Computational Neuroscience seminars

This talk will focus on the generative modelling of resting state time series or endogenous neuronal activity. I will survey developments in modelling distributed neuronal fluctuations – spectral dynamic causal modelling (DCM) for functional MRI – and how this modelling rests upon functional connectivity. The dynamics of brain connectivity has recently attracted a lot of attention among brain mappers. I will also show a novel method to identify dynamic effective connectivity using spectral DCM. Further, I will summarise the development of the next generation of DCMs towards large-scale, whole-brain schemes which are computationally inexpensive, to the other extreme of the development using more sophisticated and biophysically detailed generative models based on the canonical microcircuits.

Ever since Bliss and Lømo discovered the phenomenon of long-term potentiation (LTP) in rabbit dentate gyrus in the 1960s, Hebb’s rule—neurons that fire together wire together—gained popularity to explain learning and memory. Accumulating evidence, however, suggests that neural activity is homeostatically regulated. Homeostatic mechanisms are mostly interpreted to stabilize network dynamics. However, recent theoretical work has shown that linking the activity of a neuron to its connectivity within the network provides a robust alternative implementation of Hebb’s rule, although entirely based on negative feedback. In this setting, both natural and artificial stimulation of neurons can robustly trigger network rewiring. We used computational models of plastic networks to simulate the complex temporal dynamics of network rewiring in response to external stimuli. In parallel, we performed optogenetic stimulation experiments in the mouse anterior cingulate cortex (ACC) and subsequently analyzed the temporal profile of morphological changes in the stimulated tissue. Our results suggest that the new theoretical framework combining neural activity homeostasis and structural plasticity provides a consistent explanation of our experimental observations.

In a famous philosophical paradox, Buridan's ass perishes because he is equally hungry and thirsty, and cannot make up his mind whether to first drink or eat. We are faced daily with the need to pick between alternatives that are equally attractive (or not) to us. What are the processes that allow us to avoid paralysis and to rapidly select between such equal options when there are no preferences or rational reasons to rely on? One solution that was offered is that although on a higher cognitive level there is symmetry between the alternatives, on a neuronal level the symmetry does not maintain. What is the nature of this asymmetry of the neuronal level? In this talk I will present experiments addressing this important phenomenon using measures of human behavior, EEG, EMG and large scale neural network modeling, and discuss mechanisms involved in the process of intention formation and execution, in the face of alternatives to choose from. Specifically, I will show results revealing the temporal dynamics of rapid intention formation and, moreover, ‘change of intention’ in a free choice picking scenario, in which the alternatives are on a par for the participant. The results suggest that even in arbitrary choices, endogenous or exogenous biases that are present in the neural system for selecting one or another option may be implicitly overruled; thus creating an implicit and non-conscious ‘change of mind’. Finally, the question is raised: in what way do such rapid implicit ‘changes of mind’ help retain one’s self-control and free-will behavior?

Behavior relies on the ability of sensory systems to infer changing properties of the environment from incoming sensory stimuli. However, the demands that detecting and adjusting to changes in the environment place on a sensory system often differ from the demands associated with performing a specific behavioral task. This necessitates neural coding strategies that can dynamically balance these conflicting needs. I will discuss our ongoing theoretical work to understand how this balance can best be achieved. We connect ideas from efficient coding and Bayesian inference to ask how sensory systems should dynamically allocate limited resources when the goal is to optimally infer changing latent states of the environment, rather than reconstruct incoming stimuli. We use these ideas to explore dynamic tradeoffs between the efficiency and speed of sensory adaptation schemes, and the downstream computations that these schemes might support. Finally, we derive families of codes that balance these competing objectives, and we demonstrate their close match to experimentally-observed neural dynamics during sensory adaptation. These results provide a unifying perspective on adaptive neural dynamics across a range of sensory systems, environments, and sensory tasks.

How our senses work both separately and together involves rich computational problems. I will discuss the spatial and representational problems faced by the visual and auditory system, focusing on two issues. 1. How does the brain correct for discrepancies in the visual and auditory spatial reference frames? I will describe our recent discovery of a novel type of otoacoustic emission, the eye movement related eardrum oscillation, or EMREO (Gruters et al, PNAS 2018). 2. How does the brain encode more than one stimulus at a time? I will discuss evidence for neural time-division multiplexing, in which neural activity fluctuates across time to allow representations to encode more than one simultaneous stimulus (Caruso et al, Nat Comm 2018). These findings all emerged from experimentally testing computational models regarding spatial representations and their transformations within and across sensory pathways. Further, they speak to several general problems confronting modern neuroscience such as the hierarchical organization of brain pathways and limits on perceptual/cognitive processing.

There is an avalanche of new data on activity in neural networks and the biological brain, revealing the collective dynamics of vast numbers of neurons. In principle, these collective dynamics can be of almost arbitrarily high dimension, with many independent degrees of freedom — and this may reflect powerful capacities for general computing or information. In practice, neural datasets reveal a range of outcomes, including collective dynamics of much lower dimension — and this may reflect other desiderata for neural codes. For what networks does each case occur? We begin by exploring bottom-up mechanistic ideas that link tractable statistical properties of network connectivity with the dimension of the activity that they produce. We then cover “top-down” ideas that describe how features of connectivity and dynamics that impact dimension arise as networks learn to perform fundamental computational tasks.

In our everyday lives, we form connections and build up social networks that allow us to function successfully as individuals and as a society. Our social networks tend to include well-connected individuals who link us to other groups of people that we might otherwise have limited access to. In addition, we are more likely to befriend individuals who a) live nearby and b) have mutual friends. Interestingly, neurons tend to do the same…until development is perturbed. Just like social networks, neuronal networks require highly connected hubs to elicit efficient communication at minimal cost (you can’t befriend everybody you meet, nor can every neuron wire with every other!). This talk will cover some of Alex’s work showing that microscopic (cellular scale) brain networks inferred from spontaneous activity show similar complex topology to that previously described in macroscopic human brain scans. The talk will also discuss what happens when neurodevelopment is disrupted in the case of a monogenic disorder called Rett Syndrome. This will include simulations of neuronal activity and the effects of manipulation of model parameters as well as what happens when we manipulate real developing networks using optogenetics. If functional development can be restored in atypical networks, this may have implications for treatment of neurodevelopmental disorders like Rett Syndrome.

Neuronal dendritic trees display a wide range of nonlinear input integrations due to their voltage-dependent active calcium channels. We reveal that in vivo-like fluctuating input enhances nonlinearity substantially in a single dendritic compartment and shifts the input-output relation to exhibiting nonmonotonous or bistable dynamics. In particular, with the slow activation of calcium dynamics, we analyze noise-induced bistability and its timescales. We show bistability induces long-timescale fluctuation that can account for observed dendritic plateau potentials in vivo conditions. In a multicompartmental model neuron with realistic synaptic input, we show that noise-induced bistability persists in a wide range of parameters. Using Fredholm's theory to calculate the spiking rate of multivariable neurons, we discuss how dendritic bistability shifts the spiking dynamics of single neurons and its implications for network phenomena in the processing of in vivo–like fluctuating input.

Interest in psychedelic compounds is growing due to their remarkable potential for understanding altered neural states and their breakthrough status to treat various psychiatric disorders. However, there are major knowledge gaps regarding how psychedelics affect the brain. The Computational Neuroscience Laboratory at the Turner Institute for Brain and Mental Health, Monash University, uses multimodal neuroimaging to test hypotheses of the brain’s functional reorganisation under psychedelics, informed by the accounts of hierarchical predictive processing, using dynamic causal modelling (DCM). DCM is a generative modelling technique which allows to infer the directed connectivity among brain regions using functional brain imaging measurements. In this webinar, Associate Professor Adeel Razi and PhD candidate Devon Stoliker will showcase a series of previous and new findings of how changes to synaptic mechanisms, under the control of serotonin receptors, across the brain hierarchy influence sensory and associative brain connectivity. Understanding these neural mechanisms of subjective and therapeutic effects of psychedelics is critical for rational development of novel treatments and for the design and success of future clinical trials. Associate Professor Adeel Razi is a NHMRC Investigator Fellow and CIFAR Azrieli Global Scholar at the Turner Institute of Brain and Mental Health, Monash University. He performs cross-disciplinary research combining engineering, physics, and machine-learning. Devon Stoliker is a PhD candidate at the Turner Institute for Brain and Mental Health, Monash University. His interest in consciousness and psychiatry has led him to investigate the neural mechanisms of classic psychedelic effects in the brain.

Multisensory perception is often studied through the effects of inter-sensory conflict, such as in the McGurk effect, the Ventriloquist illusion, and the Rubber Hand Illusion. Moreover, Bayesian approaches to cue fusion and causal inference overwhelmingly draw on cross-modal conflict to measure and to model multisensory perception. Given the prevalence of conflict, it is remarkable that accounts of multisensory perception have so far neglected the theory of conflict monitoring and cognitive control, established about twenty years ago. I hope to make a case for the role of conflict monitoring and resolution during multisensory perception. To this end, I will present EEG and fMRI data showing that cross-modal conflict in speech, resulting in either integration or segregation, triggers neural mechanisms of conflict detection and resolution. I will also present data supporting a role of these mechanisms during perceptual conflict in general, using Binocular Rivalry, surrealistic imagery, and cinema. Based on this preliminary evidence, I will argue that it is worth considering the potential role of conflict in multisensory perception and its incorporation in a causal inference framework. Finally, I will raise some potential problems associated with this proposal.

Spike-driven adaptation involves intracellular mechanisms that are initiated by neural firing and lead to the subsequent reduction of spiking rate followed by a recovery back to baseline. We report on long (>0.5 second) recovery times from adaptation in a thalamic-like structure in weakly electric fish. This adaptation process is shown via modeling and experiment to encode in a spatially invariant manner the time intervals between event encounters, e.g. with landmarks as the animal learns the location of food. These cells also come in two varieties, ones that care only about the time since the last encounter, and others that care about the history of encounters. We discuss how the two populations can share in the task of representing sequences of events, supporting path integration and converting from ego-to-allocentric representations. The heterogeneity of the population parameters enables the representation and Bayesian decoding of time sequences of events which may be put to good use in path integration and hilus neuron function in hippocampus. Finally we discuss how all the cells of this gateway to the pallium exhibit mixed selectivity of social features of their environment. The data and computational modeling further reveal that, in contrast to a long-held belief, these gymnotiform fish are endowed with a corollary discharge, albeit only for social signalling.

The intensity and features of sensory stimuli are encoded in the activity of neurons in the cortex. In the visual and piriform cortices, the stimulus intensity re-scales the activity of the population without changing its selectivity for the stimulus features. The cortical representation of the stimulus is therefore intensity-invariant. This emergence of network invariant representations appears robust to local changes in synaptic strength induced by synaptic plasticity, even though: i) synaptic plasticity can potentiate or depress connections between neurons in a feature-dependent manner, and ii) in networks with balanced excitation and inhibition, synaptic plasticity determines the non-linear network behavior. In this study, we investigate the consistency of invariant representations with a variety of synaptic states in balanced networks. By using mean-field models and spiking network simulations, we show how the synaptic state controls the emergence of intensity-invariant or intensity-dependent selectivity by inducing changes in the network response to intensity. In particular, we demonstrate how facilitating synaptic states can sharpen the network selectivity while depressing states broaden it. We also show how power-law-type synapses permit the emergence of invariant network selectivity and how this plasticity can be generated by a mix of different plasticity rules. Our results explain how the physiology of individual synapses is linked to the emergence of invariant representations of sensory stimuli at the network level.

Macroscopic brain organisation emerges early in life, even prenatally, and continues to develop through adolescence and into early adulthood. The emergence and continual refinement of large-scale brain networks, connecting neuronal populations across anatomical distance, allows for increasing functional integration and specialisation. This process is thought crucial for the emergence of complex cognitive processes. But how and why is this process so diverse? We used structural neuroimaging collected from a large diverse cohort, to explore how different features of macroscopic brain organisation are associated with diverse cognitive trajectories. We used diffusion-weighted imaging (DWI) to construct whole-brain white-matter connectomes. A simulated attack on each child's connectome revealed that some brain networks were strongly organized around highly connected 'hubs'. The more children's brains were critically dependent on hubs, the better their cognitive skills. Conversely, having poorly integrated hubs was a very strong risk factor for cognitive and learning difficulties across the sample. We subsequently developed a computational framework, using generative network modelling (GNM), to model the emergence of this kind of connectome organisation. Relatively subtle changes within the wiring rules of this computational framework give rise to differential developmental trajectories, because of small biases in the preferential wiring properties of different nodes within the network. Finally, we were able to use this GNM to implicate the molecular and cellular processes that govern these different growth patterns.

The ability to reach, grasp, and manipulate objects is a remarkable expression of motor skill, and the loss of this ability in injury, stroke, or disease can be devastating. These behaviors are controlled by the coordinated activity of tens of millions of neurons distributed across many CNS regions, including the primary motor cortex. While many studies have characterized the activity of single cortical neurons during reaching, the principles governing the dynamics of large, distributed neural populations remain largely unknown. Recent work in primates has suggested that during the execution of reaching, motor cortex may autonomously generate the neural pattern controlling the movement, much like the spinal central pattern generator for locomotion. In this seminar, I will describe recent work that tests this hypothesis using large-scale neural recording, high-resolution behavioral measurements, dynamical systems approaches to data analysis, and optogenetic perturbations in mice. We find, by contrast, that motor cortex requires strong, continuous, and time-varying thalamic input to generate the neural pattern driving reaching. In a second line of work, we demonstrate that the cortico-cerebellar loop is not critical for driving the arm towards the target, but instead fine-tunes movement parameters to enable precise and accurate behavior. Finally, I will describe my future plans to apply these experimental and analytical approaches to the adaptive control of locomotion in complex environments.

Deep learning has made tremendous progress in the last year but it's high computational and memory requirements impose challenges in using deep learning on edge devices. There has been some progress in lowering memory requirements of deep neural networks (for instance, use of half-precision) but there has been minimal effort in developing alternative efficient computational paradigms. Inspired by the brain, Spiking Neural Networks (SNN) provide an energy-efficient alternative to conventional rate-based neural networks. However, SNN architectures that employ the traditional feedforward and feedback pass do not fully exploit the asynchronous event-based processing paradigm of SNNs. In the first part of my talk, I will present my work on predictive coding which offers a fundamentally different approach to developing neural networks that are particularly suitable for event-based processing. In the second part of my talk, I will present our work on development of approaches for SNNs that target specific problems like low response latency and continual learning. References Dora, S., Bohte, S. M., & Pennartz, C. (2021). Deep Gated Hebbian Predictive Coding Accounts for Emergence of Complex Neural Response Properties Along the Visual Cortical Hierarchy. Frontiers in Computational Neuroscience, 65. Saranirad, V., McGinnity, T. M., Dora, S., & Coyle, D. (2021, July). DoB-SNN: A New Neuron Assembly-Inspired Spiking Neural Network for Pattern Classification. In 2021 International Joint Conference on Neural Networks (IJCNN) (pp. 1-6). IEEE. Machingal, P., Thousif, M., Dora, S., Sundaram, S., Meng, Q. (2021). A Cross Entropy Loss for Spiking Neural Networks. Expert Systems with Applications (under review).

To prevail in a dynamic and noisy environment, the brain must create reliable and meaningful representations from sensory inputs that are often ambiguous or corrupt. Since only information that permeates the cortical hierarchy can influence sensory perception and decision-making, it is critical that noisy external stimuli are encoded and propagated through different processing stages with minimal signal degradation. Here we hypothesize that stimulus-specific pathways akin to cortical topographic maps may provide the structural scaffold for such signal routing. We investigate whether the feature-specific pathways within such maps, characterized by the preservation of the relative organization of cells between distinct populations, can guide and route stimulus information throughout the system while retaining representational fidelity. We demonstrate that, in a large modular circuit of spiking neurons comprising multiple sub-networks, topographic projections are not only necessary for accurate propagation of stimulus representations, but can also help the system reduce sensory and intrinsic noise. Moreover, by regulating the effective connectivity and local E/I balance, modular topographic precision enables the system to gradually improve its internal representations and increase signal-to-noise ratio as the input signal passes through the network. Such a denoising function arises beyond a critical transition point in the sharpness of the feed-forward projections, and is characterized by the emergence of inhibition-dominated regimes where population responses along stimulated maps are amplified and others are weakened. Our results indicate that this is a generalizable and robust structural effect, largely independent of the underlying model specificities. Using mean-field approximations, we gain deeper insight into the mechanisms responsible for the qualitative changes in the system’s behavior and show that these depend only on the modular topographic connectivity and stimulus intensity. The general dynamical principle revealed by the theoretical predictions suggest that such a denoising property may be a universal, system-agnostic feature of topographic maps, and may lead to a wide range of behaviorally relevant regimes observed under various experimental conditions: maintaining stable representations of multiple stimuli across cortical circuits; amplifying certain features while suppressing others (winner-take-all circuits); and endow circuits with metastable dynamics (winnerless competition), assumed to be fundamental in a variety of tasks.

Modular structures in myriad forms — genetic, structural, functional — are ubiquitous in the brain. While modularization may be shaped by genetic instruction or extensive learning, the mechanisms of module emergence are poorly understood. Here, we explore complementary mechanisms in the form of bottom-up dynamics that push systems spontaneously toward modularization. As a paradigmatic example of modularity in the brain, we focus on the grid cell system. Grid cells of the mammalian medial entorhinal cortex (mEC) exhibit periodic lattice-like tuning curves in their encoding of space as animals navigate the world. Nearby grid cells have identical lattice periods, but at larger separations along the long axis of mEC the period jumps in discrete steps so that the full set of periods cluster into 5-7 discrete modules. These modules endow the grid code with many striking properties such as an exponential capacity to represent space and unprecedented robustness to noise. However, the formation of discrete modules is puzzling given that biophysical properties of mEC stellate cells (including inhibitory inputs from PV interneurons, time constants of EPSPs, intrinsic resonance frequency and differences in gene expression) vary smoothly in continuous topographic gradients along the mEC. How does discreteness in grid modules arise from continuous gradients? We propose a novel mechanism involving two simple types of lateral interaction that leads a continuous network to robustly decompose into discrete functional modules. We show analytically that this mechanism is a generic multi-scale linear instability that converts smooth gradients into discrete modules via a topological “peak selection” process. Further, this model generates detailed predictions about the sequence of adjacent period ratios, and explains existing grid cell data better than existing models. Thus, we contribute a robust new principle for bottom-up module formation in biology, and show that it might be leveraged by grid cells in the brain.