Name: standing neurophysiological assessment of lower extremity muscles post-stroke
Uploaded: 2021-07-26T14:00:00
Description: Watch this Scientific Journal Video about Standing Neurophysiological Assessment of Lower Extremity Muscles Post-Stroke at JoVE.com

The authors would like to acknowledge Mr. Brian Cence and Mrs. Alyssa Chestnut for their contributions to participant recruitment and data collection.
Funding for this project was provided in part by a Technical Development Award from the NIH National Center for Neuromodulation for Rehabilitation (NM4R) (HD086844) and by Veteran&#39;s Affairs Rehabilitation Research and Development Career Development Award 1 (RX003126) and Merit award (RX002665).
The contents of this report do not represent the views of the U.S. Department of Veterans Affairs, U.S. National Institutes of Health, or the United States Government.

All procedures were approved by the Institutional Review Board at the Medical University of South Carolina and conformed to the Declaration of Helsinki.
1. Participant recruitment
<ol>
	<li>Recruit individuals post-stroke from the local database. For this experiment, 16 individuals were recruited from a local electronic recruitment database. In some instances, participants were recruited specifically because they had failed to respond to TMS at rest in previous studies performed by our resea...

<ol>
	<li>Kesar, T. M., Stinear, J. W., Wolf, S. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+use+of+transcranial+magnetic+stimulation+to+evaluate+cortical+excitability+of+lower+limb+musculature:+Challenges+and+opportunities.">The use of transcranial magnetic stimulation to evaluate cortical excitability of lower limb musculature: Challenges and opportunities.</a> Restorative Neurology and Neuroscience. 36 (3), 333-348 (2018).</li><li>Sivaramakrishnan, A., Madhavan, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Absence+of+a+transcranial+magnetic+stimulation-induced+lower+limb+corticomotor+response+does+not+affect+walking+speed+in+chronic+stroke+survivors.">Absence of a transcranial magnetic stimulation-induced lower limb corticomotor response does not affect walking speed in chronic stroke survivors.</a> Stroke. 49 (8), 2004-2007 (2018).</li><li>Kindred, J. H., 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=Individualized+responses+to+ipsilesional+high-frequency+and+contralesional+low-frequency+rTMS+in+chronic+stroke:+A+pilot+study+to+support+the+individualization+of+neuromodulation+for+rehabilitation.">Individualized responses to ipsilesional high-frequency and contralesional low-frequency rTMS in chronic stroke: A pilot study to support the individualization of neuromodulation for rehabilitation.</a> Frontiers in Human Neuroscience. 14, 578127 (2020).</li><li>Lu, M., Ueno, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+the+induced+fields+using+different+coil+configurations+during+deep+transcranial+magnetic+stimulation.">Comparison of the induced fields using different coil configurations during deep transcranial magnetic stimulation.</a> PLoS One. 12 (6), 0178422 (2017).</li><li>Hess, C. W., Mills, K. R., Murray, N. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Responses+in+small+hand+muscles+from+magnetic+stimulation+of+the+human+brain.">Responses in small hand muscles from magnetic stimulation of the human brain.</a> The Journal of Physiology. 388, 397-419 (1987).</li><li>Petersen, N., Christensen, L. O., Nielsen, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effect+of+transcranial+magnetic+stimulation+on+the+soleus+H+reflex+during+human+walking.">The effect of transcranial magnetic stimulation on the soleus H reflex during human walking.</a> The Journal of Physiology. 513, 599-610 (1998).</li><li>Capaday, C., Lavoie, B. A., Barbeau, H., Schneider, C., Bonnard, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Studies+on+the+corticospinal+control+of+human+walking.+I.+Responses+to+focal+transcranial+magnetic+stimulation+of+the+motor+cortex.">Studies on the corticospinal control of human walking. I. Responses to focal transcranial magnetic stimulation of the motor cortex.</a> Journal of Neurophysiology. 81 (1), 129-139 (1999).</li><li>Schubert, M., Curt, A., Colombo, G., Berger, W., Dietz, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Voluntary+control+of+human+gait:+conditioning+of+magnetically+evoked+motor+responses+in+a+precision+stepping+task.">Voluntary control of human gait: conditioning of magnetically evoked motor responses in a precision stepping task.</a> Experimental Brain Research. 126 (4), 583-588 (1999).</li><li>Ackermann, H., Scholz, E., Koehler, W., Dichgans, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+posture+and+voluntary+background+contraction+upon+compound+muscle+action+potentials+from+anterior+tibial+and+soleus+muscle+following+transcranial+magnetic+stimulation.">Influence of posture and voluntary background contraction upon compound muscle action potentials from anterior tibial and soleus muscle following transcranial magnetic stimulation.</a> Electroencephalography and Clinical Neurophysiology. 81 (1), 71-80 (1991).</li><li>Lavoie, B. A., Cody, F. W., Capaday, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cortical+control+of+human+soleus+muscle+during+volitional+and+postural+activities+studied+using+focal+magnetic+stimulation.">Cortical control of human soleus muscle during volitional and postural activities studied using focal magnetic stimulation.</a> Experimental Brain Research. 103 (1), 97-107 (1995).</li><li>Soto, O., Valls-Sol&#233;, J., Shanahan, P., Rothwell, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reduction+of+intracortical+inhibition+in+soleus+muscle+during+postural+activity.">Reduction of intracortical inhibition in soleus muscle during postural activity.</a> Journal of Neurophysiology. 96 (4), 1711-1717 (2006).</li><li>Kesar, T. M., Eicholtz, S., Lin, B. J., Wolf, S. L., Borich, M. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+posture+and+coactivation+on+corticomotor+excitability+of+ankle+muscles.">Effects of posture and coactivation on corticomotor excitability of ankle muscles.</a> Restorative Neurology and Neuroscience. 36 (1), 131-146 (2018).</li><li>Nandi, T., 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=In+standing,+corticospinal+excitability+is+proportional+to+COP+velocity+whereas+M1+excitability+is+participant-specific.">In standing, corticospinal excitability is proportional to COP velocity whereas M1 excitability is participant-specific.</a> Frontiers in Human Neuroscience. 12, 303 (2018).</li><li>Tokuno, C. D., Keller, M., Carpenter, M. G., M&#225;rquez, G., Taube, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alterations+in+the+cortical+control+of+standing+posture+during+varying+levels+of+postural+threat+and+task+difficulty.">Alterations in the cortical control of standing posture during varying levels of postural threat and task difficulty.</a> Journal of Neurophysiology. 120 (3), 1010-1016 (2018).</li><li>Mouthon, A., Taube, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intracortical+inhibition+increases+during+postural+task+execution+in+response+to+balance+training.">Intracortical inhibition increases during postural task execution in response to balance training.</a> Neuroscience. 401, 35-42 (2019).</li><li>Charalambous, C. C., Liang, J. N., Kautz, S. A., George, M. S., Bowden, M. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bilateral+assessment+of+the+corticospinal+pathways+of+the+ankle+muscles+using+navigated+transcranial+magnetic+stimulation.">Bilateral assessment of the corticospinal pathways of the ankle muscles using navigated transcranial magnetic stimulation.</a> Journal of Visualized Experiments: JoVE. (144), (2019).</li><li>Hermens, H. J., Freriks, B., Disselhorst-Klug, C., Rau, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+recommendations+for+SEMG+sensors+and+sensor+placement+procedures.">Development of recommendations for SEMG sensors and sensor placement procedures.</a> Journal of Electromyography and Kinesiology. 10 (5), 361-374 (2000).</li><li>Tankisi, H., 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=Standards+of+instrumentation+of+EMG.">Standards of instrumentation of EMG.</a> Clinical Neurophysiology. 131 (1), 243-258 (2020).</li><li>Mishory, 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=The+maximum-likelihood+strategy+for+determining+transcranial+magnetic+stimulation+motor+threshold,+using+parameter+estimation+by+sequential+testing+is+faster+than+conventional+methods+with+similar+precision.">The maximum-likelihood strategy for determining transcranial magnetic stimulation motor threshold, using parameter estimation by sequential testing is faster than conventional methods with similar precision.</a> The Journal of ECT. 20 (3), 160-165 (2004).</li><li>Borckardt, J. J., Nahas, Z., Koola, J., George, M. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Estimating+resting+motor+thresholds+in+transcranial+magnetic+stimulation+research+and+practice:+a+computer+simulation+evaluation+of+best+methods.">Estimating resting motor thresholds in transcranial magnetic stimulation research and practice: a computer simulation evaluation of best methods.</a> The Journal of ECT. 22 (3), 169-175 (2006).</li><li>McNemar, Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Note+on+the+sampling+error+of+the+difference+between+correlated+proportions+or+percentages.">Note on the sampling error of the difference between correlated proportions or percentages.</a> Psychometrika. 12 (2), 153-157 (1947).</li><li>Rossi, 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=Safety+and+recommendations+for+TMS+use+in+healthy+subjects+and+patient+populations,+with+updates+on+training,+ethical+and+regulatory+issues:+Expert+Guidelines.">Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines.</a> Clinical Neurophysiology. 132 (1), 269-306 (2021).</li><li>McDonnell, M. N., Stinear, C. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=TMS+measures+of+motor+cortex+function+after+stroke:+A+meta-analysis.">TMS measures of motor cortex function after stroke: A meta-analysis.</a> Brain Stimulation. 10 (4), 721-734 (2017).</li><li>Reis, 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=Contribution+of+transcranial+magnetic+stimulation+to+the+understanding+of+cortical+mechanisms+involved+in+motor+control.">Contribution of transcranial magnetic stimulation to the understanding of cortical mechanisms involved in motor control.</a> The Journal of Physiology. 586 (2), 325-351 (2008).</li><li>Chen, G., Patten, C., Kothari, D. H., Zajac, F. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gait+differences+between+individuals+with+post-stroke+hemiparesis+and+non-disabled+controls+at+matched+speeds.">Gait differences between individuals with post-stroke hemiparesis and non-disabled controls at matched speeds.</a> Gait &amp; Posture. 22 (1), 51-56 (2005).</li><li>Knarr, B. A., Reisman, D. S., Binder-Macleod, S. A., Higginson, J. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Understanding+compensatory+strategies+for+muscle+weakness+during+gait+by+simulating+activation+deficits+seen+post-stroke.">Understanding compensatory strategies for muscle weakness during gait by simulating activation deficits seen post-stroke.</a> Gait &amp; Posture. 38 (2), 270-275 (2013).</li><li>Ammann, C., 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+framework+to+assess+the+impact+of+number+of+trials+on+the+amplitude+of+motor+evoked+potentials.">A framework to assess the impact of number of trials on the amplitude of motor evoked potentials.</a> Scientific Reports. 10 (1), 21422 (2020).</li></ol>

The experimental protocol was well tolerated by most participants. One individual was unable to complete the standing TMS evaluation due to preexisting decubitus ulcers secondary to diabetic complications and orthopedic issues involving preexisting knee pain. The amount of loading/unloading of body weight from the legs was minimal. However, there was, on average, a slightly greater downward force measured during the application of the TMS pulses. This is likely due to the weight of the coil and the downward pressure appl...

Transcranial magnetic stimulation (TMS) is an instrument used to measure the behavior of neural circuits. The majority of TMS investigations focusing on the study of motor control/performance have been conducted in the upper extremities. The imbalance between the upper and lower extremity studies is in part due to the additional challenges in measuring the lower extremity corticomotor response (CMR). Some of these methodological obstacles include the smaller cortical representations of the lower extremity muscles within the motor cortex and the deeper location of the representations relative to the scalp1. In populations with neurological injury, additional hurdles are also present. For example, approximately half of the individuals post-stroke show no response to TMS at rest in lower extremity muscles2,3. The lack of post-stroke response to TMS is even seen when patients maintain some volitional control of the muscles, indicating at least a partially intact corticospinal tract.
The lack of measurable TMS responses with maintained motor function contributes to our decreased understanding of post-stroke postural and walking-specific motor control and the neurophysiological effects of neurorehabilitation. However, some of the challenges of lower extremity post-stroke neurophysiological assessments have been overcome. For example, a double-cone coil can be used to reliably activate the lower extremity motoneurons located deep in the interhemispheric fissure1. The double-cone coil produces a larger and stronger magnetic field that penetrates deeper into the brain than the more commonly used figure-of-eight coil4. Another methodological change that can be implemented to increase the responsiveness to TMS is measuring the CMR during a slight voluntary contraction5. Generally, this contraction is performed at a predetermined level of either maximal voluntary joint torque or maximal electromyographic (EMG) muscle activity. Peripheral nerve stimulation can also be used to elicit a maximal muscle response and the recorded EMG of this response can be used to set the targeted voluntary activation of the muscle.
Performing TMS assessment post-stroke during active muscle contraction is fairly common in the upper extremities where isometric tasks can mimic functional activities, for example, grasping/holding objects. In contrast, walking is accomplished through the bilateral activation of multiple muscle groups via cortical, subcortical, and spinal cord structures and requires postural muscle activation to resist the effects of gravity. This activation state is likely not reflected when measuring isolated muscles producing an isometric contraction. Several previous studies directed at understanding postural and walking-specific motor control have delivered TMS pulses while participants were walking6,7,8 and standing9,10,11,12,13,14,15. The measurement of the CMR in the upright position allows for the activation of postural muscles and subcortical components of the postural and gait motor-control networks. To date, there have not been any reports of performing standing TMS assessments in individuals post-stroke.
This study proposes a standardized methodology, built upon the existing body of literature of standing TMS methods6,7,8,9,10,11,12,13,14,15, for standing TMS assessment of the CMR post-stroke. This methodology can be utilized by research groups studying, but not limited to, postural deficits and walking-specific motor control post-stroke and establish greater consistency of TMS procedures. The purpose of this methodological investigation was to determine whether standing TMS assessments are feasible in individuals post-stroke with moderate gait impairments. We hypothesized that performing assessments in the standing position would 1) increase the likelihood of eliciting a measurable response (motor evoked potential, MEP) and 2) that the stimulator power/intensity used to perform standing TMS assessments would be lower than that of the usually performed sitting/resting assessments. We believe the successful completion and widespread use of this protocol may lead to a greater understanding of the neurophysiological aspects of post-stroke postural and walking-specific motor control and the effects of neurorehabilitation.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Data Acquisition Software</td>
			<td>MathWorks</td>
			<td>MatLab</td>
			<td>The custom data collection program was written in Matlab. However, other software/hardware providers can be used (e.g. National Instruments, AD Instruments, CED Spike2 or Signal)</td>
		</tr>
		<tr>
			<td>Double-cone coil</td>
			<td>Magstim</td>
			<td>D110</td>
			<td>Double-cone coil for TMS pulse delivery</td>
		</tr>
		<tr>
			<td>Dual force plate</td>
			<td>Advanced Mechanical Technology Inc (AMTI)</td>
			<td>Dual-top Accusway</td>
			<td>Force plate used to measure force/weight distrobution under each leg independently.</td>
		</tr>
		<tr>
			<td>Dual-pulse TMS</td>
			<td>Magstim</td>
			<td>Bistim 200</td>
			<td>Connects two Magstim 200 units together for dual-pulse applications</td>
		</tr>
		<tr>
			<td>EMG pre-amplifiers</td>
			<td>Motion Labs Inc</td>
			<td>MA-422</td>
			<td>Preamplifiers for disposable surface EMG electrodes</td>
		</tr>
		<tr>
			<td>EMG system</td>
			<td>Motion Labs Inc</td>
			<td>MA400</td>
			<td>EMG system for data collection</td>
		</tr>
		<tr>
			<td>Neuronavigation System</td>
			<td>Rogue Research</td>
			<td>Brainsight</td>
			<td>Software and hardware used to ensure consistent placement/delivery of magnetic stimulations. Marking the stimulation location on a participant&#39;s head or on a place showercap can also be used in the absence of neuronavigational software.</td>
		</tr>
		<tr>
			<td>Recruitment Database</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Electronic database including names of possible individuals who are eligble for your studies.</td>
		</tr>
		<tr>
			<td>TMS unit (x2)</td>
			<td>Magstim</td>
			<td>Magstim 200</td>
			<td>Delivers TMS pulses</td>
		</tr>
	</tbody>
</table>

standing neurophysiological assessment of lower extremity muscles post-stroke

Transcranial magnetic stimulation (TMS) is a common tool used to measure the behavior of motor circuits in healthy and neurologically impaired populations. TMS is used extensively to study motor control and the response to neurorehabilitation of the upper extremities. However, TMS has been less utilized in the study of lower extremity postural and walking-specific motor control. The limited use and the additional methodological challenges of lower extremity TMS assessments have contributed to the lack of consistency in lower extremity TMS procedures within the literature. Inspired by the decreased ability to record lower extremity TMS motor evoked potentials (MEP), this methodological report details steps to enable post-stroke TMS assessments in a standing posture. The standing posture allows for the activation of the neuromuscular system, reflecting a state more akin to the system's state during postural and walking tasks. Using dual-top force plates, we instructed participants to equally distribute their weight between their paretic and non-paretic legs. Visual feedback of the participants' weight distribution was provided. Using image guidance software, we delivered single TMS pulses via a double-cone coil to the participants' lesioned and non-lesioned hemispheres and measured the corticomotor response of the paretic and non-paretic tibialis anterior and soleus muscles. Performing assessments in the standing position increased the TMS response rate and allowed for the use of the lower stimulation intensities compared to the standard sitting/resting position. Utilization of this TMS protocol can provide a common approach to assess the lower extremity corticomotor response post-stroke when the neurorehabilitation of postural and gait impairments are of interest.

One participant was removed from the analysis due to the inability to tolerate the standing TMS procedure due to preexisting knee pain and a diabetic wound received before their arrival to the research laboratory, leaving a final sample size of 15. The diabetic wound was directly over the TA and precluded any sEMG measures of this muscle. There were no major adverse events reported to the investigators during either the sitting or standing TMS procedures. Several minor adverse events were reported, such as neck muscle pa...

Watch this Scientific Journal Video about Standing Neurophysiological Assessment of Lower Extremity Muscles Post-Stroke at JoVE.com

Standing Neurophysiological Assessment of Lower Extremity Muscles Post-Stroke

This protocol describes the process for performing a neurophysiological assessment of the lower extremity muscles, tibialis anterior and soleus, in a standing position using TMS in people post-stroke. This position provides a greater probability of eliciting a post-stroke TMS response and allows for the use of reduced stimulator power during neurophysiological assessments.

Transcranial magnetic stimulation (TMS) is a common tool used to measure the behavior of motor circuits in healthy and neurologically impaired ...

This protocol allows for the neurophysiologic assessment of the lower extremity corticospinal tract post-stroke when gait and balance are of primary interest. The main advantage of this technique is that it allows an increased probability of eliciting a motor evoked potential in a population where many individuals do not show a resting response. This method can be used in any neurological population where investigating the neurophysiology of the corticospinal tract is of interest, especially as it relates to gait and balance.Begin by visually inspecting the signal quality once the electrodes are attached. Then wrap the shanks with an elastic bandage to minimize any movement of the electrodes and the resultant artifact during testing. Open the data collection software and start a new trial to calibrate the dual top force plate.Click start and begin an FP0 trial. Collect three to five seconds of data with no load on the force plate and then click stop. Once the force plate is calibrated, the participant has been registered to the image guidance system.And the sEMG electrodes have been placed and tested for the signal quality, then fit them with a safety harness. Instruct the participant to step onto the force plate and standardize their foot placement with masking tape pre-applied to the force plate to signify the foremost position of the foot and medial edges of the feet equal distances from the midline. Attach the participant's safety harness to the ceiling support.Place a rollator or similar device around the force plate to provide participants with something to steady themselves with during testing if needed. Measure and collect the participant's weight as they stand on the force plate by clicking start and selecting an FP static trial. Record two to five seconds worth of data and click stop to end the trial.And standing on the force plates ensure that the data collection software displays two bar graphs, representing the weight or force under each of the participants feet. When the participant shifts their weight to one side, the bar graphs will change in height. If a participant unloads the weight on their legs to their arms, ensure the bar graph displayed changes color.After a participant becomes comfortable standing with equal weight distributed between their legs, measuring the CMR can commence. Begin the neurophysiological assessments by identifying a stimulator intensity that produces consistent motor evoked potentials or MEPs. That is EMG signal amplitude greater than 50 microvolts in a visible cortical silent period in the active muscles in the target tibialis anterior and soleus muscle.Test the periodic limb first by applying transcranial magnetic stimulation or TMS pulses to the lesion hemisphere. Begin by setting the TMS stimulator power level to 50%maximum stimulator output or a percent MSO by turning the output control knob. Apply a single pulse at 50%MSO to the middle grid point located just lateral to the longitudinal fissure by pressing the trigger button on the stimulator.Applied two to three pulses with an inter stimulus interval of 5 to 10 seconds. If responses are not seen in the tibialis anterior and soleus, increase the stimulator power by 10%MSO by turning the output control knob and deliver two to three TMS pulses. If no responses are seen after increasing the stimulator to 60%MSO, again, increase the power by 10%MSO.If no MEPs are elicited at 70%MSO, randomly select several grid points and apply TMS pulses to determine whether there is a response at the current power setting. If no responses are recorded at any grid point at the current 70%MSO, return to the initial target grid point. And continue to increase the stimulator power by increments of 10%MSO and apply two to three stimulations as previously described.Once the stimulator power that produces a consistent response has been identified, begin identifying the hotspot. That is the scalp location that produces the largest response to the applied TMS pulses. Start a new hotspot trial by clicking start and selecting hotspot.Apply a single pulse stimulation to each of the 15 grid points at the super threshold power level identified in the previous steps. Using the image guidance system, move the coil to the first grid point. Once the coil is in the proper position, apply the TMS pulse by pressing the trigger button on the stimulator unit.Next, move the coil to the next grid location and apply another single TMS pulse. Continue until a single stimulation has been applied to each grid point and click on stop to end the trial. Examine the amplitudes of the sEMG signals recorded at each grid point.Visually identify the grid points with the largest MEP amplitude recorded in the sEMG signals for each targeted muscle. The grid locations with the largest MEP amplitudes are the hotspots and will be used to measure the cortico motor response. Then to determine the motor threshold of the targeted muscle, use the simple adaptive parameter estimation by sequential testing or PEST.Open the PEST program and set the initial stimulator intensity to the super threshold value used to identify the hotspot by typing the value into the box. Begin a new PEST trial clicking the start tab in the data collection software and select PEST. Using the initial percent MSO intensity displayed in the PEST program, apply a single TMS pulse to the identified target muscles hotspot.Indicate in the PEST program that a response was observed in the muscles sEMG signal by typing Y or N.The PEST program will automatically calculate the next stimulation intensity. Adjust the stimulators power level to match the PEST program and apply another single TMS pulse. Continue this process until the PEST program determines the motor threshold, indicated by a change in color of the stimulation intensity.And end the data collection trial by clicking on the stop tab. After the target muscles hotspot and motor threshold have been identified, begin the CMR evaluation. Set the intensity of the stimulator to 120%of the determined motor threshold.Initiate a new trial and the data collection software by clicking on the start tab and select an MEP trial. Allow for 5 to 10 seconds between each stimulation. Record the evoked sEMG responses for offline analysis.Allow the participant to rest ad libitum and for sufficient time between testing procedures to reduce the likelihood of the participant developing fatigue, affecting the results. Click on the stop tab after recording the MEPs to end the trial. Motor thresholds were measured in four separate muscles, mainly the paretic and non-paretic tibialis anterior and soleus muscles.When individuals were presented with measurable motor thresholds in the sitting and standing positions, the measured thresholds in the standing position were found to be lower. When applying TMS pulses ensure the participant is distributing their weight on their legs equally. And that their weight is not being unloaded from their legs onto the arms.In addition to single pulse TMS measures, paired pulse TMS can be performed in the standing position to assess intracortical inhibition and facilitation of the corticospinal tract.

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Research

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Anatomy and Physiology

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Unit 1

The Muscular System

SCIENTISTS IN ACTION

Assessing the Multiple Dimensions of Engagement to Characterize Learning: A Neurophysiological Perspective

In a recent theoretical synthesis on the concept of engagement, Fredricks, Blumenfeld and Paris1 defined engagement by its multiple dimensions: behavioral, emotional and cognitive. They observed that individual types of engagement had not been studied in conjunction, and little information was available about interactions or synergy between the dimensions; consequently, more studies would contribute to creating finely tuned teaching interventions. Benefiting from the recent technological advances in neurosciences, this paper presents a recently developed methodology to gather and synchronize data on multidimensional engagement during learning tasks. The technique involves the collection of (a) electroencephalography, (b) electrodermal, (c) eye-tracking, and (d) facial emotion recognition data on four different computers. This led to synchronization issues for data collected from multiple sources. Post synchronization in specialized integration software gives researchers a better understanding of the dynamics between the multiple dimensions of engagement. For curriculum developers, these data could provide informed guidelines for achieving better instruction/learning efficiency. This technique also opens up possibilities in the field of brain-computer interactions, where adaptive learning or assessment environments could be developed.

This paper aims to describe the techniques involved in the collection and synchronization of the multiple dimensions (behavioral, affective and cognitive) of learners&#8217; engagement during a task.

In a recent theoretical synthesis on the concept of engagement, Fredricks, Blumenfeld and Paris1 defined engagement by its multiple dimensions: ...

Measurement of Neurophysiological Signals of Ignoring and Attending Processes in Attention Control

Attention control is the ability to selectively attend to some sensory signals while ignoring others. This ability is thought to involve two processes: enhancement of sensory signals that are to be attended and the attenuation of sensory signals that are to be ignored. The overall strength of attentional modulation is often measured by comparing the amplitude of a sensory neural response to an external input when attended versus when ignored. This method is robust for detecting attentional modulation, but precludes the ability to assess the separate dynamics of attending and ignoring processes. Here, we describe methodology to measure independently the neurophysiological signals of attending and ignoring using the intermodal attention task (IMAT). This task, when combined with electroencephalography, isolates neurophysiological sensory responses in auditory and visual modalities, when either attending or ignoring, with respect to a passive control. As a result, independent dynamics of attending and of a ignoring can be assessed in either modality. Our results using this task indicate that the timing and cortical sources of attending and ignoring effects differ, as do their contributions to the attention modulation effect, pointing to unique neural trajectories and demonstrating sample utility of measuring them separately.

Attention control comprises enhancement of target signals and attenuation of distractor signals. We describe an approach to measure separately but concurrently, the neurophysiology of attending and ignoring in sustained intermodal attention, utilizing a passive control condition during which neither process is continuously engaged.

Attention control is the ability to selectively attend to some sensory signals while ignoring others. This ability is thought to involve two processes: ...

Combined Invasive Subcortical and Non-invasive Surface Neurophysiological Recordings for the Assessment of Cognitive and Emotional Functions in Humans

In spite of the success in applying non-invasive electroencephalography (EEG), magneto-encephalography (MEG) and functional magnetic resonance imaging (fMRI) for extracting crucial information about the mechanism of the human brain, such methods remain insufficient to provide information about physiological processes reflecting cognitive and emotional functions at the subcortical level. In this respect, modern invasive clinical approaches in humans, such as deep brain stimulation (DBS), offer a tremendous possibility to record subcortical brain activity, namely local field potentials (LFPs) representing coherent activity of neural assemblies from localized basal ganglia or thalamic regions. Notwithstanding the fact that invasive approaches in humans are applied only after medical indication and thus recorded data correspond to altered brain circuits, valuable insight can be gained regarding the presence of intact brain functions in relation to brain oscillatory activity and the pathophysiology of disorders in response to experimental cognitive paradigms. In this direction, a growing number of DBS studies in patients with Parkinson&#39;s disease (PD) target not only motor functions but also higher level processes such as emotions, decision-making, attention, memory and sensory perception. Recent clinical trials also emphasize the role of DBS as an alternative treatment in neuropsychiatric disorders ranging from obsessive compulsive disorder (OCD) to chronic disorders of consciousness (DOC). Consequently, we focus on the use of combined invasive (LFP) and non-invasive (EEG) human brain recordings in assessing the role of cortical-subcortical structures in cognitive and emotional processing trough experimental paradigms (e.g. speech stimuli with emotional connotation or paradigms of cognitive control such as the Flanker task), for patients undergoing DBS treatment.

The present protocol aims at assessing cognitive-emotional functions in the basal ganglia by simultaneous neurophysiological recording of local field potentials and non-invasive brain cortical activity (EEG). The procedure is exemplified by the use of paradigms involving speech stimuli with emotional connotation or the Flanker task involving cognitive control.

In spite of the success in applying non-invasive electroencephalography (EEG), magneto-encephalography (MEG) and functional magnetic resonance imaging ...

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

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

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

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

Paradigms of Lower Extremity Electrical Stimulation Training After Spinal Cord Injury

Skeletal muscle atrophy, increased adiposity and reduced physical activity are key changes observed after spinal cord injury (SCI) and are associated with numerous cardiometabolic health consequences. These changes are likely to increase the risk of developing chronic secondary conditions and impact the quality of life in persons with SCI. Surface neuromuscular electrical stimulation evoked resistance training (NMES-RT) was developed as a strategy to attenuate the process of skeletal muscle atrophy, decrease ectopic adiposity, improve insulin sensitivity and enhance mitochondrial capacity. However, NMES-RT is limited to only a single muscle group. Involving multiple muscle groups of the lower extremities may maximize the health benefits of training. Functional electrical stimulation-lower extremity cycling (FES-LEC) allows for the activation of 6 muscle groups, which is likely to evoke greater metabolic and cardiovascular adaptation. Appropriate knowledge of the stimulation parameters is key to maximizing the outcomes of electrical stimulation training in persons with SCI. Adopting strategies for long-term use of NMES-RT and FES-LEC during rehabilitation may maintain the integrity of the musculoskeletal system, a pre-requisite for clinical trials aiming to restore walking after injury. The current manuscript presents a combined protocol using NMES-RT prior to FES-LEC. We hypothesize that muscles conditioned for 12 weeks prior to cycling will be capable of generating greater power, cycle against higher resistance and result in greater adaptation in persons with SCI.

Spinal cord injury is a traumatic medical condition that may result in elevated risks of chronic secondary metabolic disorders. Here, we presented a protocol using surface neuromuscular electrical stimulation-resistance training in conjunction with functional electrical stimulation-lower extremities cycling as a strategy to ameliorate several of these medical problems.

Skeletal muscle atrophy, increased adiposity and reduced physical activity are key changes observed after spinal cord injury (SCI) and are associated with ...

Assessment of Social Transmission of Food Preferences Behaviors

Olfactory recognition deficits are suggested to be able to serve as clinical marker to differentiate Alzheimer&#39;s disease (AD) subjects from healthy aging groups. For example, olfactory dysfunction in AD can present as impairment in olfactory recognition, emerging during early stages of the disease and worsening while the disease progresses. The social transmission of food preferences (STFP) task is based on a rudimentary form of communication between rodents concerning distant foods dependent on the transmission of olfactory cues. Healthy wild-type mice would prefer to eat a novel, flavored food that was previously cued by a conspecific, and this food preference would be hampered in transgenic AD mice, such as the APP/PS1 model. Indeed, a strong preference for the cued food in C57Bl6/J mice of 3 months of age was found, and this was reduced in 3 months old transgenic APP/PS1 mice. In summary, STFP task could be a powerful measure to be integrated in present subclinical detection assays of AD.

This paper presents a protocol for the investigation of social transmission of food preference in mice. The advantages and possible applications for this procedure, for instance, in detecting early changes in AD mouse models, are highlighted. To conclude, interpretation of the results in light of critical details are discussed.

Olfactory recognition deficits are suggested to be able to serve as clinical marker to differentiate Alzheimer&#39;s disease (AD) subjects from healthy ...

A Middle Cerebral Artery Occlusion Technique for Inducing Post-stroke Depression in Rats

Post-stroke depression (PSD) is the most recurrent of all psychiatric complications resulting from an ischemic stroke. A greater majority (about 60%) of all ischemic stroke patients suffer from PSD, a disorder considered to be an ischemic stroke-related precursor for increased death and degradation in health. The pathophysiology of PSD is still obscure. To study the mechanism of development and occurrence of PSD further, and to find out a therapy, we attempted to develop a new protocol that requires occluding the middle cerebral artery (MCA) via the internal carotid artery (ICA) in rats. This protocol describes a model of PSD induced in rats through the middle cerebral artery occlusion (MCAO). Also used in the experiment are the Porsolt forced swim test and the sucrose preference test to confirm and evaluate the depressive mood of the rats under investigation. Rather than inserting the catheter through the external carotid artery (ECA), as stipulated for the original procedure, this MCAO technique has the monofilament passing directly through the ICA. This MCAO technique was developed a few years ago and leads to a reduction in mortality and variability. It is generally accepted that the criteria used are preferred in the selection of biological models. The data obtained with this protocol show that this model of MCAO could be a way of inducing PSD in rats and could potentially lead to the understanding of the pathophysiology and the future development of new drugs and other neuroprotective agents.

Here we present a protocol to induce post-stroke depression in rats by occluding the middle cerebral artery via the internal carotid artery. We use the Porsolt forced swim test and the sucrose preference test to confirm and evaluate induced depressive moods.

Post-stroke depression (PSD) is the most recurrent of all psychiatric complications resulting from an ischemic stroke. A greater majority (about 60%) of ...

Multi-Modal Signals for Analyzing Pain Responses to Thermal and Electrical Stimuli

The assessment of pain relies mostly on methods that require a person to communicate. However, for people with cognitive and verbal impairments, existing methods are not sufficient as they lack reliability and validity. To approach this problem, recent research focuses on an objective pain assessment facilitated by parameters of responses derived from physiology, and video and audio signals. To develop reliable automated pain recognition systems, efforts have been made in creating multimodal databases in order to analyze pain and detect valid pain patterns. While the results are promising, they only focus on discriminating pain or pain intensities versus no pain. In order to advance this, research should also consider the quality and duration of pain as they provide additional valuable information for more advanced pain management. To complement existing databases and the analysis of pain regarding quality and length, this paper proposes a psychophysiological experiment to elicit, measure, and collect valid pain reactions. Participants are subjected to painful stimuli that differ in intensity (low, medium, and high), duration (5 s / 1 min), and modality (heat / electric pain) while audio, video (e.g., facial expressions, body gestures, facial skin temperature), and physiological signals (e.g., electrocardiogram [ECG], skin conductance level [SCL], facial electromyography [EMG], and EMG of M. trapezius) are being recorded. The study consists of a calibration phase to determine a subject&#8217;s individual pain range (from low to intolerable pain) and a stimulation phase in which pain stimuli, depending on the calibrated range, are applied. The obtained data may allow refining, improving, and evaluating automated recognition systems in terms of an objective pain assessment. For further development of such systems and to investigate pain reactions in more detail, additional pain modalities such as pressure, chemical, or cold pain should be included in future studies. Recorded data of this study will be released as the &#8220;X-ITE Pain Database&#8221;.

This article focuses on the experimental elicitation of pain through heat (thermal) and electrical stimulation while recording physiological, visual, and paralinguistic responses. It aims at collecting valid multimodal data for analyzing pain based on its intensity, quality, and duration.&#160;

The assessment of pain relies mostly on methods that require a person to communicate. However, for people with cognitive and verbal impairments, existing ...

Assessment of Sexual Behavior of Male Mice

Sexual behavior is highly species-specific. Although rodents have slightly different sexual behaviors, mice and rats have a similar sexual behavioral pattern. The purpose of this article is to describe the hormone-induced estrus ovariectomized female model and the experimental procedure for the assessment of sexual behavior of male mice. The most important sexual behavioral elements are demonstrated in the video and illustrations. The critical steps, advantages, and limitations of the sexual behavior test are explained as well. Finally, the behavior parameters are presented, and mounting, intromission, and ejaculation processes in mating are distinguished. Behavioral parameters are assessed in terms of the occurred duration and counts during the test period.

This article describes how to perform sexual behavior tests in male mice.

Sexual behavior is highly species-specific. Although rodents have slightly different sexual behaviors, mice and rats have a similar sexual behavioral ...

Comparative Analysis of Lower Limb Kinematics between the Initial and Terminal  Phase  of 5km Treadmill Running

Running is beneficial for physical health, but it is also accompanied by many injuries. However, the main factors leading to running injury remain unexplained. This study investigated the effects of long running distance on lower-limb kinematic variables and the lower limb kinematic difference of between the initial (IR) and terminal phase (TR) of 5 km running was compared. Ten amateur runners ran on a treadmill at the speed of 10 km/h. Dynamic kinematic data was collected at the phase of IR (0.5 km) and TR (5 km), respectively. The peak angle, peak angular velocities, and range of motion were recorded in this experiment. The main results demonstrated the following: ankle eversion and knee abduction were increased at TR; ROMs of ankle and knee were increased in the frontal plane at TR than IR; a larger peak angular velocity of ankle dorsiflexion and hip interrotation were found in TR compared to IR. These changes during the long distance running may provide some specific details for exploring potential reasons of running injuries.

This study investigated the biomechanical characteristics of the lower extremity kinematic variables between the initial and terminal phase of 5 km treadmill running. The lower-limb kinematic data of 10 runners were collected using a three-dimensional motion capture system on a treadmill at the initial phase (0.5 km) and the terminal phase (5 km), respectively.