They Don't Know It's Therapy

Music therapy is so enjoyable that the elderly clients at the daycare center do not even know it is therapy. When the music starts, not only do their faces but entire bodies light up. That in itself is therapy-- increasing attention and alertness in individuals who have lost the normal ability to focus and concentrate. This is a technique known as Musical Sensory Orientation Training (MSOT), where music is used facilitate responsiveness and awareness of person, time, and place.

The therapists play fun and challenging games with the clients that are designed to improve different aspects of physical and cognitive function. One of these is called “popcorn drumming,” where the participants sit in a large circle and the therapist, holding two hand drums, presents them at different heights for individuals to hit with their hands. She does it in quick succession and can go to any person at any time, keeping the participants on their toes and maintaining high levels of concentration. This game employs a technique called Therapeutic Instrumental Music Performance (TIMP), which stimulates functional patterns of movement and orients the participant to their position as they reach out to hit a drum. It is meant to improve range of motion and limb coordination, as well as engage the participant mentally.

On Wednesday the therapist let me have a go at it, moving the drums all around for me to hit as fast as possible. I noticed the experience is very similar to the phone app Piano Tiles where you must tap the black tiles as fast as possible before they leave the screen. The app engages the player in the exact same way as popcorn drumming engages the participants, except popcorn drumming has the added aspect of space as well. It is a surprisingly fun challenge!

Other examples of TIMP are foot placement or tapping and leg movement. The videos below show how this incorporates music. The steady timing and beat of each movement allows for strengthened cognitive planning and for the patient to overcome their difficulty in coordination. It also strengthens the muscles used in the process.

More to come soon!

Now for some Music

I realize I have been talking quite a bit about the brain, and not as much about music and how it relates to the brain!

While certain functions and senses of the human body are controlled by one or a few particular areas, music overlaps multiple systems across the entire brain. It engages motor, sensory, auditory, and visual cortices, as well as centers for behavior, decision-making, emotion, and memory. I find the diagram below particularly insightful.

Music affects components throughout the entire brain. So what? The real value of this knowledge lies in our ability to apply it practically. This is what neurologic music therapy does; it uses these neuroscience principles to treat people suffering from neurological injuries and disorders such as dementia, Alzheimer's, Parkinson's, epilepsy, brain tumors and aneurysms, and stroke. It has been proven to improve strength, motor coordination, cardiorespiratory fitness, gait, memory, attention, verbal expression, and motivation, as well as provide an outlet for self-expression and a source of enjoyment.

For the purpose of this project, the sessions I attend with the Neurological Music Therapy Services of Arizona involve primarily patients with Alzheimer's, Dementia, and Parkinson's. This way, I can understand the physiological mechanisms of these neurodegenerative diseases as well as how individuals can heal using music as a treatment.

Until next time!

Experimenting with Immunohistochemistry...

As I thought, this week has had a lot more going on! The lab staff has begun to give me more responsibility, and I have now begun my first protocol: a two-day Immunohistochemistry (IHC) experiment.

Autocorrect tells me "immunohistochemistry" is not a word. Trust me, it is. I would be just as lost if not for my internship in Dr. Gallitano's biomedical lab at the University of Arizona this past Summer. IHC, colloquially known as "immuno," is a process I am already very familiar with, and have performed before at the last lab under different conditions. Instead of using mouse brain tissue floating in solution, we are using human brain tissue that has already been mounted onto slides.

So what is immunohistochemistry? It is a process that allows us to stain certain proteins in cells such that they can be seen and documented. The best way to explain it is to break down the word itself. First, we have "immuno." Just as it sounds, this means IHC involves immunology, in this case, the use of antibodies (found in the immune system), that bind to certain antigens (proteins on the surface of or in cells). Next, we have "histo," as in "histology"- the study of animal tissues. So we are using immunology techniques such as the use of antibodies in animal tissues. Lastly, we have chemistry-- the chemical analysis of whatever tissue we are studying using this technique. In one definition, immunohistochemistry is the process of introducing specific antibodies to animal tissue in order to bind specific antigens, and thus be able to visualize those proteins under a microscope. Hopefully I haven't lost you yet.

The diagram above is very helpful. At my old lab, we did the protocol on right, immunofluorescence. At the Mufson lab, we do the one on the left, indirect immunohistochemistry. Both follow the same general principles.

You start with a protein you want to "label", the one you want to be able to visualize in the cells to confirm their presence (or absence). At this lab it might be plaques, abnormal clusters of beta-amyloid proteins that build up between brain cells and are characteristic of Alzheimer's disease. So, if you want to label for beta-amyloid, you have to introduce the antibody that will bind to it, anti-beta-amyloid. Because this is in humans, the antibody needs to be made in a different species such as mouse, so it will not bind to any other human proteins. This first antibody we use, the primary antibody, in this case would be mouse anti-beta-amyloid. In the diagram above, the primary antibody is in red. In the immunofluorescence protocol on the right, this antibody has a fluorescent tag bound to it, a protein that fluoresces under certain light. At the old lab we used green fluorescent protein (GFP) produced in jellyfish that indicated the cells which housed our target protein.

In this lab we need a secondary antibody that binds to the first in order to label our target protein. Because the secondary antibody is binding to the primary, it needs to be anti-whatever the primary antibody was made in. If our primary was mouse anti-beta amyloid, the secondary would have to be something anti-mouse. It could be goat, chicken, or horse anti-mouse, as long as it is produced in a different species and targets the mouse primary. In the diagram above, the secondary is in blue. Attached to the secondary antibody (represented by the pink circle) is a protein enzyme called horseradish peroxidase (HRPO). Yes, it is derived from the horseradish plant, specifically the roots. By itself, it does not do much. However, when we add diaminobenzidine (DAB) and some hydrogen peroxide (H2O2), the HRPO catalyzes a reaction between the two that produces an insoluble brown precipitate (colored solid) attached wherever your antibody has bound to your target antigen. You have labelled your protein!

The images below from leicabiosystems.com show actual indirect immunohistochemistry staining.

This image depicts beta-amyloid immunohistochemical staining of an Alzheimer's Disease affected brain. The brown staining of the plaques is very clear.

Similarly, this image depicts immunohistochemical staining in AD affected brain tissue for something called amyloid precursor protein (APP). Beta amyloid is produced as a fragment of this protein, and so the presence of APP is also considered a characteristic of Alzheimer's Disease, and is identified through IHC protocol.

I am conducting an IHC experiment that I will write about soon! I'll keep you posted.

Citations:

Brains and Brawn - Antibodies in Research and Diagnosis. (n.d.). Retrieved February 15, 2017, from http://www.leicabiosystems.com/pathologyleaders/brains-and-brawn-antibodies-in-research-and-diagnosis/

Welcome to the Lab

We have a fridge full of human brain tissue: containers upon containers stacked one on top of the other, each filled nearly to the brim with floating segments of formalin soaked tissue. Each one holds segments of one individual-- possibly a non-dementia affected control, or a Parkinson’s (PD) and/or Alzheimer’s disease (AD) affected tissue. The glass is labelled as such: control, PD, AD, or PD + AD, as well as for how many years the person was affected, the date the brain was received, all the days and times it was fixed so that the tissue remains preserved, and an ID-- the series of three letters starting with ‘R.’ In the image below, the pink taped container in the top center has been preserved since 1995.

The container below was once very full of tissue, however multiple segments have been removed and dissected.

The scientist-- an expert in neuroanatomy-- lays the pieces out on the bench and cuts out particular sections to be sliced and mounted onto slides to be studied.

The fridge contains upwards of 200 of these containers, arranged in alphabetical order, and the lab is constantly retrieving different ones to collect particular segments of the brain they wish to study.

Of particular interest is a small group of neurons called the Nucleus basalis of Meynert (nbM), located in the basal forebrain (see image below). It is part of what is called the cholinergic system, a neurotransmitter system that uses acetylcholine to transmit nerve impulses. The system projects throughout the neocortex and the hippocampus of the brain (again, see image below), and is involved with memory, learning, and arousal. “[N]euronal loss within the cholinergic nucleus basalis of Meynert (nbM) correlates with cognitive decline in dementing disorders such as Alzheimer’s disease (AD)” (Liu, Chang, Pearce, & Gentleman, 2015). The Mufson lab hopes to discover more.

Citations

Liu, A. K., Chang, R. C., Pearce, R. K., & Gentleman, S. M. (2015). Nucleus basalis of Meynert revisited: anatomy, history and differential involvement in Alzheimer’s and Parkinson’s disease. Acta Neuropathologica, 129(4), 527-540. doi:10.1007/s00401-015-1392-5

Just Getting Started

This week I became an official volunteer at St. Joseph's Hospital so that I could work in Dr. Elliott Mufson's lab at Barrow Neurological. The hospital staff here are extremely friendly and are just as eager as I am for me to get started. They are also very helpful with directions, as this campus is huge and I am lost constantly.

The Mufson lab uses human brain tissue to study primarily Alzheimer's Disease, and more recently, Down Syndrome, as the two disorders have the shared occurrence of tau tangles and plaques that are thought to cause the problems with neurological function and the development of dementia common in affected individuals. While I do not yet know much more than this, I have a few research papers to read that I am sure will go into more detail.

This is only my second day in the lab, so I do not have much about which to write. Next week, because it will be my first full week, will likely have much more activity. Also, starting next week on Mondays, Wednesdays, and Fridays, I will be attending the Neurological Music Therapy Services of Arizona's (NMTSA) music therapy sessions, first as an observer, but then hopefully as a participant.

My opportunities and responsibilities as an intern will not be completely clear until next week. Whatever they may be, I look forward to the experience and will learn as much as I can about music and its workings in the brain.

Let's Begin

Hello all and welcome to my Senior Research Project (SRP) blog.

My name is Anila Tynan, and I am a senior at BASIS Phoenix. I joined the school as an eighth grader when it opened in 2012, and after five challenging, yet educationally enlightening years, I have the opportunity to forego my classes and pursue a senior project fro the entire third trimester. As a BASIS student, I have been exposed to all the subjects equally-- the social/applied/natural sciences, arts, humanities, languages-- but now it is time to pursue the topics that have really captured my interest and that I hope to pursue after I graduate in May.

Very little is known about how music affects the human brain. What we do know is how it makes us feel. Music can rouse us to sing and dance, give us goosebumps, and make us cry. It brings people together, defines cultures, and spans the entire globe. People of all ages can recognize and even create some sort of "music," and in the United States alone, the music industry is worth over $130 billion. No other species regards music as we do-- it defines us as human.

This clear impact that music has on the brain has infinite unexplored implications, especially in regards to neuroscience. Music and the Brain: How music affects our memories serves as an introduction to this field and how music might relate to the study of neurodegenerative diseases such as Alzheimer's, Dementia, and Parkinson's. Over the next eleven weeks, I will be working in a research laboratory at the Barrow Neurological Institute learning lab techniques and studying Alzheimer's and Dementia, as well as participating in music therapy sessions run by the Neurological Music Therapy Services of Arizona, working with clients who suffer from neurodegenerative diseases, and seeing firsthand how music impacts their lives.

Overtime, as I expand my knowledge of the workings of the brain and of these diseases, as well as of the physical, mental, and emotional effects music therapy has on clients with these disorders, I hope to be able to decipher a fraction of what there is to discover about how music and the brain are connected.

Check out my SRP Proposal as well as the links to my internship websites to the right, and subscribe to keep updated on my project!