Recent advances in mapping cortical areas in the human brain provide a basis for investigating the significance of their spatial arrangement. Here we describe a dominant gradient in cortical features that spans between sensorimotor and transmodal areas. We propose that this gradient constitutes a core organizing axis of the human cerebral cortex, and describe an intrinsic coordinate system on its basis. Studying the cortex with respect to these intrinsic dimensions can inform our understanding of how the spectrum of cortical function emerges from structural constraints. The Significance of Cortical LocationFor more than a century, neuroscientists have studied the cerebral cortex by delineating individual cortical areas (see Glossary) and mapping their function [1]. This agenda has substantially advanced in recent years, as automated parcellation methods improve and data sets of unprecedented size and quality become available [2][3][4]. Nevertheless, our understanding of how the complex structure of the cerebral cortex emerges and gives rise to its elaborate functions remains fragmentary. To complement the description of individual cortical areas, we propose an inquiry into the significance of their spatial arrangement, asking the basic question: Why are cortical areas located where they are?Early formulations of this question date to theories from classical neuroanatomy [1,[5][6][7]. They state that the spatial layout of cortical areas is not arbitrary, but a consequence of developmental mechanisms, shaped through evolutionary selection. The location of an area among its neighbors thus provides insight into its microstructural characteristics [6], its connections to other parts of the brain [7], and eventually its position in global processing hierarchies [8]. Consider, for example, the well-researched visual system of the macaque monkey [9,10]. Along the visual hierarchy, low-level visual features are increasingly abstracted and integrated with information from other systems. Traditionally, areas are ordered based on their degree of microstructural differentiation, and the classification of their connections as feedforward or feedback [11]. The framework we advocate emphasizes that an area's position in the visual processing hierarchy -and thus many of its microstructural and connectional features -is strongly related to its distance from the primary visual area [12,13].More generally, we propose that the spatial arrangement of areas along a global gradient between sensorimotor and transmodal regions is a key feature of human cortical organization. A gradient is an axis of variance in cortical features, along which areas fall in a spatially continuous order. Areas that resemble each other with respect to the feature of interest occupy similar positions along the gradient. As we will point out, there is a strong relationship between the similarity of two areas -that is, their relative position along the gradient -and their relative position along the cortical surface. This important role of cortical location pro...

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Research in the macaque monkey suggests that cortical areas with similar microstructure are more likely to be connected. Here, we examine this link in the human cerebral cortex using 2 magnetic resonance imaging (MRI) measures: quantitative  T1 maps, which are sensitive to intracortical myelin content and provide an in vivo proxy for cortical microstructure, and resting-state functional connectivity. Using ultrahigh-resolution MRI at 7 T and dedicated image processing tools, we demonstrate a systematic relationship between T1-based intracortical myelin content and functional connectivity. This effect is independent of the proximity of areas. We employ nonlinear dimensionality reduction to characterize connectivity components and identify specific aspects of functional connectivity that are linked to myelin content. Our results reveal a consistent spatial pattern throughout different analytic approaches. While functional connectivity and myelin content are closely linked in unimodal areas, the correspondence is lower in transmodal areas, especially in posteromedial cortex and the angular gyrus. Our findings are in agreement with comprehensive reports linking histologically assessed microstructure and connectivity in different mammalian species and extend them to the human cerebral cortex in vivo.

The cytoarchitectonic map as proposed by Brodmann currently dominates models of human sensorimotor cortical structure, function, and plasticity. According to this model, primary motor cortex, area 4, and primary somatosensory cortex, area 3b, are homogenous areas, with the major division lying between the two. Accumulating empirical and theoretical evidence, however, has begun to question the validity of the Brodmann map for various cortical areas. Here, we combined in vivo cortical myelin mapping with functional connectivity analyses and topographic mapping techniques to reassess the validity of the Brodmann map in human primary sensorimotor cortex. We provide empirical evidence that area 4 and area 3b are not homogenous, but are subdivided into distinct cortical fields, each representing a major body part (the hand and the face). Myelin reductions at the hand–face borders are cortical layer-specific, and coincide with intrinsic functional connectivity borders as defined using large-scale resting state analyses. Our data extend the Brodmann model in human sensorimotor cortex and suggest that body parts are an important organizing principle, similar to the distinction between sensory and motor processing.

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The human neocortex is organized radially into six layers which differ in their myelination and the density and arrangement of neuronal cells. This cortical cyto-and myeloarchitecture plays a central role in the anatomical and functional neuroanatomy but is primarily accessible through invasive histology only. To overcome this limitation, several non-invasive MRI approaches have been, and are being, developed to resolve the anatomical cortical layers. As a result, recent studies on large populations and structure-function relationships at the laminar level became possible. Early proof-of-concept studies targeted conspicuous laminar structures such as the stria of Gennari in the primary visual cortex. Recent work characterized the laminar structure outside the visual cortex, investigated the relationship between laminar structure and function, and demonstrated layer-specific maturation effects. This paper reviews the methods and in-vivo MRI studies on the anatomical layers in the human cortex based on conventional and quantitative MRI (excluding diffusion imaging). A focus is on the related challenges, promises and potential future developments. The rapid development of MRI scanners, motion correction techniques, analysis methods and biophysical modeling promise to overcome the challenges of spatial resolution, precision and specificity of systematic imaging of cortical laminae. Need for non-invasive mapping of cortical laminationThe neocortex of the human brain consists of six layers which differ in their pattern of myelination (Nieuwenhuys, 2013;Vogt and Vogt, 1919) and the density and arrangement of neuronal cells (Brodmann, 1909;Zilles and Amunts, 2010). Those differences gave rise to the broad research field of myelo-and cyto-architecture, which is based on invasive histology. To facilitate studies of the human brain in large populations and longitudinally, non-invasive methods are much needed for visualizing intracortical anatomy in-vivo, since histological methods can only be applied ex-vivo. A promising approach is magnetic resonance imaging (MRI) as it is non-invasive and highly sensitive to the presence of myelin (and iron) in the cortex (Stüber et al., 2014). It is expected to reflect the myeloarchitecture rather than the cyto-architecture, although there is a strong correspondence between the two . Scope of the reviewThis paper reviews the recent in-vivo MRI studies on the anatomical layers in the human neocortex. An additional focus is on the related challenges, promises and potential future developments. Studies using diffusion weighted MRI are excluded from this review, since they are covered by Assaf et al. (2017) in the same special issue on "Prospects for cortical laminar MRI: functional and anatomical imaging of cerebral cortical layers". MRI studies of cortical layers Studies of the stria of GennariAs the cortex is only 2-4 mm thick and convoluted (Fischl and Dale, 2000), mapping cortical layers requires sub-millimeter isotropic resolution. Another challenge is that the differences in myelo-ar...

Longitudinal changes in whole-brain and tract-specific diffusion tensor imaging indices and magnetization transfer ratio can be reliably quantified, suggesting that small clinical trials using these outcome measures are feasible.

Segmentation of brain images often requires a statistical atlas for providing prior information about the spatial position of different structures. A major limitation of atlas-based segmentation algorithms is their deficiency in analyzing brains that have a large deviation from the population used in the construction of the atlas. We present an expectation-maximization framework based on a Dirichlet distribution to adapt a statistical atlas to the underlying subject. Our model combines anatomical priors with the subject's own anatomy, resulting in a subject specific atlas which we call an "adaptive atlas". The generation of this adaptive atlas does not require the subject to have an anatomy similar to that of the atlas population, nor does it rely on the availability of an ensemble of similar images. The proposed method shows a significant improvement over current segmentation approaches when applied to subjects with severe ventriculomegaly, where the anatomy deviates significantly from the atlas population. Furthermore, high levels of accuracy are maintained when the method is applied to subjects with healthy anatomy.