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

CanICA: Model-based extraction of reproducible group-level ICA patterns from fMRI time series

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 meaningful patterns without prior information. However, ICA is not robust to mild data variation and remains a parameter-sensitive algorithm. The validity of the extracted patterns is hard to establish, as well as the significance of differences between patterns extracted from different groups of subjects. We start from a generative model of the fMRI group data to introduce a probabilistic ICA pattern-extraction algorithm, called CanICA (Canonical ICA). Thanks to an explicit noise model and canonical correlation analysis, our method is auto-calibrated and identifies the group-reproducible data subspace before performing ICA. We compare our method to state-of-the-art multi-subject fMRI ICA methods and show that the features extracted are more reproducible

Investigating human audio-visual object perception with a combination of hypothesis-generating and hypothesis-testing fMRI analysis tools

Primate multisensory object perception involves distributed brain regions. To investigate the network character of these regions of the human brain, we applied data-driven group spatial independent component analysis (ICA) to a functional magnetic resonance imaging (fMRI) data set acquired during a passive audio-visual (AV) experiment with common object stimuli. We labeled three group-level independent component (IC) maps as auditory (A), visual (V), and AV, based on their spatial layouts and activation time courses. The overlap between these IC maps served as definition of a distributed network of multisensory candidate regions including superior temporal, ventral occipito-temporal, posterior parietal and prefrontal regions. During an independent second fMRI experiment, we explicitly tested their involvement in AV integration. Activations in nine out of these twelve regions met the max-criterion (A < AV > V) for multisensory integration. Comparison of this approach with a general linear model-based region-of-interest definition revealed its complementary value for multisensory neuroimaging. In conclusion, we estimated functional networks of uni- and multisensory functional connectivity from one dataset and validated their functional roles in an independent dataset. These findings demonstrate the particular value of ICA for multisensory neuroimaging research and using independent datasets to test hypotheses generated from a data-driven analysis

Explore the Functional Connectivity between Brain Regions during a Chemistry Working Memory Task.

Previous studies have rarely examined how temporal dynamic patterns, event-related coherence, and phase-locking are related to each other. This study assessed reaction-time-sorted spectral perturbation and event-related spectral perturbation in order to examine the temporal dynamic patterns in the frontal midline (F), central parietal (CP), and occipital (O) regions during a chemistry working memory task at theta, alpha, and beta frequencies. Furthermore, the functional connectivity between F-CP, CP-O, and F-O were assessed by component event-related coherence (ERCoh) and component phase-locking (PL) at different frequency bands. In addition, this study examined whether the temporal dynamic patterns are consistent with the functional connectivity patterns across different frequencies and time courses. Component ERCoh/PL measured the interactions between different independent components decomposed from the scalp EEG, mixtures of time courses of activities arising from different brain, and artifactual sources. The results indicate that the O and CP regions' temporal dynamic patterns are similar to each other. Furthermore, pronounced component ERCoh/PL patterns were found to exist between the O and CP regions across each stimulus and probe presentation, in both theta and alpha frequencies. The consistent theta component ERCoh/PL between the F and O regions was found at the first stimulus and after probe presentation. These findings demonstrate that temporal dynamic patterns at different regions are in accordance with the functional connectivity patterns. Such coordinated and robust EEG temporal dynamics and component ERCoh/PL patterns suggest that these brain regions' neurons work together both to induce similar event-related spectral perturbation and to synchronize or desynchronize simultaneously in order to swiftly accomplish a particular goal. The possible mechanisms for such distinct component phase-locking and coherence patterns were also further discussed

Mining SOM expression portraits: Feature selection and integrating concepts of molecular function

Background: 
Self organizing maps (SOM) enable the straightforward portraying of high-dimensional data of large sample collections in terms of sample-specific images. The analysis of their texture provides so-called spot-clusters of co-expressed genes which require subsequent significance filtering and functional interpretation. We address feature selection in terms of the gene ranking problem and the interpretation of the obtained spot-related lists using concepts of molecular function.

Results: 
Different expression scores based either on simple fold change-measures or on regularized Students t-statistics are applied to spot-related gene lists and compared with special emphasis on the error characteristics of microarray expression data. The spot-clusters are analyzed using different methods of gene set enrichment analysis with the focus on overexpression and/or overrepresentation of predefined sets of genes. Metagene-related overrepresentation of selected gene sets was mapped into the SOM images to assign gene function to different regions. Alternatively we estimated set-related overexpression profiles over all samples studied using a gene set enrichment score. It was also applied to the spot-clusters to generate lists of enriched gene sets. We used the tissue body index data set, a collection of expression data of human tissues, as an illustrative example. We found that tissue related spots typically contain enriched populations of gene sets well corresponding to molecular processes in the respective tissues. In addition, we display special sets of housekeeping and of consistently weak and highly expressed genes using SOM data filtering. 

Conclusions:
The presented methods allow the comprehensive downstream analysis of SOM-transformed expression data in terms of cluster-related gene lists and enriched gene sets for functional interpretation. SOM clustering implies the ability to define either new gene sets using selected SOM spots or to verify and/or to amend existing ones

Within-Subject Joint Independent Component Analysis of Simultaneous fMRI/ERP in an Auditory Oddball Paradigm

The integration of event-related potential (ERP) and functional magnetic resonance imaging (fMRI) can contribute to characterizing neural networks with high temporal and spatial resolution. This research aimed to determine the sensitivity and limitations of applying joint independent component analysis (jICA) within-subjects, for ERP and fMRI data collected simultaneously in a parametric auditory frequency oddball paradigm. In a group of 20 subjects, an increase in ERP peak amplitude ranging 1–8 μV in the time window of the P300 (350–700 ms), and a correlated increase in fMRI signal in a network of regions including the right superior temporal and supramarginal gyri, was observed with the increase in deviant frequency difference. JICA of the same ERP and fMRI group data revealed activity in a similar network, albeit with stronger amplitude and larger extent. In addition, activity in the left pre- and post-central gyri, likely associated with right hand somato-motor response, was observed only with the jICA approach. Within-subject, the jICA approach revealed significantly stronger and more extensive activity in the brain regions associated with the auditory P300 than the P300 linear regression analysis. The results suggest that with the incorporation of spatial and temporal information from both imaging modalities, jICA may be a more sensitive method for extracting common sources of activity between ERP and fMRI

Disruption to control network function correlates with altered dynamic connectivity in the wider autism spectrum.

Autism is a common developmental condition with a wide, variable range of co-occurring neuropsychiatric symptoms. Contrasting with most extant studies, we explored whole-brain functional organization at multiple levels simultaneously in a large subject group reflecting autism's clinical diversity, and present the first network-based analysis of transient brain states, or dynamic connectivity, in autism. Disruption to inter-network and inter-system connectivity, rather than within individual networks, predominated. We identified coupling disruption in the anterior-posterior default mode axis, and among specific control networks specialized for task start cues and the maintenance of domain-independent task positive status, specifically between the right fronto-parietal and cingulo-opercular networks and default mode network subsystems. These appear to propagate downstream in autism, with significantly dampened subject oscillations between brain states, and dynamic connectivity configuration differences. Our account proposes specific motifs that may provide candidates for neuroimaging biomarkers within heterogeneous clinical populations in this diverse condition