BackgroundThe objective was to examine functional connectivity linked to the auditory system in patients with bothersome tinnitus. Activity was low frequency (< 0.1 Hz), spontaneous blood oxygenation level-dependent (BOLD) responses at rest. The question was whether the experience of chronic bothersome tinnitus induced changes in synaptic efficacy between co-activated components. Functional connectivity for seed regions in auditory, visual, attention, and control networks was computed across all 2 mm3 brain volumes in 17 patients with moderate-severe bothersome tinnitus (Tinnitus Handicap Index: average 53.5 ± 3.6 (range 38-76)) and 17 age-matched controls.ResultsIn bothersome tinnitus, negative correlations reciprocally characterized functional connectivity between auditory and occipital/visual cortex. Negative correlations indicate that when BOLD response magnitudes increased in auditory or visual cortex they decreased in the linked visual or auditory cortex, suggesting reciprocally phase reversed activity between functionally connected locations in tinnitus. Both groups showed similar connectivity with positive correlations within the auditory network. Connectivity for primary visual cortex in tinnitus included extensive negative correlations in the ventral attention temporoparietal junction and in the inferior frontal gyrus and rostral insula - executive control network components. Rostral insula and inferior frontal gyrus connectivity in tinnitus also showed greater negative correlations in occipital cortex.ConclusionsThese results imply that in bothersome tinnitus there is dissociation between activity in auditory cortex and visual, attention and control networks. The reciprocal negative correlations in connectivity between these networks might be maladaptive or reflect adaptations to reduce phantom noise salience and conflict with attention to non-auditory tasks.

Objective To explore the feasibility of ecological momentary assessments (EMAs) as a tool to more accurately assess the level of bother from tinnitus. Study Design Longitudinal observational study. Setting Washington University Department of Otolaryngology - Head and Neck Surgery faculty practice plan. Subjects and Methods Twenty participants with moderately to severely bothersome tinnitus were enrolled. All participants owned a smartphone device and all communications were conducted via email, phone, and text messaging. Participants received four EMAs per day for two weeks via text message and a final survey on the fifteenth day. In each survey, participants recorded their level of tinnitus bother, their location at the time of response, their stress level, how they were feeling and what they were doing. Response rates as a proxy for the feasibility of the program. Results There were a total of 1120 surveys sent to 20 participants (56 surveys per participant) and 889 (79.4%) of the surveys were completed and returned. The median time to response from the moment of receiving text message was 7 minutes. The distribution of responses to the EMA question, "In the last 5 minutes, how bothered have you been by your tinnitus?" displayed both high between and within subject variability. At the end of 2 weeks, the median score on the THI was 37 with range 10–82 points; the median TFI was 43 with range 10– 82 points. Conclusion This study suggests bothered tinnitus patients will use smartphones as part of ecological momentary assessment.

Objective The goal of this study was to examine the effectiveness and safety of low-frequency rTMS to the temporoparietal junction in a cohort of patients with bothersome tinnitus. Design Cross-over, double-blind, randomized clinical trial. Setting Outpatient, academic medical center Participants 14 adults between the ages of 42 and 59 with subjective, unilateral or bilateral, non-pulsatile tinnitus of 6 months duration or greater, and a score of 38 or greater on the Tinnitus Handicap Inventory (THI). Interventions Low-frequency (1 Hz) 110% motor threshold rTMS or sham to left temporoparietal junction for 2 weeks. Main Outcome Measure The difference in the change of the Tinnitus Handicap Inventory score between active and sham rTMS. Results Active treatment was associated with a median (95% CI) reduction in THI of 5 points (0 to 14) and sham treatment was associated with a median reduction in THI of 6 points (−2 to 12). The difference in THI between the change associated with active and sham rTMS ranged from 34 points reduction in THI score after active treatment when compared to THI score after sham, to an increase of 22 points, with a median difference change of only 1 point (−6 to 4). Conclusions Daily low-frequency rTMS to the left temporoparietal junction area for 2 weeks was no more effective than placebo for patients with chronic bothersome tinnitus. Possible explanations for the negative findings are short duration of treatment, failure of rTMS stimulation over the temporoparietal area to affect auditory cortex buried within the Sylvian fissure, or more widespread cortical network changes associated with severe bothersome tinnitus not amenable to localized rTMS effects.

Objective To evaluate the impact of an MBSR program in patients with chronic bothersome tinnitus on the 1) severity of symptoms of tinnitus and 2) functional connectivity in neural attention networks. Study Design Open-label interventional pilot study. Setting Outpatient academic medical center. Subjects A total of 13 adult participants with a median age of 55 years, suffering from bothersome tinnitus. Methods An 8-week MBSR program was conducted by a trained MBSR instructor. The primary outcome measure was the difference in patient-reported tinnitus symptoms using the Tinnitus Handicap Index (THI) and Tinnitus Functional Index (TFI) between pre-intervention, post-MBSR, and 4-week post-MBSR assessments. Secondary outcomes included change in measurements of depression, anxiety, mindfulness and cognitive abilities. Functional connectivity MRI was performed at pre- and post- MBSR intervention time points to serve as a neuroimaging biomarker of critical cortical networks. Results Scores on the THI and TFI showed statistically significant and clinically meaningful improvement over the course of the study with a median ΔTHI of −16 and median ΔTFI of −14.8 between baseline and 4-week follow-up scores. Except for depression, there was no significant change in any of the secondary outcome measures. Analysis of the rs-fcMRI data showed increased connectivity in the post-MBSR group in attention networks but not the default network. Conclusion Participation in an MBSR program is associated with decreased severity in tinnitus symptoms and depression, and connectivity changes in neural attention networks. MBSR is a promising treatment option for chronic bothersome tinnitus that is both noninvasive and inexpensive.

Importance This research examines the impact of 4 weeks of repetitive transcranial magnetic stimulation (rTMS) stimulation to the temporoparietal junction and compares the results of this longer duration of treatment with a similar stimulus protocol of only 2 weeks’ duration. Objective To examine the effectiveness and safety of 4 weeks of low-frequency rTMS to the left temporoparietal junction in a cohort of patients with bothersome tinnitus. Design Crossover, double-blind, randomized controlled trial. Setting Outpatient academic medical center. Participants The study population comprised 14 adults aged between 22 and 59 years with subjective, unilateral or bilateral, nonpulsatile tinnitus of 6 months’ duration or greater and a score of 34 or greater on the Tinnitus Handicap Inventory (THI). Interventions Low-frequency (1 Hz) 110% motor threshold rTMS or sham to the left temporoparietal junction for 4 weeks. Main Outcome and Measure The difference of the change in the THI score between active rTMS and sham rTMS. Results Active treatment was associated with a median reduction in THI score of 10 (range, −20 to −4) points, and sham treatment was associated with a median reduction of 6 (range, −24 to −12) points. The median difference in THI score between the change associated with active and sham rTMS was 4 (95% CI, −9 to 10; and range, −32 to +14) points. Conclusions and Relevance Daily low-frequency active rTMS to the left temporoparietal junction area for 4 weeks was no more effective than sham for patients with chronic bothersome tinnitus. Possible explanations for this negative study include the failure of rTMS to stimulate deeper parts of auditory cortex within the sylvian fissure and more widespread cortical network changes not amenable to localized rTMS effects. Trial Registration clinicaltrials.gov Identifier: NCT00567892