Complexity Analysis of the Default Mode Network Using Resting-State fMRI in Down Syndrome: Relationships Highlighted by A Neuropsychological Assessment

Background: Studies on complexity indicators in the field of functional connectivity derived from resting-state fMRI (rs-fMRI) in Down syndrome (DS) samples and their possible relationship with cognitive functioning variables are rare. We analyze how some complexity indicators estimated in the subareas that constitute the default mode network (DMN) might be predictors of the neuropsychological outcomes evaluating Intelligence Quotient (IQ) and cognitive performance in persons with DS. Methods: Twenty-two DS people were assessed with the Kaufman Brief Test of Intelligence (KBIT) and Frontal Assessment Battery (FAB) tests, and fMRI signals were recorded in a resting state over a six-minute period. In addition, 22 controls, matched by age and sex, were evaluated with the same rs-fMRI procedure. Results: There was a significant difference in complexity indicators between groups: the control group showed less complexity than the DS group. Moreover, the DS group showed more variance in the complexity indicator distributions than the control group. In the DS group, significant and negative relationships were found between some of the complexity indicators in some of the DMN networks and the cognitive performance scores. Conclusions: The DS group is characterized by more complex DMN networks and exhibits an inverse relationship between complexity and cognitive performance based on the negative parameter estimates

SEARCHING NEUROIMAGING BIOMARKERS IN MENTAL DISORDERS WITH GRAPH AND MULTIMODAL FUSION ANALYSIS OF FUNCTIONAL CONNECTIVITY

Mental disorders such as schizophrenia (SZ), bipolar (BD), and major depression disorders (MDD) can cause severe symptoms and life disruption. They share some symptoms, which can pose a major clinical challenge to their differentiation. Objective biomarkers based on neuroimaging may help to improve diagnostic accuracy and facilitate optimal treatment for patients. Over the last decades, non-invasive in-vivo neuroimaging techniques such as magnetic resonance imaging (MRI) have been increasingly applied to measure structure and function in human brains. With functional MRI (fMRI) or structural MRI (sMRI), studies have identified neurophysiological deficits in patients’ brain from different perspective. Functional connectivity (FC) analysis is an approach that measures functional integration in brains. By assessing the temporal coherence of the hemodynamic activity among brain regions, FC is considered capable of characterizing the large-scale integrity of neural activity. In this work, we present two data analysis frameworks for biomarker detection on brain imaging with FC, 1) graph analysis of FC and 2) multimodal fusion analysis, to better understand the human brain. Graph analysis reveals the interaction among brain regions based on graph theory, while the multimodal fusion framework enables us to utilize the strength of different imaging modalities through joint analysis. Four applications related to FC using these frameworks were developed. First, FC was estimated using a model-based approach, and revealed altered the small-world network structure in SZ. Secondly, we applied graph analysis on functional network connectivity (FNC) to differentiate BD and MDD during resting-state. Thirdly, two functional measures, FNC and fractional amplitude of low frequency fluctuations (fALFF), were spatially overlaid to compare the FC and spatial alterations in SZ. And finally, we utilized a multimodal fusion analysis framework, multi-set canonical correlation analysis + joint independent component analysis (mCCA+jICA) to link functional and structural abnormalities in BD and MDD. We also evaluated the accuracy of predictive diagnosis through classifiers generated on the selected features. In summary, via the two frameworks, our work has made several contributions to advance FC analysis, which improves our understanding of underlying brain function and structure, and our findings may be ultimately useful for the development of biomarkers of mental disease

Altered Small-World Brain Networks in Schizophrenia Patients during Working Memory Performance

Impairment of working memory (WM) performance in schizophrenia patients (SZ) is well-established. Compared to healthy controls (HC), SZ patients show aberrant blood oxygen level dependent (BOLD) activations and disrupted functional connectivity during WM performance. In this study, we examined the small-world network metrics computed from functional magnetic resonance imaging (fMRI) data collected as 35 HC and 35 SZ performed a Sternberg Item Recognition Paradigm (SIRP) at three WM load levels. Functional connectivity networks were built by calculating the partial correlation on preprocessed time courses of BOLD signal between task-related brain regions of interest (ROIs) defined by group independent component analysis (ICA). The networks were then thresholded within the small-world regime, resulting in undirected binarized small-world networks at different working memory loads. Our results showed: 1) at the medium WM load level, the networks in SZ showed a lower clustering coefficient and less local efficiency compared with HC; 2) in SZ, most network measures altered significantly as the WM load level increased from low to medium and from medium to high, while the network metrics were relatively stable in HC at different WM loads; and 3) the altered structure at medium WM load in SZ was related to their performance during the task, with longer reaction time related to lower clustering coefficient and lower local efficiency. These findings suggest brain connectivity in patients with SZ was more diffuse and less strongly linked locally in functional network at intermediate level of WM when compared to HC. SZ show distinctly inefficient and variable network structures in response to WM load increase, comparing to stable highly clustered network topologies in HC

Big Data Analytics and Information Science for Business and Biomedical Applications II

The analysis of big data in biomedical, business and financial research has drawn much attention from researchers worldwide. This collection of articles aims to provide a platform for an in-depth discussion of novel statistical methods developed for the analysis of Big Data in these areas. Both applied and theoretical contributions to these areas are showcased

Using Persistent Homology Topological Features to Characterize Medical Images: Case Studies on Lung and Brain Cancers

Tumor shape is a key factor that affects tumor growth and metastasis. This paper proposes a topological feature computed by persistent homology to characterize tumor progression from digital pathology and radiology images and examines its effect on the time-to-event data. The proposed topological features are invariant to scale-preserving transformation and can summarize various tumor shape patterns. The topological features are represented in functional space and used as functional predictors in a functional Cox proportional hazards model. The proposed model enables interpretable inference about the association between topological shape features and survival risks. Two case studies are conducted using consecutive 143 lung cancer and 77 brain tumor patients. The results of both studies show that the topological features predict survival prognosis after adjusting clinical variables, and the predicted high-risk groups have significantly (at the level of 0.01) worse survival outcomes than the low-risk groups. Also, the topological shape features found to be positively associated with survival hazards are irregular and heterogeneous shape patterns, which are known to be related to tumor progression

Development and Application of Chemometric Methods for Modelling Metabolic Spectral Profiles

The interpretation of metabolic information is crucial to understanding the functioning of a biological system. Latent information about the metabolic state of a sample can be acquired using analytical chemistry methods, which generate spectroscopic profiles. Thus, nuclear magnetic resonance spectroscopy and mass spectrometry techniques can be employed to generate vast amounts of highly complex data on the metabolic content of biofluids and tissue, and this thesis discusses ways to process, analyse and interpret these data successfully. The evaluation of J -resolved spectroscopy in magnetic resonance profiling and the statistical techniques required to extract maximum information from the projections of these spectra are studied. In particular, data processing is evaluated, and correlation and regression methods are investigated with respect to enhanced model interpretation and biomarker identification. Additionally, it is shown that non-linearities in metabonomic data can be effectively modelled with kernel-based orthogonal partial least squares, for which an automated optimisation of the kernel parameter with nested cross-validation is implemented. The interpretation of orthogonal variation and predictive ability enabled by this approach are demonstrated in regression and classification models for applications in toxicology and parasitology. Finally, the vast amount of data generated with mass spectrometry imaging is investigated in terms of data processing, and the benefits of applying multivariate techniques to these data are illustrated, especially in terms of interpretation and visualisation using colour-coding of images. The advantages of methods such as principal component analysis, self-organising maps and manifold learning over univariate analysis are highlighted. This body of work therefore demonstrates new means of increasing the amount of biochemical information that can be obtained from a given set of samples in biological applications using spectral profiling. Various analytical and statistical methods are investigated and illustrated with applications drawn from diverse biomedical areas

Deviations in neural activity and network integration underpinning the co-occurrence of emotion dysregulation and attention-deficit/hyperactivity disorder: Analyses of fMRI task activations and functional brain network topology

The aim of this thesis was to improve our understanding of the relationship between Attention-deficit/hyperactivity disorder (ADHD) and emotion dysregulation and the underlying neural activity. Three research articles examine specific aspects of the relationship between ADHD and emotion dysregulation, namely the perception of emotional stimuli, the association between functional brain topology and emotion dysregulation in different ADHD presentations, and emotion dysregulation-related neurobiological and phenotypical predictors of the course of ADHD. All three articles are based on functional magnetic resonance imaging (fMRI) data. Individuals with ADHD exhibited aberrant amygdala reactivity and ventromedial prefrontal cortex coupling in the perception and processing of emotional face stimuli. Moreover, functional network topology of the right insula was shown to affect emotion dysregulation in ADHD and emotion dysregulation and integration of emotion-related brain networks were shown to affect intraindividual change in ADHD severity throughout late adolescence. In Summary, the thesis provides evidence that neural activity and functional connectivity between brain structures affecting emotion may be related to the co-occurrence of emotion dysregulation and ADHD. ADHD and the common co-occurring emotional problems should not be attributed to single, isolated systems, e.g., for executive functions and cognitive control. The neurobiological roots appear to be complex and heterogeneous, involving the interplay of different brain networks that are at least partly emotion-related