biostudies-literatureUnknown46(12)Muganga THelmholtz Portfolio Theme "Supercomputing and Modelling for the Human Brain"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.Human brain mappinge70323https://www.ebi.ac.uk/biostudies/studies/S-EPMC12368596biostudies-literatureVoxel-Wise or Region-Wise Nuisance Regression for Functional Connectivity Analyses: Does It Matter?PMC12368596Patil KRSasse LEickhoff SBNieto NLarabi DICaspers JMuganga TfalseVoxel-Wise or Region-Wise Nuisance Regression for Functional Connectivity Analyses: Does It Matter?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.2025-01-01T00:00:00Z2025 Aug2026-05-07T05:05:42.053Z2026-04-07T22:34:19.575ZS-EPMC123685964083847410.1002/hbm.70323