AN INVESTIGATION OF FUNCTIONAL MAGNETIC RESONANCE IMAGING ACTIVATION IN WHITE MATTER AT 4 TESLA

Abstract

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that allows for visualization of active brain regions. Although white matter (WM) constitutes approximately 50% of brain tissue, fMRI activation in WM has conventionally been dismissed. There are two main reasons WM fMRI remains controversial: 1) the blood oxygen level dependent (BOLD) fMRI signal depends on cerebral blood flow and volume, which are lower in WM than gray matter and 2) fMRI signal has been associated with post-synaptic potentials as opposed to action potentials. Despite these observations, there is no direct evidence against measuring fMRI activation in WM. This thesis is comprised of four manuscripts that investigate fMRI activation in WM at 4T. The first study evaluated whether it was possible to detect WM activation using an interhemispheric transfer task and examined whether certain MRI contrast mechanisms were more sensitive to activation in WM. Activation was detected in the anterior corpus callosum at the individual and group level and we discovered that T2 weighted imaging may provide increased sensitivity to activation in WM. The second study used two established interhemispheric transfer tasks to examine whether callosal activation could be experimentally manipulated using a within subjects design. The results replicated previous findings and demonstrated an ability to map functional activation in the corpus callosum that was task dependent. The third study examined WM fMRI activation in a different structure and focused on the posterior limb of the internal capsule using a motor task; activation was elicited at both individual and group levels. The fourth study linked advances in the ability to detect WM fMRI activation to current clinical approaches to the assessment of WM dysfunction. An adapted Symbol Digit Modalities Test was used to evaluate WM activation in healthy controls. The results revealed individual level activation in both the corpus callosum and internal capsule. Taken together this stream of research represents a major advance in the methods used to non-invasively study brain function. Future applications may include improved assessment methods for patients with WM dysfunction.