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>
	<li>Fried, I., Rutishauser, U., Cerf, M., Kreiman, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Single Neuron Studies of the Human Brain: Probing Cognition. , (2014).</li><li>Minxha, J., Mamelak, A. N., Rutishauser, U., Sillitoe, R. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surgical+and+Electrophysiological+Techniques+for+Single-Neuron+Recordings+in+Human+Epilepsy+Patients.">Surgical and Electrophysiological Techniques for Single-Neuron Recordings in Human Epilepsy Patients.</a> Extracellular Recording Approaches. , 267-293 (2018).</li><li>Rutishauser, U., Mamelak, A. N., Schuman, E. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Single-Trial+Learning+of+Novel+Stimuli+by+Individual+Neurons+of+the+Human+Hippocampus-Amygdala+Complex.">Single-Trial Learning of Novel Stimuli by Individual Neurons of the Human Hippocampus-Amygdala Complex.</a> Neuron. 49, 805-813 (2006).</li><li>Rutishauser, U., Ross, I. B., Mamelak, A. N., Schuman, E. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+memory+strength+is+predicted+by+theta-frequency+phase-locking+of+single+neurons.">Human memory strength is predicted by theta-frequency phase-locking of single neurons.</a> Nature. 464, 903-907 (2010).</li><li>Wang, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neurons+in+the+human+amygdala+selective+for+perceived+emotion.">Neurons in the human amygdala selective for perceived emotion.</a> Proceedings of the National Academy of Sciences. 111, E3110-E3119 (2014).</li><li>Wang, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+human+amygdala+parametrically+encodes+the+intensity+of+specific+facial+emotions+and+their+categorical+ambiguity.">The human amygdala parametrically encodes the intensity of specific facial emotions and their categorical ambiguity.</a> Nature Communications. 8, 14821 (2017).</li><li>Minxha, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fixations+Gate+Species-Specific+Responses+to+Free+Viewing+of+Faces+in+the+Human+and+Macaque+Amygdala.">Fixations Gate Species-Specific Responses to Free Viewing of Faces in the Human and Macaque Amygdala.</a> Cell Reports. 18, 878-891 (2017).</li><li>Wang, S., Mamelak, A. N., Adolphs, R., Rutishauser, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Encoding+of+Target+Detection+during+Visual+Search+by+Single+Neurons+in+the+Human+Brain.">Encoding of Target Detection during Visual Search by Single Neurons in the Human Brain.</a> Current Biology. 28, 2058-2069 (2018).</li><li>Holmqvist, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Eye tracking: A comprehensive guide to methods and measures. , (2011).</li><li>Liversedge, S. P., Findlay, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Saccadic+eye+movements+and+cognition.">Saccadic eye movements and cognition.</a> Trends in Cognitive Sciences. 4, 6-14 (2000).</li><li>Rehder, B., Hoffman, A. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Eyetracking+and+selective+attention+in+category+learning.">Eyetracking and selective attention in category learning.</a> Cognitive Psychology. 51, 1-41 (2005).</li><li>Blair, M. R., Watson, M. R., Walshe, R. C., Maj, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Extremely+selective+attention:+Eye-tracking+studies+of+the+dynamic+allocation+of+attention+to+stimulus+features+in+categorization.">Extremely selective attention: Eye-tracking studies of the dynamic allocation of attention to stimulus features in categorization.</a> Journal of Experimental Psychology: Learning, Memory, and Cognition. 35, 1196 (2009).</li><li>Rutishauser, U., Koch, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Probabilistic+modeling+of+eye+movement+data+during+conjunction+search+via+feature-based+attention.">Probabilistic modeling of eye movement data during conjunction search via feature-based attention.</a> Journal of Vision. 7, (2007).</li><li>Wang, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Autism+spectrum+disorder,+but+not+amygdala+lesions,+impairs+social+attention+in+visual+search.">Autism spectrum disorder, but not amygdala lesions, impairs social attention in visual search.</a> Neuropsychologia. 63, 259-274 (2014).</li><li>Wang, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Atypical+Visual+Saliency+in+Autism+Spectrum+Disorder+Quantified+through+Model-Based+Eye+Tracking.">Atypical Visual Saliency in Autism Spectrum Disorder Quantified through Model-Based Eye Tracking.</a> Neuron. 88, 604-616 (2015).</li><li>Wang, S., Tsuchiya, N., New, J., Hurlemann, R., Adolphs, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preferential+attention+to+animals+and+people+is+independent+of+the+amygdala.">Preferential attention to animals and people is independent of the amygdala.</a> Social Cognitive and Affective Neuroscience. 10, 371-380 (2015).</li><li>Fried, I., MacDonald, K. A., Wilson, C. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Single+Neuron+Activity+in+Human+Hippocampus+and+Amygdala+during+Recognition+of+Faces+and+Objects.">Single Neuron Activity in Human Hippocampus and Amygdala during Recognition of Faces and Objects.</a> Neuron. 18, 753-765 (1997).</li><li>Kreiman, G., Koch, C., Fried, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Category-specific+visual+responses+of+single+neurons+in+the+human+medial+temporal+lobe.">Category-specific visual responses of single neurons in the human medial temporal lobe.</a> Nature Neuroscience. 3, 946-953 (2000).</li><li>Squire, L. R., Stark, C. E. L., Clark, R. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Medial+Temporal+Lobe.">The Medial Temporal Lobe.</a> Annual Review of Neuroscience. 27, 279-306 (2004).</li><li>Chelazzi, L., Miller, E. K., Duncan, J., Desimone, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+neural+basis+for+visual+search+in+inferior+temporal+cortex.">A neural basis for visual search in inferior temporal cortex.</a> Nature. 363, 345-347 (1993).</li><li>Schall, J. D., Hanes, D. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+basis+of+saccade+target+selection+in+frontal+eye+field+during+visual+search.">Neural basis of saccade target selection in frontal eye field during visual search.</a> Nature. 366, 467-469 (1993).</li><li>Wolfe, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=What+Can+1+Million+Trials+Tell+Us+About+Visual+Search?.">What Can 1 Million Trials Tell Us About Visual Search?.</a> Psychological Science. 9, 33-39 (1998).</li><li>Wolfe, J. M., Horowitz, T. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=What+attributes+guide+the+deployment+of+visual+attention+and+how+do+they+do+it?.">What attributes guide the deployment of visual attention and how do they do it?.</a> Nature Review Neuroscience. 5, 495-501 (2004).</li><li>Sheinberg, D. L., Logothetis, N. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Noticing+Familiar+Objects+in+Real+World+Scenes:+The+Role+of+Temporal+Cortical+Neurons+in+Natural+Vision.">Noticing Familiar Objects in Real World Scenes: The Role of Temporal Cortical Neurons in Natural Vision.</a> The Journal of Neuroscience. 21, 1340-1350 (2001).</li><li>Bichot, N. P., Rossi, A. F., Desimone, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Parallel+and+Serial+Neural+Mechanisms+for+Visual+Search+in+Macaque+Area+V4.">Parallel and Serial Neural Mechanisms for Visual Search in Macaque Area V4.</a> Science. 308, 529-534 (2005).</li><li>Rutishauser, U., Schuman, E. M., Mamelak, A. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Online+detection+and+sorting+of+extracellularly+recorded+action+potentials+in+human+medial+temporal+lobe+recordings,+in+vivo.">Online detection and sorting of extracellularly recorded action potentials in human medial temporal lobe recordings, in vivo.</a> Journal of Neuroscience Methods. 154, 204-224 (2006).</li></ol>

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 ...

A principle advantage of our technique is that it allows the simultaneous recording of case position, pupil size, and single neurons in patients implanted with depth electrodes at the bedside. This allows us to determine whether there are neurons in the human brain whose activity is sensitive to eye movements and to the identity of the currently fixated stimulus. While this technique is not designed to study a particular disease, it is well-suited to study neurological diseases that result in abnormal eye movements or other ocular motor abnormalities.Demonstrating the procedure will be Nand Chandravadia and James Lee, research associates from my laboratory. And Erika Quan, a neurodiagnostic technician at Cedars-Sinai. To begin, connect the electrodes to the recording system and position the patient sitting upright.Then, connect the stimulus computer to the electrophysiology system and eye tracker. Place the remote non-invasive infrared eye tracking system on a robust mobile cart. Then, attach a flexible arm that holds an LCD display to the cart.Place a fully charged uninterrupted power supply on the eye tracking cart and connect all devices related to eye tracking to the power supply rather than to an external power source. Make sure the IV device connected to the patient is running on battery and is not plugged into the wall. Start the eye tracking software.Adjust the distance between the patient and the LCD screen to between 60 and 70 centimeters. Also adjust the angle of the LCD screen so that the surface of the screen is approximately parallel to the patient's face. Place a sticker on the patient's forehead so that the eye tracker can adjust for head movements.Now, adjust the height of the screen relative to the patient's head such that the camera of the eye tracker is approximately at the height of the patient's nose. Provide the patient with a button box or keyboard. Verify that triggers and button press are recorded properly before starting the experiment.Start the acquisition software. First visually inspect the broadband local field potentials and make sure they are not contaminated by line noise. Otherwise follow standard procedures to remove noise.To identify single-neurons, band pass filter the signal from 300 hertz to eight kilohertz. Select one of the eight microwires as a reference for each microwire bundle. Enable saving the data as an nrd file before recording.Adjust the distance and angle between the eye tracker and the patient so that the target marker, head distance, pupil, and corneal reflection are marked as ready. This is shown in green in the eye tracking software. Click on the eye to be recorded and set the sampling rate to 500 hertz.Use the auto adjustment of the pupil and corneal reflection threshold. Calibrate the eye tracker with the built-in grid method at the beginning of each block. Confirm the eye positions register nicely as a grid.Otherwise, redo the calibration. Accept the calibration and do the validation. Accept the validation if the maximal validation error is less than two degrees and the average validation error is less than one degree.Otherwise, redo the validation. Then, perform drift correction and proceed to the actual experiment. In this visual search task, use the stimuli from a previous study performed by this group and follow the task procedure as described before.Provide task instructions to the participants. Instruct the participants to find a target item in the search array and respond as soon as possible. Instruct the participants to press the left button of a response box if they find the target and press the right button if they think the target is absent.Explicitly instruct the participants that there will be target-present and target-absent trials. Start stimulus presentation software and run the task. Present a target cue for one second and present the search array using the stimulus presentation software.Record the button presses and provide trial by trial feedback to the participants. To illustrate the usage of this method, 228 single neurons were recorded from the human medial temporal lobe while patients were performing a visual search task as shown here. During this task, it was investigated whether the activity of neurons differentiated between fixations on targets and distractors.When responses were aligned at the button press, neurons were found that showed differential activity between target-present trials and target-absent trials. Black lines represent the onset and offset of the search queue. This neuron increased its firing rate for target-present trials but not for target-absent trials.Conversely, this neuron decreased its firing rate for target-present trials but not for target-absent trials. A subset of medial temporal lobe neurons showed significantly different activities between fixations on targets versus distractors. Furthermore, one type of such target neuron had a greater response to targets relative to distractors whereas the other had a greater response to distractors relative to targets.Together, this result demonstrates that a subset of medial temporal lobe neurons encode whether the present fixation landed on a target or not. It is critical to make sure that the eye tracker does not introduce noise into the recording. Any noise must be removed before the experiments are performed.If noise persists, ensure the screen used to display the stimulus to the subject has an external power supply. Exchange power supplies for more high quality power supplies typically used for high-end audio applications. Following this procedure, analysis of spikes and eye movements are performed to extract information from the data that will allow researcher to investigate the neuronal responses to eye movements.This method paves the way to explore many unanswered questions that require analysis of fixations, such as how neurons collectively drive fixations to interesting objects in a scene.

simultaneous-eye-tracking-single-neuron-recordings-human-epilepsy

Research

JoVE Journal

Behavior

A Method to Quantify Visual Information Processing in Children Using Eye Tracking

Visual problems that occur early in life can have major impact on a child's development. Without verbal communication and only based on observational methods, it is difficult to make a quantitative assessment of a child's visual problems. This limits accurate diagnostics in children under the age of 4 years and in children with intellectual disabilities. Here we describe a quantitative method that overcomes these problems. The method uses a remote eye tracker and a four choice preferential looking paradigm to measure eye movement responses to different visual stimuli. The child sits without head support in front of a monitor with integrated infrared cameras. In one of four monitor quadrants a visual stimulus is presented. Each stimulus has a specific visual modality with respect to the background, e.g., form, motion, contrast or color. From the reflexive eye movement responses to these specific visual modalities, output parameters such as reaction times, fixation accuracy and fixation duration are calculated to quantify a child's viewing behavior. With this approach, the quality of visual information processing can be assessed without the use of communication. By comparing results with reference values obtained in typically developing children from 0-12 years, the method provides a characterization of visual information processing in visually impaired children. The quantitative information provided by this method can be advantageous for the field of clinical visual assessment and rehabilitation in multiple ways. The parameter values provide a good basis to: (i) characterize early visual capacities and consequently to enable early interventions; (ii) compare risk groups and follow visual development over time; and (iii), construct an individual visual profile for each child.

A method is described to quantify the quality of visual information processing based on reflexive eye movements in response to specific visual modalities. Reaction times and fixation output parameters are used to characterize visual performance in children with and without visual impairments from 6 months of age.

Visual problems that occur early in life can have major impact on a child's development. Without verbal communication and only based on observational ...

Eye-Tracking Control to Assess Cognitive Functions in Patients with Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with pathological involvement of upper and lower motoneurons, subsequently leading to progressive loss of motor and speech abilities. In addition, cognitive functions are impaired in a subset of patients. To evaluate these potential deficits in severely physically impaired ALS patients, eye-tracking is a promising means to conduct cognitive tests. The present article focuses on how eye movements, an indirect means of communication for physically disabled patients, can be utilized to allow for detailed neuropsychological assessment. The requirements, in terms of oculomotor parameters that have to be met for sufficient eye-tracking in ALS patients are presented. The properties of stimuli, including type of neuropsychological tests and style of presentation, best suited to successfully assess cognitive functioning, are also described. Furthermore, recommendations regarding procedural requirements are provided. Overall, this methodology provides a reliable, easy to administer and fast approach for assessing cognitive deficits in patients who are unable to speak or write such as patients with severe ALS. The only confounding factor might be deficits in voluntary eye movement control in a subset of ALS patients.

Cognitive deficits are common in about one third of patients with amyotrophic lateral sclerosis, a neurological condition leading to progressive impairments in speech and movement abilities. To conduct cognitive tests in patients unable to speak or write a reliable and easy to administer eye-tracking paradigm was developed.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with pathological involvement of upper and lower motoneurons, subsequently leading to ...

Eye Tracking During Visually Situated Language Comprehension: Flexibility and Limitations in Uncovering Visual Context Effects

The present work is a description and an assessment of a methodology designed to quantify different aspects of the interaction between language processing and the perception of the visual world. The recording of eye-gaze patterns has provided good evidence for the contribution of both the visual context and linguistic/world knowledge to language comprehension. Initial research assessed object-context effects to test&#160;theories of modularity in language processing. In the introduction, we describe how subsequent investigations have taken the role of the wider visual context in language processing as a research topic in its own right, asking questions such as how our visual perception of events and of speakers contributes to&#160;comprehension informed by&#160;comprehenders&#39; experience. Among the examined aspects of the visual context are actions, events, a speaker&#39;s gaze, and emotional facial expressions, as well as spatial object configurations. Following an overview of the eye-tracking method and its different applications, we list the key steps of the methodology in the protocol, illustrating how to successfully use it to study visually-situated language comprehension. A final section presents three sets of representative results and illustrates the benefits and limitations of eye tracking for investigating the interplay between the perception of the visual world and language comprehension.

The present article reviews an eye-tracking methodology for studies on language comprehension. To obtain reliable data, key steps of the protocol must be followed. Among these are the correct set-up of the eye tracker (e.g., ensuring good quality of the eye and head images) and accurate calibration.

The present work is a description and an assessment of a methodology designed to quantify different aspects of the interaction between language processing ...

Eye-tracking to Distinguish Comprehension-based and Oculomotor-based Regressive Eye Movements During Reading

Regressive eye movements are eye movements that move backwards through the text and comprise approximately 10-25% of eye movements during reading. As such, understanding the causes and mechanisms of regressions plays an important role in understanding eye movement behavior. Inhibition of return (IOR) is an oculomotor effect that results in increased latency to return attention to a previously attended target versus a target that was not previously attended. Thus, IOR may affect regressions. This paper describes how to design materials to distinguish between regressions caused by comprehension-related and oculomotor processes; the latter is subject to IOR. The method allows researchers to identify IOR and control the causes of regressions. While the method requires tightly controlled materials and large numbers of participants and materials, it allows researchers to distinguish and control the types of regressions that occur in their reading studies.

The method was designed to investigate the role of inhibition of return (IOR) in regressive eye movements during reading. The focus is on differentiating between regressions triggered as a result of comprehension difficulty versus those triggered from oculomotor error, including the role of IOR in the two types of regressions.

Regressive eye movements are eye movements that move backwards through the text and comprise approximately 10-25% of eye movements during reading. As ...

Gaze in Action: Head-mounted Eye Tracking of Children's Dynamic Visual Attention During Naturalistic Behavior

Young children's visual environments are dynamic, changing moment-by-moment as children physically and visually explore spaces and objects and interact with people around them. Head-mounted eye tracking offers a unique opportunity to capture children's dynamic egocentric views and how they allocate visual attention within those views. This protocol provides guiding principles and practical recommendations for researchers using head-mounted eye trackers in both laboratory and more naturalistic settings. Head-mounted eye tracking complements other experimental methods by enhancing opportunities for data collection in more ecologically valid contexts through increased portability and freedom of head and body movements compared to screen-based eye tracking. This protocol can also be integrated with other technologies, such as motion tracking and heart-rate monitoring, to provide a high-density multimodal dataset for examining natural behavior, learning, and development than previously possible. This paper illustrates the types of data generated from head-mounted eye tracking in a study designed to investigate visual attention in one natural context for toddlers: free-flowing toy play with a parent. Successful use of this protocol will allow researchers to collect data that can be used to answer questions not only about visual attention, but also about a broad range of other perceptual, cognitive, and social skills and their development.

Gaze in Action: Head-mounted Eye Tracking of Children&#039;s Dynamic Visual Attention During Naturalistic Behavior

Young children do not passively observe the world, but rather actively explore and engage with their environment. This protocol provides guiding principles and practical recommendations for using head-mounted eye trackers to record infants' and toddlers' dynamic visual environments and visual attention in the context of natural behavior.

Young children's visual environments are dynamic, changing moment-by-moment as children physically and visually explore spaces and objects and interact ...

Simultaneous Recordings of Cortical Local Field Potentials and Electrocorticograms in Response to Nociceptive Laser Stimuli from Freely Moving Rats

Electrocortical responses, elicited by laser heat pulses that selectively activate nociceptive free nerve endings, are widely used in many animal and human studies to investigate the cortical processing of nociceptive information. These laser-evoked brain potentials (LEPs) consist of several transient responses that are time-locked to the onset of laser stimuli. However, the functional properties of the LEP responses are still largely unknown, due to the lack of a sampling technique that can simultaneously record neural activities at the surface of the cortex (i.e., electrocorticogram [ECoG] and scalp electroencephalogram [scalp EEG]) and inside the brain (i.e., local field potential [LFP]). To address this issue, we present here an animal protocol using freely moving rats. This protocol is composed of three main procedures: (1) animal preparation and surgical procedures, (2) a simultaneous recording of ECoG and LFP in response to nociceptive laser stimuli, and (3) data analysis and feature extraction. Specifically, with the help of a 3D-printed protective shell, both ECoG and LFP electrodes implanted on the rat&#39;s skull were securely held together. During data collection, laser pulses were delivered on the rat&#39;s forepaws through gaps in the bottom of the chamber when the animal was in spontaneous stillness. Ongoing white noise was played to avoid the activation of the auditory system by the laser-generated ultrasounds. As a consequence, only nociceptive responses were selectively recorded. Using the standard analytical procedures (e.g., band-pass filtering, epoch extraction, and baseline correction) to extract stimulus-related brain responses, we obtained results showing that LEPs with a high signal-to-noise ratio were simultaneously recorded from ECoG and LFP electrodes. This methodology makes the simultaneous recording of ECoG and LFP activities possible, which provides a bridge of electrocortical signals at the mesoscopic and macroscopic levels, thereby facilitating the investigation of nociceptive information processing in the brain.

We developed a technique that simultaneously records both electrocorticography and local field potentials in response to nociceptive laser stimuli from freely moving rats. This technique helps establish a direct relationship of electrocortical signals at the mesoscopic and macroscopic levels, which facilitates the investigation of nociceptive information processing in the brain.

Electrocortical responses, elicited by laser heat pulses that selectively activate nociceptive free nerve endings, are widely used in many animal and ...

Investigating the Deployment of Visual Attention Before Accurate and Averaging Saccades via Eye Tracking and Assessment of Visual Sensitivity

This experimental protocol was designed to investigate whether visual attention is obligatorily deployed at the endpoint of saccades. To this end, we recorded the eye position of human participants engaged in a saccade task via eye tracking and assessed visual orientation discrimination performance at various locations during saccade preparation. Importantly, instead of using a single saccade target paradigm for which the saccade endpoint typically coincides roughly with the target, this protocol comprised the presentation of two nearby saccade targets, leading to a distinct spatial dissociation between target locations and saccade endpoint on a substantial number of trials. The paradigm allowed us to compare presaccadic visual discrimination performance at the endpoint of accurate saccades (landing at one of the saccade targets) and of averaging saccades (landing at an intermediate location in between the two targets). We observed a selective enhancement of visual sensitivity at the endpoint of accurate saccades but not at the endpoint of averaging saccades. Rather, before the execution of averaging saccades, visual sensitivity was equally enhanced at both targets, suggesting that saccade averaging follows from unresolved attentional selection among the saccade targets. These results argue against a mandatory coupling between visual attention and saccade programming based on a direct measure of presaccadic visual sensitivity rather than saccadic reaction times, which have been used in other protocols to draw similar conclusions. While our protocol provides a useful framework to investigate the relationship between visual attention and saccadic eye movements at the behavioral level, it can also be combined with electrophysiological measures to extend insights at the neuronal level.

This experimental protocol combined eye tracking and the assessment of presaccadic visual sensitivity in a dual task paradigm, consisting of a free choice saccade task and a visual discrimination task, to investigate the deployment of visual spatial attention before both, accurate and averaging saccades.

This experimental protocol was designed to investigate whether visual attention is obligatorily deployed at the endpoint of saccades. To this end, we ...

Defining the Role Of Language in Infants' Object Categorization with Eye-tracking Paradigms

Assessing infant category learning is a challenging but vital aspect of studying infant cognition. By employing a familiarization-test paradigm, we straightforwardly measure infants&#8217; success in learning a novel category while relying only on their looking behavior. Moreover, the paradigm can directly measure the impact of different auditory signals on the infant categorization across a range of ages. For instance, we assessed how 2-year-olds learn categories in a variety of labeling environments: in our task, 2-year-olds successfully learned categories when all exemplars were labeled&#160;or the first two exemplars were labeled, but they failed to categorize when no exemplars were labeled or only the final two exemplars were labeled. To determine infants&#8217; success in such tasks, researchers can examine both the overall preference displayed by infants in each condition and infants&#8217; pattern of looking over the course of the test phase, using an eye-tracker to provide fine-grained time-course data. Thus, we present a powerful paradigm for identifying the role of language, or any auditory signal, in infants&#8217; object category learning.

Defining the Role Of Language in Infants&#039; Object Categorization with Eye-tracking Paradigms

Here we present a protocol for familiarization-test paradigms which provide a direct test of infant categorization and help to define the role of language in early category learning.

Assessing infant category learning is a challenging but vital aspect of studying infant cognition. By employing a familiarization-test paradigm, we ...

Exploring Infant Sensitivity to Visual Language using Eye Tracking and the Preferential Looking Paradigm

We discuss the use of the preferential looking paradigm in eye tracking studies in order to study how infants develop, understand, and attend to the world around them. Eye tracking is a safe and non-invasive way to collect gaze data from infants, and the preferential looking paradigm is simple to design and only requires the infant to be attending to the screen. By simultaneously showing two visual stimuli that differ in one dimension, we can assess whether infants show different looking behavior for either stimulus, thus demonstrating sensitivity to that difference. The challenges in such experimental approaches are that experiments must be kept brief (no more than 10 min) and be carefully controlled such that the two stimuli differ in only one way. The interpretation of null results must also be carefully considered. In this paper, we illustrate a successful example of an infant eye tracking study with a preferential looking paradigm to discover that 6-month-olds are sensitive to linguistic cues in a signed language despite having no prior exposure to signed language, suggesting that infants possess intrinsic or innate sensitivities to these cues.

Eye tracking studies using a preferential looking paradigm can be used to study infants&#39;&#160;emerging understanding of, and attention to, their external visual world.

We discuss the use of the preferential looking paradigm in eye tracking studies in order to study how infants develop, understand, and attend to the world ...

Loneliness Assuaged: Eye-Tracking an Audience Watching Barrage Videos

Researchers usually theorize media exposure based on assumptions of legacy media. However, a new interactive video viewing format, in this case barrage video where viewers&#8217; comments are overlaid over visual content, challenges past perspectives. This study proposes an activation and match satisfaction model to study viewing behaviors of lonely people and to challenge previous claims. It presents a protocol to examine the mechanism of how loners use barrage videos by combining eye tracking and self-report measures. Eye tracking documents the audience&#39;s conscious and subconscious watching behaviors in real time and allows for inference of the amount of allocated cognitive resources in response to rational and emotional content. The self-report gauges the amount of satisfaction obtained. Overall, results from the measures supported an activation and match satisfaction model regarding loners and their barrage video viewing behaviors. Implications are discussed.

The study proposes an activation-match model to study how loneliness is mitigated when a lonely audience watches barrage videos of rational and emotional appeals. The protocol uses eye tracking to document duration and fixation, accounting for the degree of satisfaction when emotional needs are appeased by content and barrage.

Researchers usually theorize media exposure based on assumptions of legacy media. However, a new interactive video viewing format, in this case barrage ...