Episodic memory is a fundamental part of human experience that provides direction for current behavior based on past events. Memory retrieval is theorized to be mediated by oscillatory communication between the medial temporal lobe (MTL) and the neocortex. Recently, ripple oscillations have emerged as a potential neural substrate for this communication dynamic in rodents. However this mechanism is poorly understood in humans, and efforts thus far have not revealed the role of oscillations in mediating memory processes across the human brain. This project therefore seeks to characterize the relevant oscillatory neural dynamics that may underlie the mechanisms of human memory. We will use intracranial EEG (iEEG) recordings during a verbal memory task to investigate oscillatory activity in the human brain, potentially demonstrating that ripple oscillations are coupled between the human medial temporal lobe and neocortex during memory retrieval. As we have previously shown that distributed neural oscillations are reinstated upon successful memory retrieval, we expect that ripples may also orchestrate this process in the human brain. Additionally, through microarray recordings, we aim to demonstrate the relationship between oscillations and single neuron spiking activity, particularly if ripples influence the replay of cortical multi-unit activity that also may underlie human memory. Connecting the macro neural activity at the iEEG scale to the spiking of individual neurons will allow us to develop a more nuanced understanding of the oscillatory communication between brain areas in the service of memory. Finally, we will model any interactions between oscillatory and spiking activity in the human brain during memory processes in order to develop a more principled understanding of cognitively relevant interactions between the neural activities on these different spatial scales. This theoretical approach will allow for a mechanistic and potentially causal explanation of neural activity during memory retrieval. Taken together, we will employ both empirical and theoretical approaches to investigate if oscillatory activity between the medial temporal lobe and neocortex underlies successful memory retrieval in the human brain.

Public Health Relevance

Memory dysfunction is a pervasive part of clinical practice, affecting patients in an increasing volume with an aging population. As such, finding targetable mechanisms of memory function is of great significance in improving the quality of life of those suffering from memory disorders. By directly examining neural signals during memory processes in humans, we aim to elucidate a neural oscillatory mechanism for human memory retrieval, thereby narrowing the scope of future pharmacological or neuromodulatory interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31NS113400-01
Application #
9833048
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Babcock, Debra J
Project Start
2019-07-01
Project End
2022-05-31
Budget Start
2019-07-01
Budget End
2020-06-30
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Duke University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705