Trial reportProceedings of the National Academy of Sciences of the United States of America2012
NMDA receptor function in large-scale anticorrelated neural systems with implications for cognition and schizophrenia.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02533232 (Minocycline Augmentation of Clozapine for Treatment Resistant Schizophrenia), which is not on this map. Cited by 146 papers, 1 of them a synthesis that pooled 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.
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.
Minocycline Augmentation of Clozapine for Treatment Resistant Schizophrenia: A Randomised Placebo-controlled Double-blind Trial
Who cites it
146 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A systematic review of the role of the nociceptin receptor system in stress, cognition, and reward: relevance to schizophrenia.Translational psychiatry · 2018Pooled it
- Ketamine induces multiple individually distinct whole-brain functional connectivity signatures.eLife · 2024Trial
- Higher-order functional brain networks and anterior cingulate glutamate + glutamine (Glx) in antipsychotic-naïve first episode psychosis patients.Translational psychiatry · 2024Trial
- Region- and time- specific effects of ketamine on cerebral blood flow: a randomized controlled trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Trial
- Validation of ketamine as a pharmacological model of thalamic dysconnectivity across the illness course of schizophrenia.Molecular psychiatry · 2022Trial
- Effects of Ketamine and Midazolam on Simultaneous EEG/fMRI Data During Working Memory Processes.Brain topography · 2021Trial
- A robust and reproducible connectome fingerprint of ketamine is highly associated with the connectomic signature of antidepressants.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Trial
- Memantine Effects on Electroencephalographic Measures of Putative Excitatory/Inhibitory Balance in Schizophrenia.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2020Trial
- Trial
- Dose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects.Biological psychiatry · 2018Trial
- Group II metabotropic glutamate receptor agonist prodrugs LY2979165 and LY2140023 attenuate the functional imaging response to ketamine in healthy subjects.Psychopharmacology · 2018Trial
- Is a Responsive Default Mode Network Required for Successful Working Memory Task Performance?The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Trial
- Ketamine-Induced Modulation of the Thalamo-Cortical Network in Healthy Volunteers As a Model for Schizophrenia.The international journal of neuropsychopharmacology · 2015Trial
- Selective augmentation of striatal functional connectivity following NMDA receptor antagonism: implications for psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Trial
- Integrated Network Pharmacology, Molecular Docking, and Experimental Validation Elucidating the Therapeutic Mechanism ofFood science & nutrition · 2026Article
- Pharmacological MRI: Utility in Understanding Drug Mechanisms in Psychiatric Disorders.Journal of magnetic resonance imaging : JMRI · 2026Review
- Understanding Schizophrenia Pathophysiology via fMRI-Based Information Theory and Multiplex Network Analysis.Entropy (Basel, Switzerland) · 2026Article
- NMDA receptor kinetics drive distinct routes to chaotic firing in pyramidal neurons.Frontiers in computational neuroscience · 2026Article
- Investigation of the effective connectivity between the anti-NMDAR encephalitis default mode network and the medial temporal lobe network using spectral dynamic causal modelling.Brain imaging and behavior · 2025Article
- Studying Time-Resolved Functional Connectivity via Communication Theory: On the Complementary Nature of Phase Synchronization and Sliding Window Pearson Correlation.Brain connectivity · 2025Article
86 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
Abstract
Glutamatergic neurotransmission mediated by N-methyl-d-aspartate (NMDA) receptors is vital for the cortical computations underlying cognition and might be disrupted in severe neuropsychiatric illnesses such as schizophrenia. Studies on this topic have been limited to processes in local circuits; however, cognition involves large-scale brain systems with multiple interacting regions. A prominent feature of the human brain's global architecture is the anticorrelation of default-mode vs. task-positive systems. Here, we show that administration of an NMDA glutamate receptor antagonist, ketamine, disrupted the reciprocal relationship between these systems in terms of task-dependent activation and connectivity during performance of delayed working memory. Furthermore, the degree of this disruption predicted task performance and transiently evoked symptoms characteristic of schizophrenia. We offer a parsimonious hypothesis for this disruption via biophysically realistic computational modeling, namely cortical disinhibition. Together, the present findings establish links between glutamate's role in the organization of large-scale anticorrelated neural systems, cognition, and symptoms associated with schizophrenia in humans.
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Registered trials
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.