Task-evoked Negative BOLD Response and Functional Connectivity in the Default Mode Network are Representative of Two Overlapping but Separate Neurophysiological Processes

The topography of the default mode network (DMN) can be obtained with one of two different functional magnetic resonance imaging (fMRI) methods: either from the spontaneous but organized synchrony of the low-frequency fluctuations in resting-state fMRI (rs-fMRI), known as “functional connectivity”, or from the consistent and robust deactivations in task-based fMRI (tb-fMRI), here referred to as the “negative BOLD response” (NBR). These two methods are fundamentally different, but their results are often used interchangeably to describe the brain’s resting-state, baseline, or intrinsic activity. While the DMN was initially defined by consistent task-based decreases in blood flow in a set of specific brain regions using PET imaging, recently nearly all studies on the DMN employ functional connectivity in rs-fMRI. In this study, we first show the high level of spatial overlap between NBR and functional connectivity of the DMN extracted from the same tb-fMRI scan; then, we demonstrate that the NBR in putative DMN regions can be significantly altered without causing any change in their overlapping functional connectivity. Furthermore, we present evidence that in the DMN, the NBR is more closely related to task performance than the functional connectivity. We conclude that the NBR and functional connectivity of the DMN reflect two separate but overlapping neurophysiological processes, and thus should be differentiated in studies investigating brain-behavior relationships in both healthy and diseased populations. Our findings further raise the possibility that the macro-scale networks of the human brain might internally exhibit a hierarchical functional architecture.