Contributions in computational intelligence with results in functional neuroimaging

This thesis applies computational intelligence methodologies to study functional brain images. It is a state-of-the-art application relative to unsupervised learning domain to functional neuroimaging. There are also contributions related to computational intelligence on topics relative to clustering validation and spatio-temporal clustering analysis. Speci_cally, there are the presentation of a new separation measure based on fuzzy sets theory to establish the validity of the fuzzy clustering outcomes and the presentation of a framework to approach the parcellation of functional neuroimages taking in account both spatial and temporal patterns. These contributions have been applied to neuroimages obtained with functional Magnetic Resonance Imaging, using both active and passive paradigm and using both in-house data and fMRI repository. The results obtained shown, globally, an improvement on the quality of the neuroimaging analysis using the methodological contributions proposed

Neuroinformatics in Functional Neuroimaging

This Ph.D. thesis proposes methods for information retrieval in functional neuroimaging through automatic computerized authority identification, and searching and cleaning in a neuroscience database. Authorities are found through cocitation analysis of the citation pattern among scientific articles. Based on data from a single scientific journal it is shown that multivariate analyses are able to determine group structure that is interpretable as particular “known ” subgroups in functional neuroimaging. Methods for text analysis are suggested that use a combination of content and links, in the form of the terms in scientific documents and scientific citations, respectively. These included context sensitive author ranking and automatic labeling of axes and groups in connection with multivariate analyses of link data. Talairach foci from the BrainMap ™ database are modeled with conditional probability density models useful for exploratory functional volumes modeling. A further application is shown with conditional outlier detection where abnormal entries in the BrainMap ™ database are spotted using kernel density modeling and the redundancy between anatomical labels and spatial Talairach coordinates. This represents a combination of simple term and spatial modeling. The specific outliers that were found in the BrainMap ™ database constituted among others: Entry errors, errors in the article and unusual terminology

Probing resting-state functional connectivity in the infant brain: methods and potentiality

Early brain development is characterized by rapid growth and perpetual reconfiguration, driven by a dynamic milieu of heterogeneous processes. Moreover, potent postnatal brain plasticity engenders increased vulnerability to environmental stimuli. However, little is known regarding the ontogeny and temporal manifestations of inter- and intra-regional functional connectivity that comprise functional brain networks. Recently, resting-state functional magnetic resonance imaging (fMRI) emerged as a promising non-invasive neuroinvestigative tool, measuring spontaneous fluctuations in blood oxygen level dependent (BOLD) signal at rest that reflect baseline neuronal activity. Its application has expanded to infant populations in the past decade, providing unprecedented insight into functional organization of the developing brain, as well as early biomarkers of abnormal/ disease states. However, rapid extension of the resting-state technique to infant populations leaves many methodological issues need to be resolved prior to standardization of the technique. The purpose of this thesis is to describe a protocol for intrinsic functional connectivity analysis, and extraction of resting-state networks in infants <12 months of age using the data-driven approach independent component analysis (ICA). To begin, we review the evolution of resting-state fMRI application in infant populations, including the biological premise for neural networks. Next, we present a protocol designed such that investigators without previous knowledge in the field can implement the analysis and reliably obtain viable results consistent with previous literature. Presented protocol provides detailed, albeit basic framework for RSN analysis, with interwoven discussion of basic theory behind each technique, as well as the rationale behind selecting parameters. The overarching goal is to catalyze efforts towards development of robust, infant-specific acquisition and preprocessing pipelines, as well as promote greater transparency by researchers regarding methods used. Finally, we review the literature, current methodological challenges and potential future directions for the field of infant resting-state fMRI

A combinatorial framework to quantify peak/pit asymmetries in complex dynamics

LL’s acknowledges funding from an EPSRC Early Career Fellowship EP/P01660X/1

Automated Knowledge Discovery from Functional Magnetic Resonance Images using Spatial Coherence

Functional Magnetic Resonance Imaging (fMRI) has the potential to unlock many of the mysteries of the brain. Although this imaging modality is popular for brain-mapping activities, clinical applications of this technique are relatively rare. For clinical applications, classification models are more useful than the current practice of reporting loci of neural activation associated with particular disorders. Also, since the methods used to account for anatomical variations between subjects are generally imprecise, the conventional voxel-by-voxel analysis limits the types of discoveries that are possible. This work presents a classification-based framework for knowledge discovery from fMRI data. Instead of voxel-centric knowledge discovery, this framework is segment-centric, where functional segments are clumps of voxels that represent a functional unit in the brain. With simulated activation images, it is shown that this segment-based approach can be more successful for knowledge discovery than conventional voxel-based approaches. The spatial coherence principle refers to the homogeneity of behavior of spatially contiguous voxels. Auto-threshold Contrast Enhancing Iterative Clustering (ACEIC) - a new algorithm based on the spatial coherence principle is presented here for functional segmentation. With benchmark data, it is shown that the ACEIC method can achieve higher segmentation accuracy than Probabilistic Independent Component Analysis - a popular method used for fMRI data analysis. The spatial coherence principle can also be exploited for voxel-centric image-classification problems. Spatially Coherent Voxels (SCV) is a new feature selection method that uses the spatial coherence principle to eliminate features that are unlikely to be useful for classification. For a Substance Use Disorder dataset, it is demonstrated that feature selection with SCV can achieve higher classification accuracies than conventional feature selection methods

Any-way and Sparse Analyses for Multimodal Fusion and Imaging Genomics

This dissertation aims to develop new algorithms that leverage sparsity and mutual information across data modalities built upon the independent component analysis (ICA) framework to improve the performance of current ICA-based multimodal fusion approaches. These algorithms are further applied to both simulated data and real neuroimaging and genomic data to examine their performance. The identified neuroimaging and genomic patterns can help better delineate the pathology of mental disorders or brain development. To alleviate the signal-background separation difficulties in infomax-decomposed sources for genomic data, we propose a sparse infomax by enhancing a robust sparsity measure, the Hoyer index. Hoyer index is scale-invariant and well suited for ICA frameworks since the scale of decomposed sources is arbitrary. Simulation results demonstrate that sparse infomax increases the component detection accuracy for situations where the source signal-to-background (SBR) ratio is low, particularly for single nucleotide polymorphism (SNP) data. The proposed sparse infomax is further extended into two data modalities as a sparse parallel ICA for applications to imaging genomics in order to investigate the associations between brain imaging and genomics. Simulation results show that sparse parallel ICA outperforms parallel ICA with improved accuracy for structural magnetic resonance imaging (sMRI)-SNP association detection and component spatial map recovery, as well as with enhanced sparsity for sMRI and SNP components under noisy cases. Applying the proposed sparse parallel ICA to fuse the whole-brain sMRI and whole-genome SNP data of 24985 participants in the UK biobank, we identify three stable and replicable sMRI-SNP pairs. The identified sMRI components highlight frontal, parietal, and temporal regions and associate with multiple cognitive measures (with different association strengths in different age groups for the temporal component). Top SNPs in the identified SNP factor are enriched in inflammatory disease and inflammatory response pathways, which also regulate gene expression, isoform percentage, transcription expression, or methylation level in the frontal region, and the regulation effects are significantly enriched. Applying the proposed sparse parallel ICA to imaging genomics in attention-deficit/hyperactivity disorder (ADHD), we identify and replicate one SNP component related to gray matter volume (GMV) alterations in superior and middle frontal gyri underlying working memory deficit in adults and adolescents with ADHD. The association is more significant in ADHD families than controls and stronger in adults and older adolescents than younger ones. The identified SNP component highlights SNPs in long non-coding RNAs (lncRNAs) in chromosome 5 and in several protein-coding genes that are involved in ADHD, such as MEF2C, CADM2, and CADPS2. Top SNPs are enriched in human brain neuron cells and regulate gene expression, isoform percentage, transcription expression, or methylation level in the frontal region. Moreover, to increase the flexibility and robustness in mining multimodal data, we propose aNy-way ICA, which optimizes the entire correlation structure of linked components across any number of modalities via the Gaussian independent vector analysis and simultaneously optimizes independence via separate (parallel) ICAs. Simulation results demonstrate that aNy-way ICA recover sources and loadings, as well as the true covariance patterns with improved accuracy compared to existing multimodal fusion approaches, especially under noisy conditions. Applying the proposed aNy-way ICA to integrate structural MRI, fractal n-back, and emotion identification task functional MRIs collected in the Philadelphia Neurodevelopmental Cohort (PNC), we identify and replicate one linked GMV-threat-2-back component, and the threat and 2-back components are related to intelligence quotient (IQ) score in both discovery and replication samples. Lastly, we extend the proposed aNy-way ICA with a reference constraint to enable prior-guided multimodal fusion. Simulation results show that aNy-way ICA with reference recovers the designed linkages between reference and modalities, cross-modality correlations, as well as loading and component matrices with improved accuracy compared to multi-site canonical correlation analysis with reference (MCCAR)+joint ICA under noisy conditions. Applying aNy-way ICA with reference to supervise structural MRI, fractal n-back, and emotion identification task functional MRIs fusion in PNC with IQ as the reference, we identify and replicate one IQ-related GMV-threat-2-back component, and this component is significantly correlated across modalities in both discovery and replication samples.Ph.D