Inducing Mirth to Improve Memory in Depression

据估计，严重抑郁障碍(MDD)每年影响1730万美国成年人，这些地方 这给受影响的个人和我们的医疗系统带来了巨大的负担。一个未被研究的人，但 抑郁症的有害成分是它对人们记忆快乐事件的能力的有害影响。如果我们 对神经过程有了清楚的了解，在这种积极记忆缺陷的基础上，我们会更好 配备了缓解这种干扰的设备。关于这种记忆缺陷的一个有希望的模型假设，对积极记忆的编码 抑郁会削弱记忆，因为抑制的多巴胺(DA)爆发通常会有帮助 对积极信息进行编码(Dillon&Pizzagalli，2018)。此外，愉快的活动可能不会有效 转换为长期记忆存储(因此更难检索)，因为它们不一致 忧郁症患者的焦虑不安情绪。当前提案的目标是使用与事件相关的- 势(ERPs)和计算模型，通过确定是否为正的来检验和扩展该模型 情绪诱导(通过愉悦)可以缓解MDD患者的积极记忆缺陷。PI将唤起一种 成年受试者(96名MDD和96名健康对照；HCS)在记忆编码任务中的P300事件相关电位 检查其波幅(即神经反应的强度)是否与参与者的诊断和记忆有关 性能。所有受试者将在第一天(第一次会议)完成临床访谈，完成积极的情绪 第二天(第二节课)对120幅图片进行归纳(或控制任务)和编码。在第三天，在24小时后允许 为了巩固记忆，参与者将完成记忆识别测试(会话3)。P300 ERP将成为 在内存编码期间响应正、负和中性图像而触发，通过呈现这些 图片与正方形混合的频率很低(9%)(91%)。这一设计将使我们能够测量 MDD患者P300波幅(DA介导的预测误差的信号)是否降低， 相对于HCS，当它们编码正片时(目标1)。我们还将应用分层漂移扩散 模型到记忆识别数据，以测试患有MDD的成年人将表现出较慢的预测 证据积累(因此，记忆重建受损)，因为他们检索积极的图像，而不是 目标2)。最后，我们将检验欢笑诱导将产生积极影响的预测，促进P300 对积极图片的反应，并减少患有MDD的成年人的积极记忆缺陷(目标3)。通过 完成这一项目，PI将获得应用脑电(EEG)的出色培训， 面向翻译研究的计算建模和情绪诱导技术。这一培训将建立 在结构神经成像方面的专业知识，使他能够进行更具临床影响力的研究。 McLean医院将为PI提供进行这项研究的世界级环境，并提供全力支持 私家侦探的训练。完成这个项目和培训最终将使私家侦探能够实现他的目标 成为翻译研究的领导者，专注于积极情感的变化。

Major Depressive Disorder (MDD) impacts an estimated 17.3 million adult Americans per year, which places an enormous burden on the affected individuals as well as our healthcare system. An understudied but pernicious component of depression is its harmful impact on people’s ability to remember happy events. If we gained a clear understanding of neural processes that underly this positive memory deficit, we would be better equipped to alleviate this disruption. A promising model of this memory deficit posits that encoding of positive memories is weakened by depression because of dampened dopaminergic (DA) bursts that typically help encode positive information (Dillon & Pizzagalli, 2018). Furthermore, pleasant events might not effectively translate into long-term memory storage (and consequently be harder to retrieve) because of their incongruity with depressed individuals’ dysphoric mood. The goals of the current proposal are to use Event-Related- Potentials (ERPs) and computational modeling to test and extend this model by determining whether positive mood induction (via mirth) can alleviate the positive memory deficit in individuals with MDD. The PI will evoke a P300 ERP in adult participants (96 MDD and 96 Healthy Controls; HCs) during a memory encoding task and examine whether its amplitude (i.e. strength of neural response) relates to participants’ diagnosis and memory performance. All subjects will complete a clinical interview on day 1 (Session 1), complete a positive mood induction (or a control task) and encode 120 pictures day 2 (Session 2). On day 3, following 24-hours to allow for memory consolidation, participants will complete a memory recognition test (Session 3). P300 ERP will be triggered in response to positive, negative, and neutral images during memory encoding, by presenting these pictures at an infrequent (9%) rate intermixed with squares (91% rate). This design will allow us to measure whether P300 amplitude (which signals DA mediated prediction errors) is lowed in participants with MDD, relative to HCs, when they encode positive pictures (Aim 1). We will also apply the Hierarchical Drift Diffusion Model to memory recognition data, in order to test the prediction that adults with MDD will exhibit slower evidence accumulation (thus, impaired memory reconstruction) as they retrieve positive images, in contrast to HCs (Aim 2). Finally, we will test the prediction that a mirth induction will raise positive affect, boost P300 responses to positive pictures, and reduce the positive memory deficit in adults with MDD (Aim 3). By completing this project, the PI will obtain excellent training in applying electroencephalography (EEG), computational modeling, and mood induction techniques towards translational research. This training will build on the PI’s expertise in structural neuroimaging and enable him to conduct more clinically impactful research. McLean Hospital will provide the PI with a world-class environment for conducting this study, with full support for the PI’s training. Completion of this project and training will ultimately enable the PI to accomplish his goal of becoming a leader in translational research with a focus on alterations in positive affect.