Search Results (537)

Objectives: The primary objective was to investigate and compare the effects of three paired-pulse repetitive trans-spinal magnetic stimulation (PP-rTSMS) protocols on balance control and corticospinal network function. Methods: PP-rTSMS (800 pulses, frequency 100 Hz, intensity 70% of the resting motor threshold) was applied over the eighth thoracic vertebra (Th8) in twenty-seven young healthy individuals. Each proband received three verum sessions (using a verum coil with handle oriented (i) cranially, (ii) caudally, and (iii) laterally) and (iv) one sham session (using a sham coil) in a randomised order. Balance ability (Y Balance Test) and corticospinal network functions (motor evoked potentials (MEPs), cortical silent periods (SCPs)) were tested immediately (i) prior to and (ii) after each interventional session. Results: Each verum session induced a significant improvement in balance ability (cranially (F_1,26 = 8.009; p = 0.009; η² = 0.236), caudally (F_1,26 = 4.846; p = 0.037; η² = 0.157), and laterally (F_1,26 = 23,804; p ≤ 0.001; η² = 0.478) oriented grip) as compared to the sham session. In addition, the laterally oriented coil grip was associated with significantly greater balance benefits than both the cranial (F_1,26 = 10.173; p = 0.004; η² = 0.281) and caudal (F_1,26 = 14.058; p ≤ 0.001; η² = 0.351) grip orientations. No significant intervention-induced effects were detected on corticospinal network functions. Conclusions: Our data show that PP-rTSMS effectively supports balance control and that coil orientation significantly influences these effects. Further studies should test variations of this promising approach on healthy and disabled cohorts. Full article

Background/Objectives: Schizophrenia exhibits symptoms linked to the hippocampus and parahippocampal gyrus. This includes the entorhinal cortex (ERC) and perirhinal cortex (PRC) as anterior parts, along with the posterior segment known as the parahippocampal cortex (PHC). However, recent research has detailed atlases based on cytoarchitectural characteristics and the hippocampus divided into four subregions: cornu ammonis (CA), dentate gyrus (DG), subiculum (SUB), and hippocampal–amygdaloid transition (HATA). This study aimed to explore the functional connectivity (FC) changes between these hippocampal subregions and the parahippocampal gyrus structures (ERC, PRC, and PHC) as well as between hippocampal subregions and various functional brain networks in schizophrenia. Methods: In total, 50 individuals with schizophrenia and 50 matched healthy subjects were examined using resting state functional magnetic resonance imaging (rs-fMRI). Results: The results showed alterations characterized by increases and decreases in the strength of the positive connectivity between the parahippocampal gyrus structures and the four hippocampal subregions when comparing patients with schizophrenia with healthy subjects. Alterations were observed among the hippocampal subregions and functional brain networks, as well as the formation of new connections and absence of connections. Conclusions: There is strong evidence that the different subregions of the hippocampus have unique functions and their connectivity with the parahippocampal cortices and brain networks are affected by schizophrenia. Full article

Kinesthetic motor imagery (KMI), the mental rehearsal of a motor task without its actual performance, constitutes one of the most common techniques used for brain–computer interface (BCI) control for movement-related tasks. The effect of neural injury on motor cortical activity during execution and imagery remains under investigation in terms of activations, processing of motor onset, and BCI control. The current work aims to conduct a post hoc investigation of the event-related potential (ERP)-based processing of KMI during BCI control of anthropomorphic robotic arms by spinal cord injury (SCI) patients and healthy control participants in a completed clinical trial. For this purpose, we analyzed 14-channel electroencephalography (EEG) data from 10 patients with cervical SCI and 8 healthy individuals, recorded through Emotiv EPOC BCI, as the participants attempted to move anthropomorphic robotic arms using KMI. EEG data were pre-processed by band-pass filtering (8–30 Hz) and independent component analysis (ICA). ERPs were calculated at the sensor space, and analysis of variance (ANOVA) was used to determine potential differences between groups. Our results showed no statistically significant differences between SCI patients and healthy control groups regarding mean amplitude and latency (p < 0.05) across the recorded channels at various time points during stimulus presentation. Notably, no significant differences were observed in ERP components, except for the P200 component at the T8 channel. These findings suggest that brain circuits associated with motor planning and sensorimotor processes are not disrupted due to anatomical damage following SCI. The temporal dynamics of motor-related areas—particularly in channels like F3, FC5, and F7—indicate that essential motor imagery (MI) circuits remain functional. Limitations include the relatively small sample size that may hamper the generalization of our findings, the sensor-space analysis that restricts anatomical specificity and neurophysiological interpretations, and the use of a low-density EEG headset, lacking coverage over key motor regions. Non-invasive EEG-based BCI systems for motor rehabilitation in SCI patients could effectively leverage intact neural circuits to promote neuroplasticity and facilitate motor recovery. Future work should include validation against larger, longitudinal, high-density, source-space EEG datasets. Full article

Brain organoid technology has revolutionized in vitro modeling of human neurodevelopment and disease, providing unprecedented insights into cortical patterning, neural circuit assembly, and pathogenic mechanisms of neurological disorders. Critically, human brain organoids uniquely recapitulate human-specific developmental processes—such as the expansion of outer radial glia and neuromelanin—that are absent in rodent models, making them indispensable for studying human brain evolution and dysfunction. However, a major bottleneck persists: Extended culture periods (≥6 months) are empirically required to achieve late-stage maturation markers like synaptic refinement, functional network plasticity, and gliogenesis. Yet prolonged conventional 3D culture exacerbates metabolic stress, hypoxia-induced necrosis, and microenvironmental instability, leading to asynchronous tissue maturation—electrophysiologically active superficial layers juxtaposed with degenerating cores. This immaturity/heterogeneity severely limits their utility in modeling adult-onset disorders (e.g., Alzheimer’s disease) and high-fidelity drug screening, as organoids fail to recapitulate postnatal transcriptional signatures or neurovascular interactions without bioengineering interventions. We summarize emerging strategies to decouple maturation milestones from rigid temporal frameworks, emphasizing the synergistic integration of chronological optimization (e.g., vascularized co-cultures) and active bioengineering accelerators (e.g., electrical stimulation and microfluidics). By bridging biological timelines with scalable engineering, this review charts a roadmap to generate translationally relevant, functionally mature brain organoids. Full article

Migrastatic strategies are considered as candidate therapeutic approaches to suppress cancer invasion into local surrounding tissues and metastatic spread. The F-actin cytoskeleton is responsible for key properties regulating (cancer) cell migration. The cortical F-actin network controls cell stiffness, which, in turn, determines cell migration strategies and efficiency. Moreover, the dynamic remodeling of F-actin networks mediating filopodia, lamellipodia, and F-actin stress fibers is crucial for cell migration. Here, we have used a conditional knockout approach to delete cofilin, an F-actin-binding protein that controls severing. We find that the deletion of cofilin prevents the migration of cancer cells from tumoroids into the surrounding extracellular matrix without affecting their viability. This identifies cofilin as a candidate target to suppress metastatic spread. Pharmacological inhibitors interfering with F-actin dynamics have been developed but their effects are pleiotropic, including severe toxicity, and their impact on 3D tumor cell migration has not been tested or separated from this toxicity. Using concentration ranges of a panel of inhibitors, we select cytochalasins based on the suppression of 2D migration at non-toxic concentrations. We then show that these attenuate the escape of tumor cells from tumoroids and their migration into the surrounding extracellular matrix without toxicity in 3D cultures. This effect is accompanied by suppression of cell stiffness at such non-toxic concentrations, as measured by acoustic force spectroscopy. These findings identify cytochalasins B and D as candidate migrastatic drugs to suppress metastatic spread. Full article

The SCARECROW (SCR) transcription factor governs cell-type patterning in plant roots and Kranz anatomy of leaves, serving as a master regulator of root and shoot morphogenesis. Foxtail millet (Setaria italica), characterized by a compact genome, self-pollination, and a short growth cycle, has emerged as a C₄ model plant. Here, we revealed two SCR paralogs in foxtail millet—SiSCR1 and SiSCR2—which exhibit high sequence conservation with ZmSCR1/1h (Zea mays), OsSCR1/2 (Oryza sativa), and AtSCR (Arabidopsis thaliana), particularly within the C-terminal GRAS domain. Both SiSCR genes exhibited nearly identical secondary structures and physicochemical profiles, with promoter analyses revealing five conserved cis-regulatory elements. Robust phylogenetic reconstruction resolved SCR orthologs into monocot- and dicot-specific clades, with SiSCR genes forming a sister branch to SvSCR from its progenitor species Setaria viridis. Spatiotemporal expression profiling demonstrated ubiquitous SiSCR gene transcription across developmental stages, with notable enrichment in germinated seeds, plants at the one-tip-two-leaf stage, leaf 1 (two days after heading), and roots during the seedling stage. Co-expression network analysis revealed that there is a correlation between SiSCR genes and other functional genes. Abscisic acid (ABA) treatment led to a significant downregulation of the expression level of SiSCR genes in Yugu1 roots, and the expression of the SiSCR genes in the roots of An04 is more sensitive to PEG6000 treatment. Drought treatment significantly upregulated SiSCR2 expression in leaves, demonstrating its pivotal role in plant adaptation to abiotic stress. Analysis of heterologous expression under the control of the 35S promoter revealed that SiSCR genes were expressed in root cortical/endodermal initial cells, endodermal cells, cortical cells, and leaf stomatal complexes. Strikingly, ectopic expression of SiSCR genes in Arabidopsis led to hypersensitivity to ABA, and ABA treatment resulted in a significant reduction in the length of the meristematic zone. These data delineate the functional divergence and evolutionary conservation of SiSCR genes, providing critical insights into their roles in root/shoot development and abiotic stress signaling in foxtail millet. Full article

Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) has emerged as a transformative tool for probing cortical dynamics with millisecond precision. This review examines the state-dependent nature of TMS-EEG, a critical yet underexplored dimension influencing measurement reliability and clinical applicability. By integrating TMS’s neuromodulatory capacity with EEG’s temporal resolution, this synergy enables real-time analysis of brain network dynamics under varying neural states. We delineate foundational mechanisms of TMS-evoked potentials (TEPs), discuss challenges posed by temporal and inter-individual variability, and evaluate advanced paradigms such as closed-loop and task-embedded TMS-EEG. The former leverages real-time EEG feedback to synchronize stimulation with oscillatory phases, while the latter aligns TMS pulses with task-specific cognitive phases to map transient network activations. Current limitations—including hardware constraints, signal artifacts, and inconsistent preprocessing pipelines—are critically analyzed. Future directions emphasize adaptive algorithms for neural state prediction, phase-specific stimulation protocols, and standardized methodologies to enhance reproducibility. By bridging mechanistic insights with personalized neuromodulation strategies, state-dependent TMS-EEG holds promise for advancing both basic neuroscience and precision medicine, particularly in psychiatric and neurological disorders characterized by dynamic neural dysregulation. Full article

Functional near-infrared spectroscopy (fNIRS) allows non-invasive assessment of cortical activity during naturalistic tasks. This study aimed to compare cortical activation dynamics—specifically the latency (t_max) and amplitude (ΔoxyHb) of oxygenated haemoglobin changes—in passive observation and an interactive task using the Nefroball system. A total of 117 healthy adults performed two tasks involving rhythmic hand movements: a passive protocol and an interactive game-controlled condition. fNIRS recorded signals from the visual, parietal, motor, and prefrontal cortices of the left hemisphere. The Mann–Whitney test revealed significantly shorter t_max in all areas during the interactive task, suggesting faster recruitment of cortical networks. ΔoxyHb amplitude was significantly higher only in the visual cortex during the interactive task, indicating increased visual processing demand. No significant ΔoxyHb differences were observed in the motor, prefrontal, or parietal cortices. Weak but significant positive correlations were found between tmax and ΔoxyHb in the motor and prefrontal regions, but only in the passive condition. These findings support the notion that interactive tasks elicit faster, though not necessarily stronger, cortical responses. The results have potential implications for designing rehabilitation protocols and brain–computer interfaces involving visual–motor integration. Full article

Prognostication of neurodevelopmental outcomes for neonates with hypoxic–ischemic encephalopathy (HIE) is primarily reliant on structural assessment using conventional brain magnetic resonance imaging in the clinical setting. Diffuse optical tomography (DOT) can provide complementary information on brain function at the bedside, further enhancing prognostic accuracy. The predictive accuracy and generalizability of DOT-based neuroimaging markers are unknown. This study aims to test the feasibility of prospectively recruiting and retaining neonates for 12 months in a larger study that investigates the prognostic utility of DOT-based biomarkers of HIE. The study will recruit 25 neonates with HIE over one year and follow them beyond NICU discharge at 6 and 12 months of age. Study subjects will undergo resting-state DOT measurement within 7 days of life for a 30–45-min period without sedation. A customized neonatal cap with 10 sources and eight detectors per side will be used to quantify cortical functional connectivity and to generate brain networks using MATLAB-based software (version 24.2). The Ages and Stages Questionnaires—3rd edition will be used for standardized developmental assessments at follow-up. This feasibility study will help refine the design and sample-size calculation for an adequately powered larger study that determines the clinical utility of DOT-based neuroimaging in perinatal brain injury. Full article

Background: Olfactory dysfunction (OD)—including anosmia and hyposmia—is a common and often persistent outcome of viral infections. This systematic review consolidates findings from structural and functional MRI studies to explore how COVID-19 SARS-CoV-2-induced smell loss alters the brain. Considerable heterogeneity was observed across studies, influenced by differences in methodology, population characteristics, imaging timelines, and OD classification. Methods: Following PRISMA guidelines, we conducted a systematic search of PubMed/MEDLINE, Scopus, and Web of Science to identify MRI-based studies examining COVID-19’s SARS-CoV-2 OD. Twenty-four studies were included and categorized based on imaging focus: (1) olfactory bulb (OB), (2) olfactory sulcus (OS), (3) grey and white matter changes, (4) task-based brain activation, and (5) resting-state functional connectivity. Demographic and imaging data were extracted and analyzed accordingly. Results: Structural imaging revealed consistent reductions in olfactory bulb volume (OBV) and olfactory sulcus depth (OSD), especially among individuals with OD persisting beyond three months, suggestive of inflammation and neurodegeneration in olfactory-associated regions like the orbitofrontal cortex and thalamus. Functional MRI studies showed increased connectivity in early-stage OD within regions such as the piriform and orbitofrontal cortices, possibly reflecting compensatory activity. In contrast, prolonged OD was associated with reduced activation and diminished connectivity, indicating a decline in olfactory processing capacity. Disruptions in the default mode network (DMN) and limbic areas further point to secondary cognitive and emotional effects. Diffusion tensor imaging (DTI) findings—such as decreased fractional anisotropy (FA) and increased mean diffusivity (MD)—highlight white matter microstructural compromise in individuals with long-term OD. Conclusions: COVID-19’s SARS-CoV-2 olfactory dysfunction is associated with a range of cerebral alterations that evolve with the duration and severity of smell loss. Persistent dysfunction correlates with greater neural damage, underscoring the need for longitudinal neuroimaging studies to better understand recovery dynamics and guide therapeutic strategies. Full article

Background: Huntington’s disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the HTT gene, with a rare juvenile-onset form (JoHD) marked by early, rigid motor symptoms. This study examined cortical and subcortical resting-state connectivity in JoHD, hypothesizing preserved cortical networks but altered striatal connectivity, in line with early subcortical atrophy despite relatively spared cortical volume. Methods: Participants included children and young adults with clinician-confirmed Juvenile-Onset Huntington’s Disease (JoHD; n = 19) and gene-non-expanded (GNE) controls (n = 64), both drawn from longitudinal studies at the University of Iowa. Resting-state functional MRI scans were analyzed to assess canonical cortical network and striatal connectivity, and linear mixed-effects models tested group differences and associations with motor, cognitive, and clinical outcomes. Results: JoHD participants showed reduced connectivity within the left somatomotor network and striatal circuits, despite largely typical cortical network connectivity. Striatal connectivity was associated with disease burden and cognitive ability, while left somatomotor connectivity was unrelated to clinical outcomes. Conclusions: These findings support the hypothesis of antagonistic pleiotropy in JoHD, where early neural advantages—such as relatively preserved or possibly enhanced cortical function—may contribute to later striatal vulnerability and degeneration. The observed left-lateralized somatomotor hypoconnectivity aligns with prior volumetric and gene expression research, highlighting the role of excitotoxic glutamatergic input and the selective vulnerability of high-functioning circuits in disease progression. Full article

Introduction: Chewing gum is a widespread, seemingly mundane behaviour that has been linked to diverse benefits such as improved cognitive performance, reduced stress, and enhanced alertness. While animal and human research indicate that mastication engages extensive sensorimotor networks and may also modulate higher-order cognitive and emotional processes, questions remain about the specific neural mechanisms involved. This review combines findings from neuroimaging studies—including fMRI, fNIRS, and EEG—that investigate how chewing gum alters brain activity in humans. Methods: Using a targeted search strategy, we screened the major databases (PubMed/Medline, Scopus, ResearchGate, Google Scholar, and Cochrane) from January 1980 to March 2025 for clinical studies published in English. Eligible studies explicitly measured brain activity during gum chewing using EEG, fNIRS, or fMRI. Results: After a title/abstract screening and a full-text review, thirty-two studies met the inclusion criteria for this review: 15 utilising fMRI, 10 using fNIRS, 2 using both fNIRS and EEG, and 5 employing EEG. Overall, the fMRI investigations consistently reported strong activation in bilateral motor and somatosensory cortices, the supplementary motor area, the insula, the cerebellum, and the thalamus, during gum chewing, with several studies also noting involvement of higher-order prefrontal and cingulate regions, particularly under stress conditions or when participants chewed flavoured gum. The fNIRS findings indicated that chewing gum increased oxygenated haemoglobin in the prefrontal cortex, reflecting heightened cortical blood flow; these effects were often amplified when the gum was flavoured or when participants were exposed to stressful stimuli, suggesting that both sensory and emotional variables can influence chewing-related cortical responses. Finally, the EEG studies documented transient increases in alpha and beta wave power during gum chewing, particularly when flavoured gum was used, and reported short-lived enhancements in vigilance or alertness, which tended to subside soon after participants ceased chewing. Conclusions: Neuroimaging data indicate that chewing gum reliably engages broad sensorimotor circuits while also influencing regions tied to attention, stress regulation, and possibly memory. Although these effects are often short-lived, the range of outcomes—from changes in cortical oxygenation to shifts in EEG power—underscores chewing gum’s capacity to modulate brain function beyond simple oral motor control. However, at this time, the neural changes associated with gum chewing cannot be directly linked to the positive behavioural and functional outcomes observed in studies that measure these effects without the use of neuroimaging techniques. Future research should address longer-term impacts, refine methods to isolate flavour or stress variables, and explore potential therapeutic applications for mastication-based interventions. Full article

Transcranial pulse stimulation (TPS) is a non-invasive neuromodulation method that uses, high-intensity acoustic shockwaves to deliver focused mechanical stimulation to neural tissue with minimal thermal effects. The mechanism of action includes but is not limited to promotion of blood flow and angiogenesis through mechanotransduction. Clinical data to date are limited and preliminary. In Alzheimer’s disease (AD), TPS has demonstrated cognitive and mood improvements in pilot studies and secondary endpoint analysis in first randomized trials. The enhancement of gamma-band oscillations and network connectivity has been reported. Clinical observations in Parkinson’s disease (PD) suggest TPS as a hypothesis-generating approach to address non-motor symptoms—such as depression, cognitive decline, and the freezing of gait—through theoretical modulation of basal ganglia–cortical circuits. TPS is CE-marked in Europe for AD and shows a favorable safety profile; however, ethical considerations arise from the limited evidence base, potential impairment of patient autonomy and judgment in dementia, and the risk of withholding established treatments. TPS should only be offered under structured scientific protocols or within patient registries to ensure rigorous oversight. Ensuring that consent processes account for cognitive capacity, and that TPS is applied as adjunct rather than replacement therapy, is paramount. Future research must include large-scale randomized controlled trials (RCTs), standardize stimulation protocols, deepen mechanistic insight, and embed robust ethical frameworks. Full article

Background: Multicultural education and second-language acquisition engaged neural networks, supporting executive function, memory, and social cognition in adulthood, represent powerful forms of brain-inspired multisensory learning. The neuroeducational framework integrates neuroscience with pedagogical practice to understand how linguistically and culturally rich environments drive neuroplasticity and cognitive adaptation in adult learners. Objective: This systematic review synthesizes findings from 80 studies examining neuroplasticity and cognitive outcomes in adults undergoing multicultural and second-language acquisition, focusing on underlying neural mechanisms and educational effectiveness. Methods: The analysis included randomized controlled trials and longitudinal studies employing diverse neuroimaging techniques (fMRI, MEG, DTI) to assess structural and functional brain network changes. Interventions varied in terms of immersion intensity (ranging from limited classroom contact to complete environmental immersion), multimodal approaches (integrating visual, auditory, and kinesthetic elements), feedback mechanisms (immediate vs. delayed, social vs. automated), and learning contexts (formal instruction, naturalistic acquisition, and technology-enhanced environments). Outcomes encompassed cognitive domains (executive function, working memory, attention) and socio-emotional processes (empathy, cultural adaptation). Results: Strong evidence demonstrates that multicultural and second-language acquisition induce specific neuroplastic adaptations, including enhanced connectivity between language and executive networks, increased cortical thickness in frontal–temporal regions, and white matter reorganization supporting processing efficiency. These neural changes are correlated with significant improvements in working memory, attentional control, and cognitive flexibility. Immersion intensity, multimodal design features, learning context, and individual differences, including age and sociocultural background, moderate the effectiveness of interventions across adult populations. Conclusions: Adult multicultural and second-language acquisition represents a biologically aligned educational approach that leverages natural neuroplastic mechanisms to enhance cognitive resilience. Findings support the design of interventions that engage integrated neural networks through rich, culturally relevant environments, with significant implications for cognitive health across the adult lifespan and for evidence-based educational practice. Full article

Introduction: Combat sport athletes are exposed to repetitive head impacts yet also develop distinct performance-related brain adaptations. Electroencephalography (EEG) provides millisecond-level insight into both processes; however, findings are dispersed across decades of heterogeneous studies. This mechanistic review consolidates and interprets EEG evidence to elucidate how participation in combat sports shapes brain function and to identify research gaps that impede clinical translation. Methods: A structured search was conducted in March 2025 across PubMed/MEDLINE, Scopus, Cochrane Library, ResearchGate, Google Scholar, and related databases for English-language clinical studies published between January 1980 and March 2025. Eligible studies recorded raw resting or task-related EEG in athletes engaged in boxing, wrestling, judo, karate, taekwondo, kickboxing, or mixed martial arts. Titles, abstracts, and full texts were independently screened by two reviewers. Twenty-three studies, encompassing approximately 650 combat sport athletes and 430 controls, met the inclusion criteria and were included in the qualitative synthesis. Results: Early visual EEG and perfusion studies linked prolonged competitive exposure in professional boxers to focal hypoperfusion and low-frequency slowing. More recent quantitative studies refined these findings: across boxing, wrestling, and kickboxing cohorts, chronic participation was associated with reduced alpha and theta power, excess slow-wave activity, and disrupted small-world network topology—alterations that often preceded cognitive or structural impairments. In contrast, elite athletes in karate, fencing, and kickboxing consistently demonstrated neural efficiency patterns, including elevated resting alpha power, reduced task-related event-related desynchronization (ERD), and streamlined cortico-muscular coupling during cognitive and motor tasks. Acute bouts elicited transient increases in frontal–occipital delta and high beta power proportional to head impact count and cortisol elevation, while brief judo chokes triggered short-lived slow-wave bursts without lasting dysfunction. Methodological heterogeneity—including variations in channel count (1 to 64), reference schemes, and frequency band definitions—limited cross-study comparability. Conclusions: EEG effectively captures both the adverse effects of repetitive head trauma and the cortical adaptations associated with high-level combat sport training, underscoring its potential as a rapid, portable tool for brain monitoring. Standardizing acquisition protocols, integrating EEG into longitudinal multimodal studies, and establishing sex- and age-specific normative data are essential for translating these insights into practical applications in concussion management, performance monitoring, and regulatory policy. Full article