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Quantifying and Mitigating Site Effects in Multi-Site Consortium Studies

Award Number: F32MH139340
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/10/2026
PERIOD OF PERFORMANCE END DATE: 09/09/2027

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Quantifying and Mitigating Site Effects in Multi-Site Consortium Studies - PROJECT SUMMARY AND ABSTRACT The emergence of high-fidelity neuroimaging techniques has unleashed a wealth of data for neuroscientists. One such domain, connectomics, leverages magnetic resonance imaging datasets to produce graphs describing brain connectivity, and may hold insights into individual-specific neurological phenotypes such as cognitive capacities or mental illness. These datasets, often obtained through costly macro-scale collection efforts limited to local participant recruitment, are generally aggregated through mega-studies using standardized imaging protocols across multiple sites to enhance demographic diversity. Unfortunately, many of these neuroimaging modalities suffer from site effects, wherein site-specific biases are imparted to the measurements. This problem is compounded by a core aim of mega-studies, in that the phenotypic and demographic diversity across sites can confound attempts to isolate veridical biological signals from spurious site effects. The magnitude of these site effects creates hurdles for generalizing neuroimaging insights to new datasets, and may complicate efforts to translate neuroscientific conclusions to clinical practice. This project aims to address these challenges by quantifying, understanding, and establishing best practices for managing site effects in connectome data from neuroimaging mega-studies. We propose to use the Adolescent Brain Cognitive Development Study, an expansive dataset from over 10,000 children across 21 sites. Aim 1 explores the impact of data pre-processing choices on measurement harmonization. We propose the use of a novel statistic for quantifying site effects in high-dimensional connectomics data coupled with a multiverse analysis to identify strategies that, while potentially desirable in some regards, may worsen the harmonization of subsequent derivatives downstream. Aim 2 seeks to identify the sensitivity of data harmonization to data collection procedures. While the techniques that underpin existing data harmonization strategies are known to be sensitive to unmeasured variables, it is unknown the extent to which traditionally unobserved phenotypic and demographic information may obfuscate the identification of site effects downstream. Aim 3 is to devise novel techniques for estimating and removing site effects in connectome data. While existing techniques for site effect correction heavily leverage feature-by-feature linear modeling approaches, cutting-edge graph analytic approaches have the potential to radically alter the applicability, flexibility, and generalizability of data harmonization for connectomes. This project has the potential to provide a holistic understanding of site effects, an often overlooked dimension of variability in neuroimaging data. By doing so, it will contribute to refining best practices for collecting, processing, and analyzing current and future neuroimaging mega-studies, ultimately enhancing the reliability and applicability of neuroscientific insights derived from these datasets.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $75,520 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	000	1	3/10/2026	NEW	$75,520
														Subtotal = $75,520

Grand Total All Awards = $75,520

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Quantifying and Mitigating Site Effects in Multi-Site Consortium Studies

Award Number: F32MH139340

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/10/2026

PERIOD OF PERFORMANCE END DATE: 09/09/2027

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