Data_Sheet_1_Layer-dependent stability of intracortical recordings and neuronal cell loss.docx

Intracortical recordings can be used to voluntarily control external devices via brain-machine interfaces (BMI). Multiple factors, including the foreign body response (FBR), limit the stability of these neural signals over time. Current clinically approved devices consist of multi-electrode arrays with a single electrode site at the tip of each shank, confining the recording interface to a single layer of the cortex. Advancements in manufacturing technology have led to the development of high-density electrodes that can record from multiple layers. However, the long-term stability of neural recordings and the extent of neuronal cell loss around the electrode across different cortical depths have yet to be explored. To answer these questions, we recorded neural signals from rats chronically implanted with a silicon-substrate microelectrode array spanning the layers of the cortex. Our results show the long-term stability of intracortical recordings varies across cortical depth, with electrode sites around L4-L5 having the highest stability. Using machine learning guided segmentation, our novel histological technique, DeepHisto, revealed that the extent of neuronal cell loss varies across cortical layers, with L2/3 and L4 electrodes having the largest area of neuronal cell loss. These findings suggest that interfacing depth plays a major role in the FBR and long-term performance of intracortical neuroprostheses.

皮层内记录（intracortical recordings）可通过脑机接口（brain-machine interfaces, BMI）实现对外部设备的自主控制。多种因素——包括异物反应（foreign body response, FBR）——会随时间推移限制此类神经信号的稳定性。当前获批临床应用的设备多采用多电极阵列，每个探针尖端仅配备单个电极位点，将记录界面局限于单层皮层。随着制造技术的进步，现已开发出可同时记录多层皮层活动的高密度电极阵列。然而，不同皮层深度下电极周围神经元细胞丢失的程度，以及皮层内神经记录的长期稳定性，仍有待进一步探索。为解答上述问题，我们对长期植入了跨皮层各层的硅基微电极阵列（silicon-substrate microelectrode array）的大鼠进行了神经信号记录。研究结果显示，皮层内记录的长期稳定性随皮层深度而异，位于L4-L5层周围的电极位点稳定性最高。借助我们开发的新型组织学技术DeepHisto——一种基于机器学习辅助分割的方法——研究发现，神经元细胞丢失的范围随皮层层数变化，L2/3层与L4层的电极周围神经元丢失区域面积最大。上述研究结果表明，植入深度对皮层内神经假体（intracortical neuroprostheses）的异物反应与长期性能具有重要影响。