Decades of research and clinical observations have established that episodic memory, the ability to remember recently experienced events, depends on the hippocampus and associated structures in the medial temporal lobe (MTL), including entorhinal, perirhinal and parahippocampal cortices [1, 2]. It is thought that the neuronal mechanisms supporting episodic memory for spatial context involves place and grid cells found in the MTL that increase in firing rate when an animal is in a specific location during navigation [3-7]. Furthermore, successful formation and retrieval of spatial memory is thought to be dependent upon the integration of MTL structures through coordinated oscillatory activity related to spike timing dependent plasticity [8-15]. The proposed project will investigate the relationship between spatial navigation, human memory, oscillatory activity, and spatially selective cells using intracranial single-unit and local field potential (LFP) recordings in humans. We will examine patients who are implanted with the Neuropace Responsive Neurostimulator (RNS) or DEPTH electrodes for clinical evaluation and treatment of epilepsy. The RNS device will allow us to stimulate and record LFP activity from the MTL during real world and virtual reality (VR) spatial navigation using simultaneous full body motion capture and immersive VR headset technology. The DEPTH electrodes will allow us to stimulate and record single-unit and LFP activity during immersive VR spatial navigation. Together these studies will have access to over 30 subjects over the project period through an interdepartmental collaboration among clinical and basic science leaders at UCLA. Since our studies address basic questions about the role of oscillations and single neurons in memory, it is anticipated that such basic studies will contribute to bridging of findings between species and laying the scientific foundation for helping future patients with diseases where memory is impaired such as Alzheimer's disease and epilepsy.

Public Health Relevance

Clinical circumstances that allow for direct recordings from individual neurons within the human brain provide a rare opportunity to investigate single cell mechanisms underlying cognition. The results from the proposed studies will bring in line major discoveries in rodent physiology with the human medial temporal lobe (MTL) system and extend it to particular aspects of real world human spatial navigation and memory. These translational studies will address questions about the relationship between deep brain stimulation, single neurons, oscillatory activity, spatial navigation, and memory, and help lay the foundation for future treatments for illnesses marked by memory impairment.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZNS1)
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Gnadt, James W
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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Suthana, Nanthia; Aghajan, Zahra M; Mankin, Emily A et al. (2018) Reporting Guidelines and Issues to Consider for Using Intracranial Brain Stimulation in Studies of Human Declarative Memory. Front Neurosci 12:905
Reggente, Nicco; Essoe, Joey K-Y; Aghajan, Zahra M et al. (2018) Enhancing the Ecological Validity of fMRI Memory Research Using Virtual Reality. Front Neurosci 12:408
Titiz, Ali S; Hill, Michael R H; Mankin, Emily A et al. (2017) Theta-burst microstimulation in the human entorhinal area improves memory specificity. Elife 6:
M Aghajan, Zahra; Schuette, Peter; Fields, Tony A et al. (2017) Theta Oscillations in the Human Medial Temporal Lobe during Real-World Ambulatory Movement. Curr Biol 27:3743-3751.e3