This work was supported by the National Institute of Mental Health Grant Number 1 R43MH0842-01A2 and the National Institute of Mental Health Grant Number 2 R44MH084240-02.&#160;

1. Installing the Assessment
<ol>
	<li>Insert the assessment software into a computer that meets the requirements in the Equipment Table.</li>
	<li>If the folder does not automatically open, go to "My Computer" and open the CD Drive</li>
	<li>Double click "NeuroCog.build.319"</li>
	<li>Double click "Installer"</li>
	<li>Double click "Setup.exe"</li>
	<li>Click the "Next" button at the bottom of the setup screen</li>
	<li>Click "Agree" on the licensing agreement</li>
	<li>Click "Next"</li>
	<li>Click "Next"</li>
	<li>Click "Install"</li>
	<li>Click "Finish&#34;</li>
</ol>
2. Setting-up the Study Room
<ol>
	<li>Install the assessment on a computer in a quiet room and free of distractions. Make sure that the subject does not have access to any materials that can be used to take notes.
	<ol>
		<li>Ensure that the computer is at a table or desk at a comfortable sitting height. Place a wired mouse on the table with enough room for the subject to rest their arm in order to prevent fatigue.</li>
		<li>Plug in the external speakers prior to starting the program.</li>
	</ol>
	</li>
	<li>Set up two chairs, one directly in front of the computer for the subject and one to the side and slightly behind the other chair for the administrator to sit in. A rater should be present at all times during the administration of the assessment.</li>
	<li>Prior to administering the assessment, set up the program.
	<ol>
		<li>Double Click on the icon labeled "Play VRFCAT."</li>
		<li>If this is a returning subject, enter in the previously created Patient ID and Password and click "Confirm." If this is a new subject, click New Profile and then create a new Patient ID and Password for the subject and click "Confirm."</li>
		<li>Type in the Site Number, select the subject's Date of Birth, type in the Age, select the subject's Handedness and Gender, type in the Rater Initials, select the Study,* and select the Visit*. Then click "Confirm." NOTE: *These elements can be customized. Please see the assessment manual for further information.</li>
	</ol>
	</li>
</ol>
3. Administering the Assessment
<ol>
	<li>To initiate the administration of the task, sit the subject down at the chair directly in front of the computer. If this is the subject's first time with the assessment, use the default Scenario: "Tutorial" and the default Mini Scenario: "Apartment."
	<ol>
		<li>If this is not the subject's first time with the assessment select the appropriate test version from the Scenario drop down menu and click "Confirm." Please note that the previous version the subject completed will have turned from green to red. This will help to ensure that the same version is not administered twice to a subject.</li>
		<li>A rater should remain present during the entire administration of the assessment. If the subject asks what they are supposed to be doing, direct the subject to click on the audio icon in the top left corner. If the subject stops paying attention or at any point looks away from the screen, redirect the subject back to the task.</li>
		<li>Take the necessary precautions to try to ensure that the subject will not need a break during the administration of the assessment, but in extreme circumstances, the assessment can be paused and continued at a later time. To do so, press the "Esc" key on the keyboard, and a menu labeled Game Paused will appear.
		<ol>
			<li>In the event that the subject is taking a short break, simply click "Main Menu," type in the Admin Code, "admin," and click "Yes." The assessment will then go back to the screen to select what Mini Scenario is needed to start the subject on when they return. All completed Mini Scenarios will have turned from green to red.</li>
			<li>If the subject is unable to complete the entire version that day, and must come back another day, click "Exit" on the Game Paused menu, type in the Admin Code, "admin," and click "Yes." This will shut down the program. Once the subject returns, log back into the program with the correct Patient ID and password, and select the appropriate Scenario and Mini Scenario from the drop down menus. All completed Mini Scenarios will have turned from green to red.</li>
		</ol>
		</li>
	</ol>
	</li>
	<li>Once the subject has completed all four Mini Scenarios (Apartment, Bus to Store, Store, and Bus to Apartment) a screen saying "Congratulations! You have completed the task! Please let your test administrator know that you have finished," will appear. Click "Continue," and on the next screen click "Begin New Scenario."In the box labeled "Admin Code" type in "admin" and click "Yes."
	<ol>
		<li>If the subject completed the test version instead of the tutorial, click "Exit Application." In the box labeled "Admin Code" type in "admin," click "Yes," and the session is complete.
		</li>
	</ol>
	</li>
	<li>Select the appropriate test version from the Scenario drop down menu and click "Confirm." NOTE: The Scenario labeled Tutorial should now have changed from green to red because the subject has completed the entire Scenario.</li>
	<li>Once the subject has completed all four Mini Scenarios a screen will appear that says, "Congratulations! You have completed the task! Please let your test administrator know that you have finished." Click "Continue," and on the next screen click "Exit Application." In the box labeled "Admin Code" type in "admin" and click "Yes," and the session is complete.</li>
</ol>
4. Potential Deviations
<ol>
	<li>If the subject attempts to complete any of the objectives out of order, remind them that they must complete the task described in the instructions at the top of the screen before moving onto the next task.</li>
	<li>If the subject has used up all of their virtual change during the Tutorial scenario and is unable to complete the final objective, escape out of the game using the above listed methods to return to the Scenario selection menu. Encourage the subject to try to not to use up all of their coins during the early objectives, and readminster the entire tutorial.
	</li>
	<li>If the subject has used up all of their virtual change during the any of the other scenarios and is unable to complete the final objective, escape out of the game using the above listed methods to return to the Scenario selection menu. This data point will be considered missing, and do not readminister any of the scenarios.
	</li>
</ol>

<ol>
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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=Neuropsychological+status+of+subjects+at+high+risk+for+a+first+episode+of+psychosis.">Neuropsychological status of subjects at high risk for a first episode of psychosis.</a> Schizophr Res. 67 (2-3), 115-122 (2004).</li><li>Green, M. F., Braff, D. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Translating+the+basic+and+clinical+cognitive+neuroscience+of+schizophrenia+to+drug+development+and+clinical+trials+of+antipsychotic+medications.">Translating the basic and clinical cognitive neuroscience of schizophrenia to drug development and clinical trials of antipsychotic medications.</a> Biol Psychiatry. 49 (4), 374-384 (2001).</li><li>Heinrichs, R. W., Zakzanis, K. 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F., 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=Functional+co-primary+measures+for+clinical+trials+in+schizophrenia:+Results+from+the+MATRICS+psychometric+and+standardization+study.">Functional co-primary measures for clinical trials in schizophrenia: Results from the MATRICS psychometric and standardization study.</a> Am J Psychiatry. 165 (2), 221-228 (2008).</li><li>Keefe, R. S. E., Poe, M., Walker, T. M., Harvey, P. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+relationship+of+the+Brief+Assessment+of+Cognition+in+Schizophrenia+(BACS)+to+functional+capacity+and+real-world+functional+outcome.">The relationship of the Brief Assessment of Cognition in Schizophrenia (BACS) to functional capacity and real-world functional outcome.</a> J Clin Exp Neuropsychol. 28 (2), 260-269 (2006).</li><li>Ventura, 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=The+cognitive+assessment+interview+(CAI):+Development+and+validation+of+an+empirically+derived,+brief+interview-based+measure+of+cognition.">The cognitive assessment interview (CAI): Development and validation of an empirically derived, brief interview-based measure of cognition.</a> Schizophr Res. 121 (1-3), 24-31 (2010).</li><li>Bowie, C. R., Twamley, E. W., Anderson, H., Halpern, B., Patterson, T. L., Harvey, P. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Self-assessment+of+functional+status+in+schizophrenia.">Self-assessment of functional status in schizophrenia.</a> J Psychiatr Res. 41 (12), 1012-1018 (2007).</li><li>Harvey, P. D., Velligan, D. I., Bellack, A. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Performance-based+measures+of+functional+skills:+Usefulness+in+clinical+treatment+studies.">Performance-based measures of functional skills: Usefulness in clinical treatment studies.</a> Schizophrenia Bull. 33 (5), 1138-1148 (2007).</li><li>Bellack, A. S., Sayers, M., Mueser, K. 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The author, Richard S.E. Keefe, is the Founder and CEO of NeuroCog Trials, Inc. and a Professor of Psychiatry Behavioral Sciences at Duke University Medical Center.
The author, Philip D. Harvey, is a Professor of Psychiatry &#38; Behavioral Sciences, Chief, Division of Psychology, Department of Psychiatry &#38; Behavioral Sciences, University of Miami Miller School of Medicine and Senior Clinical Research Scientist, Miami Veterans Affairs Healthcare System.
The author, K. Ranga Rama Krishnan, is a Professor of Psychiatry and Behavioral Sciences at Duke University Medical Center and the Dean of the Duke-NUS Graduate Medical Center.
The author, Stacy A. Ruse, is an employee of NeuroCog Trials, Inc.
The author, Vicki G. Davis, is an employee of NeuroCog Trials, Inc.
The author, Alexandra S. Atkins, is an employee of NeuroCog Trials, Inc.
The author, Kolleen H. Fox is a former employee of NeuroCog Trials, Inc.

The pilot study showed encouraging results with the test retest data yielded an intraclass correlation (ICC) of 0.61 and Pearson&#8217;s correlation of 0.67.

During the initial analysis of the data, it was observed that one of the versions of the application, Scenario 4, had significant outlying data and did not perform in a manner consistent with the other five versions.&#160; Because of the qualitative data that was received we hypothesized that the location of one of the ingredients on the recipe in Scenario 4 was causing the outlying data.&#160; The ingredient was updated to more closely resemble the other versions.&#160; Validation of this version is currently underway as part of an NIMH SBIR Phase II Grant.&#160;

For software troubleshooting, please contact the company who developed the assessment.&#160; 
The protocol for administering the assessment has several limitations.&#160; The assessment requires the use of a computer.&#160; The technique as currently configured will have the most successful outcome if there is an administrator present during the entire administration of the assessment.&#160; The subject who is completing the assessment should not be left alone at any point.&#160; Also, the conclusions drawn from the pilot study are limited by several factors.&#160; The sample was a group of healthy controls from one site in Durham, North Carolina.&#160; This sample consisted of mainly Caucasian (59%) females (61%).&#160; This sample is not representative of the population of people with schizophrenia.&#160; The sample size was also relatively small (n=46).&#160;

Currently the assessment is being validated in several different studies.&#160; The National Institute of Mental Health has provided funding to validate the assessment in a sample of 160 patients and 160 healthy controls.&#160; The validation study will look at the validity, sensitivity, and reliability of the assessment as a primary measure of functional capacity in schizophrenia.&#160; As well as the assessment&#8217;s ability to quantify changes in functional capacity by comparing it to the UPSA-2-VIM, determining the association between performance on the assessment and performance on the MCCB, and examining the association between the assessment and the Schizophrenia Cognition Rating Scale (SCoRS).

The assessment is also a part of the Validation of Everyday Real world Outcomes (VALERO) study, phase 2.&#160; The VALERO study recruited patients with schizophrenia who in addition to the assessment received a modified version of the MCCB32, the Wide Range Achievement Test, 3rd edition (WRAT-3)33, and the UPSA-B34.&#160; Further, this assessment is being examined in conjunction with a set of complementary functional scenarios (using an automated teller machine; refilling a prescription; and understanding instructions from a physician), in another federally funded study of older people with schizophrenia.

Once validated, it is a goal for the assessment to become a gold standard measure of functional capacity, specifically for patients with schizophrenia in clinical drug trials.&#160; The easy administration will also permit the assessment to be used in a clinical setting allowing clinicians to be able to measure change in a patient over time.&#160; Finally, remote delivery is feasible and would allow for assessment in participant&#8217;s homes, in the event that they were self administering an intervention without clinic visits.

It is very important to pay close attention to step 3.1.1 of the protocol.&#160; The tutorial should always be administered the first time a subject receives the assessment, and in order to prevent practice effects, it is imperative that the correct version of the assessment be administered.&#160; Step 3.1.3 points out the importance of ensuring that breaks are limited as much as possible to ensure the assessment is administered in a consistent manner with little interruptions.&#160; As steps 4.1 and 4.2 point out, if the subject has used up all of their coins during the Tutorial scenario and is unable to complete the final objective, escape out of the game using the above listed methods to return to the Scenario selection menu.&#160; Encourage the subject to try to not to use up all of their virtual currency during the early objectives, and readminster the entire tutorial.&#160; If the subject has used up all of their virtual currency during any of the other versions and is unable to complete the final objective, escape out of the game using the above listed methods to return to the Scenario selection menu.&#160; This data point will be considered missing, and do not readminister any of the scenarios.&#160;

Schizophrenia is a serious mental illness that affects over two million Americans and costs about $63 billion in total with $22.7 billion dollars a year for direct treatment and community services, with unemployment comprising an additional $32 billion of non-direct costs1,2. &#160;This disorder is typically accompanied by cognitive deficits that precede the onset of psychosis and remain throughout the course of the illness3-8.&#160; These cognitive deficits lead to adverse consequences, such as the reduced success in social, vocational, and independent living domains. Impaired cognition is a substantial contributor to functional disability in patients with schizophrenia9.&#160; Current antipsychotics are effective at controlling the psychotic symptoms of schizophrenia such as delusions and hallucinations, but these therapies provide minimal cognitive benefits10-13.&#160; Pharmacological and nonpharmacological treatments to improve cognitive functioning for patients with schizophrenia are in development at the present time.&#160; Cognitive functioning in schizophrenia, both at baseline and as a function of changes associated with treatment, can be reliably assessed by measures with proven sensitivity14.&#160; However, FDA guidance mandates that treatment studies demonstrate the clinical meaningfulness of changes in cognitive functioning15,16.&#160;
Representatives from the Food and Drug Administration (FDA), the National Institute of Mental Health (NIMH), and the pharmaceutical industry, as well as experts in cognition from academia, met as part of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) project15.&#160; The purpose of the MATRICS project was to develop standard methods in the development of treatments of cognitive impairment associated with schizophrenia.&#160; During the course of this work, FDA representatives asserted that cognitive improvements alone, as measured by standardized neuropsychological assessments, are not sufficient to demonstrate drug efficacy for cognitive enhancers.&#160; The approval of new treatments for cognitive impairments would therefore require evidence that the cognitive improvements are clinically meaningful15.&#160; As a result, clinical trials of cognitive enhancing treatments in schizophrenia now must demonstrate improvement on a standard cognitive measure and improvement on a measure indicating that any cognitive improvements have meaningful benefit to the patient&#8217;s functioning.&#160; This is known as a &#8216;co primary requirement&#8217;.&#160; The MATRICS project made very specific recommendations about which standard cognitive measures would indicate cognitive change, and developed a battery of tests for this purpose.&#160;

Although, the MATRICS Group validated a cognitive outcomes battery, the MATRICS Consensus Cognitive Battery (MCCB), they did not recommend that changes in real world functioning should be a prerequisite for the approval of a treatment aimed at cognition. This argument was based on the following concerns: 1) There are many domains of real world functioning in schizophrenia, such as the patient&#8217;s ability to hold employment, live independently, and maintain social relationships.&#160; 2) Changes in these domains might not be observed in a treatment study because they are likely to take longer than the duration of a typical clinical trial.&#160; 3) Furthermore, real world functional change is dependent upon a variety of circumstances unrelated to treatment, such as whether a patient is receiving disability payments17.&#160; As a result, the MATRICS group thus recommended that clinical meaningfulness should be demonstrated through the use of tools measuring the potential to demonstrate real world functional improvements associated with cognitive change.&#160; At that time, the MATRICS group made no firm recommendations regarding what measure or measures should be used as the &#8216;co primary measure&#8217;, choosing to &#160;make &#8220;soft&#8221; recommendations about the types of co primary measures that might be used in clinical trials18.&#160; Current co primary measures used in schizophrenia pharmaceutical trials are of two types:&#160; interview based measures and performance based measures.

Interview based measures of cognition are coprimary measures typically completed by the patient or an informant.&#160; They include the Schizophrenia Cognition Rating Scale (SCoRS), the Clinical Global Impression of Cognition in Schizophrenia (CGI-CogS), and the Cognitive Assessment Interview (CAI)18-20.&#160; &#160;&#160;These measures have only modest correlations with cognitive performance measures when self reported by patients, in that patients with serious mental illness and other CNS disorders are limited in their ability to accurately report their own cognitive abilities21.&#160; Further, although informant ratings have considerable validity, many patients with mental illnesses do&#160;not have an informant who can provide meaningful ratings18,22.&#160;&#160;When informants are available, they&#160;can be limited by selective observations of the patient&#39;s behavior or a variety of potential response biases.&#160;

Performance based measures of functional capacity are measures that require the performance of critical everyday skills in a controlled format.&#160; These measures have been found to demonstrate a&#160;closer association to cognitive test data than self reports obtained with the interview based measures&#160;described above18,21.&#160; Several performance based measures&#160;have recently been investigated.&#160; Two of these,&#160;The Maryland Assessment of Social Competence (MASC)&#160;and&#160;the Social Skills Performance Assessment (SSPA),&#160;measure socially oriented functional capacity through a rater&#39;s observation of&#160;patient&#160;behavior during role playing22-24.&#160; A more broadly focused and widely used measure of functional capacity is the University of California, San Diego Performance Based Skills Assessment (UPSA)25.&#160; The UPSA takes about 30 minutes and measures performance in several domains of everyday living, such as finances, communication, planning, and household activities. The original UPSA has been modified to create both extended versions involving medication management (UPSA-2) and an abbreviated version examining just communication and finances (UPSA-Brief). All versions of the UPSA have been found to have substantial correlations with cognitive performance26.

The UPSA-2 and UPSA-B are currently the preferred coprimary measures, based on a systematic comparative study of their relationships with performance on the MCCB27.&#160; However, the different versions of the UPSA have several potential limitations, in terms of lacking alternative forms, inability to deliver the test remotely, and the fact that their paper and pencil format makes rapid development of alternate forms and new assessment scenarios challenging.&#160; Further, their use in repeated assessment situations such as clinical trials is limited as some patients perform close to perfectly at their initial assessment.&#160; With this in mind, the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) was designed to address these concerns and to reliably assess functional capacity within the context of a simulated real-world environment.

There have been several previous developments in the area of computerized and virtual reality assessments.&#160; For instance, Freeman and colleagues28 developed a series of virtual reality simulations that were designed to induce paranoid ideation.&#160; In the area of functional capacity assessment, Kurtz and colleagues29 developed an apartment based virtual reality medication management simulation.&#160; Finally, a computerized version of the UPSA has also been developed30.&#160; This simulation is not a true virtual reality procedure in that an examiner is present and administers the assessments, which are completed on the computer.&#160; This test does have the potential for remote delivery, although it is conceptually quite different from a gaming based test.

The VRFCAT (further referred to as &#8220;assessment&#8221;) is a novel gaming based virtual reality measure of functional capacity that uses a realistic simulated environment to recreate several routine activities of daily living with an eye toward assessment of both baseline levels of impairment and treatment related changes in functional capacity.&#160; The assessment&#8217;s realistic, interactive, and immersive environment consists of 6 versions of 4 mini scenarios that include navigating a kitchen, getting on a bus to go to a grocery store, finding/purchasing food in a grocery store, and returning home on a bus.&#160; The assessment measures the amount of time subjects spend completing 12 different objectives (listed in Table 2) as well as how many errors the subject makes.&#160; If a subject takes too much time or commits too many errors, the subject will be automatically progressed to the next objective.&#160; Subjects complete the scenarios through a progressive storyboard design.&#160; This unique high resolution software application was developed and pilot tested in the NIMH SBIR Phase 1 project with the stated goals of determining the stability and usability of the program (first portion) and measuring the test retest reliability in groups of healthy controls (second portion).&#160; After successfully developing the software in collaboration with Virtual Heroes, Inc., a division of Applied Research Associates, Inc., Phase 1 funding also enabled pilot testing of the assessment as well.

Phase 1 usability and reliability pilot testing examined a sample of 102 healthy controls from Durham, North Carolina.&#160; The study was approved by the Western IRB and all participants signed an informed consent form.&#160; The average age of the subjects included in the reliability portion of the study was 38.1 with a standard deviation of 12.98.&#160; The sample was 61% female and 59% Caucasian, 39% African American and 2% other ethnicity.&#160; Reliability findings from the Phase 1 pilot testing met expectations with a test-retest ICC of 0.61 and Pearson r of 0.67 despite the use of multiple test versions and relatively few research participants per version.&#160; In a previous study with a much larger sample (n=195) of schizophrenia patients, we had found a single form test retest reliability for the UPSA-B of ICC =.76 at a follow up between 6 weeks and 6 months31.

The assessment is currently being tested in an SBIR Phase 2 project that will validate the assessment against other measures of functional capacity and cognition, and examine the ability of this procedure to discriminate a population with schizophrenia from a healthy control group.&#160; Part of the goals of the Phase 2 study is the development of normative standards for healthy controls&#8217; performance and understanding the extent of impairment in people with schizophrenia.

<table border="0" cellpadding="0" cellspacing="0" width="100%">
	<tbody>
		<tr>
			<td width="20%">Computer</td>
			<td width="20%">N/A</td>
			<td width="20%">N/A</td>
			<td width="40%">Computer requirements: 
			&#183; Windows 2000/XP or compatible system &#183; 3-D graphics card with 128 MB memory 
			&#183; 1.6 GHz processor or equivalent 
			&#183; 512 MB RAM 
			&#183; 3.5GB of uncompressed hard disk space 
			&#183; DirectX 9.0 or compatible soundcard 
			&#183; 56kbps modem or better network connection 
			&#183; Motherboard/ soundcard containing Dolby Digital 
			&#183; Interactive Content Encoder</td>
		</tr>
		<tr>
			<td>Hard Wired Mouse</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Any functional hard wired mouse that fits comfortably into the subject&#8217;s hand will suffice</td>
		</tr>
		<tr>
			<td>External Speakers</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Any functional external speakers that allow the volume to be adjusted will suffice</td>
		</tr>
		<tr>
			<td>VRFCAT Software</td>
			<td>NeuroCog Trials, Inc.</td>
			<td>N/A</td>
			<td>Visit www.neurocogtrials.com for further information</td>
		</tr>
	</tbody>
</table>

development of a virtual reality assessment of everyday living skills

Cognitive impairments affect the majority of patients with schizophrenia and these impairments predict poor long term psychosocial outcomes.&#160; Treatment studies aimed at cognitive impairment in patients with schizophrenia not only require demonstration of improvements on cognitive tests, but also evidence that any cognitive changes lead to clinically meaningful improvements.&#160; Measures of &#8220;functional capacity&#8221; index the extent to which individuals have the potential to perform skills required for real world functioning. &#160;Current data do not support the recommendation of any single instrument for measurement of functional capacity.&#160; The Virtual Reality Functional Capacity Assessment Tool (VRFCAT) is a novel, interactive gaming based measure of functional capacity that uses a realistic simulated environment to recreate routine activities of daily living. Studies are currently underway to evaluate and establish the VRFCAT&#8217;s sensitivity, reliability, validity, and practicality.&#160;This new measure of functional capacity is practical, relevant, easy to use, and has several features that improve validity and sensitivity of measurement of function in clinical trials of patients with CNS disorders.

During the development phase, 102 healthy controls were tested with 1 of 6 randomly selected versions of the assessment and then asked to return for retest with a different randomly selected version 7 to 14 days later. 90 of those 102 returned for testing with a different version of the application. Due to an initial data management problem that was later rectified, only 69 of the 90 who returned had complete data sets. A significant outlier was discovered and removed from data analysis, leaving 68 completed data sets. 
During the initial analysis of the data, it was observed that one of the versions of the application, Scenario 4, had significant outlying data and did not perform in an equitable way to the other five versions. As a result, Scenario 4 was excluded from the analyses for the pilot data and the final analyses for this measure did not include data from this version. The final sample size was n=46 (see Table 1 for demographic information). This version was updated for the current version as described below. 
We performed a factor analysis (unrotated principal components) of performance on the 12 objectives of the assessment that are presented in Table 2. Table 3 shows the Factor Analysis that explained 91% of the variance and revealed three factors which were labeled: Reasoning and Problem Solving, Speed of Processing, and Working Memory. The domains were combined into a composite and the test-retest data yielded an intraclass correlation (ICC) of 0.61 and Pearson's correlation of 0.67. A scatterplot depicting performance at both visits is shown in Figure 1 below. 
Towards the end of the study the data were reviewed and it was determined that there were errors that subjects were making on Visit 1 but not Visit 2. For the remaining 13 subjects we instituted having the subject's complete the tutorial before the test version and the data were showing promise that the tutorial helped to wash out some of the main practice effects that were being seen. Because of that we recommend that the first time the assessment is administered that the tutorial should always be administered before a test version.
<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td></td>
			<td>Subjects (N=46)</td>
		</tr>
		<tr>
			<td>Age</td>
			<td>38.1 (SD=12.98; Range=19-68)</td>
		</tr>
		<tr>
			<td>Gender</td>
			<td>Female - 28 (61%) 
			Male - 18 (39%)</td>
		</tr>
		<tr>
			<td>Race</td>
			<td>Caucasian - 27 (59%) 
			African American - 18 (39%) 
			Other - 1 (2%)</td>
		</tr>
	</tbody>
</table>
Table 1. Pilot Study Demographic Information 
<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>Objective</td>
			<td>Description</td>
		</tr>
		<tr>
			<td>1</td>
			<td>Pick up the Recipe</td>
		</tr>
		<tr>
			<td>2</td>
			<td>Search for Ingredients</td>
		</tr>
		<tr>
			<td>3</td>
			<td>Cross Off Correct Ingredients &#38; Pick up Bus Schedule </td>
		</tr>
		<tr>
			<td>4</td>
			<td>Pick up the Billfold</td>
		</tr>
		<tr>
			<td>5</td>
			<td>Exit the Apartment </td>
		</tr>
		<tr>
			<td>6</td>
			<td>Catch the Bus</td>
		</tr>
		<tr>
			<td>7</td>
			<td>Pay for the Bus</td>
		</tr>
		<tr>
			<td>8</td>
			<td>Select an Aisle</td>
		</tr>
		<tr>
			<td>9</td>
			<td>Shop for Groceries</td>
		</tr>
		<tr>
			<td>10</td>
			<td>Pay for Groceries</td>
		</tr>
		<tr>
			<td>11</td>
			<td>Catch the Bus </td>
		</tr>
		<tr>
			<td>12</td>
			<td>Pay for the Bus</td>
		</tr>
	</tbody>
</table>
Table 2. VRFCAT Objectives
<table border="0" cellpadding="0" cellspacing="0" width="922">
	<tbody>
		<tr>
			<td rowspan="3">Objective</td>
			<td colspan="3">Factors</td>
		</tr>
		<tr>
			<td>1</td>
			<td>2</td>
			<td>3</td>
		</tr>
		<tr>
			<td>(Reasoning/ 
			Problem Solving)</td>
			<td>(Speed of Processing)</td>
			<td>(Working Memory)</td>
		</tr>
		<tr>
			<td>Time to add bus fare</td>
			<td>0.92</td>
			<td>0.19</td>
			<td>0.14</td>
		</tr>
		<tr>
			<td>Errors adding bus fare</td>
			<td>0.92</td>
			<td>0.12</td>
			<td>0.16</td>
		</tr>
		<tr>
			<td>Time to add grocery money</td>
			<td>0.87</td>
			<td>0.16</td>
			<td>0.09</td>
		</tr>
		<tr>
			<td>Errors adding grocery money</td>
			<td>0.79</td>
			<td>0.13</td>
			<td>0.12</td>
		</tr>
		<tr>
			<td>No. times bus schedule accessed</td>
			<td>0.5</td>
			<td>0.34</td>
			<td>0.25</td>
		</tr>
		<tr>
			<td>Errors adding bus fare</td>
			<td>0.48</td>
			<td>0.24</td>
			<td>0.08</td>
		</tr>
		<tr>
			<td>Time to shop for items</td>
			<td>0.29</td>
			<td>0.82</td>
			<td>0.28</td>
		</tr>
		<tr>
			<td>Errors shopping for items</td>
			<td>0.11</td>
			<td>0.82</td>
			<td>0.21</td>
		</tr>
		<tr>
			<td>Time to board bus</td>
			<td>0.25</td>
			<td>0.78</td>
			<td>0.01</td>
		</tr>
		<tr>
			<td>Time to board bus</td>
			<td>0.13</td>
			<td>0.69</td>
			<td>-0.06</td>
		</tr>
		<tr>
			<td>Time to cross off items</td>
			<td>0.21</td>
			<td>0.04</td>
			<td>0.9</td>
		</tr>
		<tr>
			<td>Errors crossing off items</td>
			<td>0.31</td>
			<td>0.01</td>
			<td>0.86</td>
		</tr>
		<tr>
			<td>No. times recipe accessed</td>
			<td>0</td>
			<td>0.2</td>
			<td>0.68</td>
		</tr>
	</tbody>
</table>
Table 3. Pilot Study Factor Analysis
<img alt="Figure 1" fo:content-width="6in" src="/files/ftp_upload/51405/51405fig1highres.jpg" width="500" /> 
Figure 1. Relationship between Performance at Visit 1 and Visit 2 by Gender

Watch this Scientific Journal Video about Development of a Virtual Reality Assessment of Everyday Living Skills at JoVE.com

Development of a Virtual Reality Assessment of Everyday Living Skills

A challenge for proving treatment efficacy for cognitive impairments in schizophrenia is finding the optimizing measurement of skills related to everyday functioning.&#160; The Virtual Reality Functional Capacity Assessment Tool (VRFCAT) is an interactive gaming based computerized measure aimed at skills associated with everyday functioning, including baseline impairments and treatment related changes.

Cognitive impairments affect the majority of patients with schizophrenia and these impairments predict poor long term psychosocial outcomes.&#160; ...

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Using Virtual Reality to Transfer Motor Skill Knowledge from One Hand to Another

As far as acquiring motor skills is concerned, training by voluntary physical movement is superior to all other forms of training (e.g. training by observation or passive movement of trainee&#39;s hands by a robotic device). This obviously presents a major challenge in the rehabilitation of a paretic limb since voluntary control of physical movement is limited. Here, we describe a novel training scheme we have developed that has the potential to circumvent this major challenge. We exploited the voluntary control of one hand and provided real-time movement-based manipulated sensory feedback as if the other hand is moving. Visual manipulation through virtual reality (VR) was combined with a device that yokes left-hand fingers to passively follow right-hand voluntary finger movements. In healthy subjects, we demonstrate enhanced within-session performance gains of a limb in the absence of voluntary physical training. Results in healthy subjects suggest that training with the unique VR setup might also be beneficial for patients with upper limb hemiparesis by exploiting the voluntary control of their healthy hand to improve rehabilitation of their affected hand.

We describe a novel virtual-reality based setup which exploits voluntary control of one hand to improve motor-skill performance in the other (non-trained) hand. This is achieved by providing real-time movement-based sensory feedback as if the non-trained hand is moving. This new approach may be used to enhance rehabilitation of patients with unilateral hemiparesis.

As far as acquiring motor skills is concerned, training by voluntary physical movement is superior to all other forms of training (e.g. training by ...

Mobile Game-based Virtual Reality Program for Upper Extremity Stroke Rehabilitation

Stroke rehabilitation requires repetitive, intensive, goal-oriented therapy. Virtual reality (VR) has the potential to satisfy these requirements. Game-based therapy can promote patients&#39; engagement in rehabilitation therapy as a more interesting and a motivating tool. Mobile devices such as smartphones and tablet PCs can provide personalized home-based therapy with interactive communication between patients and clinicians. In this study, a mobile VR upper extremity rehabilitation program using game applications was developed. The findings from the study show that the mobile game-based VR program effectively promotes upper extremity recovery in patients with stroke. In addition, patients completed two weeks of treatment using the program without adverse effects and were generally satisfied with the program. This mobile game-based VR upper extremity rehabilitation program can substitute for some parts of the conventional therapy that are delivered one-on-one by an occupational therapist. This time-efficient, easy to implement, and clinically effective program would be a good candidate tool for tele-rehabilitation for upper extremity recovery in patients with stroke. Patients and therapists can collaborate remotely through these e-health rehabilitation programs while reducing economic and social costs.

Here, we present a protocol to develop and apply a mobile game-based virtual reality program for the recovery of upper limb dysfunction in patients with stroke. The present study shows that the mobile program is feasible and effectively promotes upper limb recovery in stroke patients.

Stroke rehabilitation requires repetitive, intensive, goal-oriented therapy. Virtual reality (VR) has the potential to satisfy these requirements. ...

An Objective and Child-friendly Assessment of Arm Function by Using a 3-D Sensor

Progressive and irreversible muscle atrophy characterizes Spinal Muscular Atrophy (SMA) and other similar muscle disorder diseases. Objective assessment of muscle functions is an essential and important, although challenging, prerequisite for successful clinical trials. Current clinical rating scales restrain the movement abnormalities to certain predefined coarse-grained individual items. The Kinect 3-D sensor has emerged as a low-cost and portable motion sensing technology used to capture and track people&#39;s movement in many medical and research fields. A novel approach using this 3-D sensor was developed and a game-like test was designed to objectively measure the upper limb function of patients with SMA. The prototype test targeted joint movement capability. While sitting in a virtual scene, the patient was instructed to extend, flex, and lift the whole arm in order to reach and place some objects. Both kinematic and spatiotemporal characteristics of upper limb movement were extracted and analyzed, e.g., elbow extension and flexion angles, hand velocity, and acceleration. The first study included a small cohort of 18 ambulant SMA patients and 19 age- and gender-matched healthy controls. A comprehensive analysis of arm movement was achieved; however, no significant difference between the groups were found due to the mismatch of patient&#39;s capability and the test difficulty. Based on this experience, a second version of the test consisting of a modified version of the first game with increased difficulties and a second game targeting muscle endurance were designed and implemented. The new test has not been conducted in any patient groups yet. Our work has demonstrated the potential capability of the 3-D sensor in assessing such muscle function and suggested an objective approach to complement the clinical rating scales.

An objective measure of muscle functions is challenging especially in children. Based on a commercially available digital 3-D sensor, a child-friendly gaming test was developed to assess upper limb function for clinical trials.

Progressive and irreversible muscle atrophy characterizes Spinal Muscular Atrophy (SMA) and other similar muscle disorder diseases. Objective assessment ...

The inability to complete instrumental activities of daily living (IADL) is a precursor to various neuropsychological diseases. Questionnaire-based assessments of IADL are easy to use but prone to subjective bias. Here, we describe a novel virtual reality (VR) test to assess two complex IADL tasks: handling financial transactions and using public transportation. While a participant performs the tasks in a VR setting, a motion capture system traces the position and orientation of the dominant hand and head in a three-dimensional Cartesian coordinate system. Kinematic raw data are collected and converted into &#39;kinematic performance measures,&#39; i.e., motion trajectory, moving distance, and time to completion. Motion trajectory is the path of a particular body part (e.g., dominant hand or head) in space. Moving distance refers to the total distance of the trajectory, and time to completion is how long it took to complete an IADL task. These kinematic measures could discriminate patients with cognitive impairment from healthy controls. The development of this kinematic measuring protocol allows detection of early IADL-related cognitive impairments.

We designed a virtual reality test to assess instrumental activities of daily living (IADL) with a motion capture system. We propose a detailed kinematic analysis to interpret the participant&#39;s various movements, including trajectory, moving distance, and time to completion to evaluate IADL capabilities.

The inability to complete instrumental activities of daily living (IADL) is a precursor to various neuropsychological diseases. Questionnaire-based ...

Investigating the interactions among multiple participants is a challenge for researchers from various disciplines, including the decision sciences and spatial cognition. With a local area network and dedicated software platform, experimenters can efficiently monitor the behavior of the participants that are simultaneously immersed in a desktop virtual environment and digitalize the collected data. These capabilities allow for experimental designs in spatial cognition and navigation research that would be difficult (if not impossible) to conduct in the real world. Possible experimental variations include stress during an evacuation, cooperative and competitive search tasks, and other contextual factors that may influence emergent crowd behavior. However, such a laboratory requires maintenance and strict protocols for data collection in a controlled setting. While the external validity of laboratory studies with human participants is sometimes questioned, a number of recent papers suggest that the correspondence between real and virtual environments may be sufficient for studying social behavior in terms of trajectories, hesitations, and spatial decisions. In this article, we describe a method for conducting experiments on decision-making and navigation with up to 36 participants in a networked desktop virtual reality setup (i.e., the Decision Science Laboratory or DeSciL). This experiment protocol can be adapted and applied by other researchers in order to set up a networked desktop virtual reality laboratory.

This paper describes a method for conducting multi-user experiments on decision-making and navigation using a networked computer laboratory.

Investigating the interactions among multiple participants is a challenge for researchers from various disciplines, including the decision sciences and ...

Virtual reality (VR) experiments are increasingly employed because of their internal and external validity compared to real-world observation and laboratory experiments, respectively. VR is especially useful for geographic visualizations and investigations of spatial behavior. In spatial behavior research, VR provides a platform for studying the relationship between navigation and physiological measures (e.g., skin conductance, heart rate, blood pressure). Specifically, physiological measures allow researchers to address novel questions and constrain previous theories of spatial abilities, strategies, and performance. For example, individual differences in navigation performance may be explained by the extent to which changes in arousal mediate the effects of task difficulty. However, the complexities in the design and implementation of VR experiments can distract experimenters from their primary research goals and introduce irregularities in data collection and analysis. To address these challenges, the Experiments in Virtual Environments (EVE) framework includes standardized modules such as participant training with the control interface, data collection using questionnaires, the synchronization of physiological measurements, and data storage. EVE also provides the necessary infrastructure for data management, visualization, and evaluation. The present paper describes a protocol that employs the EVE framework to conduct navigation experiments in VR with physiological sensors. The protocol lists the steps necessary for recruiting participants, attaching the physiological sensors, administering the experiment using EVE, and assessing the collected data with EVE evaluation tools. Overall, this protocol will facilitate future research by streamlining the design and implementation of VR experiments with physiological sensors.

Virtual reality (VR) experiments can be difficult to implement and require meticulous planning. This protocol describes a method for the design and implementation of VR experiments that collect physiological data from human participants. The Experiments in Virtual Environments (EVE) framework is employed to accelerate this process.

Virtual reality (VR) experiments are increasingly employed because of their internal and external validity compared to real-world observation and ...

A Behavioral Test Battery for the Repeated Assessment of Motor Skills, Mood, and Cognition in Mice

Pharmacological and toxicological studies in neurodegeneration require comprehensive behavioral analysis in mice because motor dysfunctions and dysfunctions in mood and cognition are common and often shared symptoms in neurodegenerative diseases. Shown here is a behavioral test battery for motor, mood, and cognition, which can be repeatedly tested in a longitudinal study. This battery assesses the overall behavioral phenotype in mice by examining each domain of behavior with at least two independent well-accepted tests (i.e., open-field test and rotarod test for motor function, social interaction test, elevated plus maze test, and forced swim test for emotional function, and Morris water maze test and novel object recognition test for cognitive function). Therefore, this sensitive and comprehensive test battery is a powerful tool for the study of behavioral alternation in neurodegeneration.

A comprehensive behavioral test battery of motor skills, mood&#8212;including social interaction, depression, and anxiety&#8212;and cognition is designed for the repeated assessment of neurodegeneration-related behavioral changes in mice.

Pharmacological and toxicological studies in neurodegeneration require comprehensive behavioral analysis in mice because motor dysfunctions and ...

Virtual reality (VR) has shown great educational potential because it makes it possible to simulate any desired situation or event, thus playing an important role in addressing current educational challenges. Despite the unlimited learning possibilities that VR may offer, unless users are willing to apply virtual devices to education, the investment of time, money, and effort will be fruitless. It is therefore crucial to assess the educational interest of the first generation of VR users and to identify their current needs. To this end, in this study we designed an online questionnaire and applied it through the SaaS (Software as a service) of a private server. The sample consisted of 117 early VR adopters recruited via a main portal of communication and information technologies in Spain. In order to engage participants, we posted a thread in the main forum, which is dedicated to the advances and potential uses of VR. Once the responses were gathered, we analyzed the relationship between 12 variables (mean contrasts with Snedecor&#39;s F, and contingency analysis with chi-square and Sommer&#39;s d). The results showed that the current profile of a VR user is a male over 35 years old, with university studies, and who has purchased his viewer recently (&#60;1 year). As for the learning and teaching applications that these users were interested in, only 13.7% of the participants in this study use VR for educational purposes, although 28.2% were interested, indicating that perhaps the lack of applications or learning experiences may be hampering the use of VR within education. Almost half of the early adopters surveyed would like to learn using VR technology and are somehow optimistic about the relationship between VR and education, particularly those who are younger.

This article describes the profile of Spanish early adopters of virtual reality and their interests and preferences regarding learning and educational applications for this technology. To this aim, we designed an online questionnaire and interviewed 117 users of the main virtual reality forum on the Internet.

Virtual reality (VR) has shown great educational potential because it makes it possible to simulate any desired situation or event, thus playing an ...