The cognitive neuroscience of memory function and dysfunction in schizophrenia

Abstract

Patients with schizophrenia have pronounced deficits in memory for events--episodic memory. These deficits severely affect patients' quality of life and functional outcome, and current medications have only a modest effect, making episodic memory an important domain for translational development of clinical trial paradigms. The current article provides a brief review of the significant progress that cognitive neuroscience has made in understanding basic mechanisms of episodic memory formation and retrieval that were presented and discussed at the first CNTRICS (Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia) meeting in Washington, D.C. During that meeting a collaborative decision was made that measures of item-specific and relational memory were the most promising constructs for immediate translational development. A brief summary of research on episodic memory in schizophrenia is presented to provide a context for investigating item-specific and relational memory processes. Candidate brain regions are also discussed.

Figure 1

Schematic diagram of the processes that support memory encoding and retrieval. (A) Episodic memories require the binding of perceptual, conceptual, and action processes that are engaged during an event. Cognitive control processes play a particular role in determining the types of processing that will be engaged, as well as the types of information to be suppressed. (B) During retrieval, contextual cues, along with more specific retrieval cues can elicit the recovery of episodic information. Cognitive control processes play a critical role in generation of retrieval cues, filtering of recovered information, and selection of criteria that will be used to make attributions based on what is recovered.

Figure 2

Results from Murray & Ranganath (66), showing that activity in dorsolateral prefrontal cortex (DLPFC) is specifically correlated with memory for associations between items. In this study, participants were scanned while encoding pairs of words, and later participants were tested on memory for the items and associations that were studied. In the left DLPFC (Brodmann’s area [BA] 46; top row), analyses of data based on associative memory accuracy (left graph) showed that activity during encoding was greater for pairs that were subsequently remembered (yellow trace), as compared with pair associations that were later forgotten (blue trace). However, when trials were analyzed as a function of accurate recognition of the items in each pair (right graph), no significant differences were observed between subsequently remembered (yellow trace) and subsequently forgotten (blue trace) items. Activity in VLPFC (BA 45/47; bottom row) was also enhanced during processing of pairs that were subsequently remembered, as compared with pairs that were forgotten. However, unlike DLPFC, activity in VLPFC was also increased during processing of items that were later remembered, as compared with subsequently forgotten items.