Relational Memory as a Model of Behavioral (Dys)Function in Adults with Traumatic Brain Injury
R01 NIH NS110661; 3/2020 – 2/2025
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.