Theodore D. Satterthwaite

Eli J. Cornblath, Evelyn Tang, Graham L. Baum et al.

Executive function emerges late in development and displays different developmental trends in males and females. Sex differences in executive function in youth have been linked to vulnerability to psychopathology as well as to behaviors that impinge on health. Yet, the neurobiological basis of these differences is not well understood. Here we test the hypothesis that sex differences in executive function in youth stem from sex differences in the controllability of structural brain networks as they rewire over development. Combining methods from network neuroscience and network control theory, we characterize the network control properties of structural brain networks estimated from diffusion imaging data acquired in males and females in a sample of 882 youth aged 8-22 years. We summarize the control properties of these networks by estimating average and modal controllability, two statistics that probe the ease with which brain areas can drive the network towards easy- versus difficult-to-reach states. We find that females have higher modal controllability in frontal, parietal, and subcortical regions while males have higher average controllability in frontal and subcortical regions. Furthermore, average controllability values in the medial frontal cortex and subcortex, both higher in males, are negatively related to executive function. Finally, we find that average controllability predicts sex-dependent individual differences in activation during an n-back working memory task. Taken together, our findings support the notion that sex differences in the controllability of structural brain networks can partially explain sex differences in executive function. Controllability of structural brain networks also predicts features of task-relevant activation, suggesting the potential for controllability to represent context-specific constraints on network state more generally.

Evangelos Sariyanidi, John D. Herrington, Lisa Yankowitz et al.

Measuring the statistical dependence between observed signals is a primary tool for scientific discovery. However, biological systems often exhibit complex non-linear interactions that currently cannot be captured without a priori knowledge or large datasets. We introduce a criterion for dependence, whereby two time series are deemed dependent if one can construct a classifier that distinguishes between temporally aligned vs. misaligned segments extracted from them. We show that this criterion, concurrence, is theoretically linked with dependence, and can become a standard approach for scientific analyses across disciplines, as it can expose relationships across a wide spectrum of signals (fMRI, physiological and behavioral data) without ad-hoc parameter tuning or large amounts of data.

Evangelos Sariyanidi, John D. Herrington, Lisa Yankowitz et al.

Measuring the statistical dependence between observed signals is a primary tool for scientific discovery. However, biological systems often exhibit complex non-linear interactions that currently cannot be captured without a priori knowledge regarding the nature of dependence. We introduce a self-supervised approach, concurrence, which is inspired by the observation that if two signals are dependent, then one should be able to distinguish between temporally aligned vs. misaligned segments extracted from them. Experiments with fMRI, physiological and behavioral signals show that, to our knowledge, concurrence is the first approach that can expose relationships across such a wide spectrum of signals and extract scientifically relevant differences without ad-hoc parameter tuning or reliance on a priori information, providing a potent tool for scientific discoveries across fields. However, dependencies caused by extraneous factors remain an open problem, thus researchers should validate that exposed relationships truly pertain to the question(s) of interest.

Vishnu M. Bashyam, Jimit Doshi, Guray Erus et al.

Conventional and deep learning-based methods have shown great potential in the medical imaging domain, as means for deriving diagnostic, prognostic, and predictive biomarkers, and by contributing to precision medicine. However, these methods have yet to see widespread clinical adoption, in part due to limited generalization performance across various imaging devices, acquisition protocols, and patient populations. In this work, we propose a new paradigm in which data from a diverse range of acquisition conditions are "harmonized" to a common reference domain, where accurate model learning and prediction can take place. By learning an unsupervised image to image canonical mapping from diverse datasets to a reference domain using generative deep learning models, we aim to reduce confounding data variation while preserving semantic information, thereby rendering the learning task easier in the reference domain. We test this approach on two example problems, namely MRI-based brain age prediction and classification of schizophrenia, leveraging pooled cohorts of neuroimaging MRI data spanning 9 sites and 9701 subjects. Our results indicate a substantial improvement in these tasks in out-of-sample data, even when training is restricted to a single site.

Dushyant Sahoo, Theodore D. Satterthwaite, Christos Davatzikos

The study of hierarchy in networks of the human brain has been of significant interest among the researchers as numerous studies have pointed out towards a functional hierarchical organization of the human brain. This paper provides a novel method for the extraction of hierarchical connectivity components in the human brain using resting-state fMRI. The method builds upon prior work of Sparse Connectivity Patterns (SCPs) by introducing a hierarchy of sparse overlapping patterns. The components are estimated by deep factorization of correlation matrices generated from fMRI. The goal of the paper is to extract interpretable hierarchical patterns using correlation matrices where a low rank decomposition is formed by a linear combination of a high rank decomposition. We formulate the decomposition as a non-convex optimization problem and solve it using gradient descent algorithms with adaptive step size. We also provide a method for the warm start of the gradient descent using singular value decomposition. We demonstrate the effectiveness of the developed method on two different real-world datasets by showing that multi-scale hierarchical SCPs are reproducible between sub-samples and are more reproducible as compared to single scale patterns. We also compare our method with existing hierarchical community detection approaches. Our method also provides novel insight into the functional organization of the human brain.

Hao-Ting Wang, Jonathan Smallwood, Janaina Mourao-Miranda et al.

Since the beginning of the 21st century, the size, breadth, and granularity of data in biology and medicine has grown rapidly. In the example of neuroscience, studies with thousands of subjects are becoming more common, which provide extensive phenotyping on the behavioral, neural, and genomic level with hundreds of variables. The complexity of such big data repositories offer new opportunities and pose new challenges to investigate brain, cognition, and disease. Canonical correlation analysis (CCA) is a prototypical family of methods for wrestling with and harvesting insight from such rich datasets. This doubly-multivariate tool can simultaneously consider two variable sets from different modalities to uncover essential hidden associations. Our primer discusses the rationale, promises, and pitfalls of CCA in biomedicine.

Hongming Li, Theodore D. Satterthwaite, Yong Fan

Brain age prediction based on neuroimaging data could help characterize both the typical brain development and neuropsychiatric disorders. Pattern recognition models built upon functional connectivity (FC) measures derived from resting state fMRI (rsfMRI) data have been successfully used to predict the brain age. However, most existing studies focus on coarse-grained FC measures between brain regions or intrinsic connectivity networks (ICNs), which may sacrifice fine-grained FC information of the rsfMRI data. Whole brain voxel-wise FC measures could provide fine-grained FC information of the brain and may improve the prediction performance. In this study, we develop a deep learning method to use convolutional neural networks (CNNs) to learn informative features from the fine-grained whole brain FC measures for the brain age prediction. Experimental results on a large dataset of resting-state fMRI demonstrate that the deep learning model with fine-grained FC measures could better predict the brain age.