ArticlePsychopharmacology2015
Ketamine induces a robust whole-brain connectivity pattern that can be differentially modulated by drugs of different mechanism and clinical profile.
Article in Psychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 3 of them syntheses that pooled it.
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The trial behind it
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Who cites it
45 citing papers in PubMed, 3 syntheses or guidelines pooled it, 76 citations in OpenAlex.
- Functional imaging studies of acute administration of classic psychedelics, ketamine, and MDMA: Methodological limitations and convergent results.Neuroscience and biobehavioral reviews · 2023Pooled it
- Pooled it
- Pharmacodynamic Interactions Between Ketamine and Psychiatric Medications Used in the Treatment of Depression: A Systematic Review.The international journal of neuropsychopharmacology · 2021Pooled it
- Ketamine induces multiple individually distinct whole-brain functional connectivity signatures.eLife · 2024Trial
- Validation of ketamine as a pharmacological model of thalamic dysconnectivity across the illness course of schizophrenia.Molecular psychiatry · 2022Trial
- Oxytocin modulates local topography of human functional connectome in healthy men at rest.Communications biology · 2021Trial
- Modulation of simultaneously collected hemodynamic and electrophysiological functional connectivity by ketamine and midazolam.Human brain mapping · 2020Trial
- Effects of ketamine and midazolam on resting state connectivity and comparison with ENIGMA connectivity deficit patterns in schizophrenia.Human brain mapping · 2020Trial
- Association between dynamic resting-state functional connectivity and ketamine plasma levels in visual processing networks.Scientific reports · 2019Trial
- Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: effects on cognition.Psychopharmacology · 2018Trial
- Pharmacological fMRI: Effects of subanesthetic ketamine on resting-state functional connectivity in the default mode network, salience network, dorsal attention network and executive control network.NeuroImage. Clinical · 2018Trial
- Effects of ketamine on brain function during smooth pursuit eye movements.Human brain mapping · 2016Trial
- Species-conserved reconfigurations of brain network topology induced by ketamine.Translational psychiatry · 2016Trial
- Modulatory effects of ketamine, risperidone and lamotrigine on resting brain perfusion in healthy human subjects.Psychopharmacology · 2015Trial
- Pharmacological MRI: Utility in Understanding Drug Mechanisms in Psychiatric Disorders.Journal of magnetic resonance imaging : JMRI · 2026Review
- The nitric oxide synthase inhibitor 7-nitroindazole attenuates social withdrawal and memory impairments induced by Blockade of the NMDA receptor in the rat.Psychopharmacology · 2025Article
- Molecular Mechanisms Underlying Chronic High-Dose Ketamine-Induced Apoptosis in the Hippocampus: A Narrative Review.Neurochemical research · 2025Review
- Connectome harmonic decomposition tracks the presence of disconnected consciousness during ketamine-induced unresponsiveness.British journal of anaesthesia · 2025Article
- Measuring acute effects of subanesthetic ketamine on cerebrovascular hemodynamics in humans using TD-fNIRS.Scientific reports · 2023Article
- The Role of fMRI in Drug Development: An Update.Advances in neurobiology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has been studied in relation to the glutamate hypothesis of schizophrenia and increases dissociation, positive and negative symptom ratings. Ketamine effects brain function through changes in brain activity; these activity patterns can be modulated by pre-treatment of compounds known to attenuate the effects of ketamine on glutamate release. Ketamine also has marked effects on brain connectivity; we predicted that these changes would also be modulated by compounds known to attenuate glutamate release. Here, we perform task-free pharmacological magnetic resonance imaging (phMRI) to investigate the functional connectivity effects of ketamine in the brain and the potential modulation of these effects by pre-treatment of the compounds lamotrigine and risperidone, compounds hypothesised to differentially modulate glutamate release. Connectivity patterns were assessed by combining windowing, graph theory and multivariate Gaussian process classification. We demonstrate that ketamine has a robust effect on the functional connectivity of the human brain compared to saline (87.5 % accuracy). Ketamine produced a shift from a cortically centred, to a subcortically centred pattern of connections. This effect is strongly modulated by pre-treatment with risperidone (81.25 %) but not lamotrigine (43.75 %). Based on the differential effect of these compounds on ketamine response, we suggest the observed connectivity effects are primarily due to NMDAR blockade rather than downstream glutamatergic effects. The connectivity changes contrast with amplitude of response for which no differential effect between pre-treatments was detected, highlighting the necessity of these techniques in forming an informed view of the mechanistic effects of pharmacological compounds in the human brain.
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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.