Measuring Resting State Functional Connectivity in Awake Mouse’s Brain Using fMRI

Restricted (Penn State Only)
Unsal, Hayreddin Said
Graduate Program:
Master of Science
Document Type:
Master Thesis
Date of Defense:
December 14, 2017
Committee Members:
  • Nanyin Zhang, Thesis Advisor
  • Jian Yang, Committee Member
  • William O Hancock, Committee Member
  • functional connectivity
  • resting state fMRI
  • brain
  • mouse
  • awake animal
Functional magnetic resonance imaging (fMRI) allows non-invasive measurement of changes in blood-oxygenation-level dependent (BOLD) level over time and to draw inferences about the underlying neural activity. BOLD is responsive to changes in oxygen consumption in blood, cerebral blood flow and blood volume. A number of fMRI studies have been conducted in anesthetized animals, but their interpretations are controversial because anesthetic agents can significantly disrupt brain hemodynamics, leading to changes in BOLD signals that might not represent the neurovascular coupling relationship during the awake state. Neuroimaging studies conducted in awake animals are important because they can more accurately detect changes in brain hemodynamics. Resting state fMRI (rsfMRI) is a technique that can be used for assessing functional connectivity of brain networks when subjects are not performing a task or receiving sensory stimulation. rsfMRI can potentially be used to investigate the influence of genetic manipulations, environmental interactions, pharmacological treatments, and neuropathology on brain function in humans and animals. While there are numerous rsfMRI studies in humans during the awake state, much fewer awake rsfMRI studies have been conducted in animals. Thus, establishing an awake rsfMRI procedure for rodents will help broaden understanding of brain function. An established awake rsfMRI procedure in mice is especially important, given the availability of a variety of transgenic mice that can be used to investigate the relationship between genetic and the function of normal and diseased brains. If successful, this could stimulate more awake mice rsfMRI studies and those results can inform human studies. In this thesis, we established an awake mouse rsfMRI protocol. This involved the design of a customized radiofrequency (RF) coil and procedures for acclimating mice to the imaging restrainer to reduce motion artifacts. Data processing was performed in MATLAB, including seed-based analysis, which produced accurate and reproducible resting state functional connectivity between major brain regions. The seed regions of interest included the thalamus, amygdala, hippocampus, hypothalamus and cortical ribbon in healthy mice.