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细胞相关的定义的心理功能。动物研究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用于研究单个神经元及其网络如何引起特定的行为。然而，正是这种细节水平在人类研究中缺失。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典型例子的细胞机制，即我们计数，测量和排列项目的能力。数字刺激是灵长类前额叶皮层的强大驱动输入，非常适合研究这个大脑区域如何处理抽象的心理概念。我们将记录大规模的细胞外活动，从个别神经元和他们的局部网络在前额叶皮层的神经外科病人谁是清醒的手术切除脑肿瘤。在此过程中，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数指定的集合大小（数字）。我们将解决两个主要的问题，不能回答非侵入性实验，例如功能性神经成像。首先，非符号量在人类单细胞水平上是如何编码的？第二，人类神经元的数字代码是否会在数量被符号化时发生变化，或者它是符号不变的，即真正抽象的？该提案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的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.