Research 1-Hogeveen

研究1-霍格文

• 批准号: 10679094
• 负责人: Jeremy P Hogeveen
• 金额: $ 13.15万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10679094
• 关键词: Affect; Amygdaloid structure; Anterior; Apple; Automobile Driving; Behavior; Behavioral; Biological Assay; Brain; Brain Diseases; Chronic; Clinical; Cognitive; Cognitive Therapy; Consult; Corpus striatum structure; Data; Decision Making; Deep Brain Stimulation; Development; Dorsal; Effectiveness; Environment; Event; Functional Magnetic Resonance Imaging; Funding; Future; Goals; Health Benefit; Human; Impairment; Insula of Reil; Intervention; Laboratories; Learning; Mentors; Methods; Motivation; National Institute of Mental Health; Neurologic; Neurology; Neurosciences; New Mexico; Outcome; Participant; Pathologic; Pathology; Patients; Penetrating Brain Injury; Pharmacotherapy; Pre-Post Tests; Prefrontal Cortex; Psychiatric therapeutic procedure; Records; Recovery; Rehabilitation therapy; Research; Research Personnel; Resources; Rewards; Risk; Scientist; Site; Social support; Specificity; Stimulus; Symptoms; System; TBI Patients; Task Performances; Transcranial magnetic stimulation; Traumatic Brain Injury; Traumatic injury; United States National Institutes of Health; Universities; Ventral Striatum; Work; arm; base; cingulate cortex; clinically significant; cognitive ability; cognitive function; common symptom; disabling symptom; effective therapy; experience; experimental study; functional MRI scan; high reward; innovation; insight; motivated behavior; nervous system disorder; neural; neural circuit; neural stimulation; neuroregulation; noninvasive brain stimulation; novel; personalized approach; personalized medicine; precision medicine; programs; recruit; repaired; repetitive transcranial magnetic stimulation; reward anticipation; side effect; willingness

PROJECT SUMMARY The overarching goals of the current CoBRE mentored PI project are to better understand, and precisely modulate, the neurocomputational mechanisms underlying apathy in patients with chronic moderate-to-severe traumatic brain injury (msTBI). Previous studies have established that apathy–characterized by a loss of motivation–is a common and debilitating symptom of msTBI, but the underlying neural pathologies causing apathy in msTBI remain unknown. Clinically, existing treatments for apathy in msTBI have limited efficacy, either due to their reliance on high-level cognitive abilities that are often impaired in msTBI (e.g. cognitive behavioral therapy), or their potential to induce unwanted and deleterious side effects due to a lack of circuit- specificity (e.g. pharmacotherapies that modulate dopaminergic tone throughout the brain). Therefore, there are significant needs for i) rigorous experimental neuroscience studies on the specific motivated behavior circuits that–when damaged–cause apathy in msTBI, and ii) the development of circuit-specific approaches for modulating motivation circuits in apathetic patients, not reliant on high-level cognitive functioning. In this project, the PI will use task-based functional magnetic resonance imaging (fMRI) to determine whether apathy in msTBI is associated with damage to the functional neural circuits involved in computing the anticipated reward value of stimuli in the environment (i.e., stimulus valuation), and/or damage to the circuits involved in determining whether a given reward is worth the effort required to obtain it (i.e., willingness-to-engage effort). Additionally, the PI will leverage the insights derived from this msTBI project to determine whether task fMRI- guided repetitive transcranial magnetic stimulation (rTMS) is a viable approach for circuit-specific modulation of value and effort circuits. By establishing the effectiveness of fMRI-guided rTMS for selectively engaging value and effort computation circuits, this project will form the bedrock for future R01 projects refining personalized rTMS approaches for treating neurological and psychiatric patients experiencing a loss of motivation. The PI’s goal is to build a world-class human neuroscience laboratory that develops innovative methods for characterizing and stimulating the neural circuits underlying aberrant motivated behavior through independent R01 funding. The current mentored PI project provides an ideal opportunity for the PI to jump-start this research program. The senior mentors Drs. Mayer and Pirio Richardson have proven track records with NIH funding and extensive experience using fMRI to elucidate the functional deficits caused by TBI (Dr. Mayer) and using rTMS as a treatment for neurological patients (Dr. Pirio Richardson). Additionally, two leading scientists (Drs. Husain, Claus, and Costa) who conduct state-of-the-art research on the neurocomputational bases of motivated behavior and its pathologies have committed to consult on the proposed project. Therefore, the mentoring team will be well-suited to guide the PI as he leads this project, and will facilitate his transition to becoming an independent R01-funded investigator.

项目摘要 当前的毛绒修改PI项目的总体目标是更好地理解，并且恰恰是 调节，慢性现代至重度患者的冷漠的神经计算机制 创伤性脑损伤（MSTBI）。先前的研究已经确定，由于丧失的冷漠而表征 动机 - 是MSTBI的常见且令人衰弱的症状，但导致的潜在神经病理 MSTBI的冷漠仍然未知。在临床上，MSTBI的现有冷漠治疗效率有限， 要么由于他们对MSTBI经常受到损害的高级认知能力的依赖（例如认知 行为疗法），或由于缺乏电路而引起不必要和有害的副作用的潜力 - 特异性（例如，调节整个大脑多巴胺能张力的药物疗法）。因此，那里 i）对特定动机行为的严格实验神经科学研究 电路（当时损坏时）是由于MSTBI的原因，而II）开发了特定电路的方法 调节冷漠患者的动机电路，对高级认知功能不可靠。在这个 项目，PI将使用基于任务的功能磁共振成像（fMRI）来确定是否冷漠 在MSTBI中，与涉及计算预期的功能中性电路的损害有关 刺激在环境中的奖励价值（即刺激价值）和/或对所涉及的电路的损害 确定给定的奖励是否值得获得获得它的努力（即意愿到参与的努力）。 此外，PI将利用该MSTBI项目得出的见解来确定任务是否fmri- 引导重复的经颅磁刺激（RTMS）是用于特定电路调制的可行方法 价值和努力电路。通过建立fMRI引导的RTM的有效性以选择性吸引价值 和努力计算电路，该项目将构成未来R01项目的基石，以完善个性化 RTMS治疗丧失动力的神经系统和精神病患者的方法。 PI的目标是建立一个世界一流的人类神经科学实验室，该实验室为 表征和刺激通过独立行为异常行为的神经回路 R01资金。当前的修改PI项目为PI提供了理想的机会，可以启动这一点 研究计划。高级导师博士。 Mayer和Pirio Richardson已与NIH一起验证了记录 利用fMRI的资金和丰富的经验来阐明由TBI（Mayer博士）和 使用RTM作为神经系统患者的治疗方法（Pirio Richardson博士）。此外，两位主要科学家 （Husain博士，Claus和Costa）对神经计算基础进行最先进的研究 动机行为及其病理已致力于就拟议项目咨询。因此， 指导团队将非常适合指导PI在他领导该项目时，并将促进他的过渡到 成为一名独立的R01资助的研究者。