Name: State-Dependency Effects on TMS: A Look at Motive Phosphene Behavior (Video) | JoVE Journal
Uploaded: 2010-12-28T18:00:00.000+00:00
Duration: 12 min 38 s
Description: Explore state dependency effects on TMS-induced phosphene behavior using visual adaptation. This method reveals how priming neural pathways with specific stimuli influences predictable phosphene responses in neuroscience research.

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5 minutes

1)	Preparation
<ol>
<li>To begin, seat the subject in a comfortable chair in front of a computer screen.</li>
<li>Use a tape measure to ensure the distance between the screen and the subject's nasion is 60 cm.</li>
<li>Finally, place a light-blocking mask over the subject's eyes.</li>
</ol>
2) Determining Phosphene Threshold over V1/V2
<ol>
<li>Knowing the subject's phosphene threshold will be important when exploring phosphenic behavior later in this protocol. To determine this threshold, first set the TMS machine to 70% power.</li>
<li>Hold the coil so the top of the figure-8 faces cranial midline.</li>
<li>Begin single-pulse stimulation at a point about 3 cm above the inion.</li>
<li>After each pulse, ask the subject to report any phosphenic experience.</li>
<li>Begin moving the coil in a small search grid around this region (V1/V2).</li>
<li>Determine the location where stimulation elicits consistent and unambiguous phosphene reports from the subject. It has been theorized that TMS will be unable to elicit phosphenes in around 40% of the population, so there is a chance the subject will not report anything. If this is the case, unfortunately, this experiment will not work. The subject should be allowed to leave.</li>
<li>Once the phosphenic "hotspot" has been located, adjust the TMS power output up and down until the subject reports phosphenes for exactly 3 of 6 consecutive pulses. This power level is the subject's V1/V2 threshold. If available, neuronavigation can be used to achieve greater spatial precision when locating and targeting the V1/V2 hotspot.</li>
</ol>
3) Determining Phosphenic Threshold over the V5/MT+ Complex
<ol>
<li>Using the same aforementioned procedure and parameters, we will now determine phosphene threshold over the V5/MT+ complex. To locate this region, begin at a point 3 cm dorsal and 5 cm lateral to the subject's inion.</li>
<li>After each pulse, ask the subject to report any phosphenic experience.</li>
<li>Again, using single pulses, begin a small search grid pattern until unambiguous and consistent phosphenes are elicited.</li>
<li>Finally, adjust the TMS power output up and down until the subject reports phosphenes for exactly 3 of 6 consecutive pulses. This power level is the subject's V5/MT+ complex threshold. Again, if available, neuronavigation can be used to achieve greater spatial precision when locating and targeting the V5/MT+ hotspot.</li>
</ol>
4)	Determining Baseline Phosphene Behavior
<ol>
<li>Once phosphene threshold has been determined for both visual areas, we need to measure baseline phosphenic behavior. To do this, first remove the subject's light-blocking mask.</li>
<li>Next, instruct the subject to stare at a stable fixation cross presented in the center of the computer screen for 60 seconds.</li>
<li>Replace the mask and, over the V1/V2 hot spot, generate a single pulse train for 3-seconds at 120% V1/V2 threshold.</li>
<li>Wait five-seconds and conduct another train.</li>
<li>Again, wait five-seconds and conduct a third train.</li>
<li>After the third single pulse train, ask the subject to describe the location and motive characteristics of any elicited phosphenes. This will be the baseline.</li>
<li>Repeat this same procedure over the V5/MT+ hot spot (remember to reset the TMS power to 120% of the V5/MT+ threshold).</li>
</ol>
5) Condition Number One
<ol>
<li>Once the phophenic baseline has been determined, remove the subject's light-blocking mask once again.</li>
<li>Instruct the subject to stare at a stable fixation cross presented in the center of the computer screen for 60 seconds. This time, rather than a blank screen, we will embed a series of moving dots at several locations around the cross. 
<img src="/files/ftp_upload/2273/2273fig1.jpg" alt="Vector field diagram illustrating fluid dynamics with directional flow arrows." data-altupdatedat="1788235205000" data-alt="Figure 1"> 
Figure 1. Adapting stimuli for condition one: simple translational motion. All dots move coherently either to the left or right. 
Make sure all the dots are moving in the same direction. This stimulus should serve to engender visual adaptation: a phenomenon in which changes in neural excitability as induced by prolonged exposure to a stimuli serves to bias the perception of subsequently presented stimuli.</li>
<li>After 60 seconds, replace the mask and, over the V1/V2 hotspot, generate a single pulse train for 3 seconds at 120% V1/V2 threshold.</li>
<li>Wait five-seconds and repeat two more times.</li>
<li>After three trains, ask the subject to report the locations and motive characteristics of any elicited phosphenes. If available, the use of an eye movement tracking system in a dark room can help achieve greater precision and quantitative monitoring of the eye movements made by subjects during phosphene elicitations.</li>
<li>Continue this three-train/report sequence until phosphene behavior returns to baseline activity.</li>
<li>Repeat this procedure for the V5/MT+ complex hotspot.</li>
</ol>
6)	Condition Number Two
<ol>
<li>In this second condition, repeat the same procedure utilized for condition one. This time, however, rather than presenting the subject with a series of dots moving in a singular direction, present the subject with a series of dots each moving in its relative cardinal direction away from a central point - similar to a "star burst" pattern. 
<img src="/files/ftp_upload/2273/2273fig2.jpg" alt="Static equilibrium diagram, ΣFx=0, force vectors, visual representation of balance in mechanical systems." data-altupdatedat="1788235205000" data-alt="Figure 2"> 
Figure 2. Adapting stimuli for condition two: radial motion. Dots move in respective cardinal directions either towards or away from a central point.</li>
<li>As before, after 60 seconds, replace the mask, conduct a series of three, 120% threshold trains over V1/V2, ask for a subject report, and continue until baseline returns.</li>
<li>Repeat for V5/MT+.</li>
</ol>
7) Diagram
<ol>
<li>As an option, after each condition (or after all conditions are completed), ask the subject to draw the regions and motive behavior of each series of phopsphenes onto a graph. This is not an integral step but will supply you with another set of interpretable data.</li>
</ol>
8) Representative Results

Visual adaptation to the uni-directional motive stimuli should elicit an identical phosphenic movement over V1/V2. 
<img src="/files/ftp_upload/2273/2273fig3.jpg" alt="Phosphene adaptation diagrams: pre and post-adaptation, visual perception study analysis." data-altupdatedat="1788235205000" data-alt="Figure 3"> 
Figure 3. Examples of phosphenes induced from V1/V2 in the right and left hemisphere during condition one (based on the drawings of subjects). 
The V5/MT+ complex phosphenes should also be affected, such that the phosphene now will appear as a sum of the motion direction in the adapting stimulus and the baseline phosphene.
However, visual adaptation to the starburst pattern should elicit an identical starburst phosphenic movement from the V5/MT+ complex, but should not change the V1/V2 baseline. 
<img src="/files/ftp_upload/2273/2273fig4.jpg" alt="Phosphenes adaptation diagram; pre- and post-adaptation circular data with directional vectors." data-altupdatedat="1788235205000" data-alt="Figure 4"> 
Figure 4. Examples of phosphenes induced from the V5/MT+ complex in the right and left hemisphere during condition two (based on the drawings of subjects).

<ol><li>Pascual-Leone, A., Davey, M., Wassermann, E. M., Rothwell, J., Puri, B. <a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=author%3aPascual-Leone%2C+A+%22Handbook+of+Transcranial+Magnetic+Stimulation%22">Handbook of Transcranial Magnetic Stimulation</a>. , Edward Arnold. London. (2002).</li>
<li>Walsh, V., Pascual-Leone, A. <a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=author%3aWalsh%2C+V+%22Transcranial+Magnetic+Stimulation%3A+A+Neurochronometrics+of+Mind%22">Transcranial Magnetic Stimulation: A Neurochronometrics of Mind</a>. , MIT Press. Cambridge. (2005).</li>
<li>Silvanto, J., Muggleton, N. G., Cowey, A., Walsh, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Neural+adaptation+reveals+state-dependent+effects+of+transcranial+magnetic+stimulation%5BTitle%5D)+AND+%22European+Journal+of+Neuroscience%22%5BJournal%5D)">Neural adaptation reveals state-dependent effects of transcranial magnetic stimulation.</a> European Journal of Neuroscience. 25, 1874-1881 (2007).</li>
<li>Silvanto, J., Pascual-Leone, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((State-Dependency+of+Transcranial+Magnetic+Stimulation%5BTitle%5D)+AND+%22Brain+Topography%22%5BJournal%5D)">State-Dependency of Transcranial Magnetic Stimulation.</a> Brain Topography. 21, 1-10 (2008).</li>
<li>Silvanto, J., Cattaneo, Z., Battelli, L., Pascual-Leone, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Baseline+cortical+excitablility+determines+whether+TMS+disrupts+or+facilitates+behavior%5BTitle%5D)+AND+%22Journal+of+Neurophysiology%22%5BJournal%5D)">Baseline cortical excitablility determines whether TMS disrupts or facilitates behavior.</a> Journal of Neurophysiology. 99, 2725-2730 (2008).</li>
<li>Silvanto, J., Muggleton, N. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Testing+the+validity+of+the+TMS+state-dependency+approach%3A+targeting+functionally+distinct+motion-selective+neural+populations%5BTitle%5D)+AND+%22Neuroimage%22%5BJournal%5D)">Testing the validity of the TMS state-dependency approach: targeting functionally distinct motion-selective neural populations.</a> Neuroimage. 40, 1841-1848 (2008).</li>
<li>Tootell, R. B., Rappas, J. B., Kwong, K. K., Malach, R., Born, R. T., Brady, T. J., Rosen, B. R., Belliveau, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Functional+analysis+of+human+MT+and+related+visual+cortical+areas+using+magnetic+resonance+imaging%5BTitle%5D)+AND+%22Journal+of+Neuroscience%22%5BJournal%5D)">Functional analysis of human MT and related visual cortical areas using magnetic resonance imaging.</a> Journal of Neuroscience. 15, 3215-3230 (1995).</li>
<li>Singh, K. D., Smith, A. T., Greenlee, M. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Spatiotemporal+frequency+and+direction+sensitivities+of+human+visual+areas+measured+using+fMRI%5BTitle%5D)+AND+%22Neuroimage%22%5BJournal%5D)">Spatiotemporal frequency and direction sensitivities of human visual areas measured using fMRI.</a> Neuroimage. 12, 550-564 (2000).</li>
<li>Rutchmann, R. M., Schrauf, M., Greenlee, M. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Brain+activation+during+dichoptic+presentation+of+optic+flow+stimuli%5BTitle%5D)+AND+%22Exp+Brain+Res%22%5BJournal%5D)">Brain activation during dichoptic presentation of optic flow stimuli.</a> Exp Brain Res. 134, 533-537 (2000).</li>
<li>Morrone, M. C., Tosetti, M., Montanaro, D., Fiorentini, A., Cioni, G., Burr, D. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+cortical+area+that+responds+specifically+to+optic+flow+revealed+by+fMRI%5BTitle%5D)+AND+%22Nat.+Neuroscience%22%5BJournal%5D)">A cortical area that responds specifically to optic flow revealed by fMRI.</a> Nat. Neuroscience. 3, 1322-1328 (2000).</li>
</ol>

No conflicts of interest declared.

This experiment gets at the heart of state dependency. Neurons in V1/V2 are thought to correspond with simple, directional movement.7,8 Therefore, adaptation to the uni-directional motive stimuli increased the excitability of neurons registering this movement - as such, they should be the first to react to the TMS pulse. The V5/MT+ complex also contains neurons tuned to simple translational motion, therefore the phosphenes induced from this region should also be affected by the adapting stimulus. However, th...

<table><tbody><tr><td>Light Blocking Eye Mask</td><td></td><td></td><td></td></tr><tr><td>Ear Plugs</td><td></td><td></td><td></td></tr><tr><td>Swim Cap</td><td></td><td></td><td></td></tr><tr><td>Marker</td><td></td><td></td><td></td></tr><tr><td>Tape Measure</td><td></td><td></td><td></td></tr><tr><td>Blank Graph Paper</td><td></td><td></td><td></td></tr><tr><td>Stimuli Developed &amp;amp; Presented on Computer using Adobe Photoshop</td><td></td><td></td><td></td></tr><tr><td>Any Single Pulse Capable TMS Device</td><td></td><td></td><td></td></tr><tr><td>Any Figure-of-Eight Coil</td><td></td><td></td><td></td></tr></tbody></table>

state-dependency effects on tms:  a look at motive phosphene behavior

State-Dependency Effects on TMS:  A Look at Motive Phosphene Behavior

Transcranial magnetic stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability (either increasing or decreasing it) via the application of localized magnetic field pulses.1,2 Within the field of TMS, the term state dependency refers to the initial, baseline condition of the particular neural region targeted for stimulation. As can be inferred, the effects of TMS can (and do) vary according to this primary susceptibility and responsiveness of the targeted cortical area.3,4,5

In this experiment, we will examine this concept of state dependency through the elicitation and subjective experience of motive phosphenes. Phosphenes are visually perceived flashes of small lights triggered by electromagnetic pulses to the visual cortex. These small lights can assume varied characteristics depending upon which type of visual cortex is being stimulated. In this particular study, we will be targeting motive phosphenes as elicited through the stimulation of V1/V2 and the V5/MT+ complex visual regions.6

In this article, we examine the effects of visually relevant state dependency on TMS induced motive phosphenic presentations.

Transcranial magnetic stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate ...

The overall goal of this procedure is to explore state dependency effects on phos phenic behavior as elicited through transcranial magnetic stimulation. This is accomplished by first determining baseline phos threshold and behavior over both V one, V two and V five MT plus. The second step of the procedure is to prime specific neural reactions via visual adaptation as achieved through the presentation of specific visual stimuli.The third step of the procedure is to determine new phosphoric behavior over both V one V two and V five MT plus. The final step of the procedure is to chart and compare the second set of induced phosphines with the original baseline set of phosphines. Ultimately, results can be obtained that show specific predictable phosphine behavior can be engendered through visual adaptation to unique visual stimuli.The implications of this technique extend to therapy for numerous neurological or physical melodies currently treated by TMS as it reveals. Guided activity undertaken before therapeutic treatment such as light physical therapy or psychotherapy may have important and predictable effects upon TMS and its outcomes. To begin, seat the subject in a comfortable chair in front of a computer screen adjacent to the TMS setup.Take a moment to explain the details of the experiment and be sure to screen the subject to assure that there are no counter indications to TMS at this point. Both the subject and the researcher should insert earplugs for hearing protection. Now, introduce the subject to the TMS machine by discharging a few pulses so that he or she can hear the clicking sound Again.There you go. And feel the tapping sensation so that the stimulation locations can be marked in subsequent steps. Place a swim cap over the patient's head assuring that it fits well and will not slip during the experiment.Next, use a tape measure to ensure the distance between the computer screen and the subject's nasion is 60 centimeters. Make sure the subject can remain seated comfortably for the rest of the experiment so that this distance does not change. Finally, place a light blocking mask over the subject's eyes.The mask should be adjusted to fit well with no light leaks so that phosphines can easily be detected and reported by the subject during the rest of the experiment. Next, the subject's phosphine threshold will need to be determined since knowing this will be important when exploring phosphoric behavior later in the protocol. To determine this threshold, first, set the TMS machine to 70%power.Now hold the coil so the top of the figure eight faces the cranial midline and to point about three centimeters above the inion and begin single pulse stimulation. Here we are stimulating the left hemisphere. Move the coil in a small search grid around this region to determine the location where stimulation elicits consistent and unambiguous phosphine reports from the subject.Oh, did you see anything? Yeah, it's kind of like a, like a blobby thing over here. However, keep in mind that TMS may be unable to elicit phosphines in around 40%of the population, so there is a chance that the subject will not report anything.If this is the case. Unfortunately, this experiment will not work and the subject should be allowed to leave. If a phos phenic hotspot can be located, be sure to mark this location on the subject scalp.Now adjust the TMS power output up and down until the subject reports phosphines for exactly three of six consecutive pulses. Record this power level as the subject's V one V two threshold. Next, using the same procedure and parameters as in the previous step, we will determine phosphine threshold over the V five mt plus complex to locate this region First, move the coil to a 0.3 centimeters dorsal and five centimeters lateral to the subjects in Ian.Now begin single pulse stimulation. See anything? And once again, after each pulse, ask the subject to report any phostic experience.Could you point to it and describe It's right here. It's a ball that goes Whoop. Again, using single pulses, begin a small search grid pattern.Moving the coil until unambiguous and consistent phosphines are elicited. Mark this location as the subject's V five MT plus hotspot. Finally adjust the TMS power output up and down until the subject reports phosphines for exactly three of six consecutive pulses.Record this power level as the subject's V five MT plus complex threshold. Once phosphine threshold has been determined for both visual areas, the subject's baseline phospho behavior will need to be measured. To do this, dim the lights in the room and remove the subject's light blocking mask.Now instruct the subject to stare at a stable fixation cross presented in the center of the computer screen for 60 seconds. It is important that the eyes remain centered on the cross. Replace the mask and over the V one V two hotspot.Generate a single pulse train for three seconds at 120%of the V one V two threshold. Then wait five seconds and conduct another train. Again, wait five seconds and then conduct a third train.After the third single pulse train, ask the subject to describe the location and motive characteristics of any elicited phosphines. Yeah, I saw just the same things we were talking about earlier. Just right over here.Just This will be the subject's baseline phosphine response Every time you zapping. Next, reset the TMS power to 120%of the V five empty plus threshold and move the coil over the V five empty plus hotspot. Repeat this same procedure in this location administering three pulse trains and record the elicited phosphine description here as well.Now that the phosphoric baseline has been determined, her game, remove the subject's light blocking mask and instruct the subject to stare at a stable fixation cross presented in the center of the computer screen for 60 seconds. However, rather than a blank screen this time, we will embed a series of moving dots at several locations around the cross, all moving in the same direction. This stimulus should serve to engender visual adaptation so that prolonged exposure to the stimuli should serve to bias the perception of subsequently presented stimuli.After 60 seconds, replace the mask and over the V one V two hotspot. Generate a single pulse train for three seconds at 120%of the V one V two threshold. Wait five seconds and repeat two more times.After these three trains, ask the subject to report the locations and motive characteristics of any elicited phosphines. Continue this three train report sequence until phosphine behavior returns to baseline activity. After V one V two phosphine behavior returns to baseline remove the subject's mask and again, have him watch the stimulus after 60 seconds, replace the mask.Finally move the stimulation coil to the V five empty plus complex hotspot and repeat this step in the protocol for this location. At 120%of the V five MT plus threshold stimulation for the second condition uses the same procedure as condition one. However, rather than presenting the subject with a series of dots moving in a single direction, present a series of dots each moving in its relative cardinal direction away from a central point similar to a starburst pattern as seen here as before.After 60 seconds, replace the mask. Conduct a series of three, 120%threshold trains over V one V two. Ask the subject to report phosphenes and continue until baseline returns.Once more, remove the mask and ask the subject to watch the starburst stimuli for 60 seconds. Then again, using the same stimulation parameters as the previous step, repeat this procedure for the V five mt plus hotspot.Okay. Could you describe To me what you Saw?Sure.It was like a, a starburst type, like a like a firework thing over here going As an option. After each condition or after both conditions are completed, ask the subject to draw the region's emotive behavior of each set of phosphines onto a graph. This is not an integral step, but it will provide another set of interpretable data.Here we again see the adapting stimuli for condition. One simple translational motion. All dots move coherently either to the left or right.The phosphines induced from V one V two in the right and left hemisphere. During condition one should elicit an identical phospho movement over V one V two as seen here. Here we see the adapting stimuli for condition two radial motion dots moving respective cardinal directions, either towards or away from a central point, and here we see example drawings of phosphines induced from the V five mt plus complex in the right and left hemisphere during condition two.Visual adaptation to the starburst pattern should elicit an identical starburst phospho movement from the V five mt plus complex, but should not change the V one V two baseline. After watching this video, you should have a good understanding of how to engender specific and predictable spheric behavior via visual adaptation before TMS stimulation. This is the essence of state dependency.Identical stimulation or identical neural regions can and will elicit varied responses depending upon the initial neural state of each subject.

state-dependency-effects-on-tms-a-look-at-motive-phosphene-behavior

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Explore state dependency effects on TMS-induced phosphene behavior using visual adaptation. This method reveals how priming neural pathways with specific stimuli influences predictable phosphene responses in neuroscience research.

State-Dependency Effects on TMS: A Look at Motive Phosphene Behavior

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