Image informatics strategies for deciphering neuronal network connectivity

Brain function relies on an intricate network of highly dynamic neuronal connections that rewires dramatically under the impulse of various external cues and pathological conditions. Among the neuronal structures that show morphologi- cal plasticity are neurites, synapses, dendritic spines and even nuclei. This structural remodelling is directly connected with functional changes such as intercellular com- munication and the associated calcium-bursting behaviour. In vitro cultured neu- ronal networks are valuable models for studying these morpho-functional changes. Owing to the automation and standardisation of both image acquisition and image analysis, it has become possible to extract statistically relevant readout from such networks. Here, we focus on the current state-of-the-art in image informatics that enables quantitative microscopic interrogation of neuronal networks. We describe the major correlates of neuronal connectivity and present workflows for analysing them. Finally, we provide an outlook on the challenges that remain to be addressed, and discuss how imaging algorithms can be extended beyond in vitro imaging studies

Abstract computation in schizophrenia detection through artificial neural network based systems

Schizophrenia stands for a long-lasting state of mental uncertainty that may bring to an end the relation among behavior, thought, and emotion; that is, it may lead to unreliable perception, not suitable actions and feelings, and a sense of mental fragmentation. Indeed, its diagnosis is done over a large period of time; continuos signs of the disturbance persist for at least 6 (six) months. Once detected, the psychiatrist diagnosis is made through the clinical interview and a series of psychic tests, addressed mainly to avoid the diagnosis of other mental states or diseases. Undeniably, the main problem with identifying schizophrenia is the difficulty to distinguish its symptoms from those associated to different untidiness or roles. Therefore, this work will focus on the development of a diagnostic support system, in terms of its knowledge representation and reasoning procedures, based on a blended of Logic Programming and Artificial Neural Networks approaches to computing, taking advantage of a novel approach to knowledge representation and reasoning, which aims to solve the problems associated in the handling (i.e., to stand for and reason) of defective information.This work is funded by National Funds through the FCT, Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) within projects PEstOE/EEI/UI0752/2014 and PEst-OE/QUI/UI0619/2012

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

Chapter References

This book offers a provocative account of interdisciplinary research across the neurosciences, social sciences and humanities. Setting itself against standard accounts of interdisciplinary 'integration,' and rooting itself in the authors' own experiences, the book establishes a radical agenda for collaboration across these disciplines. Rethinking Interdisciplinarity does not merely advocate interdisciplinary research, but attends to the hitherto tacit pragmatics, affects, power dynamics, and spatial logics in which that research is enfolded. Understanding the complex relationships between brains, minds, and environments requires a delicate, playful and genuinely experimental interdisciplinarity, and this book shows us how it can be done

The BrainMap strategy for standardization, sharing, and meta-analysis of neuroimaging data

<p>Abstract</p> <p>Background</p> <p>Neuroimaging researchers have developed rigorous community data and metadata standards that encourage meta-analysis as a method for establishing robust and meaningful convergence of knowledge of human brain structure and function. Capitalizing on these standards, the BrainMap project offers databases, software applications, and other associated tools for supporting and promoting quantitative coordinate-based meta-analysis of the structural and functional neuroimaging literature.</p> <p>Findings</p> <p>In this report, we describe recent technical updates to the project and provide an educational description for performing meta-analyses in the BrainMap environment.</p> <p>Conclusions</p> <p>The BrainMap project will continue to evolve in response to the meta-analytic needs of biomedical researchers in the structural and functional neuroimaging communities. Future work on the BrainMap project regarding software and hardware advances are also discussed.</p

On pattern recognition of brain connectivity in resting-state functional MRI

Dissertação de mestrado integrado em Biomedical Engineering (specialization on Medical Informatics)The human urge and pursuit for information have led to the development of increasingly complex technologies, and new means to study and understand the most advanced and intricate biological system: the human brain. Large-scale neuronal communication within the brain, and how it relates to human behaviour can be inferred by delving into the brain network, and searching for patterns in connectivity. Functional connectivity is a steady characteristic of the brain, and it has been proved to be very useful for examining how mental disorders affect connections within the brain. The detection of abnormal behaviour in brain networks is performed by experts, such as physicians, who limit the process with human subjectivity, and unwittingly introduce errors in the interpretation. The continuous search for alternatives to obtain faster and robuster results have put Machine Learning and Deep Learning in the leading position of computer vision, as they enable the extraction of meaningful patterns, some beyond human perception. The aim of this dissertation is to design and develop an experiment setup to analyse functional connectivity at a voxel level, in order to find functional patterns. For the purpose, a pipeline was outlined to include steps from data download to data analysis, resulting in four methods: Data Download, Data Preprocessing, Dimensionality Reduction, and Analysis. The proposed experiment setup was modeled using as materials resting state fMRI data from two sources: Life and Health Sciences Research Institute (Portugal), and Human Connectome Project (USA). To evaluate its performance, a case study was performed using the In-House data for concerning a smaller number of subjects to study. The pipeline was successful at delivering results, although limitations concerning the memory of the machine used restricted some aspects of this experiment setup’s testing. With appropriate resources, this experiment setup may support the process of analysing and extracting patterns from any resting state functional connectivity data, and aid in the detection of mental disorders.O desejo e a busca intensos do ser humano por informação levaram ao desenvolvimento de tecnologias cada vez mais complexas e novos meios para estudar e entender o sistema biológico mais avançado e intrincado: o cérebro humano. A comunicação neuronal em larga escala no cérebro, e como ela se relaciona com o comportamento humano, pode ser inferida investigando a rede neuronal cerebral e procurando por padrões de conectividade. A conectividade funcional é uma característica constante do cérebro e provou ser muito útil para examinar como os distúrbios mentais afetam as conexões cerebrais. A deteção de anormalidades em imagens de ressonância magnética é realizada por especialistas, como médicos, que limitam o processo com a subjetividade humana e, inadvertidamente, introduzem erros na interpretação. A busca contínua de alternativas para obter resultados mais rápidos e robustos colocou as técnicas de machine learning e deep learning na posição de liderança de visão computacional, pois permitem a extração de padrões significativos e alguns deles para além da percepção humana. O objetivo desta dissertação é projetar e desenvolver uma configuração experimental para analisar a conectividade funcional ao nível do voxel, a fim de encontrar padrões funcionais. Nesse sentido, foi delineado um pipeline para incluir etapas a começar no download de dados até à análise desses mesmos dados, resultando assim em quatro métodos: Download de Dados, Pré-processamento de Dados, Redução de Dimensionalidade e Análise. A configuração experimental proposta foi modelada usando dados de ressonância magnética funcional de resting-state de duas fontes: Instituto de Ciências da Vida e Saúde (Portugal) e Human Connectome Project (EUA). Para avaliar o seu desempenho, foi realizado um estudo de caso usando os dados internos por considerar um número menor de participantes a serem estudados. O pipeline foi bem-sucedido em fornecer resultados, embora limitações relacionadas com a memória da máquina usada tenham restringido alguns aspetos do teste desta configuração experimental. Com recursos apropriados, esta configuração experimental poderá servir de suporte para o processo de análise e extração de padrões de qualquer conjunto de dados de conectividade funcional em resting-state e auxiliar na deteção de transtornos mentais

Childhood Adversity Linked to Neurological Circuitry Changes and Mental Health Disorders. Narrative Review

Children who experience adversity have increased risk for psychiatric disorders. However, little is known about the exact alterations that occur in the neural circuitry and how that information may help lead to early diagnosis or preventive medicine. Research has shown that there are specific changes in neurological functional connectivity in the brain associated with childhood adversity. This review will examine recent papers that have investigated the correlation between these changes in brain connectivity and specific psychiatric disorders. Understanding the changes may help with preventive medicine by ensuring clinicians monitor patients with more severe history of adversity who are therefore at higher risk for developing a psychiatric disorder. This paper will also address potential recommendations that could be implemented in the future as research offers more conclusive evidence. Research is now beginning to address the questions of whether these changes can be attenuated, either during childhood or as adults

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