Memory-Based Prediction Deficits and Dorsolateral Prefrontal Dysfunction in Schizophrenia - PubMed (original) (raw)

Memory-Based Prediction Deficits and Dorsolateral Prefrontal Dysfunction in Schizophrenia

Ashley B Williams et al. Biol Psychiatry Cogn Neurosci Neuroimaging. 2023 Jan.

Abstract

Background: Theories suggest that people with schizophrenia (SZ) have problems generating predictions based on past experiences. The dorsolateral prefrontal cortex (DLPFC) and hippocampus participate in memory-based prediction. We used functional magnetic resonance imaging to investigate DLPFC and hippocampal function in healthy control (HC) subjects and people with SZ during memory-based prediction.

Methods: Prior to scanning, HC subjects (n = 54) and people with SZ (n = 31) learned 5-object sequences presented in fixed or random orders on each repetition. During scanning, participants made semantic decisions (e.g., "Can this object fit in a shoebox?") on a continuous stream of objects from fixed and random sequences. Sequence prediction was demonstrated by faster semantic decisions for objects in fixed versus random sequences because memory could be used to anticipate and more efficiently process semantic information about upcoming objects in fixed sequences. Representational similarity analyses were used to determine how each sequence type was represented in the posterior hippocampus and DLPFC.

Results: Sequence predictions were reduced in individuals with SZ relative to HC subjects. Representational similarity analyses revealed stronger memory-based predictions in the DLPFC of HC subjects than people with SZ, and DLPFC representations correlated with more successful predictions in HC subjects only. For the posterior hippocampus, voxel pattern similarity was increased for fixed versus random sequences in HC subjects only, but no significant between-group differences or correlations with prediction success were observed.

Conclusions: Individuals with SZ are capable of learning temporal sequences; however, they are impaired using memory to predict upcoming events as efficiently as HC subjects. This deficit appears related to disrupted neural representation of sequence information in the DLPFC.

Keywords: Episodic memory; Hippocampus; Prediction; Prefrontal cortex; Relational memory; Schizophrenia.

Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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Conflict of interest statement

Disclosures

All authors have nothing to disclose.

Figures

Figure 1.

Figure 1.

Schematic of the paradigm. Fixed sequences show the same objects in the same position for each repetition. Random sequences show the same objects but in a different position each repetition.

Figure 2.

Figure 2.

Sequence prediction indicated by the difference in RT for objects 2–5 between fixed and random sequences. RT for fixed sequences was faster than random sequences for both groups with HC showing a significantly greater difference.

Figure 3.

Figure 3.

In the bilateral DLPFC (Fig. 3A and 3B), HC showed significantly greater similarity for fixed sequences compared to random while SZ did not. The left posterior hippocampus showed no group or sequence differences (Fig. 3C and 3D). In the right posterior hippocampus, in HC only, fixed sequences showed significantly greater similarity for fixed versus random sequences.

Figure 4.

Figure 4.

Scatter plot of correlations between pattern similarity in the left DLPFC and sequence prediction success. For HC (Fig. 4A and 4B), greater pattern similarity for fixed versus random sequences in the left DLPFC was correlated with better sequence prediction. These correlations were not significant in people with SZ (Fig. 4C and 4D).

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