PMID- 25141922 OWN - NLM STAT- MEDLINE DCOM- 20160315 LR - 20230209 IS - 1740-634X (Electronic) IS - 0893-133X (Print) IS - 0893-133X (Linking) VI - 40 IP - 3 DP - 2015 Feb TI - Selective augmentation of striatal functional connectivity following NMDA receptor antagonism: implications for psychosis. PG - 622-31 LID - 10.1038/npp.2014.210 [doi] AB - The psychotomimetic effect of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine is thought to arise from a functional modulation of the brain's fronto-striato-thalamic (FST) circuits. Animal models suggest a pronounced effect on ventral 'limbic' FST systems, although recent work in patients with psychosis and high-risk individuals suggests specific alterations of dorsal 'associative' FST circuits. Here, we used functional magnetic resonance imaging to investigate the effects of a subanesthetic dose of ketamine on measures of functional connectivity as indexed by the temporal coherence of spontaneous neural activity in both dorsal and ventral FST circuits, as well as their symptom correlates. We adopted a placebo-controlled, double-blind, randomized, repeated-measures design in which 19 healthy participants received either an intravenous saline infusion or a racemic mixture of ketamine (100 ng/ml) separated by at least 1 week. Compared with placebo, ketamine increased functional connectivity between the dorsal caudate and both the thalamus and midbrain bilaterally. Ketamine additionally increased functional connectivity of the ventral striatum/nucleus accumbens and ventromedial prefrontal cortex. Both connectivity increases significantly correlated with the psychosis-like and dissociative symptoms under ketamine. Importantly, dorsal caudate connectivity with the ventrolateral thalamus and subthalamic nucleus showed inverse correlation with ketamine-induced symptomatology, pointing to a possible resilience role to disturbances in FST circuits. Although consistent with the role of FST in mediating psychosis, these findings contrast with previous research in clinical samples by suggesting that acute NMDAR antagonism may lead to psychosis-like experiences via a mechanism that is distinct from that implicated in frank psychotic illness. FAU - Dandash, Orwa AU - Dandash O AD - 1] Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia [2] Monash Clinical and Imaging Neuroscience Laboratory, School of Psychology and Psychiatry, Monash University, Clayton, VIC, Australia. FAU - Harrison, Ben J AU - Harrison BJ AD - Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia. FAU - Adapa, Ram AU - Adapa R AD - 1] Division of Anaesthesia, University of Cambridge, Cambridge, UK [2] Addenbrooke's Hospital, Cambridge, UK. FAU - Gaillard, Raphael AU - Gaillard R AD - 1] Universite Paris Descartes, Sorbonne Paris Cite, INSERM UMR S894, Paris, France [2] Centre Hospitalier Sainte-Anne, Department of Psychiatry, Service Hospitalo-Universitaire, Paris, France [3] INSERM, Laboratoire de Physiopathologie des Maladies Psychiatriques, Centre de Psychiatrie et Neurosciences, UMR S894, Paris, France. FAU - Giorlando, Francesco AU - Giorlando F AD - Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia. FAU - Wood, Stephen J AU - Wood SJ AD - 1] Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia [2] School of Psychology, University of Birmingham, Birmingham, UK. FAU - Fletcher, Paul C AU - Fletcher PC AD - Department of Psychiatry, Brain Mapping Unit and Behavioural and Clinical Neurosciences Institute, School of Clinical Medicine, University of Cambridge, Cambridge, UK. FAU - Fornito, Alex AU - Fornito A AD - 1] Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia [2] Monash Clinical and Imaging Neuroscience Laboratory, School of Psychology and Psychiatry, Monash University, Clayton, VIC, Australia. LA - eng GR - 095692/WT_/Wellcome Trust/United Kingdom GR - G0001354/MRC_/Medical Research Council/United Kingdom GR - WT_/Wellcome Trust/United Kingdom GR - 064351/WT_/Wellcome Trust/United Kingdom GR - G1000183/MRC_/Medical Research Council/United Kingdom GR - 083660/Z/07/Z/WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20140821 PL - England TA - Neuropsychopharmacology JT - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JID - 8904907 RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 690G0D6V8H (Ketamine) SB - IM MH - Adult MH - Corpus Striatum/*drug effects/*physiology MH - Double-Blind Method MH - Female MH - Frontal Lobe/drug effects/physiology MH - Functional Neuroimaging MH - Humans MH - Ketamine/pharmacology MH - Magnetic Resonance Imaging MH - Male MH - Mesencephalon/drug effects/physiology MH - Neural Pathways/*drug effects/*physiology MH - Nucleus Accumbens/drug effects/physiology MH - Prefrontal Cortex/drug effects MH - Psychoses, Substance-Induced/*physiopathology MH - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors MH - Thalamus/drug effects/physiology MH - Young Adult PMC - PMC4246009 MID - EMS59769 OID - NLM: EMS59769 EDAT- 2014/08/22 06:00 MHDA- 2016/03/16 06:00 PMCR- 2016/02/01 CRDT- 2014/08/22 06:00 PHST- 2014/03/08 00:00 [received] PHST- 2014/07/20 00:00 [revised] PHST- 2014/07/23 00:00 [accepted] PHST- 2014/08/22 06:00 [entrez] PHST- 2014/08/22 06:00 [pubmed] PHST- 2016/03/16 06:00 [medline] PHST- 2016/02/01 00:00 [pmc-release] AID - npp2014210 [pii] AID - 10.1038/npp.2014.210 [doi] PST - ppublish SO - Neuropsychopharmacology. 2015 Feb;40(3):622-31. doi: 10.1038/npp.2014.210. Epub 2014 Aug 21.