Frontiers in Computational Neuroscience最新文献

Understanding how functional connectivity between cortical neurons varies with spatial distance is crucial for characterizing large-scale neural dynamics. However, inferring these spatial patterns is challenging when spike trains are collected from large populations of neurons. Here, we present a maximum likelihood estimation (MLE) framework to quantify distance-dependent functional interactions directly from observed spiking activity. We validate this method using both synthetic spike trains generated from a linear Poisson model and biologically realistic simulations performed with Izhikevich neurons. We then apply the approach to large-scale electrophysiological recordings from V1 cortical neurons. Our results show that the proposed MLE approach robustly captures spatial decay in functional connectivity, providing insights into the spatial structure of population-level neural interactions.

Introduction: The effectiveness of neural interfacing devices depends on the anatomical and physiological properties of the target region. Multielectrode arrays, used for neural recording and stimulation, are influenced by electrode placement and stimulation parameters, which critically impact tissue response. This study presents a multiscale computational model that predicts responses of neurons in the hippocampus-a key brain structure primarily involved in memory formation, especially the conversion of short-term memories into long-term storage-to extracellular electrical stimulation, providing insights into the effects of electrode positioning and stimulation strategies on neuronal response.

Methods: We modeled the rat hippocampus with highly detailed axonal projections, integrating the Admittance Method to model propagation of the electric field in the tissue with the NEURON simulation platform. The resulting model simulates electric fields generated by virtual electrodes in the perforant path of entorhinal cortical (EC) axons projecting to the dentate gyrus (DG) and predicts DG granule cell activation via synaptic inputs.

Results: We determined stimulation amplitude thresholds required for granule cell activation at different electrode placements along the perforant path. Membrane potential changes during synaptic activation were validated against experimental recordings. Additionally, we assessed the effects of bipolar electrode placements and stimulation amplitudes on direct and indirect activation.

Conclusion: Stimulation amplitudes above 750 μA consistently activate DG granule cells. Lower stimulation amplitudes are required for axonal activation and downstream synaptic transmission when electrodes are placed in the molecular layer, infra-pyramidal region, and DG crest.

Significance: The study and underlying methodology provide useful insights to guide the stimulation protocol required to activate DG granule cells following the stimulation of EC axons; the complete realistic 3D model presented constitutes an invaluable tool to strengthen our understanding of hippocampal response to electrical stimulation and guide the development and placement of prospective stimulation devices and strategies.

The energy demands of modern AI systems have reached unprecedented levels, driven by the rapid scaling of deep learning models, including large language models, and the inefficiencies of current computational architectures. In contrast, biological neural systems operate with remarkable energy efficiency, achieving complex computations while consuming orders of magnitude less power. A key mechanism enabling this efficiency is subthreshold processing, where neurons perform computations through graded, continuous signals below the spiking threshold, reducing energy costs. Despite its significance in biological systems, subthreshold processing remains largely overlooked in AI design. This perspective explores how principles of subthreshold dynamics can inspire the design of novel AI architectures and computational methods as a step toward advancing TinyAI. We propose pathways such as algorithmic analogs of subthreshold integration, including graded activation functions, dendritic-inspired hierarchical processing, and hybrid analog-digital systems to emulate the energy-efficient operations of biological neurons. We further explore neuromorphic and compute-in-memory hardware platforms that could support these operations, and propose a design stack aligned with the efficiency and adaptability of the brain. By integrating subthreshold dynamics into AI architecture, this work provides a roadmap toward sustainable, responsive, and accessible intelligence for resource-constrained environments.

Functional connectivity (FC) is a widely used indicator of brain function in health and disease, yet its neurobiological underpinnings still need to be firmly established. Recent advances in computational modelling allow us to investigate the relationship of both static FC (sFC) and dynamic FC (dFC) with neurobiology non-invasively. In this study, we modelled the brain activity of 200 healthy individuals based on empirical resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data. Simulations were conducted using a group-averaged structural connectome and four parameters guiding global integration and local excitation-inhibition balance: (i) G, a global coupling scaling parameter; (ii) J _i , an inhibitory coupling parameter; (iii) J _N , the excitatory NMDA synaptic coupling parameter; and (iv) w _p , the excitatory population recurrence weight. For each individual, we optimised the parameters to replicate empirical sFC and temporal correlation (TC). We analysed associations between brain-wide sFC and TC features with optimal model parameters and fits with a univariate correlation approach and multivariate prediction models. In addition, we used a group-average perturbation approach to investigate the effect of coupling in each region on overall network connectivity. Our models could replicate empirical sFC and TC but not the FC variance or node cohesion (NC). Both fits and parameters exhibited strong associations with brain connectivity. G correlated positively and J _N negatively with a range of static and dynamic FC features (|r| > 0.2, p _FDR < 0.05). TC fit correlated negatively, and sFC fit positively with static and dynamic FC features. TC features were predictive of TC fit, sFC features of sFC fit (R ² > 0.5). Perturbation analysis revealed that the sFC fit was most impacted by coupling changes in the left paracentral gyrus (Δr = 0.07), TC fit by alterations in the left pars triangularis (Δr = 0.24). Our findings indicate that neurobiological characteristics are associated with individual variability in sFC and dFC, and that sFC and dFC are shaped by small sets of distinct regions. By modelling both sFC and dFC, we provide new evidence of the role of neurophysiological characteristics in establishing brain network configurations.

Memory impairment is a prevalent symptom in patients with Alzheimer's disease (AD), with working memory loss being the most prominent deficit. Recent experimental evidence suggests that abnormal calcium levels in the Endoplasmic Reticulum (ER) may disrupt synaptic transmission, leading to memory loss in AD patients. However, the specific mechanisms by which intracellular calcium homeostasis influences memory formation, storage, and recall in the context of AD remain unclear. In this study, we investigate the effects of intracellular calcium homeostasis on AD-related working memory (WM) using a spiking network model. We quantify memory storage by measuring the similarity between images during the training and testing phases. The model results indicate that ~90% of memory can be stored in the WM network under normal conditions. In contrast, the presence of amyloid beta (Aβ), associated with AD, significantly reduces this similarity, allowing only 54%-58% of memory to be stored, this alteration trend is consistent with previous experimental findings. Further analysis reveals that downregulating the activation of inositol triphosphate (IP ₃) receptors and upregulating the activation of the sarco-endoplasmic reticulum Ca ²⁺ ATPase (SERCA) pumps can enhance memory performance, achieving about 78% and 77%, respectively. Moreover, simultaneously manipulating both IP ₃ and SERCA activations can increase memory capacity to around 81%. These findings suggest several potential therapeutic targets for addressing memory impairment in Aβ aggregation induced AD patients. Additionally, our network model could serve as a foundation for exploring further mechanisms that modulate memory dysfunction at the genetic, cellular, and network levels.

Many computational models that incorporate spike-timing-dependent plasticity (STDP) have shown the ability to learn from stimuli, supporting theories that STDP is a sufficient basis for learning and memory. However, to prevent runaway activity and potentiation, particularly within recurrent networks, additional global mechanisms are commonly necessary. A STDP-based learning rule, which involves local resource-dependent potentiation and heterosynaptic depression, is shown to enable stable learning in recurrent spiking networks. A balance between potentiation and depression facilitates synaptic homeostasis, and learned synaptic characteristics align with experimental observations. Furthermore, this resource-based STDP learning rule demonstrates an innate compensatory mechanism for synaptic degeneration.

Despite state-of-the-art technologies like artificial intelligence, human judgment is critically essential in cooperative systems, such as the multi-agent system (MAS), which collect information among agents based on multiple-cue judgment. Human agents can prevent impaired situational awareness of automated agents by confirming situations under environmental uncertainty. System error caused by uncertainty can result in an unreliable system environment, and this environment affects the human agent, resulting in non-optimal decision-making in MAS. Thus, it is necessary to know how human behavior is changed to capture system reliability under uncertainty. Another issue affecting MAS is time delay, which can delay agent information transfer, resulting in low performance and instability. However, it is difficult to find studies on the influence of time delay on human agents. This study is about understanding the human decision-making process under a specific system reliability environment by uncertainty with time delay. We used concepts of expected and unexpected uncertainty to implement reliability of the system usage environment with three types of time delay conditions: no time delay, regular time delay, and irregular time delay conditions. We used electroencephalogram (EEG) for human cognitive neural mechanisms in multiple-cue judgment systems to understand human decision-making. In the reliability of system usage environment, the unreliable system environment significantly creates less memory load by less utilization of system rules for decision-making. In terms of time delay, delayed information delivery does not significantly affect memory load for decision-making.