Webler Ryan D, Morales Carrasco Cristian, Cooper Samuel E, Chen Mo, Hunt Christopher O, Hennessy Sierra, Cao Lancy, Lam Carol, Chiu Allen, Differding Cash, Todd Erin, Hendrickson Timothy J, Oathes Desmond J, Widge Alik S, Hermosillo Robert J M, Nelson Steven M, Fair Damien A, Lissek Shmuel M, Nahas Ziad
Department of Psychology, University of Minnesota, Minneapolis, Minnesota.
Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, Minnesota.
Biol Psychiatry Glob Open Sci. 2024 Mar 22;4(3):100309. doi: 10.1016/j.bpsgos.2024.100309. eCollection 2024 May.
Fear overgeneralization is a promising pathogenic mechanism of clinical anxiety. A dominant model posits that hippocampal pattern separation failures drive overgeneralization. Hippocampal network-targeted transcranial magnetic stimulation (HNT-TMS) has been shown to strengthen hippocampal-dependent learning/memory processes. However, no study has examined whether HNT-TMS can alter fear learning/memory.
Continuous theta burst stimulation was delivered to individualized left posterior parietal stimulation sites derived via seed-based connectivity, precision functional mapping, and electric field modeling methods. A vertex control site was also stimulated in a within-participant, randomized controlled design. Continuous theta burst stimulation was delivered prior to 2 visual discrimination tasks (1 fear based, 1 neutral). Multilevel models were used to model and test data. Participants were undergraduates with posttraumatic stress symptoms (final = 25).
Main analyses did not indicate that HNT-TMS strengthened discrimination. However, multilevel interaction analyses revealed that HNT-TMS strengthened fear discrimination in participants with lower fear sensitization (indexed by responses to a control stimulus with no similarity to the conditioned fear cue) across multiple indices (anxiety ratings: β = 0.10, 95% CI, 0.04 to 0.17, = .001; risk ratings: β = 0.07, 95% CI, 0.00 to 0.13, = .037).
Overgeneralization is an associative process that reflects deficient discrimination of the fear cue from similar cues. In contrast, sensitization reflects nonassociative responding unrelated to fear cue similarity. Our results suggest that HNT-TMS may selectively sharpen fear discrimination when associative response patterns, which putatively implicate the hippocampus, are more strongly engaged.
恐惧泛化是临床焦虑症一种有前景的致病机制。一种主流模型认为海马体模式分离失败会导致泛化。海马体网络靶向经颅磁刺激（HNT-TMS）已被证明可增强海马体依赖的学习/记忆过程。然而，尚无研究考察HNT-TMS是否能改变恐惧学习/记忆。
通过基于种子的连接性、精准功能映射和电场建模方法确定个体化的左侧顶叶后部刺激部位，对其进行连续theta爆发刺激。在参与者内随机对照设计中，也对一个顶点控制部位进行刺激。在两项视觉辨别任务（一项基于恐惧，一项中性）之前进行连续theta爆发刺激。使用多级模型对数据进行建模和测试。参与者为有创伤后应激症状的大学生（最终样本量 = 25）。
主要分析未表明HNT-TMS增强了辨别能力。然而，多级交互分析显示，HNT-TMS在恐惧敏化程度较低的参与者（以对与条件恐惧线索无相似性的对照刺激的反应为指标）中，通过多个指标增强了恐惧辨别能力（焦虑评分：β = 0.10，95%可信区间，0.04至0.17，P = .001；风险评分：β = 0.07，95%可信区间，0.00至0.13，P = .037）。
泛化是一个关联过程，反映了对恐惧线索与相似线索的辨别不足。相比之下，敏化反映了与恐惧线索相似性无关的非关联反应。我们的结果表明，当假定涉及海马体的关联反应模式更强时，HNT-TMS可能会选择性地增强恐惧辨别能力。
