Mathematical Modeling seminars

How do humans stabilize an inverted pendulum, and why does a balanced pole eventually fall? Drawing on 25 years of fingertip pole-balancing research, this talk examines neural correction delays: longer poles move more slowly relative to the nervous system’s response time. Delay-differential models can stabilize the upright position, yet skilled people still experience falls. The proposed explanation is microchaos arising from interactions among delay, sensory dead zones and frequency-dependent force encoding. A region of transient falling solutions lies next to stable microchaotic dynamics. Such microchaos is absent in virtual frontal-plane balancing tasks, while models of standing postural sway lack the corresponding transient regime. The comparison suggests that human falls, unlike pole falls, are more plausibly associated with medical events or slips and trips.

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.

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.

When we attend a demanding task, our performance is poor at low arousal (when drowsy) or high arousal (when anxious), but we achieve optimal performance at intermediate arousal. This celebrated Yerkes-Dodson inverted-U law relating performance and arousal is colloquially referred to as being "in the zone." In this talk, I will elucidate the behavioral and neural mechanisms linking arousal and performance under the Yerkes-Dodson law in a mouse model. During decision-making tasks, mice express an array of discrete strategies, whereby the optimal strategy occurs at intermediate arousal, measured by pupil, consistent with the inverted-U law. Population recordings from the auditory cortex (A1) further revealed that sound encoding is optimal at intermediate arousal. To explain the computational principle underlying this inverted-U law, we modeled the A1 circuit as a spiking network with excitatory/inhibitory clusters, based on the observed functional clusters in A1. Arousal induced a transition from a multi-attractor (low arousal) to a single attractor phase (high arousal), and performance is optimized at the transition point. The model also predicts stimulus- and arousal-induced modulations of neural variability, which we confirmed in the data. Our theory suggests that a single unifying dynamical principle, phase transitions in metastable dynamics, underlies both the inverted-U law of optimal performance and state-dependent modulations of neural variability.

All animal locomotion is rhythmic,whether it is achieved through undulatory movement of the whole body or the coordination of articulated limbs. Neurobiologists have long studied locomotor circuits that produce rhythmic activity with non-rhythmic input, also called central pattern generators (CPGs). However, the cellular and microcircuit implementation of a walking CPG has not been described for any limbed animal. New comprehensive connectomes of the fruit fly ventral nerve cord (VNC) provide an opportunity to study rhythmogenic walking circuits at a synaptic scale.We use a data-driven network modeling approach to identify and characterize a putative walking CPG in the Drosophila leg motor system.

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.

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.

This webinar brings together three leaders in theoretical and computational neuroscience—Larry Abbott, Haim Sompolinsky, and Terry Sejnowski—to discuss how neural circuits generate fundamental aspects of the mind. Abbott illustrates mechanisms in electric fish that differentiate self-generated electric signals from external sensory cues, showing how predictive plasticity and two-stage signal cancellation mediate a sense of self. Sompolinsky explores attractor networks, revealing how discrete and continuous attractors can stabilize activity patterns, enable working memory, and incorporate chaotic dynamics underlying spontaneous behaviors. He further highlights the concept of object manifolds in high-level sensory representations and raises open questions on integrating connectomics with theoretical frameworks. Sejnowski bridges these motifs with modern artificial intelligence, demonstrating how large-scale neural networks capture language structures through distributed representations that parallel biological coding. Together, their presentations emphasize the synergy between empirical data, computational modeling, and connectomics in explaining the neural basis of cognition—offering insights into perception, memory, language, and the emergence of mind-like processes.

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.

Theoretical neuroscience aims to understand the relationship between neuron dynamics and connectivity in recurrent circuits. This has been intensively studied at the local level, where dynamics is described by pairwise correlations. Recent advances in simultaneous recordings of many neurons have allowed researchers to address the question at the global level, such as for the dimensionality of population dynamics. Our work contributes to this effort by analyzing the impact of connectivity statistics, including certain motifs, on the bulk and outlier covariance eigenvalues. By considering linearized dynamics around a steady state, we obtained analytically the covariance spectrum which exhibits a signature long tail robust to model variants and matches zebrafish calcium imaging data. This provides a local circuit mechanism for shaping the geometry of population dynamics and a quantitative benchmark for interpreting data. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2024-05-22. Recording duration: 00:53:15.

Neural computation is inextricably bound to decisions that must be made under time pressure and uncertainty. At the level of neural circuits, single neurons need to decide whether to spike. On longer timescales, the component circuitry needs to decide whether to reconfigure to store memories and adapt to novel situations. In this talk I will focus on two fun ideas in each of these contexts by showing how nonlinearities in neural components naturally form excitable switches that enable reliable decisions to be made in fluctuating environments. I will also issue propaganda that the kind of high level, cognitive faculties that we normally associate with decision making apply equally well and are understudied at the level of neural and synaptic populations. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2024-04-17. Recording duration: 00:41:08.

Learning in biological systems takes place in contexts and with dynamics not often accounted for by simple models. I will describe the learning dynamics of two model systems that incorporate either architectural or dynamic constraints from biological observations. In the first case, inspired by the observed mesoscopic structure of the mouse brain as revealed by the Allen Mouse Brain Connectivity Atlas, as well as multiple examples of parallel pathways in mammalian brains, I present a mathematical analysis of learning dynamics in networks that have parallel computational pathways driven by the same cost function. We use the approximation of deep linear networks with large hidden layer sizes to show that, as the depth of the parallel pathways increases, different features of the training set (defined by the singular values of the input-output correlation) will typically concentrate in one of the pathways. This result is derived analytically and demonstrated with numerical simulation with both linear and non-linear networks. Thus, rather than sharing stimulus and task features across multiple pathways, parallel network architectures learn to produce sharply diversified representations with specialized and specific pathways, a mechanism which may hold important consequences for codes in both biological and artificial systems. In the second case, I discuss learning dynamics in a generalization of Hebbian rules and show that these rules allow a neuron to learn tensor decompositions of higher-order input correlations. Unlike the case of the Oja rule and PCA, the resulting learned representation is not unique but selects amongst the tensor eigenvectors according to initial conditions. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2024-04-10. Recording duration: 00:30:39.

Inhibition has long been thought to stabilize the activity of cortical networks at low rates, and to shape significantly their response to sensory inputs. In this talk, I will describe three recent collaborative projects that shed light on these issues. (1) I will show how optogenetic excitation of inhibition neurons is consistent with cortex being inhibition stabilized even in the absence of sensory inputs, and how this data can constrain the coupling strengths of E-I cortical network models. (2) Recent analysis of the effects of optogenetic excitation of pyramidal cells in V1 of mice and monkeys shows that in some cases this optogenetic input reshuffles the firing rates of neurons of the network, leaving the distribution of rates unaffected. I will show how this surprising effect can be reproduced in sufficiently strongly coupled E-I networks. (3) Another puzzle has been to understand the respective roles of different inhibitory subtypes in network stabilization. Recent data reveal a novel, state dependent, paradoxical effect of weakening AMPAR mediated synaptic currents onto SST cells. Mathematical analysis of a network model with multiple inhibitory cell types shows that this effect tells us in which conditions SST cells are required for network stabilization.