Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, Maryland, United States.
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, United States.
J Neurophysiol. 2023 May 1;129(5):1157-1176. doi: 10.1152/jn.00445.2022. Epub 2023 Apr 5.
The otolith end organs inform the brain about gravitational and linear accelerations, driving the otolith-ocular reflex (OOR) to stabilize the eyes during translational motion (e.g., moving forward without rotating) and head tilt with respect to gravity. We previously characterized OOR responses of normal chinchillas to whole body tilt and translation and to prosthetic electrical stimulation targeting the utricle and saccule via electrodes implanted in otherwise normal ears. Here we extend that work to examine OOR responses to tilt and translation stimuli after unilateral intratympanic gentamicin injection and to natural/mechanical and prosthetic/electrical stimulation delivered separately or in combination to animals with bilateral vestibular hypofunction after right ear intratympanic gentamicin injection followed by surgical disruption of the left labyrinth at the time of electrode implantation. Unilateral intratympanic gentamicin injection decreased natural OOR response magnitude to about half of normal, without markedly changing OOR response direction or symmetry. Subsequent surgical disruption of the contralateral labyrinth at the time of electrode implantation surgery further decreased OOR magnitude during natural stimulation, consistent with bimodal-bilateral otolith end organ hypofunction (ototoxic on the right ear, surgical on the left ear). Delivery of pulse frequency- or pulse amplitude-modulated prosthetic/electrical stimulation targeting the left utricle and saccule in phase with whole body tilt and translation motion stimuli yielded responses closer to normal than the deficient OOR responses of those same animals in response to head tilt and translation alone. Previous studies to expand the scope of prosthetic stimulation of the otolith end organs showed that selective stimulation of the utricle and saccule is possible. This article further defines those possibilities by characterizing a diseased animal model and subsequently studying its responses to electrical stimulation alone and in combination with mechanical motion. We show that we can partially restore responses to tilt and translation in animals with unilateral gentamicin ototoxic injury and contralateral surgical disruption.
耳石末端器官向大脑报告重力和线性加速度，驱动耳石-眼反射（OOR）在平移运动（例如，不旋转地向前移动）和头部相对于重力倾斜时稳定眼睛。我们之前已经描述了正常南美栗鼠对全身倾斜和平移以及对通过植入正常耳朵中的电极靶向前庭和球囊的假体电刺激的 OOR 反应。在这里，我们将扩展这项工作，以研究单侧鼓室内庆大霉素注射后对倾斜和平移刺激的 OOR 反应，以及在右侧鼓室内庆大霉素注射后双侧前庭功能低下的动物中单独或组合使用自然/机械和假体/电刺激的 OOR 反应。随后，在电极植入时手术破坏左侧迷路。单侧鼓室内庆大霉素注射使自然 OOR 反应幅度降低到正常的约一半，而没有明显改变 OOR 反应方向或对称性。随后在电极植入手术时手术破坏对侧迷路进一步降低了自然刺激期间的 OOR 幅度，与双侧耳石末端器官双模态功能低下（右侧耳毒性，左侧手术）一致。与全身倾斜和平移运动刺激相位同步的针对左侧前庭和球囊的脉冲频率或脉冲幅度调制的假体/电刺激的传递产生的反应比同一动物仅对头部倾斜和平移的反应的缺陷 OOR 反应更接近正常。先前扩展假体刺激耳石末端器官范围的研究表明，选择性刺激前庭和球囊是可能的。本文通过对患病动物模型进行特征描述，并随后研究其对单独电刺激和与机械运动组合的反应，进一步定义了这些可能性。我们表明，我们可以在单侧庆大霉素耳毒性损伤和对侧手术破坏的动物中部分恢复对倾斜和平移的反应。
