2. Transcranial magnetic stimulation

which can only increase the masking volume at night or in quiet environments where tinnitus

Cognitive behavioral therapy has been shown to be effective in the treatment of tinnitusrelated 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

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 oxaze-

At this time, there are no medications approved by the US Food and Drug Administration

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.

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

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

is intensified. Masking is only a substitute solution for tinnitus and not a cure.

1.1.6.3. Cognitive behavioral therapy (CBT)

74 Transcranial Magnetic Stimulation in Neuropsychiatry

pam) have been investigated as tinnitus treatments.

Evidence for efficacy of these therapies for tinnitus does not exist.

alone [51].

1.1.6.4. Medical therapy

(FDA) for treatment of tinnitus.

patients with primary tinnitus.

1.1.6.6. Acupuncture

[53–58].

1.1.6.5. Dietary supplements

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 [66–68]. 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 highfrequency (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].

and these results were higher when compared with the literature [44, 50]. In general literature,

Transcranial Magnetic Stimulation in the Treatment of Tinnitus

http://dx.doi.org/10.5772/intechopen.73221

77

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

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

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 [102–104]. Functional MRI activity could demonstrate tinnitusmatched 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

and activity in the central auditory pathways and also nonauditory brain areas [98].

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 [107–109]. 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

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

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

THI is used in the evaluation of tinnitus before and after the treatment [16, 50, 94–96].

tinnitus of all patients before the treatment was 6450 Hz.

[101, 112–114].

to years [116–118].

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 [76–79]. 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, 94–96].

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

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 [76–79]. 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

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

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

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

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,

applied to suggests that it may also be effective in the treatment of tinnitus [8, 9, 85].

subject, studies are providing very little information, but the results seem promising.

study, tinnitus is a serious problem for 2.6% of the local population [91].

does not stimulate the surrounding tissues [73].

76 Transcranial Magnetic Stimulation in Neuropsychiatry

provide an effective tinnitus therapy for some patients.

2.1. TMS in the treatment of tinnitus

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 [102–104]. Functional MRI activity could demonstrate tinnitusmatched 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 [107–109]. 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, 112–114].

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 [116–118].

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].

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

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, 126–130]. 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.
