Mapping Short Association Fibers in the Early Cortical Visual Processing Stream Using In Vivo Diffusion Tractography

Short association fibers (U-fibers) connect proximal cortical areas and constitute the majority of white matter connections in the human brain. U-fibers play an important role in brain development, function, and pathology but are underrepresented in current descriptions of the human brain connectome, primarily due to methodological challenges in diffusion magnetic resonance imaging (dMRI) of these fibers. High spatial resolution and dedicated fiber and tractography models are required to reliably map the U-fibers. Moreover, limited quantitative knowledge of their geometry and distribution makes validation of U-fiber tractography challenging. Submillimeter resolution diffusion MRI-facilitated by a cutting-edge MRI scanner with 300 mT/m maximum gradient amplitude-was used to map U-fiber connectivity between primary and secondary visual cortical areas (V1 and V2, respectively) in vivo. V1 and V2 retinotopic maps were obtained using functional MRI at 7T. The mapped V1-V2 connectivity was retinotopically organized, demonstrating higher connectivity for retinotopically corresponding areas in V1 and V2 as expected. The results were highly reproducible, as demonstrated by repeated measurements in the same participants and by an independent replication group study. This study demonstrates a robust U-fiber connectivity mapping in vivo and is an important step toward construction of a more complete human brain connectome

On the Mapping of Cortical Columns in Humans Using High-Resolution Functional Magnetic Resonance Imaging

Recent developments in functional magnetic resonance imaging (fMRI) methods at high magnetic field strengths (≥7 T) promise the non-invasive indirect measurement of neural activation at the spatial scale of cortical columns and layers. However, the achievable spatial specificity of fMRI, which is ultimately limited by the spatio-temporal properties of the hemodynamic response, is still waiting to be fully characterized. To examine the spatial specificity of the blood oxygenation level dependent (BOLD) contrast exploited by fMRI, the spatial point spread function (PSF) of the gradient echo (GE) and the spin echo (SE) BOLD signal tangential to the cortical surface was determined at different cortical depths. Both GE- and SE-BOLD showed a loss in spatial specificity toward the pial surface, demonstrating the impact of unspecific macrovascular contributions to both contrasts and only a minor advantage of the SE-BOLD signal for high-resolution fMRI applications. However, unidirectional draining of deoxygenated blood mainly limits spatial specificity in the radial direction. To examine the discriminability of laminar information, ocular dominance columns (ODCs) in the primary visual cortex (V1) were mapped using fMRI sensitive to either the BOLD contrast or cerebral blood volume (CBV) changes, and the stimulated eye was decoded using a machine learning classifier at different cortical depths. Only CBV-fMRI showed increased prediction accuracies at the cortical depth that matched neurophysiological expectations, showing its improved spatial specificity and potential for layer-specific fMRI in humans. Furthermore, the thin-thick-pale stripe pattern in the secondary visual cortex (V2) was targeted, exploiting the sensitivity to color and binocular disparity of thin and thick stripes, respectively. The structure-function relationship of the stripe architecture to cortical myelin was studied, which so far has shown inconsistent findings in multiple histological experiments. High-resolution quantitative MRI (qMRI) parameter maps of the longitudinal relaxation rate (R1) were used as a proxy for cortical myelin content. The comparison of fMRI and qMRI maps showed that both thin and thick stripes have lower R1 than surrounding cortical tissue, pointing toward higher myelin content of pale stripes. While macrovascular contributions in fMRI must be considered cautiously, the thesis demonstrates the capabilities to study structure-function relationships and retrieval of laminar information at the spatial scale of cortical columns with high-resolution fMRI at 7 T.:List of figures List of tables List of acronyms 1 Introduction 1.1 Imaging the human brain 1.2 The visual cortex 1.3 Vascular supply of the cerebral cortex 1.4 Thesis outline 2 Background 2.1 Nuclear magnetic resonance 2.1.1 Nuclear magnetic moment 2.1.2 Zeeman effect 2.1.3 Bulk magnetization 2.1.4 Excitation 2.1.5 Relaxation 2.1.6 Refocusing 2.1.7 Detection 2.2 Magnetic resonance imaging 2.2.1 Gradients 2.2.2 Spatial encoding 2.2.3 Echo-planar imaging 2.3 Functional magnetic resonance imaging 2.3.1 Blood 2.3.2 Hemodynamic response 2.3.3 BOLD-fMRI 2.3.4 CBV-fMRI 2.4 Spatial specificity 2.4.1 Point spread function 2.4.2 Imaging PSF 2.4.3 Physiological PSF 3 Cortical depth-dependent spatial specificity of GE- and SE-BOLD 3.1 Introduction 3.2 Theory 3.3 Materials and methods 3.3.1 Participants 3.3.2 General procedure 3.3.3 Visual stimulation 3.3.4 Imaging 3.3.5 Data preprocessing 3.3.6 MTF model fitting using MCMC 3.4 Results 3.4.1 GE- and SE-BOLD maps 3.4.2 Percent signal changes across cortical depth 3.4.3 Cortical distances along iso-eccentricity lines 3.4.4 MCMC diagnostics 3.4.5 Estimated MTF parameters 3.4.6 MTF within veins 3.5 Discussion 4 Laminar profile of human ocular dominance columns 4.1 Introduction 4.2 Materials and methods 4.2.1 Participants 4.2.2 General procedure 4.2.3 Visual stimulation 4.2.4 Imaging 4.2.5 Data preprocessing 4.2.6 Pattern classification 4.3 Results 4.3.1 Topography of ocular dominance columns 4.3.2 Reproducibility of ocular dominance maps 4.3.3 Univariate contrasts across cortical depth 4.3.4 Decoding accuracies across cortical depth 4.4 Discussion 5 Cortical myelination of the secondary visual cortex (V2) 5.1 Introduction 5.2 Materials and methods 5.2.1 Participants 5.2.2 General procedure 5.2.3 Visual stimulation 5.2.4 Imaging 5.2.5 Data analysis 5.3 Results 5.3.1 Functional mapping of color-selective and disparity-selective stripes 5.3.2 Consistent qMRI maps across cortical regions and cortical depth 5.3.3 Higher myelination of pale stripes 5.4 Discussion 6 General discussion A Gradient-based boundary registration B Construction of anaglyph spectacles C Supplementary data for chapter 3 D Supplementary data for chapter 4 E Supplementary data for chapter 5 F Analysis of registration accuracy Acknowledgements Bibliography Curriculum vitae Declaration of authorshi

Perceived and mentally rotated contents are differentially represented in cortical depth of V1

Primary visual cortex (V1) in humans is known to represent both veridically perceived external input and internally-generated contents underlying imagery and mental rotation. However, it is unknown how the brain keeps these contents separate thus avoiding a mixture of the perceived and the imagined which could lead to potentially detrimental consequences. Inspired by neuroanatomical studies showing that feedforward and feedback connections in V1 terminate in different cortical layers, we hypothesized that this anatomical compartmentalization underlies functional segregation of external and internally-generated visual contents, respectively. We used high-resolution layer-specific fMRI to test this hypothesis in a mental rotation task. We found that rotated contents were predominant at outer cortical depth bins (i.e. superficial and deep). At the same time perceived contents were represented stronger at the middle cortical bin. These results identify how through cortical depth compartmentalization V1 functionally segregates rather than confuses external from internally-generated visual contents. These results indicate that feedforward and feedback manifest in distinct subdivisions of the early visual cortex, thereby reflecting a general strategy for implementing multiple cognitive functions within a single brain region

High resolution quantitative and functional MRI indicate lower myelination of thin and thick stripes in human secondary visual cortex

This OSF project contains data for the fMRI/qMRI study on estimating myelination differences within the secondary visual cortex of several living humans. For more details please refer to https://elifesciences.org/articles/7875