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Functional magnetic resonance imaging (fMRI) functional connectivity between brain regions is often computed using parcellations defined by functional or structural atlases. Typically, some kind of voxel averaging is performed to obtain a single temporal correlation estimate per region pair. However, several estimators can be defined for this task, with various assumptions and degrees of robustness to local noise, global noise, and region size. In this paper, we systematically present and study the properties of 9 different functional connectivity estimators taking into account the spatial structure of fMRI data, based on a simple fMRI data spatial model. These include 3 existing estimators and 6 novel estimators. We demonstrate the empirical properties of the estimators using synthetic, animal, and human data, in terms of graph structure, repeatability and reproducibility, discriminability, dependence on region size, as well as local and global noise robustness. We prove analytically the link between regional intra-correlation and inter-region correlation, and show that the choice of estimator has a strong influence on inter-correlation values. Some estimators, including the commonly used correlation of averages (ca), are positively biased, and have more dependence to region size and intra-correlation than robust alternatives, resulting in spatially-dependent bias. We define the new local correlation of averages estimator with better theoretical guarantees, lower bias, significantly lower dependence on region size (Spearman correlation 0.40 vs 0.55, paired t-test T=27.2, 𝑝 = 1.1𝑒−47), at negligible cost to discriminative power, compared to the ca estimator. The difference in connectivity pattern between the estimators is not distributed uniformly throughout the brain, but rather shows a clear ventral-dorsal gradient, suggesting that region size and intra-correlation plays an important role in shaping functional networks defined using the ca estimator, and leading to non- trivial differences in their connectivity structure. We provide an open source R package and equivalent Python implementation to facilitate the use of the new estimators, together with preprocessed rat time-series.
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Large-scale correlation screening under dependence for brain functional connectivity network inference
Data produced by resting-state functional Magnetic Resonance Imaging are widely used to infer brain functional connectivity networks. Such networks correlate neural signals to connect brain regions, which consist in groups of dependent voxels. Previous work has focused on aggregating data across voxels within predefined regions. However, the presence of within-region correlations has noticeable impacts on inter-regional correlation detection, and thus edge identification. To alleviate them, we propose to leverage techniques from the large-scale correlation screening literature, and derive simple and practical characterizations of the mean number of correlation discoveries that flexibly incorporate intra-regional dependence structures. A connectivity network inference framework is then presented. First, inter-regional correlation distributions are estimated. Then, correlation thresholds that can be tailored to one’s application are constructed for each edge. Finally, the proposed framework is implemented on synthetic and real-world datasets. This novel approach for handling arbitrary intra-regional correlation is shown to limit false positives while improving true positive rates.
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- Award ID(s):
- 2135859
- PAR ID:
- 10547930
- Publisher / Repository:
- Springer
- Date Published:
- Journal Name:
- Statistics and Computing
- Volume:
- 34
- Issue:
- 2
- ISSN:
- 0960-3174
- Subject(s) / Keyword(s):
- Brain functional connectivity Correlation screening Correlation threshold Network inference Rs-fMRI
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1007/s11222-024-10411-x
