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Anderson M. Winkler

Publications and source records attributed to Anderson M. Winkler.

3 recordsLinked to original sources

A comprehensive framework for statistical testing of brain dynamics

Neural activity data can be associated with behavioral and physiological variables by analyzing their changes in the temporal domain. However, such relationships are often difficult to quantify and test, requiring advanced computational modeling approaches. Here, we provide a protocol for the statistical analysis of brain dynamics and for testing their associations with behavioral, physiological and other non-imaging variables. The protocol is based on an open-source Python package built on a generalization of the hidden Markov model (HMM) - the Gaussian-linear HMM - and supports multiple experimental modalities, including task-based and resting-state studies, often used to explore a wide range of questions in neuroscience and mental health. Our toolbox is available as both a Python library and a graphical interface, so it can be used by researchers with or without programming experience. Statistical inference is performed by using permutation-based methods and structured Monte Carlo resampling, and the framework can easily handle confounding variables, multiple testing corrections and hierarchical relationships within the data, among other features. The package includes tools developed to facilitate the intuitive visualization of statistical results, along with comprehensive documentation and step-by-step tutorials for data interpretation. Overall, the protocol covers the full workflow for the statistical analysis of functional neural data and their temporal dynamics.

q-bio.NC

False Discovery Rate and Localizing Power

False discovery rate (FDR) is commonly used for correction for multiple testing in neuroimaging studies. However, when using two-tailed tests, making directional inferences about the results can lead to a vastly inflated error rate, even approaching 100% in some cases. This happens because FDR controls the error rate only globally, over all tests, not within subsets, such as among those in only one or another direction. Here we consider and evaluate different strategies for FDR control in such cases, using both synthetic and real imaging data. Approaches that separate the tests by direction of the hypothesis test, or by the direction of the resulting test statistic, more properly control the directional error rate and preserve FDR benefits, albeit with a doubled risk of errors under complete absence of signal. Strategies that combine tests in both directions, or that use simple two-tailed p-values, can lead to invalid directional conclusions, even if these tests remain globally valid. A solution to this problem is through the use of selective inference, whereby positive and negative tails are treated as sets (families), which are screened locally, then subjected to FDR at a modified level that controls average FDR over those that survive the initial screening. Moreover, the BKY procedure can be used in place of the well-known Benjamini-Hochberg, yielding additional power. These methods are easy to implement. Finally, to enable valid thresholding for directional inference, we suggest that imaging software should allow the user to set asymmetrical thresholds for the two sides of the statistical map. While FDR continues to be a valid, powerful procedure for multiple testing correction, care is needed when making directional inferences for two-tailed tests, or more broadly, when making any localized inference.

stat.ME

Permutation Inference for Canonical Correlation Analysis

Canonical correlation analysis (CCA) has become a key tool for population neuroimaging, allowing investigation of associations between many imaging and non-imaging measurements. As other variables are often a source of variability not of direct interest, previous work has used CCA on residuals from a model that removes these effects, then proceeded directly to permutation inference. We show that such a simple permutation test leads to inflated error rates. The reason is that residualisation introduces dependencies among the observations that violate the exchangeability assumption. Even in the absence of nuisance variables, however, a simple permutation test for CCA also leads to excess error rates for all canonical correlations other than the first. The reason is that a simple permutation scheme does not ignore the variability already explained by previous canonical variables. Here we propose solutions for both problems: in the case of nuisance variables, we show that transforming the residuals to a lower dimensional basis where exchangeability holds results in a valid permutation test; for more general cases, with or without nuisance variables, we propose estimating the canonical correlations in a stepwise manner, removing at each iteration the variance already explained, while dealing with different number of variables in both sides. We also discuss how to address the multiplicity of tests, proposing an admissible test that is not conservative, and provide a complete algorithm for permutation inference for CCA.

stat.ME