Biology subjects

George, T. M.

Publications and source records attributed to George, T. M..

5 recordsLinked to original sources

bioRxiv2024

SIMPL: Scalable and hassle-free optimization of neural representations from behaviour

Neural activity in the brain is known to encode low-dimensional, time-evolving, behaviour-related variables. A long-standing goal of neural data analysis has been to identify these variables and their mapping to neural activity. A productive and canonical approach has been to simply visualise neural "tuning curves" as a function of behaviour. In reality, significant discrepancies between behaviour and the true latent variables--such as an agent thinking of position Y whilst located at position X--distort and blur the tuning curves, decreasing their interpretability. To address this, latent variable models propose to learn the latent variable from data; these are typically expensive, hard to tune, or scale poorly, complicating their adoption. Here we propose SIMPL (Scalable Iterative Maximization of Population-coded Latents), an EM-style algorithm which iteratively optimises latent variables and tuning curves. SIMPL is fast, scalable and exploits behaviour as an initial condition to further improve convergence and identifiability. It can accurately recover latent variables in spatial and non-spatial tasks. When applied to a large hippocampal dataset SIMPL converges on smaller, more numerous, and more uniformly sized place fields than those based on behaviour, suggesting the brain may encode space with greater resolution than previously thought.

neuroscience↗

bioRxiv2023

A generative model of the hippocampal formation trained with theta driven local learning rules

Advances in generative models have recently revolutionised machine learning. Meanwhile, in neuroscience, generative models have long been thought fundamental to animal intelligence. Understanding the biological mechanisms that support these processes promises to shed light on the relationship between biological and artificial intelligence. In animals, the hippocampal formation is thought to learn and use a generative model to support its role in spatial and non-spatial memory. Here we introduce a biologically plausible model of the hippocampal formation tantamount to a Helmholtz machine that we apply to a temporal stream of inputs. A novel component of our model is that fast theta-band oscillations (5-10 Hz) gate the direction of information flow throughout the network, training it akin to a high-frequency wake-sleep algorithm. Our model accurately infers the latent state of high-dimensional sensory environments and generates realistic sensory predictions. Furthermore, it can learn to path integrate by developing a ring attractor connectivity structure matching previous theoretical proposals and flexibly transfer this structure between environments. Whereas many models trade-off biological plausibility with generality, our model captures a variety of hippocampal cognitive functions under one biologically plausible local learning rule.

neuroscience↗

bioRxiv2022

RatInABox: A toolkit for modelling locomotion and neuronal activity in continuous environments

Generating synthetic locomotory and neural data is a useful yet cumbersome step commonly required to study theoretical models of the brains role in spatial navigation. This process can be time consuming and, without a common framework, makes it difficult to reproduce or compare studies which each generate test data in different ways. In response we present RatInABox, an open-source Python toolkit designed to model realistic rodent locomotion and generate synthetic neural data from spatially modulated cell types. This software provides users with (i) the ability to construct one-or two-dimensional environments with configurable barriers and visual cues, (ii) a physically realistic random motion model fitted to experimental data, (iii) rapid online calculation of neural data for many of the known self-location or velocity selective cell types in the hippocampal formation (including place cells, grid cells, boundary vector cells, head direction cells) and (iv) a framework for constructing custom cell types, multi-layer network models and data-or policy-controlled motion trajectories. The motion and neural models spatially and temporally continuous as well as topographically sensitive to boundary conditions and walls. We demonstrate that out-of-the-box parameter settings replicate many aspects of rodent foraging behaviour such as velocity statistics and the tendency of rodents to over-explore walls. Numerous tutorial scripts are provided, including examples where RatInABox is used for decoding position from neural data or to solve a navigational reinforcement learning task. We hope this tool significantly streamline computational research into the brains role in navigation.

neuroscience↗

bioRxiv2022

Rapid learning of predictive maps with STDP and theta phase precession

The predictive map hypothesis is a promising candidate principle for hippocampal function. A favoured formalisation of this hypothesis, called the successor representation, proposes that each place cell encodes the expected state occupancy of its target location in the near future. This predictive framework is supported by behavioural as well as electrophysiological evidence and has desirable consequences for both the generalisability and efficiency of reinforcement learning algorithms. However, it is unclear how the successor representation might be learnt in the brain. Error-driven temporal difference learning, commonly used to learn successor representations in artificial agents, is not known to be implemented in hippocampal networks. Instead, we demonstrate that spike-timing dependent plasticity (STDP), a form of Hebbian learning, acting on temporally compressed trajectories known as "theta sweeps", is sufficient to rapidly learn a close approximation to the successor representation. The model is biologically plausible - it uses spiking neurons modulated by theta-band oscillations, diffuse and overlapping place cell-like state representations, and experimentally matched parameters. We show how this model maps onto known aspects of hippocampal circuitry and explains substantial variance in the temporal difference successor matrix, consequently giving rise to place cells that demonstrate experimentally observed successor representation-related phenomena including backwards expansion on a 1D track and elongation near walls in 2D. Finally, our model provides insight into the observed topographical ordering of place field sizes along the dorsal-ventral axis by showing this is necessary to prevent the detrimental mixing of larger place fields, which encode longer timescale successor representations, with more fine-grained predictions of spatial location.

neuroscience↗

bioRxiv2019

Unsupervised Machine Learning for Data Encoding appliedto Ovarian Cancer Transcriptomes

Machine learning algorithms are revolutionising how information can be extracted from complex and high-dimensional data sets via intelligent compression. For example, unsupervised Autoen-coders train a deep neural network with a low-dimensional "bottlenecked" central layer to reconstruct input vectors. Variational Autoencoders (VAEs) have shown promise at learning meaningful latent spaces for text, image and more recently, gene-expression data. In the latter case they have been shown capable of capturing biologically relevant features such as a patients sex or tumour type. Here we train a VAE on ovarian cancer transcriptomes from The Cancer Genome Atlas and show that, in many cases, the latent spaces learns an encoding predictive of cisplatin chemotherapy resistance. We analyse the effectiveness of such an architecture to a wide range of hyperparameters as well as use a state-of-the-art clustering algorithm, t-SNE, to embed the data in a two-dimensional manifold and visualise the predictive power of the trained latent spaces. By correlating genes to resistance-predictive encodings we are able to extract biological processes likely responsible for platinum resistance. Finally we demonstrate that variational autoencoders can reliably encode gene expression data contaminated with significant amounts of Gaussian and dropout noise, a necessary feature if this technique is to be applicable to other data sets, including those in non-medical fields.

cancer biology↗