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.

<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. 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The authors declare they have no real or perceived conflicts of interest related to the reported work.

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><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&#039;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 ...

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2.4K Views.  Ralph H. Johnson Veterans Administration Medical Center. Dit protocol maakt de neurofysiologische beoordeling van de corticospinale tractus van de onderste extremiteit na een beroerte mogelijk wanneer gang en evenwicht van primair belang zijn. Het belangrijkste voordeel van deze techniek is dat het een verhoogde kans biedt om een motorisch opgeroepen potentieel op te wekken in een populatie waar veel individuen geen rustreactie vertonen. Deze methode kan worden gebruikt in elke neurologische populatie waar het onderzoeken van de neurofysiologie van...

Video: Standing Neurophysiological Assessment of Lower Extremity Muscles Post-Stroke

Methods to Quantify Pharmacologically Induced Alterations in Motor Function in Human Incomplete SCI

Spinal cord injury (SCI) is a debilitating disorder, which produces profound deficits in volitional motor control. Following medical stabilization, recovery from SCI typically involves long term rehabilitation. While recovery of walking ability is a primary goal in many patients early after injury, those with a motor incomplete SCI, indicating partial preservation of volitional control, may have the sufficient residual descending pathways necessary to attain this goal. However, despite physical interventions, motor impairments including weakness, and the manifestation of abnormal involuntary reflex activity, called spasticity or spasms, are thought to contribute to reduced walking recovery. Doctrinaire thought suggests that remediation of this abnormal motor reflexes associated with SCI will produce functional benefits to the patient. For example, physicians and therapists will provide specific pharmacological or physical interventions directed towards reducing spasticity or spasms, although there continues to be little empirical data suggesting that these strategies improve walking ability.
In the past few decades, accumulating data has suggested that specific neuromodulatory agents, including agents which mimic or facilitate the actions of the monoamines, including serotonin (5HT) and norepinephrine (NE), can initiate or augment walking behaviors in animal models of SCI. Interestingly, many of these agents, particularly 5HTergic agonists, can markedly increase spinal excitability, which in turn also increases reflex activity in these animals. Counterintuitive to traditional theories of recovery following human SCI, the empirical evidence from basic science experiments suggest that this reflex hyper excitability and generation of locomotor behaviors are driven in parallel by neuromodulatory inputs (5HT) and may be necessary for functional recovery following SCI. 
The application of this novel concept derived from basic scientific studies to promote recovery following human SCI would appear to be seamless, although the direct translation of the findings can be extremely challenging. Specifically, in the animal models, an implanted catheter facilitates delivery of very specific 5HT agonist compounds directly onto the spinal circuitry. The translation of this technique to humans is hindered by the lack of specific surgical techniques or available pharmacological agents directed towards 5HT receptor subtypes that are safe and effective for human clinical trials. However, oral administration of commonly available 5HTergic agents, such as selective serotonin reuptake inhibitors (SSRIs), may be a viable option to increase central 5HT concentrations in order to facilitate walking recovery in humans. Systematic quantification of how these SSRIs modulate human motor behaviors following SCI, with a specific focus on strength, reflexes, and the recovery of walking ability, are missing.
This video demonstration is a progressive attempt to systematically and quantitatively assess the modulation of reflex activity, volitional strength and ambulation following the acute oral administration of an SSRI in human SCI. Agents are applied on single days to assess the immediate effects on motor function in this patient population, with long-term studies involving repeated drug administration combined with intensive physical interventions.

This video demonstrates modulation of reflex activity, volitional strength and ambulation through clinical and quantitative assessments in individuals with motor incomplete SCI as a result of acute oral administration of a serotonin reuptake inhibitor (SSRI).

Spinal cord injury (SCI) is a debilitating disorder, which produces profound deficits in volitional motor control. Following medical stabilization, ...

Medicine

Compensatory Limb Use and Behavioral Assessment of Motor Skill Learning Following Sensorimotor Cortex Injury in a Mouse Model of Ischemic Stroke

Mouse models have become increasingly popular in the field of behavioral neuroscience, and specifically in studies of experimental stroke. As models advance, it is important to develop sensitive behavioral measures specific to the mouse. The present protocol describes a skilled motor task for use in mouse models of stroke. The Pasta Matrix Reaching Task functions as a versatile and sensitive behavioral assay that permits experimenters to collect accurate outcome data and manipulate limb use to mimic human clinical phenomena including compensatory strategies (i.e., learned non-use) and focused rehabilitative training. When combined with neuroanatomical tools, this task also permits researchers to explore the mechanisms that support behavioral recovery of function (or lack thereof) following stroke. The task is both simple and affordable to set up and conduct, offering a variety of training and testing options for numerous research questions concerning functional outcome following injury. Though the task has been applied to mouse models of stroke, it may also be beneficial in studies of functional outcome in other upper extremity injury models.

Mouse models have become increasingly popular in studies of behavioral neuroscience. As models advance, it is important to develop sensitive behavioral measures specific to the mouse. This protocol describes the Pasta Matrix Reaching Task, which is a skilled motor task for use in mouse models of stroke.

Mouse models have become increasingly popular in the field of behavioral neuroscience, and specifically in studies of experimental stroke. As models ...

Asymmetric Walkway: A Novel Behavioral Assay for Studying Asymmetric Locomotion

Behavioral assays are commonly used for the assessment of sensorimotor impairment in the central nervous system (CNS). The most sophisticated methods for quantifying locomotor deficits in rodents is to measure minute disturbances of unconstrained gait overground (e.g., manual BBB score or automated CatWalk). However, cortical inputs are not required for the generation of basic locomotion produced by the spinal central pattern generator (CPG). Thus, unconstrained walking tasks test locomotor deficits due to motor cortical impairment only indirectly. In this study, we propose a novel, precise foot-placement locomotor task that evaluates cortical inputs to the spinal CPG. An instrumented peg-way was used to impose symmetrical and asymmetrical locomotor tasks mimicking lateralized movement deficits. We demonstrate that shifts from equidistant inter-stride lengths of 20% produce changes in the forelimb stance phase characteristics during locomotion with preferred stride length. Furthermore, we propose that the asymmetric walkway allows for measurements of behavioral outcomes produced by cortical control signals. These measures are relevant for the assessment of impairment after cortical damage.

Here, we present a protocol to quantify precise stepping in rodents. Cortical and the spinal central pattern generator signals are required for precise foot-placement during obstructed locomotion. We report here the novel constrained walking task that directly examines precise stepping behavior.

Behavioral assays are commonly used for the assessment of sensorimotor impairment in the central nervous system (CNS). The most sophisticated methods for ...

Quantitative Static and Dynamic Assessment of Balance Control in Stroke Patients

In patients with stroke, damage to the central nervous system (CNS) can affect the postural stability and increase the risk of falling. Therefore, accurately assessing the balance is important to understand the type, extent, and causes of balance deficit, and to identify individualized interventions. Clinical assessment methods for balance function can be broadly divided into observation, scale assessment, and balance instrument testing. Here, a clinical protocol is presented for static and dynamic balance assessment in stroke patients, which includes three semiquantitative balance function scale assessments (i.e., Berg Balance Scale, Timed Up and Go Test, and Fugl-Meyer Assessment) and three quantitative instrumental balance evaluation (i.e., Stability Assessment Module, Proprioceptive Assessment Module, and Limit of Stability Module). It is recommended that clinicians consider the use of both classic clinical balance scales and instrumental balance measurements when assessing stroke patients to improve the accuracy of assessments, leading to a better individualized treatment plan.

Presented here is a quantitative, clinical balance assessment method suitable for stroke patients with balance disorders.

In patients with stroke, damage to the central nervous system (CNS) can affect the postural stability and increase the risk of falling. Therefore, ...

A Human-machine-interface Integrating Low-cost Sensors with a Neuromuscular Electrical Stimulation System for Post-stroke Balance Rehabilitation

A stroke is caused when an artery carrying blood from heart to an area in the brain bursts or a clot obstructs the blood flow to brain thereby preventing delivery of oxygen and nutrients. About half of the stroke survivors are left with some degree of disability. Innovative methodologies for restorative neurorehabilitation are urgently required to reduce long-term disability. The ability of the nervous system to reorganize its structure, function and connections as a response to intrinsic or extrinsic stimuli is called neuroplasticity. Neuroplasticity is involved in post-stroke functional disturbances, but also in rehabilitation. Beneficial neuroplastic changes may be facilitated with non-invasive electrotherapy, such as neuromuscular electrical stimulation (NMES) and sensory electrical stimulation (SES). NMES involves coordinated electrical stimulation of motor nerves and muscles to activate them with continuous short pulses of electrical current while SES involves stimulation of sensory nerves with electrical current resulting in sensations that vary from barely perceivable to highly unpleasant. Here, active cortical participation in rehabilitation procedures may be facilitated by driving the non-invasive electrotherapy with biosignals (electromyogram (EMG), electroencephalogram (EEG), electrooculogram (EOG)) that represent simultaneous active perception and volitional effort. To achieve this in a resource-poor setting, e.g., in low- and middle-income countries, we present a low-cost human-machine-interface (HMI) by leveraging recent advances in off-the-shelf video game sensor technology. In this paper, we discuss the open-source software interface that integrates low-cost off-the-shelf sensors for visual-auditory biofeedback with non-invasive electrotherapy to assist postural control during balance rehabilitation. We demonstrate the proof-of-concept on healthy volunteers.

A novel low-cost human-machine interface for interactive post-stroke balance rehabilitation system is presented in this article. The system integrates off-the-shelf low-cost sensors towards volitionally driven electrotherapy paradigm. The proof-of-concept software interface is demonstrated on healthy volunteers.

A stroke is caused when an artery carrying blood from heart to an area in the brain bursts or a clot obstructs the blood flow to brain thereby preventing ...

Neuroscience

Bilateral Assessment of the Corticospinal Pathways of the Ankle Muscles Using Navigated Transcranial Magnetic Stimulation

Distal leg muscles receive neural input from motor cortical areas via the corticospinal tract, which is one of the main motor descending pathway in humans and can be assessed using transcranial magnetic stimulation (TMS). Given the role of distal leg muscles in upright postural and dynamic tasks, such as walking, a growing research interest in the assessment and modulation of the corticospinal tracts relative to the function of these muscles has emerged in the last decade. However, methodological parameters used in previous work have varied across studies making the interpretation of results from cross-sectional and longitudinal studies less robust. Therefore, use of a standardized TMS protocol specific to the assessment of leg muscles&#39; corticomotor response (CMR) will allow for direct comparison of results across studies and cohorts. The objective of this paper is to present a protocol that provides the flexibility to simultaneously assess the bilateral CMR of two main ankle antagonistic muscles, the tibialis anterior and soleus, using single pulse TMS with a neuronavigation system. The present protocol is applicable while the examined muscle is either fully relaxed or isometrically contracted at a defined percentage of maximum isometric voluntary contraction. Using each subject&#39;s structural MRI with the neuronavigation system ensures accurate and precise positioning of the coil over the leg cortical representations during assessment. Given the inconsistency in CMR derived measures, this protocol also describes a standardized calculation of these measures using automated algorithms. Though this protocol is not conducted during upright postural or dynamic tasks, it&#160;can be used to assess bilaterally any pair of leg muscles, either antagonistic or synergistic, in both neurologically intact and impaired subjects.

The present protocol describes the simultaneous, bilateral assessment of the corticomotor response of the tibialis anterior and soleus during rest and tonic voluntary activation using a single pulse transcranial magnetic stimulation and neuronavigation system.

Distal leg muscles receive neural input from motor cortical areas via the corticospinal tract, which is one of the main motor descending pathway in humans ...

Determining the Functional Status of the Corticospinal Tract Within One Week of Stroke

High interindividual variability in the recovery of upper limb (UL) function after stroke means it is difficult to predict an individual&#39;s potential for recovery based on clinical assessments alone. The functional integrity of the corticospinal tract is an important prognostic biomarker for recovery of UL function, particularly for those with severe initial UL impairment. This article presents a protocol for evaluating corticospinal tract function within 1 week of stroke. This protocol can be used to select and stratify patients in trials of interventions designed to improve UL motor recovery and outcomes after stroke. The protocol also forms part of the PREP2 algorithm, which predicts UL function for individual patients 3 months poststroke. The algorithm sequentially combines a UL strength assessment, age, transcranial magnetic stimulation, and stroke severity, within a few days of the stroke. The benefits of using PREP2 in clinical practice are described elsewhere. This article focuses on the use of a UL strength assessment and transcranial magnetic stimulation to evaluate corticospinal tract function.

This protocol is for evaluating corticospinal tract function within 1 week of stroke. It can be used to select and stratify patients in trials of interventions designed to improve upper limb motor recovery and outcomes and in clinical practice for predicting upper limb functional outcomes 3 months after stroke.

High interindividual variability in the recovery of upper limb (UL) function after stroke means it is difficult to predict an individual&#39;s potential ...

Lower Limb Biomechanical Analysis of Healthy Participants

Biomechanical analysis techniques are useful in the study of human movement. The aim of this study was to introduce a technique for the lower limb biomechanical assessment in healthy participants using commercially available systems. Separate protocols were introduced for the gait analysis and muscle strength testing systems. To ensure maximum accuracy for gait assessment, attention should be given to the marker placements and self-paced treadmill acclimatization time. Similarly, participant positioning, a practice trial, and verbal encouragement are three critical stages in muscle strength testing. The current evidence suggests that the methodology outlined in this article may be effective for the assessment of lower limb biomechanics.

This article introduces a comprehensive experimental methodology on two of the latest technologies available to measure the lower limb biomechanics of individuals.

Biomechanical analysis techniques are useful in the study of human movement. The aim of this study was to introduce a technique for the lower limb ...

Electroencephalography Network Indices as Biomarkers of Upper Limb Impairment in Chronic Stroke

Alteration of electroencephalography (EEG) signals during task-specific movement of the impaired limb has been reported as a potential biomarker for the severity of motor impairment and for the prediction of motor recovery in individuals with stroke. When implementing EEG experiments, detailed paradigms and well-organized experiment protocols are required to obtain robust and interpretable results. In this protocol, we illustrate a task-specific paradigm with upper limb movement and methods and techniques needed for the acquisition and analysis of EEG data. The paradigm consists of 1 min of rest followed by 10 trials comprising alternating 5 s and 3 s of resting and task (hand extension)-states, respectively, over 4 sessions. EEG signals were acquired using 32 Ag/AgCl scalp electrodes at a sampling rate of 1,000 Hz. Event-related spectral perturbation analysis associated with limb movement and functional network analyses at the global level in the low-beta (12-20 Hz) frequency band were performed. Representative results showed an alteration of the functional network of low-beta EEG frequency bands during movement of the impaired upper limb, and the altered functional network was associated with the degree of motor impairment in chronic stroke patients. The results demonstrate the feasibility of the experimental paradigm in EEG measurements during upper limb movement in individuals with stroke. Further research using this paradigm is needed to determine the potential value of EEG signals as biomarkers of motor impairment and recovery.

The experimental protocol demonstrates the paradigm for acquiring and analyzing electroencephalography (EEG) signals during upper limb movement in individuals with stroke. The alteration of the functional network of low-beta EEG frequency bands was observed during the movement of the impaired upper limb and was associated with the degree of motor impairment.

Alteration of electroencephalography (EEG) signals during task-specific movement of the impaired limb has been reported as a potential biomarker for the ...

Evaluating Brain Activation by fNIRS During a Lower Limb Robotic Therapy Session

An Experiment Using Functional Near-Infrared Spectroscopy and Robot-Assisted Multi-Joint Pointing Movements of the Lower Limb

Stroke affects approximately 17 million individuals worldwide each year and is a leading cause of long-term disability. Robotic therapy has shown promise in helping stroke patients regain lost motor functions. One potential avenue for increasing the understanding of how motor recovery occurs is to study brain activation during the movements that are targeted by therapy in healthy individuals. Functional Near-Infrared Spectroscopy (fNIRS) has emerged as a promising neuroimaging technique for examining neural underpinnings of motor function. This study aimed to investigate fNIRS neural correlates of complex lower limb movements in healthy subjects. Participants were asked to perform cycles of rest and movement for 6 min using a robotic device for motor rehabilitation. The task required coordinated knee and ankle joint movements to point to targets displayed on a computer screen. Two experimental conditions with different levels of movement assistance provided by the robot were explored. The results showed that the fNIRS protocol effectively detected brain regions associated with motor control during the task. Notably, all subjects exhibited greater activation in the contralateral premotor area during the no-assistance condition compared to the assisted condition. In conclusion, fNIRS appears to be a valuable approach for detecting changes in oxyhemoglobin concentration associated with multi-joint pointing movements of the lower limb. This research might contribute to the understanding of stroke motor recovery mechanisms and might pave the way for improved rehabilitation treatments for stroke patients. However, further research is needed to fully elucidate the potential of fNIRS in studying motor function and its applications in clinical settings.

Author Spotlight: Assessing Brain Activity in Robotic-Assisted Lower Limb Rehabilitation Using fNIRS

It is estimated that 1 in 6 individuals worldwide will have a stroke in their lifetime, causing long-term disability, whose rehabilitation mechanisms are still poorly understood. This study proposes a protocol to evaluate brain activation by functional near-infrared spectroscopy (fNIRS) during a lower limb robotic therapy session.

Stroke affects approximately 17 million individuals worldwide each year and is a leading cause of long-term disability. Robotic therapy has shown promise ...

Standing Neurophysiological Assessment of Lower Extremity Muscles Post-Stroke

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