How Can We Process Microelectrode Data to Isolate Single Neurons in Humans?

Extracellular recordings of single neurons are a commonly used method to study the neural mechanisms of cognition and disease. While extensively used in animal models, rare clinical cases also allow such recordings from the human brain using high-impedance microwires. These recordings allow the study of the activity of individual human neurons during cognitive tasks at single-spike resolution. Here, we discuss one such clinical scenario: Microwires embedded in depth electrodes implanted in epilepsy patients. We outline the three main processing steps to derive well isolated putative single neurons from such recordings: Signal processing, spike detection, and spike sorting. We provide an overview of the state of the art in the acquisition and processing of extracellular recordings with microwires, review a typical experimental setup, spike sorting and detection algorithms. We conclude by providing a step-by-step example, visualizing each intermediate processing step. Together, this chapter provides a practical guide on how to utilize signal processing, spike detection, and spike sorting to derive high-quality single-neuron recordings.