Age-Related Changes in the Relationship Between Auditory Brainstem Responses and Envelope-Following Responses

Abstract

Hearing thresholds and wave amplitudes measured using auditory brainstem responses (ABRs) to brief sounds are the predominantly used clinical measures to objectively assess auditory function. However, frequency-following responses (FFRs) to tonal carriers and to the modulation envelope (envelope-following responses or EFRs) to longer and spectro-temporally modulated stimuli are rapidly gaining prominence as a measure of complex sound processing in the brainstem and midbrain. In spite of numerous studies reporting changes in hearing thresholds, ABR wave amplitudes, and the FFRs and EFRs under neurodegenerative conditions, including aging, the relationships between these metrics are not clearly understood. In this study, the relationships between ABR thresholds, ABR wave amplitudes, and EFRs are explored in a rodent model of aging. ABRs to broadband click stimuli and EFRs to sinusoidally amplitude-modulated noise carriers were measured in young (3-6 months) and aged (22-25 months) Fischer-344 rats. ABR thresholds and amplitudes of the different waves as well as phase-locking amplitudes of EFRs were calculated. Age-related differences were observed in all these measures, primarily as increases in ABR thresholds and decreases in ABR wave amplitudes and EFR phaselocking capacity. There were no observed correlations between the ABR thresholds and the ABR wave amplitudes. Significant correlations between the EFR amplitudes and ABR wave amplitudes were observed across a range of modulation frequencies in the young. However, no such significant correlations were found in the aged. The aged click ABR amplitudes were found to be lower than would be predicted using a linear regression model of the young, suggesting altered gain mechanisms in the relationship between ABRs and FFRs with age. These results suggest that ABR thresholds, ABR wave amplitudes, and EFRs measure complementary aspects of overlapping neurophysiological processes and the relationships between these measurements changes asymmetrically with age. Hence, measuring all three metrics provides a more complete assessment of auditory function, especially under pathological conditions like aging.

Age-Related Changes in Processing Simultaneous Amplitude Modulated Sounds Assessed Using Envelope Following Responses

“…2B, E, H; gray dashed lines). This is ∼50 dB SPL, above the auditory thresholds for the aged animals in the frequency regions tested (Parthasarathy et al 2014).…”

“…The experimental protocols have been described in detail previously (Parthasarathy et al 2014). The experiments were performed in a 9' × 9', doublewalled acoustic chamber (Industrial Acoustics Corporation) lined with 2^anechoic foam.…”

“…1, bottom row), for the three ΔF C conditions. The carrier frequencies for the three ΔF C conditions were selected to be in the most sensitive region of the rat's audiogram, which shows minimal changes in thresholds with age (Parthasarathy et al 2014). The modulation frequencies of the sAM1 FL and the sAM2 VL were chosen such that the two frequencies are close to two octaves apart but not harmonically related.…”

“…For the normalized condition, the amplitudes obtained from the other SNRs in each run were then normalized to FFT amplitude at 60 dB SNR of that run, for each stimulus condition to enable a direct comparison with the normalized EFR data. For modeling age-related changes in hearing thresholds, the audiograms of the aged animals (Parthasarathy et al 2014) were used in the Bfit audiogram^function of the AN model to arrive at the values for OHC and IHC function. These values were then used in the AN fiber simulations.…”

“…These neural deficits can be detected objectively in both human populations and animal models using auditory evoked potentials such as auditory brainstem responses (ABRs) a n d e n v e l o p e f o l l o w i n g r e s p o n s e s ( E F R s ) (Parthasarathy and Bartlett 2011;Ruggles et al 2012;Sergeyenko et al 2013;Shaheen et al 2015). EFRs represent summed, sustained, synchronized activities of populations of neurons from the auditory pathway which provide additional complementary information to metrics obtained from more established responses like ABRs (Parthasarathy et al 2014), with the major generators being the auditory brainstem and midbrain (Kuwada et al 2002;Chandrasekaran and Kraus 2010;Parthasarathy and Bartlett 2012).…”