MAPPING MOOD IN THE SUBTHALAMIC NUCLEUS IN PD

描述(由申请人提供)：抑郁和焦虑在帕金森病患者中非常普遍(25%-40%)，是导致该人群生活质量下降的主要原因。入住养老院和照顾者压力最大的影响是帕金森氏症的精神共病，而不是帕金森氏症的主要运动症状。因此，了解帕金森病患者抑郁或焦虑发展的神经回路和预测变量是一个具有重要临床意义的重要研究领域。研究帕金森病情绪并发症潜在神经回路脆弱性的一种方法是研究接受丘脑底核深部脑刺激(DBS STN)治疗的个体。DBS STN的最佳治疗对许多PD患者有显著的运动益处。然而，DBS STN可能会对情绪产生意想不到的影响，部分原因可能是活动联系人(S)在功能不同的STN中的位置。已知的解剖通路连接腹内侧STN到情绪系统(如腹侧苍白球、腹侧纹状体、前扣带回)和背侧STN到大脑运动系统(如壳核、初级运动皮质)。关于刺激腹内侧STN比刺激背侧STN对情绪剧烈变化的影响更大这一假设的直接测试尚未完成。此外，DBS STN反应中的任何急性情绪变化对于了解帕金森病患者慢性、临床上有意义的情绪障碍的神经病理生理学的意义尚不清楚。我们将使用DBS STN和一种新的、有效的方法来定位STN内的联系人位置，以解决帕金森病患者急性和慢性情绪功能障碍背后的神经回路问题。这些方法提供了一个独特的机会来映射STN区域(例如背侧与腹内侧；左侧与右侧)与情绪反应之间的关系。此外，我们将确定刺激STN情绪区域的急性反应是否受到过去或未来临床情绪障碍预测的影响。这些实验不能在正常志愿者或非人类动物身上进行。除了对患有和不患有DBS的PD患者有直接的临床相关性外，更好地了解参与情绪变化的神经回路也可能为其他人提供有用的信息(例如，患有基础神经节功能改变的人，如亨廷顿氏病患者，非PD严重抑郁或焦虑患者)。与公共健康相关的抑郁和焦虑在帕金森病患者中非常普遍(25%-40%)，是导致该人群生活质量下降的主要原因。这项研究将有助于确定帕金森病情绪变化所涉及的神经回路，并可能为其他人群(如基底节功能改变的人，如亨廷顿病，患有严重抑郁或焦虑的非帕金森病患者)提供有用的信息。

DESCRIPTION (provided by applicant): Depression and anxiety are highly prevalent (25-40%) in individuals with Parkinson disease (PD) and are the main cause of decreased quality of life in this population. Admissions to nursing homes and caregiver strain are influenced most by the psychiatric comorbidities of PD, not the cardinal motor symptoms of PD. Thus, understanding the neural circuits and predictive variables for the development of depression or anxiety in PD is an important area of research with significant clinical implications. One method for investigating the vulnerability of neural circuits underlying mood complications in PD is to study individuals treated with deep brain stimulation of the subthalamic nucleus (DBS STN). Optimal treatment with DBS STN has significant motor benefits for many PD patients. However, DBS STN can have unintended consequences on mood, perhaps due in part to the location of the active contact(s) within the functionally heterogeneous STN. It is known that anatomical pathways connect ventromedial STN to emotional systems (e.g. ventral pallidum, ventral striatum, anterior cingulate) and dorsal STN to motor systems in the brain (e.g. putamen, primary motor cortex). Direct tests of the hypothesis that stimulation of ventromedial STN influences acute changes in mood more than dorsal STN have not yet been done. In addition, the significance of any acute mood changes in response to DBS STN for understanding the neuropathophysiology of chronic, clinically significant mood disorders in PD is not known. We will use DBS STN and a novel, validated method for locating the site of contacts within the STN to address questions about the neural circuitry underlying acute and chronic mood dysfunction in Parkinson's disease. These methods provide a unique opportunity to map the relationship between STN regions (e.g. dorsal vs. ventromedial; left vs. right) and mood responses. In addition, we will determine if acute responses to stimulation of emotional areas of the STN are influenced by past or predictive of future clinical mood disorders. These experiments cannot be addressed in normal volunteers or in nonhuman animals. In addition to the direct clinical relevance for PD patients both with and without DBS, a better understanding of the neural circuitry involved in mood changes may provide useful information for others as well (e.g. individuals with altered basal ganglia functioning such as Huntington's disease, patients with non- PD major depression or anxiety). PUBLIC HEALTH RELEVANCE Depression and anxiety are highly prevalent (25-40%) in individuals with Parkinson disease (PD) and are the main cause of decreased quality of life in this population. This research will help to determine the neural circuitry involved in mood changes in PD and may provide useful information for other populations as well (e.g. individuals with altered basal ganglia functioning such as Huntington's disease, non-PD patients with major depression or anxiety).