Assessing arousal regulation in post-stroke apathy using amantadine and EEG.

描述（由申请人提供）：这是一个培训奖，以支持Goldfine博士发展成为一名独立的临床研究者，研究大脑唤醒系统在中风和创伤性脑损伤恢复中的作用。唤醒是中风恢复的一个重要目标，因为支持它的大脑系统广泛地激发神经元，从而可以增强各种损伤的恢复。在此期间，Goldfine博士将接受唤醒机制系统神经科学的正式培训，沿着通常与唤醒受损相关的行为和认知缺陷的量化。他还将学习如何使用MRI和脑电图（qEEG）的定量分析来表征网络级别的大脑功能。为了支持这项培训，Goldfine博士将开展一项关于中风后冷漠的病理生理学的指导研究项目。冷漠，也被称为abulia，是一种目标导向行为的减少，超出了运动功能障碍的预期，而不是由于嗜睡。冷漠在中风后很常见（35%的患者），并与更严重的残疾，恢复速度较慢，需要机构护理有关。目前没有治疗方法，冷漠的潜在病理生理学尚不清楚。在这里，Goldfine博士将测试一个模型，即目标导向行为的减少可能是由于大脑唤醒调节系统的功能障碍-内侧前额叶皮层，前扣带，以及基底神经节和中央丘脑的连接区域。他将通过两个目标来测试该模型：1）通过使用qEEG和血流的MRI测量来测量唤醒调节网络的功能; 2）通过确定用金刚烷胺激活唤醒调节系统是否改善冷漠。Goldfine博士将首先进行一项横断面研究，比较有和没有冷漠的中风受试者的qEEG和MRI。Goldfine博士将在正在接受急性康复的中风后冷漠患者中进行一项金刚烷胺的安慰剂对照试验。在试验中，将使用横断面研究的qEEG测量值来确定冷漠的消退是否与觉醒调节系统功能的改善相关。从这项工作中获得的对卒中后冷漠潜在的神经元功能障碍的更好理解将为科学家和临床医生提供治疗目标 和诊断测试，以改善中风后冷漠患者的预后。

DESCRIPTION (provided by applicant): This is a training award to support Dr. Goldfine in his development to become an independent clinical investigator studying the role of the brain's arousal systems in recovery from stroke and traumatic brain injury. Arousal is an important target for stroke recovery, as brain systems supporting it excite neurons widely, and can thereby enhance recovery across a wide range of impairments. During this award period, Dr. Goldfine will undertake formal training in the systems neuroscience of arousal mechanisms, along with quantification of behavioral and cognitive deficits typically associated with impaired arousal. He will also learn how to use quantitative analysis of MRI and electroencephalography (qEEG) to characterize brain function at the network level. To support this training, Dr. Goldfine will conduct a mentored research project on the pathophysiology of post-stroke apathy. Apathy, also known as abulia, is a reduction of goal-directed behavior beyond expected from motor dysfunction and not due to somnolence. Apathy is common after stroke (35% of patients) and associated with worse disability, slower rate of recovery, and need for institutional care. There i currently no treatment, and the underlying pathophysiology of apathy is not known. Here, Dr. Goldfine will test a model that reduction of goal-directed behavior can be due to dysfunction of the brain's arousal regulation system - medial prefrontal cortex, anterior cingulate, and connected areas of basal ganglia and central thalamus. He will test the model across two aims: 1) by measuring function of the arousal regulation network using qEEG and an MRI measure of blood flow; and 2) by determining if activation of the arousal regulation system with amantadine improves apathy. Dr. Goldfine will first conduct a cross-sectional study, comparing qEEG and MRI in subjects with stroke with, versus without apathy. Dr. Goldfine will then conduct a placebo-controlled trial of amantadine in subjects with post-stroke apathy who are undergoing acute rehabilitation. In the trial, the qEEG measure from the cross-sectional study will be used to determine if resolution of apathy is associated with improved function of the arousal regulation system. The improved understanding of the neuronal dysfunction underlying post-stroke apathy obtained from this work will provide scientists and clinicians with treatment targets and diagnostic tests to improve outcomes in patients with post-stroke apathy.