Worry Modifies the Relationship between Locus Coeruleus Activity and Emotional Mnemonic Discrimination

Abstract

Background: The locus coeruleus (LC) plays a critical role in modulating emotional memory performance via widespread connections to the medial temporal lobe (MTL). Interestingly, both the LC and MTL are affected during aging. Therefore, we aimed to investigate whether worry during cognitive aging changes the relationship between memory performance and the neural activity patterns during an emotional memory task.

Methods: Twenty-eight participants aged 60-83 years from the Maastricht Aging study conducted an emotional mnemonic discrimination task during a 7T fMRI-scan. We performed a robust multiple linear regression to examine the association between worry and mnemonic memory performance under different levels of arousal. Subsequently, we examined if worry modifies the relationship between neuronal activity and mnemonic memory performance.

Results: We observed that under low arousal, only participants with low compared to high levels of worry benefitted from additional LC activity. Under high arousal, additional LC activity was associated with lower mnemonic memory performance.

Conclusion: Our results suggest there might be an optimal involvement of the NA-system for optimal memory discrimination performance, as we observed that under low levels of worry and with lower levels of arousal, higher LC activity might be needed to achieve similar levels of optimal memory performance as achieved under higher arousal when LC activity remained lower.

Keywords: aging; emotional mnemonic discrimination; locus coeruleus; worry.

Figure 1

Schematic representation of the mnemonic discrimination task. Encoding consisted of 100 everyday objects shown in either a high (e.g., tiger) or low (e.g., buttons) arousing context. After a 7-min resting-state period participants were asked to indicate if the item was the same or different as seen during the encoding phase (retrieval phase).

Figure 2

Memory performance under high and low arousal. More False Positives were observed for high arousal trials compared to low arousal trials. No differences were observed for Hits and False Negatives. Y-axis equals the mean proportion of Hits, False Positives, and False Negatives. Boxplots reflect the median and inter quartile range * p < 0.05.

Figure 3

Association between mean ROI activity and memory performance under high arousal. Higher mean activity during high arousal compared to low arousal trials in the (A) DG is related to a higher proportion of hits (B) CA1 is related to a higher proportion of hits. (C) Greater deactivation in the amygdala for Hits compared to FP is associated with more high arousal Hits. Figures include the unadjusted p-values and colored bands representing the 95% CI. Abbreviations: CA = Cornu Ammonis, DG = dentate gyrus, Hit= correct answers, FP = false positives, HA = high arousal, LA = low arousal.

Figure 4

Visualization of the interaction between worry and LC activation on memory performance. (A) lower LC activity under high arousal is associated with higher hits for participants with a low compared to a high level of worry (B) Under low arousal higher LC activity for Hit trials than FP is associated with a higher proportion of hits in participants with low compared to high levels of worry (C) for participants with low compared to a high level of worry less deactivation of the LC is associated with more FP under low arousal. For visualization purposes the continuous variable worry is depicted as mean and +/− 1SD, as analyses were done with worry and activation as continuous variables (see Table 3). The color of the dots represents the continuous worry score of the participants. Abbreviations: LC = locus coeruleus, FP = false positives, HA = high arousal, LA = low arousal.

Figure 5

Schematic representation of the interactions and interpretations of the results in our paper. (A) High arousal effects are represented in orange. Low arousal effects are represented in blue. + represents higher ROI activation that is related to an improvement in memory performance. – represents a lower memory performance related to higher ROI activation. The dotted line depicts a relation we did not test but hypothesize based on previous literature. (B) Represents the model we hypothesize in which for optimal memory performance one source of arousal (high arousal stimuli or LC activation) leads to optimal performance which two sources of arousal push too far and leads to poor memory performance.