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ATA - F u n d e d R e s e A R c h

rTMS for the Treatment of Chronic Tinnitus: Optimization by Stimulation of the Cortical Tinnitus Network
by Astrid Lehner, Dipl.Psych., Martin Schecklmann, Ph.D., Berthold Langguth, M.D., Ph.D.

Intent of Our Work


Repetitive transcranial magnetic stimulation (rTMS) of auditory brain regions has been applied as a treatment option in patients with chronic tinnitus for several years. This technique works with magnetic fields which normalize brain activity in the auditory cortex (AC). Forty to fifty percent of patients treated with rTMS experience a reduction in their tinnitus. Recent studies suggest additional non-auditory brain regions may play a role in tinnitus as well. Therefore, we tried to find out if an extension of rTMS to non-auditory brain areas is able to enhance treatment effects. We also aim to gain more insight into the neural correlates of chronic tinnitus by using neuroimaging methods before and after rTMS. (Figure 1) and are able to influence the activity of neurons lying beneath the coil. If placed over the AC, rTMS is assumed to normalize the altered AC activity and ease tinnitus complaints. For this purpose, rTMS is usually applied on 10 consecutive working days with each of the sessions lasting about 30 to 45 minutes. In recent years, many studies have shown that rTMS is able to reduce tinnitus severity in some patients. The effects of this treatment are only small to moderate however.

Chronic Subjective Tinnitus: Neural Correlates and rTMS


Scientists have dealt with the causes of tinnitus for many years now and although we have still not found the key to turning it off, many important insights concerning its generation and manifestation were gained during the past decade. Some years ago, scientists realized that the long-held assumption that tinnitus was an inner-ear issue was not truly the case. They began to focus on the auditory pathway the route starting in the ear and leading to the AC in the brain. Realizing the relevance of the brain for generation and maintenance of tinnitus was a milestone in tinnitus research and brought many scientists to examine tinnitus-related alterations within the auditory pathway. Studies which analyzed the structure and activity of auditory brain regions found abnormalities. For example, the AC is more active in tinnitus patients. This led to the idea that if the hyperactivity could be reduced, this should have an effect on the tinnitus percept. As a result, new treatment approaches were developed which target this hyperactivity of the AC. One of those treatment approaches is repetitive transcranial magnetic stimulation. rTMS is a technique which applies strong magnetic fields to the brain for modulating neural activity. The magnetic fields are produced within a coil which is placed on the scalp 12
Tinnitus Today | Summer 2012

Figure 1. Transcranial magnetic stimulation for the treatment of tinnitus.

This is where the second important milestone of tinnitus research comes into play. Recent studies suggest that in order to fully understand the neural correlates of chronic tinnitus it is not enough to solely concentrate on altered activity within the auditory pathway. Rather, non-auditory brain areas should be additionally taken into account. It is understood that a sound no matter if it is a normal sound or tinnitus only enters consciousness if non-auditory areas are involved in its processing. Some studies have found alterations of the activity within these non-auditory structures in patients with tinnitus. Currently, this theory of both auditory and non-auditory brain areas being important for tinnitus is being refined by some scientists. The idea is emerging that we should not concentrate on the activity within each of these brain regions separately, but instead focus

on a tinnitus network of interconnected auditory and non-auditory brain areas which exert influence on each other. This could be the reason for the limited effects of rTMS on the AC. While the AC is treated with rTMS, the remaining brain areas of the tinnitus network maintain their altered activity. Due to the connections within the network, the auditory cortex is still influenced by non-auditory sites, narrowing the benefit of rTMS.

Aims of Our Study


The idea of a network of interconnected brain areas being involved in the tinnitus percept allows for a promising refinement of rTMS treatment. If several core regions of this network are targeted by rTMS, a more pronounced reduction of tinnitus severity might be possible than by exclusive stimulation of the AC. Therefore, our study examines a new rTMS stimulation protocol which involves three stimulation sites instead of only one. In the past, rTMS was applied over the temporal cortex of the left (or the right) hemisphere as this is where the AC is located. In our study, the temporoparietal cortex of both hemispheres plus the left frontal cortex are stimulated (see Figure 2). By targeting these three stimulation sites, several nodes of the tinnitus network are covered.

Figure 2. Schematic illustration of the three stimulation sites (blue circles) targeted with multisite rTMS.

Besides the enhancement of rTMS treatment effects, we are also interested in the neural correlates of the tinnitus percept. Therefore, each patient participating in our study is examined with electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) before and after ten days of rTMS treatment. In addition, a control group of non-tinnitus subjects are also examined. These data offer several possibilities to gain insight into the neural mechanisms underlying tinnitus. When data from persons with and without tinnitus are compared, we are able to analyze if altered connectivity between auditory and non-auditory brain regions can be found in persons with tinnitus as suggested by recent studies. Because all patients are examined twice, we are also able to explore the neural changes that are induced by rTMS treatment.
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rTMS for the Treatment of Chronic Tinnitus: Optimization by Stimulation of the Cortical Tinnitus Network
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If those changes go along with an improvement of tinnitus, conclusions can be drawn about the neural mechanisms underlying the tinnitus percept. Additionally, this may help to identify patients who will benefit from rTMS prior to the treatment.

First results
In a pilot study, we have already applied the new rTMS protocol in some patients with chronic tinnitus. Multisite stimulation was well tolerated by all patients who were

treated and no serious side effects were observed. Compared to classical stimulation, the new multisite stimulation protocol led to a more pronounced and a longer lasting improvement of tinnitus severity. This better long-term effect is a very promising result which underscores the relevance of network stimulation and highly encourages us to explore both the clinical and neurobiological effects of the new protocol in more detail.

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