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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r r Abstract: Characterization of large-scale brain networks using blood-oxygenation-level-dependent functional magnetic resonance imaging is typically based on the assumption of network stationarity across the duration of scan. Recent studies in humans have questioned this assumption by showing that within-network functional connectivity fluctuates on the order of seconds to minutes. Time-varying profiles of resting-state networks (RSNs) may relate to spontaneously shifting, electrophysiological network states and are thus mechanistically of particular importance. However, because these studies acquired data from awake subjects, the fluctuating connectivity could reflect various forms of conscious brain processing such as passive mind wandering, active monitoring, memory formation, or changes in attention and arousal during image acquisition. Here, we characterize RSN dynamics of anesthetized macaques that control for these accounts, and compare them to awake human subjects. We find that functional connectivity among nodes comprising the ''oculomotor (OCM) network'' strongly fluctuated over time during awake as well as anaesthetized states. For time dependent anal- ysis with short windows (<60 s), periods of positive functional correlations alternated with prominent anticor- relations that were missed when assessed with longer time windows. Similarly, the analysis identified network nodes that transiently link to the OCM network and did not emerge in average RSN analysis. Further- more, time-dependent analysis reliably revealed transient states of large-scale synchronization that spanned all seeds. The results illustrate that resting-state functional connectivity is not static and that RSNs can exhibit non- stationary, spontaneous relationships irrespective of conscious, cognitive processing. The findings imply that mechanistically important network information can be missed when using average functional connectivity as the single network measure.Hum Brain Mapp 00:000-000, 2012. V C 2012 Wiley Periodicals, Inc. Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intrapariet al area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of pariet al and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition. 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. 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. Connectomics is an emerging field in neuroscience that aims to reconstruct the 3-dimensional morphology of neurons from electron microscopy (EM) images. Recent studies have successfully demonstrated the use of convolutional neural networks (ConvNets) for segmenting cell membranes to individuate neurons. However, there has been comparatively little success in high-throughput identification of the intercellular synaptic connections required for deriving connectivity graphs. In this study, we take a compositional approach to segmenting synapses, modeling them explicitly as an intercellular cleft co-located with an asymmetric vesicle density along a cell membrane. Instead of requiring a deep network to learn all natural combinations of this compositionality, we train lighter networks to model the simpler marginal distributions of membranes, clefts and vesicles from just 100 electron microscopy samples. These feature maps are then combined with simple rules-based heuristics derived from prior biological knowledge. Our approach to synapse detection is both more accurate than previous state-of-the-art (7 higher recall and 5 higher F1-score) and yields a 20-fold speed-up compared to the previous fastest implementations. We demonstrate by reconstructing the first complete, directed connectome from the largest available anisotropic microscopy dataset (245 GB) of mouse somatosensory cortex (S1) in just 9.7 hours on a single shared-memory CPU system. We believe that this work marks an important step toward the goal of a microscope-pace streaming connectomics pipeline. The brain appears to adhere to two principles of functional organization; junctional segregation and functional intryration. The integration within and between functionally specialized areas is mediated by functional or ejectiue connectioity. The characterization of this sort of connectivity is an important theme in many areas of neuroscience. This article presents one approach that has been used in functional imaging. This article reviews the basic distinction between functional and effective connectivity (as the terms are used in neuroimaging) and their role in addressing several aspects of functional organization (e.g. the topography of distributed systems, integration between cortical areas, time-dependent changes in connectivity and nonlinear interactions). Emphasis is placed on the points of contact between the apparently diverse applications of these concepts and in particular the central role of eigenimages or spatial modes. Although the framework that has been developed is inherently linear, it has been extended to assess nonlinear interactions among cortical areas. 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. Reconstructing a synaptic wiring diagram, or connectome, from electron microscopy (EM) images of brain tissue currently requires many hours of manual annotation or proofreading (Kasthuri and Lichtman, 2010; Lichtman and Sanes, 2008; Seung, 2009). The desire to reconstruct ever larger and more complex networks has pushed the collection of ever larger EM datasets. A cubic millimeter of raw imaging data would take up 1 PB of storage and present an annotation project that would be impractical without relying heavily on automatic segmentation methods. The RhoanaNet image processing pipeline was developed to automatically segment large volumes of EM data and ease the burden of manual proofreading and annotation. Based on (, 2015), we updated every stage of the software pipeline to provide better throughput performance and higher quality segmentation results. We used state of the art deep learning techniques to generate improved membrane probability maps, and Gala (Nunez-, 2014) was used to agglomerate 2D segments into 3D objects. We applied the RhoanaNet pipeline to four densely annotated EM datasets, two from mouse cortex, one from cerebellum and one from mouse lateral geniculate nucleus (LGN). All training and test data is made available for benchmark comparisons. The best segmentation results obtained gave @math scores of 0.9054 and 09182 for the cortex datasets, 0.9438 for LGN, and 0.9150 for Cerebellum. The RhoanaNet pipeline is open source software. All source code, training data, test data, and annotations for all four benchmark datasets are available at this http URL. 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 Diffusion-sensitized magnetic resonance imaging probes the cellular structure of the human brain, but the primary microstructural information gets lost in averaging over higher-level, mesoscopic tissue organization such as different orientations of neuronal fibers. While such averaging is inevitable due to the limited imaging resolution, we propose a method for disentangling the microscopic cell properties from the effects of mesoscopic structure. We further avoid the classical fitting paradigm and use supervised machine learning in terms of a Bayesian estimator to estimate the microstructural properties. The method finds detectable parameters of a given microstructural model and calculates them within seconds, which makes it suitable for a broad range of neuroscientific applications. Research in neuroevolution---that is, evolving artificial neural networks (ANNs) through evolutionary algorithms---is inspired by the evolution of biological brains, which can contain trillions of connections. Yet while neuroevolution has produced successful results, the scale of natural brains remains far beyond reach. This article presents a method called hypercube-based NeuroEvolution of Augmenting Topologies (HyperNEAT) that aims to narrow this gap. HyperNEAT employs an indirect encoding called connective compositional pattern-producing networks (CPPNs) that can produce connectivity patterns with symmetries and repeating motifs by interpreting spatial patterns generated within a hypercube as connectivity patterns in a lower-dimensional space. This approach can exploit the geometry of the task by mapping its regularities onto the topology of the network, thereby shifting problem difficulty away from dimensionality to the underlying problem structure. Furthermore, connective CPPNs can represent the same connectivity pattern at any resolution, allowing ANNs to scale to new numbers of inputs and outputs without further evolution. HyperNEAT is demonstrated through visual discrimination and food-gathering tasks, including successful visual discrimination networks containing over eight million connections. The main conclusion is that the ability to explore the space of regular connectivity patterns opens up a new class of complex high-dimensional tasks to neuroevolution. 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. Recent advances in neuroimaging techniques provide great potentials for effective diagnosis of Alzheimer's disease (AD), the most common form of dementia. Previous studies have shown that AD is closely related to the alternation in the functional brain network, i.e., the functional connectivity among different brain regions. In this paper, we consider the problem of learning functional brain connectivity from neuroimaging, which holds great promise for identifying image-based markers used to distinguish Normal Controls (NC), patients with Mild Cognitive Impairment (MCI), and patients with AD. More specifically, we study sparse inverse covariance estimation (SICE), also known as exploratory Gaussian graphical models, for brain connectivity modeling. In particular, we apply SICE to learn and analyze functional brain connectivity patterns from different subject groups, based on a key property of SICE, called the "monotone property" we established in this paper. Our experimental results on neuroimaging PET data of 42 AD, 116 MCI, and 67 NC subjects reveal several interesting connectivity patterns consistent with literature findings, and also some new patterns that can help the knowledge discovery of AD. The brain network is usually constructed by estimating the connectivity matrix and thresholding it at an arbitrary level. The problem with this standard method is that we do not have any generally accepted criteria for determining a proper threshold. Thus, we propose a novel multiscale framework that models all brain networks generated over every possible threshold. Our approach is based on persistent homology and its various representations such as the Rips filtration, barcodes, and dendrograms. This new persistent homological framework enables us to quantify various persistent topological features at different scales in a coherent manner. The barcode is used to quantify and visualize the evolutionary changes of topological features such as the Betti numbers over different scales. By incorporating additional geometric information to the barcode, we obtain a single linkage dendrogram that shows the overall evolution of the network. The difference between the two networks is then measured by the Gromov-Hausdorff distance over the dendrograms. As an illustration, we modeled and differentiated the FDG-PET based functional brain networks of 24 attention-deficit hyperactivity disorder children, 26 autism spectrum disorder children, and 11 pediatric control subjects. 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. 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. 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. This review considers state-of-the-art analyses of functional integration in neuronal macrocircuits. We focus on detecting and estimating directed connectivity in neuronal networks using Granger causality (GC) and dynamic causal modelling (DCM). These approaches are considered in the context of functional segregation and integration and — within functional integration — the distinction between functional and effective connectivity. We review recent developments that have enjoyed a rapid uptake in the discovery and quantification of functional brain architectures. GC and DCM have distinct and complementary ambitions that are usefully considered in relation to the detection of functional connectivity and the identification of models of effective connectivity. We highlight the basic ideas upon which they are grounded, provide a comparative evaluation and point to some outstanding issues. 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. Functional imaging studies have shown that certain brain regions, including posterior cingulate cortex (PCC) and ventral anterior cingulate cortex (vACC), consistently show greater activity during resting states than during cognitive tasks. This finding led to the hypothesis that these regions constitute a network supporting a default mode of brain function. In this study, we investigate three questions pertaining to this hypothesis: Does such a resting-state network exist in the human brain? Is it modulated during simple sensory processing? How is it modulated during cognitive processing? To address these questions, we defined PCC and vACC regions that showed decreased activity during a cognitive (working memory) task, then examined their functional connectivity during rest. PCC was strongly coupled with vACC and several other brain regions implicated in the default mode network. Next, we examined the functional connectivity of PCC and vACC during a visual processing task and show that the resultant connectivity maps are virtually identical to those obtained during rest. Last, we defined three lateral prefrontal regions showing increased activity during the cognitive task and examined their resting-state connectivity. We report significant inverse correlations among all three lateral prefrontal regions and PCC, suggesting a mechanism for attenuation of default mode network activity during cognitive processing. This study constitutes, to our knowledge, the first resting-state connectivity analysis of the default mode and provides the most compelling evidence to date for the existence of a cohesive default mode network. Our findings also provide insight into how this network is modulated by task demands and what functions it might subserve.