Day 11: As Thorough As Airport Security

I always hear jokes and stories about TSA agents and how they are very thorough when it comes to searching people. Similarly, I have molested Google, searching for a response to "What is TMS?" After more searches I found two websites other than Wikipedia that are informational about the TMS, and both are of great universities: University of Pennsylvania and Johns Hopkins University. These two universities actually offer TMS services to treat people with neuropsychiatric disorders. I don't know though if this service is limited to students only or available to the public. But if you'd like to learn more, here are the links to their websites:

1. http://www.med.upenn.edu/tms/overview.html
2. http://www.hopkinsmedicine.org/psychiatry/specialty_areas/brain_stimulation/tms/index.html.

Back to TMS...

Image belongs to Johns Hopkins Medicine

TMS stands for transcranial magnetic stimulation. It is a noninvasive procedure that stimulates areas of the brain through electromagnetic induction. A weak electric current is induced using a coil that "generates short magnetic pulses," similar to those of an MRI machine, that are able to go through the surface of the head and into the brain (Johns Hopkins Medicine). Because of the electromagnetic induction, the coil only needs to rest on the scalp. The image to the right is an example of TMS being employed on a patient.

There are two modes of stimulation: Single or paired pulse and repetitive.

• Single or paired pulse TMS is what my project uses. This mode of stimulation discharges an action potential and, if used on the primary motor cortex (M1, refer to Day 6), it produces muscle activity, which we measure as MEP (motor evoked potentials).
• Repetitive TMS (rTMS) is used more for therapeutic applications, treating neuropsychiatric disorders. The two universities, UPenn and Johns Hopkins, use this mode of stimulation for treatment. rTMS has effects that last longer than single/paired pulse TMS (Wikipedia).

There are so many more exciting things to learn about TMS that relates to my project, such as risks, techniques, and different kinds of coils, but I'd like to research more so that I will be able to explain it to my readers. Feel free to comment any questions. Until next time!

References:

1. Transcranial Magnetic Stimulation (TMS) Service. Johns Hopkins Medicine. http://www.hopkinsmedicine.org/psychiatry/specialty_areas/brain_stimulation/tms/index.html (accessed Feb 19, 2013).
2. Transcranial Magnetic Stimulation. Wikipedia. http://en.wikipedia.org/wiki/Transcranial_magnetic_stimulation (accessed Feb 19, 2013)

Day 9: Thumb's Up

Yesterday was especially exciting because I was allowed to play around with some of the equipment! The instruments that I used were the ones that measured muscle activity/excitability by measuring the voltages of finger muscles with electrodes (the black thing shown on my palm on the right and another shown on the back of my hand in the image to the left). To find where the muscle is so you can attach the electrode, you tense up the muscle. The muscles that I examined here are the first dorsal interroseus (FDI) and the abductor pollicis brevis (APB). Both of these muscles function to abduct (or move away from the body) the index finger and the thumb, respectively. The picture on the left above shows me abducting my index finger and stopping it with my thumb to emphasize the location of my FDI muscle where my FDI electrode is placed.

After setting up the system and running the program, I let the computer record the motor-evoked potentials (MEP, measured in millivolts) in those two muscles. The monitor displays these values on a graph of MEP vs. time. The top bumpy line measures APB activity and the bottom FDI. Throughout the time period during which I recorded data, I maintained a steady rhythm abducting my fingers, making it seem like the muscles had a steady pulse, as illustrated by the graph.

After abducting and resting and abducting and resting and abducting and resting these muscles for at least 5 minutes, I decided that I should add another finger muscle! So I end up adding my abductor digiti minimi (ADM), the abductor muscle of the pinky. I tape the electrode on there as shown in the picture below. It was around this time that one of my mentors tell me that people test the equipment on themselves before testing on others. I think he was trying to tell me that I'll be able to test on people! Not really. I wish he were though. The entire thing was quite informational for me.

Anyway, so the electrode is now attached to my FDI, APB, and ADM. What's that on your wrist? you might ask. Well that is a "dermatrode." I think it's an electrode that is used as a control for the muscle activity measurements. There might be extraneous movements in other muscles affecting the muscles being measured so this helps remove those anomalies. So here is an image of the graphs (to the right). The first static-y line represents the MEP of the ADM, second APB, third FDI. ON TO THE ABDUCTING (of muscles, not people).

Take note of the background image of the graphs. The monitor shows the graph in real time so the x-axis (time) moves, so the graphs are created from the right side of the monitor. More black you see on the graph = More abduction action.

ABDUCT ALL THE FINGERS

rest

Look at the very right side of the screen

ABDUCT 

rest 

Thumb abduction

Index finger abduction

Pinky abduction

After I was done abducting my fingers, I put everything back. The clean-up was as easy as the set-up. So that's how we collect data from the trials! All the equipment--everything in the picture except the tape--is really expensive, and I'm very grateful that I was given the opportunity to experiment with them.

And now, I continue my search for information of how to use the TMS. A significant majority of the websites that I have found always state how the TMS is a therapeutic tool that is now mainly used to treat major depression. Although they are really interesting, they do not relate to my project nor do they mention how and why the TMS is used to stimulate muscles or to locate areas in the brain or even how/why is it used in experiments. Why is that stimulation necessary to obtain results? These are the questions I'm searching the answers for. Wish me luck on my arduous journey.

Day 7: Brains!

I've recently taken a liking to a movie/novel called Warm Bodies by Isaac Marion (I'm currently reading the book after watching the movie twice (Yes, yes. Shame on me for seeing the movie before reading the book)). In the story, brains are the best part to eat for zombies, because by eating the fresh brain, the zombie collects the memories and emotions of the brain's previous owner, making them feel, for a little while, more human.

But how does this relate to my project? Well, the fact that it has to do with brains! With my project, the brain is stimulated through transcranial magnetic stimulation (TMS). Hypothetically, I can stimulate a part of your brain that controls your hand using this procedure, moving your fingers as a result. We use this methodology to find the amount of voltage needed to move the finger muscles. Before I could be a part of this project, I had to spend a month reading chapters about human ethics so that I can be allowed to analyze data. I'm not experienced enough (or probably old enough) to use the TMS on humans but I was taught how to use it, which is impressive in itself.

So I had decided to dedicate this week to reading articles and publications referring to Transcranial Magnetic Stimulation--how the procedures goes, what is involved, MagStim, the difference between single and paired pulse, if there's a difference between rTMS and TMS. I realize that I really should know more. How do I not know more about how TMS works?

I first begin at Google, where everyone student begins. "What is Transcranial Magnetic Stimulation?" I type in the Search bar. What results is the typical Wikipedia  page which actually turned out to be pretty helpful , but unfortunately, Wikipedia  is not known to be a reliable source. So I continue on, but my findings are fruitless. Nothing except for Wikipedia  tell me how the procedure of TMS goes. All refer to the TMS as a treatment or therapy to mental disorders, especially major depression. I release a big sigh and renew my Search bar. "How to use transcranial magnetic stimulation," "The procedure of transcranial magnetic stimulation," "rTMS vs. TMS," "Single vs. paired pulse transcranial magnetic stimulation" (feel free to leave any suggestions in the Comments). Fortunately, I find a few good points on Johns Hopkins University's (my dream school) Medicine website, hopkinsmedicine.org. It wasn't quite futile, yet it wasn't substantial either. I try looking up the references Wikipedia  used for some informational points I found, and I come upon a book which I was excited to read until I saw the price tag on Amazon. $350.00 for a USED  book. Words cannot describe my anger and disappointment. So many questions that remain unanswered. I remember why I don't know much about TMS now.

PROOF! (click to enlarge)

The search continues...

Day 6: Speed of Light Rail

Today marked the first day I used public transit on my own! Despite what its name suggests, the Light Rail does not travel the speed of light. It wasn't very exciting, but it does feel nice having a little more independence. I took a bus ride downtown to where my dad works then took the Light Rail all the way to ASU's Tempe campus.

So what did I learn today? I finally finished that article I started Monday. It studies the significance of the primary motor cortex in humans. The primary motor cortex is located in the green area of the image of the human brain below.

The motor cortex is also labeled as M1 in many instances. The primary motor cortex is the key component for the "storage and processing of new motor information" (Muellbacher et al. 643).

Now remember in my post, "Day 2: An Unexpected Turn," how I mentioned we hypothesized that the PMd and PMv are responsible for force application and positioning, respectively. What I highlighted above in the brain picture are those two areas in the brain. The red is the PMd. The blue PMv. I'd just like to point out a problem that could occur during the experiment. Notice how the PMd (red) is very close to M1 (primary motor cortex). Because of this, instead of stimulating the PMd, which is a small area in the brain, the motor cortex would be stimulated.

There's so much to say about my project that it's really hard for me to only post twice a week, but at the same time, I don't want to overwhelm you, my beloved readers. I will be in Chicago Thursday and Friday so today is the last day of this week I will be in the lab. I'll be back Monday. Thank you for reading!

References:

1. Muellbacher, W., Ziemann, U., Wissel, J., Dang, N., Kofler, M., Facchini, S., Boroojerdi, B., Poewe, W., Hallett, M. Early consolidation in human primary motor cortex. Nature. [Online] 2002. 415, 640-644. http://www.nature.com/nature/journal/v415/n6872/full/nature712.html

Day 5: Numb from Numbers

Did you know the brain has no pain receptors? So during brain surgeries, you're wide awake...

I spent this morning analyzing data using Excel spreadsheets! Oh the joy from putting numbers together using Excel functions and getting new numbers to put together to get new numbers. It didn't take me long though--about an hour for 2 Excel documents filled with data. Each Excel document had 6 books, one for each "block," which represents the time in which the subject was not taking a break. During testing, in between each block was a break period for the subject for him/her to relax.

Image intentionally made illegible for confidentiality reasons.
The red font represents data that just wasn't good enough.

This is a snapshot of the Excel document showing Block 6. For each block, I use all the data on the left and average the MEP values for different sets of conditions, different sets of times where the TMS pulse came in, and for each muscle. The 3 times of conditions are Digit (position), Pa&Fc (position and force), and Baseline. And the different times for the TMS (TMS time) are 500, 750, 1000, 1100, 1200, 1300, 1400, 1500 ms. The main muscles examined in the trials are the index finger muscle (FDI), the thumb muscle (APB), and the forearm muscle (FCR). The pinky finger muscle (ADM) was also examined as a control. The light green in the image contains the averages at every possible combination of condition and TMS time for each muscle. Below the green are the normalized MEP values. Normalized MEP values are divided by the Baseline so they're a percentage. 

This process is repeated for all 6 blocks and compiled into a Summary chart (below).

Image intentionally made illegible for confidentiality reasons.

This image contains all normalized MEP values from the 6 blocks (on top half, white and gray, copy-pasted from each block). The data to the left of the graph are the averages of the 6 blocks' normalized MEP values for FDI, APB, ADM, and FCR at each TMS time interval. The graph is a representation of the average normalized MEP values. This was my main task, which was actually easier than I expected it to be. I only needed to insert formulas and operations into the cells (the boxes in Excel) and expand it to apply it to other cells, so it was really like a copy-paste task. I question if they actually need me to do all of that or if they don't think they'll need me for anything so they instead give me what they think is busy work. It was actually fun learning about how Excel works, and I can add that to my resume.

I'd say I've done enough work this morning, and now it's time for lunch!

Day 4: To the Laboratory!

If you caught my "Dexter's Laboratory" reference in my title, I'm impressed! Kudos to you.

On Day 1, I mentioned how I had to read about if TMS and fMRI can predict the outcome of a hemispherectomy for Friday. The article was a case study of a 14-year-old girl with cerebral palsy and untreatable epilepsy. When we discussed the article ("Unaffected motor cortex remodeling after hemispherectomy in an epileptic cerebral palsy patient. A TMS and fMRI study"), the Journal Club came to the conclusion that it was inaccurate due to its inconsistency in testing. For example, when comparing the pre-operative fMRI study and post-operative fMRI study, they used two different tasks. For the pre-operative study, they obtained the results during a right hand finger-tapping task, but for the post-operative study, they obtained the results during a repetitive thumb-last finger tapping (Pilato et al. 248). It would be helpful if they had mentioned why they changed the tasks. Maybe the girl couldn't move one of her fingers after the surgery? I wasn't able to fully understand the article because (1) it had words and abbreviations that I had never learned before and (2) it wasn't very consistent with its testing.

So Day 3 was a very busy day. Before Journal Club at 12:00 pm, we had a lab group meeting in the conference room at 9:00 am. Many of the 14 people that attended I've never met. I did not know about this meeting until the moment I arrived at the lab. In these meetings, we discuss other people's projects and see if we can improve or help them in any way. It was quite interesting learning about other projects being done here. Now that I think about it, I've never really said much about the actually lab here at ASU.

I do not own this picture. 

This is Physical Education East, or PEBE. I've pondered on the use of the B in the abbreviation, since most buildings here at ASU don't have B in their abbreviations, but I'd like to think it's because if the B weren't there, the initials would spell "pee." So I came to the conclusion that B stood for building. The PEBE is located on Terrace Rd. and is just a 5-minute walk from Memorial Union. This building used to be for the Engineering department, but when the Engineering department moved, the building was converted into the ASU School of Dance. The reason why I go here is because the labs are still in this building. So now, we're here.

I do not own this picture.

All the projects done in this department investigate motor control in a variety of situations: how it relates to the brain, how can it be improved, how certain mental illnesses affect it. The lab I work in is filled with friendly students, and I even have my own desk! But I can't get to it because I don't have a key to any of the doors here. (Look at my Photo Gallery for pictures!)

So back to today... Day 4 will be spent reading a new article: "Early consolidation in human primary cortex." I haven't started reading it yet but it seems to be easier to understand than the last one. Since I won't be here Friday, I won't be able to attend Journal Club, and therefore, I won't be able to discuss with you the credibility of the article in quite as much detail as the Journal Club does. 

References:

1. Pilato, F., Dileone, M., Capone, F., Profice, P., Caulo, M., Battaglia, D., Ranieri, F., Oliviero, A., Florio, L., Graziano, A., Di Rocco, C., Massimi, L., Di Lazzaro, V. Unaffected motor cortex remodeling after hemispherectomy in an epileptic cerebral palsy patient. A TMS and fMRI study. ELSEVIER. 2009 85, 243-251.

Day 2: An Unexpected Turn

In my last post, I mentioned how what I thought I would be doing isn't what I will be doing over the next few months. The difference in excitability of the motor cortex for planning position (P) versus planning the application of force along with position (P+F) was seen in the "pre-experiment," where the results showed that the MEP (motor evoked potential) values of P were higher than those of P+F. Additionally, the MEP values of both variables showed inhibition (the difference of the MEP values from the Baseline), which takes place during the planning. There are a few questions we will try to answer with this new experiment following up this "pre-experiment." Why is there a difference in the excitability between P and P+F? Is it due to different inputs or different gain from the same input? Why do we see inhibition? 

We hypothesize that two areas of the brain--the dorsal premotor cortex (PMd) and the ventral premotor cortex (PMv)--are the two areas that we should be focusing on. PMd has been linked to arbitrary force cues and associative learning. It has also been seen to be responsible for the delay in hand transport by the forearm muscle and temporal relationship between gripping an object and lifting. PMv is said to be linked to the difference between planning the position of 2 fingers (index and thumb) and the whole hand. So to see if PMd and PMv is responsible for planning force application and position, respectively, we inhibit each of the areas using the TMS!

This is where it gets really exciting!

We will use continuous theta-burst stimulation (cTBS), "where TMS bursts are applied at a frequency of 5 Hz over a period of 20 or 40 s," causing a decrease of MEP values (Gentner et al., 2007). In other words, the cTBS is a type of TMS that temporarily shuts down an area and creates a virtual lesion. When I mentioned this to Jeff today at lunch, he responded, with a worried face, "Imagine trying to grab and object and your hand gets there. 'Oh my gosh I can't squeeze the object!'" It's almost really just that.

So when we disable the PMd, ideally, we would like the results to show this.

Click on image to enlarge

By disabling PMd, which we hope will remove the force application (F=0), we would expect the MEP values of P and P+F to be equal.

Likewise with PMv and position.

Click on image to enlarge

By removing the ability of planning the position of the digits, we would expect the MEP values of P to be at the Baseline, meaning that there was no excitability nor inhibition. P+F would increase since there will be no inhibition caused by the planning of digit positioning.

However, because of the sheer complexity of the brain, our expectations could be completely off. The MEP values of P+F could possibly turn out greater than those of P. Because of all these possibilities and unpredictability, our hypothesis may be wrong.

I will continue to update you more on the change of my focus of my research project. If you want to learn more, feel free to leave me a question (or questions) in the comments.

References:

1. Gentner, R., Wankerl, K., Reinsberger, C., Zeller, D. Depression of Human Corticospinal Excitability Induced by Magnetic Theta-burst Stimulation: Evidence of Rapid Polarity-Reversing Metaplasticity. Oxford Journals. [Online] 2007 2046-2053. http://cercor.oxfordjournals.org/content/18/9/2046.full (accessed Feb 7 2013).

Day 1: The New Girl

Daily, the lab here in the Physical Education Building East opens at 9:00am, and being the eager engineer-hopeful that I am, I arrived here at 7:45am. I enter the lab to see three of the people who have accepted me into their lab group: one who just received his doctorate, one who is aiming for a doctorate, and an undergraduate student. They all treat me with the right amount of authority and respect, just enough to make me feel like a college student yet not so much that they think I'm a college student, which is what I had hoped for. Everyone here only recognizes me as the high school student. Although at one point, a doctorate student came up to me thinking I was a college student and asked if I could be a subject for his experiment, and I agreed, forgetting about the age requirements. Luckily, Dr. Parikh told him not to because I'm under 18.

But what exactly did I do today that was relevant to my research paper? Read. I read all day. Since we weren't conducting any trials today, I was given the task to read this paper on a TMS and fMRI study (right), which I will update you on Friday, which is the day of the weekly Journal Club meetings where we discuss similar articles to improve our understanding of the uses of the TMS. The paper this week is about the effects of hemispherectomy, a surgical procedure used in very few cases of epilepsy where one half of the brain is removed or disabled. The TMS in this study was used to predict the outcome of the hemispherectomy. I will read it a few more times to try to have a better understanding of the study's results.

The most important and exciting part of today is that I was part of a lab group meeting. For the most part, it was for my knowledge. The meeting became interactive and I knew the right answers, but my shyness got the best of me and I refused to speak. During the meeting, I obtained a better understanding of the experiment that will be conducted, and it was a bit more complicated than I thought. Due to the intensity of the application of force, there is a difference in excitability between planning to position the fingers (P) vs. planning to position and apply a force (P+F). This was discovered in the “pre-experiment,” which was conducted in the fall, while I was preparing a proposal for my senior research project. The “pre-experiment” resulted in a lower value of MEP (motor evoked potentials) for P+F.

MEP values below the Baseline show an inhibition in the action, meaning that the brain is keeping the fingers from acting during the planning (being above the Baseline shows excitation, which is not shown in the image). So Baseline resembles a sort-of inactivity in the area of the brain that controls finger movement (M1). There is a greater inhibition with the addition of planning force application due to the intensity of force application.

I have a feeling that I may need to update my proposal because my proposal focuses more on the pre-experiment rather than the CAUSE  of the difference in excitability, which is what the main experiment focuses on. Once I read more articles and receive confirmation on the methodology of the main experiment, I will renovate my proposal accordingly.