A dynamical systems hypothesis of schizophrenia

PLoS Comput Biol. 2007 Nov;3(11):e228. doi: 10.1371/journal.pcbi.0030228.

Abstract

We propose a top-down approach to the symptoms of schizophrenia based on a statistical dynamical framework. We show that a reduced depth in the basins of attraction of cortical attractor states destabilizes the activity at the network level due to the constant statistical fluctuations caused by the stochastic spiking of neurons. In integrate-and-fire network simulations, a decrease in the NMDA receptor conductances, which reduces the depth of the attractor basins, decreases the stability of short-term memory states and increases distractibility. The cognitive symptoms of schizophrenia such as distractibility, working memory deficits, or poor attention could be caused by this instability of attractor states in prefrontal cortical networks. Lower firing rates are also produced, and in the orbitofrontal and anterior cingulate cortex could account for the negative symptoms, including a reduction of emotions. Decreasing the GABA as well as the NMDA conductances produces not only switches between the attractor states, but also jumps from spontaneous activity into one of the attractors. We relate this to the positive symptoms of schizophrenia, including delusions, paranoia, and hallucinations, which may arise because the basins of attraction are shallow and there is instability in temporal lobe semantic memory networks, leading thoughts to move too freely round the attractor energy landscape.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Brain / physiopathology*
  • Computer Simulation
  • Humans
  • Models, Neurological*
  • Nerve Net / physiopathology*
  • Receptors, GABA / metabolism*
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Schizophrenia / physiopathology*
  • Synaptic Transmission*

Substances

  • Receptors, GABA
  • Receptors, N-Methyl-D-Aspartate