Date of Award
Open Access Thesis
Medical Doctor (MD)
Brainstem Auditory Evoked Potentials and Network Dysfunction in Mild Traumatic Brain Injury
Theresa L. Williamson BS1,2, Amanda R. Rabinowitz PhD1, Victoria E. Johnson MD1, John A. Wolf PhD1, Michael L. McGarvey MD3, Douglas H. Smith MD1 University of Pennsylvania Department of Neurosurgery Philadelphia, PA 191041, Yale School of Medicine New Haven, CT 065112, University of Pennsylvania Department of Neurology Philadelphia, PA 191043
Mild traumatic brain injury (mTBI) challenges clinicians as symptoms do not map in a lesion-specific manner and there is no objective diagnostic measure. Diffuse axonal injury is a main mechanism of injury in mTBI [1, 2]. Injury to axons is proposed to alter the brain's networks and underlie common symptoms such as slow processing speed, poor concentration and memory. Clinical studies show that the auditory network is also commonly disrupted in mTBI and therefore the auditory pathway is a useful surrogate for study to understand network dysfunction as it relates to axonal pathology and signal processing speed.
Decades of research using a rotational acceleration injury model in pigs scaled to the known mechanical loading conditions in humans demonstrates multi-focal swelling of axons . This study utilizes a known model of mTBI to relate diffuse axonal injury to the physiologic functioning of a network. The technique is to record latency, amplitude and morphology of the auditory evoked potential response before, immediately after, and three days after injury as well as conduct a histopathologic investigation of the brainstem auditory pathway for evidence of axonal injury.
We have identified increased latency and morphologic changes of the brainstem auditory evoked potential waveforms in swine following injury that correspond to pathology in regions in the upper brainstem, immediately after and at three days post-injury as compared to a pre-injury control measurements. Additionally, we have identified axonal pathology, indicated by amyloid precursor protein positive axonal swellings, in the region of the lateral lemniscus and inferior colliculus.
This data shows that in a clinically relevant model of mild traumatic brain injury, damage to axons in a pathway corresponds to functional delay in the pathway's processing. Identifying a link between axonal pathology and function in the auditory pathway is useful to represent network injury throughout the brain shedding light on mTBI's diffuse nature that underlies a group of symptoms that are both difficult to diagnose and treat.
Williamson, Theresa Lynn, "Brainstem Auditory Evoked Potentials And Network Dysfunction In Mild Traumatic Brain Injury" (2014). Yale Medicine Thesis Digital Library. 1934.