Neuro-Informatics seminars

Behavioural difficulties are seen as hallmarks of many neurodevelopmental conditions. Differences in functional brain organisation have been observed in these conditions, but little is known about how they are related to a child’s profile of behavioural difficulties. We investigated whether behavioural difficulties are associated with how the brain is functionally organised in an intentionally heterogeneous and transdiagnostic sample of 957 children aged 5-15. We used consensus community detection to derive data-driven profiles of behavioural difficulties and constructed functional connectomes from a subset of 238 children with resting-state functional Magnetic Resonance Imaging (fMRI) data. We identified three distinct profiles of behaviour that were characterised by principal difficulties with hot executive function, cool executive function, and learning. Global organisation of the functional connectome did not differ between the groups, but multivariate patterns of connectivity at the level of Intrinsic Connectivity Networks (ICNs), nodes, and hubs significantly predicted group membership in held-out data. Fronto-parietal connector hubs were under-connected in all groups relative to a comparison sample, and children with hot vs cool executive function difficulties were distinguished by connectivity in ICNs associated with cognitive control, emotion processing, and social cognition. This demonstrates both general and specific neurodevelopmental risk factors in the functional connectome. (https://www.medrxiv.org/content/10.1101/2021.09.15.21262637v1)

Given the intrinsically large and complex data sets collected in neuroimaging research, coupled with the extensive array of shared data and tools amassed in the research community, ReproNim seeks to lower the barriers for efficient: use of data; description of data and process; use of standards and best practices; sharing; and subsequent reuse of the collective ‘big’ data. Aggregation of data and reuse of analytic methods have become critical in addressing concerns about the replicability and power of many of today’s neuroimaging studies.

Large-scale neural recordings contain high-dimensional structure that cannot be easily captured by existing data visualization methods. We therefore developed an embedding algorithm called Rastermap, which captures highly nonlinear relationships between neurons, and provides useful visualizations by assigning each neuron to a location in the embedding space. Compared to standard algorithms such as t-SNE and UMAP, Rastermap finds finer and higher dimensional patterns of neural variability, as measured by quantitative benchmarks. We applied Rastermap to a variety of datasets, including spontaneous neural activity, neural activity during a virtual reality task, widefield neural imaging data during a 2AFC task, artificial neural activity from an agent playing atari games, and neural responses to visual textures. We found within these datasets unique subpopulations of neurons encoding abstract properties of the environment.

The standard method for staining structures in the brain is to slice the brain into 2D sections. Each slice is treated using a technique such as in-situ hybridization to examine the spatial expression of a particular molecule at a given developmental timepoint. Depending on the brain structures being studied, slices can be made coronally, sagitally, or at any angle that is thought to be optimal for analysis. However, assimilating the information presented in the 2D slice images to gain quantitiative and informative 3D expression patterns is challenging. Even if expression levels are presented as voxels, to give 3D expression clouds, it can be difficult to compare expression across individuals and analysing such data requires significant expertise and imagination. In this talk, I will describe a new approach to examining histology slices, in which the user defines the brain structure of interest by drawing curves around it on each slice in a set and the depth of tissue from which to sample expression. The sampled 'curves' are then assembled into a 3D surface, which can then be transformed onto a common reference frame for comparative analysis. I will show how other neuroscientists can obtain and use the tool, which is called Stalefish, to analyse their own image data with no (or minimal) changes to their slice preparation workflow.

The brain is complex over multiple length-scales, from many protein molecules forming intricate nano-machines in a synapse to many neurons forming interconnected networks across the brain. Unraveling this multi-scale complexity is fundamental to our understanding of brain function and disease. In this lecture, I will introduce advances in visualizing the complex, multi-scale structures in the brain. Emphasis will be on new imaging techniques, including cryo electron tomography and correlative light-electron microscopy that enabled revealing in situ organization of synaptic molecules, and ultra-high speed volumetric imaging method VISoR developed to map brain-wide circuits at subcellular resolution. I will also discuss challenges and opportunities for interdisciplinary research collaboration to analyze and understand the enormous data generated by these cutting-edge technologies.

Large-scale, single neuron resolution recordings are inherently high-dimensional, with as many dimensions as neurons. To make sense of them, for many the answer is: reduce the number of dimensions. In this talk I argue we can distinguish weak and strong principles of neural dimension reduction. The weak principle is that dimension reduction is a convenient tool for making sense of complex neural data. The strong principle is that dimension reduction moves us closer to how neural circuits actually operate and compute. Elucidating these principles is crucial, for which we subscribe to provides radically different interpretations of the same dimension reduction techniques applied to the same data. I outline experimental evidence for each principle, but illustrate how we could make either the weak or strong principles appear to be true based on innocuous looking analysis decisions. These insights suggest arguments over low and high-dimensional neural activity need better constraints from both experiment and theory.

The combination of two-photon microscopy recordings and powerful calcium-dependent fluorescent sensors enables simultaneous recording of unprecedentedly large populations of neurons. While these sensors have matured over several generations of development, computational methods to process their fluorescence are often inefficient and the results hard to interpret. Here we introduce Suite2p: a fast, accurate, parameter-free and complete pipeline that registers raw movies, detects active and/or inactive cells (using Cellpose), extracts their calcium traces and infers their spike times. Suite2p runs faster than real time on standard workstations and outperforms state-of-the-art methods on newly developed ground-truth benchmarks for motion correction and cell detection.

The analysis of functional magnetic resonance imaging (fMRI) data can greatly benefit from flexible analytic approaches. In particular, the advent of data-driven approaches to identify whole-brain time-varying connectivity and activity has revealed a number of interesting relevant variation in the data which, when ignored, can provide misleading information. In this lecture I will provide a comparative introduction of a range of data-driven approaches to estimating time-varying connectivity. I will also present detailed examples where studies of both brain health and disorder have been advanced by approaches designed to capture and estimate time-varying information in resting fMRI data. I will review several exemplar data sets analyzed in different ways to demonstrate the complementarity as well as trade-offs of various modeling approaches to answer questions about brain function. Finally, I will review and provide examples of strategies for validating time-varying connectivity including simulations, multimodal imaging, and comparative prediction within clinical populations, among others. As part of the interactive aspect I will provide a hands-on guide to the dynamic functional network connectivity toolbox within the GIFT software, including an online didactic analytic decision tree to introduce the various concepts and decisions that need to be made when using such tools

In this webinar, Dr Ye Tian and A/Prof Andrew Zalesky will present new research on mapping the functional architecture of the human subcortex. They used 3T and 7T functional MRI from more than 1000 people to map one of the most detailed functional atlases of the human subcortex to date. Comprising four hierarchical scales, the new atlas reveals the complex topographic organisation of the subcortex, which dynamically adapts to changing cognitive demands. The atlas enables whole-brain mapping of connectomes and has been used to optimise targeting of deep brain stimulation. This joint work with Professors Michael Breakspear and Daniel Margulies was recently published in Nature Neuroscience. In the second part of the webinar, Dr Ye Tian will present her current research on the biological ageing of different body systems, including the human brain, in health and degenerative conditions. Conducted in more than 30,000 individuals, this research reveals associations between the biological ageing of different body systems. She will show the impact of lifestyle factors on ageing and how advanced ageing can predict the risk of mortality. Associate Professor Andrew Zalesky is a Principal Researcher with a joint appointment between the Faculties of Engineering and Medicine at The University of Melbourne. He currently holds a NHMRC Senior Research Fellowship and serves as Associate Editor for Brain Topography, Neuroimage Clinical and Network Neuroscience. Dr Zalesky is recognised for the novel tools that he has developed to analyse brain networks and their application to the study of neuropsychiatric disorders. Dr Ye Tian is a postdoctoral researcher at the Department of Psychiatry, University of Melbourne. She received her PhD from the University of Melbourne in 2020, during which she established the Melbourne Subcortex Atlas. Dr Tian is interested in understanding brain organisation and using brain imaging techniques to unveil neuropathology underpinning neuropsychiatric disorders.

The Group Iterative Multiple Model Estimation (GIMME) framework has emerged as a promising method for characterizing connections between brain regions in functional neuroimaging data. Two of the most appealing features of this framework are its ability to estimate the directionality of connections between network nodes and its ability to determine whether those connections apply to everyone in a sample (group-level) or just to one person (individual-level). However, there are outstanding questions about the validity and stability of these estimates, including: 1) how recovery of connection directionality is affected by features of data sets such as scan length and autoregressive effects, which may be strong in some imaging modalities (resting state fMRI, fNIRS) but weaker in others (task fMRI); and 2) whether inferences about directionality at the group and individual levels are stable across time. This talk will provide an overview of the GIMME framework and describe relevant results from a large-scale simulation study that assesses directionality recovery under various conditions and a separate project that investigates the temporal stability of GIMME’s inferences in the Human Connectome Project data set. Analyses from these projects demonstrate that estimates of directionality are most precise when autoregressive and cross-lagged relations in the data are relatively strong, and that inferences about the directionality of group-level connections, specifically, appear to be stable across time. Implications of these findings for the interpretation of directional connectivity estimates in different types of neuroimaging data will be discussed.

The "mind of the worm", the first electron microscopy-based connectome of C. elegans, was an early sign of where connectomics is headed, followed by a long time of little progress in a field held back by the immense manual effort required for data acquisition and analysis. This changed over the last few years with several technological breakthroughs, which allowed increases in data set sizes by several orders of magnitude. Brain tissue can now be imaged in 3D up to a millimeter in size at nanometer resolution, revealing tissue features from synapses to the mitochondria of all contained cells. These breakthroughs in acquisition technology were paralleled by a revolution in deep-learning segmentation techniques, that equally reduced manual analysis times by several orders of magnitude, to the point where fully automated reconstructions are becoming useful. Taken together, this gives neuroscientists now access to the first wiring diagrams of thousands of automatically reconstructed neurons connected by millions of synapses, just one line of program code away. In this talk, I will cover these developments by describing the past few years' technological breakthroughs and discuss remaining challenges. Finally, I will show the potential of automated connectomics for neuroscience by demonstrating how hypotheses in reinforcement learning can now be tackled through virtual experiments in synaptic wiring diagrams of the songbird basal ganglia.

Tractography datasets, calculated from dMRI, represent the main WM structural connections in the brain. Thanks to advances in image acquisition and processing, the complexity and size of these datasets have constantly increased, also containing a large amount of artifacts. We present some examples of algorithms, most of them based on classical machine learning approaches, to analyze these data and identify common connectivity patterns among subjects.

Information that is shared across brains is encoded in idiosyncratic fine-scale functional topographies. Hyperalignment jointly models shared information and idiosyncratic topographies. Pattern vectors for neural responses and connectivities are projected into a common, high-dimensional information space, rather than being aligned in a canonical anatomical space. Hyperalignment calculates individual transformation matrices that preserve the geometry of pairwise dissimilarities between pattern vectors. Individual cortical topographies are modeled as mixtures of overlapping, individual-specific topographic basis functions, rather than as contiguous functional areas. The fundamental property of brain function that is preserved across brains is information content, rather than the functional properties of local features that support that content.