Frontiers in Systems Neuroscience最新文献

A theory of self-organization in the central nervous system is described, proposing that additive and dissipative synaptodendritic summation leads to synchronous oscillation as the equilibrium state, thereby underpinning a primary mechanism of prediction error minimization. As a consequence, synaptic connections become arranged in mirror-symmetric paired patterns, wherein exchanges of synaptic flux within each pattern form coupled spatial eigenmodes. The mirror-reflection axis between each pair functions as a Markov blanket that maintains excitatory-inhibitory equilibrium, while multiway exchanges among mirror pairs converge toward overall error minimization and mutual organization. The primary organization of this type is evident in the spinal cord. During cortical embryogenesis, connections develop in topographies interpretable as mirror reflections with broken symmetry, aligning along the radial and circumferential axes of cortical growth, as described by the Structural Model, and subsequently manifest at the millimetric scale throughout the cortex. The proposed framework integrates a diverse range of experimental data and provides an explanatory basis for how generative models with agency can emerge through both species evolution and individual learning.

Despite impressive performance in various tasks, large language models (LLMs) are subject to the symbol grounding problem, so from the cognitive science perspective, one can argue that they are merely statistics-driven distributional models without a deeper understanding. Modern multimodal versions of LLMs (MLLMs) are trying to avoid this problem by linking language knowledge with other modalities such as vision (Vision Language Models called VLM) or action (Vision Language Action Models called VLA) when, for instance, a robotic agent, is acting in the world. If eventually successful, MLLMs could be taken as pathway for symbol grounding. In this work, we explore the extent to which MLLMs integrated with embodied agents can achieve such grounded understanding through interaction with the physical world. We argue that closing the gap between symbolic tokens, neural representations, and embodied experience will require deeper developmental integration of continuous sensory data, goal-directed behavior, and adaptive neural learning in real-world environments. We raise a concern that MLLMs do not currently achieve a human-like level of deep understanding, largely because their random learning trajectory deviates significantly from human cognitive development. Humans typically acquire knowledge incrementally, building complex concepts upon simpler ones in a structured developmental progression. In contrast, MLLMs are often trained on vast, randomly ordered datasets. This non-developmental approach, which circumvents a structured simple-to-complex conceptual scaffolding, inhibits the ability to build a deep and meaningful grounded knowledge base, posing a significant challenge to achieving human-like semantic comprehension.

The hippocampus plays a prominent role in spatial navigation and memory. However, differences exist along the hippocampus longitudinal axis in function and connectivity. The current study focuses on the dorsal and intermediate subregions of the hippocampus. Single unit CA1 activity was recorded in a fixed route task with a change in emotional valence. We hypothesized the intermediate subregion to show greater changes in general firing activity and place cell remapping in response to emotional change in context compared to the dorsal subregion. Animals were trained to run back and forth for food on a U-shaped maze. In half the trials, animals were presented with a tone which signaled an active shock zone at the apex of the maze. Therefore, animals alternated between "safe" and "unsafe" emotional states, while the spatial configuration of the maze stayed the same. Single-unit activity was recorded and cells were classified by their locations in dorsal hippocampus (DH), anterior intermediate hippocampus (aIH), and posterior intermediate hippocampus (pIH) as well as by spike waveform. Information content was lower and firing rate was higher in the pIH compared to the DH and aIH. A decrease in firing rate was seen in zones close to the shock zone across all three subregions. Contrary to our hypothesis, in well trained animals DH and aIH showed more place cell remapping in response to the tone compared to intermediate regions. Cells in these regions also showed a decrease in firing prior to receiving information regarding the next trial.

Prenatal hypoxia (PH) significantly impacts the central nervous system (CNS) development, often resulting in long-term cognitive, behavioral, and neurological deficits due to oxidative stress, mitochondrial dysfunction, and neuroapoptosis. The brain's endogenous protective mechanisms are often insufficient under prolonged hypoxia, necessitating the development of novel neuroprotective strategies. This study aimed to evaluate the neuroprotective efficacy of nasal administration of Angiolin gel-a novel pharmacological agent-in experimental model of PH. Chronic intrauterine hypoxia was induced in pregnant rats via sodium nitrite administration. Newborn rats were divided into groups receiving either Angiolin gel intranasally, Piracetam intraperitoneally, or saline (control) for 30 days. Biochemical, morphometric, histoimmunochemical, and neurophysiological methods were employed to assess outcomes. The results demonstrated that PH induced mitochondrial dysfunction, oxidative and nitrosative stress, GABAergic system impairment, and neuroapoptosis, leading to increased neonatal mortality and deficits in cognitive and motor functions. Angiolin gel administration significantly enhanced energy metabolism by restoring mitochondrial enzyme activities (SDH, MDH, and CPK), increasing ATP production, and reducing lactate accumulation. It also normalized GABAergic parameters, increased the activity of antioxidant enzymes (Cu/Zn-SOD, GPX1/4) and decreased nitrosative stress markers (iNOS, nitrotyrosine). Histomorphometric analysis revealed preserved neuronal density and reduced apoptosis in the hippocampus, alongside enhanced Fos/Bcl-2 expression. Behavioral tests demonstrated improved motor activity, memory retention, and exploratory behavior, with a 47% reduction in early mortality. Comparative analysis showed superior efficacy of Angiolin over Piracetam, which exacerbated lactate acidosis. These findings suggest that intranasal administration of Angiolin gel effectively targets multiple pathophysiological pathways triggered by PH, providing robust neuroprotection and promoting functional recovery. Given its favorable safety profile and the non-invasive nature of intranasal delivery, Angiolin gel represents a promising therapeutic approach for mitigating the long-term neurological consequences of prenatal hypoxia and warrants further clinical investigation in neonatal and pediatric neurology.

Background: Aging humans show a remarkable heterogeneity in agility, dexterity, and mobility. Once motor functions are impaired, their restoration may be challenging or even impossible. Thus, it is crucial to anticipate and address declines in mobility due to age- and disease-related reductions in cognitive and motor resources. Quantification of the individual motor adaptive capacity, or "motor reserve" (mR), is essential for the development of innovative treatments enhancing this reserve.

Objective: To assess whether biographical, behavioral, and neuroimaging measures can serve as quantifiable indicators of mR.

Methods: Twenty-four healthy adults aged 21-80 years underwent cross-sectional assessment. Adolescent and recent physical activity was gathered via questionnaires. Current adaptability was investigated using a locomotor adaptation task on a split-belt treadmill and a visuomotor adaptation hand task. Magnetic resonance imaging (MRI) was used to assess grey matter volume and resting-state functional connectivity in motor and locomotor brain centres.

Results: As expected, six-minute walking distance declined with age, largely reflecting reductions in grey matter volume. In contrast, motor adaptation abilities were preserved across the age span. Locomotor adaptation rates were positively associated with structural and functional integrity of motor networks, which were, in turn, influenced by long-term physical activity.

Conclusion: Variability in motor adaptability among older adults may be explained by individual differences in motor network integrity and lifelong physical activity. The findings of this exploratory cross-sectional study support the potential of MRI-based connectivity measures and locomotor adaptation performance as surrogate markers of motor reserve. Enhancing mR through targeted interventions may help sustain mobility and functional independence in aging populations.

Introduction: This study introduces the FOUndatioNal trait-BaseD Characterization (FOUND) questionnaire, specifically developed to assess stable characteristics of perceptual, cognitive, and emotional domains associated with effective performance in mediated settings.

Materials and methods: Items were derived from interviews with professionals in remote technology fields (e.g., robotic surgeons, drone pilots, crane operators) and grouped into four domains: cognitive-behavioral, socio-emotional, functional-organic, and value-based. Items, rated on a 4-point Likert scale, were designed to reflect stable traits. A panel of nine experts evaluated content validity; items with a CVI > 0.78 and a mean relevance ≥3 were retained, resulting in a 26-item scale. The factorial structure of FOUND was validated in a sample of 300 Italian participants, with convergent validity assessed, and participants were subsequently categorized into high and low procedural skill professions for known-groups comparisons (Study 1). Additionally, a separate sample of 34 remote operators (Study 2) was included to further evaluate known-groups validity.

Results: Exploratory and confirmatory factor analyses yielded a final 22-item structure, identifying four factors: Perception and Action, Empathic Attitude, Stress Management, and Group-Oriented Values. Convergent validity analysis using questionnaires that assess personality and stable characteristics (Five Facet Mindfulness Questionnaire-15, Big Five Inventory-10) did not yield significant correlations, indicating that the FOUND questionnaire may provide independent information. Known-groups validity was assessed by comparing scores between professions requiring high and low procedural skills identified in the 300 participants, revealing higher scores in Perception and Action, Empathic Attitude, and Stress Management for the first group (Study 1). Comparing remote operators (i.e., drone pilots) with the general population showed that remote operators scored higher in Perception and Action and Group-Oriented Values but lower in Stress Management, highlighting distinctive characteristics of individuals engaged in remote operations (Study 2).

Conclusion: The FOUND assesses perceptual, motor, cognitive, and socio-emotional constructs associated with performance in mediated and remote operations. It allows evaluation of stable traits and performance-related attitudes in contexts such as robotic surgery, telemedicine, education, and emergency response. By identifying these traits, the questionnaire can inform the design of personalized interventions and training programs tailored to individual characteristics, enhancing effectiveness in mediated environments.

Introduction: Quantifying natural behavior from video recordings is a key component in ethological studies. Markerless pose estimation methods have provided an important step toward that goal by automatically inferring kinematic body keypoints. Such methodologies warrant efficient organization and interpretation of keypoints sequences into behavioral categories. Existing approaches for behavioral interpretation often overlook the importance of representative samples in learning behavioral classifiers. Consequently, they either require extensive human annotations to train a classifier or rely on a limited set of annotations, resulting in suboptimal performance.

Methods: In this work, we introduce a general toolset which reduces the required human annotations and is applicable to various animal species. In particular, we introduce OpenLabCluster, which clusters temporal keypoint segments into clusters in the latent space, and then employ an Active Learning (AL) approach that refines the clusters and classifies them into behavioral states. The AL approach selects representative examples of segments to be annotated such that the annotation informs clustering and classification of all temporal segments. With these methodologies, OpenLabCluster contributes to faster and more accurate organization of behavioral segments with only a sparse number of them being annotated.

Results: We demonstrate OpenLabCluster performance on four different datasets, which include different animal species exhibiting natural behaviors, and show that it boosts clustering and classification compared to existing methods, even when all segments have been annotated.

Discussion: OpenLabCluster has been developed as an open-source interactive graphic interface which includes all necessary functions to perform clustering and classification, informs the scientist of the outcomes in each step, and incorporates the choices made by the scientist in further steps.

Transcranial alternating current stimulation (tACS) is a non-invasive technique that modulates brain oscillatory activity in a frequency-specific manner, offering potential for improving sensory and cognitive functions. Steady-state responses (SSRs), which are periodic neural responses to rhythmic sensory stimulation, provide a robust and objective means to assess tACS effects. The present work systematically reviews the existing literature on tACS modulation of SSR. 16 studies that used either auditory (ASSR) or visual (SSVEP) SSR were included in the review. Findings indicate that tACS can enhance or suppress SSRs depending on stimulation parameters. Although ASSR studies reported mixed findings, generally, gamma tACS enhanced ASSR, whereas tACS at lower frequencies resulted in ASSR inhibition. For SSVEPs, modulation was shown to be phase- and frequency-dependent, with congruent tACS and flicker frequencies producing the most reliable effects. Despite methodological heterogeneity and inconsistent results, the reviewed evidence highlights the potential of SSRs as sensitive markers of tACS outcomes. Future studies should aim for well-planned protocols tailored to specific aims and target populations.

Background: The pathophysiology of primary blepharospasm (BSP) remains incompletely understood. This study aimed to characterize whole-brain functional network topology in treatment-naive BSP patients.

Methods: Thirty-nine treatment-naive BSP patients and 39 matched healthy controls (HCs) underwent resting-state fMRI. Graph theoretical analysis was applied to assess global and nodal network metrics. Network-Based Statistics (NBS) identified subnetworks with altered functional connectivity (FC). Correlations between network metrics and clinical variables [Jankovic Rating Scale (JRS), illness duration] were explored.

Results: Compared to HCs, BSP patients exhibited significantly lower local efficiency [p = 0.0002, false discovery rate (FDR) corrected], while global efficiency, characteristic path length, clustering coefficient, normalized clustering coefficient, normalized characteristic path length, or small-worldness were preserved (all p > 0.05, FDR corrected). Nodal analysis revealed decreased efficiency/degree in the bilateral thalamus and left supplementary motor area, and increased efficiency/degree in the bilateral precentral gyri, right postcentral gyrus, and left insula (all p < 0.05, FDR corrected). NBS identified subnetworks with altered FC across sensorimotor, limbic-subcortical, frontoparietal, and default mode networks, featuring both hyper- and hypo-connectivity (p < 0.05, NBS-corrected). Notably, left thalamic efficiency negatively correlated with illness duration (r = -0.481, p = 0.0019), and right precentral gyrus efficiency positively correlated with JRS total score (r = 0.395, p = 0.0129).

Conclusion: BSP is characterized by complex functional network disruptions, including impaired local information processing, altered nodal importance in key motor and relay hubs, and widespread connectivity changes. These findings reinforce BSP as a network disorder. These network alterations may serve as objective markers for disease progression and could guide the development of targeted neuromodulation therapies.

[This corrects the article DOI: 10.3389/fnsys.2025.1611293.].