title: Placebo-controlled vagus nerve stimulation paired with tones in a patient with refractory tinnitus: a case report.
abstract: OBJECTIVE
  Classical neuromodulation consists of applying electrical or magnetic stimuli to the nervous system to modulate ongoing activity and connectivity. However, recently, an exciting novel neuromodulation technique was developed in which stimulation of the vagal nerve was paired with simultaneous presentation of tones, demonstrating that it reverses a tinnitus percept in noise-exposed rats.
  
  
  METHODS
  To determine whether this therapy could also be effective in humans, we delivered a similar therapy in a patient with chronic tinnitus unresponsive to previous therapies. In this report, we describe the case of a 59-year-old man who suffered from bilateral tinnitus for 14 years that arose after a cervical fusion operation. Pharmacotherapy, transcranial magnetic stimulation, transcranial direct current stimulation, neurofeedback, and bilateral auditory cortex stimulation via implanted electrodes did not improve the tinnitus. After implanting the vagal nerve stimulator, the patient received daily vagus nerve stimulation tone pairings for 4 weeks in a non-placebo-controlled way.
  
  
  RESULTS
  At the end of therapy, the patient experienced a significant reduction in tinnitus symptoms that lasted for 2 months after treatment. Tinnitus Handicap Inventory and Tinnitus Reaction Questionnaire were reduced by 48% and 68%, respectively. Symptoms of depression were also improved by 40%, as quantified by the Beck Depression Inventory. Three months after ending therapy, placebo stimulation was performed consisting of only tone presentation without the simultaneous electrical stimuli. This resulted in further continuation of the gradual relapse to the baseline state, without renewed improvement.
  
  
  CONCLUSIONS
  Our results suggest that vagus nerve stimulation paired with tones could become an effective therapy for the treatment of tinnitus.
authors.affiliation: *Section of Neurosurgery, Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Otago, New Zealand; and †University of Texas at Dallas, Richardson; and ‡MicroTransponder Inc., Austin, Texas, U.S.A.
authors.forename: Dirk
authors.initials: D
authors.lastname: De Ridder
authors.forename: Michael
authors.initials: M
authors.lastname: Kilgard
authors.forename: Navzer
authors.initials: N
authors.lastname: Engineer
authors.forename: Sven
authors.initials: S
authors.lastname: Vanneste
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods*; D002908:Chronic Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D014012:Tinnitus / Q000628:therapy*; D016896:Treatment Outcome; D055536:Vagus Nerve Stimulation / Q000379:methods*