# Pharmacologic modulation of hippocampal activity in psychosis

> **NIH NIH F30** · VANDERBILT UNIVERSITY · 2022 · $42,956

## Abstract

PROJECT SUMMARY/ABSTRACT
The development of better treatments for schizophrenia requires that we identify novel treatment targets. A
recently proposed target is hippocampal hyperactivity, demonstrated with neuroimaging methods. Emerging
evidence suggests that increased hippocampal activity in schizophrenia patients limits the ability to recruit the
hippocampus during cognitive task performance. However, the neural basis underlying hippocampal
dysfunction (i.e., hyperactivity and impaired recruitment) in schizophrenia is poorly understood. In order to
better understand the neural mechanisms of this potential treatment target, I propose to a) measure
hippocampal activity with two complementary, non-invasive neuroimaging techniques and b) use
pharmacologic intervention in a 2-way crossover, randomized, double-blind, placebo-controlled design to test
the hypothesis that hyperactivity leading to impaired recruitment is a consequence of an excitation-inhibition
imbalance in the hippocampus. This work will demonstrate that the pathologic neural processes underlying
hippocampal hyperactivity can be modulated through perturbation of hippocampal micro-circuitry with a
pharmacologic intervention, levetiracetam (LEV). I hypothesize that a LEV intervention will normalize
hippocampal activity in schizophrenia patients. First, arterial spin labeling (ASL) will be used to quantify
anterior hippocampal cerebral blood flow, a measure of resting state activity, after placebo and oral, low-dose
LEV administration in schizophrenia patients and controls. Serum levels of LEV will be measured to assess the
relationship of LEV concentration with the change in hippocampal resting state activity. This study is a proof of
concept to show that LEV reduces anterior hippocampal resting state activity and can be quantified using ASL.
Second, the BOLD signal will be used to measure anterior hippocampal recruitment after placebo and oral,
low-dose LEV administration in schizophrenia patients and controls. This will reveal whether a pharmacologic
intervention can normalize hippocampal recruitment in schizophrenia patients. Third, the relationship between
anterior hippocampus resting state activity and recruitment will be assessed. This will demonstrate whether
resting state activity can be used to predict recruitment. Additionally, we will investigate whether LEV
intervention is able to normalize the relationship of resting state activity and recruitment in the schizophrenia
cohort. Normalization of hippocampal activity will provide novel evidence of a treatment target in schizophrenia.
This project, when combined with rigorous clinical and scientific training, will provide an opportunity for
interdisciplinary collaboration with experts and mastery of multiple techniques in neuroimaging and
interventional study design, well-equipping me to become a psychiatrist-scientist leader in neuroscience.

## Key facts

- **NIH application ID:** 10468656
- **Project number:** 5F30MH125507-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Maxwell J Roeske
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $42,956
- **Award type:** 5
- **Project period:** 2021-09-01 → 2023-05-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468656

## Citation

> US National Institutes of Health, RePORTER application 10468656, Pharmacologic modulation of hippocampal activity in psychosis (5F30MH125507-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10468656. Licensed CC0.

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