REFINEMENTS TO THE CURRENT UNDERSTANDING OF FUNCTIONAL MRI ACTIVATION IN WHITE MATTER

Abstract

Functional magnetic resonance imaging (fMRI) is a widely used, noninvasive technique to map brain activation, and has provided considerable insight into human brain function over the past two decades. Until recently, fMRI studies have focused on gray matter; however, reports of fMRI activation in white matter are mounting. White matter fMRI activation has the potential to greatly expand the breadth of brain connectivity research, as well as improve the assessment and diagnosis of white matter and connectivity disorders. Despite these potential benefits, white matter fMRI activation remains controversial. The controversy is partially due to the existence of incompletely understood facets of fMRI signals in white matter. This thesis describes three experiments that aim to refine what is currently known about white matter fMRI activation. In the first experiment, one of the main concerns about fMRI activation in white matter was addressed; namely, whether white matter has sufficient cerebrovascular reactivity to support hemodynamic changes that can be measured with fMRI. It was demonstrated that white matter has the capacity to support detectable hemodynamic changes in the absence of partial volume effects. In the second experiment, the effect of static magnetic field strength on sensitivity to white matter fMRI activation was explored as a possible cause of the relative paucity of reports of white matter fMRI activation. The results showed greater sensitivity to white matter fMRI activation at 4 T relative to 1.5 T MRI. In the third experiment, the relationship between white matter activation and the activated network of gray matter regions was explored. This was accomplished using fMRI-guided tractography in which structural connections between activated clusters are evaluated. Structural connectivity between white matter fMRI activation and regions of gray matter activation was demonstrated, providing evidence of the functional significance of fMRI activation in white matter. These experiments provide important insights, which will allow for improved investigations of white matter fMRI activation in the future. In addition, it is posited that experimenter bias, via selective reporting of activation clusters, has contributed to the slow acceptance of fMRI activation in white matter.