# Mechanisms of Memory Enhancement by Deep Brain Stimulation in Humans

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $589,267

## Abstract

Project Summary/Abstract
Loss of the ability to form new memories and retrieve old ones is one of the most dreaded afflictions of the human
condition. It is present in various neurological disorders, including temporal lobe epilepsy, traumatic brain
injury and is one of the first features of Alzheimer’s Disease (AD) affecting millions of people in the US and
many more worldwide. Decades of research have established that declarative memory, the ability to remember
recently experienced facts and events, depends on the hippocampus and associated structures in the medial
temporal lobe (MTL), including the entorhinal cortex. Our laboratory has been a leader in single neuron
physiology of the human MTL for last two decades and was the first group to publish findings using deep brain
stimulation (DBS) of the entorhinal-hippocampal circuitry in humans to modulate human memory. Our approach
is based on the unique opportunity to record activity of single neurons, neuronal assemblies and local field
potentials (LFPs), as well as to apply deep brain stimulation of neural circuits in neurosurgical patients. These
are patients with intractable epilepsy who have intracranial depth electrodes implanted in order to identify their
seizure focus for possible surgical cure. Our initial findings showed dramatic spatial memory enhancement when
DBS was applied to the entorhinal area during learning [1]. In the initial funding period of this project, we built on
this success by testing DBS across a wide variety of hippocampal-dependent memory tasks and demonstrating
that the critical predictor of whether stimulation would improve memory was the precise spatial targeting of the
stimulating electrode to the white matter of the entorhinal area (angular bundle). In the renewed grant, we will
further refine our modulation of the entorhinal–hippocampal circuitry by using microstimulation to more
precisely identify the spatial and temporal features of applied DBS that lead to enhanced memory. Through
simultaneous microstimulation and recording, the project will elucidate the complex relationship between single
neuronal responses, LFP oscillations, and DBS that underlies memory enhancement. A primary objective
will be to expand the investigation of DBS from encoding to the critical memory phases of consolidation and
retrieval, across three memory tasks. Importantly, we will probe the effects of DBS on consolidation during
sleep which provides an intriguing and feasible time window for potential clinical intervention. A critical
component of our modulation will involve the use of novel closed-loop technology to provide stimulation
coordinated in time with endogenous oscillations that have been shown to be critically important for encoding,
retrieval, and for consolidation during sleep. The project aims at developing critical insights into the mechanisms
of human memory and its enhancement through closed-loop DBS in humans, and thus may contribute
significantly to the development...

## Key facts

- **NIH application ID:** 10242009
- **Project number:** 5R01NS084017-09
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** ITZHAK FRIED
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $589,267
- **Award type:** 5
- **Project period:** 2013-06-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242009

## Citation

> US National Institutes of Health, RePORTER application 10242009, Mechanisms of Memory Enhancement by Deep Brain Stimulation in Humans (5R01NS084017-09). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10242009. Licensed CC0.

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