The fact that people think or behave differently from one another is rooted in individual differences in brain anatomy and connectivity. Here, we used repeated-measurement resting-state functional ...MRI to explore intersubject variability in connectivity. Individual differences in functional connectivity were heterogeneous across the cortex, with significantly higher variability in heteromodal association cortex and lower variability in unimodal cortices. Intersubject variability in connectivity was significantly correlated with the degree of evolutionary cortical expansion, suggesting a potential evolutionary root of functional variability. The connectivity variability was also related to variability in sulcal depth but not cortical thickness, positively correlated with the degree of long-range connectivity but negatively correlated with local connectivity. A meta-analysis further revealed that regions predicting individual differences in cognitive domains are predominantly located in regions of high connectivity variability. Our findings have potential implications for understanding brain evolution and development, guiding intervention, and interpreting statistical maps in neuroimaging.
► Functional connectivity is most variable in association cortex ► Connectivity variability is rooted in evolutionary cortical expansion ► Variability is associated with cortical folding and long-range connection ► Brain regions of high connectivity variability predict behavioral differences
Mueller et al. quantified interindividual variability in functional connectivity across the human brain and identified its relation to evolutionary cortical expansion and some anatomical characteristics.
We present VoxelMorph, a fast learning-based framework for deformable, pairwise medical image registration. Traditional registration methods optimize an objective function for each pair of images, ...which can be time-consuming for large datasets or rich deformation models. In contrast to this approach and building on recent learning-based methods, we formulate registration as a function that maps an input image pair to a deformation field that aligns these images. We parameterize the function via a convolutional neural network and optimize the parameters of the neural network on a set of images. Given a new pair of scans, VoxelMorph rapidly computes a deformation field by directly evaluating the function. In this paper, we explore two different training strategies. In the first (unsupervised) setting, we train the model to maximize standard image matching objective functions that are based on the image intensities. In the second setting, we leverage auxiliary segmentations available in the training data. We demonstrate that the unsupervised model's accuracy is comparable to the state-of-the-art methods while operating orders of magnitude faster. We also show that VoxelMorph trained with auxiliary data improves registration accuracy at test time and evaluate the effect of training set size on registration. Our method promises to speed up medical image analysis and processing pipelines while facilitating novel directions in learning-based registration and its applications. Our code is freely available at https://github.com/voxelmorph/voxelmorph .
•Principled connection between classical and learning-based registration methods.•Probabilistic generative model and resulting unsupervised learning-based inference algorithm uses insights from ...classical registration methods and makes use of recent developments in convolutional neural networks (CNNs).•Model naturally extends to anatomical surfaces.•Method is demonstrated on a 3D brain registration task for both images and anatomical surfaces, along with extensive empirical analyses of the algorithm.•The approach results in state of the art accuracy and very fast runtimes, while providing diffeomorphic guarantees.•The implementation is available online at http://voxelmorph.csail.mit.edu.
Classical deformable registration techniques achieve impressive results and offer a rigorous theoretical treatment, but are computationally intensive since they solve an optimization problem for each image pair. Recently, learning-based methods have facilitated fast registration by learning spatial deformation functions. However, these approaches use restricted deformation models, require supervised labels, or do not guarantee a diffeomorphic (topology-preserving) registration. Furthermore, learning-based registration tools have not been derived from a probabilistic framework that can offer uncertainty estimates.
In this paper, we build a connection between classical and learning-based methods. We present a probabilistic generative model and derive an unsupervised learning-based inference algorithm that uses insights from classical registration methods and makes use of recent developments in convolutional neural networks (CNNs). We demonstrate our method on a 3D brain registration task for both images and anatomical surfaces, and provide extensive empirical analyses of the algorithm. Our principled approach results in state of the art accuracy and very fast runtimes, while providing diffeomorphic guarantees. Our implementation is available online at http://voxelmorph.csail.mit.edu.
There is significant interest in the development and application of deep neural networks (DNNs) to neuroimaging data. A growing literature suggests that DNNs outperform their classical counterparts ...in a variety of neuroimaging applications, yet there are few direct comparisons of relative utility. Here, we compared the performance of three DNN architectures and a classical machine learning algorithm (kernel regression) in predicting individual phenotypes from whole-brain resting-state functional connectivity (RSFC) patterns. One of the DNNs was a generic fully-connected feedforward neural network, while the other two DNNs were recently published approaches specifically designed to exploit the structure of connectome data. By using a combined sample of almost 10,000 participants from the Human Connectome Project (HCP) and UK Biobank, we showed that the three DNNs and kernel regression achieved similar performance across a wide range of behavioral and demographic measures. Furthermore, the generic feedforward neural network exhibited similar performance to the two state-of-the-art connectome-specific DNNs. When predicting fluid intelligence in the UK Biobank, performance of all algorithms dramatically improved when sample size increased from 100 to 1000 subjects. Improvement was smaller, but still significant, when sample size increased from 1000 to 5000 subjects. Importantly, kernel regression was competitive across all sample sizes. Overall, our study suggests that kernel regression is as effective as DNNs for RSFC-based behavioral prediction, while incurring significantly lower computational costs. Therefore, kernel regression might serve as a useful baseline algorithm for future studies.
•We review the biomedical multi atlas segmentation (MAS) literature.•We present how MAS evolved, and now relates to alternative methods.•We present our perspective on the future of MAS.
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Multi-atlas segmentation (MAS), first introduced and popularized by the pioneering work of Rohlfing, et al. (2004), Klein, et al. (2005), and Heckemann, et al. (2006), is becoming one of the most widely-used and successful image segmentation techniques in biomedical applications. By manipulating and utilizing the entire dataset of “atlases” (training images that have been previously labeled, e.g., manually by an expert), rather than some model-based average representation, MAS has the flexibility to better capture anatomical variation, thus offering superior segmentation accuracy. This benefit, however, typically comes at a high computational cost. Recent advancements in computer hardware and image processing software have been instrumental in addressing this challenge and facilitated the wide adoption of MAS. Today, MAS has come a long way and the approach includes a wide array of sophisticated algorithms that employ ideas from machine learning, probabilistic modeling, optimization, and computer vision, among other fields. This paper presents a survey of published MAS algorithms and studies that have applied these methods to various biomedical problems. In writing this survey, we have three distinct aims. Our primary goal is to document how MAS was originally conceived, later evolved, and now relates to alternative methods. Second, this paper is intended to be a detailed reference of past research activity in MAS, which now spans over a decade (2003–2014) and entails novel methodological developments and application-specific solutions. Finally, our goal is to also present a perspective on the future of MAS, which, we believe, will be one of the dominant approaches in biomedical image segmentation.
Machine learning techniques have gained prominence for the analysis of resting-state functional Magnetic Resonance Imaging (rs-fMRI) data. Here, we present an overview of various unsupervised and ...supervised machine learning applications to rs-fMRI. We offer a methodical taxonomy of machine learning methods in resting-state fMRI. We identify three major divisions of unsupervised learning methods with regard to their applications to rs-fMRI, based on whether they discover principal modes of variation across space, time or population. Next, we survey the algorithms and rs-fMRI feature representations that have driven the success of supervised subject-level predictions. The goal is to provide a high-level overview of the burgeoning field of rs-fMRI from the perspective of machine learning applications.
Heritability estimation provides important information about the relative contribution of genetic and environmental factors to phenotypic variation, and provides an upper bound for the utility of ...genetic risk prediction models. Recent technological and statistical advances have enabled the estimation of additive heritability attributable to common genetic variants (SNP heritability) across a broad phenotypic spectrum. Here, we present a computationally and memory efficient heritability estimation method that can handle large sample sizes, and report the SNP heritability for 551 complex traits derived from the interim data release (152,736 subjects) of the large-scale, population-based UK Biobank, comprising both quantitative phenotypes and disease codes. We demonstrate that common genetic variation contributes to a broad array of quantitative traits and human diseases in the UK population, and identify phenotypes whose heritability is moderated by age (e.g., a majority of physical measures including height and body mass index), sex (e.g., blood pressure related traits) and socioeconomic status (education). Our study represents the first comprehensive phenome-wide heritability analysis in the UK Biobank, and underscores the importance of considering population characteristics in interpreting heritability.
Abstract
Resting-state functional magnetic resonance imaging (rs-fMRI) offers the opportunity to delineate individual-specific brain networks. A major question is whether individual-specific network ...topography (i.e., location and spatial arrangement) is behaviorally relevant. Here, we propose a multi-session hierarchical Bayesian model (MS-HBM) for estimating individual-specific cortical networks and investigate whether individual-specific network topography can predict human behavior. The multiple layers of the MS-HBM explicitly differentiate intra-subject (within-subject) from inter-subject (between-subject) network variability. By ignoring intra-subject variability, previous network mappings might confuse intra-subject variability for inter-subject differences. Compared with other approaches, MS-HBM parcellations generalized better to new rs-fMRI and task-fMRI data from the same subjects. More specifically, MS-HBM parcellations estimated from a single rs-fMRI session (10 min) showed comparable generalizability as parcellations estimated by 2 state-of-the-art methods using 5 sessions (50 min). We also showed that behavioral phenotypes across cognition, personality, and emotion could be predicted by individual-specific network topography with modest accuracy, comparable to previous reports predicting phenotypes based on connectivity strength. Network topography estimated by MS-HBM was more effective for behavioral prediction than network size, as well as network topography estimated by other parcellation approaches. Thus, similar to connectivity strength, individual-specific network topography might also serve as a fingerprint of human behavior.
The specificity and sensitivity of resting state functional MRI (rs-fMRI) measurements depend on preprocessing choices, such as the parcellation scheme used to define regions of interest (ROIs). In ...this study, we critically evaluate the effect of brain parcellations on machine learning models applied to rs-fMRI data. Our experiments reveal an intriguing trend: On average, models with stochastic parcellations consistently perform as well as models with widely used atlases at the same spatial scale. We thus propose an ensemble learning strategy to combine the predictions from models trained on connectivity data extracted using different (e.g., stochastic) parcellations. We further present an implementation of our ensemble learning strategy with a novel 3D Convolutional Neural Network (CNN) approach. The proposed CNN approach takes advantage of the full-resolution 3D spatial structure of rs-fMRI data and fits non-linear predictive models. Our ensemble CNN framework overcomes the limitations of traditional machine learning models for connectomes that often rely on region-based summary statistics and/or linear models. We showcase our approach on a classification (autism patients versus healthy controls) and a regression problem (prediction of subject's age), and report promising results.
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•We propose 3D CNN framework for functional connectomes.•Ensemble learning with stochastic parcellations outperform atlas-based models.•We showcase our method for classification of autism vs. healthy and predicting age.
Global signal regression (GSR) is one of the most debated preprocessing strategies for resting-state functional MRI. GSR effectively removes global artifacts driven by motion and respiration, but ...also discards globally distributed neural information and introduces negative correlations between certain brain regions. The vast majority of previous studies have focused on the effectiveness of GSR in removing imaging artifacts, as well as its potential biases. Given the growing interest in functional connectivity fingerprinting, here we considered the utilitarian question of whether GSR strengthens or weakens associations between resting-state functional connectivity (RSFC) and multiple behavioral measures across cognition, personality and emotion.
By applying the variance component model to the Brain Genomics Superstruct Project (GSP), we found that behavioral variance explained by whole-brain RSFC increased by an average of 47% across 23 behavioral measures after GSR. In the Human Connectome Project (HCP), we found that behavioral variance explained by whole-brain RSFC increased by an average of 40% across 58 behavioral measures, when GSR was applied after ICA-FIX de-noising. To ensure generalizability, we repeated our analyses using kernel regression. GSR improved behavioral prediction accuracies by an average of 64% and 12% in the GSP and HCP datasets respectively. Importantly, the results were consistent across methods. A behavioral measure with greater RSFC-explained variance (using the variance component model) also exhibited greater prediction accuracy (using kernel regression). A behavioral measure with greater improvement in behavioral variance explained after GSR (using the variance component model) also enjoyed greater improvement in prediction accuracy after GSR (using kernel regression). Furthermore, GSR appeared to benefit task performance measures more than self-reported measures.
Since GSR was more effective at removing motion-related and respiratory-related artifacts, GSR-related increases in variance explained and prediction accuracies were unlikely the result of motion-related or respiratory-related artifacts. However, it is worth emphasizing that the current study focused on whole-brain RSFC, so it remains unclear whether GSR improves RSFC-behavioral associations for specific connections or networks. Overall, our results suggest that at least in the case for young healthy adults, GSR strengthens the associations between RSFC and most (although not all) behavioral measures. Code for the variance component model and ridge regression can be found here: https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/preprocessing/Li2019_GSR.
•Global signal regression improves RSFC-behavior associations.•Global signal regression improves RSFC-based behavioral prediction accuracies.•Improvements replicated across two large-scale datasets and methods.•Task-performance measures enjoyed greater improvements than self-reported ones.•GSR beneficial even after ICA-FIX.
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