Open access peer-reviewed chapter

Transcranial Magnetic Stimulation in the Treatment of Tinnitus

Written By

Yetkin Zeki Yilmaz and Mehmet Yilmaz

Submitted: 14 June 2017 Reviewed: 18 December 2017 Published: 12 September 2018

DOI: 10.5772/intechopen.73221

From the Edited Volume

Transcranial Magnetic Stimulation in Neuropsychiatry

Edited by Libor Ustohal

Chapter metrics overview

2,658 Chapter Downloads

View Full Metrics

Abstract

Tinnitus is a disturbing noise that is heard without any hearing stimulus, affects the quality of life of the individual, and leads to psychosocial problems. Its prevalence characteristically increases with aging. It is seen in 33% of the general population. Pathophysiology of tinnitus known to accompany nearly all disorders in auditory system has not been fully understood; therefore, there are some difficulties in evaluation and treatment thereof. Despite the restrictive factors of tinnitus treatment, progress in auditory neuroscience provides a positive view of tinnitus treatment. Transcranial magnetic stimulation (TMS) is a method based on the stimulation of neuronal tissue without depending on the transfer of electrical current by means of electrodes or the skin. TMS is used in the treatment of various diseases with developing neuroscience. In the recent years, the number of studies on TMS application with repetitive low frequency for the treatment of tinnitus has increased, and most of these studies have given successful results. Repetitive use of TMS in tinnitus is very novel; however, it is commonly used in psychiatric disorders, especially in the treatment of drug-resistant depression. The chapter shows that low-frequency repetitive TMS (rTMS) is useful in the treatment of chronic tinnitus.

Keywords

  • tinnitus
  • transcranial magnetic stimulation
  • tinnitus handicap inventory
  • rTMS
  • THI

1. Introduction

1.1. Tinnitus

Along with the development of technology and urbanization, there are some additional burdens along with the convenience of our lives. Increasing traffic with urbanization, increasing use of mobile phones from early ages, and listening to loud music with headphones cause our life to become more loud and tense.

Tinnitus is a symptom thought to be heard without a voice stimulus. The presence of tinnitus also affects the quality of life of individuals and causes psychosocial problems. It is characteristic that it becomes more common with aging. It is present in one third of the general population [1].

Forty-sixty million people in the United States have a tinnitus on one occasion, and according to most of them, this does not pose any problem for any treatment. Only 1–5% of individuals with tinnitus have severe and uncomfortable ear tinnitus [2, 3].

Tinnitus occurs with 30-dB hearing loss at the rate of 75%. As the hearing level decreases, its incidence increases. It was detected that exposure to high sound or noise increases tinnitus prevalence.

Pathophysiology of tinnitus known to accompany nearly all disorders in auditory system has not been fully understood; therefore, there are some difficulties in evaluation and treatment thereof. Tinnitus is still a subject of research on neurotology. However, the etiology and physiopathology are not well known. Therefore, tinnitus treatment has not yet been clarified.

Tinnitus can also have a large economic effect. The lack of standardization of tinnitus diagnosis and treatment management increases the cost of health care [4]. Tinnitus reduces the concentration of the person, restricts their participation in professional activities, thus reducing the work efficiency of the person [5, 6, 7].

Despite the restrictive factors of tinnitus treatment, progress in auditory neuroscience provides a positive view of tinnitus treatment.

Transcranial magnetic stimulation (TMS) is a method based on the stimulation of neuronal tissue without depending on the transfer of electrical current by means of electrodes or the skin. TMS is used in the treatment of various diseases with developing neuroscience. Good news is coming from recent studies on TMS application with repetitive low frequency in tinnitus treatment. TMS inhibits abnormal cortical activities in the affected area. Tinnitus treatment is applied to auditory cortex. Positive results have been revealed during the studies [8, 9].

This chapter is devoted to evaluate the effects of transcranial magnetic stimulation (TMS) on the treatment of subjective tinnitus.

1.1.1. Tinnitus pathophysiology

The auditory system is a complex system and contains a large number of central nuclei that provide the cortical organ peripheral fibers in the spiral laminates, multiple afferent and efferent delivery channels, and complex integration in the upper centers of the central nervous system [10, 11, 12]. The pathologies that occur anywhere in these regions cause an increase in the perception of sound through unknown mechanisms. Researchers have tried to explain the formation and perception of tinnitus with many different mechanisms.

  • Damage to inner and outer hair cells

  • Ion imbalance in the cochlea

  • Dysfunction in the cochlear neurotransmitter system

  • Heterogeneous activation in the cochlear efferent system

  • Heterogeneous activation in type I and II cochlear afferents

  • Cross links between the eight nerve fibrils [13]

Every nerve fiber has an electrical discharge even at rest. This is called the spontaneous activity of that nerve. There is an increase in spontaneous activity in patients with tinnitus. All of the assumptions put forward to explain the pathogenesis of tinnitus are based on this spontaneous activity increase [1, 14]. Recent studies suggest that tinnitus is an event based on hyperactivity of the auditory system, which is temporarily adjusted by TMS [15]. Theories about pathophysiology of tinnitus can be grouped as follows:

According to Moller, some of the adjacent nerve fibers are damaged for some reason, resulting in artificial synapse between the nerve fibers, and these synapses between the fibers cause pathological transmissions. This results in increased spontaneous activity and tinnitus [1, 14, 16].

Jastreboff and Hazell note that when the temporal cortex is reduced in hearing impulses, there is an increase in neuronal sensitivity in the subcortical centers. For this reason, a tinnitus patient with normal hearing is thought to be associated with subcortical centers, which we hear as weak voices in auditory cues (e.g., in quiet rooms) [13].

Tonndorf states that tinnitus can originate from all levels of the auditory system. If tinnitus is acoustically masked, it is originated from peripheral auditory system, whereas if tinnitus masking is not present, it is originated from central auditory system. There is a chemical imbalance between the tinnitus cell membrane and the stereocilia. This leads to hyperactive flickering hair or hyperactive nerve fibers. For this reason, even very low spontaneous activities are perceived by these shaky hair or nerve fibers. This condition could be likened to postamputation phenomenon [1, 14, 17, 18]. In 1965, Melzack and Wall proposed the door control theory for chronic pain. Tonndorf proposed this theory for tinnitus [19, 20]. The balance of the impulse that comes from the afferent inner hair cell and the outer hair cell to brainstem, respectively, seems to shift unilaterally when one or more of the hair cell’s subsystem is damaged. Tonndorf suggests that this imbalance of warning may cause tinnitus.

Salvi and Ahroon reported that spontaneous neural activity in the area of the cochlea lesion leads to tinnitus, that acoustic trauma affects cochlea when exposed to noise, and that spontaneous discharges more frequently occur in the high-frequency region of cochlea than in other regions. This increase in spontaneous activity level is expressed as tinnitus [21, 22].

According to Kiang, there are abnormal stereocilia. In the transition between normal and abnormal stereocilia, the suppression of normal cells is lost. This leads to increased spontaneous activity. This leads to tinnitus [14]. Sellick et al. argued that the displacement of the membrane towards to scala tympani causes hyperactivity. It is thought that tinnitus occurs in this way [14].

In 1984, Eggermont assumed that there was hypersensitivity in stereocilia. This may be due to a reduction in the inhibition applied by the central route. Thus, nerve fibers perceive sounds that would normally not be heard. That said, tinnitus may be the cause [1, 14, 23]. In addition, Eggermont suggested in 1990 that the balance between stereocilia activities and nerve fiber activities could have contributed to tinnitus [24].

Although inner ear damage occurs and the eighth cranial nerve is cut, the continuation of tinnitus in some patients supports the concept of ‘central tinnitus.’ Peripheral tinnitus may be localized in one or two ears, while central tinnitus is usually not localized at one point. The major causes of central tinnitus are occupied lesions, inflammations, and vascular anomalies, and often masking does not succeed. Auditory brainstem response (ABR) is helpful in the diagnosis of central tinnitus [25].

Tinnitus can be defined as objective or subjective. Objective tinnitus can be detected by another person or physician.

Objective tinnitus usually has a pulsatile or rhythmic quality. Table 1 lists common causes of objective tinnitus.

Pulsatile
  • Venous etiologies

    • Venous hum

    • Hypertension

    • Pseudotumor cerebri

    • Sigmoid sinus and jugular bulb anomalies

  • Arterial etiologies

    • Paraganglioma (glomus tympanicum or jugulare)

    • Persistent stapedial artery

    • Intratympanic carotid artery

    • Arteriovenous fistula or malformation

    • Increased cardiac output (pregnancy and thyrotoxicosis)

    • Carotid artery stenosis

    • Vascular compression of cranial nerve VII

    • Intraosseous (Paget disease and otosclerosis)

  • Tensor tympani or stapedial muscle myoclonus

  • Palatal myoclonus

Nonpulsatile
  • Patulous Eustachian tube

  • Spontaneous otoacoustic emission

  • Idiopathic stapedial muscle spasm

Table 1.

Objective tinnitus subtypes.

Objective tinnitus can be caused by auditory and nonauditory disorders such as Ménière’s disease, Eustachian tube disorders, intracranial hypertension, middle ear diseases etc [26].

Objective tinnitus treatment depends on the underlying disease. This subject will not be discussed in this chapter.

1.1.2. Subjective tinnitus

The most common form of tinnitus is subjective tinnitus. Unlike objective tinnitus, subjective tinnitus cannot be heard by anyone else. The prevalence of subjective tinnitus is estimated between 8% and 30% and tinnitus should be defined according to the population of the study, the severity of tinnitus, and the evaluation of the methodology [2, 27, 28].

The most important cause of tinnitus is exposure to sound. The main problem in most patients is unknown [29].

Subjective tinnitus most commonly occurs due to sensorineural hearing loss (SNHL), which is caused by the presbycusis and acoustic trauma, conductive hearing loss, endolymphatic hydrops, and cerebellopontine angle neoplasia, which are more rare causes of tinnitus. Subjective tinnitus is the most common form that affects adults, and it is the focus of this chapter. Tinnitus subtype classification schemes can be useful to identify forms of tinnitus that are responsive to specific targeted treatment programs. Table 2 lists common causes of subjective tinnitus.

1.1.2.1. Hearing loss

Urbanization and industrialization are accompanied by increased hearing loss due to noise. Noise-induced hearing loss (NIHL) is a significant and increasing health problem. Unfortunately, many people do not care about industrial noise, fire alarms, listening to music loudly and other noises, or how unaware they are. According to a study conducted, 61% of people who went to the concert found hearing loss and temporary ringing of ears after the concert [30]. The prevalence of chronic tinnitus associated with NIHL is 50–70% [31].

Presbycusis is a sensorineural hearing loss that occurs with aging. Personal and environmental factors play a role in the development of presbycusis, but it mainly involves complex genetic factors. The best-known environmental factor is noise, and hearing is better protected in elderly people who are not exposed to high sound.

1.1.2.2. Somatic tinnitus

Somatic tinnitus can be modulated by maneuvers or stimulation of the head and neck region. Patients with temporomandibular joint (TMJ) disorder had higher incidence of tinnitus compared to control groups [32]. When tinnitus occurs in association with disorders of the head and neck such as TMJ dysfunction, unilateral facial pain, otalgia, and occipital or temporal headache, successful tinnitus alleviation may be possible using interventions that target the somatic dysfunction [17].

1.1.2.3. Typewriter tinnitus

This type of tinnitus may be confused with tinnitus that arises from a muscular source, such as spasm of the tensor tympani or stapedius muscles, or palatal myoclonus. Typewriter tinnitus is defined, as its name implies, by the characteristic sensation of a staccato quality to tinnitus, similar to a typewriter tapping, popcorn popping, or Morse code signaling. Typewriter tinnitus is distinct from these somatic sources, as illustrated by a patient with typewriter tinnitus that failed to respond to tensor tympani and stapedius resection [33].

1.1.2.4. Psychological factors

Emotional distress and disturbance of sleep are often associated with severe tinnitus. Stress often increases the perception of tinnitus severity, and depression frequently accentuates the complaint. In some cases, tinnitus itself may be the cause of the psychological disorder. Depression is common in patients with tinnitus, but it is not always clear whether depression is primary or secondary.

1.1.2.5. Pharmacological factors

The pharmaceutical industry has developed in the last 50 years. Despite the developing world, rational drug use is not yet fully established. Almost every medication can be considered as a possible cause for tinnitus. The main ones responsible are listed in Table 3.

  • Otologic factors

    • Presbycusis

    • Noise-induced hearing loss

    • High-frequency hearing loss

    • Outer hair cell dysfunction

    • Ménière’s disease

  • Somatic tinnitus

    • Temporomandibular joint syndrome

  • Typewriter tinnitus

  • Psychological factors

    • Anxiety

    • Depression

  • Pharmacological factors

    • Aspirin compounds

    • Nonsteroidal anti-inflammatory drugs

    • Aminoglycosides

    • Heavy metals

  • Metabolic factors

    • Hypothyroidism

    • Hyperthyroidism

    • Hyperlipidemia

    • Vitamin deficiency

  • Neurologic abnormalities

    • Multiple sclerosis

    • Meningitic effects

    • Skull fracture or closed head trauma

Table 2.

Subjective tinnitus subtypes.

Nonsteroidal anti-inflammatory drugs
  • Ibuprofen

  • Indomethacin

  • Naproxen

  • Phenylbutazone

  • Sulindak

Amikacin
Aminoglycoside antibiotics
  • Streptomycin

  • Neomycin

  • Gentamycin

  • Tobramycin

Aspirin and aspirin-containing compounds
  • Darvon

  • Percodan

  • Ecotrin

  • Bufferin

Heterocyclic antidepressants
  • Nortriptyline

  • Amitriptyline

  • Trazodone

  • Amoxapine

  • Doxepin

  • Trimipramine

Table 3.

Medications that cause tinnitus.

The aim of tinnitus treatment is to reduce or, if it is possible, to eliminate the voice that disturbs the patients [22]. Symptomatic treatment options are important because etiologic causes are detected in 5% of the cases [34, 35].

1.1.3. Examination and tests

In order to be able to treat patients with tinnitus or to improve the effectiveness of treatment, detailed evaluation of the patients and the investigation of the etiology are required. We have not created a successful standard protocol for evaluating tinnitus until now. Assessment of tinnitus is medically and audiologically interpreted and is used to make individual plans for tinnitus treatment [36]. The transactions to be made in the evaluation can be listed as follows:

  1. History: the major importance in the evaluation of tinnitus patients is anamnesis [37, 38]. A detailed history of the patient should be taken. Age at which tinnitus began, audiovestibular symptoms (hearing loss and dizziness), the nature of tinnitus (intensity and frequency) and daytime changes, family history, history of exposure to noise, smoking, alcohol use, systemic diseases, head trauma, ototoxic drug use, epilepsy, otosclerosis, and past meningitis must be questioned.

  2. Physical examination: after obtaining a complete history of the patient with tinnitus, clinical management should begin with a general medical evaluation followed by a complete head and neck examination. All tinnitus patients should undergo neurological examination including a detailed ENT examination, temporomandibular joint examination and diapason tests, general medical evaluation, and cranial nerve examination [10, 11].

  3. Audiologic evaluation: pure audio audiometry, speech audiometry, percentage of speech discrimination, disturbing auditory height, impedance metric evaluation, otoacoustic emission (OAE), and auditory brainstem response (ABR) can be performed [39, 40, 41, 42].

  4. Laboratory tests: complete blood cell count and extensive biochemical examinations should be performed routinely. If the patient is suspected of any metabolic or medical condition, more detailed examination should be performed.

  5. Radiological evaluation: temporomandibular joint disease should be excluded by radiological evaluation. In patients with unilateral hearing loss, radiological evaluation may be needed to exclude posterior fossa tumors. Computed tomography (CT) is sufficient in the evaluation of most tumors and anomalies. MRI should be performed to exclude vestibular schwannoma or other cerebellopontine angle sister neoplasms if there is a clinical suspicion for patients with nonpulsatile tinnitus [43].

1.1.4. Tinnitus and audiologic findings

1.1.4.1. Pure sound audiogram

It has been reported that 13% of tinnitus cases have transmission-type hearing loss and 39% have sensorineural-type hearing loss. Hearing loss was more frequent in the high-frequency range of the sensorineural hearing loss group [37].

1.1.4.2. Otoacoustic emissions (OAE)

It is thought that OAE is a special evaluation method for cochlear auditory dysfunction in the light of the studies performed and objectively confirms cochlear dysfunction in patients with normal audiogram and tinnitus complaints [44].

Tyler and his colleagues reported that only one of their 25 patients had spontaneous OAEs and found no connection between spontaneous OAEs and tinnitus curtain or severity [45]. Penner and Burns investigated whether the SOAE measurement would be of an objective value in terms of tinnitus correlation, but they could not find a relationship [46]. As a result of some studies on the relationship between SOAE and tinnitus, only a small group of patients has been identified [45, 47]. Studies are underway to investigate the relationship between distortion product otoacoustic emissions (DPOAE) and tinnitus. In these studies, it was revealed that there is a significant relationship between the frequency of tinnitus emergence and DPOAE responses [48].

1.1.4.3. Auditory brainstem response (ABR)

It is a diagnostic measure to help determine the type of tinnitus. There was no difference in the ABR test of the tinnitus patient group in the study of all normal hearing individuals [49].

1.1.5. Evaluation of findings

There are many questionnaires to evaluate the severity of tinnitus and its negative impact on the patient. A standard assessment is needed to document and report the results of clinical trials. Tinnitus, which is defined and graded on this scale, is standardized, and the common denominator in the treatment approach is unified.

Various methods can be used to evaluate the findings of the patients. Tinnitus handicap inventory (THI) is an easily applicable test that is not affected by age, sex, and hearing loss of the patient [50]. A confidence interval of 95% for THI is 20 points, which suggests that a difference in scores of 20 points or greater represents a statistically and clinically significant change.

1.1.6. Tinnitus treatment strategies

Tinnitus is a complex, multifactorial problem with many potential options that can help the patient cope with the condition. You cannot cure tinnitus without understanding tinnitus. We try to approach some treatment modalities for subjective tinnitus after excluding organic causes. Currently, there are some treatment options for patients with tinnitus. Based on the 2014 tinnitus guidelines, the treatment options are shown in Table 4 [26].

  • Education and counseling

  • Sound therapy

  • Cognitive behavioral therapy

  • Medical therapy

  • Dietary supplements

  • Acupuncture

  • Transcranial magnetic stimulation

Table 4.

Tinnitus treatment options.

1.1.6.1. Education and counseling

Patient education should instead emphasize that tinnitus itself is a symptom and not a dangerous disease, and a comprehensive assessment can exclude any associated medical conditions that require prompt treatment.

When counseling the patient, it is absolutely necessary to explain the importance of avoiding noise. The relationship between noise and tinnitus should be reminded.

1.1.6.2. Sound therapy

Acoustic stimulation has an important place in the treatment of tinnitus. Sound therapy can decrease the subjective loudness of tinnitus, which can significantly decrease the annoyance, but this may require weeks to months of daily application. Acoustic stimulation can be achieved in many ways. Masking of tinnitus is based on the principle of suppressing the inner voice from the outside. Masking can be applied with various methods such as hearing aids, tinnitus instruments, and maskers.

A hearing aid is a simple method that can be used in patients with hearing loss who have tinnitus. The hearing aid reduces tinnitus by masking the annoying sound the patient perceives by increasing the volume of the sound coming from the outside.

The tinnitus instrument is a device that includes both the properties of the hearing aid and the masking device. Hearing aid input and masking device input are independent of each other, which can only increase the masking volume at night or in quiet environments where tinnitus is intensified. Masking is only a substitute solution for tinnitus and not a cure.

1.1.6.3. Cognitive behavioral therapy (CBT)

Cognitive behavioral therapy has been shown to be effective in the treatment of tinnitus-related disorders. In many patients, stress or depression is a major factor in the intensity and severity of their complaints. Cognitive behavioral therapy (CBT) is a psychotherapy based on identification and modification of maladaptive behaviors using therapist-mediated cognitive restructuring techniques. Andersson and Lyttkens analyzed 18 studies of psychological treatments for tinnitus and concluded that CBT was more effective than behavioral treatments alone [51].

1.1.6.4. Medical therapy

With the development of the pharmaceutical industry, in the last 50 years, pharmacological treatment for tinnitus has come to the forefront. Drugs used in the treatment of tinnitus are used as useful medicines in terms of improving the emotional state of the patient, reducing anxiety, and improving sleep. Anesthetics (lidocaine, tocainide, and mexiletine), anticonvulsants (carbamazepine and gabapentin), and tranquilizers (diazepam, clonazepam, and oxazepam) have been investigated as tinnitus treatments.

At this time, there are no medications approved by the US Food and Drug Administration (FDA) for treatment of tinnitus.

1.1.6.5. Dietary supplements

Tinnitus appears to be a disease that is unlikely to be treated for most patients. This situation forces the physicians and patients to try other treatment methods. Ginkgo biloba and melatonin are the products of recent use that is increasing. G. biloba extract contains multiple compounds with vasotropic, potential neuroprotective, and antioxidant effects. Several other dietary supplements have been used for tinnitus, including lipoflavonoids, garlic, homeopathy, traditional Chinese/Korean herbal medicine, honeybee larvae, and other various vitamins and minerals. Evidence for efficacy of these therapies for tinnitus does not exist.

Further study is needed to investigate the side effects that may occur in the use of G. biloba, melatonin, or dietary supplements, as well as the use of such products in the treatment of patients with primary tinnitus.

1.1.6.6. Acupuncture

Acupuncture is a form of alternative medicine in which thin needles are inserted into the body. It is a key component of traditional Chinese medicine. The role of acupuncture in tinnitus patients is still controversial. Although unblinded studies have suggested positive results, they have not been reproduced in blinded studies [52]. There is general consensus that acupuncture is a relatively safe treatment when administered by well-trained and experienced practitioners [53, 54, 55, 56, 57, 58].

The objective of the current chapter is to evaluate the effect of TMS on the treatment of subjective tinnitus, so you can find detailed information about other treatments of tinnitus in the literature.

Advertisement

2. Transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is a method based on the stimulation of neuronal tissue without depending on the transfer of electrical current by means of electrodes or the skin. Magnetic stimulation causes transient disturbances of neural activity in different regions of the cortex. The depth of penetration is limited to less than 2 cm [59]. With stimulation, it forms a temporary lesion in the region. This reversible lesion allows the investigator to provide information about whether the cortical region contributes to a particular perception or behavior [60]. To better understand motor responses and corticospinal mechanisms to deep brain stimuli in Parkinson’s patients [61, 62], phantom muscle contractions were used for cortical silent period studies [63]. In 1980, Merton and Morton have shown that motor neurons can be stimulated by a single, high-voltage, short-duration electrical stimulus applied to a rigid scalp with an electrical stimulator [64]. In 1985, Barker and colleagues began to use transcranial magnetic stimulation, which is transmitted through tissues like the same electrical stimulator and applied with a magnetic stimulator that stimulates the cerebral motor cortex and is more painless [65]. Since then, transcranial magnetic stimulation became widely used in areas such as clinical neurophysiology, neurology, and psychiatry. In the following years, transcranial magnetic stimulation became widely used in the evaluation of many other cerebral functions as well as studies in the developing peripheral nerves and muscles that stimulate magnetic stimulation producing coils to stimulate a small area of the cortex [66, 67, 68]. Today, advanced TMS machines can deliver up to 60 stimuli.

The magnetic field affected by a single pulse is measured for milliseconds for a short time. Repeated stimuli cause superficial cortex to change from a few seconds to a few minutes of neuronal depolarization. Repeated stimuli produce different responses depending on the frequency of the region. The application of repetitive stimuli is termed repetitive TMS (rTMS). Low-frequency (<1 Hz) repetitive TMS decreases cortical excitability [69], whereas high-frequency (5–20 Hz) repetitive TMS increases cortical excitability [70]. 1 Hz or slower is called slow rTMS; faster than 1 Hz is called fast rTMS. In the practice of TMS, when the head piece was placed on the scalp corresponding to the projection of the motor cortex and stimulated, the opposite extremities were seen to move painlessly [65]. The diameter of the electrodes used for magnetic stimulation is the most important factor affecting the magnetic field configuration. Electrodes are divided into “circular” or “butterfly” type. Those in butterfly type are called “double shape” or “eight shaped.” Their difference from the circular types is that the maximum current intensity is below the center point. These electrodes are more suitable for selective excitation by producing more localized currents [71, 72]. A magnetic exciter consists of a high-capacity series capacitor and a copper winder. With the discharge of the capacitor, a sudden and high-power (1–4.3 T) magnetic field exchange occurs around the coil. With this effect, ion currents emerge in the neural tissues adjacent to the region where it is placed on the coil and stimulate the neural tissue. If enough magnitude and a rapidly changing magnetic pulse are generated at a sufficient depth, this pulse will cause a secondary ion current in the neuronal tissue [68]. This leads to depolarization of the membrane in the stimulated region of the neuronal tissue. Magnetic stimulation reaches the neuronal tissue without being hindered by intervening tissues such as skin and bone, which does not cause any obvious pain because it does not stimulate the surrounding tissues [73].

The therapeutic response of magnetic stimulation has been observed to be more pronounced with frequent repetitive stimulation (repetitive magnetic stimulation) and studies have shifted to this direction. For this purpose, it was most commonly used in psychiatric disorders [74]. In drug-resistant depressions, repetitive transcranial magnetic stimulation resulted in improvements of 40–50% [75]. TMS has been studied and is still being studied in psychiatric disorders such as schizophrenia, obsessive-compulsive disorder, posttraumatic stress disorder, and mania even though it is not the same size as depression. TMS is one of the safest and painless methods used in the evaluation of the nervous system and in the treatment of the mentioned psychiatric disorders [76, 77, 78, 79]. It is not recommended to be applied in patients who have clips with neurosurgical operation and patients with heart pace because they can stimulate an epileptic seizure on the stroke [80, 81]. Although the use of repetitive TMS (rTMS) in tinnitus is very recent, there are many studies on the efficacy [8, 9, 82]. TMS has opened a new vision into investigating the causes and associations of tinnitus-related cortical activity, and it may provide an effective tinnitus therapy for some patients.

Imaging methods can show asymmetric metabolic activity in the hearing cortex of patients with tinnitus. Functional magnetic resonance imaging and fluorodeoxyglucose positron emission tomography provide it [83, 84]. The fact that rTMS has an inhibitory effect on the area it is applied to suggests that it may also be effective in the treatment of tinnitus [8, 9, 85].

2.1. TMS in the treatment of tinnitus

Tinnitus is still a subject of research on neurotology; however, recent studies in literature are not sufficient enough to enlighten the etiology or pathophysiology of tinnitus, and because of this uncertainty, treatment options are limited. Success rate of medical treatment of tinnitus according to the literature is between 30 and 80%, and most of these studies underline the effectiveness of placebo [86, 87]. TMS application for tinnitus treatment is a relatively new subject, studies are providing very little information, but the results seem promising.

It is important to determine the frequency and loudness of tinnitus because these are correlated with affects of tinnitus on the patients’ life [88, 89]. Tinnitus is present in 65% of the population with hearing problems, and tinnitus in 50% of them is a serious problem [90]. According to one study, tinnitus is a serious problem for 2.6% of the local population [91].

The probability of tinnitus is increasing in patients with hearing loss [92]. If external hair cell damage is not up to 30%, the hearing thresholds do not get affected. This could explain tinnitus in patients who do not have hearing loss [20]. The loudness and frequency of tinnitus must be determined for rehabilitation [93]. In Yilmaz et al.’s study, the mean (SD) scores in the TMS group before the treatment was 7.069 (1.42) and 7.073 (1.52) points in the placebo group, and these results were higher when compared with the literature [44, 50]. In general literature, THI is used in the evaluation of tinnitus before and after the treatment [16, 50, 94, 95, 96].

Detection of the frequency at which tinnitus is occurring is almost always difficult [93]. It has been determined that the frequency of tinnitus changes in 60% of cases according to the studies [97]. According to general opinion, tinnitus frequency is above 2000 Hz and mostly at 4000 Hz [86]. In Yilmaz et al.’s study [50], the mean (SD) frequency of tinnitus in the TMS group before the treatment was 7234 (2818) and 5626 (2494) Hz in the placebo group. The mean frequency of tinnitus of all patients before the treatment was 6450 Hz.

Good news is coming from recent studies on TMS application with repetitive low frequency in tinnitus treatment. TMS inhibits abnormal cortical activities in the affected area. Tinnitus treatment is applied to the auditory cortex. Positive results have been revealed during the studies [8, 9]. Animal models and functional human brain imaging studies, which were designed to investigate the pathophysiology of tinnitus, suggest that there is increased signals and activity in the central auditory pathways and also nonauditory brain areas [98].

Many studies suggested radiological findings were used to determine the coil positioning in order to increase efficacy. One suggested method is using positron emission tomography (PET) to determine the hyperactive auditory cortex [99]. Electroencephalography (EEG) also suggested resting state auditory gamma activity as a marker for tinnitus [100]. However, no association was demonstrated between tinnitus loudness and auditory gamma band. Also Langguth’s study showed no superiority of EEG over PET, and this study could not demonstrate PET-guided coil positioning’s superiority over standard-positioned coils [101]. Anatomical magnetic resonance imaging (MRI) is used as a guide in recent studies to position the coil to the primary auditory cortex [102, 103, 104]. Functional MRI activity could demonstrate tinnitus-matched sounds’ effect on specific cortex areas, but evidence of this kind of navigation for tinnitus is not available [105]. Noh et al.’s recent study showed that there was no significant difference between EEG-guided or neuronavigation-guided coil placement [106].

Functional magnetic resonance imaging and F-18 fluorodeoxyglucose positron emission tomography have shown asymmetric metabolic activity in the hearing cortex of patients with unilateral or bilateral tinnitus [83]. Coactivation of prefrontal areas was detected in imaging studies. This may be related to the affective compacts of tinnitus [107, 108, 109]. Frontothalamic gating system may be formed by limbic and paralimbic structures for tinnitus [110]. James et al.’s study demonstrated with functional MRI that left superior dorsolateral prefrontal cortex had a greater role in predicting tinnitus awareness [111]. Combined prefrontal and temporal cortex rTMS was found to be more effective than temporal cortex rTMS alone [101, 112, 113, 114].

rTMS’s antiapoptotic mechanism was demonstrated in Yoon et al.’s recent animal model [115]. Repeated stimulation induces neuroplastic changes. Single session effects seem to be short and immediate, and daily treatment over 4 weeks seem to have longer results that last over months to years [116, 117, 118].

Kleinjung et al. reported that, after rTMS application to the patients with chronic tinnitus, the mean score of tinnitus decreased at the rate of 7.5% [8]. De Ridder and colleagues found positive results in half of the patients with rTMS in unilateral tinnitus treatment in 114 patients [9]. Kleinjung and colleagues found that application of low-frequency rTMS for 5 days had significant effects on tinnitus treatment [8]. In another study, 3 patients were treated with 1 Hz rTMS (2000 stimulus/day) for 5 days and 2 of the patients had a positive result [99]. In Langguth et al.’s study, 28 patients were treated with 1 Hz rTMS (2000 stimulus/day) for 10 days and 67.8% of the patients had a positive result [119]. Folmer et al.’s study demonstrated that 1 Hz rTMS for chronic tinnitus is an effective treatment method. The application of rTMS daily for 10 days had significantly better outcomes of chronic tinnitus patients [120].

In order to suppress tinnitus, various stimulation patterns have been reported as effective such as 1 Hz, 10 Hz, and burst stimulation [82, 103, 121, 122, 123, 124].

A new TMS protocol was introduced by Huang et al. in 2008 [125]: the protocol named theta burst stimulation [TBS], which is a repeated application of triplets of 50 Hz pulses with 200 ms (5 Hz; theta) pulse interval [125]. Huang et al. suggested that this protocol is superior to tonic rTMS [125]. However, literature findings are controversial. De Riddler et al., Lorenz et al., and Poreiz et al. showed the efficacy of TBS but Chung et al.’s and Plewnia et al.’s studies did not find the same efficacy [103, 126, 127, 128, 129, 130]. Many studies showed low-frequency 1 Hz rTMS to be effective for tinnitus. Khedr et al. suggested that 10 or 20 Hz stimulation could also be effective [123]. James et al.’s study demonstrated that 1 Hz rTMS seemed to significantly decrease the awareness, loudness, and annoyance of tinnitus, but 10 Hz stimulus seemed to decrease only the awareness of tinnitus [111].

Kreuzer et al.’s study suggested that individualized rTMS sessions’ outcomes were better, since tinnitus is a personal symptom and hard to generalize [131]. In Yilmaz et al.’s study, THI score decreased by 8 points after the application of low-frequency rTMS, and also a statistically significant decrease was observed in tinnitus loudness and subjective score after the application of rTMS [50]. Park et al. studied the difference between 6000 pulse and 12,000 pulse rTMS to temporal and prefrontal cortex. Patients who received 12,000 pulses of rTMS seemed to have better outcomes. This study seems to be the first in literature that underlines the importance of pulse rate, at least 12,000 pulses of rTMS seems to achieve a favorable outcome [132].

The chapter showed that low-frequency rTMS is useful in the treatment of chronic tinnitus.

References

  1. 1. Jastreboff PJ, Gray WC, Mattox DE. Tinnitus and hyperacusis. In: Cummings CW, Fredrickson JM, Harker LA, et al., editors. Otolaryngology Head and Neck Surgery. 3rd ed. St Louis: Mosby-Year Book; 1998. pp. 3198-3222
  2. 2. Nondahl DM, Cruickshanks KJ, Wiley TL, et al. Prevalence and 5-year incidence of tinnitus among older adults: The epidemiology of hearing loss study. Journal of the American Academy of Audiology. 2002;13(6):323-331
  3. 3. Cooper JC Jr. Health and nutrition examination survey of 1971-75: Part II. Tinnitus, subjective hearing loss, and well-being. Journal of the American Academy of Audiology. 1994;5(1):37-43
  4. 4. Hoare DJ, Gander PE, Collins L, Smith S, Hall DA. Management of tinnitus in English NHS audiology departments: An evaluation of current practice. Journal of Evaluation in Clinical Practice. 2012;18:326-334
  5. 5. Henry JA, Dennis KC, Schechter MA. General review of tinnitus: Prevalence, mechanisms, effects, and management. Journal of Speech, Language, and Hearing Research. 2005;48:1204-1235
  6. 6. Kim KS. Occupational hearing loss in Korea. Journal of Korean Medical Science. 2010;25:S62-S69
  7. 7. Steinmetz LG, Zeigelboim BS, Lacerda AB, Morata TC, Marques JM. Evaluating tinnitus in industrial hearing loss prevention programs. The International Tinnitus Journal. 2008;14:152-158
  8. 8. Kleinjung T, Eichhammer P, Langguth B, et al. Long-term effects of repetitive transcranial magnetic stimulation (rTMS) in patients with chronic tinnitus. Otolaryngology and Head and Neck Surgery. 2005;132:566-569
  9. 9. De Ridder D, Verstraeten E, Van der Kelen K, et al. Transcranial magnetic stimulation for tinnitus: Influence of tinnitus durationon stimulation parameter choice and maximal tinnitussuppression. Otology & Neurotology. 2005;26:616-619
  10. 10. Çakır Ö. “Tinnitus Tedavisinde Çinko Kullanımı” Ankara Numune Hastanesi 1. Kulak Burun Boğaz Baş Boyun Cerrahisi Kliniği. Ankara: Uzmanlık Tezi; 2001
  11. 11. Jerger J. Clinical experience with impedance audiometry. Archives of Otolaryngology. 1970;92:311-324
  12. 12. Mitchhell SM, Michael JC. Subspecialty clinics: Otorhinolaryngology, tinnitus. Mayo Clinic Proceedings. 1991;66:614-620
  13. 13. Jastreboff PJ, Hazell WP. A neurophysiological approach to tinnitus: Clinical implications. British Journal of Audiology. 1993;27:7-17
  14. 14. Akyıldız N. Tinnitus, Kulak hastalıkları ve mikrocerrahisi II. Ankara: Bilimsel tıp yayınevi; 2002. pp. 67-81
  15. 15. Ridder DD, Mulder GD. Primary and secondary auditory cortex stimulation for intractable tinnitus. ORL. 2006;68:48-55
  16. 16. Moller AR. Pathophysiology of tinnitus. Otolaryngologic Clinics of North America. 2003;36:349-266
  17. 17. Celik O. Tinnitus, Kulak burun boğaz hastalıkları ve baş boyun cerrahisi, Turgut yayıncılık, Đstanbul, Ozluoğlu L. Ataş A. 2002;1(5):88-98
  18. 18. Tonndorf J. Acute cochlear disorders; the combination of hearing loss, recruitment, poor speech discrimination, and tinnitus. The Annals of Otology, Rhinology, and Laryngology. 1980;89:353-358
  19. 19. Melzack R, Wall PD. Pain mechanisms: A new theory. Science. 1965;150:971-979
  20. 20. Tonndorf J. The analogy between tinnitus and pain: A suggestion for a physiological basis of chronic tinnitus. Hearing Research. 1987;28(2–3):271-275
  21. 21. Salvi RJ, Ahroon WA. Tinnitus and neural activity. Journal of Speech and Hearing Research. 1983;26:629-632
  22. 22. Perucca E, Jackson P. A controlled study of the suppression of tinnitus by lidocaine infusion (relationship of therapeutic effect with serum lidocaine levels). The Journal of Laryngology and Otology. 1985;99:657-661
  23. 23. Eggermont JJ. Tinnitus: Some thought about its origin. The Journal of Laryngology and Otology. Supplement. 1984;9:31
  24. 24. Charles WC. Otolaringoloji Bas Ve Boyun Cerrahisi Cilt 4, Koc C (Cev), 4. Đstanbul, Gunes Tıp Kitapevi: Basım; 2007
  25. 25. Shulman A, Seitz MR. Central tinnitus diagnosis and treatment. Laryngoscope. 1981;91:2025-2034
  26. 26. Tunkel DE, Bauer CA, Sun GH, Rosenfeld RM, Chandrasekhar SS, Cunningham ER Jr, et al. Clinical practice guideline: Tinnitus. Otolaryngology and Head and Neck Surgery. Oct 2014;151(2 Suppl):S1-S40
  27. 27. Evered D, Lawrenson G. Tinnitus. Ciba Foundation Symposium; 85, Summit, NJ. Ciba Pharmaceutical Co. Medical Education Administration. viii; 1981. p. 325
  28. 28. Sindhusake D, Golding M, Newall P, et al. Risk factors for tinnitus in a population of older adults: The blue mountains hearing study. Ear and Hearing. 2003;24(6):501-507
  29. 29. Eggermont JJ. Central tinnitus. Auris Nasus Larynx. 2003;30(suppl):7-12
  30. 30. Chung JH, Des Roches CM, Meunier J, et al. Evaluation of noise-induced hearing loss in young people using a web-based survey technique. Pediatrics. 2005;115(4):861-867
  31. 31. Axelsson A, Sandh A. Tinnitus in noise-induced hearing loss. British Journal of Audiology. 1985;19(4):271-276
  32. 32. Chole RA, Parker WS. Tinnitus and vertigo in patients with temporomandibular disorder. Archives of Otolaryngology—Head & Neck Surgery. 1992;118(8):817-821
  33. 33. Flint Paul W. Cummings Otolaryngology—Head & Neck Surgery. 6th ed. Philadelphia, PA: Elsevier/Saunders; 2015. pp. 2336-2345
  34. 34. House JW. Tinnitus: Evaluation and treatment. The American Journal of Otology. 1984;5:1472-1475
  35. 35. Basut O, Ozdilek T, Coşkun H, et al. The incidence of hyperinsulinemia in patients with tinnitus and the effect of a diabetic diet on tinnitus [Turkish]. Kulak Burun Boğaz Ihtisas Dergisi. 2003;10:183-187
  36. 36. Shulman A. Tinnitus medical evaluation. Otolaryngologic Clinics of North America. 1991;36:239-292
  37. 37. Cenik Z, Gul O. Tinnitus etyolojisi. S.U. Tıp Fakultesi Dergisi. 1989;5(4):4-10
  38. 38. Luxon LM. Tinnitus: Its causes, diagnosis and treatment. BMJ. 1993;306:1490-1491
  39. 39. Meyerhoff WL, Cooper JC. Tinnitus. In: Paperalla M, Shumrick DA, Gluckman JL, Meyerhoff W, editors. Otolaryngology, Vol. 2, 3rd ed. W.B. Saunders Comp, Philadelphia; 1991. pp. 1169-1179
  40. 40. House JW. Therapies for tinnitus. The American Journal of Otology. 1989;10(3):163-165
  41. 41. Mattox DE, Richtsmeier WJ. Tinnitus—The initial evaluation. Otolaryngology and Head and Neck Surgery. 1987;96:172-174
  42. 42. Coles RRA, Baskill JL, Sheldrake JB. Measurement and management of tinnitus, part I measurement. The Journal of Laryngology and Otology. December 1984;98:1171-1176
  43. 43. Weissman JL, Hirsch BE. Imaging of tinnitus: A review. Radiology. 2000;216:342-349
  44. 44. Goodwin PE, Johnson RM. The loudness of tinnitus. Acta OtoLaryngologica. 1980;90(5-6):353
  45. 45. Tyler RS, Conrad-Armes D. Spontaneous acoustic Cochlear emissions and sensorineuraltinnitus. British Journal of Audiology. 1982;16:193
  46. 46. Penner MJ, Burns EM. The dissociation of SOAEs and tinnitus. Journal of Speech and Hearing Research. 1987;30:396-403
  47. 47. Penner MJ. Linking spontaneous otoacoustic emissions and tinnitus. British Journal of Audiology. 1992;26:115-123
  48. 48. Shiomi Y, Tsuji J, Naito Y. Characteristics of DPOAE audiogram in tinnitus patients. Hearing Research. 1997;108:83-88
  49. 49. Barnea G, Attias J, Gold S, Shahar A. Tinnitus with normal hearing sensitivity: Extended high frequency audiometry and auditory-nerve brain stem-evoked response. Audiology. 1990;29:36-45
  50. 50. Yilmaz M, Yener MH, Turgut NF, Aydin F, Altug T. Effectiveness of transcranial magnetic stimulation application in treatment of tinnitus. The Journal of Craniofacial Surgery. Jul 1984;25(4):1315-1318
  51. 51. Andersson G, Lyttkens L. A meta-analytic review of psychological treatments for tinnitus. British Journal of Audiology. 1999;33:201-210
  52. 52. Park J, White AR, Ernst E. Efficacy of acupuncture as a treatment for tinnitus: A systematic review. Archives of Otolaryngology—Head & Neck Surgery. Apr 2000;126(4):489-492
  53. 53. Witt CM, Pach D, Brinkhaus B, et al. Safety of acupuncture: Results of a prospective observational study with 229,230 patients and introduction of a medical information and consent form. Forschende Komplementärmedizin. 2009;16:91-97
  54. 54. Endres HG, Molsberger A, Lungenhausen M, Trampisch HJ. An internal standard for verifying the accuracy of serious adverse event reporting: The example of an acupuncture study of 190,924 patients. European Journal of Medical Research. 2004;9:545-551
  55. 55. Macpherson H, Scullion A, Thomas KJ, Walters S. Patient reports of adverse events associated with acupuncture treatment: A prospective national survey. Quality & Safety in Health Care. 2004;13:349-355
  56. 56. Melchart D, Weidenhammer W, Streng A, et al. Prospective investigation of adverse effects of acupuncture in 97 733 patients. Archives of Internal Medicine. 2004;164:104-105
  57. 57. White A, Hayhoe S, Hart A, Ernst E. Survey of adverse events following acupuncture (SAFA): A prospective study of 32,000 consultations. Acupuncture in Medicine. 2001;19:84-92
  58. 58. Norheim AJ. Adverse effects of acupuncture: A study of the literature for the years 1981–1994. Journal of Alternative and Complementary Medicine. 1996;2:291-297
  59. 59. Wagner T, Gangitano M, Romero R, et al. Intracranial measurement of current densities induced by transcranial magnetic stimulation in the human brain. Neuroscience Letters. 2004;354(2):91-94
  60. 60. Bestmann S, Ruff CC, Blakemore C, et al. Spatial attention changes excitability of human visual cortex to direct stimulation. Current Biology. 2007;17(2):134-139
  61. 61. Costa J, Valls-Sole J, Valledeoriola F, Rumia J, Tolosa E. Motor responses of muscles supplied by cranial nerves to subthalmic nucleus deep brain stimuli. Brain. 2007;130:245-255
  62. 62. Molnar GF, Sailer A, Gunraj CA, et al. Changes in cortical excitability with thalamic deep brain stimulation. Neurology. 2005;64:1913-1919
  63. 63. Tazoe T, Endoh T, Nakajima T, Sakmoto M, Komiyama T. Disinhibition of upper limb motor area by voluntary contraction of the lower limb muscle. Experimental Brain Research. 2007;177:419-430
  64. 64. Muray NMF. Motor evoked potentials. In: Aminoff MJ, editor. Electrodiagnosis in Clinical Neurology. USA: Churchill Livingstone; 1992. pp. 605-626
  65. 65. Barker AT, Jalinous II. Non-invasive magnetic stimulation of human motor cortex. The Lancet. May 1985;11:1106-1107
  66. 66. Gürelik M, Karadağ Ö, Polat S, Özüm Ü, Aslan A, et al. The effect of the electrical stimulation of the nasal mucosa on cortical cerebral blood flow in rabbits. Neuroscience Letters. 2004;365:210-213
  67. 67. Legatt AD, Ellen R. Grass lecture: Motor evoked potential monitoring. American Journal of Electroneurodiagnostic Technology. 2004;44:223-243
  68. 68. Taylor JL, Gandevia SC. Noninvasive stimulation of the human corticospinal tract. Journal of Applied Physiology. 2004;96:1496-1503
  69. 69. Chen R, Cohen LG, Hallett M. Role of the ipsilateral motor cortex in voluntary movement. The Canadian Journal of Neurological Sciences. 1997;24(4):284-291
  70. 70. Pascual-Leone A, Valls-Solé J, Wassermann EM, et al. Responses to rapid-rate transcranial magnetic stimulation of the humanmotor cortex. Brain. 1994;117(Pt 4):847-858
  71. 71. Epstein CM, Schwartzberg DG, Davey KR, Sudderth DB. Localizing the site of magnetic brain stimulation in humans. Neurology. 1990;40:666-670
  72. 72. Geddes LA. Optimal stimulus duration for extracranial cortical stimulation. Neurosurgery. 1987;20:94-99
  73. 73. Cohen LG, Roth BJ, Nilsson J, Dang N, et al. Effects of coil design on delivery of focal magnetic stimulation. Technical considerations. Electroencephalography and Clinical Neurophysiology. 1990;75:350-357
  74. 74. Maeda F, Pascual-Leone A. Transcranial magnetic stimulation: Studying motor neurophysiology of psychiatric disorders. Psychopharmacology. 2003;168:359-376
  75. 75. George MS, Nahas Z, Molloy M. A controlled trial of daily left prefrontal cortex TMS for treating depression. Biological Psychiatry. 2000;48:962-970
  76. 76. Pennisi G, Rapisarda G, Bella R, Calabrese V, et al. Absence of response to early transcranial magnetic stimulation in ischemic stroke patients: Prognostic value for hand motor recovery. Stroke. Dec 1999;30(12):2666-2670
  77. 77. Trompetto C, Assini A, Buccolieri A, Marchese R, Abbruzzese G. Motor recovery following stroke: A transcranial magnetic stimulation study. Clinical Neurophysiology. Oct 2000;111(10):1860-1867
  78. 78. Escudero JV, Sancho J, Bautista D, Escudero M, López-Trigo J. Prognostic value of motor evoked potential obtained by transcranial magnetic brain stimulation in motor function recovery in patients with acute ischemic stroke. Stroke. Sep 1998;29(9):1854-1859
  79. 79. Feydy A, Carlier R, Roby-Brami A, Bussel B, Cazalis F, et al. Longitudinal study of motor recovery after stroke: Recruitment and focusing of brain activation. Stroke. 2002;33(6):1610-1617
  80. 80. Eisen A. Cortical and peripheral nerve magnetic stimulation. Journal of Clinical Neurophysiology. 1992;3:65-80
  81. 81. Barker AT, Berardelli A, Caramia MD, Caruso G, et al. Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: Basic principles and procedures for routine clinical application. Report of an IFCN committee. Electroencephalography and Clinical Neurophysiology. Aug 1994;91(2):79-92
  82. 82. Plewnia C, Bartels M, Gerloff C. Transient suppression of tinnitus by transcranial magnetic stimulation. Annals of Neurology. 2003;53:263Y6
  83. 83. Arnold W, Bartenstein P, Oestreicher E, et al. Focal metabolic activation in the predominant left auditory cortex in patients suffering from tinnitus: A PET study with [18F]deoxyglucose. ORL: Journal for Otorhinolaryngology and its Related Specialties. 1996;58:195-199
  84. 84. Langguth B, Eichhammer P, Wiegand R, et al. Neuronavigated rTMS in a patient with chronic tinnitus. Effects of 4 weeks treatment. Neuroreport. 2003;14:977-980
  85. 85. Chen R, Classen J, Gerloff C, et al. Depression of motor cortex excitability by low frequency transcranial magnetic stimulation. Neurology. 1997;48:1398-1403
  86. 86. Yilmaz Đ, Akkuzu B, Cakmak O, et al. Misoprostol in the treatment of tinnitus: A double-blind study. Otolaryngology and Head and Neck Surgery. 2004;130:604-610
  87. 87. Cekkayan S, Ozluoğlu L, Yoloğlu S, et al. Tinnituslu hastalarda beta-histin ve ginkgo biloba ekstresinin etkinliğinin karsilastirilmasi. KBB ve BBC Dergisi. 1996;4:19-22
  88. 88. Hazell J. Tinnitus and disability with ageing: Adaptation and management. Acta Oto-Laryngologica. 1991;476:202-208
  89. 89. Sadlier M, Stephens SD. An approach to the audit of tinnitus management. The Journal of Laryngology and Otology. 1995;109:826-829
  90. 90. Salomon G. Hearing problems in the elderly: Qualitative aspects of hearing problems and influence of tinnitus on hearing. Danish Medical Bulletin Supplement. 1986;33:14-15
  91. 91. Axelsson A, Ringdahl A. Tinnitus: A study of its prevalence and characteristics. British Journal of Audiology. 1989;23:53-62
  92. 92. Chung DY, Gannon RP, Mason K. Factors affecting the prevalence of tinnitus. Audiology. 1984;23:441-452
  93. 93. Goldstein B, Shulman A. Tinnitus evaluation. In: Vernon JA, Moller AR, editors. Tinnitus Diagnosis and Treatment. Philadelphia: Lea and Febiger, 1991. pp. 293-318
  94. 94. American Tinnitus Association. Tinnitus Patient Survey: Information from the American Tinnitus Association. Portland, OR: ATA; 1986
  95. 95. Newman CW, Sandridge SA, Jacobson GB. Psychometric adequacy of the tinnitus handicap inventory (THI) for evaluating treatment outcome. Journal of the American Academy of Audiology. 1998;9:153-160
  96. 96. Hazell JWP, Jastreboff PJ, Meerton LE, et al. Electrical tinnitus suppression: Frequency dependence of effect. Audiology. 1993;32:68-77
  97. 97. Lenarz T, Schreiner C, Snyder RL, et al. Neural mechanisms of tinnitus. European Archives of Oto-Rhino-Laryngology. 1993;249:441-446
  98. 98. Eggermont JJ. Correlated neural activity as the driving force for functional changes in auditory cortex. Hearing Research. 2007;229(1-2):69-80
  99. 99. Eichhammer P, Langguth B, Marienhagen J, et al. Neuronavigated repetitive transcranial magnetic stimulation in patients with tinnitus: A short case series. Biological Psychiatry. 2003;54:862-865
  100. 100. Müller N, Lorenz I, Langguth B, Weisz N. rTMS induced tinnitus relief is related to an increase in auditory cortical alpha activity. PLoS One. 2013;8(2):e55557
  101. 101. Langguth B, Landgrebe M, Frank E, et al. Efficacy of different protocols of transcranial magnetic stimulation for the treatment of tinnitus: Pooled analysis of two randomized controlled studies. World Journal of Biological Psychiatry. 2014;15:276Y85
  102. 102. Barwood CH, Wilson WJ, Malicka AN, et al. The effect of rTMS on auditory processing in adults with chronic, bilateral tinnitus: A placebo-controlled pilot study. Brain Stimulation. Sep 2013;6(5):752-759
  103. 103. Chung HK, Tsai CH, Lin YC, et al. Effectiveness of theta-burst repetitive transcranial magnetic stimulation for treating chronic tinnitus. Audiology and Neurotology. 2012;17:112Y20
  104. 104. Lefaucheur JP, Brugières P, Guimont F, Iglesias S, Franco-Rodrigues A, et al. Navigated rTMS for the treatment of tinnitus: A pilot study with assessment by fMRI and AEPs. Neurophysiologie Clinique. Apr 2012;42(3):95-109
  105. 105. De Ridder D, Vanneste S, Kovacs S, Sunaert S, Menovsky T, et al. Transcranial magnetic stimulation and extradural electrodes implanter on secondary auditory cortex for tinnitus suppression. Journal of Neurosurgery. Apr 2011;114(4):903-911
  106. 106. Noh TS, Rah YC, Kyong JS, Kim JS, Park MK, et al. Comparison of treatment outcomes between 10 and 20 EEG electrode location system-guided and neuronavigation-guided repetitive transcranial magnetic stimulation in chronic tinnitus patients and target localization in the Asian brain. Acta Oto-Laryngologica. Sep 2017;137(9):945-951
  107. 107. Langguth B, Landgrebe M, Kleinjung T, Sand GP, Hajak G. Tinnitus and depression. The World Journal of Biological Psychiatry. 2011;12(7):489-500. DOI: 10.3109/1562 2975.2011.575178
  108. 108. De Ridder D, Elgoyhen AB, Romo R, Langguth B. Phantom percepts: Tinnitus and pain as persisting aversive memory networks. Proceedings of the National Academy of Sciences of the United States of America. 2011;108:8075-8080. DOI: 10.1073/pnas.1018466108
  109. 109. Vanneste S, Plazier M, Der Loo E, De Heyning PV, et al. The neural correlates of tinnitus-related distress. NeuroImage. 2010;52:470-480. DOI: 10.1016/j.neuroimage.2010.04.029 24
  110. 110. Rauschecker JP, Leaver AM, Muhlau M. Tuning out the noise: Limbic-auditory interactions in tinnitus. Neuron. 2010;66:819-826. DOI: 10.1016/ j.neuron.2010.04.032
  111. 111. James GA, Thostenson JD, Brown G, Carter G, Hayes H, et al. Neural activity during attentional conflict predicts reduction in tinnitus perception following rTMS. Brain Stimulation. 2017;10(5):934-943
  112. 112. Kleinjung T, Eichhammer P, Landgrebe M, et al. Combined temporal and prefrontal transcranial magnetic stimulation for tinnitus treatment: A pilot study. Otolaryngology–Head and Neck Surgery. 2008;138:497Y501
  113. 113. Vanneste S, De Ridder D. The involvement of the left ventrolateral prefrontal cortex in tinnitus: a TMS study. Experimental Brain Research. 2012;221:345Y50
  114. 114. Lehner A, Schecklmann M, Poeppl TB, et al. Multisite rTMS for the treatment of chronic tinnitus: Stimulation of the cortical tinnitus networkVa pilot study. Brain Topography. 2013;26:501Y10
  115. 115. Yoon KJ, Lee YT, Han TR. Mechanism of functional recovery after repetitive transcranial magnetic stimulation (rTMS) in the subacute cerebral ischemic rat model: Neural plasticity or anti-apoptosis? Experimental Brain Research. Oct 2011;214(4):549-556
  116. 116. Dayan E, Censor N, Buch ER, Sandrini M, Cohen LG. Noninvasive brain stimulation: From physiology to network dynamics and back. Nature Neuroscience. Jul 2013;16(7):838-844
  117. 117. Thut G, Pascual-Leone A. A review of combined TMS-EEG studies to characterize lasting effects of repetitive TMS and assess their usefulness in cognitive and clinical neuroscience. Brain Topography. Jan 2010;22(4):219-232
  118. 118. Wassermann EM, Zimmermann T. Transcranial magnetic brain stimulation: Therapeutic promises and scientific gaps. Pharmacology & Therapeutics. Jan 2012;133(1):98-107
  119. 119. Langguth B, Zowe M, Landgrebe M, et al. Transcranial magnetic stimulation for the 11 treatment of tinnitus: A new coil positioning method and first results. Brain Topography. 2006;18:241-247
  120. 120. Folmer RL, Theodoroff SM, Casiana L, Shi Y, et al. Repetitive transcranial magnetic stimulation treatment for chronic tinnitus: A randomized clinical trial. JAMA Otolaryngology. Head & Neck Surgery. Aug 2015;141(8):716-722
  121. 121. Khedr EM, Rothwell JC, El-Atar A. One-year follow up of patients with chronic tinnitus treated with left temporoparietal rTMS. European Journal of Neurology. 2009;16:404Y8
  122. 122. Rossi S, De Capua A, Ulivelli M, et al. Effects of repetitive transcranial magnetic stimulation on chronic tinnitus: A randomised, crossover, double blind, placebo controlled study. Journal of Neurology, Neurosurgery, and Psychiatry. 2007;78:857Y63
  123. 123. Khedr EM, Rothwell JC, Ahmed MA, El-Atar A. Effect of daily repetitive transcranial magnetic stimulation for treatment of tinnitus: Comparison of different stimulus frequencies. Journal of Neurology, Neurosurgery, and Psychiatry. 2008;79:212Y5
  124. 124. Vanneste S, Plazier M, van der Loo E, Ost J, et al. Burst transcranial magnetic stimulation: Which tinnitus characteristics influence the amount of transient tinnitus suppression? European Journal of Neurology. 2010;17:1141Y7
  125. 125. Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005;45(2):201-206
  126. 126. De Ridder D, van der Loo E, Van der Kelen K, Menovsky T, et al. Theta, alpha and beta burst transcranial magnetic stimulation: Brain modulation in tinnitus. International Journal of Medical Sciences. 2007 Oct 9;4(5):237-241
  127. 127. Lorenz I, Muller N, Schlee W, Langguth B, Weisz N. Short-term effects of single repetitive TMS sessions on auditory evoked activity in patients with chronic tinnitus. Journal of Neurophysiology. 2010;104(3):1497-1505
  128. 128. Poreisz C, Paulus W, Moser T, Lang N. Does a single session of theta-burst transcranial magnetic stimulation of inferior temporal cortex affect tinnitus perception? BMC Neuroscience. 2009 May 29;10:54
  129. 129. Plewnia C, Vonthein R, Wasserka B, Arfeller C, et al. Treatment of chronic tinnitus with θ burst stimulation: A randomized controlled trial. Neurology. 2012 May 22;78(21):1628-1634
  130. 130. Schecklmann M, Giani A, Tupak S, Langguth B, Raab V, et al. Neuronavigated left temporal continuous theta burst stimulation in chronic tinnitus. Restorative Neurology and Neuroscience. 2016;34(2):165-175
  131. 131. Kreuzer PM, Poeppl TB, Rupprecht R, Vielsmeier V, et al. Individualized repetitive transcranial magnetic stimulation treatment in chronic tinnitus? Frontiers in Neurology. 2017 Apr 6;8:126
  132. 132. Park JH, Noh TS, Lee JH, et al. Difference in tinnitus treatment outcome according to the pulse number of repetitive transcranial magnetic stimulation. Otology & Neurotology. Sep 2015;36(8):1450-1456

Written By

Yetkin Zeki Yilmaz and Mehmet Yilmaz

Submitted: 14 June 2017 Reviewed: 18 December 2017 Published: 12 September 2018