Higher and deeper: Bringing layer fMRI to association cortex

Recent advances in fMRI have enabled non-invasive measurements of brain function in awake, behaving humans at unprecedented spatial resolutions, allowing us to separate activity in distinct cortical layers. While most layer fMRI studies to date have focused on primary cortices, we argue that the next big steps forward in our understanding of cognition will come from expanding this technology into higher-order association cortex, to characterize depth-dependent activity during increasingly sophisticated mental processes. We outline phenomena and theories ripe for investigation with layer fMRI, including perception and imagery, selective attention, and predictive coding. We discuss practical and theoretical challenges to cognitive applications of layer fMRI, including localizing regions of interest in the face of substantial anatomical heterogeneity across individuals, designing appropriate task paradigms within the confines of acquisition parameters, and generating hypotheses for higher-order brain regions where the laminar circuitry is less well understood. We consider how applying layer fMRI in association cortex may help inform computational models of brain function as well as shed light on consciousness and mental illness, and issue a call to arms to our fellow methodologists and neuroscientists to bring layer fMRI to this next frontier.