Department of Biomedical Engineering, Center for Neural Engineering, University of Southern California, Los Angeles, CA 90089-1111, United States of America.
J Neural Eng. 2018 Feb;15(1):016017. doi: 10.1088/1741-2552/aa9451.
The success of a cortical prosthetic device relies upon its ability to attain resolvable spikes from many neurons in particular neural networks over long periods of time. Traditionally, lifetimes of neural recordings are greatly limited by the body's immune response against the foreign implant which causes neuronal death and glial scarring. This immune reaction is posited to be exacerbated by micromotion between the implant, which is often rigid, and the surrounding, soft brain tissue, and attenuates the quality of recordings over time.
In an attempt to minimize the foreign body response to a penetrating neural array that records from multiple brain regions, Parylene C, a flexible, biocompatible polymer was used as the substrate material for a functional, proof-of-concept neural array with a reduced elastic modulus. This probe array was designed and fabricated to have 64 electrodes positioned to match the anatomy of the rat hippocampus and allow for simultaneous recordings between two cell-body layers of interest. A dissolvable brace was used for deep-brain penetration of the flexible array.
Arrays were electrochemically characterized at the benchtop, and a novel insertion technique that restricts acute insertion injury enabled accurate target placement of four, bare, flexible arrays to greater than 4 mm deep into the rat brain. Arrays were tested acutely and in vivo recordings taken intra-operatively reveal spikes in both targeted regions of the hippocampus with spike amplitudes and noise levels similar to those recorded with microwires. Histological staining of a sham array implanted for one month reveals limited astrocytic scarring and neuronal death around the implant.
This work represents one of the first examples of a penetrating polymer probe array that records from individual neurons in structures that lie deep within the brain.
皮质假体设备的成功依赖于其在长时间内从特定神经网络中的许多神经元获得可分辨尖峰的能力。传统上,神经记录的寿命受到身体对异物植入体的免疫反应的极大限制,这种免疫反应会导致神经元死亡和胶质瘢痕形成。这种免疫反应被认为会因植入体与周围柔软脑组织之间的微运动而加剧,随着时间的推移,会降低记录的质量。
为了最大限度地减少对穿透性神经阵列的异物反应,该阵列可从多个脑区进行记录,我们使用聚对二甲苯 C 作为柔性、生物相容的聚合物作为基底材料,制作具有降低弹性模量的功能性、概念验证性神经阵列。该探头阵列的设计和制造具有 64 个电极,位置与大鼠海马体的解剖结构相匹配,并允许同时记录两个感兴趣的细胞体层之间的信号。使用可溶解的支撑物来进行柔性阵列的深部脑穿透。
在台式机上对阵列进行了电化学特性表征,并采用了一种新的插入技术,该技术限制了急性插入损伤,从而能够将四个裸露的柔性阵列准确地放置到大鼠大脑中超过 4mm 的深度。对阵列进行了急性测试,术中进行的体内记录显示,在海马体的目标区域中都记录到了尖峰,其尖峰幅度和噪声水平与使用微丝记录的尖峰相似。植入一个月的假阵列的组织学染色显示,植入体周围的星形胶质细胞瘢痕和神经元死亡有限。
这项工作代表了在大脑深部结构中从单个神经元进行记录的穿透性聚合物探头阵列的首批实例之一。