Should rTMS for tinnitus be performed left‐sided, ipsilaterally or contralaterally, and is it a treatment or merely investigational?

Tinnitus is characterized by the perception of sound or noise in the absence of any objective external physical source. It has a prevalence of 15% in the western world, which in 2–3% of the population leads to a decrease in their quality of life, sleep disturbances and depression sometimes leading to suicide as a desperate escape from this potentially very troublesome symptom, as no proven treatments exist. Functional neuroimaging and electrophysiological studies in humans suggest many forms of non-pulsatile tinnitus can be considered an auditory phantom phenomenon evoked by auditory deafferentation, analogous to phantom pain. Tinnitus is considered an expression of maladaptive neuroplasticity of the auditory system and auditory cortex consisting of topographical reorganization, similarly to what has been described for phantom pain [1]. It is also characterized by an increased synchrony and increased spontaneous gamma band activity in the contralateral auditory cortex [2]. Tinnitus intensity is usually measured by a visual analogue scale or tinnitus matching, tinnitus-related distress by validated questionnaires. Transcranial magnetic stimulation (TMS) is a noninvasive tool delivering a rapidly changing magnetic field, which induces an electrical current that can alter the neural activity at the applied area and at remote areas functionally connected to the stimulated area. The magnetic pulses aimed at the secondary auditory cortex might modulate the ongoing pathological spontaneous synchronous hyperactivity by decreasing excitability and exert similar beneficial effects for tinnitus suppression as anodal transcranial direct current stimulation [3]. As always, initially TMS for tinnitus seemed rather simple. Single sessions of both low (1 Hz) and high frequency (3–20 Hz) TMS were capable of suppressing tinnitus transiently, in the order of seconds, and were merely used as an investigational tool used to elucidate the pathophysiology of tinnitus [3,4] or as a potential prognostic tool for more invasive treatments such as implants of electrodes on the auditory cortex. Repeated transcranial magnetic stimulation (rTMS) sessions on the other hand proposed as a potential treatment were always performed at 1 Hz [5]. And irrespective of whether TMS was used in single or repetitive sessions, as a treatment or investigational tool, irrespective of the stimulation frequency, irrespective of the side of the stimulation, irrespective of whether outcome was measured in intensity or distress improvement, almost all performed studies resulted in approximately 50% response rate [3–5]. The only factor that seemed to matter was the tinnitus duration [4]. Similarly to pain, chronicity results in poorer response rates [4]. However, a couple of problems remained. Should one always use 1 Hz rTMS when used as a treatment? Is the clinical effect sufficiently long lasting to be proposed as a treatment? Should other stimulation designs be used? Should different subgroups of tinnitus be treated in a different way by different rTMS protocols? Should one stimulate left or right side or contralaterally to the side on which the tinnitus is perceived? Is the tinnitus improvement clinically relevant and can it therefore be proposed as a treatment? The first two of these questions were addressed by the same authors demonstrating that both 1 Hz and high frequency (10 and 25 Hz) rTMS could be used and that 10 days of high frequency rTMS was better than 1 Hz TMS, with beneficial results remaining stable in 25% of patients even after 1 year of followup [6]. Whether tinnitus duration is important in selecting stimulation frequencies for treatment purposes remains unknown. An earlier single-session investigational TMS study had shown that high frequency stimulation was better for tinnitus of recent onset and low frequency stimulation was better for chronic tinnitus [4]. The third and fourth questions were investigated by the use of burst TMS consisting of delivering 3–5 closely spaced pulses at 50 Hz, 5, 10 or 20 times a second, called theta, alpha and beta burst, respectively [7]. These studies suggested that burst stimulation might be better for noise-like tinnitus and tonic TMS for pure tone tinnitus [7]. However, the article in this issue by Khedr et al. [8] tries to solve a long standing and sometimes heated controversy in the tinnitus TMS field. Which side should be stimulated, always the left side or the side contralaterally to where the tinnitus is perceived? This is based on the fact that PET studies usually find increased metabolism on the left auditory cortex, irrespective of the side on which the tinnitus is perceived and that left-sided TMS can suppress this metabolic activity [9]. On the other hand, functional magnetic resonance imaging and magnetoencephalography studies suggest the neural generator might be located contralaterally to the tinnitus side. Therefore, this study, which compares ipsilateral to contralateral stimulation is important, as well as the subanalysis comparing left-sided to