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（PD）患者中非常普遍（25-40%），是该人群生活质量下降的主要原因。疗养院的入院和照顾者的压力受帕金森病精神合并症的影响最大，而不是帕金森病的主要运动症状。因此，了解PD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PD患者情绪并发症神经回路脆弱性的一种方法是对接受丘脑下核深部脑刺激治疗的个体进行研究。DBS STN的最佳治疗对许多PD患者具有显著的运动益处。然而，DBS STN可能会对情绪产生意想不到的影响，部分原因可能是在功能异构的STN内的主动接触位置。已知解剖通路将腹内侧STN连接到情绪系统（如腹侧白质、腹侧纹状体、前扣带）和背侧STN连接到大脑的运动系统（如壳核、初级运动皮层）。腹内侧STN的刺激比背侧STN更能影响心境的急性变化，这一假说的直接检验尚未完成。此外，对DBS STN反应的任何急性情绪变化对于理解PD慢性临床显着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、经过验证的方法来定位STN内的接触部位，以解决帕金森病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绘制STN区域（例如背侧vs.腹内侧；左vs.右）和情绪反应之间的关系。此外，我们将确定对STN情绪区域刺激的急性反应是否受到过去或预测未来临床情绪障碍的影响。这些实验不能在正常志愿者或非人类动物中进行。除了与PD患者的直接临床相关性外，更好地了解与情绪变化有关的神经回路也可能为其他人提供有用的信息（例如，患有基底神经节功能改变的个体，如亨廷顿病，非PD严重抑郁或焦虑的患者）。抑郁和焦虑在帕金森病患者（PD）中非常普遍（25-40%），是该人群生活质量下降的主要原因。这项研究将有助于确定PD患者参与情绪变化的神经回路，并可能为其他人群提供有用的信息（例如，患有基底神经节功能改变的个体，如亨廷顿病，患有严重抑郁或焦虑的非PD患者）。

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).