578 research outputs found
Scalable Machine Learning Methods for Massive Biomedical Data Analysis.
Modern data acquisition techniques have enabled biomedical researchers to collect and analyze datasets of substantial size and complexity. The massive size of these datasets allows us to comprehensively study the biological system of interest at an unprecedented level of detail, which may lead to the discovery of clinically relevant biomarkers. Nonetheless, the dimensionality of these datasets presents critical computational and statistical challenges, as traditional statistical methods break down when the number of predictors dominates the number of observations, a setting frequently encountered in biomedical data analysis. This difficulty is compounded by the fact that biological data tend to be noisy and often possess complex correlation patterns among the predictors. The central goal of this dissertation is to develop a computationally tractable machine learning framework that allows us to extract scientifically meaningful information from these massive and highly complex biomedical datasets. We motivate the scope of our study by considering two important problems with clinical relevance: (1) uncertainty analysis for biomedical image registration, and (2) psychiatric disease prediction based on functional connectomes, which are high dimensional correlation maps generated from resting state functional MRI.PhDElectrical Engineering: SystemsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111354/1/takanori_1.pd
Formal Models of the Network Co-occurrence Underlying Mental Operations
International audienceSystems neuroscience has identified a set of canonical large-scale networks in humans. These have predominantly been characterized by resting-state analyses of the task-uncon-strained, mind-wandering brain. Their explicit relationship to defined task performance is largely unknown and remains challenging. The present work contributes a multivariate statistical learning approach that can extract the major brain networks and quantify their configuration during various psychological tasks. The method is validated in two extensive datasets (n = 500 and n = 81) by model-based generation of synthetic activity maps from recombination of shared network topographies. To study a use case, we formally revisited the poorly understood difference between neural activity underlying idling versus goal-directed behavior. We demonstrate that task-specific neural activity patterns can be explained by plausible combinations of resting-state networks. The possibility of decomposing a mental task into the relative contributions of major brain networks, the "network co-occurrence architecture" of a given task, opens an alternative access to the neural substrates of human cognition
Multivariate MR Biomarkers Better Predict Cognitive Dysfunction in Mouse Models of Alzheimers Disease
To understand multifactorial conditions such as Alzheimers disease (AD) we
need brain signatures that predict the impact of multiple pathologies and their
interactions. To help uncover the relationships between brain circuits and
cognitive markers we have used mouse models that represent, at least in part,
the complex interactions altered in AD. In particular, we aimed to understand
the relationship between vulnerable brain circuits and memory deficits measured
in the Morris water maze, and we tested several predictive modeling approaches.
We used in vivo manganese enhanced MRI voxel based analyses to reveal regional
differences in volume (morphometry), signal intensity (activity), and magnetic
susceptibility (iron deposition, demyelination). These regions included the
hippocampus, olfactory areas, entorhinal cortex and cerebellum. The image based
properties of these regions were used to predict spatial memory. We next used
eigenanatomy, which reduces dimensionality to produce sets of regions that
explain the variance in the data. For each imaging marker, eigenanatomy
revealed networks underpinning a range of cognitive functions including memory,
motor function, and associative learning. Finally, the integration of
multivariate markers in a supervised sparse canonical correlation approach
outperformed single predictor models and had significant correlates to spatial
memory. Among a priori selected regions, the fornix also provided good
predictors, raising the possibility of investigating how disease propagation
within brain networks leads to cognitive deterioration. Our results support
that modeling approaches integrating multivariate imaging markers provide
sensitive predictors of AD-like behaviors. Such strategies for mapping brain
circuits responsible for behaviors may help in the future predict disease
progression, or response to interventions.Comment: 23 pages, 3 Tables, 6 Figures; submitted for publicatio
Complex biomarker discovery in neuroimaging data: Finding a needle in a haystack
AbstractNeuropsychiatric disorders such as schizophrenia, bipolar disorder and Alzheimer's disease are major public health problems. However, despite decades of research, we currently have no validated prognostic or diagnostic tests that can be applied at an individual patient level. Many neuropsychiatric diseases are due to a combination of alterations that occur in a human brain rather than the result of localized lesions. While there is hope that newer imaging technologies such as functional and anatomic connectivity MRI or molecular imaging may offer breakthroughs, the single biomarkers that are discovered using these datasets are limited by their inability to capture the heterogeneity and complexity of most multifactorial brain disorders. Recently, complex biomarkers have been explored to address this limitation using neuroimaging data. In this manuscript we consider the nature of complex biomarkers being investigated in the recent literature and present techniques to find such biomarkers that have been developed in related areas of data mining, statistics, machine learning and bioinformatics
Tensor Analysis and Fusion of Multimodal Brain Images
Current high-throughput data acquisition technologies probe dynamical systems
with different imaging modalities, generating massive data sets at different
spatial and temporal resolutions posing challenging problems in multimodal data
fusion. A case in point is the attempt to parse out the brain structures and
networks that underpin human cognitive processes by analysis of different
neuroimaging modalities (functional MRI, EEG, NIRS etc.). We emphasize that the
multimodal, multi-scale nature of neuroimaging data is well reflected by a
multi-way (tensor) structure where the underlying processes can be summarized
by a relatively small number of components or "atoms". We introduce
Markov-Penrose diagrams - an integration of Bayesian DAG and tensor network
notation in order to analyze these models. These diagrams not only clarify
matrix and tensor EEG and fMRI time/frequency analysis and inverse problems,
but also help understand multimodal fusion via Multiway Partial Least Squares
and Coupled Matrix-Tensor Factorization. We show here, for the first time, that
Granger causal analysis of brain networks is a tensor regression problem, thus
allowing the atomic decomposition of brain networks. Analysis of EEG and fMRI
recordings shows the potential of the methods and suggests their use in other
scientific domains.Comment: 23 pages, 15 figures, submitted to Proceedings of the IEE
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
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