The Cognitive Neuroscience of Working Memory: Relevance to CNTRICS and Schizophrenia

Abstract

Working memory is one of the central constructs in cognitive science and has received enormous attention in the theoretical and empirical literature. Similarly, working memory deficits have long been thought to be one of the core cognitive deficits in schizophrenia, making it a ripe area for translation. The current article provides a brief overview of the current theories and data on the psychological and neural mechanisms involved in working memory, which is a summary of the presentation and discussion on working memory that occurred at the first CNTRICS meeting in Washington, D.C. At this meeting, the consensus was that the constructs of goal maintenance and interference control were the most ready to be pursued as part of a translational cognitive neuroscience effort in the remaining CNTRICS meetings. The group felt that the constructs of longterm memory reactivation, capacity, and strategic encoding were of great clinical interest, but required more basic research. In addition, the group felt that the constructs of maintenance over time and updating in working memory had growing construct validity at the psychological and neural levels, but required more research in schizophrenia before knowing whether they should be targets for a clinical trials setting.Working memory is perhaps one of the most frequently studied domains in both cognitive science and cognitive neuroscience, with a wealth of accumulated theoretical and empirical work at both the psychological and neural level [1]. Further, a large body of work has demonstrated that individuals with schizophrenia have deficits on a varied set of working memory tasks [e.g., 2,3] that are associated with impairments in a range of neural mechanisms [4]. There is some data to suggest that the degree of impairment in certain aspects of working memory predicts later onset of schizophrenia [5,6]. In addition, the level of working memory impairment predicts the degree of social and occupational impairment in individuals with schizophrenia [e.g., 7,8]. Further, individuals who share unexpressed genetic components of vulnerability to schizophrenia also experience impairments in working memory function [e.g., 9,10].

Epigenetic Regulation of Gene Expression in Physiological and Pathological Brain Processes

“…This is well-exemplified in Rubinstein-Taybi syndrome (RTS), a rare congenital disorder (1:100,000 -125,000 prevalence in the United States) that is characterized by varying degrees of mental retardation, craniofacial and skeletal abnormalities, as well as increased risk of cancer (272). In the brain of affected people, RTS manifests gross abnormalities such as abnormal cortical infolding and decreased white matter, as well as regional hypoplasia (18,306). Most RTS patients have mutations that are mapped to the gene coding for the HAT CBP, and many of these mutations have been shown to result in a loss of HAT activity.…”

Schizophrenia from a neural circuitry perspective: advancing toward rational pharmacological therapies

“…Working memory involves a number of component processes, including temporary storage of information, manipulation of that information, protection from interference by competing information, and maintenance of goal representations (29). Although individuals with schizophrenia exhibit relatively little impairment when performing tasks that depend primarily on the storage of information in working memory, they consistently show impairment in the manipulation of such information and in the maintenance of goal representations (30).…”

Medial prefrontal lesions in mice impair sustained attention but spare maintenance of information in working memory

“…A deficit in working memory, the ability to actively maintain and manipulate information over short time intervals (Baddeley 1992), is a core cognitive symptom of schizophrenia (Park and Holzman 1992;Barch and Smith 2008) and depression (Harvey et al 2004;Rose and Ebmeier 2006). Working memory is a complex construct that involves a number of discrete psychological processes, including the maintenance of information, flexible updating and manipulation, and sensitivity to interference, and it is strongly influenced by attentional processes (see the NIMH Research Domain Criteria working memory workshop proceedings [Research Domain Criteria Project 2010] and Awh and Jonides 2001).…”