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COBRE指导PI项目的总体目标是更好地理解和精确调节慢性中重度创伤性脑损伤（msTBI）患者冷漠的神经计算机制。 以前的研究已经确定，冷漠的特点是失去动力，是一种常见的和衰弱的症状msTBI，但潜在的神经病理导致冷漠msTBI仍然未知。 在临床上，用于msTBI中的冷漠的现有治疗具有有限的功效，这是由于它们依赖于在msTBI中经常受损的高水平认知能力（例如认知行为疗法），或者由于缺乏回路特异性（例如调节整个大脑的多巴胺能张力的药物疗法），它们可能诱导不想要的和有害的副作用。 因此，有显着的需求，i）严格的实验神经科学研究的具体动机行为电路，当损坏时，导致冷漠的msTBI，和ii）电路的发展，具体的方法来调节动机电路冷漠的患者，不依赖于高层次的认知功能。 在本项目中，PI将使用基于任务的功能性磁共振成像（fMRI）来确定msTBI中的冷漠是否与计算环境中刺激的预期奖励值（即，刺激评价），和/或对涉及确定给定奖励是否值得获得它所需的努力的电路的损害（即，（willingness to engage effort） 此外，PI将利用从该msTBI项目中获得的见解来确定任务fMRI引导的重复经颅磁刺激（rTMS）是否是价值和努力回路的回路特定调制的可行方法。 通过建立fMRI引导的rTMS选择性地参与价值和努力计算电路的有效性，该项目将成为未来R 01项目的基石，该项目将改进个性化的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级的人类神经科学实验室，通过独立的R 01资金开发创新方法，用于表征和刺激异常动机行为背后的神经回路。 目前指导PI项目提供了一个理想的机会，PI启动这一研究计划。 Mayer博士和Pierio Richardson博士已经证明了NIH资助的trach记录和使用fMRI阐明TBI引起的功能缺陷的丰富经验（Mayer博士）以及使用rTMS作为神经系统患者的治疗（Pirio Richardson博士）。 此外，两位领先的科学家（Husain，Claus和Costa博士）对动机行为及其病理学的神经计算基础进行了最先进的研究，他们承诺就拟议的项目提供咨询。 因此，咨询委员会将非常适合指导PI领导本项目，并将促进其成为R 01资助的独立研究者。