Impaired associative inference in patients with schizophrenia

Abstract

The ability to learn, store, and retrieve information about relationships is impaired in schizophrenia. Here, we tested 38 control and 61 schizophrenia subjects for their ability to identify the novel pairing of stimuli, based on associations learned during training. Subjects were trained on 3 sets of paired associates: 30 face-house pairs (H-F1), 30 face-house pairs (H-F2, same house with new face), and 30 face-face pairs (F3-F4). After training, participants were tested on the 3 explicitly trained pair types, as well as 30 new face-face pairs (F1-F2), which could only be linked together via the same house during the H-F1/H-F2 training blocks. Of 99 subjects tested, 37 patients with schizophrenia and 36 age-matched healthy control subjects learned the premise pairs and performed the relational memory test. Healthy control subjects were significantly more accurate in identifying the inferential (F1-F2) pairs than the noninferential (F3-F4) pairs. In contrast, schizophrenia patients were equally accurate on inferential and noninferential pairs, providing evidence for a relational memory deficit in schizophrenia. However, the current version of the associative inference paradigm, suggested by the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia initiative, has limited feasibility, calling into question the generalizability of the findings for the larger schizophrenia population.

Figures

Fig. 1.

Experimental Paradigm. Subjects were trained on 3 sets of paired associates: 30 face-house pairs (H-F1), 30 face-house pairs (H-F2, same house paired with a novel face), and 30 face-face pairs. Each set of 30 pairs was presented for either 4 study-test sessions (face-house pairs) or 1 study-test session (face-face pairs). In each study-test session, subjects first viewed all 30 pairs and then completed an immediate 2 alternative forced-choice test with no feedback. After training, subjects completed a final test on all explicitly trained pairs (H-F1, H-F2, and F3-F4) and an additional set of 30 novel face-face pairs (F1-F2), which could only be linked together via the same house during the H-F1/H-F2 training blocks.

Fig. 2.

Training and Test Accuracy Data (Mean and SE Values) for House-Face Pairs (H-F1 and H-F2) for Healthy Controls (HC), Patients With Schizophrenia Who Met Training Criterion (Good Learners) and Patients With Schizophrenia Who did not Meet Training Criterion (Poor Learners). Test data for the poor learners are not shown.

Fig. 3.

Test Accuracy Performance (Mean and SE values) for Face-Face Pairs (Trained F3-F4 Pairs and Novel-Related F1-F2 Pairs) for HC and Schizophrenia Subjects (SZ).

Fig. 4.

Accuracy Differential for Relational (F1-F2) vs Nonrelational (F3-F4) Pairs for HC and Schizophrenia Subjects. Red bars indicate subjects who achieved greater than chance performance (≥66.67%) on the relational condition.