Name: using the race model inequality to quantify behavioral multisensory integration effects
Uploaded: 2019-05-10T14:45:00
Description: Watch this Scientific Journal Video about Using the Race Model Inequality to Quantify Behavioral Multisensory Integration Effects at JoVE.com

The current body of work is supported by the National Institute on Aging at the National Institute of Health (K01AG049813 to JRM). Supplementary funding was provided by the Resnick Gerontology Center of the Albert Einstein College of Medicine. Special thanks to all the volunteers and research staff for exceptional support with this project.

All participants provided written informed consent to the experimental procedures, which were approved by the institutional review board of the Albert Einstein College of Medicine.
1. Participant Recruitment, Inclusion Criteria, and Consent
<ol>
	<li>Recruit a relatively large cohort of English-speaking individuals who can ambulate independently and are free of significant sensory loss; active neurological or psychiatric disorders that interfere with experimental evaluations; and current/fut...

<ol>
	<li>Foxe, 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=Auditory-somatosensory+multisensory+processing+in+auditory+association+cortex:+an+fMRI+study.">Auditory-somatosensory multisensory processing in auditory association cortex: an fMRI study.</a> Journal of Neurophysiology. 88 (1), 540-543 (2002).</li><li>Molholm, 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=Multisensory+auditory-visual+interactions+during+early+sensory+processing+in+humans:+a+high-density+electrical+mapping+study.">Multisensory auditory-visual interactions during early sensory processing in humans: a high-density electrical mapping study.</a> Brain Research: Cognitive Brain Research. 14 (1), 115-128 (2002).</li><li>Murray, M. 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=Grabbing+your+ear:+rapid+auditory-somatosensory+multisensory+interactions+in+low-level+sensory+cortices+are+not+constrained+by+stimulus+alignment.">Grabbing your ear: rapid auditory-somatosensory multisensory interactions in low-level sensory cortices are not constrained by stimulus alignment.</a> Cerebral Cortex. 15 (7), 963-974 (2005).</li><li>Molholm, 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=Audio-visual+multisensory+integration+in+superior+parietal+lobule+revealed+by+human+intracranial+recordings.">Audio-visual multisensory integration in superior parietal lobule revealed by human intracranial recordings.</a> Journal of Neurophysiology. 96 (2), 721-729 (2006).</li><li>Peiffer, A. M., Mozolic, J. L., Hugenschmidt, C. E., Laurienti, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Age-related+multisensory+enhancement+in+a+simple+audiovisual+detection+task.">Age-related multisensory enhancement in a simple audiovisual detection task.</a> Neuroreport. 18 (10), 1077-1081 (2007).</li><li>Brandwein, A. 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C., Oh-Park, M., Verghese, J., Holtzer, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multisensory+integration+across+the+senses+in+young+and+old+adults.">Multisensory integration across the senses in young and old adults.</a> Brain Research. 1426, 43-53 (2011).</li><li>Foxe, J. J., Ross, L. A., Molholm, S., Stein, B. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ch.+38.">Ch. 38.</a> The New Handbook of Multisensory Processing. , 691-706 (2012).</li><li>Kinchla, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Detecting+target+elements+in+multielement+arrays:+A+confusability+model.">Detecting target elements in multielement arrays: A confusability model.</a> Perception and Psychophysics. 15, 149-158 (1974).</li><li>Miller, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Divided+attention:+Evidence+for+coactivation+with+redundant+signals.">Divided attention: Evidence for coactivation with redundant signals.</a> Cognitive Psychology. 14 (2), 247-279 (1982).</li><li>Eriksen, C. W., Goettl, B., St James, J. D., Fournier, L. 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J., Yuille, A. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Data Fusion for Sensory Information Processing Systems. , (1990).</li><li>Ernst, M. O., Banks, M. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Humans+integrate+visual+and+haptic+information+in+a+statistically+optimal+fashion.">Humans integrate visual and haptic information in a statistically optimal fashion.</a> Nature. 415 (6870), 429-433 (2002).</li><li>Mahoney, J. R., Verghese, J., Dumas, K., Wang, C., Holtzer, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effect+of+multisensory+cues+on+attention+in+aging.">The effect of multisensory cues on attention in aging.</a> Brain Research. 1472, 63-73 (2012).</li><li>Mahoney, J. R., Holtzer, R., Verghese, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Visual-somatosensory+integration+and+balance:+evidence+for+psychophysical+integrative+differences+in+aging.">Visual-somatosensory integration and balance: evidence for psychophysical integrative differences in aging.</a> Multisensory Research. 27 (1), 17-42 (2014).</li><li>Mahoney, J. R., Dumas, K., Holtzer, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Visual-Somatosensory+Integration+is+linked+to+Physical+Activity+Level+in+Older+Adults.">Visual-Somatosensory Integration is linked to Physical Activity Level in Older Adults.</a> Multisensory Research. 28 (1-2), 11-29 (2015).</li><li>Dumas, K., Holtzer, R., Mahoney, J. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Visual-Somatosensory+Integration+in+Older+Adults:+Links+to+Sensory+Functioning.">Visual-Somatosensory Integration in Older Adults: Links to Sensory Functioning.</a> Multisensory Research. 29 (4-5), 397-420 (2016).</li><li>Couth, S., Gowen, E., Poliakoff, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Using+race+model+violation+to+explore+multisensory+responses+in+older+adults:+Enhanced+multisensory+integration+or+slower+unisensory+processing.">Using race model violation to explore multisensory responses in older adults: Enhanced multisensory integration or slower unisensory processing.</a> Multisensory Research. 31 (3-4), 151-174 (2017).</li><li>Gondan, M., Minakata, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+tutorial+on+testing+the+race+model+inequality.">A tutorial on testing the race model inequality.</a> Attention, Perception &amp; Psychophysics. 78 (3), 723-735 (2016).</li><li>Gondan, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+permutation+test+for+the+race+model+inequality.">A permutation test for the race model inequality.</a> Behavior Research Methods. 42 (1), 23-28 (2010).</li><li>Kiesel, A., Miller, J., Ulrich, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Systematic+biases+and+Type+I+error+accumulation+in+tests+of+the+race+model+inequality.">Systematic biases and Type I error accumulation in tests of the race model inequality.</a> Behavior Research Methods. 39 (3), 539-551 (2007).</li><li>Mahoney, J., Cotton, K., Verghese, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multisensory+Integration+Predicts+Balance+and+Falls+in+Older+Adults.">Multisensory Integration Predicts Balance and Falls in Older Adults.</a> Journal of Gerontology: Medical Sciences. , (2018).</li><li>Mahoney, J. 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The goal of the current study was to detail the process behind the establishment of a robust multisensory integration phenotype. Here, we provide the necessary and critical steps required to acquire multisensory integration effects that can be utilized to predict important cognitive and motor outcomes relying on similar neural circuitry. Our overall objective was to provide a step-by-step tutorial for calculating the magnitude of multisensory integration in an effort to facilitate innovative and novel translational multi...

Interactions across sensory systems are essential for everyday functions. While multisensory integration effects are measured across a wide array of populations using assorted sensory combinations and different neuroscience approaches [including but not limited to the psychophysical, electrophysiological, and neuroimaging methodologies]1,2,3,4,5,6,7,8,9, currently a gold standard for quantifying multisensory integration is lacking. Given that multisensory experiments typically contain&#160;a behavioral component, reaction time (RT) data is often examined to determine the existence of a well-known phenomenon called the redundant signals effect10. As its name suggests, simultaneous sensory signals provide redundant information, which typically yield quicker RTs. Race and co-activation models are used to explain the above mentioned redundant signals effect11. Under race models, the unisensory signal that is processed the fastest is the winner of the race and is responsible for producing the behavioral response. However, evidence for co-activation occurs when responses to multisensory stimuli are quicker than what race models predict.
Earlier versions of the race model are inherently controversial12,13 as they are referred to by some as overly conservative14,15 and purportedly contain limitations regarding the independence between the constituent unisensory detection times inherent in the multisensory condition16. In an effort to address some of these limitations, Colonius &#38; Diederich16 developed a more conventional race model test:
<img alt="Equation 1" src="/files/ftp_upload/59575/59575eq1.jpg" />,
where the cumulative distribution frequencies (CDFs) of the unisensory conditions (e.g., A &#38; B; with an upper limit of one) are compared to the CDF of the simultaneous multisensory condition (e.g., AB) for any given latency (t)11,16,17. In general, a CDF determines how often an RT occurs, within a given range of RTs, divided by the total number of stimulus presentations (i.e., trials). If the CDF of the actual multisensory condition <img alt="Equation 2" src="/files/ftp_upload/59575/59575eq2.jpg" /> is less than or equal to the predicted CDF derived from the unisensory conditions
<img alt="Equation 3" src="/files/ftp_upload/59575/59575eq3.jpg" />,
then the race model is accepted and there is no evidence for sensory integration. However, when the multisensory CDF is greater than the predicted CDF derived from the unisensory conditions, the race model is rejected. Rejection of the race model indicates that multisensory interactions from redundant sensory sources combine&#160;in a non-linear manner, resulting in a speeding up of RTs (e.g., RT facilitation) to multisensory stimuli.
One main hurdle that multisensory researchers face is how to best quantify integration effects. For instance, in the case of the most basic behavioral multisensory paradigm, where participants are asked to perform a simple reaction time task, information regarding accuracy and speed is collected. Such multisensory data can be used at the face-value or manipulated using various mathematical applications including but not limited to Maximum Likelihood Estimation18,19, CDFs11, and various other statistical approaches. The majority of our previous multisensory studies employed both quantitative and probabilistic approaches where multisensory integrative effects were calculated by 1) subtracting the mean reaction time (RT) to a multisensory event from the mean reaction time (RT) to the shortest unisensory event, and 2) by employing CDFs to determine whether RT facilitation resulted from synergistic interactions facilitated by redundant sensory information8,20,21,22,23. However, the former methodology was likely not sensitive to the individual differences in integrative processes and researchers have since posited that the later methodology (i.e., CDFs) may provide a better proxy for quantifying multisensory integrative effects24.
Gondan and Minakata recently published a tutorial on how to accurately test the Race Model Inequality (RMI) since researchers all too often make countless errors during the acquisition and pre-processing stages of RT data collection and preparation25. First, the authors posit that is unfavorable to apply data trimming procedures where certain a priori minimum and maximum RT limits are set. They recommend that slow and omitted responses be set to infinity, rather than excluded. Second, given that the RMI may be violated at any latency, multiple t-tests are often used to test the RMI at different time points (i.e., quantiles); unfortunately, this practice leads to the increased Type I error and substantially reduced statistical power. To avoid these issues, it is recommended that the RMI be tested over one specific time range. Some researchers have suggested that it makes sense to test the fastest quartile of responses (0-25%)26 or some pre-identified windows (i.e., 10-25%)24,27 as multisensory integration effects are typically observed during that time interval; however, we argue that the percentile range to be tested must be dictated by the actual dataset (see Protocol Section 5). The problem with relying on published data from young adults or computer simulations is that older adults manifest very different RT distributions, likely due to the age-related declines in sensory systems. Race model significance testing should only be tested over violated portions (positive values) of group-averaged difference wave between actual and predicted CDFs from the study cohort.
To this end, a protective effect of multisensory integration in healthy older adults using the conventional test of the race model16 and the principles set forth by Gondan and colleagues25 has been demonstrated. In fact, greater magnitude of visual-somatosensory RMI (a proxy for multisensory integration) was found to be linked to better balance performance, lower probability of incident falls and increased spatial gait performance28,29.
The objective of the current experiment is to provide researchers with a step-by-step tutorial to calculate the magnitude of multisensory integration effects using the RMI, to facilitate the increased production of diverse translational research studies across many different clinical populations. Note that data presented in the current study are from recently published visual-somatosensory experiments conducted on healthy older adults28,29, but this methodology can be applied to various cohorts across many different experimental designs, utilizing a wide-array of multisensory combinations.

<table>
	<tbody>
		<tr>
			<td>stimulus generator</td>
			<td>Zenometrics, LLC; Peekskill, NY, USA</td>
			<td>n/a</td>
			<td>custom-built</td>
		</tr>
		<tr>
			<td>Excel</td>
			<td>Microsoft Corporation</td>
			<td></td>
			<td>spreadsheet program</td>
		</tr>
		<tr>
			<td>Eprime</td>
			<td>Psychology Software Tools (PST)</td>
			<td></td>
			<td>stimulus presentation software</td>
		</tr>
	</tbody>
</table>

using the race model inequality to quantify behavioral multisensory integration effects

Multisensory integration research investigates how the brain processes simultaneous sensory information. Research on animals (mainly cats and primates) and humans reveal that intact multisensory integration is crucial for functioning in the real world, including both cognitive and physical activities. Much of the research conducted over the past several decades documents multisensory integration effects using diverse psychophysical, electrophysiological, and neuroimaging techniques. While its presence has been reported, the methods used to determine the magnitude of multisensory integration effects varies and typically faces much criticism. In what follows, limitations of previous behavioral studies are outlined and a step-by-step tutorial for calculating the magnitude of multisensory integration effects using robust probability models is provided.

The purpose of this study was to provide a step-by-step tutorial of a methodical approach to quantify the magnitude of VS integration effects, to foster the publication of new multisensory studies using similar experimental designs and setups (see Figure 1). Screenshots of each step and calculation needed to derive magnitude of multisensory integration effects, as measured by RMI AUC, are delineated above and illustrated in Figures&#160;2-8.
<stro...

Watch this Scientific Journal Video about Using the Race Model Inequality to Quantify Behavioral Multisensory Integration Effects at JoVE.com

Using the Race Model Inequality to Quantify Behavioral Multisensory Integration Effects

The current study aims to provide a step-by-step tutorial for calculating the magnitude of multisensory integration effects in an effort to facilitate the production of translational research studies across diverse clinical populations.

Multisensory integration research investigates how the brain processes simultaneous sensory information. Research on animals (mainly cats and primates) ...

Establishing a reproducible method for calculating the magnitude of multisensory integration effects is significant, as it will aid in the facilitation of future translational research across diverse clinical populations. The main advantage to our technique is that we're able to quantify a robust phenotype of multisensory integration that is subsequently associated with important cognitive and motor outcomes in aging, like balance, falls, gait, and executive functions. Begin by using stimulus presentation software to program a simple reaction time experiment with three experimental conditions, visual alone, somatosensory alone, and simultaneous visual-somatosensory.Use a stimulus generator with three control boxes. The left and right control boxes contain bilateral blue light-emitting diodes that illuminate for visual stimulation and bilateral motors with 0.8 G vibration amplitude that vibrate for somatosensory stimulation, as well as plastic housing for the stimulators. Next, place a center dummy control box equidistant from the left and right control boxes, and affix a visual target sticker to serve as the fixation point.After the experiment has been set up, escort the participant to the testing room. Have the participant sit upright and comfortably rest their hands upon the left and right control boxes. Strategically place index fingers over the vibratory motors mounted to the back of the control box and thumbs on the front of the control box under the LEDs, to not block the light.Ensure that the somatosensory stimuli are inaudible by providing participants with headphones over which continuous white noise is played at a comfortable level. Have the participant use a foot pedal located under the right foot as the response pad. Finally, have the participant respond to each stimulus as quickly as possible regardless of whether they feel it, see it, or feel it and see it.Begin analysis by excluding participants that are not able to attain an accuracy of 70%correct or greater on any one stimulus condition. Consider trials inaccurate if a participant fails to respond to a stimulus within the set response time period, and set corresponding reaction time, or RT, to infinity rather than excluding the trial from the analysis. RT data are sorted in ascending order by the experimental condition.Place visual, somatosensory, and VS conditions in separate columns of sorted RT data. Ensure each row represents one trial and each cell represents the actual RT.Note, do not employ data-trimming procedures that delete very slow RTs, as this will bias the distribution of RT data. Ensure RTs that are clearly outliers are set to infinity.Then, to bin the RT data, identify the fastest and the slowest RT.Subtract the slowest RT from the fastest in order to calculate the individual's RT range across all test conditions. Bin RT data from the 0%to the 100%in 5%increments by taking the fastest RT and gradually adding 5%to the previously calculated RT range until 100%of the RT data is accounted for, to result in 21 time bins. Next, within a computer spreadsheet, use a frequency function where array one equals the actual RTs for one of the experimental conditions and array two equals the 21 quantized RT bins previously calculated divided by the total number of trials, 45, per condition.Then, create the cumulative distribution frequency, or CDF, by summing the running total of probabilities across the quantized bins for each of three experimental conditions. The CDF of the multisensory condition represents the actual CDF. To calculate the predicted CDF, sum the two unisensory CDFs with an upper limit set to one.Use this formula across each one of the 21 quantized time bins. Start at the zeroth percentile, and continue all the way down to the 100th percentile for bin 21. Next, to conduct the Test of the Race Model Inequality, subtract the predicted CDF from the actual CDF for each of the 21 quantized time bins to obtain the difference values.Plot these 21 values as a line graph, where the x-axis represents each one of the quantized time bins and the y-axis represents the probability difference between the actual and predicted CDFs. Here, positive values at any latency indicate the integration of the unisensory stimuli and reflect a violation of the RMI. To quantify the multisensory effect at a group level, group-average the individual RMI data across all participants.Use a spreadsheet to assign individuals to rows and time bins to columns. Then, in a new spreadsheet, place the previously calculated 21 difference values into individual rows and average values within time bins to create one group-averaged difference waveform. Then, plot the group average 21 values as a line graph, where the x-axis represents each one of the quantized time bins and the y-axis represents the probability difference between the CDFs.Finally, calculate the area under the curve for each individual by using participant one's data as an example. Sum the CDF difference value at time bin one with the CDF difference value at time bin two, and then divide by two. Visually inspect each consecutive pair of time bins containing positive values.Then, sum these results to generate the total AUC of the CDF difference wave during the violated percentile range of 0.00 to 0.10. Results indicate a group-averaged violation occurring over the zero to 10%percentile range for a sample of 333 older adults. The total number of positive values, zero, one, two, or three, for those three quantiles, 0.00 to 0.10, determines which multisensory classification group a person is assigned to, either deficient, poor, good, or superior, respectively.As we have previously described, it is critical to avoid data-trimming procedures, as it biases the RT distributions. Slow reaction times and omitted trials need to be set to infinity. The main objective here was to develop a robust phenotype of multisensory integration.Having said that, we are aware of differential multisensory integration patterns in aging, and our next step will be to uncover the neural networks responsible for such integrative processes while determining how specific structural or functional alterations contribute to the differential integration patterns. We are working on identifying the neural correlates associated with visual-somatosensory integration in aging, and we believe that such developments will provide insights into several diseases, including but not limited to Alzheimer's and Parkinson's.

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Behavior

Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station (INBEST)

Due to rapid advances in genetic engineering, small rodents have become the preferred subjects in many disciplines of biomedical research. In studies of chronic CNS disorders, there is an increasing demand for murine models with high validity at the behavioral level. However, multiple pathogenic mechanisms and complex functional deficits often impose challenges to reliably measure and interpret behavior of chronically sick mice. Therefore, the assessment of peripheral pathology and a behavioral profile at several time points using a battery of tests are required. Video-tracking, behavioral spectroscopy, and remote acquisition of physiological measures are emerging technologies that allow for comprehensive, accurate, and unbiased behavioral analysis in a home-base-like setting. This report describes a refined phenotyping protocol, which includes a custom-made monitoring apparatus (Integrated Behavioral Station, INBEST) that focuses on prolonged measurements of basic functional outputs, such as spontaneous activity, food/water intake and motivated behavior in a relatively stress-free environment. Technical and conceptual improvements in INBEST design may further promote reproducibility and standardization of behavioral studies.

Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station INBEST

Prolonged and comprehensive monitoring of mice in a home-cage environment provides a deeper understanding of aberrant behavior in murine models of brain diseases. This paper describes the Integrated Behavioral Station (INBEST) as the key component of contemporary behavioral analysis.

Due to rapid advances in genetic engineering, small rodents have become the preferred subjects in many disciplines of biomedical research. In studies of ...

The Forced Swim Test as a Model of Depressive-like Behavior

The goal of the present protocol is to describe the forced swim test (FST), which is one of the most commonly used assays for the study of depressive-like behavior in rodents. The FST is based on the assumption that when placing an animal in a container filled with water, it will first make efforts to escape but eventually will exhibit immobility that may be considered to reflect a measure of behavioral despair. This test has been extensively used because it involves the exposure of the animals to stress, which was shown to have a role in the tendency for major depression. Additionally, the FST has been shown to share some of the factors that are influenced or altered by depression in humans, including changes in food consumption, sleep abnormalities and drug-withdrawal-induced anhedonia. The main advantages of this procedure are that it is relatively easy to perform and that its results are easily and quickly analyzed. Moreover, its sensitivity to a broad range of antidepressant drugs that makes it a suitable screening test is one of the most important features leading to its high predictive validity. Despite its appeal, this model has a number of disadvantages. First, the issue of chronic augmentation is problematic in this test because in real life patients need to be treated for at least several weeks before they experience any relief from their symptoms. Last, due to the aversiveness of the FST, it is important to take into account possible influences it might have on brain structure/function if brain analyses are to be carried out following this procedure.

This protocol describes the forced swim test, which is used for the study of depressive-like behavior in rodents. This procedure involves placing an animal in a container filled with water that eventually will lead to the exhibition of immobility behavior, which is considered to reflect behavioral despair.

The goal of the present protocol is to describe the forced swim test (FST), which is one of the most commonly used assays for the study of depressive-like ...

Applying Stereotactic Injection Technique to Study Genetic Effects on Animal Behaviors

Stereotactic injection is a useful technique to deliver high titer lentiviruses to targeted brain areas in mice. Lentiviruses can either overexpress or knockdown gene expression in a relatively focused region without significant damage to the brain tissue. After recovery, the injected mouse can be tested on various behavioral tasks such as the Open Field Test (OFT) and the Forced Swim Test (FST). The OFT is designed to assess locomotion and the anxious phenotype in mice by measuring the amount of time that a mouse spends in the center of a novel open field. A more anxious mouse will spend significantly less time in the center of the novel field compared to controls. The FST assesses the anti-depressive phenotype by quantifying the amount of time that mice spend immobile when placed into a bucket of water. A mouse with an anti-depressive phenotype will spend significantly less time immobile compared to control animals. The goal of this protocol is to use the stereotactic injection of a lentivirus in conjunction with behavioral tests to assess how genetic factors modulate animal behaviors.

Stereotactic injection of lentiviruses expressing cDNAs or shRNAs can modulate gene expression in specific brain areas of mice. Here, we present a protocol to combine stereotactic injections with behavioral tasks, such as the Open Field Test (OFT) and the Forced Swim Test (FST).

Stereotactic injection is a useful technique to deliver high titer lentiviruses to targeted brain areas in mice. Lentiviruses can either overexpress or ...

Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been maintaining the behavior. There is close correspondence between fear and human anxiety, and therefore studies of extinction learning might provide insight into the biological nature of anxiety-related disorders such as post-traumatic stress disorder, and they might help to develop strategies to treat them. Preclinical research aims to aid extinction learning and to induce targeted plasticity in extinction circuits to consolidate the newly formed memory. Vagus nerve stimulation (VNS) is a powerful approach that provides tight temporal and circuit-specific release of neurotransmitters, resulting in modulation of neuronal networks engaged in an ongoing task. VNS enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here, we provide a detailed protocol for the preparation of custom-made parts and the surgical procedures required for VNS in rats. Using this protocol we show how VNS can facilitate the extinction of conditioned fear responses in an auditory fear conditioning task. In addition, we provide evidence that VNS modulates synaptic plasticity in the pathway between the infralimbic (IL) medial prefrontal cortex and the basolateral complex of the amygdala (BLA), which is involved in the expression and modulation of extinction memory.

Vagus nerve stimulation (VNS) has emerged as a tool to induce targeted synaptic plasticity in the forebrain to modify a range of behaviors. This protocol describes how to implement VNS to facilitate the consolidation of fear extinction memory.

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been ...

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 ...

Behavioral Disturbances: An Innovative Approach to Monitor the Modulatory Effects of a Nutraceutical Diet

In dogs, diets are often used to modulate behavioral disturbances related to chronic anxiety and stress caused by intense and restless activity. However, the traditional ways to monitor behavioral changes in dogs are complicated and not efficient. In the current clinical evaluation, a new, simple monitoring system was used to assess the effectiveness of a specific diet in positively modulating the intense and restless activity of 24 dogs of different ages and breeds. This protocol describes how to easily and rapidly evaluate improvement in a set of symptoms related to generalized anxiety by using a specific sensor, a mobile phone app, a wireless router, and a computer. The results showed that dogs treated with specific diets showed significant improvement in the times spent active and at rest after 10 days (p &lt; 0.01 and p &lt; 0.05, respectively). These dogs also showed an overall significant improvement in clinical and behavioral symptoms. A specific sensor, along with its related hardware, was demonstrated to successfully monitor behavioral changes relating to movement in dogs.

We report a simple approach to evaluate the effectiveness of a specific diet in positively modulating the daily activity and clinical and behavioral symptoms of dogs with evident behavioral disturbances.

In dogs, diets are often used to modulate behavioral disturbances related to chronic anxiety and stress caused by intense and restless activity. However, ...

Using the FishSim Animation Toolchain to Investigate Fish Behavior: A Case Study on Mate-Choice Copying In Sailfin Mollies

Over the last decade, employing computer animations for animal behavior research has increased due to its ability to non-invasively manipulate the appearance and behavior of visual stimuli, compared to manipulating live animals. Here, we present the FishSim Animation Toolchain, a software framework developed to provide researchers with an easy-to-use method for implementing 3D computer animations in behavioral experiments with fish. The toolchain offers templates to create virtual 3D stimuli of five different fish species. Stimuli are customizable in both appearance and size, based on photographs taken of live fish. Multiple stimuli can be animated by recording swimming paths in a virtual environment using a video game controller. To increase standardization of the simulated behavior, the prerecorded swimming path may be replayed with different stimuli. Multiple animations can later be organized into playlists and presented on monitors during experiments with live fish.
In a case study with sailfin mollies (Poecilia latipinna), we provide a protocol on how to conduct a mate-choice copying experiment with FishSim. We utilized this method to create and animate virtual males and virtual model females, and then presented these to live focal females in a binary choice experiment. Our results demonstrate that computer animation may be used to simulate virtual fish in a mate-choice copying experiment to investigate the role of female gravid spots as an indication of quality for a model female in mate-choice copying.
Applying this method is not limited to mate-choice copying experiments but can be used in various experimental designs. Still, its usability depends on the visual capabilities of the study species and first needs validation. Overall, computer animations offer a high degree of control and standardization in experiments and bear the potential to &#39;reduce&#39; and &#39;replace&#39; live stimulus animals as well as to &#39;refine&#39; experimental procedures.

Using the FishSim Animation Toolchain to Investigate Fish Behavior: A Case Study on Mate-Choice Copying In Sailfin Mollies

Using the novel FishSim Animation Toolchain, we present a protocol for non-invasive visual manipulation of public information in the context of mate-choice copying in sailfin mollies. FishSim Animation Toolchain provides an easy-to-use framework for the design, animation and presentation of computer-animated fish stimuli for behavioral experiments with live test fish.

Over the last decade, employing computer animations for animal behavior research has increased due to its ability to non-invasively manipulate the ...

Behavioral Assessments of Spontaneous Locomotion in a Murine MPTP-induced Parkinson's Disease Model

Parkinson&#8217;s disease (PD) is a common neurodegenerative disorder disease, causing the phenomenon of shaking, rigidity, slowness of movement and dementia. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can lead to some Parkinson&#8217;s-like symptoms by destroying dopaminergic neurons in the substantia nigra of the brain. It has been thus used to establish PD models in various animal studies. Here, mice receive MPTP injections (20 mg/kg/day) for seven days and the behavioral tests are performed on the eighth day. This model is adapted efficiently in the study of PD. The behavioral tests here include the cylinder test and the open field test. The cylinder experiment is used to detect the animals&#8217; ability to lift their front paws when put into a different environment. As the PD model mice show arching&#8212;the mouse arches its back&#8212;the number of paw liftings decrease. This test is easy to execute. The open field test is used to detect the amount of time the mice spend on running, walking, and remaining immobile. We analyze animals&#8217; movements in open field using software and obtain data. Lastly, we use L-DOPA, one of the most commonly used PD drugs, as one example to show how to apply this model to the study of PD drugs. Our results indicate that MPTP neurotoxicity induces motor deficit which can be mitigated by L-DOPA.

Behavioral Assessments of Spontaneous Locomotion in a Murine MPTP-induced Parkinson&#039;s Disease Model

We describe establishment of a murine model for Parkinson's disease using MPTP, and behavioral assessments using cylinder and open field tests to measure motor function. We then use L-DOPA as one example to show how to apply this model in the study of PD drugs.

Parkinson&#8217;s disease (PD) is a common neurodegenerative disorder disease, causing the phenomenon of shaking, rigidity, slowness of movement and ...

Assessing the Autonomic and Behavioral Effects of Passive Motion in Rats using Elevator Vertical Motion and Ferris-Wheel Rotation

The overall goal of this study is to assess the autonomic and behavioral effects of passive motion in rodents using the elevator vertical motion and Ferris-wheel rotation devices. These assays can help confirm the integrity and normal functioning of the autonomic nervous system. They are coupled to quantitative measures based on defecation counting, open-field examination, and balance beam crossing. The advantages of these assays are their simplicity, reproducibility, and quantitative behavioral measures. The limitations of these assays are that the autonomic reactions could be epiphenomena of non-vestibular disorders and that a functioning vestibular system is required. Examination of disorders such as motion sickness will be greatly aided by the detailed procedures of these assays.

Protocols are presented to assess the autonomic and behavioral effects of passive motion in rodents using elevator vertical motion and Ferris-wheel rotation.

The overall goal of this study is to assess the autonomic and behavioral effects of passive motion in rodents using the elevator vertical motion and ...

Using Practice Testing, Public Speaking, and Source Monitoring to Examine the Influences of Learning Strategies and Stress on Episodic Memory

Prior research demonstrated that learning information via retrieval practice, which entails studying and taking practice tests, resulted in less memory impairment under stress than learning information via repeated studying. The present experiment combined three experimental procedures to further examine the memory mechanisms underlying the efficacy of retrieval practice in the context of stress. A list-discrimination task was implemented, in which participants learned two distinct wordlists. This was combined with a retrieval-practice manipulation, as half of the participants engaged in practice testing and half engaged in conventional studying during learning. A week later, participants underwent stress induction, using the Trier Social Stress Test. Before and after stress induction, participants completed tests of item and source memory (i.e., list discrimination). The combination of these three procedures yielded informative results: retrieval practice, in the context of stress, improved item memory but not source memory relative to conventional studying. Limitations and future directions for the use of this methodology are discussed.

The present experiment combined three experimental procedures &#8212; a retrieval-practice learning manipulation, a list-discrimination task, and a stress-induction technique &#8212; to examine the influences of different learning strategies and acute stress on multiple measures of episodic memory.

Prior research demonstrated that learning information via retrieval practice, which entails studying and taking practice tests, resulted in less memory ...