Assessing variability of thefMRI BOLD response to neural activity

Functional Magnetic Resonance Imaging (fMRI) has become extremely popular since the first description of the Blood Oxygen Level Dependent (BOLD) signal less than 15 years ago. fMRI noninvasively measures the BOLD signal, a marker of neural activity. In the past several years, researchers have started to apply fMRI to studies of aging and disease. Few of those studies considered non-neural factors such as altered vasculature or cerebral blood flow, which could alter the BOLD signal in these populations or even within a control population. There are currently no standardized ways to test for non-neural variations across populations or to correct for these variations.; The specific aims of the research described in this dissertation were to: (1) Characterize fMRI signal variation within and across individuals and populations and (2) To find ways to account for signal variation in statistical analyses. The broad goal of this work is to make fMRI a clinically applicable tool. Until researchers can recognize what is normal or abnormal variation within an individual, the practical applications of fMRI will be limited.; The results presented in this dissertation show: (1) The fMRI responses to a simple visuomotor saccade task showed more variability, even in healthy, young volunteers than previously assumed. This variability significantly affects the results of some common statistical analyses. Estimating a hemodyanamic response for each subject can improve the results of statistical analyses across a population. The BOLD response in older volunteers had lower magnitudes and delayed peaks in some regions. Still, the intersubject variability within each population was larger than the differences between populations. (2) Hypercapnia induced by breath holding produced a large BOLD signal change in most brain regions due to increases in cerebral blood flow. In young and old volunteers, the magnitude of this change was linearly correlated to the magnitude of the response to a visuomotor saccade task. Since the signal change due to hypercapnia is primarily vascular in nature, it can be used to remove some of the non-neural sources of variability.