15,533 research outputs found
Image analysis and statistical inference in neuroimaging with R
R is a language and environment for statistical computing and graphics.
It can be considered an alternative implementation of the S language
developed in the 1970s and 1980s for data analysis and graphics (Becker and
Chambers, 1984; Becker et al., 1988). The R language is part of the GNU
project and offers versions that compile and run on almost every major
operating system currently available. We highlight several R packages built
specifically for the analysis of neuroimaging data in the context of
functional MRI, diffusion tensor imaging, and dynamic contrast-enhanced MRI.
We review their methodology and give an overview of their capabilities for
neuroimaging. In addition we summarize some of the current activities in the
area of neuroimaging software development in R
Faster Family-wise Error Control for Neuroimaging with a Parametric Bootstrap
In neuroimaging, hundreds to hundreds of thousands of tests are performed
across a set of brain regions or all locations in an image. Recent studies have
shown that the most common family-wise error (FWE) controlling procedures in
imaging, which rely on classical mathematical inequalities or Gaussian random
field theory, yield FWE rates that are far from the nominal level. Depending on
the approach used, the FWER can be exceedingly small or grossly inflated. Given
the widespread use of neuroimaging as a tool for understanding neurological and
psychiatric disorders, it is imperative that reliable multiple testing
procedures are available. To our knowledge, only permutation joint testing
procedures have been shown to reliably control the FWER at the nominal level.
However, these procedures are computationally intensive due to the increasingly
available large sample sizes and dimensionality of the images, and analyses can
take days to complete. Here, we develop a parametric bootstrap joint testing
procedure. The parametric bootstrap procedure works directly with the test
statistics, which leads to much faster estimation of adjusted \emph{p}-values
than resampling-based procedures while reliably controlling the FWER in sample
sizes available in many neuroimaging studies. We demonstrate that the procedure
controls the FWER in finite samples using simulations, and present region- and
voxel-wise analyses to test for sex differences in developmental trajectories
of cerebral blood flow
Topological inference for EEG and MEG
Neuroimaging produces data that are continuous in one or more dimensions.
This calls for an inference framework that can handle data that approximate
functions of space, for example, anatomical images, time--frequency maps and
distributed source reconstructions of electromagnetic recordings over time.
Statistical parametric mapping (SPM) is the standard framework for whole-brain
inference in neuroimaging: SPM uses random field theory to furnish -values
that are adjusted to control family-wise error or false discovery rates, when
making topological inferences over large volumes of space. Random field theory
regards data as realizations of a continuous process in one or more dimensions.
This contrasts with classical approaches like the Bonferroni correction, which
consider images as collections of discrete samples with no continuity
properties (i.e., the probabilistic behavior at one point in the image does not
depend on other points). Here, we illustrate how random field theory can be
applied to data that vary as a function of time, space or frequency. We
emphasize how topological inference of this sort is invariant to the geometry
of the manifolds on which data are sampled. This is particularly useful in
electromagnetic studies that often deal with very smooth data on scalp or
cortical meshes. This application illustrates the versatility and simplicity of
random field theory and the seminal contributions of Keith Worsley
(1951--2009), a key architect of topological inference.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS337 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Increasing power for voxel-wise genome-wide association studies : the random field theory, least square kernel machines and fast permutation procedures
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
Generative discriminative models for multivariate inference and statistical mapping in medical imaging
This paper presents a general framework for obtaining interpretable
multivariate discriminative models that allow efficient statistical inference
for neuroimage analysis. The framework, termed generative discriminative
machine (GDM), augments discriminative models with a generative regularization
term. We demonstrate that the proposed formulation can be optimized in closed
form and in dual space, allowing efficient computation for high dimensional
neuroimaging datasets. Furthermore, we provide an analytic estimation of the
null distribution of the model parameters, which enables efficient statistical
inference and p-value computation without the need for permutation testing. We
compared the proposed method with both purely generative and discriminative
learning methods in two large structural magnetic resonance imaging (sMRI)
datasets of Alzheimer's disease (AD) (n=415) and Schizophrenia (n=853). Using
the AD dataset, we demonstrated the ability of GDM to robustly handle
confounding variations. Using Schizophrenia dataset, we demonstrated the
ability of GDM to handle multi-site studies. Taken together, the results
underline the potential of the proposed approach for neuroimaging analyses.Comment: To appear in MICCAI 2018 proceeding
Cluster Failure Revisited: Impact of First Level Design and Data Quality on Cluster False Positive Rates
Methodological research rarely generates a broad interest, yet our work on
the validity of cluster inference methods for functional magnetic resonance
imaging (fMRI) created intense discussion on both the minutia of our approach
and its implications for the discipline. In the present work, we take on
various critiques of our work and further explore the limitations of our
original work. We address issues about the particular event-related designs we
used, considering multiple event types and randomisation of events between
subjects. We consider the lack of validity found with one-sample permutation
(sign flipping) tests, investigating a number of approaches to improve the
false positive control of this widely used procedure. We found that the
combination of a two-sided test and cleaning the data using ICA FIX resulted in
nominal false positive rates for all datasets, meaning that data cleaning is
not only important for resting state fMRI, but also for task fMRI. Finally, we
discuss the implications of our work on the fMRI literature as a whole,
estimating that at least 10% of the fMRI studies have used the most problematic
cluster inference method (P = 0.01 cluster defining threshold), and how
individual studies can be interpreted in light of our findings. These
additional results underscore our original conclusions, on the importance of
data sharing and thorough evaluation of statistical methods on realistic null
data
Can parametric statistical methods be trusted for fMRI based group studies?
The most widely used task fMRI analyses use parametric methods that depend on
a variety of assumptions. While individual aspects of these fMRI models have
been evaluated, they have not been evaluated in a comprehensive manner with
empirical data. In this work, a total of 2 million random task fMRI group
analyses have been performed using resting state fMRI data, to compute
empirical familywise error rates for the software packages SPM, FSL and AFNI,
as well as a standard non-parametric permutation method. While there is some
variation, for a nominal familywise error rate of 5% the parametric statistical
methods are shown to be conservative for voxel-wise inference and invalid for
cluster-wise inference; in particular, cluster size inference with a cluster
defining threshold of p = 0.01 generates familywise error rates up to 60%. We
conduct a number of follow up analyses and investigations that suggest the
cause of the invalid cluster inferences is spatial auto correlation functions
that do not follow the assumed Gaussian shape. By comparison, the
non-parametric permutation test, which is based on a small number of
assumptions, is found to produce valid results for voxel as well as cluster
wise inference. Using real task data, we compare the results between one
parametric method and the permutation test, and find stark differences in the
conclusions drawn between the two using cluster inference. These findings speak
to the need of validating the statistical methods being used in the
neuroimaging field
The empirical replicability of task-based fMRI as a function of sample size
Replicating results (i.e. obtaining consistent results using a new independent dataset) is an essential part of good science. As replicability has consequences for theories derived from empirical studies, it is of utmost importance to better understand the underlying mechanisms influencing it. A popular tool for non-invasive neuroimaging studies is functional magnetic resonance imaging (fMRI). While the effect of underpowered studies is well documented, the empirical assessment of the interplay between sample size and replicability of results for task-based fMRI studies remains limited. In this work, we extend existing work on this assessment in two ways. Firstly, we use a large database of 1400 subjects performing four types of tasks from the IMAGEN project to subsample a series of independent samples of increasing size. Secondly, replicability is evaluated using a multi-dimensional framework consisting of 3 different measures: (un)conditional test-retest reliability, coherence and stability. We demonstrate not only a positive effect of sample size, but also a trade-off between spatial resolution and replicability. When replicability is assessed voxelwise or when observing small areas of activation, a larger sample size than typically used in fMRI is required to replicate results. On the other hand, when focussing on clusters of voxels, we observe a higher replicability. In addition, we observe variability in the size of clusters of activation between experimental paradigms or contrasts of parameter estimates within these
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