Situating the default-mode network along a principal gradient of macroscale cortical organization

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...

The study of neuroanatomy using imaging enables key insights into how our brains function, are shaped by genes and environment, and change with development, aging, and disease. Developments in MRI acquisition, image processing, and data modelling have been key to these advances. However, MRI provides an indirect measurement of the biological signals we aim to investigate. Thus, artifacts and key questions of correct interpretation can confound the readouts provided by anatomical MRI. In this review we provide an overview of the methods for measuring macro-and mesoscopic structure and inferring microstructural properties; we also describe key artefacts and confounds that can lead to incorrect conclusions. Ultimately, we believe that, though methods need to improve and caution is required in its interpretation, structural MRI continues to have great promise in furthering our understanding of how the brain works.

ObjectiveTo investigate whether a unified brain system manages one’s orientation to different places, events and people in one’s environment, and test the hypothesis that failure of this system (disorientation) is an early sign of Alzheimer’s disease (AD).MethodsA total of 46 participants (patients along the AD continuum and cognitively normal control subjects) were tested in a personalized, ecologically valid task of orientation relating to the participant’s own world in space, time and person under high–density electroencephalography. As a first step, we used evoked potential mapping to search for brain topography correlated with participants’ performance in orientating themselves to different places (space), events (time) and people (person) (Experiment 1). We then compared behavioral and electrophysiological changes in patients along the AD continuum (Experiment 2).ResultsWe identified a specific brain topography (“orientation map”) that was active for orientation in space, time and person in correlation to participants’ performance. Both performance and the map’s strength gradually decreased from health to mild cognitive impairment (MCI) and from MCI to AD. Another map, immediately preceding the orientation map, showed the longest activity in patients with MCI, significantly more than both patients with AD and cognitively normal controls.InterpretationOur findings demonstrate that the same brain topography accounts for orientation in the different domains of space, time and person and provide a nexus between deterioration in patients’ orientation with the aggravation of Alzheimer’s disease.