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need to think it over before startling. For the purposes of assessing tinnitus, a continuous sound is played in the background and a brief gap is presented before the loud startling stimulus, called gap prepule inhibition of an acoustic startle (GPIAS). However, if tinnitus is present and the background continuous sound is similar in pitch to the tinnitus, the animals will be unable to reliably detect the gap and there will be no reduction or smaller reduc- tions in the ASR. This paradigm can be used to assess both the presence of tinnitus as well as the frequency range of the tinnitus. For example, Lobarinas et al. (2015) dem- onstrated that rats with evidence of noise-related tinnitus based on the ASR showed an improved startle response (i.e., less tinnitus filling gap) when treated with the drug cyclobenzaprine (a tricyclic antidepressant).
Reflexive models such as the GPIAS have the main advan- tage of precluding overt and long behavioral training. However, these models are not without their limitations, such as habituation of the ASR (Lobarinas et al., 2013a) and loss of reactivity to loud startling stimuli following unilateral HL. Although these drawbacks have called the widespread use of the GPIAS into question, it remains the most popular paradigm used in preclinical models of tinnitus. One way to overcome one of the limitations of the GPIAS is to elicit the startling response with a tactile stimulus. Thus, an acoustic stimulus can be used to cue the imminent startling stimulus without concerns of the effi- cacy of an acoustic startle elicitor. Lobarinas et al. (2013a) demonstrated success using an air puff to the animal’s back to elicit a robust startle response. Cuing the air puff with an acoustic stimulus reduced the startle response to the air puff. Using a tactile stimulus such as the air puff has allowed the model to be used to study unilateral and bilat- eral tinnitus as well as other auditory phenomena such as hearing in noise and suprathreshold deficits associated with subclinical HL (Lobarinas et al., 2017).
Lost in Translation
Animal and human findings relative to tinnitus often have conflicting results. For example, the idea that tinnitus fills in perception of a silent gap works in animals but is not so clear that it does so in humans. Continued improvements in animal models will make it possible to evaluate physiological correlates and basic mechanisms under controlled tinnitus-inducing conditions as well as to evaluate hypotheses generated from studying human participants.
It is also worth noting that these animal models of tin- nitus all focus on the perception; no animal models of the affective/emotional reaction to tinnitus are well accepted. Here we will consider two tinnitus-related phenomena that have been lost in translation between animals and humans: (1) tinnitus filling in a silent gap and (2) how peripheral hearing damage creates tinnitus.
Tinnitus “Filling in the Gap”
The application of gap detection and suppression of a startle reflex has become a common high-throughput model of tinnitus assessment in animals. In simple terms, the paradigm suggests that the presence of tinnitus dis- rupts the ability of the animal to detect the silent gap, and thus the startle response is less suppressed. Attempts to translate this measure to humans has been less promising.
For example, Fournier and Hebert (2013) used a GPIAS model measuring reflexive eye blink activity in participants with tinnitus compared with controls. They observed that participants with tinnitus had decreased inhibition of eye blink activity when it was preceded by a silent gap in noise compared with control participants. Nonetheless, despite all tinnitus participants reporting high-pitch ringing tin- nitus, the decreased inhibition was found for both low- and high-frequency noise stimuli. In other words, the decreased inhibition was not limited to gaps in noise reflective of the tinnitus perception (high frequency). The findings contra- dicted the assertation that tinnitus is simply filling in the gap and frequency-specific deficits observed in some animal models but did show altered ASR of eye blinking.
In the same year, Campolo et al. (2013) performed a simi- lar study of tinnitus filling in the gap but alternatively focused on perception of a silent gap than on an effect on an ASR. Applying methods comparable to animal experi- ments (50-ms silent intervals in varying noise bands), they observed no deficits in detecting the silent gap in persons with or without tinnitus. Similar findings were reported by Boyen et al. (2015), including no difference in detecting shorter gap durations.
The difference in findings of these studies may be explained by different neural circuits underlying reflexive responses andbehavioral-/perception-basedresponses.Fournierand Hebert (2013) were relying on a startle reflex (eye blink) compared with a conscious perception of a sound (or silent gap) as in Campolo et al. (2013) and Boyen et al. (2015).
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