Psychophysiology of Emotion in Parkinsons Disease

描述（由申请人提供）：拟议项目的总体目标是增加对帕金森病情绪处理的理解。帕金森病是最常见的老年神经退行性疾病之一，影响了1-2%的65岁以上人群。它是由多巴胺消耗引起的运动、认知和情感后果。虽然在运动症状方面取得了进展，但情绪和神经精神方面的变化（抑郁、冷漠、焦虑）仍然非常普遍，可能是该疾病最令人不安、致残和最复杂的方面。我们小组最近进行的两项关于情绪反应的研究，在精神正常的非痴呆帕金森患者身上得出了相互矛盾的结果。一项研究发现，对厌恶图片的情绪反应迟钝，这可以通过惊眼眨眼反应来体现（Bowers et al., 2006），而另一项研究表明，瞳孔扩张反应是正常的，对情绪图片的反应比中性图片大（Dietz et al., 2010）。对这些不同发现的一种解释是，瞳孔扩张和惊吓眨眼是情绪处理级联的不同组成部分，即增加的唤醒/定向（瞳孔）和防御回路的启动（惊吓反射）。鉴于这些发现，这项拟议的研究旨在检查，在同一组帕金森患者中，情绪级联的组成部分，从情绪唤醒，提高注意力和警惕性，到目标导向行为的动员。为了做到这一点，非痴呆和非抑郁的帕金森患者和对照组将接受两项任务的测试，一项涉及简单的图片观看，另一项基于Low， Lang， Smith和Bradley（2008）的“捕食者-猎物”任务。在后者中，暗示潜在奖励/损失或中立的线索逐渐逼近，直到最后的“打击区”，即要求参与者按下按钮，在目标试验中，要么获得（金钱）奖励，要么避免损失。事件相关电位（LPP, P3）、惊视眨眼和运动反应时间将用于在动机相关和中性任务条件下的唤醒/注意、警觉性和调节行为的指数。基于已知的受多巴胺耗损影响的神经回路畸变，我们假设PD患者在情绪处理级联的早期会相对保持唤醒/动机性注意指数的表现，但随着奖励/损失的前景变得迫在眼前，会变得越来越异常。如果得到支持，这项研究的结果可能为观察帕金森病患者的动机缺陷提供一个框架，包括常见的神经精神症状，如冷漠。

DESCRIPTION (provided by applicant): The overarching goal of the proposed project is to increase understanding of emotional processing in Parkinson's disease. Parkinson's disease is one of the most common neurodegenerative disorders of late life affecting 1-2% of people over the age of 65. It is caused by dopamine depletion with motor, cognitive, and emotional consequences. While advances have been made with respect to motor symptoms, emotional and neuropsychiatric changes (depression, apathy, anxiety) remain highly prevalent and can be the some of the most disturbing, disabling, and complex aspects of the disorder. Two recent studies of emotional responding from our group yielded conflicting results in non-demented Parkinson patients who were psychiatrically normal. One study found blunted emotional reactivity to aversive pictures, as indexed by the startle eye blink response (Bowers et al., 2006), while the other demonstrated normal reactivity as reflected by pupil dilation responses that were larger to emotional than neutral pictures (Dietz et al., 2010). One interpretation of these divergent findings is that pupil dilation and startle eye blink index different components of the emotion processing cascade, namely increased arousal/orienting (pupil) vs. priming of the defense circuitry (startle reflex). In light of these findings, the proposed study is designed to examine, in the same group of Parkinson patients, components of the emotion cascade from emotional arousal, heightened attention and vigilance, to mobilization for goal-directed behavior. To do so, non-demented and non-depressed Parkinson patients and controls will be tested on two tasks, one involving simple picture viewing and the other based on the "predator- prey" task of Low, Lang, Smith, and Bradley (2008). In the latter, cues that signal potential reward/loss or neutrality loom progressively closer until a final "strike-zone" where the participant is required to make a button press, and in target trials either to gain (monetary) reward or avoid a loss. Event-related potentials (LPP, P3), startle eye-blink, and motor reaction times will be used to index arousal/attention, vigilance, and modulated behavior during motivationally relevant and neutral task conditions. Based on known aberrations in neural circuitries affected by dopamine depletion, it is hypothesized that PD patients will have relatively preserved performance on indices of arousal/motivated attention early in the emotion processing cascade but will become increasingly aberrant as the prospect of reward/loss becomes imminent. If supported, findings from this study may suggest a framework for viewing motivational deficits in patients with Parkinson disease, including commonly occurring neuropsychiatric symptoms such as apathy. PUBLIC HEALTH RELEVANCE: Although Parkinson's disease is typically viewed as a motor disorder, it is a complex multi-system disorder that also causes significant emotional and mood changes including depression, apathy, and anxiety in up to 80% of patients. These non-motor changes are often the most disturbing, disabling, and complex aspects of the disorder affecting quality of life, cognitive decline, interpersonal relationships, and caregiver burden. The purpose of the proposed research is to better understand the nature of some of the emotional processing deficits in Parkinson disease by using contemporary emotion neuroscience paradigms with the ultimate hope of providing information leading to better treatment approaches for some of the emotional disturbances in Parkinson disease.