Changes in Auditory Evoked Responses Due to Blast and Aging

Hearing loss of various types is increasingly plaguing our modern world (Geneva: World Health Organization 2018). As the life expectancy increased in the industrialized world, age-related hearing loss (ARHL) has become more prevalent. The wars and terrorism of the modern world also created a significant body of blast-induced hearing loss (BIHL) patients. Both types of hearing loss present significant challenges for listeners even at suprathreshold sound levels. However, increasing bodies of clinical and laboratory evidence have suggested that the difficulties in the processing of time-varying auditory features in speech and other natural sounds may not be sufficiently diagnosed by threshold changes and simple auditory electrophysiological measures (Snell and Frisina 2000; Saunders et al. 2015; Bressler et al. 2017; Guest et al. 2018). Studies have emphasized that excitatory/inhibitory neurotransmission imbalance plays important roles in ARHL (Caspary et al. 2008) and may also be key in BIHL, as hinted by the strong presence of GABA regulation in non-blast TBI (O’Dell et al. 2000; Cantu et al. 2015; Guerriero et al. 2015). The current studies focus on age-related and blast-induced hearing deficits by examining changes in the processing of simple, brief stimuli and complex, sustained, temporally modulated sounds. Through post hoc circular analysis of single-unit, in vivorecording of young and aged inferior colliculus (IC) neurons responding to amplitude modulation (AM) stimuli and modulation depth changes, we observed evidence of central compensation in the IC manifesting as increased sensitivity to presynaptic input, which was measured via local field potentials (LFPs). We also found decreased sensitivity to decreasing modulation depth. Agerelated central gain in the IC single units, while preserving and even overcompensating for temporal phase coding in the form of vector strength, was unable to make up for the loss of envelope shape coding. Through careful, longitudinal measurements of auditory evoked potential (AEP) responses towards simple sounds, AM and speech-like iterated rippled noise (IRN), we documented the development and recovery of BIHL induced by a single mild blast in a previously established (Song et al. 2015; Walls et al. 2016; Race et al. 2017) rat blast model over the course of two months. We identified crucial acute (day 1-4 post-exposure) and early recovery (day 7-14) time windows in which drastic changes in electrophysiology take place. Challenging conditions and broadband, speech-like stimuli can better elucidate mild bTBI-induced auditory deficits during the sub-acute period. The anatomical significance of the aforementioned time windows was demonstrated with immunohistochemistry methods, showing two distinct waves of GABA inhibitory transmission changes taking place in the auditory brainstem, the IC, and the auditory thalamus. These changes were in addition to axonal and oxidative damage evident in the acute phase. We examined the roles and patterns of excitatory/inhibitory imbalance in BIHL, its distinction compared to that of ARHL, and demonstrated the complexity of its electrophysiological consequences. Blast traumatizes the peripheral auditory system and auditory brainstem, evident through membrane damage and acrolein-mediated oxidative stress. These initial traumas kickstart a unique, interlocking cascade of excitatory/inhibitory imbalances along the auditory neuraxis that is more complex and individually varied than the gradual, non-traumatic degradations in ARHL. Systemic treatment with the FDA-approved acrolein scavenger Hydralazine (HZ) was attempted with limited effects. Taken together, the current study provided insights into the similarities and distinctions between the mechanisms of ARHL and BIHL and called for innovative and individual diagnostic and therapeutic measures