Pre-Neural Source of the Envelope-Following Response Revealed in Cases of Auditory Neuropathy.

OBJECTIVES: Complex stimuli such as two-tone stimuli (f 1 and f 2 ) elicit frequency-following responses that reflect phase-locking to the stimulus envelope (f 2 - f 1 ) and temporal fine structure at multiple stages of the auditory pathway, from the cochlea to the cortex. The relative contribution of these structures to the scalp-recorded envelope-following response (EFR) remains a matter of debate. Although subcortical sources have been proposed as the main contributors, near-field recordings close to the cochlea contain pre-neural components and have recently been reported in auditory steady-state responses (ASSRs), a version of the EFR used to measure thresholds at the four frequencies (0.5, 1, 2, 4 kHz) most relevant for objective audiogram estimations. The present study evaluated the EFR in 26 auditory neuropathy spectrum disorder (ANSD) cases and 79 children with normal electrophysiological thresholds and distortion product otoacoustic emissions (controls). In addition, this study presents data from a battery of auditory neurophysiological objective tests applied to the 26 ANSD cases.

DESIGN: EFRs were recorded using horizontal (EFR-H) and vertical (EFR-V) channels and the generalized primary tone phase variation method, allowing isolation of the EFR waveforms in the time domain to obtain direct latency and phase-locking value (PLV) measurements. EFRs detected in ANSD cases were compared with those of the controls. The standard audiological objective tests included tympanograms, distortion product otoacoustic emissions, click-evoked auditory brainstem responses (ABRs), and ASSRs.

RESULTS: EFR-H was detected in five ANSD cases, showing shorter onset latencies, shorter response durations, and lower PLVs than controls. Lower PLVs were also observed in the EFR-H from the contralateral ears of unilateral ANSD cases. The EFR-V was undetected in all ANSD patients except for two, who showed milder neural desynchronization in their click-evoked ABRs and exhibited the lowest ABR thresholds within the ANSD cases. In 15 ANSD cases, with totally absent neural click-evoked ABRs, ASSRs were detected for at least one tested frequency, indicating a discrepancy between ABR and ASSR-estimated thresholds.

CONCLUSIONS: The EFR-H observations suggested a pre-neural origin, with the asymmetrical mechanoelectrical transduction process at the sensory hair cells as the main contributor. These findings provide further evidence of a pre-neural potential explaining the discrepancy between ABR and ASSR threshold estimations in ANSD. In addition, the results from the contralateral ears of unilateral ANSD cases may reveal subtle deficits typically undetected by standard audiological techniques. Overall, the study of noninvasive EFR recordings in ANSD may contribute to refining their diagnosis, ultimately improving their treatment.