Challenges and opportunities of mesoscopic brain mapping with fMRI

Layer fMRI, requiring 7T scanners, sophisticated pulse sequences, and advanced post processing methods, has emerged and matured as a field in the past decade. In the past two years, the rate of layer fMRI papers published has grown sharply as the noninvasive delineation of mesoscopic scale functional organization promises to uncover new insight into human brain processing. Understanding laminar activity and connectivity throughout the brain will take fMRI beyond being able to simply identify where and when activation is taking place as delineating laminar location will provide detailed directional feedforward and feedback activity which will add to the sophistication of circuit and network models, thus providing a bridge between invasive measures and those typically carried out on humans. This review outlines the methods used to achieve layer fMRI as well as the challenges. It emphasizes the value and necessity of deep imaging of individuals rather than relying on pooled multi-subject databases to boost sensitivity. It highlights recent studies that have explored layer fMRI in cognitive tasks as well as resting state connectivity studies that have revealed cortical hierarchy. Finally, it concludes with a perspective on what the field promises, the challenges that lay ahead, and the direction that the field may evolve.