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Title page for ETD etd-03222012-105034

Type of Document Dissertation
Author Coaster, Mariam
Author's Email Address mariam.coaster@vanderbilt.edu
URN etd-03222012-105034
Title Structural and functional evaluation of the human midbrain dopaminergic system using high resolution MRI at 7 T
Degree PhD
Department Neuroscience
Advisory Committee
Advisor Name Title
Frank Tong Committee Chair
Adam W. Anderson Committee Member
David H. Zald Committee Member
John C. Gore Committee Member
Ron Cowan Committee Member
  • Human midbrain
  • 7 Tesla
  • structure
  • function
  • dopamine
  • MRI
Date of Defense 2012-03-19
Availability unrestricted
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.

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