This research was funded by NIA grant number R43AG057238 to Peter Kallestrup.

The study is a randomized trial, where half of the research participants (stratified by cognitive status) are randomized 1 to 1 to receive computerized cognitive training (CCT) on the Double-Decision task from the Posit Science Brain HQ training software combined with the CFST and the others are trained on the CFST alone. This research was reviewed and approved by the University of Miami Institutional Review Board and all participants provided signed informed consent.
1. Preparation
<ol>
	<li>Obtain written informed consent.</li>
	<li>Screen the participant with the Montreal Cognitive Assessment (MOCA)11.
	<ol>
		<li>Have the participant connect numbers and letters in sequence.</li>
		<li>Show the participant 3 pictures of animals and have them name them.</li>
		<li>Read 3 verbal learning words and have participant recall them.</li>
	</ol>
	</li>
	<li>Perform a baseline cognitive assessment using the tablet version of the Brief Assessment of Cognition (Figure 1)12. Administer all of the subtests on the tablet app. The subtests are Verbal Learning and Memory, Digit Sequencing, Token Motor Task, Symbol Coding, Verbal Fluency Examinations, and Tower of London.
	<ol>
		<li>Present the overall instructions for the assessment on the app.</li>
		<li>Present the instructions for the Symbol Coding Task.</li>
		<li>Have the participant do practice coding.</li>
		<li>Watch the participant perform the coding task for 15 seconds.</li>
		<li>Present the instructions for the Tower of London Task.</li>
		<li>Have the participant do the practice items.</li>
		<li>Watch the participant solve the first test item.</li>
	</ol>
	</li>
	<li>Assess the participant with 6 different functional tasks (Figure 2) in a fixed difficulty format. 
	NOTE: During the fixed difficulty assessment, there is no training provided, and if a participant makes an error, the instructions are simply repeated. When a participant completes a task, they proceed to the next one. When all of the tasks are completed, training begins. The representative task demands of each task are presented below.</li>
</ol>
2. Task demands for fixed difficulty and training simulations
<ol>
	<li>Launch the Ticket Purchase Task.
	<ol>
		<li>Select purchase a new ticket.</li>
		<li>Select Purchase a single ride ticket.</li>
		<li>Check the balance on the transit card.</li>
		<li>Add $60.00 to the transit card.</li>
	</ol>
	</li>
	<li>Launch the telephone refill task.
	<ol>
		<li>Dial the number for the pharmacy.</li>
		<li>Enter the prescription number.</li>
		<li>Select the time to pick up the medication.</li>
	</ol>
	</li>
	<li>Launch the ATM banking task.
	<ol>
		<li>Enter the PIN to start the session.</li>
		<li>Check the balance in the checking account.</li>
		<li>Withdraw $180.00 from the checking account.</li>
	</ol>
	</li>
	<li>Launch the medication label comprehension task.
	<ol>
		<li>Choose the correct time of day to take the medication.</li>
		<li>Correctly identify how many pills to take each day.</li>
		<li>Launch the medication organizer subtask.</li>
		<li>Pack up a day&#39;s worth of medications.</li>
	</ol>
	</li>
	<li>Launch the internet banking task.
	<ol>
		<li>Enter the User ID and password.</li>
		<li>Check the balance in the checking account.</li>
		<li>Make a transfer of $15.00 from savings to checking.</li>
	</ol>
	</li>
	<li>Launch the internet prescription refill and online shopping task.
	<ol>
		<li>Enter the userID and password.</li>
		<li>Verify your identity by selecting the correct city (Miami), Street (Micapony) and Car color (Blue).</li>
		<li>Select Prinivil and no generic equivalent.</li>
		<li>Select Correct date and time for pickup.</li>
	</ol>
	</li>
</ol>
3. Training after the fixed difficulty assessment
<ol>
	<li>CFST alone condition
	<ol>
		<li>Explain the training task to the participant, stating that all 6 tasks will be trained.</li>
		<li>Launch the ATM banking task.</li>
		<li>Enter PIN.</li>
		<li>Select transaction (check balance in checking).</li>
		<li>Visualize the process of program-delivered feedback for errors.</li>
		<li>Present 4 errors in sequence to demonstrate the feedback process.</li>
	</ol>
	</li>
	<li>CCT + CFST Condition 
	NOTE: The CFST training is the same as CFST alone but is for 30 minutes only. Brain HQ DoubleDecision is the computerized cognitive training task in the combined condition. Figure 3 depicts the Double-Decision Task.
	<ol>
		<li>Explain the process of Training on Computerized cognitive training as well as skills training.</li>
		<li>Launch Brain HQ double Decision Task.</li>
		<li>Perform the practice items.</li>
		<li>Perform the actual test items.</li>
		<li>Visualize this process for about 30 seconds.</li>
	</ol>
	</li>
</ol>
4. Post-training assessment
NOTE: After graduation from all six training tasks or completion of 24 sessions, participants complete a post-test. This next section should be presented as a verbal description of the post training assessments
<ol>
	<li>Have participants perform different versions of all six trained tasks. They will be told that the tasks are the same, but the content demands are different.</li>
	<li>Have participants perform the BAC App assessment again.</li>
</ol>

<ol>
	<li>Berkowsky, R. W., Sharit, J., Czaja, S. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Factors+Predicting+Decisions+About+Technology+Adoption+Among+Older+Adults.">Factors Predicting Decisions About Technology Adoption Among Older Adults.</a> Innovations in Aging. 2 (1), (2018).</li><li>Harvey, P. D., Keefe, R. S. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Technology,+society,+and+mental+illness:+challenges+and+opportunities+for+assessment+and+treatment.">Technology, society, and mental illness: challenges and opportunities for assessment and treatment.</a> Innovations in Clinical Neuroscience. 9, 47-50 (2012).</li><li>Taha, J., Czaja, S. J., Sharit, J., Morrow, D. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Factors+affecting+usage+of+a+personal+health+record+(PHR)+to+manage+health.">Factors affecting usage of a personal health record (PHR) to manage health.</a> Psychology and Aging. 28, 1124-1139 (2013).</li><li>Czaja, S. J., Loewenstein, D. A., Sabbag, S. A., Curiel, R. E., Crocco, E., 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=A+Novel+Method+for+Direct+Assessment+of+Everyday+Competence+Among+Older+Adults.">A Novel Method for Direct Assessment of Everyday Competence Among Older Adults.</a> Journal of Alzheimers Disease. 57 (4), 1229-1238 (2017).</li><li>Czaja, S. J., Loewenstein, D. A., Lee, C. C., Fu, S. H., 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=Assessing+functional+performance+using+computer-based+simulations+of+everyday+activities.">Assessing functional performance using computer-based simulations of everyday activities.</a> Schizophrenia Research. 183, 130-136 (2017).</li><li>Harvey, P. D., McGurk, S. R., Mahncke, H., Wykes, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Controversies+in+computerized+cognitive+training.">Controversies in computerized cognitive training.</a> Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 3, 907-915 (2018).</li><li>Sherman, D. S., Mauser, J., Nuno, M., Sherzai, 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+Efficacy+of+Cognitive+Intervention+in+Mild+Cognitive+Impairment+(MCI):+a+Meta-Analysis+of+Outcomes+on+Neuropsychological+Measures.">The Efficacy of Cognitive Intervention in Mild Cognitive Impairment (MCI): a Meta-Analysis of Outcomes on Neuropsychological Measures.</a> Neuropsychology Review. 27, 440-484 (2017).</li><li>Edwards, J. D., Delahunt, P. B., Mahncke, H. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+speed+of+processing+training+delays+driving+cessation.">Cognitive speed of processing training delays driving cessation.</a> Journal of Gerontology. 64, 1262-1267 (2009).</li><li>Rebok, G. W., 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=Ten-year+effects+of+the+Advanced+Cognitive+Training+for+Independent+and+Vital+Elderly+cognitive+training+trial+on+cognition+and+everyday+functioning+in+older+adults.">Ten-year effects of the Advanced Cognitive Training for Independent and Vital Elderly cognitive training trial on cognition and everyday functioning in older adults.</a> Journal of the American Geriatrics Society. 62, 16-24 (2014).</li><li>Edwards, 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=Speed+of+processing+training+results+in+lower+risk+of+dementia.">Speed of processing training results in lower risk of dementia.</a> Alzheimers Dementia. 3, 603-611 (2017).</li><li>Nasreddine, Z. 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+Montreal+cognitive+assessment,+MoCA:+a+brief+screening+tool+for+mild+cognitive+impairment.">The Montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment.</a> Journal of the American Geriatrics Society. 53, 695-699 (2005).</li><li>Atkins, A. 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=Validation+of+the+tablet-administered+Brief+Assessment+of+Cognition+(BAC+App).">Validation of the tablet-administered Brief Assessment of Cognition (BAC App).</a> Schizophrenia Research. 181, 100-106 (2017).</li><li>Gobel, E. W., 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=Implicit+perceptual-motor+skill+learning+in+mild+cognitive+impairment+and+Parkinson's+disease.">Implicit perceptual-motor skill learning in mild cognitive impairment and Parkinson's disease.</a> Neuropsychology. 27 (3), 314-321 (2013).</li><li>Oudman, E., Nijboer, T. C., Postma, A., Wijnia, J. W., Van der Stigchel, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Procedural+Learning+and+Memory+Rehabilitation+in+Korsakoff's+Syndrome+-+a+Review+of+the+Literature.">Procedural Learning and Memory Rehabilitation in Korsakoff's Syndrome - a Review of the Literature.</a> Neuropsychology Review. 25 (2), 134-148 (2015).</li></ol>

In the past year Dr. Harvey has received consulting fees or travel reimbursements from Alkermes, Boehringer Ingelheim, Intra-Cellular Therapies, Jazz Pharma, Minerva Pharma, Otsuka America, Roche Pharma, Sanofi Pharma, Sunovion Pharma, Takeda Pharma, and Teva. He receives royalties from the Brief Assessment of Cognition in Schizophrenia. He is Chief Scientific Officer for i-Function. Peter Kallestrup is CEO of i-Function. Lize Tibiri&#231;&#225; is a part time employee of i-Function. Sara Czaja is Chief Scientific officer of i-Function.

CSFT training led to substantial and rapid treatment gains with as few as 6 training sessions, with results applicable to both NC and MCI participants. Both participant groups evidenced substantial improvements in task performance. CCT supplementation led to similar CFST gains with half as many CFST training sessions. Importantly, NC participants who received skills training alone required an average of only 6 sessions per task (out of a possible 24) to perfect their performance. In summary: 1) both groups of participants demonstrated improvements in performance across all tasks; 2) the HC participants proceeded through the training fairly rapidly even without CCT supplementation; and 3) MCI participants required more training sessions but learned equivalently. These findings replicate our previous findings with older patients with schizophrenia and a separate sample of healthy controls.
Of primary importance is the improvement in training associated with computerized functional skills training in participants with MCI. These cases had substantial impairments in their episodic memory. However, they were still able to make substantial gains, proportionately equivalent to people with NC, across 6 different training simulations. Previous studies have shown dissociation of procedural and verbal memory learning in MCI and amnestic conditions13,14. Thus, this study shows that functional skills can be learned fairly rapidly and efficiently, with few dropouts.
Supplementation of computerized skills training with CCT increased the efficiency of the skills training considerably, with gains doubled per unit training session compared to skills training alone. Thus, a combined intervention with CCT and CFST in individuals with MCI would likely have multiple benefits. First, dementia prevention may be facilitated by CCT. Skills training may also lead to increased independence or delay progressive functional changes in MCI. As a result, the potential benefits of combined training seem considerable and a major topic for further study with this protocol.
Later studies will focus on real-world functional gains. Demonstration of such real-world gains would solidify the benefits of this training protocol. Implementing the protocol was quite efficient and participants reported high levels of satisfaction with their gains. For example, 98% or more of the participants stated that they &#34;definitely&#34; would be more able to do each of the 6 tasks in the real world.

Many contemporary functional tasks are performed using technology. This includes banking and other financial management tasks, travel and transit tasks, and healthcare management. The challenges of using technology daily are amplified in older people whose lifetime exposure to technology may be more limited. Technology-based tasks can also be cognitively demanding. Older people and people with different challenges, such as severe mental illness1,2 or cognitive deficits, may not have the financial or cognitive resources to use challenging technologies. These individuals have difficulty negotiating today&#39;s digitized world, which is a threat to their independence.
Our previous research has shown that many healthy older people also have problems in performing everyday functional tasks efficiently3. Further, people with mild cognitive impairment have proportionately greater challenges performing these tasks4. Our research has shown that component cognitive abilities in healthy aging4, severe mental illness5 and MCI populations, is consistently correlated with the ability to perform veridical simulations of everyday functional tasks. Thus, cognitive ability is a rate limiter for people&#39;s ability to initially perform, and learn, functional tasks using technology. This problem is exacerbated by the fact that many of these tasks, such as using an ATM, are thought of as &#34;walk up tasks&#34; or tasks that are intuitive and do not require training.
Currently, training in the performance of technology-relevant everyday functional is not systematically delivered. New technology, such as iPhones, tablets, and computers, are commonly delivered without any instructions for their use. Instructions for using websites are not commonly available. For example, the New York Metropolitan Transit Authority (MTA), website has no instructions on using their ticket kiosks other than instructions on how to refill a Metrocard.
The incremental deficits in cognitive performance can be partially addressed with computerized cognitive training (CCT) for some populations. Recent data have suggested that both healthy older people6 and people with MCI7 can make cognitive gains with CCT on the cognitive abilities targeted by the training. Thus, it would be expected that performance of functional tasks would also be facilitated with CCT efforts. However, the widely reported success of CCT in both older adult and MCI populations has not been accompanied by spontaneous improvements in the ability to perform novel functional skills. While previously acquired skills, such as driving8, can be facilitated through CCT, there is no evidence across populations that CCT alone is enough to lead to acquisition of novel functional skills.
CCT has also been shown to have protective effects against development of dementia, at least with a limited set of training routines. For instance, the ACTIVE trial showed that computerized speed training was associated with persistent improvements in cognitive performance that could be detected at a 10-year follow-up9. A subsequent follow-up study also reported a 30% decrease in dementia associated with all causes at the 10-year period as well10. As a result, since certain types of CCT appear to result in cognitive benefits among older people, the combination of CCT and computerized functional skills training should result in improvements in functional skills.
Thus, the current program involved the development of a set of ecologically valid functional skills tasks that are typically performed using some sort of technology, either internet, telephone, or in-person on a device such as an ATM. The tasks are presented in Table 1 and were chosen as important to living independently. Within the program, these tasks are performed in fixed difficulty, non-training formats first. Each task has multiple different graduated sub-tasks, which vary in difficulty of functional demands. After completion of the 6 fixed difficulty tasks, all participants are then trained on the Computerized Functional Skills Training (CFST) training simulations. These simulations provide direct performance feedback to the participant. Sample feedback is presented in Table 2. There is no involvement of a human trainer, nor does a human provide feedback. When a participant makes an error on a subtask, graduated feedback is provided across that increases in corrective information. For example, in the ATM task, if an individual makes an initial error inputting their pin number, basic corrective information is provided; if they make the same error a second time more corrective information is provided.
After 4 errors, the task proceeds to the next training step. However, when the participant returns to train later, this step is re-trained until it is passed. Each of the training modules is considered complete and the participant graduates after performing the entire task two times without any errors.
The study includes two research participant groups: (1) cognitively normal (CN) healthy older and (2) medically healthy older people with mild cognitive impairment (MCI). CN was defined as a Montreal Cognitive Assessment (MOCA)11 score of 26 or more and no cognitive complaints. MCI was defined with a systematic assessment that included the MOCA, assessments of subjective complaints, and assessment with a structured neuropsychological assessments. Participants were excluded if their cognitive performance reflected impairment greater than MCI. Training was conducted on Windows computers although the software can be deployed in iOS as well. Training was proctored in a ratio of approximately 6 trainees per proctor.
The goal of the study is to determine 1) if CFST is efficacious in healthy older people, defined by improvements in performance of computer-based functional skills; (2) the relative efficacy of functional skills training for those with MCI as compared to those who are non-impaired; and (3) whether the provision of CCT enhances the CFST and if there is a differential effect for the MCI as compared to the NC.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Bac App</td>
			<td>Verasci, Inc.</td>
			<td>N/A</td>
			<td>Cognitive testing software</td>
		</tr>
		<tr>
			<td>Computerized Functional Skills Assessment and Training Software</td>
			<td>i-Function</td>
			<td>N/A</td>
			<td>Computerized Software</td>
		</tr>
	</tbody>
</table>

a computerized functional skills assessment and training program targeting technology based everyday functional skills

Today, many functional skills are technology-based, so development of a technology-based training program has broad importance. Here we present a computerized functional skills training program that was paired in half of the participants with a commercially available cognitive training (CCT) program.
Non-impaired older individuals (NC) aged 60+ (n=45) and similarly aged individuals with mild cognitive impairment (MCI; n=50) were randomized to receive 12 weeks of twice-weekly computerized functional skills training (CFST) or 12 weeks of twice-weekly sessions split between CCT and CFST. Skills trained were use of an ATM; internet banking; ticket kiosk; telephone and internet prescription refill; medication management; and internet shopping. As with previous functional capacity assessments, we focus on completion time for each simulation.
51 participants completed the training program, either by mastering all 6 tasks (34) or completing 12 weeks of training. 44 more participants completed 4 or more training sessions so they were also analyzed for improvement up to their last training session. Completion time for all 6 tests significantly improved from the baseline assessment to the final training session in both groups of participants (all p&#60;0.001 with an average improvement in task completion time of 45%). Further, there was no differential improvement in MCI and NC in the 6 tests from baseline to end of training (all t&#60;1.66, all p&#62;0.12). Finally, combined CCT plus CFST did not differ from CSFT alone on any of the percent-change score measures (all t&#60;1.64, all p&#62;0.11).
Both NC and MCI groups evidenced substantial improvements in performance. CCT supplementation led to similar functional gains with half as many training sessions. The NC participants proceeded through the training fairly rapidly even without CCT supplementation; MCI participants required more training but learned equivalently. These findings suggest that even in cases with memory impairments, functional skills can be efficiently learned with training.

The patient flow is shown in Table 3. The first subject was screened on July 14, 2018. Screened participants included 78 females and 76 males, of whom 53 (33%) were Latino and 52 (33%) are of African American descent. Mean levels of educational attainment were similar across ethnic groups and averaged 15 years. However, there were cases who were training who had less than 8 years of education. 131 cases completed the eligibility assessment, with 16 cases excluded because of possible dementia and 4 cases excluded because of motor or vision problems. Of those 121 randomized 46% (n=56) were HC and 54% (n=65) were diagnosed at MCI and 50% in each group was randomized to CFST training alone. 51 cases completed training with 34 of them graduating, which translates into perfect performance twice in sequence on 30 individual subtasks. 44 cases are still training and 15 cases are waiting to train. The drop-out rate after any training was 9%. The mean MOCA score was 28.38 (SD=1.70) for the NC group and 22.68 (SD=3.02) for the MCI group.
Figure 4 presents the training results for completers and Figure 5 presents the results for all participants who trained. These data are presented in terms of time to completion, although several other dependent variables are collected. Paired t-tests found that completion time for all 6 tests significantly improved from the baseline assessment to the final training assessment in completers (all t&#62;8.16, all p&#60;.001). Further, none of the simulations improved differentially in the NC and MCI samples, as indexed by percentage of improvement from baseline to end of training, all t&#60;1.66, all p&#62;.12. Finally, combined CCT plus CFSAT did not differ from CSFAT alone on any of the %-change score measures: All t&#60;1.44, all p&#62;.16. CCT supplementation led to similar CFSAT gains with half as many CFSAT training sessions and this improvement was consistent in the MCI and NC groups in both conditions. All t-tests for the six tests, across the MCI vs. NC samples and the skills training only vs. combined assessments are in Table 4. Both groups evidenced substantial improvements in performance on alternative versions of the assessment tasks. Importantly, NC participants who received skills training alone required an average of only 6 trainings per module to perfect their performance. The participants randomized to CCT &#38; CFSAT trained an average number of 11 days on CCT, achieving an average of 50 levels per participant.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/60330/60330fig1.jpg" /> 
Figure 1: Representative stimuli from the BAC App showing the tower of London and Symbol coding subtests. <a href="https://jove.unicartagenaproxy.elogim.com/files/ftp_upload/60330/60330fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/60330/60330fig2.jpg" /> 
Figure 2: The 6 CFST training tasks. These tests include Ticket Purchase, ATM and Internet Banking, Phone and Internet Prescription Refill and Shopping, and Medication Management <a href="https://jove.unicartagenaproxy.elogim.com/files/ftp_upload/60330/60330fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/60330/60330fig3.jpg" /> 
Figure 3: Brain HQ Double Decision Task Stimulus. <a href="https://jove.unicartagenaproxy.elogim.com/files/ftp_upload/60330/60330fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/60330/60330fig4.jpg" /> 
Figure 4: Training gains from baseline in individuals who completed training. This is depicted in terms of time to completion at the first assessment, the final training session, and the alternate form of the simulations, across the 6 training tasks. <a href="https://jove.unicartagenaproxy.elogim.com/files/ftp_upload/60330/60330fig4large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/60330/60330fig5.jpg" /> 
Figure 5: Percentage improvement per training session for NC and MCI completers and cases still training. This is depicted in terms of the proportion of the total baseline to last session training gains in time to completion per training session completed. <a href="https://jove.unicartagenaproxy.elogim.com/files/ftp_upload/60330/60330fig5large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>ATM Banking</td>
		</tr>
		<tr>
			<td>Internet Banking</td>
		</tr>
		<tr>
			<td>Ticket Purchase with Kiosk</td>
		</tr>
		<tr>
			<td>Medication Management and Daily Organizer</td>
		</tr>
		<tr>
			<td>Interactive Telephone Voice Menu for Prescription Refill</td>
		</tr>
		<tr>
			<td>Internet Prescription Refill and On-Line Shopping</td>
		</tr>
	</tbody>
</table>
Table 1: Computerized functional skills training (CFST) tasks
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Error 1 Repeat Instruction:</td>
			<td>Your Pin is 1234. Please enter your PIN</td>
		</tr>
		<tr>
			<td>Error 2. Guidance:</td>
			<td>Your PIN is 1234. Please use the keypad to enter your PIN</td>
		</tr>
		<tr>
			<td>Error 3 Direction:</td>
			<td>Your PIN is 1234. Enter 1, followed by 2, followed by 3, followed by 4</td>
		</tr>
		<tr>
			<td>Error 4 Demonstration</td>
			<td>The four keys are lit up in sequence and the participants is instructed to touch them when they light up.</td>
		</tr>
	</tbody>
</table>
Table 2: Error feedback.
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td colspan="3">Participant Flow in Clinical Trial (July 2018 to Present)</td>
		</tr>
		<tr>
			<td>Screened and signed consent</td>
			<td>154</td>
			<td></td>
		</tr>
		<tr>
			<td>Ineligible</td>
			<td>20</td>
			<td></td>
		</tr>
		<tr>
			<td>Withdrew before baseline</td>
			<td>4</td>
			<td></td>
		</tr>
		<tr>
			<td>Baseline not completed</td>
			<td>9</td>
			<td></td>
		</tr>
		<tr>
			<td>Completed baseline assessment</td>
			<td>121</td>
			<td></td>
		</tr>
		<tr>
			<td>Completed training</td>
			<td>51</td>
			<td>42%</td>
		</tr>
		<tr>
			<td>Still training</td>
			<td>44</td>
			<td>36%</td>
		</tr>
		<tr>
			<td>Waiting to train</td>
			<td>15</td>
			<td>12%</td>
		</tr>
		<tr>
			<td>Dropped out after training</td>
			<td>11</td>
			<td>9%</td>
		</tr>
	</tbody>
</table>
Table 3: The CONSORT Diagram for the clinical trial.
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td colspan="4">ATM Banking</td>
			<td>t</td>
			<td>p</td>
		</tr>
		<tr>
			<td></td>
			<td colspan="3">HC VS MCI</td>
			<td>0.98</td>
			<td>0.33</td>
		</tr>
		<tr>
			<td></td>
			<td colspan="3">Skills only vs. Combined Training</td>
			<td>0.86</td>
			<td>0.4</td>
		</tr>
		<tr>
			<td colspan="4">Medication Management</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td colspan="3">HC VS MCI</td>
			<td>0.57</td>
			<td>0.57</td>
		</tr>
		<tr>
			<td></td>
			<td colspan="3">Skills only vs Combined Training</td>
			<td>0.91</td>
			<td>0.37</td>
		</tr>
		<tr>
			<td colspan="4">On-Line Banking</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td colspan="3">NC vs. MCI</td>
			<td>1.66</td>
			<td>0.12</td>
		</tr>
		<tr>
			<td></td>
			<td colspan="3">Skills only vs Combined Training</td>
			<td>0.56</td>
			<td>0.96</td>
		</tr>
		<tr>
			<td colspan="4">Prescription Refill</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td colspan="3">NC vs. MCI</td>
			<td>0.21</td>
			<td>0.84</td>
		</tr>
		<tr>
			<td></td>
			<td colspan="3">Skills only vs. Combined Training</td>
			<td>1.44</td>
			<td>0.16</td>
		</tr>
		<tr>
			<td colspan="4">Ticket Purchase Task</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td colspan="3">NC vs. MCI</td>
			<td>1.25</td>
			<td>0.22</td>
		</tr>
		<tr>
			<td></td>
			<td colspan="3">Skills only vs. Combined Training</td>
			<td>0.25</td>
			<td>0.81</td>
		</tr>
		<tr>
			<td colspan="4">Internet Prescription Refill and Shopping</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td colspan="3">NC vs. MCI</td>
			<td>1.55</td>
			<td>0.19</td>
		</tr>
		<tr>
			<td></td>
			<td colspan="3">Skills Only vs. Combined Training</td>
			<td>0.16</td>
			<td>0.87</td>
		</tr>
	</tbody>
</table>
Table 4: Results of t-tests comparing MCI vs. NC training gains and Skills only vs. Combined Treatment.

Watch this Scientific Journal Video about A Computerized Functional Skills Assessment and Training Program Targeting Technology Based Everyday Functional Skills at JoVE.com

A Computerized Functional Skills Assessment and Training Program Targeting Technology Based Everyday Functional Skills

This training protocol uses computerized training to teach technology-related everyday functional skills. These skills include financial skills, travel and transit, as well as medication management.

Today, many functional skills are technology-based, so development of a technology-based training program has broad importance. Here we present a ...

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6.6K Views.  University of Miami Miller School of Medicine. This training protocol uses computerized training to teach technology-related everyday functional skills. These skills include financial skills, travel and transit, as well as medication management.

Video: A Computerized Functional Skills Assessment and Training Program Targeting Technology Based Everyday Functional Skills

Development of an Audio-based Virtual Gaming Environment to Assist with Navigation Skills in the Blind

Audio-based Environment Simulator (AbES) is virtual environment software designed to improve real world navigation skills in the blind. Using only audio based cues and set within the context of a video game metaphor, users gather relevant spatial information regarding a building's layout. This allows the user to develop an accurate spatial cognitive map of a large-scale three-dimensional space that can be manipulated for the purposes of a real indoor navigation task. After game play, participants are then assessed on their ability to navigate within the target physical building represented in the game. Preliminary results suggest that early blind users were able to acquire relevant information regarding the spatial layout of a previously unfamiliar building as indexed by their performance on a series of navigation tasks. These tasks included path finding through the virtual and physical building, as well as a series of drop off tasks. We find that the immersive and highly interactive nature of the AbES software appears to greatly engage the blind user to actively explore the virtual environment. Applications of this approach may extend to larger populations of visually impaired individuals.

Audio-based Environment Simulator (AbES) is virtual environment software designed to improve real world navigation skills in the blind.

Audio-based Environment Simulator (AbES) is virtual environment software designed to improve real world navigation skills in the blind. Using only audio ...

Computerized Dynamic Posturography for Postural Control Assessment in Patients with Intermittent Claudication

Computerized dynamic posturography with the EquiTest is an objective technique for measuring postural strategies under challenging static and dynamic conditions. As part of a diagnostic assessment, the early detection of postural deficits is important so that appropriate and targeted interventions can be prescribed. The Sensory Organization Test (SOT) on the EquiTest determines an individual&#39;s use of the sensory systems (somatosensory, visual, and vestibular) that are responsible for postural control. Somatosensory and visual input are altered by the calibrated sway-referenced support surface and visual surround, which move in the anterior-posterior direction in response to the individual&#39;s postural sway. This creates a conflicting sensory experience. The Motor Control Test (MCT) challenges postural control by creating unexpected postural disturbances in the form of backwards and forwards translations. The translations are graded in magnitude and the time to recover from the perturbation is computed.
Intermittent claudication, the most common symptom of peripheral arterial disease, is characterized by a cramping pain in the lower limbs and caused by muscle ischemia secondary to reduced blood flow to working muscles during physical exertion. Claudicants often display poor balance, making them susceptible to falls and activity avoidance. The Ankle Brachial Pressure Index (ABPI) is a noninvasive method for indicating the presence of peripheral arterial disease and intermittent claudication, a common symptom in the lower extremities. ABPI is measured as the highest systolic pressure from either the dorsalis pedis or posterior tibial artery divided by the highest brachial artery systolic pressure from either arm. This paper will focus on the use of computerized dynamic posturography in the assessment of balance in claudicants.

Individuals with intermittent claudication exhibit poor balance compared to healthy controls. Computerized dynamic posturography is an objective method for measuring an individual's postural responses to balance disturbances. This provides an objective reflection of the person&#x2019;s ability to respond to situations under which sensory stimuli are altered and unexpected perturbations occur.

Computerized dynamic posturography with the EquiTest is an objective technique for measuring postural strategies under challenging static and dynamic ...

Myocardial Infarction and Functional Outcome Assessment in Pigs

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One important prerequisite is a good understanding of all safety and efficacy aspects obtained in a large animal model that validly reflect the human scenario of myocardial infarction (MI). Pigs are widely used in this regard since their cardiac size, hemodynamics, and coronary anatomy are close to that of humans. Here, we present an effective protocol for using the porcine MI model using a closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. This approach is based on 90 min of myocardial ischemia, inducing large left ventricle infarction of the anterior, septal and inferoseptal walls. Furthermore, we present protocols for various measures of outcome that provide a wide range of information on the heart, such as cardiac systolic and diastolic function, hemodynamics, coronary flow velocity, microvascular resistance, and infarct size. This protocol can be easily tailored to meet study specific requirements for the validation of novel cardioregenerative biologics at different stages (i.e. directly after the acute ischemic insult, in the subacute setting or even in the chronic MI once scar formation has been completed). This model therefore provides a useful translational tool to study MI, subsequent adverse remodeling, and the potential of novel cardioregenerative agents.

This protocol describes the porcine myocardial infarction (MI) model using a 90 min closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. Furthermore, the protocol for several outcome parameters, such as cardiac function, hemodynamics, microvascular resistance, and infarct size, are also presented.

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One ...

Longitudinal In Vivo Imaging of the Cerebrovasculature: Relevance to CNS Diseases

Remodeling of the brain vasculature is a common trait of brain pathologies. In vivo imaging techniques are fundamental to detect cerebrovascular plasticity or damage occurring overtime and in relation to neuronal activity or blood flow. In vivo two-photon microscopy allows the study of the structural and functional plasticity of large cellular units in the living brain. In particular, the thinned-skull window preparation allows the visualization of cortical regions of interest (ROI) without inducing significant brain inflammation. Repetitive imaging sessions of cortical ROI are feasible, providing the characterization of disease hallmarks over time during the progression of numerous CNS diseases. This technique accessing the pial structures within 250 &#956;m of the brain relies on the detection of fluorescent probes encoded by genetic cellular markers and/or vital dyes. The latter (e.g., fluorescent dextrans) are used to map the luminal compartment of cerebrovascular structures. Germane to the protocol described herein is the use of an in vivo marker of amyloid deposits, Methoxy-O4, to assess Alzheimer&#39;s disease (AD) progression. We also describe the post-acquisition image processing used to track vascular changes and amyloid depositions. While focusing presently on a model of AD, the described protocol is relevant to other CNS disorders where pathological cerebrovascular changes occur.

Longitudinal In Vivo Imaging of the Cerebrovasculature: Relevance to CNS Diseases

This manuscript describes a procedure to track the remodeling of the cerebrovasculature during amyloid plaque accumulation in vivo using longitudinal two-photon microscopy. A thinned-skull preparation enables the visualization of fluorescent dyes to assess the progression of cerebrovascular damage in a mouse model of Alzheimer&#39;s disease.

Remodeling of the brain vasculature is a common trait of brain pathologies. In vivo imaging techniques are fundamental to detect cerebrovascular ...

Establishment of a Clinic-based Biorepository

The incidence of skin cancer (e.g., squamous cell carcinoma, basal cell carcinoma, and melanoma) has been increasing over the past several years. It is expected that there will be a parallel demand for cutaneous tumor samples for biomedical research studies. Tissue availability, however, is limited due the cost of establishing a biorepository and the lack of protocols available for obtaining clinical samples that do not interfere with clinical operations. A protocol was established to collect and process cutaneous tumor and associated blood and saliva samples that has minimal impact on routine clinical procedures on the date of a Mohs surgery. Tumor samples are collected and processed from patients undergoing their first layer of Mohs surgery for biopsy-proven cutaneous malignancies by the Mohs histotechnologist. Adjacent normal tissue is collected at the time of surgical closure. Additional samples that may be collected are whole-blood and buccal swabs. By utilizing tissue samples that are normally discarded, a biorepository was generated that offers several key advantages by being based in the clinic versus the laboratory setting. These include a wide range of collected samples; access to de-identified patient records, including pathology reports; and, for the typical donor, access to additional samples during follow-up visits.

Cutaneous tumors are often discarded following Mohs micrographic surgery. A protocol is described here that enables clinical support staff to effectively process and store cutaneous tumor (e.g., squamous cell carcinoma, basal cell carcinoma, and melanoma) samples for downstream laboratory applications without interfering with clinical operations.

The incidence of skin cancer (e.g., squamous cell carcinoma, basal cell carcinoma, and melanoma) has been increasing over the past several years. It is ...

Model Surgical Training: Skills Acquisition in Fetoscopic Laser Photocoagulation of Monochorionic Diamniotic Twin Placenta Using Realistic Simulators

Fetoscopic laser coagulation of arterio-venous anastomoses (AVA) in a monochorionic placenta is the standard of care for twin-twin transfusion syndrome (TTTS), but is technically challenging and can lead to significant complications. Acquiring and maintaining the necessary surgical skills require consistent practice, a critical caseload, and time. Training on realistic surgical simulators can potentially shorten this steep learning curve and enables several proceduralists to acquire procedure-specific skills simultaneously. Here we describe realistic simulators designed to allow the user familiarity with the equipment and specific steps required in the surgical treatment of TTTS, including fetoscopic handling, approaches to anterior and posterior placenta, recognition of anastomoses, and efficient coagulation of vessels. We describe the skills that are especially important in conducting placental laser coagulation that the surgeon can practice on the model and apply in a clinical case. These models can be adapted easily depending on the availability of materials and require standard fetoscopy equipment. Such training systems are complementary to traditional surgical apprenticeships and can be useful aids for fetal medicine units that provide this clinical service.

Practicing the specific skills required for fetoscopic laser coagulation of monochorionic placental anastomoses on realistic models can aid less experienced surgeons in overcoming the steep learning curve associated with this procedure that is now regarded as the standard of care for twin-twin transfusion syndrome.

Fetoscopic laser coagulation of arterio-venous anastomoses (AVA) in a monochorionic placenta is the standard of care for twin-twin transfusion syndrome ...

Muscle Imbalances: Testing and Training Functional Eccentric Hamstring Strength in Athletic Populations

Many hamstring injuries that occur during physical activity occur while the muscles are lengthening, during eccentric hamstring muscle actions. Opposite of these eccentric hamstring actions are concentric quadriceps actions, where the larger and likely stronger quadriceps straighten the knee. Therefore, to stabilize the lower limbs during movement, the hamstrings must eccentrically combat against the strong knee-straightening torque of the quadriceps. As such, eccentric hamstring strength expressed relative to concentric quadricep strength is commonly referred to as the &#34;functional ratio&#34; as most movements in sports require simultaneous concentric knee extension and eccentric knee flexion. To increase the strength, resiliency, and functional performance of the hamstrings, it is necessary to test and train the hamstrings at different eccentric speeds. The main purpose of this work is to provide instructions for measuring and interpreting eccentric hamstring strength. Techniques for measuring the functional ratio using isokinetic dynamometry are provided and sample data will be compared. Additionally, we briefly describe how to address hamstring strength deficiencies or unilateral strength differences using exercises that specifically focus on increasing eccentric hamstring strength.

The hamstrings are a group of muscles that are sometimes problematic for athletes, resulting in soft tissue injury in the lower limbs. To prevent such injuries, functional training of the hamstrings requires intensive eccentric contractions. Additionally, hamstring function should be tested in relation to quadricep function at different contraction speeds.

Many hamstring injuries that occur during physical activity occur while the muscles are lengthening, during eccentric hamstring muscle actions. Opposite ...

Murine Salivary Functional Assessment via Pilocarpine Stimulation Following Fractionated Radiation

Hyposalivation is commonly observed in the autoimmune reaction of Sj&#246;gren's syndrome or following radiation injury to the major salivary glands. In these cases, questions remain regarding disease pathogenesis and effective interventions. An optimized technique that allows functional assessment of the salivary glands is invaluable for investigating exocrine gland biology, dysfunction, and therapeutics. Here, we present a step by step approach to performing pilocarpine stimulated saliva secretion, including tracheostomy and the dissection of the three major murine salivary glands. We also detail the appropriate murine head and neck anatomy accessed during these techniques. This approach is scalable, allowing for multiple mice to be processed simultaneously, thus improving the efficiency of the work flow. We aim to improve the reproducibility of these methods, each of which has further applications within the field. In addition to saliva collection, we discuss metrics for quantifying and normalizing functional capacity of these tissues. Representative data are included from submandibular glands with depressed salivary gland function 2 weeks following fractionated radiation (4 doses of 6.85 Gy).

We present a detailed approach to performing saliva collection, including murine tracheostomy and the isolation of three major salivary glands.

Hyposalivation is commonly observed in the autoimmune reaction of Sj&#246;gren's syndrome or following radiation injury to the major salivary glands. In ...

Functional and Physiological Methods of Evaluating Median Nerve Regeneration in the Rat

The main goal of this investigation is to show how to create and repair different types of median nerve (MN) lesions in the rat. Moreover, different methods of simulating postoperative physiotherapy are presented. Multiple standardized strategies are used to assess motor and sensory recovery using an MN model of peripheral nerve lesion and repair, thus permitting easy comparison of the results. Several options are included for providing a postoperative physiotherapy-like environment to rats that have undergone MN injuries. Finally, the paper provides a method to evaluate the recovery of the MN using several noninvasive tests (i.e., grasping test, pin prick test, ladder rung walking test, rope climbing test, and walking track analysis), and physiological measurements (infrared thermography, electroneuromyography, flexion strength evaluation, and flexor carpi radialis muscle weight determination). Hence, this model seems particularly appropriate to replicate a clinical scenario, facilitating extrapolation of results to the human species.
Although the sciatic nerve is the most studied nerve in peripheral nerve research, analysis of the rat MN presents various advantages. For example, there is a reduced incidence of joint contractures and automutilation of the affected limb in MN lesion studies. Furthermore, the MN is not covered by muscle masses, making its dissection easier than that of the sciatic nerve. In addition, MN recovery is observed sooner, because the MN is shorter than the sciatic nerve. Also, the MN has a parallel path to the ulnar nerve in the arm. Hence, the ulnar nerve can be easily used as the nerve graft for repairing MN injuries. Finally, the MN in rats is located in the forelimb, akin to the human upper limb; in humans, the upper limb is the site of most peripheral nerve lesions.

Presented is a protocol to produce different types of median nerve (MN) lesions and repair in the rat. Additionally, the protocol shows how to evaluate the functional recovery of the nerve using several noninvasive behavioral tests and physiological measurements.

The main goal of this investigation is to show how to create and repair different types of median nerve (MN) lesions in the rat. Moreover, different ...

A Training Program Using an Agility Ladder for Community-Dwelling Older Adults

Aging impairs physical and cognitive functions and limits daily activities. Agility training can improve or maintain physical functioning in older people. The purpose of this study is to report the physical fitness benefits of a training program for independent community-dwelling older adults using an agility ladder. Each training session lasted approximately 30 minutes, and the benefits were achieved with two sessions per week for 14 weeks. Training was timed and involved four different drills and varying levels of difficulty through time. The exercises were performed at the School of Physical Education of the University of Campinas, S&#227;o Paulo state, Brazil. The study participants (n = 16; mean age of 66.9 &#177; 5.0 years) were instructed to perform the exercises as quickly as possible without making mistakes and were assisted by a physical trainer when they made mistakes. Assessments were performed both before and after training using five functional tests (i.e., Illinois agility, five times sit-to-stand, timed up-and-go, walking usual speed, and one-leg stand). Although the study sample was not compared with a control group, the results indicate that training protocols using an agility ladder are easy and practical and improve physical function performance in older adults.

The aim of this study is to present an agility training program for older people. The feasibility of this program is described, and the training protocol demonstrated by video imaging.

Aging impairs physical and cognitive functions and limits daily activities. Agility training can improve or maintain physical functioning in older people. ...

A Computerized Functional Skills Assessment and Training Program Targeting Technology Based Everyday Functional Skills

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Development of an Audio-based Virtual Gaming Environment to Assist with Navigation Skills in the Blind

Computerized Dynamic Posturography for Postural Control Assessment in Patients with Intermittent Claudication

Myocardial Infarction and Functional Outcome Assessment in Pigs

Longitudinal In Vivo Imaging of the Cerebrovasculature: Relevance to CNS Diseases

Establishment of a Clinic-based Biorepository

Model Surgical Training: Skills Acquisition in Fetoscopic Laser Photocoagulation of Monochorionic Diamniotic Twin Placenta Using Realistic Simulators

Muscle Imbalances: Testing and Training Functional Eccentric Hamstring Strength in Athletic Populations

Murine Salivary Functional Assessment via Pilocarpine Stimulation Following Fractionated Radiation

Functional and Physiological Methods of Evaluating Median Nerve Regeneration in the Rat

A Training Program Using an Agility Ladder for Community-Dwelling Older Adults