NeuroSci

Since its discovery, TRPC6 has been associated with a variety of physiological and pathophysiological processes in different tissues. It functions as a non-selective cation channel and belongs to the group of TRP channels. Its importance in the development of pain hypersensitivity is becoming increasingly apparent. This condition has already been associated with increased expression of TRPC6 in dorsal root ganglia. Apart from the fact that most of the evidence has been obtained from samples of animal origin, it remains unclear whether the channel is also expressed in peripheral nerves outside the dorsal root ganglia. The aim of this work was therefore to examine peripheral nerves from human samples for TRPC6. For this purpose, samples of both the sciatic and ulnar nerves were taken from a total of eight body donors and analyzed by immunohistochemistry. Both longitudinal and transverse sections were obtained from the samples and stained. In total, 43 of 48 histological sections showed a positive immunosignal. There were no major differences between the sciatic and ulnar nerves with regard to staining. There was a slight difference in the staining intensity of transverse and longitudinal sections. The longitudinal sections of both nerves were consistently colored slightly more intensely. However, the inter-individual differences between the donors were more pronounced. Interestingly, the samples of a donor who suffered from chronic pain syndrome during his lifetime were particularly strongly stained. This is consistent with the knowledge gained to date, largely from animal experiments, that the channel shows increased expression in pain conditions in dorsal root ganglia. In the future, TRPC6 could therefore be a target in pain therapy. Full article

Limbic encephalitis (LE) associated with anti-LGI1 antibodies is an autoimmune disorder characterized by memory decline, behavioral changes, and temporal lobe epilepsy. Faciobrachial dystonic seizures (FBDS) are a hallmark symptom, often preceding cognitive and psychiatric issues. This report presents an 80-year-old male with LGI1 encephalitis, initially manifesting as FBDS. A lung adenocarcinoma was diagnosed two months after the onset of neurological symptoms. Clinical and paraclinical data, including MRI and [18]FDG PET imaging, are described. The patient responded to immunotherapy, including steroids and plasma exchange, along with tumor resection. Following treatment, neurological symptoms resolved, except for mild anxiety and apathy. Further research is needed to determine whether LGI1 encephalitis may occasionally have a paraneoplastic origin, potentially influencing screening and management strategies. Full article

This paper proposes a theoretical model of meaning-making grounded in proprioceptive awareness and embodied imagination, arguing that human cognition is inherently multimodal, anticipatory, and sensorimotor. Drawing on Peircean semiotics, Lotman’s model of cultural cognition, and current research in neuroscience, we show that readiness to act—a proprioceptively grounded anticipation of movement—plays a fundamental role in the emergence of meaning, from perception to symbolic abstraction. Contrary to traditional approaches that reduce language to a purely symbolic or visual system, we argue that meaning arises through the integration of sensory, motor, and affective processes, structured by axial proprioceptive coordinates (vertical, horizontal, sagittal). Using Peirce’s triadic model of interpretants, we identify proprioception as the modulatory interface between sensory stimuli, emotional response, and logical reasoning. A study on skilled pianists supports this view, showing that mental rehearsal without physical execution improves performance via motor anticipation. We define this process as proprioceptive resonance, a dynamic synchronization of embodied states that enables communication, language acquisition, and social intelligence. This framework allows for a critique of linguistic abstraction and contributes to ongoing debates in semiotics, enactive cognition, and the origin of syntax, challenging the assumption that symbolic thought precedes embodied experience. Full article

Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex neurodevelopmental disorder with a multifactorial etiology involving genetic, epigenetic, and environmental factors. This review focuses on the current understanding of these contributing elements, examining how they interact to influence ADHD development. Genetic predispositions, environmental exposures, and epigenetic modifications collectively shape the risk and manifestation of the disorder. Despite advancements in research, significant challenges remain in identifying precise mechanisms and translating them into effective treatments. The variability of symptoms across individuals, influenced by factors such as age, gender, and cultural background, further complicates diagnosis and treatment. Addressing these challenges requires a deeper investigation into the underlying causes of ADHD and the development of tailored interventions. This review aims to highlight both the progress made in understanding ADHD etiology and the current gaps in treatment approaches, calling for more targeted research and personalized therapeutic strategies. Full article

Neurocysticercosis (NCC), a parasitic infection caused by Taenia solium larvae, remains a leading cause of acquired epilepsy worldwide, particularly in regions with inadequate sanitation and healthcare access. We present a case of NCC reactivation in a 64-year-old female who developed anomic aphasia—a rare manifestation of NCC—decades after her initial diagnosis. The patient’s clinical course was complicated by a potential trigger of semaglutide, which potentially attenuated the protective inflammatory response maintained by astrocytes and microglia, leading to the reactivation of dormant cysts. Brain imaging confirmed localized cystic changes, and treatment with antiparasitic agents and corticosteroids led to marked clinical improvement. This case highlights the complexity of NCC reactivation, highlighting the interplay of metabolic, immune, and parasitic factors. It emphasizes the need for vigilance in managing patients with dormant infections and investigating potential risks associated with novel therapeutic agents like GLP-1 receptor agonists. Further research is essential to unravel the mechanisms linking metabolic modulation to parasitic reactivation, offering insights into prevention and treatment strategies. Full article

Background:Mesenchymal stem/stromal cells (MSCs) are non-hematopoietic, plastic-adherent, and self-renewing cells capable of in vitro trilineage differentiation into fat, bone, and cartilage tissue. Suggestively, MSCs have additional plasticity, as demonstrated by their ability to differentiate in vitro into myocytes, neuron-like cells, and hepatocytes. MSCs are ideal for therapeutic application owing to their numerous advantages; they exhibit limited growth and differentiation abilities, leading to heterogeneous cell populations with inconsistent functions. However, highly purified MSCs, namely, rapidly expanding clones (RECs) that are isolated by single-cell sorting, display uniform functionality. RECs have the potential to offer many benefits, such as transplantable cells for treating several disorders of bone, heart, peripheral nerves, brain, and other organs. This study aimed to assess the effects of RECs on the pheochromocytoma (PC12) cell line, a well-known neuronal cell model.Methods: PC12 cells were cultured under the following conditions: co-culture with RECs, treatment with REC-derived conditioned medium (CM), or co-culture with RECs using Transwell inserts for 7 days. The cells were stained with anti-βIII-tubulin antibody; the lengths of neurites were measured by image analysis. Results: Regarding the co-culture with RECs, PC12’s outgrowth was significantly increased. The RECs expressed nerve growth factor (NGF), a neurotrophic factor that could act on PC12 cells to trigger cellular differentiation.Conclusions: Our findings suggest that RECs via direct culture, intercellular communication in Transwell culture, and RECs CM promoted PC12 cell survival and outgrowth via NGF signaling. Full article

The SCN9A gene, a critical regulator of pain perception, encodes the voltage-gated sodium channel Nav1.7, a key mediator of pain signal transmission. This study conducts a multimodal assessment of SCN9A, integrating genetic variation, structural architecture, and molecular dynamics to elucidate its role in pain regulation. Using advanced computational methods, I-TASSER simulations generated structural decoys of the SCN9A homology domain, producing an ensemble of conformational states. SPICKER clustering identified five representative models with a C-score of −3.19 and TM-score of 0.36 ± 0.12, reflecting moderate structural similarity to experimental templates while highlighting deviations that may underpin functional divergence. Validation via ProSA-web supported model reliability, yielding a Z-score of −1.63, consistent with native-like structures. Central to the analysis was the R1150W non-synonymous variant, a potential pathogenic variant. Structural modeling revealed localized stability in the mutant conformation but disrupted hydrogen bonding and altered charge distribution. Its pathogenicity was underscored by a high MetaRNN score (0.7978498) and proximity to evolutionarily conserved regions, suggesting functional importance. Notably, the variant lies within the Sodium-Ion-Transport-Associated Domain, where perturbations could impair ion conductance and channel gating—mechanisms critical for neuronal excitability. These findings illuminate how SCN9A variants disrupt pain signaling, linking genetic anomalies to molecular dysfunction. While computational insights advance mechanistic understanding, experimental validation is essential to confirm the variant’s impact on Nav1.7 dynamics and cellular physiology. By refining SCN9A’s molecular blueprint and highlighting its therapeutic potential as a target for precision analgesics, this work provides a roadmap for mitigating pain-related disorders through channel-specific modulation. Integrating structural bioinformatics with functional genomics, this study deciphers SCN9A’s role in pain biology, laying the groundwork for novel strategies to manage pathological pain. Full article

Penetrating brain injuries (PBI) constitute a significant subset of traumatic brain injuries, characterized by high morbidity and mortality due to their unique pathophysiological mechanisms. Despite its clinical prevalence in civilian and military settings, progress in translational research remains limited due to a lack of well-characterized pre-clinical models that accurately replicate human PBI. Existing models often fail to adequately simulate critical aspects such as ballistic dynamics, tissue cavitation, and secondary injury cascades, limiting their translational relevance and hindering therapeutic advancements. This scoping review aims to systematically evaluate existing pre-clinical models, including animal, computational, ballistic, and hybrid simulations, to assess their methodological rigor, translational applicability and reported outcome measures. Using PRISMA-ScR guidelines, we will conduct a comprehensive literature search across multiple databases, extracting data on model characteristics, injury induction techniques, histopathological findings, biomolecular markers, and functional assessments. Additionally, bibliometric analyses will provide insights into research trends and gaps in PBI modeling, particularly concerning replicating real-world injury mechanisms and long-term functional outcomes. Through this evaluation, we aim to identify optimal experimental frameworks for studying PBI pathophysiology and recovery mechanisms while informing future model development for therapeutic advancements. The findings from this review will serve as a foundation for advancing pre-clinical PBI research, guiding future model development and therapeutic innovations, and ultimately enhancing treatment strategies and patient outcomes. Full article

The sensation of dyspnea is related to various cardiopulmonary and neuromuscular diseases and is characterized by its sensory and affective qualities. Although there is a vast number of studies investigating its pathophysiology, less is known about the neuroanatomy of dyspnea perception. An activation likelihood estimation (ALE) meta-analysis of 13 studies investigating different breathing challenges using either PET or fMRI was performed to demonstrate the neuroanatomical correlates of dyspnea perception. The ALE meta-analysis was performed using the GingerAle software 3.0.2 and was displayed with the Mango software 4.1. Synthesizing the results of all included studies, clusters involving the insula and cingulated cortex in both hemispheres were observed. Subgroup analysis for the restrained breathing condition revealed activation involving the right and left cingulate cortex and left anterior cingulate cortex. For the loaded breathing condition, statistically significant activation was found for the postcentral gyrus, the superior temporal gyrus, and the right thalamus. The combined ALE map for both conditions showed activity patterns in the right cingulate cortex, the right insula, and the right thalamus. This ALE meta-analysis demonstrates that two separate neuronal pathways related to either the affective or intensity domain are involved in the central processing of dyspnea perception. Full article

Eye tracking is a tool that is widely used in scientific research, enabling the acquisition of precise and detailed data on an individual’s eye movements during interaction with visual stimuli, thus offering a rich source of information on visual perception and associated cognitive processes. In this work, a new software called SPEED (labScoc Processing and Extraction of Eye tracking Data) is presented to process data acquired by Pupil Lab Neon (Pupil Labs, Berlin, Germany). The software is written in Python which helps researchers with the feature extraction step without any coding skills. This work also presents a pilot study in which five healthy subjects were included in research investigating oculomotor correlates during MDMT (Moral Decision-Making Task) and testing possible autonomic predictors of participants’ performance. A statistically significant difference was observed in reaction times and in the number of blinks made during the choice between the conditions of the personal and impersonal dilemma. Full article

Background: Stent-assisted coil embolization (SACE) is a common endovascular technique for managing intracranial aneurysms. The permanent presence of a stent inside the cerebral artery necessitates the postoperative use of antiplatelets. However, a consensus about how long to continue on it remains debated. This systematic review aims to discuss and quantify the risk of ischemic complications after antiplatelet discontinuation following SACE. Methods: PubMed, Cochrane Library, Scopus, and Web of Science (WOS) were systematically searched for studies assessing the outcomes after antiplatelet discontinuation following SACE for cerebral aneurysms. The primary outcome was the odds of ischemic complications after antiplatelet discontinuation. Using a random-effects model, the pooled event rate, along with a 95% confidence interval (CI), was calculated. The Comprehensive Meta-Analysis software (CMA) software was used for the analysis. The Newcastle–Ottawa Scale (NOS) was used for the quality assessment. Results: A total of five observational cohort studies were included in this systematic review. The studies recruited cases from 2009 and 2020, predominantly in Korea and Japan. Data from 18,425 cases obtained from four studies were analyzed. The duration of antiplatelet therapy varied widely across the included studies. Additionally, most studies reported a median follow-up of 24 months or more after antiplatelet discontinuation. We extracted and analyzed the odds of thromboembolic complications occurring within 6 to 24 months after the discontinuation of antiplatelets. The pooled rate of thromboembolism after antiplatelet discontinuation in this meta-analysis was 0.01 (95% CI: 0.006 to 0.018). Conclusion: This review demonstrates that the risk of thromboembolic complications after discontinuing antiplatelet therapy post-SACE is low. However, no strong consensus exists on the ideal duration for maintaining dual- or single-antiplatelet therapy. Further prospective studies with longer follow-ups are warranted to clarify the optimal durations needed to balance thromboembolic risk with hemorrhagic complications. Full article

The objective of the study was to determine the relationship between burning, xerostomia, dysgeusia and other subjective symptoms in patients with burning mouth syndrome (BMS). This cross-sectional study was conducted at the Dental Polyclinic Split, Split, Croatia. A total of 71 patients with BMS, i.e., 60 women and 11 men, were included in the study. The patients were divided into four subgroups: burning (B), burning and xerostomia (BX), burning and dysgeusia (BD), burning, xerostomia and dysgeusia (BXD). The following data were collected from all patients: sociodemographic status, comorbidities, medications, characteristics of the burning, presence of other subjective symptoms, topography of the burning. The majority of patients with BMS were women (86.0%) with an average age of about 65 years. Gastrointestinal diseases were the most common comorbidity (48.35%), and the most commonly used medications were proton pump inhibitors (PPIs) (29.8%). In the largest number of patients (N = 34), the burning symptom worsened in the evening hours (p = 0.059). The majority of BMS patients suffered from burning symptoms that occurred continuously (N = 54, 75.13%) and from an improvement (reduction/cessation) of symptoms during meals (N = 54, 76.65%). Of the other subjective symptoms, changes in the morphology of the tongue (10.6%) and a feeling of swelling (9.1%) were the most common. The tongue was the most common localization (67.35%). The multivariable logistic regression analysis showed a statistically significant effect of female gender (p = 0.049) as a potential positive predictor in subgroup B. The sociodemographic and medical data collected cannot explain the different occurrence of symptoms in the four subgroups of patients with BMS. Full article

In prior studies, desynchronization of the induced alpha band (non-phase-locked but time-locked) has been observed across various cognitive tasks. Proposed hypotheses for the cognitive role of this alpha decrement include neural activation, an inhibition/timing mechanism, or a reduction in “neural noise”. This study aimed to examine the effect of cognitive load on induced alpha activity using two versions of a go/no-go visual task: a single-target (ST) version with one target and one distractor, and a double-target (DT) version with two targets and two distractors. EEG was recorded from 58 electrodes, and Temporal Spectral Evolution (TSE) was used for time–frequency analysis. Behavioral results revealed faster reaction times in the ST task compared to the DT task. The P3 component displayed delayed latency and reduced amplitude under increased cognitive load, consistent with prior findings. However, the latencies and amplitudes of evoked and induced alpha responses were unaffected by cognitive load. This suggests that increased alpha desynchronization in subjects with cognitive impairment should not be interpreted as enhanced neural resource recruitment due to task difficulty. Instead, it may reflect other mechanisms unrelated to cognitive load differences in task performance. Full article

Background: Volumetric analysis and segmentation of magnetic resonance imaging (MRI) data is an important tool for evaluating neurological disease progression and neurodevelopment. Fully automated segmentation pipelines offer faster and more reproducible results. However, since these analysis pipelines were trained on or run based on atlases consisting of neurotypical controls, it is important to evaluate how accurate these methods are for neurodegenerative diseases. In this study, we compared five fully automated segmentation pipelines, including FSL, Freesurfer, volBrain, SPM12, and SimNIBS, with a manual segmentation process in GM1 gangliosidosis patients and neurotypical controls. Methods: We analyzed 45 MRI scans from 16 juvenile GM1 gangliosidosis patients, 11 MRI scans from 8 late-infantile GM1 gangliosidosis patients, and 19 MRI scans from 11 neurotypical controls. We compared the results for seven brain structures, including volumes of the total brain, bilateral thalamus, ventricles, bilateral caudate nucleus, bilateral lentiform nucleus, corpus callosum, and cerebellum. Results: We found volBrain’s vol2Brain pipeline to have the strongest correlations with the manual segmentation process for the whole brain, ventricles, and thalamus. We also found Freesurfer’s recon-all pipeline to have the strongest correlations with the manual segmentation process for the caudate nucleus. For the cerebellum, we found a combination of volBrain’s vol2Brain and SimNIBS’ headreco to have the strongest correlations, depending on the cohort. For the lentiform nucleus, we found a combination of recon-all and FSL’s FIRST to give the strongest correlations, depending on the cohort. Lastly, we found segmentation of the corpus callosum to be highly variable. Conclusions: Previous studies have considered automated segmentation techniques to be unreliable, particularly in neurodegenerative diseases. However, in our study, we produced results comparable to those obtained with a manual segmentation process. While manual segmentation processes conducted by neuroradiologists remain the gold standard, we present evidence to the capabilities and advantages of using an automated process that includes the ability to segment white matter throughout the brain or analyze large datasets, which pose feasibility issues to fully manual processes. Future investigations should consider the use of artificial intelligence-based segmentation pipelines to determine their accuracy in GM1 gangliosidosis, lysosomal storage disorders, and other neurodegenerative diseases. Full article

Primary cervical dystonia (PCD), or spasmodic torticollis, is a focal dystonia characterized by involuntary and often painful muscle contractions, leading to abnormal cervical movements and postures. While botulinum toxin injections are the first-line treatment, additional therapies, such as segmental muscle vibration (SMV), remain underexplored. SMV, a non-invasive neuromodulation technique, may enhance motor cortex excitability and promote neuroplasticity, offering potential benefits in PCD management. This single-center triple-blinded randomized controlled trial evaluates SMV’s efficacy in reducing dystonic pain and improving quality of life in PCD patients undergoing standardized rehabilitation after botulinum toxin treatment. Participants with a pain level of ≥3 on the Numerical Rating Scale will be randomized into two groups. The experimental group will receive 80 Hz SMV during a 10-session rehabilitation program, while the control group will undergo sham SMV. Both groups will follow identical physiotherapy and occupational therapy protocols. The primary outcomes include changes in pain intensity and function, assessed at baseline, mid-treatment, and post-treatment using validated scales. The secondary outcomes will evaluate quality of life and patient satisfaction. This study hypothesizes that SMV will significantly reduce dystonic pain and enhance quality of life, supporting its integration into multidisciplinary rehabilitation for dystonic disorders. Trial registration number: NCT06748846. Full article

Intrinsic connectivity of the fusiform face area (FFA) was assessed using resting-state functional magnetic resonance imaging (fMRI) to compare adults with autism spectrum disorder (ASD; n = 17) and age-, sex-, and IQ-matched typically developing controls (TD; n = 22). The FFA seed region was delineated in each participant using a functional localizer task. Whole brain analyses of FFA connectivity revealed increased connectivity between the right FFA and the vermis, sensorimotor cortex, and extended face-processing network in individuals with ASD compared to TD participants; the TD group did not demonstrate increased functional connectivity. No group differences were observed from the left FFA. The relationship between FFA connectivity and the ability to remember faces significantly differed between the groups. Better face memory performance was positively correlated with increased connectivity within general visual processing areas in the ASD participants; whereas for the TD group, better face memory performance was associated with increased connectivity with brain regions related to face encoding, recognition, and retrieval. FFA overconnectivity with face, emotion, and memory processing areas, along with atypical relationships between FFA–occipito-temporal connections and face memory performance highlights a possible mechanism underlying social dysfunction in individuals with ASD. Full article

Reserpine is used as a cheap and effective first-line antihypertensive, and presently, it is applied as treatment for difficult-to-control cases of hypertension. Despite its significance, reserpine’s neuroendocrine toxicity remains largely underexplored. Here, we investigated the effects of reserpine on development, locomotion, central nervous system (CNS) neurons, thyroid development, and the expression of genes related to neurodevelopment, endocrine, learning and memory, and depression in zebrafish exposed to different doses of reserpine ranging from 0.5 mg/L to 16 mg/L. The results of our study demonstrated that reserpine exerts dose-dependent toxicity on the neuroendocrine system (NES). An investigation into its underlying mechanism suggests that reserpine disrupted the hypothalamic–pituitary–thyroid (HPT) axis via down-regulating hhex, tg, and tshβ genes, impairing thyroid hormone synthesis and endocrine balance. Meanwhile, it affected neurodevelopment, as evidenced by the reduced expression of gfap, gap43, mbp, syn2a, and tuba1b genes, which compromised neuronal structure and function, while impaired neurotransmitter release and uptake could occur due to the suppression of crhb and mao genes. To conclude, these findings illustrate the interconnected impact of pathways involved in endocrine and neurodevelopment in reserpine-induced toxicity. Full article

Many neurobehavioral tests are used for the assessment of human-like behaviors in animals. Most of them were developed in rodents and are used for the assessment of animal models that mimic human neurodevelopmental and neuropsychiatric disorders (NDDs). We have described tests for assessing social behavior, social interaction, and social communication; tests for restricted and repetitive behaviors; tests for cognitive impairment, for sensory stimuli, for anxiety like behavior, and for motor coordination deviations. These tests are used to demonstrate autistic-like behavior as well as other NDDs. We described possible general pitfalls in the performance of such studies, as well as probable individual errors for each group of tests assessing specific behavior. The mentioned pitfalls may induce crucial errors in the interpretation of the results, minimizing the reliability of specific models of defined human NDD. It is imperative to minimize these pitfalls and use sufficient and reliable tests that can demonstrate as many of the traits of the human disorder, grade the severity of the specific deviations and the severity of the tested NDD by using a scoring system. Due to possible gender differences in the clinical presentations of NDD, it is important to carry out studies on males and females. Full article

Background: Photobiomodulation (PBM), also referred to as low-level light therapy (LLLT), is an emerging non-pharmacological approach. This treatment is considered low-risk, cost-effective, and non-invasive, utilizing near-infrared light (NIR). The purpose of this paper is to explore the underlying mechanism of action and conduct a systematic review of pre-clinical and clinical research on the use of PBM for psychiatric disorders. Methods: A search on the PubMed, Cochrane Library, and EMBASE databases was performed on 18 and 26 January 2024. Publications focused on PBM treatment in psychiatric disorders such as major depressive disorder, general anxiety disorder, dementia, Parkinson’s disease, traumatic brain injury, schizophrenia, and sexual disfunctions were included (n = 23). Results: Near-infrared stimulation is presented as an effective method, comparable to psychopharmacological treatment. The primary suggested mechanism for PBM is the stimulation of mitochondrial metabolism following the absorption of NIR energy by cytochrome C oxidase. Because of the method of implementation, which omits the liver metabolism of cytochrome P450, PMB is recognized as safe as it does not interact with other drugs. Limitations: Clinical studies vary in terms of population and treatment parameters, and most do not include a suitable control group. Conclusions: Preliminary results support the potential of NIR stimulation as a novel and innovative treatment for psychiatry. Further studies are needed to estimate the proper protocols of parameters singly for any disease. Full article