Lateralization of neural activity associated with tinnitus

Sir, I am writing to comment on the article “Lateralization of functional magnetic resonance imaging (fMRI) activation in the auditory pathway of patients with lateralized tinnitus” by Smits et al. that was published online in Neuroradiology in April 2007 [1]. One of the article’s coauthors, Dr. Dirk de Ridder, was the first author of a 2005 report [2] that utilized transcranial magnetic stimulation (TMS) to suppress patients’ perception of tinnitus. In this study, 106 of 114 experimental subjects perceived unilateral tinnitus; 8 perceived tinnitus bilaterally. The authors stated “TMS was performed using a super rapid stimulator (Magstim, Whitland, UK), with the circular coil placed over the contralateral auditory cortex.” After reading the 2005 report, I wrote a letter to the editor of Otology & Neurotology [3], in which I stated “The authors apparently believe that unilateral tinnitus is generated by contralateral auditory cortex. However, because some functional MRI [4] and PET [5] studies demonstrated that ipsilateral brain structures also contribute to tinnitus generation, this possibility should be investigated during TMS procedures.” My main motivation for questioning de Ridder’s selection of the contralateral hemisphere for TMS was this: he is so certain that unilateral tinnitus is generated by contralateral auditory cortex, his team surgically implants stimulating electrodes over this area in attempts to suppress tinnitus [6, 7]. The first problem is that, because the laterality of cortical activity associated with tinnitus is in question, de Ridder et al. might be implanting electrodes on the wrong side of the patients’ brain. In response to my letter, de Ridder wrote [8], “Most functional imaging studies performed specifically for unilateral tinnitus demonstrate auditory cortex hyperactivity contralateral to the side to which the tinnitus is perceived. Indeed, in Arnold’s paper [5], a predominant left-sided focal hypermetabolism is noted, irrespective of the tinnitusside. But other PET studies by Lockwood [9], functional magnetic resonance imaging studies by Melcher [10], and Smits [11], and a magnetic source imaging (MSI) study by Muhlnickel [12] all demonstrate involvement of the contralateral auditory pathways.” The recent article in Neuroradiology by Smits et al. [1] presents functional MRI results from 42 tinnitus patients and 10 non-tinnitus control subjects who listened to binaural music. The results indicated that non-tinnitus subjects and patients with left-sided tinnitus exhibited greater activity in the left auditory cortex (compared to the right); patients with right-sided tinnitus exhibited greater activity in the right auditory cortex (compared to the left); patients with bilateral, symmetrical tinnitus did not exhibit asymmetries in neural activity. The second problem is that patterns of brain activity in response to external sounds do not necessarily reflect similar patterns of neural activity associated with tinnitus generation or perception. Figure 1 that contains functional MR images from one patient who experiences high-pitched (12,000 Hz) tinnitus on the right side only. While the patient was in a 3-T MR scanner, white noise was played for 30 s through headphones on one side, followed by 30 s of silence (when the patient could hear his tinnitus), followed by 30 s of white noise played through headphones to the other side. This sequence was repeated 20 times. The results indicated increased activity in the right auditory cortex (colored blue Neuroradiology (2007) 49:689–691 DOI 10.1007/s00234-007-0255-8