ArticlemedRxiv : the preprint server for health sciences2026
Convergent multidimensional neural phenotypes in human patients and schizophrenia-relevant mouse models identify reduced recurrent excitation in cortical circuits.
Kenneth Wengler, Jordan P Hamm, Yuriy Shymkiv, Kenneth D Miller, Rafael Yuste, Guillermo Horga
Abstract readPreprint
In one paragraphArticle in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
6 authors.
Kenneth WenglerDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.ORCID 0000-0002-8153-5183 Jordan P HammNeurotechnology Center, Department of Biological Sciences, Columbia University, New York, New York.ORCID 0000-0002-9868-6121 Yuriy ShymkivNeurotechnology Center, Department of Biological Sciences, Columbia University, New York, New York.ORCID 0000-0001-9086-8273 Kenneth D MillerMortimer B. Zuckerman Mind Brain and Behavior Institute, Columbia University, New York, New York.
Rafael YusteNeurotechnology Center, Department of Biological Sciences, Columbia University, New York, New York.
Guillermo HorgaDepartment of Psychiatry, Columbia University and New York State Psychiatric Institute, New York, New York.ORCID 0000-0002-9049-9786 Funding
Transcranial Direct Current Stimulation for Treatment of Auditory Verbal HalluciP20GM103472 · NIGMS · THE MIND RESEARCH NETWORK · PI BEDRICK, EDWARD J · 2012 to 2017
$14.3MNEURAL MECHANISMS OF SCHIZOPHRENIAP20RR021938 · NCRR · THE MIND RESEARCH NETWORK · PI HANLON, FAITH MARIE · 2008 to 2011
$9.4MHuman Translational Applications Core (HTA - Core) (7 of 8)PL1MH083271 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BILDER, ROBERT M · 2007 to 2011
$5.8MTranslational Methods/Facilities Core (TMF - Core) (8 of 8)PL1NS062410 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EVANS, CHRISTOPHER J. · 2007 to 2011
$4.6MNEUROMORPHOMETRY IN SCHIZOPHRENIA BY COMPUTER ALGORITHMR01MH056584 · NIMH · WASHINGTON UNIVERSITY · PI CSERNANSKY, JOHN G · 1998 to 2011
$4.2MTranslational Models of Memory and Cognitive Control (Component 5 of 8)RL1MH083270 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JENTSCH, J. DAVID · 2007 to 2011
$2.6MBiophysical modeling as a translational bridge for understanding neural ensemble alterations in schizophrenia.R01MH134973 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Kenneth Wengler · 2024 to 2026
$2.3MWhole Genome Assoc. Analysis Strategies for Multi. PhenotypesRL1MH083268 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREIMER, NELSON B. · 2007 to 2011
$2.1MConsortium for Neuropsychiatric Phenomics-Coordinating Center (1 of 8)UL1DE019580 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BILDER, ROBERT M · 2008 to 2011
$1.9MMemory Mechanisms and Mental DisordersRL1MH083269 · NIMH · YALE UNIVERSITY · PI CANNON, TYRONE D · 2007 to 2011
$1.8MResponse Inhibition and Dopamine Neurotransmission (RI) (4 of 8)RL1DA024853 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LONDON, EDYTHE DANICK · 2007 to 2011
$1.7MBrain Glutamate and Outcome in SchizophreniaR01MH084898 · NIMH · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI BUSTILLO, JUAN RICARDO · 2009 to 2013
$1.7MNCRR NIH HHS P20 RR021938NIDA NIH HHS RL1 DA024853NIDCR NIH HHS UL1 DE019580NIGMS NIH HHS P20 GM103472NIMH NIH HHS PL1 MH083271NIMH NIH HHS R01 MH056584NIMH NIH HHS R01 MH084898NIMH NIH HHS R01 MH134973NIMH NIH HHS RL1 MH083268NIMH NIH HHS RL1 MH083269NIMH NIH HHS RL1 MH083270NINDS NIH HHS PL1 NS062410NLM NIH HHS RL1 LM009833
6 · The paper itselfAbstract
Objective: NMDA-receptor hypofunction has been implicated as a core pathophysiological mechanism in schizophrenia, but conflicting evidence exists regarding the locus of the hypofunction-i.e. predominantly affecting receptors on pyramidal neurons or interneurons. To investigate the locus of NMDA-receptor hypofunction we integrated imaging data from humans and mice with biophysical model simulations. Methods: Translational imaging measures-intrinsic neural timescales (INT) and spontaneous co-activation pattern similarity-were investigated in three schizophrenia-relevant mouse models (chronic ketamine administration, n=6; Results: We identified convergent neural phenotypes of shorter intrinsic neural timescales (INT) and reduced spontaneous co-activation pattern similarity in both the schizophrenia-relevant mouse models and the individuals with schizophrenia compared to matched controls. Conclusions: These results identify NMDA-receptor hypofunction on pyramidal neurons as a general and translationally valid mechanism for NMDA-receptor hypofunction in schizophrenia. These convergent translational findings suggest prioritizing the development of treatments for schizophrenia that increase recurrent excitation.
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PMID42818486
PMCPMC13622416
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