Dose-dependent attenuation of auditory phantom perception (tinnitus) by PET-guided repetitive transcranial magnetic stimulation

Recent data suggest that chronic tinnitus is a "phantom auditory perception" caused by maladaptive neuroplasticity and subsequent hyperactivity in an extended neuronal network including the primary auditory cortex, higher-order association areas, and parts of the limbic system. It was suggested that attenuation of this tinnitus-associated hyperactivity may offer a rational option for lasting tinnitus reduction. Here, we tested the hypothesis that tinnitus loudness can be attenuated by low-frequency repetitive transcranial magnetic stimulation (rTMS) individually navigated to cortical areas with excessive tinnitus-related activity as assessed by [O-15]H2O positron-emission tomography (PET). Nine patients with chronic tinnitus underwent this combined functional imaging and rTMS-study. Group analysis of the PET data showed tinnitus-related increases of regional cerebral blood flow in the left middle and inferior temporal as well as right temporoparietal cortex and posterior cingulum. Repetitive TMS was performed at 1 Hz and 120% of the motor threshold for 5, 15, and 30 min, navigated to the individual maximum of tinnitus-related cortical hyperactivity. A noncortical stimulation site with the same distance to the ear served as sham control. Tinnitus loudness was reduced after temporoparietal, PET-guided low-frequency rTMS. This reduction, lasting up to 30 min, was dependent on the number of stimuli applied, differed from sham stimulation, and was negatively correlated with the length of the medical history of tinnitus in our patients. These data show the feasibility and effectiveness of rTMS guided by individual functional imaging to induce a lasting, dose-dependent attenuation of tinnitus. Of note, these effects were related to stimulation of cortical association areas, not primary auditory cortex, emphasizing the crucial role of higher-order sensory processing in the pathophysiology of chronic tinnitus.