Human caudate nucleus subdivisions in tinnitus modulation

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The object of this study was to define caudate nucleus locations responsive to intraoperative direct electrical stimulation for tinnitus loudness modulation and relate those locations to functional connectivity maps between caudate nucleus subdivisions and auditory cortex.


Six awake study participants who underwent bilateral deep brain stimulation (DBS) electrode placement in the caudate nucleus as part of a phase I clinical trial were analyzed for tinnitus modulation in response to acute stimulation at 20 locations. Resting-state 3-T functional MRI (fMRI) was used to compare connectivity strength between centroids of tinnitus loudness-reducing or loudness-nonreducing caudate locations and the auditory cortex in the 6 DBS phase I trial participants and 14 other neuroimaging participants with a Tinnitus Functional Index > 50.


Acute tinnitus loudness reduction was observed at 5 caudate locations, 4 positioned at the body and 1 at the head of the caudate nucleus in normalized Montreal Neurological Institute space. The remaining 15 electrical stimulation interrogations of the caudate head failed to reduce tinnitus loudness. Compared to the caudate head, the body subdivision had stronger functional connectivity to the auditory cortex on fMRI (p < 0.05).


Acute tinnitus loudness reduction was more readily achieved by electrical stimulation of the caudate nucleus body. Compared to the caudate head, the caudate body has stronger functional connectivity to the auditory cortex. These first-in-human findings provide insight into the functional anatomy of caudate nucleus subdivisions and may inform future target selection in a basal ganglia–centric neuromodulation approach to treat medically refractory tinnitus.

Clinical trial registration no.: NCT01988688 (

ABBREVIATIONS DBS = deep brain stimulation; EPI = echo-planar imaging; fMRI = functional MRI; LC = locus of caudate; MER = microelectrode recording; MNI = Montreal Neurological Institute; TFI = Tinnitus Functional Index.

Article Information

Correspondence Steven W. Cheung: University of California, San Francisco, CA.

INCLUDE WHEN CITING Published online February 8, 2019; DOI: 10.3171/2018.10.JNS181659.

Disclosures Ms. Heath has been a consultant for Medtronic, and she and Dr. Larson have received honoraria from Medtronic.

© AANS, except where prohibited by US copyright law.



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    All 20 locations of DBS electrode placement with macrostimulation are displayed in MNI space. Caudate nucleus locations with (green) and without (red) tinnitus loudness reduction are displayed. Within the caudate head, there is 1 location with tinnitus loudness reduction and 15 locations without.

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    Anteroposterior map of the caudate nucleus for tinnitus modulation. The caudate head is anterior (positive, left) and the body is posterior (negative, right). Data are aggregated from both hemispheres. The outcome of tinnitus loudness interrogation at each anteroposterior coordinate is coded by a box. Increase and decrease in tinnitus loudness modulation is more strongly expressed for MNI coordinates between −8 and −15 (caudate body).

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    Heat map display of functional connectivity of the left posterior caudate body seed compared to the left anterior caudate head seed. The left caudate body demonstrates increased auditory corticostriatal functional connectivity with both superior temporal gyri. Yellow indicates relatively higher connectivity compared to that indicted by orange. Positive contrast was performed using second-level analysis in the CONN toolbox, with a height threshold of p < 0.05 and cluster correction threshold of p < 0.05, using a false discovery rate correction.



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