Identifying the mechanisms of latent inhibition to prevent dental fear

项目摘要 我们最近的研究结果以及其他人，显示预暴露于牙齿刺激之前，条件反射事件的结果 潜伏抑制（LI）。反之亦然，缺乏前接触与更大的恐惧，更差的口头 健康，取消牙科预约的可能性增加，遵守 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。 尽管研究结果都认为LI与预防牙科恐惧症具有临床相关性，但这一事实 还没有被用来制定预防计划，也没有必要的实验研究。 已进行，以确定目标机制负责LI的牙科恐惧。目前没有 牙科恐惧症的循证预防策略和相关焦虑症的现有预防策略 疾病通常是低剂量版本的扩散治疗计划，没有特定的机制， 行动上拟议研究的目的是确定牙科恐惧LI的潜在机制， 允许更精确地参与这些目标，并检查个体差异是否相关 种族，可以帮助解释观察到的口腔健康和牙科恐惧的差异，与 这些目标的参与。我们假设，预测误差和注意力的变化， 预先暴露解释了条件性恐惧的潜在抑制，更高的疼痛敏感性增加了 这些机制的参与。我们提出了在一个新的虚拟现实中操纵预曝光的研究 范例，由我们的团队成员开发和验证，以影响目标机制。除了 评估注意力和预测错误，我们将使用行为指标来检查恐惧的终点， 主观情绪和生理变化。这项研究的创新之处在于它是第一个应用于 使用实验医学方法学习牙科恐惧LI的良好表征模型;它使用 一种新的范式，允许在临床相关条件下评估行为， 混合的接近/回避动机，以及允许检测个体的环境突发事件 差异，包括那些有可能解决口腔健康差距。此外，使用的方法 包括整个生命周期的男女参与者，以及短期和长期保留测试，注意到遗漏 关于人类恐惧条件反射的现存文献中。这些研究与公共卫生有关，因为超过40 数百万美国人患有严重的牙科恐惧症，可能会对口腔健康产生负面影响， 下游健康后遗症所提出的研究与临床实践相关，因为缺乏精确的 预防牙科恐惧的明确和可测量的目标是发展的关键障碍， 以证据为基础的、具有成本效益的预防战略，其规模可扩大，以影响人口的变化。 此外，拟议的研究响应了NIDCR在2030年远景规划倡议中确定的优先事项， 整合口腔健康和整体健康，实现精确、个性化护理，并解决口腔健康差异。

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.