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。入住疗养院和照顾者压力最受帕金森病的精神病合并症的影响，而不是帕金森病的主要运动症状。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重要的研究领域，具有重要的临床意义。研究帕金森病患者情绪并发症背后神经回路脆弱性的一种方法是研究接受丘脑底核脑深部电刺激（DBS）治疗的个体。对于许多PD患者来说，使用DBS起搏器的最佳治疗具有显著的运动获益。然而，DBS脑电刺激可能对情绪产生意想不到的后果，这可能部分是由于功能异质性脑电刺激内活动接触的位置。已知解剖学通路将腹内侧丘脑连接到情感系统（例如腹侧苍白球、腹侧纹状体、前扣带），并且将背侧丘脑连接到大脑中的运动系统（例如壳核、初级运动皮质）。刺激腹内侧肌比刺激背侧肌更能影响情绪的急性变化，这一假设尚未得到直接检验。此外，对于了解PD患者慢性、临床显著情绪障碍的神经病理生理学，DBS治疗后任何急性情绪变化的意义尚不清楚。我们将使用DBS脑电刺激和一种新的，经过验证的方法来定位脑电刺激内的接触部位，以解决有关帕金森病急性和慢性情绪功能障碍的神经回路的问题。这些方法提供了一个独特的机会，映射之间的关系，脑区（如背与腹内侧;左与右）和情绪反应。此外，我们将确定是否急性反应刺激的情绪领域的大脑受到过去或预测未来的临床情绪障碍。这些实验无法在正常志愿者或非人类动物中进行。除了与有和没有DBS的PD患者的直接临床相关性之外，更好地理解涉及情绪变化的神经回路也可以为其他人提供有用的信息（例如基底神经节功能改变的个体，如亨廷顿病，患有非PD重度抑郁或焦虑的患者）。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。这项研究将有助于确定参与PD情绪变化的神经回路，并可能为其他人群提供有用的信息（例如基底神经节功能改变的个体，如亨廷顿病，患有重度抑郁或焦虑的非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).