MOOD EFFECTS OF DEEP BRAIN STIMULATION IN PARKINSONS

帕金森病的深部脑刺激对情绪的影响

• 批准号: 6233681
• 负责人: MARK S GEORGE
• 金额: $ 46.37万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6233681
• 关键词: Parkinson's disease; behavioral /social science research tag; brain electronic stimulator; central neural pathway /tract; clinical research; emotions; functional magnetic resonance imaging; human subject; human therapy evaluation; lenticular nucleus; mood disorders; nervous system disorder therapy; subthalamus

DESCRIPTION (Adapted from the Applicant's Abstract): Deep Brain Stimulation (DBS) of the thalamus, globus pallidus (GPi) or subthalamic nucleus (STN) is a new treatment for essential tremor and bradykinesia in Parkinson's Disease (PD). The neuropsychological and mood effects of stimulation at these sites are poorly categorized and understood. Major depression (MD) occurs in up to 40% of PD patients. The functional neuroanatomy of normal mood regulation in health and the pathological changes in MD are becoming better understood but still lag behind the neuroanatomical knowledge of motor dysfunction in PD. A key concept developed by the PI and others is that mood is regulated through changes in activity in the anterior paralimbic circuit (APLC) (amygdala, septum, anterior cingulate cortex, anterior temporal poles and orbitofrontal cortex) and that this system functions abnormally in MD. The PI and others have pioneered new treatments for MD JMS, VNS) that have indirectly stimulated this brain circuit. In modem research, no one has used DBS for the primary treatment of MD, although mood effects of DBS have been observed. Based on functional imaging, case report and animal model data, we hypothesize that DBS will cause acute mood changes in PD patients only when DBS affects the APLC. To test this theory that APLC activation is necessary for mood-altering and perhaps antidepressant effects of DBS, we propose to recruit 32 PD patients over a three year period who would fulfill PD clinical indications for DBS (e.g. resistant akinesia, postural rigidity). We will randomly assign these subjects to bilateral DBS at one of two sites either the STN or the GPi. Two days following implantation we will use interleaved DBS/fMRI and intermittently stimulate at the 4 sites on each electrode (bilaterally coordinated), examining changes in self rated mood, psychophysiological measures (HR, BP, GSR, Oxygen saturation), and most importantly, rCBF changes locally and in secondary limbic regions (APLQ. In a masked clinical trial, we will then examine the effects of 4 weeks of a fixed dose of clinically indicated DBS at the implanted site (GPi, STN) on movement, mood and cognition. Subjects with depression symptoms following the 'standard' care will be treated for 4 weeks at the electrode site that on fMRI had the most APLC involvement. The goals of this study are to test this APLC hypothesis of mood regulation and to develop a better working knowledge of the effects of DBS on mood in PD. Thus, we plan to use interleaved fMRI and DBS to directly examine the effects of DBS on hypothesized brain circuits and to correlate this with immediate and longer-term (4 week) behavioral outcomes (mood and cognition).

描述（根据申请人的摘要改编）：深脑刺激 （DB）的（DB），Globus Pallidus（GPI）或丘脑下核（STN）是A 帕金森氏病的基本震颤和黄铁菌的新疗法 （PD）。这些部位刺激的神经心理学和情绪影响是 分类和理解不足。重度抑郁症（MD）发生在多达40％ PD患者。正常情绪调节健康的功能性神经解剖学 医学博士的病理变化变得更好地理解了，但仍然滞后 PD中运动功能障碍的神经解剖学知识的背后。一个关键概念 由PI和其他人开发的是，通过变化来调节心情 前旁皮电路（APLC）的活性（杏仁核，隔膜，前 扣带皮层，前颞杆和轨道额皮层） 该系统在MD中异常起作用。 PI和其他人开创了新的 MD JM，VNS的治疗）间接刺激了该大脑回路。 在调制解调器研究中，没有人使用DBS进行MD的主要治疗 尽管已经观察到了DBS的情绪影响。基于功能成像， 病例报告和动物模型数据，我们假设DBS会引起急性 仅当DBS影响APLC时，PD患者的情绪变化。 为了测试这一理论，即APLC激活对于改变情绪和 也许DBS的抗抑郁作用，我们建议招募32名PD患者 在三年的时间内，他们会满足DBS的PD临床指示 （例如，抗性运动，姿势僵硬）。我们将随机分配这些 受到双侧DBS的受试者在STN或GPI的两个位置之一。二 植入后的几天我们将使用交织的DBS/fMRI并间歇性地使用 在每个电极上的4个位点刺激（双侧协调），检查 自评级情绪，心理生理措施的变化（HR，BP，GSR，氧气 饱和），最重要的是，RCBF在本地和次级边缘发生变化 区域（APLQ。在一项掩盖临床试验中，我们将检查 植入部位的固定剂量临床指示的DBS的固定剂量为4周（GPI， STN）关于运动，情绪和认知。患有抑郁症状的受试者 遵循“标准”护理将在电极部位进行4周的治疗 FMRI上的APLC参与最多。这项研究的目标是测试 情绪调节的APLC假设并发展出更好的工作 了解DBS对PD情绪的影响。因此，我们计划使用交错 fMRI和DBS直接检查DBS对假设大脑的影响 电路并将其与立即和长期（4周）相关联 行为结果（情绪和认知）。