August 27, 2015

August’s featured paper is "Repetitive Transcranial Magnetic Stimulation Treatment for Chronic Tinnitus: A Randomized Clinical Trial" published in JAMA Otolaryngology—Head and Neck Surgery. The paper is by a team from the Folmer Lab.

Imagine a constant sound, perhaps a buzzing or clicking, that only you can hear. Initially you can easily ignore the noise, but over time, the continual sound probably causes you to be a little irritable. Eventually you begin to lose sleep and experience fatigue, perhaps you even become depressed. These are some of the symptoms and associated complications of chronic tinnitus. Millions of people experience tinnitus, and for some of these patients, the condition can be severely distressing and sometimes debilitating. 

"Tinnitus can have substantial impact on patients' quality of life, but the sensations are subjective and can't be seen with a molecular marker or blood test," said Mary Heinricher, Ph.D., associate dean for basic research in the OHSU School of Medicine. "We now recognize that tinnitus is caused by dysregulation in brain sensory circuits, but that only makes treatment more challenging."

"Some tinnitus management strategies are available such as hearing aids, but few effective treatments for tinnitus have been developed," said Robert Folmer, Ph.D., associate professor of otolaryngology/head and neck surgery and a primary investigator at the Portland VA National Center for Rehabilitative Auditory Research (NCRAR). "My research focuses on using transcranial magnetic stimulation as a treatment."

Previously, Dr. Folmer and colleagues had found that repetitive transcranial magnetic stimulation (rTMS) could suppress tinnitus for some people. Transcranial magnetic stimulation is a non-invasive intervention that involves delivering electromagnetic pulses through a coil to the patient's scalp. Ultimately, some of this energy is transmitted through the skull and affects the activity of underlying neural tissue.  

"Depending on the simulation parameters and scalp or neural target, TMS can either increase or suppress neural activity," said Dr. Folmer. "This type of therapy has been approved by the FDA for treatment of depression, but it hadn't been extensively evaluated for tinnitus treatment."  

Dr. Folmer's work found that delivery of magnetic stimulation at one pulse per second for 2000 pulses per session increased the effectiveness of rTMS for tinnitus.

In order to further investigate rTMS, Dr. Folmer and colleagues mounted the largest clinical trial of its type in the U.S., bringing in over 60 participants for a longitudinal study. During the clinical trial, Dr. Folmer's team administrated 1 Hz TMS to a scalp target overlying the auditory cortex. "The goal was to suppress neural activity associated with tinnitus perception and severity," said Dr. Folmer.

Their results were recently published in the journal JAMA Otolaryngology—Head and Neck Surgery. The trial was conducted at NCRAR from 2011 to 2014. Thirty-two tinnitus patients received 2,000 pulses of "active" 1 Hz rTMS per session for 10 consecutive work days, while 32 other tinnitus patients received 2,000 pulses of "sham" (placebo) 1 Hz rTMS per session for 10 consecutive work days. Assessments were conducted at baseline, immediately after the last rTMS session, and 1, 2, 4, 13 and 26 weeks after that. 

"Our primary outcome measure was the patients' score on the Tinnitus Functional Index (TFI), a 25-item questionnaire that assesses tinnitus severity," said Dr. Folmer. Patients were considered "responders" to rTMS treatment if they improved by >7 points on the TFI immediately after the last rTMS session compared to the baseline TFI score.  

"Using this criterion, 56% of participants in the active rTMS group compared to 22% in the placebo rTMS group were responders to rTMS treatment," said Dr. Folmer. "Also, the improvement in TFI score exhibited by the group of responders to rTMS treatment was sustained throughout 6 months of follow-up assessments."   

"This rigorous study showing that a non-invasive brain stimulation protocol can improve tinnitus for many patients is therefore incredibly encouraging," said Dr. Heinricher. "Although previous studies reported that rTMS can be effective for tinnitus, the degree and duration of improvement were usually less than Dr. Folmer's team found in this study," she added.    

"There are a few reasons why our findings were more robust than previous research, ranging from our target specificity and rTMS intensity to our outcome measurement tool," said Dr. Folmer. "In order to verify the efficacy of rTMS for tinnitus and refine our protocols, we will conduct additional trials."  

Questions Dr. Folmer's group will be addressing in the future include optimizing session length, treatment scalp placement, and identification of characteristics that might confound or enhance treatment.

"I believe that these findings could have implications for some similar disorders," said Dr. Heinricher. "When we know that the underlying problem is a disorder of brain circuitry, such as with functional pain syndromes, rTMS could become an effective treatment."

As Dr. Folmer and colleagues continue to work on refining and optimizing their rTMS treatment, those with persistent ringing in their ears may find some peace and quiet through their cutting-edge research. 

Resources

• Read the paper
• Learn about Dr. Folmer
• View media release

Citation

Repetitive Transcranial Magnetic Stimulation Treatment for Chronic Tinnitus: A Randomized Clinical Trial
JAMA Otolaryngol Head Neck Surg. 2015 Jul 16. doi: 10.1001/jamaoto.2015.1219.  141(8):716-722
Robert L. Folmer, PhD; Sarah M. Theodoroff, PhD; Linda Casiana, MS, CCRP; Yongbing Shi, MD, PhD; Susan Griest, MPH; Jay Vachhani, AuD

Pictured above, from left to right: Susan Griest, M.P.H.; Jay Vachhani, Au.D.; Linda Casiana, M.S.; Robert Folmer, Ph.D.; Sarah Theodoroff, Ph.D.

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