arXiv subjects

Benjamin B. Risk

Publications and source records attributed to Benjamin B. Risk.

5 recordsLinked to original sources

arXiv2026

Causal Inference for Preprocessed Outcomes with an Application to Functional Connectivity

In biomedical research, repeated measurements within each subject are often processed to remove artifacts and unwanted sources of variation. The resulting data are used to construct derived outcomes that act as proxies for scientific outcomes that are not directly observable. Although intra-subject processing is widely used, its impact on inter-subject statistical inference has not been systematically studied, and a principled framework for causal analysis in this setting is lacking. In this article, we propose a semiparametric framework for causal inference with derived outcomes obtained after intra-subject processing. This framework applies to settings with a modular structure, where intra-subject analyses are conducted independently across subjects and are followed by inter-subject analyses based on parameters from the intra-subject stage. We develop multiply robust estimators of causal parameters under rate conditions on both intra-subject and inter-subject models, which allows the use of flexible machine learning. We specialize the framework to a mediation setting and focus on the natural direct effect. For high dimensional inference, we employ a step-down procedure that controls the exceedance rate of the false discovery proportion. Simulation studies demonstrate the superior performance of the proposed approach. We apply our method to estimate the impact of stimulant medication on brain connectivity in children with autism spectrum disorder.

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arXiv2024

Nonparametric Motion Control in Functional Connectivity Studies in Children with Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition associated with difficulties with social interactions, communication, and restricted or repetitive behaviors. To characterize ASD, investigators often use functional connectivity derived from resting-state functional magnetic resonance imaging of the brain. However, participants' head motion during the scanning session can induce motion artifacts. Many studies remove participants with excessive motion, and then estimate the effect of diagnosis on functional connectivity using linear regression. However, participant exclusions and linearity assumptions can cause biases. We propose an estimand that quantifies the difference in average functional connectivity in autistic and non-ASD children while standardizing motion relative to the low motion distribution in scans that pass motion quality control. We introduce a nonparametric estimator for motion control, called MoCo, that uses all participants and flexibly models the impacts of motion and other relevant features using an ensemble of machine learning methods. We establish large-sample efficiency and multiple robustness of our proposed estimator. The framework is applied to estimate the difference in functional connectivity between 132 autistic and 245 non-ASD children, of which 34 and 126 pass motion quality control, respectively. MoCo appears to dramatically reduce motion artifacts compared to a standard approach with no participant removal, while more efficiently utilizing participant data and accounting for possible selection biases compared to participant removal.

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arXiv2019

ACE of Space: Estimating Genetic Components of High-Dimensional Imaging Data

It is of great interest to quantify the contributions of genetic variation to brain structure and function, which are usually measured by high-dimensional imaging data (e.g., magnetic resonance imaging). In addition to the variance, the covariance patterns in the genetic effects of a functional phenotype are of biological importance, and covariance patterns have been linked to psychiatric disorders. The aim of this paper is to develop a scalable method to estimate heritability and the non-stationary covariance components in high-dimensional imaging data from twin studies. Our motivating example is from the Human Connectome Project (HCP). Several major big-data challenges arise from estimating the genetic and environmental covariance functions of functional phenotypes extracted from imaging data, such as cortical thickness with 60,000 vertices. Notably, truncating to positive eigenvalues and their eigenfunctions from unconstrained estimators can result in large bias. This motivated our development of a novel estimator ensuring positive semidefiniteness. Simulation studies demonstrate large improvements over existing approaches, both with respect to heritability estimates and covariance estimation. We applied the proposed method to cortical thickness data from the HCP. Our analysis suggests fine-scale differences in covariance patterns, identifying locations in which genetic control is correlated with large areas of the brain and locations where it is highly localized.

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arXiv2017

Optimization and Testing in Linear Non-Gaussian Component Analysis

Independent component analysis (ICA) decomposes multivariate data into mutually independent components (ICs). The ICA model is subject to a constraint that at most one of these components is Gaussian, which is required for model identifiability. Linear non-Gaussian component analysis (LNGCA) generalizes the ICA model to a linear latent factor model with any number of both non-Gaussian components (signals) and Gaussian components (noise), where observations are linear combinations of independent components. Although the individual Gaussian components are not identifiable, the Gaussian subspace is identifiable. We introduce an estimator along with its optimization approach in which non-Gaussian and Gaussian components are estimated simultaneously, maximizing the discrepancy of each non-Gaussian component from Gaussianity while minimizing the discrepancy of each Gaussian component from Gaussianity. When the number of non-Gaussian components is unknown, we develop a statistical test to determine it based on resampling and the discrepancy of estimated components. Through a variety of simulation studies, we demonstrate the improvements of our estimator over competing estimators, and we illustrate the effectiveness of the test to determine the number of non-Gaussian components. Further, we apply our method to real data examples and demonstrate its practical value.

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arXiv2017

Linear Non-Gaussian Component Analysis via Maximum Likelihood

Independent component analysis (ICA) is popular in many applications, including cognitive neuroscience and signal processing. Due to computational constraints, principal component analysis is used for dimension reduction prior to ICA (PCA+ICA), which could remove important information. The problem is that interesting independent components (ICs) could be mixed in several principal components that are discarded and then these ICs cannot be recovered. We formulate a linear non-Gaussian component model with Gaussian noise components. To estimate this model, we propose likelihood component analysis (LCA), in which dimension reduction and latent variable estimation are achieved simultaneously. Our method orders components by their marginal likelihood rather than ordering components by variance as in PCA. We present a parametric LCA using the logistic density and a semi-parametric LCA using tilted Gaussians with cubic B-splines. Our algorithm is scalable to datasets common in applications (e.g., hundreds of thousands of observations across hundreds of variables with dozens of latent components). In simulations, latent components are recovered that are discarded by PCA+ICA methods. We apply our method to multivariate data and demonstrate that LCA is a useful data visualization and dimension reduction tool that reveals features not apparent from PCA or PCA+ICA. We also apply our method to an fMRI experiment from the Human Connectome Project and identify artifacts missed by PCA+ICA. We present theoretical results on identifiability of the linear non-Gaussian component model and consistency of LCA.

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