Archival Report
Replicable Patterns of Memory Impairments in Children With Autism and Their Links to Hyperconnected Brain Circuits

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Abstract

Background

Memory impairments have profound implications for social communication and educational outcomes in children with autism spectrum disorder (ASD). However, the precise nature of memory dysfunction in children with ASD and the underlying neural circuit mechanisms remain poorly understood. The default mode network (DMN) is a brain network that is associated with memory and cognitive function, and DMN dysfunction is among the most replicable and robust brain signatures of ASD.

Methods

We used a comprehensive battery of standardized episodic memory assessments and functional circuit analyses in 25 8- to 12-year-old children with ASD and 29 matched typically developing control children.

Results

Memory performance was reduced in children with ASD compared with control children. General and face memory emerged as distinct dimensions of memory difficulties in ASD. Importantly, findings of diminished episodic memory in children with ASD were replicated in 2 independent data sets. Analysis of intrinsic functional circuits associated with the DMN revealed that general and face memory deficits were associated with distinct, hyperconnected circuits: Aberrant hippocampal connectivity predicted diminished general memory while aberrant posterior cingulate cortex connectivity predicted diminished face memory. Notably, aberrant hippocampal-posterior cingulate cortex circuitry was a common feature of diminished general and face memory in ASD.

Conclusions

Our results represent a comprehensive appraisal of episodic memory function in children with ASD and identify extensive and replicable patterns of memory reductions in children with ASD that are linked to dysfunction of distinct DMN-related circuits. These findings highlight a role for DMN dysfunction in ASD that extends beyond face memory to general memory function.

Section snippets

Participants

All study protocols were approved by the Stanford University Institutional Review Board, and informed written consent was obtained from the legal guardian of each child. Fifty-four 8- to 12-year-old children (25 children with ASD and 29 matched TD children) completed the study (Table 1). The diagnosis of ASD was confirmed by an experienced clinical psychologist using the standard criteria based on the Autism Diagnostic Interview-Revised (28) and/or the Autism Diagnostic Observation Schedule (29

General Memory Reductions in Children With ASD (WRAML2)

We first examined general memory function, assessed using the WRAML2, in children with ASD, compared to TD children. A linear mixed model on 5 memory subscores from the WRAML2 showed a significant main effect of group (β = 4.86, p = .002). There was no significant main effect of retrieval type, type of material, or delay interval or their interactions with group (βs < 1.25, ps > .14) (Table S3). A planned two-sample t test on the total general memory score from the WRAML2 revealed that children

Discussion

Memory abilities and their links to functional brain circuitry are a crucial but understudied area of childhood ASD. Our survey of the existing literature revealed a lack of comprehensive assessments of general and face memory in a within-subject design, inconsistent behavioral findings, limited characterization of the underlying neural circuitry, and lack of replication (Table S1). We used a comprehensive battery of standardized memory assessments and functional circuit analyses in a

Acknowledgments and Disclosures

This research was supported by the National Institutes of Health (Grant Nos. HD059205, MH084164, HD094623, and MH121069 [to VM]) and by the Stanford Maternal & Child Health Research Institute Postdoctoral Support Awards (to HC and JL).
We thank the participating families and Drs. Jennifer Phillips and Kaustubh Supekar for assistance with the study.
The authors report no biomedical financial interests or potential conflicts of interest.

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