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

Abstract

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 [(15)O]H(2)O 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.

Changes in interoceptive processes following brain stimulation

“…Second, further support stems from research on the auditory cortex where the topographic situation is directly comparable to the attempts to stimulate primary auditory cortex in the case of tinnitus. It has been shown that chronic tinnitus with a functional correlate in primary auditory cortex can be modulated by rTMS [62,63], despite the larger distance of the coil to the primary auditory cortex ( planum temporale [64]). Because we compared effects from the frontal stimulation site with two other sites, we are sure that the frontal effects are not unspecific but related to the particular stimulation site, at least close to the anterior insula.…”

Association of Chronic Subjective Tinnitus with Neuro-Cognitive Performance

“…It is conscious perception due to the multiple, parallel and overlapping brain networks 4 . Chronic tinnitus is maladaptive neuronal plasticity and subsequent hyperactivity in primary and secondary auditory pathways, higher-order association areas and parts of the limbic system 2,3,[5][6][7] . Tinnitus might be associated with hyperacusis, sound distortion, sleep disturbances and psychological symptoms such as affective disorders, phonophobia, and/or depression 2,5,8 .…”

Functional Connectivity Networks in Nonbothersome Tinnitus

“…The median age of the NBT group (n = 18) was 54 years (interquartile range [IQR], 52-57), 66% were male, median Tinnitus Handicap Inventory (THI) score was 8 (IQR, [4][5][6][7][8][9][10][11][12][13][14], and a median BDI-II score was 1 (IQR, 0-5). A THI <16 characterizes the least severe tinnitus grade, 33 and a BDI-II <14 is considered minimally depressed.…”

“…Early studies captured blood flow changes in frontal, parietal, and temporal areas via positron emission tomography (PET) with lidocaine injection, [9][10][11][12] behavioral task, 13 and tinnitus modulating behaviors. 6,14 Using radioactive glucose in PET allowed visualization of asymmetrical increased metabolic activity of the auditory cortex.…”

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AbstractObjective-To assess functional connectivity in cortical networks in patients with nonbothersome tinnitus compared with a normal healthy nontinnitus control group by measuring low-frequency (<0.1 Hz) spontaneous blood oxygenation level-dependent (BOLD) signals at rest.

Design-Case-control.

Setting-Academic medical center.Participants-Nonbothersome, idiopathic subjective tinnitus for at least 6 months (n = 18) and a normal healthy nontinnitus control group (n = 23).Main Outcome Measure-Functional connectivity differences in 58 a priori selected seed regions of interest encompassing cortical loci in the default mode, attention, auditory, visual, somatosensory, and cognitive networks.Results-The median age of the 18 subjects was 54 years (interquartile range [IQR], 52-57), 66% were male, 90% were white, median Tinnitus Handicap Inventory (THI) score was 8 (IQR,(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), and a median Beck Depression Index score was 1 (IQR, 0-5). The median age for the control group was 46 years (IQR,(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54), and 52% were male.

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