Moderate therapeutic efficacy of positron emission tomography-navigated repetitive transcranial magnetic stimulation for chronic tinnitus: a randomised, controlled pilot study

Abstract

Background: Tinnitus has been shown to respond to modulations of cortical activity by high-frequency and low-frequency repetitive transcranial magnetic stimulation (rTMS). Objective: To determine the tinnitus-attenuating effects of a 2-week daily regimen of rTMS, navigated to the maximum of tinnitus-related increase in regional cerebral blood flow. Methods: Six patients with chronic tinnitus were enrolled in this sham-controlled crossover study and treated with 262 weeks of suprathreshold 1 Hz rTMS (30 min) applied to the region with maximal tinnitus-related increase in regional cerebral blood flow delineated by functional imaging with [ 15 O]H 2 O positron emission tomography and a control area. Tinnitus-related distress was assessed before and after each treatment and 2 weeks after the end of the 4-week course of stimulation using a validated tinnitus questionnaire. Additional self-assessment scores of tinnitus change, loudness and annoyance were obtained. Results: In five of six patients, rTMS induced greater reduction of the tinnitus questionnaire score than sham stimulation. In two patients, all parameters measured (tinnitus change score, tinnitus loudness, tinnitus annoyance) showed unequivocal improvement. At the group level, the degree of response in the tinnitus questionnaire score was correlated with tinnitus-associated activation of the anterior cingulate cortex. Two weeks after the final stimulation, tinnitus had returned to baseline in all patients but one. Conclusion: Tinnitus can be attenuated by low-frequency rTMS navigated to each person's maximum tinnitusrelated cortical hyperactivity. The effects are only moderate; interindividual responsiveness varies and the attenuation seems to wear off within 2 weeks after the last stimulation session. Notably, tinnitus-related anterior cingulate cortex activation seems to predict the response to rTMS treatment.

Bilateral Low-Frequency Repetitive Transcranial Magnetic Stimulation of the Auditory Cortex in Tinnitus Patients Is Not Effective: A Randomised Controlled Trial

“…The study of Khedr et al [2008] showed a positive effect of rTMS and treated a population with a fairly short tinnitus duration; the greatest proportion of patients had a duration (much) shorter than 4.5 years. A shorter duration of tinnitus has been observed to have a positive effect on treatment outcome [de Ridder et al, 2005;Khedr et al, 2008;Kleinjung et al, 2007;Plewnia et al, 2007b], although other studies do not find this effect [Lehner et al, 2012;Smith et al, 2007], including 1 study [Lehner et al, 2012] correcting for possible confounding effects. The study of Marcondes et al [2010] showed a positive effect of rTMS and was performed only on normally hearing subjects.…”

“…Six randomised crossover studies have been performed on small patient groups ( table 1 ), half of them showing a positive effect [Kleinjung et al, 2005;Plewnia et al, 2007a;Rossi et al, 2007] and the other half of them showing no (significant) effect [Piccirillo et al, 2011;Plewnia et al, 2007b;Smith et al, 2007]. On average, these studies combined showed a decrease of 4 points on the TQ (20 patients) [Kleinjung et al, 2005;Plewnia et al, 2007b], an improvement on the THI of 4 points compared with placebo (14 patients) [Piccirillo et al, 2011], and a general VAS score improvement of 11 points compared with placebo (20 patients) [Rossi et al, 2007;Smith et al, 2007].…”

Masking Treatment and its Effect on Tinnitus Parameters

“…There is no certain method or pharmacological agent for the treatment of tinnitus, which is due to the uncertainty in the etiology of tinnitus 7 . Tinnitus, which affects 17% of the general population, is the primary complaint experienced by 60% of patients in the field of audiology 8 .…”

Reply: Not-So-Random Errors: Randomized Controlled Trials Are Not the Only Evidence of the Value of PET

“…The fact that the study by Plewina et al (16) included only 6 patients does not in our view undermine its "validity" as Hicks et al point out. A crossover design as applied in this study enhances statistical power (17).…”