The question arises whether functional connectivity (FC) changes between the distress and tinnitus loudness network during resting state depends on the amount of distress tinnitus patients' experience. Fifty-five patients with constant chronic tinnitus were included in this study. Electroencephalography (EEG) recordings were performed and seed-based (at the auditory cortex) source localized FC (lagged phase synchronization) was computed for the different EEG frequency bands. Results initially demonstrate that the correlation between loudness and distress is nonlinear. Loudness correlates with beta3 and gamma band activity in the auditory cortices, and distress with alpha1 and beta3 changes in the subgenual, dorsal anterior, and posterior cingulate cortex. In comparison to nontinnitus controls, seed-based FC differed between the left auditory cortices for the alpha1 and beta3 bands in a network encompassing the posterior cingulate cortex extending into the parahippocampal area, the anterior cingulate, and insula. Furthermore, distress changes the FC between the auditory cortex, encoding loudness, and different parts of the cingulate, encoding distress: the subgenual anterior, the dorsal anterior, and the posterior cingulate. These changes are specific for the alpha1 and beta3 frequency bands. These results fit with a recently proposed model that states that tinnitus is generated by multiple dynamically active separable but overlapping networks, each characterizing a specific aspect of the unified tinnitus percept, but adds to this concept that the interaction between these networks is a complex interplay of correlations and anti-correlations between areas involved in distress and loudness depending on the distress state of the tinnitus patient.
Microvascular compressions of the cochlear nerve can lead to tinnitus. The tinnitus initially is related to nonsynchronous signal transmission in the auditory nerve, neurophysiologically characterized by a peak II amplitude decrease. Chronic compression can lead to a focal demyelination, resulting in an increase in Iinterpeak latency I-III with tinnitus and frequency-specific hearing loss as a consequence. Decompressing the cochlear nerve may result in improvement in tinnitus if the auditory nerve is not too damaged for recovery. The aim of the study is to find a cut-off point for this recovery based on clinical data.Twenty patients undergo a microvascular decompression of the vestibulocochlear nerve for unilateral intractable tinnitus. Pre- and postoperative visual analogue scale for tinnitus intensity and tinnitus questionnaires for tinnitus distress are analyzed before and after microvascular decompression.Of the 20 patients studied, 10 had improvements on their tinnitus visual analogue score intensity postoperatively, 8 were unchanged, and 2 worsened. On the Tinnitus Questionnaire scores, 7 of 13 patients improved and 6 of the 13 patients worsened. If decompression is performed before the end of the 4th year of tinnitus duration, a significant tinnitus intensity improvement can be obtained (P < .05); after 4 years, improvement cannot be obtained (P = .55). However, the tinnitus distress does not seem to decrease significantly.Microvascular decompression of the cochlear nerve can improve tinnitus intensity in selected patients if decompression is performed early, before the end of the 4th year. Tinnitus distress does not seem to change.
In Reply: We currently only study unilateral tinnitus because it simplifies the development of a pathophysiological model of how unilateral tinnitus arises. 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 (1), a predominant left-sided focal hypermetabolism is noted, irrespective of the tinnitus-side. But other PET studies by Lockwood (2), functional magnetic resonance imaging studies by Melcher (3), and Smits (4), and a magnetic source imaging (MSI) study by Muhlnickel (5) all demonstrate involvement of the contralateral auditory pathways. In Folmer's study (6), all 7 patients (3 patients with usable functional magnetic resonance imaging data) suffered bilateral tinnitus. Based on the fact that bilateral tinnitus might be the result of a different pathophysiological mechanism in comparison to unilateral tinnitus and the small number of subjects scanned in his report, we do not think this sufficiently argues against the prevailing idea that unilateral tinnitus is related to contralateral auditory cortex dysfunction. In the first 10 of our patients, we used auditory fMRI based neuronavigated transcranial magnetic stimulation (TMS) for exact localization of the spot of contralateral auditory cortex dysfunction. We stopped doing this due to the poor spatial localization of the TMS coil we use (8 shaped coil, P/N 9790, Magstim Inc, Wales, U.K.), which has a focality of 33 cm, 2 cm below the coil (7). We now target an area 5- to-6-cm cranially to the external auditory meatus in a coronal plane and look for the spot of maximal suppression by moving the coil in an anteroposterior and superoinferior way by 1-cm increments, thus covering the area where the auditory cortex is located. Once the spot of maximal suppression is located, it is marked and the standard stimulation protocol initiated. I do agree that this methodology should be compared to neuronavigated TMS, based on functional imaging. Our subjects wear ear plugs as hearing protection, though this is more for comfort than methodology reasons. In an initial unpublished pilot series, we stimulated 10 patients (without ear plugs at that time) with unilateral tinnitus both on the ipsilateral and contralateral auditory cortex in separate settings. Ipsilateral stimulation did not suppress tinnitus in any of those patients even though the external sound ipsilaterally was louder. A second reason why I believe the external sound is of little importance is that when we perform sham stimulation by placing the coil perpendicular to the cranium, the sound generated is equal to the real stimulation, and it still induces no tinnitus suppression in placebo negative patients. Whether the clinical benefit of real stimulation might be the result of a kind of somatosensory interference, as described by Levine (8) and also suggested by Dr Folmer in his letter to the editor, has not been investigated yet. We think this is unlikely due to our experience with extradural (9, 10) and intradural (10) implantations of electrodes on the secondary and primary auditory cortex, respectively, where a tinnitus suppression can be obtained (in TMS responders) as well. For extradural implantations, the argument could be presented that the dura has sensory innervation as well, but the dura is coagulated during the procedure (without suppressing tinnitus permanently) to prevent postoperative pain sensation due to dural stimulation and the pia mater has no sensory innervation whatsoever (in intradural electrical stimulations). With regards to placebo stimulation, in 37% of TMS responders, there was no placebo effect. In 12%, a placebo effect was consistently less than 50% of the response obtained by real stimulation, and in 51% of TMS responders sham stimulation was equally potent to suppress tinnitus. We have no explanation yet for this high placebo rate in TMS responders. In conclusion, we fully agree that much more experience is required with this novel noninvasive technique in order to assess its value both for pathophysiological and clinical applications. Dirk De Ridder Department of Neurosurgery, University Hospital Antwerp, Antwerp, Belgium
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