From the outset, the CNTRICS initiative appreciated that long-term memory (LTM) is a broad and multidimensional construct, encompassing multiple stages of information processing and engaging distinct neural systems, some of which are likely to be more central to the memory problems that limit the daily function of individuals with schizophrenia. A great deal of this understanding grew from clinical research employing traditional neuropsychological memory tasks such as the California Verbal Learning Test1
and Wechsler Memory Scale.2
However, unlike the previous MATRICS initiative3
that focused on these neuropsychological measures, the goal of the CNTRICS initiative was to identify tasks from the cognitive neuroscience world that hold promise for translational development for drug discovery.4
Accordingly, during the second of 3 CNTRICS meetings, 2 LTM domains5
were identified as the most promising constructs for immediate translational development: (1) relational encoding
, defined as “the processes involved in memory for stimuli/elements and how they were associated with coincident context, stimuli or events” and (2) item encoding
, defined as “the processes involved in memory for individual stimuli or elements irrespective of contemporaneously presented context or elements.” The LTM group was also assigned the construct of reinforcement learning
, defined as “acquired behavior as a function of both positive and negative reinforcers including the ability to (a) associate previously neutral stimuli with value, as in Pavlovian conditioning; (b) rapidly modify behavior as a function of changing reinforcement contingencies; and (c) slowly integrate over multiple reinforcement experiences to determine probabilistically optimal behaviors in the long run.” At the end of the second meeting, a call went out to the scientific community to engage in an online submission process to nominate tasks that assess these 3 constructs to be considered for ongoing development.
As part of the nomination process, scientists were asked to provide evidence for each task's construct validity, link to neural circuits, clarity of cognitive mechanisms, availability of an animal model, link to neural systems through neuropsychopharmacology, amenability for use in neuroimaging, evidence of impairment in schizophrenia, and psychometric characteristics. In the third CNTRICS meeting, the LTM breakout group was asked to select the 2 most promising tasks within each construct based on these same criteria, with an understanding that although all tasks may not meet all requirements (eg, animal model, psychometric characteristics), tasks without clear evidence of construct validity and link to a neural circuit should not be given further consideration. The purpose of this article is to report on the outcome of this deliberation process and provide the reader with the nominating authors’ description of the (1) item encoding and retrieval, (2) relational encoding and retrieval, and (3) reinforcement learning tasks that were judged to be ready for immediate translational development.
For the construct of relational encoding and retrieval, 2 tasks—associative inference paradigm (AIP) and relational and item encoding and retrieval (RIER)—were judged ready for further development and will be described below. The third nominated task was a transitive inference paradigm (TIP). Group members were impressed with TIP's link to neural circuits, availability of an animal model, link to neuropsychopharmacology, and evidence of impairment in schizophrenia. However, the greater complexity of the TIP vs AIP resulted in a somewhat lower score for construct validity and led to a decision to select the AIP over the TIP for immediate development. Two tasks were considered for the item encoding and retrieval construct—RIER and inhibition of current irrelevant memories task. Of these, only the RIER (which assesses both item and relational memory) was chosen. The nominating author's acknowledgement that the inhibition of current irrelevant memories task has “unknown” construct validity precluded it from further consideration. Within the reinforcement learning construct, the complementary nature of several of the nominated tasks lead the working group to recommend 3 tasks for further development—the probabilistic reward task, the probabilistic selection task, and the probabilistic reversal learning task. The weather prediction task was the fourth task nominated. Because the nominating author described 3 different possible learning strategies, questions arose about the task's construct validity and it did not receive further consideration. The recommended tasks are shown in . Below are the nominating authors' descriptions of the selected tasks within each of the 3 LTM constructs.
Long-Term Memory in Schizophrenia