title: Semantic disturbance in schizophrenia and its relationship to the cognitive neuroscience of attention.
abstract: We view schizophrenia as producing a failure of attentional modulation that leads to a breakdown in the selective enhancement or inhibition of semantic/lexical representations whose biological substrata are widely distributed across left (dominant) temporal and frontal lobes. Supporting behavioral evidence includes word recall studies that have pointed to a disturbance in connectivity (associative strength) but not network size (number of associates) in patients with schizophrenia. Paralleling these findings are recent neural network simulation studies of the abnormal connectivity effect in schizophrenia through 'lesioning' network connection weights while holding constant network size. Supporting evidence at the level of biology are in vitro studies examining N-methyl-D-aspartate (NMDA) receptor antagonists on recurrent inhibition; simulations in neural populations with realistically modeled biophysical properties show NMDA antagonists produce a schizophrenia-like disturbance in pattern association. We propose a similar failure of NMDA-mediated recurrent inhibition as a candidate biological substrate for attention and semantic anomalies of schizophrenia.
authors.affiliation: Department of Psychiatry, Harvard Medical School, Brockton VAMC-116A, 940 Belmont Street, Brockton, MA 02401, USA. paul.nestor@umb.edu
authors.forename: P G
authors.initials: PG
authors.lastname: Nestor
authors.forename: S D
authors.initials: SD
authors.lastname: Han
authors.forename: M
authors.initials: M
authors.lastname: Niznikiewicz
authors.forename: D
authors.initials: D
authors.lastname: Salisbury
authors.forename: K
authors.initials: K
authors.lastname: Spencer
authors.forename: M E
authors.initials: ME
authors.lastname: Shenton
authors.forename: R W
authors.initials: RW
authors.lastname: McCarley
mesh_terms: D001288:Attention / Q000502:physiology*; D001931:Brain Mapping; D004292:Dominance, Cerebral / Q000502:physiology; D005625:Frontal Lobe / Q000503:physiopathology*; D006801:Humans; D009415:Nerve Net / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012559:Schizophrenia / Q000503:physiopathology*; D012564:Schizophrenic Language; D012660:Semantics; D013702:Temporal Lobe / Q000503:physiopathology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate