Emotion regulation during encoding reduces negative and enhances neutral mnemonic discrimination in individuals with depressive symptoms.

Individuals with depression exhibit dysfunctional emotion regulation, general episodic memory deficits, and a negativity bias, where negative experiences are better remembered. Recent work suggests that the negativity bias in depression may be driven by enhanced mnemonic discrimination, a memory measure that relies on hippocampal pattern separation - a computation that processes experiences with overlapping features as unique. Previously, we found that individuals with depressive symptoms show enhanced negative and impaired neutral mnemonic discrimination. The current study aimed to investigate emotion regulation as an approach toward modifying memory encoding of negative and neutral events in individuals with depressive symptoms. Here we show that applying psychological distancing (a cognitive reappraisal strategy characterized by taking a third-person perspective toward negative events) during encoding was associated with reduced negative and enhanced neutral mnemonic discrimination during retrieval in individuals with depressive symptoms. These results suggest that applying emotion regulation techniques during encoding may provide an effective approach toward altering dysfunctional memory in those with depressive symptoms. Given that pharmacological treatments often fail to treat depression, emotion regulation provides a powerful and practical approach toward modifying cognitive and emotional processes. Future neuroimaging studies will be important to determine how emotion regulation impacts the neural mechanisms underlying these findings.

Perceived antidepressant efficacy associated with reduced negative and enhanced neutral mnemonic discrimination.

Introduction: While antidepressants are one of the first-line treatments for depression, the mechanisms underlying antidepressant action are unclear. Furthermore, the extent to which antidepressants impact emotional and cognitive dysfunction in depression requires more fine-grained approaches toward measuring these impacts in humans. Depression is associated with emotion and mood dysregulation in addition to cognitive deficits. Depressed individuals experience general memory impairment as well as a negativity bias in episodic memory, where negative events are better remembered than positive or neutral events. One potential mechanism hypothesized to underlie the negativity bias in memory is dysfunctional hippocampal pattern separation, in which depressed individuals tend to show impaired general pattern separation but enhanced negative pattern separation. Mnemonic discrimination tasks have been designed to tax hippocampal pattern separation in humans and provide a powerful approach to develop a mechanistic account for cognitive dysfunction in depression. While antidepressants have been examined primarily in rodent models in the context of hippocampal pattern separation, this has yet to be examined in humans. Methods: Here, we investigated how antidepressant usage and their perceived efficacy was associated with emotional mnemonic discrimination, given our prior work indicating a negativity bias for mnemonic discrimination in individuals with greater depressive symptoms. Results: We found that individuals who reported a greater improvement in their depressive symptoms after taking antidepressants (responders) showed reduced negative and enhanced neutral mnemonic discrimination compared to those with little to no improvement (non-responders). Perceived antidepressant efficacy was the strongest predictor of a reduction in the negativity bias for mnemonic discrimination, even when controlling for current depressive symptoms, antidepressant type, and other relevant factors. Discussion: These results suggest that antidepressants, when effective, can shift memory dynamics toward healthy function.

Development of a mnemonic discrimination task using naturalistic stimuli with applications to aging and preclinical Alzheimer's disease.

Most tasks test memory within the same day, however, most forgetting occurs after 24 h. Further, testing memory for simple words or objects does not mimic real-world memory experiences. We designed a memory task showing participants video clips of everyday kinds of experiences, including positive, negative, and neutral stimuli, and tested memory immediately and 24 h later. During the memory test, we included repeated and similar stimuli to tax both target recognition and lure discrimination ability. Participants' memory was worse after 24 h, especially the ability to discriminate similar stimuli. Emotional videos were better remembered when tested immediately, however, after 24 h we find gist versus detail trade-offs in emotional forgetting. We also applied this paradigm to a sample of cognitively normal older adults that also underwent amyloid and tau PET imaging. We found that older adults performed worse on the task compared to young adults. While both young and older adults showed similar patterns of forgetting of repeated emotional and neutral clips, older adults showed preserved neutral compared to emotional discrimination after 24 h. Further, lure discrimination performance correlated with medial temporal lobe tau in older adults with preclinical Alzheimer's disease. These results suggest factors such as time between encoding and retrieval, emotion, and similarity influence memory performance and should be considered when examining memory performance for an accurate picture of memory function and dysfunction.