Tinnitus and the Role of the Basal Ganglia in Auditory Perception
We are collaborating with Dr. Steven Cheung in Otolaryngology on studies related to the role of the basal ganglia in auditory perception. Our early work involved acute deep brain stimulation (DBS) of the caudate in a cohort of movement disorders patients with comorbid tinnitus undergoing DBS surgery. This led to the discovery of a specific area of the caudate (area LC) that modulates tinnitus when stimulated. We subsequently discovered that acute stimulation of area LC causes triggering of phantom sounds in patients without tinnitus. These experiments provided evidence for the first time that the caudate is involved in phantom auditory perception, and led to a proposed new model for the human basal ganglia to account for these findings and explain the natural history of tinnitus.
We were granted an IDE from the FDA in 2012 and received a U01 grant from the NIH (NIDCD) in 2013 for a first-in-human phase 1 clinical trial to investigate the use of DBS in patients with medically refractory tinnitus. This study was completed in late 2018 and publications describing the outcomes from this trial are forthcoming. Additional studies are currently underway.
Key Team Members and Collaborators
Steven Cheung, MD
Sarah Wang, PhD
Caroline Racine Belkoura, PhD
Carly Demopoulos, PhD
Srikantan Nagarajan, PhD
Doris Wang, MD, PhD
Annette Molinaro, PhD
Cheung SW, Larson PS. Tinnitus modulation by deep brain stimulation in locus of caudate neurons (area LC). Neuroscience 169(4):1768-78, 2010. Epub 10 Jun 2010. PMID: 20541595
Larson PS, Cheung SW. Deep brain stimulation in area LC controllably triggers auditory phantom percepts. Neurosurgery 70(2):398-405, Feb 2012. PMID: 21849922
Larson PS, Cheung SW. A stroke of silence: tinnitus suppression following placement of deep brain stimulation electrode with infarction in area LC. J Neurosurg 118(1):192-4, 2013. Epub 19 Oct 2012. PMID: 23082889
Perez PL, Wang SS, Heath S, Henderson-Sabes J, Mizuiri D, Hinkley LB, Nagarajan SS, Larson PS, Cheung SW. Human caudate nucleus subdivisions in tinnitus modulation. J Neurosurg. 8 Feb 2019 [Epub ahead of print]. PMID: 30738400