Donna Jo Bridge, Ph.D. - US grants

DESCRIPTION (provided by applicant): Memory provides a means by which we are able to reflect on the past, and at the same time, it enables us to adapt to ever-changing environments by integrating new information into stored representations. A prominent feature of memory impairment is the inability to successfully update old memories to adapt to new situational demands; however, little research has focused on the intersection of memory change and stability. The goal of the proposed research project is to identify the brain mechanisms involved in flexibly updating memories with new information. Motivated by results from our recent functional neuroimaging studies, we will test mechanisms of flexible updating in patients with focal damage to the hippocampus due to surgical resection (performed as treatment for refractory temporal lobe epilepsy). Concurrent eye-tracking and behavioral measures will be utilized to assess memory dysfunction, with a primary focus on the ability to incorporate new, relevant information into existing memory representations. The combination of the proposed methods - brain lesion, eye tracking, and behavioral measures - will collectively provide a thorough account of the memory processes related to flexible updating that are disrupted by brain damage. With this information, new training regimens may be developed to circumvent the necessity of the impaired memory processes by promoting the use of alternative cognitive strategies to aid in daily functioning. The implementation of the proposed training plan will serve to extend the applicant's current training, providing experience working directly with clinical populations, including identifying brain damage using MRI, administering neuropsychological evaluations, modifying experimental designs to obtain valid behavioral and eye-tracking data, and implementing meaningful experiments to identify the nature of cognitive impairment in brain-damaged individuals. Hands-on experience in combination with guidance from established experts in the field of cognitive neuroscience, coursework, and career-development training offered through the applicant's home institution, will serve to promote a well- rounded research career in the field of neuroscience.

Project Summary The hippocampus is crucial for episodic memory, although the mechanisms underlying its contributions are not fully understood. A major obstacle for understanding hippocampal function is the difficulty in linking neural activity to rapidly occurring memory processes that unfold with millisecond time scales. For instance, viewing behavior influences memory formation and retrieval, with ~4 visual fixations on average occurring every second during feats of memory. To address this challenge, the proposed research combines records of viewing behavior obtained via eye-movement tracking with recordings of hippocampal activity from depth electrodes implanted chronically in human subjects for the treatment of epilepsy. This approach yields spatially and temporally precise measurement of hippocampal activity corresponding to the rapid series of visual fixations that occurs during memory formation and retrieval. The primary goal is to identify hippocampal neural activity associated with viewing behavior that reflects novelty detection versus retrieval processes during memory formation. We focus on novelty detection and retrieval because these are two fundamental aspects of hippocampal function that have not been adequately segregated in previous experiments due to their rapid and interactive nature. By linking intracranial recordings of hippocampal neural activity with eye movements that reflect novelty detection versus retrieval in a tightly controlled experimental memory task, the proposed project would advance knowledge of how specific memory functions that occur dynamically during memory formation are supported by the hippocampus. The mechanistic knowledge provided by this proposed research would advance understanding of normal memory function and memory abnormalities in individuals with impairments, including epilepsy and other neurological and psychiatric disorders. Furthermore, establishing relationships between memory-related eye movements and hippocampal function could motivate novel diagnostics for specific hippocampal abnormalities in individuals with memory impairments.