Abstract

The mesoscopic organization of the human neocortex is of great interest for cognitive neuroscience. However, fMRI in humans typically maps the functional units of cognitive processing on a macroscopic level. With the advent of ultra-high field MRI (≥7T), it has become possible to acquire fMRI data with sub-millimetre resolution, enabling probing the laminar and columnar circuitry in humans. Currently, laminar BOLD responses are not directly observed but inferred via data analysis, due to coarse spatial resolution of fMRI (e.g. 0.7–0.8 mm isotropic) relative to the extent of histological laminae. In this study, we introduce a novel approach for mapping the cortical BOLD response at the spatial scale of cortical layers and columns at 7T (an unprecedented 0.1 mm, either in the laminar or columnar direction). We demonstrate experimentally and using simulations, the superiority of the novel approach compared to standard approaches for human laminar fMRI in terms of effective spatial resolution in either laminar or columnar direction. In addition, we provide evidence that the laminar BOLD signal profile is not homogeneous even over short patches of cortex. In summary, the proposed novel approach affords the ability to directly study the mesoscopic organization of the human cortex, thus, bridging the gap between human cognitive neuroscience and invasive animal studies.

Highlights

  • The human cortex is structured into a myriad of structural and functional units[1]

  • We demonstrate the feasibility of the novel Anisotropic Voxel FLASH (AVF) acquisition to obtain laminar- and columnar-specific functional magnetic resonance imaging (fMRI) signals in the human visual cortex

  • This study demonstrates the feasibility of directly assessing the laminar and columnar cortical organization in humans, non-invasively, using ultra-high spatial resolution fMRI, a scientific domain previously reserved for invasive animal studies

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Summary

Introduction

The human cortex is structured into a myriad of structural and functional units[1]. These units can be indexed along both the normal and tangential coordinates with respect to the surface of the cortex[2]. The tangential coordinates represent the distance along the cortical ribbon, and the structural-functional units along this axis are called brain areas and columns, on the macroscopic and mesoscopic scales, respectively These subdivisions are characterized by their distinctive histological profiles[3,4] or by their specific responsiveness to external stimuli and role in cognitive and physiological processes[5,6]. FMRI has proven to be an invaluable non-invasive imaging tool for mapping brain areas involved in cognitive and/or sensory processing[10] or resting-state activity[11] It typically utilizes the blood oxygenation level-dependent (BOLD) contrast[12,13] to probe neuronal activity indirectly via changes in blood oxygenation and cerebral blood volume (CBV)[14].

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