Investigation of non-invasive brain stimulation for the treatment of apathy

候选人和培训：斯克勒罗夫博士，医学博士，医学硕士，运动障碍训练有素的神经学家， 在她的整个培训和早期职业生涯中，都参与了以患者为中心的研究。斯克勒罗夫博士拥有终身教职 北卡罗来纳大学神经学助理教授职位，她正在那里攻读 帕金森氏病(PD)非运动性症状的研究和临床兴趣。斯克勒罗夫博士的长期 职业目标是成为领先的独立临床研究人员，开发新的治疗方法 神经学和精神病学疾病的神经精神症状。该培训计划是与 她的导师和顾问将允许申请者实现她的目标：1)获得使用 脑电(EEG)在脑刺激研究中的应用2)积累使用和应用经验 经颅磁刺激(TMS)，3)扩大临床试验设计的知识和经验， 以及4)培养支持独立研究的资质和专业发展技能 职业生涯。她的导师团队包括Flavio Frohlich博士和David Rubinow博士。 研究：冷漠，或对以前有趣的事情缺乏热情或关心，是一种常见的现象 以及神经学和精神病学疾病中的衰弱动机障碍。冷漠与更高的水平有关 认知障碍、抑郁、护理伙伴压力水平，以及更严重的精神和神经学 疾病，而且往往难以治疗。经颅磁刺激(TMS)--一种非侵入性脑刺激 当以背外侧前额叶皮质(DLPFC)为靶点时，刺激在治疗抑郁症方面有效，但 在冷漠中学习有限。大脑内侧结构的破坏，如内侧前额叶皮质(MPFC) 和前扣带回皮质(ACC)，是动机障碍的常见发现，无论潜在的 疾病。帕金森病(PD)患者的内侧脑结构在病理上优先受累 检查，而其他大脑区域，如DLPFC，则幸免于难。建议的总体目标是 研究的目的是开发冷漠的TMS目标。目标1将调查受激励的 激励性任务(冷漠的一种衡量标准)，回应针对mPFC的TMS。Aim 2将调查其使用情况 脑电(EEG)作为目标交战的替代测量。开发一种大脑刺激 冷漠的目标有可能改善数百万美国人的生活质量和疾病病程 与精神和神经疾病作斗争。完成这里建议的研究和培训将使 申请者需要获得建立其创新研究计划所需的初步数据和专业知识 并申请R01级资金。我们期待这项研究将提高我们对顽固性冷漠的理解， 并促进开发一种广泛可用的、安全的治疗冷漠的选择。

Candidate and training: Dr. Sklerov, MD MS, is a movement disorders trained neurologist who has been involved in patient-oriented research throughout her training and early career. Dr. Sklerov holds a tenure track position of Assistant Professor of Neurology at the University of North Carolina, where she is pursuing her research and clinical interests in non-motor symptoms of Parkinson’s disease (PD). Dr. Sklerov’s long-term career goal is to become a leading independent clinical researcher in developing novel treatments for neuropsychiatric symptoms of neurologic and psychiatric diseases. The training plan, created in conjunction with her mentors and advisors, will allow the applicant to achieve her goals: 1) To obtain training in the use of electroencephalography (EEG) in brain stimulation research, 2) To gain experience in the use and applications of transcranial magnetic stimulation (TMS), 3) To expand her knowledge and experience in clinical trial design, and 4) To develop grantsmanship and professional development skills for supporting an independent research career. Her mentorship team includes Drs. Flavio Frohlich, Ph.D, and Dr. David Rubinow, MD. Research: Apathy, or lack of enthusiasm or concern for things that were previously interesting, is a common and debilitating motivational disturbance in neurologic and psychiatric diseases. Apathy is linked to higher levels of cognitive impairment, depression, care partner stress levels, and more severe psychiatric and neurologic disease, and is often refractory to treatment. Transcranial magnetic stimulation (TMS), a form non-invasive brain stimulation, is effective in treating depression when targeting the dorsolateral prefrontal cortex (DLPFC) but has had limited study in apathy. Disruption in medial brain structures, such as the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC), is a common finding in motivational disorders, regardless of underlying disease. Medial brain structures are preferentially affected in Parkinson’s disease (PD) on pathologic examination, while other brain regions, such as the DLPFC, are spared. The overarching goal of the proposed research is to develop apathy TMS targets. Aim 1 will investigate change in performance of an incentivized motivational task (a measure of apathy) in response to TMS targeting the mPFC. Aim 2 will investigate the use of electroencephalography (EEG) as a surrogate measure of target engagement. Developing a brain stimulation target for apathy has the potential to improve quality of life and disease course for millions of Americans struggling with psychiatric and neurologic illness. Completing the research and training proposed here will allow the applicant to obtain the preliminary data and expertise necessary to build her innovative research program and apply for R01 level funding. We expect that this research will improve our understanding of refractory apathy, and promote development of a widely-available and safe therapeutic option for apathy.