Research 1-Hogeveen

研究1-霍格文

基本信息

批准号：
10468696
负责人：
Jeremy P Hogeveen
金额：
$ 28.98万
依托单位：
UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
依托单位国家：
美国
项目类别：
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/10468696
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 Lead Learning Mentors Methods Motivation National Institute of Mental Health Neurologic Neurology Neurosciences New Mexico Outcome Participant Pathologic Pathology Patients Penetrating Brain Injury Pharmacotherapy 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 image guided innovation insight motivated behavior nervous system disorder neural circuit neuroregulation noninvasive brain stimulation novel personalized approach personalized medicine precision medicine programs recruit relating to nervous system repaired repetitive transcranial magnetic stimulation side effect willingness

项目摘要

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.

项目概要当前 CoBRE 指导的 PI 项目的总体目标是更好地理解并准确地调节慢性中度至重度患者冷漠背后的神经计算机制创伤性脑损伤（msTBI）之前的研究已经证实，冷漠的特点是丧失能力。动机——是 msTBI 的一种常见且令人衰弱的症状，但引起这种症状的潜在神经病理学 msTBI 中的冷漠仍然未知临床上，现有的针对 msTBI 中冷漠的治疗方法效果有限。要么是因为他们对高水平认知能力的依赖，而这种能力在 MSTBI 中经常受到损害（例如，行为疗法），或由于缺乏回路而可能引起不必要的有害副作用特异性（例如调节整个大脑多巴胺能张力的药物疗法）。是对 i) 对特定动机行为进行严格的实验神经科学研究的重大需求当受损时会导致 MSTBI 冷漠的电路，以及 ii）针对特定电路的方法的开发调节冷漠患者的动机回路，不依赖于高级认知功能。项目中，PI 将使用基于任务的功能磁共振成像 (fMRI) 来确定冷漠是否 msTBI 中的损伤与参与计算预期的功能神经回路的损伤有关环境中刺激的奖励价值（即刺激评估），和/或对涉及的电路的损害确定给定的奖励是否值得为获得它而付出努力（即愿意付出努力）。此外，PI 将利用从该 msTBI 项目中获得的见解来确定任务 fMRI 是否引导重复经颅磁刺激 (rTMS) 是一种针对电路特定调制的可行方法通过建立功能磁共振成像引导的 rTMS 选择性参与价值的有效性。和努力计算电路，该项目将构成未来 R01 项目完善个性化的基石 rTMS 方法用于治疗失去动力的神经和精神病患者。 PI 的目标是建立一个世界一流的人类神经科学实验室，开发创新方法通过独立来表征和刺激异常动机行为背后的神经回路当前指导的 PI 项目为 PI 启动这一项目提供了理想的机会。高级导师 Mayer 博士和 Pirio Richardson 博士在 NIH 拥有良好的记录。使用功能磁共振成像来阐明 TBI 引起的功能缺陷的资金和丰富经验（Mayer 博士）和另外，两位领先科学家还使用 rTMS 作为神经系统患者的治疗方法（Pirio Richardson 博士）。（Husain、Claus 和 Costa 博士）对神经计算基础进行了最先进的研究因此，动机行为及其病理学已承诺就拟议项目进行咨询。指导团队将非常适合在 PI 领导该项目时为其提供指导，并将促进他过渡到成为 R01 资助的独立调查员。