Mathematical Modeling seminars

Large recurrent networks are important models in several fields, including neuroscience, machine learning, physics, and applied mathematics. Yet their dynamics are difficult to study directly, because high-dimensional nonlinear systems can exhibit rich behavior that is hard to summarize in terms of individual trajectories. In this talk, I will discuss an approach that seeks to understand such dynamics through the structure of the network’s equilibria. I will focus on a random balanced network of threshold-linear units that undergoes a transition from a single stable equilibrium to extensive chaos as the disorder strength crosses a critical value. Using a combination of Kac–Rice theory, replica calculations, numerical root-finding, and dynamical mean-field theory, we show that the chaotic regime contains an exponentially large number of equilibria. These equilibria are all saddles, but with only a fractionally small number of unstable directions. Surprisingly, despite the completely random connectivity, the equilibria are not scattered randomly through phase space. Instead, they are strongly correlated and confined to a comparatively small region. The chaotic attractor lies within this same region, suggesting a direct geometric link between the organization of unstable equilibria and the collective structure of the dynamics. This picture helps explain why networks with extensive chaos can nevertheless display dynamics dominated by a relatively small number of collective modes. More broadly, the results suggest that the geometry of equilibria provides a useful complementary perspective to dynamical mean-field theory for understanding high-dimensional neural dynamics. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2026-05-27. Recording duration: 00:46:40.

Networks of interconnected neurons display diverse patterns of activity. Relating these patterns to the structure of the network is a central goal of theoretical neuroscience. Classic neural field and rate models have been powerful tools for this purpose due to their analytical tractability. Here, we show that the recently-developed combinatorial threshold-linear network (CTLN) model is a mean-field theory for excitatory-inhibitory Hawkes networks, with clustered connectivity, in an inhibition-stabilized regime. This mapping allows us to leverage powerful analytical results for CTLN networks to predict diverse macroscopic dynamics of clustered Hawkes networks, including metastability between various macroscopic fixed points, limit cycles, and chaotic attractors. We will then examine an extension of this approach to models with nonlinear dendritic dynamics, focusing on dendritic calcium spikes.We uncover a marked point process mean-field theory for these n etworks and use this to examine how somatic vs dendritic-targeting connectivity shapes the mean-field equilibrium phase diagram. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2026-05-13. Recording duration: 00:54:14.

How does a cat gracefully walk and suddenly freeze when spotting a mouse? In this talk, we look at how networks in the spinal cord generate movement. In particular, we address the fundamental yet poorly understood question of motor control: How can rhythmic movements, such as walking, be generated and stopped at any point in the cycle while posture is preserved? Since conventional models of spinal motor function rely on alternation between flexor and extensor modules, which are limited to just two phases, this question exposes the essential shortcoming of the conventional understanding: How can a system with only two phases generate and stop walking in any phase? To address this question and better understand the generation and stopping of motor activity, we use Neuropixels probes in the rat spinal cord during voluntary, freely moving locomotion. We utilize optogenetic activation of a brainstem nucleus to induce stopping. During locomotion, neuronal manifold activity exhibits robust rotational patterns that are topologically invariant with respect to speed (Linden 2022). Furthermore, this trajectory converges on a stable point-attractor precisely at the moment of arrest, and it persists until the movement is resumed. Through computational modeling, we propose that the walk-to-stop represents a bifurcation from a limit cycle to a fixed point attractor. We also propose a structural network mechanism for its physical implementation (Komi 2026). The structural mechanism entails a longitudinal projectome with a skewed Mexican hat topology, i.e., primarily local recurrent excitation and longer-range inhibition. Such a network can generate motor patterns via traveling waves, with frequency and amplitude controlled independently, and rhythm induced without requiring cellular pacemaker mechanisms. Together, our experimental observations support a new theory for the mechanism behind the generation of movement by networks in the spinal cord. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2026-03-25. Recording duration: 00:37:44.

Much is known about the neural representations of current environmental location and direction within the hippocampal formation, but use of such a “cognitive map” requires the online representation of desired locations and how to get there, and the neural basis for this function has been more elusive. I will discuss how “theta sweeps” of place and grid cell firing encode the current location (at early phases of each theta cycle) while, at later phases, sampling around the forward direction during exploration and indicating the direction to desired locations during goal-directed navigation. I will show how a relatively simple attractor model captures these results, but requires inputs signalling movement-direction and goal-direction.I will discuss why it is useful to consider the hippocampus as a generative model (in which head-direction, rather than movement-direction, is required, to translate egocentric sensory inputs to allocentric latent representations and back again) in explaining its roles in both spatial cognition and memory consolidation. “Replay sequences” are thought to support offline consolidation, and likely resemble theta sweeps more than behavioural experience. I will finish (given time) by considering how human memory consolidation can be seen as extraction of latent variables from replay via self-supervised learning, and how this perspective explains aspects of human memory such as gist-based distortions, imagination and planning. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2026-02-25. Recording duration: 00:46:52.

In sensory systems, stimuli are represented through the diverse firing responses and receptive fields of neurons. These features emerge from the interaction between excitatory (E) and inhibitory (I) neuron populations within the network. Changes in sensory inputs alter this balance, leading to shifts in firing patterns and the input-output properties of individual neurons and the network. While these phenomena have been studied extensively with experiments and theory, the underlying principles for combining E and I inputs are still unclear. Here, the rules for probabilistically combining E and I inputs are derived that describe how neurons in a feedforward inhibitory circuit respond to stimuli. This simple model is broadly applicable, capturing a wide range of response features that would otherwise require multiple separate models and offers insights into the cellular and network mechanisms influencing the input-output properties of neurons, gain modulation, and the emergence of diverse temporal firing patterns. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2026-02-11. Recording duration: 00:48:34.

Many animals rely on persistent internal representations of continuous angular variables for working memory, motor control, and navigation. Theories have proposed that such representations are maintained by a class of recurrently connected networks called ring attractor networks. These networks rely on large numbers of neurons to maintain continuous and stable representations and to accurately integrate incoming signals. The head direction system of the fruit fly, however, seems to achieve these properties with a remarkably small network. These findings challenge our understanding of ring attractors and their putative implementation in neural circuits. In this talk, I will show analytically how small networks can overcome the constraints of their size to generate a ring attractor and are hence capable of stably maintaining an internal representation of a continuous, periodic variable. Further, I will show how ring attractors emerge in small threshold linear networks through the coordination of a discrete set of line attractors. More broadly, this work informs our understanding of the functional capabilities of small, discrete systems. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2026-02-04. Recording duration: 00:44:59.

Computations in neural circuits are often construed as being implemented through the coordinated dynamics of neurons. In this picture, the role of synaptic connectivity is to sculpt neuronal dynamics to implement computations of interest. Of course, synapses are not static but change on a variety of timescales, including fast timescales comparable to those of neurons. Thus, a more accurate view of computation in neural circuits may involve the coupled dynamics of neurons and synapses. This form of computation is closer to what is implemented by Transformers via an equivalence between ongoing synaptic plasticity and self-attention. I will first describe a nonlinear recurrent neural-network model with ongoing Hebbian dynamics of “fast” synapses atop unstructured “slow” synapses. I will then describe two computations implemented through neuronal-synaptic dynamics, which can be studied in this model using techniques including dynamical mean-field theory and random-matrix theory. First, there exists a novel phase termed “freezable chaos” in which a stable fixed point of neuronal dynamics is continuously destabilized by synaptic dynamics. This allows for the creation of a stable fixed point at any neuronal state visited by the network by halting synaptic plasticity. Second, I will describe an effect termed “persistent oscillations” in which, following stimulation by a periodic signal, a plastic network continues to autonomously reproduce a similar signal for a duration exceeding any intrinsic timescale in the system. Thus, ongoing Hebbian plasticity can provide a dynamic form of working memory, complementing the static form provided by freezable chaos. Ongoing experimental work suggests that this effect is realized in cortical organoids. Overall, this line of work suggests that synapses should be promoted to first-class dynamical degrees of freedom in our conceptual understanding of neural-circuit function. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2026-01-14. Recording duration: 00:43:14.

Recurrent networks with balanced excitation-inhibition explain a wide range of neurophysiological observations, but can only implement a limited set of transformations on their input. On the other hand networks of firing-rate units with low-rank connectivity have universal computational capabilities, but do not work with spikes or generate noise self-consistently. Although empirical approaches to merge these two computational frameworks have been constructed, there is no established theory describing their unification. Here we develop such a theory. We study analytically and numerically networks with connectivity comprising random “strong”, and low-rank “weak” components. When the low-rank connectivity is slow, a well-defined notion of instantaneous firing rate emerges which implies universal computation as previously shown. However, the fact that such time-varying rates are the result of E-I balance has important implications. We show that internally or externally generated fluctuations along particular latent modes tend to break the E-I balance. Its maintenance is obtained through the emergence of a spontaneous coupling between the mean and the variance of the membrane potential and the norm of the latent state driving these modes. This leads to several predictions, the most counterintuitive of which is that coherent global fluctuations in subthreshold membrane potential (Vm) should coexist with desynchronized activity at constant firing rates when the dynamics of these modes is excited. To test our theory, we show that the coupling between the average Vm and the latent state adds new non-linear dimensions to the low-dimensional manifold of the network, which lead to a frequency doubling when the input to the network is periodic, a prediction that is borne out in population recordings from mouse V1. Our results unify two prevalent frameworks for cortical computation and clarify the relationship between computation, dynamics and geometry in circuits of spiking neurons. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-11-26. Recording duration: 00:39:26.

Minimising cortical prediction errors is thought to be a key computation underlying perception, action, and learning. Yet, how the cortex represents and uses uncertainty in this process remains unclear. In the first part of this talk, I will present a normative framework showing how uncertainty can modulate prediction error activity to yield uncertainty-modulated prediction errors (UPEs), hypothesised to be represented by layer 2/3 pyramidal neurons. We propose that these UPEs are computed through inhibitory mechanisms involving SST and PV interneurons. A circuit model demonstrates how cortical cell types can locally compute means, variances, and UPEs, leading to adaptive learning rates. In the second part, I will discuss how uncertainty modulation could be controlled by higher-level representations. We formally derived neural dynamics that minimise prediction errors under the assumption that cortical areas must not only predict the activity in other areas and sensory streams but also jointly project their inverse expected uncertainty about their predictions, which we call “confidence”. This yields a confidence-weighted integration of bottom-up and top-down signals, consistent with Bayesian principles, and predicts the existence of second-order errors that compare confidence with performance. We predict that these second-order errors propagate alongside classical prediction errors through the cortical hierarchy, and simulations demonstrate that this mechanism enables nonlinear classification within a single cortical area. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-11-12. Recording duration: 00:29:21.

Measurements from hippocampal place cells in small enclosures have led to a classical view of highly stereotyped neural tuning functions with smooth, unimodal tuning fields that uniformly tile the environment. However, recent experiments conducted in large spaces across multiple species have revealed a much more irregular neural code than suggested by the classical view. Indeed, place cells in large environments typically fire in multiple locations, and the multiple firing fields of individual cells, as well as those of the entire population, vary considerably in size and shape. We recently showed that a simple mathematical model, wherein firing fields are generated by thresholding realizations of a random Gaussian process, accounts for the statistical properties of place fields in precise quantitative detail. This model captures the observed statistics of field sizes and positions and generates new quantitative predictions on field shapes and topologies. Moreover, these statistics are universal across species, but sensitive to the size and dimensionality of the environment. We quantitatively verified these predictions using multiple recent datasets from bats and rodents in one, two, and three dimensions, across both small and large environments. Collectively, these findings imply that common mechanism underlie the diverse statistical features observed in different experiments and suggest that synaptic projections to CA1 are predominantly random. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-05-28. Recording duration: 00:42:45.

Pharmacokinetics in the eye is an important factor for the success of ocular drug delivery and treatment. Pharmacokinetic features determine the feasible routes of drug administration, dosing levels and intervals, and it has impact on eventual drug responses. Several physical, biochemical, and flow-related barriers limit drug exposure of anterior and posterior ocular target tissues during treatment during local (topical, subconjunctival, intravitreal) and systemic administration (intravenous, per oral). Mathematical models integrate joint impact of various barriers on ocular pharmacokinetics (PKs) thereby helping drug development. The models are useful in describing (top-down) and predicting (bottom-up) pharmacokinetics of ocular drugs. This is useful also in the design and development of new drug molecules and drug delivery systems. Furthermore, the models can be used for interspecies translation and probing of disease effects on pharmacokinetics. In this lecture, ocular pharmacokinetics and current modelling methods (noncompartmental analyses, compartmental, physiologically based, and finite element models) are introduced. Future challenges are also highlighted (e.g. intra-tissue distribution, prediction of drug responses, active transport).

In the brain, while early sensory areas encode and process external inputs rapidly, higher-association areas are endowed with slow dynamics to benefit information accumulation over time. This property raises the question of why diverse timescales are well localized rather than being mixed up across the cortex, despite high connection density and an abundance of feedback loops that support reliable signal propagation. In this talk, we will address this question by analyzing a large-scale network model of the primate cortex, and we identify a novel dynamical regime termed "interference-free propagation". In this regime, the mean components of the synaptic currents to each downstream area are imbalanced to ensure signals to propagate reliably, while the temporally fluctuating components of the synaptic inputs governed by upstream areas' timescales are largely canceled out, leading to the localization of its own timescale in each downstream area. Our result provides new insights into the operational regime of the cortex, leading to the coexistence of hierarchical timescale localization and reliable signal propagation. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-02-26. Recording duration: 00:48:02.

Brain Emulation Challenge workshop will tackle cutting-edge topics such as ground-truthing for validation, leveraging artificial datasets generated from virtual brain tissue, and the transformative potential of virtual brain platforms, such as applied to the forthcoming Brain Emulation Challenge.

Brain Emulation Challenge workshop will tackle cutting-edge topics such as ground-truthing for validation, leveraging artificial datasets generated from virtual brain tissue, and the transformative potential of virtual brain platforms, such as applied to the forthcoming Brain Emulation Challenge.

Brain Emulation Challenge workshop will tackle cutting-edge topics such as ground-truthing for validation, leveraging artificial datasets generated from virtual brain tissue, and the transformative potential of virtual brain platforms, such as applied to the forthcoming Brain Emulation Challenge.

Networks of excitatory and inhibitory (EI) neurons form a canonical circuit in the brain. Classical theoretical analyses of dynamics in EI networks have revealed key principles such as EI balance or paradoxical responses to external inputs. These seminal results assume that synaptic strengths depend on the type of neurons they connect but are otherwise statistically independent. However, recent synaptic physiology datasets have uncovered connectivity patterns that deviate significantly from independent connection models. Simultaneously, studies of task-trained recurrent networks have emphasized the role of connectivity structure in implementing neural computations. Despite these findings, integrating detailed connectivity structures into mean-field theories of EI networks remains a substantial challenge. In this talk, I will outline a theoretical approach to understanding dynamics in structured EI networks by employing a low-rank approximation based on an analytical computation of the dominant eigenvalues of the full connectivity matrix. I will illustrate this approach by investigating the effects of pair-wise connectivity motifs on linear dynamics in EI networks. Specifically, I will present recent results demonstrating that an over-representation of chain motifs induces a strong positive eigenvalue in inhibition-dominated networks, generating a potential instability that challenges classical EI balance criteria. Furthermore, by examining the effects of external input, we found that chain motifs can, on their own, induce paradoxical responses, wherein an increased input to inhibitory neurons leads to a counterintuitive decrease in their activity through recurrent feedback mechanisms. Altogether, our theoretical approach opens new avenues for relating recorded connectivity structures with dynamics and computations in biological networks. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-01-22. Recording duration: 00:47:27.

The dynamics of learning in natural and artificial environments is a problem of great interest to both neuroscientists and artificial intelligence experts. However, standard analyses of animal training data either treat behavior as fixed, or track only coarse performance statistics (e.g., accuracy and bias), providing limited insight into the dynamic evolution of behavioral strategies over the course of learning. To overcome these limitations, we propose a dynamic psychophysical model that efficiently tracks trial-to-trial changes in behavior over the course of training. In this talk, I will describe recent work based on a dynamic logistic regression model that captures the time-varying dependencies of behavior on stimuli and other task covariates, which we applied to mouse training data from the International Brain Lab (IBL). Secondly, I will discuss efforts to infer animal learning rules from time-varying behavior in order to characterize how they adjust their policy in response to reward. Finally, I will describe recent work on adaptive optimal training, which combines ideas from reinforcement learning and adaptive experimental design to formulate methods for inferring animal learning rules from behavior, and using these rules to speed up animal training. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-01-15. Recording duration: 00:49:39.

Continuous attractors offer a unique class of solutions for storing continuous-valued variables in recurrent system states for indefinitely long time intervals. Unfortunately, continuous attractors suffer from severe structural instability in general---they are destroyed by most infinitesimal changes of the dynamical law that defines them. This fragility limits their utility especially in biological systems as their recurrent dynamics are subject to constant perturbations. We observe that the bifurcations from continuous attractors in theoretical neuroscience models display various structurally stable forms. Although their asymptotic behaviors to maintain memory are categorically distinct, their finite-time behaviors are similar. We build on the persistent manifold theory to explain the commonalities between bifurcations from and approximations of continuous attractors. Fast-slow decomposition analysis uncovers the existence of a persistent slow manifold that survives the seemingly destructive bifurcation, relating the flow within the manifold to the size of the perturbation. Moreover, this allows the bounding of the memory error of these approximations of continuous attractors. Finally, we train recurrent neural networks on analog memory tasks to support the appearance of these systems as solutions and their generalization capabilities. Therefore, we conclude that continuous attractors are functionally robust and remain useful as a universal analogy for understanding analog memory. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2024-11-27. Recording duration: 00:59:01.

In recent years, my lab and others have demonstrated the value of vector symbolic algebras (VSAs) for capturing a wide variety of neural and behavioural results. In this talk I discuss the surprising and compelling variety of tasks and styles of reasoning that are well-suited to descriptions using a specific VSA. These tasks include path integration, navigation, Bayesian reasoning, sampling, memorization, and logical inference. The resulting spiking neural network models capture various hippocampal cell types (grid, place, border, etc.), behavioural errors, and a variety of observed neural dynamics. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2024-11-20. Recording duration: 00:47:23.

Among all prevalent diseases with a central neurodegeneration, AMD can be considered the most promising in terms of prevention and early intervention, due to several factors surrounding the neural geometry of the foveal singularity. • Steep gradients of cell density, deployed in a radially symmetric fashion, can be modeled with a difference of Gaussian curves. • These steep gradients give rise to huge, spatially aligned biologic effects, summarized as the Center of Cone Resilience, Surround of Rod Vulnerability. • Widely used clinical imaging technology provides cellular and subcellular level information. • Data are now available at all timelines: clinical, lifespan, evolutionary • Snapshots are available from tissues (histology, analytic chemistry, gene expression) • A viable biogenesis model exists for drusen, the largest population-level intraocular risk factor for progression. • The biogenesis model shares molecular commonality with atherosclerotic cardiovascular disease, for which there has been decades of public health success. • Animal and cell model systems are emerging to test these ideas.