Global effects in fMRI reveal brain markers of state and trait anxiety

BackgroundTo personalize the diagnosis and treatment of anxiety, there is a need to identify biological constructs that underlie self-reported symptoms. Notably, physiological responses and altered levels of arousal are constituents of anxiety and have widespread ("global") effects on fMRI signals across the brain. Therefore, fMRI signatures of global cortical arousal and autonomic physiological responses may provide valuable neuroimaging biomarkers of anxiety. Additionally, these effects may also contribute to relationships observed between large scale network dynamics and anxiety level. MethodsDrawing upon data from a large community sample of 543 subjects (F= 369, M=174) we examine whether the global mean fMRI signal, and a data-driven estimate of cortical arousal effects in fMRI, relate to state and trait anxiety. Additionally, we investigate if autonomic physiological measures (heart rate) in fMRI patterns relate to state and trait anxiety in a subsample of these subjects (240 subjects; F=154, M=86). Finally, we investigate if these three global fMRI effects influence the relationship between functional brain network connectivity and state and trait anxiety. ResultsWe observe that the spatial patterns of the global mean fMRI signal and the cortical arousal-related fMRI signal related to both state and trait anxiety. These results support current theories that cortical arousal is closely tied to the anxious experience. Additionally, we observe that global component regression had variable effects on the relationship between anxiety and brain networks. ConclusionsThese findings suggest that global effects in fMRI signals hold valuable information about both state and trait anxiety. These observations also underscore the importance of understanding global fMRI effects as a source of information as opposed to a confound.