Dissociation between medial temporal lobe and basal ganglia memory systems in schizophrenia Szabolcs Ke ´ri a, * , Orsolya Nagy b , Oguz Kelemen b , Catherine E. Myers c , Mark A. Gluck c a Departments of Psychiatry, University of Szeged, Semmelweis u. 6, Szeged, H-6725, Hungary b Ba ´cs-Kiskun County Hospital, Psychiatry Center, Kecskeme ´t, Hungary c Rutgers Memory Disorders Project, Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, USA Received 26 January 2005; received in revised form 22 March 2005; accepted 26 March 2005 Available online 12 May 2005 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 et al. (2003) [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. D 2005 Elsevier B.V. All rights reserved. Keywords: Schizophrenia; Learning; Memory; Antipsychotics; Parkinsonism; Medial temporal lobe; Basal ganglia; Acquired equivalence 1. Introduction Memory dysfunction is one of the most consis- tently reported cognitive abnormalities in schizophre- 0920-9964/$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2005.03.024 * Corresponding author. Tel.: +36 62 545 363, +36 20 937 2427. E-mail address: szkeri@phys.szote.u-szeged.hu (S. Ke ´ri). Schizophrenia Research 77 (2005) 321 – 328 www.elsevier.com/locate/schres