The impact of early life unpredictability on reward processing, learning, and memory

项目摘要 不良的早期生活经历可能对心理健康产生显著持久的负面影响， 许多不同的精神疾病都有这种发展的根源。然而， 对这些病症的不利经历仍然知之甚少。阻碍进展的一个复杂因素是 这一领域是，以前的工作往往集中在逆境的许多不同方面，可能会创造一个 识别治疗干预的具体机制的障碍。拟议的研究解决了这一问题 通过关注早期生活逆境的一个特定方面-照顾者的不可预测性-旨在 理解神经系统如何合理地适应这种逆境，神经系统- 这种适应的计算结果。我们提出了一个计算模型， 当面对不可预测的情况时，遵循进化最优适应原则的神经系统如何能够 早期生活环境，产生受损的奖励学习，减少奖励的期望，和记忆 缺陷-所有这些都是先前确定的早期生活不可预测性的结果，也是常见的 与早期生活不可预测性相关的精神疾病症状。将模型转换为 假设的神经生物学基础产生了关于早期生活如何 不可预测性会改变奖励系统和记忆系统之间的相互作用。也就是说，我们预测早期- 生活的不可预测性将改变奖励对核心记忆计算的影响（模式完成和 分离），这反过来又会影响记忆如何指导奖励的决定。我们将直接测试这些 使用多管齐下的方法整合计算建模， 行为与内侧颞叶亚结构的高分辨率功能性神经成像及其 与奖励区域的协同激活。在这样做的过程中，我们的目标是精确地确定早期生活的不可预测性如何改变 奖励和记忆之间的相互作用。在目标1中，我们将确定早期生活的不可预测性 形成奖励对记忆的影响。在目标2中，我们将确定早期生活不可预测性的影响 记忆引导的奖励决策。从拟议的研究结果将确定是否行为 在早期生活不可预测性之后，奖励处理和记忆的缺陷可以被理解为 合理适应早期生活环境的结构和统计的结果。

PROJECT SUMMARY Adverse early life experiences can have remarkably enduring negative consequences on mental health, with numerous, varied psychiatric conditions sharing this developmental origin. Yet, the mechanisms linking adverse experiences to these conditions remain poorly understood. One complication that impedes progress in this area is that prior work has often aggregated over many distinct aspects of adversity, potentially creating a barrier to identifying specific mechanisms for therapeutic intervention. The proposed research addresses this gap by focusing on one particular dimension of early life adversity – caregiver unpredictability — aiming to understand how neural systems may rationally adapt in response to this adversity, and the neuro- computational consequences of this adaptation. We have proposed a computational model that demonstrates how neural systems that follow statistically-optimal adaptation principles can, when faced with an unpredictable early life environment, produce impaired reward learning, diminished expectation of reward, and memory deficits – all of which are previously identified outcomes of early-life unpredictability, and are also common symptoms of psychiatric conditions associated with early-life unpredictability. Translating the model into its hypothesized neurobiological underpinnings generates novel predictions regarding how early-life unpredictability should alter interactions between reward and memory systems. Namely, we predict that early- life unpredictability will alter reward’s effect on core mnemonic computations (pattern completion and separation), and that this will in turn affect how memory guides decisions for reward. We will directly test these predictions across two experiments using a multi-pronged approach integrating computational modeling of behavior with high-resolution functional neuroimaging of medial temporal lobe substructures and their coactivation with reward regions. In doing so, we aim to precisely identify how early-life unpredictability alters reciprocal interactions between reward and memory. In Aim 1, we will determine how early-life unpredictability shapes the influence of reward on memory. In Aim 2, we will determine the impact of early-life unpredictability on memory-guided decisions for reward. Findings from the proposed studies will determine whether behavioral deficits in reward processing and memory following early-life unpredictability can be understood as the consequence of rational adaptation to the structure and statistics of the early life environment.