The midbrain dopamine system located within the ventral tegmental area (VTA) and substantia nigra (SN) contain dopaminergic (DA) neurons that are known to mediate various goal directed behaviors. Although research with animals provides a framework for understanding DA function, the differential role of midbrain VTA and SNc in normal human brain function remains to be elucidated.
Functional Magnetic Resonance Imaging (fMRI) at lower field strengths (1.5 T and 3 T) has demonstrated blood oxygen level dependent (BOLD) responses in the human midbrain. However, these studies lacked the sensitivity and resolution to distinguish activation within the VTA and SN. FMRI at ultra-high fields (7 T and higher) has been shown to provide better spatial resolution and higher sensitivity for BOLD signal contrast, suggesting its suitability for assessing VTA and SN functions in humans.
The aims of this thesis were to delineate the structural architecture and the functional significance of the human midbrain DA system using 7 T MRI. High resolution anatomical images revealed fine details of structures within the midbrain, emphasizing the iron rich SN and red nuclei, as well as microvasculature. These images enabled detailed volumetric analysis of the midbrain nuclei in healthy humans. A reward-related task was used in the functional studies that probed both reward anticipation and reward outcome behavioral constructs. However, we failed to observe significant BOLD-related activity in the midbrain across participants for selected different MR sequences in the functional studies.
The low significance of task-related signal changes was examined in detail and it was concluded that the MR signal variance in the midbrain was problematically high. Various algorithms designed to mitigate known noise sources did not significantly reduce this variance. Preliminary evidence that some signal variations in the midbrain may reflect physiological baseline fluctuations of neural origin deserves further investigation. Overall, this thesis has demonstrated the value of ultra-high field MRI for evaluating structural changes associated with neurodegenerative diseases pertinent to the midbrain, and has comprehensively evaluated the challenges of functional studies of this important brain region.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-03222012-105034 |
| Date | 31 March 2012 |
| Creators | Coaster, Mariam |
| Contributors | Frank Tong, John C. Gore, David H. Zald, Ron Cowan, Adam W. Anderson |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-03222012-105034/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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