Simultaneous Eye Tracking and Single-Neuron Recordings in Human Epilepsy Patients

Summary

We describe a method to conduct single-neuron recordings with simultaneous eye tracking in humans. We demonstrate the utility of this method and illustrate how we used this approach to obtain neurons in the human medial temporal lobe that encode targets of a visual search.

Abstract

Intracranial recordings from patients with intractable epilepsy provide a unique opportunity to study the activity of individual human neurons during active behavior. An important tool for quantifying behavior is eye tracking, which is an indispensable tool for studying visual attention. However, eye tracking is challenging to use concurrently with invasive electrophysiology and this approach has consequently been little used. Here, we present a proven experimental protocol to conduct single-neuron recordings with simultaneous eye tracking in humans. We describe how the systems are connected and the optimal settings to record neurons and eye movements. To illustrate the utility of this method, we summarize results that were made possible by this setup. This data shows how using eye tracking in a memory-guided visual search task allowed us to describe a new class of neurons called target neurons, whose response was reflective of top-down attention to the current search target. Lastly, we discuss the significance and solutions to potential problems of this setup. Together, our protocol and results suggest that single-neuron recordings with simultaneous eye tracking in humans are an effective method to study human brain function. It provides a key missing link between animal neurophysiology and human cognitive neuroscience.

Introduction

Human single-neuron recordings are a unique and powerful tool to explore the function of the human brain with extraordinary spatial and temporal resolution¹. Recently, single-neuron recordings have gained wide use in the field of cognitive neuroscience because they permit the direct investigation of cognitive processes central to human cognition. These recordings are made possible by the clinical need to determine the position of epileptic foci, for which depth electrodes are temporarily implanted into the brains of patients with suspected focal epilepsy. With this setup, single-neuron recordings can be obtained using microwires protruding from....

Protocol

1. Participants

1. Recruit neurosurgical patients with intractable epilepsy who are undergoing placement of intracranial electrodes to localize their epileptic seizures.
2. Insert depth electrodes with embedded microwires into all clinically indicated target locations, which typically include a subset of amygdala, hippocampus, anterior cingulate cortex and pre-supplementary motor area. See details for implantation in our previous protocol².
3. Once the patient returns to the epilepsy monitoring unit, connect the recording equipment for both macro- and micro- recordings. This includes carefully preparing a head-wrap that i....

Results

To illustrate the usage of the above-mentioned method, we next briefly describe a use-case that we recently published⁸. We recorded 228 single neurons from the human medial temporal lobe (MTL; amygdala and hippocampus) while the patients were performing a visual search task (Figure 3A, B). During this task, we investigated whether the activity of neurons differentiated between fixations on targets and distractors.

.......

Discussion

In this protocol, we described how to employ single-neuron recordings with concurrent eye tracking and described how we used this method to identify target neurons in the human MTL.

The setup involves three computers: one executing the task (stimulus computer), one running the eye tracker, and one running the acquisition system. To synchronize between the three systems, the parallel port is used to send TTL triggers from the stimulus computer to the electrophysiology system (

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Cedrus Response Box	Cedrus (https://cedrus.com/)	RB-844	Button box
Dell Laptop	Dell (https://dell.com)	Precision 7520	Stimulus Computer
EyeLink Eye Tracker	SR Research (https://www.sr-research.com)	1000 Plus Remote with laptop host computer and LCD arm mount	Eye tracking
MATLAB	MathWorks Inc	R2016a (RRID: SCR_001622)	Data analysis
Neuralynx Neurophysiology System	Neuralynx (https://neuralynx.com)	ATLAS 128	Electrophysiology
Osort	Open source	v4.1 (RRID: SCR_015869)	Spike sorting algorithm
Psychophysics Toolbx	Open source	PTB3 ( RRID: SCR_002881)	Matlab toolbox to implement psychophysical experiments