Name: eye-tracking control to assess cognitive functions in patients with amyotrophic lateral sclerosis
Uploaded: 2016-10-13T15:00:00
Description: Watch this Scientific Journal Video about Eye-Tracking Control to Assess Cognitive Functions in Patients with Amyotrophic Lateral Sclerosis at JoVE.com

The authors would like to thank Ralf K&#252;hne for technical support. This work was funded by the Deutsche Forschungsgemeinschaft (DFG) and the Bundesministerium f&#252;r Bildung und Forschung (BMBF #01GM1103A). This is an EU Joint Programme-Neurodegenerative Disease Research (JPND) project. The project is supported through the following organizations under the aegis of JPND-e.g., Germany, Bundesministerium f&#252;r Bildung und Forschung (BMBF, FKZ), Sweden, Vetenskapr&#229;det Sverige, Poland, Narodowe Centrum Bada&#324; i Rozwoju (NCBR).

The study was approved by the Ethics Committee of the University of Ulm (Statement No. 19/12) and the protocol described therefore follows their guidelines. All participants gave written informed consent.
1. Stimuli and Testing Environment
<ol>
	<li>To keep distractions to a minimum perform the research in a dark or a very dimly lit and quiet room.</li>
	<li>Use an appropriate eye tracking device. 
	NOTE: There are a wide variety of devices available to perform eye movement studies. In ...

<ol>
	<li>Kiernan, M. C., 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=Amyotrophic+lateral+sclerosis.">Amyotrophic lateral sclerosis.</a> Lancet. 377 (9769), 942-955 (2011).</li><li>Neumann, M., 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=Ubiquitinated+TDP-43+in+frontotemporal+lobar+degeneration+and+amyotrophic+lateral+sclerosis.">Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.</a> Science. 314 (5796), 130-133 (2006).</li><li>Beeldman, E., Raaphorst, J., Klein Twennaar, ., de Visser, M., Schmand, B. A., de Haan, R. 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Psychiatry. 83 (1), 102-108 (2012).</li><li>Elamin, M., 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=Executive+dysfunction+is+a+negative+prognostic+indicator+in+patients+with+ALS+without+dementia.">Executive dysfunction is a negative prognostic indicator in patients with ALS without dementia.</a> Neurology. 76 (14), 1263-1269 (2011).</li><li>Martin, N. A., 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=Psychological+as+well+as+illness+factors+influence+acceptance+of+non-invasive+ventilation+(NIV)+and+gastrostomy+in+amyotrophic+lateral+sclerosis+(ALS):+a+prospective+population+study.">Psychological as well as illness factors influence acceptance of non-invasive ventilation (NIV) and gastrostomy in amyotrophic lateral sclerosis (ALS): a prospective population study.</a> Amyotroph. Lateral. Scler. Frontotemporal. Degener. 15 (5-6), 376-387 (2014).</li><li>Chi&#242;, A., 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=Neurobehavioral+symptoms+in+ALS+are+negatively+related+to+caregivers'+burden+and+quality+of+life.">Neurobehavioral symptoms in ALS are negatively related to caregivers' burden and quality of life.</a> Eur. J. Neurol. 17 (10), 1298-1303 (2010).</li><li>Lakerveld, J., Kotchoubey, B., K&#252;bler, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+function+in+patients+with+late+stage+amyotrophic+lateral+sclerosis.">Cognitive function in patients with late stage amyotrophic lateral sclerosis.</a> J. Neurol. Neurosurg. Psychiatry. 79 (1), 25-29 (2008).</li><li>Sharma, R., Hicks, S., Berna, C. M., Kennard, C., Talbot, K., Turner, M. 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Neurosci. 34 (43), 14260-14271 (2014).</li><li>Gorges, M., 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=Eye+Movement+Deficits+Are+Consistent+with+a+Staging+Model+of+pTDP-43+Pathology+in+Amyotrophic+Lateral+Sclerosis.">Eye Movement Deficits Are Consistent with a Staging Model of pTDP-43 Pathology in Amyotrophic Lateral Sclerosis.</a> PLoS One. 10 (11), 0142546 (2015).</li><li>Hicks, S. L., 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=An+eye-tracking+version+of+the+trail-making+test.">An eye-tracking version of the trail-making test.</a> PLoS One. 8 (12), 84061 (2013).</li><li>Keller, 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=Eye-tracking+controlled+cognitive+function+tests+in+patients+with+amyotrophic+lateral+sclerosis:+a+controlled+proof-of-principle+study.">Eye-tracking controlled cognitive function tests in patients with amyotrophic lateral sclerosis: a controlled proof-of-principle study.</a> J. Neurol. 262 (8), 1918-1926 (2015).</li><li>Raven, J. C., Court, J. H., Raven, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Manual for Raven's progressive matrices and vocabulary scales. Section 2, the coloured progressive matrices. , (1998).</li><li>Brickenkamp, 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> Aufmerksamkeits-Belastungs-Test (Test d2), 8th edn. , (1994).</li><li>Elamin, M., 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=Cognitive+changes+predict+functional+decline+in+ALS.">Cognitive changes predict functional decline in ALS.</a> Neurology. 80 (17), 1590-1597 (2013).</li><li>Ludolph, A. C., 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=Frontal+lobe+function+in+amyotrophic+lateral+sclerosis:+a+neuropsychologic+and+positron+emission+tomography+study.">Frontal lobe function in amyotrophic lateral sclerosis: a neuropsychologic and positron emission tomography study.</a> Acta. Neurol. Scand. 85 (2), 81-89 (1992).</li><li>Schneider, E., 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=Eye-SeeCam:+an+eye+movement-driven+head+camera+for+the+examination+of+natural+visual+exploration.">Eye-SeeCam: an eye movement-driven head camera for the examination of natural visual exploration.</a> Ann. N. Y. Acad. Sci. 1164, 461-467 (2009).</li><li>Lul&#233;, D., 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+Edinburgh+Cognitive+and+Behavioural+Amyotrophic+Lateral+Sclerosis+Screen:+a+cross-sectional+comparison+of+established+screening+tools+in+a+German-Swiss+population.">The Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen: a cross-sectional comparison of established screening tools in a German-Swiss population.</a> Amyotroph. Lateral. Scler. Frontotemporal. Degener. 16 (1-2), 16-23 (2015).</li><li>Olney, R. 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=The+effects+of+executive+and+behavioral+dysfunction+in+the+course+of+ALS.">The effects of executive and behavioral dysfunction in the course of ALS.</a> Neurology. 65 (11), 1774-1777 (2005).</li><li>Donaghy, C., Thurtell, M. J., Pioro, E. P., Gibson, J. M., Leigh, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Eye+movements+in+amyotrophic+lateral+sclerosis+and+its+mimics:+a+review+with+illustrative+cases.">Eye movements in amyotrophic lateral sclerosis and its mimics: a review with illustrative cases.</a> J. Neurol. Neurosurg. Psychiatry. 82 (1), 110-116 (2011).</li><li>Mizutani, T., 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=Development+of+ophthalmoplegia+in+amyotrophic+lateral+sclerosis+during+long-term+use+of+respirators.">Development of ophthalmoplegia in amyotrophic lateral sclerosis during long-term use of respirators.</a> J. Neurol. Sci. 99 (2-3), 311-319 (1990).</li><li>Khin Khin, E., Minor, D., Holloway, A., Pelleg, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Decisional+Capacity+in+Amyotrophic+Lateral+Sclerosis.">Decisional Capacity in Amyotrophic Lateral Sclerosis.</a> J. Am. Acad. Psychiatry Law. 43 (2), 210-217 (2015).</li><li>K&#252;bler, A., 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=Patients+with+ALS+can+use+sensorimotor+rhythms+to+operate+a+brain-computer+interface.">Patients with ALS can use sensorimotor rhythms to operate a brain-computer interface.</a> Neurology. 64 (10), 1775-1777 (2005).</li><li>Connolly, S., Galvin, M., Hardiman, O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=End-of-life+management+in+patients+with+amyotrophic+lateral+sclerosis.">End-of-life management in patients with amyotrophic lateral sclerosis.</a> Lancet Neurol. 14 (4), 435-442 (2015).</li></ol>

It is a challenging task to successfully assess the cognitive status of patients with ALS who are unable to speak and write. The use of videooculography systems provides a promising approach. The hereby presented technique is reliable in detecting cognitive deficits, which play a pivotal role in the context of carer burden and disease management20 in ALS patients. Also, the oculomotor versions of the CPM and the D2-test correlate significantly with their respective standard paper-pencil versions, but further s...

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder usually leading to death within 3 to 5 years. In the course of the pathology, patients present with progressive loss of respiratory and bulbar functioning as well as impairments in movement abilities1. It shares some clinical, pathological, and genetic features with frontotemporal dementia2 and it is well documented that about 30% of ALS patients exhibit cognitive deficits3. These deficits are most prominent in the domains of executive function, verbal fluency and language4 and have an influence on survival5, compliance6 and carer burden7. Thus, reliable neuropsychological assessment is crucial in this disease.
Advancing impairments in motor and speech abilities are, however, a limiting factor for thorough evaluation of cognitive abilities in later stages of the disease8. Here, oculomotor based approaches seem to be very promising, as basic eye movement control remains intact for a comparably long time during the course of ALS for the majority of patients9. Eye-tracking parameters itself have been used to gain information about the cognitive status of patients with ALS10 and also correlate with the sequential spreading pattern of ALS11. Eye movement as a means to control cognitive tests in the context of ALS has also been studied in previous works. One study has successfully demonstrated its usability in healthy controls using an oculomotor based version of the Trail-Making Test12, whereas another found it suitable to distinguish between healthy controls and ALS patients based on cognitive performance and to discriminate between cognitively more and less impaired patients13.
The research described here used an oculomotor based methodology to study cognitive impairments in ALS patients, specifically in the domain of executive functioning. Two well validated and commonly used neuropsychological tests were adapted to eye movement control: the Raven&#39;s coloured progressive matrices (CPM)14 and the D2-test15. The CPM is a non-verbal instrument used to measure executive and visuospatial abilities as well as fluid intelligence. The D2-test is also a non-verbal tool used to uncover executive dysfunction in the domains of selective and sustained attention and visual processing speed. Both are widely used clinical tools which have been successfully employed in previous studies assessing potential cognitive decline during the course of the disease16 and the neuropsychological status of ALS patients compared to healthy controls17.
The goal of this work was to show the requirements for successful evaluation of cognitive deficits in ALS independent of movement and speech disabilities using a reliable, eye-tracking based version of the CPM and the D2-test. Importantly, the method described here has the potential to be expanded to study other populations of patients with severe motor impairments.

<table border="0" cellpadding="0" cellspacing="0" width="1081">
	<tbody>
		<tr height="21">
			<td>EyeSeeCam</td>
			<td>EyeSeeTec GmbH; 82256 F&#252;rstenfeldbruck, Germany</td>
			<td></td>
			<td>Videooculography device</td>
		</tr>
	</tbody>
</table>

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.

For the purpose of the research presented here, i.e.,&#160;the development of a reliable oculomotor based neuropsychological assessment for ALS patients, in-house developed software stores the subject&#39;s choices of the CPM in a separate file, allowing for manual computation of the percentage of correct answers. For the D2-test, a record of the vertical eye movements is manually analyzed using a threshold of + 5&#176; for detection of a relevant response. Recordings are assigne...

Watch this Scientific Journal Video about Eye-Tracking Control to Assess Cognitive Functions in Patients with Amyotrophic Lateral Sclerosis at JoVE.com

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

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 ...

The overall goal of this eye-tracking paradigm is to use an oculomotor based technique to assess cognitive functions in patients with Amyotrophic Lateral Sclerosis or ALS who are unable to speak and write. This method can help answer key questions in the field of potential cognitive deficits in patients with severe physical impairments, such as ALS. The main advantage of this technique is that it uses eye movement to conduct neuropsychological testing in ALS patients, and therefore is suited for patients who are unable to speak or write.Though this method was developed for patients with ALS it can also be applied to other patient samples unable to speak and write but within intact oculomotor control. For this experiment, use a portable eye movement recording device with goggles. Optimize eye movement detection by adjusting the cameras in all six degrees of freedom.Next, set up a standardized oculomotor testing paradigm such as a series of saccadic tasks in order to detect deficits in eye movement control. Use software to present these tasks on a hemicylindrical screen via a projector that is mounted above where the participant will sit. Finally, in preparation for the second part of the experiment, check that a red laser spot, which will be used for the eye-tracking based version of the D2 test, appears correctly on the screen.Begin by asking the participant to turn off all potentially disturbing devices, such as mobile phones or pagers. Bring a participant who does not have substantial visual impairments into the testing room. Seat them on an elevated chair in front of an adjustable chin rest that is 150 centimeters from the computer screen.Ask the participant to place their head on the chin rest. And then place the video-oculography goggles on their head. Adjust the goggles to properly fit the head shape and size.Ensure that both eyes are visible on the experimenter's screen, and focus the cameras within the goggles so that the images of each eye are centered on the screen. Next, check that the system is continuously recording eye movements at all times by instructing the participant to look in each corner of the hemicylindrical screen. Start the standardized oculomotor testing paradigm and have the participant complete a second calibration.Ask the participant to track a single spot on the screen oscillating horizontally and then vertically with a frequency of 0.125 hertz in order to map the non-calibrated orthogonalized raw data from the eye movement recording device with respect to the true orthoganlized eye position. Finally, check if the calibration is acceptable, meaning the true eye movement and the raw data are spatially and temporally synchronized. If so, instruct the participant to keep their head as still as possible.For the first part of the experiment the Raven's colored progressive matrices, or CPM test, displays a series of matrices 22 degrees long and 15 degrees high on the screen with a blank space cut out. Instruct the participant to identify the missing piece below each matrix. After making a choice, have the subject close their eyes for at least 250 milliseconds to start off a green frame outlining the six possible alternatives of missing pieces for 1500 milliseconds each.Ask the participant to designate the alternative they think is correct by closing their eyes for at least 250 milliseconds while their choice is within the green frame. Project the participant's choice separately on the hemicylindrical screen, in order to confirm, instruct them to close their eyes again for at least 250 milliseconds. Have the participant complete further training by selecting the missing piece in the next three matrices.Answer any questions the participant may have about the procedure. Then have the participant complete the full CPM task. For the second part of the experiment, the D2 test, ask the participant to direct their gaze to the center of the screen.Tell them to observe each of the 47 letters with a height of 11 degrees and a width of 2.5 degrees, one after the other in the middle of the screen in which each stimulus lasts for 2000 milliseconds. Whenever the letter d with two dashes is presented instruct the participant to look at the red laser spot positioned above the letter until the next stimulus appears. Finally, after the training is complete, have the participant complete the full D2 test, consisting of five blocks of 47 stimuli each.In a sample of patients with Amyotrophic Lateral Sclerosis, or ALS, there was a good congruency between the eye-tracking and standard version of the CPM test. Furthermore, there's significant group differences in the CPM test and the D2 test, indicating that this technique reliably distinguishes between more and less cognitively impaired ALS patients. Once mastered this technique can be completed in 25 minutes if it is performed properly.For ALS patients with insufficient oculomotor control other methods, such as the brain-computer interface can be utilized in order to assess their cognitive functioning. After watching this video, you should have good understanding of how to perform eye movement based neural psychological testing with ALS patients.

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Research

JoVE Journal

Behavior

A Method for Investigating Age-related Differences in the Functional Connectivity of Cognitive Control Networks Associated with Dimensional Change Card Sort Performance

The ability to adjust behavior to sudden changes in the environment develops gradually in childhood and adolescence. For example, in the Dimensional Change Card Sort task, participants switch from sorting cards one way, such as shape, to sorting them a different way, such as color. Adjusting behavior in this way exacts a small performance cost, or switch cost, such that responses are typically slower and more error-prone on switch trials in which the sorting rule changes as compared to repeat trials in which the sorting rule remains the same. The ability to flexibly adjust behavior is often said to develop gradually, in part because behavioral costs such as switch costs typically decrease with increasing age. Why aspects of higher-order cognition, such as behavioral flexibility, develop so gradually remains an open question. One hypothesis is that these changes occur in association with functional changes in broad-scale cognitive control networks. On this view, complex mental operations, such as switching, involve rapid interactions between several distributed brain regions, including those that update and maintain task rules, re-orient attention, and select behaviors. With development, functional connections between these regions strengthen, leading to faster and more efficient switching operations. The current video describes a method of testing this hypothesis through the collection and multivariate analysis of fMRI data from participants of different ages.

This video presents a method of examining age-related changes in functional connectivity of cognitive control networks engaged by targeted tasks/processes. The technique is based on multi-variate analysis of fMRI data.

The ability to adjust behavior to sudden changes in the environment develops gradually in childhood and adolescence. For example, in the Dimensional ...

Uncovering Beat Deafness: Detecting Rhythm Disorders with Synchronized Finger Tapping and Perceptual Timing Tasks

A set of behavioral tasks for assessing perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) is presented here with the goal of uncovering rhythm disorders, such as beat deafness. Beat deafness is characterized by poor performance in perceiving durations in auditory rhythmic patterns or poor synchronization of movement with auditory rhythms (e.g., with musical beats). These tasks include the synchronization of finger tapping to the beat of simple and complex auditory stimuli and the detection of rhythmic irregularities (anisochrony detection task) embedded in the same stimuli. These tests, which are easy to administer, include an assessment of both perceptual and sensorimotor timing abilities under different conditions (e.g., beat rates and types of auditory material) and are based on the same auditory stimuli, ranging from a simple metronome to a complex musical excerpt. The analysis of synchronized tapping data is performed with circular statistics, which provide reliable measures of synchronization accuracy (e.g., the difference between the timing of the taps and the timing of the pacing stimuli) and consistency. Circular statistics on tapping data are particularly well-suited for detecting individual differences in the general population. Synchronized tapping and anisochrony detection are sensitive measures for identifying profiles of rhythm disorders and have been used with success to uncover cases of poor synchronization with spared perceptual timing. This systematic assessment of perceptual and sensorimotor timing can be extended to populations of patients with brain damage, neurodegenerative diseases (e.g., Parkinson&#8217;s disease), and developmental disorders (e.g., Attention Deficit Hyperactivity Disorder).

Behavioral tasks that allow for the assessment of perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) are presented. Synchronization of finger tapping to the beat of an auditory stimuli and detecting rhythmic irregularities provides a means of uncovering rhythm disorders.

A set of behavioral tasks for assessing perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) is presented here ...

Recording Mouse Ultrasonic Vocalizations to Evaluate Social Communication

Mice emit ultrasonic vocalizations in different contexts throughout development and in adulthood. These vocal signals are now currently used as proxies for modeling the genetic bases of vocal communication deficits. Characterizing the vocal behavior of mouse models carrying mutations in genes associated with neuropsychiatric disorders such as autism spectrum disorders will help to understand the mechanisms leading to social communication deficits. We provide here protocols to reliably elicit ultrasonic vocalizations in pups and in adult mice. This standardization will help reduce inter-study variability due to the experimental settings. Pup isolation calls are recorded throughout development from individual pups isolated from dam and littermates. In adulthood, vocalizations are recorded during same-sex interactions (without a sexual component) by exposing socially motivated males or females to an unknown same-sex conspecific. We also provide a protocol to record vocalizations from adult males exposed to an estrus female. In this context, there is a sexual component in the interaction. These protocols are established to elicit a large amount of ultrasonic vocalizations in laboratory mice. However, we point out the important inter-individual variability in the vocal behavior of mice, which should be taken into account by recording a minimal number of individuals (at least 12 in each condition). These recordings of ultrasonic vocalizations are used to evaluate the call rate, the vocal repertoire and the acoustic structure of the calls. Data are combined with the analysis of synchronous video recordings to provide a more complete view on social communication in mice. These protocols are used to characterize the vocal communication deficits in mice lacking ProSAP1/Shank2, a gene associated with autism spectrum disorders. More ultrasonic vocalizations recordings can also be found on the mouseTube database, developed to favor the exchange of such data.

Mouse ultrasonic vocalizations are used as proxies to model the genetic bases of vocal communication deficits in mouse models for neuropsychiatric disorders. The present protocol describes three experimental contexts that reliably elicit ultrasonic vocalizations from pups (throughout development) and adult mice (same-sex interactions, male-estrus female interactions).

Mice emit ultrasonic vocalizations in different contexts throughout development and in adulthood. These vocal signals are now currently used as proxies ...

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 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 ...

Comparing Eye-tracking Data of Children with High-functioning ASD, Comorbid ADHD, and of a Control Watching Social Videos

Children with autism spectrum disorders (ASD) are known to have sensory-perceptual processing deficits that weaken their abilities to attend and perceive social stimuli in daily living contexts. Since daily social episodes consist of subtle dynamic changes in social information, any failure to attend to or process subtle human nonverbal cues, such as facial expression, postures, and gestures, might lead to inappropriate social interaction. Traditional behavioral rating scales or assessment tools based on static social scenes have limitations in capturing the moment-to-moment changes in social scenarios. An eye-tracking assessment, which can be administered in a video-based mode, is therefore preferred, to augment clinical observation. In this study, using the single-case comparison design, the eye-tracking data of three participants, a child with autism spectrum disorder (ASD), another with comorbid attention deficit-hyperactive disorder (ADHD), and a neurotypical control, are captured while they view a video of social scenarios. The eye-tracking experiment has helped answer the research question: How does social attention differ between the three participants? By predefining areas of interest (AOIs), their visual attention on relevant or irrelevant social stimuli, how fast each participant attends to the first social stimuli appearing in the videos, for how long each participant continues to attend to those stimuli within the AOIs, and the gaze shifts between multiple social stimuli appearing concurrently in the same social scene are captured, compared, and analyzed in a video-based eye-tracking experiment.

This is a qualitative comparative case study analysis of eye-tracking data on the first moments of social video scenes as viewed by three participants: one with autism spectrum disorder, one with comorbid attention deficit-hyperactive disorder, and one neurotypical control.

Children with autism spectrum disorders (ASD) are known to have sensory-perceptual processing deficits that weaken their abilities to attend and perceive ...

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.

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 ...

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.

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 ...