Name: the rodent psychomotor vigilance test (rpvt): a method for assessing neurobehavioral performance in rats and mice
Uploaded: 2016-12-29T12:00:00
Description: Watch this Scientific Journal Video about The Rodent Psychomotor Vigilance Test rPVT: A Method for Assessing Neurobehavioral Performance in Rats and Mice at JoVE.com

This research was supported by NASA (NNX15AC17G to CMD), and by NASA cooperative agreement NCC 9-58 (E000010 to CMD, NBPF02802 and NBPF04201 to RDH) with the National Space Biomedical Research Institute.

Laboratory animal care was according to Public Health Service (PHS) Policy on the Humane Care and Use of Laboratory Animals. All procedures were carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The Institutional Animal Care and Use Committee of the Johns Hopkins University approved the protocol and all procedures. Johns Hopkins also maintains accreditation of their program by the Association for the Assessment and Accreditation of Laborator...

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F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sleep,+circadian+rhythms,+and+psychomotor+vigilance.">Sleep, circadian rhythms, and psychomotor vigilance.</a> Clin Sports Med. 24 (2), 237-249 (2005).</li><li>Van Dongen, H. P., 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=Caffeine+eliminates+psychomotor+vigilance+deficits+from+sleep+inertia.">Caffeine eliminates psychomotor vigilance deficits from sleep inertia.</a> Sleep. 24 (7), 813-819 (2001).</li><li>Blatter, 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=Gender+and+age+differences+in+psychomotor+vigilance+performance+under+differential+sleep+pressure+conditions.">Gender and age differences in psychomotor vigilance performance under differential sleep pressure conditions.</a> Behav Brain Res. 168 (2), 312-317 (2006).</li><li>Lim, J., Dinges, D. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sleep+deprivation+and+vigilant+attention.">Sleep deprivation and vigilant attention.</a> Annals of the New York Academy of Sciences. 1129, 305-322 (2008).</li><li>Basner, 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=Mars+520-d+mission+simulation+reveals+protracted+crew+hypokinesis+and+alterations+of+sleep+duration+and+timing.">Mars 520-d mission simulation reveals protracted crew hypokinesis and alterations of sleep duration and timing.</a> Proc Natl Acad Sci U S A. 110, 2635-2640 (2013).</li><li>Christie, M. 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=Microdialysis+elevation+of+adenosine+in+the+basal+forebrain+produces+vigilance+impairments+in+the+rat+psychomotor+vigilance+task.">Microdialysis elevation of adenosine in the basal forebrain produces vigilance impairments in the rat psychomotor vigilance task.</a> Sleep. 31, 1393-1398 (2008).</li><li>Christie, M. A., McKenna, J. T., Connolly, N. P., McCarley, R. W., Strecker, R. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=24+hours+of+sleep+deprivation+in+the+rat+increases+sleepiness+and+decreases+vigilance:+introduction+of+the+rat-psychomotor+vigilance+task.">24 hours of sleep deprivation in the rat increases sleepiness and decreases vigilance: introduction of the rat-psychomotor vigilance task.</a> J. Sleep Res. 17, 376-384 (2008).</li><li>Oonk, M., Davis, C. J., Krueger, J. M., Wisor, J. P., Van Dongen, H. 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D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+rodent+model+of+the+human+psychomotor+vigilance+test:+Performance+comparisons.">A rodent model of the human psychomotor vigilance test: Performance comparisons.</a> J Neurosci Methods. 259, 57-71 (2016).</li><li>Lim, 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=Imaging+brain+fatigue+from+sustained+mental+workload:+an+ASL+perfusion+study+of+the+time-on-task+effect.">Imaging brain fatigue from sustained mental workload: an ASL perfusion study of the time-on-task effect.</a> Neuroimage. 49, 3426-3435 (2010).</li><li>Tucker, A. M., Basner, R. C., Stern, Y., Rakitin, B. 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S., Parasuraman, R., Matthews, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Vigilance+requires+hard+mental+work+and+is+stressful.">Vigilance requires hard mental work and is stressful.</a> Hum Factors. 50, 433-441 (2008).</li><li>Blatter, 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=Gender+and+age+differences+in+psychomotor+vigilance+performance+under+differential+sleep+pressure+conditions.">Gender and age differences in psychomotor vigilance performance under differential sleep pressure conditions.</a> Behav Brain Res. 168, 312-317 (2006).</li><li>Raymann, R. J., Van Someren, E. 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The methodology described herein results in rPVT performances in rats that compare favorably in many aspects to the typical PVT performance reported in the human literature. Using the present techniques, one can quickly train rats to perform the rPVT, and the performances obtained with these techniques are characterized by clear discriminations (i.e., high levels of correct responding, low levels of both premature responding and lapses). Further, the reaction time distributions obtained with the rPVT are quite s...

The human psychomotor vigilance test (PVT) is a widely used, well-validated tool for measuring vigilance and sustained attention in humans, and was originally developed by Dinges et al. 1-3 for assessing the stability in reaction times and attention (e.g., errors in terms of premature responses and lapses in attention), both within sessions as a whole and across time within individual sessions. Over the years, the human PVT has been modified and updated4-11 to track temporal changes in various aspects attention, and has been demonstrated to be sensitive to changes in sleep deprivation and fatigue, and is affected by drug use and age of subjects12,13. The PVT is a seemingly simple procedure in which a subject briefly touches a screen when a stimulus (typically an LED number display) appears randomly in time, typically after 2 - 10 s. In the human version, the number display is incremented in ms and stopped when the screen is touched, thus indicating the subject&#39;s reaction time (RT). Decreases in vigilance are indicated by 1) slowed reaction times, 2) an increase in lapses (termed &#34;errors of omission&#34; in the human literature, and usually defined as RTs that are &#62; 500 ms in length), and 3) an increase in premature responding (termed &#34;errors of commission&#34; or &#34;false starts&#34; in the human literature). Other measures can also be obtained with the PVT for examining such variables as gender and age differences; for a review of these measures, see Basner and Dinges4. Finally, the PVT has been employed in the general area of human risk assessment, and has been successfully used under a wide range of operational areas that include the military, aviation and railway industries, first responders, and extreme environments such as NASA&#39;s Extreme Environment Missions Operations (NEEMO), the international Mars500 Project14, and on the International Space Station (ISS). On the ISS, the PVT is called the &#34;Reaction Self-Test&#34; and is employed to provide astronauts with individualized fatigue-related feedback (e.g., changes in RTs or lapses in attention).
The human PVT has been in use for decades, as have rodent versions of simple reaction time tasks (which are somewhat similar). It has been only recently, however, that a direct rodent counterpart to the human PVT has been reported in the literature. Christie and colleagues described a version of the human PVT for rats, and reported decreases in vigilance following sleep deprivation15,16. Additional recent studies have reported versions of the rPVT17-19. These reports have described changes in sustained attention following various sleep deprivation techniques; however, the data from these studies have also reported high levels of premature responding (e.g., in some cases, more than 40% of the total number of responses); such performances are quite unlike any PVT performances with humans. Such a large difference in rodent vs. human performances are likely due to differences in specific parameters employed in the human vs. the rodent versions of the PVT; for example, the Christie et al. study employed a randomly varying 3 - 7 s foreperiod, while a human PVT normally employs a 2 - 10 s foreperiod (although see Basner et al.5 for a 3-min version of the human PVT that uses a 1 - 4 s foreperiod). The use of relatively short foreperiod values can often result in animals &#34;timing&#34; their responses, and thus can promote, via accidental reinforcement, increased numbers of premature responses, as have been reported in the current rodent rPVT studies.
The version of the rPVT described here is based on our previously published article20, and provides a detailed description of the techniques and procedures involved. It differs from previously published versions of the rPVT in the following respects: 1) rats were trained with variable foreperiod values of 3 - 10 s, and 2) rats had to respond quickly, since only responses within a short response window (also termed a &#34;limited hold&#34;) following stimulus onset were reinforced (1.5 s in the present study; 3.0 s in the previous published versions of the rPVT). Using these modifications as well as brief timeouts for incorrect responding resulted in greater levels of stimulus control, as indicated by significant improvements in accuracy and reduced levels of premature responding. The present report also describes predictable changes in performance variables (e.g., lapses in attention, RTs) that parallel those seen in humans when examining vigilance decrements21, and when examining other performance measures including the human &#34;time on task&#34; effect and the response-stimulus interval (RSI) effect that is observed in the human PVT22.
The final version of the rPVT described here begins by turning on a house light (see Figure 1). After a variable interval (foreperiod) of 3 - 10 s elapses, the nose-poke key is illuminated for a maximum of 1.5 s. (To insure an equal distribution of foreperiods durations, values are randomly generated without replacement from a list of 36 possible values that range from 3 to 10 s, based on 200 ms increments.) Illumination of the nosepoke key is the signal for an animal to respond, and a response that occurs between 150 to 1,500 ms following the light onset is reinforced with a 45-mg pellet. After a reinforced response, both the nose-poke key light and the house light are turned off and a 1 s inter-trial interval (ITI; house light off) ensues. Nose-pokes at before light onset produce an 8 s timeout (TO) from the experimental contingencies that is signaled by extinguishing the house light. If no responses occur within the 1.5 s response window, both the nosepoke light and house light are turned off, and a 1 s ITI ensues. The next scheduled foreperiod value for the subsequent trial begins after either the 1 s ITI or the 8 s TO, whichever occurred during the prior trial. Sessions are conducted daily (5 days/week), normally consist of about 200 trials, and end after 30 min. This results with each trial having a duration of about 7.5 s, on average.
Shaping stable baseline performance on the rPVT is accomplished by 1) initially adapting a rat to take food pellets out of the food tray in the chamber, 2) hand-shaping a rat to respond on a nose poke key by reinforcing successive approximations to the final nose poke response, and 3) conducting daily sessions where the parameters of the rPVT procedure (i.e., foreperiod, ITI, TO, and key-illumination times) are gradually adjusted over a session, depending on how well each rat is performing during each session (described in detail below).

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			<td>This catalog number has 8 outputs and 4 inputs which is the minimum needed to run the rPVT; SmartCtrl can also be purchased with 16 outputs and 8 inputs for more flexibility</td>
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			<td height="84" style="height:84px;width:315px;">PC computer with PCI card slot</td>
			<td style="width:71px;">Any manfacturer (e.g., Dell)</td>
			<td style="width:119px;"></td>
			<td>Use of the PCI operating package requires a computer with a PCI card slot. Systems that use PCIe are available. Contact Med Associates for details.</td>
		</tr>
		<tr height="210">
			<td height="210" style="height:210px;width:315px;">Dustless Precision pellets 45-mg rodent grain-based diet</td>
			<td style="width:71px;">Bio Serv</td>
			<td style="width:119px;">FO165</td>
			<td style="width:167px;">Bio-Serv 
			One 8th Street, Suite 1 
			Frenchtown, NJ 08825, USA 
			Phone: (800)-996-9908;&#160;&#160; Standard chow pellets are commonly used. Different pellets (e.g., sucrose) can be acquired from Bio Serv.</td>
		</tr>
	</tbody>
</table>

the rodent psychomotor vigilance test (rpvt): a method for assessing neurobehavioral performance in rats and mice

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article describes a rodent version of the PVT&#8212;termed the &#34;rPVT&#34;&#8212;that measures similar aspects of attention (i.e., performance accuracy, motor speed, premature responding, and lapses in attention). Data are presented that demonstrate both the short- and long-term usefulness of the rPVT when employed with laboratory rats. Rats easily learn the rPVT, and learning to perform the basic procedure takes less than two weeks of training. Once acquired, rat performances in the rPVT show a high degree of similarity to these same performance measures in the human PVT, including similarities in, lapses in attention, reaction times, vigilance decrements across session time (i.e., the human &#34;time-on-task&#34; effects), and the response-stimulus interval (RSI) effect described for humans. Thus the rPVT can be an extremely valuable tool for assessing the effects of a wide range of variables on sustained attention quite similar to human PVT performances, and thus can be useful for developing novel treatments for neurobehavioral dysfunctions.

Baseline Rat rPVT Performances
With the parameters detailed here, 86.7% of the 122 male rats reached the final rPVT parameters within an average of 9.0 (SD = 10.13; n = 122) computer-automated training sessions (described in 4.1 - 4.9 rPVT Training; in our experience, only approximately 2% of rats will not acquire the rPVT). Using the current methodology, rats averaged 73.4% correct responding, 18.6% lapses in attention, and 10.6% ...

Watch this Scientific Journal Video about The Rodent Psychomotor Vigilance Test rPVT: A Method for Assessing Neurobehavioral Performance in Rats and Mice at JoVE.com

The Rodent Psychomotor Vigilance Test rPVT: A Method for Assessing Neurobehavioral Performance in Rats and Mice

A rat version of the human Psychomotor Vigilance Test (PVT) is described that measures aspects of attention similar to those measured with the human PVT, including aspects of human vigilance such as performance accuracy, motor speed, premature responding, and lapses in attention.

The Rodent Psychomotor Vigilance Test (rPVT): A Method for Assessing Neurobehavioral Performance in Rats and Mice

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article ...

The overall goal of this protocol is to measure aspects of attention in rats and mice, similar to those measured by the human Psychomotor Vigilance Test, such as accuracy, motor speed, and vigilance. This method can help answer key questions regarding neurobehavioral performances in rodents, including the effects of lesions, pharmacological manipulations, genetic modifications, and sleep deprivation or restriction. The main advantage of this technique is that it provides a stable baseline for assessing the effects of a wide variety of experimental manipulations.To pretrain the rodents, first assign each animal to an operant chamber, where it will be tested each day at approximately the same time, prior to daily feeding. It is critical that the behavioral data be examined each day before moving them to the next training step. If it is not done at the right time, the result will be poor performance.Prepare the operant chamber by loading the pellet dispenser with food pellets. Then deliver 10 to 20 food pellets to the food receptacle in the chamber. Then, weigh the animal, in this case a rat, and place it in the operant chamber.For pre-training, the experimental parameters should be low, fixed values. Once started, the computer program controls the presentation of the house lights, the nose poke key illumination, and automatic dispensing of food pellets. Use settings that will give the animal ample time to explore and be rewarded, such as 10 seconds of nose poke key illumination.Once the rat finishes the food pellets, start to manually shape the rat's behavior. Leave the cubicle open and watch the rat's behavior. Using a handheld switch wired to the feeder, provide pellets as quickly as possible after the rat performs the desired behavior.Shape successive approximations of the desired behavior. For example, once the rat reliably retrieves food pellets from the food receptacle, shape it to move to the left after retrieving a food pellet, towards the nose poke key. During the shaping process, keep the computer program running and controlling the house light, nose poke key, and feeder.Thus, if the rat pokes the key, the computer program reinforces the behavior automatically. After the session, count the total number of pellets the rat receives, and subtract this total mass of food from the rat's daily food allotment. 30 minutes or more after the session, feed the rat the remainder of its daily rations.Clean the operant chamber daily with a gentle disinfectant. Use 70%ethanol sparingly. Check the nose poke key functionality daily, and clean it as needed.Pretrain each rat until it scores at least 40 computer reinforced responses on the illuminated key and retrieves each food pellet. Usually two or three half hour sessions will be enough. Once the rat's behavior is shaped, train the rat with an initial two second, foreperiod interval, and two second timeout.Illuminate the nose poke key as long as needed to get a response, such as nine seconds. This is the limited hold value of the program. Use the timeout as a punishment for premature responses, or when the rat responds prior to the illumination of the nose poke key.During the timeout, the rat has no opportunity to earn food. Proceed by running the 30 minute session. Once the rat completes eight out of 10 correct trials at the current foreperiod value, have the computer increase the foreperiod value and timeout by a tenth of a second.And also, shorten the limited hold value by a tenth of a second. These tenth of a second increases to the foreperiod and timeout values, and decreases to the limited hold values, occur repeatedly within each session as the rat completes eight out of 10 correct trials at each foreperiod value. Once the 30 minute session is over, record the maximum foreperiod length achieved by the rat in a session, and how many pellets were earned.As during pretraining, subtract the amount of food consumed from the rat's daily allotment. The next day, start the 30 minute training session with a foreperiod that is 300 milliseconds slower than the maximum value achieved in the previous session. As the rat achieves eight out of 10 correct trials at each foreperiod value, the computer program will continue to automatically increase this value just as the day before.When the timeout reaches eight seconds, and the limited hold reaches 1.5 seconds, advance these variables no further. The foreperiod can get as long as tolerated. Analyze the rat's daily performance as the percentage of correct trials, premature trials, and misses.Rats commonly maintain an average of 40 to 90%correct responses with steady improvement. Once the rat reaches a foreperiod of 10 seconds or more, vary every foreperiods in the trial from seven and 10 seconds, while keeping the other parameters fixed at eight and 1.5 seconds. When a rat is able to get 70%of the trials correct, with a variable foreperiod, extend the range of the variable foreperiod to five to 10 seconds.This often occurs within a session, so it is good to keep a close eye on the data. Again, after the rat is able to complete 70%of the trials successfully, broaden the variable foreperiod range to three to 10 seconds. It is really important that the rat get 70%or better success before advancing the degree of difficulty.Because some rats will adopt a strategy of responding randomly, instead of waiting for the stimulus. With the parameters detailed here, 86.7%of 122 male rats reached the final rPVT parameters within an average of of nine computer automated training sessions. The reaction time of rats was then compared to that of humans performing the PVT.Like humans, rats show the expected sharp rise in reaction times at the lower values, with a longer rightward tail at the higher values. As seen in the human PVT, the rats'response speed decreases over time on task, which indicates a vigilance decrement, or a decrease in performance, as the amount of time performing the task increases. Foreperiod time had a significant impact on the rats'performance.At lower foreperiod values, performance was slower and contained a greater percentage of lapses. However, as the foreperiod time increased, correct responding decreased while reaction times were faster, and the percentage of premature responses increased. After watching this video, you should have a good understanding of how to train rats and mice to accurately perform a rodent version of the human PVT, and obtain stable, consistent performances on a daily basis for months.Once mastered, this technique can be used to train rodents to perform the rodent PVT within 10 to 15 days, and produce stable performances thereafter.

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