Graphene Nanoribbons and Spinal Cord Repair

Catalyst Volume 10

The same technology that has been used to strengthen polymers¹, de-ice helicopter wings², and create more efficient batteries³ may one day help those with damaged or even severed spinal cords walk again. The Tour Lab at Rice University, headed by Dr. James Tour, is harnessing the power of graphene nanoribbons to create a special new material called Texas-PEG that may revolutionize the way we treat spinal cord injuries; one day, it may even make whole body transplants a reality.

Dr. Tour, the T.T. and W.F. Chao Professor of Chemistry, Professor of Materials Science and NanoEngineering, and Professor of Computer Science at Rice University, is a synthetic organic chemist who mainly focuses on nanotechnology. He currently holds over 120 patents and has published over 600 papers, and was inducted into the National Academy of Inventors in 2015.⁴ His lab is currently working on several different projects, such as investigating various applications of graphene, creating and testing nanomachines, and the synthesizing and imaging of nanocars. The Tour Lab first discovered graphene nanoribbons while working with graphene back in 2009.⁵ Their team found a way to “unzip” graphene nanotubes into smaller strips called graphene nanoribbons by injecting sodium and potassium atoms between nanotube layers in a nanotube stack until the tube split open. “We fell upon the graphene nanoribbons,” says Dr. Tour. “I had seen it a few years ago in my lab but I didn’t believe it could be done because there wasn’t enough evidence. When I realized what we had, I knew it was enormous.”

This discovery was monumental: graphene nanoribbons have been used in a variety of different applications because of their novel characteristics. Less than 50 nm wide ( which is about the width of a virus), graphene nanoribbons are 200 times stronger than steel and are great conductors of heat and electricity. They can be used to make materials significantly stronger or electrically conductive without adding much additional weight. It wasn’t until many years after their initial discovery, however, that the lab discovered that graphene nanoribbons could be used to heal severed spinal cords.

The idea began after one of Dr. Tour’s students read about European research on head and whole body transplants on Reddit. This research was focused on taking a brain dead patient with a healthy body and pairing them with someone who has brain activity but has lost bodily function. The biggest challenge, however, was melding the spine together. The neurons in the two separated parts of the spinal cord could not communicate with one another, and as a result, the animals involved with whole body and head transplant experiments only regained about 10% of their original motor function. The post-graduate student contacted the European researchers, who then proposed using the Tour lab’s graphene nanoribbons in their research, as Dr. Tour’s team had already proven that neurons grew very well along graphene.

“When a spinal cord is severed, the neurons grow from the bottom up and the top down, but they pass like ships in the night; they never connect. But if they connect, they will be fused together and start working again. So the idea was to put very thin nanoribbons in the gap between the two parts of the spinal cord to get them to align,” explains Dr. Tour. Nanoribbons are extremely conductive, so when their edges are activated with polyethylene glycol, or PEG, they form an active network that allows the spinal cord to reconnect. This material is called Texas-PEG, and although it is only about 1% graphene nanoribbons, this is still enough to create an electric network through which the neurons in the spinal cord can connect and communicate with one another.

The Tour lab tested this material on rats by severing their spinal cords and then using Texas-PEG to see how much of their mobility was recovered. The rats scored about 19/21 on a mobility scale after only 3 weeks, a remarkable advancement from the 10% recovery in previous European trials. “It was just phenomenal. There were rats running away after 3 weeks with a totally severed spinal cord! We knew immediately that something was happening because one day they would touch their foot and their brain was detecting it,” says Dr. Tour. The first human trials will begin in 2017 overseas. Due to FDA regulations, it may be awhile before we see trials in the United States, but the FDA will accept data from successful trials in other countries. Graphene nanoribbons may one day become a viable treatment option for spinal injuries.

This isn’t the end of Dr. Tour’s research with graphene nanoribbons. “We’ve combined our research with neurons and graphene nanoribbons with antioxidants: we inject antioxidants into the bloodstream to minimize swelling. All of this is being tested in Korea on animals. We will decide on an optimal formulation this year, and it will be tried on a human this year,” Dr. Tour explained. Most of all, Dr. Tour and his lab would like to see their research with graphene nanoribbons used in the United States to help quadriplegics who suffer from limited mobility due to spinal cord damage. What began as a lucky discovery now has the potential to change the lives of thousands.

References

1. Wijeratne, Sithara S., et al. Sci. Rep. 2016, 6.
2. Raji, Abdul-Rahman O., et al. ACS Appl. Mater. Interfaces. 2016, 8 (5), 3551-3556.
3. Salvatierra, Rodrigo V., et al. Adv. Energy Mater. 2016, 6 (24).
4. National Academy of Inventors. http://www.academyofinventors.org/ (accessed Feb. 1, 2017).
5. Zehtab Yazdi, Alireza, et al. ACS Nano. 2015, 9 (6), 5833-5845.

Microbes: Partners in Cancer Research

Catalyst Volume 10

To millions around the world, the word ‘cancer’ evokes emotions of sorrow and fear. For decades, scientists around the world have been trying to combat this disease, but to no avail. Despite the best efforts of modern medicine, about 46% of patients diagnosed with cancer still pass away as a direct result of the disease.¹ However, the research performed by Dr. Michael Gustin at Rice University may change the field of oncology forever.

Cancer is a complex and multifaceted disease that is currently not fully understood by medical doctors and scientists. Tumors vary considerably between different types of cancers and from patient to patient, further complicating the problem. Understanding how cancer develops and responds to stimuli is essential to producing a viable cure, or even an individualized treatment.

Dr. Gustin’s research delves into the heart of this problem. The complexity of the human body and its component cells are currently beyond the scope of any one unifying model. For this reason, starting basic research with human subjects would be detrimental. Researchers turn instead to simpler eukaryotes in order to understand the signal pathways involved in the cell cycle and how they respond to stress.² Through years of hard work and research, Dr. Gustin’s studies have made huge contributions to the field of oncology.

Dr. Gustin studied a species of yeast, Saccharomyces cerevisiae, and its response to osmolarity. His research uncovered the high osmolarity glycerol (HOG) pathway and mitogen-activated protein kinase (MAPK) cascade, which work together to maintain cellular homeostasis. The HOG pathway is much like a “switchboard [that] control[s] cellular behavior and survival within a cell, which is regulated by the MAPK cascade through the sequential phosphorylation of a series of protein kinases that mediates the stress response.”³ These combined processes allow the cell to respond to extracellular stress by regulating gene expression, cell proliferation, and cell survival and apoptosis. To activate the transduction pathway, the sensor protein Sln1 recognizes a stressor and subsequently phosphorylates, or activates, a receiver protein that mediates the cellular response. This signal transduction pathway leads to the many responses that protect a cell against external stressors. These same protective processes, however, allow cancer cells to shield themselves from the body’s immune system, making them much more difficult to attack.

Dr. Gustin has used this new understanding of the HOG pathway to expand his research into similar pathways in other organisms. Fascinatingly, the expression of human orthologs of HOG1 proteins within yeast cells resulted in the same stimulation of the pathway despite the vast evolutionary differences between yeast and mammals. Beyond the evolutionary implications of this research, this illustrates that the “[HOG] pathway defines a central stress response signaling network for all eukaryotic organisms”.³ So much has already been learned through studies on Saccharomyces cerevisiae and yet researchers have recently discovered an even more representative organism. This fungus, Candida albicans, is the new model under study by Dr. Gustin and serves as the next step towards producing a working model of cancer and its responses to stressors. Its more complex responses to signalling make it a better working model than Saccharomyces cerevisiae.⁴ The research that has been conducted on Candida albicans has already contributed to the research community’s wealth of information, taking great strides towards eventual human applications in the field of medicine. For example, biological therapeutics designed to combating breast cancer cells have already been tested on both Candida albicans biofilms and breast cancer cells to great success.⁵

This research could eventually be applied towards improving current chemotherapy techniques for cancer treatment. Eventual applications of this research are heavily oriented towards fighting cancer through the use of chemotherapy techniques. Current chemotherapy techniques utilize cytotoxic chemicals that damage and kill cancerous cells, thereby controlling the size and spread of tumors. Many of these drugs can disrupt the cell cycle, preventing the cancerous cell from proliferating efficiently. Alternatively, a more aggressive treatment can induce apoptosis, programmed cell death, within the cancerous cell.⁶ For both methods, the chemotherapy targets the signal pathways that control the vital processes of the cancer cell. Dr. Gustin’s research plays a vital role in future chemotherapy technologies and the struggle against mutant cancer cells.

According to Dr. Gustin, current chemotherapy is only effective locally, and often fails to completely incapacitate cancer cells that are farther away from the site of drug administration where drug toxicity is highest. As a result, distant cancer cells are given the opportunity to develop cytoprotective mechanisms that increase their resistance to the drug.⁷ Currently, a major goal of Dr. Gustin’s research is to discover how and why certain cancer cells are more resistant to chemotherapy. The long-term goal is to understand the major pathways involved with cancer resistance to apoptosis, and to eventually produce a therapeutic product that can target the crucial pathways and inhibitors. With its specificity, this new drug would vastly increase treatment efficacy and provide humanity with a vital tool with which to combat cancer, saving countless lives in the future.

References   

1. American Cancer Society. https://www.cancer.org/latest-new/cancer-facts-and-figures-death-rate-down-25-since-1991.html (February 3 2017).                  
2. Radmaneshfar, E.; Kaloriti, D.; Gustin, M.; Gow, N.; Brown, A.; Grebogi, C.; Thiel, M. Plos ONE, 2013, 8, e86067.                
3. Brewster, J.; Gustin, M. Sci. Signal. 2014, 7, re7.
4. Rocha, C.R.; Schröppel, K.; Harcus, D.; Marcil, A.; Dignard, D.; Taylor, B.N.; Thomas, D.Y.; Whiteway, M.; Leberer, E. Mol. Biol. Cell. 2001, 12, 3631-3643.
5. Malaikozhundan, B.; Vaseeharan, B.; Vijayakumar, S.; Pandiselvi K.; Kalanjiam R.; Murugan K.; Benelli G. Microbial Pathogenesis 2017, 102, n.p. Manuscript in progress.
6. Shapiro, G. and Harper, J.; J Clin Invest. 1999, 104, 1645–1653.
7. Das, B.; Yeger, H.; Baruchel, H.; Freedman, M.H.; Koren, G.; Baruchel, S. Eur. J. Cancer. 2003, 39, 2556-2565.

Visualizing the Future of Medicine

Catalyst Volume 10

What do you do when you get sick? Most likely you schedule a doctor’s appointment, show up, and spend ten to fifteen minutes with the doctor. The physician quickly scans your chart, combines your narrative of your illness with your medical history and his or her observations so that you can leave with diagnosis and prescription in hand. While few give the seemingly routine process a second thought, the very way in which healthcare providers approach the doctor-patient experience is evolving. There is a growing interest in the medical humanities, a more interdisciplinary study of illness. According to Baylor College of Medicine, the aim of the medical humanities is “understanding the profound effects of illness and disease on patients, health professionals, and the social worlds in which they live and work.”¹ Yet medical humanities is somewhat of a catch all term. It encompasses disciplines including literature, anthropology, sociology, philosophy, the fine arts and even “science and technology studies.”¹ This nuanced approach to medicine is exactly what Dr. Kirsten Ostherr, one of the developers of Rice University’s medical humanities program, promotes.

Dr. Ostherr uses this interdisciplinary approach to study the intersection of technology and medicine. She has conducted research on historical medical visualizations through media such as art and film and its application to medicine today. Originally a PhD recipient of American Studies and Media Studies at Brown University, Dr. Ostherr’s interest in medicine and media was sparked while working at the Department of Public Health at Oregon Health Sciences University, where researchers were using the humanities as a lens through which they could analyze health data. “I noticed that the epidemiologists there used narrative to make sense of data, and that intrigued me,” she said. This inspired Dr. Ostherr to use her background in media and public health to explore how film and media in general have affected medicine and to predict where the future of medical media lies.

While the integration of medicine and media may seem revolutionary, it is not a new concept. In her book, Medical Visions, Dr. Ostherr says that “We know we have become a patient when we are subjected to a doctor’s clinical gaze,” a gaze that is powerfully humanizing and can “transform subjects into patients.”² With the integration of technology and medicine, this “gaze” has extended to include the visualizations vital to understanding the patient and decoding disease. Visualizations have been a part of the doctor-patient experience for longer than one might think, from X-rays in 1912 to the electronic medical records used by physicians today.³

In her book, Dr. Ostherr traces and analyzes a series of different types of medical visualizations throughout history. Her research begins with the study of scientific films of the early twentieth century, and their attempt to bridge the gap between scientific knowledge and the general public.² The use of film in medical education was also significant in the 20th century. These technical films helped facilitate the globalization of health and media in the postwar era. Another form of medical visualizations that emerged with the advent of medicine on television. At the intersection of entertainment and education, medical documentary evolved into “health information programming” in the 1980’s which in turn transitioned into the rise of medical reality television.² The history of this diverse and expanding media, she says, proves that the use of visualizations in healthcare and our daily lives has made medicine “a visual science.”

One of the main takeaways from Dr. Ostherr’s historical analysis of medical visualizations was the deep-rooted relationship between visualizations and their role in spreading medical knowledge to the average person. While skeptics may argue against this characterization, “this is a broad social change that is taking place,” Dr. Ostherr said, citing new scientific research emerging on human centered design and the use of visual arts in medical training. “It’s the future of medicine,” she said. There is already evidence that such a change is taking place: the method of recording patient information using health records has begun to change. In recent years there has been a movement to adopt electronic health records due to their potential to save the healthcare industry millions of dollars and improve efficiency.⁴ Yet recent studies show that the current systems in place are not as effective as predicted.⁵ Online patient portals allow patients to keep up with their health information, view test results and even communicate with their health care providers, but while these portals can involve patients as active participants in their care, they can also be quite technical.⁶ As a result, there is a push to develop electronic health records with more readily understandable language.

In order to conduct further research in the field including projects such as the development of better, easier to understand electronic health records, Dr. Ostherr co-founded and is the director of the Medical Futures Lab. The lab draws resources from Baylor College of Medicine, University of Texas Health Science Center, and Rice University and its diverse team ranges from humanist scholars to doctors to computer scientists.⁷ The use of technology in medicine has continued to develop rapidly alongside the increasing demand for personalized, humanizing care. While it seems like there is an inherent conflict between the two, Dr. Ostherr believes medicine needs the “right balance of high tech and high touch” which is what her team at the Medical Futures Lab (MFL) works to find. The MFL team works on projects heavily focused on deconstructing and reconstructing the role of the patient in education and diagnosis.⁷

The increasingly integrated humanistic and scientific approach to medicine is revolutionizing healthcare. As the Medical Futures Lab explores the relationship between personal care and technology, the world of healthcare is undergoing a broad cultural shift. Early on in their medical education, physicians are being taught the value of incorporating the humanities and social sciences into their training, and that science can only teach one so much about the doctor-patient relationship. For Dr. Ostherr, the question moving forward will be “what is it that is uniquely human about healing?” What are the limitations of technology in healing and what about healing process can be done exclusively by the human body? According to Dr. Ostherr, the histories of visualizations in medicine can serve as a roadmap and an inspiration for the evolution and implementation of new media and technology in transforming the medical subject into the patient.

References

1. Baylor University Medical Humanities. http://www.baylor.edu/medical_humanities/ (accessed Nov. 27, 2017).
2. Ostherr, K. Medical visions: producing the patient through film, television, and imaging technologies; Oxford University Press: Oxford, 2013.
3. History of Radiography. https://www.nde-ed.org/EducationResources/CommunityCollege/Radiography/Introduction/history.htm (accessed Jan. 2017).
4. Abelson, R.; Creswell, J. In Second Look, Few Savings From Digital Health Records. New York Times [Online], January 11, 2013. http://www.nytimes.com/2013/01/11/business/electronic-records-systems-have-not-reduced-health-costs-report-says.html (accessed Jan 2017).
5. Abrams, L. The Future of Medical Records. The Atlantic [Online], January 17, 2013 http://www.theatlantic.com/health/archive/2013/01/the-future-of-medical-records/267202/ (accessed Jan. 25, 2017).
6. Rosen, M. D. L. High Tech, High Touch: Why Technology Enhances Patient-Centered Care. Huffington Post [Online], December 13, 2012. http://www.huffingtonpost.com/lawrence-rosen-md/health-care-technology_b_2285712.html (accessed Jan 2017).
7. Medical Futures Lab. http://www.medicalfutureslab.org/ (accessed Dec 2017).

The Fight Against Neurodegeneration

Catalyst Volume 10

“You know that it will be a big change, but you really don’t have a clue about your future.”A 34-year-old postdoctoral researcher at the Telethon Institute of Genetics and Medicine in Italy at the time, Dr. Sardiello had made a discovery that would change his life forever. Eight years later, Dr. Sardiello is now the principal investigator of a lab in the Jan and Dan Duncan Neurological Research Institute (NRI) where he continues the work that had brought him and his lab to America.

Throughout his undergraduate career, Sardiello knew he wanted to be involved in some manner with biology and genetics research, but his passion was truly revealed in 2000: the year he began his doctoral studies. It was during this year that the full DNA sequence of the common fruit fly was released, which constituted the first ever complete genome of a complex organism. At the time, Sardiello was working in a lab that used fruit flies as a model, and this discovery served to spur his interest in genetics. As the golden age of genetics began, so did Sardiello’s love for the subject, leading to his completion of a PhD in Genetic and Molecular Evolution at the Telethon Institute of Genetics and Medicine. It was at this institute that his team made the discovery that would bring him to America: the function of Transcription Factor EB, colloquially known as TFEB.

Many knew of the existence of TFEB, but no one knew of its function. Dr. Sardiello and his team changed that. In 2009, they discovered that the gene is the master regulator for lysosomal biogenesis and function. In other words, TFEB works as a genetic switch that turns on the production of new lysosomes, an exciting discovery.¹ Before the discovery of TFEB’s function, lysosomes were commonly known as the incinerator or the garbage can of the cell, as these organelles were thought to be essentially specialized containers that get rid of cellular waste. However, with the discovery of TFEB’s function, we now know that lysosomes have a much more active role in catabolic pathways and the maintenance of cell homeostasis. Sardiello’s groundbreaking findings were published in Science, one of the most prestigious peer reviewed journals in the scientific world. Speaking about his success, Sardiello said, “The bottom line was that there was some sort of feeling that a big change was about to come, but we didn’t have a clue what. There was just no possible measure at the time.”

Riding the success of his paper, Sardiello moved to the United States and established his own lab with the purpose of defeating the family of diseases known as Neuronal Ceroid Lipofuscinosis (NCLs). NCLs are genetic diseases caused by the malfunction of lysosomes. This malfunction causes waste to accumulate in the cell and eventually block cell function, leading to cell death. While NCLs cause cell death throughout the body, certain specialized cells such as neurons do not regenerate. Therefore, NCLs are generally neurodegenerative diseases. While there are many variants of NCLs, they all result in premature death after loss of neural functions such as sight, motor ability, and memory.

“With current technology,” Sardiello said, “the disease is incurable, since it is genetic. In order to cure a genetic disease, you have to somehow bring the correct gene into every single cell of the body.” With our current understanding of biology, this is impossible. Instead, doctors can work to treat the disease, and halt the progress of the symptoms. Essentially, his lab has found a way using TFEB to enhance the function of the lysosomes in order to fight the progress of the NCL diseases.

In addition to genetic enhancement, Sardiello is also focusing on finding drugs that will activate TFEB and thereby increase lysosomal function. To test these new methods, the Sardiello lab uses mouse models that encapsulate most of the symptoms in NCL patients. “Our current results indicate that drug therapy for NCLs is viable, and we are working to incorporate these strategies into clinical therapy,” Sardiello said. So far the lab has identified three different drugs or drug combinations that may be viable for treatment of this incurable disease.

While it might be easy to talk about NCLs and other diseases in terms of their definitions and effects, it is important to realize that behind every disease are real people and real patients. The goal of the Sardiello Lab is not just to do science and advance humanity, but also to help patients and give them hope. One such patient is a boy named Will Herndon. Will was diagnosed with NCL type 3, and his story is one of resilience, strength, and hope.

When Will was diagnosed with Batten Disease at the age of six, the doctors informed him and his family that there was little they could do. At the time, there was little to no viable research done in the field. However, despite being faced with terminal illness, Will and his parents never lost sight of what was most important: hope. While others might have given up, Missy and Wayne Herndon instead founded The Will Herndon Research Fund - also known as HOPE - in 2009, playing a large role in bringing Dr. Sardiello and his lab to the United States. Yearly, the foundation holds a fundraiser to raise awareness and money that goes towards defeating the NCL diseases. Upon its inception, the fundraiser had only a couple of hundred attendees- now, only half a decade later, thousands of like-minded people arrive each year to support Will and others with the same disease. “Failure is not an option,” Missy Herndon said forcefully during the 2016 banquet. “Not for Will, and not for any other child with Batten disease.” It was clear from the strength of her words that she believed in the science, and that she believed in the research.

“I have a newborn son,” Sardiello said, recalling the speech. “I can’t imagine going through what Missy and Wayne had to. I felt involved and I felt empathy, but most of all, I felt respect for Will’s parents. They are truly exceptional people and go far and beyond what anyone can expect of them. In face of adversity, they are tireless, they won’t stop, and their commitment is amazing.”

When one hears about science and labs, it usually brings to mind arrays of test tubes and flasks or the futuristic possibilities of science. In all of this, one tends to forget about the people behind the test bench: the scientists that conduct the experiments and uncover the next step in the collective knowledge of humanity, people like Dr. Sardiello. However, Sardiello isn’t alone in his endeavors, as he is supported by the members of his lab.

Each and every one of the researchers in Marco’s lab is an international citizen, hailing from at least four different countries in order to work towards a common cause: Parisa Lombardi from Iran, Lakshya Bajaj, Jaiprakash Sharma, and Pal Rituraj from India, Abdallah Amawi, from Jordan, and of course, Marco Sardiello and Alberto di Ronza, from Italy. Despite the vast distances in both geography and culture, the chemistry among the team was palpable, and while how they got to America varied, the conviction that they had a responsibility to help other people and defeat disease was always the same.

Humans have always been predisposed to move forwards. It is because of this propensity that humans have been able to eradicate disease and change the environments that surround us. However, behind all of our achievements lies scientific advancement, and behind it are the people that we so often forget. Science shouldn’t be detached from the humans working to advance it, but rather integrated with the men and women working to make the world a better place. Dr. Sardiello and his lab represent the constant innovation and curiosity of the research community, ideals that are validated in the courage of Will Herndon and his family. In many ways, the Sardiello lab embodies what science truly represents: humans working for something far greater than themselves.

References

1. Sardiello, M.; Palmieri, M.; di Ronza, A.; Medina, D.L.; Valenza, M.; Alessandro, V. Science. 2009, 325, 473-477.

Cognitive Neuroscience: A Glimpse of the Future

Catalyst Volume 10

Cognitive Neuroscience is a branch of science that addresses the processes in the brain that occur during cognitive activity. The discipline addresses how psychological and cognitive activities are caused by and correlated to the neural connections in our brain. It bridges psychology and neuroscience.

Dr. Simon Fischer-Baum, an assistant professor and researcher at Rice University,  co-directs the neuroplasticity lab at the BioScience Research Collaborative. He received his B.A. in Neuroscience and Behavior from Columbia University in 2003 and received his Ph.D. in Cognitive Sciences from Johns Hopkins University in 2010.

Dr. Fischer-Baum describes his research as the “intersection of psychology and neuroscience and computer science to some extent.” He is interested in instances of how we understand and pronounce a word once we see it. He also studies memory and how information is encoded in the brain. In his opinion, functional magnetic resonance imaging (fMRI) and other tools of cognitive neuroscience are extremely relevant to cognitive psychology despite public perception. For example, he believes that there is a “serious disconnect” as a result of the belief that the methods and findings of cognitive neuroscience do not apply to cognitive psychology. Cognitive psychologists have been attempting to discover the variation between the different levels of processing and how information travels between these levels. Cognitive neuroscience can help achieve these goals through the use of fMRIs.

fMRI shows which parts of the brain are active when the subject is performing a task. During any task, multiple regions of the brain are involved, with each region processing different types of information. For example, reading a word involves processing both visual information and meaning; when you are reading a word, multiple regions of the brain are active. However, one problem with fMRIs is that while they demonstrate what regions of the brain are active, they do not convey what function each region is carrying out.  One of the main objectives of Dr. Fischer-Baum’s work is to pioneer new methods similar to computer algorithms to decode what data from an fMRI tells us about what tasks the brain is performing. “I want to be able to take patterns of activity and decode and relate it back to the levels of representation that cognitive psychologists think are going on in research,” Dr. Fischer-Baum explains.

Recently, Dr. Fischer-Baum published a study of a patient who suffered severe written language impairments after experiencing a hemorrhagic stroke. Although this patient’s reading of familiar words improved throughout the years, he still presented difficulties in processing abstract letter identity information for individual letters. Someone who is able to utilize abstract letter representations can  recognize letters independent of case or font; in other words, this person  is able to identify letters regardless of the whether they are upper case, lower case, or a different font. In the studied patient, Dr. Fischer-Baum’s team observed contralesional reorganization. Compromised regions of the left hemisphere that contained orthography-processing regions (regions that process the set of conventions for writing a language) were organized into homologous regions in the right hemisphere. Through the use of fMRI, the research team determined that the patient’s residual reading ability was supported by functional take-over, which is when injury-damaged functions are taken over by healthy brain regions. These results were found by scanning the brain of the patient as he read and comparing the data with that of a control group of young healthy adults with normal brain functions.

While Dr. Fischer-Baum has made substantial progress in this project, the research has not been without challenges. The project began in 2013 and took three years to complete, which is a long time for Dr. Fischer-Baum’s field of study. Due to this, none of the co-authors from Rice University know each other despite all working on the project at some point in time with another. Because of the amount of time spent on the project, many of the students rotated in and out while working on various parts; the students never worked on the project at the same time as their peers. In addition, the project’s  interdisciplinary approach required the input of  many collaborators with different abilities. All of the Rice undergraduate students that worked on the project were from different majors although most were from the Cognitive Sciences Department and the Statistics Department. At times, this led to miscommunication between the different students and researchers on the project. Since the students came from different backgrounds, they had different approaches to solving problems. This led to the students at times not being harmonious during many aspects of the project.  

Another major setback occurred in bringing ideas to fruition. “You realize quickly when you begin a project that there are a million different ways to solve the problem that you are researching, and trying to decide which is the right or best way can sometimes be difficult,” Dr. Fischer-Baum said. As a result of this, there have been a lot of false starts, and it has taken a long time in order to get work off the ground. How did Dr. Fischer-Baum get past this problem? “Time, thinking, discussion, and brute force,” he chuckled. “You realize relatively quickly that you need to grind it out and put in effort in order to get the job done.”

Despite these obstacles, Dr. Fischer-Baum has also undertaken other projects in order to keep his mind busy. In one, he works with stroke patients with either reading or writing deficits to understand how written language is broken down in the mind. He studies specific patterns in the patients’ brain activity to investigate how reading and writing ability differ from each other. In another of Dr. Fischer-Baum’s projects he works with Dr. Paul Englebretson of the Linguistics Department in order to research the brain activity of blind people as they read Braille. “There is a lot of work on how the reading system works, but a lot of it is based on the perspective of reading by sight,” Dr. Fischer-Baum acknowledged. “I am very interested to see how the way we read is affected by properties of our visual system. Comparing sight and touch can show how much senses are a factor in reading.”

Ultimately, Dr. Fischer-Baum conducts his research with several goals in mind. The first is to build an approach to cognitive neuroscience that is relevant to the kinds of theories that we have in the other cognitive sciences, especially cognitive psychology. “While it feels like studying the mind and studying the brain are two sides of the same coin and that all of this data should be relevant for understanding how the human mind works, there is still a disconnect between the two disciplines,” Dr. Fischer-Baum remarked. He works on building methods in order to bridge this disconnect.

In addition to these goals for advancing the field of cognitive neuroscience, there are clinical implications as well to Dr. Fischer-Baum’s research. Gaining more insight into brain plasticity following strokes can be used to build better treatment and recovery programs. Although the research requires further development, the similarity between different regions and their adaptations following injury can lead to a better understanding of the behavioral and neural differences in patterns of recovery. Additionally, Dr. Fischer-Baum aims to understand the relationship between spontaneous and treatment-induced recovery and how the patterns of recovery of language differ as a result of the initial brain injury type and location. Through the combined use of cognitive psychology and fMRI data, the brains of different stroke patients can be mapped and the data can be used to create more successful treatment-induced methods of language recovery. By virtue of Dr. Fischer-Baum’s research, not only can cognitive neuroscience be applied to many other disciplines, but it can also significantly improve the lives of millions of people around the world.  

Tactile Literacy: The Lasting Importance of Braille

Catalyst Volume 10

On June 27th, 1880, a baby girl was born. At nineteen months old, the little girl contracted a severe fever, and once the fever dissipated, she woke up to a world of darkness and silence. This little girl was Helen Keller. By the age of two, Helen Keller had completely lost her sense of sight and hearing.

Over a century later, it is estimated that 285 million people are visually impaired worldwide, of which 39 million are blind.¹ Blindness is defined as the complete inability to see with a corrected vision of 20/200 or worse.² For Keller to absorb the information around her, she relied on the sensation of touch. The invention of the braille alphabet by Frenchman Louis Braille in the early 1800s allowed Keller to learn about the world and to communicate with others. Like Keller, the majority of the visually impaired today rely on braille as their main method of reading.

The technological advances of smartphones, artificial intelligence, and synthetic speech dictations have opened a whole new world for blind readers. With the advent of the electronic information age, it’s easy to think that blind people don’t need to rely on braille anymore to access information. In fact, braille literacy rates for school-age blind children have already declined from 50 percent 40 years ago to only 12 percent today.³ While current low literacy rates may be in part due to the inclusion of students with multiple disabilities that inhibit language acquisition, these statistics still reveal a major concern about literacy amongst the visually impaired. To substitute synthetic speech for reading and writing devalues the importance of learning braille.

“There are many misunderstandings and stereotypes of braille readers,” says Dr. Robert Englebretson, Professor of Linguistics at Rice University. “When a person reads, they learn about spelling and punctuation, and it’s the exact same for tactile readers. Humans better process information when they actively process it through reading instead of passively listening.”

Dr. Englebretson is also blind, and one part of his research agenda is a collaborative project with Dr. Simon Fischer-Baum in Psychology and pertains to understanding the cognitive and linguistic importance of braille to braille readers. He explores the questions surrounding the nature of perception and reading and explores the ways the mind groups the input of touch into larger pieces to form words.

In order to understand how written language is processed by tactile readers compared to visual readers, Dr. Englebretson conducted experiments to find out if braille readers exhibit an understanding of sublexical structures, or parts of words, similar to that of visual readers. An understanding of sublexical structures is crucial in recognizing letter groupings and acquiring reading fluency. Visual readers recognize sublexical structures automatically as the eye scans over words, whereas tactile readers rely on serially scanning fingers across a line of text.

To explore whether the blind have an understanding of sublexical structures, Dr. Englebretson studied the reaction time of braille readers in order to judge their understanding of word structures. The subjects were given tasks to determine whether the words were real or pseudowords, and the time taken to determine the real words from the pseudowords were recorded. The first experiment tested the ability for braille readers to identify diagraphs or parts of words, and the second experiment test the ability for braille readers to identify morphemes, or the smallest unit of meaning or grammatical function of a word. For braille readers, Dr. Englebretson and his team developed a foot pedal system that enabled braille readers to indicate their answer without pausing to click a screen as the visual readers did. This enabled the braille readers to continuously use their hands while reading. From the reaction times of the braille readers when presented with a morphologically complex word, the findings show evidence of braille readers processing the meaning of words and recognizing these diagraphs and morphemes.⁴

“What we discovered was that tactile readers do rely on sublexical structures and have similar cognitive processes to print readers,” says Dr. Englebretson. “The belief that braille is old-fashioned and not needed anymore is far from the truth. Tactile reading provides an advantage in learning just as visual reading does.”

Dr. Englebretson also gathered a large sample of braille readers and videotaped them reading using a finger tracking system. Similar to an eye tracking system that follows eye movements, the finger tracking system used LED lights on the backs of fingernails to track the LED movements over time using a camera. The movements of the LED lights on the x-y coordinates are then plotted on a graph. This system can track where each finger is, how fast they are moving, and the movements that are made during regressions, or the right-to-left re-reading movement of the finger.⁵ While this test was independent from the experiment about understanding sublexical structures, the data collected offers a paradigm for researchers about braille reading.

The outcome of these studies has not only scientific and academic implications, but also important social implications. “At the scientific level, we now better understand how perception [of written language] works, how the brain organizes and processes written language, and how reading works for tactile and visual readers,” says Dr. Englebretson. “Through understanding how tactile readers read, we will hopefully be able to implement policy on how teachers of blind and visually impaired students teach, and on how to guide the people who are working on updating and maintaining braille.”

With decreasing literacy rates among braille readers, an evidence-base approach to the teaching of braille is as critical as continuing to implement braille literacy programs. With an understanding of braille, someone who is blind can not only access almost infinite pages of literature, but also make better sense of their language and world.

References

1. World Health Organization. http://www.who.int/mediacentre/factsheets/fs282/en/ (accessed Jan. 9, 2017).
2. National Federation of the Blind. https://nfb.org/blindness-statistics (accessed Jan. 9, 2017).
3. National Braille Press. https://www.nbp.org/ic/nbp/braille/needforbraille.html (accessed Jan. 10, 2017).
4. Fischer-Baum,S.; Englebretson, R. Science Direct. 2016, http://www.sciencedirect.com/science/article/pii/S0010027716300762 (accessed Jan. 10, 2017)
5. Ulusoy, M.; Sipahi, R. PLoS ONE. 2016, 11. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0148356 (accessed Jan. 10, 2017)

The Secret Behind Social Stigma

Catalyst Volume 10

How do you accurately quantify something as subjective and controversial as discrimination? What about stigma - a superficial mark imposed upon a prototypical group of individuals? How do you attempt to validate what is seemingly invisible? Dr. Michelle “Mikki” Hebl and her team in the Industrial/Organizational (I/O) department of social psychology at Rice University attempt to answer these questions.

In the world of social psychology, where human interactions are often unpredictable, researchers must get creative to control variables as much as possible while simultaneously mimicking real-life situations. Dr. Hebl integrates both laboratory procedures and field studies that involve standardized materials. “My research is fairly novel,” she notes. Unlike the majority of existing stigma and discrimination research, which depends on self-reported assessments, her studies examine real, non-simulated social interactions. Although her approach seeks to provide more realistic and unbiased settings, “it’s messier,” she adds, laughing about the many trials discarded due to uncontrollable circumstances. That attitude— optimistic, determined, and creative—is held proudly by Dr. Hebl. It is clear that her lab’s overall mission—to reduce discrimination and increase equity—is worth undertaking.

Dr. Hebl and her team focus on a form of behavior they call “interpersonal discrimination,” a type of discrimination that occurs implicitly while still shaping the impressions we form and the decisions we make.¹ This kind of bias, rooted in stereotypes and negative social stigma, is far more subtle than some of the more well-known, explicit forms of discrimination. For example, in a field study evaluating bias against homosexual applicants in Texas, Dr. Hebl found that the members of both the experimental and control group, who were wearing hats that said “Gay and Proud” and “Texan and Proud” respectively, did not experience formal bias when entering stores to seek employment. For example, none of the subjects were denied job applications. What she did find, however, was a pattern of interpersonal reactions against the experimental group. Discrete recording devices worn by the subjects revealed a pattern of decreased word count per sentence and shorter interactions for the stigmatized group. Their self-reports further indicated on average a higher perceived negativity and lower perceived employer interest.1 In another study evaluating obesity-related stigma, results showed that obese individuals - in this case subjects wearing obese prosthetic suits - experience similarly negative interactions.²

While many of her studies evaluated biases in seeking employment, Dr. Hebl also explored the presence of interpersonal discrimination against lesser-known groups that experience bias. One surprising finding indicated negative stigmatization against cancer survivors.³ In other studies, the team found patterns relating to stereotypicality; this relatively new phenomena explores the lessened interpersonal discrimination against those who deviate from the stereotypical prototype of their minority group, i.e. a more light-skinned Hispanic male.⁴ A holistic review of her research reveals a pattern of discrimination against stigmatized groups on an implicit level. Once researchers like Dr. Hebl find these patterns, they can investigate them in the lab by further isolating variables to develop a more refined and widely-applicable conclusion.

What can make more subtle forms of bias so detrimental is the ambiguity surrounding them. When someone discriminates against another in a clear and explicit form, one can easily attribute the behavior to the person’s biases. On the other hand, when this bias is perceived in the form of qualitative behavior, such as shortened conversations and body language, it raises questions regarding the person’s intentions. In these cases, the victim often internalizes the negative treatment, questioning the effect of traits that they cannot control—be it race, sexual orientation, or physical appearance. This degree of uncertainty raises conflict and tension between differing groups, thus potentially hindering progress in today’s increasingly diverse workplaces, schools, and universities.⁵

Dr. Hebl knew that exploring the presence of this tension between individuals was only the first step. “One of the most exciting aspects of social psychology is that just learning about these things makes you inoculated against them,” she said. Thus emerges the search for practical solutions involving education and reformation of conventional practices in the workplace. Her current work looks at three primary methods: The first is acknowledging biases on an individual level. This strategy involves individuation, or the recognition of one’s own stigma and subsequent compensation for it.⁶ The second involves implementing organizational methods in the workplace, such as providing support for stigmatized groups and awareness training.⁷ The third, which has the most transformative potential, is the use of research to support reformation of policies that could protect these individuals.

“I won't rest…until we have equity,” she affirmed when asked about the future of her work. For Dr. Hebl, the ultimate goal is education and change. Human interactions are incredibly complex, unpredictable, and difficult to quantify. But they influence our daily decisions and actions, ultimately impacting how we view ourselves and others. Social psychology research suggests that biases, whether we realize it or not, are involved in the choices we make every day: from whom we decide to speak to whom we decide to work with. Dr. Hebl saw this and decided to do something about it. Her work brings us to the complex source of these disparities and suggests that understanding their foundations can lead to a real, desirable change.

References

1. Hebl, M. R.; Foster, J. B.; Mannix, L. M.; Dovidio, J. F. Pers. Soc. Psychol. B. 2002, 28 (6), 815–825.
2. Hebl, M. R.; Mannix, L. M. Pers. Soc. Psychol. B. 2003, 29 (1), 28–38.
3. Martinez, L. R.; White, C. D.; Shapiro, J. R.; Hebl, M. R. J. Appl. Psychol. 2016, 101 (1), 122–128.
4. Hebl, M. R.; Williams, M. J.; Sundermann, J. M.; Kell, H. J.; Davies, P. G. J. Exp. Soc. Psychol. 2012, 48 (6), 1329–1335.
5. Szymanski, D. M.; Gupta, A. J. Couns. Psychol. 2009, 56 (2), 300–300.
6. Singletary, S. L.; Hebl, M. R. J. Appl. Psychol. 2009, 94 (3), 797–805.
7. Martinez, L. R.; Ruggs, E. N.; Sabat, I. E.; Hebl, M. R.; Binggeli, S. J. Bus. Psychol. 2013, 28 (4), 455–466.

Haptics: Touching Lives

Catalyst Volume 10

Everyday you use a device that has haptic feedback: your phone. Every little buzz for notifications, key presses, and failed unlocks are all examples of haptic feedback. Haptics is essentially tactile feedback, a form of physical feedback that uses vibrations. It is a field undergoing massive development and applications of haptic technology are expanding rapidly. Some of the up-and-coming uses for haptics include navigational cues while driving, video games, virtual reality, robotics, and, as in Dr. O’Malley’s case, in the medical field with prostheses and medical training tools.

Dr. Marcia O’Malley has been involved in the biomedical field ever since working in an artificial knee implant research lab as an undergraduate at Purdue University. While in graduate school at Vanderbilt University, she worked in a lab focused on human-robot interfaces where she spent her time designing haptic feedback devices. Dr. O’Malley currently runs the Mechatronics and Haptic Interfaces (MAHI) Lab at Rice University, and she was recently awarded a million dollar National Robotics Initiative grant for one of her projects. The MAHI Lab “focuses on the design, manufacture, and evaluation of mechatronic or robotic systems to model, rehabilitate, enhance or augment the human sensorimotor control system.”¹ Her current research is focused on prosthetics and rehabilitation with an effort to include haptic feedback. She is currently working on the MAHI EXO- II. “It’s a force feedback exoskeleton, so it can provide forces, it can move your limb, or it can work with you,” she said. The primary project involving this exoskeleton is focused on “using electrical activity from the brain captured with EEG… and looking for certain patterns of activation of different areas of the brain as a trigger to move the robot.” In other words, Dr. O’Malley is attempting to enable exoskeleton users to control the device through brain activity.

Dr. O’Malley is also conducting another project, utilizing the National Robotics Initiative grant, to develop a haptic cueing system to aid medical students training for endovascular surgeries. The idea for this haptic cueing system came from two different sources. The first part was her prior research which consisted of working with joysticks. She worked on a project that involved using a joystick, incorporated with force feedback, to swing a ball to hit targets.² As a result of this research, Dr. O’Malley found that “we could measure people’s performance, we could measure how they used the joystick, how they manipulated the ball, and just from different measures about the characteristics of the ball movement, we could determine whether you were an expert or a novice at the task… If we use quantitative measures that tell us about the quality of how they’re controlling the tools, those same measures correlate with the experience they have.” After talking to some surgeons, Dr. O’Malley found that these techniques of measuring movement could work well for training surgeons.

The second impetus for this research came from an annual conference about haptics and force feedback. At the conference she noticed that more and more people were moving towards wearable haptics, such as the Fitbit, which vibrates on your wrist. She also saw that everyone was using these vibrational cues to give directional information. However, “nobody was really using it as a feedback channel about performance,” she said. These realizations led to the idea of the vibrotactile feedback system.

Although the project is still in its infancy, the current anticipated product is a virtual reality simulator which will track the movements of the tool. According to Dr. O’Malley, the technology would provide feedback through a single vibrotactile disk worn on the upper limb. The disk would use a voice coil actuator that moves perpendicular to the wearer’s skin. Dr. O’Malley is currently working with Rice psychologist Dr. Michael Byrne to determine which frequency and amplitude to use for the actuator, as well as the timing of the feedback to avoid interrupting or distracting the user.

Ultimately, this project would measure the medical students’ smoothness and precision while using tools, as well as give feedback to the students regarding their performance. In the future, it could also be used in surgeries during which a doctor operates a robot and receives force feedback through similar haptics. During current endovascular surgery, a surgeon uses screens that project a 2D image of the tools in the patient. Incorporating 3D views would need further FDA approval and could distract and confuse surgeons given the number of screens they would have to monitor. This project would offer surgeons a simpler way to operate. From exoskeletons to medical training, there is a huge potential for haptic technologies. Dr. O’Malley is making this potential a reality.

References

1. Mechatronics and Haptic Interfaces Lab Home Page. http://mahilab.rice.edu (accessed   Nov. 7, 2016).
2. O’Malley, M. K. et al. J. Dyn. Sys., Meas., Control. 2005, 128 (1), 75-85.

The Depressive Aftermath of Brain Injury

Catalyst Volume 10

One intuitively knows that experiencing a brain injury is often painful and terrifying; the fact that it can lead to the onset of depression, however, is a lesser known but equally serious concern. Dr. Roberta Diddel, a clinical psychologist and member of the adjunct faculty in the Psychology Department at Rice University, focuses on the treatment of individuals with mental health issues and cognitive disorders. In particular, she administers care to patients with cognitive disorders due to traumatic brain injury (TBI). Dr. Diddel acquired a PhD in clinical psychology from Boston University and currently runs a private practice in Houston, Texas. Patients who experience TBI often experience depression; Dr. Diddel uses her understanding of how this disorder comes about to create and administer potential treatments.

Traumatic brain injury (TBI) affects each patient differently based on which region of the brain is damaged. If a patient has a cerebellar stroke, affecting the region of the brain which regulates voluntary motor movements, he or she might experience dizziness and have trouble walking. However, that patient would be able to take a written test because the injury has not affected higher order cognitive functions such as language processing and critical reasoning.

Dr. Diddel said, “Where you see depression the most is when there is a more global injury, meaning it has affected a lot of the brain. For example, if you hit your forehead in a car accident or playing a sport, you’re going to have an injury to the front and back parts of your brain because your brain is sitting in cerebrospinal fluid, causing a whiplash of sorts. In turn, this injury will cause damage to your frontal cortex, responsible for thought processing and problem solving, and your visual cortex, located in the back of your brain. When your brain is bouncing around like that, you often have swelling which creates intracranial pressure. Too much of this pressure prevents the flow of oxygen-rich blood to the brain. That can cause more diffuse brain injury.”

In cases where people experience severe brain injury such as head trauma due to an explosion or a bullet, surgeons may remove blood clots that may have formed in order to relieve intracranial pressure and repair skull fractures.⁴ They may also remove a section of the skull for weeks or months at a time to let the brain swell, unrestricted to the small, cranial cavity. That procedure alone significantly reduces the damage that occurs from those sorts of injuries and is especially useful in the battlefield where urgent care trauma centers may not be available.

Depression is a common result of TBI. The Diagnostic and Statistical Manual of Mental Disorders (DSM) defines depression as a loss of interest or pleasure in daily activities for more than two weeks, a change in mood, and impaired function in society.¹ These symptoms are caused by brain-related biochemical deficiencies that disrupt the nervous system and lead to various symptoms. Usually, depression occurs due to physical changes in the prefrontal cortex, the area of the brain associated with decision-making, social behavior, and personality. People with depression feel overwhelmed, anxious, lose their appetite, and have a lack of energy, often because of depleted serotonin levels. The mental disorder is a mixture of chemical imbalances and mindstate; if the brain is not correctly functioning, then a depressed mindstate will follow.

Dr. Diddel mentioned that in many of her depressed patients, their lack of motivation prevents them from addressing and improving their toxic mindset. “If you’re really feeling bad about your current situation, you have to be able to say ‘I can’t give in to this. I have to get up and better myself and my surroundings.’ People that are depressed are struggling to do that,” she said.

The causes of depression vary from patient to patient and often depends on genetic predisposition to the disease. Depression can arise due to physical changes in the brain such as the alterations in the levels of catecholamines, neurotransmitters that works throughout the sympathetic and central nervous systems. Catecholamines are broken down into other neurotransmitters such as serotonin, epinephrine, and dopamine, which are released during times of positive stimulation and help increase activity in specific parts of the brain. A decrease in these chemicals after an injury can affect emotion and thought process. Emotionally, the patient might have a hard time dealing with a new disability or change in societal role due to the trauma. Additionally, patients who were genetically loaded with genes predisposing them to depression before the injury are more prone to suffering from the mental disorder after the injury.^2,3

Depression is usually treated with some form of therapy or antidepressant medication. In cognitive behavior therapy (CBT), the psychologist tries to change the perceptions and behavior that exacerbate a patient’s depression. Generally, the doctor starts by attempting to change the patient’s behavior because it is the only aspect of his or her current situation that can can described. Dr. Diddel suggests such practices to her patients, saying things like “I know you don’t feel like it, but I want you to go out and walk everyday.” Walking or any form of exercise increases catecholamines, which essentially increases the activity of serotonin in the brain and improves the patient’s mood. People who exercise as part of their treatment regimen are also less likely to experience another episode of depression.

The efficacy of antidepressant medication varies from patient to patient depending on the severity of depression a patient faces. People with mild to moderate depression generally respond better to CBT because the treatment aims to change their mindset and how they perceive the world around them. CBT can result in the patient’s depression gradually resolving as he or she perceives the surrounding stimuli differently, gets out and moves more, and pursues healthy endeavors. Psychologists usually begin CBT, and if the patient does not respond to that well, then they are given medication. Some medications increase serotonin levels while others target serotonin, dopamine, and norepinephrine; as a result, they boost the levels of neurotransmitters that increase arousal levels and dampen negative emotions. The population of patients with moderate to severe depressions usually respond better to antidepressant medication. Medication can restore ideal levels of neurotransmitters, which in turn encourages the patient to practice healthier behavior.

According to the Center for Disease Control and Prevention, the US saw about 2.5 million cases of traumatic brain injury in 2010 alone.⁵ That number rises every year and with it brings a number of patients who suffer from depression in the aftermath.⁵ Though the mental disorder has been studied for decades and treatment options and medications are available, depression is still an enigma to physicians and researchers alike. No two brains are wired the same, making it very difficult to concoct a treatment plan with a guaranteed success rate. The work of researchers and clinical psychologists like Dr. Diddel, however, aims to improve the currently available treatment. While no two patients are the same, understanding each individual’s depression and tailoring treatment to the specific case can vasty improve the patient’s outcome.

References

1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC, 2013.
2. Fann, J. Depression After Traumatic Brain Injury. Model Systems Knowledge Translation Center [Online]. http://www.msktc.org/tbi/factsheets/Depression-After-Traumatic-Brain-Injury (accessed Dec. 28, 2016).
3. Fann, J.R., Hart, T., Schomer, K.G. J. Neurotrauma. 2009, 26, 2383-2402.
4. Mayo Clinic Staff. Traumatic Brain Injury. Mayo Clinic, May 15, 2014. http://www.mayoclinic.org/diseases-conditions/traumatic-brain-injury/basics/treatment/con-20029302 (accessed Dec. 29, 2016).
5. Injury Prevention and Control. Centers for Disease Control and Prevention. https://www.cdc.gov/traumaticbraininjury/get_the_facts.html (accessed Dec. 29, 2016).