Improving Between-Group Effect Size for Multi-Site Functional Connectivity Data via Site-Wise De-Meaning

Background: Multi-site functional MRI (fMRI) databases are becoming increasingly prevalent in the study of neurodevelopmental and psychiatric disorders. However, multi-site databases are known to introduce site effects that may confound neurobiological and measures such as functional connectivity (F...

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Main Authors: Alexandra M. Reardon, Kaiming Li, Xiaoping P. Hu
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-12-01
Series:Frontiers in Computational Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fncom.2021.762781/full
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author Alexandra M. Reardon
Kaiming Li
Xiaoping P. Hu
Xiaoping P. Hu
author_facet Alexandra M. Reardon
Kaiming Li
Xiaoping P. Hu
Xiaoping P. Hu
author_sort Alexandra M. Reardon
collection DOAJ
description Background: Multi-site functional MRI (fMRI) databases are becoming increasingly prevalent in the study of neurodevelopmental and psychiatric disorders. However, multi-site databases are known to introduce site effects that may confound neurobiological and measures such as functional connectivity (FC). Although studies have been conducted to mitigate site effects, these methods often result in reduced effect size in FC comparisons between controls and patients.Methods: We present a site-wise de-meaning (SWD) strategy in multi-site FC analysis and compare its performance with two common site-effect mitigation methods, i.e., generalized linear model (GLM) and Combining Batches (ComBat) Harmonization. For SWD, after FC was calculated and Fisher z-transformed, the site-wise FC mean was removed from each subject before group-level statistical analysis. The above methods were tested on two multi-site psychiatric consortiums [Autism Brain Imaging Data Exchange (ABIDE) and Bipolar and Schizophrenia Network on Intermediate Phenotypes (B-SNIP)]. Preservation of consistent FC alterations in patients were evaluated for each method through the effect sizes (Hedge’s g) of patients vs. controls.Results: For the B-SNIP dataset, SWD improved the effect size between schizophrenic and control subjects by 4.5–7.9%, while GLM and ComBat decreased the effect size by 22.5–42.6%. For the ABIDE dataset, SWD improved the effect size between autistic and control subjects by 2.9–5.3%, while GLM and ComBat decreased the effect size by up to 11.4%.Conclusion: Compared to the original data and commonly used methods, the SWD method demonstrated superior performance in preserving the effect size in FC features associated with disorders.
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spelling doaj.art-563ba66469a5488ea1c832fe160e18732022-12-21T20:08:01ZengFrontiers Media S.A.Frontiers in Computational Neuroscience1662-51882021-12-011510.3389/fncom.2021.762781762781Improving Between-Group Effect Size for Multi-Site Functional Connectivity Data via Site-Wise De-MeaningAlexandra M. Reardon0Kaiming Li1Xiaoping P. Hu2Xiaoping P. Hu3Department of Bioengineering, University of California, Riverside, Riverside, CA, United StatesDepartment of Bioengineering, University of California, Riverside, Riverside, CA, United StatesDepartment of Bioengineering, University of California, Riverside, Riverside, CA, United StatesCenter for Advanced Neuroimaging, University of California, Riverside, Riverside, CA, United StatesBackground: Multi-site functional MRI (fMRI) databases are becoming increasingly prevalent in the study of neurodevelopmental and psychiatric disorders. However, multi-site databases are known to introduce site effects that may confound neurobiological and measures such as functional connectivity (FC). Although studies have been conducted to mitigate site effects, these methods often result in reduced effect size in FC comparisons between controls and patients.Methods: We present a site-wise de-meaning (SWD) strategy in multi-site FC analysis and compare its performance with two common site-effect mitigation methods, i.e., generalized linear model (GLM) and Combining Batches (ComBat) Harmonization. For SWD, after FC was calculated and Fisher z-transformed, the site-wise FC mean was removed from each subject before group-level statistical analysis. The above methods were tested on two multi-site psychiatric consortiums [Autism Brain Imaging Data Exchange (ABIDE) and Bipolar and Schizophrenia Network on Intermediate Phenotypes (B-SNIP)]. Preservation of consistent FC alterations in patients were evaluated for each method through the effect sizes (Hedge’s g) of patients vs. controls.Results: For the B-SNIP dataset, SWD improved the effect size between schizophrenic and control subjects by 4.5–7.9%, while GLM and ComBat decreased the effect size by 22.5–42.6%. For the ABIDE dataset, SWD improved the effect size between autistic and control subjects by 2.9–5.3%, while GLM and ComBat decreased the effect size by up to 11.4%.Conclusion: Compared to the original data and commonly used methods, the SWD method demonstrated superior performance in preserving the effect size in FC features associated with disorders.https://www.frontiersin.org/articles/10.3389/fncom.2021.762781/fullautism spectrum disordereffect sizefunctional connectivitymulti-siteresting-state functional MRISchizophrenia
spellingShingle Alexandra M. Reardon
Kaiming Li
Xiaoping P. Hu
Xiaoping P. Hu
Improving Between-Group Effect Size for Multi-Site Functional Connectivity Data via Site-Wise De-Meaning
Frontiers in Computational Neuroscience
autism spectrum disorder
effect size
functional connectivity
multi-site
resting-state functional MRI
Schizophrenia
title Improving Between-Group Effect Size for Multi-Site Functional Connectivity Data via Site-Wise De-Meaning
title_full Improving Between-Group Effect Size for Multi-Site Functional Connectivity Data via Site-Wise De-Meaning
title_fullStr Improving Between-Group Effect Size for Multi-Site Functional Connectivity Data via Site-Wise De-Meaning
title_full_unstemmed Improving Between-Group Effect Size for Multi-Site Functional Connectivity Data via Site-Wise De-Meaning
title_short Improving Between-Group Effect Size for Multi-Site Functional Connectivity Data via Site-Wise De-Meaning
title_sort improving between group effect size for multi site functional connectivity data via site wise de meaning
topic autism spectrum disorder
effect size
functional connectivity
multi-site
resting-state functional MRI
Schizophrenia
url https://www.frontiersin.org/articles/10.3389/fncom.2021.762781/full
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