"Functional connectivity" techniques are commonplace tools for studying brain organization. A critical element of these analyses is to distinguish variance due to neurobiological signals from variance due to nonneurobiological signals. Multiecho fMRI techniques are a promising means for making such distinctions based on signal decay properties. Here, we report that multiecho fMRI techniques enable excellent removal of certain kinds of artifactual variance, namely, spatially focal artifacts due to motion. By removing these artifacts, multiecho techniques reveal frequent, large-amplitude blood oxygen level-dependent (BOLD) signal changes present across all gray matter that are also linked to motion. These whole-brain BOLD signals could reflect widespread neural processes or other processes, such as alterations in blood partial pressure of carbon dioxide (pCO2) due to ventilation changes. By acquiring multiecho data while monitoring breathing, we demonstrate that whole-brain BOLD signals in the resting state are often caused by changes in breathing that co-occur with head motion. These widespread respiratory fMRI signals cannot be isolated from neurobiological signals by multiecho techniques because they occur via the same BOLD mechanism. Respiratory signals must therefore be removed by some other technique to isolate neurobiological covariance in fMRI time series. Several methods for removing global artifacts are demonstrated and compared, and were found to yield fMRI time series essentially free of motion-related influences. These results identify two kinds of motion-associated fMRI variance, with different physical mechanisms and spatial profiles, each of which strongly and differentially influences functional connectivity patterns. Distance-dependent patterns in covariance are nearly entirely attributable to non-BOLD artifacts.
Trial registration: ClinicalTrials.gov NCT01031407.
Keywords: fMRI; functional connectivity; motion artifact; multiecho; respiration.