From: Am J Med. 2010 Aug;123(8):711-8

Tinnitus, derived from the Latin word tinnire meaning “to ring,” is the perception of noise in the absence of an acoustic stimulus. It is a common condition that is usually subjective, perceived only by the patient, and therefore diagnosis and monitoring rely on self-report. Data from the 1996 National Health Interview Survey (NHIS) showed tinnitus was experienced by approximately 35-50 million adults in the US, with 12 million seeking medical care, and 2-3 million reporting symptoms that were severely debilitating. Cases and proposed etiologies of tinnitus are clinically heterogeneous and, although several treatment options have been tried, no single cure exists for the condition.

Patients who experience tinnitus often report significant associated morbidities. Lifestyle detriment, emotional difficulties, sleep deprivation, work hindrance, interference with social interaction, and decreased overall health have been attributed to tinnitus. Although causative relations are yet unknown, patients with tinnitus can have increased risk for depression, anxiety, and insomnia.

A limited number of risk factors for tinnitus have been suggested, the best described of which include increasing age, hearing loss, and loud noise exposure. These associations merit further exploration in a large cohort. Furthermore, the relations between tinnitus and other demographic and health factors are minimally characterized in the current literature. Therefore, the authors examined the relation between tinnitus and several potential risk factors using data from the National Health and Nutrition Examination Survey (NHANES), a large nationally representative survey.

The overall prevalence of tinnitus in the US was 25.3%, corresponding to a national estimate of 50 million adults. This prevalence is consistent with the upper range of the overall estimate previously reported from the NHIS (35-50 million). Similar to data from the Beaver Dam cohort, the prevalence of tinnitus in our study increased with age until the age of 60-69 years, after which it decreased with increasing age. This inverse relationship between age and tinnitus in older age groups has been demonstrated in several previous studies. One possible mechanism for this observation is that tinnitus may be associated with other conditions that confer a selective mortality disadvantage among individuals with tinnitus. The possibility also exists, however, that late symptomatic improvement may be part of the natural history of tinnitus.

The results of this study showed that non-Hispanic blacks and Hispanics had lower prevalence of any and frequent tinnitus than non-Hispanic whites. Although decreased prevalence in hearing loss has been reported previously in non-Hispanic blacks and Hispanics compared with non-Hispanic whites, this study is the first to report this association between race/ethnicity and tinnitus. The fact that significant associations between race/ethnicity and tinnitus were maintained in participants without hearing impairment suggests a mechanism for tinnitus that is independent of hearing impairment.

The significant associations between tinnitus and smoking and hypertension in this study suggest that vascular disease might have a greater contribution to the etiology of tinnitus than previously reported. Associations between cigarette smoking and hearing loss have previously been suggested, but data on the association between smoking and tinnitus remains scant. The data from the authors showed that current and past smoking confer increased odds of experiencing tinnitus. Although multiple past studies have analyzed the relation between cardiovascular disease and tinnitus, information on the association between hypertension and tinnitus has, up to now, been limited to cases of pulsatile tinnitus from vascular etiologies. These cases likely represent a minority of patients with tinnitus, as most patients with tinnitus present with subjective, sensorineural tinnitus.

Loud noise exposure is generally considered an important risk factor for developing tinnitus. In this study, history of leisure-time, occupational, and firearm noise exposure were all associated with increased odds of tinnitus. The relation between noise exposure and frequent tinnitus, however, differed depending on the presence or absence of hearing impairment. Occupational noise exposure was associated with increased odds of frequent tinnitus in participants with hearing impairment, while leisure-time noise exposure was associated with increased odds of frequent tinnitus in participants without hearing impairment. Occupational noise exposure has been reported to be strongly associated with both tinnitus and hearing loss, possibly due to its chronic effects on inner hair cell, outer hair cell, and acoustic nerve function. However, after an acute acoustic trauma, tinnitus is reported in the initial stages in 90% of the cases, and often persists even when the hearing loss is temporary. The differential vulnerability of cochlear and central components to duration and intensity of noise exposure may explain the variability between tinnitus and hearing loss in noise-exposed subjects.

These results demonstrate an important relation between tinnitus and mental health, as both anxiety and major depressive disorder were associated with increased odds of tinnitus. Participants with a history of either major depressive disorder or generalized anxiety disorder had greater than twice the odds of reporting any tinnitus compared with those not affected by these disorders. In addition, participants with a history of generalized anxiety disorder had >6 times the odds of reporting tinnitus compared with unaffected participants. Although this study is the first nationally representative study to find an association between tinnitus and mental health disorders, numerous smaller studies have reported similar associations. The cause for these associations is not yet known. Tinnitus can result in sleep deprivation, decreased work productivity, and overall lifestyle detriment. These factors might cause psychological distress and bring about or worsen symptoms of anxiety and depression. Major depressive disorder and generalized anxiety disorder, on the other hand, may exacerbate tinnitus, and their treatment might alleviate tinnitus.

Several strengths and limitations of this study should be considered. Data from NHANES is comprehensive and nationally representative, drawing from a large and diverse sample of participants. The study is, however, cross-sectional, making causative relationships impossible to determine. Tinnitus is most often a subjective complaint without a means of objective diagnosis. Therefore, comparisons between participants and studies are difficult. But, during the period of this study, consistency was maintained in assessing the presence and quality of tinnitus among participants.

In conclusion, these results offer insight into the prevalence of tinnitus and identify potentially vulnerable groups. We have demonstrated that, although the prevalence of tinnitus is generally higher at older ages, it also is frequently reported in young adults. Likewise, the potential risk factors for developing tinnitus are significant even in the younger adults. Therefore, opportunities may exist to prevent tinnitus, starting at a younger age. As no known cure exists for tinnitus, it is important to investigate potentially modifiable risk factors for tinnitus. Future research should examine the prospective relations between smoking, hypertension, noise exposure, and mental health conditions and tinnitus.

Clinical Significance:
•Tinnitus is a very common and potentially disabling condition, but few risk factors for its development are currently known.
•The relations between tinnitus and other demographic and health factors are minimally characterized in the current literature.
•Because tinnitus currently has no known cure, identifying potentially vulnerable groups and establishing potential risk factors in a large, nationally representative study is important for decreasing the burden of this condition.

From: Eur Arch Otorhinolaryngol. 2010 Jun 25. [Epub ahead of print]

The aim of this work is to study the characteristics of tinnitus both in normal hearing subjects and in patients with hearing loss. The study considered tinnitus sufferers, ranging from 21 to 83 years of age, who were referred to the Audiology Section of Palermo University in the years 2006-2008. The following parameters were considered: age, sex, hearing threshold, tinnitus laterality, tinnitus duration, tinnitus measurements and subjective disturbance caused by tinnitus. The sample was divided into Group1 (G1), 115 subjects with normal hearing, and Group2 (G2), 197 subjects with hearing loss. Especially for G2, there was a predominance of males compared to females; the highest percentage of tinnitus resulted in the decades 61-70 and >70 with a significant difference for G2 demonstrating that the hearing status and the elderly represent the principal tinnitus-related factors.

The hearing impairment resulted in most cases of sensorineural hearing loss type and was limited to the high frequencies; the 72.1% of the patients with sensorineural hearing loss had a high-pitched tinnitus, while the 88.4% of the patients with a high-frequency sensorineural hearing loss had a high-pitched tinnitus. As to the subjective discomfort, the catastrophic category was the most representative among G1 with a significant difference between the two groups; no correlation was found between the level of tinnitus intensity and the tinnitus annoyance confirming the possibility that tinnitus discomfort is elicited by a certain degree of psychological distress as anxiety, depression, irritability and phobias.

In Auris Nasus Larynx. 2010 Apr 27. Characteristics of tinnitus with or without hearing loss: Clinical observations in Sicilian tinnitus patients. It was concluded that the hearing status and the elderly represent the principal tinnitus related factors; moreover tinnitus characteristics differ in the two groups for tinnitus pitch. There is, in fact, a statistically significant association between high-pitched tinnitus and high-frequency sensorineural hearing loss suggesting that the auditory pathway reorganization induced by hearing loss could be one of the main source of the tinnitus sensation.

In Eur Arch Otorhinolaryngol. 2008 Nov;265(11):1295-300. Tinnitus with or without hearing loss: are its characteristics different? This study confirmed that tinnitus is most frequently associated with hearing loss. The characteristics of tinnitus in normal hearing subjects, except for the subjective judgment of tinnitus intensity, the pitch and the inhibition, are significantly different for those observed in subjects with hearing loss. The association of tinnitus and hearing deficit seems to increase the perceived severity of the symptom.

From: J Sleep Res. 2010 Jun 16. [Epub ahead of print]

Chronic tinnitus, or the perception of hearing sounds without the presence of external stimulation, is estimated at about 10-15% of the population, with highest prevalence after 50 years of age. Sleep complaints are among the most prominent complaints accompanying tinnitus, but objective data are rare. In this study, we examined prospectively the subjective and objective sleep parameters of this patient population in order to determine differences in sleep disturbances associated with chronic tinnitus compared to matched controls. Forty-four subjects (22 with tinnitus and 22 controls without tinnitus), unselected with respect to sleep complaints, participated in this study. The analysis involved 1-week sleep diaries, subjective sleep questionnaires and 1 night of polysomnographic (PSG) assessment. Compared to matched controls, the tinnitus group showed lower subjective sleep quality as measured with the Pittsburgh Sleep Quality Index (PSQI) and sleep diaries, but no significant difference in objective polysomnograph sleep parameters (i.e. sleep latency, efficiency). However, quantitative non-rapid eye movement sleep analysis revealed lower spectral power in the delta frequency band in the tinnitus group compared to controls, and this decrease was correlated with subjective sleep complaints (the lower the delta spectral power, the greater the complaints). This is the first report of an electrophysiological correlate of sleep difficulties supportive of subjective sleep complaints in the tinnitus population.

From: Exp Brain Res. 2010 May 28. [Epub ahead of print]

Somatic tinnitus has been defined as tinnitus temporally associated to a somatic disorder involving the head and neck. Several studies have demonstrated the interactions between the somatosensory and auditory system at the dorsal cochlear nucleus, inferior colliculus, and parietal association areas. The objective is to verify the effect of transcutaneous electrical nerve stimulation of the upper cervical nerve (C2) in the treatment of somatic tinnitus. As electrical stimulation of C2 increases activation of the dorsal cochlear nucleus through the somatosensory pathway and enlarges the inhibitory role of the dorsal cochlear nucleus on the central nervous system, C2 TENS can be considered for tinnitus modulation. A total of 240 patients in whom tinnitus is modulated by somatosensory events (e.g., tinnitus change with rotation, retro- and antiflexion of neck) or modulated by pressure on head or face were included in this study. Both a real and a sham TENS treatment were applied for 30 min (10 min of 6 Hz, followed by 10 min of 40 Hz and 10 min of sham). Significant tinnitus suppression was found. Only 17.9% (N = 43) of the patients with tinnitus responded to C2 TENS. They had an improvement of 42.92%, and six patients had a reduction of 100%.

From: Prog Brain Res. 2007;166:389-94. Trans-electrical nerve stimulation (TENS) for somatic tinnitus.

The somatic tinnitus syndrome includes those forms of tinnitus that are associated with a somatic disorder involving the head and upper neck. It has been suggested that physiological mechanisms where interactions occur between the somatosensory and auditory systems are the etiology for that kind of tinnitus. Trans-electrical nerve stimulation (TENS) of areas of skin close to the ear increases the activation of the dorsal cochlear nucleus through the somatosensory pathway and may augment the inhibitory role of this nucleus on the CNS and thereby ameliorate tinnitus. In a prospective descriptive study of 26 patients with the probable diagnosis of somatic tinnitus we found that TENS could improve the tinnitus in 46% of the participants (23% did not hear it anymore, and in 23% its intensity was reduced). VAS scores improved from 6.5 to 6.0 after 2 weeks of treatment. Patients used TENS at home for 2h, once per day during 2 weeks (alternating ramped burst, 150 pps, with pulse duration of 100 micro s, amplitude 0-60 mA; average TENS intensity was 27 mA). Intermittent “typewriter” type of tinnitus was the most responsive. Somatic tinnitus without otologic disease had better response than tinnitus associated to otological causes.

From: J Laryngol Otol. 2006 Jun;120(6):442-5. Epub 2006 Mar 24. Treatment of tinnitus with transcutaneous electrical nerve stimulation improves patients’ quality of life.

Tinnitus can adversely affect patients’ quality of life. Transcutaneous electrical nerve stimulation (TENS) may be effective in the management of tinnitus. No study has investigated the efficacy of TENS for the management of tinnitus by means of quality of life measures. In this study, we evaluated the efficacy of TENS for the management of tinnitus symptoms by using the visual analogue scale (VAS), tinnitus handicap inventory test, Nottingham health profile (NHP) and short form-36 (SF-36) questionnaires. Twenty-two patients were included in this study (male/female, 16/6; mean age, 48.04 +/- 15.57 years). Nine patients had unilateral and 13 patients had bilateral tinnitus. After TENS, improvement measured by VAS was only marginally significant. However, after TENS, there were statistically significant improvements regarding tinnitus severity scores, tinnitus handicap inventory scores, NHP fatigue, social isolation and emotional problems scores, and many parameters measured by the SF-36 (physical functioning, general health, vitality, social functioning, role limitations due to emotional problems, and mental health). Transcutaneous electrical nerve stimulation is a useful method to improve the quality of life of patients with tinnitus.

From: Otolaryngol Pol. 2008;62(5):601-5. Electrical stimulation as an alternative method of tinnitus treatment.

The aim of the study was to evaluate the influence of the selective electrical stimulation of the hearing organ on tinnitus in people with sensorineural hearing loss. The study comprised 248 tinnitus patients treated by using electrical stimulation. The material was divided into two groups, regarding the method of stimulation. In group I–168 people, transtympanal electrical stimulation of the promontory was applied, whereas in group II–80 people, hydrotransmissive technique was used. ENT examination, audiological and radiological diagnostics, as well as the evaluation of the audiometric parameters of tinnitus was performed. The patients were asked to fill in the questionnaire concerning tinnitus. In 80 patients hydrotransmissive electrical stimulation was conducted using the own prototype device, in 168 patients–transtympanal stimulation, after local anaesthesia with Xylocain gel. RESULTS: On the whole, in group of 248 patients, subjective improvement (decrease in the severity of tinnitus) was noticed in 130 people (52.4%), comprising 32 cases (13%) of total relief. In 93 patients (37.5%) tinnitus remained unchanged, and in 25 (10.1%) the deterioration was observed. The comparison of the results of two electrical stimulation methods, showed the superiority of hydrotransmissive one (improvement in 58.75% of patients), however, the number of cases of total relief was greater in the case of transtympanal method (15.5%). Considering subjective evaluation, as well as audiometric (the intensity and the frequency parameters, MML) the hydrotransmissive method appeared to be more effective (improvement in 53.75%) comparing to transtympanal stimulation (improvement in 44.6%). On the basis of studies conducted in the Clinic and the long history of the electrical stimulation administration in tinnitus treatment, it can be stated that this method may by applied in cases, in which other therapeutical methods failed.

From: Acta Otolaryngol Suppl. 2006 Dec;(556):20-6. Summary of evidence pointing to a role of the dorsal cochlear nucleus in the etiology of tinnitus.

Evidence has accumulated in the last decade that the dorsal cochlear nucleus may be an important site in the etiology of tinnitus. This evidence comes from a combination of studies conducted in animals and humans. This paper will review the key findings, as follows. 1) Direct electrical stimulation of the dorsal cochlear nucleus leads to changes in the loudness of tinnitus. This suggests that the loudness of tinnitus may be linked to changes in the level of neural activity in the dorsal cochlear nucleus. 2) Exposure to tinnitus inducers, such as intense sound or cisplatin, causes neural activity in the dorsal cochlear nucleus to become chronically elevated, a condition known as neuronal hyperactivity. 3) This hyperactivity is very similar to the activity that is evoked in the dorsal cochlear nucleus by sound stimulation, suggesting that the hyperactivity represents a code that signals the presence of sound, even when there is no longer any sound stimulus. 4) Noise-induced hyperactivity in the dorsal cochlear nucleus is correlated with tinnitus. Behavioral studies have demonstrated that animals exposed to the same intense sound that causes hyperactivity in the dorsal cochlear nucleus develop tinnitus-like percepts. The correlation between the level of hyperactivity and the behavioral index of tinnitus was found to be statistically significant. 5) The dorsal cochlear nucleus is a polysensory integration center, and electrophysiological studies have shown that both spontaneous activity and hyperactivity of neurons in the dorsal cochlear nucleus can be modulated by stimulation of certain ipsilateral cranial nerves, such as the sensory branch of the trigeminal nerve. This ipsilateral modulation of dorsal cochlear nucleus activity offers a plausible explanation of how tinnitus, when perceived on one side, can be modulated by certain manipulations of the head and neck on the side ipsilateral to the tinnitus, but rarely on the contralateral side. 6) The dorsal cochlear nucleus exhibits various forms of neuronal plasticity that parallel the various forms of plasticity that characterize tinnitus. These findings collectively strengthen the view that the dorsal cochlear nucleus may be a key structure that should be included as a target of anti-tinnitus treatment.

The dorsal cochlear nucleus as a participant in the auditory, attentional and emotional components of tinnitus

From: Am J Otolaryngol. 2010 Apr 29. [Epub ahead of print]

The pathophysiology of tinnitus is obscure and its treatment is therefore elusive. Significant progress in this field can only be achieved by determining the mechanisms of tinnitus generation, and thus, histopathologic findings of the cochlea in presbycusis with tinnitus become crucial. We revealed the histopathologic findings of the cochlea in subjects with presbycusis and tinnitus.

The subjects were divided into 2 groups, presbycusis with tinnitus (tinnitus) group and presbycusis without tinnitus (control) group, with each group comprising 8 temporal bones from 8 subjects. We quantitatively analyzed the number of spiral ganglion cells, loss of cochlear inner and outer hair cells, and areas of the stria vascularis and spiral ligament.

There was a significantly greater loss of outer hair cells in the tinnitus group compared with the control group in the basal and upper middle turns. The stria vascularis was more atrophic in the tinnitus group compared with the control group in the basal turn. Tinnitus is more common in patients with presbycusis who have more severe degeneration of outer hair cells and stria vascularis.

Note: We have changed the format of our Tinnitus Handicap Inventory to a form which generates scores and definitions online for immediate results.

Tags: tinnitus,, hair, cells,, presbycusis,, degeneration

From: BMC Neurosci. 2010 Mar 24;11(1):40. [Epub ahead of print]

Tinnitus is an auditory phantom perception, reported subjectively as a tone and/or a noise, in the absence of an external stimulus. Approximately 5-15 % of the general population experience tinnitus. In 1-3% of the general population the tinnitus affects the quality of life, involving sleep disturbance, work impairment and psychological distress. The underlying physiological mechanisms that lead to phantom sensation are still being explored. In most cases, tinnitus is accompanied by an audiometrically measurable hearing loss, and even in a majority of those cases with normal audiograms abnormal outer or inner hair-cell function has been reported correlating with the presence of tinnitus.

Contemporary views of tinnitus emphasize the role of the central auditory system. Studies in anaesthetized animals suggest enhanced firing rate and /or synchronized firing to be a necessary neurophysiological mechanism underlying tinnitus. A reduction of tinnitus intensity in patients has been correlated to reduction of delta band power.

Alterations in spontaneous central neuronal activity patterns after peripheral deafferentations have recently been proposed to be essential in the genesis of tinnitus. A relevance for peripheral deafferentation has also been proposed in the field of neurogenic pain, which prompted some authors to envisage that a similar mechanism might be at the source of tinnitus and neurogenic pain. Peripheral deafferentation leads to thalamic deactivation, which in turn disrupts normal thalamocortical interaction, thus leading to the appearance of tinnitus. The effects of an abnormal thalamocortical interaction can be analysed at the cortical level using magnetoencephalogram or electroencephalogram. This sequential view integrates both the induction in the periphery and the generation at the thalamocortical level of tinnitus. In the following, the authors refer to a mechanism that focuses on thalamocortical interplay. First evidence for this mechanism in tinnitus was the finding of low-threshold calcium spike bursts in the medial thalamus. 50% of neuronal activity in the medial thalamus (central lateral nucleus, central lateral nucleus) was characterized as low-threshold calcium spike bursts. Low-threshold calcium spike bursts displayed a delta/theta rhythmicity, with a mean interburst discharge rate of 4 Hz. low-threshold calcium spikes have been described intracellularly in in vitro and in vivo experiments and have been related to a state of membrane hyperpolarization. In tinnitus this would be a consequence of auditory deprivation caused by peripheral damage.

The central lateral nucleus is part of the medial thalamus, is diffusely connected to wide cortical areas and is thought to serve as a non-specific amplifier of thalamocortical activity. The thalamocortical loop constitutes an important component contributing to the rhythmicity of scalp electroencephalogram and magnetoencephalogram. The 4 Hz discharge rate of thalamic low-threshold calcium spike bursts may be supposed to attract the thalamocortical system into low electroencephalogram frequencies, a proposition which is at the base of this and other studies. Thus analyzing spectral features of continuously recorded electroencephalogram offers a window for the investigation of abnormal thalamocortical interplay in tinnitus patients. Surprisingly, even though spontaneous activity has been a frequent research target in animal models of tinnitus, studies in humans have been rare. A few studies have looked at the resting oscillatory electroencephalogram/magnetoencephalogram in tinnitus patients as compared to healthy controls. In a resting electroencephalogram study of patients with severe tinnitus as compared to healthy controls a significant increase of Z-score power over the frequency ranges from 0.5 to 22 Hz was reported, which was dominant in fronto-temporal electrodes. Another electroencephalogram study described an increase and decrease of average total power in female and male patients as compared to healthy controls, respectively. A further study of spontaneous brain activity reported temporal and fronto-temporal changes (increases and decreases) of relative power in individuals with severe tinnitus. Most recently, an magnetoencephalogram study found an increase and decrease of delta and alpha power respectively in tinnitus patients as compared to healthy controls.

Further studies emphasized the relevance of gamma (> 40 Hz) activity to the pathophysiology of tinnitus. The aforementioned findings have been incongruous, showing both increase and decrease in different frequency band power. Therefore the characteristic of different frequency bands remains an ongoing debate in the pathogenesis of tinnitus. Otherwise, attempts to study tinnitus in humans have focused on the use of designs that measure neurophysiological responses to sounds or experimental manipulations that enhance or reduce the perceived loudness. In a recent experiment of that kind, Kahlbrock and Weisz found transient reductions of tinnitus intensity following the offset of a masker (so-called residual inhibition, residual inhibition), accompanied by significant reduction in the delta frequency band. These changes were specific to a masker inducing residual inhibition and not observed with maskers that do not.

In light of the high variability of results we still lack sufficient knowledge of the anomalies of the resting electroencephalogram state in tinnitus patients, and the localization of cortical generators at the source of the observed power excesses has not been investigated in detail.

In the present study, the authors use power spectrum analysis and source localization of electroencephalogram data to identify cortical regions with changes in the underlying spontaneous activity patterns in individuals with tinnitus under both conditions eyes closed and eyes open as compared to healthy controls.

The authors findings can be added to the microphysiological and magnetoencephalographic evidence for a thalamocortical dysrhythmic process at the source of tinnitus, characterised by a low frequency overproduction in thalamocortical loops.

This study on chronic tinnitus shows power enhancement of the spontaneous electroencephalogram activity, and localizes corresponding cortical generators of this dysrhythmic activity. Our most striking finding in the electroencephalogram spectra of the patient group is the delta and theta electroencephalogram power enhancement. An increase of cortical activity is in line with a previous magnetoencephalogram report of excess power in the whole frequency range for positive symptoms and an increase of delta in tinnitus patients compared to healthy controls. It is at variance with an earlier report. This variance may be due to 1) the size of the patient groups and/or the selection of patients, and 2) the specific choice of frequency bands entering the statistical analysis. The authors analysis is less likely to be biased in this respect, since Z-values are calculated for each frequency point. Concerning the statistics for band powers, the authors have corrected for multiple comparisons using false discovery rate, yielding more potent statistical inference to this study.

The general increase in power in delta, theta and beta frequency ranges is confirmed if individual electrodes are analysed. This increase is generalized for theta and delta, and limited to fronto-centro-parietal sites in the beta domain. An increase of alpha is also found in the eyes open condition, localized on similar areas as delta and theta and indicating thus a participation of this frequency band in the thalamocortical dysrhythmia tinnitus process. An increase in low and high frequencies is in line with the concept of thalamocortical dysrhythmia and may reflect the outspoken and chronic thalamocortical dysrhythmia involvement of our patient group. This may explain the differences with the study of Weisz et al., where only delta increase and a reduction of alpha were observed. Reduction of delta band power and theta band power after neurofeedback speaks for a causal relevance of slow oscillation increase in tinnitus. In an magnetoencephalogram case study, Llinas et al. obtained a general (delta to beta) spectral power reduction after tinnitus masking.

In the delta, theta, alpha and beta bands, the cortical generators of excess electroencephalogram power were located in dominantly left auditory (Brodmann area) temporo-parietal, insular posterior, cingulate anterior and parahippocampal cortical areas. Such a localization is in accordance with data from metabolic studies and speaks for a dysrhythmic co-involvement of associative and paralimbic areas in the pathogenesis of tinnitus, which is consistent with their topographic and functional vicinity with the auditory system. Many other studies pointed out the involvement of associative/paralimbic areas and the importance of reactive emotional factors in tinnitus has been repeatedly reported, as well as reciprocal involvement of auditory and associative/paralimbic areas. The authors observe a dominance on the left side for both thalamocortical dysrhythmia and tinnitus. At the time, the authors can only speculate that this observation is related to cognitive/emotional factors, e.g. the relevance of the non-acceptance of, and related frustration about, the presence of tinnitus. This non-acceptance may be viewed as primarily conceptual, i.e. left-side dominant.

Following the proposition of Llinas of a central relevance of thalamocortical interaction in the genesis of hemispheric function and encouraged by earlier finding of strong thalamocortical coupling, the authors propose here an interpretation of results in the framework of thalamocortical dysrhythmia. This thalamocortical concept for neurogenic pain, abnormal movements, epilepsy, tinnitus and neuropsychiatric disorders was proposed on the basis of experimental, and clinical evidence in the mentioned diseases. It may be characterized by the following sequential set of events:

(1) A lesion leads to deafferentation of excitatory inputs on thalamic relay cells and initiates the tinnitus syndrome. The deafferentation of excitatory inputs results in disfacilitation and cell membrane hyperpolarization.

(2) In the hyperpolarized state, deinactivation of calcium T-channels causes thalamic relay neurons to fire low-threshold calcium spike bursts at delta/theta frequency.

(3) Bursting thalamic relay neurons exert a rhythmic influence on thalamocortical loops in the delta/theta frequency band. Thalamic and cortical areas are densely and reciprocally interconnected. The tight functional coupling between thalamus and cortex is confirmed by the high theta coherence between the two. This coupling is sustained by thalamocorticothalamic and also by thalamoreticulothalamic and corticoreticulothalamic recurrent projections. The tendency of the thalamocortical network to maintain a given functional modality reinforces the hyperpolarized state over time.

(4) Divergent thalamocortical, corticothalamic and reticulothalamic projections provide the anatomical substrate for diffusion of low frequency activity to an increasing number of neighbouring thalamocortical loops.

(5) After recruitment of a sufficiently large number of thalamocortical loops, excess delta/theta power becomes measurable. Increased low-frequency oscillations also occur during sleep and cognitive tasks, where they are considered as normal. It is the continuous, widespread and state-independent overproduction of slow rhythms in the awake brain that characterizes thalamocortical dysrhythmia.

(6) The final step towards the production of tinnitus is related to the reciprocal cortico-cortical inhibition mediated by GABrodmann areaergic interneurons, which is a general feature of cortical organization (Fig. 6C). thalamocortical modules in delta/theta mode exert less collateral inhibition on neighboring modules, which are thereby overactivated in high (beta/gamma) frequencies. This event has been termed “edge effect”. The concept is inspired by the effect of lateral inhibition in the retina. It has also been considered in the periphery of the auditory system. The asymmetrical inhibition between a low frequency cortical area and neighbouring high frequency domains provides a ring of reduced inhibition onto, and thus activation of, the cortex surrounding this low frequency area. Support for such an effect was first provided by the increased interfrequency covariation between theta and beta ranges in magnetoencephalogram. Recently, the increase of high frequency activation around a core of theta modules could be demonstrated in a slice preparation.

Plasticity mechanisms have been proposed to be at the base of the appearance of tinnitus. The following observations speak however for the necessity of at least another mechanism. The presence of a deficit after a damage to the auditory system and the induction of plastic mechanisms are both seen to happen in all deafferentation situations, whereas tinnitus, quite like neurogenic pain, develops and maintains itself along years only in a small (less than 10%) percentage of all deafferented subjects. Plastic map reorganizations, as argued by Weisz and collaborators, certainly contribute to the new post-lesional situation, but cannot satisfactorily explain the emergence and maintenance of tinnitus.

Accumulating evidence from electroencephalogram and magnetoencephalogram studies underscores the fact that conceptual and emotional activations increase hemispheric theta activity. The electroencephalogram source localization data confirm other studies demonstrating the coactivation of cortical auditory and associative/paralimbic areas. This provides a substrate for a role of mental functions in the reactive modulation of neurogenic (i.e. due to auditory deafferentation) tinnitus and the generation of psychogenic tinnitus. Indeed, a top-down activation of the divergent corticothalamic projection from associative/paralimbic onto auditory areas, when strong and long-lasting enough to cause sustained thalamic overinhibition, might be at the source of an increase of theta production and, thus, of an amplification of neurogenic tinnitus mechanisms. It may even be at the origin of psychogenic tinnitus. One of the most deleterious conceptual/emotional dynamics is, in this experience, frustration and non-acceptance of the disease-related health impairment. The conceptual and practical consequences of these considerations are obvious and have a wide range of implications for the therapeutic support of neurogenic and psychogenic tinnitus patients. These include the recognition of a dual origination of tinnitus (neurogenic and psychogenic), in body and mind, respectively, but the existence of a common thalamocortical mechanism for both.

Source: Temporo-insular enhancement of EEG low and high frequencies in patients with chronic tinnitus

From: Cochrane Database Syst Rev. 2010 Mar 17;3:CD007330

Tinnitus is described as the perception of sound or noise in the absence of real acoustic stimulation. Although an outright cure for tinnitus remains elusive, various management strategies have been developed to help to lessen the impact of the symptom. Following the publication of a neurophysiological model of tinnitus, Tinnitus Retraining Therapy was developed. Using a combination of directive counselling and sound therapy in a strict framework, this is one of the most commonly used treatment modalities for tinnitus. Many studies refer to the use of Tinnitus Retraining Therapy where in fact a modified version of this therapy is actually being implemented. It is therefore important to confirm the use of authentic Tinnitus Retraining Therapy when reviewing any study that reports its use.

To assess the efficacy of Tinnitus Retraining Therapy in the treatment of tinnitus, the search included the Cochrane ENT Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE and reference lists of identified publications. The date of the most recent search was 26 August 2009. Randomised controlled trials of Tinnitus Retraining Therapy versus no treatment, or other forms of treatment, in adult patients with tinnitus were selected. Both authors critically appraised the retrieved studies for risk of bias and extracted data independently. Where necessary, we contacted the original study authors for further information.

Only one trial (123 participants) was included in the review. Several excluded trials did not follow the strict protocol for Tinnitus Retraining Therapy, evaluating instead a modified form of Tinnitus Retraining Therapy. The included trial showed Tinnitus Retraining Therapy to be more effective than a tinnitus masking approach. In this study outcome data for tinnitus severity were presented using three instruments (Tinnitus Handicap Inventory, Tinnitus Handicap Questionnaire, Tinnitus Severity Index) for patients in three groups (participants’ tinnitus being a ‘moderate problem’, big problem’ or ‘very big problem’).

At 18 months, improvements for the three groups in the three scores (Tinnitus Retraining Therapy versus Tinnitus Masking) were respectively: ‘moderate problem’ – Tinnitus Handicap Inventory: 18.2 versus 4.6, Tinnitus Handicap Questionnaire: 489 versus 178, Tinnitus Severity Index 7.5 versus 1.6; ‘big problem’ – Tinnitus Handicap Inventory: 29.2 versus 16.7, Tinnitus Handicap Questionnaire: 799 versus 256, Tinnitus Severity Index: 12.1 versus 6.7; and ‘very big problem’ – Tinnitus Handicap Inventory: 50.4 versus 10.3, Tinnitus Handicap Questionnaire; 1118 versus 300, Tinnitus Severity Index: 19.7 versus 4.8.

A single, low-quality randomised controlled trial suggests that Tinnitus Retraining Therapy is much more effective as a treatment for patients with tinnitus than tinnitus masking.

Related Sources:

Tinnitus retraining therapy: implementing the neurophysiological model |
Guide to conducting tinnitus retraining therapy initial and follow-up interviews | Tinnitus Retraining Therapy | The TRT method in practice

From: Med Hypotheses. 2010 Mar 6. [Epub ahead of print]

Melatonin has been proposed as a treatment for tinnitus, especially on the basis of its favourable effects on sleep and its vasoactive and antioxidant properties. However, to the authors knowledge no attempts of interpretation have been advanced through a detailed analysis of the various specific properties of melatonin possibly cooperating in a coincidental way to relieve tinnitus: among these, its modulatory effect on central nervous system resulting in a protective mechanism against an exaggerated sympathetic drive; its capacity to induce a more steady hemodynamic condition, through a multifactorial and multi-organ activity, resulting in a more regular labyrinthine perfusion; a possible action on the skeletal muscle tending to a reduction of the muscular tone, which could relieve tinnitus of muscular origin deriving from tensor tympani tonic contractions; its possible reported antidepressive effect, which could indirectly act on tinnitus; a direct regulation of inner ear immunity as proposed in literature when melatonin was reported to be present in the inner ear.

All these observations seem to indicate melatonin as a tool deserving a greater attention than other antioxidants in the attempt of relieving tinnitus, justifying its application from a more precise rationale based on a series of physio-pathological aspects.

From: HNO. 2010 Mar 4. [Epub ahead of print] [Article in German]

Comorbidity is the presence of one or more disorders in addition to the main disorder. Comorbidities negatively influence the development of the main disease. For patients with tinnitus a comorbidity is an additional component complicating the habituation of ear noise and patients with decompensated tinnitus often have psychological comorbidities, e.g. affective, somatoform or anxiety disorders. At the time of first presentation and also during further follow-up, it is essential to pay particular attention to the presence of potential comorbid mental disorders. This is of special importance for patients with decompensated ear noise (severity grades 3 and 4). For ENT specialists it is important that the mental discomfort of patients must be taken seriously and should be identified through a targeted diagnosis. Effective treatment of the co-symptoms using cognitive behavior therapy (CBT) in conjunction with medication often reduces the severity of tinnitus perception and discomfort.

From: Exp Brain Res. 2010 Feb 26. [Epub ahead of print]

Tinnitus is considered as an auditory phantom percept. Preliminary evidence indicates that transcranial direct current stimulation of the temporo-parietal area might reduce tinnitus. Transcranial direct current stimulation studies of the prefrontal cortex have been successful in reducing depression, impulsiveness and pain. Recently, it was shown that the prefrontal cortex is important for the integration of sensory and emotional aspects of tinnitus. As such, frontal transcranial direct current stimulation might suppress tinnitus as well. In an open label study, a total of 478 tinnitus patients received bilateral transcranial direct current stimulation on dorsolateral prefrontal cortex (448 patients anode right, cathode left and 30 anode left, cathode right) for 20 min. Treatment effects were assessed with visual analogue scale for tinnitus intensity and distress.

No tinnitus suppressing effect was found for transcranial direct current stimulation with left anode and right cathode. Analyses show that transcranial direct current stimulation with right anode and left cathode modulates tinnitus perception in 29.9% of the tinnitus patients. For these responders a significant reduction was found for both tinnitus related distress and tinnitus intensity. In addition, the amount of suppression for tinnitus related distress is moderated by an interaction between tinnitus type and tinnitus laterality. This was, however, not the case for tinnitus intensity. This study supports the involvement of the prefrontal cortex in the pathophysiology of tinnitus.

Related: Chronic Back Pain Is Associated with Decreased Prefrontal and Thalamic Gray Matter Density There was a relationship between the dorsolateral prefrontal cortex and perceived pain. The authors suggested that the pattern of brain atrophy is directly related to the perceptual and behavioral properties of chronic back pain. Gray matter density was reduced in bilateral dorsolateral prefrontal cortex and right thalamus and was strongly related to pain characteristics in a pattern distinct for neuropathic and non-neuropathic chronic back pain.

Is there a relationship between chronic pain and tinnitus?