Neuro-Biological Aspect of Hyperacusis
The mechanisms underlying hyperacusis are unknown. One possibility is
that neurons that normally respond at higher sound levels begin to respond to
sounds with lower levels, leading to the perception of increased loudness.
Another possibility is that hyperacusis (as well as tinnitus) may result from
increased neural synchrony and reorganization of the tonotopic map in the
auditory cortex. Although there is limited evidence for increased brain
activity in the auditory cortex of people with hyperacusis, there is a growing
body of literature suggesting such changes in the brains of animals with
salicylate-induced or noise-induced hearing loss (Eggermont 2012; Eggermont & Roberts 2004; Norena
et al. 2002; Roberts et al. 2010; Sun et al. 2012; Sun et al. 2008).
Behavioral experiments with these animals showed enhanced acoustic startle
responses, which are assumed to be related to hyperacusis. However, the
interpretation of the results of such animal experiments is difficult and it is
not clear whether the observed neurophysiological changes are related to
hearing loss, hyperacusis or tinnitus (Eggermont 2012).
Knipper (Department of Molecular Physiology of Hearing, Hearing Research
Institute Tübingen, Germany) presented data from animals studies that aimed to
distinguish the effects of hyperacusis from those of tinnitus and hearing loss.
Her laboratory previously developed a behavioral animal model of tinnitus (Ruttiger et al.
2013; Singer et al. 2013). With this model, certain biomarkers
could be used to distinguish equally hearing-impaired animals with and without
tinnitus. These biomarkers included molecular changes in hair cells and their
synapses, changes in the number of auditory fiber numbers, changes in
activity-dependent plasticity genes, and several physiological changes,
including tests of outer hair cell function, summed auditory nerve activity,
suprathreshold early and late sound-evoked response amplitudes, and field
potentials. For reviews see Knipper et al.
(2015), Knipper et al.
(2013), and Ruttiger et al.
(2017). Building on this work, Knipper’s
laboratory has now developed an animal model for hyperacusis. It is known that
exposure to a very intense noise often, but not always, leads to tinnitus
and/or hyperacusis in humans. In Knipper’s laboratory, animals were exposed to
the type of noise that produces tinnitus and/or hyperacusis in humans. It seems
reasonable to assume that some animals exposed to the noise will develop
tinnitus and/or hyperacusis, and some will not. Despite no distinguishable
hearing threshold difference (based on the measurement of auditory brainstem
responses), it was found that the animals could be subdivided on the basis of
behavioral measures into groups with (i) no tinnitus and no hyperacusis, (ii)
tinnitus but no hyperacusis, (iii) hyperacusis but no tinnitus, and (iv)
tinnitus and hyperacusis. The results also confirmed what has been reported
previously for men and rodents: hyperacusis is not primarily linked to an
elevation of hearing thresholds or impairment of outer hair cell function.
Rather, whether or not hyperacusis and tinnitus occur is related to differences
in central responsiveness to peripheral auditory fiber damage. The findings
also indicate that differences in central responsiveness linked with tinnitus
and hyperacusis are associated with differences in a memory reinforcement
system that is involved in strengthening auditory circuits. Moreover, the
findings support a crucial role of the history of stress levels in driving
central adaptive responses to peripheral neuronal impairments that lead to
tinnitus or hyperacusis (Singer et al.
2013). The differences in central
response pattern observed between animals with various combinations of
hyperacusis and tinnitus are currently being compared with features in defined
patient groups with matched degrees of hearing loss.
Martin Schecklmann (Department of
Psychiatry and Psychotherapy, University of Regensburg, Germany) described
earlier work of his group demonstrating that hyperacusis as indicated by
screening questions from the Tinnitus Research Initiative database (Landgrebe et
al. 2010; Langguth et al. 2007) is associated with specific
demographic, tinnitus, and clinical characteristics (Schecklmann et
al. 2014). For example, patients with chronic
tinnitus and hyperacusis (in contrast to patients with only tinnitus) were more
seriously handicapped, showed a higher influence of stress on their tinnitus,
and rated the pitch and loudness of their tinnitus as higher and their hearing
function as worse. However, measures of tinnitus pitch, tinnitus loudness and
hearing thresholds did not reveal group differences. In another work Schecklmann et al. (2015) validated the screening questions of the
Tinnitus Research Initiative (TRI) database (Landgrebe et
al. 2010; Langguth et al. 2007) by using the German hyperacusis
questionnaire “GÜF” for a sample of patients with chronic tinnitus, some of
whom also had hyperacusis (Nelting et al.
2002). The original proposed factor
structure of the GÜF could not be replicated. Factors of the GÜF for this sample
of patients were found to be quality of life, hearing difficulties, and
fear-pain hyperacusis. These factors match well with the characteristics of
patients with hyperacusis as determined using the TRI database analysis (Schecklmann et
al. 2014). Relative to patients with tinnitus
alone, patients with hyperacusis were more seriously handicapped and had a
reduced quality of life. The latter also reported that their tinnitus was more
strongly modulated by stress induced by emotional factors. These findings
highlight the need to consider hyperacusis subtypes both in clinical settings
and for scientific work.
Schecklmann then presented
preliminary data on resting state electroencephalography (EEG) for a sample of
42 patients with chronic tinnitus, some of whom also had hyperacusis. The aim
of this work was to assess whether those without and with hyperacusis had
different resting state brain oscillatory activity. This was done by
determining the correlation between scores for single items of the GÜF and the
amount of EEG activity in different frequency bands. Theta activity in
bilateral temporal and frontal areas was correlated with emotional aspects of
the GÜF, central beta3 activity was correlated with quality of life, and gamma
activity over all sensors was correlated with hyperacusis in general. These
findings corroborate the existence of hyperacusis subtypes on a phenotypic and
neuronal level. EEG might be helpful in disentangling different forms of
hyperacusis for patients with chronic tinnitus.
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