Linking Microcircuit Dysfunction to Cognitive Impairment: Effects of Disinhibition Associated with Schizophrenia in a Cortical Working Memory Model
Cerebral Cortex November 29, 2012 John D. Murray, Alan Anticevic, Mark G. Gancsos et al. 278 citations
Disruption of the balance between excitation and inhibition in the prefrontal cortex is thought to underlie cognitive problems in schizophrenia. A computational model of spatial working memory showed that disinhibition—caused by perturbing NMDA receptors on interneurons—broadens the tuning of memory-related neural activity, leading to more variable and less precise stored information and a reduced ability to filter out distractions. This prediction was tested with behavioral data from humans given ketamine, which induces disinhibition, and ketamine increased errors as the model predicted. The model also showed that restoring excitation-inhibition balance could reverse these working memory deficits, pointing to new experimental approaches for studying memory problems in schizophrenia.