Reinforcement Learning Neuropathologies Underlying Psychiatric Sequelae in Traumatic Brain Injury

脑外伤后遗症的强化学习神经病理学

• 批准号: 10130954
• 负责人: Jeremy P Hogeveen
• 金额: $ 19.83万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2020-07-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10130954
• 关键词: Reinforcement; Learning; Neuropathologies; Underlying; Psychiatric

Project Summary for Hogeveen Research Project 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 Pierio Richardson have proven trach 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 advisory committee 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.

Hogeveen研究项目的项目摘要 当前的COBRE指导PI项目的总体目标是更好地理解，精确调节慢性现代至重度创伤性脑损伤（MSTBI）患者的冷漠的神经计算机制。先前的研究已经确定，由于动机的丧失而表现为冷漠 - 是MSTBI的常见且令人衰弱的症状，但是在MSTBI中引起冷漠的潜在神经病理学仍然未知。在临床上，MSTBI的现有治疗方法的有效性有限，这是由于它们依赖于MSTBI中经常受到损害的高级认知能力（例如认知行为疗法），或者由于缺乏电路特异性造成的副作用而导致不受欢迎和有害的副作用（例如，在造成电路特异性造成的副作用）（例如，脑液）的可能性（例如，脑力治疗量）。因此，i）对特定动机行为回路进行严格的实验神经科学研究，而当MSTBI中的损伤原因和ii）开发了用于调节冷漠患者的动机电路的电路特异性方法的发展，对高水平认知功能而言并不可靠。在该项目中，PI将使用基于任务的功能磁共振成像（fMRI）来确定MSTBI中的冷漠是否与计算涉及的功能性中性电路的损害有关，而在环境（即刺激价值）中，STIMULLI的预期奖励值（即刺激价值）和/或损害所涉及的通电性是否值得确定愿意的努力（I.此外，PI将利用从该MSTBI项目得出的见解来确定fMRI引导的重复经颅磁刺激（RTMS）是否是用于电路特定的值和努力电路的可行方法。通过建立fMRI指导的RTMS对有选择性吸引价值和努力计算电路的有效性，该项目将为未来的R01项目构成基石，以精炼个性化的RTMS方法，用于治疗损失动机的神经系统和精神病患者。 PI的目标是建立一个世界一流的人类神经科学实验室，该实验室开发了创新的方法来表征和刺激通过独立的R01资金来表征和刺激异常动机行为的神经元电路。当前的Mendored PI项目为PI提供了理想的机会，可以启动该研究计划。高级换人博士。 Mayer和Pierio Richardson已经证明了TRACH记录具有NIH的资金和丰富的利用fMRI的经验，以阐明由TBI（Mayer博士）引起的功能性缺陷，并使用RTMS作为神经系统患者的治疗方法（Pirio Richardson博士）。此外，对动机行为的神经计算基础进行最先进的研究及其病理学的两名领先科学家（Husain，Claus和Costa博士）致力于就拟议项目进行咨询。因此，咨询委员会将非常适合指导PI在他领导该项目时，并将促进他过渡成为一名独立的R01资助的调查员。