Neuropsychologia 46 (2008) 336–347 Inefficient executive cognitive control in schizophrenia is preceded by altered functional activation during information encoding: An fMRI study Ralf G.M. Schl ¨ osser a,∗ , Kathrin Koch a , Gerd Wagner a , Igor Nenadic a , Martin Roebel a , Claudia Schachtzabel a , Martina Axer a , Christoph Schultz a , J¨ urgen R. Reichenbach b , Heinrich Sauer a a Department of Psychiatry and Psychotherapy, Friedrich-Schiller-University Jena, Philosophenweg 3, 07740 Jena, Germany b Medical Physics Group, Institute for Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, Philosophenweg 3, 07740 Jena, Germany Received 3 January 2007; received in revised form 27 June 2007; accepted 9 July 2007 Available online 19 July 2007 Abstract Working memory deficits are a core feature of schizophrenia. Previous working memory studies suggest a load dependent storage deficit. However, explicit studies of higher executive working memory processes are limited. Moreover, few studies have examined whether subcomponents of working memory such as encoding and maintenance of information are differentially affected by these deficits. Therefore, the aim of the present study was to examine the neural substrates of working memory subprocesses requiring stimulus encoding, maintenance and higher executive processing. Using functional magnetic resonance imaging a modified Sternberg working memory task involving verbal stimulus material was applied. The event-related design enabled the segregation of encoding, active maintenance and executive manipulation of information. Forty-one patients with schizophrenia and 41 healthy subjects were included. Relative to normal controls, schizophrenic patients demonstrated a significantly stronger activation pattern in a fronto-parietal network during executive information manipulation. Additionally, significant relative hypoactivity was detectable in the thalamus. Conversely, during stimulus encoding the patients demonstrated lower activation relative to controls in the prefrontal cortex and the anterior cingulate gyrus. The present findings indicate a pronounced prefrontal functional hyperactivation within the neural network subserving higher executive working memory control processes in schizophrenia. Moreover, they suggest that these altered activations during executive control are related to a preceding abnormality of information encoding. During encoding, a reduced activation in mainly dorsolateral prefrontal and anterior cingulate regions was observed. These results could be explained by increased top-down control processing from prefrontal cortex as a compensation for functional deficits occurring during encoding. © 2007 Elsevier Ltd. All rights reserved. Keywords: Working memory; Cognition; DLPFC; ACC 1. Introduction Converging lines of evidence suggest that cognitive deficits are a core feature of schizophrenia. In particular, schizophrenic patients exhibit dysfunctions in complex working memory (WM) tasks demanding a high amount of cognitive control. WM ∗ Corresponding author. Tel.: +49 3641 9 35284; fax: +49 3641 9 35444. E-mail address: ralf.schloesser@uni-jena.de (R.G.M. Schl¨ osser). enables the short-term storage of information and manipulation of this information while being kept in storage. In the classical WM model of Baddeley a central executive is residing above a verbal and a visuo-spatial sketchpad (Repovs & Baddeley, 2006). According to this model, the sketchpad “slave” systems mainly support short-term maintenance of information. The cen- tral executive exerts cognitive control and allows for higher mnemonic processes such as manipulation of information. Functional imaging studies have provided evidence that the neural substrates underlying short-term maintenance might be 0028-3932/$ – see front matter © 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuropsychologia.2007.07.006