Dysfunction in different phases of working memory in schizophrenia: Evidence from ERP recordings Yan Li Zhao a, 1 , Shu Ping Tan a, 1 , Fu De Yang a , Li Li Wang b , Wen Feng Feng c , Raymond C.K. Chan d, e , Xiao Gao f, g , Dong Feng Zhou h , Bin Bin Li a , Chong Sheng Song a , Feng Mei Fan a , Yun Long Tan a , Jin Guo Zhang a , Yun Hui Wang a , Yi Zhuang Zou a, ⁎ a Center for Psychiatric Research, Beijing Huilongguan Hospital, Beijing 100096, China b State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China c Department of Neurosciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0608, USA d Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China e Neuropsychology and Applied Cognitive Neuroscience Laboratory, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China f Key Laboratory of Cognition and Personality (SWU), Ministry of Education 400715, China g School of Psychology, Southwest University, Chong Qing 400715, China h Institute of Mental Health, Peking University, Beijing 100091, China abstract article info Article history: Received 3 December 2010 Received in revised form 5 September 2011 Accepted 17 September 2011 Available online 19 October 2011 Keywords: Working memory Schizophrenia Event-related potentials Sternberg The present study combined a time-locked paradigm and high-time-resolution event-related potential (ERP) recordings to examine different phases of working memory, including early visual processing and late mem- ory-related processes of encoding, maintenance, and retrieval, in 67 adults with schizophrenia and 46 healthy controls. Alterations in ERP components were correlated with task performance. Patients performed significantly worse in the working memory task than healthy subjects, although all subjects' accuracy exceeded 80%. During encoding, the N1 and P2 component amplitudes were lower while the P300 amplitude was higher in schizophrenic patients compared to healthy controls. There were no differences between groups with respect to the mean amplitudes of the negative slow waves in the early stage (the first 400 ms) of the maintenance phase. However, in the next 500-ms time window, the patients exhibited a more negative deflection in the middle fronto-central region than the control group. Likewise, a similar pat- tern was observed in the second 500-ms period in the middle fronto-central region, although the effect was marginally significant. There were no differences between groups in the remaining 1000 ms. During retrieval, the P1, N1 and P2 amplitudes were lower while the P300 amplitude and latency were higher in schizophrenic patients. The present results indicate early visual deficits in the working memory task in adults with schizo- phrenia. Impairments in the maintenance phase were confined to the late rehearsal stage. The increased P300 amplitude at the fronto-central electrode sites along with the poorer behavioral performance suggests that schizophrenic patients have an inefficient working memory system. © 2011 Elsevier B.V. All rights reserved. 1. Introduction In the working memory system, information is represented, main- tained, and updated for a short period (Lee and Park, 2005). Working memory has 3 stages: encoding, maintenance, and retrieval. Working memory deficits are a major cognitive dysfunction in schizophrenia (Silver et al., 2003). However, the specific stages of working memory that are specifically impaired in schizophrenia and the neuronal substrates underlying such abnormalities are not well understood (Hashimoto et al., 2010). Behavioral (Hill et al., 2010; Mazhari et al., 2010; Zilles et al., 2010) and functional magnetic resonance imaging (fMRI) studies have found deficits in the maintenance stage of working memory in schizophrenic patients (Driesen et al., 2008; Henseler et al., 2009). Smith and Jonides (1998) propose a visual–verbal working memory maintenance process involving multiple cognitive processes. First, visual stimulus representations are translated into corresponding phonological representations; these phonological representations remain active and are rehearsed subvocally and refreshed. The phonological translation process is mediated by the posterior parietal area, inferior frontal cortex, and superior temporal cortex; storage of phonological representations is mediated by the posterior parietal areas, whereas rehearsal is mediated by the frontal speech areas (Smith and Jonides, 1998). At present, it re- mains unclear which component(s) of the maintenance stage are im- paired in schizophrenic patients. While some studies suggest that the Schizophrenia Research 133 (2011) 112–119 ⁎ Corresponding author at: Beijing Hui-Long-Guan Hospital, Beijing 100096, China. Tel.: +86 10 62716905; fax: +86 10 62718210. E-mail address: yzouy@263.net (Y.Z. Zou). 1 Both authors contributed equally to this study. 0920-9964/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2011.09.017 Contents lists available at SciVerse ScienceDirect Schizophrenia Research journal homepage: www.elsevier.com/locate/schres