NeuroSci

Cognitive impairment is a prevalent and disabling feature of multiple sclerosis (MS), significantly impacting patients’ quality of life (QoL) and psychological well-being. Despite its clinical relevance, there are currently no approved pharmacological treatments for cognitive deficits in MS, highlighting the need for effective non-pharmacological interventions. This narrative review explores evidence from studies evaluating the efficacy of cognitive re-education (CR) approaches (including traditional, group-based, computer-assisted, virtual reality, and innovative methods such as music therapy) on cognitive and QoL outcomes in people with MS. The findings demonstrate that while CR consistently influences cognitive domains such as memory, attention, and executive function, its effects on QoL are more variable and often depend on intervention type, duration, and individual patient characteristics. Notably, integrative approaches like virtual reality and music therapy show promising results in enhancing both cognitive performance and psychosocial well-being. Several studies report that cognitive gains are accompanied by improvements in mental health and functional QoL, particularly when interventions are tailored to individual needs and delivered within multidisciplinary frameworks. However, some interventions yield only limited or transient QoL benefits, underlining the importance of personalized, goal-oriented strategies that address both cognitive and psychosocial dimensions. Further research is needed to optimize intervention strategies and clarify the mechanisms linking cognitive and QoL outcomes. Full article

Background: Combined cognitive and exercise training improves exercise endurance, including submaximal muscular endurance. Its effects on maximal muscular strength have yet to be determined. Accordingly, we tested the effects of combined training on muscular strength (one repetition maximum, 1RM) and endurance (as many repetitions as possible, AMRAP). Methods: Resistance-trained adults (five males, three females) completed ten sessions (four testing, six training) over 4 weeks. In each testing session, they were assessed for bench press 1RM before they completed AMRAP at 50% of initial 1RM. In each training session, they performed five bench press sets (five repetitions at 80% current 1RM), with each set followed by a hard 5 min cognitive task (Time-Load Dual-Back or Color Multi-Source Interference). Ratings of perceived exertion (RPE) were averaged to provide a session RPE. At the end of each session, participants completed a Psychomotor Fatigue Threshold Test and rated mental fatigue. Results: ANOVAs (four testing sessions) showed that combined training increased 1RM (p < 0.001; averaging 8.0 kg or 11% from sessions 1–4) and AMRAP (p < 0.01; 5.1 repetitions or 22%). Moreover, training increased RPE (p < 0.05; 0.3 or 5%) and decreased mental fatigue ratings (p < 0.001; −1.2 or −49%) but did not affect Psychomotor Fatigue Threshold Test reaction times (p > 0.05; 2 ms or 0%). Conclusions: A 4-week training program that combined high-intensity cognitive and resistance exercise tasks improved maximal and submaximal resistance exercise performance. This pilot study provides preliminary evidence that high-intensity combined training can enhance muscular strength and endurance. Full article

Background: Chronic pain is closely associated with dysregulation of the autonomic nervous system, often reflected by reduced heart rate variability (HRV). While observational studies have demonstrated this association, the extent to which pain interventions modulate HRV and the impact of individual factors on HRV changes remain unclear. Objective: To evaluate the impact of pain interventions on HRV parameters through meta-analysis of randomized controlled trials (RCTs), and to examine whether intervention type and individual factors such as body mass index (BMI) moderate HRV responses. Methods: We conducted a systematic review of 23 RCTs and a meta-analysis of 21 RCTs (1262 subjects) involving patients with acute and chronic pain. HRV outcomes were extracted pre- and post-intervention. Both between-group (active vs. sham/control) and one-group (pre-post within active group) analyses were performed for time-domain indices—standard deviation of normal-to-normal intervals (SDNN), root mean square of successive differences (RMSSD), and percentage of successive normal-to-normal intervals > 50 ms (pNN50)—and frequency-domain indices—high-frequency (HF) and low-frequency (LF) components. Meta-regressions tested moderators including BMI, age, and pain phenotype. The protocol was registered in PROSPERO (CRD42023448264). Results: Twenty-three RCTs involving 1262 participants with a wide range of pain conditions were included. Meta-analysis of time-domain HRV parameters showed a trend toward improvement: SDNN (g = 0.435, p = 0.059) approached significance, while RMSSD (g = 0.361, p = 0.099) and pNN50 (g = 0.222, p = 0.548) showed smaller, non-significant effects. Frequency-domain analysis revealed a significant moderate reduction in the LF/HF ratio (g = −0.378, p = 0.003), suggesting a shift toward parasympathetic dominance. HF and LF showed small, non-significant changes. One-group meta-analysis confirmed significant improvements in vagally mediated HRV, with large effects for RMSSD (g = 1.084, p < 0.001) and HF (g = 0.622, p < 0.001), and a moderate effect for SDNN (g = 0.455, p = 0.004). Meta-regression identified BMI as a significant moderator: higher BMI was associated with attenuated improvements in HF and RMSSD and a slight shift toward sympathetic predominance. Conclusions: Pain interventions can significantly modulate autonomic function, as reflected in HRV improvements, particularly in vagally mediated indices. These effects are influenced by patient characteristics such as BMI. HRV may serve as a valuable biomarker for both treatment efficacy and autonomic recovery in pain management. In this context, HRV highlights its role as a biomarker for pain dysregulation and compensatory failure, reflecting shared top-down modulation between nociception and autonomic regulation. Full article

Glutamate and dopamine receptors play a crucial role in regulating synaptic plasticity throughout the sleep–wake cycle. These receptors form various heterocomplexes in synaptic areas; however, the role of this protein interactome in sleep–wake cycles remains unclear. Co-immunoprecipitation experiments were conducted to observe the complexation of the NMDA glutamate receptor (NMDAR) subunits GluN2A and GluN2B, metabotropic glutamate receptors mGluR1/5, and dopamine receptors (D1R and D2R) with the scaffold protein Homer in the synaptic membranes of the hippocampus after six hours of sleep deprivation (SD) in rats. Our findings indicate that the level of Homer in the GluN2A/mGluR1/D1R interactome decreased during SD, while the content of Homer remained unchanged in the GluN2B/mGluR1/D2R heterocomplex. Moreover, Homer immunoprecipitated a reduced amount of inositol trisphosphate receptor (IP3R) in the microsomal and synaptic fractions, confirming the dissociation of the ternary supercomplex Homer/mGluR1/IP3R during SD. Additionally, our findings indicate that SD increases the synaptic content of the AMPA receptor (AMPAR) subunit GluA1. Unlike AMPAR, NMDAR subunits in synaptic membranes do not undergo significant changes. Furthermore, the G-to-F actin ratio decreases during SD. Changes in the assembly of actin filaments occur due to the dephosphorylation of cofilin. These results suggest that SD causes the dissociation of the GluN2A/mGluR1/D1R/Homer/IP3R heterocomplex in synaptic and endoplasmic membranes. 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

Peripheral nerve injury initiates a complex cascade of events coordinating immune responses, extracellular matrix (ECM) remodeling, and neuronal repair. While β2-microglobulin (B2M) is well known for its role in MHC class I-mediated antigen presentation and CD8⁺ T-cell differentiation, its potential contributions to non-immune processes remain underexplored. In this study, we investigated the role of B2M in peripheral nerve regeneration using a chronic constriction injury (CCI) model in wild-type and B2M-deficient (B2M-KO) mice. Flow cytometry, RNA sequencing (RNA-seq), and quantitative PCR (qPCR) were performed to assess T-cell subset dynamics and gene expression following injury. Flow cytometric analysis showed that CD3⁺CD4⁺ and CD3⁺CD8⁺ T-cell populations increased by day 7 post-injury. While CD3⁺CD4⁺ T-cell expansion occurred in both groups, a significant increase in CD3⁺CD8⁺ T cells was observed only in wild-type mice. RNA-seq analysis at 3 days post-injury—prior to substantial T-cell accumulation—revealed marked downregulation of ECM-related genes in B2M-KO mice, including collagens, matrix-associated proteins, and other key ECM components. KEGG analysis identified suppression of ECM–receptor interaction, PI3K-Akt, and TGF-β signaling pathways. qPCR confirmed reduced expression of Thbs1 in B2M-KO mice. These findings suggest that B2M plays a critical, CD8⁺ T-cell-independent role in regulating ECM dynamics and regenerative signaling during early nerve repair, expanding the conceptual framework of B2M’s function beyond classical immune roles. Full article

Background: We aimed to determine the utility of different electrodiagnostic (EDx) methods in diagnosing meralgia paresthetica (MP). Methods: Twenty-nine MP patients and 26 controls were included. Sensory nerve action potential (SNAP) and somatosensory evoked potential (SEP) of the lateral femoral cutaneous nerve (LFCN) and tibial SEPs were measured bilaterally. Results: At least one LFCN SNAP was unobtainable in 18 patients (62%) and two controls (8%). In all remaining 11 patients, SNAPs were abnormal at least unilaterally. By contrast, LFCN SEPs were recorded bilaterally in all subjects and were abnormal in 16 patients (sensitivity 48%). Patients’ tibial SEP latency was significantly larger than that of controls (p < 0.001). Conclusions: LFCN NCSs are superior to SEP in the evaluation of MP. However, SEP studies may be useful in old (>60 years) and obese subjects with unobtainable LFCN SNAP. Longer tibial SEP points to subclinical neuropathy in MP patients predisposed to LFCN entrapment. Full article

At the 14th Panhellenic Conference on Alzheimer’s Disease and 6th Mediterranean Conference on neurodegenerative diseases, we experienced an exciting journey, following the patient through the stages of their neurodegenerative disease: onset, diagnosis, progression, and eventual outcome. Fighting alongside him are researchers, doctors, psychologists, biologists, chemists, pharmacists, nurses, trainers, physiotherapists, speech therapists, occupational therapists, electrical engineers, architects, and other scientists, even actors and musicians, who aim to prevent and cure the disease, limit its progression, and improve the quality of life of those affected by it. Among them, their caregivers stand out as the most dedicated companions. In a collection of abstracts that reflects the work of all of the above, we capture the results of our biennial scientific meeting, which, thanks to them, is constantly evolving in a promising way. 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

Emotional attunement, or emotional co-regulation in a relationship, can manifest as interpersonal neural synchrony, where partners exhibit similar anti-phase or phase-shifted brain activity. In adult romantic relationships, emotional attunement may differ according to relationship satisfaction. No study has examined how relationship satisfaction difference influences interpersonal neural synchrony. This exploratory pilot study on 17 couples (unmarried Chinese undergraduate couples in a Southeast Asian university) investigated whether relationship satisfaction difference influenced interpersonal neural synchrony during a shared emotive experience. Each couple wore an fNIRS cap to measure brain activity in their prefrontal cortex (PFC) while co-viewing seven videos intended to evoke positive, negative or neutral emotions. We found preliminary evidence that relationship satisfaction difference modulated interpersonal neural synchrony in the right ventral PFC regions, including the right ventromedial PFC (involved in the encoding of emotional values to stimuli and emotional regulation), right ventrolateral PFC (involved in voluntary emotional regulation) and the right orbitofrontal cortex (involved in processing of emotional experiences and regulation of emotions). This suggested that couples with mismatched relationship satisfaction displayed greater interpersonal neural synchrony, possibly due to mutual social cognitive processes when viewing emotive videos together. Further studies can replicate the findings with larger, diverse samples. Full article

Background: Disparities in neuro-oncological care between high-income and low- and middle-income countries (LMICs) are well documented, yet region-specific data from Latin America remain limited. This review evaluates epidemiologic trends, access to care, and systemic challenges in brain tumor management across Latin American LMICs, using Argentina as a case study. Methods: A systematic review of peer-reviewed literature was conducted focusing on brain tumor incidence, mortality, risk factors, and availability of diagnostics and treatments in Latin America. Socioeconomic, cultural, and systemic barriers were also analyzed. Results: Latin America exhibits some of the highest global brain tumor mortality rates, with Brazil reporting age-standardized rates exceeding 4.5 per 100,000. Glioblastomas are frequently diagnosed at younger ages, often in the fifth decade of life, compared to the global average. Meningioma incidence has increased by 15–20% over the last decade, yet region-wide data remain fragmented. Access to neuroimaging, neurosurgery, radiotherapy, and chemotherapy is limited, with up to 60% of patients relying solely on under-resourced public health systems. Less than 30% of hospitals in rural areas have MRI availability, and continuous professional training is infrequent. Innovative adaptations, such as awake craniotomy, are used in some LMIC centers in response to equipment scarcity. Conclusions: Brain tumor care in Latin America is hindered by limited epidemiological data, restricted access to diagnostics and treatment, and insufficient workforce training. Targeted investments in healthcare infrastructure, international educational collaborations, and policy-level reforms are critical to reducing disparities and improving outcomes in neuro-oncology across the region. 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

Gliomas are the most common central nervous system tumors and account for 30% of all primary brain tumors, 80% of all malignant ones, and the vast majority of deaths that are caused by brain tumors. Among them, glioblastoma multiforme has the most aggressive and invasive course. Due to its heterogeneity, it is difficult to treat, and one of the reasons for this are glioma stem cells (GSCs). Therapies such as radiotherapy and chemotherapy are used to treat gliomas but do not bring the expected results. Therefore, treatments targeting glioma stem cells are emerging. A promising strategy is to target GSCs with natural compounds. This review aims to describe the problem of glioma stem cells, the treatment of gliomas, and therapies based on natural compounds, which are promising for the future. Full article

In the face of the limitations in pharmacological and surgical interventions for neurological conditions such as Parkinson’s and Alzheimer’s disease, patients are increasingly turning to non-pharmacological and alternative therapies to manage their symptoms and improve their quality of life. This shift underscores the urgent need for accessible, effective, and affordable treatments. This literature review examines a range of alternative and personalized therapies, including game therapy, animal-assisted therapy, dance therapy, art therapy, music therapy, aroma therapy, and shinrin-yoku therapy. These modalities have demonstrated promising results in mitigating symptoms and enhancing well-being among individuals grappling with neurological disorders. Moreover, these therapies offer a holistic approach that complements traditional medical interventions, underscoring the importance of integrating diverse treatment modalities. Despite their historical roots in non-clinical settings, their potential in modern clinical practice remains untapped. The findings suggest the necessity for further research, particularly large cohort studies, to validate the efficacy of these personalized therapies and advocate for their widespread adoption. In an era marked by escalating healthcare costs, the exploration of alternative therapies presents a compelling avenue for enhancing patient care while simultaneously addressing economic challenges within the healthcare system. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, heterogeneous at the molecular level and characterized by diverse and complex pathological features. Such features are known to accumulate silently in the brain over years or even decades before the onset of detectable symptoms. Despite long years of intense research activities, the disease remains orphaned of either disease-modifying therapies or a specific blood test capable of predicting the disease in the pre-symptomatic stages. This disappointing outcome of such efforts can be attributed to a number of factors. One of these factors is the failure of earlier research to capture the heterogeneity of the disease. Such failure has the direct consequence of poor patient stratification, which in turn impacts negatively on the development of specific and effective therapy. The second factor is the absence of detailed and accurate information on proteins and associated post-translational modifications, which may influence the initiation and progress of the disease. Recent studies have demonstrated that the quantification of various isoforms of phosphorylated tau protein in plasma and other biofluids can be considered as potential biomarkers for the early detection of Alzheimer’s disease. Mass spectrometry-based proteomics and immunoassay-based multiplex proteomics are the two technologies in current use for probing the human proteome, both in tissues and biofluids. In the present review, we discuss the contribution of MS-based proteomics to efforts aimed at the identification and eventual characterization of the heterogeneity of the disease, and the key role of the same technique in the analysis of protein post-translational modifications associated with the disease is also discussed. Full article

Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms of fibroblastic origin. In this study, we report a rare case of cervical SFT in a pediatric patient, a rare phenomenon since the incidence is particularly rare in pediatric patients according to the literature. Typical radiological features of the lesion may lead to misdiagnosis. Image study and immunohistochemistry are crucial for its correct diagnosis. Their imaging characteristics often resemble meningiomas or schwannomas, making differential diagnosis challenging. Immunohistochemical markers such as CD34 and STAT6 remain essential for definitive diagnosis. Full article

Insomnia is common in individuals with opioid use disorder (OUD). Biopsychosocial factors are important in sleep health, yet this intersection has yet to be fully elucidated in people on buprenorphine for OUD. The objective is to report on patient-reported biopsychosocial factors among people with and without insomnia, specifically among women and men in outpatient OUD treatment. The parent study enrolled adults stabilized on buprenorphine from February 2022–September 2023. Scores of ≥11 on the Insomnia Severity Index (ISI) indicated clinically significant insomnia. Differences were detected by the presence of insomnia, stratified by men and women, using chi-squared and Fisher’s exact tests. Of the overall participants (N = 130), most (n = 77; 59.2%) met the criteria for clinically significant insomnia. Women with insomnia were more likely to report social stressors including discrimination for substance use (p = 0.040), food insecurity (p = 0.032), and transportation difficulties accessing healthcare (p = 0.043) than women without insomnia. Men with insomnia were more likely to report financial difficulties accessing healthcare (p = 0.023) than men without insomnia. These findings provide a unique perspective to consider in the development and implementation of sleep interventions for women and men receiving medication treatment for OUD. Full article

SH-SY5Y neuroblastoma cells can be effectively differentiated into a neuronal phenotype using retinoic acid (RA) and brain-derived neurotrophic factor (BDNF), making them a valuable in vitro model for studying neuronal differentiation. This study aimed to investigate the electrophysiological properties of SH-SY5Y cells following prolonged differentiation, with a focus on membrane characteristics, evoked action potentials, and the functionality of cellular components such as N-methyl-D-aspartate (NMDA) receptor. Whole-cell patch-clamp recordings were employed to evaluate ionic currents and action potentials in embryonic mouse cortical neurons (mCNs) and in both differentiated and undifferentiated SH-SY5Y neuroblastoma cells. Differentiated SH-SY5Y cells exhibited neurite outgrowth, evoked action potential firing, and functional NMDA receptor-mediated currents. Notably, atorvastatin significantly modulated the duration and firing of action potentials as well as NMDA receptor-mediated currents in differentiated SH-SY5Y cells. These findings highlight that neuronally differentiated SH-SY5Y cells expressing functional NMDA receptor-mediated currents serve as a robust and convenient model for investigating the molecular mechanisms of NMDA receptor function and for screening pharmacological agents targeting these receptors. Full article

Background: Parkinson’s disease (PD) is a debilitating neurodegenerative disorder affecting millions of people worldwide. PD results in motor and cognitive dysfunction. While there is no proven cure for PD, it is widely agreed that aerobic exercises and occupations can help slow the progression of the disease and keep some motor-related symptoms from developing. The most effective forms of exercise to slow the progression of motor symptoms in Parkinson’s disease have also been studied. Research Question: This research article aims to compare the differences in outcomes of exercise on cognitive outcomes in Parkinson’s Disease, as evaluated by meta-analysis. Methods: Key terms were Parkinson’s Disease and exercise terms. These search terms were then entered to electronic databases—Ovid MEDLINE, SCOPUS, and CINAHL—from March 2018 to May 2023. An ancestral bibliography was also performed. Results: Two reviewers screened the title and abstract records (n = 528) found in the initial search. Our review identified 18 studies which met inclusion criteria for meta-analysis. The meta-analysis found an effect of exercise on cognition of patients with PD (d = −0.03) which was not significant (CI95% of −0.13 < µ < 0.08; p > 0.05, as the CI includes zero). Additionally, the homogeneity analysis was not significant (Q (17) = 2.83; p > 0.05). Full article