title: Comparing single-site with multisite rTMS for the treatment of chronic tinnitus - clinical effects and neuroscientific insights: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Several years ago, repetitive transcranial magnetic stimulation (rTMS) of the auditory cortex has been introduced as a treatment approach for chronic tinnitus. Even if this treatment is beneficial for a subgroup of patients, the overall effects are limited. This limitation may be due to the fact that the auditory cortex is only one of several brain areas involved in tinnitus. Whereas auditory areas are considered to code for tinnitus loudness, conscious perception of and attention allocation to tinnitus is supposed to be reflected by network activity involving frontal and parietal cortical areas. The aim of the present study is to influence this frontoparietal network more efficiently by perturbing the most important nodes with rTMS.
  
  
  METHODS
  This is a randomized, double-blind, parallel-group study. Patients receive rTMS treatment on 10 consecutive working days using either the multisite rTMS protocol (left dorsolateral prefrontal, 1,000 stimuli, 20 Hz; left temporoparietal, 1,000 stimuli, 1 Hz; right temporoparietal stimulation, 1,000 stimuli, 1 Hz) or a single-site protocol (unilateral stimulation of the temporoparietal cortex, 3,000 stimuli, 1 Hz). Individuals aged 18 to 70 years with chronic tinnitus ≥6-month duration and a Tinnitus Handicap Inventory score ≥38 are recruited for the study. A total of 50 patients are needed to detect a clinical relevant change of tinnitus severity (α = 0.05; 1 - β = 0.80). Primary outcome measures are the change in the Tinnitus Questionnaire score from baseline to the end of treatment as well as the number of treatment responders as defined by a reduction in the Tinnitus Questionnaire score of ≥5 points. Furthermore, changes in brain structure and activity are assessed using (functional) magnetic resonance imaging and electroencephalography in the resting state. Those measurements are also performed in 25 healthy control subjects.
  
  
  CONCLUSIONS
  This study is designed to reveal whether network stimulation is superior to single-site stimulation in the treatment of chronic tinnitus. Furthermore, the comparison between tinnitus patients and healthy controls and the longitudinal effects of both rTMS treatment protocols on brain structure and function allow inferences to be made about the neural correlates of tinnitus.
  
  
  BACKGROUND
  Clinical Trials: NCT01663324.
authors: Department of Psychiatry and Psychotherapy, University of Regensburg, Universitaetsstraße 84, Regensburg 93053, Germany. Astrid.Lehner@medbo.de
authors: Astrid
authors: A
authors: Lehner
authors: Martin
authors: M
authors: Schecklmann
authors: Peter M
authors: PM
authors: Kreuzer
authors: Timm B
authors: TB
authors: Poeppl
authors: Rainer
authors: R
authors: Rupprecht
authors: Berthold
authors: B
authors: Langguth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D002985:Clinical Protocols; D004185:Disability Evaluation; D004311:Double-Blind Method; D004569:Electroencephalography; D005625:Frontal Lobe / Q000473:pathology / Q000503:physiopathology*; D005858:Germany; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology; D010296:Parietal Lobe / Q000473:pathology / Q000503:physiopathology*; D012107:Research Design; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D014012:Tinnitus / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
references: Proc Natl Acad Sci U S A. 2011 May 17;108(20):8075-80
references: 21502503
references: PLoS One. 2012;7(5):e36222
references: 22574141
references: Biol Psychiatry. 2003 Oct 15;54(8):862-5
references: 14550687
references: Eur J Neurol. 2010 Jul;17(7):976-83
references: 20236173
references: BMC Neurosci. 2012 Jan 04;13:3
references: 22217183
references: Hear Res. 2009 Jul;253(1-2):15-31
references: 19364527
references: Br J Clin Psychol. 1988 Sep;27(3):213-22
references: 3191301
references: HNO. 1994 Mar;42(3):166-72
references: 8175381
references: J Neurol Neurosurg Psychiatry. 2007 Aug;78(8):857-63
references: 17314192
references: CNS Neurosci Ther. 2011 Oct;17(5):449-61
references: 20626436
references: J Neurosci. 2010 Nov 10;30(45):14972-9
references: 21068300
references: Prog Brain Res. 2007;166:61-70
references: 17956772
references: Electroencephalogr Clin Neurophysiol Suppl. 1999;52:3-6
references: 10590970
references: ORL J Otorhinolaryngol Relat Spec. 1996 Jul-Aug;58(4):195-9
references: 8883104
references: Hear Res. 2009 Sep;255(1-2):1-13
references: 19545617
references: PLoS One. 2008;3(11):e3720
references: 19005566
references: Curr Med Res Opin. 2011 Aug;27(8):1635-43
references: 21699365
references: J Neurophysiol. 2000 Feb;83(2):1058-72
references: 10669517
references: Otolaryngol Head Neck Surg. 2005 Apr;132(4):566-9
references: 15806046
references: BMC Neurosci. 2009 Feb 19;10:11
references: 19228390
references: Am J Audiol. 2008 Dec;17(2):S148-61
references: 18978198
references: Neurology. 2012 May 22;78(21):1628-34
references: 22539568
references: Int Tinnitus J. 2009;15(2):154-60
references: 20420340
references: Prog Brain Res. 2007;166:525-36
references: 17956816
references: Biol Psychiatry. 1999 Jul 1;46(1):130-2
references: 10394483
references: BMC Biol. 2009 Nov 23;7:80
references: 19930625
references: Brain Topogr. 2013 Jul;26(3):501-10
references: 23229756