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Cited by 475Advanced Neuroimaging Techniques and ApplicationsAnatomy and Medical TechnologyMedical Image Segmentation Techniques

Comprehensive cellular‐resolution atlas of the adult human brain

Open access
Ding, Song‐Lin, Royall, Joshua J., Sunkin, Susan M., Ng, Lydia, Facer, Benjamin A.C., Lesnar, Phil, Guillozet‐Bongaarts, Angie, McMurray, Bergen +32 more·2016·Journal of Comparative Neurology
DOI 10.1002/cne.24080PMC PMC5054943
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Abstract

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.

AI snapshot

Written from the paper’s full text.

TL;DR

The paper presents a digital adult human brain atlas combining ex vivo MRI, DWI, and high-resolution histology from a complete adult female brain, with 1,356 cellular-resolution anatomical plates and 862 annotated structures. It is publicly accessible, interactive, and integrated with existing Allen Institute human brain gene expression atlases.

Key findings

  • The atlas includes MRI, DWI, and 1,356 large-format cellular-resolution (1 µm/pixel) Nissl and immunohistochemistry plates from the same adult female brain; 106 Nissl-stained sections were annotated for 862 structures using 11,398 polygons, including 117 white matter tracts.
  • Annotations cover modified Brodmann areas, sulci/gyri, subcortical nuclei, brainstem, and cerebellum, and identify novel or newly detailed structures/subdivisions such as MDam in the thalamus, BMm in the amygdala, the lateral olfactory area (LOA), area prostriata (APro), and the basal interstitial nucleus of the cerebellum (BIcb).
  • Correlated histology and MRI allowed feature extraction and transfer: the medial geniculate nucleus showed high signal intensity and the dorsal lateral geniculate nucleus low signal intensity, enabling identification in MRI from other Allen Human Brain Atlas cases; 76 coronal MRI slices at 2-mm intervals were annotated.
  • The resource is freely accessible online and linked to adult and developing human brain transcriptional atlases.

Methods

  • Single 34-year-old female donor with no history of neurological disease; brain was fixed, scanned ex vivo with 7 T structural MRI and 3 T DWI, bisected, slabbed, and sectioned coronally at 50 µm. Of 2,716 total sections, 679 were Nissl-stained (200-µm interval), 339 NFP-immunostained (400-µm interval), and 338 PV-immunostained (400-µm interval); 1,356 sections were digitized at 1 µm/pixel.
  • Anatomical delineation used 106 selected Nissl sections with sampling intervals of 0.4–3.4 mm, combined with adjacent NFP and PV sections; outlines were drawn on printouts, converted to digital polygons, and linked to a hierarchical whole-brain ontology.
  • MRI annotations were made on 76 coronal slices at 2-mm intervals; DWI tractography used the FACT algorithm with a 60° angular threshold, tracts longer than 20 mm, and 90% skip applied.

Limitations

  • Stated: the atlas is based on a single representative brain specimen, and the authors note that interindividual variability makes it unrealistic to map histological annotations from one specimen directly into a probabilistic reference space.
  • Stated: transposing Nissl-based delineations into full 3D annotations registered to MRI is challenging because of incomplete and nonuniform sampling of the annotated plates.
  • Stated: sectioning and mounting produced artifacts including large cracks and smaller tears in some sections; evident from the text, the resource is descriptive and single-donor, with no group-level statistical validation, and annotations are manual and could be reannotated by other researchers.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1002/cne.24080

Cites

90 of 90 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 60 cited sources checked · 0 supported · 0 flagged

  • Findingnone given

    The atlas annotations were transferred onto the matching MRI dataset.

    “and these annotations were transferred onto the matching MRI dataset.”
    Quote in the paperSubstantial claim
  • Findingown data

    The atlas includes several novel cyto- and chemoarchitecturally defined structures.

    “and several novel cyto‐ and chemoarchitecturally defined structures”
    Quote in the paperSubstantial claim
  • Findingown data

    The paper presents a digital human brain atlas incorporating neuroimaging, high-resolution histology, and chemoarchitecture across a complete adult female brain.

    “We present the first digital human brain atlas to incorporate neuroimaging, high‐resolution histology, and chemoarchitecture across a complete adult female brain”
    Quote in the paperSubstantial claim
    • Rests on an assumption: A single adult female brain without neurological disease is representative of the adult human brain for the purpose of a reference atlas.
  • Findingnone given

    The interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases.

    “This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases”
    Quote in the paperNot a substantial claim
  • Findingown data

    The atlas consists of MRI, DWI, and 1,356 large-format cellular resolution (1 μm/pixel) Nissl and immunohistochemistry anatomical plates.

    “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”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 33
  • May combine two claims. 34

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    The atlas is publicly accessible as a resource for the neuroscience community.

    “and is publicly accessible as a resource for the neuroscience community.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Findingnone given

    Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations.

    “Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Findingreasoning

    We used Brodmann's nomenclature as the primary reference because it is more commonly used, with modifications based on modern literature and the combined whole-brain large-scale cyto- and chemoarchitectural analysis here.

    “We used Brodmann's nomenclature as the primary reference because it is more commonly used, with modifications based on modern literature (see below) and the combined whole‐brain large‐scale cyto‐ and chemoarchitectural analysis here.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    A total of 1,356 sections on 3- × 5-inch slides were digitized for this resource.

    “A total of 1,356 sections on 3‐ × 5‐inch slides were digitized for this resource”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Where smaller subcortical structures are more abundant, a much denser sampling was used (0.4-1.0-mm interval).

    “Where smaller subcortical structures are more abundant, a much denser sampling was used (0.4–1.0‐mm interval).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    For the insular cortex, three major subdivisions were delineated: agranular, dysgranular, and granular insula, with the latter two further divided into rostral and caudal parts.

    “Finally, for the insular cortex that was not numbered by Brodmann in human (1909; see Simić and Hof, 2015), three major subdivisions were delineated and these included agranular, dysgranular, and granular insula (e.g., Bauernfeind et al., 2013; Morel et al., 2013), with the latter two further divided into rostral and caudal parts.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Bauernfeind et al., 2013

      Not checked in the free run.

    • cites Morel et al., 2013

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  • May combine two claims.

    Findingown data

    Structures from the ontology were delineated as polygons on each Nissl digital image, including both gyral and modified Brodmann areas of the neocortex.

    “Structures from the ontology were delineated as polygons on each Nissl digital image (Fig. 2H), and these structures include both gyral (Fig. 2I1) and modified Brodmann areas (Fig. 2I2) of the neocortex.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    For detailed anatomical delineation, 106 Nissl-stained sections were selected out of 679.

    “For detailed anatomical delineation, 106 Nissl‐stained sections were selected out of 679.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Findingown data

    The ontology is fundamentally divided into the basic subdivisions of forebrain, midbrain, and hindbrain, further divided into four major branches comprising gray matter, white matter, ventricles, and surface features.

    “The ontology is fundamentally divided into the basic subdivisions of forebrain, midbrain, and hindbrain, further divided into four major branches comprising gray matter, white matter, ventricles, and surface features.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    We created a whole-brain ontology spanning all adult structures and including a developmental axis for transient structures observed during specification and cytoarchitectural maturation.

    “We created a whole‐brain ontology spanning all adult structures (Table 3) and including a developmental axis for transient structures observed during the specification and cytoarchitectural maturation (Miller et al. 2014).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Miller et al. 2014

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Sampling intervals varied from 0.4 to 3.4 mm across the full anterior-posterior extent of the entire left hemisphere.

    “Sampling intervals varied from 0.4 to 3.4 mm across the full anterior–posterior (A‐P) extent of the entire left hemisphere.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Sparser sampling (3.4 mm) was selectively applied to the most anterior (prefrontal) and posterior (occipital) cortical levels that primarily contain cortex and a few large subcortical structures.

    “Sparser sampling (3.4 mm) was selectively applied to the most anterior (prefrontal) and posterior (occipital) cortical levels that primarily contain cortex and a few large subcortical structures.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    The preparation appeared to result in a slight elongation of the brain.

    “This preparation appeared to result in a slight elongation of the brain.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In situ hybridization data of acetylcholinesterase (ACHE) and neurotensin (NTS) are selectively enriched in MDam compared with the main part of the MD, supporting this partition.

    “In situ hybridization data of both acetylcholinesterase (ACHE) and neurotensin (NTS) supports this partition, as they are selectively enriched in this region compared with the main part of the MD (Fig. 10B and inset).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the ventral temporal neocortex, the border between areas 36 and 20 can be more accurately defined with PV immunostaining than Nissl alone, as area 20 (20i) displays significantly stronger PV immunoreactivity than area 36.

    “Similarly, in the ventral temporal neocortex, the border between areas 36 and 20 can be more accurately defined with PV immunostaining than Nissl alone, as area 20 (20i) displays significantly stronger PV immunoreactivity than area 36 (Fig. 5D,E).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The Pir has a dark and continuous layer 2 and a less darkly stained layer 3.

    “In contrast, the Pir has a dark and continuous layer 2 and a less darkly stained layer 3.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the same brain, the medial geniculate nucleus (MG) has high and the dorsal lateral geniculate nucleus (DLG) low signal intensity on MRI.

    “A comparison of the architecture‐based atlas (Fig. 14A) and the corresponding MRI plate (Fig. 14B) from the same brain shows that the MG has high and the DLG low signal intensity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Many large pyramidal neurons in layer 5 of the primary motor cortex (M1C) are NFP-immunoreactive, while only a small number of medium-sized neurons are observed in that layer of the primary somatosensory cortex (S1C).

    “For example, many large pyramidal neurons in layer 5 of the primary motor cortex (M1C; Fig. 6A) are NFP‐immunoreactive, while only a small number of medium‐sized neurons are observed in that layer of the primary somatosensory cortex (S1C; Fig. 6B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Compared with the Pir, the LOA lacks a dark, densely packed layer 2 on Nissl stain and has much stronger NFP immunoreactivity.

    “Compared with the Pir, the LOA does not have a dark, densely packed layer 2 on Nissl stain and has much stronger NFP immunoreactivity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The BIcb in the human brain is located deep to the medial interpositus nucleus (InPM; globose nucleus) of the cerebellum and consists of scattered large NFP-immunoreactive neurons.

    “The BIcb in the human brain is located deep to the medial interpositus nucleus (InPM; globose nucleus) of the cerebellum and consists of scattered large NFP‐immunoractive neurons (Fig. 13).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The optic radiation and auditory radiation are clearly visible in the 7 T MRI images and can be followed for a long distance due to their darker appearance than the surrounding white matter.

    “Some well‐known white matter tracts such as the optic radiation (“or” in Fig. 19, levels 42–69) and auditory radiation (“ar”) are clearly visible in the 7 T MRI images and can be clearly followed for a long distance due to their darker appearance than the surrounding white matter.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    A freely accessible online atlas browser was created to allow easy visualization and navigation.

    “A freely accessible online atlas browser was created to allow easy visualization and navigation, and the resource is integrated with other human brain cellular resolution gene expression and transcriptomic atlases (Hawrylycz et al., 2012; Miller et al., 2014).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    Together, this comprehensive ontology covers all brain regions and can be used interactively to browse and search delineated structure polygons.

    “Together, this comprehensive ontology covers all brain regions and can be used interactively to browse and search delineated structure polygons.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The inferior parietal area (rostrodorsal area 40) has a narrower band of superficial layer labeling and a stronger bilaminar pattern.

    “In contrast, the inferior parietal area (rostrodorsal area 40 [area 40rd], located posterior to S1C; Fig. 6C), has a narrower band of superficial layer labeling and a stronger bilaminar pattern.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Individual Nissl plates can be matched to corresponding planes of the MRI data, allowing identification of features of specific structures that can then be mapped onto MRI data from other brains without accompanying architecture-based delineations.

    “However, individual Nissl plates can be matched to corresponding planes of the MRI data to allow the identification of features of specific structures that can then be mapped onto MRI data from other brains without accompanying architecture‐based delineations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    A new area, the lateral olfactory area (LOA), runs along the side of the lateral olfactory stria, medial to the piriform cortex (Pir) and lateral to the substantia innominata (SI), and has distinct histological features from the neighboring Pir and SI.

    “Another new area was identified running along the side of lateral olfactory stria, situated medially to the piriform cortex (Pir) and laterally to the substantia innominata (SI). This was termed the lateral olfactory area (LOA) and was found to have distinct histological features from the neighboring Pir and SI (Fig. 11).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Dark NFP and PV immunoreactivity highlights SuS and PrSc, respectively, and these complementary and corroborating data allowed a consensus digital annotation of these regions.

    “Dark NFP and PV immunoreactivity highlights SuS and PrSc, respectively, and these complementary and corroborating data allowed a consensus digital annotation of these regions (Fig. 5C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The SI does not display laminar organization, while the LOA has a clear but discontinuous layer 2 and one deep layer.

    “The SI does not display laminar organization, while the LOA has a clear but discontinuous layer 2 and one deep layer.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    At level 40 of Figure 19, the callosal and cingulate bundles, superior longitudinal fasciculus (slf-m, slf-I, and slf-l), and somatosensory radiation can be easily localized with the guide of the annotated MRI atlas.

    “For example, at level 40 of Figure 19, the callosal and cingulate bundles, superior longitudinal fasciculus (slf‐m, slf‐I, and slf‐l), and somatosensory radiation can be easily localized with the guide of the annotated MRI atlas.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains.

    “Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Anatomical delineations and annotations based on this one brain can be transferred to MRI data from other brains.

  • May combine two claims.

    Premisecitation

    Interpretation of neuroimaging data relies heavily on anatomical reference atlases for localization of underlying anatomical partitions and provides a common framework for communicating within and across allied disciplines.

    “Interpretation of these data relies heavily on anatomical reference atlases for localization of underlying anatomical partitions, which also provides a common framework for communicating within and across allied disciplines”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Mazziotta et al., 2001

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    • cites Toga et al., 2006

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    • cites Evans et al., 2012

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    Premisecitation

    Neuroimaging data are typically registered to probabilistic reference frameworks to deal with interindividual variation.

    “While neuroimaging data are typically registered to probabilistic reference frameworks (Das et al., 2016) to deal with interindividual variation”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Das et al., 2016

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Additional efforts have used ultra-high-resolution MRI of ex vivo brains to build intrinsically 3D models of cytoarchitectural boundaries, and quantify the predictive power of macroscopic features for localizing microscopically defined boundaries.

    “Additional efforts have used ultra‐high‐resolution MRI of ex vivo brains to build intrinsically 3D models of cytoarchitectural boundaries, and quantify the predictive power of macroscopic features for localizing microscopically defined boundaries”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Augustinack et al., 2005

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    • cites Fischl et al., 2008

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    • cites Iglesias et al., 2015

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The brain used for this reference atlas was from a 34-year-old female donor with no history of neurological diseases or remarkable brain abnormality.

    “The brain used for this reference atlas was from a 34‐year‐old female donor with no history of neurological diseases or remarkable brain abnormality obtained from the University of Maryland Brain and Tissue Bank”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    The anti-NFP antibody (SMI-32) is a mouse monoclonal IgG1 recognizing a double band at MW 200,000 and 180,000, which merge into a single neurofilament H line on 2D blots.

    “The antibody against NFP (BioLegend, Cat.# SMI‐32, RRID: AB_2314904) is a mouse monoclonal IgG1 recognizing a double band at MW 200,000 and 180,000, which merge into a single neurofilament H line on 2D blots (Sternberger and Sternberger, 1983)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Sternberger and Sternberger, 1983

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    These artifacts are easily identifiable but should not be confused with structural features of the underlying tissues.

    “In general these artifacts are easily identifiable but should not be confused with structural features of the underlying tissues.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A 3D model of an adult human brain based on whole-brain serial sectioning, silver staining, and MRI was recently created.

    “a 3‐dimensional (3D) model of an adult human brain based on whole‐brain serial sectioning, silver staining, and MRI (Amunts et al., 2013) was recently created”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Amunts et al., 2013

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  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    There is a strong need to bridge these levels of resolution to understand structure-function relationships in the human brain.

    “There is therefore a strong need to bridge these levels of resolution to understand structure–function relationships in the human brain (Caspers et al., 2013a; Pascual et al., 2015).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Caspers et al., 2013a

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    • cites Pascual et al., 2015

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    All work was performed according to guidelines for the research use of human brain tissue and with approval by the Human Investigation Committees and Institutional Ethics Committees of the University of Maryland, the institution from which the sample was obtained.

    “All work was performed according to guidelines for the research use of human brain tissue and with approval by the Human Investigation Committees and Institutional Ethics Committees of the University of Maryland, the institution from which the sample was obtained.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The most commonly used cytoarchitecture-based human brain atlas is Brodmann's cortical map.

    “The most commonly used cytoarchitecture‐based human brain atlas is Brodmann's cortical map (Brodmann, 1909; Talairach and Tournoux, 1988; Simić and Hof, 2015)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Brodmann, 1909

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    • cites Talairach and Tournoux, 1988

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    • cites Simić and Hof, 2015

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A probabilistic cytoarchitectural atlas (JuBrain) is being generated.

    “and a probabilistic cytoarchitectural atlas (JuBrain; see Caspers et al., 2013a) is also being generated.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Caspers et al., 2013a

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Certain artifacts in the tissue sections are present, including large cracks through most of the section in some cases as well as smaller tears in white and gray matter structures.

    “Due to the challenges of sectioning and mounting thin sections from complete hemispheres, certain artifacts in the tissue sections are present. These artifacts include large cracks through most of the section in some cases as well as smaller tears in white and gray matter structures.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisereasoning

    The staining of these specimens is limited, the imaging of the histology data currently lacks cellular resolution, and detailed annotation or parcellation of all brain regions based on cytoarchitecture remains to be performed.

    “However, the staining of these specimens is limited, the imaging of the histology data currently lacks cellular resolution, and detailed annotation or parcellation of all brain regions based on cytoarchitecture remains to be performed.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In human and monkey cerebral cortex, the anti-NFP antibody stains a subpopulation of large pyramidal neurons with labeling largely restricted to dendritic processes and soma.

    “In human and monkey cerebral cortex, the antibody stains a subpopulation of large pyramidal neurons with the labeling largely restricted to dendritic processes and soma (Campbell and Morrison, 1989; Hof et al., 1995a, 1995b; Nimchinsky et al., 1997; Ding et al., 2003, 2009).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Campbell and Morrison, 1989

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    • cites Hof et al., 1995a

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    • cites Ding et al., 2009

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  • Probably not a substantial claim: may not pass S2 (checkable).

    Premisereasoning

    Cytoarchitectural resolution is essential for more detailed studies of structural and cellular organization of the brain.

    “which is essential for more detailed studies of structural and cellular organization of the brain.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Premisenone given

    An essential component of modern interactive digital atlases is a unifying hierarchical structural ontology that provides unique IDs (and colors for representation) for each structure in a parent-child architecture.

    “An essential component of modern interactive digital atlases is a unifying hierarchical structural ontology that provides unique IDs (and colors for representation) for each structure in a parent–child architecture.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The immunostaining of sections through human temporal cortex produced a pattern of NFP labeling that was identical to previous descriptions.

    “The immunostaining of sections through human temporal cortex produced a pattern of NFP labeling that was identical to previous descriptions (Ding et al., 2009).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ding et al., 2009

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    A subset of Nissl-stained sections was selected for detailed anatomical delineation with sampling density higher in regions with greater structural complexity.

    “A subset of Nissl‐stained sections was selected for detailed anatomical delineation with sampling density higher in regions with greater structural complexity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Macroscopic landmarks (cortical sulci and gyri) were used as guides to match histological and MRI planes of section, and local topography was used to label identifiable structures including all neocortical areas and major subcortical regions.

    “Macroscopic landmarks such as cortical sulci and gyri were used as guides to match histological and MRI planes of section, and local topography was used (e.g. see Figs. 14, 15) to label identifiable structures including all neocortical areas and major subcortical regions.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    In this 7 T MRI dataset, the sr stands out from surrounding white matter like the optic and auditory radiations, and thus deserves an independent term (somatosensory radiation).

    “In this 7 T MRI dataset, like the “or” and “ar,” the “sr” is observed to stand out from surrounding white matter and thus deserves an independent term (i.e., somatosensory radiation) as do optic and auditory radiations.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The somatosensory radiation is normally treated as part of the superior radiation in the literature and mainly originates from the ventroposterior lateral nucleus of the thalamus and targets the primary somatosensory cortex.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisenone given

    The somatosensory radiation is normally treated as part of the superior radiation in the literature and mainly originates from the ventroposterior lateral nucleus of the thalamus and targets the primary somatosensory cortex.

    “The “sr” is normally treated as part of the superior radiation in the literature and mainly originates from the ventroposterior lateral nucleus of the thalamus and targets the primary somatosensory cortex.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Premisecitation

    Brain reference atlases are essential resources for neuroscience research, serving to identify and annotate the complex anatomical architecture of the brain and allow communication across laboratories and various research disciplines attempting to link structure to function.

    “Brain reference atlases are essential resources for neuroscience research, serving to identify and annotate the complex anatomical architecture of the brain and allow communication across laboratories and various research disciplines attempting to link structure to function (Fischl et al., 1999; Toga et al., 2006; Amunts et al., 2007; Evans et al., 2012).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Fischl et al., 1999

      Not checked in the free run.

    • cites Toga et al., 2006

      Not checked in the free run.

    • cites Amunts et al., 2007

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    APro has been described in detail in macaque monkey and is important for fast processing of peripheral vision.

    “It has been described in detail in macaque monkey (Morecraft et al., 2000; Ding et al., 2003) and is important for fast procession of peripheral vision (Yu et al., 2012).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Morecraft et al., 2000

      Not checked in the free run.

    • cites Ding et al., 2003

      Not checked in the free run.

    • cites Yu et al., 2012

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    One brain may have area 35 located in the medial bank of a deep collateral sulcus, while another may have its area 35 in the lateral bank of a shallow collateral sulcus, or even the crown of the anterior fusiform gyrus.

    “For instance, one brain may have area 35 located in the medial bank of a deep collateral sulcus (CoS), while another may have its area 35 in the lateral bank of a shallow CoS, or even the crown of the anterior fusiform gyrus (Ding and Van Hoesen, 2010).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Ding and Van Hoesen, 2010

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    This versatile and publicly accessible resource gives a range of users a means to learn, teach, and investigate human brain structure and function, including the diagnosis and treatment of brain disease.

    “This versatile and publicly accessible resource gives a range of users a means to learn, teach, and investigate human brain structure and function, including the diagnosis and treatment of brain disease.”
    Quote in the paperNot a substantial claim
55 of 55

  • The paper relies on this without support.

    A single adult female brain without neurological disease is representative of the adult human brain for the purpose of a reference atlas.

    “The brain used for this reference atlas was from a 34‐year‐old female donor with no history of neurological diseases or remarkable brain abnormality”

  • The paper relies on this without support.

    Anatomical delineations and annotations based on this one brain can be transferred to MRI data from other brains.

    “Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains.”

  • The paper relies on this without support.

    The homologs of MDam and BMm in other species have not been reported.

    “The homologs of MDam and BMm in other species have not been reported.”

  • The paper relies on this without support.

    The exact location and extent of area prostriata in the human brain has not been reported in detail so far.

    “Although its existence in the human brain was briefly described, its exact location and extent has not been reported in detail so far.”

  • The paper relies on this without support.

    The somatosensory radiation is normally treated as part of the superior radiation in the literature and mainly originates from the ventroposterior lateral nucleus of the thalamus and targets the primary somatosensory cortex.

    “The “sr” is normally treated as part of the superior radiation in the literature and mainly originates from the ventroposterior lateral nucleus of the thalamus and targets the primary somatosensory cortex.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Anti-NFP antibody dilution differs between methods and Table 2

    Minor

    The methods give the SMI-32 dilution as 1:3,000, while Table 2 lists 1:5,000 for the same antibody.

  • Reported section dimensions cannot fit on the stated slides

    Minor

    A section described as approximately 3.2 × 4.3 metres cannot be mounted on a 3 × 5 inch slide. The dimension or its unit is inconsistent with the stated slide size.

  • Figure 2 cortical-map labels are reversed

    Minor

    The Figure 2 caption assigns modified Brodmann areas to I1 and the gyral map to I2, but the results text assigns them the other way around.

  • Figure 6 references swap the nerve-root and commissure panels

    Minor

    The results cite panel G for motor roots and panel F for the inferior-colliculus commissure. The Figure 6 caption identifies F as a nerve-root panel and G as the commissure panel.

  • Figure 17 repeats section 05_047 at levels 44 and 65

    Minor

    The same section identifier appears at two widely separated anterior-to-posterior levels. Level 65 also falls among entries identified as slab 06 rather than slab 05.

5 of 5

Cites

Flagged first, then by citations

1 of the 91 references couldn’t be matched to a known paper.

Research works printed but not linked: 5

  1. Brodmann K, 1909, Localisation in the cerebral cortex
  2. Jones EG, 2007, The thalamus
  3. Mai JK, 2008, Atlas of the human brain
  4. Sarkisov SA, 1955, Atlas of the cytoarchitectonics of the human cerebral cortex
  5. WangR BennerT SoresenAG WedeenVJ.2007.Diffusion Toolkit: a software package for diffusion imaging data processing and tractograpy. Proceedings of 15th Annual Meeting of International Society for Magnetic Resonance in Medicine p3720.

Cited by

Sorted by citations

Related

Authors
Ding, S., Royall, J. J., Sunkin, S. M., Ng, L., Facer, B. A. C., Lesnar, P., Guillozet‐Bongaarts, A., McMurray, B., Szafer, A., Dolbeare, T. A., Stevens, A., Tirrell, L., Benner, T., Caldejon, S., Dalley, R. A., Dee, N., Lau, C., Nyhus, J., Reding, M., Riley, Z. L., Sandman, D., Shen, E., van der Kouwe, A., Varjabedian, A., Write, M., Zollei, L., Dang, C., Knowles, J. A., Koch, C., Phillips, J. W., Sestan, N., Wohnoutka, P., Zielke, H. R., Hohmann, J. G., Jones, A. R., Bernard, A., Hawrylycz, M. J., Hof, P. R., Fischl, B., & Lein, E. S.
Affiliations
  • Allen Institute for Brain Science (US)
  • Harvard University (US)
  • Department of Radiology, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging Massachusetts General Hospital Charlestown Massachusetts 02129
  • University of Southern California (US)
  • Allen Institute for Brain Science Seattle Washington 98109
  • Department of Neurobiology and Kavli Institute for Neuroscience Yale University School of Medicine New Haven Connecticut 06510
  • University of Maryland, Baltimore (US)
  • Icahn School of Medicine at Mount Sinai (US)
Corresponding author
  • Ding, Song‐Lin
  • Lein, Ed S.
ORCID
Venue
Journal of Comparative Neurology
Publisher
Wiley
Published
2016-09-15
Volume
524
Issue
16
Pages
3127-3481
ISSN
  • 0021-9967 (ISSN-L)
  • 1096-9861
DOI
10.1002/cne.24080
PMC
PMC5054943
OpenAlex
W2504912000
Cited by
447
References
91
Citations by year
2026: 39 · 2025: 59 · 2024: 52 · 2023: 55 · 2022: 46 · 2021: 49 · 2020: 50 · 2019: 42 · 2018: 35 · 2017: 18 · 2016: 2
FWCI
28.05
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Comparative Neurology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders
  • National Institutes of Health (RC2 MH089921)
  • NIH Blueprint for Neuroscience Research (5U01‐MH093765)
  • National Institute on Aging (5R01AG008122 & R01AG016495)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
  • Physical Sciences › Engineering › Biomedical Engineering › Anatomy and Medical Technology
  • Physical Sciences › Computer Science › Computer Vision and Pattern Recognition › Medical Image Segmentation Techniques
Keywords
digital brain atlas, white matter tracts, cytoarchitecture, chemoarchitecture, Nissl staining, immunohistochemistry, diffusion-weighted imaging, MRI-histology correlation, Brodmann areas, female brain
MeSH terms
Adult, Anatomy, Artistic, Brain, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Parvalbumins, Neurofilament Proteins, Diffusion Magnetic Resonance Imaging

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-08.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-08.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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