Evidence map›Paper›PMID 31474560›Full record

ArticleCell stem cell2019

Complex Oscillatory Waves Emerging from Cortical Organoids Model Early Human Brain Network Development.

Cleber A Trujillo, Richard Gao, Priscilla D Negraes, Jing Gu, Justin Buchanan, Sebastian Preissl, Allen Wang, Wei Wu, Gabriel G Haddad, Isaac A Chaim and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 500 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
500citing papers in PubMed, 1 pooled it
–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

500 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Modelling mitochondrial diseases in neuronsJournal of neuromuscular diseases · 2025
    Pooled it
  2. Human-biasedLife science alliance · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Using Brain Organoids to Explore Human Neurobiology.Cellular and molecular neurobiology · 2026
    Review
  8. Article
  9. Article
  10. Article
  11. Three-dimensional microelectrode arrays forBiomedical engineering letters · 2026
    Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review

440 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Cleber A TrujilloDepartment of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular & Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Richard GaoNeurosciences Graduate Program, Institute for Neural Computation, Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92093, USA.
Priscilla D NegraesDepartment of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular & Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Jing GuCenter for Epigenomics, Department of Cellular & Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Justin BuchananCenter for Epigenomics, Department of Cellular & Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Sebastian PreisslCenter for Epigenomics, Department of Cellular & Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Allen WangCenter for Epigenomics, Department of Cellular & Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Wei WuDepartment of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Gabriel G HaddadDepartment of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
Isaac A ChaimDepartment of Cellular & Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Alain DomissyDepartment of Cellular & Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Matthieu VandenbergheDepartment of Radiology, Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
Anna DevorDepartment of Radiology, Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA; Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Gene W YeoDepartment of Cellular & Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Bradley VoytekNeurosciences Graduate Program, Institute for Neural Computation, Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92093, USA; Kavli Institute for Brain and Mind and Halıcıoğlu Data Science Institute, University of California, San Diego, La Jolla, CA 92093, USA.
Alysson R MuotriDepartment of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular & Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Kavli Institute for Brain and Mind and Halıcıoğlu Data Science Institute, University of California, San Diego, La Jolla, CA 92093, USA; Center for Academic Research and Training in Anthropogeny (CARTA), La Jolla, CA 92093, USA. Electronic address: muotri@ucsd.edu.

Funding

UCSD/SDSU IRACDAK12GM068524 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TREJO, JOANN · 2003 to 2025
$24.4M
Proteogenetics of Autism Spectrum DisordersR01MH100175 · NIMH · SCRIPPS RESEARCH INSTITUTE, THE · PI MUOTRI, ALYSSON R., YATES III, JOHN R · 2013 to 2025
$7.4M
MICROSCOPIC FOUNDATION OF MULTIMODAL HUMAN IMAGINGR01MH111359 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DALE, ANDERS M, DEVOR, ANNA · 2016 to 2020
$5.6M
Integrative functional genomic study of pathways impacted by recurrent autism CNVR01MH108528 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IAKOUCHEVA, LILIA M, MUOTRI, ALYSSON R. · 2016 to 2020
$2.6M
Evaluating the effect of splicing mutations on isoform networks in autismR01MH109885 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IAKOUCHEVA, LILIA M, MUOTRI, ALYSSON R. · 2016 to 2020
$2.5M
The Impact of L1retrotransposition in the nervous systemR01MH094753 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MUOTRI, ALYSSON R. · 2011 to 2015
$1.9M
A human neurodevelopmental model for Williams syndromeR56MH109587 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MUOTRI, ALYSSON R., SEMENDEFERI, KATERINA · 2016 to 2016
$376k
NIGMS NIH HHS K12 GM068524NIMH NIH HHS R01 MH094753NIMH NIH HHS R01 MH100175NIMH NIH HHS R01 MH108528NIMH NIH HHS R01 MH109885NIMH NIH HHS R01 MH111359NIMH NIH HHS R56 MH109587
6 · The paper itself

Abstract

Structural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, whether this is true for functional network activity remains unknown, primarily due to experimental inaccessibility of the initial stages of the living human brain. Here, we developed human cortical organoids that dynamically change cellular populations during maturation and exhibited consistent increases in electrical activity over the span of several months. The spontaneous network formation displayed periodic and regular oscillatory events that were dependent on glutamatergic and GABAergic signaling. The oscillatory activity transitioned to more spatiotemporally irregular patterns, and synchronous network events resembled features similar to those observed in preterm human electroencephalography. These results show that the development of structured network activity in a human neocortex model may follow stable genetic programming. Our approach provides opportunities for investigating and manipulating the role of network activity in the developing human cortex.

Indexed as

Biological ClocksCells, CulturedCerebellar CortexElectromagnetic Radiationgamma-Aminobutyric AcidGene Expression ProfilingHumansInduced Pluripotent Stem CellsNeocortexNerve NetNeurogenesisOrganoidsSignal TransductionSingle-Cell AnalysisSynaptic Transmissiongamma-Aminobutyric Acidcortical organoidsnetwork oscillationsphase-amplitude couplingpreterm electroencephalographysingle-cell transcriptomicsstem cells

Identifiers

PMID31474560
PMCPMC6778040

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.