Hippocampal and prefrontal contributions to memory integration

描述(由申请人提供)：领先的记忆理论强调新的学习是在现有知识的背景下发生的。在新的经历中检索先前的知识，可以将新的信息整合到现有的记忆中，从而形成与离散事件相关的丰富、紧密的记忆网络。这种整合过程是为了促进新的学习，并使记忆超越直接经验而扩展到预测事件之间的关系。然而，记忆换证据表明，神经生物学无法直接测量在新体验期间重新激活的记忆的内容。为了解决这一关键差距，建议的研究采用了一种新的实验范式，该范式使用应用于功能神经成像数据的高度敏感的模式分类器算法来量化新事件编码过程中偶然的记忆重新激活。量化记忆的重新激活使我们能够测试关于过去的记忆如何影响现在的学习的机械性预测。目的1将使用这一范式来测试假设，即海马体和腹内侧额叶皮质(VMPFC)协同工作，以支持新的学习过程中的记忆整合。我们认为，通过将新信息与成熟的记忆联系起来，这种由海马-VMPFC介导的编码过程改善了新的学习，并使人们能够对不同事件之间的关系做出新的判断。目标2将考察时间背景和记忆强度如何影响相关事件的综合记忆痕迹的形成。我们认为，在相同的时间背景下学习重叠事件通过增强记忆重新激活和招募海马-VMPFC编码过程来促进记忆整合。我们还将在两种不同的学习理论观点之间做出裁决，这些观点对强记忆或弱记忆是否会增强记忆整合做出了相互矛盾的预测。Aim 3将使用专注于内侧颞叶的高分辨率功能磁共振成像来确定作为记忆整合基础的精确的海马体计算和编码策略。我们将确定记忆重新激活与海马失配反应之间的关系，这些失配反应是当前事件和现有记忆之间差异的信号，以检验失配反应触发记忆整合的假设。我们还将使用模式信息分析来测试海马体通过为相关事件形成重叠的神经代码来创建整合记忆的假设。总的来说，这项工作将确定内部生成的内容如何影响新的学习，并将隔离作为记忆整合基础的精确神经网络、计算和编码策略。了解大脑如何使用先前的经验来理解新信息将为整合方面的翻译工作奠定基础，其功能意义严重缺乏，主要是由于对需要获得和维持新行为的治疗精神和神经疾病的有效干预。

DESCRIPTION (provided by applicant): Leading memory theories emphasize that new learning occurs on the background of existing knowledge. Retrieving prior knowledge during new experiences allows new information to be integrated into existing memories, resulting in the formation of rich, cohesive memory networks that relate discrete events. This integration process is proposed to facilitate new learning and enable memories to extend beyond direct experience to anticipate the relationships among events. However, memory for evidence neurobiological inability to directly measure the contents of reactivated memories during new experiences. To address this critical gap, the proposed studies employ a new experimental paradigm that uses highly sensitive pattern classifier algorithms applied to functional neuroimaging data to quantify incidental memory reactivation during new event encoding. Quantifying memory reactivation allows us to test mechanistic predictions about how past memories influence learning in the present. Aim 1 will use this paradigm to test the hypothesis that hippocampus and ventromedial prefrontal cortex (VMPFC) work in concert to support memory integration during new learning. We propose that by linking new information with well-established memories, this hippocampal-VMPFC mediated encoding process improves new learning and enables novel judgments about relationships among distinct events. Aim 2 will examine how temporal context and memory strength influence the formation of integrated memory traces for related events. We propose that learning overlapping events within the same temporal context facilitates memory integration by enhancing memory reactivation and recruiting hippocampal-VMPFC encoding processes. We will also adjudicate between opposing theoretical perspectives of learning that make competing predictions for whether strong or weak memories lead to enhanced memory integration. Aim 3 will use high- resolution fMRI focused on the medial temporal lobe to determine the precise hippocampal computations and coding strategies that underlie memory integration. We will determine the relationship between memory reactivation and hippocampal mismatch responses that signal differences between current events and existing memories to test the hypothesis that mismatch responses trigger memory integration. We will also use pattern- information analysis to test the hypothesis that the hippocampus creates integrated memories by forming overlapping neural codes for related events. Collectively, this work will determine how internally generated content influences new learning and will isolate the precise neural networks, computations, and coding strategies that underlie memory integration. Understanding how the brain uses prior experience to make sense of new information will lay the foundation for translational work onintegration and its functional significance is sorely lacking due primarily to an effective for interventions therapeutic psychiatric and neurological disorders that require acquisition and maintenance of new behaviors.