Rivera Núñez M Vanessa, McMakin Dana, Mattfeld Aaron T
bioRxiv. 2023 Nov 27:2023.11.14.567068. doi: 10.1101/2023.11.14.567068.
Anxiety affects 4.4-million children in the United States with an onset between childhood and adolescence, a period marked by neural changes that impact emotions and memory. Negative overgeneralization - or responding similarly to innocuous events that share features with past aversive experiences - is common in anxiety but remains mechanistically underspecified. The nucleus reuniens (RE) has been considered a crucial candidate in the modulation of memory specificity. Our study investigated its activation and functional connectivity with the medial prefrontal cortex (mPFC) and hippocampus (HPC) as neurobiological mechanisms of negative overgeneralization in anxious youth.
As part of a secondary data analysis, we examined data from 34 participants between 9-14 years (mean age ± SD, 11.4 ± 2.0 years, 16 females) with varying degrees of anxiety severity. During the Study session participants rated images as negative, neutral, and positive. After 12-hours, participants returned for a Test session, where they performed a memory recognition test with repeated (targets) and similar (lures) images. Labeling negative relative to neutral lures as "old" (false alarms) was our operational definition of negative overgeneralization.
Negative relative to neutral false alarmed stimuli displayed elevated RE activation (at Study and Test) and increased functional connectivity with the CA1 (at Test only). Elevated anxiety severity was associated with reductions in the RE-mPFC functional coupling for neutral relative to negative stimuli. Exploratory analyses revealed similar patterns in activation and functional connectivity with positive stimuli.
Our findings demonstrate the importance of the RE in the overgeneralization of memories in anxious youth.
在美国，焦虑症影响着440万儿童，其发病期在童年和青春期之间，这一时期的神经变化会影响情绪和记忆。消极过度泛化——即对与过去厌恶经历有共同特征的无害事件做出类似反应——在焦虑症中很常见，但在机制上仍未明确。 reunien核（RE）被认为是调节记忆特异性的关键候选者。我们的研究调查了其与内侧前额叶皮质（mPFC）和海马体（HPC）的激活及功能连接，将其作为焦虑青少年消极过度泛化的神经生物学机制。
作为二次数据分析的一部分，我们检查了34名年龄在9至14岁（平均年龄±标准差，11.4±2.0岁，16名女性）、焦虑严重程度不同的参与者的数据。在研究阶段，参与者将图像评为消极、中性和积极。12小时后，参与者返回进行测试阶段，在该阶段他们对重复（目标）和相似（诱饵）图像进行记忆识别测试。将相对于中性诱饵标记为“旧的”（错误警报）的消极情况作为我们对消极过度泛化的操作定义。
相对于中性错误警报刺激，消极刺激在研究和测试时显示出RE激活升高，并且仅在测试时与CA1的功能连接增加。焦虑严重程度升高与中性相对于消极刺激的RE-mPFC功能耦合减少有关。探索性分析揭示了与积极刺激在激活和功能连接方面的类似模式。
我们的研究结果证明了RE在焦虑青少年记忆过度泛化中的重要性。
