Evidence map›Paper›PMID 40791449›Full record

ArticlebioRxiv : the preprint server for biology2025

Spatio-molecular gene expression reflects dorsal anterior cingulate cortex structure and function in the human brain.

Kinnary Shah, Michael S Totty, Svitlana V Bach, Madeline R Valentine, Atharv Chandra, Heena R Divecha, Ryan A Miller, Sang Ho Kwon, Anthony D Ramnauth, Madhavi Tippani and 9 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Kinnary ShahDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.ORCID 0000-0001-7098-2116
Michael S TottyDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.ORCID 0000-0002-9292-8556
Svitlana V BachLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.ORCID 0000-0003-1134-9585
Madeline R ValentineLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.ORCID 0000-0001-6078-2794
Atharv ChandraLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.ORCID 0009-0000-3019-7308
Heena R DivechaLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.ORCID 0000-0002-1959-0675
Ryan A MillerLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.ORCID 0000-0003-3477-7443
Sang Ho KwonLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.ORCID 0000-0001-5328-0956
Anthony D RamnauthLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.ORCID 0000-0001-5373-0857
Madhavi TippaniLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.ORCID 0000-0002-6465-6418
Sanjana TyagiLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
Joel E KleinmanLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.ORCID 0000-0002-4210-6052
Leonardo Collado-TorresDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.ORCID 0000-0003-2140-308X
Shizhong HanLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.ORCID 0000-0002-5114-6742
Thomas M HydeLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.ORCID 0000-0002-8746-3037
Stephanie C PageLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.ORCID 0000-0002-1951-7398
Kristen R MaynardLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.ORCID 0000-0003-0031-8468
Stephanie C HicksDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.ORCID 0000-0002-7858-0231
Keri MartinowichLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.ORCID 0000-0002-5237-0789

Funding

Registration of spatial gene expression in key nodes of reward-related circuitry in the human brainR01DA053581 · NIDA · LIEBER INSTITUTE, INC. · PI MARTINOWICH, KERI · 2021 to 2025
$3.7M
Molecular, cellular and physiological correlates of sustained attention in the locus coeruleus to anterior cingulate cortex circuitR21MH130066 · NIMH · LIEBER INSTITUTE, INC. · PI HALLOCK, HENRY L, MARTINOWICH, KERI · 2023 to 2023
$444k
Neural substrates of extinction deficits in pathological fearF32MH135620 · NIMH · JOHNS HOPKINS UNIVERSITY · PI Michael Totty · 2023 to 2026
$224k
IMPLICIT AND EXPLICIT MEMORY FOR FACES IN SOCIAL PHOBIAF31MH013006 · NIMH · TEMPLE UNIVERSITY · PI COLES, MEREDITH ELLEN · 2001 to 2002
$26k
NIDA NIH HHS R01 DA053581NIMH NIH HHS F31 MH013006NIMH NIH HHS F32 MH135620NIMH NIH HHS R21 MH130066
6 · The paper itself

Abstract

In the human brain, the dorsal anterior cingulate cortex (dACC) plays key roles in various components of cognitive control, and is particularly relevant for reward processing and conflict monitoring. The dACC regulates expression of fear and pain, and its dysfunction is implicated in a number of neuropsychiatric disorders. Compared to more recently specialized neocortical areas, such as the dorsolateral prefrontal cortex (dlPFC), the dACC is evolutionarily older. The region's agranular structure, and other evolutionary specializations, such as the presence of von Economo neurons (VENs), contribute to its specialized roles in cognitive and emotional processing. Here, we generated paired spatially-resolved transcriptomics (SRT) and single-nucleus RNA-sequencing (snRNA-seq) data from adjacent tissue sections of the dACC in ten adult neurotypical donors to define molecular profiles for dACC cell types and spatial domains. Using non-negative matrix factorization (NMF), we integrated these data by identifying gene expression patterns within the snRNA-seq data, which were projected onto the SRT data to infer the spatial localization. Combining these data with publicly available resources, we revealed insights about molecular profiles, spatial topography, enrichment of disease risk, and putative connectivity of spatially-localized dACC cell types, including VENs. Utilizing published dlPFC snRNA-seq and SRT data collected in the same neurotypical brain donors used here, we deployed cross-region comparison analyses between dACC and dlPFC to understand spatio-molecular specializations and laminar organization across human brain evolution. To make this comprehensive molecular resource accessible to the scientific community, we made both raw and processed data freely available, including through interactive web applications.

Indexed as

dorsal anterior cingulate cortexpostmortem human brainsingle-nucleus RNA-sequencingspatially-resolved transcriptomics

Identifiers

PMID40791449
PMCPMC12338615

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.