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CNTRICS Final Task Selection: Working Memory Schizophrenia Bulletin vol. 35 no. 1 pp. 136–152, 2009 doi:10.1093/schbul/sbn153 Advance Access publication on November 5, 2008 CNTRICS Final Task Selection: Working Memory Deanna M. Barch1,2, Marc G. Berman3, Randy Engle4, port working memory. Not surprisingly, working mem- Jessica Hurdelbrink Jones6, John Jonides3, ory is a multidimensional construct, and research has Angus MacDonald, III6, Derek Evan Nee3, Thomas increasingly indicated that it involves a number of differ- S. Redick4, and Scott R. Sponheim5,6 ent subcomponents.4–6 2Departments of Psychology, Psychiatry, and Radiology, In the psychological literature, working memory refers Washington University, St Louis, Mo; 3Department of Psychology, to a cognitive system involved in the maintenance and University of Michigan; 4School of Psychology, Georgia Institute of manipulation information over a short period of time Technology; 5Veterans Affairs Medical Center in Minneapolis; (up to ;30 s), serving as a temporary workspace (eg, 6 Department of Psychology, University of Minnesota a ‘‘mental blackboard’’) enabling complex cognitive operations, such as planning, problem solving, and rea- soning. Moreover, the contents of working memory are The third meeting of the Cognitive Neuroscience Treat- thought to be ‘‘buffered,’’ such that they are protected ment Research to Improve Cognition in Schizophrenia from interference due to either distracting information (CNTRICS) was focused on selecting promising measures or decay over time. The information actively maintained for each of the cognitive constructs selected in the first in working memory includes both specific stimuli that CNTRICS meeting. In the domain of working memory, will need to be used at a later point in time, as well the 2 constructs of interest were goal maintenance and in- the task goals that govern the current behavioral set.7 terference control. CNTRICS received 3 task nominations In addition, working memory capacity is inextricably for each of these constructs, and the breakout group for tied to the ability to resist intrusion from currently irrel- working memory evaluated the degree to which each of evant information. This idea is supported by demonstra- these tasks met prespecified criteria. For goal maintenance, tions that proactive interference plays a prominent role in the breakout group for working memory recommended the forgetting in working memory.8–10 AX-Continuous Performance Task/Dot Pattern Expec- Some models of working memory, such as Baddeley’s,11 tancy task for translation for use in clinical trial contexts suggest that there are at least 3 major components of in schizophrenia research. For interference control, the working memory; (1) a short-term storage buffer for breakout group recommended the recent probes and oper- visual information that is often referred to as the visuospa- ation/symmetry span tasks for translation for use in clinical tial scratch pad; (2) a short-term storage buffer for verbal trials. This article describes the ways in which each of these information referred to as the phonological loop (which tasks met the criteria used by the breakout group to recom- includes both articulatory rehearsal and phonological mend tasks for further development. processing; (3) a central executive component that guides the manipulation and transformation of information Key words: inference control/goal maintenance/ held within the storage buffers. In recent years, the model schizophrenia has also included an episodic buffer, in which complex, multimodal events are integrated and stored online.5 Working memory function has perhaps been one of the In a model such as Baddley’s, maintenance of specific most well studied cognitive domains in schizophrenia, 1 information is governed by the buffer systems, while the since the seminal work of Park and Holtzman. Further- regulation and coordination of this information—ie, more, working memory is a domain that has received updating and maintenance of task goals, management enormous attention in cognitive behavioral studies, as of interference, and manipulation and transformations well as in both human and animal cognitive neurosci- 2,3 of stored content—are handled by the central executive. ence. Thus, there is a large body of extant work that Other models of working memory, such as the one put outlines the psychological and neural processes that sup- forth by Cowan, suggests that there are not qualitative or structural differences in the representations used to 1To whom correspondence should be addressed; Department of support working memory as compared to episodic mem- Psychology, Washington University, St Louis, MO, 63130; tel: ory, in the sense of there being dedicated storage buffers 314-935-8729, fax: 314-935-8790, e-mail: [email protected]. that only maintain information ‘‘contained’’ in working Ó The Author 2008. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: [email protected]. 136 Working Memory memory. Instead, Cowan’s model suggests that the ference,14,33 but the effects tend to be weaker and less ro- information contained in working memory is simply the bust than that observed in high interference situations. activated portion of long-term memory that is currently For example, the seminal work of Oltmanns and Neale in the focus of attention.6 demonstrated a differential deficit in working memory Numerous studies have examined the integrity of dif- span in the face of distraction as compared with no distrac- ferent aspects of working memory in schizophrenia. tion,34 a finding that has been replicated by a number of There have been repeated demonstrations that individu- researchers.35,36 In more recent work, Brahmbhatt and als with schizophrenia exhibit deficits on a wide range of colleagues have shown heightened sensitivity to proactive working memory tasks and that these deficits are associ- interference among individuals with schizophrenia in the ated with impairments in the function of neural circuits context of an n-back working memory task; a number of that support working memory function.12–15 Some re- other studies have suggested impaired distractibility in the search even suggests that the degree of impairment in cer- context of working memory tasks in schizophrenia.37,38 tain aspects of working memory predicts later onset of As described in the other articles in this special issue, schizophrenia.16,17 Further, the severity of working mem- the goal of the third CNTRICS meeting was to solicit and ory impairment predicts the degree of social and occupa- evaluate nominations for promising tasks that would tional impairment in individuals with schizophrenia.18,19 measure each of these 2 constructs. Nominations were In addition, there is evidence to suggest that working solicited from both basic and clinical scientists, from memory deficits are endophenotypic markers of risk both academia and industry. The nominators were asked for schizophrenia because individuals who share unex- to provide a description of the task and to provide infor- pressed genetic components of vulnerability to schizo- mation on five domains relevant to selecting the most phrenia also experience impairments in working promising tasks: (1) cognitive construct validity, (2) neu- memory function.20,21 ral construct validity, (3) reliability, (4) other psychomet- Given the research outlined above, both the ric characteristics, and (5) the availability of animal MATRICS and the Cognitive Neuroscience Treatment models. The overview article at the beginning of this spe- Research to Improve Cognition in Schizophrenia cial section outlines why these criteria were selected and (CNTRICS) initiatives included working memory as describes how they were applied during the group discus- one of the core cognitive domains to focus upon in sions. Here, we briefly review the ways in which each of work geared toward developing more effective treat- these tasks met the criteria used for selection. ments for enhancing cognitive function in schizophrenia. At the first CNTRICS meeting, it was decided that 2 Goal Maintenance components of working memory were ready for immedi- ate translation for development and use in clinical trials CNTRICS received 3 initial nominations for the goal in schizophrenia: (1) goal maintenance and (2) interfer- maintenance component of working memory: (1) the ence control. AX-Continuous Performance Task (CPT)/Dot Pattern Goal maintenance was defined as: ‘‘The processes in- Expectancy (DPX) task, (2) probabilistic reversal learn- volved in activating task related goals or rules based on ing, and (3) the operation span/symmetry span. The endogenous or exogenous cues, actively representing working memory discussion group decided that the them in a highly accessible form, and maintaining this in- AX-CPT/DPX task would be recommended for further formation over an interval during which that information development as a measure of goal maintenance in work- is needed to bias and constrain attention and response ing memory but that the other 2 tasks would not. The selection.’’22 reasons for this are described next. Interference control was defined as ‘‘The processes in- volved in protecting the contents of working memory Tasks Not Selected for Translation as Measures of Goal from interference from either other competing internal Maintenance representations or external stimuli.’’22 Much of the extant literature points to the greatest In
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