Our overall goal is to provide a better understanding of the neuronal basis of human memory in health and disease. Despite considerable research, there is a critical dearth of data at the single neuron level in humans on brain mechanisms underlying declarative memory. Such data can bridge the gap between basic neuronal research in animals, and human functional magnetic resonance imaging (fMRI) research. Direct recording from depth electrodes implanted in human medial temporal lobe (MIL) areas is possible because our subjects are epilepsy patients who require electrode placement to identify the seizure focus for later resection. Our NIH-funded studies to date have elucidated key characteristics of single neuron responses to complex visual stimuli during encoding and retrieval. Now our primary objective is to characterize single neuronal responses and local field potentials (LFPs) during all three major aspects of human declarative memory processes: (1) associative representations, (2) temporal sequential organization of events, and (3) abstraction of common features among related memories. We propose to use tasks that more closely approximate human episodic memory, including sequences of stimuli and stimulus associations and an immersive virtual reality navigational task. The central hypothesis of this study is that neurons in the medial temporal lobe use two codes for declarative memory: (1) a rate code, based on neuronal firing rate, which is sparse, accentuated by inhibition, highly specific to complex stimuli, yet strikingly abstract. It is this code that underlies associative representations and abstraction of common features. And (2) a temporal code, based on timing of spikes that is driven by oscillatory patterns and phase locking of neuronal firing. It is this code that underlies temporal sequential organization of events. We remain the main group in a position to address these fundamental questions about human memory at both the single neuron level and the level of local field potentials. Our studies pave the way to understanding and managing memory impairment in Alzheimer's, temporal lobe epilepsy and other neurological diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS033221-13
Application #
8015996
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Babcock, Debra J
Project Start
1996-09-16
Project End
2012-09-29
Budget Start
2011-02-01
Budget End
2012-09-29
Support Year
13
Fiscal Year
2011
Total Cost
$326,783
Indirect Cost
Name
University of California Los Angeles
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Weiss, Shennan A; Orosz, Iren; Salamon, Noriko et al. (2016) Ripples on spikes show increased phase-amplitude coupling in mesial temporal lobe epilepsy seizure-onset zones. Epilepsia 57:1916-1930
Weiss, Shennan Aibel; Alvarado-Rojas, Catalina; Bragin, Anatol et al. (2016) Ictal onset patterns of local field potentials, high frequency oscillations, and unit activity in human mesial temporal lobe epilepsy. Epilepsia 57:111-21
Andrillon, Thomas; Nir, Yuval; Cirelli, Chiara et al. (2015) Single-neuron activity and eye movements during human REM sleep and awake vision. Nat Commun 6:7884
Suthana, Nanthia A; Parikshak, Neelroop N; Ekstrom, Arne D et al. (2015) Specific responses of human hippocampal neurons are associated with better memory. Proc Natl Acad Sci U S A 112:10503-8
Suthana, Nanthia; Fried, Itzhak (2014) Deep brain stimulation for enhancement of learning and memory. Neuroimage 85 Pt 3:996-1002
Lopour, Beth A; Tavassoli, Abtine; Fried, Itzhak et al. (2013) Coding of information in the phase of local field potentials within human medial temporal lobe. Neuron 79:594-606
Jacobs, Joshua; Weidemann, Christoph T; Miller, Jonathan F et al. (2013) Direct recordings of grid-like neuronal activity in human spatial navigation. Nat Neurosci 16:1188-90
Tankus, Ariel; Fried, Itzhak; Shoham, Shy (2012) Sparse decoding of multiple spike trains for brain-machine interfaces. J Neural Eng 9:054001
Howard, Marc W; Viskontas, Indre V; Shankar, Karthik H et al. (2012) Ensembles of human MTL neurons "jump back in time" in response to a repeated stimulus. Hippocampus 22:1833-47
Suthana, Nanthia; Fried, Itzhak (2012) Percepts to recollections: insights from single neuron recordings in the human brain. Trends Cogn Sci 16:427-36

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