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，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。觉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激活神经元，从而可以增强各种损伤的恢复。在此奖励期间，Goldfine博士将接受唤醒机制系统神经科学的正式培训，以及与觉醒受损相关的典型行为和认知缺陷的量化。他还将学习如何使用核磁共振成像和脑电图（qEEG）的定量分析来表征网络水平的脑功能。为了支持这一培训，Goldfine博士将进行一个关于中风后冷漠的病理生理学的指导研究项目。冷漠，也被称为失读症，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。中风后冷漠很常见（占患者的35%），并与更严重的残疾、更慢的恢复速度和需要机构护理有关。目前尚无治疗方法，冷漠的潜在病理生理机制尚不清楚。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、基底神经节和中央丘脑的连接区域。他将通过两个目标测试该模型：1)通过使用qEEG和MRI测量血流量来测量唤醒调节网络的功能；2)通过确定金刚烷胺激活唤醒调节系统是否能改善冷漠。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。然后，Goldfine博士将对正在进行急性康复的中风后冷漠患者进行金刚烷胺的安慰剂对照试验。在试验中，横断面研究的qEEG测量将被用来确定冷漠的消退是否与觉醒调节系统功能的改善有关。从这项工作中获得的对脑卒中后冷漠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

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.