Journal Article FZJ-2025-03561

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Voxel‐Wise or Region‐Wise Nuisance Regression for Functional Connectivity Analyses: Does It Matter?

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2025
Wiley-Liss New York, NY

Human brain mapping 46(12), e70323 () [10.1002/hbm.70323]

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Abstract: Removal of nuisance signals (such as motion) from the BOLD time series is an important aspect of preprocessing to obtain meaningful resting-state functional connectivity (rs-FC). The nuisance signals are commonly removed using denoising procedures at the finest resolution, that is the voxel time series. Typically, the voxel-wise time series are then aggregated into predefined regions or parcels to obtain an rs-FC matrix as the correlation between pairs of regional time series. Computational efficiency can be improved by denoising the aggregated regional time series instead of the voxel time series. However, a comprehensive comparison of the effects of denoising on these two resolutions is missing. In this study, we systematically investigate the effects of denoising at different time series resolutions (voxel-level and region-level) in 370 unrelated subjects from the HCP-YA dataset. Alongside the time series resolution, we considered additional factors such as aggregation method (Mean and first eigenvariate [EV]) and parcellation granularity (100, 400, and 1000 regions). To assess the effect of those choices on the utility of the resulting whole-brain rs-FC, we evaluated the individual specificity (fingerprinting) and the capacity to predict age and three cognitive scores. Our findings show generally equal or better performance for region-level denoising with notable differences depending on the aggregation method. Using Mean aggregation yielded equal individual specificity and prediction performance for voxel-level and region-level denoising. When EV was employed for aggregation, the individual specificity of voxel-level denoising was reduced compared to region-level denoising. Increasing parcellation granularity generally improved individual specificity. For the prediction of age and cognitive test scores, only fluid intelligence indicated worse performance for voxel-level denoising in the case of aggregating with the EV. Based on these results, we recommend the adoption of region-level denoising for brain-behavior investigations when using Mean aggregation. This approach offers equal individual specificity and prediction capacity with reduced computational resources for the analysis of rs-FC patterns.

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Contributing Institute(s):
  1. Gehirn & Verhalten (INM-7)
Research Program(s):
  1. 5252 - Brain Dysfunction and Plasticity (POF4-525) (POF4-525)
  2. JL SMHB - Joint Lab Supercomputing and Modeling for the Human Brain (JL SMHB-2021-2027) (JL SMHB-2021-2027)

Appears in the scientific report 2025
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 Record created 2025-08-25, last modified 2025-08-27


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