title: Glutamate, obsessive-compulsive disorder, schizophrenia, and the stability of cortical attractor neuronal networks.
abstract: A computational neuroscience approach to the symptoms of obsessive-compulsive disorder based on a stochastic neurodynamical framework is described. An increased depth in the basins of attraction of attractor neuronal network states in the brain makes each state too stable, so that it tends to remain locked in that state, and cannot easily be moved on to another state. It is suggested that the different symptoms that may be present in obsessive--compulsive disorder could be related to changes of this type in different brain regions. In integrate-and-fire network simulations, an increase in the NMDA and/or AMPA receptor conductances, which increases the depth of the attractor basins, increases the stability of attractor networks, and makes them less easily moved on to another state by a new stimulus. Increasing GABA-receptor activated currents can partly reverse this overstability. There is now some evidence for overactivity in glutamate transmitter systems in obsessive-compulsive disorder, and the hypothesis presented here shows how some of the symptoms of obsessive-compulsive disorder could be produced by the increase in the stability of attractor networks that is produced by increased glutamatergic activity. In schizophrenia, a reduction of the firing rates of cortical neurons caused for example by reduced NMDA receptor function, present in schizophrenia, can lead to instability of the high firing rate attractor states that normally implement short-term memory and attention, contributing to the cognitive and negative symptoms of schizophrenia. Reduced cortical inhibition caused by a reduction of GABA neurotransmission, present in schizophrenia, can lead to instability of the spontaneous firing states of cortical networks, leading to a noise-induced jump to a high firing rate attractor state even in the absence of external inputs, contributing to the positive symptoms of schizophrenia.
authors.affiliation: Oxford Centre for Computational Neuroscience, Oxford, UK. Edmund.Rolls@oxcns.org
authors.forename: Edmund T
authors.initials: ET
authors.lastname: Rolls
mesh_terms: D005971:Glutamates / Q000502:physiology*; D006801:Humans; D009415:Nerve Net; D009771:Obsessive-Compulsive Disorder / Q000503:physiopathology*; D012559:Schizophrenia / Q000503:physiopathology*
chemical_list: D005971:Glutamates