A group model for stable multi-subject ICA on fMRI datasets

Spatial Independent Component Analysis (ICA) is an increasingly used data-driven method to analyze functional Magnetic Resonance Imaging (fMRI) data. To date, it has been used to extract sets of mutually correlated brain regions without prior information on the time course of these regions. Some of these sets of regions, interpreted as functional networks, have recently been used to provide markers of brain diseases and open the road to paradigm-free population comparisons. Such group studies raise the question of modeling subject variability within ICA: how can the patterns representative of a group be modeled and estimated via ICA for reliable inter-group comparisons? In this paper, we propose a hierarchical model for patterns in multi-subject fMRI datasets, akin to mixed-effect group models used in linear-model-based analysis. We introduce an estimation procedure, CanICA (Canonical ICA), based on i) probabilistic dimension reduction of the individual data, ii) canonical correlation analysis to identify a data subspace common to the group iii) ICA-based pattern extraction. In addition, we introduce a procedure based on cross-validation to quantify the stability of ICA patterns at the level of the group. We compare our method with state-of-the-art multi-subject fMRI ICA methods and show that the features extracted using our procedure are more reproducible at the group level on two datasets of 12 healthy controls: a resting-state and a functional localizer study

Multimodal Fusion With Reference: Searching for Joint Neuromarkers of Working Memory Deficits in Schizophrenia

Multimodal fusion is an effective approach to take advantage of cross-information among multiple imaging data to better understand brain diseases. However, most current fusion approaches are blind, without adopting any prior information. To date, there is increasing interest to uncover the neurocognitive mapping of specific behavioral measurement on enriched brain imaging data; hence, a supervised, goal-directed model that enables a priori information as a reference to guide multimodal data fusion is in need and a natural option. Here we proposed a fusion with reference model, called “multi-site canonical correlation analysis with reference plus joint independent component analysis” (MCCAR+jICA), which can precisely identify co-varying multimodal imaging patterns closely related to reference information, such as cognitive scores. In a 3-way fusion simulation, the proposed method was compared with its alternatives on estimation accuracy of both target component decomposition and modality linkage detection. MCCAR+jICA outperforms others with higher precision. In human imaging data, working memory performance was utilized as a reference to investigate the covarying functional and structural brain patterns among 3 modalities and how they are impaired in schizophrenia. Two independent cohorts (294 and 83 subjects respectively) were used. Interestingly, similar brain maps were identified between the two cohorts, with substantial overlap in the executive control networks in fMRI, salience network in sMRI, and major white matter tracts in dMRI. These regions have been linked with working memory deficits in schizophrenia in multiple reports, while MCCAR+jICA further verified them in a repeatable, joint manner, demonstrating the potential of such results to identify potential neuromarkers for mental disorders

Independent component analysis of interictal fMRI in focal epilepsy: comparison with general linear model-based EEG-correlated fMRI

The general linear model (GLM) has been used to analyze simultaneous EEG–fMRI to reveal BOLD changes linked to interictal epileptic discharges (IED) identified on scalp EEG. This approach is ineffective when IED are not evident in the EEG. Data-driven fMRI analysis techniques that do not require an EEG derived model may offer a solution in these circumstances. We compared the findings of independent components analysis (ICA) and EEG-based GLM analyses of fMRI data from eight patients with focal epilepsy. Spatial ICA was used to extract independent components (IC) which were automatically classified as either BOLD-related, motion artefacts, EPI-susceptibility artefacts, large blood vessels, noise at high spatial or temporal frequency. The classifier reduced the number of candidate IC by 78%, with an average of 16 BOLD-related IC. Concordance between the ICA and GLM-derived results was assessed based on spatio-temporal criteria. In each patient, one of the IC satisfied the criteria to correspond to IED-based GLM result. The remaining IC were consistent with BOLD patterns of spontaneous brain activity and may include epileptic activity that was not evident on the scalp EEG. In conclusion, ICA of fMRI is capable of revealing areas of epileptic activity in patients with focal epilepsy and may be useful for the analysis of EEG–fMRI data in which abnormalities are not apparent on scalp EEG

Towards Patient-Specific Brain Networks Using Functional Magnetic Resonance Imaging

fMRI applications are rare in translational medicine and clinical practice. What can be inferred from a single fMRI scan is often unreliable due to the relative low signal-to-noise ratio compared to other neuroimaging modalities. However, the potential of fMRI is promising. It is one of the few neuroimaging modalities to obtain functional brain organisation of an individual during task engagement and rest. This work extends on current fMRI image processing approaches to obtain robust estimates of functional brain organisation in two resting-state fMRI cohorts. The first cohort comprises of young adults who were born at extremely low gestations and age-matched healthy controls. Group analysis between term- and preterm-born adults revealed differences in functional organisation, which were discovered to be predominantly caused by underlying structural and physiological differences. The second cohort comprises of elderly adults with young onset Alzheimer’s disease and age-matched controls. Their corresponding resting-state fMRI scans are short in scanning time resulting in unreliable spatial estimates with conventional dual regression analysis. This problem was addressed by the development of an ensemble averaging of matrix factorisations approach to compute single subject spatial maps characterised by improved spatial reproducibility compared to maps obtained by dual regression. The approach was extended with a haemodynamic forward model to obtain surrogate neural activations to examine the subject’s task behaviour. This approach applied to two task-fMRI cohorts showed that these surrogate neural activations matched with original task timings in most of the examined fMRI scans but also revealed subjects with task behaviour different than intended by the researcher. It is hoped that both the findings in this work and the novel matrix factorisation approach itself will benefit the fMRI community. To this end, the derived tools are made available online to aid development and validation of methods for resting-state and task fMRI experiments

PARALLEL INDEPENDENT COMPONENT ANALYSIS WITH REFERENCE FOR IMAGING GENETICS: A SEMI-BLIND MULTIVARIATE APPROACH

Imaging genetics is an emerging field dedicated to the study of genetic underpinnings of brain structure and function. Over the last decade, brain imaging techniques such as magnetic resonance imaging (MRI) have been increasingly applied to measure morphometry, task-based function and connectivity in living brains. Meanwhile, high-throughput genotyping employing genome-wide techniques has made it feasible to sample the entire genome of a substantial number of individuals. While there is growing interest in image-wide and genome-wide approaches which allow unbiased searches over a large range of variants, one of the most challenging problems is the correction for the huge number of statistical tests used in univariate models. In contrast, a reference-guided multivariate approach shows specific advantage for simultaneously assessing many variables for aggregate effects while leveraging prior information. It can improve the robustness of the results compared to a fully blind approach. In this dissertation we present a semi-blind multivariate approach, parallel independent component analysis with reference (pICA-R), to better reveal relationships between hidden factors of particular attributes. First, a consistency-based order estimation approach is introduced to advance the application of ICA to genotype data. The pICA-R approach is then presented, where independent components are extracted from two modalities in parallel and inter-modality associations are subsequently optimized for pairs of components. In particular, prior information is incorporated to elicit components of particular interests, which helps identify factors carrying small amounts of variance in large complex datasets. The pICA-R approach is further extended to accommodate multiple references whose interrelationships are unknown, allowing the investigation of functional influence on neurobiological traits of potentially related genetic variants implicated in biology. Applied to a schizophrenia study, pICA-R reveals that a complex genetic factor involving multiple pathways underlies schizophrenia-related gray matter deficits in prefrontal and temporal regions. The extended multi-reference approach, when employed to study alcohol dependence, delineates a complex genetic architecture, where the CREB-BDNF pathway plays a key role in the genetic factor underlying a proportion of variation in cue-elicited brain activations, which plays a role in phenotypic symptoms of alcohol dependence. In summary, our work makes several important contributions to advance the application of ICA to imaging genetics studies, which holds the promise to improve our understating of genetics underlying brain structure and function in healthy and disease

A Parcellation Based Nonparametric Algorithm for Independent Component Analysis with Application to fMRI Data

Independent Component analysis (ICA) is a widely used technique for separating signals that have been mixed together. In this manuscript, we propose a novel ICA algorithm using density estimation and maximum likelihood, where the densities of the signals are estimated via p-spline based histogram smoothing and the mixing matrix is simultaneously estimated using an optimization algorithm. The algorithm is exceedingly simple, easy to implement and blind to the underlying distributions of the source signals. To relax the identically distributed assumption in the density function, a modified algorithm is proposed to allow for different density functions on different regions. The performance of the proposed algorithm is evaluated in different simulation settings. For illustration, the algorithm is applied to a research investigation with a large collection of resting state fMRI datasets. The results show that the algorithm successfully recovers the established brain networks