Neuroimaging Community Research Articles

Data Citation in Neuroimaging: Proposed Best Practices for Data Identification and Attribution.

Data sharing and reuse, while widely accepted as good ideas, have been slow to catch on in any concrete and consistent way. One major hurdle within the scientific community has been the lack of widely accepted standards for citing that data, making it difficult to track usage and measure impact. Within the neuroimaging community, there is a need for a way to not only clearly identify and cite datasets, but also to derive new aggregate sets from multiple sources while clearly maintaining lines of attribution. This work presents a functional prototype of a system to integrate Digital Object Identifiers (DOI) and a standardized metadata schema into a XNAT-based repository workflow, allowing for identification of data at both the project and image level. These item and source level identifiers allow any newly defined combination of images, from any number of projects, to be tagged with a new group-level DOI that automatically inherits the individual attributes and provenance information of its constituent parts. This system enables the tracking of data reuse down to the level of individual images. The implementation of this type of data identification system would impact researchers and data creators, data hosting facilities, and data publishers, but the benefit of having widely accepted standards for data identification and attribution would go far toward making data citation practical and advantageous.

Resting-state networks in 6-to-10 year old children.

Resting-state functional magnetic resonance imaging provides a non-invasive approach to the study of intrinsic functional brain networks. When applied to the study of brain development, most studies consist of relatively small samples that are not always representative of the general population. Descriptions of these networks in the general population offer important insight for clinical studies examining, for instance, psychopathology or neurological conditions. Thus our goal was to characterize resting-state networks in a large sample of children using independent component analysis (ICA). The study further aimed to describe the robustness of these networks by examining which networks occur frequently after repeated ICA. Resting-state networks were obtained from a sample of 536 6-to-10 year old children. Distributions of networks were built from repeated subsampling and group ICA analyses, and meta-ICA was used to construct a representative set of components. Within- and between-network properties were tested for age-related developmental associations using spatio-temporal regression. After repeated ICA, many networks were present over 95% of the time suggesting the components are highly reproducible. Some networks were less robust, and were observed less than 70% of the time. Age-related associations were also observed in a selection of networks, including the default-mode network, offering further evidence of development in these networks at an early age. ICA-derived resting-state networks appear to be robust, although some networks should further scrutinized if subjected to group-level statistical analyses, such as spatiotemporal regression. The final set of ICA-derived networks and an age-appropriate T1 -weighted template are made available to the neuroimaging community, https://www.nitrc.org/projects/genr. Hum Brain Mapp 37:4286-4300, 2016. © 2016 Wiley Periodicals, Inc.

Sprite tree: an efficient image-based representation for networked virtual environments

In this paper we present a pipeline for automatic analysis of neuronal morphology: from detection, modeling to digital reconstruction. First, we present an automatic, unsupervised object detection framework using stochastic marked point process. It extracts connected neuronal networks by fitting special configuration of marked objects to the centreline of the neurite branches in the image volume giving us position, local width and orientation information. Semantic modeling of neuronal morphology in terms of critical nodes like bifurcations and terminals, generates various geometric and morphology descriptors such as branching index, branching angles, total neurite length, internodal lengths for statistical inference on characteristic neuronal features. From the detected branches we reconstruct neuronal tree morphology using robust and efficient numerical fast marching methods. We capture a mathematical model abstracting out the relevant position, shape and connectivity information about neuronal branches from the microscopy data into connected minimum spanning trees. Such digital reconstruction is represented in standard SWC format, prevalent for archiving, sharing, and further analysis in the neuroimaging community. Our proposed pipeline outperforms state of the art methods in tracing accuracy and minimizes the subjective variability in reconstruction, inherent to semi-automatic methods.

Only time will tell - why temporal information is essential for our neuroscientific understanding of semantics.

Theoretical developments about the nature of semantic representations and processes should be accompanied by a discussion of how these theories can be validated on the basis of empirical data. Here, I elaborate on the link between theory and empirical research, highlighting the need for temporal information in order to distinguish fundamental aspects of semantics. The generic point that fast cognitive processes demand fast measurement techniques has been made many times before, although arguably more often in the psychophysiological community than in the metabolic neuroimaging community. Many reviews on the neuroscience of semantics mostly or even exclusively focus on metabolic neuroimaging data. Following an analysis of semantics in terms of the representations and processes involved, I argue that fundamental theoretical debates about the neuroscience of semantics can only be concluded on the basis of data with sufficient temporal resolution. Any “semantic effect” may result from a conflation of long-term memory representations, retrieval and working memory processes, mental imagery, and episodic memory. This poses challenges for all neuroimaging modalities, but especially for those with low temporal resolution. It also throws doubt on the usefulness of contrasts between meaningful and meaningless stimuli, which may differ on a number of semantic and non-semantic dimensions. I will discuss the consequences of this analysis for research on the role of convergence zones or hubs and distributed modal brain networks, top-down modulation of task and context as well as interactivity between levels of the processing hierarchy, for example in the framework of predictive coding.

Transformation Invariant Control ofVoxel-Wise False Discovery Rate

Multiple testing for statistical maps remains a critical and challenging problem in brain mapping. Since the false discovery rate (FDR) criterion was introduced to the neuroimaging community a decade ago, many variations have been proposed, mainly to enhance detection power. However, a fundamental geometrical property known as transformation invariance has not been adequately addressed, especially for the voxel-wise FDR. Correction of multiple testing applied after spatial transformation is not necessarily equivalent to transformation applied after correction in the original space. Without the invariance property, assigning different testing spaces will yield different results. We find that normalized residuals of linear models with Gaussian noises are uniformly distributed on a unit high-dimensional sphere, independent of t-statistics and F-statistics. By defining volumetric measure in the hyper-spherical space mapped by normalized residuals, instead of the image's Euclidean space, we can achieve invariant control of the FDR under diffeomorphic transformation. This hyper-spherical measure also reflects intrinsic "volume of randomness" in signals. Experiments with synthetic, semi-synthetic and real images demonstrate that our method significantly reduces FDR inconsistency introduced by the choice of testing spaces.

Semi-automated registration-based anatomical labelling, voxel based morphometry and cortical thickness mapping of the mouse brain

BackgroundMorphoanatomical MRI methods have recently begun to be applied in the mouse. However, substantial differences in the anatomical organisation of human and rodent brain prevent a straightforward extension of clinical neuroimaging tools to mouse brain imaging. As a result, the vast majority of the published approaches rely on tailored routines that address single morphoanatomical readouts and typically lack a sufficiently-detailed description of the complex workflow required to process images and quantify structural alterations. New methodHere we provide a detailed description of semi-automated registration-based procedures for voxel based morphometry, cortical thickness estimation and automated anatomical labelling of the mouse brain. The approach relies on the sequential use of advanced image processing tools offered by ANTs, a flexible open source toolkit freely available to the scientific community. ResultsTo illustrate our procedures, we described their application to quantify morphological alterations in socially-impaired BTBR mice with respect to normosocial C57BL/6J controls, a comparison recently described by us and other research groups. We show that the approach can reliably detect both focal and large-scale grey matter alterations using complementary readouts. Comparison with existing methodsNo detailed operational workflows for mouse imaging are available for direct comparison with our methods. However, empirical assessment of the mapped inter-strain differences is in good agreement with the findings of other groups using analogous approaches. ConclusionThe detailed operational workflows described here are expected to help the implementation of rodent morphoanatomical methods by non-expert users, and ultimately promote the use of these tools across the preclinical neuroimaging community.

Frontiers for the Early Diagnosis of AD by Means of MRI Brain Imaging and Support Vector Machines.

The emergence of Alzheimer's Disease (AD) as a consequence of increasing aging population makes urgent the availability of methods for the early and accurate diagnosis. Magnetic Resonance Imaging (MRI) could be used as in vivo, non invasive tool to identify sensitive and specific markers of very early AD progression. In recent years, multivariate pattern analysis (MVPA) and machine- learning algorithms have attracted strong interest within the neuroimaging community, as they allow automatic classification of imaging data with higher performance than univariate statistical analysis. An exhaustive search of PubMed, Web of Science and Medline records was performed in this work, in order to retrieve studies focused on the potential role of MRI in aiding the clinician in early diagnosis of AD by using Support Vector Machines (SVMs) as MVPA automated classification method. A total of 30 studies emerged, published from 2008 to date. This review aims to give a state-of-the-art overview about SVM for the early and differential diagnosis of AD-related pathologies by means of MRI data, starting from preliminary steps such as image pre-processing, feature extraction and feature selection, and ending with classification, validation strategies and extraction of MRI-related biomarkers. The main advantages and drawbacks of the different techniques were explored. Results obtained by the reviewed studies were reported in terms of classification performance and biomarker outcomes, in order to shed light on the parameters that accompany normal and pathological aging. Unresolved issues and possible future directions were finally pointed out.

The first step for neuroimaging data analysis: DICOM to NIfTI conversion

BackgroundClinical imaging data are typically stored and transferred in the DICOM format, whereas the NIfTI format has been widely adopted by scientists in the neuroimaging community. Therefore, a vital initial step in processing the data is to convert images from the complicated DICOM format to the much simpler NIfTI format. While there are a number of tools that usually handle DICOM to NIfTI conversion seamlessly, some variations can disrupt this process. New methodWe provide some insight into the challenges faced with image conversion. First, different manufacturers implement the DICOM format differently which complicates the conversion. Second, different modalities and sub-modalities may need special treatment during conversion. Lastly, the image transferring and archiving can also impact the DICOM conversion. ResultsWe present results in several error-prone domains, including the slice order for functional imaging, phase encoding direction for distortion correction, effect of diffusion gradient direction, and effect of gantry correction for some imaging modality. Comparison with existing methodsConversion tools are often designed for a specific manufacturer or modality. The tools and insight we present here are aimed at different manufacturers or modalities. ConclusionsThe imaging conversion is complicated by the variation of images. An understanding of the conversion basics can be helpful for identifying the source of the error. Here we provide users with simple methods for detecting and correcting problems. This also serves as an overview for developers who wish to either develop their own tools or adapt the open source tools created by the authors.

Neurite Tracing With Object Process

In this paper we present a pipeline for automatic analysis of neuronal morphology: from detection, modeling to digital reconstruction. First, we present an automatic, unsupervised object detection framework using stochastic marked point process. It extracts connected neuronal networks by fitting special configuration of marked objects to the centreline of the neurite branches in the image volume giving us position, local width and orientation information. Semantic modeling of neuronal morphology in terms of critical nodes like bifurcations and terminals, generates various geometric and morphology descriptors such as branching index, branching angles, total neurite length, internodal lengths for statistical inference on characteristic neuronal features. From the detected branches we reconstruct neuronal tree morphology using robust and efficient numerical fast marching methods. We capture a mathematical model abstracting out the relevant position, shape and connectivity information about neuronal branches from the microscopy data into connected minimum spanning trees. Such digital reconstruction is represented in standard SWC format, prevalent for archiving, sharing, and further analysis in the neuroimaging community. Our proposed pipeline outperforms state of the art methods in tracing accuracy and minimizes the subjective variability in reconstruction, inherent to semi-automatic methods.

Neuroimaging Evidence of a Bilateral Representation for Visually Presented Numbers.

This fMRI study shows for the first time a cluster of neurons selective for visually presented numbers in healthy human adults. This visual number form area (NFA) was found in both hemispheres. Crucially, numbers have gained importance for humans too recently for neuronal specialization to be established by evolution. Therefore, investigations of this region will greatly advance our understanding of learning and plasticity in the brain. In addition, these results will aid our knowledge regarding related neurological illnesses (e.g., dyscalculia). To overcome the fMRI signal dropout in the neighborhood of the NFA, we combined high spatial resolution with liberal smoothing. We believe that this approach will be useful to the broad neuroimaging community.

Graph theoretic analysis on large DCM models

Graph theoretic analysis on large DCM models

Detecting network states in white noise

Nonstationarity of neural dynamics is a ubiquitous property that is crucial to understanding many key phenomena of both healthy and diseased brain function, including circadian rhythms, dynamics of epileptic activity as well as cognitive processing. Detecting switching of brain states has recently become of growing interest in the human brain neuroimaging community. However, from the data analysis/modelling perspective the task is quite challenging, and competing approaches exist [1]. One widely adopted approach is the use of clustering methods in the temporal domain to detect temporally contiguous clusters of time points with a similar structure of some instantaneous property - e.g. neural activity or functional connectivity profile. While this approach may in principle help to explore the switching structure of brain dynamics, it comes with technical challenges related the presence of noise in both the dynamics and measurements. In particular, as we documented in a recent study [2], comparison of the results with an appropriate null hypothesis is necessary to avoid spurious detection of nonstationarity markers such as switching of neural network states. We document this danger by applying an example analysis pipeline used in [3] to simulated EEG datasets. The simulated data are generated as realizations of temporally white noise process (either spatially uncorrelated or spatially correlated in a pattern corresponding to real EEG data). In each case, one hundred realizations of a 5 seconds long epoch of N = 20 'electrodes' (each of 2500 time points corresponding to 2ms sampling rate). A k-means clustering algorithm with k = 2 to 10 is applied to cluster the instantaneous synchronization likelihood matrix estimates with parameters as in [3]. The key observation stable across all setting is that the applied typical network switching analysis pipeline leads to spurious discovery of a multitude of network states in the stationary process realizations, with dominant state duration timescales of several tens to hundreds milliseconds qualitatively similar to the original results reported in [3]. These results suggest that observations of network switching should be always cautiously interpreted and tested against appropriate null models.

Dynamic Data Visualization with Weave and Brain Choropleths.

This article introduces the neuroimaging community to the dynamic visualization workbench, Weave (https://www.oicweave.org/), and a set of enhancements to allow the visualization of brain maps. The enhancements comprise a set of brain choropleths and the ability to display these as stacked slices, accessible with a slider. For the first time, this allows the neuroimaging community to take advantage of the advanced tools already available for exploring geographic data. Our brain choropleths are modeled after widely used geographic maps but this mashup of brain choropleths with extant visualization software fills an important neuroinformatic niche. To date, most neuroinformatic tools have provided online databases and atlases of the brain, but not good ways to display the related data (e.g., behavioral, genetic, medical, etc). The extension of the choropleth to brain maps allows us to leverage general-purpose visualization tools for concurrent exploration of brain images and related data. Related data can be represented as a variety of tables, charts and graphs that are dynamically linked to each other and to the brain choropleths. We demonstrate that the simplified region-based analyses that underlay choropleths can provide insights into neuroimaging data comparable to those achieved by using more conventional methods. In addition, the interactive interface facilitates additional insights by allowing the user to filter, compare, and drill down into the visual representations of the data. This enhanced data visualization capability is useful during the initial phases of data analysis and the resulting visualizations provide a compelling way to publish data as an online supplement to journal articles.

The MNI data-sharing and processing ecosystem

Neuroimaging has been facing a data deluge characterized by the exponential growth of both raw and processed data. As a result, mining the massive quantities of digital data collected in these studies offers unprecedented opportunities and has become paramount for today's research. As the neuroimaging community enters the world of “Big Data”, there has been a concerted push for enhanced sharing initiatives, whether within a multisite study, across studies, or federated and shared publicly. This article will focus on the database and processing ecosystem developed at the Montreal Neurological Institute (MNI) to support multicenter data acquisition both nationally and internationally, create database repositories, facilitate data-sharing initiatives, and leverage existing software toolkits for large-scale data processing.

Open Science CBS Neuroimaging Repository: Sharing ultra-high-field MR images of the brain

Magnetic resonance imaging at ultra high field opens the door to quantitative brain imaging at sub-millimeter isotropic resolutions. However, novel image processing tools to analyze these new rich datasets are lacking. In this article, we introduce the Open Science CBS Neuroimaging Repository: a unique repository of high-resolution and quantitative images acquired at 7T. The motivation for this project is to increase interest for high-resolution and quantitative imaging and stimulate the development of image processing tools developed specifically for high-field data. Our growing repository currently includes datasets from MP2RAGE and multi-echo FLASH sequences from 28 and 20 healthy subjects respectively. These datasets represent the current state-of-the-art in in-vivo relaxometry at 7T, and are now fully available to the entire neuroimaging community.

Neuroinformatics Software Applications Supporting Electronic Data Capture, Management, and Sharing for the Neuroimaging Community.

Accelerating insight into the relation between brain and behavior entails conducting small and large-scale research endeavors that lead to reproducible results. Consensus is emerging between funding agencies, publishers, and the research community that data sharing is a fundamental requirement to ensure all such endeavors foster data reuse and fuel reproducible discoveries. Funding agency and publisher mandates to share data are bolstered by a growing number of data sharing efforts that demonstrate how information technologies can enable meaningful data reuse. Neuroinformatics evaluates scientific needs and develops solutions to facilitate the use of data across the cognitive and neurosciences. For example, electronic data capture and management tools designed to facilitate human neurocognitive research can decrease the setup time of studies, improve quality control, and streamline the process of harmonizing, curating, and sharing data across data repositories. In this article we outline the advantages and disadvantages of adopting software applications that support these features by reviewing the tools available and then presenting two contrasting neuroimaging study scenarios in the context of conducting a cross-sectional and a multisite longitudinal study.

Considerations for resting state functional MRI and functional connectivity studies in rodents

Resting state functional MRI (rs-fMRI) and functional connectivity mapping have become widely used tools in the human neuroimaging community and their use is rapidly spreading into the realm of rodent research as well. One of the many attractive features of rs-fMRI is that it is readily translatable from humans to animals and back again. Changes in functional connectivity observed in human studies can be followed by more invasive animal experiments to determine the neurophysiological basis for the alterations, while exploratory work in animal models can identify possible biomarkers for further investigation in human studies. These types of interwoven human and animal experiments have a potentially large impact on neuroscience and clinical practice. However, impediments exist to the optimal application of rs-fMRI in small animals, some similar to those encountered in humans and some quite different. In this review we identify the most prominent of these barriers, discuss differences between rs-fMRI in rodents and in humans, highlight best practices for animal studies, and review selected applications of rs-fMRI in rodents. Our goal is to facilitate the integration of human and animal work to the benefit of both fields.

Multimodal Imaging Brain Connectivity Analysis (MIBCA) toolbox.

Aim. In recent years, connectivity studies using neuroimaging data have increased the understanding of the organization of large-scale structural and functional brain networks. However, data analysis is time consuming as rigorous procedures must be assured, from structuring data and pre-processing to modality specific data procedures. Until now, no single toolbox was able to perform such investigations on truly multimodal image data from beginning to end, including the combination of different connectivity analyses. Thus, we have developed the Multimodal Imaging Brain Connectivity Analysis (MIBCA) toolbox with the goal of diminishing time waste in data processing and to allow an innovative and comprehensive approach to brain connectivity.Materials and Methods. The MIBCA toolbox is a fully automated all-in-one connectivity toolbox that offers pre-processing, connectivity and graph theoretical analyses of multimodal image data such as diffusion-weighted imaging, functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). It was developed in MATLAB environment and pipelines well-known neuroimaging softwares such as Freesurfer, SPM, FSL, and Diffusion Toolkit. It further implements routines for the construction of structural, functional and effective or combined connectivity matrices, as well as, routines for the extraction and calculation of imaging and graph-theory metrics, the latter using also functions from the Brain Connectivity Toolbox. Finally, the toolbox performs group statistical analysis and enables data visualization in the form of matrices, 3D brain graphs and connectograms. In this paper the MIBCA toolbox is presented by illustrating its capabilities using multimodal image data from a group of 35 healthy subjects (19–73 years old) with volumetric T1-weighted, diffusion tensor imaging, and resting state fMRI data, and 10 subjets with 18F-Altanserin PET data also.Results. It was observed both a high inter-hemispheric symmetry and an intra-hemispheric modularity associated with structural data, whilst functional data presented lower inter-hemispheric symmetry and a high inter-hemispheric modularity. Furthermore, when testing for differences between two subgroups (<40 and >40 years old adults) we observed a significant reduction in the volume and thickness, and an increase in the mean diffusivity of most of the subcortical/cortical regions.Conclusion. While bridging the gap between the high numbers of packages and tools widely available for the neuroimaging community in one toolbox, MIBCA also offers different possibilities for combining, analysing and visualising data in novel ways, enabling a better understanding of the human brain.

About connections.

Despite the attention attracted by “connectomics”, one can lose sight of the very real questions concerning “What are connections?” In the neuroimaging community, “structural” connectivity is ground truth and underlying constraint on “functional” or “effective” connectivity. It is referenced to underlying anatomy; but, as increasingly remarked, there is a large gap between the wealth of human brain mapping and the relatively scant data on actual anatomical connectivity. Moreover, connections have typically been discussed as “pairwise”, point x projecting to point y (or: to points y and z), or more recently, in graph theoretical terms, as “nodes” or regions and the interconnecting “edges”. This is a convenient shorthand, but tends not to capture the richness and nuance of basic anatomical properties as identified in the classic tradition of tracer studies. The present short review accordingly revisits connectional weights, heterogeneity, reciprocity, topography, and hierarchical organization, drawing on concrete examples. The emphasis is on presynaptic long-distance connections, motivated by the intention to probe current assumptions and promote discussions about further progress and synthesis.

Synthetic neuronal datasets for benchmarking directed functional connectivity metrics.

Background. Datasets consisting of synthetic neural data generated with quantifiable and controlled parameters are a valuable asset in the process of testing and validating directed functional connectivity metrics. Considering the recent debate in the neuroimaging community concerning the use of these metrics for fMRI data, synthetic datasets that emulate the BOLD signal dynamics have played a central role by supporting claims that argue in favor or against certain choices. Generative models often used in studies that simulate neuronal activity, with the aim of gaining insight into specific brain regions and functions, have different requirements from the generative models for benchmarking datasets. Even though the latter must be realistic, there is a tradeoff between realism and computational demand that needs to be contemplated and simulations that efficiently mimic the real behavior of single neurons or neuronal populations are preferred, instead of more cumbersome and marginally precise ones.Methods. This work explores how simple generative models are able to produce neuronal datasets, for benchmarking purposes, that reflect the simulated effective connectivity and, how these can be used to obtain synthetic recordings of EEG and fMRI BOLD signals. The generative models covered here are AR processes, neural mass models consisting of linear and nonlinear stochastic differential equations and populations with thousands of spiking units. Forward models for EEG consist in the simple three-shell head model while the fMRI BOLD signal is modeled with the Balloon-Windkessel model or by convolution with a hemodynamic response function.Results. The simulated datasets are tested for causality with the original spectral formulation for Granger causality. Modeled effective connectivity can be detected in the generated data for varying connection strengths and interaction delays.Discussion. All generative models produce synthetic neuronal data with detectable causal effects although the relation between modeled and detected causality varies and less biophysically realistic models offer more control in causal relations such as modeled strength and frequency location.