Contributions to the study of Austism Spectrum Brain conectivity

164 p.Autism Spectrum Disorder (ASD) is a largely prevalent neurodevelopmental condition with a big social and economical impact affecting the entire life of families. There is an intense search for biomarkers that can be assessed as early as possible in order to initiate treatment and preparation of the family to deal with the challenges imposed by the condition. Brain imaging biomarkers have special interest. Specifically, functional connectivity data extracted from resting state functional magnetic resonance imaging (rs-fMRI) should allow to detect brain connectivity alterations. Machine learning pipelines encompass the estimation of the functional connectivity matrix from brain parcellations, feature extraction and building classification models for ASD prediction. The works reported in the literature are very heterogeneous from the computational and methodological point of view. In this Thesis we carry out a comprehensive computational exploration of the impact of the choices involved while building these machine learning pipelines

Interrogating autism from a multidimensional perspective: an integrative framework.

Autism Spectrum Disorder (ASD) is a condition characterized by social and behavioral impairments, affecting approximately 1 in every 44 children in the United States. Common symptoms include difficulties in communication, interpersonal interactions, and behavior. While symptoms can manifest as early as infancy, obtaining an accurate diagnosis may require multiple visits to a pediatric specialist due to the subjective nature of the assessment, which may yield varying scores from different specialists. Despite growing evidence of the role of differences in brain development and/or environmental and/or genetic factors in autism development, the exact pathology of this disorder has yet to be fully elucidated by scientists. At present, the diagnosis of ASD typically involves a set of gold-standard diagnostic evaluations, such as the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview-Revised (ADI-R), and the more cost-effective Social Responsive Scale (SRS). Administering these diagnostic tests, which involve assessing communication and behavioral patterns, along with obtaining a clinical history, requires the expertise of a team of qualified clinicians. This process is time-consuming, effortful, and involves a degree of subjectivity due to the reliance on clinical judgment. Aside from conventional observational assessments, recent developments in neuroimaging and machine learning offer a fast and objective alternative for diagnosing ASD using brain imaging. This comprehensive work explores the use of different imaging modalvities, namely structural MRI (sMRI) and resting-state functional MRI (rs-fMRI), to investigate their potential for autism diagnosis. The proposed study aims to offer a new approach and perspective in comprehending ASD as a multidimensional problem, within a behavioral space that is defined by one of the available ASD diagnostic tools. This dissertation introduces a thorough investigation of the utilization of feature engineering tools to extract distinctive insights from various brain imaging modalities, including the application of novel feature representations. Additionally, the use of a machine learning framework to aid in the precise classification of individuals with autism is also explored in detail. This extensive research, which draws upon large publicly available datasets, sheds light on the influence of various decisions made throughout the pipeline on diagnostic accuracy. Furthermore, it identifies brain regions that may be impacted and contribute to an autism diagnosis. The attainment of high global state-of-the-art cross-validated, and hold-out set accuracy validates the advantages of feature representation and engineering in extracting valuable information, as well as the potential benefits of employing neuroimaging for autism diagnosis. Furthermore, a suggested diagnostic report has been put forth to assist physicians in mapping diagnoses to underlying neuroimaging markers. This approach could enable an earlier, automated, and more objective personalized diagnosis

Decoding Task-Based fMRI Data Using Graph Neural Networks, Considering Individual Differences

Functional magnetic resonance imaging (fMRI) is a non-invasive technology that provides high spatial resolution in determining the human brain\u27s responses and measures regional brain activity through metabolic changes in blood oxygen consumption associated with neural activity. Task fMRI provides an opportunity to analyze the working mechanisms of the human brain during specific task performance. Over the past several years, a variety of computational methods have been proposed to decode task fMRI data that can identify brain regions associated with different task stimulations. Despite the advances made by these methods, several limitations exist due to graph representations and graph embeddings transferred from task fMRI signals. In the present study, we proposed an end-to-end graph convolutional network by combining the convolutional neural network with graph representation, with three convolutional layers to classify task fMRI data from the Human Connectome Project (302 participants, 22–35 years of age). One goal of this dissertation was to improve classification performance. We applied four of the most widely used node embedding algorithms—NetMF, RandNE, Node2Vec, and Walklets—to automatically extract the structural properties of the nodes in the brain functional graph, then evaluated the performance of the classification model. The empirical results indicated that the proposed GCN framework accurately identified the brain\u27s state in task fMRI data and achieved comparable macro F1 scores of 0.978 and 0.976 with the NetMF and RandNE embedding methods, respectively. Another goal of the dissertation was to assess the effects of individual differences (i.e., gender and fluid intelligence) on classification performance. We tested the proposed GCN framework on sub-datasets divided according to gender and fluid intelligence. Experimental results indicated significant differences in the classification predictions of gender, but not high/low fluid intelligence fMRI data. Our experiments yielded promising results and demonstrated the superior ability of our GCN in modeling task fMRI data

Synergizing human-machine intelligence: Visualizing, labeling, and mining the electronic health record

We live in a world where data surround us in every aspect of our lives. The key challenge for humans and machines is how we can make better use of such data. Imagine what would happen if you were to have intelligent machines that could give you insight into the data. Insight that will enable you to better 1) reason about, 2) learn, and 3) understand the underlying phenomena that produced the data. The possibilities of combined human-machine intelligence are endless and will impact our lives in ways we can not even imagine today. Synergistic human-machine intelligence aims to facilitate the analytical reasoning and inference process of humans by creating machines that maximize a human's ability to 1) reason about, 2) learn, and 3) understand large, complex, and heterogeneous data. Combined human-machine intelligence is a powerful symbiosis of mutual benefit, in which we depend on the computational capabilities of the machine for the tasks we are not good at, and the machine requires human intervention for the tasks it performs poorly on. This relationship provides a compelling alternative to either approach in isolation for solving today's and tomorrow's arising data challenges. In his regard, this dissertation proposes a diverse analytical framework that leverages synergistic human-machine intelligence to maximize a human's ability to better 1) reason about, 2) learn, and 3) understand different biomedical imaging and healthcare data present in the patient's electronic health record (EHR). Correspondingly, we approach the data analyses problem from the 1) visualization, 2) labeling, and 3) mining perspective and demonstrate the efficacy of our analytics on specific application scenarios and various data domains. In the first part of this dissertation we explore the question how we can build intelligent imaging analytics that are commensurate with human capabilities and constraints, specifically for optimizing data visualization and automated labeling workflows. Our journey starts with heuristic rule-based analytical models that are derived from task-specific human knowledge. From this experience, we move on to data-driven analytics, where we adapt and combine the intelligence of the model based on prior information provided by the human and synthetic knowledge learned from partial data observations. Within this realm, we propose a novel Bayesian transductive Markov random field model that requires minimal human intervention and is able to cope with scarce label information to learn and infer object shapes in complex spatial, multimodal, spatio-temporal, and longitudinal data. We then study the question how machines can learn discriminative object representations from dense human provided label information by investigating learning and inference mechanisms that make use of deep learning architectures. The developed analytics can aid visualization and labeling tasks, which enables the interpretation and quantification of clinically relevant image information. The second part explores the question how we can build data-driven analytics for exploratory analysis in longitudinal event data that are commensurate with human capabilities and constraints. We propose human-intuitive analytics that enable the representation and discovery of interpretable event patterns to ease knowledge absorption and comprehension of the employed analytics model and the underlying data. We propose a novel doubly-constrained convolutional sparse-coding framework that learns interpretable and shift-invariant latent temporal event patterns. We apply the model to mine complex event data in EHRs. By mapping the event space to heterogeneous patient encounters in the EHR we explore the linkage between healthcare resource utilization (HRU) in relation to disease severity. This linkage may help to better understand how disease specific co-morbidities and their clinical attributes incur different HRU patterns. Such insight helps to characterize the patient's care history, which then enables the comparison against clinical practice guidelines, the discovery of prevailing practices based on common HRU group patterns, and the identification of outliers that might indicate poor patient management

Phenotyping functional brain dynamics:A deep learning prespective on psychiatry

This thesis explores the potential of deep learning (DL) techniques combined with multi-site functional magnetic resonance imaging (fMRI) to enable automated diagnosis and biomarker discovery for psychiatric disorders. This marks a shift from the convention in the field of applying standard machine learning techniques on hand-crafted features from a single cohort.To enable this, we have focused on three main strategies: utilizing minimally pre-processed data to maintain spatio-temporal dynamics, developing sample-efficient DL models, and applying emerging DL training techniques like self-supervised and transfer learning to leverage large population-based datasets.Our empirical results suggest that DL models can sometimes outperform existing machine learning methods in diagnosing Autism Spectrum Disorder (ASD) and Major Depressive Disorder (MDD) from resting-state fMRI data, despite the smaller datasets and the high data dimensionality. Nonetheless, the generalization performance of these models is currently insufficient for clinical use, raising questions about the feasibility of applying supervised DL for diagnosis or biomarker discovery due to the highly heterogeneous nature of the disorders. Our findings suggest that normative modeling on functional brain dynamics provides a promising alternative to the current paradigm

An analysis of connectivity

Recent evidence in biology indicates crossmodal, which is to say information sharing between the different senses, influences in the brain. This helps to explain such phenomenon as the McGurk effect, where even though a person knows that he is seeing the lip movement “GA” and is hearing the sound “BA”, the person usually can’t help but think that they are hearing the sound “DA”. The McGurk effect is an example of where the visual sense influences the perception of the audio sense. These discoveries transition old feedforward models of the brain to ones that rely on feedback connections and, more recently, crossmodal connections. Although we have many software systems that rely on some form of intelligence, i.e. person recognition software, speech to text software, etc, very few take advantage of crossmodal influences. This thesis provides an analysis of the importance of connections between explicit modalities in a recurrent neural network model. Each modality is represented as an individual recurrent neural network. The connections between the modalities and the modalities themselves are trained by applying a genetic algorithm to generate a population of the full model to solve certain types of classification problems. The main contribution of this work is to experimentally show the relative importance of feedback and crossmodal connections. From this it can be argued that the utilization of crossmodal information at an earlier stage of decision making can boost the accuracy and reliability of intelligent systems

Characterizing and comparing acoustic representations in convolutional neural networks and the human auditory system

Le traitement auditif dans le cerveau humain et dans les systèmes informatiques consiste en une cascade de transformations représentationnelles qui extraient et réorganisent les informations pertinentes pour permettre l'exécution des tâches. Cette thèse s'intéresse à la nature des représentations acoustiques et aux principes de conception et d'apprentissage qui soutiennent leur développement. Les objectifs scientifiques sont de caractériser et de comparer les représentations auditives dans les réseaux de neurones convolutionnels profonds (CNN) et la voie auditive humaine. Ce travail soulève plusieurs questions méta-scientifiques sur la nature du progrès scientifique, qui sont également considérées. L'introduction passe en revue les connaissances actuelles sur la voie auditive des mammifères et présente les concepts pertinents de l'apprentissage profond. Le premier article soutient que les questions philosophiques les plus pressantes à l'intersection de l'intelligence artificielle et biologique concernent finalement la définition des phénomènes à expliquer et ce qui constitue des explications valables de tels phénomènes. Je surligne les théories pertinentes de l'explication scientifique que j’espére fourniront un échafaudage pour de futures discussions. L'article 2 teste un modèle populaire de cortex auditif basé sur des modulations spectro-temporelles. Nous constatons qu'un modèle linéaire entraîné uniquement sur les réponses BOLD aux ondulations dynamiques simples (contenant seulement une fréquence fondamentale, un taux de modulation temporelle et une échelle spectrale) peut se généraliser pour prédire les réponses aux mélanges de deux ondulations dynamiques. Le troisième article caractérise la spécificité linguistique des couches CNN et explore l'effet de l'entraînement figé et des poids aléatoires. Nous avons observé trois régions distinctes de transférabilité: (1) les deux premières couches étaient entièrement transférables, (2) les couches 2 à 8 étaient également hautement transférables, mais nous avons trouvé évidence de spécificité de la langue, (3) les couches suivantes entièrement connectées étaient plus spécifiques à la langue mais pouvaient être adaptées sur la langue cible. Dans l'article 4, nous utilisons l'analyse de similarité pour constater que la performance supérieure de l'entraînement figé obtenues à l'article 3 peuvent être attribuées aux différences de représentation dans l'avant-dernière couche: la deuxième couche entièrement connectée. Nous analysons également les réseaux aléatoires de l'article 3, dont nous concluons que la forme représentationnelle est doublement contrainte par l'architecture et la forme de l'entrée et de la cible. Pour tester si les CNN acoustiques apprennent une hiérarchie de représentation similaire à celle du système auditif humain, le cinquième article compare l'activité des réseaux «freeze trained» de l'article 3 à l'activité IRMf 7T dans l'ensemble du système auditif humain. Nous ne trouvons aucune évidence d'une hiérarchie de représentation partagée et constatons plutôt que tous nos régions auditifs étaient les plus similaires à la première couche entièrement connectée. Enfin, le chapitre de discussion passe en revue les mérites et les limites d'une approche d'apprentissage profond aux neurosciences dans un cadre de comparaison de modèles. Ensemble, ces travaux contribuent à l'entreprise naissante de modélisation du système auditif avec des réseaux de neurones et constituent un petit pas vers une science unifiée de l'intelligence qui étudie les phénomènes qui se manifestent dans l'intelligence biologique et artificielle.Auditory processing in the human brain and in contemporary machine hearing systems consists of a cascade of representational transformations that extract and reorganize relevant information to enable task performance. This thesis is concerned with the nature of acoustic representations and the network design and learning principles that support their development. The primary scientific goals are to characterize and compare auditory representations in deep convolutional neural networks (CNNs) and the human auditory pathway. This work prompts several meta-scientific questions about the nature of scientific progress, which are also considered. The introduction reviews what is currently known about the mammalian auditory pathway and introduces the relevant concepts in deep learning.The first article argues that the most pressing philosophical questions at the intersection of artificial and biological intelligence are ultimately concerned with defining the phenomena to be explained and with what constitute valid explanations of such phenomena. I highlight relevant theories of scientific explanation which we hope will provide scaffolding for future discussion. Article 2 tests a popular model of auditory cortex based on frequency-specific spectrotemporal modulations. We find that a linear model trained only on BOLD responses to simple dynamic ripples (containing only one fundamental frequency, temporal modulation rate, and spectral scale) can generalize to predict responses to mixtures of two dynamic ripples. Both the third and fourth article investigate how CNN representations are affected by various aspects of training. The third article characterizes the language specificity of CNN layers and explores the effect of freeze training and random weights. We observed three distinct regions of transferability: (1) the first two layers were entirely transferable between languages, (2) layers 2--8 were also highly transferable but we found some evidence of language specificity, (3) the subsequent fully connected layers were more language specific but could be successfully finetuned to the target language. In Article 4, we use similarity analysis to find that the superior performance of freeze training achieved in Article 3 can be largely attributed to representational differences in the penultimate layer: the second fully connected layer. We also analyze the random networks from Article 3, from which we conclude that representational form is doubly constrained by architecture and the form of the input and target. To test whether acoustic CNNs learn a similar representational hierarchy as that of the human auditory system, the fifth article presents a similarity analysis to compare the activity of the freeze trained networks from Article 3 to 7T fMRI activity throughout the human auditory system. We find no evidence of a shared representational hierarchy and instead find that all of our auditory regions were most similar to the first fully connected layer. Finally, the discussion chapter reviews the merits and limitations of a deep learning approach to neuroscience in a model comparison framework. Together, these works contribute to the nascent enterprise of modeling the auditory system with neural networks and constitute a small step towards a unified science of intelligence that studies the phenomena that are exhibited in both biological and artificial intelligence

Improving Access and Mental Health for Youth Through Virtual Models of Care

The overall objective of this research is to evaluate the use of a mobile health smartphone application (app) to improve the mental health of youth between the ages of 14–25 years, with symptoms of anxiety/depression. This project includes 115 youth who are accessing outpatient mental health services at one of three hospitals and two community agencies. The youth and care providers are using eHealth technology to enhance care. The technology uses mobile questionnaires to help promote self-assessment and track changes to support the plan of care. The technology also allows secure virtual treatment visits that youth can participate in through mobile devices. This longitudinal study uses participatory action research with mixed methods. The majority of participants identified themselves as Caucasian (66.9%). Expectedly, the demographics revealed that Anxiety Disorders and Mood Disorders were highly prevalent within the sample (71.9% and 67.5% respectively). Findings from the qualitative summary established that both staff and youth found the software and platform beneficial

The Impact of Digital Technologies on Public Health in Developed and Developing Countries

This open access book constitutes the refereed proceedings of the 18th International Conference on String Processing and Information Retrieval, ICOST 2020, held in Hammamet, Tunisia, in June 2020.* The 17 full papers and 23 short papers presented in this volume were carefully reviewed and selected from 49 submissions. They cover topics such as: IoT and AI solutions for e-health; biomedical and health informatics; behavior and activity monitoring; behavior and activity monitoring; and wellbeing technology. *This conference was held virtually due to the COVID-19 pandemic