# Hippocampal-orbitofrontal interactions and reward learning

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $455,016

## Abstract

Project summary (<30 lines)
Dysfunction of both the hippocampus and the orbitofrontal cortex have been implicated in a wide variety of
neuropsychiatric disorders, including obsessive-compulsive disorder, mood disorders and addiction. However,
their exact contribution remains unclear. A major problem is that most research on hippocampal mechanisms
is derived from rodent work. However, the structure of the hippocampus has undergone dramatic changes
across the course of evolution, particularly in those parts associated with psychopathologies. This necessitates
the use of primate models, but there have been few studies of hippocampus in the primate. The current grant
will investigate the neuronal properties of hippocampus in the primate and determine how it interacts with
orbitofrontal cortex.
The theoretical framework that we will employ is derived from computational psychiatry, with a particular focus
on how the computational processes underlying reinforcement learning might contribute to neuropsychiatric
disease. Our hypothesis is that both hippocampus and orbitofrontal cortex make critical contributions to
model-based reinforcement learning, whereby hippocampus is responsible for constructing the cognitive map
that instantiates the neural representation of the task model, and orbitofrontal cortex is responsible for using
the cognitive map to generate reward predictions that can be used to guide decision-making. To test this
hypothesis, we will use a combination of high-channel count neuronal recordings and electrical
microstimulation.
We will record from single neurons in the hippocampus during performance of a reward-based learning task
and examine whether hippocampal neurons show value place tuning. We will then examine how hippocampus
might communicate this information to orbitofrontal cortex by recording from both structures simultaneously.
Our prediction is that this communication will be mediated via synchronization of theta rhythms. However, such
measures are correlative. Establishing a causal role for neural rhythms has proven challenging, since it is
difficult to manipulate a specific neuronal rhythm without affecting other neuronal rhythms and/or neuronal
firing rates. We have recently developed a closed-loop approach, which involves recording rhythms in real-time
and using those signals to control the application of electrical microstimulation. This allows us to disrupt a
neuronal rhythm of a specific frequency. We will use this method to examine whether there is a causal role for
the theta oscillation in reward-based learning.
Taken together, the results of this proposal will provide convergent correlative and causal evidence for the role
of hippocampus and orbitofrontal cortex in reward-based learning and the mechanism by which they
communicate. This will help lay the groundwork for future potential therapeutic approaches for frontolimbic
dysfunction based on closed-loop microstimulation.

## Key facts

- **NIH application ID:** 10064645
- **Project number:** 5R01MH121448-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Joni D Wallis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $455,016
- **Award type:** 5
- **Project period:** 2019-12-03 → 2024-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064645

## Citation

> US National Institutes of Health, RePORTER application 10064645, Hippocampal-orbitofrontal interactions and reward learning (5R01MH121448-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10064645. Licensed CC0.

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