Content uploaded by Olav V.G. Wagenaar
Author content
All content in this area was uploaded by Olav V.G. Wagenaar on Dec 05, 2022
Content may be subject to copyright.
66
International Tinnitus Journal, Vol. 16, No 1 (2010)
www.tinnitusjournal.com
A Cognitive Model of Tinnitus and Hyperacusis; A Clinical
Tool for Patient Information, Appeasement and Assessment
Abstract
Olav Wagenaar1,
Marjan Wieringa2,
Hans Verschuure1
1 Erasmus Medical Center, Dept. of Otorhinolaryngology, Head & Neck Surgery, Center of Hearing and Speech, Rotterdam, The Netherlands.
2 Erasmus Medical Center, Dept. of Otorhinolaryngology, Head & Neck Surgery, Rotterdam, The Netherlands.
Corresponding author:
O.V.G. Wagenaar
Postbus 2040
3000 CA Rotterdam
Tel.: +31 107034586/ Fax: +31 107035660
E-mail: o.wagenaar@erasmusmc.nl / o.wagenaar@parnassia.nl
Tinnitus and hyperacusis are both aggravating audiological symptoms. Their underlying mechanisms are not fully
understood, but the pathophysiology involves a central mechanism rather than a peripheral one. There is no curative
treatment. A review of the available research on tinnitus and auditory processing was conducted to connect insights
gained from different approaches to the subject; this resulted in the development of a holistic view of both conditions.
In this view, the chronic course of the symptoms is pathological and attributed to a stress-related lack of habituation.
This article adds to the literature on tinnitus and hyperacusis by presenting a schematic model of the cognitive me-
chanisms which can be used clinically in patient information sessions which are geared towards provide reassurance
and encouraging the development of coping skills. In cooperation with the patient, the model can also help in the
identification of underlying pathology. Future aims of study are suggested, elaborating on the role of tinnitus and
hyperacusis in normal auditory processing and on the value of insight. Finally, parallels are drawn between tinnitus
and positive symptom syndromes in neuropsychiatry and some of its modern visions on their treatment.
LITERATURE REVIEW
International Tinnitus Journal. 2010;16(1):66-72.
Keywords: cognitive, hyperacusis, tinnitus.
67
International Tinnitus Journal, Vol. 16, No 1 (2010)
www.tinnitusjournal.com
INTRODUCTION
The continuous perception of tinnitus is a common
and often serious health problem1-3 with considerable
costs. Hyperacusis, which is the phenomenon of de-
creased sound toleration, is a known comorbidity. The
research on hyperacusis is very scarce, but it has been
suggested that its mechanism involves peripheral disrup-
tions or the central sound processing at the subcortical
level.4 Tinnitus and hyperacusis seem to be connected
by more than coincidental factors.5 In 1993, Jastreboff
and Hazel regarded hyperacusis as a pretinnitus state.6
Tinnitus can be considered as a ‘positive symptom
disorder’ characterized by neural hyperactivity due to
the loss of afferent inhibition.7 Although tinnitus is often
related to hearing loss,7, 8 not all tinnitus sufferers have
an audiologically objective perceptive hearing loss and
many, but not all, hearing impaired people have tinnitus.
This suggests that the auditory pathway does not play a
decisive central role in tinnitogenesis alone. It has often
been suggested that hearing loss is the basis for tinnitus
development but that tinnitus must be a far more com-
plex (top-down) phenomenon than just a reorganization
of the auditory cortex after damage to the cochlear hair
cells.9 It is suggested that additional processes such as
attention, cognition and fear play a role in tinnitus.10 Since
dysfunctional neuroplastic processes are believed to be
involved in the mechanism(s) underlying tinnitus and
hyperacusis, human studies have used many different
techniques to study the brain in tinnitus patients.10-16
These studies have shown changes in activity in the ri-
ght hemisphere, tonotopic map changes in the auditory
cortex, structural changes in the thalamus, and the limbic
system and subcallosal regions, and the involvement of
a frontal and amygdalohippocampal circuit. Although
these study results have had important implications
for tinnitus modeling, most of them did not match their
control groups for hearing loss. Animal studies point at
the dorsal cochlear nucleus and inferior colliculus as
possible sites for initiating tinnitus.17, 18
Although the neuroscientific research on tinnitus
still has a lot of methodological problems to overcome,
it does reveal that there is an imbalance of excitation
and inhibition at almost every level of the auditory pa-
thway.19 This is caused by adaptive (neuroplastic) activity
changes. Early manifestations of these neuroplastic
changes are believed to be the diminishing of inhibition
and subsequently hyperactivity. Late manifestations are
the remodelling of the tonotopic areas.20
Despite extensive scientific research conducted
on this subject, a solid understanding of the underlying
mechanism has not been achieved, nor has a curative
treatment been found, although numerous therapeutic
suggestions, mostly on the management of tinnitus, have
been made. Tyler gives an extensive overview of various
possible types of treatments and counselling protocols.21
A focus on the functional interactions within and
between neural networks in auditory processing can
provide a useful perspective into the neural mechanisms
underly-ing tinnitus and hyperacusis.22 In this article we
will integrate the data on auditory processing and neu-
roplasticity related to tinnitus with psychological facts.
Based on this, we will describe tinnitus and hyperacusis
as maladaptive neuropsychological phenomena and
present a schematic model, educational for patients
and addressing their overall emotional well-being and
need for insight. This could be the basis of a very effi-
cient group intervention and be the starting point for a
multidisciplinary procedure.
The neuropsychology of auditory processing
Central auditory processes are defined as all the
mechanisms and functions which are responsible for
behavioural auditory phenomena.23 These processes are
divided into several parts or steps. First there is a con-
ductive part; this is followed by Auditory Scene Analysis,
which is subconscious.24-27 After that, the application and
regulation of emotional values takes place. The next step
involves the cortical processes where attentional bias
and reasoning lead to the behavioral outcomes related
to the initial stimulus.
In anatomical terms: after the auditory nerve enters
the brainstem, one part of the axons connects with the
reticular formation and cerebellum which is responsible
for the arousal and startle-reflex. This leads to an overall
neurophysiological state of ‘fight-or-flight-readiness’.28
Another part of the axons connects with the colliculi
inferiores through a ventral and a dorsal route.26 These
two separate routes of sound processing create a system
of perception (‘what’) and a system of orientation (‘whe-
re’). Perception and orientation are parallel processes of
auditory stimuli which influence the levels of emotional
and cognitive auditory processing.29
The ‘where’ route follows a temporo-fronto-pa-
rietal network. The temporal regions are believed to be
involved in differential processing and the parietal and
frontal areas for task related processes such as attention
regulation and motor preparation.30 Attention regulation
results in different aspects of sound perception.31 Me-
mory usage in the orientation route has been related to
the efficient processing of sound stimuli so as to diffe-
rentiate between what sound is safe and what is not.32
The ‘what’ route starts with the fibres going from
the colliculi inferiores through the medial geniculate body
of the thalamus to the cortical auditory areas.28 In Auditory
Scene Analysis, sound segregation leads to distinct au-
ditory streams. This is enhanced by information from the
‘where’ route of processing.33 Sequential elements on the
68
International Tinnitus Journal, Vol. 16, No 1 (2010)
www.tinnitusjournal.com
streams which are formed are grouped into perceptual
units, for identifying changing patterns, such as speech.34
The analysis of stimulus content depends (amongst
other things) on implicit (subconscious) memory.35-44
The memory processes are used as a template against
which incoming sounds are compared.45, 46
Memory traces may play a role in perceptual
illusions such as the continuity effect.47, 48 This is the au-
ditory analogue of a completion illusion,49, 50 the process
by which perceptual information is organised in order
to form stable representations.49 Continuity ensures the
accuracy of perception and orientation and seems to
precede the initiation of attention switches and choices,
which is important for social behaviour. The emotional
state and motivation which is needed for behaviour to
occur, involve limbic structures, including the hippo-
campal formation and the amygdala. Connected to
these limbic structures are the basal ganglia, a series of
nuclei which has an afferent part (known as the striatum)
which is involved with selective attention51. Part of the
striatum is the nucleus accumbens (NAc) which regu-
lates the transfer of motivational and emotional signals
received from the prefrontal cortex, the amygdala and
the hippocampus to adaptive behavioural responses52.
In doing so, the NAc occupies a central role in a network
for (emotional) learning.22 One aspect of emotional le-
arning is called Latent Inhibition (LI), which is a process
of habituation. The habituation of a continued stimulus
is obtained by inhibiting subsequent associations based
on hippocampal retention (memory) with a pre-exposed
sound.22 Based on a small study with functional magnetic
resonance imaging, hyperacusis might be related to the
neural network associated with the frontal lobes and
parahippocampus53.
In 2006, Muhlau and collegues found an increase
of (right sided) thalamic activity and a significant decrea-
se of the NAc volume54 in tinnitus patients. This alteration
of volume was thought to be directly related to functional
changes in brain activity55,56. A decrease of NAc activity
would result in LI disruption. Preceding chronic (patho-
logical) stress can cause this poorer functioning of the
NAc57,58,59. The result is disinhibition60 or lack of habitu-
ation. This would then cause a pathological ongoing of
completion in stimulus content analysis, consistent with
Hallam’s habituation theory61,62.
A recent study was not able to replicate these fin-
dings.11 Instead the results showed a decrease of grey
matter in the right inferior colliculus and a decreased
grey matter concentration in the (left) hippocampus.
The authors suggested that decreased inferior colliculus
indicated a compensatory mechanism, because many
other research groups found hyperactivity in that area12,
63, 64. Furthermore they suggested a direct involvement of
the hippocampus in tinnitus pathophysiology.11
It is possible that the findings of Muhlau (2006)
and Landgrebe (2009) do not conflict, but reflect diffe-
rent stages of stress regulation instead. A review of the
research on stress and memory indicates that chronic
stress, measured by cortisol levels, has a reducing effect
on the activity of the hippocampus65 and on NAc functio-
nality 57, 58, 59. There are also indications that the effects
of reduced Hippocampus activity by cortisol abolish the
cortisol response to the stressor66. Thus the damaging
effect on the NAc is abolished to recover habituation
processes. Content analysis (including continuity effects)
and Latent Inhibition depend on the hippocampus to
be able to compare new incoming auditory stimuli with
consolidated auditory information which has been ex-
perienced earlier.15 They also appear to depend on the
hippocampus because of its important role in restoring
the balance of the response to psychosocial stress66 and
thus restoring habituation.
The neuropsychology of tinnitus and hyperacusis
Feelings, cognition and knowledge of the world,
based on former personal experience, are part of audi-
tory processing and perception in general. They relate,
at least in part, to psychological and social functioning.
Consequently, hearing loss leads to perceptual and
communicational problems, and to a reduction in un-
derstanding what is around us67; in a social context, this
creates the threat of social isolation68. It is necessary for
the brain to adapt to these threats and to compensate
for them. Changes in activity within structures of the
auditory pathways after altering peripheral input19, 20 can
be seen as manifestations of adaptive compensations in
the central auditory system.
Attention has been neuropsychologically defined
as an abstract result of activation in the neural circuits69.
In speech comprehension, activity in the frontal-temporal
network can be seen (poorer signal-to-noise-ratios of
spoken sentences)70. With specific frequencies missing
in hearing (e.g. noise induced hearing loss), sound
discrimination inherent in speech comprehension also
becomes more difficult. The lack of hearing specific fre-
quencies is, therefore, associated with increased activity
in the primary auditory cortex and frontal areas70, 71. These
activation patterns induce (more) attention.
With severe hearing loss, misperception (and often
disorientation) occurs. The patient uses mental effort
trying to locate the source of the sound and, in so doing,
increases the attention given to it71. On the other hand,
with less severe hearing loss, one may not be aware of
the impairment and, in that situation, stimulus content
(e.g. speech) is deduced using implicit memory.42
In brief: cochlear damage results in decreased
perception and orientation, requiring compensation
by attention and memory through elicited (amygdalo)
69
International Tinnitus Journal, Vol. 16, No 1 (2010)
www.tinnitusjournal.com
hippocampal and frontal-temporal network activation70,
72. From this perspective hyperacusis is not a pretinnitus
state, but a symptom of its own with a distinct role in
orientation. In fact, hyperacusis might be a secondary
symptom of threat by tinnitus.
Even though the majority of tinnitus sufferers have
a certain amount of hearing loss, it is possible to expe-
rience tinnitus or hyperacusis without having a higher
than normal amount of damage to the inner ear hair cells.
To increase the sense of safety by enhancing auditory
perception and orientation73, auditory completion and
hypervigilance can also be expected in psychologically
threatening conditions. In these conditions, obviously
chronic stress is present and a decreased functioning of
the NAc57 and hippocampus65 is exhibited. Under those
circumstances, neuroplastic compensations occur even
in normal (age-related) hearing or mild hearing loss. As
humans are interactive social creatures, it can be caused
by psychological or psychosocial factors.
The relatively complex processes of auditory
completion and hypersensitivity are shown in a relatively
simple schematic model (see Figure 1).
The figure illustrates the relationship between he-
aring loss, psychological well-being and cognitive func-
tioning. For tinnitus or hyperacusis to develop, one has
to fulfill either one of two conditions (or both); a hearing
loss or a chronic (neuro)psychological overburdening.
First, with a significant hearing loss, brain activity
in the auditory areas increases producing a degree of
attentional compensation on behalf of orientation: a cons-
cious focus on sound is made and there may only be a
minor subjective complaint of hearing loss. Instead, there
is a growing complaint of fatigue and neuropsychologi-
cal overload73. This is thought to result in hyperacusis,
when orientation is diminished, or in tinnitus because of
the effort to complete perception. As a result of hearing
loss the completion is continuous and, because it is a
symptom of sensorial stress, it is perceived itself. If an
emotional (stress) reaction then occurs, a vicious circle
is created; this explains why some people are bothered
by it and others are not.
On the other hand, stress-related brain activity is
also a factor in psychopathology, in chronic psychosocial
stress and in chronic pain, or it can be a factor related
to the use of sedatives or extreme fatigue, or to psycho
stimulant withdrawal or brain trauma. As a result of the
psychological overload, normal attentional compensa-
tion and completion of very small or even normal hearing
loss (e.g. at ultra high frequencies) can be perceived
as either hyperacusis or tinnitus respectively74 and the
emotional reaction which immediately follows, corres-
ponding with the pre-existing mood, creates a vicious
circle leading to chronicity and progression.
Although a stress reaction is a normal reaction
to unknown sounds, it can lead to hyper-cortisolism
and neural damage to the areas involved in habituation
processes. The intensity of stress reactions and neural
damage depends strongly on the individual’s personality
and coping abilities and the degree of appeasement offe-
red by the health care professional who is consulted. The
focus of treatment should be on the underlying cause of
the neuropsychological stress created during the period
before the appearance of the symptom(s). From a neu-
ropsychological perspective, this may either be hearing
loss and/or chronic stress due to psychiatric, psychoso-
cial, or somatic suffering; all of which are factors which
are open to treatment once they have been identified.
Figure 1 can be clinically used in an informational
session focused on giving answers to some of the most
distressing questions that tinnitus patients present with.
The scheme can also provide a tool for a diagnostic in-
terview, and may lead to answers to the question: ‘why’.
Implications for multidisciplinary treatment
We have integrated the neurobiological findings
of tinnitus research with neuropsychological views about
auditory perception. In the modern world, with epidemic
stress or psychopathology on the one hand, and risks
of cochlear damage on the other, neuroplastic adapta-
tion can become imbalanced. The neuropsychological
approach provides an easy and accessible insight into
Figure 1. The neuropsychological model of tinnitus and hyperacusis.
This schematic model illustrates how attention and memory can be seen
as key cognitive instruments affecting auditory behavioural outcomes.
The context of increased neural activity is formed by four domains (I
- IV) in which human auditory processing takes place: what is where
in relation to ourselves versus human psychological functioning in
relation to stress toleration and life experiences. The first (innermost)
circle of the brain activity shows normal activity, the second (inner) circle
reflects the neural over-activity caused by chronic stress, either due
to audiological or to psychological threat, which causes the onset of
tinnitus or hyperacusis. The thick outer circle reflects the vicious circle
of brain hyperactivity caused by reactive stress of tinnitus/hyperacusis,
leading to progressive exacerbation of tinnitus or hyperacusis.
70
International Tinnitus Journal, Vol. 16, No 1 (2010)
www.tinnitusjournal.com
the comprehensive and highly complex neurobiological
processes. It can be clinically used during an initial in-
formation session which is aimed at reducing the stress
reaction. This stress reaction is based upon a threatening
association75. Differentiating between the initial stress
and the reactive stress by explaining the model shown
in Figure 1 to a group of patients can provide answers to
their questions; it is also reassuring because of the move
from non-treatable symptoms to controllable underlying
problems. It can, therefore, break the reactive vicious
circle. Also, the clinical use of Figure 1 presents an open-
ing for the caregiver to help the patient to overcome his/
her somatic fixation. Furthermore, this approach also
provides rationales for the various treatment options as
it suggests that, after gaining insight, successfully treat-
ing the underlying pathology and applying relaxation
exercises, hyperacusis and tinnitus can be controlled.
The first suggestion for therapy arising from the
model is to treat preceding existing hearing loss, if suf-
ficiently present. The suggested treatment for perceptive
hearing loss is the fitting of hearing aids with careful
adjustment based on a tone audiogram.
Second, the schematic model points to the need
for an extensive diagnostic interview and examination
of the patient’s (neuro)psychological well-being before
the onset or sudden aggravation of the tinnitus or hy-
peracusis; this is especially important if no significant
hearing loss is found. Underlying pathology related to
emotion (e.g. mourning, depression), impulses (anxiety,
anger, frustrations), mental strength (e.g. cerebrovascular
accidents, brain trauma, exhaustion, work related burn-
out) and physical condition (chronic pain, hormonal
imbalance) can be expected, most of which can still
(and obviously should) be treated. This is an important
distinction with counseling as usual, which is aimed at
the acceptance of tinnitus or hyperacusis.
Although similar theoretical essences have been
outlined elsewhere76, the schematic model presented in
this article is unique in that it can be used to visualize
very complex processes in a very efficient educational
group session aimed at improving the patient’s insight
and providing reassurance. What’s more, it can also be
used diagnostically in cooperation with the patient, giv-
ing rise to treatment options for the underlying pathology
of which tinnitus and hyperacusis are only the clinical
symptoms. In our opinion, education, insight, reassur-
ance and these treatment aims result in getting the better
of tinnitus by the patient, which leads to the reduction of
tinnitus distress and restored habituation.
RECOMMENDATIONS
Patients with tinnitus or hyperacusis are often in
distress and are desperately looking for treatment, infor-
mation and advice. They most often present at Ear, Nose
and Throat clinicians, who have no other therapeutic
options than to, at best, offer them psychological coun-
seling. Also in psychiatric clinics, tinnitus or hyperacusis
can be the patient’s dominant complaint(s), which is often
ignored because of the lack of understanding.
Future research could build upon this model to
provide a better understanding of tinnitus and hyper-
acusis and their functions in auditory processing and
neuropsychological functioning. In the model, networks
of non auditory areas such as the NAc, the hippocampus
and limbic structures are believed to be key sites with
respect to lack of habituation to a normal neuroplastic
phenomenon of auditory scene analysis. The NAc, in
particular, has a wide spread of connections with (nearly)
all brain areas in which hyperactivity has been shown in
tinnitus subjects. Its activity is regulated by dopaminer-
gic and glutamatergic afferents, but is also modified by
GABAergic, serotonergic, adrenergic and cholinergic
afferents57. Focusing on this region could be an extra
spur for research into pharmacological or other cura-
tive treatments for tinnitus. Furthermore, this particular
region has already turned out to be of major importance
in neuropsychiatric disorders characterized by positive
symptoms77. In that field of interest, breakthroughs have
been made by experiments with deep brain stimulation
(DBS)78. Shi (2009) has pointed out that DBS could be
promising for tinnitus patients too79.
Finally, although it is widely accepted that provid-
ing information should be one of the first interventions
in an intensive multidisciplinary protocol because of the
need for appeasement,21 the information which is taught
worldwide differs substantially and no clear consensus
exists as to what information should be taught. Research
into the effects of educational interventions based on con-
temporary knowledge is desperately needed. A precise
determination could then be made as to what information
is required to be able to reassure patients and enhance
their sense of control in the face of powerlessness, and
how this relates to the subjective perception of tinnitus
or hyperacusis80,81 and habituation or extinction.
ACKNOWLEDGEMENT
We thank Professor G. Borst of the Department of
Neuroscience, Erasmus Medical Center, Netherlands,
for his expert review of the concept version of this article
and his useful recommendations for improvements of
the schematic illustration of the model. We also thank
reviewers from earlier versions of the article for their
recommendations.
71
International Tinnitus Journal, Vol. 16, No 1 (2010)
www.tinnitusjournal.com
REFERENCES
1. Dobie RA Depression and tinnitus. Otolaryngol Clin North Am.
2003;36(2):383-8.
2. Stobik C, et al. Evidence of psychosomatic influences in compen-
sated and decompensated tinnitus. Int J Audiol. 2005; 44(6):370-8.
3. Heller AJ. Classification and epidemiology of tinnitus. Otolaryngol
Clin North Am. 2003;36(2):239-48.
4. Herraiz C, Plaza G, Aparicio JM. [Mechanisms and management
of hyperacusis (decreased sound tolerance)]. Acta Otorrinolaringol
Esp. 2006;57(8):373-7.
5. Tyler RS, Conrad-Armes D. The determination of tinnitus loud-
ness considering the effects of recruitment. J Speech Hear Res.
1983;26(1):59-72.
6. Jastreboff PJ, Hazell JW. A neurophysiological approach to tinnitus:
clinical implications. Br J Audiol. 1993;27(1):7-17.
7. Eggermont JJ. Pathophysiology of tinnitus. Prog Brain Res.
2007;166:19-35.
8. Henry JA, Dennis KC, Schechter MA. General review of tinnitus:
prevalence, mechanisms, effects, and management. J Speech
Lang Hear Res. 2005;48(5):1204-35.
9. Tyler RS. Tinnitus. In Tinnitus. Evered D, Lawrenson G. Editors.
Pitman: London; 1981. p. 136-7.
10. Weisz N et al. Abnormal auditory mismatch response in tinnitus
sufferers with high-frequency hearing loss is associated with sub-
jective distress level. BMC Neurosci. 2004;5:8.
11. Landgrebe M et al. Structural brain changes in tinnitus: Grey matter
decrease in auditory and non-auditory brain areas. Neuroimage.
2009;46(1):213-8.
12. Lanting CP et al. Functional imaging of unilateral tinnitus using
fMRI. Acta Otolaryngol. 2008;128(4):415-21.
13. Lockwood AH et al. The functional neuroanatomy of tinnitus:
evidence for limbic system links and neural plasticity. Neurology.
1998;50(1):114-20.
14. Muhlnickel W et al. Reorganization of auditory cortex in tinnitus.
Proc Natl Acad Sci USA. 1998;95(17):10340-3.
15. Shulman A. A Final Common Pathway for Tinnitus - The Medial
Temporal Lobe System. Int Tinnitus J. 1995;1(2):115-26.
16. Tremblay K et al. Central auditory plasticity: changes in the N1-P2
complex after speech-sound training. Ear Hear 2001;22(2):79-90.
17. Kaltenbach JA Afman CE. Hyperactivity in the dorsal cochlear
nucleus after intense sound exposure and its resemblance to
tone-evoked activity: a physiological model for tinnitus. Hear Res
2000;140(1-2):165-72.
18. Kaltenbach JA, Zhang J, Finlayson P. Tinnitus as a plastic pheno-
menon and its possible neural underpinnings in the dorsal cochlear
nucleus. Hear Res 2005;206(1-2):200-26.
19. Eggermont JJ. Tinnitus: neurobiological substrates. Drug Discov
Today. 2005;10(19):1283-90.
20. Bartels H, Staal MJ, Albers FW. Tinnitus and neural plasticity of the
brain. Otol Neurotol. 2007;28(2):178-84.
21. Tyler RS. Tinnitus treatment: clinical protocols. 2006, New York:
Thieme Medical Publishers, Inc.
22. Puga F et al. Functional networks underlying latent inhibition lear-
ning in the mouse brain. Neuroimage. 2007;38(1):171-83.
23. Acoustics in educational settings. Subcommittee on Acoustics
in Educational Settings of the Bioacoustics Standards and Noise
Standards Committee American Speech-Language-Hearing Asso-
ciation. ASHA Suppl. 1995;37(3 Suppl 14):15-9.
24. Bregman AS. Auditory Scene Analysis: the perceptual organization
of sound. MIT Press: Cambridge; 1990.
25. Sussman ES et al. The role of attention in the formation of auditory
streams. Percept Psychophys 2007;69(1):136-52.
26. Clarke S Thiran AB. Auditory neglect: what and where in auditory
space. Cortex. 2004;40(2):291-300.
27. Nager W et al. Preattentive evaluation of multiple perceptual streams
in human audition. Neuroreport. 2003;14(6):871-4.
28. Westman JC, Walters JR. Noise and stress: a comprehensive
approach. Environ Health Perspect. 1981;41:291-309.
29. Ceccaldi M, Clarke S, Meulemans T. [From perception to learning].
Rev Neurol (Paris). 2008;164 Suppl 3:S143-7.
30. Bidet-Caulet A Bertrand O. Dynamics of a temporo-fronto-parietal
network during sustained spatial or spectral auditory processing.
J Cogn Neurosci. 2005;17(11):1691-703.
31. Demanez L, Demanez JP. Central auditory processing assessment.
Acta Otorhinolaryngol Belg. 2003;57(4):243-52.
32. Kraut MA et al. Neuroanatomic organization of sound memory in
humans. J Cogn Neurosci. 2006;18(11):1877-88.
33. Eramudugolla R et al. The role of spatial location in auditory search.
Hear Res. 2008;238(1-2):139-46.
34. Sussman ES. Integration and segregation in auditory scene analy-
sis. J Acoust Soc Am. 2005;117(3 Pt 1):1285-98.
35. Micheyl C et al. The neurophysiological basis of the auditory
continuity illusion: a mismatch negativity study. J Cogn Neurosci.
2003;15(5):747-58.
36. Winkler I. Karmos G, Naatanen R. Adaptive modeling of the unat-
tended acoustic environment reflected in the mismatch negativity
event-related potential. Brain Res. 1996;742(1-2):239-52.
37. Ritter W, Sussman E, Molholm S. Evidence that the mismatch
negativity system works on the basis of objects. Neuroreport.
2000;11(1):61-3.
38. Sussman E et al. Feature conjunctions and auditory sensory me-
mory. Brain Res. 1998;793(1-2):95-102.
39. Sussman E, Winkler I. Dynamic sensory updating in the auditory
system. Brain Res Cogn Brain Res. 2001;12(3):431-9.
40. Ritter W et al. Memory reactivation or reinstatement and the mis-
match negativity. Psychophysiology. 2002;39(2):158-65.
41. Sussman E et al. Temporal integration: intentional sound discrimi-
nation does not modulate stimulus-driven processes in auditory
event synthesis. Clin Neurophysiol. 2002;113(12):1909-20.
42. Sussman ES, Gumenyuk V. Organization of sequential sounds in
auditory memory. Neuroreport. 2005;16(13):1519-23.
43. Naatanen R et al. The mismatch negativity (MMN) in basic rese-
arch of central auditory processing: a review. Clin Neurophysiol.
2007;118(12):2544-90.
44. Picton TW et al. Mismatch negativity: different water in the same
river. Audiol Neurootol, 2000. 5(3-4):111-39.
45. Haenschel C et al. Event-related brain potential correlates of
human auditory sensory memory-trace formation. J Neurosci.
2005;25(45):10494-501.
46. Vinogradova OS. Hippocampus as comparator: role of the two
input and two output systems of the hippocampus in selection and
registration of information. Hippocampus. 2001;11(5):578-98.
47. Naatanen R et al. “Primitive intelligence” in the auditory cortex.
Trends Neurosci. 2001;24(5):283-8.
48. Pulvermuller F et al. Memory traces for words as revealed by the
mismatch negativity. Neuroimage. 2001;14(3):607-16.
49. Miller CT, Dibble E, Hauser MD. Amodal completion of acoustic
signals by a nonhuman primate. Nat Neurosci. 2001;4(8):783-4.
50. Sasaki T et al. Time-shrinking, its propagation, and Gestalt princi-
ples. Percept Psychophys. 2002;64(6):919-31.
51. Hassler R. Striatal control of locomotion, intentional actions and of
integrating and perceptive activity. J Neurol Sci. 1978;36(2):187-
224.
52. Levita L et al. The bivalent side of the nucleus accumbens. Neuroi-
mage. 2009;44(3):1178-87.
53. Hwang JH et al. Brain activation in patients with idiopathic hypera-
cusis. Am J Otolaryngol. 2009;30(6):432-4.
54. Muhlau M et al. Structural brain changes in tinnitus. Cereb Cortex.
2006;16(9):1283-8.
55. Gaser C, Schlaug G. Brain structures differ between musicians and
non-musicians. J Neurosci. 2003;23(27):9240-5.
56. Draganski B et al. Neuroplasticity: changes in grey matter induced
by training. Nature. 2004;427(6972):311-2.
72
International Tinnitus Journal, Vol. 16, No 1 (2010)
www.tinnitusjournal.com
57. Shirayama Y, Chaki S. Neurochemistry of the nucleus accumbens
and its relevance to depression and antidepressant action in ro-
dents. Curr Neuropharmacol. 2006;4(4):277-91.
58. Di Chiara G, Loddo P, Tanda G. Reciprocal changes in prefrontal
and limbic dopamine responsiveness to aversive and rewarding
stimuli after chronic mild stress: implications for the psychobiology
of depression. Biol Psychiatry. 1999;46(12):1624-33.
59. Moreau JL et al. Chronic mild stress-induced anhedonia model of
depression; sleep abnormalities and curative effects of electroshock
treatment. Behav Pharmacol. 1995;6(7):682-7.
60. Gal G, Schiller D, Weiner I. Latent inhibition is disrupted by nucleus
accumbens shell lesion but is abnormally persistent following entire
nucleus accumbens lesion: The neural site controlling the expres-
sion and disruption of the stimulus preexposure effect. Behav Brain
Res. 2005;162(2):246-55.
61. Hallam RS. Psychological approaches of the evaluation and mana-
gement of tinnitus distress. In Tinnitus. Hazell JW. Editor. Edinburgh:
Churchill Livingstone; 1987. p. 156-175.
62. Walpurger V et al. Habituation deficit in auditory event-related
potentials in tinnitus complainers. Hear Res. 2003;181(1-2):57-64.
63. Melcher JR et al. Lateralized tinnitus studied with functional mag-
netic resonance imaging: abnormal inferior colliculus activation. J
Neurophysiol 2000;83(2):1058-72.
64. Smits M et al. Lateralization of functional magnetic resonance
imaging (fMRI) activation in the auditory pathway of patients with
lateralized tinnitus. Neuroradiology. 2007;49(8):669-79.
65. Wolf OT. Stress and memory in humans: Twelve years of progress?
Brain Res; 2009.
66. Buchanan TW, Tranel D, Kirschbaum C. Hippocampal damage
abolishes the cortisol response to psychosocial stress in humans.
Hormones and Behavior; 2009. doi: 10.1016/ j.yhbeh.2009.02.011.
67. Denham SL, Winkler I. The role of predictive models in the formation
of auditory streams. J Physiol Paris. 2006;100(1-3):154-70.
68. Monzani D et al. Psychological profile and social behaviour of
working adults with mild or moderate hearing loss. Acta Otorhino-
laryngol Ital. 2008;28(2):61-6.
69. Cohen RA. The neuropsychology of attention. New York: Plenum
Press; 1993.
70. Zekveld AA et al. Top-down and bottom-up processes in speech
comprehension. Neuroimage. 2006;32(4):1826-36.
71. Bosworth RG, Dobkins KR. The effects of spatial attention on
motion processing in deaf signers, hearing signers, and hearing
nonsigners. Brain Cogn. 2002;49(1):152-69.
72. Rosburg T et al. Hippocampal event-related potentials to tone
duration deviance in a passive oddball paradigm in humans. Neu-
roimage. 2007;37(1):274-81.
73. Kramer SE, Kapteyn TS, Houtgast T. Occupational performance:
comparing normally-hearing and hearing-impaired employees
using the Amsterdam Checklist for Hearing and Work. Int J Audiol.
2006;45(9):503-12.
74. Shim HJ et al. Hearing abilities at ultra-high frequency in patients
with tinnitus. Clin Exp Otorhinolaryngol. 2009;2(4):169-74.
75. Hazell JW, Jastreboff PJ. Tinnitus. I: Auditory mechanisms: a model
for tinnitus and hearing impairment. J Otolaryngol. 1990;19(1):1-5.
76. Haab L et al. Modeling limbic influences on habituation deficits
in chronic tinnitus aurium. Conf Proc IEEE Eng Med Biol Soc.
2009;1:4234-7.
77. van Kuyck K et al. Behavioural and physiological effects of electrical
stimulation in the nucleus accumbens: a review. Acta Neurochir
Suppl. 2007;97(Pt 2):375-91.
78. Miller G. Neuropsychiatry. Rewiring faulty circuits in the brain.
Science. 2009;323(5921):1554-6.
79. Y Shi KB, Anderson V. Martin, Deep brain stimulation effects in
patients with tinnitus. Otolaryngology - Head and Neck Surgery.
2009;141(2):285-7.
80. Loumidis KS, Hallam RS, Cadge B. The effect of written reassuring
information on out-patients complaining of tinnitus. Br J Audiol
1991;25(2):105-9.
81. Axelsson A, Nilsson S, Coles R. Tinnitus information: a study by
questionnaire. Audiology. 1995;34(6):301-10.
