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

非侵入性脑刺激治疗冷漠的研究

• 批准号: 10740475
• 负责人: Miriam Sklerov
• 金额: $ 20.12万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-17 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10740475
• 关键词: Affect; American; Anterior; Area; Autopsy; Award; Basal Ganglia; Behavioral; Brain; Brain region; Caring; Clinical; Clinical Trials Design; Cognitive; Crossover Design; Data; Dementia; Development; Diagnostic; Disease; Disease model; Dorsal; Electroencephalography; FDA approved; Frequencies; Functional disorder; Funding; Goals; Grant; Impaired cognition; Incentives; Investigation; Knowledge; Label; Learning; Link; Measures; Medial; Medical; Mental Depression; Mental disorders; Mentors; Mentorship; Methods; Modeling; Motivation; Motor; Movement Disorders; Neurodegenerative Disorders; Neurologic; Neurologist; Neurology; North Carolina; Outcome; Parkinson Disease; Participant; Pathologic; Pathology; Pattern; Performance; Persons; Physiological; Physiology; Positioning Attribute; Prefrontal Cortex; Psychiatric Diagnosis; Psychoses; Quality of life; Questionnaires; Refractory; Research; Research Personnel; Rest; Rewards; Severities; Site; Stress; Structure; Surrogate Markers; Symptoms; Testing; Therapeutic; Time; Training; Transcranial magnetic stimulation; Universities; brain health; candidate marker; career; cingulate cortex; experience; improved; innovation; interest; motivated behavior; nervous system disorder; neuroimaging; neuropsychiatric disorder; neuropsychiatric symptom; neuropsychiatry; non-motor symptom; noninvasive brain stimulation; novel; patient oriented research; professor; programs; psychiatric symptom; recruit; response; secondary outcome; sensory cortex; skill acquisition; tenure track; tool

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.

候选人和培训：医学博士Sklerov博士是一名受过运动障碍的神经科医生 在整个培训和早期职业中参与了以患者为导向的研究。 Sklerov博士拥有一条终身轨道 北卡罗来纳大学神经病学助理教授的职位，她正在追求她 帕金森氏病（PD）的非运动症状的研究和临床兴趣。 Sklerov博士的长期 职业目标是成为领先的独立临床研究人员，以开发新的治疗方法 神经系统和精神病的神经精神症状。与 她的导师和顾问将允许申请人实现她的目标：1） 脑刺激研究中的脑电图（EEG），2）获得使用和应用的经验 经颅磁刺激（TMS），3）扩大她在临床试验设计方面的知识和经验， 4）发展授予技巧和专业发展技能，以支持独立研究 职业。她的心态团队包括Drs。 Flavio Frohlich博士和医学博士David Rubinow博士。 研究：冷漠，缺乏热情或对以前有趣的事情的关注，是一个普遍的 并使神经和精神病疾病中的动机灾难使人衰弱。冷漠与更高级别有关 认知障碍，抑郁症，护理伴侣压力水平以及更严重的精神病学和神经系统 疾病，通常是对治疗的难治性。经颅磁刺激（TMS），一种非侵入性脑 刺激在靶向背外侧前额叶皮层（DLPFC）时有效治疗抑郁症 对冷漠的研究有限。内侧大脑结构的破坏，例如内侧前额叶皮层（MPFC） 和前扣带回皮层（ACC）是动机疾病中的普遍发现 疾病。媒体大脑结构在帕金森氏病（PD）上更有可能在病理上受到影响 考试，而其他大脑区域（例如DLPFC）也幸免了。拟议的总体目标 研究是开发冷漠的TMS目标。 AIM 1将调查激励的性能变化 针对针对MPFC的TMS的动机任务（一种冷漠的量度）。 AIM 2将调查使用 脑电图（EEG）作为目标参与的替代测量。发展大脑刺激 冷漠的目标有可能改善数百万美国人的生活质量和疾病课程 患有精神病和神经系统疾病。在这里提出的研究和培训将允许 申请人获得建立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。我们希望这项研究将提高我们对难治性冷漠的理解， 并促进为冷漠的广泛且安全的治疗选择开发。