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At least 19 recordsLinked to original sources

PubMed2025

Learning neural dynamics through instructive signals.

Rapid learning is essential for flexible behavior, but its basis in the brain remains unknown. Here we introduce the PRISM plasticity rule, a unifying mechanistic model of three well-established, fast-acting synaptic plasticity rules-in hippocampus, cerebellum and mushroom body-which relies exclusively on pre-synaptic activity and an "instructive signal" from another brain area. Using a multi-region network model we show that guiding PRISM plasticity with instructive signals enables the network to quickly learn extremely flexible nonlinear dynamics underlying behaviorally relevant computations, as well as to emulate unknown external system dynamics from real-time error signals, which we demonstrate with comprehensive simulations supported by exact mathematical theory. Thus, PRISM plasticity guided by instructive signals is well-suited to rapidly learn general-purpose neural computations-in contrast to canonical Hebbian rules. Finally, we show how including this plasticity rule in artificial learning algorithms can solve long-range temporal credit assignment, a long-standing challenge in machine learning.

cerebellum↗

PubMed2026

Histone H3K9 methyltransferases regulate cortical growth by coordinating heterochromatin formation and neural progenitor dynamics.

DNA packaging into heterochromatin is a fundamental mechanism of transcriptional silencing, yet its role in regulating neural progenitor behavior during brain development remains poorly understood. Trimethylation of histone H3 lysine 9 (H3K9me3), catalyzed by the methyltransferases SETDB1, SUV39H1, and SUV39H2, is a defining feature of heterochromatin, but functional redundancy among these enzymes has obscured their developmental roles. Here, we generated a cortex-specific triple knockout mouse model lacking Setdb1, Suv39h1, and Suv39h2 to directly interrogate H3K9me3 function during corticogenesis. Combined loss of H3K9 methyltransferases caused genome-wide depletion of H3K9me3, disruption of neural progenitor cell-cycle progression, and impaired cortical neurogenesis, resulting in microcephaly. H3K9 methyltransferases preserve neural progenitor identity and function by silencing clustered protocadherins, meiosis-associated genes, and a cell-cycle restraint program through H3K9me3 deposition. Loss of H3K9me3 promoted local chromatin opening and increased transcription factor occupancy, enabling transposable elements to acquire cryptic enhancer activity and modulate proximal gene expression. Together, these findings establish H3K9me3 heterochromatin as an active regulator of neural progenitor dynamics and lineage fidelity, revealing a central epigenetic mechanism that restricts aberrant transcriptional programs to ensure cortical growth.

Cerebral Cortex↗

PubMed1978

Models of the dynamics of neural populations.

Three requirements are posed for constructing models to simulate EEG dynamics. The element of the model should be an interactive ensemble of neurons and not single neurons. The observations must be statistical, such as EEG waves and averages of unit activity over time and over local neighborhoods containing neural subsets. The state variables and operations of the model must be clearly related to behavioral functions such as sensory reception and perception. A model is presented that exemplifies these requirements. Its key feature is the dependence of its levels of interaction on the level of its input, so that with each burst of input the model switches from an equilibrium state to a limit cycle state. A mechanism is described for coding sensory input into the spatial modulation of the limit cycle activity viewed as a carrier. It is suggested that sensory recepts and percepts exist at different hierarchical levels in the brain, recepts at the level of single neurones, and percepts at the level of neural ensembles, the latter being possibly manifested in the EEG.

Animals↗

PubMed1979

Structure and dynamics of neural network oscillators.

Techniques are given to represent oscillating neural networks by asynchronous logical switching networks, and to analyze the oscillating networks using a directed graph called a state transition diagram. Consideration is restricted to network oscillators containing no rhythm determining pacemaker neurons, and no neurons exhibiting self-limiting properties such as post-inhibitory rebound or accumulating refractoriness. In the state transition diagrams, stable oscillations are associated with a particular geometric configuration called a cyclic attractor (the heavy cycle in Fig. 2). We show that given the network connectivity it is possible to predict autonomous dynamic behaviour, as well as behaviour following hyperpolarizing or depolarizing inputs to neurons of the network. Conversely, given information about patterns of firing activity during cycles and transients of neural networks, the network connectivity can be predicted. The theoretical techniques can be used to generate a census of network structures capable of generating stable oscillations. Several representative network oscillators are discussed in the context of previous theoretical and experimental studies of the structure of neural network oscillators. Although the number of theoretically possile network oscillators capable of generating sustained oscillations is very large, the techniques which are given should be useful in the design of experiments capable of distinguishing between equally plausible hypotheses.

Action Potentials↗

PubMed2026

Dissociating behavioral, neural and experiential effects of prefrontal HD-tDCS during conflict resolution.

Inconsistent evidence regarding the cognitive effects of transcranial direct current stimulation (tDCS) highlights the need for more comprehensive approaches to assess its impact. This study aimed to investigate the effects of high-definition tDCS (HD-tDCS) on conflict resolution by combining behavioral, neural, and subjective experience measures. Sixty participants were randomly assigned to anodal, cathodal, or sham HD-tDCS groups and completed a 30-min flanker task. EEG was recorded during the first and last blocks (without stimulation), while stimulation was applied during the intermediate blocks of the task. Using a multidimensional methodological approach including Drift-Diffusion Modeling (DDM), EEG spectral analysis, Lempel-Ziv complexity, and Temporal Experience Tracing (TET), we assessed the cognitive, neural, and phenomenological effects of stimulation. Behavioral results indicated no significant improvements in reaction times or accuracy across the stimulation groups. Similarly, DDM parameters showed no effect of HD-tDCS on latent cognitive processes. However, EEG data revealed a significant reduction in neural complexity in the anodal group during resting-state, suggesting a stabilization or reorganization of neural dynamics. Subjective experience analysis identified two distinct clusters of task-related feelings, though time spent in these experiential states did not differ between groups. Interestingly, sensation of stimulation was significantly higher for anodal stimulation than sham when analyzed as a single dimension. Despite null behavioral effects, this study provides important insights into the neural and subjective responses to HD-tDCS and highlights the value of integrating complementary multidimensional approaches to better characterize brain stimulation effects. These findings contribute to the ongoing debate about the efficacy of tDCS in cognitive enhancement.

Humans↗

PubMed1979

Existence and stability of local excitations in homogeneous neural fields.

Dynamics of excitation patterns is studied in one-dimensional homogeneous lateral-inhibition type neural fields. The existence of a local excitation pattern solution as well as its waveform stability is proved by the use of the Schauder fixed-point theorem and a generalized version of the Perron-Frobenius theorem of positive matrices to the fuction space. The dynamcis of the field is in general multi-stable so that the field can keep short-term memory.

Humans↗

PubMed2026

Brain-wide spontaneous neural avalanches: Definition, functional dynamics and cognitive relevance.

Although spontaneous activity is ubiquitous across multiple spatiotemporal scales, its functional organization and cognitive relevance remain poorly understood. Following the classic neuronal avalanche framework, a spontaneous avalanche is defined as consecutively active frames separated by inactive time bins. Hence, multiple distinct avalanches may be considered as one avalanche, thereby ignoring their spatial and temporal distinguishability. Furthermore, group-level power-law fitting of such neural avalanches is often performed to evaluate brain criticality (referring to a system perched between order and disorder) due to the limited recording length of macroscale neuroimaging (such as functional magnetic resonance imaging), and the functional representation of brain-wide neural avalanches is largely unexplored. To address these issues, we proposed large-scale neural avalanches as a single, spatially consecutive cascade pattern and further investigated their functional dynamics, network propagation, and association with task-evoked activity. Compared with the conventional inactive-bin definition, our current approach is more favorable to power-law fitting of avalanche size and duration distributions at the individual level. We also demonstrated that participants whose brain activities were close to the critical point tend to have higher cognitive abilities. Notably, the ratio of neural avalanches that evolved from primary sensory to association networks negatively correlated with cognitive abilities. Moreover, the geometric distance between low-dimensional representations of task-evoked activity and spontaneous avalanches was associated with behavioral performance. This study not only provides a promising avenue for measuring avalanche criticality based on human whole-brain neuroimaging, but also suggests that spontaneous neural avalanches and their low-dimensional representations contribute to human cognitive abilities.

Humans↗

PubMed2024

Dynamic Pathology of Enteric Neural Network Using Curcumin-assisted Multiphoton Laser Imaging in Hirschsprung Disease.

BACKGROUND: In living tissue, it has been difficult to make microscopic-level observations without damaging the tissue. We have invented a novel intravital fluorescent observation method (IFOM) for real-time tissue observation, combining multiphoton laser scanning microscopy with curcumin vital staining (CVS-IFOM). The aim of this study was to use CVS-IFOM to analyze the enteric nervous system (ENS) in mice and human patients with hypoganglionosis and Hirschsprung disease (HSCR). METHODS: In an initial viability study, we compared live ENS images from nonfluorescent C57BL6 mice stained with curcumin (n = 5) and green fluorescent protein mice (n = 5) using multiphoton laser scanning microscopy. We then explored CVS-IFOM for the live examination of resected colon tissues from 1 patient with hypoganglionosis and 3 patients with HSCR. RESULTS: In the viability study, detailed ENS histologic features were only observed in the curcumin-stained mice. In the patient with hypoganglionosis, CVS-IFOM provided ENS details that were not visualized under hematoxylin and eosin staining or calretinin immunohistochemistry, allowing the analysis of ENS size, neural bundle number, and neural cell number per plexus. In patients with HSCR, CVS-IFOM showed a gradual hypoplastic change in the ENS from the oral edge to the anal edge, detecting disproportionate changes in the ENS within the same intestinal level, supporting a circumferentially uneven distribution of the intestinal ENS. CONCLUSIONS: CVS-IFOM may be supportive for intraoperative pathologic diagnosis during surgeries for HSCR.

Hirschsprung Disease↗

PubMed2026

dAMN: a genome-scale neural-mechanistic hybrid model to predict bacterial growth dynamics.

SUMMARY: This study presents dAMN, a genome-scale neural-mechanistic hybrid model that combines neural networks with dynamic flux balance analysis to predict bacterial growth dynamics across diverse nutrient environments. Using a residual network architecture, dAMN predicts reaction fluxes and lag-phase parameters from initial medium composition, then integrates these predictions under stoichiometric constraints derived from genome-scale metabolic models. Trained on Escherichia coli and Pseudomonas putida growth datasets across combinatorial media, dAMN accurately forecasts temporal growth dynamics and generalizes to unseen media conditions, with mean R² ≥ 0.9. The model also reproduces biologically relevant behaviors including substrate depletion, acetate overflow, and diauxic shifts, while explicitly modeling lag phases usually absent from standard dFBA. AVAILABILITY AND IMPLEMENTATION: The dAMN software, associated models, and datasets are available at https://github.com/brsynth/dAMN-main-release and via Zenodo DOI: 10.5281/zenodo.17908125.

Escherichia coli↗

PubMed2026

Refinement of Nucleus Accumbens Neuronal Dynamics during Cocaine Self-Administration Training.

Drug addiction is an acquired motivational-behavioral state that begins with drug taking, which is composed of a series of phases, including initial acquisition, stabilization, habituation, and maintenance. In rodent models of cocaine self-administration, the forebrain region nucleus accumbens (NAc) has been critically implicated in the acquisition-maintenance process of drug-taking and drug-seeking behaviors. However, it remains unknown how NAc neurons shift their activity patterns in response to these phasic transitions during cocaine taking. To examine this, we used GCaMP6m-based in vivo Ca2+ imaging in male mice to monitor activities of principal medium spiny neurons (MSNs) in the NAc across 11 d of cocaine self-administration. Behaviorally, mice exhibited progressive stabilization of operant responding and locomotion across 11 d of cocaine self-administration. During the early training days, we detected a portion of NAc neurons-a potential neuronal ensemble-that exhibited increased activities temporally contingent to the lever-press for cocaine. The number of NAc neurons exhibiting contingent activity increased progressively over the first three training days and then decreased gradually during the later training days, exhibiting expansion-refinement dynamics that may correspond to the acquisition and subsequent stabilization/maintenance of cocaine self-administration. Using a neuron-tracking technique, we found that the lever-press-contingent NAc ensemble exhibited substantial compositional dynamics, with neurons dropping into and out across training days. These activity features of lever-press-contingent neurons may represent key circuit dynamics of the NAc that transition the acquisition toward the maintenance of cocaine-taking behavior.

Animals↗

PubMed1979

Effect of boundaries on the response of a neural network.

The effect an abrupt boundary has upon the dynamical response of a neural network is investigated. The retina of the Limulus eye is used as a model system for studying this effect. A theoretical technique is presented for the quantitative prediction of the manner in which this neural network responds in the vicinity of its boundary. Corresponding experimental measurements of the response to moving stimuli by single optic neurons located near retinal boundaries are presented. Theory and experiment show detailed quantitative agreement.

Animals↗

PubMed1979

Dynamics of phospholipids in cultured cells of neural origin.

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Cell Line↗

PubMed2026

Altered EEG microstate dynamics reflect depressive symptoms in temporal lobe epilepsy.

BACKGROUND: Depressive symptoms are a common and disabling comorbidity in temporal lobe epilepsy (TLE), yet the neural mechanisms linking seizure networks to affective symptoms remain unclear. Although limbic network dysfunction has been implicated in both epilepsy and depressive disorders, it is unknown whether the time-varying dynamics of large-scale electrophysiological brain states reflect depressive symptom severity in TLE. In this study, we examined whether EEG microstate dynamics capture network alterations associated with depressive symptoms in individuals with unilateral TLE. METHODS: We analyzed resting-state, visually normal scalp EEG from 26 individuals with unilateral TLE. EEG microstates were identified by clustering global field power peaks into four canonical classes, with electrode positions mirrored to align the ictal hemisphere across subjects. Microstate dwell time, fractional occupancy, global transition entropy, and Markov transition probabilities were quantified and related to Beck Depression Inventory-II (BDI) scores. RESULTS: Individuals with high depressive symptoms (BDI ≥ 13; N = 12) exhibited longer mean dwell time in the ictal hemisphere-aligned microstate compared with individuals with low depressive symptom burden (BDI < 13; N = 14). Across subjects, dwell time in this microstate correlated with depressive symptom severity (r = 0.57, p = 0.002). TLE individuals with higher depressive symptoms exhibited reduced global transition entropy (p = 0.02), which also correlated with depressive symptom severity (r = -0.54, p = 0.004), indicating decreased flexibility of microstate transitions. Despite similar fractional occupancy of this state between groups, individuals with higher depressive symptoms were less likely to transition into the ictal hemisphere-aligned microstate from non-ictal or posterior configurations. Once engaged, however, the ictal-aligned microstate showed increased persistence, indicating prolonged stabilization of this network configuration. CONCLUSION: Higher depressive symptom burden in unilateral TLE is associated with increased temporal rigidity of the ictal hemisphere-aligned brain microstate, reflecting impaired disengagement of epileptogenic network configurations. These findings suggest that depressive symptoms in TLE may be associated with epilepsy-related disruptions in large-scale neural dynamics.

Humans↗

PubMed2025

PUS7-dependent Ψ reshapes specific synaptic gene exons to facilitate fear extinction memory formation.

RNA modifications serve as dynamic regulators of neural plasticity through their ability to fine-tune transcript stability and splicing. Pseudouridine (Ψ), an evolutionarily conserved RNA modification catalyzed by pseudouridine synthases, plays established roles in neurodevelopment, yet its functional significance in activity-dependent behavioral adaptation remains poorly defined. Here, we investigate Ψ-mediated epitranscriptomic regulation within the infralimbic prefrontal cortex (ILPFC), a brain region requiring precise synaptic remodeling for the clinically relevant form of fear extinction memory. Combining transcriptome-wide pseudouridylation profiling with behavioral analysis in mice, we identified selective Ψ enrichment at exons of synaptic regulatory genes within ILPFC during fear extinction learning. Fear extinction in the ILPFC drives concomitant exonic Ψ deposition and upregulation of synaptogenic transcripts, processes that involve pseudouridine synthase PUS7. Crucially, PUS7 knockdown in the ILPFC selectively impaired fear extinction memory formation without altering baseline fear expression, establishing a causal link between Ψ-dependent RNA processing and activity-dependent synaptic structural remodeling in this microcircuit. Our findings demonstrate that PUS7-mediated Ψ modification spatiotemporally regulates activity-dependent RNA dynamics in the ILPFC, providing the evidence that epitranscriptomic mechanisms precisely coordinate synaptic gene expression within behaviorally defined brain sub-region. This work bridges molecular RNA biology with systems neuroscience, revealing a novel mechanism for activity-dependent regulation of fear extinction in ILPFC.

Animals↗

PubMed1979

Influence of neural and humoral beta-adrenoceptor stimulation on dynamic myogenic microvascular reactivity in cat skeletal muscle.

Analysis of myogenic microvascular reactivity in terms of its recently described prominent dynamic component was performed before and during graded sympathetic stimulation and catecholamine infusion. Phenoxybenzamine and propranolol were used to differentiate between alpha- and beta-adrenoceptor effects. The study first confirmed previous findings of a beta-adrenergic inhibitory component in the neural control of microvascular resistance which attenuated the alpha-adrenergic constriction. The results concerning the interaction between adrenergic and myogenic control mechanisms corroborated the conclusion that the sympathoadrenal system, via its beta-adrenergic link, exerts effective inhibitory action on myogenic excitatory reactions. As regards the neural control, its beta-adrenergic component seemed to quite precisely compensate for the reinforcing effect on the myogenic constrictor response which results from increased vascular tone per se (in this case caused by alpha-adrenergic constriction), interpreted as a physical 'gain' effect inherent in the inverse fourth power relationship between radius and resistance. The latter complicating factor, which implies non-linearity in integrated peripheral resistance control, was thus revealed only after beta-blockade, but not on the vascular bed with intact adrenoceptors, where a given transmural pressure stimulus evoked an almost equally large myogenic constrictor response irrespective of the prevailing level of vascular tone. The beta-inhibitory action of blood-borne noradrenaline was similar to the neural one, whereas that of adrenaline was more effective, causing decline of myogenic reactivity below control.

Adrenergic beta-Agonists↗

PubMedDate not supplied

The surgical treatment of extratemporal facial paralysis: an overview.

At present there is no single surgical approach that is ideally suited to rehabilitation of the paralyzed face. Dynamic reconstruction and neural reconstitution are usually preferred to static methods, except under special circumstances. Experience with over 150 autogenous facial-nerve grafts using epineural suture technique has resulted in return of movement in 95% of properly selected patients. When grafting is not feasible, as in the obliterated central facial nerve, hypoglossal-facial-nerve crossover is a simple and powerful source of reinnervation, usually resulting in minimal intraoral crippling and mild mass movement. A newer procedure, the cross-face nerve graft, is an alternative to hypoglossal crossover, although it results in less axonal input and longer regenerative time. In cases of long-standing facial paralysis with muscle atrophy, temporalis and masseter transfers are dependable and may sometimes be combined with a nerve graft.

Cervical Plexus↗

PubMed1976

Dynamic aspects of peripheral nerve changes in progressive neural muscular atrophy: light- and electronmicroscopic studies of serial nerve biopsies.

Serial nerve biopsies were performed at an early, and at an advanced stage of the disease in 2 patients with progressive neural muscular atrophy. The early biopsy showed a complete loss of the large diameter and thickly myelinated fibres, as well as an expansion of the endoneurial interstitium in both cases. Myelinated and unmyelinated fibres exhibited axonal degeneration in all biopsies occasionally. "Onion bulb" formation, a typical feature of peripheral neuropathy in neural muscular atrophy, was found to be prominent only in the latter biopsies. As regards the formal pathogenesis of hypertrophic neuropathy in neural muscular atrophy, axonal dystrophy and interstitial changes of the endoneurium were regarded as primary phenomena, demyelination and "onion bulb" formation as secondary. A possible causal relation between axonal dystrophy and interstitial changes, observed in these cases, is discussed in the light of the present literature.

Adolescent↗

PubMed2026

Microglial modulation in general anesthesia: molecular.

General anesthetics profoundly alter brain function and consciousness, yet the mechanisms underlying these effects remain incompletely understood. Although traditional studies have primarily focused on neuronal targets, accumulating evidence suggests that microglia dynamically respond to anesthetic exposure and may participate in anesthesia-associated neurophysiological changes. Beyond their established immune functions, microglia are increasingly implicated in synaptic remodeling, metabolic regulation, neuronal activity surveillance, and neuron-glia communication. Recent studies indicate that different classes of anesthetic agents modulate microglial activity through diverse and context-dependent mechanisms involving inflammatory signaling, purinergic pathways, calcium dynamics, mitochondrial metabolism, and neural circuit interactions. These responses are associated with postoperative neurocognitive disorders, altered synaptic plasticity, and anesthesia-related changes in brain states. In this review, we summarize current evidence regarding the effects of volatile anesthetics, intravenous anesthetics, and analgesics on microglial function and discuss the molecular, functional, and circuit-level mechanisms underlying anesthesia-associated neuron-microglia interactions. We further highlight the dynamic and heterogeneous nature of microglial responses during anesthesia and discuss current limitations in the field, including the lack of temporally resolved and cell-specific approaches. Understanding these processes may provide insights into anesthesia-associated neurocognitive dysfunction and support the development of neuroimmune-targeted strategies in anesthesiology.

General anesthesia↗