U01NS123128

Decoding and Selective Modulation of Human Memory During Awake/Sleep Cycles - Project Summary/Abstract

Episodic memories integrate the content of human experience in space and time and constitute the core of one's identity. Memory formation involves processing and constructing interpretations of the incoming information in our daily lives and is one of the first functions compromised in neurodegenerative diseases such as Alzheimer's disease. With population aging, we face a "cognitive tsunami" of millions of people with memory disorders. Thus, understanding neural mechanisms of memory and finding interventions that enhance these processes is a critical endeavor with the potential to improve the lives of countless people worldwide.

Although it is established that memory is critical for cognitive well-being, and sleep is critical for memory consolidation, the underlying mechanisms in the human brain are poorly understood. Research on memory and sleep so far has suffered from a gap between non-invasive cognitive research in humans and detailed electrophysiological research in animals. Moreover, most human studies are dominated by stimulus response methodologies where the presented stimuli constitute limited, discretized aspects of memory. This approach, albeit well-controlled, is far from the rich narrative of episodes we experience.

Thus, to mechanistically probe human memory consolidation, it is imperative to:

(A) Employ methodologies that incorporate the continuous and multimodal nature of experience;
(B) Identify relevant neural activation patterns and how they are transformed and reactivated during sleep;
(C) Establish means to causally modulate memory processes during sleep.

Building upon our exploratory U01 project, this proposal seeks a breakthrough in our understanding by going beyond the state-of-the-art and via the application of integrative and multidisciplinary approaches. It capitalizes on a highly unique opportunity to record and modulate neuronal activity of a large number of single neurons and neuronal assemblies in the human brain. In parallel, it exploits the high dimensionality of the data as an asset through the use of cutting-edge deep learning (DL) algorithms, which have emerged as promising analysis tools.

Specifically, the project will investigate the presence and decoding of distributed neural patterns associated with memory for different aspects of experience during wakefulness and identify their reactivation during sleep. The proposal aims to selectively modulate memory via the application of novel closed-loop stimulation in sleep in concert with the DL model predictions.

We anticipate that this project is poised to shed light on the relationship between sleep and memory, and its modulation from a novel perspective. Such an ambitious goal can only be achieved with an unrivaled combination of experience, access to a clinical setting, and interdisciplinary collaborations such as those proposed in this project. By combining the opportunity to stimulate and record neural activity with the computational power of artificial intelligence, this project aims to offer findings with far-reaching implications for basic neuroscience and contribute to the development of novel therapies for human memory disorders.

Los Angeles University Of California

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM, RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS, RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS, IMPROVED METHODS OF DISEASE PREVENTION, NEW METHODS OF DIAGNOSIS AND TREATMENT, DRUG DEVELOPMENT, DEVELOPMENT OF NEURAL DEVICES, CLINICAL TRIALS, AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH, SYNAPSE FORMATION, FUNCTION, AND PLASTICITY, LEARNING AND MEMORY, CHANNELS, TRANSPORTERS, AND PUMPS, CIRCUIT FORMATION AND MODULATION, BEHAVIORAL AND COGNITIVE NEUROSCIENCE, SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION, NEUROENDOCRINE SYSTEMS, SLEEP AND CIRCADIAN RHYTHMS, AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE, TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM, NEURODEGENERATIVE DISORDERS, MOVEMENT DISORDERS, BRAIN TUMORS, CONVULSIVE DISORDERS, INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS, DISORDERS RELATED TO SLEEP, AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE NEUROSCIENCE WORKFORCE DEVELOPMENT, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM, TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.372 - 21st Century Cures Act - Brain Research through Advancing Innovative Neurotechnologies

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

Los Angeles, California 90095 United States

Single Zip Code

BRAIN Initiative: Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain (U01 Clinical Trial Required) (RFA-NS-19-001)

Amendment Since initial award the total obligations have increased 427% from $1,350,000 to $7,111,016.