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

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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.