Real-time fMRI neurofeedback allows to learn control over activity in a localized brain region. However, with fMRI, physiological factors such as the cardiac cycle and respiration interfere with the measurement of brain activation. In conventional fMRI studies this is usually mitigated by inclusion of motion parameters and/or physiological parameters as nuisance regressors at the analysis stage, allowing to correct for and filter out such confounders. In real-time fMRI, however, such an approach is not routinely feasible due to the necessity to process all signals during the runtime of an experiment. The absence of runtime correction can therefore compromise real-time fMRI study outcomes reporting volitional self-regulation capability as BOLD signal changes. This is especially true for BOLD signal changes in subcortical regions situated close to blood vessels or air vavities, such as the amygdala. We therefore aimed to establish the effects of motion, heart rate, heart rate variability, and respiratory volume on learning effects, which means here an increase in BOLD signal change over NF training, in an amygdala neurofeedback experiment. Specifically, we investigate motion parameters from two emotion regulation studies - performed at 3T and 7T scanners - and additionally acquired physiological variance for the latter one. Our results revealed differences in these parameters between groups and especially between regulation and resting periods within each participant. However, strictly considering these parameters as nuisance regressors in data analysis revealed that the learning of volitional self-regulation of the amygdala is not driven by motion and physiological changes. As validation of our real-time findings, we compare them to the gold standard of assessment of motion and physiology from the Human Connectome Project. Based on this, we recommend to carefully report neurofeedback study results including physiological nuisance regression. To our knowledge, this is the first study investigating the effects of motion and physiological noise correction on neurofeedback BOLD effects.

Motion and physiological noise effects on amygdala real-time fMRI neurofeedback learning