Hemodynamic Response and Connectivity of Cortical Networks during Mouse Licking Task Restricted; Files Only
Bian, Yuyang (Spring 2024)
Published
Abstract
Functional magnetic resonance imaging (fMRI) is a powerful tool for noninvasive brain imaging. Through a phenomenon known as neurovascular coupling, fMRI measures the blood oxygen level-dependent (BOLD) signal as a metabolic marker of neural activity. It is important to note the BOLD signal exhibits much slower dynamics than the neural activity it represents. Wide field optical imaging modalities such as voltage imaging can be employed to directly measure changes in the electrical potentials of neurons using genetic indicators, offering faster signal acquisition and exploration of the connection between voltage and blood flow signals.
In this study, ten genetically modified mice were imaged while performing a sensorimotor task with distinct stages of learning, or during repeated passive stimulus presentation. The objective was to characterize changes in observed blood flow and network level connectivity by comparing the voltage imaging data with the hemodynamic (blood flow-related) signals.
To investigate the relationship between neural activity and blood flow, voltage and hemodynamic signals were examined in the barrel cortex, a region known for its robust neural and hemodynamic responses during whisker stimulation. Trained mice exhibited a bimodal response in the hemodynamic signal, believed to arise from contributions of individual cell populations not captured in canonical BOLD signal. Additionally, the functional connectivity of the mouse cortex was mapped using seed-based analysis during task performance. Analysis revealed decreasing correlations of cross-network activity that aligned with task progression. Lastly, fitting hemodynamic response function parameters revealed distinct task-dependent changes in the amplitude, full width half maximum and time to peak across training phases. No significant differences were observed between individual sessions within the same phase.
The outcomes of this work shed light on the cognitive and motor processes of mice during learning. The changes observed exclusively across task phases imply that the sensorimotor response to learning remains consistent regardless of proficiency. In addition, recognizing that the BOLD signal comprises numerous individual cell populations can guide the interpretation and modeling of fMRI data, enhancing future efforts in functional connectivity analyses and mapping neural networks in rodents and human subjects.
Table of Contents
Table of Contents
Abstract
Chapter 1: Introduction
1.1 General Introduction 1
1.2 Voltage Signals in Barrel Cortex 1
1.3 Neurovascular Coupling 2
1.4 fMRI Analysis 3
1.5 Hemodynamic measurements with mCherry 4
1.6 Limitations of current imaging methods 5
1.7 Aims of thesis 6
1.8 Overview 7
Chapter 2: Methods
2.1 Animal Handling
2.1.1 Animals 8
2.1.2 Continuous Water Restriction 9
2.1.3 Directional Licking Task Trial Structure 9
2.1.4 Phases of Licking Task Training 10
2.1.5 Random Stimulus Trial Structure 11
2.2 Data Acquisition
2.2.1 JEDI-1P Widefield Optical Imaging Setup 12
2.2.2 Synchronization of Task, Imaging, and Behavior Recording 13
2.2.3 Pre-processing of Imaging Data 14
2.2.4 Initial Check, Masking, and Image Alignment 14
2.3 Data Analysis
2.3.1 Shuffled Control 15
2.3.2 Trial Averaged Response 16
2.3.3 Seed Based Functional Connectivity 16
2.3.4 Hemodynamic Response Function 17
Chapter 3: Results
3.1 Wide-field Imaging shows Distinct Task-Related Cortical Dynamics 18
3.2 ROI-driven changes in functional connectivity 21
3.3 Within Phase Stability of HRF parameters 24
3.4 HRF parameters change between phases 26
Chapter 4: Discussion 28
Citations 32
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File download under embargo until 24 May 2026 | 2024-04-08 11:14:59 -0400 | File download under embargo until 24 May 2026 |
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