Evidence map›Paper›PMID 40925365›Full record

ArticleCell reports2025

Cortical versus hippocampal network dysfunction in a human brain assembloid model of epilepsy and intellectual disability.

Colin M McCrimmon, Daniel Toker, Marie Pahos, Qing Cao, Kevin Lozano, Jack J Lin, Jack M Parent, Andrew Tidball, Jie Zheng, László Molnár and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Colin M McCrimmonDepartment of Neurology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
Daniel TokerDepartment of Neurology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
Marie PahosDepartment of Neurology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
Qing CaoDepartment of Neurology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
Kevin LozanoDepartment of Neurology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
Jack J LinDepartment of Neurology, University of California, Davis, School of Medicine, Sacramento, CA 95817, USA; Center for Mind and Brain, University of California, Davis, Davis, CA 95618, USA.
Jack M ParentDepartment of Neurology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA; VA Ann Arbor Healthcare System, Ann Arbor, MI 48105, USA.
Andrew TidballMichigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Jie ZhengDepartment of Biomedical Engineering, University of California, Davis, Davis, CA 95616, USA; Department of Neurological Surgery, University of California, Davis, School of Medicine, Sacramento, CA 95817, USA.
László MolnárDepartment of Electrical Engineering, Sapientia Hungarian University of Transylvania, Târgu-Mureş/Corunca 540485, Romania.
Istvan ModyDepartment of Neurology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA; Department of Physiology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
Bennett G NovitchDepartment of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Intellectual Development and Disabilities Research Center, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: bnovitch@g.ucla.edu.
Ranmal A SamarasingheDepartment of Neurology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA; Department of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Intellectual Development and Disabilities Research Center, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: rsamarasinghe@mednet.ucla.edu.

Funding

UCLA IDDRC: Translational CoreP50HD103557 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HARLEY IAN KORNBLUM · 2020 to 2026
$9.6M
Elucidating the molecular mechanisms behind human neurodevelopmental disorders using brain organoidsR01MH130061 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BENNETT G NOVITCH · 2022 to 2026
$3.6M
Integrative Modeling of HIV-Associated Neurocognitive Disorder in Human Brain OrganoidsR01DA051897 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREGOSO, OLIVER I, NOVITCH, BENNETT G · 2020 to 2024
$3.1M
Utilizing Human Brain Organoids to Model the Differential Effects of SCN8A Mutation on Cortex and HippocampusK08NS119747 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SAMARASINGHE, RANMAL A · 2021 to 2025
$1.1M
NICHD NIH HHS P50 HD103557NIDA NIH HHS R01 DA051897NIMH NIH HHS R01 MH130061NINDS NIH HHS K08 NS119747
6 · The paper itself

Abstract

Neurodevelopmental disorders often impair multiple cognitive domains. For instance, a genetic epilepsy syndrome might cause seizures due to cortical hyperexcitability and present with memory impairments arising from hippocampal dysfunction. This study examines how a single disorder differentially affects distinct brain regions using induced pluripotent stem cell (iPSC)-derived cortical- and hippocampal-ganglionic eminence assembloids to model developmental and epileptic encephalopathy 13, a condition arising from gain-of-function mutations in the SCN8A gene encoding the sodium channel Nav1.6. While cortical assembloids showed network hyperexcitability akin to epileptogenic tissue, hippocampal assembloids did not, and instead displayed network dysregulation patterns similar to in vivo hippocampal recordings from epilepsy patients. Predictive computational modeling, immunohistochemistry, and single-nucleus RNA sequencing revealed changes in excitatory and inhibitory neuron organization that were specific to hippocampal assembloids. These findings highlight the unique impacts of a single pathogenic variant across brain regions and establish hippocampal assembloids as a platform for studying neurodevelopmental disorders.

Indexed as

Cerebral CortexEpilepsyHippocampusIntellectual DisabilityNerve NetFemaleHumansInduced Pluripotent Stem CellsMaleNAV1.6 Voltage-Gated Sodium ChannelNeuronsNAV1.6 Voltage-Gated Sodium Channelbrain organoidscellular neuroscienceCP: Neurosciencedisease modelingepilepsyhippocampal assembloidsneural circuitsneural stem cells

Identifiers

PMID40925365
PMCPMC12674601

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.