Graph analysis of functional brain networks: practical issues in translational neuroscience

The brain can be regarded as a network: a connected system where nodes, or units, represent different specialized regions and links, or connections, represent communication pathways. From a functional perspective communication is coded by temporal dependence between the activities of different brain areas. In the last decade, the abstract representation of the brain as a graph has allowed to visualize functional brain networks and describe their non-trivial topological properties in a compact and objective way. Nowadays, the use of graph analysis in translational neuroscience has become essential to quantify brain dysfunctions in terms of aberrant reconfiguration of functional brain networks. Despite its evident impact, graph analysis of functional brain networks is not a simple toolbox that can be blindly applied to brain signals. On the one hand, it requires a know-how of all the methodological steps of the processing pipeline that manipulates the input brain signals and extract the functional network properties. On the other hand, a knowledge of the neural phenomenon under study is required to perform physiological-relevant analysis. The aim of this review is to provide practical indications to make sense of brain network analysis and contrast counterproductive attitudes

Normative model for the diagnosis of neuropsychiatric disorders using deep learning methods

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Engenharia Clínica e Instrumentação Médica) Universidade de Lisboa, Faculdade de Ciências, 2021The diagnosis of neuropsychiatric disorders (NPDs) is still exclusively dependent on the analysis of the signs and symptoms of the patients since there are no biomarkers useful for clinical practice. Considering that several signs and symptoms are shared among different NPDs, the diagnosis is sometimes incorrect. Therefore, therapeutic approaches do not always succeed, which has an impact on the quality of life of neuropsychiatric patients. Furthermore, NPDs have a global economic and demographic impact. For this reason, technological solutions, such as DL, have been researched for the optimization of diagnosis, in the non-technological field of neuropsychiatry. However, the most promising studies on the diagnosis of NPDs with deep learning (DL) are based on binary classification, which may not be the most adequate approach to deal with the continuous spectrum of NPDs. Here, a DL-based normative model was developed to investigate functional connectivity abnormalities, that may contribute to the development of a novel diagnostic procedure. This method is here used to evaluate how patients deviate from a normal pattern learned by a group of healthy people. To create and evaluate the normative model, resting-state functional magnetic resonance imaging (rs-fMRI) data from three different databases were used. In order to maximise the balance between the amount and the quality of the data, conditions were defined to restrict the variability of the scan parameters. Subsequently, rs-fMRI data were trimmed to the lowest number of time points presented in the sample (150). Then, standard preprocessing steps were performed, including removal of the first 4 volumes of functional data, motion correction, spatial smoothing, and high pass filtering. Single-session independent component analysis (ICA) was run, and the FSL-FIX tool was used to clean noise and artefacts. The functional images were then registered to the T1-weighted brain extracted structural images, and finally to the Montreal Neurosciences Institute 152 standard space. Dual regression was applied using fourteen resting-state functional brain networks (FBN) previously identified in the literature. The Pearson’s correlation coefficient between the extracted blood oxygen level-dependent (BOLD) time series of each FBN was calculated, and a 14x14 network connectivity matrix was generated for each subject. The second part of the project consisted of the creation and optimization of a normative model. The normative model consisted of an autoencoder (AE) with three hidden layers. The AE was trained only in healthy subjects and was tested in both healthy subjects and neuropsychiatric patients, including schizophrenia (SCZ), bipolar disorder (BD), and attention deficit hyperactivity disorder (ADHD) patients. The hypothesis was that the model would “fail” on reconstructing data from neuropsychiatric patients. To evaluate the model performance, graph theory metrics were applied. Besides, the mean squared error was calculated for each feature (correlation between pairs of FBN) to evaluate which regions were worse reconstructed for each group of subjects. The pipeline for NPDs was tested for a SCZ case study, with the addition of a clustering algorithm. The results of this dissertation revealed that the proposed pipeline was able to identify patterns of functional connectivity abnormality that characterize different NPDs. Moreover, the results found for the two SCZ groups of patients were similar, which demonstrated that the normative model here presented was also generalizable. However, the group-level differences did not withstand individual-level analysis, implying that NPDs are highly heterogeneous. These findings support the idea that a precision-based medical approach, focusing on the specific functional network changes of individual patients, may be more beneficial than the traditional group-based diagnostic classification. A personalised diagnosis would allow for personalised therapy, improving the quality of life of neuropsychiatric patients

Sparse temporally dynamic resting-state functional connectivity networks for early MCI identification

In conventional resting-state functional MRI (R-fMRI) analysis, functional connectivity is assumed to be temporally stationary, overlooking neural activities or interactions that may happen within the scan duration. Dynamic changes of neural interactions can be reflected by variations of topology and correlation strength in temporally correlated functional connectivity networks. These connectivity networks may potentially capture subtle yet short neural connectivity disruptions induced by disease pathologies. Accordingly, we are motivated to utilize disrupted temporal network properties for improving control-patient classification performance. Specifically, a sliding window approach is firstly employed to generate a sequence of overlapping R-fMRI sub-series. Based on these sub-series, sliding window correlations, which characterize the neural interactions between brain regions, are then computed to construct a series of temporal networks. Individual estimation of these temporal networks using conventional network construction approaches fails to take into consideration intrinsic temporal smoothness among successive overlapping R-fMRI subseries. To preserve temporal smoothness of R-fMRI sub-series, we suggest to jointly estimate the temporal networks by maximizing a penalized log likelihood using a fused sparse learning algorithm. This sparse learning algorithm encourages temporally correlated networks to have similar network topology and correlation strengths. We design a disease identification framework based on the estimated temporal networks, and group level network property differences and classification results demonstrate the importance of including temporally dynamic R-fMRI scan information to improve diagnosis accuracy of mild cognitive impairment patients

Automatic autism spectrum disorder detection using artificial intelligence methods with MRI neuroimaging: A review

Autism spectrum disorder (ASD) is a brain condition characterized by diverse signs and symptoms that appear in early childhood. ASD is also associated with communication deficits and repetitive behavior in affected individuals. Various ASD detection methods have been developed, including neuroimaging modalities and psychological tests. Among these methods, magnetic resonance imaging (MRI) imaging modalities are of paramount importance to physicians. Clinicians rely on MRI modalities to diagnose ASD accurately. The MRI modalities are non-invasive methods that include functional (fMRI) and structural (sMRI) neuroimaging methods. However, diagnosing ASD with fMRI and sMRI for specialists is often laborious and time-consuming; therefore, several computer-aided design systems (CADS) based on artificial intelligence (AI) have been developed to assist specialist physicians. Conventional machine learning (ML) and deep learning (DL) are the most popular schemes of AI used for diagnosing ASD. This study aims to review the automated detection of ASD using AI. We review several CADS that have been developed using ML techniques for the automated diagnosis of ASD using MRI modalities. There has been very limited work on the use of DL techniques to develop automated diagnostic models for ASD. A summary of the studies developed using DL is provided in the Supplementary Appendix. Then, the challenges encountered during the automated diagnosis of ASD using MRI and AI techniques are described in detail. Additionally, a graphical comparison of studies using ML and DL to diagnose ASD automatically is discussed. We suggest future approaches to detecting ASDs using AI techniques and MRI neuroimaging.Qatar National Librar

Automatic Autism Spectrum Disorder Detection Using Artificial Intelligence Methods with MRI Neuroimaging: A Review

Autism spectrum disorder (ASD) is a brain condition characterized by diverse signs and symptoms that appear in early childhood. ASD is also associated with communication deficits and repetitive behavior in affected individuals. Various ASD detection methods have been developed, including neuroimaging modalities and psychological tests. Among these methods, magnetic resonance imaging (MRI) imaging modalities are of paramount importance to physicians. Clinicians rely on MRI modalities to diagnose ASD accurately. The MRI modalities are non-invasive methods that include functional (fMRI) and structural (sMRI) neuroimaging methods. However, the process of diagnosing ASD with fMRI and sMRI for specialists is often laborious and time-consuming; therefore, several computer-aided design systems (CADS) based on artificial intelligence (AI) have been developed to assist the specialist physicians. Conventional machine learning (ML) and deep learning (DL) are the most popular schemes of AI used for diagnosing ASD. This study aims to review the automated detection of ASD using AI. We review several CADS that have been developed using ML techniques for the automated diagnosis of ASD using MRI modalities. There has been very limited work on the use of DL techniques to develop automated diagnostic models for ASD. A summary of the studies developed using DL is provided in the appendix. Then, the challenges encountered during the automated diagnosis of ASD using MRI and AI techniques are described in detail. Additionally, a graphical comparison of studies using ML and DL to diagnose ASD automatically is discussed. We conclude by suggesting future approaches to detecting ASDs using AI techniques and MRI neuroimaging

Element-centric clustering comparison unifies overlaps and hierarchy

Clustering is one of the most universal approaches for understanding complex data. A pivotal aspect of clustering analysis is quantitatively comparing clusterings; clustering comparison is the basis for many tasks such as clustering evaluation, consensus clustering, and tracking the temporal evolution of clusters. In particular, the extrinsic evaluation of clustering methods requires comparing the uncovered clusterings to planted clusterings or known metadata. Yet, as we demonstrate, existing clustering comparison measures have critical biases which undermine their usefulness, and no measure accommodates both overlapping and hierarchical clusterings. Here we unify the comparison of disjoint, overlapping, and hierarchically structured clusterings by proposing a new element-centric framework: elements are compared based on the relationships induced by the cluster structure, as opposed to the traditional cluster-centric philosophy. We demonstrate that, in contrast to standard clustering similarity measures, our framework does not suffer from critical biases and naturally provides unique insights into how the clusterings differ. We illustrate the strengths of our framework by revealing new insights into the organization of clusters in two applications: the improved classification of schizophrenia based on the overlapping and hierarchical community structure of fMRI brain networks, and the disentanglement of various social homophily factors in Facebook social networks. The universality of clustering suggests far-reaching impact of our framework throughout all areas of science

Development and evaluation of optimization based data mining techniques analysis of brain data

Neuroscience is an interdisciplinary science which deals with the study of structure and function of the brain and nervous system. Neuroscience encompasses disciplines such as computer science, mathematics, engineering, and linguistics. The structure of the healthy brain and representation of information by neural activity are among most challenging problems in neuroscience. Neuroscience is experiencing exponentially growing volumes of data obtained by using different technologies. The investigation of such data has tremendous impact on developing new and improving existing models of both healthy and diseased brains. Various techniques have been used for collecting brain data sets for addressing neuroscience problems. These data sets can be categorized into two main groups: resting-state and state-dependent data sets. Resting-state data is based on recording the brain activity when a subject does not think about any specific concept while state-dependent data is based on recording brain activity related to specific tasks. In general, brain data sets contain a large number of features (e.g. tens of thousands) and significantly fewer samples (e.g. several hundred). Such data sets are sparse and noisy. In addition to these problems, brain data sets have a few number of subjects. Brains are very complex systems and data about any brain activity reflects very complex relationship between neurons as well as different parts of the brain. Such relationships are highly nonlinear and general purpose data mining algorithms are not always efficient for their study. The development of machine learning techniques for brain data sets is an emerging research area in neuroscience. Over the last decade, various machine learning techniques have been developed for application to brain data sets. In the meantime, some well-known algorithms such as feature selection and supervised classification have been modified for analysis of brain data sets. Support vector machines, logistic regression, and Gaussian Naive Bayes classifiers are widely used for application to brain data sets. However, Support vector machines and logistic regression algorithms are not efficient for sparse and noisy data sets and Gaussian Naive Bayes classifiers do not give high accuracy. The aim of this study is to develop new and modify the existing data mining algorithms for the analysis brain data sets. Our contribution in this thesis can be listed as follow: 1. Development of new algorithms: 1.1. Development of new voxel (feature) selection algorithms for Functional magnetic resonance imaging (fMRI) data sets, and evaluation of these algorithms on the Haxby and Science 2008 data sets. 1.2. Development of new feature selection algorithm based on the catastrophe model for regression analysis problems. 2. Development and evaluation of different versions of the adaptive neuro-fuzzy model for the analysis of the spike-discharge as a function of other neuronal parameters. 3. Development and evaluation of the modified global k-means clustering algorithm for investigation of the structure of the healthy brain. 4. Development and evaluation of region of interest (ROI) method for analysis of brain functionalconnectivity in healthy subjects and schizophrenia patients.Doctor of Philosoph

Novel Biomarker Identification Approaches for Schizophrenia using fMRI and Retinal Electrophysiology

University of Minnesota Ph.D. dissertation. November 2017. Major: Biomedical Engineering. Advisors: Kelvin Lim, Theoden Netoff. 1 computer file (PDF); vi, 109 pages.Schizophrenia is a chronic mental illness. The exact cause if schizophrenia is not yet known. Extensive research has been done to identify robust biomarkers for the disease using non-invasive brain imaging techniques. A robust biomarker can be informative about pathophysiology of the disease and can guide clinicians into developing more effective interventions. The aim of this dissertation is two folds. First, we seek to identify robust biomarkers using resting state fMRI activity from a cohort of schizophrenic and healthy subjects in a purely data driven approach. We will calculate multivariate network measures and use them as features for classification of the subjects into healthy and diseased. The network measures will be calculated using nodes defined by the AAL anatomical atlas as well as a functional atlas constructed from the fMRI activity. Network measures with high classification rate may be used as potential biomarkers. We will employ double cross-validation to estimate generalizability of our results to a new population of subjects that were not used in biomarker identification. Second, we seek to identify biomarkers using electroretinogram (ERG). We will use a data driven approach to classify individuals based on the pattern of retinal activity they exhibit in response to visual stimulation. Characteristics of the ERG result in high classification rate are presented as potential biomarkers of schizophrenia

The Non-Random Brain: Efficiency, Economy, and Complex Dynamics

Modern anatomical tracing and imaging techniques are beginning to reveal the structural anatomy of neural circuits at small and large scales in unprecedented detail. When examined with analytic tools from graph theory and network science, neural connectivity exhibits highly non-random features, including high clustering and short path length, as well as modules and highly central hub nodes. These characteristic topological features of neural connections shape non-random dynamic interactions that occur during spontaneous activity or in response to external stimulation. Disturbances of connectivity and thus of neural dynamics are thought to underlie a number of disease states of the brain, and some evidence suggests that degraded functional performance of brain networks may be the outcome of a process of randomization affecting their nodes and edges. This article provides a survey of the non-random structure of neural connectivity, primarily at the large scale of regions and pathways in the mammalian cerebral cortex. In addition, we will discuss how non-random connections can give rise to differentiated and complex patterns of dynamics and information flow. Finally, we will explore the idea that at least some disorders of the nervous system are associated with increased randomness of neural connections