Neuro-Informatics seminars

With the advent of several different fMRI analysis tools and packages outside of the established ones (i.e., SPM, AFNI, and FSL), today's researcher may wonder what the best practices are for fMRI analysis. This talk will discuss some of the recent trends in neuroimaging, including design optimization and power analysis, standardized analysis pipelines such as fMRIPrep, and an overview of current recommendations for how to present neuroimaging results. Along the way we will discuss the balance between Type I and Type II errors with different correction mechanisms (e.g., Threshold-Free Cluster Enhancement and Equitable Thresholding and Clustering), as well as considerations for working with large open-access databases.

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.

We will discuss this paper on Neuroquery, a relatively new web-based meta-analysis tool: https://elifesciences.org/articles/53385.pdf. This is different from Neurosynth in that it generates meta-analysis maps using predictive modeling from the string of text provided at the prompt, instead of performing inferential statistics to calculate the overlap of activation from different studies. This allows the user to generate predictive maps for more nuanced cognitive processes - especially for clinical populations which may be underrepresented in the literature compared to controls - and can be useful in generating predictions about where the activity will be for one's own study, and for creating ROIs.

This set of short webinars will provide neuroscience researchers working in a neuroimaging setting with practical tips on strengthening credibility at different stages of the research project. Each webinar will be hosted by Cassandra Gould Van Praag from the Wellcome Centre for Integrative Neuroimaging.

This set of short webinars will provide neuroscience researchers working in a neuroimaging setting with practical tips on strengthening credibility at different stages of the research project. Each webinar will be hosted by Cassandra Gould Van Praag from the Wellcome Centre for Integrative Neuroimaging.

It is now widely accepted that openness and transparency are keys to improving the reproducibility of scientific research, but many challenges remain to adoption of these practices. I will discuss the growth of an ecosystem for open science within the field of neuroimaging, focusing on platforms for open data sharing and open source tools for reproducible data analysis. I will also discuss the role of the Brain Imaging Data Structure (BIDS), a community standard for data organization, in enabling this open science ecosystem, and will outline the scientific impacts of these resources.

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.

Neuroscientists have many questions about connectomes that revolve around the ability to compare networks. For example, comparing connectomes could help explain how neural wiring is related to individual differences, genetics, disease, development, or learning. One such question is that of bilateral symmetry: are the left and right sides of a connectome the same? Here, we investigate the bilateral symmetry of a recently presented connectome of an insect brain, the Drosophila larva. We approach this question from the perspective of two-sample testing for networks. First, we show how this question of “sameness” can be framed as a variety of different statistical hypotheses, each with different assumptions. Then, we describe test procedures for each of these hypotheses. We show how these different test procedures perform on both the observed connectome as well as a suite of synthetic perturbations to the connectome. We also point out that these tests require careful attention to parameter alignment and differences in network density in order to provide biologically meaningful results. Taken together, these results provide the first statistical characterization of bilateral symmetry for an entire brain at the single-neuron level, while also giving practical recommendations for future comparisons of connectome networks.

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.

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

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.

Rajanlab designs neural network models constrained by experimental data, and reverse engineers them to figure out how brain circuits function in health and disease. Recently, we have been developing a powerful new theory-based framework for “in-vivo tract tracing” from multi-regional neural activity collected experimentally. We call this framework CURrent-Based Decomposition (CURBD). CURBD employs recurrent neural networks (RNNs) directly constrained, from the outset, by time series measurements acquired experimentally, such as Ca2+ imaging or electrophysiological data. Once trained, these data-constrained RNNs let us infer matrices quantifying the interactions between all pairs of modeled units. Such model-derived “directed interaction matrices” can then be used to separately compute excitatory and inhibitory input currents that drive a given neuron from all other neurons. Therefore different current sources can be de-mixed – either within the same region or from other regions, potentially brain-wide – which collectively give rise to the population dynamics observed experimentally. Source de-mixed currents obtained through CURBD allow an unprecedented view into multi-region mechanisms inaccessible from measurements alone. We have applied this method successfully to several types of neural data from our experimental collaborators, e.g., zebrafish (Deisseroth lab, Stanford), mice (Harvey lab, Harvard), monkeys (Rudebeck lab, Sinai), and humans (Rutishauser lab, Cedars Sinai), where we have discovered both directed interactions brain wide and inter-area currents during different types of behaviors. With this powerful framework based on data-constrained multi-region RNNs and CURrent Based Decomposition (CURBD), we ask if there are conserved multi-region mechanisms across different species, as well as identify key divergences.

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.