Neuronal Activity and Vascular Coupling in fMRI Studies of Multiple Sclerosis

Lowe, Mark

Abstract

The goal of this proposal is to directly measure electrical activity, BOLD response, CBF response, and CMRO2 change during task performance in MS. Our hypothesis is that electrical activity, CMRO2 and BOLD will be related in all subjects, while electrical activity and CBF will be related in healthy controls and not in M patients. We also propose a simple method to correct for the uncoupling in MS, based on resting state fMRI.
Specific aim 1 will determine simultaneously neuronal activity, BOLD signal and cerebral blood flow in seven MS patients and seven healthy control subjects. Using MRI compatible EEG and our combined BOLD-ASL data acquisition, we can determine electrical activity, blood flow, and BOLD signal in response to a task. We hypothesize that BOLD signal and rCBF will correlate to EEG-determined brain activity. Furthermore, electrical activity will be significantly higher in MS patients than matched control subjects.
Specific aim 2 proposes to use spontaneous BOLD fluctuations measured in a resting-state BOLD acquisition to generate calibrated fMRI activation maps. The resulting activation from the corrected BOLD activation will reflect the differences in electrical activity shown in aim 1. This work addresses a significant need in the development of therapeutic treatments for multiple sclerosis (MS).

Public Health Relevance

The goal of this proposal is to understand the relationship between neuronal activation and cerebral hemodynamics and metabolism in multiple sclerosis. Our preliminary data indicate that regional cerebral blood flow and metabolic rate of oxygen are significantly altered in multiple sclerosis when compared to healthy subjects. We propose to directly measure underlying electrical activity during performance of simple sensory tasks and relate simultaneous measures of cerebral blood flow and metabolic rates of oxygen to observed electrical activity. This has never been done for multiple sclerosis. Our hypothesis is that electrical activity and cerebral blood flow changes will be related in healthy controls and not in multiple sclerosis patients.