# Determinants of functional brain connectivity after subarachnoid hemorrhage

> **NIH NIH K08** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $200,880

## Abstract

PROJECT SUMMARY / ABSTRACT
I am a practicing neurointensivist with a background in biochemistry, biophysics, and molecular biology. I seek
to become an independent translational neuroscientist so that I can improve outcomes in survivors of brain
aneurysm rupture. The proposed research and career development plan leverages the expertise of a
mentorship team based at Massachusetts General Hospital and Harvard Medical School to give me the
additional skills and experience necessary to obtain an R01 and reach scientific independence.
Subarachnoid hemorrhage (SAH) from a ruptured brain aneurysm is a life-changing condition which affects
more than 30,000 Americans at a cost of $5.6 billion annually. Even survivors with a good outcome on
common outcome scales suffer from persistent cognitive deficits precluding return to work. Studies using fMRI
and magnetoencephalography suggest that these cognitive deficits are associated with alterations in resting
state functional brain connectivity, an indicator of long range neuronal network integrity. However, a major gap
in knowledge remains: it is unclear how the SAH-damaged brain leads to changes in brain connectivity.
Based on pilot data and published reports, I propose the hypothesis that early after SAH (i) diffuse neuronal
death and axonal/ myelin damage lead to a decrease in global functional connectivity by decreasing the
number of structural connections between brain regions and (ii) a phenomenon called spreading depolarization
(SD) can cause an increase in local brain connectivity (“too much” connectivity) in the same hemisphere of the
SD by increasing mediators of synaptic plasticity. Pilot data suggest that both processes can lead to worse
performance on behavioral assessments. I will test this hypothesis in 3 integrated aims.
In Aim 1, I will determine the effect of SAH alone on functional connectivity and behavior. In Aim 2, I will
determine the effect of early recurrent SDs in the setting of SAH on functional connectivity and behavior. In
Aim 3, I will investigate potential mechanisms of altered functional connectivity following SAH with or without
SDs. To accomplish the aims, I will use novel mouse models which reconstitute SAH and SDs and allow for in
vivo optical and local field potential measures of functional brain connectivity. To take the first steps towards
assessing causes of altered connectivity, I will use a combination of immunohistochemistry, molecular tools,
and cortico-cortical evoked potentials. Whenever possible, I will make use of innovative non-invasive
approaches, for example, in the induction of SDs and in optical measurements of functional connectivity.
The ultimate goal of this proposal is to provide me with the experience essential to achieve scientific
independence, transition to my own lab, and become the kind of investigator who can find ways to improve
neurocognitive outcomes in survivors of aneurysm rupture and other forms of acute brain injury.

## Key facts

- **NIH application ID:** 10460462
- **Project number:** 5K08NS112601-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** David Young Chung
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $200,880
- **Award type:** 5
- **Project period:** 2019-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10460462

## Citation

> US National Institutes of Health, RePORTER application 10460462, Determinants of functional brain connectivity after subarachnoid hemorrhage (5K08NS112601-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10460462. Licensed CC0.

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