Methods for cleaning the BOLD fMRI signal

Blood oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI) has rapidly become a popular technique for the investigation of brain function in healthy individuals, patients as well as in animal studies. However, the BOLD signal arises from a complex mixture of neuronal, metabolic and vascular processes, being therefore an indirect measure of neuronal activity, which is further severely corrupted by multiple non-neuronal fluctuations of instrumental, physiological or subject-specific origin. This review aims to provide a comprehensive summary of existing methods for cleaning the BOLD fMRI signal. The description is given from a methodological point of view, focusing on the operation of the different techniques in addition to pointing out the advantages and limitations in their application. Since motion-related and physiological noise fluctuations are two of the main noise components of the signal, techniques targeting their removal are primarily addressed, including both data-driven approaches and using external recordings. Data-driven approaches, which are less specific in the assumed model and can simultaneously reduce multiple noise fluctuations, are mainly based on data decomposition techniques such as principal and independent component analysis. Importantly, the usefulness of strategies that benefit from the information available in the phase component of the signal, or in multiple signal echoes is also highlighted. The use of global signal regression for denoising is also addressed. Finally, practical recommendations regarding the optimization of the preprocessing pipeline for the purpose of denoising and future venues of research are indicated. Through the review, we summarize the importance of signal denoising as an essential step in the analysis pipeline of task-based and resting state fMRI studies.