Sustained NMDA receptor hypofunction induces compromised neural systems integration and schizophrenia-like alterations in functional brain networks

Neil Dawson, Xiaolin Xiao, Martin Dean McDonald, Desmond Higham, Brian J. Morris, Judith Pratt

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Compromised functional integration between cerebral subsystems and dysfunctional brain network organization may underlie the neurocognitive deficits seen in psychiatric disorders. Applying topological measures from network science to brain imaging data allows the quantification of complex brain network connectivity. While this approach has recently been used to further elucidate the nature of brain dysfunction in schizophrenia, the value of applying this approach in preclinical models of psychiatric disease has not been recognized. For the first time, we apply both established and recently derived algorithms from network science (graph theory) to functional brain imaging data from rats treated subchronically with the N-methyl-D-aspartic acid (NMDA) receptor antagonist phencyclidine (PCP). We show that subchronic PCP treatment induces alterations in the global properties of functional brain networks akin to those reported in schizophrenia. Furthermore, we show that subchronic PCP treatment induces compromised functional integration between distributed neural systems, including between the prefrontal cortex and hippocampus, that have established roles in cognition through, in part, the promotion of thalamic dysconnectivity. We also show that subchronic PCP treatment promotes the functional disintegration of discrete cerebral subsystems and also alters the connectivity of neurotransmitter systems strongly implicated in schizophrenia. Therefore, we propose that sustained NMDA receptor hypofunction contributes to the pathophysiology of dysfunctional brain network organization in schizophrenia.

Original languageEnglish
Pages (from-to)452-464
Number of pages13
JournalCerebral Cortex
Volume24
Issue number2
Early online date18 Oct 2012
DOIs
Publication statusPublished - Feb 2014

Keywords

  • algorithms
  • animals
  • autoradiography
  • brain
  • brain mapping
  • carbon radioisotopes
  • deoxyglucose
  • excitatory amino acid antagonists
  • hippocampus
  • male
  • neural pathways
  • phencyclidine
  • prefrontal cortex
  • rats
  • rats, inbred strains
  • receptors, N-Methyl-D-Aspartate
  • schizophrenia
  • signal processing, computer-assisted
  • systems integration
  • thalamus

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