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.
Highlights
Tinnitus, the perception of sound in the absence of an external acoustic stimulus, is a widespread health concern, affecting between 8 and 15% of the population and is debilitating in 1% (Shargorodsky et al, 2010)
We previously demonstrated that gaps in otherwise continuous background noise could inhibit cortical evoked responses to a startling stimulus in guinea pigs, in a similar manner to the gap prepulse inhibition of the acoustic startle (GPIAS) test (Berger et al, 2017), which we termed gap-induced reductions in evoked potentials (GIREP)
GIREP was evident for every electrode for all GPs during recordings made before the noise exposure
Summary
The perception of sound in the absence of an external acoustic stimulus, is a widespread health concern, affecting between 8 and 15% of the population and is debilitating in 1% (Shargorodsky et al, 2010). Tinnitus is generally identified by using a behavioural task, either reflex-based (Turner et al, 2006; Berger et al, 2013) or using a conditioning paradigm (Jastreboff et al, 1988; Bauer et al, 1999; Heffner and Harrington, 2002; Lobarinas et al, 2004; Stolzberg et al, 2013). A startling pulse (usually a short broadband stimulus) is embedded in continuous narrowband or broadband noise This produces a whole-body startle response, which can be detected using a platform with a piezo-electric transducer attached (or motion tracking cameras in the case of the Preyer reflex adaptation; Berger et al, 2013; Wu et al, 2016).
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