Name: simultaneous eye tracking and single-neuron recordings in human epilepsy patients
Uploaded: 2019-06-17T13:00:00
Description: Watch this Scientific Journal Video about Simultaneous Eye Tracking and Single-Neuron Recordings in Human Epilepsy Patients at JoVE.com

We thank all patients for their participation. This research was supported by the Rockefeller Neuroscience Institute, the Autism Science Foundation and the Dana Foundation (to S.W.), an NSF CAREER award (1554105 to U.R.), and the NIH (R01MH110831 and U01NS098961 to U.R.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.&#160;We thank James Lee, Erika Quan, and the staff of the Cedars-Sinai Simulation Center for their help in producing the demonstration video.

1. Participants
<ol>
	<li>Recruit neurosurgical patients with intractable epilepsy who are undergoing placement of intracranial electrodes to localize their epileptic seizures.</li>
	<li>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.</li>
	<li>Once the patient returns to the...

<ol>
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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 (<strong class="xfi...

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 the tip of the hybrid depth electrode (a detailed description of the surgical methodology involved in the insertion of hybrid depth electrodes is provided in the previous protocol2). Among others, this method has been used to study human memory3,4, emotion5,6, and attention7,8.
Eye tracking measures gaze position and eye movements (fixations and saccades) during cognitive tasks. Video-based eye trackers typically use the corneal reflection and the center of the pupil as features to track over time9. Eye tracking is an important method to study visual attention because the gaze location indicates the focus of attention during most natural behaviors10,11,12. Eye tracking has been used extensively to study visual attention in healthy individuals13 and neurological populations14,15,16.
While both single-neuron recordings and eye tracking are individually used extensively in humans, few studies have used both simultaneously. As a result, it still remains largely unknown how neurons in the human brain respond to eye movements and/or whether they are sensitive to the currently fixated stimulus. This is in contrast to studies with macaques, where eye-tracking with simultaneous single-neuron recordings has become a standard tool. In order to directly investigate the neuronal response to eye movements, we combined human single-neuron recordings and eye tracking. Here we describe the protocol to conduct such experiments and then illustrate the results through a concrete example.
Despite the established role of the human medial temporal lobe (MTL) in both object representation17,18 and memory3,19, it remains largely unknown whether MTL neurons are modulated as a function of top-down attention to behaviorally relevant goals. Studying such neurons is important to start to understand how goal-relevant information influences bottom-up visual processes. Here, we demonstrate the utility of eye tracking while recording neurons using guided visual search, a well-known paradigm to study goal-directed behavior20,21,22,23,24,25. Using this method, we recently described a class of neurons called target neurons, which signals whether the currently attended stimulus is the goal of an ongoing search8. In the below, we present the study protocol needed to reproduce this previous scientific study. Note that along this example, the protocol can easily be adjusted to study an arbitrary visual attention task.

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

simultaneous eye tracking and single-neuron recordings in human epilepsy patients

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.

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.
...

Watch this Scientific Journal Video about Simultaneous Eye Tracking and Single-Neuron Recordings in Human Epilepsy Patients at JoVE.com

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

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.

Intracranial recordings from patients with intractable epilepsy provide a unique opportunity to study the activity of individual human neurons during ...

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