Maladaptive memories and conditioned fear underlie many anxiety disorders such as post-traumatic stress disorder (PTSD). Many therapeutic approaches aim at manipulating these fearful memories via reconsolidation. Reconsolidation theory explains that memory stability diminishes during recall and can be modulated. Dr. Stephanie Grella and colleagues investigate a possible intervention for fearful memories via optogenetics, where memories are reactivated during reconsolidation in order to disrupt them. The results suggest that this could be a new therapeutic approach to help patients suffering from various anxiety disorders.
(Grella et al., 2021) used Tet-tag to label neurons in the dorsal dentate gyrus (dDG), which has been shown by previous research to be important for contextual fear memory encoding. Researchers found that the artificial reactivation of memories mediated by the dDG reduced fear. (Grella et al. 2021) also found that interference in the dDG does not affect other hippocampal-mediated memories, and that is specific to the fear memory. These results demonstrate disruption in the memories when they are reactivated, leading to reconsolidation of that memory trace. The results of (Grella et al., 2021) demonstrate the possibility of targeting fearful memories, unlike the non-discriminatory nature of current methods used on humans, such as trans-magnetic stimulation (TMS) and electroconvulsive therapy (ECT).
(Speer, Ibrahim, Schiller, & Delgado, 2021) use similar methods to (Grella et al., 2021) in the article “Finding positive meaning in memories of negative events adaptively updates memory”. (Speer et al., 2021) investigates reconsolidation of memories like (Grella et al., 2021), but explores how focusing on positive aspects of past negative memories can change the representation of the memory, rather than inducing positive memories artificially. These researchers found enhanced positive emotion at retrieval when participants were required to elaborate on positive aspects of the negative memory. (Speer et al., 2021) Additionally, fMRI scans revealed greater neural dissimilarity in the hippocampus and ventral striatum when participants recalled the memory after reconsolidating and considering the positive aspects of the negative event. Not only do participants feel more optimistic after considering “the bright side”, but the neural correlates in their brains do change.
These two articles pose implications for future therapeutic endeavors. (Grella et al., 2021) activated positive memories in mice to “update” the memory, while (Speer et al., 2021) “updated” memories in humans by asking them to consider positive aspects of a negative event. In a sense, both articles utilize reconsolidation to their benefit, but updating the memories in a fashion best suited for their sample: artificial reactivation for mice and cognitive regulation for humans. However, more research must be conducted to find more suitable therapies for patients suffering from anxiety disorders, as there are many ethical considerations. It may be harmful for patients to revisit these negative memories, and asking them to consider “the bright side” may be insensitive and detrimental. Neither article gives an immediate therapeutic solution, but both contribute to the ever-growing body of research surrounding maladaptive memories and their neural correlates. With a better understanding of how these fearful memories manifest and how they can be modulated, appropriate therapies can be recommended to patients.
References
Grella, S. L., Fortin, A.
H., Ruesch, E., Bladon, J. H., Reynolds, L. F., Gross, A., Shpokayte, M.,
Cincotta, C., Zaki, Y., & Ramirez, S. (2021). Reactivating
hippocampal-mediated memories during reconsolidation to disrupt fear. Nature
Communications. https://doi.org/10.1101/2021.09.16.460695
Speer, M. E., Ibrahim, S.,
Schiller, D., & Delgado, M. R. (2021). Finding positive meaning in memories
of negative events adaptively updates memory. Nature Communications, 12(1).
https://doi.org/10.1038/s41467-021-26906-4
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