Dissociation between medial temporal lobe and basal ganglia memory systems in schizophrenia

Schizophr Res. 2005 Sep 15;77(2-3):321-8. doi: 10.1016/j.schres.2005.03.024.

Abstract

The purpose of this study was to investigate basal ganglia (BG) and medial temporal lobe (MTL) dependent learning in patients with schizophrenia. Acquired equivalence is a phenomenon in which prior training to treat two stimuli as equivalent (if two stimuli are associated with the same response) increases generalization between them. The learning of stimulus-response pairs is related to the BG, whereas the MTL system participates in stimulus generalization. Forty-three patients with DSM-IV schizophrenia and 28 matched healthy controls participated. Volunteers received the Rutgers acquired equivalence task (face-fish task) by [Myers, C.E., Shohamy, D., Gluck, M.A. et al., 2003. Dissociating hippocampal versus basal ganglia contributions to learning and transfer. J. Cogn. Neurosci. 15, 185-193.], the California Verbal Learning Test (CVLT), and the n-back working memory test. The Rutgers acquired equivalence task investigates BG-dependent processes (stimulus-response learning) and MTL-dependent processes (stimulus generalization) with a single test. Results revealed that patients with schizophrenia showed a selective deficit on stimulus generalization, whereas stimulus-response learning was spared. The stimulus generalization deficit correlated with the CVLT performance (total scores from trials 1-5 and long-delay recall), but not with the n-back test performance. The number of errors during stimulus-response learning correlated with the daily chlorpromazine-equivalent dose of antipsychotics. In conclusion, this is the first study to show that patients with schizophrenia exhibit deficits during MTL-dependent learning, but not during BG-dependent learning within a single task. High-dose first generation antipsychotics may disrupt BG-dependent learning by blocking dopaminergic neurotransmission in the nigro-stiratal system.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Antipsychotic Agents / adverse effects
  • Association Learning* / drug effects
  • Basal Ganglia / pathology*
  • Case-Control Studies
  • Dopamine Antagonists / adverse effects
  • Female
  • Generalization, Psychological
  • Humans
  • Male
  • Memory Disorders / chemically induced
  • Memory Disorders / pathology*
  • Schizophrenia / drug therapy
  • Schizophrenia / pathology*
  • Temporal Lobe / pathology*
  • Transfer, Psychology

Substances

  • Antipsychotic Agents
  • Dopamine Antagonists