Affordable Access

deepdyve-link
Publisher Website

Selective augmentation of striatal functional connectivity following NMDA receptor antagonism: implications for psychosis.

Authors
  • Dandash, Orwa1
  • Harrison, Ben J2
  • Adapa, Ram3
  • Gaillard, Raphael4
  • Giorlando, Francesco5
  • Wood, Stephen J6
  • Fletcher, Paul C7
  • Fornito, Alex1
  • 1 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. , (Australia)
  • 2 Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia. , (Australia)
  • 3 1] Division of Anaesthesia, University of Cambridge, Cambridge, UK [2] Addenbrooke's Hospital, Cambridge, UK.
  • 4 1] Université Paris Descartes, Sorbonne Paris Cité, 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. , (France)
  • 5 Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia. , (Australia)
  • 6 1] Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia [2] School of Psychology, University of Birmingham, Birmingham, UK. , (Australia)
  • 7 Department of Psychiatry, Brain Mapping Unit and Behavioural and Clinical Neurosciences Institute, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Type
Published Article
Journal
Neuropsychopharmacology
Publisher
Springer Nature
Publication Date
Feb 01, 2015
Volume
40
Issue
3
Pages
622–631
Identifiers
DOI: 10.1038/npp.2014.210
PMID: 25141922
Source
Medline
License
Unknown

Abstract

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.

Report this publication

Statistics

Seen <100 times