Search Results (227)

Temporal lobe epilepsy (TLE) remains pharmacoresistant in 30–40% of patients. Peroxisome proliferator-activated receptor alpha (PPARα) agonists like fenofibrate exhibit anti-inflammatory and neuroprotective properties, but their region-specific effects during epileptogenesis and on behavioral comorbidities are unknown. We investigated fenofibrate (100 mg/kg, 7 days) in the lithium-pilocarpine rat model during the latent phase. Fenofibrate (1) reduced anxiety-like behaviors and improved exploratory deficits; (2) decreased plasma short-chain fatty acids (butyric, pentanoic, hexanoic acids); (3) exerted region-specific modulation of glutamate receptors: restored N-methyl-D-aspartate receptor (NMDAR)/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit gene expression in temporal cortex but failed to reverse and further exacerbated the downregulation of AMPAR subunits in the dorsal hippocampus; (4) prevented the upregulation of cortical neuroinflammation markers (reduced Nlrp3, Il1rn); and (5) enhanced the A2 astrocyte marker Ptx3 in the hippocampus while reducing the M2 microglial marker Arg1 in the temporal cortex. No effects on astrogliosis (Gfap), microgliosis (Aif1), or trophic factors (Bdnf, Tgfb1) were observed. This first comprehensive study demonstrates that fenofibrate differentially modulates neuroinflammation and synaptic plasticity across brain regions during epileptogenesis, providing behavioral benefits but highlighting potential hippocampal drawbacks. Its PPARα-mediated actions support further investigation as a complementary strategy for TLE, pending optimization of dosing/timing to mitigate regional disparities. Full article

Occupational burnout is ubiquitous yet still debated as a disease entity. Previous reviews surveyed multiple biomarkers but left their neural substrate unclear. We therefore asked: What, if any, reproducible magnetic-resonance signature characterises burnout? Following PRISMA principles adapted for mechanistic synthesis, two reviewers searched PubMed, Scopus, Google Scholar, ResearchGate and Cochrane from January 2000 to May 2025 using “MRI/fMRI” AND “burnout”. After duplicate removal and multi-stage screening, 17 clinical studies met predefined inclusion criteria (English language, MRI outcomes, validated burnout diagnosis). In total, ≈1365 participants were scanned, 880 with clinically significant burnout and 470 controls. Uniform Maslach Burnout Inventory thresholds defined cases; most studies matched age and sex, and all excluded primary neurological disease. Structural morphometry (8/17 studies) revealed consistent amygdala enlargement—predominantly in women—and grey-matter loss in dorsolateral/ventromedial prefrontal cortex and striatal caudate–putamen, while hippocampal volume remained unaffected, distinguishing burnout from PTSD or depression. Resting-state and task fMRI (9/17 studies) showed fronto-cortical hyper-activation, weakened amygdala–ACC coupling, and progressive fragmentation of rich-club networks, collectively indicating compensatory executive overdrive and global inefficiency. Two longitudinal cohorts and several intervention sub-studies demonstrated partial reversal of cortical thinning and limbic hyper-reactivity after mindfulness, exercise, cognitive-behavioural therapy, neurofeedback, or rTMS, underscoring plasticity. Across heterogeneous paradigms and populations, MRI converges on a coherent, sex-modulated but reversible brain-networkopathy that satisfies objective disease criteria. These findings justify early neuro-imaging-based triage, circuit-targeted therapy, and formal nosological recognition of burnout as a mental disorder, with policy ramifications for occupational health and insurance parity. Full article

Long-term physical training is known to induce brain plasticity, yet how these neural adaptations evolve across different stages of training remains underexplored. This two-year longitudinal study investigated the stage-dependent effects of endurance running on brain structure and resting-state function in healthy college students. Thirty participants were recruited into three groups based on their endurance training level: high-level runners, moderate-level runners, and sedentary controls. All participants underwent baseline and two-year follow-up MRI scans, including T1-weighted structural imaging and resting-state fMRI. The results revealed that the high-level runners exhibited a significant increase in degree centrality (DC) in the left dorsolateral prefrontal cortex (DLPFC). In the moderate-level group, more widespread changes were observed, including increased gray matter volume (GMV) in bilateral prefrontal cortices, medial frontal regions, the right insula, the right putamen, and the right temporo-parieto-occipital junction, along with decreased GMV in the posterior cerebellum. Additionally, DC decreased in the left thalamus and increased in the right temporal lobe and bilateral DLPFC; the fractional amplitude of low-frequency fluctuations (fALFF) in the right precentral gyrus was also elevated. These brain regions are involved in executive control, sensorimotor integration, and motor coordination, which may suggest potential functional implications for cognitive and motor performance; however, such interpretations should be viewed cautiously given the modest sample size and study duration. No significant changes were found in the control group. These findings demonstrate that long-term endurance training induces distinct patterns of brain plasticity at different training stages, with more prominent and widespread changes occurring during earlier phases of training. Full article

Polyetheretherketone (PEEK) is a semi-crystalline thermoplastic polymer which, due to its very high mechanical properties and high chemical resistance, has found application in the automotive, aerospace, chemical, food and medical (biomedical engineering) industries. Owing to the use of additive technologies, particularly the Fused Filament Fabrication (FFF) method, this material is the most widely used plastic to produce skull reconstruction implants, parts of dental implants and orthopedic implants, including spinal, knee and hip implants. PEEK enables the creation of personalized implants, which not only have greater elasticity compared to implants made of metal alloys but also resemble the physical properties of the cortical layer of human bone in terms of their mechanical properties. Therefore, the aim of this article is to characterize polyether ether ketone as an alternative material used in the manufacturing of implants in orthopedics and dentistry. 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

Transcranial direct current stimulation (tDCS) can modulate cortical excitability in a polarity-specific manner, yet identical protocols often produce inconsistent outcomes across sessions or individuals. This narrative review proposes that much of this variability arises from the brain’s intrinsic temporal landscape. Integrating evidence from chronobiology, sleep research, and non-invasive brain stimulation, we argue that tDCS produces reliable, polarity-specific after-effects only within a circadian–homeostatic “window of efficacy”. On the circadian (Process C) axis, intrinsic alertness, membrane depolarisation, and glutamatergic gain rise in the late biological morning and early evening, whereas pre-dawn phases are marked by reduced excitability and heightened inhibition. On the homeostatic (Process S) axis, consolidated sleep renormalises synaptic weights, widening the capacity for further potentiation, whereas prolonged wakefulness saturates plasticity and can even reverse the usual anodal/cathodal polarity rules. Human stimulation studies mirror this two-process fingerprint: sleep deprivation abolishes anodal long-term-potentiation-like effects and converts cathodal inhibition into facilitation, while stimulating at each participant’s chronotype-aligned (phase-aligned) peak time amplifies and prolongs after-effects even under equal sleep pressure. From these observations we derive practical recommendations: (i) schedule excitatory tDCS after restorative sleep and near the individual wake-maintenance zone; (ii) avoid sessions at high sleep pressure or circadian troughs; (iii) log melatonin phase, chronotype, recent sleep and, where feasible, core temperature; and (iv) consider mild pre-heating or time-restricted feeding as physiological primers. By viewing Borbély’s two-process model and allied metabolic clocks as adjustable knobs for plasticity engineering, this review provides a conceptual scaffold for personalised, time-sensitive tDCS protocols that could improve reproducibility in research and therapeutic gain in the clinic. Full article

Background/Objectives: Neuroimaging techniques have been increasingly utilized to explore neuroplasticity induced by various training regimens. Magnetic resonance imaging (MRI) enables to study these changes non-invasively. While visual and motor training have been widely studied, less is known about how auditory training affects brain activity. Our objective was to investigate the effects of sound localization training on brain activity and identify brain regions exhibiting significant changes in activation pre- and post-training to understand how sound localization training induces plasticity in the brain. Method: Six blindfolded participants each underwent 30-minute sound localization training sessions twice a week for three weeks. All participants completed functional MRI (fMRI) testing before and after the training. Results: fMRI scans revealed that sound localization training led to increased activation in several cortical areas, including the superior frontal gyrus, superior temporal gyrus, middle temporal gyrus, parietal lobule, precentral gyrus, and postcentral gyrus. These regions are associated with cognitive processes such as auditory processing, spatial working memory, planning, decision-making, error detection, and motor control. Conversely, a decrease in activation was observed in the left middle temporal gyrus, a region linked to language comprehension and semantic memory. Conclusions: These findings suggest that sound localization training enhances neural activity in areas involved in higher-order cognitive functions, spatial attention, and motor execution, while potentially reducing reliance on regions involved in basic sensory processing. This study provides evidence of training-induced neuroplasticity, highlighting the brain’s capacity to adapt through targeted auditory training intervention. Full article

Although some GABA_A receptor subtypes are involved in both the passive permeability of anions and the ATP-dependent recovery of neuronal anion concentrations, the molecular mechanisms that ensure the coordination of passive and active transport processes remain unclear. Here we used fluorescence measurements to investigate the role of genistein (tyrosine kinase inhibitor) and vanadate (tyrosine phosphatase and ATPase inhibitor) in modulating GABA_AR-mediated [Cl⁻]_i/[HCO₃⁻]_i changes and ATPase activity in rat cortical neurons and HEK 293FT cells expressing the heteropentameric α2β3γ2 GABA_AR isoform. We found that genistein plays an important role in the inhibition of passive GABA_AR-mediated Cl⁻ influx and Cl⁻ATPase activity, whereas vanadate plays an important role in the inhibition of Cl⁻, HCO₃⁻ATPase activity and ATP-dependent recovery of [HCO₃⁻]_i via changes in the formation of the phosphorylated intermediate. The effect of blockers was significantly restored in the presence of phenol. In behavioral experiments, the administration of phenol has been established to induce tremors and head twitching in rats, with the involvement of GABA_AR/ATPase in these behavioral responses. Genistein can reduce the adverse effects of phenol, thereby confirming the interaction of these chemicals when binding to binding receptor sites. While our data demonstrate the opposing roles of genistein and vanadate in modulating GABA_AR/ATPase function in a bicarbonate-dependent manner. Such multidirectional systems are considered to be bistable elements involved in the regulatory mechanisms of synaptic plasticity. Full article

Bisphenol AF (BPAF) is widely utilized as an analog of bisphenol A (BPA) in the plastics industry. However, there is limited evidence on its neurodevelopmental toxicity. Existing studies suggest that BPAF has greater accumulation in vivo than other bisphenol analogs, and could pass through the placental barrier and the blood–brain barrier. In this study, we used the human neural progenitor cells line ReNcell CX, which was derived from 14-week human cortical brain tissue, as an in vitro model to investigate the neurodevelopmental toxicity effects of BPAF and BPA on ReNcell CX cells, and explored the possible mechanism by which BPAF induced neurodevelopmental toxicity on ReNcell CX cells. The results showed that BPAF reduced the proliferation of neural progenitor cells and changed the differentiation towards neurons after exposure for 24 h. Compared with BPA, ReNcell CX cells are more susceptible to BPAF exposure. In a 3D neurospheres model, BPAF affected the distance that neurons migrated outwards at the concentration of 2 μM. Furthermore, BPAF increased ROS levels in cells and reduced the expression of key proteins in the Nrf2/HO-1 pathway and its downstream molecules, such as SOD, GSH, and CAT. In conclusion, BPAF induces damage to critical nodes in neural progenitor cell development through the Nrf2/HO-1 pathway. Therefore, clarifying its neurodevelopmental toxicity and elaborating on the neurodevelopmental toxicity effects and mechanisms of bisphenol AF will help identify intervention targets for neurodevelopmental toxicity, and will have important public health significance for the safety assessment and risk prediction of bisphenol-related chemicals. Full article

Bisphenol A diglycidyl ether (BADGE) is the main component of epoxy resin and is used for the inner coating of canned foods and plastic food containers. BADGE can easily migrate from containers and result in food contamination; the compound is known as an endocrine-disrupting chemical. We previously reported that maternal exposure to bisphenol A bis (2,3-dihydroxypropyl) ether (BADGE·2H₂O), which is the most detected BADGE derivative not only in canned foods but also in human specimens, during gestation and lactation, could accelerate neuronal differentiation in the cortex of fetuses and induce anxiety-like behavior in juvenile mice. In this study, we investigated the effects of low-dose BADGE·2H₂O (1–100 pM) treatment on neurites and the mechanism of neurite outgrowth in cortical neurons. BADGE·2H₂O exposure significantly increased the number of dendrites and neurite length in cortical neurons; these accelerating effects were inhibited by estrogen receptor (ER) antagonist ICI 182,780 and G-protein-coupled estrogen receptor (GPER) antagonist G15. BADGE·2H₂O down-regulated Hes1 expression, which is a transcriptional repressor, and increased levels of neuritogenic factor neurogenin-3 (Ngn3) in the cortical neurons; the changes were significantly blocked by G15. These data suggest that direct BADGE·2H₂O exposure can accelerate neuritogenesis and outgrowth in cortical neurons through down-regulation of Hes1 and by increasing Ngn3 levels through ERs, particularly GPER. Full article

The flight feather rachis is a lightweight, anisotropic structure that must withstand asymmetric aerodynamic loads generated during flapping flight—particularly under unidirectional compression during the wing downstroke. To accommodate this spatiotemporal loading regime, the rachis exhibits refined internal organization, especially along the dorsoventral axis. In this study, we used finite element modeling (FEM) to investigate how dorsoventral polarization in cortical keratin allocation modulates the mechanical performance of shaft-like structures under bending. All models were constructed with conserved second moments of area and identical material properties to isolate the effects of spatial material placement. We found that dorsal-biased reinforcement delays yield onset, enhances strain dispersion, and promotes elastic recovery, while ventral polarization leads to premature strain localization and plastic deformation. These outcomes align with the dorsally thickened rachises observed in flight-specialized birds and reflect their adaptation to asymmetric aerodynamic forces. In addition, we conducted a conceptual exploration of radial (cortex–medulla) redistribution, suggesting that even inner–outer asymmetry may contribute to directional stiffness tuning. Together, our findings highlight how the flight feather rachis integrates cortical material asymmetry to meet directional mechanical demands, offering a symmetry-informed framework for understanding biological shaft performance. Full article

Multisensory integration is fundamental for coherent perception and interaction with the environment. While cortical mechanisms of multisensory convergence are well studied, emerging evidence implicates specialized retinal ganglion cells—particularly melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs)—in crossmodal processing. This review explores how hierarchical brain networks (e.g., superior colliculus, parietal cortex) and ipRGCs jointly shape perception and behavior, focusing on their convergence in multisensory plasticity. We highlight ipRGCs as gatekeepers of environmental light cues. Their anatomical projections to multisensory areas like the superior colliculus are well established, although direct evidence for their role in human audiovisual integration remains limited. Through melanopsin signaling and subcortical projections, they may modulate downstream multisensory processing, potentially enhancing the salience of crossmodal inputs. A key theme is the spatiotemporal synergy between melanopsin and melatonin: melanopsin encodes light, while melatonin fine-tunes ipRGC activity and synaptic plasticity, potentially creating time-sensitive rehabilitation windows. However, direct evidence linking ipRGCs to audiovisual rehabilitation remains limited, with their role primarily inferred from anatomical and functional studies. Future implementations should prioritize quantitative optical metrics (e.g., melanopic irradiance, spectral composition) to standardize light-based interventions and enhance reproducibility. Nonetheless, we propose a translational framework combining multisensory stimuli (e.g., audiovisual cues) with circadian-timed melatonin to enhance recovery in visual disorders like hemianopia and spatial neglect. By bridging retinal biology with systems neuroscience, this review redefines the retina’s role in multisensory processing and offers novel, mechanistically grounded strategies for neurorehabilitation. Full article

Background: Bilateral movement training (BMT) and interlimb coupling have emerged as promising neurophysiologically-based rehabilitation approaches for stroke survivors. However, the underlying mechanisms and optimal implementation strategies remain incompletely understood. This systematic review explored the neurophysiological principles underlying BMT and interlimb coupling interventions that led to positive clinical post-stroke rehabilitation outcomes, focusing on identifying the most effective bilateral and interlimb movement strategies. Methods: A 10-year literature search (2014–2024) following PRISMA guidelines was conducted across PubMed, Cochrane, and Google Scholar databases using keywords including stroke rehabilitation, bilateral movement training, cross-education, interlimb coupling, and interlimb transfer. Studies were included if they involved human subjects, clinical trials, stroke survivors, and described bilateral training protocols. Data extraction focused on neurophysiological mechanisms, intervention characteristics, and clinical outcomes. Quality assessment was performed using validated methodological appraisal tools, including the Newcastle-Ottawa Scale and Cochrane RoB 2.0. Results: Of 199 initially identified studies, 28 met inclusion criteria for detailed analysis. BMT demonstrated effectiveness in enhancing motor recovery by engaging neurophysiological mechanisms, including central pattern generators, interhemispheric coupling, and cortical disinhibition. High-intensity BMT provided significant gains for individuals with moderate to severe impairments, while low-intensity training benefited early recovery stages. Interventions incorporating task-specific exercises, robotic assistance, sensory enhancement, and virtual reality showed particular promise for addressing motor recovery complexities. However, significant research gaps were identified, including limited understanding of individualized responses to BMT, insufficient research on combined upper and lower limb training, and minimal integration of advanced technologies. Conclusions: BMT and interlimb coupling play critical roles in post-stroke rehabilitation by facilitating neural plasticity and interlimb coordination. Integrating robotic assistance, sensory enhancement, and virtual reality with BMT offers a robust framework for maximizing rehabilitation outcomes. Future research should prioritize longitudinal studies, personalized rehabilitation approaches, technology integration, and stratified interventions tailored to individual needs to optimize neuroplasticity and enhance quality of life for stroke survivors. Full article

Background/Objectives: Transcranial magnetic stimulation (TMS) is a non-invasive and well-tolerated treatment, offering an effective alternative for elderly patients with depression, especially when side effects or comorbidities limit medication. Methods: This scoping review analyzes 16 studies published over the past seven years, to evaluate the efficacy, safety, and clinical applications of TMS in older adults with depression. Results: The review examines various TMS modalities, including repetitive TMS (rTMS), deep TMS, and theta burst stimulation (TBS), with most protocols targeting the dorsolateral prefrontal cortex (DLPFC). Adverse effects were rare, mild, and transient, supporting the treatment’s safety profile. Pharmacological co-treatment was common but not essential for clinical improvement, highlighting TMS’s potential as a standalone therapy. A subset of studies used neuroplasticity (SICI, ICF, CSP) or neuroimaging measures (MRI and MRI-based neuronavigation), revealing that age-related cortical inhibition may limit plasticity rather than depression itself. Conclusions: Overall, TMS demonstrates promising effectiveness and tolerability in managing late-life depression. Across studies, remission rates varied from 20% to 63%, with higher efficacy generally observed in bilateral stimulation or high-frequency protocols. Standardization of protocols and further research into individualized targeting and long-term outcomes are warranted to support broader clinical adoption. Full article