Name: traditional trail making test modified into brand-new assessment tools: digital and walking trail making test
Uploaded: 2019-11-23T14:30:00
Description: Watch this Scientific Journal Video about Traditional Trail Making Test Modified into Brand-new Assessment Tools: Digital and Walking Trail Making Test at JoVE.com

The authors thank Xiaode Chen for digital technology support.

The development of the dTMT and initial application was approved by The Seventh Medical Center of PLA Army General Hospital Review Board. Subjects signed approved informed consent documents prior to testing TMT.
1. General Method Development
<ol>
	<li>Use a tablet (e.g., Microsoft Surface Pro 2) with high-quality inertial sensors embedded within the device and a compatible electronic pen (Figure 1).</li>
	<li>Use the Intelligent Device for Energy Expenditure and...

<ol>
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A., Choi, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Driving+Trail+Making+Test+part+B:+a+variant+of+the+TMT-B.">Driving Trail Making Test part B: a variant of the TMT-B.</a> Journal of Physical Therapy Science. 28 (1), 148-153 (2016).</li><li>Bastug, G., 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=Oral+trail+making+task+as+a+discriminative+tool+for+different+levels+of+cognitive+impairment+and+normal+aging.">Oral trail making task as a discriminative tool for different levels of cognitive impairment and normal aging.</a> Archives of Clinical Neuropsychology. 28 (5), 411-417 (2013).</li><li>Perrochon, A., Kemoun, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Walking+Trail-Making+Test+is+an+early+detection+tool+for+mild+cognitive+impairment.">The Walking Trail-Making Test is an early detection tool for mild cognitive impairment.</a> Clinical Interventions in Aging. 9, 111-119 (2014).</li><li>McIntyre, R. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+THINC-Integrated+Tool+(THINC-it)+screening+assessment+for+cognitive+dysfunction:+validation+in+patients+with+major+depressive+disorder.">The THINC-Integrated Tool (THINC-it) screening assessment for cognitive dysfunction: validation in patients with major depressive disorder.</a> The Journal of Clinical Psychiatry. 78 (7), 873-881 (2017).</li><li>Schott, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Trail+Walking+Test+zur+Erfassung+der+motorisch-kognitiven+Interferenz+bei+&#228;lteren+Erwachsenen.">Trail Walking Test zur Erfassung der motorisch-kognitiven Interferenz bei &#228;lteren Erwachsenen.</a> Zeitschrift f&#252;r Gerontologie und Geriatrie. 48 (8), 722-733 (2015).</li><li>Thompson, M. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+utility+of+the+Trail+Making+Test+practice+time.">Clinical utility of the Trail Making Test practice time.</a> The Clinical Neuropsychologist. 13 (4), 450-455 (1999).</li><li>Mahurin, R. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Trail+making+test+errors+and+executive+function+in+schizophrenia+and+depression.">Trail making test errors and executive function in schizophrenia and depression.</a> The Clinical Neuropsychologist. 20 (2), 271-288 (2006).</li><li>Klaming, L., Vlaskamp, B. N. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Non-dominant+hand+use+increases+completion+time+on+part+B+of+the+Trail+Making+Test+but+not+on+part+A.">Non-dominant hand use increases completion time on part B of the Trail Making Test but not on part A.</a> Behavior Research Methods. 50 (3), 1074-1087 (2017).</li><li>Christidi, F., Kararizou, E., Triantafyllou, N., Anagnostouli, M., Zalonis, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Derived+trail+making+test+indices:+demographics+and+cognitive+background+variables+across+the+adult+life+span.">Derived trail making test indices: demographics and cognitive background variables across the adult life span.</a> Aging, Neuropsychology, and Cognition. 22 (6), 667-678 (2015).</li><li>Dahmen, J., Cook, D., Fellows, R., Schmitter-Edgecombe, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+analysis+of+a+digital+variant+of+the+Trail+Making+Test+using+machine+learning+techniques.">An analysis of a digital variant of the Trail Making Test using machine learning techniques.</a> Technology and Health Care. 25 (2), 251-264 (2017).</li><li>Woods, D. L., Wyma, J. M., Herron, T. J., Yund, E. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effects+of+aging,+malingering,+and+traumatic+brain+injury+on+computerized+Trail-Making+Test+performance.">The effects of aging, malingering, and traumatic brain injury on computerized Trail-Making Test performance.</a> Plos ONE. 10 (6), 0124345 (2014).</li><li>Naomi, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+device-aided+cognitive+function+test,+User+eXperience-Trail+Making+Test+(UX-TMT),+sensitively+detects+neuropsychological+performance+in+patients+with+dementia+and+Parkinson's+disease.">A new device-aided cognitive function test, User eXperience-Trail Making Test (UX-TMT), sensitively detects neuropsychological performance in patients with dementia and Parkinson's disease.</a> BMC Psychiatry. 18 (1), 220 (2018).</li><li>Persad, C. C., Jones, J. L., Ashton-Miller, J. A., Alexander, N. B., Giordani, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Executive+function+and+gait+in+older+adults+with+cognitive+impairment.">Executive function and gait in older adults with cognitive impairment.</a> The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 63 (12), 1350-1355 (2008).</li><li>Zhang, K., Werner, P., Sun, M., Pi-Sunyer, F. X., Boozer, C. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Measurement+of+human+daily+physical+activity.">Measurement of human daily physical activity.</a> Obesity Research. 11 (1), 33-40 (2003).</li><li>Zhang, K., Pi-Sunyer, F. X., Boozer, C. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improving+energy+expenditure+estimation+for+physical+activity.">Improving energy expenditure estimation for physical activity.</a> Medicine and Science in Sports and Exercise. 36 (5), 883-889 (2004).</li><li>Gorelick, M. L., Bizzini, M., Maffiuletti, N. A., Munzinger, J. P., Munzinger, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Test-retest+reliability+of+the+IDEEA+system+in+the+quantification+of+step+parameters+during+walking+and+stair+climbing.">Test-retest reliability of the IDEEA system in the quantification of step parameters during walking and stair climbing.</a> Clinical Physiology and Functional Imaging. 29 (4), 271-276 (2009).</li><li>Nordin, E., Moe-Nilssen, R., Ramnemark, A., Lundin-Olsson, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Changes+in+step-width+during+dual-task+walking+predicts+falls.">Changes in step-width during dual-task walking predicts falls.</a> Gait and Posture. 32 (1), 92-97 (2010).</li><li>Liebherr, M., Weiland-Breckle, H., Grewe, T., Schumacher, P. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+performance+under+motor+demands+-+On+the+influence+of+task+difficulty+and+postural+control.">Cognitive performance under motor demands - On the influence of task difficulty and postural control.</a> Brain Research. 1684, 1-8 (2018).</li><li>Herold, F., Hamacher, D., Schega, L., M&#252;ller, N. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Thinking+while+moving+or+moving+while+thinking+&#8211;+Concepts+of+motor-cognitive+training+for+cognitive+performance+enhancement.">Thinking while moving or moving while thinking &#8211; Concepts of motor-cognitive training for cognitive performance enhancement.</a> Frontiers in Aging Neuroscience. 10, 228 (2018).</li><li>Kim, H., Hsiao, C. P., Do, Y. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Home-based+computerized+cognitive+assessment+tool+for+dementia+screening.">Home-based computerized cognitive assessment tool for dementia screening.</a> Journal of Ambient Intelligence &amp; Smart Environments. 4, 429-442 (2012).</li><li>Mancini, 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=Trunk+accelerometry+reveals+postural+instability+in+untreated+Parkinson's+disease.">Trunk accelerometry reveals postural instability in untreated Parkinson's disease.</a> Parkinsonism &amp; Related Disorders. 17 (7), 557-562 (2011).</li><li>Ozinga, S. 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Traditional paper-pencil TMT has been well used worldwide for more than 50 years. However, digital TMT is advantageous. First, traditional TMT is considered as an executive function tool, while both dTMT and WTMT have aspects reflecting motor ability besides cognitive function. Considering that the cognitive-motor dual task has gained great attention in recent years26, digital technologies can provide researchers with more information on this integrated task compared with the traditional TMT<sup c...

With a rapidly aging population, dementia is considered to be a major public health concern. The number of elderly patients with dementia worldwide is about 47 million according to the World Health Organization1. Executive function impairment is not only a common type of cognitive dysfunction in aged individuals, but has been reported as a predictor of progression from mild cognitive impairment (MCI) to clinical Alzheimer&#8217;s disease (AD)2,3. As the third most widely used test in neuropsychology4, the Trail Making Test (TMT) is employed as a well-accepted tool to evaluate executive functions, especially sustained attention and set-shifting5, even in elderly patients6.
The standard TMT is a paper-pencil test consisting of two parts: tMT-A and TMT-B5. The former calls for the test-taker to draw lines connecting randomly distributed numbers (1&#8211;25) on a test paper in ascending order (1-&#62;2-&#62;3&#8230;), whereas the latter requires the test-taker to set numbers and letters (1-&#62;A-&#62;2-&#62;B&#8230;) alternatively. The performance of TMT is generally scored in the time taken to complete each part correctly7. TMT has been translated into different languages. The Chinese version of TMT was developed in 20068. Since Chinese characters are quite distinct from English letters, the Chinese version of TMT was used in our procedure.
Apart from the standard version, TMT has been modified in different ways by researchers (e.g., oral TMT9, driving TMT10, walking TMT (WTMT)11) to assess specific populations or find details under different conditions, such as driving and walking. Of note, some studies conferring different numbers compared with the standard TMT are also reported to be of high validity and reliability. For example, THINC-Integrated Tool (THINC-it) developed by the McIntyre group used 9 numbers and letters for TMT-B12; WTMT reported by Schott and colleagues used 15 numbers for TMT-A13. In the same way, many evaluating systems of TMT have been built beyond the complete time scoring, which are reported to be helpful in finding more items besides executive dysfunction, or to be accessible for participants who are not suitable to complete the standard TMT. For example, some researchers investigated the errors in TMT and found that errors in TMT-B were associated with mental tracking and working memory in patients with psychiatric disorder14. Another group from Greece suggested derived TMT scores [TMT-(B&#8722;A) or TMT(B/A)] as indices to detect impairment in cognitive flexibility across the adult life span15. Generally, alternative evaluating systems of TMT can be summarized as follows: (1) completion time analysis&#8212;TMT completion time is calculated in seconds16; (2) error analysis&#8212;different types of TMT errors are classified and quantified14; (3) intermanual differences&#8212;different abilities of completing TMT between the dominant hand and the nondominant hand are compared17; and (4) derived Trail Making Test indices&#8212;different characterizations between completing TMT-A and TMT-B are analyzed15. The alternative scoring methods provide additional information. For example, the utility of TMT error analysis could reveal cognitive deficits not traditionally captured using completion time as the sole outcome variable in patients with schizophrenia and depression14. The lack of any significant intermanual difference helped to discriminate the cognitive dysfunction from the influence of the motor disorder17. Derived TMT indices could detect impairment in cognitive flexibility across the adult life span and minimize the effect of demographics and other cognitive background variables15.
With advances in modern technology, computer-based digital applications have been increasingly integrated into traditional cognitive interventions, most of which are designed as similar to the original test as possible, rather than created as new tools. Digital or computerized TMT (dTMT) has been proven to have the potential to capture additional information, with the structure of the existing test mainly unchanged in recent years18,19.
This study aimed to introduce a computer-based Chinese version of dTMT-A and dTMT-B, as well as a WTMT. Both are modified TMTs and have been confirmed to have high sensitivity and specificity to screen patients with MCI, Parkinson&#8217;s Disease, Alzheimer&#8217;s Disease, and so forth, based on the movement of upper and lower limbs20,21. Detailed scoring methods were also presented because digital technologies incorporated into dTMT and WTMT might help capture more information compared to the paper-pencil version of TMT.

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			<td height="42" style="height:42px;width:215px;">Minisun</td>
			<td style="width:69px;">LLC</td>
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			<td style="width:415px;">Intelligent Device for Energy Expenditure and Activity (IDEEA)</td>
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traditional trail making test modified into brand-new assessment tools: digital and walking trail making test

The Trail Making Test (TMT) is a well-accepted tool for evaluating executive function. The standard TMT was invented more than 60 years ago and has been modified into many versions. With the development of digital technologies, TMT is now modified to a digitized version. The present study demonstrated digital TMT (dTMT) performed on a computer, and Walking TMT (WTMT) on the floor. Both revealed more information compared with the traditional version of TMT.

Seven aged patients with Mild Cognitive Impairment (Elderly with MCI), seven aged subjects with Parkinson&#8217;s Disease (Elderly with PD), and seven aged healthy individuals (Healthy Elderly) were recruited, and dTMT-A, dTMT-B, WTMT-A, and WTMT-B, were performed. After the tests, data were collected and analyzed using SPSS software.
As a whole, the demographical data of participants showed that all groups were matched well in terms of age, gender, educational level, dominant hand, Clinical D...

Watch this Scientific Journal Video about Traditional Trail Making Test Modified into Brand-new Assessment Tools: Digital and Walking Trail Making Test at JoVE.com

Traditional Trail Making Test Modified into Brand-new Assessment Tools: Digital and Walking Trail Making Test

Here, we present a protocol to show how to perform two types of cognitive assessment tools derived from the paper-pencil version of the Trail Making Test.

The Trail Making Test (TMT) is a well-accepted tool for evaluating executive function. The standard TMT was invented more than 60 years ago and has been ...

Traditional trail making test are used for executive function to assess. While opposed, the digital Walking Trail Making Test assess the motor ability in addition to cognitive function. Considering that cognitive motor test has gained immense attention recently, the main advantage of this integrated test paradigm is that it provides more information than conventional assessments.Both the new and modified trail making tests can be used for clinical patients with cognitive and movement disorders. For those patients with upper limb disability, the Walking Trail Making Test is particularly useful. As both of the tests collect information in real time and the subjects needs complete the test quickly, take care to explain the test processes in detail before each trial.Visual demonstration can be helpful in minimizing misunderstandings, destractions, or other types of delays during the test, all of which can confound the data. To carry out a digital trail making test A procedure, seat each participant in front of a desk in a quiet and comfortable environment and adjust the computer position, background light, and electronic pen. Check the near-visual acuity of the participant to ensure that they can easily read the numbers on the screen, and show the instructions to the participant, indicating that they will need to use the pen to draw a line as rapidly as possible to join consecutive numbers in the circles randomly distributed on the screen.When the participant is ready, initiate a 150-second maximum pre-test trial demonstrating that if the circles have been correctly joined, the color of the first circle will change. If the circles are not correctly joined, the color will remain unchanged, and the participant will need to restart the task from the last circle. Encourage the participant to draw the line as fluently and accurately as possible while avoiding errors and time wastage.At the end of the pre-trial have the participant select part A to complete the Digital Trail Making Test A without interruption. When the Digital Trail Making Test A has been completed, carry out a Digital Trail Making Test B in similar manner. First showing the digital trail making test B guidelines to the participant that instruct the participant to draw a line as rapidly as possible to alternatively join the numbers and Chinese characters within the circles randomly distributed on the screen.To perform the Walking Trail Making Test A, in a quiet and comfortable environment with a full room light, randomly distribute coins with numbers at each of 15 positions in a 16-meter squared area. Connect the intelligent device for energy expenditure and activity to a computer and enter the anthropometric data for the participant. When the data has been entered, bring the participant into the room and use medical tape to attach one biaxial mini accelerometer over the sternum, one to the front side of each thigh, and one under each foot.Use thin, flexible cables to attach all of the accelerometers to a microprocessor storage unit. And use a clip to attach the unit to the participant's clothes. When the participant is ready, ask them to walk up and down a walkway without any targets at a comfortable pace.After the warm-up, show the participant the Walking Trail Making Test A instructions, which ask the participant to walk on numbered targets in a sequential order as rapidly but accurately as possible, joining consecutive numbers on the coins randomly distributed on the floor. Take care to ensure the safety of the participants as dual-task walking in a challenging environment may increase the risk of falling. For Walking Trail Making Test B, after disturbing the coins as just demonstrated, show the Walking Trail Making Test B instructions to the participant.And have the participant walk on the numbered targets in sequential order as rapidly as possible to alternatively join the numbers and Chinese characters on the coins randomly distributed on the floor. In this representative analysis, most of the Digital Trail Making Test A data between healthy elderly, elderly with mild cognitive impairment, and elderly with Parkinson's disease were similar. However, elderly with Parkinson's disease exhibited a larger total pathway deviation of each step, a larger variability of pathway deviation, and a lower velocity of drawing.In completing Digital Trail Making Test B, aged patients with mild cognitive impairment needed a longer time of completion with more errors, more time inside the circle and the tolerance circle, more pathway deviation, and a lower drawing velocity compared to healthy elderly individuals. Elderly with Parkison's disease also needed a longer time of completion, had more errors, more time inside the circle, less time inside the tolerance circle, more pathway deviation, a larger variability of pathway deviation, and a lower drawing velocity for each step compared to aged healthy individuals. Gate data in the Walking Trail Making Test A revealed differences in the elderly with Parkison's disease group in terms of speed, step length, and stride length.The gate data in the Walking Trail Making Test B revealed that aged patients with mild cognitive impairment and Parkinson's disease needed a longer time and more steps to complete the test with a shorter step and stride length relative to aged healthy participants. In addition, aged patients with Parkinson's disease showed an even more severe trend compared to mild cognitive impairment subjects with marked differences in step length, stride length, and step length gait variability. The most important thing to remember is to show the instructions to the participants before the test to prevent any misunderstandings or delays that might occur during the test.Following this procedure, the left-handed Digital Trail Making Test can be performed to assess intermanual differences or movement assessments can be performed to evaluate the pure walking ability of participants. This technique has paved the way for the study of cognitive and motor functions here in an incorporated manner suitable for patients with motor cognitive risk syndrome.

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Medicine

Making Sense of Listening: The IMAP Test Battery

The ability to hear is only the first step towards making sense of the range of information contained in an auditory signal. Of equal importance are the abilities to extract and use the information encoded in the auditory signal. We refer to these as listening skills (or auditory processing AP). Deficits in these skills are associated with delayed language and literacy development, though the nature of the relevant deficits and their causal connection with these delays is hotly debated.
When a child is referred to a health professional with normal hearing and unexplained difficulties in listening, or associated delays in language or literacy development, they should ideally be assessed with a combination of psychoacoustic (AP) tests, suitable for children and for use in a clinic, together with cognitive tests to measure attention, working memory, IQ, and language skills. Such a detailed examination needs to be relatively short and within the technical capability of any suitably qualified professional. Current tests for the presence of AP deficits tend to be poorly constructed and inadequately validated within the normal population. They have little or no reference to the presenting symptoms of the child, and typically include a linguistic component. Poor performance may thus reflect problems with language rather than with AP. To assist in the assessment of children with listening difficulties, pediatric audiologists need a single, standardized child-appropriate test battery based on the use of language-free stimuli.
We present the IMAP test battery which was developed at the MRC Institute of Hearing Research to supplement tests currently used to investigate cases of suspected AP deficits. IMAP assesses a range of relevant auditory and cognitive skills and takes about one hour to complete. It has been standardized in 1500 normally-hearing children from across the UK, aged 6-11 years. Since its development, it has been successfully used in a number of large scale studies both in the UK and the USA. IMAP provides measures for separating out sensory from cognitive contributions to hearing. It further limits confounds due to procedural effects by presenting tests in a child-friendly game-format. Stimulus-generation, management of test protocols and control of test presentation is mediated by the IHR-STAR software platform. This provides a standardized methodology for a range of applications and ensures replicable procedures across testers. IHR-STAR provides a flexible, user-programmable environment that currently has additional applications for hearing screening, mapping cochlear implant electrodes, and academic research or teaching.

A test battery (IMAP) for performing an in-depth assessment of auditory and cognitive abilities contributing to listening skills is described. It is quick to administer, child-friendly and free from linguistic confounds. Stimulus generation and protocol management are controlled via a software platform (IHR-STAR) to ensure replicable procedures.

The ability to hear is only the first step towards making sense of the range of information contained in an auditory signal. Of equal importance are the ...

The Trier Social Stress Test Protocol for Inducing Psychological Stress

This article demonstrates a psychological stress protocol for use in a laboratory setting. Protocols that allow researchers to study the biological pathways of the stress response in health and disease are fundamental to the progress of research in stress and anxiety.1 Although numerous protocols exist for inducing stress response in the laboratory, many neglect to provide a naturalistic context or to incorporate aspects of social and psychological stress. Of psychological stress protocols, meta-analysis suggests that the Trier Social Stress Test (TSST) is the most useful and appropriate standardized protocol for studies of stress hormone reactivity.2 In the original description of the TSST, researchers sought to design and evaluate a procedure capable of inducing a reliable stress response in the majority of healthy volunteers.3 These researchers found elevations in heart rate, blood pressure and several endocrine stress markers in response to the TSST (a psychological stressor) compared to a saline injection (a physical stressor).3 Although the TSST has been modified to meet the needs of various research groups, it generally consists of a waiting period upon arrival, anticipatory speech preparation, speech performance, and verbal arithmetic performance periods, followed by one or more recovery periods. The TSST requires participants to prepare and deliver a speech, and verbally respond to a challenging arithmetic problem in the presence of a socially evaluative audience.3 Social evaluation and uncontrollability have been identified as key components of stress induction by the TSST.4 In use for over a decade, the goal of the TSST is to systematically induce a stress response in order to measure differences in reactivity, anxiety and activation of the hypothalamic-pituitary-adrenal (HPA) or sympathetic-adrenal-medullary (SAM) axis during the task.1 Researchers generally assess changes in self-reported anxiety, physiological measures (e.g. heart rate), and/or neuroendocrine indices (e.g. the stress hormone cortisol) in response to the TSST. Many investigators have adopted salivary sampling for stress markers such as cortisol and alpha-amylase (a marker of autonomic nervous system activation) as an alternative to blood sampling to reduce the confounding stress of blood-collection techniques. In addition to changes experienced by an individual completing the TSST, researchers can compare changes between different treatment groups (e.g. clinical versus healthy control samples) or the effectiveness of stress-reducing interventions.1

This article describes a protocol for inducing psychological stress in participants, which enables researchers to measure psychological, physiological and neuroendocrine responses to stress within single participants or between groups.

This article demonstrates a psychological stress protocol for use in a laboratory setting.  Protocols that allow researchers to study the biological ...

An in vivo Assay to Test Blood Vessel Permeability

This method is based on the intravenous injection of Evans Blue in mice as the test animal model. Evans blue is a dye that binds albumin. Under physiologic conditions the endothelium is impermeable to albumin, so Evans blue bound albumin remains restricted within blood vessels. In pathologic conditions that promote increased vascular permeability endothelial cells partially lose their close contacts and the endothelium becomes permeable to small proteins such as albumin. This condition allows for extravasation of Evans Blue in tissues. A healthy endothelium prevents extravasation of the dye in the neighboring vascularized tissues. Organs with increased permeability will show significantly increased blue coloration compared to organs with intact endothelium. The level of vascular permeability can be assessed by simple visualization or by quantitative measurement of the dye incorporated per milligram of tissue of control versus experimental animal/tissue. Two powerful aspects of this assay are its simplicity and quantitative characteristics. Evans Blue dye can be extracted from tissues by incubating a specific amount of tissue in formamide. Evans Blue absorbance maximum is at 620 nm and absorbance minimum is at 740 nm. By using a standard curve for Evans Blue, optical density measurements can be converted into milligram dye captured per milligram of tissue. Statistical analysis should be used to assess significant differences in vascular permeability.

An in vivo Assay to Test Blood Vessel Permeability

We are presenting an in vivo assay to test blood vessel permeability. This assay is based on intravenous injection of a dye and subsequent visualization of its diffusion into interstitial spaces.

This method is based on the intravenous injection of Evans Blue in mice as the test animal model. Evans blue is a dye that binds albumin. Under ...

Assessment of Gastric Emptying in Non-obese Diabetic Mice Using a [13C]-octanoic Acid Breath Test

Gastric emptying studies in mice have been limited by the inability to follow gastric emptying changes in the same animal since the most commonly used techniques require killing of the animals and postmortem recovery of the meal1,2. This approach prevents longitudinal studies to determine changes in gastric emptying with age and progression of disease. The commonly used [13C]-octanoic acid breath test for humans3 has been modified for use in mice4-6 and rats7 and we previously showed that this test is reliable and responsive to changes in gastric emptying in response to drugs and during diabetic disease progression8. In this video presentation the principle and practical implementation of this modified test is explained. As in the previous study, NOD LtJ mice are used, a model of type 1 diabetes9. A proportion of these mice develop the symptoms of gastroparesis, a complication of diabetes characterized by delayed gastric emptying without mechanical obstruction of the stomach10.
This paper demonstrates how to train the mice for testing, how to prepare the test meal and obtain 4 hr gastric emptying data and how to analyze the obtained data. The carbon isotope analyzer used in the present study is suitable for the automatic sampling of the air samples from up to 12 mice at the same time. This technique allows the longitudinal follow-up of gastric emptying from larger groups of mice with diabetes or other long-standing diseases.

Assessment of Gastric Emptying in Non-obese Diabetic Mice Using a [13C]-octanoic Acid Breath Test

Determination of gastric emptying with a non-invasive [13C]-octanoic acid breath test for tracking gastroparesis in female NOD LtJ mice.

Gastric emptying studies in mice have been limited by the inability to follow gastric emptying changes in the same animal since the most commonly used ...

The Multiple Sclerosis Performance Test (MSPT): An iPad-Based Disability Assessment Tool

Precise measurement of neurological and neuropsychological impairment and disability in multiple sclerosis is challenging. We report a new test, the Multiple Sclerosis Performance Test (MSPT), which represents a new approach to quantifying MS related disability. The MSPT takes advantage of advances in computer technology, information technology, biomechanics, and clinical measurement science. The resulting MSPT represents a computer-based platform for precise, valid measurement of MS severity. Based on, but extending the Multiple Sclerosis Functional Composite (MSFC), the MSPT provides precise, quantitative data on walking speed, balance, manual dexterity, visual function, and cognitive processing speed. The MSPT was tested by 51 MS patients and 49 healthy controls (HC). MSPT scores were highly reproducible, correlated strongly with technician-administered test scores, discriminated MS from HC and severe from mild MS, and correlated with patient reported outcomes. Measures of reliability, sensitivity, and clinical meaning for MSPT scores were favorable compared with technician-based testing. The MSPT is a potentially transformative approach for collecting MS disability outcome data for patient care and research. Because the testing is computer-based, test performance can be analyzed in traditional or novel ways and data can be directly entered into research or clinical databases. The MSPT could be widely disseminated to clinicians in practice settings who are not connected to clinical trial performance sites or who are practicing in rural settings, drastically improving access to clinical trials for clinicians and patients. The MSPT could be adapted to out of clinic settings, like the patient&#8217;s home, thereby providing more meaningful real world data. The MSPT represents a new paradigm for neuroperformance testing. This method could have the same transformative effect on clinical care and research in MS as standardized computer-adapted testing has had in the education field, with clear potential to accelerate progress in clinical care and research.

The Multiple Sclerosis Performance Test MSPT: An iPad-Based Disability Assessment Tool

Precise measurement of neurological and neuropsychological impairment and disability in multiple sclerosis is challenging. We report methodologic details on a new test, the Multiple Sclerosis Performance Test (MSPT). This new approach to the objective of quantification of MS related disability provides a computer-based platform for precise, valid measurement of MS severity.

Precise measurement of neurological and neuropsychological impairment and disability in multiple sclerosis is challenging. We report a new test, the ...

Design, Fabrication, and Administration of the Hand Active Sensation Test (HASTe)

The concept of personalizing neurologic rehabilitation, based on individual impairments, has experienced a recent surge. In parallel, the number of outcome measures of upper extremity motor performance has grown. However, clinicians and researchers lack practical, quantitative measures of the hand&#8217;s natural role as a receptor of the environment. The Hand Active Sensation Test (HASTe), developed by Williams and colleagues in 2006, is a valid and reliable measure of haptic performance. Though not available commercially, the HASTe can be fabricated from inexpensive materials, and it has been used successfully to identify impairments in haptic touch in individuals with stroke. (Williams, 2006). This paper presents the methods of design and fabrication of the HASTe testing kit, as well as a visual screen to be used during administration, and instructions for the tests administration and scoring.

Design, Fabrication, and Administration of the Hand Active Sensation Test HASTe

The Hand Active Sensation Test (HASTe) is a valid and reliable measure of haptic performance, which has been used successfully to identify impaired haptic touch in individuals with stroke. The purpose of this paper is to describe the design, fabrication and administration of the HASTe.

The concept of personalizing neurologic rehabilitation, based on individual impairments, has experienced a recent surge. In parallel, the number of ...

Ultrasound Assessment of Endothelial Function: A Technical Guideline of the Flow-mediated Dilation Test

Cardiovascular disease is the primary cause of mortality and a major cause of disability worldwide. The dysfunction of the vascular endothelium is a pathological condition characterized mainly by a disruption in the balance between vasodilator and vasoconstrictor substances and is proposed to play an important role in the development of atherosclerotic cardiovascular disease. Therefore, a precise evaluation of endothelial function in humans represents an important tool that could help better understand the etiology of multiple cardio-centric pathologies.
Over the past twenty-five years, many methodological approaches have been developed to provide an assessment of endothelial function in humans. Introduced in 1989, the FMD test incorporates a forearm occlusion and subsequent reactive hyperemia that promotes nitric oxide production and vasodilation of the brachial artery. The FMD test is now the most widely utilized, non-invasive, ultrasonic assessment of endothelial function in humans and has been associated with future cardiovascular events.
Although the FMD test could have clinical utility, it is a physiological assessment that has inherited several confounding factors that need to be considered. This article describes a standardized protocol for determining FMD including the recommended methodology to help minimize the physiological and technical issues and improve the precision and reproducibility of the assessment.

The flow mediated dilation (FMD) test is the most commonly utilized, non-invasive, ultrasound assessment of endothelial function in humans. Although the FMD test has been related with the prediction of future cardiovascular disease and events, it is a physiological assessment with many inherent confounding factors that need to be considered.

Cardiovascular disease is the primary cause of mortality and a major cause of disability worldwide. The dysfunction of the vascular endothelium is a ...

Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT)

Obesity represents the most important single risk factor in the pathogenesis of type 2 diabetes, a disease which is characterized by a resistance to insulin-stimulated glucose uptake and a gross decompensation of systemic glucose metabolism. Despite considerable progress in the understanding of glucose metabolism, the molecular mechanisms of its regulation in health and disease remain under-investigated, while novel approaches to prevent and treat diabetes are urgently needed. Diet derived glucose stimulates the pancreatic secretion of insulin, which serves as the principal regulator of cellular anabolic processes during the fed-state and thus balances blood glucose levels to maintain systemic energy status. Chronic overfeeding triggers meta-inflammation, which leads to alterations in peripheral insulin receptor-associated signaling and thus reduces the sensitivity to insulin-mediated glucose disposal. These events ultimately result in elevated fasting glucose and insulin levels as well as a reduction in glucose tolerance, which in turn serve as important indicators of insulin resistance. Here, we present a protocol for the generation and metabolic characterization of high-fat diet (HFD)-fed mice as a frequently used model of diet-induced insulin resistance. We illustrate in detail the oral glucose tolerance test (OGTT), which monitors the peripheral disposal of an orally administered glucose load and insulin secretion over time. Additionally, we present a protocol for the insulin tolerance test (ITT) to monitor whole-body insulin action. Together, these methods and their downstream applications represent powerful tools to characterize the general metabolic phenotype of mice as well as to specifically assess alterations in glucose metabolism. They may be especially useful in the broad research field of insulin resistance, diabetes and obesity to provide a better understanding of pathogenesis as well as to test the effects of therapeutic interventions.

Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test OGTT and Insulin Tolerance Test ITT

The current article describes the generation and metabolic characterization of high-fat diet-fed mice as a model of diet-induced insulin resistance and obesity. It further features detailed protocols to perform the oral glucose tolerance test and the insulin tolerance test, monitoring whole-body alterations of glucose metabolism in vivo.

Obesity represents the most important single risk factor in the pathogenesis of type 2 diabetes, a disease which is characterized by a resistance to ...

Taste Exam: A Brief and Validated Test

The emerging importance of taste in medicine and biomedical research, and new knowledge about its genetic underpinnings, has motivated us to supplement classic taste-testing methods in two ways. First, we explain how to do a brief assessment of the mouth, including the tongue, to ensure that taste papillae are present and to note evidence of relevant disease. Second, we draw on genetics to validate taste test data by comparing reports of perceived bitterness intensity and inborn receptor genotypes. Discordance between objective measures of genotype and subjective reports of taste experience can identify data collection errors, distracted subjects or those who have not understood or followed instructions. Our expectation is that fast and valid taste tests may persuade researchers and clinicians to assess taste regularly, making taste testing as common as testing for hearing and vision. Finally, because many tissues of the body express taste receptors, taste responses may provide a proxy for tissue sensitivity elsewhere in the body and, thereby, serve as a rapid, point-of-care test to guide diagnosis and a research tool to evaluate taste receptor protein function.

This protocol measures human taste responses and includes a brief anatomical assessment, a short taste test, and a validation method using the subject&#39;s reported sensation and taste receptor genotype.

The emerging importance of taste in medicine and biomedical research, and new knowledge about its genetic underpinnings, has motivated us to supplement ...

A Blood-based Test for the Detection of ROS1 and RET Fusion Transcripts from Circulating Ribonucleic Acid Using Digital Polymerase Chain Reaction

We have developed novel methods for the isolation and characterization of tumor-derived circulating ribonucleic acid (cRNA) for blood-based liquid biopsy. Robust detection of cRNA recovered from blood represents a solution to a critical unmet need in clinical diagnostics. The test begins with the collection of whole blood into blood collection tubes containing preservatives that stabilize cRNA. Cell-free, exosomal, and platelet-associated RNA is isolated from plasma in this test system. The cRNA is reverse transcribed to complementary DNA (cDNA) and amplified using digital polymerase chain reaction (dPCR). Samples are evaluated for both the target biomarker as well as a control gene. Test validation included limit of detection, accuracy, and robustness studies with analytic samples. The method developed as a result of these studies reproducibly detect multiple fusion variants for ROS1 (C-Ros proto-oncogene 1; 8 variants) and RET (rearranged during transfection proto-oncogene; 8 variants). The sample processing workflow has been optimized so that test results can consistently be generated within 72 hours of sample receipt.

Detection of circulating ribonucleic acid (cRNA) from blood is an unmet need in clinical diagnostics. Here we describe methods that characterize cRNA from non-small cell lung cancer patients using sensitive and specific digital polymerase chain reaction. The tests meet design requirements to detect fusion variants within 72 hours.

We have developed novel methods for the isolation and characterization of tumor-derived circulating ribonucleic acid (cRNA) for blood-based liquid biopsy. ...