# Single-neuron mechanisms of executive control of long-term memory processes in humans

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2020 · $432,847

## Abstract

Project Summary/Abstract
Deficient control and monitoring of memory processes is a key feature of major psychiatric diseases, including
schizophrenia, bipolar disorder, and PTSD. The long-term goal of this research is to understand how individual
brain areas within the temporal-and frontal lobes interact, how these interactions are coordinated and how
disruption of such coordination results in mental disease. The proposed experiments will utilize rare
neurosurgical opportunities to directly record from individual neurons in several areas of the human medial
frontal cortex and the hippocampus to study the role of theta-mediated coordination in the executive control of
memory. This approach is motivated by previous work from this laboratory, which has revealed a candidate
microcircuit for declarative memories consisting of groups of cells that signal memory strength and a second
group that signals highly processed sensory information independent of memories (VS/MS neurons). The
overall objective of this application is to understand how information provided by these hippocampal neurons is
utilized by areas in the medial frontal lobes to make decisions and how such memory-based decision making
processes are monitored and controlled. We will achieve this objective by recording single-neurons from the
hippocampus and three medial frontal cortical areas important for monitoring and control of memory
processes: the ACC, pre-SMA, and vmPFC. Our central hypothesis is that Frontal-Hippocampal coordination is
mediated by theta-band oscillations such that subsets of medial frontal neurons transiently phase-lock to
hippocampal theta oscillations in order to gain access to task-relevant information provided by subsets of
VS/MS neurons in the hippocampus. Our specific aims are to determine how medial frontal neurons
accumulate evidence provided by the hippocampus (Aim 1), to determine whether medial frontal neurons exert
top-down control over the hippocampus (Aim 2), and to test the causality of theta-mediated medial frontal-
hippocampal coordination for memory (Aim 3). The contribution is significant because it will provide an
unprecedented characterization of the role of medial frontal-hippocampal coordination in the control of memory
processes through bottom-up and top-down interactions and their causal necessity. The approach is innovative
because we directly test, in humans, a hypothesis of high significance for psychiatric disease which cannot be
tested by non-invasive fMRI/EEG/MEG studies nor by animal models due to the unclear homologies of frontal
areas. The work proposed in this application will advance knowledge on the normal mechanisms of frontal-
temporal coordination by theta oscillations and might thereby enable the development of new treatments to
restore or improve such coordination in cases of mental disease.

## Key facts

- **NIH application ID:** 9983148
- **Project number:** 5R01MH110831-05
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Ueli Rutishauser
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $432,847
- **Award type:** 5
- **Project period:** 2016-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983148

## Citation

> US National Institutes of Health, RePORTER application 9983148, Single-neuron mechanisms of executive control of long-term memory processes in humans (5R01MH110831-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9983148. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*