system-for-focal-closed-system-central-nervous-system-injury

System for Focal, Closed-System Central Nervous System Injury

The prevalence of closed-system central nervous system (CNS) injuries underscores the need for an enhanced understanding of these traumas to improve ...

Vanderbilt University

Clinical auditory physiological measures (e.g., auditory brainstem responses, ABRs, and distortion product otoacoustic emissions, DPOAEs) provide diagnostic specificity for differentially diagnosing overt hearing impairments, but they remain limited in their ability to detect specific sites of lesion and subtle levels of cochlear damage. Studies in animal models may hold the key to improve differential diagnosis due to the ability to induce tightly controlled and histologically verifiable subclinical cochlear pathologies. Here, we present a normative set of traditional and clinically novel physiological measures using ABRs and DPOAEs measured in a large cohort of male macaque monkeys. Given the high similarities between macaque and human auditory anatomy, physiology, and susceptibility to hearing damage, this normative data set will serve as a crucial baseline to investigate novel physiological measures to improve diagnostics. DPOAE amplitudes were robust at f = 1.22, L/L = 65/55, increased with frequency up to 10 kHz, and exhibited high test re-test reliability. DPOAE thresholds were lowest from 2-10 kHz and highest < 2 kHz. ABRs with a standard clinical electrode montage (vertex-to-mastoid, VM) produced Waves I-IV with a less frequently observed Wave-I, and lower thresholds. ABRs with a vertex-to-tympanic membrane (VT) electrode montage produced a more robust Wave-I, but absent Waves II-IV and higher thresholds. Further study with the VM montage revealed amplitudes that increased with stimulus level and were largest in response to click stimuli, with Wave-II showing the largest ABR amplitude, followed by -IV and -I, with high inter- and intra-subject variability. ABR wave latencies decreased with stimulus level and frequency. When stimulus presentation rate increased or stimuli were presented in close temporal proximity, ABR amplitude decreased, and latency increased. These findings expand upon existing literature of normative clinical physiological data in nonhuman primates and lay the groundwork for future studies investigating the effects of noise-induced pathologies in macaques.

Audiologic characterization using clinical physiological measures: Normative data from macaque monkeys.

Auditory complaints are frequently reported by individuals with mild traumatic brain injury (mTBI) yet remain difficult to detect in the absence of clinically significant hearing loss. This highlights a growing need to identify sensitive indices of auditory-related mTBI pathophysiology beyond pure-tone thresholds for improved hearing healthcare diagnosis and treatment. Given the heterogeneity of mTBI etiology and the diverse peripheral and central processes required for normal auditory function, the present study sought to determine the audiologic assessments sensitive to mTBI pathophysiology at the group level using a well-rounded test battery of both peripheral and central auditory system function. This test battery included pure-tone detection thresholds, word understanding in quiet, sentence understanding in noise, distortion product otoacoustic emissions (DPOAEs), middle-ear muscle reflexes (MEMRs), and auditory evoked potentials (AEPs), including auditory brainstem responses (ABRs), middle latency responses (MLRs), and late latency responses (LLRs). Each participant also received magnetic resonance imaging (MRI). Compared to the control group, we found that individuals with mTBI had reduced DPOAE amplitudes that revealed a compound effect of age, elevated MEMR thresholds for an ipsilateral broadband noise elicitor, longer ABR Wave I latencies for click and 4 kHz tone burst elicitors, longer ABR Wave III latencies for 4 kHz tone bursts, larger MLR Na and Nb amplitudes, smaller MLR Pb amplitudes, longer MLR Pa latencies, and smaller LLR N1 amplitudes for older individuals with mTBI. Further, mTBI individuals with combined hearing difficulty and noise sensitivity had a greater number of deficits on thalamic and cortical AEP measures compared to those with only one/no self-reported auditory symptoms. This finding was corroborated with MRI, which revealed significant structural differences in the auditory cortical areas of mTBI participants who reported combined hearing difficulty and noise sensitivity, including an enlargement of left transverse temporal gyrus (TTG) and bilateral planum polare (PP). These findings highlight the need for continued investigations toward identifying individualized audiologic assessments and treatments that are sensitive to mTBI pathophysiology.

Comprehensive behavioral and physiologic assessment of peripheral and central auditory function in individuals with mild traumatic brain injury.

Individuals with mild traumatic brain injury (TBI) often report vision problems despite having normal visual acuity and fundus examinations. Diagnostics are needed for these patients.

Article	Year
Audiologic characterization using clinical physiological measures: Normative data from macaque monkeys. Hearing research\| PubMed ID: 35896044	2022
Comprehensive behavioral and physiologic assessment of peripheral and central auditory function in individuals with mild traumatic brain injury. Hearing research\| PubMed ID: 38086151	2024
Primary Visual Pathway Changes in Individuals With Chronic Mild Traumatic Brain Injury. JAMA ophthalmology\| PubMed ID: 39602146	2024

Amy N. Stahl

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