Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 83-90).Tinnitus, the ongoing perception of sound in the absence of a physical stimulus, and hyperacusis, the intolerance of sound intensities considered comfortable by most people, are two often co-occurring clinical conditions lacking effective treatments. This thesis identified neural correlates of these poorly understood disorders using functional magnetic resonance imaging (fMRI) and auditory brainstem responses (ABRs) to measure sound-evoked activity in the auditory pathway. Subjects with clinically normal hearing thresholds, with and without tinnitus, underwent fMRI or ABR testing and behavioral assessment of sound-level tolerance (SLT). The auditory midbrain, thalamus, and primary auditory cortex (PAC) showed elevated fMRI activation related to reduced SLT (i.e. hyperacusis). PAC, but not midbrain or thalamus, showed elevated fMRI activation related to tinnitus, perhaps reflecting undue attention to the auditory domain. In contrast to fMRI activation, ABRs showed relationships only to tinnitus, not SLT. Wave I of the ABR, which reflects auditory nerve activity, was reduced in tinnitus subjects, while wave V, reflecting input activity to the midbrain, was elevated. Wave I reduction in tinnitus subjects suggests that auditory nerve dysfunction apparent only above threshold is a factor in tinnitus. Because ABRs reflect activity in only one of multiple pathways from cochlear nucleus to midbrain, the wave V elevation implicates this particular pathway in tinnitus. The results directly link tinnitus and hyperacusis to hyperactivity within the central auditory system. Because fMRI and ABRs reflect different aspects of neural activity, the dependence of fMRI activation on SLT and ABR activity on tinnitus in the midbrain raises the possibility that tinnitus and hyperacusis arise in parallel from abnormal activity in separate brainstem pathways.by Jianwen Wendy Gu.Ph.D
