A Literature Review of Tinnitus
Andrew Folz
Rockhurst University

Abstract

Tinnitus is the perception of sound within the human ear when no actual sound is present. Tinnitus usually interpreted as a ringing sound that varies in frequency and loudness. There are many causes of tinnitus along with symptoms that are caused by tinnitus. Millions of people, primarily men, are affected with chronic tinnitus that usually leads to hearing loss. This literary review of Tinnitus will cover a current, basic knowledge of tinnitus, possible causes of tinnitus, conditions that may cause tinnitus, experiments involving mice to discover new findings in tinnitus research, and possible treatments that are currently being studied.

Tinnitus is the perception of sound within the human ear when no actual sound is present. Though often unrecognized, tinnitus affects millions of people worldwide. Tinnitus is one of the most common physical symptoms. It affects 10-15% of the population at some point in their lives (Holmes and Padgham, 2009). Derived from the Latin word, “tinnire,” which means to ring, tinnitus is commonly experienced as high-pitched noise with mechanical, electrical, or musical qualities. The underlying pathophysiology of tinnitus is unclear. It seems unlikely there is a single underlying cause, but tinnitus may accompany almost any auditory dysfunction. Damage to the middle ear, cochlea, audiovestibular nerve, and cerebral pathways between the cochlear nucleus and primary auditory cortex may explain its origins (Holmes and Padgham, 2009). Tinnitus is the most common injury arising from the conflicts in Afghanistan and Iraq. About 75% of young adults who attend nightclubs and concerts experience temporary tinnitus from the loud music. Tinnitus also may arise during periods of stress, like finals week for college students. Tinnitus may be unilateral or bilateral. It may also be pulsatile, which means it coincides with the heartbeat. This suggests a vascular source whereas the more non-pulsatile tinnitus is continuous and constant. The prevalence of tinnitus increases with age. Over time, 85% of patients with tinnitus also have hearing loss. Tinnitus is a symptom, not a disease. This review of tinnitus will highlight some of the conditions that cause tinnitus (especially depression), discuss animal testing and other methods used for tinnitus research, and discuss the most recent studies on possible treatment of tinnitus. Tinnitus can be the cause for substantial deterioration of life quality. In particular, severely distressing tinnitus tends to be associated with increased levels of depression, anxiety, and somatic symptom severity (Balkenhol et al., 2013). Traumatic brain injury is one of the leading causes of tinnitus. Recent studies show that 15.8% of service members in the Iraq war experienced traumatic brain injury experienced traumatic brain injury (Kreuzer et al., 2012). Trauma to the head, especially the ear, is often associated to tinnitus. Patients suffering from trauma-associated tinnitus suffer from a high mental burden than tinnitus patients presenting with phantom perceptions based on other or unknown factors. Kreuzer et al.’s study also indicated that there was a high percentage of males with tinnitus (2012). Over 70% of the patients who reported tinnitus related to exposure to a loud noise were male. Many studies have investigated rates of depression amongst people with tinnitus. Past studies of tinnitus have assumed that any emotional component and limbic system involvement will reflect a learned response to distress (Languth et al., 2011). Insomnia, depression, or anxiety were believed to give proof of this relationship. Recent research though has suggested that the interplay between tinnitus and emotions may be more complex. In some cases, depressive symptoms will manifest as a reaction to tinnitus. Tinnitus patients do not have all of the signs of depression. Tinnitus patients frequently complain about fatigues, irritability, insomnia, exhaustion, and concentration. These are secondary symptoms of depression; primary symptoms of depression like depressed mood and loss of interest are often less pronounced in tinnitus (Languth et al, 2011).

Tinnitus and depressive like symptoms continue to be linked. In a two-year study, researchers found that when patients with tinnitus and depression were treated for the depression like symptoms, both the depression and the tinnitus symptoms decreased (Hebert et al, 2012). Hearing loss and change in hearing loss are stronger predictors for tinnitus prevalence. Tinnitus severity and prevalence were reduced when the depression like symptoms were treated. The study suggests that depression and tinnitus and depression are associated with each other and may be due to comorbidity.
Tinnitus may also be linked with post traumatic stress disorder. Case history reports indicated that veterans associated tinnitus-related disruptions with recall of traumatic events, nightmares, and exaggerated startle responses to unexpected sounds that interfered with patients’ daily activities (Fagelson, 2007). The patients with tinnitus and PTSD were more likely to present with the most severe tinnitus. Reviews of imaging studies conducted on patients with either tinnitus or PTSD revealed that both conditions were associated with, or produced, physical changes to the thalamus, hippocampus, and the amygdala, all of which are involved in the limbic system. The study therefore concluded that there must be a common mechanism that is activating both PTSD and tinnitus, especially when the trauma involved loud noises such gunshots. Discovering new information and finding new treatments on tinnitus can be dangerous to humans. Instead of using humans for research, especially in the beginning stages, rodents and other animals are used to test various theories associated with tinnitus. For instance, researchers realized that tinnitus is almost always associated with peripheral hearing loss.
This led to the hypothesis that damage to peripheral auditory structures leads to central reorganization and that this maladaptive reorganization may lead to tinnitus (Llano et al, 2012). The finding has led to many different animal models. One study used 13 male mice to examine the earliest level of cortical processing by studying the effects of stimulating afferents to the auditory cortex with behavioral evidence of tinnitus (Llano et al, 2012). Auditory cortical activation was measured using flavoprotein autofluorescence. Of the 13 mice, 6 were exposed to noise trauma, 4 were exposed to sham (placebo) conditions, and 3 were used as a control. The study confirmed its hypothesis in that animals with noise exposure demonstrate changes in auditory cortical responses to afferent stimulation. Noise-exposed animals show a greater magnitude of auditory cortical activation and show a diminished sensitivity to GABA(a). blockade compared to control animals. Sensitivity to the auditory complex did not appear to be altered. This research proved why GABA enhancers like benzodiazepines seem to help with the effects of tinnitus. They come at a cost though, as benzodiazepines also sedate the patients. Other therapies that dampen synaptic transmission , such as transcrainal magnetic stimulation, may also excite these GABA(a) interneurons leading to lesser tinnitus. Another study involving the diminished cortical inhibition in an aging mouse of chronic tinnitus validated the previously mentioned (Middleton, et al., 2011). Again, there was a decrease in GABA(a) in the corticocortical areas of the brain, especially as the mouse got older. Chronic tinnitus seems to get worse as patients get older, until they eventually go deaf. This decrease in GABA(a) and the mechanism for why it decreases needs to be recognized for better understanding for the cognitive causes of tinnitus.

Using animals and other sources of current technology have led to some interesting research for possible cures to tinnitus. Although a definite cure has not yet been found, there have been breakthroughs in possible methods to at least make the tinnitus manageable so chronic symptoms like depressive like symptoms do not occur. A popular method for possible treatment is transcranial direct current stimulation (Vanneste, 2011). When electrodes are placed over the dorsolateral prefrontal cortex, suppression of tinnitus insensity and tinnitus-related distress can be obtained associated with changes in spontaneous regional brain activity. The DLPFC is connected with the ipsilateral auditory cortex via the parahippocampus. Transcranial direct current stimulation may work because the PHC is involved in sensory gating, and when stimulated may reduce the redundant or irrelevant auditory information.
Another method of treatment is using transcranial magnetic stimulation (Vanneste, 2010). Burst of Transcranial magnetic stimulation of the superior temporal gyrus for male individuals is an effective method for transiently suppressing tinnitus. Male individuals were used in the study because males usually have worse and more prevalent symptoms of tinnitus than females. Burst TMS might be modulating both unilateral and bilateral tinnitus, both high and low distress and both pure tones and narrow band tinnitus. As of now, there is no good explanation for the differential effect of burst TMS on pure tones and noise=-like tinnitus. It has been speculation that this could be because of a differential effect of tonic and burst TMS on the lemniscal and extralemniscal system, but no firm proof exists for this idea. This study also indicated that there might be lateral difference of tinnitus in the brain.
Tinnitus related distress has been link to a right sided front-parietal network, and left sided tinnitus has been shown to be more distressing than right-sided tinnitus. This could be related to the assumption that left sided tinnitus is related to a right superior temporal gyrus generator. Evidence points to the fact that PTSD patients who suffer from tinnitus have significantly greater superior temporal gyrus gray matter volumes than controls, suggesting that right superior temporal gyrus is involved in the generation of distress. Homeostatic mechanism theories are being proposed to possibly treat tinnitus, specifically loss-induced tinnitus (Yang, 2013). The theory is there is accumulating evidence that tinnitus is associated with hyper-excitability of the central auditory pathway mediated by imbalanced neuronal excitation and inhibition. A possible cause for the imbalance is neuroplasticity in the form of reduced inhibitory tone, enhanced excitability and tinnitus. Rehabilitating the sensory organ (the ear) and reversing the central mechanisms of tinnitus could treat chronic tinnitus. Some ear damage, especially to the fine hairs involved in auditory stimulation, are irreversible. With those patients with partial hearing loss, there are ways to improve hearing through physical therapy. This behaviorial sensory training restores an/or enhances sensory input to sensory deprived auditory neurons. The rehabilitation could reverse the homeostatic plasticity of inhibitory neurotransmitter release, which causes the tinnitus.
There have been other studies that have not been successful in finding treatment to tinnitus. One of these studies involved caffeine abstinence (Stothart, et al, 2010).
Sixty participants who had tinnitus and who had a high caffeine intake (150 mg/day) were asked to abstain from caffeine for 30 days.
Patients did not have relief from tinnitus, and in fact the caffeine withdrawal increased the stress patients already had from chronic tinnitus. An study after the failure of this study could be to see if there is a link between the high caffeine intake of the patients and the onset of tinnitus. There could be interesting findings if the patients started to increase caffeine intake when tinnitus severity also increased. Although there has not been a cure to tinnitus, there has been increased interest within the last five years of understanding and finding treatment for tinnitus. All of the research conducted for this literately review was within the last ten years. The biggest findings in the last five years involves the decrease of GABA(a) in those with tinnitus and hearing loss and the fact that there seems to be a difference in the brain between left ear tinnitus and right ear tinnitus. The Homeostatic treatment theory offers some interesting possibilities in the future of tinnitus treatment. A possible medication for tinnitus and hearing loss are also not out of the question. Current research in the medical field involves the regeneration of hair cells in the ear through stem cell research that could possibly cure tinnitus (Edge & Chen, 2008). The future of finding the cure to tinnitus will involve more animal testing focusing on finding a more specific mechanism of tinnitus in relations to how left-ear and right-ear tinnitus are different. The psychology field as a whole will continue to make huge strides in understanding and finding more treatments to curing tinnitus throughout the next 10 years. Finding reliable treatments will help soldiers, construction workers, and many other hard working individuals who suffer from the effects of tinnitus.

References

Balkenhol, T., Wallhäusser-Franke, E., & Delb, W. 2013; Psychoacoustic Tinnitus Loudness and Tinnitus-Related Distress Show Different Associations with Oscillatory Brain Activity. Plos ONE, 8(1), 1-13.

Fagelson, M. 2007; The Association Between Tinnitus and Posttraumatic Stress Diisorder. American Journal of Audiology 16: 107-117.

Edge, A.S. & Chen, Z. T. 2008; Hair Cell Regeneration. Curr Opin Neurobiol, 18(4), 377-382.

Hébert, S., Canlon, B., Hasson, D., Magnusson Hanson, L. L., Westerlund, H., & Theorell, T. 2012; Tinnitus severity is reduced with reduction of depressive mood — A prospective population study in Sweden. PLoS ONE 7(5)

Holmes, S., & Padgham, N. D. 2009; Review paper: More than ringing in the ears: A review of tinnitus and its psychosocial impact. Journal Of Clinical Nursing
13(1):97-108

Langguth, B., Landgrebe, M., Kleinjung, T., Sand, G., & Hajak, G. 2011; Tinnitus and depression. World Journal Of Biological Psychiatry, 12(7),

Llano, D., Turner, J., & Caspary, D. 2012; Diminished Cortical Inhibition in an Aging Mouse Model of Chronic Tinnitus. The Journal of Neuroscience 32(46).

Middleton, J. W., Kiritani, T., Pedersen, C., Turner, J. G., Shepherd, G. M. G. & Tzounopoulos, T., Mice with behavioral evidence of tinnitus exhibit dorsal cochlear nucleus hyperactivity because of decreased GABAergic inhibition. PNAS Proceeding of the National Academy of Sciences of he United States of America. 108(18), 7601-7606.

Stothart, G., Laurence, M., Rogers, P. J., 2010; Caffeine abstinence: An Ineffective and Potentially Distressing Tinnitus Therapy, International Journal of Audiology, 49: 24-29.

Vanneste, Sven, 2011; Bifrontal Transcranial Direct Current Stimulation Moduates Tinnitues Intensity and Tinnitus-Distress-Related Brain Activity, European Journal of Neuroscience, 34(4): 605-614.

Vanneste, S., can der Loo, E., Ost, J., Van de Heyning, P., & De Ridder, D. 2010; Burst Transcranial Magnetic Stimulation: Which Tinnitus Characteristics influence the Amount of Transient Tinnitus Suppression? Europearn Journal of Neurology. 17(9): 1141-1147.

Yang, S., 2013; Homeostatic Mechanisms and Treatment of Tinnitus, Restorative Neurology and Neuroscience, 31(2), 99-108.