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

摘要 患有创伤性脑损伤（TBI）的成年人在灵活性和目标导向行为方面存在缺陷， 残疾与负面结果以及重返社区和独立性差有关。的 额叶及其执行控制和工作记忆的假定功能，已经占据了重要地位， 而且几乎完全是在对灵活和适应性行为的机械论解释中， TBI患者行为功能障碍的潜在性质。然而，旨在针对 额叶并没有在行为或社区独立性方面产生显著的改善。我们 我认为额叶可能是错误的，或者不是唯一的，导致不灵活的损伤机制。 和适应不良的行为我们的目的是表明，灵活和目标导向的行为取决于关键 海马关系记忆系统的运作，是观察到的 行为功能障碍和不良预后。拟议的研究计划 代表了创伤性脑损伤研究的一个新方向，具有实质性的基础科学和临床意义。 翻译意义该提案围绕四个目标组织：（1）描述 海马系统结构的完整性及其对个体关系记忆的影响 创伤性脑损伤(2)为了描述关系记忆障碍对灵活性和目标性的影响， 脑外伤患者的定向行为(3)为了调查中断的影响 海马系统和关系记忆在更大的网络结构参与灵活， 目标导向行为在创伤性脑损伤患者中的作用(4)来确定 创伤后精神分裂症患者的关系记忆、社区整合和独立性受损 脑损伤这一建议在该领域是独一无二的，并且对于理解 TBI的行为功能障碍，并最终改善康复干预结果。持续增 拟议的工作为鉴定客观和诊断生物标志物奠定了重要基础， TBI后的行为功能障碍和新的康复目标的发展。链接行为 脑外伤对海马关系记忆系统的功能障碍也将为脑外伤的特征提供信息。 其他神经系统的数量（例如，中风、TBI、阿尔茨海默病），精神病（例如，精神分裂症， 抑郁症），和发育（例如，自闭症）影响海马体关系记忆的条件， 缺乏灵活性和目标导向的行为也是一个标志。

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.