Illustration by Kenneth Probst, Xavier Studio
Using advanced neuroimaging, UCSF researchers are exploring the root causes of tinnitus and developing novel treatments for this potentially debilitating condition, which affects more than 50 million Americans.
“We are working on an emerging precision medicine method to target brain structures that would deliver uniform, superior benefits for patients with tinnitus," said Steven W. Cheung, MD, otologist, neurotologist and skull base surgeon, who co-led the research.
Phantom perceptions in the brain
Tinnitus is typically treated as a problem in the auditory system. Over the last decade, Cheung and other UCSF researchers have conducted a series of functional magnetic resonance imaging (fMRI) studies involving patients with and without tinnitus. The findings suggest the roots of tinnitus lie in an area of the brain that is not part of the classical auditory pathway: the caudate nucleus, where neural networks integrate and gate sensory perception.
These neural networks should shut out phantom perceptions but may be impaired in people with tinnitus, making it difficult for sufferers to ignore the phantom noises. The studies show that this subjective perception of sound in the ear has a physiological basis in the brain. “We’ve been able to see it using advanced brain imaging. That’s a new biology,” Cheung said.
Cheung was prompted to explore the caudate nucleus by a chance observation. A patient with Parkinson’s disease underwent deep brain stimulation (DBS) to control her tremors. The DBS lead was placed in a location traversing the caudate nucleus. The treatment relieved not only her tremors, but also her tinnitus.
Since then, Cheung has conducted a series of studies attempting to identify the structures and pathways that play a role in the disorder.
DBS for treatment-resistant tinnitus
Cheung was co-principal investigator on an open-label, non-randomized trial to evaluate the efficacy and safety of bilateral caudate nucleus DBS for treatment-resistant tinnitus. The 2020 study followed five patients. Each underwent stereotactically guided functional neurosurgery to implant DBS leads into both caudate nuclei. After optimal stimulation was determined for each individual, the participants were given 24 weeks of continuous DBS.
The results were encouraging. All but one of the patients reported clinically significant improvement in their tinnitus symptoms, although there was wide variability in the effect of the treatment. One patient responded exceptionally well, with a 70-point drop in her Tinnitus Functional Index (TFI) score, while another had only a 2.4-point drop in his TFI. What accounted for the difference? Cheung suspected it was due to differing connections to the striatum from parts of the brain involved with hearing that may be specific to individual patients.
Identifying the neural networks of tinnitus
To explore these connections, Cheung and colleagues conducted a pair of complementary studies that used high-field resting-state fMRI to delineate tinnitus-associated striatal networks of caudate nucleus subdivisions – the first such study of its kind.
Cheung and the research team recruited 68 participants and divided them into four matched cohorts: those with:
- normal hearing;
- hearing loss alone;
- tinnitus alone; and
- hearing loss and tinnitus.
All underwent fMRI scans of their caudate nuclei. Analysis of the cohorts’ images showed distinct differences in functional neural connectivity to other parts of the brain, allowing the researchers to delineate striatal networks associated with tinnitus and its severity as well as with hearing loss.
Cheung then reanalyzed scans of two of the participants in the 2020 study: the subject who had the strongest response to DBS and the one who reported no change in his tinnitus. The scans revealed clear differences in functional connectivity of their striatal networks. For instance, only the responder had increased connectivity between the caudate tail and tinnitus networks. The findings suggest striatal networks may be highly personalized, indicating the need for precision medicine approaches to diagnosis and treatment.
New diagnostic study
While Cheung has used DBS to chart this new biological understanding of tinnitus, the goal is to translate those findings into a less invasive treatment. He’s also drawing on the research to improve diagnostic methods. Cheung and his team are currently recruiting patients for a diagnostic study using neuroimaging techniques to investigate differences in brain signals between people with and without tinnitus.
“We’re working towards identifying the variations in brain pathways that individual patients may have,” Cheung said. “Then we can create a specific map for each patient to target tinnitus treatment more precisely.”
To learn more
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