Negative association between anterior insula activation and resilience during sustained attention: an fMRI twin study

Background While previous studies have suggested that higher levels of cognitive performance may be related to greater wellbeing and resilience, little is known about the associations between neural circuits engaged by cognitive tasks and wellbeing and resilience, and whether genetics or environment contribute to these associations. Methods The current study consisted of 253 monozygotic and dizygotic adult twins, including a subsample of 187 early-life trauma-exposed twins, with functional Magnetic Resonance Imaging data from the TWIN-E study. Wellbeing was measured using the COMPAS-W Wellbeing Scale while resilience was defined as a higher level of positive adaptation (higher levels of wellbeing) in the presence of trauma exposure. We probed both sustained attention and working memory processes using a Continuous Performance Task in the scanner. Results We found significant negative associations between resilience and activation in the bilateral anterior insula engaged during sustained attention. Multivariate twin modelling showed that the association between resilience and the left and right insula activation was mostly driven by common genetic factors, accounting for 71% and 87% of the total phenotypic correlation between these variables, respectively. There were no significant associations between wellbeing/resilience and neural activity engaged during working memory updating. Conclusions The findings suggest that greater resilience to trauma is associated with less activation of the anterior insula during a condition requiring sustained attention but not working memory updating. This possibly suggests a pattern of ‘neural efficiency’ (i.e. more efficient and/or attenuated activity) in people who may be more resilient to trauma.

Prediction errors disrupt hippocampal representations and update episodic memories

The brain supports adaptive behavior by generating predictions, learning from errors, and updating memories to incorporate new information. Prediction error, or surprise, triggers learning when reality contradicts expectations. Prior studies have shown that the hippocampus signals prediction errors, but the hypothesized link to memory updating has not been demonstrated. In a human functional MRI study, we elicited mnemonic prediction errors by interrupting familiar narrative videos immediately before the expected endings. We found that prediction errors reversed the relationship between univariate hippocampal activation and memory: greater hippocampal activation predicted memory preservation after expected endings, but memory updating after surprising endings. In contrast to previous studies, we show that univariate activation was insufficient for understanding hippocampal prediction error signals. We explain this surprising finding by tracking both the evolution of hippocampal activation patterns and the connectivity between the hippocampus and neuromodulatory regions. We found that hippocampal activation patterns stabilized as each narrative episode unfolded, suggesting sustained episodic representations. Prediction errors disrupted these sustained representations and the degree of disruption predicted memory updating. The relationship between hippocampal activation and subsequent memory depended on concurrent basal forebrain activation, supporting the idea that cholinergic modulation regulates attention and memory. We conclude that prediction errors create conditions that favor memory updating, prompting the hippocampus to abandon ongoing predictions and make memories malleable.

Identification of the Similarities and Differences of Molecular Networks Associated With Fear Memory Formation, Extinction, and Updating in the Amygdala

Abnormality of fear memory is one of the important pathogenic factors leading to post-traumatic stress disorder (PTSD), anxiety disorder, and other mental disorders. Clinically, although exposure therapy, which is based on the principle of fear memory extinction, has a certain effect on these diseases, it still relapses frequently in some cases. These troubles can be effectively solved by retrieving the memory in a certain time window before the extinction of fear memory. Therefore, it is generally believed that the extinction of fear memory is the result of forming new safe memory to competitively inhibit the original fear memory, while the retrieval-extinction operation is the updating or erasure of the original fear memory, thus, which has greater clinical therapeutic potential. However, what are the detailed molecular networks, specifically the circular RNAs (circRNAs), involved in fear memory updating, and the differences with fear extinction, are still unknown. In this study, we systematically observed the expression of mRNAs, microRNAs (miRNA), long non-coding RNAs (lncRNAs), and circRNAs in the basolateral amygdala of mice after fear memory formation, extinction, and updating by whole-transcriptional sequencing, then a variety of inter-group comparison and bioinformatics analysis were used to find the differential expressed RNAs, enrich the function of them, and construct the molecular interaction networks. Moreover, competing endogenous RNA (ceRNA) molecular networks and transcriptional regulatory networks for the candidate circRNAs were constructed. Through these analyses, we found that about 10% of molecules were both involved in the fear memory extinction and formation, but the molecules and their signaling pathways were almost completely different between fear memory extinction and updating. This study describes a relatively detailed molecular network for fear memory updating, which might provide some novel directions for further mechanism research, and help to develop a specific physical method for fear memory intervention, based on the regulation of these key molecules.

Finding positive meaning in memories of negative events adaptively updates memory

Finding positive meaning in past negative memories is associated with enhanced mental health. Yet it remains unclear whether it leads to updates in the memory representation itself. Since memory can be labile after retrieval, this leaves the potential for modification whenever its reactivated. Across four experiments, we show that positively reinterpreting negative memories adaptively updates them, leading to the re-emergence of positivity at future retrieval. Focusing on the positive aspects after negative recall leads to enhanced positive emotion and changes in memory content during recollection one week later, remaining even after two months. Consistent with a reactivation-induced reconsolidation account, memory updating occurs only after a reminder and twenty four hours, but not a one hour delay. Multi-session fMRI showed adaptive updates are reflected in greater hippocampal and ventral striatal pattern dissimilarity across retrievals. This research highlights the mechanisms by which updating of maladaptive memories occurs through a positive emotion-focused strategy.

Mechanisms of Memory Updating: State Dependency vs. Reconsolidation

Reactivating a memory trace has been argued to put it in a fragile state where it must undergo a stabilization process known as reconsolidation. During this process, memories are thought to be susceptible to interference and can be updated with new information. In the spatial context paradigm, memory updating has been shown to occur when new information is presented in the same spatial context as old information, an effect attributed to a reconsolidation process. However, the integration concept holds that memory change can only occur when reactivation and test states are the same, similar to a state-dependent effect. Thus, in human episodic memory, memory updating should only be found when state is the same across the study, reactivation, and test sessions. We investigated whether memory updating can be attributed to state dependency in two experiments using mood as a state. We found evidence of memory updating only when mood was the same across all sessions of the experiments, lending support to the integration concept and posing a challenge to a reconsolidation explanation.