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Updated: Apr 21, 2026
A Protocol for the Administration of Real-Time fMRI Neurofeedback Training
Published on: August 24, 2017
A novel treatment for tinnitus and tinnitus-related cognitive difficulties using computer-based cognitive training
James G Krings1, Andre Wineland2, Dorina Kallogjeri2
1Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St Louis, Missouri2Doris Duke Clinical Research Fellowship, Washington University School of Medicine, St Louis, Missouri3Stanford Medical Scholars Fellowship, St.
Importance:
Tinnitus affects more than 40 million people in the Unites States, and cognitive difficulties are among the most commonly associated symptoms.
Objective:
To test the feasibility and preliminarily the effectiveness of using a putative neuroplasticity-enhancing drug, D-cycloserine, to facilitate a computer-assisted CT program for improving tinnitus bother and related cognitive difficulties.
Design, Setting, And Participants:
Double-blind, randomized clinical trial at an outpatient academic medical center of 34 participants aged 35 to 65 years with subjective, unilateral or bilateral, nonpulsatile tinnitus of at least 6 months' duration.
Interventions:
Five weeks of twice-weekly computer-based CT with either 250 mg D-cycloserine or placebo orally prior to computer CT sessions.
Main Outcomes And Measures:
Difference in the change in Tinnitus Functional Index (TFI) score between the 2 groups.
Results:
After excluding 1 participant lost to follow-up, 1 who withdrew, 1 who did not complete 90% of sessions, and 1 outlier, 30 participants were included in the analysis. The D-cycloserine plus CT group showed a significant improvement in median TFI score (-5.8 [95% CI, -9.4 to -1.1]) and self-reported cognitive deficits (-4.5 [95% CI, -11.5 to -1.0]), but the placebo group did not (-1.0 [95% CI, -11.7 to 4.9] and -2.0 [95% CI, -5.1 to 2.0], respectively). After controlling for age and duration of tinnitus, there was no significant difference in TFI score change between the 2 groups (P = .41). After confounders were controlled for, the D-cycloserine group demonstrated a significantly greater improvement in self-reported cognitive deficits as compared with the placebo group (P = .03). No serious adverse events were reported.
Conclusions And Relevance:
Use of a computer-based CT program with a putative neuroplasticity-sensitizing drug, D-cycloserine, was feasible and well tolerated. With the limited sample size, the adjuvant use of D-cycloserine was no more effective than placebo at improving tinnitus bother. The finding that D-cycloserine use was more effective than placebo at improving self-reported cognitive difficulties could be important given the high rate of concern for cognitive deficits in patients with tinnitus. D-cycloserine and other putative neuroplasticity-facilitating agents could be investigated in the future as a strategy to enhance neuroplasticity-based tinnitus treatments.
Trial Registration:
clinicaltrials.gov Identifier: NCT01550796.
