Is it time to put rest to rest?

Abstract

The so-called resting state, in which participants lie quietly with no particular inputs or outputs, represented a paradigm shift from conventional task-based studies in human neuroimaging. Our foray into rest was fruitful from both a scientific and methodological perspective, but at this point, how much more can we learn from rest on its own? While rest still dominates in many subfields, data from tasks have empirically demonstrated benefits, as well as the potential to provide insights about the mind in addition to the brain. I argue that we can accelerate progress in human neuroscience by de-emphasizing rest in favor of more grounded experiments, including promising integrated designs that respect the prominence of self-generated activity while offering enhanced control and interpretability.

Keywords: brain–behavior prediction; functional connectivity; naturalistic tasks; resting state; task-based.

Figure 1.. From task, to rest, to a “third wave” in human neuroimaging.

The first wave of functional neuroimaging consisted largely of investigators (represented by the boat) using highly controlled task paradigms (represented by the boxcar, denoting “task on”-“task off” periods) to attempt to isolate specific cognitive processes. While this approach could generate and localize small ripples in brain activity, ultimately, it ignored a large fraction of variance that arose from task-unrelated, seemingly spontaneous signals. In the second wave, investigators (represented by the submarine) dove headlong into the depths to characterize the spatiotemporal structure of this resting-state activity. But because we had little to anchor our observations to, it was difficult to interpret these signals in the context of ongoing cognition. The third wave calls for us to partially resurface and regain some experimental control, while still respecting the importance of self-generated activity in dynamic patterns of brain function.

Figure 2.. Third-wave integrated designs that blend task- and rest-inspired approaches.

In the third wave, we have an opportunity to draw from the best of both worlds during acquisition and analysis. Four families of integrated designs are depicted. Annotated rest refers to acquiring introspection data—i.e., first-person reports of ongoing mental experiences during or after the scan—that can be linked to spatiotemporal features of brain activity. Naturalistic tasks (e.g., movie watching, story listening) are richer, more dynamic, and in some ways more ecologically valid than traditional tasks. These paradigms thus create stronger yet more organic ripples, bringing surface-level and deeper phenomena closer together. In task-signature echoes, activity patterns are characterized using data with a known task manipulation, and then rest data are mined to see if echoes of these signatures can be detected at rest, suggesting a kind of replay, reinstatement, or engagement in similar mental activities. Finally, in state-informed approaches, experimenters monitor brain state (either post hoc, or online using real-time neuroimaging), and deliver tasks at certain intervals to causally test the role of ongoing activity in shaping perception and behavior toward an external stimulus.