Strategies and prospects for cortical depth dependent T2 and T2* weighted BOLD fMRI studies

Technological advancements in fMRI have afforded the opportunity to conduct submillimeter investigations into human brain function. The ability to do cortical depth dependent (or layer-specific) fMRI could allow probing intrinsic neuronal organizations and inter-connections, including the directionality of interregional information flow, while ultimately shedding light on uniquely human behaviors. The methodological development and applications of cortical depth dependent fMRI has been ongoing for nearly a decade, yet a consensus on protocols, analysis pipelines and interpretations of data has yet to be reached. In this article we discuss the current status and understandings of high resolution fMRI data and methods. In particular, the spatial signal characteristics of the BOLD contrast are examined in relation to the intra-cortical vasculature and associated underlying contrast mechanisms for three pulse sequences used in laminar fMRI: gradient echo (GE), spin echo (SE) and 3D-GRASE. We conclude with a short overview of factors to be taken into account when designing a specific study, including the choice of pulse sequence, experimental design, and data analysis strategy.