Identifying the mechanisms of latent inhibition to prevent dental fear

项目总结 我们的最新发现以及其他发现表明，在条件作用事件结果之前，预先暴露于牙科刺激 潜伏抑制(LI)。反之亦然，缺乏预接触与更大的恐惧、更差的口语有关 健康，取消牙科预约的可能性增加，遵守规定的可能性降低 建议的牙科就诊时间表，以及未能与牙科诊所保持持续的关系。 尽管所有研究的结果都集中在LI上，认为它与预防牙科恐惧有关，但这一事实 没有被用来制定预防方案，也没有必要的实验调查 已着手确定牙科恐惧症LI的靶机制。目前没有 牙科恐惧症的循证预防策略和相关焦虑的现有预防策略 疾病通常是低剂量的弥散治疗方案，没有特定的机制 行动。拟议研究的目的是确定牙科恐惧症的潜在机制(S)， 允许更精确地接触这些目标(S)，并检查个体差异是否与 可能有助于解释在口腔健康和牙齿恐惧方面观察到的差异的种族，与 这些目标的交战。我们假设预测误差和注意力的变化是由 暴露前是条件性恐惧潜在抑制的原因，而较高的疼痛敏感度会增加 这些机制的接合。我们提出了在一种新的虚拟现实中操纵预曝光的研究 由我们团队成员开发和验证的模式，以影响目标机制。除了……之外 评估注意力和预测错误，我们将使用行为测量来检查恐惧的终点， 主观情绪，生理变化。这项拟议的研究具有创新性，因为它是第一个应用于 使用实验医学方法学习牙科恐惧症的一个特征良好的模型；它使用 一种较新的范例，允许在临床相关条件下评估行为 混合的方法/回避动机，以及允许检测个人的环境意外情况 差异，包括那些有可能解决口腔健康差异的问题。此外，使用的方法 包括两种性别的参与者的寿命，以及短期和长期保留测试，注意到的遗漏 在现存的关于人类恐惧条件作用的文献中。这些研究与公共健康有关，因为超过40项 数百万美国人患有严重的牙科恐惧症，有可能对口腔健康和 下游健康后遗症。拟议的研究与临床实践相关，因为缺乏准确的 预防牙科恐惧症的明确和可衡量的目标是发展 以证据为基础、成本效益高的预防战略，并具有可伸缩性，以实现人口变化。 此外，拟议的研究响应了NIDCR在2030年展望倡议中确定的优先事项，以 整合口腔健康和整体健康，实现精准、个性化的护理，并解决口腔健康差距。

PROJECT SUMMARY Our recent findings as well as others, show pre-exposure to dental stimuli prior to a conditioning event results in latent inhibition (LI). The reverse is also true, lack of pre-exposure is related to greater fear, poorer oral health, increased likelihood of cancellation of dental appointments, decreased likelihood of compliance with the recommended schedule of dental visits, and failure to maintain an ongoing relationship with a dental office. Although findings across studies converge on LI as clinically relevant for the prevention of dental fear, this fact has not been leveraged to develop prevention programs nor have the necessary experimental investigations been undertaken to identify the target mechanisms responsible for LI of dental fear. There are currently no evidence-based prevention strategies for dental fear and existing prevention strategies for related anxiety disorders are typically low-dose versions of diffuse treatment programs without a specified mechanism of action. The purpose of the proposed study is to identify the mechanism(s) underlying the LI of dental fear, allowing for more precise engagement of these target(s), and to examine whether individual differences related to ethnicity that could help account for the disparities observed in oral health and dental fear, are related to the engagement of these targets. We hypothesize that changes in prediction errors and attention that result from pre-exposure account for latent inhibition of conditioned fear and that higher pain sensitivity increases the engagement of these mechanisms. We propose studies that manipulate pre-exposure in a novel virtual reality paradigm, developed and validated by members of our team, to affect the target mechanisms. In addition to assessing attention and prediction errors, we will examine the endpoint of fear, using measures of behavior, subjective emotion, and physiological change. The proposed research is innovative in that it is the first to apply a well-characterized model of learning to the LI of dental fear using an experimental medicine approach; it uses a newer paradigm that allows for the assessment of behavior in the context of clinically-relevant conditions of mixed approach/avoidance motivation, with environmental contingencies that allow for detection of individual differences, including those with the potential to address oral health disparities. Moreover, the approach used includes participants of both sexes across the lifespan, and short and longterm retention tests, noted omissions in the extant literature on human fear conditioning. These studies are relevant to public health because over 40 million Americans suffer from significant dental fear with the potential to negatively impact oral health and downstream health sequalae. The proposed studies are relevant to clinical practice because the lack of precisely defined and measurable targets for prevention of dental fear is a critical barrier to the development of evidence-based, cost-effective prevention strategies with the scalability to effect change in the population. Moreover, the proposed research responds the priorities identified by NIDCR in the 2030 visioning initiative to integrate oral health and overall health, enable precise, personalized care, and, address oral health disparities.