8 to 3, corresponding to a 62.5% reduction in pain intensity and exceeding the minimal clinically important difference (MCID) for VAS. Functional status improved significantly, with ODI scores decreasing from 74% to 38%, markedly surpassing the established MCID threshold. A clinically meaningful reduction in pain (≥50%) was achieved in the majority of patients. All patients requiring opioid analgesics at baseline discontinued their use following SCS implantation, and a reduction in overall analgesic consumption was observed across the cohort. Conclusions: These findings suggest that burst SCS may be an effective treatment option for carefully selected patients with chronic neuropathic spinal pain who are not candidates for conventional spine surgery. However, the results should be interpreted with caution due to the enriched study design and limited follow-up period. Full article
(This article belongs to the Section Orthopedics)
22 pages, 1113 KB  
Review
Neurocosmetics and the Skin–Brain Axis from a Psychological and Psychiatric Standpoint
by Giuseppe Marano, Oksana Di Giacomi, Marco Lanzetta, Camilla Scialpi, Antonio Sottile, Gianandrea Traversi, Osvaldo Mazza, Claudia d’Abate, Eleonora Gaetani and Marianna Mazza
Cosmetics 2026, 13(3), 102; https://doi.org/10.3390/cosmetics13030102 - 24 Apr 2026
Viewed by 74
Abstract
The skin–brain axis constitutes a complex, bidirectional network integrating cutaneous sensory, immune, and neuroendocrine systems with central neural circuits involved in emotion regulation, stress responsivity, and social cognition. Advances in psychodermatology and cosmetic science have progressively extended this framework to the emerging field [...] Read more.
The skin–brain axis constitutes a complex, bidirectional network integrating cutaneous sensory, immune, and neuroendocrine systems with central neural circuits involved in emotion regulation, stress responsivity, and social cognition. Advances in psychodermatology and cosmetic science have progressively extended this framework to the emerging field of neurocosmetics, which explores how topical formulations, sensorial properties, and cutaneous neuromodulators may influence psychological well-being, affective states, and perceived stress. The aim of this narrative review is to synthesize current evidence on the biological foundations of the skin–brain axis and to critically examine the implications of these mechanisms for neurocosmetic interventions from a psychological and psychiatric perspective. It describes the biological substrates underlying skin–brain communication, including the cutaneous hypothalamic–pituitary–adrenal axis, neuropeptides, neurotrophins, transient receptor potential channels, and endocannabinoid signaling, and examines how these pathways are targeted by neurocosmetic interventions. Particular attention is devoted to neuroactive compounds, such as peptides, cannabinoids, botanicals, and aromatherapeutic molecules, as well as to sensorial strategies involving texture, temperature, and olfactory cues, which may modulate mood, anxiety, and self-perception through peripheral mechanisms. From a psychological and psychiatric perspective, the review discusses the intersection between stress-related skin conditions, body image disturbances, and emotional dysregulation, highlighting how cosmetic practices may influence subjective well-being beyond purely aesthetic outcomes. Methodological limitations of the existing literature, including the heterogeneity of study designs and outcome measures, as well as ethical considerations related to mood- and stress-related claims in cosmetic products, are critically examined. Finally, future research directions are outlined, and a translational framework is proposed to integrate dermatology, neuroscience, and mental health within next-generation cosmetic science. Full article
(This article belongs to the Special Issue Feature Papers in Cosmetics in 2026)
15 pages, 769 KB  
Perspective
Concurrent/Interleaved TMS–fMRI as an MR-Guided Framework for Target Engagement
by Chiara Di Fazio and Sara Palermo
Appl. Sci. 2026, 16(9), 4135; https://doi.org/10.3390/app16094135 - 23 Apr 2026
Viewed by 105
Abstract
Concurrent/interleaved transcranial magnetic stimulation combined with functional MRI (TMS–fMRI) enables causal perturbation of targeted cortical regions while measuring whole-brain MR-based responses during stimulation. This perspective argues that the main translational value of concurrent/interleaved TMS–fMRI lies in operationalizing target engagement and network-level propagation as [...] Read more.
Concurrent/interleaved transcranial magnetic stimulation combined with functional MRI (TMS–fMRI) enables causal perturbation of targeted cortical regions while measuring whole-brain MR-based responses during stimulation. This perspective argues that the main translational value of concurrent/interleaved TMS–fMRI lies in operationalizing target engagement and network-level propagation as measurable endpoints, bridging stimulation “dose” to clinically meaningful effects. Rather than proposing a validated gold-standard protocol, we frame concurrent/interleaved TMS–fMRI as a measurement-driven translational approach in which MRI-informed targeting and MR-based readouts can be integrated to quantify target engagement under clearly specified methodological and quality-control conditions. This perspective specifically aims to make explicit an intermediate verification step that remains only partially formalized in current clinical neuromodulation workflows. We propose that MRI-based neuronavigation should move beyond template coordinates toward individualized anatomical and network-informed targeting, with the aim of improving precision, reproducibility, and safety. Building on the field’s evolution from technical feasibility to emerging clinical applications, we outline a staged framework from feasibility to biomarker potential, summarize representative protocol archetypes, and provide pragmatic recommendations for reporting and study design to improve comparability. This framework is intended to guide future concurrent/interleaved TMS–fMRI studies toward biomarker-ready designs and more clinically informative network neuromodulation. We further distinguish offline MRI-informed targeting from potential future real-time or closed-loop implementations, and we emphasize that current biomarker claims should remain proportional to the still heterogeneous evidence base. Full article
(This article belongs to the Special Issue MR-Based Neuroimaging, 2nd Edition)
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33 pages, 2829 KB  
Review
Restless Legs Syndrome: A Network Model of Iron-Dependent Neuromodulation—A Narrative Review
by Oscar Arias-Carrión
Brain Sci. 2026, 16(5), 440; https://doi.org/10.3390/brainsci16050440 - 22 Apr 2026
Viewed by 299
Abstract
Restless legs syndrome (RLS) is traditionally conceptualized as a dopamine-responsive sensorimotor disorder; however, new evidence suggests a more complex and heterogeneous neurobiological basis. Findings from neuroimaging, genetic studies, circadian biology, and clinical research indicate that dopaminergic dysfunction occurs within a broader context of [...] Read more.
Restless legs syndrome (RLS) is traditionally conceptualized as a dopamine-responsive sensorimotor disorder; however, new evidence suggests a more complex and heterogeneous neurobiological basis. Findings from neuroimaging, genetic studies, circadian biology, and clinical research indicate that dopaminergic dysfunction occurs within a broader context of neuromodulatory imbalance involving iron metabolism, adenosinergic signalling, glutamatergic excitability, and, potentially, noradrenergic pathways. In parallel, quantitative susceptibility mapping and related approaches have provided indirect evidence of altered brain iron distribution, although results remain variable across studies. Clinically, RLS extends beyond nocturnal discomfort and is associated with sleep fragmentation, impaired quality of life, and neuropsychiatric comorbidity, as well as treatment-related complications such as augmentation. However, current diagnostic frameworks remain predominantly phenomenological, and available biomarkers lack sufficient validation for routine clinical use. In this narrative review, the available clinical, genetic, and neuroimaging evidence is synthesized to propose an integrative, network-based model in which iron-dependent neuromodulatory processes influence excitability across cortico–striatal–thalamo–limbic circuits. This framework is intended as a hypothesis-generating model rather than a definitive explanation of disease mechanisms. Substantial heterogeneity across studies, together with variability in clinical presentation and limited reproducibility of candidate biomarkers, underscores the need for standardized methodologies and longitudinal, multimodal investigations. Future work should aim to test this model empirically, refine biological stratification, and determine whether network-informed approaches can improve diagnosis and therapeutic targeting in RLS. Full article
(This article belongs to the Special Issue Sleep Disorders: Bridging Basic Mechanisms and Clinical Translation)
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42 pages, 2032 KB  
Perspective
The Therapeutic Home Environment for Chronic Diseases: A Transdisciplinary Ecosystem for Achieving Migraine Freedom and Managing Comorbid Anxiety, Insomnia, and Chronic Pain
by Dorothy Day Huntsman, Desiree Jenkinson and Grzegorz Bulaj
Healthcare 2026, 14(9), 1123; https://doi.org/10.3390/healthcare14091123 - 22 Apr 2026
Viewed by 123
Abstract
Home has been recognized as a health infrastructure through hospital-at-home, home care, and direct-to-consumer wellness and fitness products. However, the patient home environment has been largely overlooked by healthcare as a means to improve therapy outcomes for difficult-to-treat chronic conditions, such as migraine; [...] Read more.
Home has been recognized as a health infrastructure through hospital-at-home, home care, and direct-to-consumer wellness and fitness products. However, the patient home environment has been largely overlooked by healthcare as a means to improve therapy outcomes for difficult-to-treat chronic conditions, such as migraine; high-impact pain; and treatment-resistant depression, anxiety, or insomnia. Growing research evidence enables the formulation of a therapeutic home environment standard consisting of three pillars: biophilic design, indoor environmental quality, and intentional self-care spaces that serve as habit cues and foster sleep hygiene, stress management, relaxation, physical activity, and social interactions. Together, these environmental and behavioral interventions can transform real-world inputs into clinical benefits through autonomic, circadian, and emotional regulation. We also highlight the converging roles of self-management, self-efficacy, self-regulation, and self-compassion in sustaining patient engagement and healing at home. The applicability of the therapeutic home environment as an adjunct is illustrated in the case of chronic migraine, a debilitating neurological condition commonly associated with comorbidities. Current challenges in achieving migraine freedom with FDA-approved pharmacotherapies, neuromodulation devices, and digital health technologies are underscored by the high prevalence of refractory, chronic, episodic, and pediatric migraine. Perspectives on developing a personalized, multimodal cure for migraine are illustrated through a hypothetical drug + digital combination therapy comprising anti-CGRP drugs and an AI-powered digital health platform that promotes daily self-care practices within the therapeutic home environments. In conclusion, achieving sustained freedom from high-morbidity conditions requires end-to-end care ecosystems that integrate pharmacological, cognitive, behavioral, and environmental interventions into real-world settings. Full article
(This article belongs to the Special Issue Multidisciplinary Approaches to Chronic Disease Management)
13 pages, 437 KB  
Article
Effect of Sedation on EEG During Deep Brain Stimulation Surgery in Parkinson’s Patients
by Mahta Mousavi, Dorothee Kübler-Weller, Lisa Paulsen, Friedrich Borchers, Claudia Spies, Andrea A. Kühn and Benjamin Blankertz
Anesth. Res. 2026, 3(2), 10; https://doi.org/10.3390/anesthres3020010 - 22 Apr 2026
Viewed by 172
Abstract
Background: While providing enough sedatives to avoid pain and trauma during surgery is important, studies show a link between the received sedatives and the development of postoperative delirium (POD). Therefore, predicting POD from clinical or physiological data before or during surgery is highly [...] Read more.
Background: While providing enough sedatives to avoid pain and trauma during surgery is important, studies show a link between the received sedatives and the development of postoperative delirium (POD). Therefore, predicting POD from clinical or physiological data before or during surgery is highly advantageous. This capability enables healthcare providers to proactively implement necessary measures, thereby mitigating or preventing potential complications. Methods: In this study, we focus on patients with Parkinson’s disease undergoing deep brain stimulation surgery who are particularly susceptible to POD. We investigate what aspects of EEG’s power, functional connectivity and complexity during the course of the surgery are influenced by the amount of sedative. Furthermore, we aim to determine whether and to what extent the recorded brain activity during surgery can serve as a reliable means for the prediction of POD in this group of patients. Results and Conclusions: Our results show significant correlations between various power, connectivity and complexity features of EEG and the amount of sedatives. Even though single EEG features are not significantly different between the two groups who either developed or did not develop POD, we show that a classifier based on support vector machines using the selected EEG features could predict POD. Furthermore, our results provide evidence that a classifier trained only on the amount of sedatives is unable to predict POD. Accompanying this paper, our code is published as an open-source toolbox for the analysis of the EEG signal recorded with the four-channel SEDLine Root system, which is among the widely used EEG systems in operation rooms and its recorded data come with challenges that are addressed in our toolbox. Full article
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25 pages, 4462 KB  
Review
Research Trends and Emerging Directions in Non-Pharmacological Interventions for Autism Spectrum Disorder: A Bibliometric Analysis (2001–2025)
by Yuting Lu, Wenliang Guo, Yanlin Zou, Ailing Wei and Jianwen Xu
Healthcare 2026, 14(8), 1108; https://doi.org/10.3390/healthcare14081108 - 21 Apr 2026
Viewed by 279
Abstract
Background: Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition for which non-pharmacological interventions remain the primary therapeutic approach. Although research output in this field has increased substantially, a comprehensive synthesis of its developmental trajectory and emerging directions is still lacking. Methods [...] Read more.
Background: Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition for which non-pharmacological interventions remain the primary therapeutic approach. Although research output in this field has increased substantially, a comprehensive synthesis of its developmental trajectory and emerging directions is still lacking. Methods: We conducted a bibliometric analysis of publications on non-pharmacological interventions for ASD indexed in the Web of Science Core Collection between 2001 and 2025. Knowledge structures, research hotspots, and temporal trends were visualized and analyzed using CiteSpace. Results: The field has transitioned from an early focus on behavioral interventions in children to a diversified and interdisciplinary research ecosystem spanning the lifespan. Recent growth has been driven by the integration of neuroscience-based approaches, particularly neuromodulation techniques, alongside continued refinement of behavioral, sensorimotor, and complementary therapies. Increasing attention has been paid to individual heterogeneity, methodological rigor, and mechanism-oriented research. Current frontiers emphasize multimodal intervention strategies, neural plasticity-based mechanisms, and the development of personalized precision intervention frameworks. Conclusions: This bibliometric analysis delineates the intellectual evolution of non-pharmacological intervention research for ASD and identifies key research gaps, particularly the need for longitudinal and pragmatic studies targeting individualized treatment response. The findings provide an evidence-informed overview of current concepts and emerging research directions in non-pharmacological care for ASD, with important implications for future clinical research, intervention design, and strategic research planning. Full article
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20 pages, 847 KB  
Review
Closing the Loop in Neuromodulation: A Review of Machine Learning Approaches for EEG-Guided Transcranial Magnetic Stimulation
by Elena Mongiardini and Paolo Belardinelli
Algorithms 2026, 19(4), 323; https://doi.org/10.3390/a19040323 - 21 Apr 2026
Viewed by 330
Abstract
Transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) provides a powerful framework to probe and modulate human cortical and corticospinal excitability. In recent years, brain state-dependent EEG–TMS paradigms have gained increasing interest by synchronizing stimulation to ongoing neural activity. However, traditional approaches relying [...] Read more.
Transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) provides a powerful framework to probe and modulate human cortical and corticospinal excitability. In recent years, brain state-dependent EEG–TMS paradigms have gained increasing interest by synchronizing stimulation to ongoing neural activity. However, traditional approaches relying on single oscillatory features or fixed thresholds have yielded heterogeneous and often inconsistent results, motivating the adoption of machine learning (ML) and artificial intelligence (AI) methods to model brain state in a multivariate, data-driven manner. This review synthesizes current ML and deep learning (DL) approaches aimed at predicting cortical and corticospinal excitability from pre-stimulus EEG. We contextualize these methods within brain state-dependent EEG–TMS frameworks based on oscillatory phase, power, and network-level features, and within evolving definitions of brain state that move beyond local biomarkers toward distributed, large-scale, and dynamically evolving neural representations. The reviewed studies span feature-engineered models, data-driven decoding approaches, and emerging adaptive closed-loop frameworks. Finally, we discuss key methodological challenges, translational barriers, and future directions toward personalized, interpretable, and fully closed-loop neuromodulation systems. Full article
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11 pages, 2008 KB  
Brief Report
Nano-Enhanced Optical Delivery of Multi-Characteristic Opsin Gene for Spinal Optogenetic Modulation of Pain
by Darryl Narcisse, Robert Benkowski, Matthew Dwyer and Samarendra Mohanty
Bioengineering 2026, 13(4), 479; https://doi.org/10.3390/bioengineering13040479 - 20 Apr 2026
Viewed by 335
Abstract
Optogenetic modulation employs light-sensitive proteins known as opsins to regulate cellular activity. A unique therapeutic application of this technique involves modulating pain perception by selectively targeting neural pathways within the spinal cord. Multi-Characteristic Opsin (MCO) represents an innovative optogenetic actuator capable of activation [...] Read more.
Optogenetic modulation employs light-sensitive proteins known as opsins to regulate cellular activity. A unique therapeutic application of this technique involves modulating pain perception by selectively targeting neural pathways within the spinal cord. Multi-Characteristic Opsin (MCO) represents an innovative optogenetic actuator capable of activation across a broad spectrum of light wavelengths, exhibiting a slow depolarizing phase that resembles natural photoreceptors. This study examines the current advancements in spinal optogenetic modulation utilizing MCO for pain management. Due to its high sensitivity, MCO facilitates minimally invasive, remotely controlled optogenetic modulation of spinal neurons. This approach enables the regulation of extensive spatial regions, provided the MCO channel receives sufficient light intensity to surpass the activation threshold. Nano-enhanced optical delivery (NOD) successfully transfected spinal neurons with the GAD67-MCO2-mCherry construct, as confirmed by membrane-localized mCherry fluorescence with DAPI-labeled nuclei. Using this platform, 5 Hz spinal optogenetic stimulation produced a significant reduction in formalin-evoked pain behaviors, demonstrating frequency-specific modulation of spinal pain circuits. Neither 2 Hz nor 10 Hz stimulation yielded comparable analgesic effects, underscoring the importance of precise stimulation parameters. The therapeutic impact also depended on transfection efficiency: reducing the fGNR–plasmid concentration diminished MCO expression and weakened the analgesic response. Together, these results show that effective spinal optogenetic pain modulation requires both optimal stimulation frequency and robust gene delivery. Full article
(This article belongs to the Section Nanobiotechnology and Biofabrication)
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15 pages, 3849 KB  
Article
Electrochemical Sensing of Dopamine with P-g-C3N4/ZIF-67/CPE Composite Electrodes
by Yan Deng, Yixin Liao, Teresa Murray and Shengnian Wang
Biosensors 2026, 16(4), 224; https://doi.org/10.3390/bios16040224 - 18 Apr 2026
Viewed by 212
Abstract
Dopamine is a key neurotransmitter and neuromodulator that regulates many critical brain functions. Accurate monitoring of its level is essential for neuroscience as well as the diagnosis and treatment of many brain diseases. In this work, we developed a new electrochemical sensor, comprising [...] Read more.
Dopamine is a key neurotransmitter and neuromodulator that regulates many critical brain functions. Accurate monitoring of its level is essential for neuroscience as well as the diagnosis and treatment of many brain diseases. In this work, we developed a new electrochemical sensor, comprising phosphorus-doped graphitic carbon nitride (P-g-C3N4) and zeolitic imidazolate framework 67 (ZIF-67), for dopamine detection. In this composite electrode material, ZIF-67 provides numerous adsorption and sensing sites, while P-g-C3N4 enhances overall electrical conductivity and stability. Cyclic voltammetry tests reveal the redox behavior of dopamine at the surface of the composite electrode across various pH values and scan rates. Using differential pulse voltammetry, the sensitivity and selectivity of this dopamine sensor were assessed, identifying a limit of detection of 0.39 nM. Further successful quantification of dopamine in urine samples suggests the potential practical use of this new composite electrochemical sensor for detecting dopamine and/or other neurotransmitters. Full article
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22 pages, 3662 KB  
Review
Integrative Medical Perspective on Laser Acupuncture for Pain Management
by Laura Marinela Ailioaie, Gerhard Litscher and Constantin Ailioaie
Sci 2026, 8(4), 92; https://doi.org/10.3390/sci8040092 - 17 Apr 2026
Viewed by 478
Abstract
Laser acupuncture (LA) integrates principles of traditional acupuncture with photobiomodulation (PBM) and has gained increasing attention as a non-invasive modality for pain management. PBM-based integrative LA in medicine refers to the application of low-level laser irradiation to acupuncture points, combining contemporary biomedical mechanisms [...] Read more.
Laser acupuncture (LA) integrates principles of traditional acupuncture with photobiomodulation (PBM) and has gained increasing attention as a non-invasive modality for pain management. PBM-based integrative LA in medicine refers to the application of low-level laser irradiation to acupuncture points, combining contemporary biomedical mechanisms with holistic, system-oriented therapeutic principles. This narrative review aimed to critically assess the scientific evidence on the efficacy of LA for pain management within the framework of the Principles of Clinical Integration of Photobiomodulation (PCIPBM) in LA, summarizing frequently used laser parameters and clinical indications. LA involves special protocols in standardized acupoints, using defined parameters of wavelength, irradiation, and energy density, consistent with PBM dosing principles. Therapeutic effects are mediated through point-specific neuromodulation and photobiological mechanisms, including modulation of peripheral and central nociceptive processing, reduction in pro-inflammatory mediators, improvement of microcirculation, and mitochondrial activation via cytochrome c oxidase-dependent adenosine triphosphate (ATP) synthesis. Clinical studies report statistically and clinically significant analgesic effects, particularly in chronic musculoskeletal pain, osteoarthritis, low back and neck pain, temporomandibular disorders, neuropathic pain, and selected postoperative pain conditions, when appropriate laser parameters are applied. Reported adverse effects are minimal, and tolerability is high. LA represents a safe, non-invasive therapeutic option and patient-friendly approach with clinically relevant efficacy in pain management. When applied according to PCIPBM, including evidence-based PBM parameters, it may serve as an effective adjunct or alternative to conventional pharmacologic and interventional approaches. Further standardization and high-quality randomized controlled trials are still required. Full article
(This article belongs to the Section Integrative Medicine)
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24 pages, 6370 KB  
Article
Ketogenic Diet Promotes Reward Learning by Upregulating Hippocampal CAMK2A Expression and Activating Dopamine Synaptic Signaling
by Yanan Qiao, Yubing Zeng, Chen Chen, Jinying Shen, Yi Wang, Pei Pei and Shan Wang
Int. J. Mol. Sci. 2026, 27(8), 3587; https://doi.org/10.3390/ijms27083587 - 17 Apr 2026
Viewed by 178
Abstract
Various neuromodulatory benefits of the ketogenic diet (KD) have been demonstrated, yet its influence on reward learning and underlying mechanisms remain poorly defined. This study combined proteomics and metabolomics to identify key molecular changes in the hippocampus of KD-fed mice. Our analysis revealed [...] Read more.
Various neuromodulatory benefits of the ketogenic diet (KD) have been demonstrated, yet its influence on reward learning and underlying mechanisms remain poorly defined. This study combined proteomics and metabolomics to identify key molecular changes in the hippocampus of KD-fed mice. Our analysis revealed significant upregulation of the “dopaminergic synapse” pathway, with CAMK2A emerging as a central regulator. In vitro, treatment of the hippocampal neuronal cell line HT22 with β-hydroxybutyrate (BHB), a primary KD metabolite, increased the protein expression of CAMK2A and increased the phosphorylation of its downstream target, GluA1. Crucially, Camk2a knockdown completely blocked BHB-induced p-GluA1 enhancement. To determine the behavioral relevance, we stereotaxically delivered AAV-shCamk2a into the hippocampus of KD-fed mice. Knockdown of Camk2a reversed the pro-reward effects of KD, as measured by the sucrose preference test and conditioned place preference test, without impairing general locomotor activity in the open field test. Together, these results suggest a novel BHB–CAMK2A–dopaminergic signaling axis through which KD enhances reward learning, thus bridging systemic metabolism with cognitive function and expanding our understanding of KD-mediated neuromodulation. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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