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      A Connectomic Hypothesis for the Hominization of the Brain

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          Abstract

          Cognitive abilities of the human brain, including language, have expanded dramatically in the course of our recent evolution from nonhuman primates, despite only minor apparent changes at the gene level. The hypothesis we propose for this paradox relies upon fundamental features of human brain connectivity, which contribute to a characteristic anatomical, functional, and computational neural phenotype, offering a parsimonious framework for connectomic changes taking place upon the human-specific evolution of the genome. Many human connectomic features might be accounted for by substantially increased brain size within the global neural architecture of the primate brain, resulting in a larger number of neurons and areas and the sparsification, increased modularity, and laminar differentiation of cortical connections. The combination of these features with the developmental expansion of upper cortical layers, prolonged postnatal brain development, and multiplied nongenetic interactions with the physical, social, and cultural environment gives rise to categorically human-specific cognitive abilities including the recursivity of language. Thus, a small set of genetic regulatory events affecting quantitative gene expression may plausibly account for the origins of human brain connectivity and cognition.

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          Most cited references333

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          A multi-modal parcellation of human cerebral cortex

          Understanding the amazingly complex human cerebral cortex requires a map (or parcellation) of its major subdivisions, known as cortical areas. Making an accurate areal map has been a century-old objective in neuroscience. Using multi-modal magnetic resonance images from the Human Connectome Project (HCP) and an objective semi-automated neuroanatomical approach, we delineated 180 areas per hemisphere bounded by sharp changes in cortical architecture, function, connectivity, and/or topography in a precisely aligned group average of 210 healthy young adults. We characterized 97 new areas and 83 areas previously reported using post-mortem microscopy or other specialized study-specific approaches. To enable automated delineation and identification of these areas in new HCP subjects and in future studies, we trained a machine-learning classifier to recognize the multi-modal ‘fingerprint’ of each cortical area. This classifier detected the presence of 96.6% of the cortical areas in new subjects, replicated the group parcellation, and could correctly locate areas in individuals with atypical parcellations. The freely available parcellation and classifier will enable substantially improved neuroanatomical precision for studies of the structural and functional organization of human cerebral cortex and its variation across individuals and in development, aging, and disease.
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            Rich-club organization of the human connectome.

            The human brain is a complex network of interlinked regions. Recent studies have demonstrated the existence of a number of highly connected and highly central neocortical hub regions, regions that play a key role in global information integration between different parts of the network. The potential functional importance of these "brain hubs" is underscored by recent studies showing that disturbances of their structural and functional connectivity profile are linked to neuropathology. This study aims to map out both the subcortical and neocortical hubs of the brain and examine their mutual relationship, particularly their structural linkages. Here, we demonstrate that brain hubs form a so-called "rich club," characterized by a tendency for high-degree nodes to be more densely connected among themselves than nodes of a lower degree, providing important information on the higher-level topology of the brain network. Whole-brain structural networks of 21 subjects were reconstructed using diffusion tensor imaging data. Examining the connectivity profile of these networks revealed a group of 12 strongly interconnected bihemispheric hub regions, comprising the precuneus, superior frontal and superior parietal cortex, as well as the subcortical hippocampus, putamen, and thalamus. Importantly, these hub regions were found to be more densely interconnected than would be expected based solely on their degree, together forming a rich club. We discuss the potential functional implications of the rich-club organization of the human connectome, particularly in light of its role in information integration and in conferring robustness to its structural core.
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              An Expanded View of Complex Traits: From Polygenic to Omnigenic

              A central goal of genetics is to understand the links between genetic variation and disease. Intuitively, one might expect disease-causing variants to cluster into key pathways that drive disease etiology. But for complex traits, association signals tend to be spread across most of the genome-including near many genes without an obvious connection to disease. We propose that gene regulatory networks are sufficiently interconnected such that all genes expressed in disease-relevant cells are liable to affect the functions of core disease-related genes and that most heritability can be explained by effects on genes outside core pathways. We refer to this hypothesis as an "omnigenic" model.
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                Author and article information

                Journal
                Cereb Cortex
                Cereb Cortex
                cercor
                Cerebral Cortex (New York, NY)
                Oxford University Press
                1047-3211
                1460-2199
                May 2021
                26 December 2020
                26 December 2020
                : 31
                : 5
                : 2425-2449
                Affiliations
                [1 ] CNRS UMR 3571, Institut Pasteur , 75724 Paris, France
                [2 ] Communications Cellulaires, Collège de France , 75005 Paris, France
                [3 ] Institute of Computational Neuroscience, University Medical Center Eppendorf, Hamburg University , 20246 Hamburg, Germany
                [4 ] Department of Health Sciences, Boston University , Boston, MA 02115, USA
                Author notes
                Address correspondence to Jean-Pierre Changeux CNRS UMR 3571, Institut Pasteur, 75724 Paris, France. Email: changeux@ 123456noos.fr .
                Author information
                https://orcid.org/0000-0003-0297-1583
                https://orcid.org/0000-0002-5381-0096
                https://orcid.org/0000-0003-2129-8910
                Article
                bhaa365
                10.1093/cercor/bhaa365
                8023825
                33367521
                b8865419-dc38-4b13-8df4-4deb4f8edb0d
                © The Author(s) 2020. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 August 2020
                : 30 October 2020
                : 2 November 2020
                Page count
                Pages: 25
                Funding
                Funded by: Alexander von Humboldt Foundation, DOI 10.13039/100005156;
                Funded by: Deutsche Forschungsgemeinschaft, DOI 10.13039/501100001659;
                Award ID: TRR 169/A2
                Award ID: SFB 936/A1
                Award ID: SPP 2041 HI 1286/7-1
                Funded by: Human Brain Program;
                Award ID: SGA3
                Award ID: SGA2 785907
                Categories
                Feature Article
                AcademicSubjects/MED00310
                AcademicSubjects/MED00385
                AcademicSubjects/SCI01870

                Neurology
                brain hominization,brain phenotype,connectomic fundamentals,human genome
                Neurology
                brain hominization, brain phenotype, connectomic fundamentals, human genome

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