NIH R21NS42516 to TGH Craig H Nielsen Foundation Grant 83860 to TGH NIDRR-RRTC.
APTA Doctoral Scholarship to CKT

<ol>
	<li>Miller, J. F., Paul, K. D., Rymer, W. Z., Heckman, C. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=5-HT1B/1D+agonist+CGS-12066B+attenuates+clasp+knife+reflex+in+the+cat.">5-HT1B/1D agonist CGS-12066B attenuates clasp knife reflex in the cat.</a> J Neurophysiol. 74, 453-456 (1995).</li><li>Gimenez y Ribotta, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Kinematic+analysis+of+recovered+locomotor+movements+of+the+hindlimbs+in+paraplegic+rats+transplanted+with+monoaminergic+embryonic+neurons.">Kinematic analysis of recovered locomotor movements of the hindlimbs in paraplegic rats transplanted with monoaminergic embryonic neurons.</a> Ann N Y Acad Sci. 860, 521-523 (1998).</li><li>Landry, E. S., Guertin, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+effects+of+5-HT1+and+5-HT2+receptor+agonists+on+hindlimb+movements+in+paraplegic+mice.">Differential effects of 5-HT1 and 5-HT2 receptor agonists on hindlimb movements in paraplegic mice.</a> Prog Neuropsychopharmacol Biol Psychiatry. 28, 1053-1060 (2004).</li><li>Liu, J., Jordan, L. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stimulation+of+the+parapyramidal+region+of+the+neonatal+rat+brain+stem+produces+locomotor-like+activity+involving+spinal+5-HT7+and+5-HT2A+receptors.">Stimulation of the parapyramidal region of the neonatal rat brain stem produces locomotor-like activity involving spinal 5-HT7 and 5-HT2A receptors.</a> J Neurophysiol. 94, 1392-1404 (2005).</li><li>Fong, A. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spinal+cord-transected+mice+learn+to+step+in+response+to+quipazine+treatment+and+robotic+training.">Spinal cord-transected mice learn to step in response to quipazine treatment and robotic training.</a> J Neurosci. 25, 11738-11747 (2005).</li><li>Murray, K., Nakae, A., Stephens, M. J., Rank, M., D Amico, J., Harvey, P., Li, X., Harris, L., Ballou, E. W., Anelli, R., Heckman, C. J., Mashimo, T., Vavrek, R., Sanelli, L., Gorassini, M. A., Bennett, D. J., Fouad, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recovery+of+motoneuron+and+locomotor+function+after+chronic+spinal+cord+injury+depends+on+constitutive+activity+in+5-HT2C+receptors.">Recovery of motoneuron and locomotor function after chronic spinal cord injury depends on constitutive activity in 5-HT2C receptors.</a> Nature Medicine. , (2010).</li><li>Pariente, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fluoxetine+modulates+motor+performance+and+cerebral+activation+of+patients+recovering+from+stroke.">Fluoxetine modulates motor performance and cerebral activation of patients recovering from stroke.</a> Ann Neurol. 50, 718-729 (2001).</li><li>Hornby, T. G., Lewek, M. D., Thompson, C. K., Heitz, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Repeated+maximal+volitional+effort+contractions+in+human+spinal+cord+injury:+initial+torque+increases+and+reduced+fatigue.">Repeated maximal volitional effort contractions in human spinal cord injury: initial torque increases and reduced fatigue.</a> Neurorehabil Neural Repair. 23, 928-938 (2009).</li><li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> ACSM's Guidelines for Exercise Testing and Prescription. , (2000).</li><li>Lewek, M. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Allowing+intralimb+kinematic+variability+during+locomotor+training+poststroke+improves+kinematic+consistency:+a+subgroup+analysis+from+a+randomized+clinical+trial.">Allowing intralimb kinematic variability during locomotor training poststroke improves kinematic consistency: a subgroup analysis from a randomized clinical trial.</a> Phys Ther. 89, 829-839 (2009).</li><li>Fung, J., Barbeau, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+dynamic+EMG+profile+index+to+quantify+muscular+activation+disorder+in+spastic+paretic+gait.">A dynamic EMG profile index to quantify muscular activation disorder in spastic paretic gait.</a> Electroencephalogr Clin Neurophysiol. 73, 233-244 (1989).</li><li>Bohannon, R. W., Smith, M. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interrater+reliability+of+a+modified+Ashworth+scale+of+muscle+spasticity.">Interrater reliability of a modified Ashworth scale of muscle spasticity.</a> Phys Ther. 67, 206-207 (1987).</li><li>Benz, E., TG, H. o. r. n. b. y., RK, B. o. d. e., Scheidt, R. A., Schmit, B. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+physiologically+based+clinical+measure+for+spastic+reflexes+in+spinal+cord+injury.">A physiologically based clinical measure for spastic reflexes in spinal cord injury.</a> Arch Phys Med Rehabil. 86, 52-59 (2005).</li></ol>

No conflicts of interest declared.

This video demonstration highlights methods to assess changes in reflex activity, volitional strength and ambulation following the acute oral administration of SSRIs in human SCI. This battery of assessments demonstrates that despite increases in so called abnormal reflex activity following acute oral administration of a SSRI, the individual with SCI demonstrated improvements in volitional strength, with only minor changes in locomotor ability. In these individuals the effects of augmented spasticity do not appear detrimental to ambulatory function. Additionally improvements in walking ability may be more pronounced in individuals with acute lesions. Continuing studies use these similar quantitative and clinical assessments to determine the efficacy of combined SSRIs and intensive physical interventions, as has been employed in animal models of SCI. With a sound theoretical framework based on long-standing and relatively new basic science research, these methods can help translate such information to a clinical population and may challenge some of the traditional protocols used in clinical practice to augment functional recovery in individuals with SCI.

<!DOCTYPE html PUBLIC "-//W3C//DTD XHTML 1.0 Transitional//EN" "http://www.w3.org/TR/xhtml1/DTD/xhtml1-transitional.dtd">
<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" lang="en">	
		
		<div>
		<table border="1">
		<thead>
		<tr>
		<th>Material Name</th>
		<th>Type</th>
		<th>Company</th>
		<th>Catalogue Number</th>
		<th>Comment</th>
		</tr>
		</thead>
		<tbody>
		
<tr>
<td>Isokinetic Dynamometer</td>
<td>&nbsp;</td>
<td>Biodex</td>
<td>System 3 with Rehab Toolkit</td>
<td>&nbsp;</td>
<tr>
<td>EMG system</td>
<td>&nbsp;</td>
<td>Delysis</td>
<td>Bagnoli 2.1</td>
<td>&nbsp;</td>
<tr>
<td>EMG system</td>
<td>&nbsp;</td>
<td>Noraxon</td>
<td>Mayosystem 1400a</td>
<td>&nbsp;</td>
<tr>
<td>Metabolic</td>
<td>&nbsp;</td>
<td>ConMed</td>
<td>K4B2</td>
<td>&nbsp;</td>
<tr>
<td>Load Cell</td>
<td>&nbsp;</td>
<td>ATI</td>
<td>Theta</td>
<td>&nbsp;</td>
<tr>
<td>Force Treadmill</td>
<td>&nbsp;</td>
<td>Bertec</td>
<td>FIT</td>
<td>&nbsp;</td>
<tr>
<td>Motion Capture</td>
<td>&nbsp;</td>
<td>Motion Analysis</td>
<td>Eagle 3</td>
<td>&nbsp;</td>		</tbody>
		</table>
		</div>

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.

Watch this Scientific Journal Video about Methods to Quantify Pharmacologically Induced Alterations in Motor Function in Human Incomplete SCI at JoVE.com

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

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, ...

methods-to-quantify-pharmacologically-induced-alterations-motor

Research

JoVE Journal

Medicine

13.6K Views.  Rehabilitation Institute of Chicago. 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).