The authors would like to acknowledge Jon Nelson PhD, PT, for conducting the analysis to confirm the vibration frequency of the vibrator used in this protocol.

The Institutional Review Board at the College of St. Scholastica has approved the study under which this protocol was developed and tested.
NOTE: The manufacturer&#39;s specifications of the vibrator used in this protocol indicated that the frequency on &#39;high&#39; was 11,00 rpm (183.3 Hz). This frequency was confirmed using a sample of vibration data collected through one input of a differential amplifier sampled at 2 kHz. The mean period of the signal was 5.56 x 10-3 s, which is equivalent to 180 Hz. In individuals with Raynaud&#39;s disease, vibration may cause Raynaud&#39;s phenomenon, a temporary vasoconstriction at the site of application, which may last minutes to hours, and may be accompanied by numbness, itching or pain.23 Figure 1 shows an example of Raynaud&#39;s phenomenon caused by vibration similar to that used in this protocol. Potential participants should be screened for Raynaud&#39;s prior to participating in this protocol.
1. Proprioception Knockdown Protocol:
<ol>
	<li>Gather pen, 183 Hz vibrator, 2.5-inch wide strap and a rubber band (see the Table of Materials).</li>
	<li>Palpate the ulnar nerve within the ulnar groove of the upper extremity being tested.
	<ol>
		<li>Place an &#34;x&#34; mark on the skin over the ulnar groove just superior to the line between the olecranon process of the humerus and the medial epicondyle of the ulna. 
		NOTE: Figure 2 shows this location on the dorsum of the elbow .</li>
	</ol>
	</li>
	<li>Place head of the vibrator onto marked location with handle of massager superior to head.
	<ol>
		<li>Apply the wide strap around handle portion of vibrator and participant&#39;s arm.</li>
		<li>Place rubber band around neck of vibrator head and participant&#39;s arm to hold vibrator head into place and maintain contact between participant&#39;s skin and the vibrator head, ensuring that the rubber band is a proper size to retain the head against the skin but not to restrict movement or circulation.</li>
	</ol>
	</li>
	<li>Ask the participant to bend and straighten his/her elbow. He/she should feel no interference from the straps. If he/she reports interference, adjust the straps and rubber band so that freedom of movement is ensured.</li>
	<li>Turn vibrator on high, wait for 2 min (based on unpublished data).
	<ol>
		<li>Conduct a measure of proprioception performance (results from the tablet version of the BKT are presented here) with the vibrator running on high for the duration of the test
		<ol>
			<li>Conduct the BKT. Seat the participant in a standard height chair (18-inch seat height), at a standard height table (29-inch height) with their vision occluded from the tablet using a curtain. Sit across from the participant.</li>
			<li>Guide the participants index finger, held at the distal phalanx only, from the start of the line to the end of the line (target) and back to the start of the line. Release the participant&#39;s finger and instruct them to touch the target. Complete 20 trials with each upper limb.</li>
			<li>Assign the participants&#39; scores for each upper limb as the average absolute error (distance from the target) in centimeters.</li>
		</ol>
		</li>
		<li>Conduct psychophysical measures (such as the VDT) immediately upon removal of the vibration stimulus. 
		NOTE: In the results presented, the duration of the vibration stimulus prior to the VDT was 5 &#177; 1 minute.</li>
	</ol>
	</li>
</ol>
2. Vibration Detection Threshold (adapted from13)
<ol>
	<li>Gather 128 Hz tuning fork, a stopwatch, textbook (provides a firm yet compliant surface on which to strike the tuning fork), table (29-inch height), standard chair (18-inch seat height), masking tape, and pen.
	<ol>
		<li>Create a 1 &#189; inch x 1 &#189; inch square on the textbook using masking tape to be used as a target for consistency in striking the tuning fork.</li>
		<li>Using a permanent marker, color the bottom 1 mm of the stem of the tuning fork (this mark will be used to standardize the pressure of tuning fork application during the test).</li>
		<li>Seat the participant in the chair at the table. Ask her/him to extend the forearm of the extremity being tested supinated and completely rest it on the table, including the elbow. Ask them to relax the extremities. 
		NOTE: The examiner should be seated across from the participant.</li>
	</ol>
	</li>
	<li>Mark a dot on the skin over the distal biceps tendon, approximately 1 cm superior to the elbow crease.
	<ol>
		<li>Place the book at the edge of table closest to participant, between participant&#39;s elbows.</li>
		<li>Say: &#34;This is a test of your ability to detect vibration. Now I will put this tuning fork on your biceps tendon. Please tell me if you feel any vibration, then say &#39;Now&#39; immediately when the sensation of vibration disappears. This procedure will be repeated 3 times on each arm.&#34;</li>
	</ol>
	</li>
	<li>Ensure that the discs at the ends of each prong of the tuning fork are tight prior to beginning. If they are loose they will rattle and reduce the duration of the tuning fork&#39;s resonance making the test unreliable.
	<ol>
		<li>Hold the stem of the tuning fork loosely between thumb and index finger and strike it on the book inside of the square target with enough force to produce resonance.
		<ol>
			<li>Immediately after striking, place tuning fork on the test location, using enough pressure to depress the skin and conceal the 1 mm band on the tuning fork from vision. 
			NOTE: Figure 3 shows the tuning fork on the distal biceps tendon test location used in this protocol.</li>
			<li>Using the stopwatch, quantify the time from placement of the tuning fork onto participant&#39;s skin until the participant no longer feels vibration (says &#39;Now&#39;).</li>
		</ol>
		</li>
		<li>Repeat two more times on the same arm for a total of three trials.
		<ol>
			<li>Calculate the mean time to disappearance of vibration stimulus across the three trials to determine the vibration detection threshold (VDT).</li>
		</ol>
		</li>
	</ol>
	</li>
</ol>

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P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+assessment+of+limb+position+sense+following+stroke.">Quantitative assessment of limb position sense following stroke.</a> Neurorehabilitation and neural repair. 24, 178 (2010).</li><li>Cappello, L., 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=Robot-aided+assessment+of+wrist+proprioception.">Robot-aided assessment of wrist proprioception.</a> Frontiers in human neuroscience. 9, (2015).</li><li>Han, J., Waddington, G., Adams, R., Anson, J., Liu, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessing+proprioception:+a+critical+review+of+methods.">Assessing proprioception: a critical review of methods.</a> Journal of Sport and Health Science. 5, 80-90 (2016).</li><li>Goble, D. 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C., Boisseau, &. #. 2. 0. 1. ;., Descarreaux, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sensorimotor+control+during+peripheral+muscle+vibration:+An+experimental+study.">Sensorimotor control during peripheral muscle vibration: An experimental study.</a> Journal of manipulative and physiological therapeutics. 38, 35-43 (2015).</li><li>Rolke, R., 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=Quantitative+sensory+testing:+a+comprehensive+protocol+for+clinical+trials.">Quantitative sensory testing: a comprehensive protocol for clinical trials.</a> European Journal of Pain. 10, 77-77 (2006).</li><li>Ayres, 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=Sensory+integration+and+praxis+test+(SIPT).">Sensory integration and praxis test (SIPT).</a> Los Angeles, Western Psychological Services. , (1989).</li><li>Dunn, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Somatosensation+assessment+using+the+NIH+Toolbox.">Somatosensation assessment using the NIH Toolbox.</a> Neurology. 80, S41-S44 (2013).</li><li>Dunn, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Measuring+Change+in+Somatosensation+Across+the+Lifespan.">Measuring Change in Somatosensation Across the Lifespan.</a> American Journal of Occupational Therapy. 69, 6903290020p6903290021-6903290020p6903290029 (2015).</li><li>Witchalls, J., Blanch, P., Waddington, G., Adams, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intrinsic+functional+deficits+associated+with+increased+risk+of+ankle+injuries:+a+systematic+review+with+meta-analysis.">Intrinsic functional deficits associated with increased risk of ankle injuries: a systematic review with meta-analysis.</a> Br J Sports Med. 46, 515-523 (2012).</li><li>Borstad, A. L., Nichols-Larson, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessing+and+treating+Higher-level+Somatosensory+Impairments+Post+Stroke.">Assessing and treating Higher-level Somatosensory Impairments Post Stroke.</a> Topics in Stroke Rehabilitation. 21, 290-295 (2014).</li><li>Kandel, E. R., Schwartz, J. H., Jessell, T. M., Siegelbaum, S. A., Hudspeth, 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=.">.</a> Principles of neural science. 4, (2000).</li><li>Goodwin, G. M., Mccloskey, D. I., Matthews, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+contribution+of+muscle+afferents+to+keslesthesia+shown+by+vibration+induced+illusionsof+movement+and+by+the+effects+of+paralysing+joint+afferents.">The contribution of muscle afferents to keslesthesia shown by vibration induced illusionsof movement and by the effects of paralysing joint afferents.</a> Brain. 95, 705-748 (1972).</li><li>Burke, D., Hagbarth, K. E., L&#246;fstedt, L., Wallin, B. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+responses+of+human+muscle+spindle+endings+to+vibration+of+non-contracting+muscles.">The responses of human muscle spindle endings to vibration of non-contracting muscles.</a> The Journal of physiology. 261, 673-693 (1976).</li><li>Roll, J., Vedel, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Kinaesthetic+role+of+muscle+afferents+in+man,+studied+by+tendon+vibration+and+microneurography.">Kinaesthetic role of muscle afferents in man, studied by tendon vibration and microneurography.</a> Experimental Brain Research. 47, 177-190 (1982).</li><li>Wigley, F. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Raynaud's+phenomenon.">Raynaud's phenomenon.</a> New England Journal of Medicine. 347, 1001-1008 (2002).</li><li>Oldfield, R. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+assessment+and+analysis+of+handedness:+the+Edinburgh+inventory.">The assessment and analysis of handedness: the Edinburgh inventory.</a> Neuropsychologia. 9, 97-113 (1971).</li><li>Kito, T., Hashimoto, T., Yoneda, T., Katamoto, S., Naito, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sensory+processing+during+kinesthetic+aftereffect+following+illusory+hand+movement+elicited+by+tendon+vibration.">Sensory processing during kinesthetic aftereffect following illusory hand movement elicited by tendon vibration.</a> Brain research. 1114, 75-84 (2006).</li><li>Carey, L. M., Oke, L. E., Matyas, T. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impaired+limb+position+sense+after+stroke:+a+quantitative+test+for+clinical+use.">Impaired limb position sense after stroke: a quantitative test for clinical use.</a> Arch.Phys.Med.Rehabil. 77, 1271-1278 (1996).</li><li>Roll, J., Vedel, J., Ribot, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alteration+of+proprioceptive+messages+induced+by+tendon+vibration+in+man:+a+microneurographic+study.">Alteration of proprioceptive messages induced by tendon vibration in man: a microneurographic study.</a> Experimental brain research. 76, 213-222 (1989).</li><li>Calvin-Figui&#232;re, S., Romaigu&#232;re, P., Roll, J. -. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Relations+between+the+directions+of+vibration-induced+kinesthetic+illusions+and+the+pattern+of+activation+of+antagonist+muscles.">Relations between the directions of vibration-induced kinesthetic illusions and the pattern of activation of antagonist muscles.</a> Brain research. 881, 128-138 (2000).</li><li>Fallon, J. B., Macefield, V. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Vibration+sensitivity+of+human+muscle+spindles+and+Golgi+tendon+organs.">Vibration sensitivity of human muscle spindles and Golgi tendon organs.</a> Muscle &amp; nerve. 36, 21-29 (2007).</li><li>Seizova-Cajic, T., Smith, J. L., Taylor, J. L., Gandevia, S. 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The authors have nothing to disclose.

This protocol provides a method to knock down human proprioception in the upper limb. Across 20 healthy participants the effect of proprioceptive knockdown was large as measured by VDT a psychophysical measure of sensitivity thought to reflect A&#945; afferent axon transmission. The VDT was measured as quickly as possible after removal of vibration, when A&#945; afferent discharge is reduced.25 The effect of this protocol on error in reaching to a target with visual occlusion (tBKT) was moderate. This may reflect that the protocol involves only a single vibration stimulus at the elbow, one joint in the multi-joint task of reaching. With respect to other available methods, such as ischemic nerve block,8 the method described here has two noteworthy differences. First, the application of vibration to the skin is well tolerated by participants and easy to apply. Second, this method results in reduced, but not absent, proprioceptive sense. This more closely parallels proprioceptive impairment in neurologic conditions such as stroke,26 compared to methods which produce total deafferentation.
Based on this work, and that of other researchers, three factors appear critical to proprioceptive knockdown using vibration: the frequency of vibration, timing, and location. First, higher frequency vibration is most commonly associated with proprioception impairment. Proprioception distortion by vibration was greater at 80 Hz than at 30 Hz in a force production task.12 Higher frequency vibration has been associated with error in proprioceptive signals,27 kinesthetic illusion (80 Hz),25,28,29 and reduced ability to detect movement (300 Hz).11 Second, while there is some aftereffect of vibration on kinesthetic illusion,25,30 the duration of effect of high frequency vibration on proprioceptive impairment is poorly described; therefore, most protocols apply high frequency vibration before (0.1 s,12 30 s,11 and in this protocol 2 min) and during tests that involve movement. Finally, maintaining contact of the vibration source over nerve, tendon, or muscle belly11,12 during movement without impeding movement is imperative, thus a small lightweight source of vibration is optimal. The ulnar groove was chosen for this protocol due to the superficial position of the ulnar nerve and triceps tendon. If participants report inconsistent sensation of vibration modification to the protocol may be necessary to ensure continuous contact of the vibrator with the skin, such as by using alternative strapping methods.
A minor limitation of this method is that in individuals with Raynaud&#39;s disease, vibration may cause Raynaud&#39;s phenomenon. Researchers should screen participants for Raynaud&#39;s when using this protocol. Another limitation is that the duration of the impairment caused by vibration is unknown. Although the head of the vibrator in this protocol was over the ulnar nerve in the ulnar groove, it is unknown whether the changes in proprioception resulted from vibration of the ulnar nerve or to the adjacent distal triceps tendon, or other structures.
In the future, methods could be developed and tested in which high frequency vibration is applied to more than one structure at a time to attempt to achieve a larger effect. The duration of the knockdown effect is of interest, as is a greater understanding of the neural mechanisms, which underlie the effect of vibration on proprioception. As it is, this protocol will facilitate the testing and refinement of quantitative clinical measures of proprioception, which are greatly needed.

Of all contributors to the neural control of movement, proprioception may be the least well measured. Research measures of proprioception using specialized equipment have recently achieved reliability, validity, and precision;1,2,3 in contrast, clinical measures of proprioception, the most common being limb position sense testing,4 have low resolution, are contaminated by other sensory modalities,4 and have poor or no published psychometric properties.5 New precise, reliable measures of proprioception are needed to elucidate peripheral and central mechanisms of proprioceptive control,3 for clinical diagnosis of impairment, and to measure outcomes of proprioceptive training.2,5,6,7 Toward this end, a simple, non-invasive method to temporarily impair or &#39;knockdown&#39; proprioception is needed.
Proprioceptive knockdown in healthy humans allows researchers to infer the role of proprioceptive function in a sensorimotor task, which is useful to inform the development and validation of standardized measures. Knockdown models have two main advantages over studying humans with impaired proprioception. The first is participant availability; individuals with proprioception impairment are not easily accessible to many researchers. Second, unlike in vivo proprioception impairment, knockdown models may allow the ability to control the extent of impairment across participants.
Current published methods of temporary proprioception knockdown of the upper limb are invasive, impractical, or uncomfortable for the participant. Anesthetic injections, while relatively safe, require technical expertise and may be considered invasive by some research participants. Ischemic nerve blocks cause discomfort and a blood test to screen for clotting disorders prior to their application is practiced.8 Cryotherapy also causes discomfort. The average time of application for cryotherapy to impact proprioception is 20.3 &#177; 5.3 min.9 Once cryotherapy is removed, a brief window in which to measure proprioception prior to rewarming remains, which may contribute to the inconsistent effect of cryotherapy on joint position sense.10 High frequency (300 Hz) vibration was used successfully to reduce proprioceptive acuity in a finger movement detection task; the mechanism was reported to be pacinian corpuscle-induced inhibition of input from other vibration sensitive cutaneous receptors.11 Recently, soleus muscle vibration (80 Hz) was found to decrease isometric force production accuracy by distorting proprioceptive information.12 However, a simple non-invasive method for temporary knockdown of upper limb proprioception has not been published.
The purpose of this method is to use high frequency vibration to temporarily knockdown upper limb proprioception in healthy adults. Knockdown was confirmed using two measures, the Vibration Detection Threshold (VDT) and the tablet version of the Brief Kinesthesia Test (tBKT). The VDT is a psychophysical measure of sensitivity thought to reflect A&#945; afferent axon transmission.13 Proprioceptive performance was quantified using the tBKT that is under development in our lab. The Brief Kinesthesia Test (BKT), based on the work of Ayres,14 is an experimental instrument that was tested for but not included in the National Institutes of Health (NIH) Toolbox core batteries.15,16 The BKT includes three reaching trials for each upper limb. The tBKT includes 20 reaching trials per upper limb and is being developed with the goal of improving the psychometric properties over the original test. The tBKT involves a sensory input (examiner guidance of upper limb to target), central processing (remember the spatial location of the target) and a motor output (attempting to locate the target after guidance is removed), thought to be necessary in a measure of overall proprioceptive performance.17 The VDT and the tBKT measurements, represent low and higher levels, respectively, in the somatosensory hierarchy,18 and thus should provide a more comprehensive quantification of proprioception than either measure used alone.
Two neural mechanisms relate most closely to the reduced proprioceptive acuity caused by high frequency vibration. First, Pacinian corpuscles are the cutaneous mechanoreceptor most commonly associated with vibration detection. The continuous vibration used in this protocol likely raises the receptor tuning threshold of vibration detection based on the neural mechanism of short-term habituation in the A&#945; and &#946; fiber group associated with Pacinian corpuscles.19 The physiologic result is that a vibration of the same intensity and frequency, such as 128 Hz used in the VDT test, is felt for a shorter duration. Second, it is thought that muscle spindles, via A&#945; afferent fibers, code muscle length inaccurately following high frequency vibration resulting in distorted proprioceptive information as evidenced by reduced accuracy during force reproduction,12 illusion of movement,20,21 and reduced kinesthesia.22

<table><tbody><tr><td>Pure Enrichment-Massage Mini with Built in USB Rechargeable Battery</td><td>ebay</td><td>None</td><td>183 Hz cordless vibrator, 7 inches total length including handle</td></tr><tr><td>Chattanooga 2.5 inch velcro strap&amp;nbsp;</td><td>ebay</td><td>None</td><td>used to secure vibrator to arm</td></tr><tr><td>Tuning Fork C128 ENT Surgical Medical Instruments Exam Diagnostic Tools</td><td>ebay</td><td>None</td><td>Used in VDT</td></tr><tr><td>Handheld Digital stop watch</td><td>ebay</td><td>None</td><td>Used to time VDT</td></tr><tr><td>Universal Rubber Bands Size 33, 3 1/2 x 1/8 inch</td><td>ebay</td><td>Universal - UNV00433</td><td>used to secure vibrator head to arm</td></tr><tr><td>Instructions to build Visual Screen were published here: https://www-jove-com.remotexs.ntu.edu.sg/video/53178/design-fabrication-administration-hand-active-sensation-test&amp;nbsp;</td><td></td><td></td><td></td></tr></tbody></table>

a simple non-invasive method for temporary knockdown of upper limb proprioception

Proprioception may be the least well measured of all contributors to the neural control of movement. New precise, reliable measures of proprioception are needed for clinical diagnosis of impairment, and to measure outcomes of proprioceptive training. The purpose of this simple, non-invasive method is to temporarily knockdown upper limb proprioception in healthy adults, to an extent that would be useful in the development and testing of upper limb proprioception measures. Knockdown models have two main advantages over studying humans with impaired proprioception: participant availability and the ability to control the extent of impairment across participants. Current published methods of temporary proprioception knockdown of the upper limb, such as ischemic nerve blocks and cryotherapy, are invasive, impractical, or uncomfortable for the participant. Here, vibration over the ulnar groove was used to reduce upper limb proprioception. High frequency vibration may reduce proprioceptive acuity by inhibiting pacinian corpuscle-induced input. The effect of vibration used in this protocol was confirmed using two quantitative measures. This method was simple to administer, comfortable for participants, and practical.

Using the protocol presented here, we tested 20 healthy adults, 8 were male (mean age (SD)= 32.5 (12.5) years; 19 right-, and 1 left- handed). The participants had no known pathology involving the upper extremities. Handedness was assessed using the Edinburgh Handedness Inventory.24 Study participants reported no adverse events.
Both upper limbs of each participant were tested using the VDT and the tBKT at two separate sessions, one week apart. VDT, as described in the protocol, was quantified at the distal biceps tendon. The mean of three trials was used for analysis. For the tBKT, mean absolute error across 20 trials was used for analysis. At test session two, participants completed the same measures under the condition of temporary proprioception knockdown. ThePearson product-moment correlation (r) evaluated the test-retest reliability of the Vibration Detection Threshold (VDT). A statistically significant moderate to good relationship was found between the testing time points for the right (r = 0.64, p = 0.002, n = 20) and left (r = 0.61, p = 0.004, n = 20) upper limbs (Figure 4). The intraclass correlation coefficient (ICC) for the right VDT was (ICC 1, 3) = 0.77, n = 20, for the left VDT was (ICC 1, 3) = 0.76, n = 20. The standard error of measurement for the right VDT was 0.96 seconds, 95% CI = 6.5-10.3 s, the Minimum Detectable Difference (MDD) was 2.2 s. For the left VDT, the standard error of measurement was 0.83 s, 95% CI = 6.7-9.9 s, the MDD was 1.9 s. The intraclass correlation coefficient (ICC) for the right tBKT was (ICC 1, 3) = 0.55, n = 20, for the left tBKT was (ICC 1, 3) = 0.72, n = 20.
To test the directional hypothesis that proprioception knockdown (PK) using vibration would result in proprioception impairment, one-tailed paired t-tests were used to compare mean error between week 1, week 2 and the PK conditions for the VDT and BKT. The proprioception knockdown protocol resulted in statistically poorer scores on the VDT and the tBKT for both upper limbs, while the control conditions were not statistically different (Figures 5 and 6).
The extent of proprioception knockdown that resulted from the protocol was quantified by calculating the effect size (Cohen&#39;s d). The effect size on the VDT was d = 4.04 for the right upper limb and d = 4.24 for the left. For the tBKT d= 0.68 and 0.56 for the right and left, respectively.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/57218/57218fig1.jpg" /> 
Figure 1: Raynaud&#39;s phenomenon. An example of Raynaud&#39;s phenomenon caused by vibration. <a href="/files/ftp_upload/57218/57218fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/57218/57218fig2.jpg" /> 
Figure 2: Vibration site for proprioception knockdown. The location of vibration in this protocol is on the dorsum of the elbow within the ulnar groove just superior to a line between the olecranon process and the medial epicondyle. <a href="/files/ftp_upload/57218/57218fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/57218/57218fig3.jpg" /> 
Figure 3: Site for placement of the tuning fork for the Vibration Detection Test. For this study the Vibration Detection Threshold of the distal biceps tendon was quantified using a 128 Hz tuning fork. <a href="/files/ftp_upload/57218/57218fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/57218/57218fig4.jpg" /> 
Figure 4: Correlation of VDT between week 1 and 2. Using data from participants tested under normal conditions one week apart the Pearson product-moment correlation (r) was used to evaluated test-retest reliability of the Vibration Detection Threshold (VDT). A statistically significant moderate to good relationship was found between the testing time points for the right (r = 0.64, p = 0.002) and left (r = 0.61, p = 0.004) upper limbs.
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/57218/57218fig5.jpg" /> 
Figure 5: Comparison in VDT between week 1, 2 and PK conditions. One-tailed, paired t-tests were used to compare the mean time in seconds on the Vibration Detection Threshold (VDT) between week 1, week 2 and the proprioception knockdown (PK) conditions (n=20). Error bars show the standard deviation. (*) p-value &#60; 0.001.
<img alt="Figure 6" class="xfigimg" src="/files/ftp_upload/57218/57218fig6.jpg" /> 
Figure 6: Comparison in BKT between week 1, 2 and PK conditions. One-tailed, paired t-tests were used to compare mean error in centimeters on the tablet version of the Brief Kinesthesia Test (BKT) between week 1, week 2 and the proprioception knockdown (PK) conditions (n = 20). Error bars show the standard deviation. (*) p-value &#60; 0.001; (**) p-value = 0.001; NS = Not statistically significant.

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A Simple Non-invasive Method for Temporary Knockdown of Upper Limb Proprioception

The goal of this protocol is to demonstrate a practical method to temporarily interfere with proprioception in the upper limb of healthy humans.

Proprioception may be the least well measured of all contributors to the neural control of movement. New precise, reliable measures of proprioception are ...

a-simple-non-invasive-method-for-temporary-knockdown-upper-limb

Nanyang Technological University

Research

JoVE Journal

Behavior

9.4K Views.  The College of St. Scholastica. Het doel van dit protocol is om aan te tonen van een praktische methode om tijdelijk verstoren proprioceptie in de bovenste extremiteit van gezonde mensen.

Video: A Simple Non-invasive Method for Temporary Knockdown of Upper Limb Proprioception

Functional Near Infrared Spectroscopy of the Sensory and Motor Brain Regions with Simultaneous Kinematic and EMG Monitoring During Motor Tasks

There are several advantages that functional near-infrared spectroscopy (fNIRS) presents in the study of the neural control of human movement. It is relatively flexible with respect to participant positioning and allows for some head movements during tasks. Additionally, it is inexpensive, light weight, and portable, with very few contraindications to its use. This presents a unique opportunity to study functional brain activity during motor tasks in individuals who are typically developing, as well as those with movement disorders, such as cerebral palsy. An additional consideration when studying movement disorders, however, is the quality of actual movements performed and the potential for additional, unintended movements. Therefore, concurrent monitoring of both blood flow changes in the brain and actual movements of the body during testing is required for appropriate interpretation of fNIRS results. Here, we show a protocol for the combination of fNIRS with muscle and kinematic monitoring during motor tasks. We explore gait, a unilateral multi-joint movement (cycling), and two unilateral single-joint movements (isolated ankle dorsiflexion, and isolated hand squeezing). The techniques presented can be useful in studying both typical and atypical motor control, and can be modified to investigate a broad range of tasks and scientific questions.

Monitoring brain activity during upright motor tasks is of great value when investigating the neural source of movement disorders. Here, we demonstrate a protocol that combines functional near infrared spectroscopy with continuous monitoring of muscle and kinematic activity during 4 types of motor tasks.

There are several advantages that functional near-infrared spectroscopy (fNIRS) presents in the study of the neural control of human movement. It is ...

The Knob Supination Task: A Semi-automated Method for Assessing Forelimb Function in Rats

Tasks that accurately measure dexterity in animal models are critical to understand hand function. Current rat behavioral tasks that measure dexterity largely use video analysis of reaching or food manipulation. While these tasks are easy to implement and are robust across disease models, they are subjective and laborious for the experimenter. Automating traditional tasks or creating new automated tasks can make the tasks more efficient, objective, and quantitative. Since rats are less dexterous than primates, central nervous system (CNS) injury produces more subtle deficits in dexterity, however, supination is highly affected in rodents and crucial to hand function in primates. Therefore, we designed a semi-automated task that measures forelimb supination in rats. Rats are trained to reach and grasp a knob-shaped manipulandum and turn the manipulandum in supination to receive a reward. Rats can acquire the skill within 20 &plusmn; 5 days. While the early part of training is highly supervised, much of the training is done without direct supervision. The task reliably and reproducibly captures subtle deficits after injury and shows functional recovery that accurately reflects clinical recovery curves. Analysis of data is performed by specialized software through a graphical user interface that is designed to be intuitive. We also give solutions to common problems encountered during training, and show that minor corrections to behavior early in training produce reliable acquisition of supination. Thus, the knob supination task provides efficient and quantitative evaluation of a critical movement for dexterity in rats.

This manuscript describes a semi-automated task that quantifies supination in rats. Rats reach, grasp, and supinate a spherical manipulandum. The rat is rewarded with a pellet if the turn angle exceeds a criterion set by the user. This task increases throughput, sensitivity to injury, and objectivity compared to traditional tasks.

Tasks that accurately measure dexterity in animal models are critical to understand hand function. Current rat behavioral tasks that measure dexterity ...

A Standardized Method for Measurement of Elbow Kinesthesia

Proprioception is an important component of controlled movement. The threshold to detection of passive movement (TDPM) is a commonly used method for quantifying the proprioceptive submodality of kinesthesia in research settings. The TDPM paradigm has been found to be valid and reliable; however, the equipment and methods used for TDPM vary between studies. In particular, the research laboratory apparatuses for producing passive movement of an extremity are often custom designed by individual laboratories or inaccessible due to high cost. There is a need for a standardized, valid, and reliable method for measuring TDPM using readily available equipment. The purpose of this protocol is to provide a standardized method for measurement of TDPM at the elbow that is economical, easy to administer, and that produces quantitative results for measurement purposes in research-based settings. This method was tested on 20 healthy adults without neurological impairment, and eight adults with chronic stroke. The results obtained suggest this method is a reliable way to quantify elbow TDPM in healthy adults, and provides initial support for validity. Researchers seeking a balance between equipment affordability and measurement precision are most likely to find this protocol of benefit.

Here, we present a standardized method for measurement of elbow passive kinesthesia using the threshold to detection of passive movement (TDPM) that is appropriate for a research setting.

Proprioception is an important component of controlled movement. The threshold to detection of passive movement (TDPM) is a commonly used method for ...

Measuring Contralateral Silent Period Induced by Single-Pulse Transcranial Magnetic Stimulation to Investigate M1 Corticospinal Inhibition

Contralateral silent period (cSP) is a period of suppression in the background electrical muscle activity captured by electromyography (EMG) after a motor evoked potential (MEP). To obtain this, an MEP is elicited by a suprathreshold transcranial magnetic stimulation (TMS) pulse delivered to the primary motor cortex (M1) of the target muscle selected, while the participant provides a standardized voluntary target muscle contraction. The cSP is a result of inhibitory mechanisms that occur after the MEP; it provides a broad temporal assessment of spinal inhibition in its initial ~50 ms, and cortical inhibition after. Researchers have tried to better understand the neurobiological mechanism behind the cSP to validate it as a potential diagnostic, surrogate, and predictive biomarker for different neuropsychiatric diseases. Therefore, this article describes a method to measure M1 cSP of lower and upper limbs, including a selection of target muscle, electrode placement, coil positioning, method of measuring voluntary contraction stimulation, intensity setup, and data analysis to obtain a representative result. It has the educational objective of giving a visual guideline in performing a feasible, reliable, and reproducible cSP protocol for lower and upper limbs and discussing practical challenges of this technique.

Contralateral silent period (cSP) assessment is a promising biomarker to index cortical excitability and treatment response. We demonstrate a protocol to assess cSP intended for studying M1 corticospinal inhibition of upper and lower limbs.

Contralateral silent period (cSP) is a period of suppression in the background electrical muscle activity captured by electromyography (EMG) after a motor ...

Neuroscience

Open-Source Real-Time Closed-Loop Electrical Threshold Tracking for Translational Pain Research

Nociceptors are a class of primary afferent neurons that signal potentially harmful noxious stimuli. An increase in nociceptor excitability occurs in acute and chronic pain conditions. This produces abnormal ongoing activity or reduced activation thresholds to noxious stimuli. Identifying the cause of this increased excitability is required for the development and validation of mechanism-based treatments. Single-neuron electrical threshold tracking can quantify nociceptor excitability. Therefore, we have developed an application to allow such measurements and demonstrate its use in humans and rodents. APTrack provides real-time data visualization and action potential identification using a temporal raster plot. Algorithms detect action potentials by threshold crossing and monitor their latency after electrical stimulation. The plugin then modulates the electrical stimulation amplitude using an up-down method to estimate the electrical threshold of the nociceptors. The software was built upon the Open Ephys system (V0.54) and coded in C++ using the JUCE framework. It runs on Windows, Linux, and Mac operating systems. The open-source code is available (<a data-saferedirecturl="https://www.google.com/url?q=https://github.com/Microneurography/APTrack&amp;source=gmail&amp;ust=1680789829274000&amp;usg=AOvVaw0nMk9J_EI2jUn8SlmC5JJm" href="https://github.com/Microneurography/APTrack" target="_blank">https://github.com/Microneurography/APTrack</a>). The electrophysiological recordings were taken from nociceptors in both a mouse skin-nerve preparation using the teased fiber method in the saphenous nerve and in healthy human volunteers using microneurography in the superficial peroneal nerve. Nociceptors were classified by their response to thermal and mechanical stimuli, as well as by monitoring the activity-dependent slowing of the conduction velocity. The software facilitated the experiment by simplifying the action potential identification through the temporal raster plot. We demonstrate real-time closed-loop electrical threshold tracking of single-neuron action potentials during&#160;in vivo&#160;human microneurography, for the first time, and during&#160;ex vivo&#160;mouse electrophysiological recordings of C-fibers and A&#948;-fibers. We establish proof of principle by showing that the electrical threshold of a human heat-sensitive C-fiber nociceptor is reduced by heating the receptive field. This plugin enables the electrical threshold tracking of single-neuron action potentials and allows the quantification of changes in nociceptor excitability.

APTrack is a software plugin developed for the Open Ephys platform that enables real-time data visualization and the closed-loop electrical threshold tracking of neuronal action potentials. We have successfully used this in microneurography for human C-fiber nociceptors and mouse C-fiber and A&#948;-fiber nociceptors.

Nociceptors are a class of primary afferent neurons that signal potentially harmful noxious stimuli. An increase in nociceptor excitability occurs in ...

Treatment of Phantom Limb Pain by Remote Transcranial Direct Current Stimulation

Using Home-based, Remotely Supervised, Transcranial Direct Current Stimulation for Phantom Limb Pain

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low-amplitude direct currents to alter cortical excitability. Previous trials have established the safety and tolerability of tDCS, and its potential to mitigate symptoms. However, the effects are cumulative, making it more difficult to have adherence to the treatment since frequent visits to the clinic or outpatient center are required. Moreover, the time needed for transportation to the center and the related expenses limit the accessibility of the treatment for many participants.
Following guidelines for remotely supervised transcranial direct current stimulation (RS-tDCS) implementation, we propose a protocol designed for remotely supervised and home-based participation that uses specific devices and materials modified for patient use, with real-time monitoring by researchers through an encrypted video conferencing platform. We have developed detailed instructional materials and structured training procedures to allow for self- or proxy-administration while supervised remotely in real time. This protocol has a specific design to have a series of checkpoints during training and execution of the visit. This protocol is currently in use in a large pragmatic study of RS-tDCS for phantom limb pain (PLP). In this article, we will discuss the operational challenges of conducting a home-based RS-tDCS session and show methods to enhance its efficacy with supervised sessions.

Author Spotlight: Insights into Remotely Supervised Neuromodulation Procedure for Phantom Limb Pain

The goal of this study is to describe a protocol for the home-based delivery of remotely supervised transcranial direct current stimulation (RS-tDCS) conserving the standard procedures of in-clinic practice, including safety, reproducibility, and tolerability. The participants included will be patients with phantom limb pain (PLP).

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low-amplitude direct currents to alter cortical ...

An Experimental Approach to Induce Trips in Lower-Limb Amputees

Reestablishing balance after a trip is challenging for lower-limb amputees and often results in a fall. The effectiveness of reestablishing balance following a trip depends on factors such as amputation level (transtibial or transfemoral) or which limb is tripped (prosthetic or sound/lead or trailing). Understanding the recovery responses can help identify strategies to avoid a trip becoming a fall and what trip-response functionality could be designed into a prosthesis. This study presents an experimental approach for inducing unexpected trips in individuals with amputation. Tripping was manually triggered by activating an electromagnetic device to raisea polypropylene wire to obstruct (bring to a near halt) theswinging limb during its mid-swing phase. A safety harness attached to a ceiling rail ensured participants did not hit the ground if they failed to reestablish balance following the trip (i.e., it prevented a fall from occurring). One transtibial amputee completed repeated walking trials in which a trip was induced around 1 out of 15 times to avoid it being anticipated. 3D kinematics were determined via two smartphones (60Hz) using the OpenCap software, highlighting that the experimental approach induced meaningful tripping/recovery responses dependent on which limb was tripped (prosthetic or sound). The presented methodology avoids using a rigid obstacle, potentially reducing the risk of injuries, and is inexpensive and easy to set up. Importantly it permits a trip to be unexpectedly introduced during the mid-swing phase of the gait and hence provides an approach for identifying real-world trip recovery responses. When tripping the sound limb, participants could &#39;disentangle&#39; from the trip-wire (post-trip) by plantarflexing the ankle, but such action was not possible when tripping the prosthetic limb.

An experimental approach was developed to induce trips in lower-limb amputees. The goal was to create unexpected trips and induce meaningful tripping/recovery responses. The kinematic data from one transtibial amputee confirmed that such an approach effectively elicits reactive trip recovery responses.

Reestablishing balance after a trip is challenging for lower-limb amputees and often results in a fall. The effectiveness of reestablishing balance ...

Medicine

Functional OT and Near-IR Spectroscopy to Study Brain Function Remodeling

Investigating the Effect of Different Types of Exercise on Upper Limb Functional Recovery in Patients with Right Hemisphere Damage Based on fNIRS

To investigate the effects of functional occupational therapy (FOT) combined with different types of exercise on upper limb motor function recovery and brain function remodeling in patients with right hemisphere damage (RHD) by analyzing functional near-infrared spectroscopy (fNIRS). Patients (n = 32) with RHD at Beijing Bo'ai Hospital were recruited and randomly allocated to receive either FOT combined with passive motion (N=16) or FOT combined with assisted active movement (N=16). The passive motion group (FOT-PM) received functional occupational therapy for 20 min and passive exercise for 10 min in each session, while the assisted active movement group (FOT-AAM) received functional occupational therapy for 20 min and assisted active exercise for 10 min. Both groups received conventional drug therapy and other rehabilitation therapy. Treatment was performed once a day, 5 times a week for 4 weeks. The recovery of motor function and activities of daily living (ADL) was assessed using Fugl-Meyer Assessment upper extremity (FMA-UE) and modified Barthel index (MBI) before and after treatment, and brain activation of the bilateral motor area was analyzed with fNIRS. The findings suggested that FOT combined with AAM was more effective than FOT combined with PM in improving the motor function of RHD patients' upper limbs and fingers, improving their ability to perform activities of daily living, and facilitating brain function remodeling of the motor area.

Author Spotlight: Advancing Upper Limb Rehabilitation in Patients with Right Hemisphere Damage Using Assisted Active Exercise

Here, we investigate the effect of functional occupational therapy combined with assisted active or passive motion on the upper limb function of patients with right hemisphere damage and explore the effect of functional near-infrared spectroscopy on brain function remodeling.

To investigate the effects of functional occupational therapy (FOT) combined with different types of exercise on upper limb motor function recovery and ...

Terminal H-reflex Measurements in Mice

The Hoffmann reflex (H-reflex), as an electrical analog to the stretch reflex, allows electrophysiological validation of the integrity of neural circuits after injuries such as spinal cord damage or stroke. An increase of the H-reflex response, together with symptoms like non-voluntary muscle contractions, pathologically augmented stretch reflex, and hypertonia in the corresponding muscle, is an indicator of post-stroke spasticity (PSS).
In contrast to rather nerve-unspecific transcutaneous measurements, here, we present a protocol to quantify the H-reflex directly at the ulnar and median nerves of the forepaw, which is applicable, with minor modifications, to the tibial and sciatic nerve of the hindpaw. Based on the direct stimulation and the adaptation to different nerves, the method represents a reliable and versatile tool to validate electrophysiological changes in spasticity-related disease models.

The clinical evaluation of spasticity based on the Hoffmann reflex (H-reflex) and using electrical stimulation of peripheral nerves is an established method. Here, we provide a protocol for a terminal and direct nerve stimulation for H-reflex quantification in the mouse forepaw.

The Hoffmann reflex (H-reflex), as an electrical analog to the stretch reflex, allows electrophysiological validation of the integrity of neural circuits ...

Biology

Dual Upper Limb Robotic Training in Stroke Rehabilitation

Application of a Dual Upper Limb Task-Oriented Robotic System for the Functional Recovery of the Upper Limb in Stroke Patients

Highly repetitive and task-oriented training has been shown to promote the recovery of limb function in stroke patients. Additionally, bilateral arm training can help stroke survivors regain their upper limb function and improve their daily activities. The dual upper limb task-oriented robotic system is designed to assist the healthy side of the stroke patient in driving the affected side to perform bilateral arm training through the use of a robotic device. It can also guide the patient in carrying out dual upper limb coordinated movements and engage them in a task-oriented virtual game using force feedback and human-computer interaction technology. This study aimed to assess the efficacy of the system in enhancing upper limb function and activities of daily living in stroke patients. The assessment methods used included motor evoked potential (MEP), functional test for the hemiplegic upper extremity-Hong Kong (FTHUE-HK), Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE), and modified Barthel index (MBI). The results of the study indicate that the dual upper limb task-oriented robotic system can significantly improve the corticospinal pathway, upper limb function, and activities of daily living in stroke patients after 6 weeks of treatment. This system can serve as an effective adjunct to upper limb functional rehabilitation in stroke survivors, reducing the dependence on rehabilitation therapists. In conclusion, the dual upper limb task-oriented robotic system provides a new strategy for post-stroke limb functional rehabilitation and holds great potential for application, as it offers certain social and financial benefits.

Author Spotlight: Enhancing Upper Limb Rehabilitation in Stroke Patients Through Advanced Robotic and Neuromodulation Technologies

This experimental protocol outlines the use of a dual upper limb task-oriented robotic system for stroke patients with upper limb dysfunction. The findings indicate that this system can significantly improve stroke patients' upper limb function and daily living activities.

Highly repetitive and task-oriented training has been shown to promote the recovery of limb function in stroke patients. Additionally, bilateral arm ...

A Simple Non-invasive Method for Temporary Knockdown of Upper Limb Proprioception

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