Biomarkers of Impulsivity in Parkinson's Disease

帕金森病冲动的生物标志物

• 批准号: 10409698
• 负责人: SCOTT M LEWIS
• 金额: --
• 依托单位: MINNEAPOLIS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10409698
• 关键词: Affect; Age; Basal Ganglia; Behavioral; Binge Eating; Biological Markers; Brain; Caring; Complication; Data; Decision Making; Deep Brain Stimulation; Deterioration; Development; Dimensions; Distress; Dopamine; Dopamine Agonists; Effectiveness; Electrophysiology (science); Excision; Exposure to; Family; Family Caregiver; Functional disorder; Future; Gambling; General Population; Goals; Herbicides; Impulse Control Disorders; Impulsive Behavior; Impulsivity; Individual; Intervention; Iowa; Lead; Levodopa; Link; Magnetoencephalography; Measures; Methodology; Modeling; Morbidity - disease rate; Motor; Neurodegenerative Disorders; Outcome; Parkinson Disease; Pathologic; Pathological Gambling; Patient Care; Patients; Pattern; Performance; Persons; Pharmaceutical Preparations; Predisposition; Quality of life; Questionnaires; Recurrence; Research; Research Design; Risk; Sampling; Source; Substance Withdrawal Syndrome; Time; United States; United States Department of Veterans Affairs; Veterans; Well in self; agent orange; behavior test; behavioral outcome; care burden; design; dopamine replacement therapy; experience; fall risk; improved; individualized medicine; motor symptom; negative affect; neural network; neural patterning; neuromechanism; neurophysiology; neuroregulation; prospective; relating to nervous system; response; spatiotemporal; temporal measurement; treatment response; two-dimensional

In recent years, excessive impulsivity and impulse control disorders (ICDs), which commonly include pathological gambling, compulsive shopping, binge-eating, and hypersexuality, have been recognized as an important complication of Parkinson's disease (PD). Both impulsivity and ICDs negatively affect patients and their family quality of life and emotional well-being. In addition, ICDs are a cause of considerable increase in care burden. For these reasons, the problem of excessive impulsivity has become a crucial issue in regards to the care of PD patients. Dopamine-replacement therapy (DRT), in particular dopamine agonists and to a lesser extend l-dopa, have been recognized as a major factor in the increase in impulsivity in PD patients. Accordingly, the main treatment response currently is the decrease or removal of dopamine agonist medications, which however entails the risk of development of dopamine agonist withdrawal syndrome and of recurrence of more severe motor symptoms. However, when excessive impulsivity results from l-dopa alone not much can be done currently to control both motor symptoms and impulsivity. For these reasons, more research is critically needed to better understand the pathophysiology of impulsivity in PD, and to develop more effective care. Impulsivity in PD patients has been found to be composed of two main dimensions identified as motor impulsivity and decision-making impulsivity. This distinction suggests that different neural networks may be affected across PD patients. Accordingly, the limited effectiveness of current treatments of PD-related ICDs may be due to divergent pathophysiological mechanisms, as well as to the scarce understanding of how impulsivity modulates the brain networks associated with decision-making and response planning. Some studies have investigated the neural mechanisms of motor impulsivity in PD patients, and a few have investigated those of decision-making impulsivity. However, to our knowledge no study has ever been designed to investigate specifically how DRT affects the electrophysiological activity within the neural networks associated with the two main dimensions of impulsivity and how this information can prospectively improve patient care. With this project, we intend to begin to fill this gap. We plan to identify the neural signatures of impulsivity in controls and Parkinson's patients using magnetoencephalography (MEG), which provides high temporal resolution of oscillatory activity over the whole brain. Subjects will complete questionnaires relative to impulsivity and ICDs, and then perform two tasks –go/no-go task and Iowa gambling task– assessing the two main dimensions of impulsivity (i.e., motor impulsivity and decision-making impulsivity, respectively) during MEG recording. Patients will be studied both on and off their DRT to determine its effect on the networks associated with each dimension of impulsivity. In addition, these data will be used to create neurophysiological models of the dimensions of impulsivity in PD patients and compare those to matched controls. Furthermore, we will identify the patterns of neural activity that covary with the level of dopamine-induced impulsivity. Advancing our understanding of the brain mechanisms associated with impulsivity in PD will provide a path to more individualized therapy and better outcomes. It will also define the network nodes involved in impulsivity and ICDs and therefore identify potential targets for future interventions by transcranial or deep brain stimulation.

近年来，过度的冲动性和冲动控制障碍（ICD）通常包括 病理赌博，强迫性购物，暴饮暴食和异性疾病已被认为是 帕金森氏病（PD）的重要并发症。冲动性和ICD都会对患者产生负面影响， 他们的家庭生活质量和情感福祉。此外，ICD是考虑到可考虑增加的原因 护理负担。由于这些原因，过度冲动的问题已成为有关 PD患者的护理。多巴胺替代疗法（DRT），特别是多巴胺激动剂， 较小的扩展L-DOPA已被认为是PD患者冲动性增加的主要因素。 彼此之间，目前的主要治疗反应是减少或去除多巴胺激动剂 但是，药物需要发生多巴胺激动剂戒断综合征的风险和 更严重的运动症状的复发。但是，当仅由L-DOPA引起过多的冲动性 目前无法控制运动症状和冲动性。由于这些原因，更多 需要研究以更好地了解PD冲动性的病理生理学，并发展 更有效的护理。 发现PD患者的冲动性由两个主要维度组成 冲动和决策冲动。这种区别表明不同的神经网络可能是 受PD患者的影响。彼此之间，当前与PD相关ICD的治疗的有限有限 可能是由于病理生理机制的不同，以及对 冲动性调节与决策和响应计划相关的大脑网络。一些 研究调查了PD患者运动冲动性的神经机制，其中一些 调查了决策冲动的人。但是，据我们所知，从未设计任何研究 专门研究DRT如何影响神经网络中的电生理活性 与冲动性的两个主要维度以及该信息如何前瞻性改善相关 病人护理。通过这个项目，我们打算开始填补这一空白。 我们计划使用对照组和帕金森患者的冲动性神经特征 磁脑摄影（MEG），它提供了高度暂时的振荡活性分辨率 整个大脑。受试者将填写相对于冲动性和ICD的问卷，然后执行两个 任务 - 执行/禁止任务和爱荷华州赌博任务 - 评估冲动的两个主要维度（即电机 在MEG记录期间，冲动性和决策冲动分别为）。患者将研究 在他们的DRT上和关闭drt，以确定其对与每个维度相关的网络的影响 冲动。此外，这些数据将用于创建尺寸的神经生理模型 PD患者的冲动性并将其与匹配的对照组进行比较。此外，我们将确定模式 与多巴胺诱导的脉冲水平相关的神经活动。促进我们对 与PD中冲动性相关的大脑机制将为更个性化的治疗和 更好的结果。它还将定义与冲动性和ICD相关的网络节点，从而确定 通过经颅或深脑刺激进行未来干预的潜在目标。