Comprehensive cellular‐resolution atlas of the adult human brain

Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole‐brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high‐resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion‐weighted imaging (DWI), and 1,356 large‐format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto‐ and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127–3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

[1]  A. Dale,et al.  High‐resolution intersubject averaging and a coordinate system for the cortical surface , 1999, Human brain mapping.

[2]  Koenraad Van Leemput,et al.  A computational atlas of the hippocampal formation using ex vivo, ultra-high resolution MRI: Application to adaptive segmentation of in vivo MRI , 2015, NeuroImage.

[3]  Alexander Hammers,et al.  Three‐dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe , 2003, Human brain mapping.

[4]  Tristan A. Chaplin,et al.  A Specialized Area in Limbic Cortex for Fast Analysis of Peripheral Vision , 2012, Current Biology.

[5]  G. V. Van Hoesen,et al.  Organization and detailed parcellation of human hippocampal head and body regions based on a combined analysis of Cyto‐ and chemoarchitecture , 2015, The Journal of comparative neurology.

[6]  Klaus Reinhardt,et al.  Human Brain Anatomy In Computerized Images , 2016 .

[7]  E. Jones.  Stereotactic Atlas of the Human Thalamus and Basal Ganglia, A. Morel. Informa Healthcare, New York (2007), Price: US$ 229.95 , 2008 .

[8]  David A. Boas,et al.  MRI parcellation of ex vivo medial temporal lobe , 2014, NeuroImage.

[9]  M. Torrens.  Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[10]  Karl Zilles,et al.  A volumetric comparison of the insular cortex and its subregions in primates. , 2013, Journal of human evolution.

[11]  Jesper Andersson,et al.  A multi-modal parcellation of human cerebral cortex , 2016, Nature.

[12]  B. Vogt,et al.  Human cingulate cortex: Surface features, flat maps, and cytoarchitecture , 1995, The Journal of comparative neurology.

[13]  Tristan Glatard,et al.  The MNI data-sharing and processing ecosystem , 2016, NeuroImage.

[14]  Muge M. Bakircioglu,et al.  Mapping visual cortex in monkeys and humans using surface-based atlases , 2001, Vision Research.

[15]  J. Morrison,et al.  Monoclonal antibody to neurofilament protein (SMI‐32) labels a subpopulation of pyramidal neurons in the human and monkey neocortex , 1989, The Journal of comparative neurology.

[16]  R. Bowtell,et al.  Medical imaging: MRI rides the wave , 2009, Nature.

[17]  Karla L. Miller,et al.  Diffusion tractography of post-mortem human brains: Optimization and comparison of spin echo and steady-state free precession techniques , 2012, NeuroImage.

[18]  Jörn Diedrichsen,et al.  A probabilistic MR atlas of the human cerebellum , 2009, NeuroImage.

[19]  Nikolaus Weiskopf,et al.  Multi-voxel pattern analysis in human hippocampal subfields , 2012, Front. Hum. Neurosci..

[20]  S. Kollias,et al.  Duvernoy's Atlas of the Human Brain Stem and Cerebellum , 2009 .

[21]  G. V. Van Hoesen,et al.  Borders, extent, and topography of human perirhinal cortex as revealed using multiple modern neuroanatomical and pathological markers , 2010, Human brain mapping.

[22]  Junfeng Zhu,et al.  Cross-validation of serial optical coherence scanning and diffusion tensor imaging: A study on neural fiber maps in human medulla oblongata , 2014, NeuroImage.

[23]  Alan C. Evans,et al.  BigBrain: An Ultrahigh-Resolution 3D Human Brain Model , 2013, Science.

[24]  J. Morrison,et al.  Human orbitofrontal cortex: Cytoarchitecture and quantitative immunohistochemical parcellation , 1995, The Journal of comparative neurology.

[25]  Song-Lin Ding,et al.  Comparative anatomy of the prosubiculum, subiculum, presubiculum, postsubiculum, and parasubiculum in human, monkey, and rodent , 2013, The Journal of comparative neurology.

[26]  Anders M. Dale,et al.  Automatic parcellation of human cortical gyri and sulci using standard anatomical nomenclature , 2010, NeuroImage.

[27]  Allan R. Jones,et al.  An anatomically comprehensive atlas of the adult human brain transcriptome , 2012, Nature.

[28]  Miguel Ángel García-Cabezas,et al.  Distribution of the dopamine innervation in the macaque and human thalamus , 2007, NeuroImage.

[29]  Patrick R Hof,et al.  In search of the definitive Brodmann's map of cortical areas in human , 2015, The Journal of comparative neurology.

[30]  W L Nowinski,et al.  Bridging Neuroanatomy, Neuroradiology and Neurology: Three-Dimensional Interactive Atlas of Neurological Disorders , 2013, The neuroradiology journal.

[31]  Bruce R. Rosen,et al.  Predicting the location of entorhinal cortex from MRI , 2009, NeuroImage.

[32]  Simon B. Eickhoff,et al.  Microstructural grey matter parcellation and its relevance for connectome analyses , 2013, NeuroImage.

[33]  H. Duvernoy.  The Human Brain , 1999, Springer Vienna.

[34]  J. Morrison,et al.  Neurofilament and calcium‐binding proteins in the human cingulate cortex , 1997, The Journal of comparative neurology.

[35]  A. Schleicher,et al.  Organization of the Human Inferior Parietal Lobule Based on Receptor Architectonics , 2012, Cerebral cortex.

[36]  Alexander Hammers,et al.  Volumes, spatial extents and a probabilistic atlas of the human basal ganglia and thalamus , 2007, NeuroImage.

[37]  P. Morosan,et al.  Broca's Region: Novel Organizational Principles and Multiple Receptor Mapping , 2010, PLoS biology.

[38]  Hauke Bartsch,et al.  Postmortem examination of patient H.M.’s brain based on histological sectioning and digital 3D reconstruction , 2014, Nature Communications.

[39]  Allan R. Jones,et al.  Genome-wide atlas of gene expression in the adult mouse brain , 2007, Nature.

[40]  J Mazziotta,et al.  A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM). , 2001, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[41]  G B Arden,et al.  The Visual System , 2021, AMA Guides to the Evaluation of Permanent Impairment, 6th Edition, 2021.

[42]  Song-Lin Ding,et al.  Topography, cytoarchitecture, and cellular phenotypes of cortical areas that form the cingulo‐parahippocampal isthmus and adjoining retrocalcarine areas in the monkey , 2003, The Journal of comparative neurology.

[43]  J. Price,et al.  Architectonic subdivision of the human orbital and medial prefrontal cortex , 2003, The Journal of comparative neurology.

[44]  G. Smith,et al.  Die Cytoarchitektonik der Hirnrinde des erwachsenen Menschen. , 1927 .

[45]  Katrin Amunts,et al.  Cytoarchitecture of the cerebral cortex—More than localization , 2007, NeuroImage.

[46]  L. Wald,et al.  Theory and application of array coils in MR spectroscopy , 1997, NMR in biomedicine.

[47]  K. Amunts,et al.  Consequences of large interindividual variability for human brain atlases: converging macroscopical imaging and microscopical neuroanatomy , 2005, Anatomy and Embryology.

[48]  R. Rosenfeld.  Nature , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[49]  Rainer Goebel,et al.  Chapter 37 – Visual System , 2012 .

[50]  Stephen M. Smith,et al.  A global optimisation method for robust affine registration of brain images , 2001, Medical Image Anal..

[51]  Nikos Makris,et al.  Automatically parcellating the human cerebral cortex. , 2004, Cerebral cortex.

[52]  André J. W. van der Kouwe,et al.  Predicting the location of human perirhinal cortex, Brodmann's area 35, from MRI , 2013, NeuroImage.

[53]  S. Ding.  Detailed segmentation of human hippocampal and subicular subfields using a combined approach , 2015 .

[54]  N. Logothetis,et al.  A combined MRI and histology atlas of the rhesus monkey brain in stereotaxic coordinates , 2007 .

[55]  Nikos Makris,et al.  Large-scale brain networks of the human left temporal pole: a functional connectivity MRI study. , 2015, Cerebral cortex.

[56]  A. Morel,et al.  The human insula: Architectonic organization and postmortem MRI registration , 2013, Neuroscience.

[57]  B. Vogt,et al.  Cytology of human caudomedial cingulate, retrosplenial, and caudal parahippocampal cortices , 2001, The Journal of comparative neurology.

[58]  David A. Boas,et al.  Blockface histology with optical coherence tomography: A comparison with Nissl staining , 2014, NeuroImage.

[59]  Deepak N. Pandya,et al.  The Frontal Cortex , 2012 .

[60]  D. Louis Collins,et al.  Brain templates and atlases , 2012, NeuroImage.

[61]  J. Morrison,et al.  Neurochemical phenotype of corticocortical connections in the macaque monkey: Quantitative analysis of a subset of neurofilament protein‐immunoreactive projection neurons in frontal, parietal, temporal, and cingulate cortices , 1995, The Journal of comparative neurology.

[62]  B. Vogt,et al.  Chapter 25 – Cingulate Cortex , 2012 .

[63]  K. Amunts,et al.  Individual variability is not noise , 2013, Trends in Cognitive Sciences.

[64]  Daniel Rueckert,et al.  A dynamic 4D probabilistic atlas of the developing brain , 2011, NeuroImage.

[65]  Allan R. Jones,et al.  Transcriptional Landscape of the Prenatal Human Brain , 2014, Nature.

[66]  K. Rockland,et al.  Localization of area prostriata and its projection to the cingulate motor cortex in the rhesus monkey. , 2000, Cerebral cortex.

[67]  Song-Lin Ding,et al.  Parcellation of human temporal polar cortex: A combined analysis of multiple cytoarchitectonic, chemoarchitectonic, and pathological markers , 2009, The Journal of comparative neurology.

[68]  K. Amunts,et al.  Probabilistic maps, morphometry, and variability of cytoarchitectonic areas in the human superior parietal cortex. , 2008, Cerebral cortex.

[69]  Yu Zhang,et al.  The Human Brainnetome Atlas: A New Brain Atlas Based on Connectional Architecture , 2016, Cerebral cortex.

[70]  Noam Harel,et al.  Interoperable atlases of the human brain , 2014, NeuroImage.

[71]  Denis Dooley,et al.  Atlas of the Human Brain. , 1971 .

[72]  K. Amunts,et al.  Receptor mapping: architecture of the human cerebral cortex , 2009, Current opinion in neurology.

[73]  B. Fischl,et al.  Direct Visualization of the Perforant Pathway in the Human Brain with Ex Vivo Diffusion Tensor Imaging , 2010, Front. Hum. Neurosci..

[74]  C. Gerday,et al.  Monoclonal antibodies directed against the calcium binding protein parvalbumin. , 1988, Cell calcium.

[75]  J. Pearce.  Amygdala , 2008, European Neurology.

[76]  D. Salat,et al.  Detection of entorhinal layer II using Tesla magnetic resonance imaging , 2005 .

[77]  Charles Watson,et al.  Organization of Brainstem Nuclei , 2012 .

[78]  B. Fischl,et al.  Entorhinal verrucae geometry is coincident and correlates with Alzheimer’s lesions: a combined neuropathology and high-resolution ex vivo MRI analysis , 2011, Acta Neuropathologica.

[79]  Katrin Amunts,et al.  Cortical Folding Patterns and Predicting Cytoarchitecture , 2007, Cerebral cortex.

[80]  G Mann,et al.  ON THE THALAMUS * , 1905, British medical journal.

[81]  K. Zilles,et al.  Cingulate area 32 homologies in mouse, rat, macaque and human: Cytoarchitecture and receptor architecture , 2013, The Journal of comparative neurology.

[82]  K. Amunts,et al.  Centenary of Brodmann's Map — Conception and Fate , 2022 .

[83]  J. Olmos.  CHAPTER 22 – Amygdala , 2004 .

[84]  David A Boas,et al.  Optical coherence tomography visualizes neurons in human entorhinal cortex , 2015, Neurophotonics.

[85]  P. V. van Zijl,et al.  Three‐dimensional tracking of axonal projections in the brain by magnetic resonance imaging , 1999, Annals of neurology.

[86]  Arthur W. Toga,et al.  Construction of a 3D probabilistic atlas of human cortical structures , 2008, NeuroImage.

[87]  Katrin Amunts,et al.  Chapter 18 – High-Resolution Fiber and Fiber Tract Imaging Using Polarized Light Microscopy in the Human, Monkey, Rat, and Mouse Brain , 2016 .

[88]  Trygve B. Leergaard,et al.  Waxholm Space atlas of the Sprague Dawley rat brain , 2014, NeuroImage.

[89]  G. V. Van Hoesen,et al.  Stratum radiatum of CA2 is an additional target of the perforant path in humans and monkeys , 2010, Neuroreport.

[90]  L. Sternberger,et al.  Monoclonal antibodies distinguish phosphorylated and nonphosphorylated forms of neurofilaments in situ. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[91]  P. Hof,et al.  Cytoarchitecture of the human cerebral cortex: MR microscopy of excised specimens at 9.4 Tesla. , 2002, AJNR. American journal of neuroradiology.

[92]  P. Roemer,et al.  The NMR phased array , 1990, Magnetic resonance in medicine.

[93]  M. Petrides.  The Human Cerebral Cortex: An MRI Atlas of the Sulci and Gyri in MNI Stereotaxic Space , 2011 .

[94]  K. Amunts,et al.  Towards multimodal atlases of the human brain , 2006, Nature Reviews Neuroscience.

[95]  P. Hof,et al.  Cellular distribution of the calcium-binding proteins parvalbumin, calbindin, and calretinin in the neocortex of mammals: phylogenetic and developmental patterns , 1999, Journal of Chemical Neuroanatomy.