FOR IMMEDIATE RELEASE. Frequently Asked Questions (FAQs) The following Q&A was prepared by Posit Science. 1. What is Tinnitus?

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FOR IMMEDIATE RELEASE Frequently Asked Questions (FAQs) The following Q&A was prepared by Posit Science 1. What is Tinnitus? Tinnitus is a medical condition where a person hears "ringing in their ears" a noise or other sound they hear when no actual external physical sound is happening. 2. What causes Tinnitus? Scientists generally agree that tinnitus is caused by changes in the brain, where abnormal activity among networks of neurons in the central auditory system creates the sensation of hearing a sound. It is not known what causes the start of these changes in some cases exposure to loud noise may contribute, and in other cases a disease or other disorder may start the process. Once the process has started, scientists do not yet understand why it continues in the absence of actual external sound. 3. How prevalent, persistent, and severe is Tinnitus? The US Centers for Disease Control estimates some 15% of Americans (about 50 million people) have experienced tinnitus; roughly 20 million Americans struggle with burdensome chronic tinnitus; and two million have extreme and debilitating cases. The global number has been estimated at about 360 million people. 4. How is Tinnitus treated? There is currently no scientifically established cure for tinnitus. Current treatments focus on helping people with tinnitus manage the symptoms of tinnitus, and the attentional, emotional, and cognitive consequences of living with tinnitus. Such treatments include hearing aids, masking sound generators, and cognitive behavioral therapy.

5. What is the design of this study? The study was designed as an open label, intention to treat randomized controlled clinical trial. The study participants included both people with tinnitus, who were randomized into an intervention group and a control group. Another group of people without tinnitus served as a comparison group. The tinnitus intervention group used a set of auditory brain-training exercises from Posit Science for 1 hour per day, 5 days per week, for 8 weeks. The tinnitus control group and the healthy comparison group performed no specific tasks. Each participant was measured on a number of outcome measures (see below) before and after the study. 6. Who participated in this study? The researchers recruited adults with tinnitus. The focus of the study was first responders firefighters and emergency workers, who often suffer tinnitus due to their work in noisy environments. Men and women between the ages of 20 and 65 years were recruited from the greater St Louis, Missouri area fire departments and the public at large. A total of 17 firefighters and first responders completed the study protocol. To enroll enough participants to achieve the study's recruitment goals, the researchers also solicited referrals from the Volunteers for Health at Washington University and via the Washington University otolaryngology clinic for the remainder of the study participants. People with tinnitus were required to have tinnitus for a duration of 6 months or greater and report being extremely bothered, bothered a lot, or bothered more than a little but not a lot. The healthy comparison group was matched in age to the tinnitus group. 7. Who ran and paid for this study? The study was run by a research team at Washington University in St. Louis, Missouri, USA. The authors are:

Dorina Kallogjeri, MD, MPH Jay F. Piccirillo, MD Edward Spitznagel Jr, PhD Sandra Hale, PhD Joyce E. Nicklaus, BSN, RN, CCRC Frances Mei Hardin, BA Joshua S. Shimony, MD, PhD Rebecca S. Coalson, BS Bradley L. Schlaggar, MD, PhD This study was supported by grant EMW-2010-FP-00601 from the Federal Emergency Management Agency and the Department of Homeland Security Assistance to Firefighters Grant Program Fire Prevention and Safety Grants. Posit Science donated the software but did not contribute financially to the study. 8. What did the study show? There was a reduction in the Tinnitus Handicap Index (THI) score in the brain training group, but this reduction was not significantly different compared to the control group. A clinically meaningful reduction of 17 points on the THI was observed in 7 patients (35%) randomized to the brain training group, and 3 patients (15%) randomized to the control group. There was no significant difference in cognitive test scores and other behavioral measures. There was a significant difference between baseline and follow-up in functional connectivity in cognitive control regions in the brain training group but not in the control group. Of the 20 patients in the brain-training group, 10 (50%) self-reported improvement attributable to the intervention, and 6 (30%) reported to be much improved in the domains of tinnitus, memory, attention, and concentration. 9. What were the brain exercises used in the study? The brain training group used eleven auditory brain training modules developed by Posit Science. These included six exercises previously marketed as the Brain Fitness Program and five exploratory modules now incorporated into one new exercise. The exercises used in the study are now commercially available as part of the BrainHQ online and app brain fitness subscription service. The exercises that were utilized appear on BrainHQ as:

Sound Sweeps, Fine Tuning, Syllable Stacks, Memory Grid, In The Know, To-Do List Training, and Hear-Hear. These exercises represent BrainHQ s core auditory processing suite of exercises, targeting auditory speed and accuracy. 10. What are the authors conclusions? The authors conclude: These findings suggest that the computer-based cognitive training program is associated with self-reported changes in attention, memory, and perception of tinnitus. A possible mechanistic explanation for these changes could be neuroplastic changes in key brain systems involved in cognitive control. Cognitive training programs might have a role in the future treatment of patients with tinnitus." [emphasis added] 11. How does this fit with the prior literature? This study extends work reported in 2012 in the paper Cognitive Speed as an Objective Measure of Tinnitus published in the journal Laryngoscope by the same research group that led the current study. This study looked at 92 people with tinnitus, and compared a measure of their tinnitus severity to a measure of the auditory processing speed, as evaluated with a computerized assessment from BrainHQ. Researchers found that there was a significant correlation brain speed test scores and the tinnitus handicap index in people with bothersome tinnitus (THI scores 30). Statistical analysis confirmed that auditory brain speed scores and an independent composite of depression/worry scores were independent predictors of tinnitus severity. This showed that in severe tinnitus, auditory brain speed provides an objective measure of the functional impact of tinnitus, and that brain processing speed and psychiatric state are independent predictors of self-reported tinnitus severity. These measures could help define clinical subgroups within tinnitus: one subgroup whose functional impact is primarily cognitive (related to auditory brain speed) and another whose functional impact is primarily psychiatric (related to depression/worry). This study also extends work reported in 2015 in the paper A novel treatment for tinnitus and tinnitus-related cognitive difficulties using computer-based cognitive training and D-cycloserine. That double-blind, randomized clinical trial explored the effect of a neuroplasticity-enhancing drug, D-cycloserine, to facilitate learning and tinnitus response after the use of Posit Science auditory training by 34 patients with bothersome tinnitus. The patients were randomized

into (1) a group taking D-cycloserine while doing the exercises and (2) a group taking a sugar pill placebo while doing the exercises. Both groups had a significant improvement in median Tinnitus Functional Index (TFI) score and selfreported cognitive deficits after participation in the program. Patients in the D- cycloserine group had a significantly greater improvement in self-reported cognitive deficits compared with the placebo group.