# Analysis of stroke-induced changes in connectivity and neural activity

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $444,125

## Abstract

Project Summary
Cognitive impairment is a common functional sequela of stroke, although the neural substrate underlying which
is yet to be identified. White matter hyperintensity (WMH), a progressive form of degeneration and a marker of
small vessel disease, is a major risk factor for post stroke cognitive impairment. Emerging studies support an
inverse relationship between WMH burden and the volume of the hippocampus, which is a key brain structure
for memory function and may undergo secondary degeneration. Preliminary data show that the hippocampus is
remote from cortical stroke and not affected acutely after stroke. However, our electrophysiology data suggest
that network communication between the cortex and hippocampus became disrupted during chronic stroke,
which is consistent with connectome-based analysis showing damaged cortical regions are well connected with
neural networks involved in spatial learning. We hypothesize that WM lesions predispose to post stroke cognitive
impairment due to exacerbated connectivity loss and remote degeneration in the learning and memory region.
Our immediate goal is to understand how stroke affects hippocampal function from the perspective of brain
connectivity. As a proof-of-principle translational study, we will carry it out in the spontaneously hypertensive rats
at an age when spontaneous WM lesion is detected. To determine the role of connectivity loss in post stroke
cognitive impairment in the setting of WM lesion, we will first map the lesion location and extent in both WM and
GM, and quantify hippocampal subfield volume. We will then determine the changes in structural connectivity
with the neuroVIISAS-based connectome platform built with tract tracing and DTI streamline data to reveal how
global and local networks are affected. Lesioned regions with direct or indirect connections with the hippocampus
will be identified. The dynamic effect of stroke and WM lesion on learning/memory function will be determined
by modeling the coactivation pattern between a pair of lesioned region and functional region involved in spatial
learning with FitzHugh-Nagumo neuron simulation using the weighted and directed connectome.
Electrophysiology correlates of hippocampal activity and network communication will be assessed to
complement data in neurobehavior and connectivity. We anticipate that the knowledge of lesion extent, location,
and the effect on network connectivity in the setting of hypertension will provide insight into the role of WM lesion
in post stroke cognitive decline. It may also enable the identification of relay brain regions undergoing functional
changes and possibly the progression of connectivity loss.

## Key facts

- **NIH application ID:** 10309635
- **Project number:** 1R21NS120193-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** JIALING LIU
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $444,125
- **Award type:** 1
- **Project period:** 2021-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10309635

## Citation

> US National Institutes of Health, RePORTER application 10309635, Analysis of stroke-induced changes in connectivity and neural activity (1R21NS120193-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10309635. Licensed CC0.

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