Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen University Hospital, University of Duisburg-Essen, Hufelandstraße 55, Essen 45147, Germany.
Institute for Neural Computation, Ruhr University Bochum, Bochum, Germany.
Neuroimage. 2022 Jun;253:119080. doi: 10.1016/j.neuroimage.2022.119080. Epub 2022 Mar 9.
The cerebellum is involved in the acquisition and consolidation of learned fear responses. Knowledge about its contribution to extinction learning, however, is sparse. Extinction processes likely involve erasure of memories, but there is ample evidence that at least part of the original memory remains. We asked the question whether memory persists within the cerebellum following extinction training. The renewal effect, that is the reoccurrence of the extinguished fear memory during recall in a context different from the extinction context, constitutes one of the phenomena indicating that memory of extinguished learned fear responses is not fully erased during extinction training. We performed a differential AB-A/B fear conditioning paradigm in a 7-Tesla (7T) MRI system in 31 young and healthy men. On day 1, fear acquisition training was performed in context A and extinction training in context B. On day 2, recall was tested in contexts A and B. As expected, participants learned to predict that the CS+ was followed by an aversive electric shock during fear acquisition training. Skin conductance responses (SCRs) were significantly higher to the CS+ compared to the CS- at the end of acquisition. Differences in SCRs vanished in extinction and reoccurred in the acquisition context during recall indicating renewal. Fitting SCR data, a deep neural network model was trained to predict the correct shock value for a given stimulus and context. Event-related fMRI analysis with model-derived prediction values as parametric modulations showed significant effects on activation of the posterolateral cerebellum (lobules VI and Crus I) during recall. Since the prediction values differ based on stimulus (CS+ and CS-) and context during recall, data provide support that the cerebellum is involved in context-related recall of learned fear associations. Likewise, mean β values were highest in lobules VI and Crus I bilaterally related to the CS+ in the acquisition context during early recall. A similar pattern was seen in the vermis, but only on a trend level. Thus, part of the original memory likely remains within the cerebellum following extinction training. We found cerebellar activations related to the CS+ and CS- during fear acquisition training which likely reflect associative and non-associative aspects of the task. Cerebellar activations, however, were not significantly different for CS+ and CS-. Since the CS- was never followed by an electric shock, the cerebellum may contribute to associative learning related to the CS, for example as a safety cue.
小脑参与习得性恐惧反应的获得和巩固。然而,关于其对消退学习的贡献的知识还很匮乏。消退过程可能涉及记忆的擦除,但有充分的证据表明,原始记忆的至少一部分仍然存在。我们提出了这样一个问题,即在消退训练后,记忆是否仍然存在于小脑内。再发效应,即在与消退环境不同的环境中回忆时,已消退的恐惧记忆的再次出现,是表明对已消退的习得性恐惧反应的记忆在消退训练过程中并未完全被抹去的现象之一。我们在 31 名年轻健康男性中使用 7T MRI 系统进行了差异 AB-A/B 恐惧条件反射范式。在第 1 天,在环境 A 中进行恐惧获得训练,在环境 B 中进行消退训练。在第 2 天,在环境 A 和 B 中进行回忆测试。正如预期的那样,参与者学会预测在恐惧获得训练期间,CS+ 之后会跟随令人不快的电击。在获得结束时,皮肤电导率反应 (SCR) 对 CS+ 的反应明显高于 CS-。在消退中,SCR 的差异消失,在回忆中重新出现在获得环境中,表明再发。拟合 SCR 数据,训练一个深度神经网络模型来预测给定刺激和环境下的正确冲击值。基于事件的 fMRI 分析,使用模型衍生的预测值作为参数调制,显示在回忆期间后外侧小脑(VI 叶和 Crus I)的激活具有显著影响。由于在回忆期间,预测值基于刺激(CS+ 和 CS-)和环境而不同,因此数据提供了小脑参与习得性恐惧关联的情境相关回忆的支持。同样,在早期回忆期间,在获得环境中与 CS+ 相关的双侧 VI 叶和 Crus I 的平均β值最高。在蚓部也出现了类似的模式,但仅处于趋势水平。因此,在消退训练后,部分原始记忆可能仍然存在于小脑内。我们发现,在恐惧获得训练期间,与 CS+ 和 CS- 相关的小脑激活可能反映了任务的联想和非联想方面。然而,CS+ 和 CS- 的小脑激活没有显著差异。由于 CS- 从未伴随电击,小脑可能有助于与 CS 相关的联想学习,例如作为安全线索。