skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: A Method for Multimodal IVA Fusion Within a MISA Unified Model Reveals Markers of Age, Sex, Cognition, and Schizophrenia in Large Neuroimaging Studies
ABSTRACT With the increasing availability of large‐scale multimodal neuroimaging datasets, it is necessary to develop data fusion methods which can extract cross‐modal features. A general framework, multidataset independent subspace analysis (MISA), has been developed to encompass multiple blind source separation approaches and identify linked cross‐modal sources in multiple datasets. In this work, we utilized the multimodal independent vector analysis (MMIVA) model in MISA to directly identify meaningful linked features across three neuroimaging modalities—structural magnetic resonance imaging (MRI), resting state functional MRI and diffusion MRI—in two large independent datasets, one comprising of control subjects and the other including patients with schizophrenia. Results show several linked subject profiles (sources) that capture age‐associated decline, schizophrenia‐related biomarkers, sex effects, and cognitive performance. For sources associated with age, both shared and modality‐specific brain‐age deltas were evaluated for association with non‐imaging variables. In addition, each set of linked sources reveals a corresponding set of cross‐modal spatial patterns that can be studied jointly. We demonstrate that the MMIVA fusion model can identify linked sources across multiple modalities, and that at least one set of linked, age‐related sources replicates across two independent and separately analyzed datasets. The same set also presented age‐adjusted group differences, with schizophrenia patients indicating lower multimodal source levels. Linked sets associated with sex and cognition are also reported for the UK Biobank dataset.  more » « less
Award ID(s):
2112455
PAR ID:
10560040
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Human Brain Mapping
Volume:
45
Issue:
17
ISSN:
1065-9471
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Brain signals can be measured using multiple imaging modalities, such as magnetic resonance imaging (MRI)-based techniques. Different modalities convey distinct yet complementary information; thus, their joint analyses can provide valuable insight into how the brain functions in both healthy and diseased conditions. Data-driven approaches have proven most useful for multimodal fusion as they minimize assumptions imposed on the data, and there are a number of methods that have been developed to uncover relationships across modalities. However, none of these methods, to the best of our knowledge, can discover “one-to-many associations”, meaning one component from one modality is linked with more than one component from another modality. However, such “one-to-many associations” are likely to exist, since the same brain region can be involved in multiple neurological processes. Additionally, most existing data fusion methods require the signal subspace order to be identical for all modalities—a severe restriction for real-world data of different modalities. Here, we propose a new fusion technique—the consecutive independence and correlation transform (C-ICT) model—which successively performs independent component analysis and independent vector analysis and is uniquely flexible in terms of the number of datasets, signal subspace order, and the opportunity to find “one-to-many associations”. We apply C-ICT to fuse diffusion MRI, structural MRI, and functional MRI datasets collected from healthy controls (HCs) and patients with schizophrenia (SZs). We identify six interpretable triplets of components, each of which consists of three associated components from the three modalities. Besides, components from these triplets that show significant group differences between the HCs and SZs are identified, which could be seen as putative biomarkers in schizophrenia. 
    more » « less
  2. It is becoming increasingly common to collect multiple related neuroimaging datasets either from different modalities or from different tasks and conditions. In addition, we have non-imaging data such as cognitive or behavioral variables, and it is through the association of these two sets of data—neuroimaging and non-neuroimaging—that we can understand and explain the evolution of neural and cognitive processes, and predict outcomes for intervention and treatment. Multiple methods for the joint analysis or fusion of multiple neuroimaging datasets or modalities exist; however, methods for the joint analysis of imaging and non-imaging data are still in their infancy. Current approaches for identifying brain networks related to cognitive assessments are still largely based on simple one-to-one correlation analyses and do not use the cross information available across multiple datasets. This work proposes two approaches based on independent vector analysis (IVA) to jointly analyze the imaging datasets and behavioral variables such that multivariate relationships across imaging data and behavioral features can be identified. The simulation results show that our proposed methods provide better accuracy in identifying associations across imaging and behavioral components than current approaches. With functional magnetic resonance imaging (fMRI) task data collected from 138 healthy controls and 109 patients with schizophrenia, results reveal that the central executive network (CEN) estimated in multiple datasets shows a strong correlation with the behavioral variable that measures working memory, a result that is not identified by traditional approaches. Most of the identified fMRI maps also show significant differences in activations across healthy controls and patients potentially providing a useful signature of mental disorders. 
    more » « less
  3. 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
  4. Abstract There are a growing number of neuroimaging studies motivating joint structural and functional brain connectivity. Brain connectivity of different modalities provides insight into brain functional organization by leveraging complementary information, especially for brain disorders such as schizophrenia. In this paper, we propose a multi-modal independent component analysis (ICA) model that utilizes information from both structural and functional brain connectivity guided by spatial maps to estimate intrinsic connectivity networks (ICNs). Structural connectivity is estimated through whole-brain tractography on diffusion-weighted MRI (dMRI), while functional connectivity is derived from resting-state functional MRI (rs-fMRI). The proposed structural-functional connectivity and spatially constrained ICA (sfCICA) model estimates ICNs at the subject level using a multi-objective optimization framework. We evaluated our model using synthetic and real datasets (including dMRI and rs-fMRI from 149 schizophrenia patients and 162 controls). Multi-modal ICNs revealed enhanced functional coupling between ICNs with higher structural connectivity, improved modularity, and network distinction, particularly in schizophrenia. Statistical analysis of group differences showed more significant differences in the proposed model compared to the unimodal model. In summary, the sfCICA model showed benefits from being jointly informed by structural and functional connectivity. These findings suggest advantages in simultaneously learning effectively and enhancing connectivity estimates using structural connectivity. 
    more » « less
  5. We propose a novel end-to-end framework for whole-brain and whole-genome imaging-genetics. Our genetics network uses hierarchical graph convolution and pooling operations to embed subject-level data onto a low-dimensional latent space. The hierarchical network implicitly tracks the convergence of genetic risk across well-established biological pathways, while an attention mechanism automatically identifies the salient edges of this network at the subject level. In parallel, our imaging network projects multimodal data onto a set of latent embeddings. For interpretability, we implement a Bayesian feature selection strategy to extract the discriminative imaging biomarkers; these feature weights are optimized alongside the other model parameters. We couple the imaging and genetic embeddings with a predictor network, to ensure that the learned representations are linked to phenotype. We evaluate our framework on a schizophrenia dataset that includes two functional MRI paradigms and gene scores derived from Single Nucleotide Polymorphism data. Using repeated 10-fold cross-validation, we show that our imaging-genetics fusion achieves the better classification performance than state-of-the-art baselines. In an exploratory analysis, we further show that the biomarkers identified by our model are reproducible and closely associated with deficits in schizophrenia. 
    more » « less