Search Results (45,276)

CD44, a structurally diverse cell-surface glycoprotein, plays a multifaceted and indispensable role in neural tissue across both physiological and pathological conditions. It orchestrates complex cell–extracellular matrix interactions and intracellular signaling through its variant isoforms and post-translational modifications and is broadly expressed in neural stem/progenitor cells, microglia, astrocytes, and selected neuronal populations. The interactions of CD44 with ligands such as hyaluronan and osteopontin regulate critical cellular functions, including migration, differentiation, inflammation, and synaptic plasticity. In microglia and macrophages, CD44 mediates immune signaling and phagocytic activity, and it is dynamically upregulated in neuroinflammatory diseases, particularly through pathways involving Toll-like receptor 4. CD44 expression in astrocytes is abundant during central nervous system development and in diseases, contributing to glial differentiation, reactive astrogliosis, and scar formation. Though its expression is less prominent in mature neurons, CD44 supports neural plasticity, circuit organization, and injury-induced repair mechanisms. Additionally, its expression at nervous system barriers, such as the blood–brain barrier, underscores its role in regulating vascular permeability during inflammation and ischemia. Collectively, CD44 emerges as a critical integrator of neural cell function and intercellular communication. Although the roles of CD44 in glial cells appear to be similar to those explored in other tissues, the expression of this molecule and its variants on neurons reveals peculiar functions. Elucidating the cell-type-specific roles and regulation of CD44 variants may offer novel therapeutic strategies for diverse neurological disorders. Full article

Alzheimer’s disease (AD) and major depressive disorder (MDD) are prevalent central nervous system (CNS) disorders that share overlapping symptoms but differ in underlying molecular mechanisms. Distinguishing these mechanisms is essential for developing targeted diagnostic and therapeutic strategies. In this study, we integrated multi-tissue transcriptomic datasets from brain and peripheral samples to identify differentially expressed microRNAs (miRNAs) in AD and MDD. Functional enrichment analyses (KEGG, GO) revealed that dysregulated miRNAs in AD were associated with MAPK, PI3K–Akt, Ras, and PD-1/PD-L1 signaling, pathways linked to synaptic plasticity, neuroinflammation, and immune regulation. In contrast, MDD-associated miRNAs showed enrichment in Hippo signaling and ubiquitin-mediated proteolysis, implicating altered neurogenesis and protein homeostasis. Network analysis highlighted key disease- and tissue-specific miRNAs, notably hsa-miR-1202 and hsa-miR-24-3p, with potential roles in neuronal survival and molecular network regulation. These findings suggest that miRNAs may serve as non-invasive biomarkers for diagnosis, prognosis, and treatment monitoring in both disorders. While therapeutic targeting of miRNAs offers promise, challenges such as blood–brain barrier penetration and tissue-specific delivery remain. This integrative approach provides a translational framework for advancing miRNA-based strategies in CNS disease research. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterised by cognitive decline, synaptic loss, and multifaceted pathology involving amyloid-β (Aβ) aggregation, tau hyperphosphorylation, neuroinflammation, and impaired proteostasis. In recent years, biologic therapies, such as monoclonal antibodies, vaccines, antisense oligonucleotides (ASOs), and gene therapies, have gained prominence as promising disease-modifying strategies. In this review, we provide a comprehensive synthesis of current biologic approaches under clinical evaluation for AD. Drawing on data curated from ClinicalTrials.gov (as of 2025), we systematically summarise the molecular targets, therapeutic modalities, mechanisms of action, trial phases, and sponsors of over 60 biologic agents. These include Aβ-directed antibodies targeting distinct conformers such as protofibrils, pyroglutamate-modified species, and soluble oligomers; tau-targeted immunotherapies and RNA-based interventions; and emerging platforms focused on neuroimmune modulation, peptide hormones, and microbiota-based strategies. Gene and RNA therapeutics, particularly ASOs and small interfering RNAs (siRNAs) delivered intrathecally or via lipid nanoparticles, are also reviewed for their potential to modulate intracellular targets with high specificity. We also analyse the historical landscape of biologic candidates that failed to reach approval, discussing key reasons for trial discontinuation, including lack of clinical efficacy, safety concerns (e.g., amyloid-related imaging abnormalities), or inadequate biomarker responses. These cases offer crucial insights for refining future drug design. Looking ahead, we highlight major challenges and evolving perspectives in AD biologic therapy: expanding therapeutic targets beyond Aβ and tau, overcoming delivery barriers to the brain, designing prevention-oriented and genetically stratified trials, and navigating regulatory and ethical considerations. Together, these efforts signal a paradigm shift in AD drug development, from symptomatic treatment to mechanism-based precision biologics. By integrating real-time clinical trial data with mechanistic insight, this review aims to inform both translational research and therapeutic innovation in AD. Full article

In this perspective article, we introduce Ecocebo as a novel concept describing the modulatory effects of physical environments, whether natural or built, on drug effect. Positioned as a spatial component of the placebo effect, Ecocebo is grounded in evidence-based design principles and proposes that environmental features such as natural light, greenery, spatial geometry, and calming esthetics can significantly influence sensory, emotional, and cognitive processes. These environmental factors may enhance or modify pharmacological responses, especially for analgesics, anxiolytics, and antidepressants. We highlighted how exposure to restorative spaces can reduce pain perception, stress, and the need for medication, paralleling findings in placebo research where contextual and sensory cues influence brain regions linked to emotion and pain regulation. We propose virtual reality (VR) as the most suitable methodological tool to study Ecocebo in controlled and ecologically valid settings. VR allows for the precise manipulation of spatial features and real-time monitoring of physiological and psychological responses. We also propose integrating VR with neuromodulation techniques to investigate brain–environment–drug interactions. Finally, we addressed key methodological challenges such as defining control conditions and standardizing the measurement of presence. This perspective opens new directions for the integration of non-pharmacological and pharmacological interventions and personalized therapeutic environments to optimize clinical outcomes. Full article

This study examined the neural characteristics of belief-bias reasoning in order to reveal the neurocognitive basis of critical thinking. Functional near-infrared spectroscopy was utilized to capture the real-time brain hemodynamic activity of 74 college students while they performed a belief-bias syllogistic reasoning task. Values of oxy-hemoglobin (oxy-Hb) and deoxy-hemoglobin (deoxy-Hb) in regions of interest were analyzed in relation to critical thinking skills assessed by established tests. The results reveal significant activation in both the opercular part of the right IFC and the left DLPFC when participants encountered situations where their prior beliefs contradicted logical validity during the completion of the belief-bias syllogistic reasoning task. Crucially, individuals with lower levels of critical thinking skills demonstrated heightened activation in the opercular part of the right IFC compared to those with higher levels of critical thinking skills. Furthermore, variations in hemodynamics, quantified by oxy-Hb and deoxy-Hb concentration values (area under the activity curve as absolute value), during the execution of belief-bias reasoning tasks accounted for a substantial proportion of the variability in critical thinking skills. Additionally, the hemodynamic data to a large extent explained the connection between belief-bias reasoning and critical thinking. These results provide a neural explanation for the relationship between belief-bias reasoning and critical thinking, and advance theoretical models of critical thinking by illuminating the brain’s mechanisms engaged in unbiased reasoning and metacognition. Full article

The heart–brain axis (HBA) is a dynamic system of reciprocal communication between the cardiovascular and central nervous system, incorporating neural, immunologic, molecular and hormonal pathways. The central autonomic network is described as a key regulator of cardiovascular activity and autonomic dysfunction as an important mechanism underlying various neurologic and cardiac disorders. Heart rate variability (HRV) is identified as the key biomarker of the axis reflecting autonomic nervous system balance. Increased understanding of its molecular mechanisms has led to the proposal of new therapeutic strategies focused on modulating heart–brain communication including β-blockers, vagus nerve stimulation, neurotrophin modulation, and nanoparticle-based approaches. The integration of wearables and artificial intelligence (AI) has allowed for real-time monitoring and innovative diagnostic and prognostic applications. The present narrative review summarizes current knowledge on the mechanisms comprising the heart–brain axis, their implication in neurologic and cardiac disorders, and their potential for developing novel therapies. It also highlights how advancements in wearable technology and AI systems are being integrated into clinical practice and transforming the landscape. Full article

Objectives: The need for routine brain magnetic resonance imaging (MRI) for patients presenting with unilateral facial palsy in the emergency department (ED) is a subject of ongoing debate. This study aimed to evaluate the diagnostic yield of MRI in this population and to identify clinical risk factors associated with non-idiopathic causes, to inform selective imaging strategies. Methods: This single-center, retrospective study was conducted in the ED of a tertiary-care center in Korea. We analyzed adult patients (aged ≥ 18 years) who presented with facial palsy as the primary symptom between 1 January 2020 and 31 December 2022. Patients with other neurological abnormalities detected during the initial examination or those who did not undergo brain MRI were excluded. The primary outcome was the identification of positive MRI findings, defined as brain lesions (e.g., ischemic stroke, tumor, and hemorrhage) considered causally related to the facial palsy based on anatomical correlation and radiological interpretation. Patients were categorized into positive or negative MRI groups accordingly, and baseline characteristics were compared between the groups. Results: Among the 436 patients who underwent brain MRI, 13 (3.0%) showed positive findings such as brain tumors or stroke that led to diagnoses other than Bell’s palsy, while the remaining 423 (97.0%) were ultimately diagnosed with Bell’s palsy. The proportion of patients with a history of transient ischemic attack/stroke and malignancy was significantly higher in the group with non-idiopathic facial palsy (p = 0.02 and p < 0.001, respectively). Conclusions: In adults presenting to the ED with clinically isolated unilateral facial palsy and no other neurological signs, routine brain MRI had a low diagnostic yield (3%). A history of malignancy or prior TIA/stroke was associated with alternative diagnoses. A selective imaging strategy based on risk factors may improve diagnostic efficiency without compromising safety. Full article

Background: Neurofilament light chain (NfL) is a promising biomarker of neuroaxonal injury, increasingly used to monitor neurodegeneration in Alzheimer’s disease (AD). Multiple analytical platforms are available for NfL quantification in cerebrospinal fluid (CSF), but data on cross-platform consistency remain limited. Objective: This pilot study aimed to provide CSF NfL concentrations measured using Simoa and Lumipulse immunoassays in patients with biologically confirmed AD. Methods: Twenty-eight patients with cognitive impairment fulfilling the biological criteria for AD were enrolled. CSF NfL levels were measured using both Simoa and Lumipulse immunoassays. Statistical analyses assessed intra-individual agreement, correlation between platforms, and associations with cognitive status. Results: NfL concentrations measured with Simoa and Lumipulse showed a strong positive correlation between platforms (Spearman’s ρ = 0.965, p < 0.001), demonstrating excellent analytical concordance. Conclusions: In this pilot study, Simoa and Lumipulse yielded strongly correlated CSF NfL measurements, providing initial evidence of cross-platform consistency. However, these findings require confirmation in larger and diverse cohorts before definitive validation. Full article

This study aimed to validate the Robot Acceptance Questionnaire (RAQ), a self-report instrument designed to assess user acceptance toward social robots. Originally structured around four theoretical domains—pragmatic, hedonic (identity and feelings), and attractiveness—the RAQ was empirically found to converge into two robust and inversely related dimensions: Positive Attitude (PA) and Negative Attitude (NA). A total of 208 participants (mean = 43.1; S.D. = 21.4) viewed a short video of a humanoid robot (Pepper) and completed the RAQ. Factorial structure (Principal Component Analysis), internal reliability (Cronbach’s alpha), and construct validity were assessed. Results showed excellent internal consistency for both PA and NA (α = 0.93), and intuitive associations with independent measures of ease of use, mastery, and willingness to interact. The RAQ thus offers a concise and reliable tool for assessing general robot acceptance, especially suitable for remote and large-scale studies. Full article

Ultrasound imaging is one of the most widespread biomedical imaging techniques thanks to its advantages such as being non-invasive, portable, non-ionizing, and cost-effective. Ultrasound imaging generally provides two-dimensional cross-sectional images, but the quality and interpretative ability vary based on the experience of the examiner, leading to a lack of objectivity and accuracy. To address these issues, there is a growing demand for three-dimensional ultrasound imaging. Among the various types of transducers used to obtain three-dimensional ultrasound images, this paper focuses on the most standardized probe, the linear array transducer, and provides an overview of the system implementations, imaging results, and applications of volumetric ultrasound imaging from the perspective of scanning methods. Through this comprehensive review, future researchers will gain insights into the advantages and disadvantages of various approaches to three-dimensional imaging systems using linear arrays, providing direction and applicability for system configuration and application. Full article

Background/Objectives: Pediatric acquired brain injury (ABI) often results in persistent challenges that extend beyond motor impairments, affecting quality of life (QoL), social participation, and engagement in physical activity. Given the complexity and chronicity of these outcomes, there is a pressing need for multidimensional interventions grounded in the International Classification of Functioning, Disability and Health (ICF). Sport-based exercise interventions, when developmentally adapted and tailored to individual interests, may promote intrinsic motivation, peer connection, and sustainable engagement—factors especially relevant in pediatric ABI populations, who often experience reduced physical activity and social isolation. However, standardized, replicable protocols specifically tailored to this population remain scarce. This study presents the protocol for a randomized controlled trial evaluating the effects of a 16-week sport-based intervention on QoL, social participation, physical activity engagement, and motor functioning tailored for adolescents with pediatric ABI. Methods: Participants will be randomly assigned to an intervention group or a control group receiving usual care. The intervention consists of one weekly 60-minute session, led by trained professionals in adapted physical activity and pediatric neurorehabilitation. It combines sport-based motor skill training, cooperative games, and group activities specifically tailored to each child’s developmental level, motor abilities, and preferences. Outcomes will be assessed at baseline and following the 16-week intervention period, focusing on QoL, participation, physical activity engagement, and motor functioning. Discussion: This study introduces a structured, child-centered model that bridges clinical rehabilitation and community-based sport. By integrating motor and psychosocial targets through a group sport-based intervention, it aims to enhance recovery across ICF domains. Findings may inform interdisciplinary practice and support the development of sustainable strategies to promote long-term engagement and well-being in adolescents with ABI. Full article

Background: Regional cerebral blood flow (rCBF) is a putative biomarker for neuropsychiatric disorders, including major depressive disorder (MDD). Methods: Here, we show that rCBF can be predicted from resting-state functional MRI (rsfMRI) at the voxel level while correcting for partial volume averaging (PVA) artifacts. Cortical patterns of MDD-related CBF differences decoded from rsfMRI using a PVA-corrected approach showed excellent agreement with CBF measured using single-photon emission computed tomography (SPECT) and arterial spin labeling (ASL). A support vector machine algorithm was trained to decode cortical voxel-wise CBF from temporal and power-spectral features of voxel-level rsfMRI time series while accounting for PVA. Three datasets, Amish Connectome Project (N = 300; 179 M/121 F, both rsfMRI and ASL data), UK Biobank (N = 8396; 3097 M/5319 F, rsfMRI data), and Amen Clinics Inc. datasets (N = 372: N = 183 M/189 F, SPECT data), were used. Results: PVA-corrected CBF values predicted from rsfMRI showed significant correlation with the whole-brain (r = 0.54, p = 2 × 10⁻⁵) and 31 out of 34 regional (r = 0.33 to 0.59, p < 1.1 × 10⁻³) rCBF measures from 3D ASL. PVA-corrected rCBF values showed significant regional deficits in the UKBB MDD group (Cohen’s d = −0.30 to −0.56, p < 10⁻²⁸), with the strongest effect sizes observed in the frontal and cingulate areas. The regional deficit pattern of MDD-related hypoperfusion showed excellent agreement with CBF deficits observed in the SPECT data (r = 0.74, p = 4.9 × 10⁻⁷). Consistent with previous findings, this new method suggests that perfusion signals can be predicted using voxel-wise rsfMRI signals. Conclusions: CBF values computed from widely available rsfMRI can be used to study the impact of neuropsychiatric disorders such as MDD on cerebral neurophysiology. Full article

We previously reported that the fathers of the Bien Hoa birth cohort in Vietnam showed altered brain regional gray matter volumes, as measured by magnetic resonance imaging, and social anxiety traits associated with perinatal dioxin exposure. In the present study, we aimed to compare gray matter volumes and social anxiety scale scores between dioxin-exposed fathers in Bien Hoa and unexposed controls in an unsprayed area. Fat-based bioassay-toxic equivalency levels in serum were used to indicate dioxin exposure in adulthood. Results indicated that the longer Bien Hoa residency group (≥30 years) exposed to dioxins during the perinatal period and early childhood showed higher gray matter volumes in the right and left temporal lobes than controls. However, no significant differences in temporal lobe gray matter volumes were found between the shorter Bien Hoa residency group (<30 years) and controls. Furthermore, the longer, but not shorter, Bien Hoa residency group showed higher social–emotional subscale scores than controls. Additionally, fat-based bioassay-toxic equivalency levels were inversely correlated with gray matter volumes in several right temporal gyri. These findings suggest biphasic life stage-dependent adverse effects of dioxin exposure: perinatal dioxin exposure increases gray matter volumes, especially in the temporal lobe, which leads to neurodevelopmental disorders with socio-emotional disturbances, whereas dioxin exposure after brain development decreases cortical gray matter volumes, possibly leading to cognitive dysfunction. Full article

Anxiety and depression affect millions worldwide, yet stigma and long wait times often delay access to care. Mobile mental health apps can decrease these barriers by offering on-demand screening and support. Nevertheless, many machine and deep learning methods used in such tools perform poorly under severe class imbalance, yielding biased, poorly calibrated predictions. To address this challenge, this study proposes MCoG-LDPSNet, a brain-inspired model that combines dual, orthogonal encoding pathways with a novel Loss-Driven Parametric Swish (LDPS) activation. LDPS implements a neurobiologically motivated adaptive-gain mechanism via a learnable β parameter driven by calibration and confidence-aware loss signals that amplifies minority-class patterns while preserving overall reliability, enabling robust predictions under severe data imbalance. On a benchmark mental health corpus, MCoG-LDPSNet achieved AUROC = 0.9920 and G-mean = 0.9451, outperforming traditional baselines like GLMs, XGBoost, state-of-the-art deep models (CNN-BiLSTM-ATTN), and transformer-based approaches. After transfer learning to social media text, the MCoG-LDPSNet maintained a near-perfect AUROC of 0.9937. Integrated into the EmotiZen App with enhanced app features, MCoG-LDPSNet was associated with substantial symptom reductions (anxiety 28.2%; depression 42.1%). These findings indicate that MCoG-LDPSNet is an accurate, imbalance-aware solution suitable for scalable mobile screening of individuals for anxiety and depression. Full article

Alzheimer’s disease (AD) is the leading cause of dementia worldwide and is becoming one of the most morbid diseases of this century. Recently, ocular research in AD has gained significance, as the eye, due to its close relationship with the brain, can reflect the presence of neurological disorders. Several studies have reported alterations in various ocular structures in AD, ranging from tear fluid to the retina. These changes, particularly in the retina and the optic nerve, along with cerebral atrophy affecting visual brain areas, may lead to visual dysfunctions. This narrative review summarizes and critically examines current evidence on these impairments and explores their possible underlying mechanisms. A decrease in visual acuity, contrast sensitivity, and color vision has been observed, primarily associated with retinal ganglion cell loss or damage. Furthermore, alterations in the visual field, ocular motility, and visual perception have been recorded, mainly resulting from cortical changes. These optical parameters frequently correlate with patients’ cognitive status. In conclusion, these findings highlight the importance of developing strategies to preserve visual function in these patients, helping to prevent further deterioration in their quality of life, and emphasize the potential of visual function assessment as a tool for diagnosis or predicting AD progression. Full article