Psychophysiology of Emotion in Parkinsons Disease

描述（由申请人提供）：该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1-2%的65岁以上的人。它是由多巴胺耗尽引起的，具有运动、认知和情绪后果。虽然在运动症状方面取得了进展，但情绪和神经精神变化（抑郁，冷漠，焦虑）仍然非常普遍，并且可能是该疾病最令人不安，致残和复杂的方面。我们小组最近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中得出了相互矛盾的结果。一项研究发现，对厌恶图片的情感反应迟钝，如惊吓眨眼反应所示（Bowers等人，2006），而另一个显示出正常的反应，如瞳孔扩张反应所反映的，其对情绪图片的反应大于对中性图片的反应（Dietz等人，2010年）。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，即增强的唤醒/定向（瞳孔）与防御回路的启动（惊吓反射）。鉴于这些发现，拟议的研究旨在检查，在同一组帕金森病患者中，情绪级联的组成部分，从情绪唤起，提高注意力和警惕性，到目标导向行为的动员。为此，将对非痴呆和非抑郁帕金森患者和对照组进行两项任务测试，一项涉及简单的图片观看，另一项基于Low，Lang，Smith和布拉德利（2008）的“捕食者-猎物”任务。在后者中，暗示潜在的奖励/损失或中立性的线索逐渐逼近，直到最后的“罢工区”，参与者需要按下按钮，并在目标试验中获得（金钱）奖励或避免损失。事件相关电位（LPP，P3），惊吓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索引唤醒/注意力，警惕性和调制行为。基于已知的受多巴胺耗竭影响的神经回路畸变，假设PD患者在情绪处理级联反应早期的唤醒/动机性注意指数上具有相对保留的表现，但随着奖励/损失的前景变得迫在眉睫而变得越来越异常。如果得到支持，这项研究的结果可能会提出一个框架，用于查看帕金森病患者的动机缺陷，包括常见的神经精神症状，如冷漠。 公共卫生相关性：虽然帕金森病通常被视为运动障碍，但它是一种复杂的多系统疾病，也会导致高达80%的患者出现显著的情绪和情绪变化，包括抑郁，冷漠和焦虑。这些非运动变化通常是影响生活质量、认知能力下降、人际关系和照顾者负担的障碍的最令人不安、致残和复杂的方面。拟议研究的目的是通过使用当代情绪神经科学范式更好地了解帕金森病中一些情绪处理缺陷的性质，最终希望为帕金森病中的一些情绪障碍提供更好的治疗方法。

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.