Lisa Meyer-Baese
BME PhD Proposal Presentation

Date: 2024-01-31
Time: 12:00 - 2:00 PM
Location / Meeting Link: Health Sciences Research Building (HSRB) II N600/ https://emory.zoom.us/j/98898077457

Committee Members:
Shella Keilholz (advisor); Dieter Jaeger (co-advisor); Gordon Berman; Hannah Choi; Evelyn Lake; Garrett Stanley


Title: Cortical network dynamics underlying membrane voltage and hemodynamic activity measured with wide-field optical imaging in resting state and task-related activities

Abstract:
The brain is a complex neural network whose functional dynamics provide insights into brain performance and health. Functional network dynamics represent structured, reproducible, and behaviorally relevant patterns of brain activity. These networks are inferred to be functionally connected and are thought to involve the synchrony of neuronal populations involved in a common function that are wired together through plasticity. The most common tool to non-invasively study the organization of brain-wide functional network dynamics is functional magnetic resonance imaging (fMRI). fMRI relies on an indirect and indiscriminate measure of activity through the blood oxygen level-dependent (BOLD) contrast mechanism. Interpretation of functional dynamic networks derived from fMRI studies is limited by 1) the dependence of fMRI BOLD signals on hemodynamic changes as a proxy for neural activity and 2) a limited understanding of how functional dynamics relate to different behavioral states. This knowledge gap is currently limiting the impact of this research, as it currently represents phenomenological evidence devoid of any mechanistic information. My overall objective for my proposed thesis work is to determine how multi-regional dynamic cortical networks map to neural and hemodynamic activity, and how the dynamics of these networks evolve as a function of behavioral state. Using wide-field voltage imaging I plan to track changes in voltage membrane potential and hemodynamics across dorsal cortex in awake resting and behaving mice. For Aim 1 I plan to establish the neural and hemodynamic representations of spontaneous cortical dynamics across behavioral states. Cortical imaging data will be projected onto a low-dimensional embedding where clusters separate spatial components representing the repertoire of cortical network states. Simultaneous face video will be acquired to segment data based on behavioral state by tracking changes in arousal state and orofacial movements. Aim 2 will then determine how cortical network dynamics generalize across behaviors. To this end, mice will be imaged as they receive either passive stimuli or as they learn to perform a sensorimotor lick task. Completion of these aims will determine how dynamic functional hemodynamic networks relate to excitatory neural activity and how these changes in dynamics reflect behavioral state. Resulting in a sharper understanding of the properties of neural network activity, its dependencies, and how to harness it in future fMRI studies. Results provide a mechanistic basis for network dynamics and their cognitive and behavioral manifestations which will have a major impact on new targets for therapies and more robust fMRI-based disease detection.