Pathological gambling is a complex disorder characterised by a loss of control and the persistence of behaviour despite its negative consequences. It is frequently associated with executive deficits in cognitive flexibility, inhibition, and decision-making, which contribute to the maintenance of gambling behaviour and reduce adaptive capacities. A total of 120 participants aged between 16 and 80 years, all meeting the criteria for pathological gambling, were divided into three groups: adolescents, young adults, and older adults. Executive functions were assessed using the Wisconsin Card Sorting Test (WCST), the GoStop (Stop-Signal Task), and the Iowa Gambling Task (IGT). A one-way ANOVA revealed significant effects on cognitive flexibility (WCST) and inhibition (GoStop) but not on decision-making (IGT). Post hoc Tukey tests showed that older adults made more perseverative errors and completed fewer categories on the WCST than adolescents, while young adults occupied an intermediate position without significant differences. In the GoStop task, older adults exhibited poorer inhibitory control than adolescents. On the IGT, no significant group differences were found, although a trend towards lower scores was observed in older adults. Correlation analyses indicated that perseverative errors on the WCST were strongly and negatively associated with the number of categories completed and weakly related to the GoStop and IGT scores. These findings confirm the presence of executive deficits in pathological gamblers, emerging in young adulthood and worsening with age. They highlight the need for tailored interventions focusing on impulsivity management in younger adults and improving cognitive flexibility and inhibition in older individuals.

Introduction Phytochemicals, particularly those from Salvia species, exhibit notable neuroprotective effects by modulating neurotransmission and limiting excitotoxic damage. Since excessive glutamate release and overactivation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors contribute to neuronal injury, targeting these receptors presents a promising molecular approach. This study investigates the modulatory effects of Salvia palaestina essential oil on AMPA receptor subunits to elucidate its potential role in regulating excitatory synaptic signaling.

Methods Human embryonic kidney 293T cells were transiently transfected with the DNA of four AMPA receptor subunits (GluA1, GluA2, GluA1/2, and GluA2/3) using jetPRIME. Enhanced green fluorescent protein aided expression tracking. After 36 hours, fluorescence-sorted cells were plated for whole-cell patch-clamp recordings. Currents were evoked by 10 mM glutamate with or without Salvia palaestina essential oil, and whole-cell current responses along with deactivation and desensitization kinetics were analyzed using SutterPatch and Igor Pro7 software.

Results Whole-cell recordings revealed that Salvia palaestina essential oil markedly inhibited AMPA receptor activity across all tested subunits. Current amplitudes were reduced approximately 5-fold in GluA1, GluA1/2, and GluA2/3 and 6-fold in GluA2. The oil also altered receptor kinetics, increasing deactivation rates nearly 3-fold in all subunits while slowing desensitization 4-fold in GluA2, 3-fold in GluA2/3, 2.2-fold in GluA1, and 1.4-fold in GluA1/2, indicating strong modulatory effects on receptor function.

Conclusions Salvia palaestina essential oil strongly modulates AMPA receptor function by reducing whole-cell currents and altering deactivation and desensitization kinetics. These effects suggest anti-excitotoxic potential, likely mediated by major constituents such as carvacrol, eucalyptol, and thujones, supporting its role in regulating glutamatergic transmission and synaptic activity at the molecular level.

Cognitive impairment is a defining feature of Alzheimer’s disease (AD), a progressive neurodegenerative disorder characterized by deficits in memory, learning, and recognition. Developing natural compounds that can support or restore cognitive function is of critical importance in neuroscience research. Paradol, a bioactive compound derived from plants, exhibits potential neuroprotective properties that may influence cognitive performance. In this study, we investigated the effects of Paradol on cognitive function in adult zebrafish subjected to an Alzheimer-like model induced by okadaic acid (10 nM for 4 days). Zebrafish were randomly assigned to six experimental groups (n = 10 per group): control (dimethyl sulfoxide), galantamine (1 mg/L), okadaic acid alone, and okadaic acid with Paradol at 1, 3, or 6 µg/L. Paradol was administered via immersion every three days for seven days. Cognitive assessment focused specifically on processes relevant to Cognitive Neuroscience, including spatial memory measured with the Y-maze task and recognition memory evaluated with the Novel Object Recognition (NOR) test. Statistical analysis using one-way ANOVA with Tukey’s post hoc test (p < 0.05) revealed that okadaic acid significantly impaired both spatial and recognition memory. Treatment with Paradol at 3 and 6 µg/L significantly enhanced cognitive performance, increasing exploration of the novel arm in the Y-maze and preference for the novel object in NOR. These findings highlight the potential of Paradol to improve key cognitive processes in a preclinical model of AD, providing insights into memory restoration mechanisms and offering a promising avenue for future research in Cognitive Neuroscience.

The dynamic communication between neurons and glial cells forms the molecular foundation of brain homeostasis, synaptic maintenance, and resilience to injury. Disturbances in this neuron–glia dialogue underlie many neurodegenerative disorders, where oxidative stress, mitochondrial dysfunction, and neuroinflammation converge to promote neuronal loss. The present study investigates the cellular and molecular mechanisms governing neuron–glia crosstalk under oxidative challenge, focusing on Nrf2-mediated antioxidant signaling, mitochondrial dynamics, and synaptic restoration.

Primary cortical neuron–astrocyte co-cultures were subjected to controlled oxidative stress using hydrogen peroxide (H₂O₂, 100 µM) for 24 hours, followed by treatment with Nrf2 activators (sulforaphane and curcumin). Cellular responses were assessed through RT-qPCR, Western blotting, confocal immunofluorescence, and targeted proteomic analysis. Oxidative insult significantly reduced neuronal viability (by 43%), disrupted mitochondrial membrane potential, and decreased expression of synaptic proteins (PSD-95, synaptophysin). Post-treatment, a robust activation of the Nrf2–ARE pathway was observed, with a 3–5-fold increase in antioxidant gene expression (HO-1, NQO1, and SOD2) and partial recovery of synaptic protein levels. Astrocyte-conditioned media from treated cultures enhanced neuronal survival by upregulating glutamate transporters (EAAT1/2) and reducing lipid peroxidation markers (MDA, 42% reduction). Furthermore, transmission electron microscopy revealed restoration of mitochondrial integrity and reduction in reactive astrocytosis.

These findings demonstrate that activation of Nrf2 signaling and glial antioxidant responses confer significant neuroprotection against oxidative damage. The study emphasizes the crucial role of astrocytes as metabolic and redox regulators, capable of restoring neuronal function and synaptic plasticity. Targeting the neuron–glia metabolic axis thus represents a promising therapeutic approach to mitigate oxidative neurotoxicity and promote neuroregeneration in disorders such as Alzheimer’s disease, Parkinson’s disease, and cerebral ischemia.

Introduction: TBI is a major global public health issue, and its secondary injury involves multiple pathological processes. In recent years, ferroptosis has attracted increasing attention for its role in TBI. This study aims to systematically analyze the spatiotemporal regulatory mechanism of GPX4 in TBI using single-cell sequencing and spatial transcriptome sequencing technologies.

Methods: Sequencing was performed using the 10×Genomics and Visium platforms. The data were integrated, and the expression of GPX4 was analyzed in combination with ferroptosis-related databases. At the cellular level: Primary neurons were cultured; GPX4 expression was regulated using siRNA and lentivirus; ferroptosis was induced by Erastin or RSL3; and cell viability and ferroptosis markers were detected. At the animal level: AAV was injected via stereotaxis to regulate GPX4 in the injured area, followed by behavioral evaluations and histological analyses. Co-IP was used to explore the molecular interaction mechanism of GPX4.

Results: Single-cell sequencing identified dynamic changes in cell subsets after TBI, and differential expression of ferroptosis-related genes was observed in all subsets. Spatial transcriptome sequencing revealed the specific distribution of these genes in the injured area. Integrated analysis showed that GPX4 expression changed significantly in the injured area, with obvious spatiotemporal specificity in neurons. Cellular experiments confirmed that GPX4 silencing exacerbated damage caused by ferroptosis inducers and increased lipid peroxidation levels, while GPX4 overexpression alleviated ferroptosis. Animal experiments indicated that regulating GPX4 significantly affected the recovery of neurological function and cognitive ability in TBI mice.

Conclusion: This study is the first to integrate the two sequencing technologies, revealing the spatiotemporal regulatory pattern of GPX4 in TBI and its cell-specific role. It confirms that GPX4 plays an important role in TBI-induced secondary injury, affects ferroptosis by regulating iron metabolism, and provides a new approach for TBI treatment—with significant theoretical and clinical value.

Synaptic plasticity forms the cellular foundation of learning and memory, yet its regulation under neuroinflammatory conditions remains incompletely understood. Growing evidence suggests that immune-derived cytokines dynamically influence neuronal structure and function through bidirectional communication between glial and neuronal networks.

In this study, we sought to elucidate the molecular architecture of glia–neuron crosstalk that shapes synaptic remodeling during inflammation. Using human cortical organoids and murine hippocampal slice cultures, we induced controlled inflammatory states via interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) exposure. We employed single-cell RNA sequencing, quantitative proteomics, and super-resolution imaging to map cell-type-specific transcriptional and structural responses. Gene-regulatory network reconstruction identified a cascade centered on NF-κB, complement C3, and PGC-1α, linking immune activation to metabolic reprogramming and synaptic pruning.

Functional validation using CRISPR interference and pharmacological inhibition confirmed that NF-κB blockade restored dendritic spine density, enhanced long-term potentiation (LTP), and rescued mitochondrial integrity. Conversely, astrocytic overexpression of C3 exacerbated synaptic loss, demonstrating a direct glial contribution to excitatory circuit instability. Mitochondrial respiration assays further revealed that inflammatory signaling suppresses oxidative phosphorylation while increasing glycolytic flux, coupling energy dysregulation with synaptic impairment.

Collectively, these data delineate a multi-layered signaling network whereby neuroinflammation modulates synaptic plasticity through transcriptional, metabolic, and structural mechanisms. Targeting the NF-κB–PGC-1α axis and glial complement pathways may therefore offer new strategies to restore circuit homeostasis in neurodegenerative and psychiatric disorders.

Introduction: Recurrent stroke contributes to the high global burden of this disease. Low- and middle-income countries (e.g., Brazil) are disproportionately affected by stroke and have limited access to secondary prevention. A theoretically informed intervention for risk reduction post-stroke (“iHELP Stroke: Improving Health and Lifestyle Programme”) was recently co-designed in a high-income country (Ireland). Before implementation in Brazil, adaptations were required due to cultural, social, and economic differences. This study aims to describe the adaptation of the “iHELP Stroke” to the Brazilian context and assess its feasibility among Brazilians with stroke.

Methods: A mixed-methods study was conducted following ADAPT guidance. Phase I included two stakeholder panels (15 experts and 10 stroke survivors) to adapt the intervention for adequate reach, effectiveness, cost-effectiveness, adoption, implementation, and sustainability. Phase II involved a feasibility study with 10 Brazilian individuals post-stroke, evaluating recruitment, retention, attendance, acceptability and satisfaction, and clinical outcomes (achievement of behavior change goals). Descriptive statistics were applied.

Results: Phase I identified 11 contextual themes, leading to adaptations including translation into Brazilian Portuguese, renaming as “iVIDAVC: intervenção para melhorar a saúde e o estilo de vida pós-AVC”, and the addition of an educational session. Phase II showed a recruitment rate of 13.7%, high retention (80%) and attendance (88.9%), strong acceptability and satisfaction, and complete achievement of primary goals by half of participants. Adjustments are needed: sessions with guest professionals exceeded planned duration, one participant found the eight-week programme too short, and one group session included only one participant.

Conclusions: The “iHELP Stroke” program was successfully adapted to the Brazilian context, and the resulting “iVIDAVC” program demonstrated feasibility. The next phase (a pilot study), also with an appropriate sample size, should test the full 14-week programme, ensure repeated participation of invited professionals, include at least four participants per group, and refine outcome measures for comprehensive evaluation.

Neurorehabilitation is undergoing a digital transformation, with telerehabilitation emerging as a critical tool for ensuring continuity of care. This systematic review aims to evaluate the efficacy of remote rehabilitation interventions compared to conventional in-clinic therapies in improving motor functions and quality of life for patients with neurological conditions, such as stroke and multiple sclerosis. A systematic search was conducted across PubMed, Scopus, and Web of Science for randomized controlled trials (RCTs) published between 2020 and 2025. The inclusion criteria focused on adult populations undergoing digital or remote neurorehabilitation interventions, utilizing outcomes such as the Fugl-Meyer Assessment (FMA), Berg Balance Scale (BBS), and various Quality of Life (QoL) metrics. Preliminary analysis of the selected studies indicates that telerehabilitation is at least as effective as face-to-face therapy in promoting neuroplasticity and motor recovery. Key findings suggest that digital platforms enhance patient adherence due to the convenience of home-based training. Furthermore, interventions incorporating biofeedback and synchronous monitoring showed significantly higher improvements in functional independence compared to non-monitored home exercises. Telerehabilitation represents a viable and evidence-based alternative to traditional methods, addressing geographical and mobility barriers. However, the heterogeneity of digital platforms and the need for standardized protocols remain challenges. This review highlights the potential of integrating telemedicine into routine clinical practice to optimize functional outcomes and long-term disability management.

Objective: To explore the effectiveness of perineural injection treatment with dextrose (PITD) as a cost-effective and accessible alternative for managing refractory chronic migraine in low- and middle-income countries (LMICs).
Case Report: A single-patient case study was conducted involving a 30-year-old male diagnosed with chronic migraine complicated by medication-overuse headache, based on the International Classification of Headache Disorders, 3rd edition (ICHD-3). The patient had a one-year history of right-sided daily headaches refractory to over-the-counter analgesics and conventional prophylactic therapy.
Comprehensive neurological and physical examinations were performed, followed by diagnostic investigations including electroencephalography (EEG), magnetic resonance imaging (MRI), and transcranial Doppler (TCD), all of which showed no structural or vascular abnormalities.
The therapeutic intervention consisted of biweekly perineural injection treatment with 5% dextrose (PITD), administered bilaterally to the greater and lesser occipital nerves (GON and LON). Each session involved 5 cc of 5% dextrose per side, guided by anatomical landmarks and palpation of tender points.
Concurrent pharmacological management included topiramate (50 mg twice daily) and low-dose amitriptyline (12.5 mg at bedtime). A rescue regimen of paracetamol and oral diazepam was provided for breakthrough attacks. The treatment period lasted three months, with progress assessed using the Numerical Pain Rating Scale (NPRS) at each follow-up visit.
Discussion: The patient reported significant improvement in pain severity, with the Numerical Pain Rating Scale (NPRS) decreasing from 9 to 5 over the three-month treatment period. Sustained relief was achieved by the fifth PITD session, with stabilization of symptoms and no structural abnormalities detected on follow-up MRI.
Conclusions: PITD may offer a viable, low-cost treatment for chronic migraine in resource-constrained settings, addressing both peripheral and central mechanisms of pain. This approach could reduce reliance on expensive treatments and improve patient outcomes in LMICs. Further studies are needed to validate its efficacy and long-term benefits in larger populations.

Introduction:
Although the Ponzo and Müller-Lyer illusions distort line length similarly, they may involve distinct perceptual mechanisms. Both illusions make equal line segments appear unequal, yet prior studies classify them into different categories of visual processing (Gregory, 2009; Coren et al., 1978). Evidence suggests that the N200 component reflects intermediate visual processing, bridging low- and high-level stages of perception (Yang & Sui, 2022). Eye movement studies indicate that the Müller-Lyer illusion distorts saccadic trajectories (Chen et al., 2020), whereas in the Ponzo illusion, fixations tend to be longer on the upper segment than the lower one (Yildiz et al., 2019). This study compared the psychophysiological correlates of Ponzo and Müller-Lyer illusions by analyzing electrophysiological and oculomotor activity during the perception of equal central line segments.

Methods:
Forty participants (aged 18–45, M = 24.7) underwent synchronous EEG (64-channel BrainVision ActiChamp) and eye-tracking (EyeLink 1000). Stimuli included equal and unequal line segments in three conditions: control, Ponzo, and Müller-Lyer. ERPs (N200 270–320 ms), fixation and saccade durations, and response accuracy were analyzed using a repeated-measures ANOVA and the Friedman test.

Results:
The accuracy of the responses was significantly higher in the control condition than in both illusion conditions (p < 0.0001). N2 amplitudes (F1, F3, FC1, FC3) were higher for Ponzo than for Müller-Lyer (p < 0.0001), and in FC3, the control exceeded the Müller-Lyer group (p < 0.05). Fixation durations differed between the control and Müller-Lyer (p = 0.0097) groups and the Ponzo (p < 0.0001) group, while saccades were shorter in the Ponzo group. Eye movement heat maps revealed distinct viewing patterns across conditions.

Conclusions:
It was found that Ponzo and Müller-Lyer illusions engage partially distinct visual mechanisms. Behavioral differences were minimal, suggesting compensatory higher-level cognitive processing. Oculomotor and electrophysiological data together provide a nuanced understanding of the intermediate stages of geometric illusion perception.