Gap-induced reductions of evoked potentials in the auditory cortex: A possible objective marker for the presence of tinnitus in animals

Abstract

Animal models of tinnitus are essential for determining the underlying mechanisms and testing pharmacotherapies. However, there is doubt over the validity of current behavioural methods for detecting tinnitus. Here, we applied a stimulus paradigm widely used in a behavioural test (gap-induced inhibition of the acoustic startle reflex GPIAS) whilst recording from the auditory cortex, and showed neural response changes that mirror those found in the behavioural tests. We implanted guinea pigs (GPs) with electrocorticographic (ECoG) arrays and recorded baseline auditory cortical responses to a startling stimulus. When a gap was inserted in otherwise continuous background noise prior to the startling stimulus, there was a clear reduction in the subsequent evoked response (termed gap-induced reductions in evoked potentials; GIREP), suggestive of a neural analogue of the GPIAS test. We then unilaterally exposed guinea pigs to narrowband noise (left ear; 8-10 kHz; 1 h) at one of two different sound levels - either 105 dB SPL or 120 dB SPL - and recorded the same responses seven-to-ten weeks following the noise exposure. Significant deficits in GIREP were observed for all areas of the auditory cortex (AC) in the 120 dB-exposed GPs, but not in the 105 dB-exposed GPs. These deficits could not simply be accounted for by changes in response amplitudes. Furthermore, in the contralateral (right) caudal AC we observed a significant increase in evoked potential amplitudes across narrowband background frequencies in both 105 dB and 120 dB-exposed GPs. Taken in the context of the large body of literature that has used the behavioural test as a demonstration of the presence of tinnitus, these results are suggestive of objective neural correlates of the presence of noise-induced tinnitus and hyperacusis.

Keywords: Auditory cortex; Chronic recording; Noise exposure; Tinnitus.

Fig. 1

A: An example of GIREP from one GP. Dashed blue line indicates time of startling stimulus. B: Mean (±SEM) GIREP ratios expressed as gap/no gap, for all GPs pre-NE as a function of electrode location. A value of 1 would indicate no difference in EP amplitude between gap and no gap, whilst a value lower than 1 would indicate that the gap was inhibiting the subsequent EP. C: Mean (±SEM) GIREP ratios for all GPs pre-NE as a function of background carrier frequency. ^*p < .05; ^**p < .01; ^***p < .0001.

Fig. 2

Mean (±SEM) GIREP ratios for GPs exposed to 105 dB SPL (n = 5), averaged over pre-NE recordings compared with post-NE averages, for left rostral AC (A), right rostral AC (B), left caudal AC (C) and right caudal AC (D). P-values on subplots indicate overall statistical differences between time points.

Fig. 3

Mean (±SEM) GIREP ratios for GPs exposed to 120 dB SPL (n = 4), averaged over pre-NE recordings compared with post-NE averages, for left rostral AC (A), right rostral AC (B), left caudal AC (C) and right caudal AC (D). ^*p < .05; ^**p < .01; ^***p < .0001. P-values on subplots indicate overall statistical differences between time points.

Fig. 4

Correlations between changes in GIREP ratios and changes in EP amplitude (in response to stimuli with no gap preceding) for left rostral AC (A), right rostral AC (B), left caudal AC (C) and right caudal AC (D), recorded from 120 dB GPs. Data have been fitted with linear regressions to demonstrate the lack of significant trends (solid black lines).

Fig. 5

Comparisons of peak-to-trough amplitudes, averaged across frequencies, for each area of AC. Mean (±SEM) data are shown for 105 dB SPL GPs (A) and 120 dB SPL (B), for pre-NE vs post-NE. ^*p < .05; ^**p < .01.

Fig. 6

Diagram showing the position of the recording electrodes and connector in relation to a guinea pig skull and the underlying auditory cortical areas as mapped previously (Wallace et al., 2000). The rostral recording electrode was placed over the dorsorostral belt close to the low-frequency border of the primary auditory area (AI, coloured red) whilst the caudal electrode was placed over the dorsocaudal belt close to the low-frequency border of the dorsocaudal core area (DC, coloured green). The lateral suture, which forms the border of the parietal and squamous temporal bones, provides a useful surface landmark as it runs approximately over the middle of AI before turning towards the midline and forming the coronal suture. Red and blue electrodes served as reference and ground.