Neural correlates of schema-dependent episodic memory and association with behavioral flexibility in autism spectrum disorders and typical development

Abstract

Background: Conceptual knowledge frameworks termed schemas facilitate memory formation and are posited to support flexible behavior. In adults, the medial temporal lobe (MTL) and medial prefrontal cortex (mPFC) trade-off in supporting schema-based memory formation, such that encoding of subsequently remembered schema-congruent information relies on mPFC, whereas schema-incongruent information relies on MTL. Whether this is true in the immature brain and relates to behavioral flexibility is unknown. In this preliminary investigation, we aimed to replicate the adult findings in typically developing (TD) children and to investigate the relevance to behavioral flexibility by examining a disorder with pathognomonic behavioral rigidity, autism spectrum disorder (ASD).

Methods: Children completed an associative subsequent memory paradigm, encoding object-scene pairs in an MRI scanner and subsequently completing a recognition test outside the scanner after a delay. Recognition performance was back sorted to construct remembered vs forgotten contrasts. One-way ANOVAS were conducted in MTL and mPFC masks for schema-congruency, followed by congruency by flexibility scores. Exploratory analyses were then conducted within the whole brain.

Results: As reported in adults, episodic memory was strongest for schema-congruent object-scene pairs, followed by intermediate pairs, and lowest for schema-incongruent pairs in both TD and ASD groups. However, the trade-off between mPFC and MTL in TD children differed from adult reports such that mPFC supported memory for intermediate schema-congruency and left anterior MTL supported memory for schema-congruent pairs. In ASD, mPFC engagement interacted with flexibility such that activation supporting memory for intermediate schema-congruency varied with parent-reported flexibility and was higher in those with more flexible behavior. A similar interaction was also observed in both the left dorsolateral and rostrolateral PFC in whole-brain analysis.

Conclusion: Our findings provide the first preliminary evidence for the association of schema-based episodic memory formation and behavioral flexibility, an executive function impaired in multiple developmental disorders. Upon replication, this line of research holds promise for memory-based interventions addressing executive problems of behavioral rigidity.

Keywords: Associative memory; Behavioral flexibility; Medial temporal lobe; Executive function; Prefrontal cortex; fMRI.

Fig. 1

Associative memory task. Encoding task performed by participants. a Participants viewed object-scene pairs in the scanner for 2 s with 4–10-s fixations, making a 1–3 discrimination of how well the two go together. After a 20-min delay, participants completed a recognition task outside of the scanner requiring that they b first identify if a presented object was new or old and then c which scene was paired with the object during the in-scanner encoding

Fig. 2

Behavioral performance. a At encoding, participants rated significantly more images as incongruent than intermediate or congruent, and more intermediate than congruent. There was no difference, however, between the two groups or interaction with their ratings. b Response time for intermediate pairs was significantly slower than incongruent or congruent, without any group differences. c There were no significant differences in object recognition due to either congruency or group. d The participants remembered significantly more congruent scenes than intermediate or incongruent, and more intermediate than incongruent

Fig. 3

Schema-dependent activation in TD children. a TD children exhibited a cluster sensitive to schema-congruency in the mPFC and b left MTL (lMTL). c Congruency × ROI interaction indicating a trade-off by congruency such that memory for intermediate pairs was supported by mPFC (dark bar) and congruent pairs by lMTL. d Trade-off showing lMTL activations in Congruent trials correlated with mPFC activations for Intermediate trials indicating the degree of mPFC engagement is related to left lMTL engagement

Fig. 4

Schema-dependent activation in ASD varied by behavioral flexibility. a Congruency × flexibility interaction was observed in a cluster in mPFC. Extracted beta values from mPFC cluster showing b a mild positive relationship between inflexibility (higher score) and activation congruent, c a moderate negative relationship for Intermediate, and d minimal relationship for incongruent trials

Fig. 5

Flexibility-dependent schema activation in left dlPFC and rlPFC for children with ASD. Results from whole-brain, exploratory analysis yielding a dlPFC cluster with b–d flexibility exhibiting minimal to moderate positive relationships between flexibility score and activation in congruent and incongruent pairs by a moderate negative relationship in Intermediate pairs and e rlPFC cluster with f–h flexibility exhibiting minimal to moderate positive relationships between flexibility scorer and activation in congruent and incongruent pairs by a moderate negative relationship in intermediate pairs