The goal of this project is to determine whether low frequency oscillations serve as a mechanism for coordinating cortical areas underlying human episodic memory. To address this issue, we will first employ innovative multilobular electrocortigraphic (ECOG) recordings in patients to determine the sets of interconnected brain areas underlying episodic memory, which previous research and our preliminary work strongly suggest to include the medial temporal lobes, prefrontal cortex, and parietal cortex. We will then perturb areas of high connectivity (hubs) in the same patients using chronometric stimulation, which involves simultaneous recording and stimulation from two different brain regions. Chronometric stimulation is advantageous because it involves stimulation that mimics the frequency and amplitude of on-going recorded activity in another brain region, potentially mitigating unwanted spread of stimulation to other brain areas and at the same time providing insight into how neural communication might actually occur. We will employ two different stimulation methods with this approach, either in phase or out of phase stimulation with the on-going recorded oscillations in connecting hubs. This will allow us to determine whether 1) areas with high degrees of connectivity (""""""""hubs"""""""") are necessary for episodic memory 2) whether in- phase, coherent oscillatory can enhance episodic memory retrieval 3) whether out-of- phase oscillations result in decrements in memory performance. Our approach here combines innovative tools, such as electrocorticography and chronometric stimulation in humans and analysis techniques involving graph theory. These in turn will allow us to advance our understanding of how and in what manner networks of brain regions interact as part of their role in episodic memory. This work is relevant to clinical research because it can provide insight into the extent to which other brain regions can compensate for lost function following stroke-related lesions to the medial temporal lobes, a known """"""""hub"""""""" in episodic memory. It will also advance our understanding of potential ways to design and implement deep brain stimulators to treat cognitive impairments accompanying neural disease. For example, if the experiments outlined here are successful, they would imply that devices that time stimulation to be in-phase with distant recorded oscillatory activity could restore or even enhance impaired memory function in patients suffering from neural disease.

Public Health Relevance

A critical and unresolved issue regards how multiple brain regions interact as part of their roles in memory. Addressing this issue is important because the neural mechanisms necessary for episodic memory are not currently known. We propose to address this issue in humans by mapping the brain networks underlying episodic memory using graph theory, multilobular electrocorticographical recordings, and chronometric cortical stimulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS087527-01A1
Application #
8824066
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Babcock, Debra J
Project Start
2014-09-30
Project End
2016-08-31
Budget Start
2014-09-30
Budget End
2015-08-31
Support Year
1
Fiscal Year
2014
Total Cost
$303,643
Indirect Cost
$108,583
Name
University of California Davis
Department
Neurosciences
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
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Kim, Kamin; Ekstrom, Arne D; Tandon, Nitin (2016) A network approach for modulating memory processes via direct and indirect brain stimulation: Toward a causal approach for the neural basis of memory. Neurobiol Learn Mem 134 Pt A:162-177
Vass, Lindsay K; Copara, Milagros S; Seyal, Masud et al. (2016) Oscillations Go the Distance: Low-Frequency Human Hippocampal Oscillations Code Spatial Distance in the Absence of Sensory Cues during Teleportation. Neuron 89:1180-1186
Ekstrom, Arne D (2015) Why vision is important to how we navigate. Hippocampus 25:731-5