Central auditory maturation and behavioral outcomes after cochlear implantation in prelingual auditory neuropathy spectrum disorder related to OTOF variants (DFNB9): Lessons from pilot study.

Sang-Yeon Lee,Jin Hee Han,Nayoung Yi,Byung Yoon Choi,Hoo-Kang Song,Namju Justin Kim,Jeong-Sug Kyong,Qian-Jie Fu

doi:10.1371/journal.pone.0252717

Abstract

The cortical auditory evoked potential (CAEP)-based P1 component acts as a biomarker for cochlear implantation (CI) outcomes in children with auditory neuropathy spectrum disorder (ANSD). To date, early intervention primarily before the age of two years and six months of CI usage is necessary and sufficient to achieve age-appropriate cortical maturation and good prognosis. However, varying degrees of neural dyssynchrony, resulting from the etiological heterogeneity of ANSD, may preclude uniform application of this hypothesis to ensure auditory cortical maturation. Thus, a focused evaluation of those carrying OTOF variants, which may be the salient molecular etiology of prelingual ANSD, would circumvent the issue of heterogeneity. Here, we sought to provide a much better understanding of the brain perspectives (i.e., P1 maturation) in OTOF-associated ANSD subjects and set the stage for an optimal strategy to enhance language development. We conducted a preliminary study comprising 10 subjects diagnosed with OTOF-related ANSD who underwent CI by a single surgeon and subsequently underwent measurements of the P1 component. We observed that DFNB9 subjects who received CI after 2 years of age exhibited “absent” or “anomalous” P1 components that correspond to delayed language development. However, timely implantation, as early as 12 months of age per se, might be insufficient to achieve age-appropriate cortical maturation of DFNB9 in cases with six to seven months of device use. This suggests the importance of sustained rehabilitation in DFNB9 than in other etiologies. Indeed, an additional follow-up study showed that a reduction in P1 latency was linked to an improvement in auditory performance. Collectively, our results suggest that central auditory maturation and successful outcome of CI in DFNB9 may have more demanding requirements, that is, earlier implantation and more sustained rehabilitation. We believe that the current study opens a new path toward genome-based neuroimaging in the field of hearing research.

Highlights

Auditory neuropathy spectrum disorder (ANSD) is a specific hearing condition characterized by impaired neural transmission of sound signals from the inner ear to the auditory cortex, with normally functioning outer hair cells [1,2,3]
All subjects in group 1 exhibited typical morphology consisting of reproducible and robust P1 peaks in the waveforms and P1 latencies that fell within the 95% confidence intervals for normal P1 latency development (Fig 2)
This suggests that early intervention, before the sensitive period, and sufficient rehabilitation allowed for normal cortical maturation of the central auditory system

Summary

Introduction

Auditory neuropathy spectrum disorder (ANSD) is a specific hearing condition characterized by impaired neural transmission of sound signals from the inner ear to the auditory cortex, with normally functioning outer hair cells [1,2,3]. Individuals with such a neural pathognomonic deficit in ANSD (i.e., dyssynchrony) respond to many sounds appropriately, they may experience impaired speech and language decoding, in the area of temporal processing [4]. Molecular genetic testing helps to determine whether subjects have post-synaptic or presynaptic ANSD. Genetic causes account for approximately 50% of these cases [6, 7]

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