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：Sklerov 博士，MD MS，是一位经过运动障碍训练的神经科医生， Sklerov 博士在她的培训和早期职业生涯中参与了以患者为导向的研究，并获得了终身教授职位。 她正在北卡罗来纳大学攻读神经病学助理教授职位 Sklerov 博士对帕金森病 (PD) 长期非运动症状的研究和临床兴趣。 职业目标是成为开发新疗法的领先独立临床研究员 与神经系统和精神疾病的神经精神症状一起制定的培训计划。 她的导师和顾问将帮助申请人实现她的目标： 1) 获得使用 脑电图（EEG）在脑刺激研究中的应用，2）获得使用和应用的经验 经颅磁刺激 (TMS) 的研究，3) 扩展她在临床试验设计方面的知识和经验， 4) 培养资助能力和专业发展技能以支持独立研究 她的导师团队包括 Flavio Frohlich 博士和 David Rubinow 博士。 研究：冷漠，或者对以前感兴趣的事情缺乏热情或关注，是一种常见的现象 神经和精神疾病中的使人衰弱的动机障碍与更高水平的冷漠有关。 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系统疾病 经颅磁刺激（TMS）是一种非侵入性脑部疾病，并且通常难以治疗。 当针对背外侧前额叶皮层 (DLPFC) 时，刺激可有效治疗抑郁症，但 对内侧大脑结构（例如内侧前额叶皮层（mPFC））的破坏的研究有限。 和前扣带皮层（ACC），是动机障碍的常见发现，无论潜在的情况如何 帕金森病（PD）的病理学特征是大脑内侧结构优先受到影响。 检查，而其他大脑区域，例如 DLPFC，则不受拟议的总体目标的影响。 研究的目的是开发冷漠 TMS 目标，目标 1 将调查激励后绩效的变化。 目标 2 将调查针对 mPFC 的 TMS 的激励任务（冷漠的衡量标准）。 脑电图 (EEG) 作为目标参与的替代测量方法 开发大脑刺激。 冷漠目标有可能改善数百万美国人的生活质量和疾病进程 完成此处提出的研究和培训将有助于与精神和神经疾病作斗争。 申请人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级资助，我们期望这项研究将提高我们对难治性冷漠的理解， 并促进开发一种广泛可用且安全的冷漠治疗选择。