Visually comparing brain networks, or connectomes, is an essential task in the field of neuroscience. Especially relevant to the field of clinical neuroscience, group studies that examine differences between populations or changes over time within a population enable neuroscientists to reason about effective diagnoses and treatments for a range of neuropsychiatric disorders. In this paper, we specifically explore how visual analytics tools can be used to facilitate various clinical neuroscience tasks, in which observation and analysis of meaningful patterns in the connectome can support patient diagnosis and treatment. We conduct a survey of visualization tasks that enable clinical neuroscience activities, and further explore how existing connectome visualization tools support or fail to support these tasks. Based on our investigation of these tasks, we introduce a novel visualization tool, NeuroCave, to support group studies analyses. We discuss how our design decisions (the use of immersive visualization, the use of hierarchical clustering and dimensionality reduction techniques, and the choice of visual encodings) are motivated by these tasks. We evaluate NeuroCave through two use cases that illustrate the utility of interactive connectome visualization in clinical neuroscience contexts. In the first use case, we study sex differences using functional connectomes and discover hidden connectome patterns associated with well-known cognitive differences in spatial and verbal abilities. In the second use case, we show how the utility of visualizing the brain in different topological space coupled with clustering information can reveal the brain's intrinsic structure.
The term was first coined by @cite_30 to describe the “wiring diagram” of the anatomical connectivity of the human brain. The interconnectivity found between parcellated brain regions as described above is considered the macroscale connectome. Meso- and micro- scale connectomes are at the local neuronal circuits and single neuronal cells levels respectively, and they currently require an invasive high resolution scans of dissected brains using microtome machinery. Friston defined functional connectivity as “the temporal correlation between spatially remote neurophysiological events” @cite_16 . This paper focuses on visualization tasks relevant to macroscale functional and structural connectomes, derived from functional and diffusion-weighted MRI respectively.
@cite_30 @cite_16
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Connectomics is a field of neuroscience that analyzes neuronal connections. A connectome is a complete map of a neuronal system, comprising all neuronal connections between its structures. The term "connectome" is close to the word "genome" and implies completeness of all neuronal connections, in the same way as a genome is a complete listing of all nucleotide sequences. The goal of connectomics is to create a complete representation of the brain's wiring. Such a representation is believed to increase our understanding of how functional brain states emerge from their underlying anatomical structure. Furthermore, it can provide important information for the cure of neuronal dysfunctions like schizophrenia or autism. In this paper, we review the current state-of-the-art of visualization and image processing techniques in the field of connectomics and describe some remaining challenges. This paper describes novel methods for constructing the intrinsic geometry of the human brain connectome using dimensionality-reduction techniques. We posit that the high-dimensional, complex geometry that represents this intrinsic topology can be mathematically embedded into lower dimensions using coupling patterns encoded in the corresponding brain connectivity graphs. We tested both linear and nonlinear dimensionality-reduction techniques using the diffusion-weighted structural connectome data acquired from a sample of healthy subjects. Results supported the nonlinearity of brain connectivity data, as linear reduction techniques such as the multidimensional scaling yielded inferior lower-dimensional embeddings. To further validate our results, we demonstrated that for tractography-derived structural connectome more influential regions such as rich-club members of the brain are more centrally mapped or embedded. Further, abnormal brain connectivity can be visually understood by inspecting the altered geometry of these three-dimensional (3D) embeddings that represent the topology of the human brain, as illustrated using simulated lesion studies of both targeted and random removal. Last, in order to visualize brain’s intrinsic topology we have developed software that is compatible with virtual reality technologies, thus allowing researchers to collaboratively and interactively explore and manipulate brain connectome data. The connection matrix of the human brain (the human “connectome”) represents an indispensable foundation for basic and applied neurobiological research. However, the network of anatomical connections linking the neuronal elements of the human brain is still largely unknown. While some databases or collations of large-scale anatomical connection patterns exist for other mammalian species, there is currently no connection matrix of the human brain, nor is there a coordinated research effort to collect, archive, and disseminate this important information. We propose a research strategy to achieve this goal, and discuss its potential impact. Mapping the connectivity of neurons in the brain (i.e., connectomics) is a challenging problem due to both the number of connections in even the smallest organisms and the nanometer resolution required to resolve them. Because of this, previous connectomes contain only hundreds of neurons, such as in the C.elegans connectome. Recent technological advances will unlock the mysteries of increasingly large connectomes (or partial connectomes). However, the value of these maps is limited by our ability to reason with this data and understand any underlying motifs. To aid connectome analysis, we introduce algorithms to cluster similarly-shaped neurons, where 3D neuronal shapes are represented as skeletons. In particular, we propose a novel location-sensitive clustering algorithm. We show clustering results on neurons reconstructed from the Drosophila medulla that show high-accuracy. Thanks to advances in non-invasive technologies such as functional Magnetic Resonance Imaging (fMRI) and Diffusion Tensor Imaging (DTI), highly-detailed maps of brain structure and function can now be collected. In this context, brain connectomics have emerged as a fast growing field that aims at understanding these comprehensive maps of brain connectivity using sophisticated computational models. In this paper we present BRAINtrinsic, an innovative web-based 3D visual analytics tool that allows users to intuitively and iteratively interact with connectome data. Moreover, BRAINtrinsic implements a novel visualization platform that reconstructs connectomes’ intrinsic geometry, i.e., the topological space as informed by brain connectivity, via dimensionality reduction. BRAINtrinsic is implemented with virtual reality in mind and is fully compatible with the Oculus Rift technology. Last, we demonstrate its effectiveness through a series of case studies involving both structural and resting-state MR imaging data. Abstract Can semantic corpora be coupled to dynamical simulations in such a way so as to extract new associations from the data that were hitherto unapparent? We attempt to do this within neuroscience as an application domain, by introducing the notion of the semantome and coupling it to the connectome of the human brain network. This is implemented using BrainX3, a virtual reality simulation cum data mining platform that can be used for visualization, analysis and feature extraction of neuroscience data. We use this system to explore anatomical, functional and symptomatic semantics associated to simulated neuronal activity of a healthy brain, one with stroke and one perturbed by transcranial magnetic stimulation. In particular, we find that pariet al and occipital lesions in stroke affect the visual processing pathway leading to symptoms such as visual neglect, depression and photo-sensitivity seizures. Integrating semantomics with connectomics thus generates hypotheses about symptoms, functions and brain activity that supplement existing tools for diagnosis of mental illness. Our results suggest a new approach to big data with potential applications to other domains. Tracing neurons in large-scale microscopy data is crucial to establishing a wiring diagram of the brain, which is needed to understand how neural circuits in the brain process information and generate behavior. Automatic techniques often fail for large and complex datasets, and connectomics researchers may spend weeks or months manually tracing neurons using 2D image stacks. We present a design study of a new virtual reality (VR) system, developed in collaboration with trained neuroanatomists, to trace neurons in microscope scans of the visual cortex of primates. We hypothesize that using consumer-grade VR technology to interact with neurons directly in 3D will help neuroscientists better resolve complex cases and enable them to trace neurons faster and with less physical and mental strain. We discuss both the design process and technical challenges in developing an interactive system to navigate and manipulate terabyte-sized image volumes in VR. Using a number of different datasets, we demonstrate that, compared to widely used commercial software, consumer-grade VR presents a promising alternative for scientists. Electron microscopic connectomics is an ambitious research direction with the goal of studying comprehensive brain connectivity maps by using high-throughput, nano-scale microscopy. One of the main challenges in connectomics research is developing scalable image analysis algorithms that require minimal user intervention. Recently, deep learning has drawn much attention in computer vision because of its exceptional performance in image classification tasks. For this reason, its application to connectomic analyses holds great promise, as well. In this paper, we introduce a novel deep neural network architecture, FusionNet, for the automatic segmentation of neuronal structures in connectomics data. FusionNet leverages the latest advances in machine learning, such as semantic segmentation and residual neural networks, with the novel introduction of summation-based skip connections to allow a much deeper network architecture for a more accurate segmentation. We demonstrate the performance of the proposed method by comparing it with state-of-the-art electron microscopy (EM) segmentation methods from the ISBI EM segmentation challenge. We also show the segmentation results on two different tasks including cell membrane and cell body segmentation and a statistical analysis of cell morphology. In analysis of the human connectome, the connectivity of the human brain is collected from multiple imaging modalities and analyzed using graph theoretical techniques. The dimensionality of human connectivity data is high, and making sense of the complex networks in connectomics requires sophisticated visualization and analysis software. The current availability of software packages to analyze the human connectome is limited. The Connectome Visualization Utility (CVU) is a new software package designed for the visualization and network analysis of human brain networks. CVU complements existing software packages by offering expanded interactive analysis and advanced visualization features, including the automated visualization of networks in three different complementary styles and features the special visualization of scalar graph theoretical properties and modular structure. By decoupling the process of network creation from network visualization and analysis, we ensure that CVU can visualize networks from any imaging modality. CVU offers a graphical user interface, interactive scripting, and represents data uses transparent neuroimaging and matrix-based file types rather than opaque application-specific file formats. Abstract In recent years, big brain-initiatives and consortia have created vast resources of publicly available brain data that can be used by neuroscientists for their own research experiments. This includes microscale connectivity data—brain-network graphs with billions of edges—and vast spatial gene expression resources—the representation of tens of thousands genes in brain space. Their joint analysis for higher order relations in structural or functional neuroanatomy would enable the genetic dissection of brain networks on a genome-wide scale. Current experimental workflows involve only time-consuming manual aggregation and extensive graph theoretical analysis of data from different sources, which rarely provide spatial context to operate continuously on different scales. In this paper, we propose BrainTrawler, a task-driven, web-based framework that incorporates visual analytics methods to explore heterogeneous neurobiological data. It facilitates spatial indexing to query large-scale voxel-level connectivity data and gene expression collections in real-time. Relating data to the hierarchical structure of common anatomical atlases enables the retrieval on different anatomical levels. Together with intuitive network visualization, iterative visual queries, and quantitative information this allows the genetic dissection of multimodal networks on local global scales in a spatial context. We demonstrate the relevance of our approach for neuroscience by exploring social-behavior and memory learning related functional neuroanatomy in mice. Abstract The individual course of white matter fiber tracts is an important factor for analysis of white matter characteristics in healthy and diseased brains. Diffusion-weighted MRI tractography in combination with region-based or clustering-based selection of streamlines is a unique combination of tools which enables the in-vivo delineation and analysis of anatomically well-known tracts. This, however, currently requires complex, computationally intensive processing pipelines which take a lot of time to set up. TractSeg is a novel convolutional neural network-based approach that directly segments tracts in the field of fiber orientation distribution function (fODF) peaks without using tractography, image registration or parcellation. We demonstrate that the proposed approach is much faster than existing methods while providing unprecedented accuracy, using a population of 105 subjects from the Human Connectome Project. We also show initial evidence that TractSeg is able to generalize to differently acquired data sets for most of the bundles. The code and data are openly available at https: github.com MIC-DKFZ TractSeg and https: doi.org 10.5281 zenodo.1088277 , respectively. We introduce NeuroCave, a novel immersive visualization system that facilitates the visual inspection of structural and functional connectome datasets. The representation of the human connectome as a graph enables neuroscientists to apply network-theoretic approaches in order to explore its complex characteristics. With NeuroCave, brain researchers can interact with the connectome— either in a standard desktop environment or while wearing portable VR headsets (such as Oculus Rift, Samsung Gear, or Google Daydream VR platforms)— in any coordinate system or topological space, as well as cluster brain regions into different modules on demand. Furthermore, a default side-by-side layout enables simultaneous, synchronized manipulation in 3D, utilizing modern GPU hardware architecture, and facilitates comparison tasks across different subjects or diagnostic groups or longitudinally within the same subject. Visual clutter is mitigated using a state-of-the-art edge bundling technique and through an interactive lay... The human brain is a complex system whose topological organization can be represented using connectomics. Recent studies have shown that human connectomes can be constructed using various neuroimaging technologies and further characterized using sophisticated analytic strategies, such as graph theory. These methods reveal the intriguing topological architectures of human brain networks in healthy populations and explore the changes throughout normal development and aging and under various pathological conditions. However, given the huge complexity of this methodology, toolboxes for graph-based network visualization are still lacking. Here, using MATLAB with a graphical user interface (GUI), we developed a graph-theoretical network visualization toolbox, called BrainNet Viewer, to illustrate human connectomes as ball-and-stick models. Within this toolbox, several combinations of defined files with connectome information can be loaded to display different combinations of brain surface, nodes and edges. In addition, display properties, such as the color and size of network elements or the layout of the figure, can be adjusted within a comprehensive but easy-to-use settings panel. Moreover, BrainNet Viewer draws the brain surface, nodes and edges in sequence and displays brain networks in multiple views, as required by the user. The figure can be manipulated with certain interaction functions to display more detailed information. Furthermore, the figures can be exported as commonly used image file formats or demonstration video for further use. BrainNet Viewer helps researchers to visualize brain networks in an easy, flexible and quick manner, and this software is freely available on the NITRC website (www.nitrc.org projects bnv ). Diffusion tensor imaging (DTI) is an MRI-based technique for quantifying water diffusion in living tissue. In the white matter of the brain, water diffuses more rapidly along the neuronal axons than in the perpendicular direction. By exploiting this phenomenon, DTI can be used to determine trajectories of fiber bundles, or neuronal connections between regions, in the brain. The resulting bundles can be visualized. However, the resulting visualizations can be complex and difficult to interpret. An effective approach is to pre-determine trajectories from a large number of positions throughout the white matter (full brain fiber tracking) and to offer facilities to aid the user in selecting fiber bundles of interest. Two factors are crucial for the use and acceptance of this technique in clinical studies: firstly, the selection of the bundles by brain experts should be interactive, supported by real-time visualization of the trajectories registered with anatomical MRI scans. Secondly, the fiber selections should be reproducible, so that different experts will achieve the same results. In this paper we present a practical technique for the interactive selection of fiber-bundles using multiple convex objects that is an order of magnitude faster than similar techniques published earlier. We also present the results of a clinical study with ten subjects that show that our selection approach is highly reproducible for fractional anisotropy (FA) calculated over the selected fiber bundles. Connectomics based on high resolution ssTEM imagery requires reconstruction of the neuron geometry from histological slides. We present an approach for the automatic membrane segmentation in anisotropic stacks of electron microscopy brain tissue sections. The ambiguities in neuronal segmentation of a section are resolved by using the context from the neighboring sections. We find the global dense correspondence between the sections by SIFT Flow algorithm, evaluate the features of the corresponding pixels and use them to perform the segmentation. Our method is 3.6 and 6.4 more accurate in two different accuracy metrics than the algorithm with no context from other sections. Cortical network architecture has predominantly been investigated visually using graph theory representations. In the context of human connectomics, such representations are not however always satisfactory because canonical methods for vertex–edge relationship representation do not always offer optimal insight regarding functional and structural neural connectivity. This article introduces an innovative framework for the depiction of human connectomics by employing a circular visualization method which is highly suitable to the exploration of central nervous system architecture. This type of representation, which we name a ‘connectogram’, has the capability of classifying neuroconnectivity relationships intuitively and elegantly. A multimodal protocol for MRI DTI neuroimaging data acquisition is here combined with automatic image segmentation to (1) extract cortical and non-cortical anatomical structures, (2) calculate associated volumetrics and morphometrics, and (3) determine patient-specific connectivity profiles to generate subject-level and population-level connectograms. The scalability of our approach is demonstrated for a population of 50 adults. Two essential advantages of the connectogram are (1) the enormous potential for mapping and analyzing the human connectome, and (2) the unconstrained ability to expand and extend this analysis framework to the investigation of clinical populations and animal models. Abstract We have developed a MATLAB-based toolbox, eConnectome (electrophysiological connectome), for mapping and imaging functional connectivity at both the scalp and cortical levels from the electroencephalogram (EEG), as well as from the electrocorticogram (ECoG). Graphical user interfaces were designed for interactive and intuitive use of the toolbox. Major functions of eConnectome include EEG ECoG preprocessing, scalp spatial mapping, cortical source estimation, connectivity analysis, and visualization. Granger causality measures such as directed transfer function and adaptive directed transfer function were implemented to estimate the directional interactions of brain functional networks, over the scalp and cortical sensor spaces. Cortical current density inverse imaging was implemented using a generic realistic geometry brain–head model from scalp EEGs. Granger causality could be further estimated over the cortical source domain from the inversely reconstructed cortical source signals as derived from the scalp EEG. Users may implement other connectivity estimators in the framework of eConnectome for various applications. The toolbox package is open-source and freely available at http: econnectome.umn.edu under the GNU general public license for noncommercial and academic uses. The analysis of microcircuitry (the connectivity at the level of individual neuronal processes and synapses), which is indispensable for our understanding of brain function, is based on serial transmission electron microscopy (TEM) or one of its modern variants. Due to technical limitations, most previous studies that used serial TEM recorded relatively small stacks of individual neurons. As a result, our knowledge of microcircuitry in any nervous system is very limited. We applied the software package TrakEM2 to reconstruct neuronal microcircuitry from TEM sections of a small brain, the early larval brain of Drosophila melanogaster. TrakEM2 enables us to embed the analysis of the TEM image volumes at the microcircuit level into a light microscopically derived neuro-anatomical framework, by registering confocal stacks containing sparsely labeled neural structures with the TEM image volume. We imaged two sets of serial TEM sections of the Drosophila first instar larval brain neuropile and one ventral nerve cord segment, and here report our first results pertaining to Drosophila brain microcircuitry. Terminal neurites fall into a small number of generic classes termed globular, varicose, axiform, and dendritiform. Globular and varicose neurites have large diameter segments that carry almost exclusively presynaptic sites. Dendritiform neurites are thin, highly branched processes that are almost exclusively postsynaptic. Due to the high branching density of dendritiform fibers and the fact that synapses are polyadic, neurites are highly interconnected even within small neuropile volumes. We describe the network motifs most frequently encountered in the Drosophila neuropile. Our study introduces an approach towards a comprehensive anatomical reconstruction of neuronal microcircuitry and delivers microcircuitry comparisons between vertebrate and insect neuropile. Inter-subject alignment of functional MRI (fMRI) data is necessary for group analyses. The standard approach to this problem matches anatomical features of the brain, such as major anatomical landmarks or cortical curvature. Precise alignment of functional cortical topographies, however, cannot be derived using only anatomical features. We propose a new inter-subject registration algorithm that aligns intra-subject patterns of functional connectivity across subjects. We derive functional connectivity patterns by correlating fMRI BOLD time-series, measured during movie viewing, between spatially remote cortical regions. We validate our technique extensively on real fMRI experimental data and compare our method to two state-of-the-art inter-subject registration algorithms. By cross-validating our method on independent datasets, we show that the derived alignment generalizes well to other experimental paradigms. How rich functionality emerges from the invariant structural architecture of the brain remains a major mystery in neuroscience. Recent applications of network theory and theoretical neuroscience to large-scale brain networks have started to dissolve this mystery. Network analyses suggest that hierarchical modular brain networks are particularly suited to facilitate local (segregated) neuronal operations and the global integration of segregated functions. Although functional networks are constrained by structural connections, context-sensitive integration during cognition tasks necessarily entails a divergence between structural and functional networks. This degenerate (many-to-one) function-structure mapping is crucial for understanding the nature of brain networks. The emergence of dynamic functional networks from static structural connections calls for a formal (computational) approach to neuronal information processing that may resolve this dialectic between structure and function.