An official website of the United States government
Abstract In this article, we focus on estimating the joint relationship between structural magnetic resonance imaging (sMRI) gray matter (GM), and multiple functional MRI (fMRI) intrinsic connectivity networks (ICNs). To achieve this, we propose a multilink joint independent component analysis (ml‐jICA) method using the same core algorithm as jICA. To relax the jICA assumption, we propose another extension called parallel multilink jICA (pml‐jICA) that allows for a more balanced weight distribution over ml‐jICA/jICA. We assume a shared mixing matrix for both the sMRI and fMRI modalities, while allowing for different mixing matrices linking the sMRI data to the different ICNs. We introduce the model and then apply this approach to study the differences in resting fMRI and sMRI data from patients with Alzheimer's disease (AD) versus controls. The results of the pml‐jICA yield significant differences with large effect sizes that include regions in overlapping portions of default mode network, and also hippocampus and thalamus. Importantly, we identify two joint components with partially overlapping regions which show opposite effects for AD versus controls, but were able to be separated due to being linked to distinct functional and structural patterns. This highlights the unique strength of our approach and multimodal fusion approaches generally in revealing potentially biomarkers of brain disorders that would likely be missed by a unimodal approach. These results represent the first work linking multiple fMRI ICNs to GM components within a multimodal data fusion model and challenges the typical view that brain structure is more sensitive to AD than fMRI.
more »
« less
Bayesian modeling of multiple structural connectivity networks during the progression of Alzheimer's disease
Abstract Alzheimer's disease is the most common neurodegenerative disease. The aim of this study is to infer structural changes in brain connectivity resulting from disease progression using cortical thickness measurements from a cohort of participants who were either healthy control, or with mild cognitive impairment, or Alzheimer's disease patients. For this purpose, we develop a novel approach for inference of multiple networks with related edge values across groups. Specifically, we infer a Gaussian graphical model for each group within a joint framework, where we rely on Bayesian hierarchical priors to link the precision matrix entries across groups. Our proposal differs from existing approaches in that it flexibly learns which groups have the most similar edge values, and accounts for the strength of connection (rather than only edge presence or absence) when sharing information across groups. Our results identify key alterations in structural connectivity that may reflect disruptions to the healthy brain, such as decreased connectivity within the occipital lobe with increasing disease severity. We also illustrate the proposed method through simulations, where we demonstrate its performance in structure learning and precision matrix estimation with respect to alternative approaches.
more »
« less
- PAR ID:
- 10455843
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- Biometrics
- Volume:
- 76
- Issue:
- 4
- ISSN:
- 0006-341X
- Format(s):
- Medium: X Size: p. 1120-1132
- Size(s):
- p. 1120-1132
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Modern data collection often entails longitudinal repeated measurements that assume values on a Riemannian manifold. Analyzing such longitudinal Riemannian data is challenging, because of both the sparsity of the observations and the nonlinear manifold constraint. Addressing this challenge, we propose an intrinsic functional principal component analysis for longitudinal Riemannian data. Information is pooled across subjects by estimating the mean curve with local Fréchet regression and smoothing the covariance structure of the linearized data on tangent spaces around the mean. Dimension reduction and imputation of the manifold‐valued trajectories are achieved by utilizing the leading principal components and applying best linear unbiased prediction. We show that the proposed mean and covariance function estimates achieve state‐of‐the‐art convergence rates. For illustration, we study the development of brain connectivity in a longitudinal cohort of Alzheimer's disease and normal participants by modeling the connectivity on the manifold of symmetric positive definite matrices with the affine‐invariant metric. In a second illustration for irregularly recorded longitudinal emotion compositional data for unemployed workers, we show that the proposed method leads to nicely interpretable eigenfunctions and principal component scores. Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative database.more » « less
-
Data produced by resting-state functional Magnetic Resonance Imaging are widely used to infer brain functional connectivity networks. Such networks correlate neural signals to connect brain regions, which consist in groups of dependent voxels. Previous work has focused on aggregating data across voxels within predefined regions. However, the presence of within-region correlations has noticeable impacts on inter-regional correlation detection, and thus edge identification. To alleviate them, we propose to leverage techniques from the large-scale correlation screening literature, and derive simple and practical characterizations of the mean number of correlation discoveries that flexibly incorporate intra-regional dependence structures. A connectivity network inference framework is then presented. First, inter-regional correlation distributions are estimated. Then, correlation thresholds that can be tailored to one’s application are constructed for each edge. Finally, the proposed framework is implemented on synthetic and real-world datasets. This novel approach for handling arbitrary intra-regional correlation is shown to limit false positives while improving true positive rates.more » « less
-
Abstract White matter structural connections are likely to support flow of functional activation or functional connectivity. While the relationship between structural and functional connectivity profiles, here called SC-FC coupling, has been studied on a whole-brain, global level, few studies have investigated this relationship at a regional scale. Here we quantify regional SC-FC coupling in healthy young adults using diffusion-weighted MRI and resting-state functional MRI data from the Human Connectome Project and study how SC-FC coupling may be heritable and varies between individuals. We show that regional SC-FC coupling strength varies widely across brain regions, but was strongest in highly structurally connected visual and subcortical areas. We also show interindividual regional differences based on age, sex and composite cognitive scores, and that SC-FC coupling was highly heritable within certain networks. These results suggest regional structure-function coupling is an idiosyncratic feature of brain organisation that may be influenced by genetic factors.more » « less
-
Functional connections in the brain are frequently represented by weighted networks, with nodes representing locations in the brain and edges representing the strength of connectivity between these locations. One challenge in analyzing such data is that inference at the individual edge level is not particularly biologically meaningful; interpretation is more useful at the level of so-called functional systems or groups of nodes and connections between them; this is often called “graph-aware” inference in the neuroimaging literature. However, pooling over functional regions leads to significant loss of information and lower accuracy. Another challenge is correlation among edge weights within a subject which makes inference based on independence assumptions unreliable. We address both of these challenges with a linear mixed effects model, which accounts for functional systems and for edge dependence, while still modeling individual edge weights to avoid loss of information. The model allows for comparing two populations, such as patients and healthy controls, both at the functional regions level and at individual edge level, leading to biologically meaningful interpretations. We fit this model to resting state fMRI data on schizophrenic patients and healthy controls, obtaining interpretable results consistent with the schizophrenia literature.more » « less
