Chronic incapacitating subjective tinnitus is a significant problem for a large number of Americans. Neuroimaging studies have shown such tinnitus to be associated with hyperactivity of a variety of cortical regions, especially the auditory cortices and middle temporal regions. Repetitive transcranial magnetic stimulation (rTMS) involves the application of frequent, repeated magnetic stimuli to the skull to induce electrical activity in the underlying cortical areas of the brain. At low-frequency (1 Hz) stimulation, it is believed that rTMS leads to an increase in the inhibitory activity of glutaminergic fibers in the CNS. rTMS seems to be a novel and promising treatment modality for tinnitus as it may be able to quiet the hyperactive cortical areas recently identified through neuroimaging that contribute to tinnitus. Preliminary research by the investigators included PET scan and rTMS for 6 subjects. Of the 6 subjects, 3 reported a 20-point reduction or greater in the Tinnitus Handicap Inventory (THI). When asked if they would recommend rTMS treatment to a friend, 4 patients responded favorably (""""""""maybe yes"""""""" or """"""""definitely yes""""""""). The Overall Goal in this collaborative research project is to assess the effectiveness of rTMS in a large number of tinnitus patients and to thoroughly assess whether there are patient and clinical factors that are predictors of outcome. We will also assess whether there are patient, clinical, neurocognitive, and neuroimaging changes associated with rTMS treatment. There are three Specific Aims to this project: 1) To assess the therapeutic benefit of rTMS for subjective idiopathic troublesome tinnitus. We will employ a single-blind cross-over randomized trial design of active vs. sham rTMS. Enrollment will consist of 55 subjects;the sample size will ensure sufficient power to detect a clinically meaningful difference between treatments, defined as 20-point change in the THI score. A variety of neurocognitive function tests, before and after treatment, will be included to assess whether there are any significant adverse effects of rTMS on cognition and executive function. 2) To identify predictors and correlates of response to rTMS therapy for patients with severe tinnitus. The hypothesis is that there are certain patient factors, audiological measures, clinical features, neurocognitive features, and PET scan findings at baseline and certain changes in these factors after rTMS treatment that are predictors of response to rTMS. 3) To identify a unique tinnitus patient phenotype that is more likely to respond to rTMS The hypothesis is that we will be able to identify certain patient factors, audiological measures, clinical features, and neurocognitive factors that can be used to identify patients more likely to benefit from rTMS. Upon completion of this collaborative research project, new knowledge will be gained about the efficacy of rTMS for tinnitus. This study is unique since all subjects will have thorough neurocognitive testing and PET scan imaging at baseline, after sham, and after active treatment.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Special Emphasis Panel (ZDC1-SRB-R (32))
Program Officer
Hughes, Gordon B
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Washington University
Schools of Medicine
Saint Louis
United States
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Roland, Lauren T; Peelle, Jonathan E; Kallogjeri, Dorina et al. (2016) The effect of noninvasive brain stimulation on neural connectivity in Tinnitus: A randomized trial. Laryngoscope 126:1201-6
Piccirillo, Jay F; Kallogjeri, Dorina; Nicklaus, Joyce et al. (2013) Low-frequency repetitive transcranial magnetic stimulation to the temporoparietal junction for tinnitus: four-week stimulation trial. JAMA Otolaryngol Head Neck Surg 139:388-95
Pierce, Katherine J; Kallogjeri, Dorina; Piccirillo, Jay F et al. (2012) Effects of severe bothersome tinnitus on cognitive function measured with standardized tests. J Clin Exp Neuropsychol 34:126-34
Burton, Harold; Wineland, Andre; Bhattacharya, Mousumi et al. (2012) Altered networks in bothersome tinnitus: a functional connectivity study. BMC Neurosci 13:3
Wineland, Andre M; Burton, Harold; Piccirillo, Jay (2012) Functional connectivity networks in nonbothersome tinnitus. Otolaryngol Head Neck Surg 147:900-6
Lee, Megan H; Solowski, Nancy; Wineland, Andre et al. (2012) Functional connectivity during modulation of tinnitus with orofacial maneuvers. Otolaryngol Head Neck Surg 147:757-62
Piccirillo, Jay F; Garcia, Keith S; Nicklaus, Joyce et al. (2011) Low-frequency repetitive transcranial magnetic stimulation to the temporoparietal junction for tinnitus. Arch Otolaryngol Head Neck Surg 137:221-8
Ances, B M; Christensen, J J; Teshome, M et al. (2010) Cognitively unimpaired HIV-positive subjects do not have increased 11C-PiB: a case-control study. Neurology 75:111-5
Roe, C M; Mintun, M A; Ghoshal, N et al. (2010) Alzheimer disease identification using amyloid imaging and reserve variables: proof of concept. Neurology 75:42-8