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[Preprint]. 2023 Nov 1:2023.10.27.564260.

doi: 10.1101/2023.10.27.564260.

Medial temporal lobe functional network architecture supports sleep-related emotional memory processing in older adults

Miranda G Chappel-Farley^{1

2}, Jenna N Adams^{1

2}, Richard F Betzel³, John C Janecek^{1

2}, Negin S Sattari⁴, Destiny E Berisha^{1

2}, Novelle J Meza^{1

2}, Hamid Niknazar⁵, Soyun Kim^{1

2}, Abhishek Dave^{5

4}, Ivy Y Chen⁴, Kitty K Lui⁶, Ariel B Neikrug⁴, Ruth M Benca^{1

2

4

7

8

9

10}, Michael A Yassa^{1

2

4

10

11}, Bryce A Mander^{2

5

4

10

12}

Affiliations

¹ Department of Neurobiology and Behavior, University of California Irvine, Irvine CA, 92697, USA.
² Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine CA, 92697, USA.
³ Department of Psychological and Brain Sciences, University of Indiana Bloomington, Bloomington IN, 47405.
⁴ Department of Psychiatry and Human Behavior, University of California Irvine, Irvine CA, 92697, USA.
⁵ Department of Cognitive Sciences, University of California Irvine, Irvine CA, 92697, USA.
⁶ San Diego State University/University of California San Diego, Joint Doctoral Program in Clinical Psychology, San Diego, CA, 92093, USA.
⁷ Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, 53706, USA.
⁸ Department of Psychiatry, University of Wisconsin-Madison, Madison, 53706, WI, USA.
⁹ Department of Psychiatry and Behavioral Medicine, Wake Forest University, Winston-Salem, NC, 27109, USA.
¹⁰ Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine CA, 92697, USA.
¹¹ Department of Neurology, University of California Irvine, Irvine CA, 92697, USA.
¹² Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine CA, 92697, USA.

PMID: 37961192
PMCID: PMC10634911
DOI: 10.1101/2023.10.27.564260

Medial temporal lobe functional network architecture supports sleep-related emotional memory processing in older adults

Miranda G Chappel-Farley et al. bioRxiv. 2023.

[Preprint]. 2023 Nov 1:2023.10.27.564260.

doi: 10.1101/2023.10.27.564260.

Authors

Affiliations

¹ Department of Neurobiology and Behavior, University of California Irvine, Irvine CA, 92697, USA.
² Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine CA, 92697, USA.
³ Department of Psychological and Brain Sciences, University of Indiana Bloomington, Bloomington IN, 47405.
⁴ Department of Psychiatry and Human Behavior, University of California Irvine, Irvine CA, 92697, USA.
⁵ Department of Cognitive Sciences, University of California Irvine, Irvine CA, 92697, USA.
⁶ San Diego State University/University of California San Diego, Joint Doctoral Program in Clinical Psychology, San Diego, CA, 92093, USA.
⁷ Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, 53706, USA.
⁸ Department of Psychiatry, University of Wisconsin-Madison, Madison, 53706, WI, USA.
⁹ Department of Psychiatry and Behavioral Medicine, Wake Forest University, Winston-Salem, NC, 27109, USA.
¹⁰ Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine CA, 92697, USA.
¹¹ Department of Neurology, University of California Irvine, Irvine CA, 92697, USA.
¹² Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine CA, 92697, USA.

PMID: 37961192
PMCID: PMC10634911
DOI: 10.1101/2023.10.27.564260

Update in

Individual differences in medial temporal lobe functional network architecture predict the capacity for sleep-related consolidation of emotional memories in older adults.
Chappel-Farley MG, Adams JN, Betzel RF, Sattari NS, Berisha DE, Meza NJ, Janecek JT, Niknazar H, Kim S, Dave A, Chen IY, Lui KK, Neikrug AB, Benca RM, Yassa MA, Mander BA. Chappel-Farley MG, et al. Sleep. 2025 Sep 9;48(9):zsaf117. doi: 10.1093/sleep/zsaf117. Sleep. 2025. PMID: 40442306 Free PMC article.

Abstract

Memory consolidation occurs via reactivation of a hippocampal index during non-rapid eye movement slow-wave sleep (NREM SWS) which binds attributes of an experience existing within cortical modules. For memories containing emotional content, hippocampal-amygdala dynamics facilitate consolidation over a sleep bout. This study tested if modularity and centrality-graph theoretical measures that index the level of segregation/integration in a system and the relative import of its nodes-map onto central tenets of memory consolidation theory and sleep-related processing. Findings indicate that greater network integration is tied to overnight emotional memory retention via NREM SWS expression. Greater hippocampal and amygdala influence over network organization supports emotional memory retention, and hippocampal or amygdala control over information flow are differentially associated with distinct stages of memory processing. These centrality measures are also tied to the local expression and coupling of key sleep oscillations tied to sleep-dependent memory consolidation. These findings suggest that measures of intrinsic network connectivity may predict the capacity of brain functional networks to acquire, consolidate, and retrieve emotional memories.

Keywords: consolidation; graph theory; memory; networks; resting-state; sleep.

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Conflict of interest statement

DECLARATION OF INTERESTS Financial Disclosure: None to Declare. Nonfinancial Disclosure: Dr. Benca has served as a consultant to Eisai, Idorsia, Merck, Sage, and Genentech. Dr. Mander has served as a consultant to Eisai. The other authors declare no conflicts of interest relevant to this work.

Figures

**Figure 1.**
Emotional Mnemonic Discrimination Task. The eMDT consists of three phases: incidental encoding and a surprise immediate test phase prior to sleep, and a delayed test phase following overnight sleep. During the incidental encoding phase, participants are shown a series of emotionally salient images and asked to rate them as positive, negative, or neutral via button press. Following encoding, participants perform an old/new recognition paradigm and are shown targets, foils, and high/low similarity lures modulated by valence. Following overnight sleep, participants are again shown targets, foils, and lures and are asked to indicate via button press whether it is an old or new image. Images from the incidental encoding phase are randomly split into the immediate and delayed test phases. ISI—Inter Stimulus Interval; Neg—Negative; Neu—Neutral; Pos—Positive; LSim—Low Similarity; HSim—High Similarity; Targ—Target

**Figure 2.**
Regions of Interest (ROIs) included in the analysis mask for all subjects.

**Figure 3.**
More modular brain networks express more NREM SWS sleep and exhibit worse overnight memory retention. (A) Schematic of network modularity. (B) Greater network modularity is associated with a greater percentage of sleep time spent in NREM SWS, while adjusting for age, sex, and AHI. (C) A greater percentage of sleep time spent in NREM SWS is positively associated with overnight emotional memory retention, adjusting for age, sex, AHI, and Q. (D) Greater network modularity is negatively associated with overnight emotional memory retention, adjusting for age, sex, AHI, and percentage of sleep time spent in NREM SWS.

**Figure 4.**
NREM SWS mediates the relationship between network modularity and emotional memory retention. NREM SWS percentage of sleep time is shown as a mediator of the relationship between network modularity and overnight emotional memory retention.

**Figure 5.**
Hippocampal-amygdala functional network hierarchy supports emotional memory retention. (A) Schematic of eigenvector centrality. (B) Greater hippocampal eigenvector centrality is positively associated with overnight emotional memory retention, adjusting for age, sex, and AHI. (C) Greater amygdala eigenvector centrality is positively associated with overnight emotional memory retention, adjusting for age, sex, and AHI.

**Figure 6.**
Betweenness centrality identifies distinct roles for hippocampus and amygdala in emotional memory acquisition, consolidation, and delayed retrieval. (A) Schematic of betweenness centrality. (B) Greater hippocampal betweenness centrality is positively associated with emotional memory performance at immediate test, adjusting for age, sex, and AHI. (C) Higher amygdala betweenness centrality (cube-root transformed) is positively associated with overnight emotional memory retention and (D) emotional memory performance at delayed test, adjusting for age, sex, and AHI.

**Figure 7.**
Random forest classification identifies most important graph features for sleep-related memory consolidation. (A) ROC and Gini Impurity Index output for top 3 predictors of overnight negative memory retention (LDI). (B) ROC and Gini Impurity Index output for delayed test performance for negative LDI. (C) ROC and Gini Impurity Index output for top 3 predictors of immediate test performance for negative LDI. ROC—Receiver Operating Characteristic Curve; AUC—Area Under the Curve; EC—Eigenvector Centrality; BC—Betweenness Centrality; LDI—Lure Discrimination Index

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References

1. Ebbinghaus H. (1913). Memory: A contribution to experimental psychology. (Teachers College Press; ) 10.1037/10011-000. - DOI - PMC - PubMed
1. Cahill L., and McGaugh J.L. (1996). Modulation of memory storage. Current Opinion in Neurobiology 6, 237–242. 0.1016/s0959–4388(96)80078-x. - PubMed
1. Eichenbaum H. (2004). Hippocampus: cognitive processes and neural representations that underlie declarative memory. Neuron 44, 109–120. 10.1016/j.neuron.2004.08.028. - DOI - PubMed
1. McClelland J.L., McNaughton B.L., and O’Reilly R.C. (1995). Why there are complementary learning systems in the hippocampus and neocortex: Insights from the successes and failures of connectionist models of learning and memory. Psychological Review 102, 419–457. 10.1037/0033-295X.102.3.419. - DOI - PubMed
1. Penfield W., and Milner B. (1958). Memory deficit produced by bilateral lesions in the hippocampal zone. AMA Archives of Neurological Psychiatry 79, 475–497. 10.1001/archneurpsyc.1958.02340050003001. - DOI - PubMed

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This is a preprint.

Medial temporal lobe functional network architecture supports sleep-related emotional memory processing in older adults

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Medial temporal lobe functional network architecture supports sleep-related emotional memory processing in older adults

Authors

Affiliations

Update in

Abstract

Conflict of interest statement

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References

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