34 research outputs found

    Increasing power for voxel-wise genome-wide association studies : the random field theory, least square kernel machines and fast permutation procedures

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    Imaging traits are thought to have more direct links to genetic variation than diagnostic measures based on cognitive or clinical assessments and provide a powerful substrate to examine the influence of genetics on human brains. Although imaging genetics has attracted growing attention and interest, most brain-wide genome-wide association studies focus on voxel-wise single-locus approaches, without taking advantage of the spatial information in images or combining the effect of multiple genetic variants. In this paper we present a fast implementation of voxel- and cluster-wise inferences based on the random field theory to fully use the spatial information in images. The approach is combined with a multi-locus model based on least square kernel machines to associate the joint effect of several single nucleotide polymorphisms (SNP) with imaging traits. A fast permutation procedure is also proposed which significantly reduces the number of permutations needed relative to the standard empirical method and provides accurate small p-value estimates based on parametric tail approximation. We explored the relation between 448,294 single nucleotide polymorphisms and 18,043 genes in 31,662 voxels of the entire brain across 740 elderly subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Structural MRI scans were analyzed using tensor-based morphometry (TBM) to compute 3D maps of regional brain volume differences compared to an average template image based on healthy elderly subjects. We find method to be more sensitive compared with voxel-wise single-locus approaches. A number of genes were identified as having significant associations with volumetric changes. The most associated gene was GRIN2B, which encodes the N-methyl-d-aspartate (NMDA) glutamate receptor NR2B subunit and affects both the parietal and temporal lobes in human brains. Its role in Alzheimer's disease has been widely acknowledged and studied, suggesting the validity of the approach. The various advantages over existing approaches indicate a great potential offered by this novel framework to detect genetic influences on human brains

    An Iterative Jackknife Approach for Assessing Reliability and Power of fMRI Group Analyses

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    For functional magnetic resonance imaging (fMRI) group activation maps, so-called second-level random effect approaches are commonly used, which are intended to be generalizable to the population as a whole. However, reliability of a certain activation focus as a function of group composition or group size cannot directly be deduced from such maps. This question is of particular relevance when examining smaller groups (<20–27 subjects). The approach presented here tries to address this issue by iteratively excluding each subject from a group study and presenting the overlap of the resulting (reduced) second-level maps in a group percent overlap map. This allows to judge where activation is reliable even upon excluding one, two, or three (or more) subjects, thereby also demonstrating the inherent variability that is still present in second-level analyses. Moreover, when progressively decreasing group size, foci of activation will become smaller and/or disappear; hence, the group size at which a given activation disappears can be considered to reflect the power necessary to detect this particular activation. Systematically exploiting this effect allows to rank clusters according to their observable effect size. The approach is tested using different scenarios from a recent fMRI study (children performing a “dual-use” fMRI task, n = 39), and the implications of this approach are discussed

    CoSMoMVPA: Multi-Modal Multivariate Pattern Analysis of Neuroimaging Data in Matlab/GNU Octave

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    Recent years have seen an increase in the popularity of multivariate pattern (MVP) analysis of functional magnetic resonance (fMRI) data, and, to a much lesser extent, magneto- and electro-encephalography (M/EEG) data. We present CoSMoMVPA, a lightweight MVPA (MVP analysis) toolbox implemented in the intersection of the Matlab and GNU Octave languages, that treats both fMRI and M/EEG data as first-class citizens. CoSMoMVPA supports all state-of-the-art MVP analysis techniques, including searchlight analyses, classification, correlations, representational similarity analysis, and the time generalization method. These can be used to address both data-driven and hypothesis-driven questions about neural organization and representations, both within and across: space, time, frequency bands, neuroimaging modalities, individuals, and species. It uses a uniform data representation of fMRI data in the volume or on the surface, and of M/EEG data at the sensor and source level. Through various external toolboxes, it directly supports reading and writing a variety of fMRI and M/EEG neuroimaging formats, and, where applicable, can convert between them. As a result, it can be integrated readily in existing pipelines and used with existing preprocessed datasets. CoSMoMVPA overloads the traditional volumetric searchlight concept to support neighborhoods for M/EEG and surface-based fMRI data, which supports localization of multivariate effects of interest across space, time, and frequency dimensions. CoSMoMVPA also provides a generalized approach to multiple comparison correction across these dimensions using Threshold-Free Cluster Enhancement with state-of-the-art clustering and permutation techniques. CoSMoMVPA is highly modular and uses abstractions to provide a uniform interface for a variety of MVP measures. Typical analyses require a few lines of code, making it accessible to beginner users. At the same time, expert programmers can easily extend its functionality. CoSMoMVPA comes with extensive documentation, including a variety of runnable demonstration scripts and analysis exercises (with example data and solutions). It uses best software engineering practices including version control, distributed development, an automated test suite, and continuous integration testing. It can be used with the proprietary Matlab and the free GNU Octave software, and it complies with open source distribution platforms such as NeuroDebian. CoSMoMVPA is Free/Open Source Software under the permissive MIT license. Website: http://cosmomvpa.org Source code: https://github.com/CoSMoMVPA/CoSMoMVPA

    GeoSPM: Geostatistical parametric mapping for medicine

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    The characteristics and determinants of health and disease are often organised in space, reflecting our spatially extended nature. Understanding the influence of such factors requires models capable of capturing spatial relations. Though a mature discipline, spatial analysis is comparatively rare in medicine, arguably a consequence of the complexity of the domain and the inclemency of the data regimes that govern it. Drawing on statistical parametric mapping, a framework for topological inference well-established in the realm of neuroimaging, we propose and validate a novel approach to the spatial analysis of diverse clinical data - GeoSPM - based on differential geometry and random field theory. We evaluate GeoSPM across an extensive array of synthetic simulations encompassing diverse spatial relationships, sampling, and corruption by noise, and demonstrate its application on large-scale data from UK Biobank. GeoSPM is transparently interpretable, can be implemented with ease by non-specialists, enables flexible modelling of complex spatial relations, exhibits robustness to noise and under-sampling, offers well-founded criteria of statistical significance, and is through computational efficiency readily scalable to large datasets. We provide a complete, open-source software implementation of GeoSPM, and suggest that its adoption could catalyse the wider use of spatial analysis across the many aspects of medicine that urgently demand it.Comment: 29 pages, 22 figure

    GeoSPM: Geostatistical parametric mapping for medicine

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    The characteristics and determinants of health and disease are often organised in space, reflecting our spatially extended nature. Understanding the influence of such factors requires models capable of capturing spatial relations. Though a mature discipline, spatial analysis is comparatively rare in medicine, arguably a consequence of the complexity of the domain and the inclemency of the data regimes that govern it. Drawing on statistical parametric mapping, a framework for topological inference well-established in the realm of neuroimaging, we propose and validate a novel approach to the spatial analysis of diverse clinical data - GeoSPM - based on differential geometry and random field theory. We evaluate GeoSPM across an extensive array of synthetic simulations encompassing diverse spatial relationships, sampling, and corruption by noise, and demonstrate its application on large-scale data from UK Biobank. GeoSPM is transparently interpretable, can be implemented with ease by non-specialists, enables flexible modelling of complex spatial relations, exhibits robustness to noise and under-sampling, offers well-founded criteria of statistical significance, and is through computational efficiency readily scalable to large datasets. We provide a complete, open-source software implementation of GeoSPM, and suggest that its adoption could catalyse the wider use of spatial analysis across the many aspects of medicine that urgently demand it

    Multiscale adaptive generalized estimating equations for longitudinal neuroimaging data

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    Many large-scale longitudinal imaging studies have been or are being widely conducted to better understand the progress of neuropsychiatric and neurodegenerative disorders and normal brain development. The goal of this article is to develop a multiscale adaptive generalized estimation equation (MAGEE) method for spatial and adaptive analysis of neuroimaging data from longitudinal studies. MAGEE is applicable to making statistical inference on regression coefficients in both balanced and unbalanced longitudinal designs and even twin and familial studies, whereas standard software platforms have several major limitations in handling these complex studies. Specifically, conventional voxel-based analyses in these software platforms involve Gaussian smoothing imaging data and then independently fitting a statistical model at each voxel. However, the conventional smoothing methods suffer from the lack of spatial adaptivity to the shape and spatial extent of region of interest and the arbitrary choice of smoothing extent, while independently fitting statistical models across voxels does not account for the spatial properties of imaging observations and noise distribution. To address such drawbacks, we adapt a powerful propagation–separation (PS) procedure to sequentially incorporate the neighboring information of each voxel and develop a new novel strategy to solely update a set of parameters of interest, while fixing other nuisance parameters at their initial estimators. Simulation studies and real data analysis show that MAGEE significantly outperforms voxel-based analysis

    Accurate Non-Iterative Modelling and Inference of Longitudinal Neuroimaging Data

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    In recent years, increasing efforts have been made to collect longitudinal neuroimaging data in order to study how brains change over time. However, the popular methods used to analyse such kind of data may not always be appropriate (e.g., overly sensitive to model misspecifications, difficult to specify adequately or prohibitively slow to compute) and may sometimes lead to erroneous conclusions. Motivated by these shortcomings, in this dissertation, we have proposed and studied the use of an alternative method, referred to as “the Sandwich Estimator method”, and have demonstrated that it is a fast, easy-to-specify and accurate option to analyse longitudinal or repeated-measures neuroimaging data

    Dynamic Complexity and Causality Analysis of Scalp EEG for Detection of Cognitive Deficits

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    This dissertation explores the potential of scalp electroencephalography (EEG) for the detection and evaluation of neurological deficits due to moderate/severe traumatic brain injury (TBI), mild cognitive impairment (MCI), and early Alzheimer’s disease (AD). Neurological disorders often cannot be accurately diagnosed without the use of advanced imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). Non-quantitative task-based examinations are also used. None of these techniques, however, are typically performed in the primary care setting. Furthermore, the time and expense involved often deters physicians from performing them, leading to potential worse prognoses for patients. If feasible, screening for cognitive deficits using scalp EEG would provide a fast, inexpensive, and less invasive alternative for evaluation of TBI post injury and detection of MCI and early AD. In this work various measures of EEG complexity and causality are explored as means of detecting cognitive deficits. Complexity measures include eventrelated Tsallis entropy, multiscale entropy, inter-regional transfer entropy delays, and regional variation in common spectral features, and graphical analysis of EEG inter-channel coherence. Causality analysis based on nonlinear state space reconstruction is explored in case studies of intensive care unit (ICU) signal reconstruction and detection of cognitive deficits via EEG reconstruction models. Significant contributions in this work include: (1) innovative entropy-based methods for analyzing event-related EEG data; (2) recommendations regarding differences in MCI/AD of common spectral and complexity features for different scalp regions and protocol conditions; (3) development of novel artificial neural network techniques for multivariate signal reconstruction; and (4) novel EEG biomarkers for detection of dementia
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