Neuro-Informatics seminars

Neuroscience is experiencing unprecedented growth in dataset size both within individual brains and across populations. Large-scale, multimodal datasets are transforming our understanding of brain structure and function, creating opportunities to address previously unexplored questions. However, managing this increasing data volume requires new training and technology approaches. Modern data technologies are reshaping neuroscience by enabling researchers to tackle complex questions within a Ph.D. or postdoctoral timeframe. I will discuss cloud-based platforms such as brainlife.io, that provide scalable, reproducible, and accessible computational infrastructure. Modern data technology can democratize neuroscience, accelerate discovery and foster scientific transparency and collaboration. Concrete examples will illustrate how these technologies can be applied to mapping brain connectivity, studying human learning and development, and developing predictive models for traumatic brain injury (TBI). By integrating cloud computing and scalable data-sharing frameworks, neuroscience can become more impactful, inclusive, and data-driven..

We will discuss a recent paper by Taylor et al. (2023): https://www.sciencedirect.com/science/article/pii/S1053811923002896. They discuss the merits of highlighting results instead of hiding them; that is, clearly marking which voxels and clusters pass a given significance threshold, but still highlighting sub-threshold results, with opacity proportional to the strength of the effect. They use this to illustrate how there in fact may be more agreement between researchers than previously thought, using the NARPS dataset as an example. By adopting a continuous, "highlighted" approach, it becomes clear that the majority of effects are in the same location and that the effect size is in the same direction, compared to an approach that only permits rejecting or not rejecting the null hypothesis. We will also talk about the implications of this approach for creating figures, detecting artifacts, and aiding reproducibility.

Cognitive neuroscience has witnessed great progress since modern neuroimaging embraced an open science framework, with the adoption of shared principles (Wilkinson et al., 2016), standards (Gorgolewski et al., 2016), and ontologies (Poldrack et al., 2011), as well as practices of meta-analysis (Yarkoni et al., 2011; Dockès et al., 2020) and data sharing (Gorgolewski et al., 2015). However, while functional neuroimaging data provide correlational maps between cognitive functions and activated brain regions, its usefulness in determining causal link between specific brain regions and given behaviors or functions is disputed (Weber et al., 2010; Siddiqiet al 2022). On the contrary, neuropsychological data enable causal inference, highlighting critical neural substrates and opening a unique window into the inner workings of the brain (Price, 2018). Unfortunately, the adoption of Open Science practices in clinical settings is hampered by several ethical, technical, economic, and political barriers, and as a result, open platforms enabling access to and sharing clinical (meta)data are scarce (e.g., Larivière et al., 2021). We are working with clinicians, neuroimagers, and software developers to develop an open source platform for the storage, sharing, synthesis and meta-analysis of human clinical data to the service of the clinical and cognitive neuroscience community so that the future of neuropsychology can be transdiagnostic, open, and FAIR. We call it neurocausal (https://neurocausal.github.io).

In systems neuroscience, datasets are multimodal and include data-streams of various origins: multichannel electrophysiology, 1- or 2-p calcium imaging, behavior, etc. Often, the exact nature of data streams are unique to each lab, if not each project. Analyzing these datasets in an efficient and open way is crucial for collaboration and reproducibility. In this combined webinar and tutorial, Adrien Peyrache and Guillaume Viejo will present Pynapple, a Python-based data analysis pipeline for systems neuroscience. Designed for flexibility and versatility, Pynapple allows users to perform cross-modal neural data analysis via a common programming approach which facilitates easy sharing of both analysis code and data.

Mesmerize is a platform for the annotation and analysis of neuronal calcium imaging data. Mesmerize encompasses the entire process of calcium imaging analysis from raw data to interactive visualizations. Mesmerize allows you to create FAIR-functionally linked datasets that are easy to share. The analysis tools are applicable for a broad range of biological experiments and come with GUI interfaces that can be used without requiring a programming background.

Advances in fluorescence microscopy enable monitoring larger brain areas in-vivo with finer time resolution. The resulting data rates require reproducible analysis pipelines that are reliable, fully automated, and scalable to datasets generated over the course of months. We present CaImAn, an open-source library for calcium imaging data analysis. CaImAn provides automatic and scalable methods to address problems common to pre-processing, including motion correction, neural activity identification, and registration across different sessions of data collection. It does this while requiring minimal user intervention, with good scalability on computers ranging from laptops to high-performance computing clusters. CaImAn is suitable for two-photon and one-photon imaging, and also enables real-time analysis on streaming data. To benchmark the performance of CaImAn we collected and combined a corpus of manual annotations from multiple labelers on nine mouse two-photon datasets. We demonstrate that CaImAn achieves near-human performance in detecting locations of active neurons.

In modern neuroscience, we often want to extract information from recordings of many neurons in the brain. Unfortunately, the activity of individual neurons is very noisy, making it difficult to relate to cognition and behavior. Thankfully, we can use the correlations across time and neurons to denoise the data we record. In particular, using recent advances in machine learning, we can build models which harness this structure in the data to extract more interpretable signals. In this talk, we present two such methods as well as examples of how they can help us gain further insights into the neural underpinnings of behavior.

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.

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

Neuroscientists routinely perform experiments aimed at recording or manipulating neural activity, uncovering physiological processes underlying brain function or elucidating aspects of brain anatomy. Understanding how the brain generates behaviour ultimately depends on merging the results of these experiments into a unified picture of brain anatomy and function. We present BrainGlobe, a new initiative aimed at developing common Python tools for computational neuroanatomy. These include cellfinder for fast, accurate cell detection in whole-brain microscopy images, brainreg for aligning images to a reference atlas, and brainrender for visualisation of anatomically registered data. These software packages are developed around the BrainGlobe Atlas API. This API provides a common Python interface to download and interact with reference brain atlases from multiple species (including human, mouse and larval zebrafish). This allows software to be developed agnostic to the atlas and species, increasing adoption and interoperability of software tools in neuroscience.

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.