Removal of Confounding Effects of Global Signal in Functional MRI Analyses

AbstractWhen fields lack consensus standards and ground truths for their analytic methods, reproducibility tends to be more of an ideal than a reality. Such has been the case for functional neuroimaging, where there exists a sprawling space of tools from which scientists can construct processing pipelines and draw interpretations. We provide a critical evaluation of the impact of differences observed in results across five independently developed functional MRI minimal preprocessing pipelines. We show that even when handling the same exact data, inter-pipeline agreement was only moderate, with the specific steps that contribute to the lack of agreement varying across pipeline comparisons. Using a densely sampled test-retest dataset, we show that the limitations imposed by inter-pipeline agreement mainly become appreciable when the reliability of the underlying data is high. We highlight the importance of comparison among analytic tools and parameters, as both widely debated (e.g., global signal regression) and commonly overlooked (e.g., MNI template version) decisions were each found to lead to marked variation. We provide recommendations for incorporating tool-based variability in functional neuroimaging analyses and a supporting infrastructure.

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Reproducibility of functional brain alterations in major depressive disorder: evidence from a multisite resting-state functional MRI study with 1,434 individuals

10.1101/524496 ◽

2019 ◽

Author(s):

Mingrui Xia ◽

Tianmei Si ◽

Xiaoyi Sun ◽

Qing Ma ◽

Bangshan Liu ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Functional Mri ◽

Resting State ◽

Disease Onset ◽

Low Frequency ◽

Clinical Variable ◽

Major Depressive ◽

Global Signal ◽

Mri Study

AbstractResting-state functional MRI (R-fMRI) studies have demonstrated widespread alterations in brain function in patients with major depressive disorder (MDD). However, a clear and consistent conclusion regarding a repeatable pattern of MDD-relevant alterations is still limited due to the scarcity of large-sample, multisite datasets. Here, we address this issue by including a large R-fMRI dataset with 1,434 participants (709 patients with MDD and 725 healthy controls) from five centers in China. Individual functional activity maps that represent very local to long-range connections are computed using the amplitude of low-frequency fluctuations, regional homogeneity and distance-related functional connectivity strength. The reproducibility analyses involve different statistical strategies, global signal regression, across-center consistency, clinical variables, and sample size. We observed significant hypoactivity in the orbitofrontal, sensorimotor, and visual cortices and hyperactivity in the frontoparietal cortices in MDD patients compared to the controls. These alterations are not affected by different statistical analysis strategies, global signal regression and medication status and are generally reproducible across centers. However, these between-group differences are partially influenced by the episode status and the age of disease onset in patients, and the brain-clinical variable relationship exhibits poor cross-center reproducibility. Bootstrap analyses reveal that at least 400 subjects in each group are required to replicate significant alterations (an extent threshold of P<.05 and a height threshold of P<.001) at 50% reproducibility. Together, these results highlight reproducible patterns of functional alterations in MDD and relevant influencing factors, which provides crucial guidance for future neuroimaging studies of this disorder.

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