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Global signal regression strengthens association between resting-state functional connectivity and behavior.

ABSTRACT: Global signal regression (GSR) is one of the most debated preprocessing strategies for resting-state functional MRI. GSR effectively removes global artifacts driven by motion and respiration, but also discards globally distributed neural information and introduces negative correlations between certain brain regions. The vast majority of previous studies have focused on the effectiveness of GSR in removing imaging artifacts, as well as its potential biases. Given the growing interest in functional connectivity fingerprinting, here we considered the utilitarian question of whether GSR strengthens or weakens associations between resting-state functional connectivity (RSFC) and multiple behavioral measures across cognition, personality and emotion. By applying the variance component model to the Brain Genomics Superstruct Project (GSP), we found that behavioral variance explained by whole-brain RSFC increased by an average of 47% across 23 behavioral measures after GSR. In the Human Connectome Project (HCP), we found that behavioral variance explained by whole-brain RSFC increased by an average of 40% across 58 behavioral measures, when GSR was applied after ICA-FIX de-noising. To ensure generalizability, we repeated our analyses using kernel regression. GSR improved behavioral prediction accuracies by an average of 64% and 12% in the GSP and HCP datasets respectively. Importantly, the results were consistent across methods. A behavioral measure with greater RSFC-explained variance (using the variance component model) also exhibited greater prediction accuracy (using kernel regression). A behavioral measure with greater improvement in behavioral variance explained after GSR (using the variance component model) also enjoyed greater improvement in prediction accuracy after GSR (using kernel regression). Furthermore, GSR appeared to benefit task performance measures more than self-reported measures. Since GSR was more effective at removing motion-related and respiratory-related artifacts, GSR-related increases in variance explained and prediction accuracies were unlikely the result of motion-related or respiratory-related artifacts. However, it is worth emphasizing that the current study focused on whole-brain RSFC, so it remains unclear whether GSR improves RSFC-behavioral associations for specific connections or networks. Overall, our results suggest that at least in the case for young healthy adults, GSR strengthens the associations between RSFC and most (although not all) behavioral measures. Code for the variance component model and ridge regression can be found here: https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/preprocessing/Li2019_GSR.

SUBMITTER: Li J

PROVIDER: S-EPMC6585462 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Global signal regression strengthens association between resting-state functional connectivity and behavior.

Li Jingwei J Kong Ru R Liégeois Raphaël R Orban Csaba C Tan Yanrui Y Sun Nanbo N Holmes Avram J AJ Sabuncu Mert R MR Ge Tian T Yeo B T Thomas BTT

NeuroImage 20190408

Global signal regression (GSR) is one of the most debated preprocessing strategies for resting-state functional MRI. GSR effectively removes global artifacts driven by motion and respiration, but also discards globally distributed neural information and introduces negative correlations between certain brain regions. The vast majority of previous studies have focused on the effectiveness of GSR in removing imaging artifacts, as well as its potential biases. Given the growing interest in functiona ...[more]

PMID: 30974241

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Project description:The influence of global BOLD fluctuations on resting state functional connectivity in fMRI data remains a topic of debate, with little consensus. In this study, we assessed the effects of global signal regression (GSR) on effective connectivity within and between resting state networks (RSNs) - as estimated with dynamic causal modelling (DCM) for resting state fMRI (rsfMRI). DCM incorporates a forward (generative) model that quantifies the contribution of different types of noise (including global measurement noise), effective connectivity, and (neuro)vascular processes to functional connectivity measurements. DCM analyses were applied to two different designs; namely, longitudinal and cross-sectional designs. In the modelling of longitudinal designs, we considered four extensive longitudinal resting state fMRI datasets with a total number of 20 subjects. In the analysis of cross-sectional designs, we used rsfMRI data from 361 subjects from the Human Connectome Project. We hypothesized that (1) GSR would have no discernible impact on effective connectivity estimated with DCM, and (2) GSR would be reflected in the parameters representing global measurement noise. Additionally, we performed comparative analyses of information gain with and without GSR. Our results showed negligible to small effects of GSR on effective connectivity within small (separately estimated) RSNs. However, although the effect sizes were small, there was substantial to conclusive evidence for an effect of GSR on connectivity parameters. For between-network connectivity, we found two important effects: the effect of GSR on between-network effective connectivity (averaged over all connections) was negligible to small, while the effect of GSR on individual connections was non-negligible. In the cross-sectional (but not in the longitudinal) data, some connections showed substantial to conclusive evidence for an effect of GSR. Contrary to our expectations, we found either no effect (in the longitudinal designs) or a non-specific (cross-sectional design) effect of GSR on parameters characterising (global) measurement noise. Data without GSR were found to be more informative than data with GSR; however, in small resting state networks the precision of posterior estimates was greater after GSR. In conclusion, GSR is a minor concern in DCM studies; however, quantitative interpretation of between-network connections (as opposed to average between-network connectivity) and noise parameters should be treated with some caution. The Kullback-Leibler divergence of the posterior from the prior (i.e., information gain) - together with the precision of posterior estimates - might offer a useful measure to assess the appropriateness of GSR in resting state fMRI.

Project description:BackgroundExternalizing behavior has been attributed, in part, to decreased frontolimbic control over amygdala activation. However, little is known about developmental trajectories of frontoamygdalar functional connectivity and its relation to externalizing behavior. The present study addresses this gap by examining longitudinal associations between adolescent and adult externalizing behavior and amygdala-anterior cingulate cortex (ACC) and amygdala-orbitofrontal cortex (OFC) resting-state functional connectivity in a sample of 111 typically developing participants aged 11-23 at baseline.MethodsParticipants completed two-to-four data waves spaced approximately two years apart, resulting in a total of 309 data points. At each data wave, externalizing behavior was measured using the Externalizing Behavior Broadband Scale from the Achenbach Youth/Adult Self-Report questionnaire. Resting-state fMRI preprocessing was performed using FSL. Amygdala functional connectivity was examined using AFNI. The longitudinal association between externalizing behavior and amygdala-ACC/OFC functional connectivity was examined using linear mixed effect models in R.ResultsExternalizing behavior was associated with increased amygdala-ACC and amygdala-OFC resting-state functional connectivity across adolescence and young adulthood. For amygdala-ACC connectivity, externalizing behavior at baseline primarily drove this association, whereas for amygdala-OFC functional connectivity, change in externalizing behavior relative to baseline drove the main effect of externalizing behavior on amygdala-OFC functional connectivity. No evidence was found for differential developmental trajectories of frontoamygdalar connectivity for different levels of externalizing behavior (i.e., age-by-externalizing behavior interaction effect).ConclusionsHigher externalizing behavior is associated with increased resting-state attunement between the amygdala and ACC/OFC, perhaps indicating a generally more vigilant state for neural networks important for emotional processing and control.

Dataset Information

Global signal regression strengthens association between resting-state functional connectivity and behavior.

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Global signal regression strengthens association between resting-state functional connectivity and behavior.

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