Transcranial magnetic stimulation for tinnitus

Neurology 2012;78:1624–1625 Millions of individuals experience tinnitus, the perception of sound in the absence of auditory stimulation.1 Chronic tinnitus may disrupt sleep and be associated with substantial irritability, depression, and anxiety. Treatment of disabling tinnitus may include the use of sound generators, drugs, and behavioral therapies, but is often unsatisfactory.1,2 Tinnitus is usually, but not always, associated with injury or disease of the peripheral auditory system (e.g., hearing loss due to noise exposure). Our understanding of the pathophysiologic basis of tinnitus is incomplete, but increasingly recognizes the importance of long-term central maladaptations to peripheral triggering events.1,3 Peripheral auditory injury may induce tinnitus via a type of deafferentation hypersensitivity. Indeed, a number of studies implicate hyperactivity of auditory processing networks in the temporal cortex in the pathogenesis of chronic tinnitus. Transcranial magnetic stimulation (TMS) is a noninvasive technique for inducing electrical currents in the cerebral cortex by means of time-varying magnetic fields. Repeated applications of TMS (rTMS) can transiently inhibit or excite superficial cortical targets and may cause functional alterations in more remote brain structures via effects on neural networks.4 A number of investigators have tried TMS of the auditory cortices to ameliorate chronic tinnitus, presumably by disrupting cortical perception of tinnitus or inhibiting cortical auditory hyperactivity. The results have been variable, but some studies have shown substantial benefits comparable to those of behavioral therapies.5,6 In this issue of Neurology, Plewnia et al.7 report the results of a randomized, placebo-controlled trial of theta burst stimulation in the treatment of chronic tinnitus. These authors chose to administer continuous theta burst stimulation (cTBS), a type of patterned rTMS, designed to enhance synaptic plasticity, with the goal of inducing long-lasting inhibition in cortical auditory networks. Patients were randomized into 3 equal groups and received cTBS focused on 1 of 2 cortical auditory association areas or overlying the mastoid process as a control. Unfortunately, improvements in tinnitus were small and did not differ significantly between the treatment and control groups. How are we to interpret the results of this study? As a potential treatment, TMS presents unique challenges to the conduct of adequately controlled clinical trials. TMS is noisy. A TMS coil placed against the head not only stimulates cerebral cortex, but also induces electrical currents within the skin afferents and musculature beneath the coil. These features of TMS make it difficult to devise an ideal technique for placebo or sham stimulation, which may be particularly problematic in neuropsychological disorders. One approach to this problem is to control for the effects of TMS by using attenuated stimulation of the active target. If specially constructed coils are employed and coupled with concomitant electrical stimulation of the scalp, subjects cannot distinguish between real and attenuated rTMS.8 This technique also allows for potential blinding of treatment observers. An alternative approach is to compare the effects of real TMS administered to different targets, the approach chosen by Plewnia et al. Unfortunately, this technique has the potential for unintentional stimulation of cerebral cortex by active rTMS. Furthermore, the use of different stimulation targets between patients receiving real and “placebo” stimulation might make it more difficult to blind both patients and study personnel, since the magnetic coil is applied to different scalp locations between groups. On this basis, one possible interpretation of the results of the study by Plewnia et al. is that real and sham rTMS both improved tinnitus. However, since improvement in tinnitus in both the treatment and control groups was clinically insignificant, the results are not readily attributable to placebo effects. Despite the difficulties in providing sham treatment, this is a well-designed trial that appears to provide Class I evidence that rTMS is ineffective in the