Controlling for Spurious Nonlinear Dependence in Connectivity Analyses

Recent analysis methods can capture nonlinear interactions between brain regions. However, noise sources might induce spurious nonlinear relationships between the responses in different regions. Previous research has demonstrated that traditional denoising techniques effectively remove noise-induced linear relationships between brain areas, but it is unknown whether these techniques can remove spurious nonlinear relationships. To address this question, we analyzed fMRI responses while participants watched the film Forrest Gump. We tested whether nonlinear Multivariate Pattern Dependence Networks (MVPN) outperform linear MVPN in non-denoised data, and whether this difference is reduced after CompCor denoising. Whereas nonlinear MVPN outperformed linear MVPN in the non-denoised data, denoising removed these nonlinear interactions. We replicated our results using different neural network architectures as the bases of MVPN, different activation functions (ReLU and sigmoid), different dimensionality reduction techniques for CompCor (PCA and ICA), and multiple datasets, demonstrating that CompCor's ability to remove nonlinear interactions is robust across these analysis choices and across different groups of participants. Finally, we asked whether information contributing to the removal of nonlinear interactions is localized to specific anatomical regions of no interest or to specific principal components. We denoised the data 8 separate times by regressing out 5 principal components extracted from combined white matter (WM) and cerebrospinal fluid (CSF), each of the 5 components separately, 5 components extracted from WM only, and 5 components extracted solely from CSF. In all cases, denoising was sufficient to remove the observed nonlinear interactions.