Post-retrieval stress impairs subsequent memory depending on hippocampal memory trace reinstatement during reactivation

Stress after retrieval can impair future remembering. These memory impairments may be attributed to a weakening of the original memory during reactivation-dependent reconsolidation or to the creation of competitive memory traces that can interfere with future retrieval. Although reconsolidation and interference theories predict forgetting, the neural mechanisms underlying potentially disruptive effects of post-retrieval stress on future remembering are completely unknown. Here, we used a three-day paradigm in which participants underwent functional MRI scanning during initial encoding of word-picture pairs (Day1), partial reactivation of these pairs shortly before a stress or control manipulation (Day 2), and a final cued-recall test (Day 3). Our results show that post-reactivation stress impairs subsequent memory depending on the strength of neural reinstatement of the memory trace during reactivation, as reflected in category-level reinstatement in ventrotemporal cortex (VTC), trial-wise hippocampal encoding-retrieval similarity and the connectivity of the hippocampus with the posterior cingulate cortex (PCC). Moreover, comparison of Day1 to Day3 memory representations in the PCC revealed that successful Day 3 recall was linked to Day1-Day3 pattern dissimilarity in controls, suggesting the use of a different trace, whereas stressed participants relied on the original memory representation. These neural representation changes were again dependent on VTC reinstatement during reactivation. Together, our findings suggest that the impairing effects of post-retrieval stress on future memory relate to the strength of reactivation of the original memory trace, driven by the hippocampus and its crosstalk with neocortical representation areas, revealing disruptive effects on the formation of multiple memory traces.

提取后应激可损害后续记忆。这类记忆损伤可能源于依赖再激活的再巩固（reconsolidation）过程中原始记忆的弱化，或是形成了可干扰后续提取的竞争性记忆痕迹。尽管再巩固与干扰理论均能预测遗忘现象，但提取后应激损害后续记忆的潜在神经机制仍完全不明。本研究采用为期三天的实验范式：参与者在初始阶段（第1天）对词-图配对进行编码，并完成功能磁共振成像（functional MRI）扫描；在第2天，于应激或对照处理前不久对上述配对进行部分再激活；最终在第3天完成线索回忆测试。研究结果显示，再激活后的应激会损害后续记忆，且该效应取决于再激活阶段记忆痕迹的神经复现强度——这一强度可通过腹颞叶皮层（ventrotemporal cortex, VTC）的类别水平神经复现、试次水平的海马（hippocampus）编码-提取相似性，以及海马与后扣带皮层（posterior cingulate cortex, PCC）的功能连接体现。此外，对比第1天与第3天PCC内的记忆表征发现，对照组中成功完成第3天回忆的表现与第1-3天的模式差异相关，表明其采用了不同的记忆痕迹；而应激组参与者则依赖原始记忆表征。此类神经表征变化同样依赖再激活阶段的VTC神经复现。综上，本研究结果表明，提取后应激对后续记忆的损害效应，与原始记忆痕迹的再激活强度相关，该过程由海马及其与新皮层（neocortex）表征脑区的交互所驱动，揭示了其对多重记忆痕迹形成的破坏作用。