Intraoperative large-scale extracellular recordings for studying the neuronal code for number in the human brain

神经科学的一个基本挑战是确定特定的神经功能相关细胞。动物实验的使用取得了相当大的进展，越来越多的测量和操纵神经元活动的工具可以用来研究单个神经元及其网络如何产生特定的行为。然而，正是这种程度的细节在人类研究中缺失。目前，我们对人类大脑功能如何在神经元水平上实现的理解存在巨大差距。该项目的中心目标是研究人类高级认知功能的一个典型例子的细胞机制，即我们计数、测量和排序物品的能力。数值刺激是灵长类动物前额叶皮层的一个强有力的驱动输入，非常适合研究这个大脑区域如何处理抽象的心理概念。我们将记录神经外科手术患者在清醒状态下切除脑肿瘤时，前额叶皮层单个神经元及其局部网络的大规模细胞外活动。在这个过程中，患者将执行认知任务，要求他们记住由视觉显示或阿拉伯数字中的点的数量指定的集合大小（数字）。我们将解决两个主要问题，不能回答与非侵入性实验，如功能神经成像。首先，人类单细胞水平上的非符号量是如何编码的？第二，当数量被象征性地指定时，人类神经元数字代码会改变吗？还是它是符号不变的，即真正抽象的？这一提议描述了测量和解释人脑神经元活动的新方法。通过弥合目前物种之间的实验差距，该项目将建立一个强大的新框架，以了解人类数字认知原理及其与细胞和微电路分辨率相关的高级认知功能。

A fundamental challenge in neuroscience is to identify specific cellular correlates for defined mental functions. Considerable progress is being made with the use of animal studies, where an increasing number of tools for measuring and manipulating neuronal activity is available to investigate how individual neurons and their networks give rise to specific behaviors. However, it is precisely this level of detail that is missing in human studies. There is currently a huge gap in our understanding of how brain functions are implemented at the neuronal level in humans.The central aim of this project is to investigate the cellular mechanisms of a paradigmatic example of human higher-level cognitive functioning, namely our ability to count, measure and rank items. Numerical stimuli are a strong driver input to the primate prefrontal cortex and very well suited to study how abstract mental concepts are processed by this brain area. We will record large-scale extracellular activity from individual neurons and their local networks in the prefrontal cortex of neurosurgical patients who are operated awake for the removal of brain tumors. During this procedure, patients will perform cognitive tasks requiring them to memorize set sizes (numerosities) specified by the number of dots in a visual display or Arabic numerals. We will address two major questions that cannot be answered with non-invasive experiments, e.g. functional neuroimaging. First, how are non-symbolic quantities encoded at the single-cell level in humans? Second, does the human neuronal number code change when quantities are specified symbolically or is it notation-invariant, i.e. truly abstract?This proposal describes new ways to measure and interpret neuronal activity in the human brain. By bridging the current experimental gap between species, this project will establish a powerful new framework to understand the principles of human numerical cognition and its associated higher cognitive functions with cellular and microcircuit resolution.