Relational Memory as a Model of Behavioral (Dys)Function in Adults with Traumatic Brain Injury

关系记忆作为成人创伤性脑损伤行为（异常）功能的模型

• 批准号: 10359115
• 负责人: NEAL J. COHEN
• 金额: $ 64.93万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10359115
• 关键词: Adaptive Behaviors; Address; Adult; Affect; Alzheimer' s Disease; Basic Science; Behavior; Behavioral; Behavioral Model; Brain; Chronic; Clinical; Cognition; Cognitive; Communities; Community Integration; Development; Diffuse; Environment; Foundations; Functional disorder; Generations; Goals; Heart; Heterogeneity; Hippocampus (Brain); Impairment; Individual; Individual Differences; Intervention; Laboratories; Laboratory Study; Lead; Link; Measures; Memory; Memory impairment; Mental Depression; Methods; Nature; Neurologic; Outcome; Pathology; Performance; Prefrontal Cortex; Rehabilitation therapy; Reporting; Research; Risk; Role; Sampling; Schizophrenia; Short-Term Memory; Stroke; Structure; System; Testing; Traumatic Brain Injury; Update; Volition; Work; autism spectrum disorder; behavior measurement; community reintegration; diagnostic biomarker; diagnostic tool; disability; executive function; flexibility; frontal lobe; frontal lobe function; functional independence; improved; maladaptive behavior; neural network; neuroimaging; novel; operation; peer; poor communities; prognostic tool; programs; psychosocial; recruit; relating to nervous system; relational memory; response; support network; therapy design; treatment response; visual tracking

Abstract Adults with traumatic brain injury (TBI) have deficits in flexible and goal-directed behavior and these impairments have been linked to negative outcomes and poor community reintegration and independence. The frontal lobes, and their putative functions of executive control and working memory, have figured prominently, and nearly exclusively, in mechanistic accounts of flexible and adaptive behavior and in understanding the underlying nature of behavioral dysfunction in individuals with TBI. Yet, interventions designed to target the frontal lobes have not yielded significant improvements in behavior or independence in the community. We propose that the frontal lobes may be the wrong, or not the only, mechanism of impairment leading to inflexible and maladaptive behavior in TBI. We aim to show that flexible and goal-directed behavior depends critically on the operation of the hippocampal relational memory system and is a key mechanism in the observed behavioral dysfunction and poor outcomes in individuals with TBI. The proposed program of research represents a novel direction in the study of traumatic brain injury with substantial basic science and clinical translational significance. The proposal is organized around four AIMS: (1) To characterize disruptions in the integrity of the structure of the hippocampal system and their impact on relational memory in individuals with traumatic brain injury. (2) To characterize the impact of relational memory impairments on flexible and goal- directed behavior in individuals with traumatic brain injury. (3) To investigate the impact of disruption of the hippocampal system and relational memory on the larger network of structures participating in flexible and goal-directed behavior in individuals with traumatic brain injury. (4) To determine the relationship between impairment in relational memory and community integration and independence in individuals with traumatic brain injury. This proposal is unique in the field and uniquely promising for understanding the nature of behavioral dysfunction in TBI and, ultimately, improving rehabilitation intervention outcomes. Indeed, the proposed work lays the critical foundation for the identification of objective and diagnostic biomarkers for behavioral dysfunction following TBI and for the development of new rehabilitative targets. Linking behavioral dysfunction in TBI to the hippocampal relational memory system will also inform the characterization of a number of other neurological (e.g., stroke, TBI, Alzheimer's disease), psychiatric (e.g., schizophrenia, depression), and developmental (e.g., autism) conditions that affect hippocampal relational memory and where deficits in flexible and goal-directed behavior are also hallmark.

摘要 成人创伤性脑损伤(TBI)在灵活和目标导向行为方面存在缺陷，这些 损害与消极结果以及社区重新融入和独立能力差有关。这个 额叶，以及它们被认为具有执行控制和工作记忆的功能，已经占据了突出的位置， 而且几乎是唯一的，在对灵活和适应性行为的机械性描述中，以及在理解 脑外伤患者行为功能障碍的潜在本质。然而，旨在针对 在社区中，额叶并没有在行为或独立性方面产生显著的改善。我们 提出额叶可能是错误的，或不是唯一导致僵硬的损害机制 以及脑外伤患者的不适应行为。我们的目标是证明灵活和目标导向的行为在很大程度上依赖于 而海马区关系记忆系统的运行是观察到的一个关键机制 脑外伤患者的行为障碍和不良结局。拟议的研究计划 代表了创伤性脑损伤研究的一个新方向，具有坚实的基础科学和临床基础 翻译意义。该提案围绕四个目标进行组织：(1)确定 痴呆患者海马体系统结构完整性及其对关系记忆的影响 创伤性脑损伤。(2)表征关系记忆损伤对灵活性和目标性的影响。 创伤性脑损伤患者的定向行为。(3)调查交通服务中断的影响 海马体系统和关系记忆在更大的网络结构上参与灵活和 创伤性脑损伤患者的目标导向行为。(四)确定 创伤患者的关系记忆障碍与社区整合和独立性 脑部受伤。这一建议在该领域是独一无二的，对于理解 脑外伤患者的行为障碍，并最终改善康复干预结果。事实上， 拟议的工作为确定目标和诊断生物标记物奠定了关键基础 颅脑损伤后的行为障碍和新的康复靶点的开发。链接行为 特发性脑损伤对海马区关系记忆系统的功能障碍也将提示 其他神经疾病(例如中风、脑外伤、阿尔茨海默病)、精神疾病(例如精神分裂症， 抑郁症)以及影响海马体关系记忆的发育(如自闭症)情况以及 缺乏灵活性和目标导向的行为也是标志。