Perez Philip L, Wang Sarah S, Heath Susan, Henderson-Sabes Jennifer, Mizuiri Danielle, Hinkley Leighton B, Nagarajan Srikantan S, Larson Paul S, Cheung Steven W
Departments of1Otolaryngology-Head and Neck Surgery and.
2Neurology.
J Neurosurg. 2019 Feb 8;132(3):705-711. doi: 10.3171/2018.10.JNS181659. Print 2020 Mar 1.
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 (clinicaltrials.gov).
本研究的目的是确定对术中直接电刺激有反应的尾状核位置，以调节耳鸣响度，并将这些位置与尾状核亚区和听觉皮层之间的功能连接图谱相关联。
分析了6名清醒的研究参与者，他们作为I期临床试验的一部分，在尾状核中进行了双侧深部脑刺激（DBS）电极植入，以研究20个位置的急性刺激对耳鸣的调节作用。使用静息态3-T功能磁共振成像（fMRI）来比较6名DBS I期试验参与者以及14名耳鸣功能指数>50的其他神经影像学参与者中，降低耳鸣响度或不降低耳鸣响度的尾状核位置的质心与听觉皮层之间的连接强度。
在标准化的蒙特利尔神经病学研究所空间中，在5个尾状核位置观察到急性耳鸣响度降低，其中4个位于尾状核体部，1个位于尾状核头部。对尾状核头部的其余15次电刺激未能降低耳鸣响度。与尾状核头部相比，体部亚区在fMRI上与听觉皮层的功能连接更强（p<0.05）。
通过电刺激尾状核体部更容易实现急性耳鸣响度降低。与尾状核头部相比，尾状核体部与听觉皮层的功能连接更强。这些首次在人体中的发现为尾状核亚区的功能解剖学提供了见解，并可能为未来以基底神经节为中心的神经调节方法治疗难治性耳鸣的靶点选择提供参考。临床试验注册号：NCT01988688（clinicaltrials.gov）。
