Laminar fMRI: What can the time domain tell us?

Abstract

The rapid developments in functional MRI (fMRI) acquisition methods and hardware technologies in recent years, particularly at high field (≥7 T), have enabled unparalleled visualization of functional detail at a laminar or columnar level, bringing fMRI close to the intrinsic resolution of brain function. These advances highlight the potential of high resolution fMRI to be a valuable tool to study the fundamental processing performed in cortical micro-circuits, and their interactions such as feedforward and feedback processes. Notably, because fMRI measures neuronal activity via hemodynamics, the ultimate resolution it affords depends on the spatial specificity of hemodynamics to neuronal activity at a detailed spatial scale, and by the evolution of this specificity over time. Several laminar (≤1 mm spatial resolution) fMRI studies have examined spatial characteristics of the measured hemodynamic signals across cortical depth, in light of understanding or improving the spatial specificity of laminar fMRI. Few studies have examined temporal features of the hemodynamic response across cortical depth. Temporal features of the hemodynamic response offer an additional means to improve the specificity of fMRI, and could help target neuronal processes and neurovascular coupling relationships across laminae, for example by differences in the onset times of the response across cortical depth. In this review, we discuss factors that affect the timing of neuronal and hemodynamic responses across laminae, touching on the neuronal laminar organization, and focusing on the laminar vascular organization. We provide an overview of hemodynamics across the cortical vascular tree based on optical imaging studies, and review temporal aspects of hemodynamics that have been examined across cortical depth in high spatiotemporal resolution fMRI studies. Last, we discuss the limits and potential of high spatiotemporal resolution fMRI to study laminar neurovascular coupling and neuronal processes.