Daily Papers

Recent breakthroughs in synaptic-resolution network connectomics have revealed that brain circuits feature fine-scale structural connectivity, such as pairs of correlated synaptic couplings known as second-order motifs. Large-scale recordings of neuronal activity in networks containing nonlinear neurons reveal macroscopic heterogeneous population dynamics throughout the brain. These findings rekindle the inquiry into this intriguing question: Can microscale synaptic structures contribute to macroscopic heterogeneous dynamics and computations in ways that canonical brain circuit models cannot? To answer this question, we create random RNNs with various cell types, nonlinear non-negative neural responses, and arbitrary marginal and second-order correlated synaptic statistics. We derive mean-field low-rank equations for P-population networks in which the pre- and postsynaptic neuronal population identities determine the synaptic and motif strengths. Our framework requires 2P latent dynamic variables with P variables describing mean population activity and P variables capturing within-population variability. Theoretical and simulational results demonstrate that chain motifs induce correlations in synaptic variability, enabling microscopic fluctuations to be integrated and influence mesoscopic mean population dynamics. We apply this framework to reverse engineer network connectivity that recapitulates the heterogeneous activity across the population in the mouse primary visual cortex. By bridging the gap between synaptic organization and nonlinear heterogeneous population dynamics, our results offer a principled approach and testable predictions regarding the relationship between fine-scale connectivity, heterogeneous dynamics, and functional computations.

Traveling waves of activity in neural tissue can be halted by spatial inhomogeneity in synaptic coupling. We study an integrate-and-fire network in which each neuron fires once and the coupling decays exponentially. For this model the leading-edge firing map reduces exactly to a scalar equation for the wave speed in space, with a slow unstable and a fast stable homogeneous speed, c_1 and c_2, and a periodic modulation of the coupling enters this equation pointwise. Positive periodic waves terminate in folds. For slowly varying modulation the fold amplitude approaches a plateau set by the trough of the modulation, where the local bottleneck speed is c_1 c_2; the approach to the plateau is set by the local geometry of the trough. For rapidly varying modulation the fold amplitude grows linearly with frequency, with a slope given by a full-amplitude average over the integrated modulation profile; a weak-ripple truncation of that average overestimates the slope about 2.5-fold at the default coupling. A perturbative recursion in the amplitude gives the speed profile explicitly. We distinguish loss of the periodic wave from failure of a particular launch, and the excitatory regime εle 1 from its sign-changing extension. The results are checked against direct integration of the reduced equation and first-spike firing-map simulations of the network.

We study a fully connected Hopfield-type associative memory network with online activity-dependent synaptic plasticity, where neural states and synaptic couplings coevolve during retrieval. Using the generating-functional formalism, we derive a dynamical mean-field theory (DMFT) in the large-system limit with extensively many stored random patterns, and show that the many-body dynamics reduces to an effective single-site stochastic process with colored Gaussian crosstalk noise and delayed feedback terms. Numerical solutions of the DMFT equations agree well with direct simulations. We find that moderate plasticity enlarges the basin of attraction and increases the maximum retrievable memory load by generating a positive delayed feedback that stabilizes retrieval against crosstalk noise. However, excessively strong plasticity causes the network to imprint the imperfect initial cue itself, leading to spurious attractors and degraded retrieval performance. Consequently, an optimal plasticity strength emerges from the trade-off between memory stabilization and premature cue imprinting. These results extend the DMFT description of associative memory to networks with coevolving neural and synaptic dynamics.

In order to study oscillators coupled by pulses emitted at discrete times, it is generally assumed that the effect of each pulse is an instantaneous phase shift, with a possible conduction delay between emission and receipt. However, we are interested in neural oscillators in which each pulse (action potential) activates a biexponential synapse, and at high frequencies, the duration of the synaptic conductance may be greater than the network period. Therefore, the effect of received pulses can summate over the course of several cycles. To overcome this limitation, we previously defined a mean field approach for a single synchronous population. Here, we extend it to two alternating synchronous populations by assuming a perturbation of a single oscillator from one of the synchronous populations which is represented by a single self-connected neural oscillator. The train of delayed biexponential synapses emitted by each oscillator is divided into a tonic and a phasic component. Because of the continuous rather than pulsatile nature of the input, we had to drop the concept of oscillator phase and derive self-consistent criteria for the existence and stability of an alternating firing pattern between two synchronous populations based solely on the perturbation of time intervals from their steady state values. Simulations showed that for high frequency oscillations as defined above, the mean field approach predicts the existence and stability of phase-locking between two synchronous populations better than the instantaneous phase shift approach. This approach may generalize to other forms of coupling amongst non-neural oscillators.

Learning and decision making in the brain are key processes critical to survival, and yet are processes implemented by non-ideal biological building blocks which can impose significant error. We explore quantitatively how the brain might cope with this inherent source of error by taking advantage of two ubiquitous mechanisms, redundancy and synchronization. In particular we consider a neural process whose goal is to learn a decision function by implementing a nonlinear gradient dynamics. The dynamics, however, are assumed to be corrupted by perturbations modeling the error which might be incurred due to limitations of the biology, intrinsic neuronal noise, and imperfect measurements. We show that error, and the associated uncertainty surrounding a learned solution, can be controlled in large part by trading off synchronization strength among multiple redundant neural systems against the noise amplitude. The impact of the coupling between such redundant systems is quantified by the spectrum of the network Laplacian, and we discuss the role of network topology in synchronization and in reducing the effect of noise. A range of situations in which the mechanisms we model arise in brain science are discussed, and we draw attention to experimental evidence suggesting that cortical circuits capable of implementing the computations of interest here can be found on several scales. Finally, simulations comparing theoretical bounds to the relevant empirical quantities show that the theoretical estimates we derive can be tight.

High-resolution brain imaging can now capture not just synapse locations but their molecular composition, with the cost of such mapping falling exponentially. Yet such ultrastructural data has so far told us little about local neuronal physiology - specifically, the parameters (e.g., synaptic efficacies, local conductances) that govern neural dynamics. We propose to translate molecularly annotated ultrastructure into physiology, introducing the concept of an ultrastructure-to-dynamics compiler: a learned mapping from molecularly annotated ultrastructure to simulator-ready, uncertainty-aware physiological parameters. The requirement is paired training data, with jointly acquired ultrastructure from imaging, and dynamical responses to perturbations from physiological experiments. With this data we can train models that predict local physiology directly from structure. Such a compiler would support biophysical simulations by turning anatomical maps into models of circuit dynamics, shifting structure-to-function from a descriptive program to a predictive one and opening routes to understanding neural computation and forecasting intervention effects.

Human cognition emerges from coordinated spiking dynamics in distributed neural circuits, where information is encoded via both firing rates and precise spike timing determined by brain rhythms. Inspired by this notion, we propose a brain-inspired learning primitive in which cognition-level neural synchrony emerges through iterative bottom-up and top-down interactions between micro-scale dynamics of spiking neurons and a macro-scale mechanism of oscillatory synchronization. Specifically, we model each parcel (e.g., a cortical region or an image pixel) in the target system as a spiking neuron embedded in a predefined connectivity scaffold. Low-level information is encoded in a spatiotemporal domain, where neurons are selectively grouped and fire spontaneously over time through self-organized dynamics. In the bottom-up route, oscillatory synchronization is formed from past spiking activity accumulated over a finite memory window. Since brain dynamics operate in a regime of partial and transient synchronization rather than global phase locking, we model oscillatory coordination using a time-delayed synchronization formulation, which enables a top-down modulation of heterogeneous neural spiking for a large-scale distributed system. Together, we devise a spiking-by-synchronization neural network (S2-Net) that uses rhythmic timing as a control mechanism for efficient information processing. Promising results have been achieved across a broad range of tasks, including neural activity decoding, energy-efficient signal processing, temporal binding and semantic reasoning.

The static synaptic connectivity of neuronal circuits stands in direct contrast to the dynamics of their function. As in changing community interactions, different neurons can participate actively in various combinations to effect behaviors at different times. We introduce an unsupervised approach to learn the dynamic affinities between neurons in live, behaving animals, and to reveal which communities form among neurons at different times. The inference occurs in two major steps. First, pairwise non-linear affinities between neuronal traces from brain-wide calcium activity are organized by non-negative tensor factorization (NTF). Each factor specifies which groups of neurons are most likely interacting for an inferred interval in time, and for which animals. Finally, a generative model that allows for weighted community detection is applied to the functional motifs produced by NTF to reveal a dynamic functional connectome. Since time codes the different experimental variables (e.g., application of chemical stimuli), this provides an atlas of neural motifs active during separate stages of an experiment (e.g., stimulus application or spontaneous behaviors). Results from our analysis are experimentally validated, confirming that our method is able to robustly predict causal interactions between neurons to generate behavior. Code is available at https://github.com/dyballa/dynamic-connectomes.

The approximation capability of ANNs and their RNN instantiations, is strongly correlated with the number of parameters packed into these networks. However, the complexity barrier for human understanding, is arguably related to the number of neurons and synapses in the networks, and to the associated nonlinear transformations. In this paper we show that the use of biophysical synapses, as found in LTCs, have two main benefits. First, they allow to pack more parameters for a given number of neurons and synapses. Second, they allow to formulate the nonlinear-network transformation, as a linear system with state-dependent coefficients. Both increase interpretability, as for a given task, they allow to learn a system linear in its input features, that is smaller in size compared to the state of the art. We substantiate the above claims on various time-series prediction tasks, but we believe that our results are applicable to any feedforward or recurrent ANN.

We show that in a drive-response coupling framework extreme events are suppressed in the response system by the dominance of a single driving signal. We validate this approach across three distinct response network topologies, namely (i) a pair of coupled neurons, (ii) a monolayer network of N coupled neurons and (iii) a two-layer multiplex network each composed of FitzHugh-Nagumo neuronal units. The response networks inherently exhibit extreme events. Our results demonstrate that influencing just one neuron in the response network with an appropriately tuned driving signal is sufficient to control extreme events across all three configurations. In the two-neuron case, suppression of extreme events occurs due to the breaking of phase-locking between the driving neuron and the targeted response neuron. In the case of monolayer and multiplex networks, suppression of extreme events results from the disruption of protoevent frequency dynamics and a subsequent frequency decoupling of the driven neuron from the rest of the network. We also observe that when the size of the neurons in response network connected to the drive increases, the onset of control occurs earlier indicating a scaling advantage of the method.

Multimodal data is a precious asset enabling a variety of downstream tasks in machine learning. However, real-world data collected across different modalities is often not paired, which is a significant challenge to learn a joint distribution. A prominent approach to address the modality coupling problem is Minimum Entropy Coupling (MEC), which seeks to minimize the joint Entropy, while satisfying constraints on the marginals. Existing approaches to the MEC problem focus on finite, discrete distributions, limiting their application for cases involving continuous data. In this work, we propose a novel method to solve the continuous MEC problem, using well-known generative diffusion models that learn to approximate and minimize the joint Entropy through a cooperative scheme, while satisfying a relaxed version of the marginal constraints. We empirically demonstrate that our method, DDMEC, is general and can be easily used to address challenging tasks, including unsupervised single-cell multi-omics data alignment and unpaired image translation, outperforming specialized methods.

A growing literature in computational neuroscience leverages gradient descent and learning algorithms that approximate it to study synaptic plasticity in the brain. However, the vast majority of this work ignores a critical underlying assumption: the choice of distance for synaptic changes - i.e. the geometry of synaptic plasticity. Gradient descent assumes that the distance is Euclidean, but many other distances are possible, and there is no reason that biology necessarily uses Euclidean geometry. Here, using the theoretical tools provided by mirror descent, we show that the distribution of synaptic weights will depend on the geometry of synaptic plasticity. We use these results to show that experimentally-observed log-normal weight distributions found in several brain areas are not consistent with standard gradient descent (i.e. a Euclidean geometry), but rather with non-Euclidean distances. Finally, we show that it should be possible to experimentally test for different synaptic geometries by comparing synaptic weight distributions before and after learning. Overall, our work shows that the current paradigm in theoretical work on synaptic plasticity that assumes Euclidean synaptic geometry may be misguided and that it should be possible to experimentally determine the true geometry of synaptic plasticity in the brain.

The spectral behaviour of the synaptic matrix, representing the neuronal connection strengths, is an important tool to analyze the stability and transient dynamics of a typical brain as well as its learning process and memory capacity. The complexity of the brain due to large number of neurons as well as underlying transient mechanisms e.g. homeostasis, seizure or synaptic plasticity can lead to networks with time-varying degree and type of sparsity. This renders an exact determination of the synaptic matrix not only technically difficult but also meaningless, leaving its statistical analysis as the best available theoretical approach. This motivates us to pursue a spectral analysis of the synaptic matrix models with different type of sparsity and thereby analyze latter's role on various aspects of network dynamics and stability. Our results have potential relevance for detemining the type of synaptic sparsity required to induce a specific brain function or desired transient mechanism e.g for pharmacological effects or physiological modulators.

Self-sustained neural activity in the absence of ongoing external input is a fundamental feature of nervous system dynamics, yet the conditions under which it can emerge in biophysically grounded network models remain incompletely understood. We studied whether a recurrent network of Hodgkin-Huxley neurons with spike-timing-dependent plasticity and intrinsic stochasticity can maintain autonomous activity after brief transient stimulation. The simulated network comprised 200 neurons (160 excitatory, 40 inhibitory) with 80% connection probability, incorporating excitatory and inhibitory STDP, probabilistic vesicle release, probabilistic synapse formation, receptor variability, and voltage-dependent inhibition. After a brief 200 ms initialization stimulus to 30 excitatory neurons, the network received no further external input. In one 1800 s simulation and two additional 500 s simulations, the network maintained sparse, irregular activity without ongoing drive. In the 1800 s run, 67% of neurons exhibited mean firing rates below 1 Hz, the population mean firing rate was 1.13 +/- 1.34 Hz, participation increased across longer observation windows, and population-mean Fano factors remained near 1-2, consistent with irregular spike timing. Raster activity also showed spontaneous qualitative reorganizations in collective firing patterns over time. These findings suggest that recurrent Hodgkin-Huxley networks with plastic and stochastic synapses can sustain long-duration autonomous activity in a sparse firing regime after brief initialization.

Macroscopic EEG fields can be an explicit top-down neocortical mechanism that directly drives bottom-up processes that describe memory, attention, and other neuronal processes. The top-down mechanism considered are macrocolumnar EEG firings in neocortex, as described by a statistical mechanics of neocortical interactions (SMNI), developed as a magnetic vector potential A. The bottom-up process considered are Ca^{2+} waves prominent in synaptic and extracellular processes that are considered to greatly influence neuronal firings. Here, the complimentary effects are considered, i.e., the influence of A on Ca^{2+} momentum, p. The canonical momentum of a charged particle in an electromagnetic field, mathbfΠ = p + q A (SI units), is calculated, where the charge of Ca^{2+} is q = - 2 e, e is the magnitude of the charge of an electron. Calculations demonstrate that macroscopic EEG A can be quite influential on the momentum p of Ca^{2+} ions, in both classical and quantum mechanics. Molecular scales of Ca^{2+} wave dynamics are coupled with A fields developed at macroscopic regional scales measured by coherent neuronal firing activity measured by scalp EEG. The project has three main aspects: fitting A models to EEG data as reported here, building tripartite models to develop A models, and studying long coherence times of Ca^{2+} waves in the presence of A due to coherent neuronal firings measured by scalp EEG. The SMNI model supports a mechanism wherein the p + q A interaction at tripartite synapses, via a dynamic centering mechanism (DCM) to control background synaptic activity, acts to maintain short-term memory (STM) during states of selective attention.

Contextual memory integration remains a high challenge in the development of language models, particularly in tasks that require maintaining coherence over extended sequences. Traditional approaches, such as self-attention mechanisms and memory-augmented architectures, often prioritize short-term dependencies, leading to fragmentation and inconsistency in long-range contextual understanding. Inspired by principles of synaptic plasticity observed in biological neural systems, a novel mechanism, Synaptic Resonance, is introduced to dynamically reinforce relevant memory pathways during training and inference. Unlike static memory representations, this mechanism continuously adjusts synaptic weight matrices based on contextual relevance, allowing for improved information retention without excessive computational overhead. Evaluations conducted on an open-source language model demonstrate reductions in perplexity, enhancements in contextual coherence, and increased robustness against input noise, highlighting the effectiveness of reinforcement-driven memory modulation. Comparative analysis against baseline models further reveals that the proposed approach achieves higher memory retention efficiency while maintaining computational feasibility. The architectural modifications integrate seamlessly into existing transformer-based frameworks, ensuring stable convergence and efficient inference without sacrificing scalability. Applications benefiting from improved long-term contextual consistency, such as dialogue systems and document summarization, stand to gain from this approach. Empirical findings suggest that dynamically reinforced memory pathways offer a promising alternative to conventional memory mechanisms, addressing longstanding limitations in extended sequence modeling.

Astrocytes are increasingly recognized as active regulators of neural dynamics, yet their role in large-scale synchronization remains incompletely understood. Building on the discovery of breathing cluster synchronization in neuron-astrocyte networks, we investigate whether this phenomenon persists under more biologically realistic conditions by incorporating thermosensitive neuronal dynamics, intrinsic electric-field interactions, stochastic perturbations, and delayed astrocytic feedback. Through systematic numerical simulations of a network containing structurally symmetric neuronal subsets, we show that breathing clusters characterized by intermittent alternations between synchronized and desynchronized states, remain robust across a broad range of biophysical conditions. The results reveal a non-monotonic dependence on astrocytic attenuation and feedback parameters, with intermediate values maximizing rhythmic switching through a slow push-pull regulatory mechanism. Temperature and electric-field effects primarily modulate neuronal excitability and the tolerance of the breathing state to noise, while elevated stochastic perturbations progressively destabilize cluster coherence. In contrast, the phenomenon exhibits remarkable robustness to biologically realistic astrocytic delays. Importantly, our findings indicate that the emergence of breathing synchronization remains fundamentally governed by the interplay between network symmetry and astrocyte-mediated feedback, whereas temperature, electric fields, and noise act as modulators of its stability and temporal organization. These results establish breathing cluster synchronization as a robust organizing principle of astrocyte-regulated networks and provide a quantitative framework for understanding how glial regulation shapes cortical state-switching under realistic physiological conditions.

We propose a formal mathematical model for sparse representations and active dendrites in neocortex. Our model is inspired by recent experimental findings on active dendritic processing and NMDA spikes in pyramidal neurons. These experimental and modeling studies suggest that the basic unit of pattern memory in the neocortex is instantiated by small clusters of synapses operated on by localized non-linear dendritic processes. We derive a number of scaling laws that characterize the accuracy of such dendrites in detecting activation patterns in a neuronal population under adverse conditions. We introduce the union property which shows that synapses for multiple patterns can be randomly mixed together within a segment and still lead to highly accurate recognition. We describe simulation results that provide further insight into sparse representations as well as two primary results. First we show that pattern recognition by a neuron with active dendrites can be extremely accurate and robust with high dimensional sparse inputs even when using a tiny number of synapses to recognize large patterns. Second, equations representing recognition accuracy of a dendrite predict optimal NMDA spiking thresholds under a generous set of assumptions. The prediction tightly matches NMDA spiking thresholds measured in the literature. Our model matches many of the known properties of pyramidal neurons. As such the theory provides a mathematical framework for understanding the benefits and limits of sparse representations in cortical networks.

Learning synaptic weights of spiking neural network (SNN) models that can reproduce target spike trains from provided neural firing data is a central problem in computational neuroscience and spike-based computing. The discovery of the optimal weight values can be posed as a supervised learning task wherein the weights of the model network are chosen to maximize the similarity between the target spike trains and the model outputs. It is still largely unknown whether optimizing spike train similarity of highly recurrent SNNs produces weight matrices similar to those of the ground truth model. To this end, we propose flexible heuristic supervised learning rules, termed Pre-Synaptic Pool Modification (PSPM), that rely on stochastic weight updates in order to produce spikes within a short window of the desired times and eliminate spikes outside of this window. PSPM improves spike train similarity for all-to-all SNNs and makes no assumption about the post-synaptic potential of the neurons or the structure of the network since no gradients are required. We test whether optimizing for spike train similarity entails the discovery of accurate weights and explore the relative contributions of local and homeostatic weight updates. Although PSPM improves similarity between spike trains, the learned weights often differ from the weights of the ground truth model, implying that connectome inference from spike data may require additional constraints on connectivity statistics. We also find that spike train similarity is sensitive to local updates, but other measures of network activity such as avalanche distributions, can be learned through synaptic homeostasis.

How can we build agents that keep learning from experience, quickly and efficiently, after their initial training? Here we take inspiration from the main mechanism of learning in biological brains: synaptic plasticity, carefully tuned by evolution to produce efficient lifelong learning. We show that plasticity, just like connection weights, can be optimized by gradient descent in large (millions of parameters) recurrent networks with Hebbian plastic connections. First, recurrent plastic networks with more than two million parameters can be trained to memorize and reconstruct sets of novel, high-dimensional 1000+ pixels natural images not seen during training. Crucially, traditional non-plastic recurrent networks fail to solve this task. Furthermore, trained plastic networks can also solve generic meta-learning tasks such as the Omniglot task, with competitive results and little parameter overhead. Finally, in reinforcement learning settings, plastic networks outperform a non-plastic equivalent in a maze exploration task. We conclude that differentiable plasticity may provide a powerful novel approach to the learning-to-learn problem.

Large nonlinear recurrent neural networks with random couplings generate high-dimensional, potentially chaotic activity whose structure is of interest in neuroscience and other fields. A fundamental object encoding the collective structure of this activity is the N times N covariance matrix. Prior analytical work on the covariance matrix has been limited to low-dimensional summary statistics. Recent work proposed an ansatz in which, at large N, the covariance matrix for a typical quenched realization takes the same form as that of a linear network with the same couplings, driven by independent noise, with DMFT order parameters setting the transfer function and the noise spectrum. Here, we derive this ansatz using the two-site cavity method, providing two derivations with complementary perspectives. The first decomposes each unit's activity into a linear response to its local field and a nonlinear residual, and shows that cross-covariances between residuals at distinct sites are strongly suppressed, so the residuals act as independent noise driving a linear network. The second derives a self-consistent matrix equation for the covariance matrix. A naive Gaussian closure for the joint statistics of local fields at distinct sites misses cross terms that, in a linear network, would be generated by an external drive. The cavity method recovers these terms from non-Gaussian contributions, revealing an emergent external drive. Higher-order cross-site moments follow a Wick-like decomposition into products of pairwise covariances at leading order, reducing them to the linear-equivalent form. We verify the predictions in simulations. These results extend linear equivalence from feedforward high-dimensional nonlinear systems, where the activations are independent of the weights, to recurrent networks, where the activations are correlated with the couplings that generate them.

Sensory systems across all modalities and species exhibit adaptation to continuously changing input statistics. Individual neurons have been shown to modulate their response gains so as to maximize information transmission in different stimulus contexts. Experimental measurements have revealed additional, nuanced sensory adaptation effects including changes in response maxima and minima, tuning curve repulsion from the adapter stimulus, and stimulus-driven response decorrelation. Existing explanations of these phenomena rely on changes in inter-neuronal synaptic efficacy, which, while more flexible, are unlikely to operate as rapidly or reversibly as single neuron gain modulations. Using published V1 population adaptation data, we show that propagation of single neuron gain changes in a recurrent network is sufficient to capture the entire set of observed adaptation effects. We propose a novel adaptive efficient coding objective with which single neuron gains are modulated, maximizing the fidelity of the stimulus representation while minimizing overall activity in the network. From this objective, we analytically derive a set of gains that optimize the trade-off between preserving information about the stimulus and conserving metabolic resources. Our model generalizes well-established concepts of single neuron adaptive gain control to recurrent populations, and parsimoniously explains experimental adaptation data.

We explore the effects of various plasticity functions on assemblies of neurons. To bridge the gap between experimental and computational theories we make use of a conceptual framework, the Assembly Calculus, which is a formal system for the description of brain function based on assemblies of neurons. The Assembly Calculus includes operations for projecting, associating, and merging assemblies of neurons. Our research is focused on simulating different plasticity functions with Assembly Calculus. Our main contribution is the modification and evaluation of the projection operation. We experiment with Oja's and Spike Time-Dependent Plasticity (STDP) rules and test the effect of various hyper-parameters.

Modeling spatiotemporal coupling is a key challenge in building physical intelligence across scales, from microscopic to macroscopic. Existing models capture such structure broadly through physics-motivated dynamical formulations or learning-motivated architectures. The former provide stronger priors but may constrain flexibility, whereas the latter are more flexible but leave the spatiotemporal coupling largely implicit. We therefore seek an approach that combines flexible learning with an explicit geometric bias for jointly modeling time and space. To this end, we propose Minkowski Positional Encoding (MinkowskiPE), which uses joint temporal and spatial coordinates to parameterize Lorentz transformations applied to query and key features. With MinkowskiPE, the query-key attention score depends on position only through the relative spacetime displacement between the two tokens and is therefore invariant to global translation of the coordinates. This paradigm retains the standard dot-product attention interface and remains compatible with efficient attention implementations. We evaluate MinkowskiPE on microscopic molecular dynamics and macroscopic video prediction tasks, achieving the best results on all nine multi-trajectory molecular evaluations and reducing KTH video-prediction MSE by 9.9% relative to the best baseline while using roughly one-tenth as many parameters.

We characterise the dynamics of neuronal activity, in terms of field theory, using neural units placed on a 2D-lattice modelling the cortical surface. The electrical activity of neuronal units was analysed with the aim of deriving a neural field model with a simple functional form that still able to predict or reproduce empirical findings. Each neural unit was modelled using a neural mass and the accompanying field theory was derived in the continuum limit. The field theory comprised coupled (real) Klein-Gordon fields, where predictions of the model fall within the range of experimental findings. These predictions included the frequency spectrum of electric activity measured from the cortex, which was derived using an equipartition of energy over eigenfunctions of the neural fields. Moreover, the neural field model was invariant, within a set of parameters, to the dynamical system used to model each neuronal mass. Specifically, topologically equivalent dynamical systems resulted in the same neural field model when connected in a lattice; indicating that the fields derived could be read as a canonical cortical field theory. We specifically investigated non-dispersive fields that provide a structure for the coding (or representation) of afferent information. Further elaboration of the ensuing neural field theory, including the effect of dispersive forces, could be of importance in the understanding of the cortical processing of information.

We introduce Equilibrium Propagation, a learning framework for energy-based models. It involves only one kind of neural computation, performed in both the first phase (when the prediction is made) and the second phase of training (after the target or prediction error is revealed). Although this algorithm computes the gradient of an objective function just like Backpropagation, it does not need a special computation or circuit for the second phase, where errors are implicitly propagated. Equilibrium Propagation shares similarities with Contrastive Hebbian Learning and Contrastive Divergence while solving the theoretical issues of both algorithms: our algorithm computes the gradient of a well defined objective function. Because the objective function is defined in terms of local perturbations, the second phase of Equilibrium Propagation corresponds to only nudging the prediction (fixed point, or stationary distribution) towards a configuration that reduces prediction error. In the case of a recurrent multi-layer supervised network, the output units are slightly nudged towards their target in the second phase, and the perturbation introduced at the output layer propagates backward in the hidden layers. We show that the signal 'back-propagated' during this second phase corresponds to the propagation of error derivatives and encodes the gradient of the objective function, when the synaptic update corresponds to a standard form of spike-timing dependent plasticity. This work makes it more plausible that a mechanism similar to Backpropagation could be implemented by brains, since leaky integrator neural computation performs both inference and error back-propagation in our model. The only local difference between the two phases is whether synaptic changes are allowed or not.

How neuronal circuits achieve credit assignment remains a central unsolved question in systems neuroscience. Various studies have suggested plausible solutions for back-propagating error signals through multi-layer networks. These purely functionally motivated models assume distinct neuronal compartments to represent local error signals that determine the sign of synaptic plasticity. However, this explicit error modulation is inconsistent with phenomenological plasticity models in which the sign depends primarily on postsynaptic activity. Here we show how a plausible microcircuit model and Hebbian learning rule derived within an adaptive control theory framework can resolve this discrepancy. Assuming errors are encoded in top-down dis-inhibitory synaptic afferents, we show that error-modulated learning emerges naturally at the circuit level when recurrent inhibition explicitly influences Hebbian plasticity. The same learning rule accounts for experimentally observed plasticity in the absence of inhibition and performs comparably to back-propagation of error (BP) on several non-linearly separable benchmarks. Our findings bridge the gap between functional and experimentally observed plasticity rules and make concrete predictions on inhibitory modulation of excitatory plasticity.

The structure of biological neural circuits-modular, hierarchical, and sparsely interconnected-reflects an efficient trade-off between wiring cost, functional specialization, and robustness. These principles offer valuable insights for artificial neural network (ANN) design, especially as networks grow in depth and scale. Sparsity, in particular, has been widely explored for reducing memory and computation, improving speed, and enhancing generalization. Motivated by systems neuroscience findings, we explore how patterns of functional connectivity in the mouse visual cortex-specifically, ensemble-to-ensemble communication, can inform ANN design. We introduce G2GNet, a novel architecture that imposes sparse, modular connectivity across feedforward layers. Despite having significantly fewer parameters than fully connected models, G2GNet achieves superior accuracy on standard vision benchmarks. To our knowledge, this is the first architecture to incorporate biologically observed functional connectivity patterns as a structural bias in ANN design. We complement this static bias with a dynamic sparse training (DST) mechanism that prunes and regrows edges during training. We also propose a Hebbian-inspired rewiring rule based on activation correlations, drawing on principles of biological plasticity. G2GNet achieves up to 75% sparsity while improving accuracy by up to 4.3% on benchmarks, including Fashion-MNIST, CIFAR-10, and CIFAR-100, outperforming dense baselines with far fewer computations.

Recent advances in artificial neural networks for machine learning, and language modeling in particular, have established a family of recurrent neural network (RNN) architectures that, unlike conventional RNNs with vector-form hidden states, use two-dimensional (2D) matrix-form hidden states. Such 2D-state RNNs, known as Fast Weight Programmers (FWPs), can be interpreted as a neural network whose synaptic weights (called fast weights) dynamically change over time as a function of input observations, and serve as short-term memory storage; corresponding synaptic weight modifications are controlled or programmed by another network (the programmer) whose parameters are trained (e.g., by gradient descent). In this Primer, we review the technical foundations of FWPs, their computational characteristics, and their connections to transformers and state space models. We also discuss connections between FWPs and models of synaptic plasticity in the brain, suggesting a convergence of natural and artificial intelligence.

The deep neural nets of modern artificial intelligence (AI) have not achieved defining features of biological intelligence, including abstraction, causal learning, and energy-efficiency. While scaling to larger models has delivered performance improvements for current applications, more brain-like capacities may demand new theories, models, and methods for designing artificial learning systems. Here, we argue that this opportunity to reassess insights from the brain should stimulate cooperation between AI research and theory-driven computational neuroscience (CN). To motivate a brain basis of neural computation, we present a dynamical view of intelligence from which we elaborate concepts of sparsity in network structure, temporal dynamics, and interactive learning. In particular, we suggest that temporal dynamics, as expressed through neural synchrony, nested oscillations, and flexible sequences, provide a rich computational layer for reading and updating hierarchical models distributed in long-term memory networks. Moreover, embracing agent-centered paradigms in AI and CN will accelerate our understanding of the complex dynamics and behaviors that build useful world models. A convergence of AI/CN theories and objectives will reveal dynamical principles of intelligence for brains and engineered learning systems. This article was inspired by our symposium on dynamical neuroscience and machine learning at the 6th Annual US/NIH BRAIN Initiative Investigators Meeting.

In heterogeneous networks of coupled oscillators, phase frustration typically prevents the emergence of synchronization in the Sakaguchi--Kuramoto (SK) model. In this study, we propose an analytical framework to overcome this barrier and induce complete synchronization at a specified small coupling value in oscillators governed by phase-frustrated bi-harmonic coupling. We derive an optimal set of natural frequencies that is robust against added noise and correlated with the network degree heterogeneity, along with the parameters involved in the bi-harmonic coupling function that lead to complete synchronization (r = 1). In addition, we find complete synchronization transitions accompanied by hysteresis in scale-free networks, indicating a first-order (discontinuous) phase transition, whereas Erdős--Rényi networks exhibit complete synchronization through a second-order (continuous) phase transition. Furthermore, we use the mean-field approximation in the presence of optimal frequencies to determine the critical coupling strength associated with the synchronization transition in the pure second-harmonic Sakaguchi--Kuramoto model. Here, the obtained optimal natural frequencies scale linearly with the node degree, and the critical coupling strength for the onset of synchronization is derived analytically from the self-consistent equations. In this specific regime, we observe a perfectly ordered two-cluster synchronized state. These findings remain robust for higher-order harmonic coupling schemes, as well as across a diverse range of synthetic and empirical networks, including scale-free, Erdős--Rényi, Zachary Karate Club, and the C.~elegans neural network, demonstrating their general applicability.

The brain solves the credit assignment problem remarkably well. For credit to be assigned across neural networks they must, in principle, wait for specific neural computations to finish. How the brain deals with this inherent locking problem has remained unclear. Deep learning methods suffer from similar locking constraints both on the forward and feedback phase. Recently, decoupled neural interfaces (DNIs) were introduced as a solution to the forward and feedback locking problems in deep networks. Here we propose that a specialised brain region, the cerebellum, helps the cerebral cortex solve similar locking problems akin to DNIs. To demonstrate the potential of this framework we introduce a systems-level model in which a recurrent cortical network receives online temporal feedback predictions from a cerebellar module. We test this cortico-cerebellar recurrent neural network (ccRNN) model on a number of sensorimotor (line and digit drawing) and cognitive tasks (pattern recognition and caption generation) that have been shown to be cerebellar-dependent. In all tasks, we observe that ccRNNs facilitates learning while reducing ataxia-like behaviours, consistent with classical experimental observations. Moreover, our model also explains recent behavioural and neuronal observations while making several testable predictions across multiple levels. Overall, our work offers a novel perspective on the cerebellum as a brain-wide decoupling machine for efficient credit assignment and opens a new avenue between deep learning and neuroscience.

Artificial Intelligence Virtual Cells (AIVCs) aim to learn executable, decision-relevant models of cell state from multimodal, multiscale measurements. Recent studies have introduced single-cell and spatial foundation models, improved cross-modality alignment, scaled perturbation atlases, and explored pathway-level readouts. Nevertheless, although held-out validation is standard practice, evaluations remain predominantly within single datasets and settings; evidence indicates that transport across laboratories and platforms is often limited, that some data splits are vulnerable to leakage and coverage bias, and that dose, time and combination effects are not yet systematically handled. Cross-scale coupling also remains constrained, as anchors linking molecular, cellular and tissue levels are sparse, and alignment to scientific or clinical readouts varies across studies. We propose a model-agnostic Cell-State Latent (CSL) perspective that organizes learning via an operator grammar: measurement, lift/project for cross-scale coupling, and intervention for dosing and scheduling. This view motivates a decision-aligned evaluation blueprint across modality, scale, context and intervention, and emphasizes function-space readouts such as pathway activity, spatial neighborhoods and clinically relevant endpoints. We recommend operator-aware data design, leakage-resistant partitions, and transparent calibration and reporting to enable reproducible, like-for-like comparisons.

Exposing meaningful and interpretable neural interactions is critical to understanding neural circuits. Inferred neural interactions from neural signals primarily reflect functional interactions. In a long experiment, subject animals may experience different stages defined by the experiment, stimuli, or behavioral states, and hence functional interactions can change over time. To model dynamically changing functional interactions, prior work employs state-switching generalized linear models with hidden Markov models (i.e., HMM-GLMs). However, we argue they lack biological plausibility, as functional interactions are shaped and confined by the underlying anatomical connectome. Here, we propose a novel prior-informed state-switching GLM. We introduce both a Gaussian prior and a one-hot prior over the GLM in each state. The priors are learnable. We will show that the learned prior should capture the state-constant interaction, shedding light on the underlying anatomical connectome and revealing more likely physical neuron interactions. The state-dependent interaction modeled by each GLM offers traceability to capture functional variations across multiple brain states. Our methods effectively recover true interaction structures in simulated data, achieve the highest predictive likelihood with real neural datasets, and render interaction structures and hidden states more interpretable when applied to real neural data.

This position and survey paper identifies the emerging convergence of neuroscience, artificial general intelligence (AGI), and neuromorphic computing toward a unified research paradigm. Using a framework grounded in brain physiology, we highlight how synaptic plasticity, sparse spike-based communication, and multimodal association provide design principles for next-generation AGI systems that potentially combine both human and machine intelligences. The review traces this evolution from early connectionist models to state-of-the-art large language models, demonstrating how key innovations like transformer attention, foundation-model pre-training, and multi-agent architectures mirror neurobiological processes like cortical mechanisms, working memory, and episodic consolidation. We then discuss emerging physical substrates capable of breaking the von Neumann bottleneck to achieve brain-scale efficiency in silicon: memristive crossbars, in-memory compute arrays, and emerging quantum and photonic devices. There are four critical challenges at this intersection: 1) integrating spiking dynamics with foundation models, 2) maintaining lifelong plasticity without catastrophic forgetting, 3) unifying language with sensorimotor learning in embodied agents, and 4) enforcing ethical safeguards in advanced neuromorphic autonomous systems. This combined perspective across neuroscience, computation, and hardware offers an integrative agenda for in each of these fields.

As the prevalence of Alzheimer's disease (AD) rises, improving mechanistic insight from non-invasive biomarkers is increasingly critical. Recent work suggests that circuit-level brain alterations manifest as changes in electroencephalography (EEG) spectral features detectable by machine learning. However, conventional deep learning approaches for EEG-based AD detection are computationally intensive and mechanistically opaque. Spiking neural networks (SNNs) offer a biologically plausible and energy-efficient alternative, yet their application to AD diagnosis remains largely unexplored. We propose a neuro-bridge framework that links data-driven learning with minimal, biophysically grounded simulations, enabling bidirectional interpretation between machine learning signatures and circuit-level mechanisms in AD. Using resting-state clinical EEG, we train an SNN classifier that achieves competitive performance (AUC = 0.839) and identifies the aperiodic 1/f slope as a key discriminative marker. The 1/f slope reflects excitation-inhibition balance. To interpret this mechanistically, we construct spiking network simulations in which inhibitory-to-excitatory synaptic ratios are systematically varied to emulate healthy, mild cognitive impairment, and AD-like states. Using both membrane potential-based and synaptic current-based EEG proxies, we reproduce empirical spectral slowing and altered alpha organization. Incorporating empirical functional connectivity priors into multi-subnetwork simulations further enhances spectral differentiation, demonstrating that large-scale network topology constrains EEG signatures more strongly than excitation-inhibition balance alone. Overall, this neuro-bridge approach connects SNN-based classification with interpretable circuit simulations, advancing mechanistic understanding of EEG biomarkers while enabling scalable, explainable AD detection.

Neural network models of early sensory processing typically reduce the dimensionality of streaming input data. Such networks learn the principal subspace, in the sense of principal component analysis (PCA), by adjusting synaptic weights according to activity-dependent learning rules. When derived from a principled cost function these rules are nonlocal and hence biologically implausible. At the same time, biologically plausible local rules have been postulated rather than derived from a principled cost function. Here, to bridge this gap, we derive a biologically plausible network for subspace learning on streaming data by minimizing a principled cost function. In a departure from previous work, where cost was quantified by the representation, or reconstruction, error, we adopt a multidimensional scaling (MDS) cost function for streaming data. The resulting algorithm relies only on biologically plausible Hebbian and anti-Hebbian local learning rules. In a stochastic setting, synaptic weights converge to a stationary state which projects the input data onto the principal subspace. If the data are generated by a nonstationary distribution, the network can track the principal subspace. Thus, our result makes a step towards an algorithmic theory of neural computation.

A central challenge in scaling flow models is maintaining stability in training and integration. In flow matching, this stability depends critically on how source samples are paired with data. Independent random pairing introduces substantial stochasticity, motivating minibatch optimal transport (OT) to construct online source-target couplings that reduce this randomness (Tong et al., 2024). However, as applications extend to larger and higher-dimensional datasets, small minibatches can limit these benefits, while scaling the coupling to substantially larger minibatches at every iteration is computationally prohibitive. Moreover, how OT coupling affects the full stochastic gradient and integration remains theoretically unresolved. In this work, we develop a scalable online entropic OT approximation that enables substantially larger source-target couplings while preserving the benefits of OT. We close the theoretical gap for both unregularized and entropic OT by proving strict reductions in full stochastic-gradient variance and integration error relative to independent pairing, and further characterize how these improvements strengthen as the online coupling minibatch grows. Experiments on single-cell gene interpolation-flow and image-flow training validate these predictions, showing that larger online couplings consistently improve training stability and final generation performance.

Recurrent Neural Networks (RNNs) are popular models of brain function. The typical training strategy is to adjust their input-output behavior so that it matches that of the biological circuit of interest. Even though this strategy ensures that the biological and artificial networks perform the same computational task, it does not guarantee that their internal activity dynamics match. This suggests that the trained RNNs might end up performing the task employing a different internal computational mechanism, which would make them a suboptimal model of the biological circuit. In this work, we introduce a novel training strategy that allows learning not only the input-output behavior of an RNN but also its internal network dynamics, based on sparse neural recordings. We test the proposed method by training an RNN to simultaneously reproduce internal dynamics and output signals of a physiologically-inspired neural model. Specifically, this model generates the multiphasic muscle-like activity patterns typically observed during the execution of reaching movements, based on the oscillatory activation patterns concurrently observed in the motor cortex. Remarkably, we show that the reproduction of the internal dynamics is successful even when the training algorithm relies on the activities of a small subset of neurons sampled from the biological network. Furthermore, we show that training the RNNs with this method significantly improves their generalization performance. Overall, our results suggest that the proposed method is suitable for building powerful functional RNN models, which automatically capture important computational properties of the biological circuit of interest from sparse neural recordings.

The brain is a noisy system subject to energy constraints. These facts are rarely taken into account when modelling artificial neural networks. In this paper, we are interested in demonstrating that those factors can actually lead to the appearance of robust associative memories. We first propose a simplified model of noise in the brain, taking into account synaptic noise and interference from neurons external to the network. When coarsely quantized, we show that this noise can be reduced to insertions and erasures. We take a neural network with recurrent modifiable connections, and subject it to noisy external inputs. We introduce an energy usage limitation principle in the network as well as consolidated Hebbian learning, resulting in an incremental processing of inputs. We show that the connections naturally formed correspond to state-of-the-art binary sparse associative memories.

Large language models (LLMs) currently suffer from parameter entanglement, where general reasoning capabilities (logic) and specific factual knowledge (facts) exist in a superposition state within shared weights. This coupling leads to the "memory wall," where computational capacity is squandered on simulating retrieval, often resulting in hallucinations. In this paper, we propose "digital metabolism," a thermodynamic hypothesis suggesting that targeted forgetting is necessary for distilling a pure neural logic core. To validate this hypothesis, we introduce the Regenerative Logic-Core Protocol (RLCP), a dual-stream training framework that renders specific factual dependencies linearly undecodable via deep-layer gradient reversal. Applying RLCP to Qwen2.5-0.5B, we observe a distinct phase transition: the model achieves near-zero retention of targeted factual associations (Accuracy < 7%) while exhibiting changes consistent with an emergent "structural crystallization" effect. Empirical analysis on GSM8K reveals that the "metabolized" model spontaneously adopts chain-of-thought (CoT) scaffolding, which we interpret as compensating for the loss of direct associative recall (shifting from O(1) recall to O(N) reasoning). While the causal mechanism underlying this behavioral shift requires further investigation, our findings provide a dynamic weight-level counterpart to architectural innovations like DeepSeek's Engram, paving the way for modular "Neural CPU + Symbolic RAM" architectures.

Spiking neural networks (SNNs) possess energy-efficient potential due to event-based computation. However, supervised training of SNNs remains a challenge as spike activities are non-differentiable. Previous SNNs training methods can be generally categorized into two basic classes, i.e., backpropagation-like training methods and plasticity-based learning methods. The former methods are dependent on energy-inefficient real-valued computation and non-local transmission, as also required in artificial neural networks (ANNs), whereas the latter are either considered to be biologically implausible or exhibit poor performance. Hence, biologically plausible (bio-plausible) high-performance supervised learning (SL) methods for SNNs remain deficient. In this paper, we proposed a novel bio-plausible SNN model for SL based on the symmetric spike-timing dependent plasticity (sym-STDP) rule found in neuroscience. By combining the sym-STDP rule with bio-plausible synaptic scaling and intrinsic plasticity of the dynamic threshold, our SNN model implemented SL well and achieved good performance in the benchmark recognition task (MNIST dataset). To reveal the underlying mechanism of our SL model, we visualized both layer-based activities and synaptic weights using the t-distributed stochastic neighbor embedding (t-SNE) method after training and found that they were well clustered, thereby demonstrating excellent classification ability. Furthermore, to verify the robustness of our model, we trained it on another more realistic dataset (Fashion-MNIST), which also showed good performance. As the learning rules were bio-plausible and based purely on local spike events, our model could be easily applied to neuromorphic hardware for online training and may be helpful for understanding SL information processing at the synaptic level in biological neural systems.

Spatiotemporal neural dynamics and oscillatory synchronization are widely implicated in biological information processing and have been hypothesized to support flexible coordination such as feature binding. By contrast, most deep learning architectures represent and propagate information through activation values, neglecting the joint dynamics of rate and phase. In this work, we introduce Kuramoto oscillatory Phase Encoding (KoPE) as an additional, evolving phase state to Vision Transformers, incorporating a neuro-inspired synchronization mechanism to advance learning efficiency. We show that KoPE can improve training, parameter, and data efficiency of vision models through synchronization-enhanced structure learning. Moreover, KoPE benefits tasks requiring structured understanding, including semantic and panoptic segmentation, representation alignment with language, and few-shot abstract visual reasoning (ARC-AGI). Theoretical analysis and empirical verification further suggest that KoPE can accelerate attention concentration for learning efficiency. These results indicate that synchronization can serve as a scalable, neuro-inspired mechanism for advancing state-of-the-art neural network models.

Hopfield neural networks are a possible basis for modelling associative memory in living organisms. After summarising previous studies in the field, we take a new look at learning rules, exhibiting them as descent-type algorithms for various cost functions. We also propose several new cost functions suitable for learning. We discuss the role of biases (the external inputs) in the learning process in Hopfield networks. Furthermore, we apply Newtons method for learning memories, and experimentally compare the performances of various learning rules. Finally, to add to the debate whether allowing connections of a neuron to itself enhances memory capacity, we numerically investigate the effects of self coupling. Keywords: Hopfield Networks, associative memory, content addressable memory, learning rules, gradient descent, attractor networks

Recurrent neural networks (RNNs) are widely used throughout neuroscience as models of local neural activity. Many properties of single RNNs are well characterized theoretically, but experimental neuroscience has moved in the direction of studying multiple interacting areas, and RNN theory needs to be likewise extended. We take a constructive approach towards this problem, leveraging tools from nonlinear control theory and machine learning to characterize when combinations of stable RNNs will themselves be stable. Importantly, we derive conditions which allow for massive feedback connections between interacting RNNs. We parameterize these conditions for easy optimization using gradient-based techniques, and show that stability-constrained "networks of networks" can perform well on challenging sequential-processing benchmark tasks. Altogether, our results provide a principled approach towards understanding distributed, modular function in the brain.

We propose a novel nonlinear bidirectionally coupled heterogeneous chain network whose dynamics evolve in discrete time. The backbone of the model is a pair of popular map-based neuron models, the Chialvo and the Rulkov maps. This model is assumed to proximate the intricate dynamical properties of neurons in the widely complex nervous system. The model is first realized via various nonlinear analysis techniques: fixed point analysis, phase portraits, Jacobian matrix, and bifurcation diagrams. We observe the coexistence of chaotic and period-4 attractors. Various codimension-1 and -2 patterns for example saddle-node, period-doubling, Neimark-Sacker, double Neimark-Sacker, flip- and fold-Neimark Sacker, and 1:1 and 1:2 resonance are also explored. Furthermore, the study employs two synchronization measures to quantify how the oscillators in the network behave in tandem with each other over a long number of iterations. Finally, a time series analysis of the model is performed to investigate its complexity in terms of sample entropy.

The precise timing of spikes emitted by neurons plays a crucial role in shaping the response of efferent biological neurons. This temporal dimension of neural activity holds significant importance in understanding information processing in neurobiology, especially for the performance of neuromorphic hardware, such as event-based cameras. Nonetheless, many artificial neural models disregard this critical temporal dimension of neural activity. In this study, we present a model designed to efficiently detect temporal spiking motifs using a layer of spiking neurons equipped with heterogeneous synaptic delays. Our model capitalizes on the diverse synaptic delays present on the dendritic tree, enabling specific arrangements of temporally precise synaptic inputs to synchronize upon reaching the basal dendritic tree. We formalize this process as a time-invariant logistic regression, which can be trained using labeled data. To demonstrate its practical efficacy, we apply the model to naturalistic videos transformed into event streams, simulating the output of the biological retina or event-based cameras. To evaluate the robustness of the model in detecting visual motion, we conduct experiments by selectively pruning weights and demonstrate that the model remains efficient even under significantly reduced workloads. In conclusion, by providing a comprehensive, event-driven computational building block, the incorporation of heterogeneous delays has the potential to greatly improve the performance of future spiking neural network algorithms, particularly in the context of neuromorphic chips.

Biological cortical neurons are remarkably sophisticated computational devices, temporally integrating their vast synaptic input over an intricate dendritic tree, subject to complex, nonlinearly interacting internal biological processes. A recent study proposed to characterize this complexity by fitting accurate surrogate models to replicate the input-output relationship of a detailed biophysical cortical pyramidal neuron model and discovered it needed temporal convolutional networks (TCN) with millions of parameters. Requiring these many parameters, however, could stem from a misalignment between the inductive biases of the TCN and cortical neuron's computations. In light of this, and to explore the computational implications of leaky memory units and nonlinear dendritic processing, we introduce the Expressive Leaky Memory (ELM) neuron model, a biologically inspired phenomenological model of a cortical neuron. Remarkably, by exploiting such slowly decaying memory-like hidden states and two-layered nonlinear integration of synaptic input, our ELM neuron can accurately match the aforementioned input-output relationship with under ten thousand trainable parameters. To further assess the computational ramifications of our neuron design, we evaluate it on various tasks with demanding temporal structures, including the Long Range Arena (LRA) datasets, as well as a novel neuromorphic dataset based on the Spiking Heidelberg Digits dataset (SHD-Adding). Leveraging a larger number of memory units with sufficiently long timescales, and correspondingly sophisticated synaptic integration, the ELM neuron displays substantial long-range processing capabilities, reliably outperforming the classic Transformer or Chrono-LSTM architectures on LRA, and even solving the Pathfinder-X task with over 70% accuracy (16k context length).

We put forward the dynamical study of a novel higher-order small network of Chialvo neurons arranged in a ring-star topology, with the neurons interacting via linear diffusive couplings. This model is perceived to imitate the nonlinear dynamical properties exhibited by a realistic nervous system where the neurons transfer information through higher-order multi-body interactions. We first analyze our model using the tools from nonlinear dynamics literature: fixed point analysis, Jacobian matrix, and bifurcation patterns. We observe the coexistence of chaotic attractors, and also an intriguing route to chaos starting from a fixed point, to period-doubling, to cyclic quasiperiodic closed invariant curves, to ultimately chaos. We numerically observe the existence of codimension-1 bifurcation patterns: saddle-node, period-doubling, and Neimark Sacker. We also qualitatively study the typical phase portraits of the system and numerically quantify chaos and complexity using the 0-1 test and sample entropy measure respectively. Finally, we study the collective behavior of the neurons in terms of two synchronization measures: the cross-correlation coefficient, and the Kuramoto order parameter.

Multimodal learning enhances the perceptual capabilities of cognitive systems by integrating information from different sensory modalities. However, existing multimodal fusion research typically assumes static integration, not fully incorporating key dynamic mechanisms found in the brain. Specifically, the brain exhibits an inverse effectiveness phenomenon, wherein weaker unimodal cues yield stronger multisensory integration benefits; conversely, when individual modal cues are stronger, the effect of fusion is diminished. This mechanism enables biological systems to achieve robust cognition even with scarce or noisy perceptual cues. Inspired by this biological mechanism, we explore the relationship between multimodal output and information from individual modalities, proposing an inverse effectiveness driven multimodal fusion (IEMF) strategy. By incorporating this strategy into neural networks, we achieve more efficient integration with improved model performance and computational efficiency, demonstrating up to 50% reduction in computational cost across diverse fusion methods. We conduct experiments on audio-visual classification, continual learning, and question answering tasks to validate our method. Results consistently demonstrate that our method performs excellently in these tasks. To verify universality and generalization, we also conduct experiments on Artificial Neural Networks (ANN) and Spiking Neural Networks (SNN), with results showing good adaptability to both network types. Our research emphasizes the potential of incorporating biologically inspired mechanisms into multimodal networks and provides promising directions for the future development of multimodal artificial intelligence. The code is available at https://github.com/Brain-Cog-Lab/IEMF.

Artificial neural networks achieve strong performance on benchmark tasks but remain fundamentally brittle under perturbations, limiting their deployment in real-world settings. In contrast, biological nervous systems sustain reliable function across decades through homeostatic regulation coordinated across multiple temporal scales. Inspired by this principle, this presents Multi-Scale Temporal Homeostasis (MSTH), a biologically grounded framework that integrates ultra-fast (5-ms), fast (2-s), medium (5-min) and slow (1-hrs) regulation into artificial networks. MSTH implements the cross-scale coordination system for artificial neural networks, providing a unified temporal hierarchy that moves beyond superficial biomimicry. The cross-scale coordination enhances computational efficiency through evolutionary-refined optimization mechanisms. Experiments across molecular, graph and image classification benchmarks show that MSTH consistently improves accuracy, eliminates catastrophic failures and enhances recovery from perturbations. Moreover, MSTH outperforms both single-scale bio-inspired models and established state-of-the-art methods, demonstrating generality across diverse domains. These findings establish cross-scale temporal coordination as a core principle for stabilizing artificial neural systems, positioning MSTH as a foundation for building robust, resilient and biologically faithful intelligence.

It has long been known in both neuroscience and AI that ``binding'' between neurons leads to a form of competitive learning where representations are compressed in order to represent more abstract concepts in deeper layers of the network. More recently, it was also hypothesized that dynamic (spatiotemporal) representations play an important role in both neuroscience and AI. Building on these ideas, we introduce Artificial Kuramoto Oscillatory Neurons (AKOrN) as a dynamical alternative to threshold units, which can be combined with arbitrary connectivity designs such as fully connected, convolutional, or attentive mechanisms. Our generalized Kuramoto updates bind neurons together through their synchronization dynamics. We show that this idea provides performance improvements across a wide spectrum of tasks such as unsupervised object discovery, adversarial robustness, calibrated uncertainty quantification, and reasoning. We believe that these empirical results show the importance of rethinking our assumptions at the most basic neuronal level of neural representation, and in particular show the importance of dynamical representations.

Motivated by the celebrated discrete-time model of nervous activity outlined by McCulloch and Pitts in 1943, we propose a novel continuous-time model, the McCulloch-Pitts network (MPN), for sequence learning in spiking neural networks. Our model has a local learning rule, such that the synaptic weight updates depend only on the information directly accessible by the synapse. By exploiting asymmetry in the connections between binary neurons, we show that MPN can be trained to robustly memorize multiple spatiotemporal patterns of binary vectors, generalizing the ability of the symmetric Hopfield network to memorize static spatial patterns. In addition, we demonstrate that the model can efficiently learn sequences of binary pictures as well as generative models for experimental neural spike-train data. Our learning rule is consistent with spike-timing-dependent plasticity (STDP), thus providing a theoretical ground for the systematic design of biologically inspired networks with large and robust long-range sequence storage capacity.

Collective cell responses to exogenous cues depend on cell-cell interactions. In principle, these can result in enhanced sensitivity to weak and noisy stimuli. However, this has not yet been shown experimentally, and, little is known about how multicellular signal processing modulates single cell sensitivity to extracellular signaling inputs, including those guiding complex changes in the tissue form and function. Here we explored if cell-cell communication can enhance the ability of cell ensembles to sense and respond to weak gradients of chemotactic cues. Using a combination of experiments with mammary epithelial cells and mathematical modeling, we find that multicellular sensing enables detection of and response to shallow Epidermal Growth Factor (EGF) gradients that are undetectable by single cells. However, the advantage of this type of gradient sensing is limited by the noisiness of the signaling relay, necessary to integrate spatially distributed ligand concentration information. We calculate the fundamental sensory limits imposed by this communication noise and combine them with the experimental data to estimate the effective size of multicellular sensory groups involved in gradient sensing. Functional experiments strongly implicated intercellular communication through gap junctions and calcium release from intracellular stores as mediators of collective gradient sensing. The resulting integrative analysis provides a framework for understanding the advantages and limitations of sensory information processing by relays of chemically coupled cells.

Within the complex neuroarchitecture of the brain, astrocytes play crucial roles in development, structure, and metabolism. These cells regulate neural activity through tripartite synapses, directly impacting cognitive processes such as learning and memory. Despite the growing recognition of astrocytes' significance, traditional Spiking Neural Network (SNN) models remain predominantly neuron-centric, overlooking the profound influence of astrocytes on neural dynamics. Inspired by these biological insights, we have developed an Astrocyte-Modulated Spiking Unit (AM-SU), an innovative framework that integrates neuron-astrocyte interactions into the computational paradigm, demonstrating wide applicability across various hardware platforms. Our Astrocyte-Modulated Spiking Neural Network (AstroSNN) exhibits exceptional performance in tasks involving memory retention and natural language generation, particularly in handling long-term dependencies and complex linguistic structures. The design of AstroSNN not only enhances its biological authenticity but also introduces novel computational dynamics, enabling more effective processing of complex temporal dependencies. Furthermore, AstroSNN shows low latency, high throughput, and reduced memory usage in practical applications, making it highly suitable for resource-constrained environments. By successfully integrating astrocytic dynamics into intelligent neural networks, our work narrows the gap between biological plausibility and neural modeling, laying the groundwork for future biologically-inspired neural computing research that includes both neurons and astrocytes.

Decoding approaches are widely used in neuroscience and machine learning to compare stimulus representations across neural systems, such as different brain regions, organisms, and deep learning models. Popular methods include decoding (perceptual) manifolds and alignment metrics such as Representational Similarity Analysis (RSA) and Dynamic Similarity Analysis (DSA), where similarity in decoding representations is interpreted as evidence for similar computation. This paper demonstrates a fundamental weakness behind this approach: it is misleading to assume that representational geometry is representative of a neuronal population as a whole, when such representations may actually be shaped by a very small subset of neurons. We show that the complementary encoding paradigm addresses this issue directly: it characterizes how neurons are organized globally in terms of their responses to a set of data, providing insight into how the decoding representation is implemented by neurons within a population. We demonstrate across experiments in biological systems and deep learning models that (i) surprisingly, similar decoding behavior and high representational alignment can arise from small, non-representative subpopulations of neurons; and critically, (ii) alignment metrics are insensitive to encoding manifold topology (how function is distributed across neurons), despite this being a key signature of differentiation across biological systems. A controlled MNIST experiment provides causal evidence: decoding metrics remain unchanged even when encoding topology is causally manipulated via the training loss. Overall, similarity in decoding behavior, as measured by classic alignment metrics, does not imply similarity in function or computation, motivating the use of encoding manifolds as a complementary tool for comparing neural systems.

Efficient neural network models that generate brain-like dynamic activity can be a valuable resource for generating synthetic data, analyzing differences in brain transients under conditions such as testing perturbation activity or inferring the underlying generative dynamics. However, large language models (LLMs) or standard recurrent neural networks (RNNs) ignore the anatomical organization and therefore do not produce components that align with brain regions. On the other hand, graph-based networks often have very simple message passing rules that are not sufficiently expressive for brain-like dynamics. To address this, we introduce BrainDyn, a sheaf neural ordinary differential equation (neural ODE) model for continuous-time dynamics on structured brain graphs. BrainDyn encodes the recent activity history of each brain region using a long short-term memory (LSTM) model over a sliding temporal window to produce hidden states, or stalks, that are projected through learnable restriction maps into edge-specific shared spaces. Discrepancies between neighboring nodes in these shared spaces are characterized by a sheaf Laplacian that can facilitate message passing between neuronal units. The output of these messages is then fed to a neural ODE that governs the continuous-time evolution of neuronal activity. We evaluated BrainDyn on resting-state fMRI (PNC dataset), scalp EEG with focal epilepsy (TUSZ dataset), and simulated activity from the NEST spiking network simulator. BrainDyn achieves strong forecasting ability across modalities, and the resulting representations support downstream tasks including in silico perturbation prediction.

We introduce a novel mathematical framework that unifies neural population dynamics, hippocampal sharp wave-ripple (SpWR) generation, and cognitive consistency constraints inspired by Heider's theory. Our model leverages low-dimensional manifold representations to capture structured neural drift and incorporates a balance energy function to enforce coherent synaptic interactions, effectively simulating the memory consolidation processes observed in biological systems. Simulation results demonstrate that our approach not only reproduces key features of SpWR events but also enhances network interpretability. This work paves the way for scalable neuromorphic architectures that bridge neuroscience and artificial intelligence, offering more robust and adaptive learning mechanisms for future intelligent systems.

Electroencephalography (EEG) foundation models hold significant promise for universal Brain-Computer Interfaces (BCIs). However, existing approaches often rely on end-to-end fine-tuning and exhibit limited efficacy under frozen-probing protocols, lacking the intrinsic universality required for broad generalization. This limitation stems from adapting general-purpose sequence architectures that overlook the biophysical and dynamical principles of neural activity. To bridge this gap, we propose DeeperBrain, a neuro-grounded foundation model integrating domain-specific inductive biases into its model design and learning objectives. Architecturally, DeeperBrain incorporates a volume conduction-aware channel encoding to model spatial mixing via 3D geometry, and a neurodynamics-aware temporal encoding capturing slow adaptations using oscillatory and exponential bases. For pretraining, we introduce a dual-objective strategy combining Masked EEG Reconstruction (MER) for local fidelity and Neurodynamics Statistics Prediction (NSP). NSP enforces alignment with macroscopic brain states by predicting interpretable order parameters, including spectral power, functional connectivity, cross-frequency coupling, and dynamic complexity. Extensive experiments demonstrate that DeeperBrain achieves state-of-the-art or highly competitive performance under end-to-end fine-tuning. Crucially, it maintains superior efficacy under a rigorous frozen-probing protocol, verifying that embedding neuroscientific first principles endows learned representations with the intrinsic universality essential for universal BCI. The code will be publicly available.

The Spiking Neural Network (SNN) has attracted more and more attention recently. It adopts binary spike signals to transmit information. Benefitting from the information passing paradigm of SNNs, the multiplications of activations and weights can be replaced by additions, which are more energy-efficient. However, its ``Hard Reset" mechanism for the firing activity would ignore the difference among membrane potentials when the membrane potential is above the firing threshold, causing information loss. Meanwhile, quantifying the membrane potential to 0/1 spikes at the firing instants will inevitably introduce the quantization error thus bringing about information loss too. To address these problems, we propose to use the ``Soft Reset" mechanism for the supervised training-based SNNs, which will drive the membrane potential to a dynamic reset potential according to its magnitude, and Membrane Potential Rectifier (MPR) to reduce the quantization error via redistributing the membrane potential to a range close to the spikes. Results show that the SNNs with the ``Soft Reset" mechanism and MPR outperform their vanilla counterparts on both static and dynamic datasets.

While Large Language Models (LLMs) excel at generalized reasoning, standard retrieval-augmented approaches fail to address the disconnected nature of long-term agentic memory. To bridge this gap, we introduce Synapse (Synergistic Associative Processing Semantic Encoding), a unified memory architecture that transcends static vector similarity. Drawing from cognitive science, Synapse models memory as a dynamic graph where relevance emerges from spreading activation rather than pre-computed links. By integrating lateral inhibition and temporal decay, the system dynamically highlights relevant sub-graphs while filtering interference. We implement a Triple Hybrid Retrieval strategy that fuses geometric embeddings with activation-based graph traversal. Comprehensive evaluations on the LoCoMo benchmark show that Synapse significantly outperforms state-of-the-art methods in complex temporal and multi-hop reasoning tasks, offering a robust solution to the "Contextual Tunneling" problem. Our code and data will be made publicly available upon acceptance.

Spiking neural networks (SNNs) represent a promising approach to developing artificial neural networks that are both energy-efficient and biologically plausible. However, applying SNNs to sequential tasks, such as text classification and time-series forecasting, has been hindered by the challenge of creating an effective and hardware-friendly spike-form positional encoding (PE) strategy. Drawing inspiration from the central pattern generators (CPGs) in the human brain, which produce rhythmic patterned outputs without requiring rhythmic inputs, we propose a novel PE technique for SNNs, termed CPG-PE. We demonstrate that the commonly used sinusoidal PE is mathematically a specific solution to the membrane potential dynamics of a particular CPG. Moreover, extensive experiments across various domains, including time-series forecasting, natural language processing, and image classification, show that SNNs with CPG-PE outperform their conventional counterparts. Additionally, we perform analysis experiments to elucidate the mechanism through which SNNs encode positional information and to explore the function of CPGs in the human brain. This investigation may offer valuable insights into the fundamental principles of neural computation. Our code is available at https://github.com/microsoft/SeqSNN.

We develop a dynamical mean-field theory for random recurrent networks with low-rank structure and firing-rate-driven adaptation. When the random connectivity is strong enough to generate chaos, increasing adaptation strength drives the network through four regimes: a static coherent state, noise-sustained oscillations that progress from regular to irregular, stochastic switching between symmetric wells, and a global limit cycle. The theory identifies two instability mechanisms, chaos onset from the random connectivity and a Hopf bifurcation of the coherent mode, and shows how adaptation shapes both through the frequency-dependent single-neuron transfer function. A reduced three-dimensional model captures the bifurcation structure of the full network. Above the chaos threshold, coherent population-level oscillations coexist with heterogeneous firing rates and network-generated stochasticity at the single-neuron level. The interaction of adaptation with random and low-rank connectivity produces a rich oscillatory repertoire, including waxing-and-waning rhythmic episodes, persistent state switching, and slow Up-Down alternations, dynamics that have been observed during wakefulness, sleep, and anesthesia.

We present a comprehensive analysis of how two-layer neural networks learn features to solve the modular addition task. Our work provides a full mechanistic interpretation of the learned model and a theoretical explanation of its training dynamics. While prior work has identified that individual neurons learn single-frequency Fourier features and phase alignment, it does not fully explain how these features combine into a global solution. We bridge this gap by formalizing a diversification condition that emerges during training when overparametrized, consisting of two parts: phase symmetry and frequency diversification. We prove that these properties allow the network to collectively approximate a flawed indicator function on the correct logic for the modular addition task. While individual neurons produce noisy signals, the phase symmetry enables a majority-voting scheme that cancels out noise, allowing the network to robustly identify the correct sum. Furthermore, we explain the emergence of these features under random initialization via a lottery ticket mechanism. Our gradient flow analysis proves that frequencies compete within each neuron, with the "winner" determined by its initial spectral magnitude and phase alignment. From a technical standpoint, we provide a rigorous characterization of the layer-wise phase coupling dynamics and formalize the competitive landscape using the ODE comparison lemma. Finally, we use these insights to demystify grokking, characterizing it as a three-stage process involving memorization followed by two generalization phases, driven by the competition between loss minimization and weight decay.

Models of neural responses to stimuli with complex spatiotemporal correlation structure often assume that neurons are only selective for a small number of linear projections of a potentially high-dimensional input. Here we explore recent modeling approaches where the neural response depends on the quadratic form of the input rather than on its linear projection, that is, the neuron is sensitive to the local covariance structure of the signal preceding the spike. To infer this quadratic dependence in the presence of arbitrary (e.g. naturalistic) stimulus distribution, we review several inference methods, focussing in particular on two information-theory-based approaches (maximization of stimulus energy or of noise entropy) and a likelihood-based approach (Bayesian spike-triggered covariance, extensions of generalized linear models). We analyze the formal connection between the likelihood-based and information-based approaches to show how they lead to consistent inference. We demonstrate the practical feasibility of these procedures by using model neurons responding to a flickering variance stimulus.

The brain is the perfect place to look for inspiration to develop more efficient neural networks. The inner workings of our synapses and neurons provide a glimpse at what the future of deep learning might look like. This paper serves as a tutorial and perspective showing how to apply the lessons learnt from several decades of research in deep learning, gradient descent, backpropagation and neuroscience to biologically plausible spiking neural neural networks. We also explore the delicate interplay between encoding data as spikes and the learning process; the challenges and solutions of applying gradient-based learning to spiking neural networks (SNNs); the subtle link between temporal backpropagation and spike timing dependent plasticity, and how deep learning might move towards biologically plausible online learning. Some ideas are well accepted and commonly used amongst the neuromorphic engineering community, while others are presented or justified for the first time here. The fields of deep learning and spiking neural networks evolve very rapidly. We endeavour to treat this document as a 'dynamic' manuscript that will continue to be updated as the common practices in training SNNs also change. A series of companion interactive tutorials complementary to this paper using our Python package, snnTorch, are also made available. See https://snntorch.readthedocs.io/en/latest/tutorials/index.html .

The brain understands the external world through an internal model that generates predictions and refines them based on prediction errors. A complete prediction specifies what will happen, when it will happen, and with what probability, which we refer to as a "prediction object". Existing models typically capture only what and when, omit probabilities, and rely on biologically-implausible algorithms. Here we show that a single population of spiking neurons can jointly encode the prediction object through a biologically grounded learning mechanism. We implement a heterogeneous Izhikevich spiking reservoir with readouts trained by an error-modulated, attention-gated three-factor Hebbian rule and test it on a novel paradigm that controls both the timing and probability of upcoming stimuli. By integrating real-time learning of "when" with offline consolidation of "what", the model encodes the complete prediction object, firing at the correct times with magnitudes proportional to the probabilities. Critically, it rapidly adapts to changes in both stimulus timing and probability, an ability that global least-squares methods such as FORCE lack without explicit resets. During learning, the model self-organizes its readout weights into near-orthogonal subspaces for "what" and "when," showing that multiplexed encoding arises naturally from generic recurrent dynamics under local, error-gated modulation. These results challenge the view that "what" and "when" predictions require separate modules, suggesting instead that mixed selectivity within shared populations supports flexible predictive cognition. The model also predicts phase-specific neuromodulation and overlapping neural subspaces, offering a parsimonious alternative to hierarchical predictive-coding accounts.

Spiking Neural Networks (SNNs) are computational models inspired by the structure and dynamics of biological neuronal networks. Their event-driven nature enables them to achieve high energy efficiency, particularly when deployed on neuromorphic hardware platforms. Unlike conventional Artificial Neural Networks (ANNs), which primarily rely on layered architectures, SNNs naturally support a wide range of connectivity patterns, from traditional layered structures to small-world graphs characterized by locally dense and globally sparse connections. In this work, we introduce NeuroCoreX, an FPGA-based emulator designed for the flexible co-design and testing of SNNs. NeuroCoreX supports all-to-all connectivity, providing the capability to implement diverse network topologies without architectural restrictions. It features a biologically motivated local learning mechanism based on Spike-Timing-Dependent Plasticity (STDP). The neuron model implemented within NeuroCoreX is the Leaky Integrate-and-Fire (LIF) model, with current-based synapses facilitating spike integration and transmission . A Universal Asynchronous Receiver-Transmitter (UART) interface is provided for programming and configuring the network parameters, including neuron, synapse, and learning rule settings. Users interact with the emulator through a simple Python-based interface, streamlining SNN deployment from model design to hardware execution. NeuroCoreX is released as an open-source framework, aiming to accelerate research and development in energy-efficient, biologically inspired computing.

Attractor dynamics are a fundamental computational motif in neural circuits, supporting diverse cognitive functions through stable, self-sustaining patterns of neural activity. In these lecture notes, we review four key examples that demonstrate how autoassociative neural network models can elucidate the computational mechanisms underlying attractor-based information processing in biological neural systems performing cognitive functions. Drawing on empirical evidence, we explore hippocampal spatial representations, visual classification in the inferotemporal cortex, perceptual adaptation and priming, and working-memory biases shaped by sensory history. Across these domains, attractor network models reveal common computational principles and provide analytical insights into how experience shapes neural activity and behavior. Our synthesis underscores the value of attractor models as powerful tools for probing the neural basis of cognition and behavior.

Brain simulation builds dynamical models to mimic the structure and functions of the brain, while brain-inspired computing (BIC) develops intelligent systems by learning from the structure and functions of the brain. The two fields are intertwined and should share a common programming framework to facilitate each other's development. However, none of the existing software in the fields can achieve this goal, because traditional brain simulators lack differentiability for training, while existing deep learning (DL) frameworks fail to capture the biophysical realism and complexity of brain dynamics. In this paper, we introduce BrainPy, a differentiable brain simulator developed using JAX and XLA, with the aim of bridging the gap between brain simulation and BIC. BrainPy expands upon the functionalities of JAX, a powerful AI framework, by introducing complete capabilities for flexible, efficient, and scalable brain simulation. It offers a range of sparse and event-driven operators for efficient and scalable brain simulation, an abstraction for managing the intricacies of synaptic computations, a modular and flexible interface for constructing multi-scale brain models, and an object-oriented just-in-time compilation approach to handle the memory-intensive nature of brain dynamics. We showcase the efficiency and scalability of BrainPy on benchmark tasks, highlight its differentiable simulation for biologically plausible spiking models, and discuss its potential to support research at the intersection of brain simulation and BIC.

Neuromorphic computing with spiking neural networks is promising for energy-efficient artificial intelligence (AI) applications. However, different from humans who continually learn different tasks in a lifetime, neural network models suffer from catastrophic forgetting. How could neuronal operations solve this problem is an important question for AI and neuroscience. Many previous studies draw inspiration from observed neuroscience phenomena and propose episodic replay or synaptic metaplasticity, but they are not guaranteed to explicitly preserve knowledge for neuron populations. Other works focus on machine learning methods with more mathematical grounding, e.g., orthogonal projection on high dimensional spaces, but there is no neural correspondence for neuromorphic computing. In this work, we develop a new method with neuronal operations based on lateral connections and Hebbian learning, which can protect knowledge by projecting activity traces of neurons into an orthogonal subspace so that synaptic weight update will not interfere with old tasks. We show that Hebbian and anti-Hebbian learning on recurrent lateral connections can effectively extract the principal subspace of neural activities and enable orthogonal projection. This provides new insights into how neural circuits and Hebbian learning can help continual learning, and also how the concept of orthogonal projection can be realized in neuronal systems. Our method is also flexible to utilize arbitrary training methods based on presynaptic activities/traces. Experiments show that our method consistently solves forgetting for spiking neural networks with nearly zero forgetting under various supervised training methods with different error propagation approaches, and outperforms previous approaches under various settings. Our method can pave a solid path for building continual neuromorphic computing systems.

There is renewed interest in modeling and understanding the nervous system of the nematode Caenorhabditis elegans (C. elegans), as this small model system provides a path to bridge the gap between nervous system structure (connectivity) and function (physiology). However, existing physiology datasets, whether involving passive recording or stimulation, are in distinct formats, and connectome datasets require preprocessing before analysis can commence. Here we compile and homogenize datasets of neural activity and connectivity. Our neural activity dataset is derived from 11 C. elegans neuroimaging experiments, while our connectivity dataset is compiled from 9 connectome annotations based on 3 primary electron microscopy studies and 1 signal propagation study. Physiology datasets, collected under varying protocols, measure calcium fluorescence in labeled subsets of the worm's 300 neurons. Our preprocessing pipeline standardizes these datasets by consistently ordering labeled neurons and resampling traces to a common sampling rate, yielding recordings from approximately 900 worms and 250 uniquely labeled neurons. The connectome datasets, collected from electron microscopy reconstructions, represent the entire nervous system as a graph of connections. Our collection is accessible on HuggingFace, facilitating analysis of the structure-function relationship in biology using modern neural network architectures and enabling cross-lab and cross-animal comparisons.

A hallmark of intelligence is the ability to autonomously learn new flexible, cognitive behaviors - that is, behaviors where the appropriate action depends not just on immediate stimuli (as in simple reflexive stimulus-response associations), but on contextual information that must be adequately acquired, stored and processed. While many meta-learning algorithms can design agents that autonomously learn new tasks, cognitive tasks adds another level of learning and memory to typical ``learning-to-learn'' problems. Here we evolve neural networks, endowed with plastic connections and neuromodulation, over a sizable set of simple cognitive tasks adapted from a computational neuroscience framework. The resulting evolved networks can automatically modify their own connectivity to acquire a novel simple cognitive task, never seen during evolution, from stimuli and rewards alone, through the spontaneous operation of their evolved neural organization and plasticity system. Our results emphasize the importance of carefully considering the multiple learning loops involved in the emergence of intelligent behavior.

Spiking Neural Networks (SNNs) offer a promising, biologically inspired approach for processing spatiotemporal data, particularly for time series forecasting. However, conventional neuron models like the Leaky Integrate-and-Fire (LIF) struggle to capture long-term dependencies and effectively process multi-scale temporal dynamics. To overcome these limitations, we introduce the Temporal Segment Leaky Integrate-and-Fire (TS-LIF) model, featuring a novel dual-compartment architecture. The dendritic and somatic compartments specialize in capturing distinct frequency components, providing functional heterogeneity that enhances the neuron's ability to process both low- and high-frequency information. Furthermore, the newly introduced direct somatic current injection reduces information loss during intra-neuronal transmission, while dendritic spike generation improves multi-scale information extraction. We provide a theoretical stability analysis of the TS-LIF model and explain how each compartment contributes to distinct frequency response characteristics. Experimental results show that TS-LIF outperforms traditional SNNs in time series forecasting, demonstrating better accuracy and robustness, even with missing data. TS-LIF advances the application of SNNs in time-series forecasting, providing a biologically inspired approach that captures complex temporal dynamics and offers potential for practical implementation in diverse forecasting scenarios. The source code is available at https://github.com/kkking-kk/TS-LIF.

Neural architectures that learn potential energy surfaces from molecular data have undergone fast improvement in recent years. A key driver of this success is the Message Passing Neural Network (MPNN) paradigm. Its favorable scaling with system size partly relies upon a spatial distance limit on messages. While this focus on locality is a useful inductive bias, it also impedes the learning of long-range interactions such as electrostatics and van der Waals forces. To address this drawback, we propose Ewald message passing: a nonlocal Fourier space scheme which limits interactions via a cutoff on frequency instead of distance, and is theoretically well-founded in the Ewald summation method. It can serve as an augmentation on top of existing MPNN architectures as it is computationally inexpensive and agnostic to architectural details. We test the approach with four baseline models and two datasets containing diverse periodic (OC20) and aperiodic structures (OE62). We observe robust improvements in energy mean absolute errors across all models and datasets, averaging 10% on OC20 and 16% on OE62. Our analysis shows an outsize impact of these improvements on structures with high long-range contributions to the ground truth energy.

Recurrent neural networks (RNNs) in the brain and in silico excel at solving tasks with intricate temporal dependencies. Long timescales required for solving such tasks can arise from properties of individual neurons (single-neuron timescale, tau, e.g., membrane time constant in biological neurons) or recurrent interactions among them (network-mediated timescale). However, the contribution of each mechanism for optimally solving memory-dependent tasks remains poorly understood. Here, we train RNNs to solve N-parity and N-delayed match-to-sample tasks with increasing memory requirements controlled by N by simultaneously optimizing recurrent weights and taus. We find that for both tasks RNNs develop longer timescales with increasing N, but depending on the learning objective, they use different mechanisms. Two distinct curricula define learning objectives: sequential learning of a single-N (single-head) or simultaneous learning of multiple Ns (multi-head). Single-head networks increase their tau with N and are able to solve tasks for large N, but they suffer from catastrophic forgetting. However, multi-head networks, which are explicitly required to hold multiple concurrent memories, keep tau constant and develop longer timescales through recurrent connectivity. Moreover, we show that the multi-head curriculum increases training speed and network stability to ablations and perturbations, and allows RNNs to generalize better to tasks beyond their training regime. This curriculum also significantly improves training GRUs and LSTMs for large-N tasks. Our results suggest that adapting timescales to task requirements via recurrent interactions allows learning more complex objectives and improves the RNN's performance.

This work presents the Parallelized Hierarchical Connectome (PHC), a general architectural framework that upgrades temporal-only State-Space Models (SSMs) into spatiotemporal recurrent networks. Conventional SSMs achieve parallel-scan training but are limited to temporal recurrence, lacking lateral or feedback interactions within a single timestep. PHC maps the diagonal SSM core to a shared Neuron Layer and inter-neuronal communication to a shared Synapse Layer of hierarchical regions, reconnected by a Multi-Transmission Loop iterating spatial recurrence within each temporal window, at parameter complexity Theta(D^2) versus Theta(D^2 L) of stacked SSMs. This spatiotemporal framework enables the seamless integration of neuro-physical priors typically intractable for standard SSMs, including adaptive LIF, synaptic delay, STP, Dale's Law with E/I-asymmetric topology, and STDP. The framework is instantiated as PHCSSM, the first spiking SSM that integrates all five biological priors and is evaluated on long-sequence data, achieving test accuracy competitive with state-of-the-art SSM baselines at 1,312 to 4,891 trainable parameters (1 to 4 orders of magnitude smaller than every baseline). PHCSSM further admits a sequential recurrent spiking neural network (RSNN) deployment mode that converges asymptotically to the parallel-scan training mode without artificial-neural-network-to-spiking-neural-network (ANN-to-SNN) conversion, with cross-backend reproducibility verified across four hardware backends (x86 CPU, H100 GPU, Cortex-A76, Cortex-M4F) including end-to-end deployment on the Cortex-M4F microcontroller (40 KB SRAM, 128 KB Flash). PHCSSM thereby bridges parallel-scan SSM and biologically grounded RSNN, two paradigms with previously incompatible training regimes, into a single architecture and trained weights.

We extend the capabilities of neural networks by coupling them to external memory resources, which they can interact with by attentional processes. The combined system is analogous to a Turing Machine or Von Neumann architecture but is differentiable end-to-end, allowing it to be efficiently trained with gradient descent. Preliminary results demonstrate that Neural Turing Machines can infer simple algorithms such as copying, sorting, and associative recall from input and output examples.

The impressive lifelong learning in animal brains is primarily enabled by plastic changes in synaptic connectivity. Importantly, these changes are not passive, but are actively controlled by neuromodulation, which is itself under the control of the brain. The resulting self-modifying abilities of the brain play an important role in learning and adaptation, and are a major basis for biological reinforcement learning. Here we show for the first time that artificial neural networks with such neuromodulated plasticity can be trained with gradient descent. Extending previous work on differentiable Hebbian plasticity, we propose a differentiable formulation for the neuromodulation of plasticity. We show that neuromodulated plasticity improves the performance of neural networks on both reinforcement learning and supervised learning tasks. In one task, neuromodulated plastic LSTMs with millions of parameters outperform standard LSTMs on a benchmark language modeling task (controlling for the number of parameters). We conclude that differentiable neuromodulation of plasticity offers a powerful new framework for training neural networks.

The human brain is autonomously active, being characterized by a self-sustained neural activity which would be present even in the absence of external sensory stimuli. Here we study the interrelation between the self-sustained activity in autonomously active recurrent neural nets and external sensory stimuli. There is no a priori semantical relation between the influx of external stimuli and the patterns generated internally by the autonomous and ongoing brain dynamics. The question then arises when and how are semantic correlations between internal and external dynamical processes learned and built up? We study this problem within the paradigm of transient state dynamics for the neural activity in recurrent neural nets, i.e. for an autonomous neural activity characterized by an infinite time-series of transiently stable attractor states. We propose that external stimuli will be relevant during the sensitive periods, {\it viz} the transition period between one transient state and the subsequent semi-stable attractor. A diffusive learning signal is generated unsupervised whenever the stimulus influences the internal dynamics qualitatively. For testing we have presented to the model system stimuli corresponding to the bars and stripes problem. We found that the system performs a non-linear independent component analysis on its own, being continuously and autonomously active. This emergent cognitive capability results here from a general principle for the neural dynamics, the competition between neural ensembles.

State-of-the-art systems neuroscience experiments yield large-scale multimodal data, and these data sets require new tools for analysis. Inspired by the success of large pretrained models in vision and language domains, we reframe the analysis of large-scale, cellular-resolution neuronal spiking data into an autoregressive spatiotemporal generation problem. Neuroformer is a multimodal, multitask generative pretrained transformer (GPT) model that is specifically designed to handle the intricacies of data in systems neuroscience. It scales linearly with feature size, can process an arbitrary number of modalities, and is adaptable to downstream tasks, such as predicting behavior. We first trained Neuroformer on simulated datasets, and found that it both accurately predicted simulated neuronal circuit activity, and also intrinsically inferred the underlying neural circuit connectivity, including direction. When pretrained to decode neural responses, the model predicted the behavior of a mouse with only few-shot fine-tuning, suggesting that the model begins learning how to do so directly from the neural representations themselves, without any explicit supervision. We used an ablation study to show that joint training on neuronal responses and behavior boosted performance, highlighting the model's ability to associate behavioral and neural representations in an unsupervised manner. These findings show that Neuroformer can analyze neural datasets and their emergent properties, informing the development of models and hypotheses associated with the brain.

Recurrent neural networks (RNNs) provide a powerful approach in neuroscience to infer latent dynamics in neural populations and to generate hypotheses about the neural computations underlying behavior. However, past work has focused on relatively simple, input-driven, and largely deterministic behaviors - little is known about the mechanisms that would allow RNNs to generate the richer, spontaneous, and potentially stochastic behaviors observed in natural settings. Modeling with Hidden Markov Models (HMMs) has revealed a segmentation of natural behaviors into discrete latent states with stochastic transitions between them, a type of dynamics that may appear at odds with the continuous state spaces implemented by RNNs. Here we first show that RNNs can replicate HMM emission statistics and then reverse-engineer the trained networks to uncover the mechanisms they implement. In the absence of inputs, the activity of trained RNNs collapses towards a single fixed point. When driven by stochastic input, trajectories instead exhibit noise-sustained dynamics along closed orbits. Rotation along these orbits modulates the emission probabilities and is governed by transitions between regions of slow, noise-driven dynamics connected by fast, deterministic transitions. The trained RNNs develop highly structured connectivity, with a small set of "kick neurons" initiating transitions between these regions. This mechanism emerges during training as the network shifts into a regime of stochastic resonance, enabling it to perform probabilistic computations. Analyses across multiple HMM architectures - fully connected, cyclic, and linear-chain - reveal that this solution generalizes through the modular reuse of the same dynamical motif, suggesting a compositional principle by which RNNs can emulate complex discrete latent dynamics.

Exact firing rate models, also known as next-generation neural mass models (NG-NMMs), provide a rigorous description of the dynamics of neural populations. While in its simplest form a single population only displays fixed-point activity, multi-population models may display a range of different behaviors. In this work, we study the dynamics of all-excitatory or all-inhibitory NG-NMMs coupled through sparse random networks with row-normalized network topology. Linear stability analysis of the homogeneous states of the system, representing asynchronous neural activity, provides a dispersion relation linking the emergence of spatiotemporal dynamics to the spectra of the connectivity matrix. Using bounds from random matrix theory, we identify the parameter regions where instabilities occur. In undirected networks, only inhibitory systems produce heterogeneous stationary patterns, corresponding to a winner-takes-all mechanism. In directed networks, exotic rhythmic states with high frequencies emerge in both, excitatory and inhibitory systems. Numerical simulations reveal that these hectic oscillatory states correspond to high-dimensional chaos with extensive properties.

This study introduces BrainTransformers, an innovative Large Language Model (LLM) implemented using Spiking Neural Networks (SNN). Our key contributions include: (1) designing SNN-compatible Transformer components such as SNNMatmul, SNNSoftmax, and SNNSiLU; (2) implementing an SNN approximation of the SiLU activation function; and (3) developing a Synapsis module to simulate synaptic plasticity. Our 3-billion parameter model, BrainTransformers-3B-Chat, demonstrates competitive performance across various benchmarks, including MMLU (63.2), BBH (54.1), ARC-C (54.3), and GSM8K (76.3), while potentially offering improved energy efficiency and biological plausibility. The model employs a three-stage training approach, including SNN-specific neuronal synaptic plasticity training. This research opens new avenues for brain-like AI systems in natural language processing and neuromorphic computing. Future work will focus on hardware optimization, developing specialized SNN fine-tuning tools, and exploring practical applications in energy-efficient computing environments.

Redundancies and correlations in the responses of sensory neurons seem to waste neural resources but can carry cues about structured stimuli and may help the brain to correct for response errors. To assess how the retina negotiates this tradeoff, we measured simultaneous responses from populations of ganglion cells presented with natural and artificial stimuli that varied greatly in correlation structure. We found that pairwise correlations in the retinal output remained similar across stimuli with widely different spatio-temporal correlations including white noise and natural movies. Meanwhile, purely spatial correlations tended to increase correlations in the retinal response. Responding to more correlated stimuli, ganglion cells had faster temporal kernels and tended to have stronger surrounds. These properties of individual cells, along with gain changes that opposed changes in effective contrast at the ganglion cell input, largely explained the similarity of pairwise correlations across stimuli where receptive field measurements were possible.

Networks capture our intuition about relationships in the world. They describe the friendships between Facebook users, interactions in financial markets, and synapses connecting neurons in the brain. These networks are richly structured with cliques of friends, sectors of stocks, and a smorgasbord of cell types that govern how neurons connect. Some networks, like social network friendships, can be directly observed, but in many cases we only have an indirect view of the network through the actions of its constituents and an understanding of how the network mediates that activity. In this work, we focus on the problem of latent network discovery in the case where the observable activity takes the form of a mutually-excitatory point process known as a Hawkes process. We build on previous work that has taken a Bayesian approach to this problem, specifying prior distributions over the latent network structure and a likelihood of observed activity given this network. We extend this work by proposing a discrete-time formulation and developing a computationally efficient stochastic variational inference (SVI) algorithm that allows us to scale the approach to long sequences of observations. We demonstrate our algorithm on the calcium imaging data used in the Chalearn neural connectomics challenge.

How the wiring and functional organization of cortex shape recurrent computation remains a central question in both neuroscience and machine learning. Here, we leverage data released through the Machine Intelligence from Cortical Networks (MICrONS) program--a functional connectomics resource spanning multiple areas of mouse visual cortex, in which dense calcium imaging is co-registered with high-resolution electron microscopy reconstruction from the same animal--to build biologically grounded recurrent neural networks. Using neuronal spatial coordinates, anatomical connectivity, and function-derived relationships from nearly 12,000 coregistered excitatory neurons, we initialize recurrent weights and impose communication-aware spatial constraints during learning. Across three cognitive decision-making tasks, networks constrained by cortical structure and function consistently outperform baseline and partially constrained models. Functional weight initialization provides the largest gain, while real spatial embedding yields robust additional improvements across conditions. These biologically grounded networks also develop low-entropy, modular, and small-world organization, and retain strong performance even when recurrence is restricted to positive weights. Together, our results show that the machinery of cortex--its geometry, wiring, and functional structure--can be harnessed as a powerful inductive basis for building recurrent networks that learn more effectively while converging toward key organizational principles of biological computation.

A basic question within the emerging field of mechanistic interpretability is the degree to which neural networks learn the same underlying mechanisms. In other words, are neural mechanisms universal across different models? In this work, we study the universality of individual neurons across GPT2 models trained from different initial random seeds, motivated by the hypothesis that universal neurons are likely to be interpretable. In particular, we compute pairwise correlations of neuron activations over 100 million tokens for every neuron pair across five different seeds and find that 1-5\% of neurons are universal, that is, pairs of neurons which consistently activate on the same inputs. We then study these universal neurons in detail, finding that they usually have clear interpretations and taxonomize them into a small number of neuron families. We conclude by studying patterns in neuron weights to establish several universal functional roles of neurons in simple circuits: deactivating attention heads, changing the entropy of the next token distribution, and predicting the next token to (not) be within a particular set.

In complex systems, we often observe complex global behavior emerge from a collection of agents interacting with each other in their environment, with each individual agent acting only on locally available information, without knowing the full picture. Such systems have inspired development of artificial intelligence algorithms in areas such as swarm optimization and cellular automata. Motivated by the emergence of collective behavior from complex cellular systems, we build systems that feed each sensory input from the environment into distinct, but identical neural networks, each with no fixed relationship with one another. We show that these sensory networks can be trained to integrate information received locally, and through communication via an attention mechanism, can collectively produce a globally coherent policy. Moreover, the system can still perform its task even if the ordering of its inputs is randomly permuted several times during an episode. These permutation invariant systems also display useful robustness and generalization properties that are broadly applicable. Interactive demo and videos of our results: https://attentionneuron.github.io/

Biological neural networks can operate in qualitatively distinct dynamical regimes, and transitions between these regimes are thought to underlie changes in computation and behavior. The seminal work of Sompolinsky, Crisanti, and Sommers (SCS) showed that random recurrent networks undergo a transition from quiescence to asynchronous chaos, establishing a paradigmatic link between random connectivity, dynamical instability, and internally generated fluctuations in neural circuits. Here, we extend this framework to two-population firing-rate networks with segregated excitatory and inhibitory neurons and target-specific inhibitory couplings that break excitation--inhibition balance. Using dynamical mean-field theory, we derive self-consistent equations for the macroscopic mean activities and autocorrelations, together with stability criteria distinguishing mean-driven and fluctuation-driven instabilities. We show that target-specific inhibition organizes the phase diagram into three qualitative classes: inhibition-dominated or strictly balanced networks display only quiescent activity and asynchronous chaos; excitation-dominated networks display persistent activity together with either synchronous chaos with non-vanishing mean activity or coherent oscillations, depending on the stability-matrix eigenvalues. Crucially, coherent oscillations do not coexist with chaotic fluctuations around the periodic mean trajectory; rather, their onset suppresses the chaotic component, reminiscent of input-induced suppression of chaos. These results generalize SCS theory to recurrent networks with explicit excitatory--inhibitory structure and identify target-specific inhibition as a key control parameter for large-scale neural dynamics.

Cellular form and function emerge from complex mechanochemical systems within the cytoplasm. No systematic strategy currently exists to infer large-scale physical properties of a cell from its many molecular components. This is a significant obstacle to understanding biophysical processes such as cell adhesion and migration. Here, we develop a data-driven biophysical modeling approach to learn the mechanical behavior of adherent cells. We first train neural networks to predict forces generated by adherent cells from images of cytoskeletal proteins. Strikingly, experimental images of a single focal adhesion protein, such as zyxin, are sufficient to predict forces and generalize to unseen biological regimes. This protein field alone contains enough information to yield accurate predictions even if forces themselves are generated by many interacting proteins. We next develop two approaches - one explicitly constrained by physics, the other more agnostic - that help construct data-driven continuum models of cellular forces using this single focal adhesion field. Both strategies consistently reveal that cellular forces are encoded by two different length scales in adhesion protein distributions. Beyond adherent cell mechanics, our work serves as a case study for how to integrate neural networks in the construction of predictive phenomenological models in cell biology, even when little knowledge of the underlying microscopic mechanisms exist.

Activity difference based learning algorithms-such as contrastive Hebbian learning and equilibrium propagation-have been proposed as biologically plausible alternatives to error back-propagation. However, on traditional digital chips these algorithms suffer from having to solve a costly inference problem twice, making these approaches more than two orders of magnitude slower than back-propagation. In the analog realm equilibrium propagation may be promising for fast and energy efficient learning, but states still need to be inferred and stored twice. Inspired by lifted neural networks and compartmental neuron models we propose a simple energy based compartmental neuron model, termed dual propagation, in which each neuron is a dyad with two intrinsic states. At inference time these intrinsic states encode the error/activity duality through their difference and their mean respectively. The advantage of this method is that only a single inference phase is needed and that inference can be solved in layerwise closed-form. Experimentally we show on common computer vision datasets, including Imagenet32x32, that dual propagation performs equivalently to back-propagation both in terms of accuracy and runtime.

Prior studies on the emergence in large models have primarily focused on how the functional capabilities of large language models (LLMs) scale with model size. Our research, however, transcends this traditional paradigm, aiming to deepen our understanding of the emergence within LLMs by placing a special emphasis not just on the model size but more significantly on the complex behavior of neuron interactions during the training process. By introducing the concepts of "self-organization" and "multifractal analysis," we explore how neuron interactions dynamically evolve during training, leading to "emergence," mirroring the phenomenon in natural systems where simple micro-level interactions give rise to complex macro-level behaviors. To quantitatively analyze the continuously evolving interactions among neurons in large models during training, we propose the Neuron-based Multifractal Analysis (NeuroMFA). Utilizing NeuroMFA, we conduct a comprehensive examination of the emergent behavior in LLMs through the lens of both model size and training process, paving new avenues for research into the emergence in large models.

Simulating trajectories of multi-particle systems on complex energy landscapes is a central task in molecular dynamics (MD) and drug discovery, but remains challenging at scale due to computationally expensive and long simulations. Previous approaches leverage techniques such as flow or Schrödinger bridge matching to implicitly learn joint trajectories through data snapshots. However, many systems, including biomolecular systems and heterogeneous cell populations, undergo dynamic interactions that evolve over their trajectory and cannot be captured through static snapshots. To close this gap, we introduce Entangled Schrödinger Bridge Matching (EntangledSBM), a framework that learns the first- and second-order stochastic dynamics of interacting, multi-particle systems where the direction and magnitude of each particle's path depend dynamically on the paths of the other particles. We define the Entangled Schrödinger Bridge (EntangledSB) problem as solving a coupled system of bias forces that entangle particle velocities. We show that our framework accurately simulates heterogeneous cell populations under perturbations and rare transitions in high-dimensional biomolecular systems.

Gradient descent has proven to be a powerful and effective technique for optimization in numerous machine learning applications. Recent advances in computational neuroscience have shown that learning in standard gradient descent optimization formulation is not consistent with learning in biological systems. This has opened up interesting avenues for building biologically inspired learning techniques. One such approach is inspired by Dale's law, which states that inhibitory and excitatory synapses do not swap roles during the course of learning. The resulting exponential gradient descent optimization scheme leads to log-normally distributed synaptic weights. Interestingly, the density that satisfies the Fokker-Planck equation corresponding to the stochastic differential equation (SDE) with geometric Brownian motion (GBM) is the log-normal density. Leveraging this connection, we start with the SDE governing geometric Brownian motion, and show that discretizing the corresponding reverse-time SDE yields a multiplicative update rule, which surprisingly, coincides with the sampling equivalent of the exponential gradient descent update founded on Dale's law. Furthermore, we propose a new formalism for multiplicative denoising score-matching, subsuming the loss function proposed by Hyvaerinen for non-negative data. Indeed, log-normally distributed data is positive and the proposed score-matching formalism turns out to be a natural fit. This allows for training of score-based models for image data and results in a novel multiplicative update scheme for sample generation starting from a log-normal density. Experimental results on MNIST, Fashion MNIST, and Kuzushiji datasets demonstrate generative capability of the new scheme. To the best of our knowledge, this is the first instance of a biologically inspired generative model employing multiplicative updates, founded on geometric Brownian motion.

Nowadays, neural networks act as a synonym for artificial intelligence. Present neural network models, although remarkably powerful, are inefficient both in terms of data and energy. Several alternative forms of neural networks have been proposed to address some of these problems. Specifically, spiking neural networks are suitable for efficient hardware implementations. However, effective learning algorithms for spiking networks remain elusive, although it is suspected that effective plasticity mechanisms could alleviate the problem of data efficiency. Here, we present a new framework for spiking neural networks - Spark - built upon the idea of modular design, from simple components to entire models. The aim of this framework is to provide an efficient and streamlined pipeline for spiking neural networks. We showcase this framework by solving the sparse-reward cartpole problem with simple plasticity mechanisms. We hope that a framework compatible with traditional ML pipelines may accelerate research in the area, specifically for continuous and unbatched learning, akin to the one animals exhibit.

The complete connectome of the Drosophila larva brain offers a unique opportunity to investigate whether biologically evolved circuits can support artificial intelligence. We convert this wiring diagram into a Biological Processing Unit (BPU), a fixed recurrent network derived directly from synaptic connectivity. Despite its modest size 3,000 neurons and 65,000 weights between them), the unmodified BPU achieves 98% accuracy on MNIST and 58% on CIFAR-10, surpassing size-matched MLPs. Scaling the BPU via structured connectome expansions further improves CIFAR-10 performance, while modality-specific ablations reveal the uneven contributions of different sensory subsystems. On the ChessBench dataset, a lightweight GNN-BPU model trained on only 10,000 games achieves 60% move accuracy, nearly 10x better than any size transformer. Moreover, CNN-BPU models with ~2M parameters outperform parameter-matched Transformers, and with a depth-6 minimax search at inference, reach 91.7% accuracy, exceeding even a 9M-parameter Transformer baseline. These results demonstrate the potential of biofidelic neural architectures to support complex cognitive tasks and motivate scaling to larger and more intelligent connectomes in future work.

Current techniques of neuroimaging, including electrical devices, are either of low spatiotemporal resolution or invasive, impeding multiscale monitoring of brain activity at both single cell and network levels. Overcoming this issue is of great importance to assess brain's computational ability and for neurorehabilitation projects that require real-time monitoring of neurons and concomitant networks activities. Currently, that information could be extracted from functional MRI when combined with mathematical models. Novel methods enabling quantitative and long-lasting recording at both single cell and network levels will allow to correlate the MRI data with intracortical activity at single cell level, and to refine those models. Here, we report the fabrication and validation of ultra-thin, optically transparent and flexible intracortical microelectrode arrays for combining extracellular multi-unit and fMRI recordings. The sensing devices are compatible with large-scale manufacturing, and demonstrate both fMRI transparency at 4.7 T, and high electrical performance, and thus appears as a promising candidate for simultaneous multiscale neurodynamic measurements.

The field of neuroscience and the development of artificial neural networks (ANNs) have mutually influenced each other, drawing from and contributing to many concepts initially developed in statistical mechanics. Notably, Hopfield networks and Boltzmann machines are versions of the Ising model, a model extensively studied in statistical mechanics for over a century. In the first part of this chapter, we provide an overview of the principles, models, and applications of ANNs, highlighting their connections to statistical mechanics and statistical learning theory. Artificial neural networks can be seen as high-dimensional mathematical functions, and understanding the geometric properties of their loss landscapes (i.e., the high-dimensional space on which one wishes to find extrema or saddles) can provide valuable insights into their optimization behavior, generalization abilities, and overall performance. Visualizing these functions can help us design better optimization methods and improve their generalization abilities. Thus, the second part of this chapter focuses on quantifying geometric properties and visualizing loss functions associated with deep ANNs.

We investigate Josephson arrays consisting of a dice-lattice network of superconducting weak links surrounding rhombic plaquettes of proximitized semiconductor. Josephson coupling of the weak links and electron density in the plaquettes are independently controlled by separate electrostatic gates. Applied magnetic flux results in an intricate pattern of switching currents associated with frustration, f. For depleted plaquettes, the switching current is nearly periodic in f, expected for a phase-only description, while occupied plaquettes yield a decreasing envelope of switching currents with increasing f. A model of flux dependence based on ballistic small-area junctions and diffusive large-area plaquettes yields excellent agreement with experiment.

The neurons of artificial neural networks were originally invented when much less was known about biological neurons than is known today. Our work explores a modification to the core neuron unit to make it more parallel to a biological neuron. The modification is made with the knowledge that biological dendrites are not simply passive activation funnels, but also compute complex non-linear functions as they transmit activation to the cell body. The paper explores a novel system of "Perforated" backpropagation empowering the artificial neurons of deep neural networks to achieve better performance coding for the same features they coded for in the original architecture. After an initial network training phase, additional "Dendrite Nodes" are added to the network and separately trained with a different objective: to correlate their output with the remaining error of the original neurons. The trained Dendrite Nodes are then frozen, and the original neurons are further trained, now taking into account the additional error signals provided by the Dendrite Nodes. The cycle of training the original neurons and then adding and training Dendrite Nodes can be repeated several times until satisfactory performance is achieved. Our algorithm was successfully added to modern state-of-the-art PyTorch networks across multiple domains, improving upon original accuracies and allowing for significant model compression without a loss in accuracy.

Vital to primary visual processing, retinal circuitry shows many similar structures across a very broad array of species, both vertebrate and non-vertebrate, especially functional components such as lateral inhibition. This surprisingly conservative pattern raises a question of how evolution leads to it, and whether there is any alternative that can also prompt helpful preprocessing. Here we design a method using genetic algorithm that, with many degrees of freedom, leads to architectures whose functions are similar to biological retina, as well as effective alternatives that are different in structures and functions. We compare this model to natural evolution and discuss how our framework can come into goal-driven search and sustainable enhancement of neural network models in machine learning.

Why do neurons communicate through spikes? By definition, spikes are all-or-none neural events which occur at continuous times. In other words, spikes are on one side binary, existing or not without further details, and on the other can occur at any asynchronous time, without the need for a centralized clock. This stands in stark contrast to the analog representation of values and the discretized timing classically used in digital processing and at the base of modern-day neural networks. As neural systems almost systematically use this so-called event-based representation in the living world, a better understanding of this phenomenon remains a fundamental challenge in neurobiology in order to better interpret the profusion of recorded data. With the growing need for intelligent embedded systems, it also emerges as a new computing paradigm to enable the efficient operation of a new class of sensors and event-based computers, called neuromorphic, which could enable significant gains in computation time and energy consumption -- a major societal issue in the era of the digital economy and global warming. In this review paper, we provide evidence from biology, theory and engineering that the precise timing of spikes plays a crucial role in our understanding of the efficiency of neural networks.

Regarded as the third generation of neural networks, Spiking Neural Networks (SNNs) have garnered significant traction due to their biological plausibility and energy efficiency. Recent advancements in large models necessitate spiking neurons capable of high performance, adaptability, and training efficiency. In this work, we first propose a novel functional perspective that provides general guidance for designing the new generation of spiking neurons. Following the insightful guidelines, we propose the Adaptive Spiking Neuron (ASN), which incorporates trainable parameters to learn membrane potential dynamics and enable adaptive firing. ASN adopts an integer training and spike inference paradigm, facilitating efficient SNN training. To further enhance robustness, we propose a specialized variant of ASN, the Normalized Adaptive Spiking Neuron (NASN), which integrates normalization to stabilize training. We evaluate our neuron model on 19 datasets spanning five distinct tasks in both vision and language modalities, demonstrating the effectiveness and versatility of the ASN family. Our ASN family is expected to become the new generation of general-purpose spiking neurons.

This work introduces a new computational theory of mind grounded in set theory and hyperdimensional computing. Whereas traditional neural networks rely on continuous weights and matrix multiplication, this framework works with sparse binary data. It represents information as discrete sets, directly modeling biological neural population codes. I demonstrate that associative memory emerges naturally from network topologies featuring a combinatorially expanded hidden layer. Learning is driven by topological plasticity rather than scalar weight adjustments. This architecture unifies auto-associative and hetero-associative learning under a single core algorithm: information retrieval via subset pattern matching and exact nearest-neighbor search. Operating with constant-time complexity, these mechanisms bridge perceptual data (sparse distributed representations) and symbols (sparse holographic representations) without continuous bottlenecks. Mapping this framework to neuroanatomy, I propose that both the cerebellum and the neocortex implement variants of this algorithm, making subset pattern matching the fundamental engine of cognition. Because it relies on discrete logic rather than matrix arithmetic, this algorithm translates directly into in-memory hardware. This opens a new route toward synthetic intelligence with human-level energy efficiency.

Cortical circuits exhibit intricate recurrent architectures that are remarkably similar across different brain areas. Such stereotyped structure suggests the existence of common computational principles. However, such principles have remained largely elusive. Inspired by gated-memory networks, namely long short-term memory networks (LSTMs), we introduce a recurrent neural network in which information is gated through inhibitory cells that are subtractive (subLSTM). We propose a natural mapping of subLSTMs onto known canonical excitatory-inhibitory cortical microcircuits. Our empirical evaluation across sequential image classification and language modelling tasks shows that subLSTM units can achieve similar performance to LSTM units. These results suggest that cortical circuits can be optimised to solve complex contextual problems and proposes a novel view on their computational function. Overall our work provides a step towards unifying recurrent networks as used in machine learning with their biological counterparts.

The human brain is a complex spiking neural network (SNN) that learns multimodal signals in a zero-shot manner by generalizing existing knowledge. Remarkably, the brain achieves this with minimal power consumption, using event-based signals that propagate within its structure. However, mimicking the human brain in neuromorphic hardware presents both hardware and software challenges. Hardware limitations, such as the slowdown of Moore's law and the von Neumann bottleneck, hinder the efficiency of digital computers. On the software side, SNNs are known for their difficult training, especially when learning multimodal signals. To overcome these challenges, we propose a hardware-software co-design that combines a fixed and random liquid state machine (LSM) SNN encoder with trainable artificial neural network (ANN) projections. The LSM is physically implemented using analogue resistive memory, leveraging the inherent stochasticity of resistive switching to generate random weights. This highly efficient and nanoscale in-memory computing approach effectively addresses the von Neumann bottleneck and the slowdown of Moore's law. The ANN projections are implemented digitally, allowing for easy optimization using contrastive loss, which helps to overcome the difficulties associated with SNN training. We experimentally implement this co-design on a 40nm 256Kb in-memory computing macro. We first demonstrate LSM-based event encoding through supervised classification and linear probing on the N-MNIST and N-TIDIGITS datasets.

Attending to what is relevant is fundamental to both the mammalian brain and modern machine learning models such as Transformers. Yet, determining relevance remains a core challenge, traditionally offloaded to learning algorithms like backpropagation. Inspired by recent cellular neurobiological evidence linking neocortical pyramidal cells to distinct mental states, this work shows how models (e.g., Transformers) can emulate high-level perceptual processing and awake thought (imagination) states to pre-select relevant information before applying attention. Triadic neuronal-level modulation loops among questions (Q), clues (keys, K), and hypotheses (values, V) enable diverse, deep, parallel reasoning chains at the representation level and allow a rapid shift from initial biases to refined understanding. This leads to orders-of-magnitude faster learning with significantly reduced computational demand (e.g., fewer heads, layers, and tokens), at an approximate cost of O(N), where N is the number of input tokens. Results span reinforcement learning (e.g., CarRacing in a high-dimensional visual setup), computer vision, and natural language question answering.

Recent years have witnessed Spiking Neural Networks (SNNs) gaining attention for their ultra-low energy consumption and high biological plausibility compared with traditional Artificial Neural Networks (ANNs). Despite their distinguished properties, the application of SNNs in the computationally intensive field of image generation is still under exploration. In this paper, we propose the Spiking Diffusion Models (SDMs), an innovative family of SNN-based generative models that excel in producing high-quality samples with significantly reduced energy consumption. In particular, we propose a Temporal-wise Spiking Mechanism (TSM) that allows SNNs to capture more temporal features from a bio-plasticity perspective. In addition, we propose a threshold-guided strategy that can further improve the performances by up to 16.7% without any additional training. We also make the first attempt to use the ANN-SNN approach for SNN-based generation tasks. Extensive experimental results reveal that our approach not only exhibits comparable performance to its ANN counterpart with few spiking time steps, but also outperforms previous SNN-based generative models by a large margin. Moreover, we also demonstrate the high-quality generation ability of SDM on large-scale datasets, e.g., LSUN bedroom. This development marks a pivotal advancement in the capabilities of SNN-based generation, paving the way for future research avenues to realize low-energy and low-latency generative applications. Our code is available at https://github.com/AndyCao1125/SDM.

The whole-brain connectome of a fruit fly comprises over 130K neurons connected with a probability of merely 0.02%, yet achieves an average shortest path of only 4.4 hops. Despite being highly structured at the circuit level, the network's long-range connections are broadly distributed across brain regions, functioning as stochastic shortcuts that enable efficient global communication. Inspired by this observation, we propose Stochastic Attention (SA), a drop-in enhancement for sliding-window attention (SWA) that applies a random permutation to the token sequence before windowed attention and restores the original order afterward. This transforms the fixed local window into a stochastic global one within the same O(nw) per-layer budget. Through depth, independently sampled permutations yield exponentially growing receptive fields, achieving full sequence coverage in O(log_w n) layers versus O(n/w) for SWA. We validate SA in two settings: pre-training language models from scratch, where a gated SA + SWA combination achieves the best average zero-shot accuracy, and training-free inference on Qwen3-8B and Qwen3-30B-A3B, where SA consistently outperforms SWA and matches or exceeds Mixture of Block Attention at comparable compute budgets. These results suggest that connectome-inspired stochastic routing is a practical primitive for improving the expressivity of efficient attention, complementary to existing linear and sparse approaches.

Scaling laws predict loss from compute but not how capabilities interact. We measure the coupling between reasoning and truthfulness across 63 base models from 16 families and find a regime change invisible to loss curves: below a family-dependent critical scale N_c, capabilities anticorrelate; above it, they cooperate. N_c approx 3.5B parameters [2.9B, 13.4B] (bootstrap 95% CI), but model size is not the only variable that determines phase. Architecture, data curation, and training recipe each shift N_c independently: curated training eliminated the coupling dip between Qwen generations (0.025 to 0.830 at matched scale), Gemma-4 at 4B achieves coupling 0.871, characteristic of 13B+ standard-trained models, through distillation and architectural innovation, and Phi at 1B matches web-trained coupling at 10B through data curation alone. Width normalization eliminates the anticorrelation across all tested families, supporting an output-projection bottleneck. Internally, 38 of 40 models show zero competing attention heads. A sparse-regression ODE cross-predicts held-out Llama-2 at 5.6% error. The diagnostic requires no model internals -- only public benchmark scores across a model family. The cooperative regime extends to the frontier (r = +0.72, 34 models, 10 labs). Code, data, and an open-source activation-steering tool for any open-weight model are released alongside an interactive dashboard that diagnoses any model's coupling phase, suggests concrete interventions (data curation, width, benchmark rotation), and provides ODE scaling predictions, frontier diagnostics, and eigenstructure analysis: https://zehenlabs.com/cape/.

Neuroscience employs diverse neuroimaging techniques, each offering distinct insights into brain activity, from electrophysiological recordings such as EEG, which have high temporal resolution, to hemodynamic modalities such as fMRI, which have increased spatial precision. However, integrating these heterogeneous data sources remains a challenge, which limits a comprehensive understanding of brain function. We present the Spatiotemporal Alignment of Multimodal Brain Activity (SAMBA) framework, which bridges the spatial and temporal resolution gaps across modalities by learning a unified latent space free of modality-specific biases. SAMBA introduces a novel attention-based wavelet decomposition for spectral filtering of electrophysiological recordings, graph attention networks to model functional connectivity between functional brain units, and recurrent layers to capture temporal autocorrelations in brain signal. We show that the training of SAMBA, aside from achieving translation, also learns a rich representation of brain information processing. We showcase this classify external stimuli driving brain activity from the representation learned in hidden layers of SAMBA, paving the way for broad downstream applications in neuroscience research and clinical contexts.

Spiking Neural Networks (SNNs) provide a promising framework for energy-efficient and biologically grounded computation; however, scalable learning in deep recurrent architectures with sparse connectivity remains a major challenge. In this work, we propose a structured multi-layer recurrent SNN architecture composed of locally dense recurrent layers augmented with sparse small-world long-range projections to a readout population. The long-range connectivity is largely fixed, preserving routing efficiency and hardware scalability, while synaptic adaptation is performed using strictly local plasticity mechanisms. To enable supervised learning without backpropagation or surrogate gradients, we introduce a biologically motivated learning framework that combines: (i) population-based winner-take-all (WTA) teaching signals at the output layer, (ii) fixed random broadcast alignment feedback pathways, and (iii) low-dimensional modulatory neuron populations that gate synaptic updates through three-factor learning rules with eligibility traces. This design supports deep recurrent computation with sparse global communication and purely local synaptic updates. We analyze the algorithmic properties, computational complexity, and hardware feasibility of the proposed approach, and demonstrate stable learning and competitive performance on benchmark classification tasks. The results highlight the potential of structured recurrence and neuromodulatory learning to enable scalable, hardware-compatible SNN training beyond gradient-based methods.

To model high-risk traffic densities a cellular automaton model is constructed, exhibiting Ising model-like properties. The attraction-repulsion forces between vehicles are evaluated as coupling, and the coupling function p(1-p)=g/8, where p is the initial distribution of cells with state 1, and g is the Moore neighbor count, which has roots cos^2(π/8) and sin^2(π/8) for g=1. This is achieved without the use of any trigonometric functions in the code. From the roots, the tangent polynomial tan^2(x) + tan(x) emerges. Kramers-Wannier duality is recovered and it is conjectured that the 1/2 difference between the roots serves as a fixed point for a projection mechanism from the 2-dimensional Ising model onto a 1-dimensional Ising chain through the Gudermannian function. The sigmoid evaluated at the proposed fixed point is substituted into the derivative of the logistic coupling function, σ(1/2)(1-σ(1/2)), yielding a numerical approximation to the three-dimensional Ising inverse critical coupling. Finally, the results are linked to risk densities in traffic and vehicle types, accounting for the amplification of fatal accidents.

This paper introduces a new biologically-inspired training method named Continual Learning through Adjustment Suppression and Sparsity Promotion (CLASSP). CLASSP is based on two main principles observed in neuroscience, particularly in the context of synaptic transmission and Long-Term Potentiation (LTP). The first principle is a decay rate over the weight adjustment, which is implemented as a generalization of the AdaGrad optimization algorithm. This means that weights that have received many updates should have lower learning rates as they likely encode important information about previously seen data. However, this principle results in a diffuse distribution of updates throughout the model, as it promotes updates for weights that haven't been previously updated, while a sparse update distribution is preferred to leave weights unassigned for future tasks. Therefore, the second principle introduces a threshold on the loss gradient. This promotes sparse learning by updating a weight only if the loss gradient with respect to that weight is above a certain threshold, i.e. only updating weights with a significant impact on the current loss. Both principles reflect phenomena observed in LTP, where a threshold effect and a gradual saturation of potentiation have been observed. CLASSP is implemented in a Python/PyTorch class, making it applicable to any model. When compared with Elastic Weight Consolidation (EWC) using Computer Vision and sentiment analysis datasets, CLASSP demonstrates superior performance in terms of accuracy and memory footprint.

Scientific applications increasingly demand real-time surrogate models that can capture the behavior of strongly coupled multiphysics systems driven by multiple input functions, such as in thermo-mechanical and electro-thermal processes. While neural operator frameworks, such as Deep Operator Networks (DeepONets), have shown considerable success in single-physics settings, their extension to multiphysics problems remains poorly understood. In particular, the challenge of learning nonlinear interactions between tightly coupled physical fields has received little systematic attention. This study addresses a foundational question: should the architectural design of a neural operator reflect the strength of physical coupling it aims to model? To answer this, we present the first comprehensive, architecture-aware evaluation of DeepONet variants across three regimes: single-physics, weakly coupled, and strongly coupled multiphysics systems. We consider a reaction-diffusion equation with dual spatial inputs, a nonlinear thermo-electrical problem with bidirectional coupling through temperature-dependent conductivity, and a viscoplastic thermo-mechanical model of steel solidification governed by transient phase-driven interactions. Two operator-learning frameworks, the classical DeepONet and its sequential GRU-based extension, S-DeepONet, are benchmarked using both single-branch and multi-branch (MIONet-style) architectures. Our results demonstrate that architectural alignment with physical coupling is crucial: single-branch networks significantly outperform multi-branch counterparts in strongly coupled settings, whereas multi-branch encodings offer advantages for decoupled or single-physics problems. Once trained, these surrogates achieve full-field predictions up to 1.8e4 times faster than high-fidelity finite-element solvers, without compromising solution accuracy.

Large Language Models (LLMs) have made significant strides in natural language processing, and a precise understanding of the internal mechanisms driving their success is essential. In this work, we analyze the trajectories of token embeddings as they pass through transformer blocks, linearizing the system along these trajectories through their Jacobian matrices. By examining the relationships between these block Jacobians, we uncover the phenomenon of transformer block coupling in a multitude of LLMs, characterized by the coupling of their top singular vectors across tokens and depth. Our findings reveal that coupling positively correlates with model performance, and that this relationship is stronger than with other hyperparameters such as parameter count, model depth, and embedding dimension. We further investigate how these properties emerge during training, observing a progressive development of coupling, increased linearity, and layer-wise exponential growth in token trajectories. Additionally, experiments with Vision Transformers (ViTs) corroborate the emergence of coupling and its relationship with generalization, reinforcing our findings in LLMs. Collectively, these insights offer a novel perspective on token interactions in transformers, opening new directions for studying their mechanisms as well as improving training and generalization.

In-context learning is a powerful emergent ability in transformer models. Prior work in mechanistic interpretability has identified a circuit element that may be critical for in-context learning -- the induction head (IH), which performs a match-and-copy operation. During training of large transformers on natural language data, IHs emerge around the same time as a notable phase change in the loss. Despite the robust evidence for IHs and this interesting coincidence with the phase change, relatively little is known about the diversity and emergence dynamics of IHs. Why is there more than one IH, and how are they dependent on each other? Why do IHs appear all of a sudden, and what are the subcircuits that enable them to emerge? We answer these questions by studying IH emergence dynamics in a controlled setting by training on synthetic data. In doing so, we develop and share a novel optogenetics-inspired causal framework for modifying activations throughout training. Using this framework, we delineate the diverse and additive nature of IHs. By clamping subsets of activations throughout training, we then identify three underlying subcircuits that interact to drive IH formation, yielding the phase change. Furthermore, these subcircuits shed light on data-dependent properties of formation, such as phase change timing, already showing the promise of this more in-depth understanding of subcircuits that need to "go right" for an induction head.

We address the problem of biased gradient estimation in deep Boltzmann machines (DBMs). The existing method to obtain an unbiased estimator uses a maximal coupling based on a Gibbs sampler, but when the state is high-dimensional, it takes a long time to converge. In this study, we propose to use a coupling based on the Metropolis-Hastings (MH) and to initialize the state around a local mode of the target distribution. Because of the propensity of MH to reject proposals, the coupling tends to converge in only one step with a high probability, leading to high efficiency. We find that our method allows DBMs to be trained in an end-to-end fashion without greedy pretraining. We also propose some practical techniques to further improve the performance of DBMs. We empirically demonstrate that our training algorithm enables DBMs to show comparable generative performance to other deep generative models, achieving the FID score of 10.33 for MNIST.

A new type of cooperativity termed temporal cooperativity [Biophys. Chem. 105 585-593 (2003), Annu. Rev. Phys. Chem. 58 113-142 (2007)], emerges in the signal transduction module of phosphorylation-dephosphorylation cycle (PdPC). It utilizes multiple kinetic cycles in time, in contrast to allosteric cooperativity that utilizes multiple subunits in a protein. In the present paper, we thoroughly investigate both the deterministic (microscopic) and stochastic (mesoscopic) models, and focus on the identification of the source of temporal cooperativity via comparing with allosteric cooperativity. A thermodynamic analysis confirms again the claim that the chemical equilibrium state exists if and only if the phosphorylation potential triangle G=0, in which case the amplification of sensitivity is completely abolished. Then we provide comprehensive theoretical and numerical analysis with the first-order and zero-order assumptions in phosphorylation-dephosphorylation cycle respectively. Furthermore, it is interestingly found that the underlying mathematics of temporal cooperativity and allosteric cooperativity are equivalent, and both of them can be expressed by "dissociation constants", which also characterizes the essential differences between the simple and ultrasensitive PdPC switches. Nevertheless, the degree of allosteric cooperativity is restricted by the total number of sites in a single enzyme molecule which can not be freely regulated, while temporal cooperativity is only restricted by the total number of molecules of the target protein which can be regulated in a wide range and gives rise to the ultrasensitivity phenomenon.