title: Disruption of learned irrelevance in acute schizophrenia in a novel continuous within-subject paradigm suitable for fMRI.
abstract: Learned irrelevance (LIrr) is closely related to latent inhibition (LI). In LI a to-be-conditioned stimulus (CS) is prexposed alone prior to the opportunity to learn an association between the CS and an unconditioned stimulus (UCS). In LIrr preexposure consists of intermixed presentations of both CS and UCS in a random relationship to each other. In both paradigms preexposure leads in normal subjects to reduced or retarded learning of the CS-UCS association. Acute schizophrenics fail to show LI. LI is usually demonstrated as a one-off, between-groups difference in trials to learning, so posing problems for neuroimaging. We have developed a novel, continuous, within-subject paradigm in which normal subjects show robust and repeated LIrr. We show that this paradigm is suitable for functional magnetic resonance imaging (fMRI) and gives rise, in normal subjects, to activation in the hippocampal formation, consistent with data from animal experiments on LI. We also report, consistent with previous studies of LI, loss (indeed, significant reversal) of LIrr in acute (first 2 weeks of current psychotic episode) schizophrenics. Chronic schizophrenics failed to demonstrate learning, precluding measurement in this group of LIrr. These findings establish the likely value of the new paradigm for neuroimaging studies of attentional dysfunction in acute schizophrenia.
authors.affiliation: School of Psychology, University of Leicester, University Road, Leicester LE1 7RH, UK. amjy1@le.ac.uk
authors.forename: Andrew M J
authors.initials: AM
authors.lastname: Young
authors.forename: Veena
authors.initials: V
authors.lastname: Kumari
authors.forename: Ravi
authors.initials: R
authors.lastname: Mehrotra
authors.forename: David R
authors.initials: DR
authors.lastname: Hemsley
authors.forename: Chris
authors.initials: C
authors.lastname: Andrew
authors.forename: Tonmoy
authors.initials: T
authors.lastname: Sharma
authors.forename: Stephen C R
authors.initials: SC
authors.lastname: Williams
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Gray
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001245:Association Learning / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D001931:Brain Mapping; D003214:Conditioning, Classical / Q000502:physiology*; D007839:Functional Laterality; D006801:Humans; D007266:Inhibition, Psychological; D007858:Learning / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D011930:Reaction Time / Q000502:physiology; D012559:Schizophrenia / Q000503:physiopathology*
chemical_list: D010100:Oxygen