Auditory and Visual Dysfunction in Mild Traumatic Brain Injury: Diagnostics and Translational Models

Abstract

Mild traumatic brain injury (mTBI) and repeated low-level blast (rLLB) exposure are common yet underrecognized causes of persistent auditory and visual difficulties, in part because standard audiologic and ophthalmologic tests often remain normal. This dissertation evaluates sensory pathway vulnerability to mTBI and rLLB using parallel human and translational approaches to identify sensitive functional and mechanistic markers of sensory pathway injury. In human cohorts with chronic mTBI and in Army Special Forces personnel acutely exposed to rLLB, multimodal auditory and visual test batteries revealed reproducible abnormalities in cochlear output, brainstem and cortical auditory responses, oculomotor control, and primary visual pathway integrity, even when routine clinical measures were unremarkable. To probe underlying mechanisms, a focal blast model was developed in the tree shrew (Tupaia belangeri), a species with human-like sensory neuroanatomy and genetics. Blast-exposed animals exhibited early auditory deficits that progressed from peripheral to central dysfunction, accompanied by delayed retinal and cortical hyper-responsiveness and reduced binocular integration. Together, these studies show that mTBI and rLLB produce measurable yet subclinical sensory changes in humans and reveal distinct temporal and mechanistic trajectories in an experimental model. The integration of human and animal data establishes a translational framework for improving diagnostics and identifying mechanistic biomarkers and therapeutic strategies for individuals at risk of mild traumatic brain injury.