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

Berger, Joel I.; Owen, W. G.; Wilson, Caroline A.; Hockley, Adam; Coomber, Ben; Palmer, Alan R.; Wallace, Mark N.

doi:10.1016/j.brainres.2017.11.026

Cited by 16 publications

(16 citation statements)

References 49 publications

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“…The startle stimulus was a broadband (white) noise burst of 20 ms duration that included linear rise/fall times of 1 ms. There were five different continuous background noise conditions; four 2-kHz wide narrowband noise conditions centred at 5, 9, 13, and 17 kHz, and white noise, as described previously (Berger et al., 2018). Gaps of 50 ms duration, starting 100 ms before the startling stimulus, were randomly inserted on half of the trials, resulting in 10 ‘gap’/‘no-gap’ conditions for each background noise condition.…”

Section: Methodsmentioning

confidence: 99%

“…In guinea pigs, we have overcome the problem of habituation by measuring the Preyer or pinna reflex using infrared motion tracking (Berger et al., 2013, 2018). The Preyer reflex was first described in guinea pigs in the late 19th century (Preyer, 1882).…”

Section: Introductionmentioning

confidence: 99%

“…The broader PPI measured by the eye-blink reflex is altered by certain psychiatric conditions such as schizophrenia and obsessive compulsive disorder (Kohl et al., 2013) and so studying modification of the pure acoustic reflex may be more appropriate for acoustic conditions such as temporal processing or tinnitus. The Preyer reflex shows robust PPI in rats (Cassella and Davis, 1986), as well as GPIAS in guinea pigs that can be used to identify tinnitus (Berger et al., 2013, 2018; Wu et al., 2016).

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Section: Introductionmentioning

confidence: 99%

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Gap-induced inhibition of the post-auricular muscle response in humans and guinea pigs

et al. 2019

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A common method for measuring changes in temporal processing sensitivity in both humans and animals makes use of GaP-induced Inhibition of the Acoustic Startle (GPIAS). It is also the basis of a common method for detecting tinnitus in rodents. However, the link to tinnitus has not been properly established because GPIAS has not yet been used to objectively demonstrate tinnitus in humans. In guinea pigs, the Preyer (ear flick) myogenic reflex is an established method for measuring the acoustic startle for the GPIAS test, while in humans, it is the eye-blink reflex. Yet, humans have a vestigial remnant of the Preyer reflex, which can be detected by measuring skin surface potentials associated with the Post-Auricular Muscle Response (PAMR). A similar electrical potential can be measured in guinea pigs and we aimed to show that the PAMR could be used to demonstrate GPIAS in both species. In guinea pigs, we compare the GPIAS measured using the pinna movement of the Preyer reflex and the electrical potential of the PAMR to demonstrate that the two are at least equivalent. In humans, we establish for the first time that the PAMR provides a reliable way of measuring GPIAS that is a pure acoustic alternative to the multimodal eye-blink reflex. Further exploratory tests showed that while eye gaze position influenced the size of the PAMR response, it did not change the degree of GPIAS. Our findings confirm that the PAMR is a sensitive method for measuring GPIAS and suggest that it may allow direct comparison of temporal processing between humans and animals and may provide a basis for an objective test of tinnitus.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fig.…”

Section: Introductionmentioning

confidence: 99%

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Gap-induced inhibition of the post-auricular muscle response in humans and guinea pigs

et al. 2019

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“…Animals that showed a significantly reduced GPIAS (see below) were classified as noise-exposed tinnitus. Noise exposure was conducted as previously described (Berger et al, 2018). Anaesthesia was induced with ketamine (50 mg/kg, i.p.)…”

Section: Tinnitus Induction and Behavioural Confirmationmentioning

confidence: 99%

Nitric oxide increases gain in the ventral cochlear nucleus of guinea pigs with tinnitus

Hockley

Berger

Palmer

et al. 2020

Eur J of Neuroscience

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Previous work has led to the hypothesis that, during the production of noise‐induced tinnitus, higher levels of nitric oxide (NO), in the ventral cochlear nucleus (VCN), increase the gain applied to a reduced input from the cochlea. To test this hypothesis, we noise‐exposed 26 guinea pigs, identified evidence of tinnitus in 12 of them and then compared the effects of an iontophoretically applied NO donor or production inhibitor on VCN single unit activity. We confirmed that the mean driven firing rate for the tinnitus and control groups was the same while it had fallen in the non‐tinnitus group. By contrast, the mean spontaneous rate had increased for the tinnitus group relative to the control group, while it remained the same for the non‐tinnitus group. A greater proportion of units responded to exogenously applied NO in the tinnitus (56%) and non‐tinnitus groups (71%) than a control population (24%). In the tinnitus group, endogenous NO facilitated the driven firing rate in 37% (7/19) of neurons and appeared to bring the mean driven rate back up to control levels by a mechanism involving N‐methyl‐D‐aspartic acid (NMDA) receptors. By contrast, in the non‐tinnitus group, endogenous NO only facilitated the driven firing rate in 5% (1/22) of neurons and there was no facilitation of driven rate in the control group. The effects of endogenous NO on spontaneous activity were unclear. These results suggest that NO is involved in increasing the gain applied to driven activity, but other factors are also involved in the increase in spontaneous activity.

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“…Stress, sleep, hearing loss, gender and age are all associated with tinnitus (Kim et al, ; Park et al, ). Patients with tinnitus often report a history of acoustic overexposure (Schmuzigert, Fostiropoulos, & Probst, ), and noise exposure is widely used as a method of tinnitus induction in animal models (Berger et al, ; Marks et al, ; Wu, Martel, & Shore, ).…”

Section: Introductionmentioning

confidence: 99%

Remodeling of cholinergic input to the hippocampus after noise exposure and tinnitus induction in Guinea pigs

Zhang

Martel

et al. 2018

Hippocampus

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Here, we investigate remodeling of hippocampal cholinergic inputs after noise exposure and determine the relevance of these changes to tinnitus. To assess the effects of noise exposure on the hippocampus, guinea pigs were exposed to unilateral noise for 2 hr and 2 weeks later, immunohistochemistry was performed on hippocampal sections to examine vesicular acetylcholine transporter (VAChT) expression. To evaluate whether the changes in VAChT were relevant to tinnitus, another group of animals was exposed to the same noise band twice to induce tinnitus, which was assessed using gap‐prepulse Inhibition of the acoustic startle (GPIAS) 12 weeks after the first noise exposure, followed by immunohistochemistry. Acoustic Brainstem Response (ABR) thresholds were elevated immediately after noise exposure for all experimental animals but returned to baseline levels several days after noise exposure. ABR wave I amplitude‐intensity functions did not show any changes after 2 or 12 weeks of recovery compared to baseline levels. In animals assessed 2‐weeks following noise‐exposure, hippocampal VAChT puncta density decreased on both sides of the brain by 20–60% in exposed animals. By 12 weeks following the initial noise exposure, changes in VAChT puncta density largely recovered to baseline levels in exposed animals that did not develop tinnitus, but remained diminished in animals that developed tinnitus. These tinnitus‐specific changes were particularly prominent in hippocampal synapse‐rich layers of the dentate gyrus and areas CA3 and CA1, and VAChT density in these regions negatively correlated with tinnitus severity. The robust changes in VAChT labeling in the hippocampus 2 weeks after noise exposure suggest involvement of this circuitry in auditory processing. After chronic tinnitus induction, tinnitus‐specific changes occurred in synapse‐rich layers of the hippocampus, suggesting that synaptic processing in the hippocampus may play an important role in the pathophysiology of tinnitus.

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

Cited by 16 publications

References 49 publications

Gap-induced inhibition of the post-auricular muscle response in humans and guinea pigs

Gap-induced inhibition of the post-auricular muscle response in humans and guinea pigs

Nitric oxide increases gain in the ventral cochlear nucleus of guinea pigs with tinnitus

Remodeling of cholinergic input to the hippocampus after noise exposure and tinnitus induction in Guinea pigs

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