IMS Magazine Spring 2016 by IMS Magazine

IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS | 1

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IN THIS ISSUE Letter from the Editor .............. Director’s Message.................. Commentary ............................ Important Dates ...................... Twitter Feature ........................ Feature: Sensory System ........ Faculty Interviews ................... Synesthesia ............................. Special BMC Feature .............. Viewpoint ................................ Book Review ........................... Faculty Spotlight...................... Student Spotlight .................... Travel Bites .............................. Future Directions ..................... Diversions ............................... Past Events ..............................

~45,000 students enrolled

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Sensory Systems

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MAGAZINE STAFF EDITOR-IN-CHIEF EXECUTIVE EDITORS JOURNALISTS & EDITORS

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PhD Facts Around the World

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Most countries require students to have an honours degree or a master’s degree.

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The IMS Magazine is a student-run initiative. Any opinions expressed by the author(s) United Kingdom Sweden are in no way affiliated with the Institute of Medical Science or the University of Finland Toronto. France = 1 ye ar Ireland

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Cover design by Sarah Kim “This cover portrays the cellular rods and cones that allow our eyes to detect light and colour. They are just a small part of our body’s intricate and vast sensory system.” IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS | 3

LETTER FROM THE EDITOR

Photo credit Tahani Baakdhah

LETTER FROM THE

EDITOR O

ur sensory system is flooded with information from the minute we are born as we perceive and recognize the warmth of a human touch, the friendly sound of a parent’s cooing, or the unpleasant taste of mashed peas. The senses work together to capture snapshots of the world around us, each dominating over the other at times. When our senses collide dramatically (a phenomenon known as synesthesia), the number “5” can bask in a halo of purple, the name “Derek” might taste like earwax, and a symphony may smell of your morning coffee. In this issue of the IMS Magazine, we dive into our senses with some of the leading researchers in the field of vision, hearing, and somatosensory integration—many of whom I discovered are alumni of our department. Dr. Agnes Wong and Dr. Martin Steinbach discuss the development of the visual system and treatment for visual disorders such as macular degeneration and pediatric strabismus. Dr. Karen Gordon explains her findings on the 4 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS

effectiveness of cochlear implant use to initiate changes in our brain in children who are born deaf. In addition, Dr. Vincent Lin describes his basic science research into regenerating inner ear hair cells to restore hearing. Finally, to wrap things up, we discuss how the brain integrates this information, and how this process is affected by aging with Dr. Bernhard Ross. Part of our work at the IMS Magazine involves encouraging people to stay curious. We asked whether PhD degrees around the world were made equal, and accompany the piece with an infographic highlighting global statistics on PhD completion times. I encourage you to have a look at our ‘Travel Bites’ pieces highlighting conference experiences from Paris and closer to home, in Ottawa. We discuss life after IMS with alumni and now family physician Dr. Joe Gabriel. Finally, our ‘Spotlight’ with IMS students Brent Bates and David Chen, and IMS faculty Dr. Jonathan Irish offer a glimpse of the many compelling stories of who we are at

the IMS, and I strongly encourage you to have a look. I would like to thank Dr. Mingyao Liu and the IMS department for their ongoing support, and congratulate the design team on another fantastic production of this magazine. Thank you to the incredible IMS Magazine team for their dedication and enthusiasm. To you, our readers and supporters, please feel free to add your own thoughts to any of the stories in this issue as we continue to showcase to you the best of the IMS. Tweet us @IMSMagazine, or leave us your comments on our website, imsmagazine.com, or directly to our inbox at theimsmagazine@gmail.com. Happy reading!

Annette Ye, Editor-in-Chief, IMS Magazine

DIRECTOR’S MESSAGE Mingyao Liu has been the Director of IMS since 2015. He is currently a Senior Scientist at the University Health Network, Toronto General Research Institute, and a Professor of Surgery, Medicine Photo credit Tahani Baakdhah

and Physiology in the Faculty of Medicine at University of Toronto. Dr. Liu has published over 250 peer-reviewed research articles, and is the recipient of the Queen Elizabeth II Diamond Jubilee Medal for his work in developing molecular therapies for lung injury during and after lung transplantation.

DIRECTOR’S MESSAGE I

t is a pleasure to present the 17th issue of the IMS Magazine featuring the research and people within the IMS. I often talk about the research achievements of our department, but many of our faculty and trainees are clinician-scientists. Did you know that Dr. Vincent Lin, an IMS faculty, performed Canada’s first cochlear implant to treat single-sided deafness? Or that Dr. Agnes Wong, IMS alumnus and now IMS faculty member, established a test to distinguish causes of vertical strabismus (misalignment of the eyes) in the clinic? This issue highlights these faculty members and others in an issue focused on vision and hearing within the sensory system. Over the years, the IMS community has grown widely as many alumni relocate outside Canada. However, many alumni return to the University of Toronto as

faculty, and several were featured in this issue: Dr. Agnes Wong, Dr. Jonathan Irish, Dr. Joe Gabriel, and Dr. Karen Gordon. I hope their stories provide inspiration and encouragement for current and future students. On Friday, May 20, 2016, IMS will host our Annual Scientific Day at the St. Andrew’s Club and Conference Centre. This year’s keynote address will be given by Dr. Victor Dzau from the Institute of Medicine at the National Academy of Sciences. His talk is titled, “Healing and Regenerating Hearts: 21st Century Prometheus?” Dr. Dzau is a pioneer and leader in cardiovascular medicine, genetics, and healthcare innovation. We will also have parallel symposium sessions on various topics from tumor supressors to education, and even the relation between sleep and mental health. I am looking forward to an insightful day with

IMS students and faculty as we celebrate excellence in both research and teaching. Congratulations to Annette Ye and her team for their continued dedication and collective creative energies in producing this publication. The IMS Magazine has been a tremendous success and is just one of the many wonderful, student-led initiatives to make the IMS a very special institute. I fully support the ongoing publication and look forward to reading and learning about the outstanding research that is being conducted by our faculty and trainees in IMS. I look forward to seeing you at Scientific Day on May 20. Sincerely, Mingyao Liu, MD, MSc Director, Institute of Medical Science IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS | 5

COMMENTARY

THE IMMUNE SYSTEM AND THE CENTRAL NERVOUS SYSTEM

AN INTIMATE RELATIONSHIP FINALLY REVEALED New landscape or seeing with new eyes? By Antigona Ulndreaj and Meital Yerushalmi

“

The real voyage of discovery consists not in seeking new landscapes but in having new eyes.”1 This quote by Marcel Proust resonated in my mind while reading the article “Immune Privilege Within the Central Nervous System: It’s Not Always What It Seems” in IMS Magazine’s Winter 2015 issue. As Proust conveys in his book, an artist invests themselves into their art to express reality through their unique viewpoints. Not unlike artists, scientists approach discoveries with their unique set of skills, as they interpret scientific phenomena through their field of expertise. The immune system and the central nervous system (CNS) have been considered to function independently from each other. Along with other arguments, the absence of lymphatic vessels within the CNS supported the view of an immune-privileged CNS. This notion, however, has been challenged in the past two decades by studies demonstrating the involvement of the immune system in CNS health and disease.

In 2015, the discovery of functional lymphatic vessels in the CNS was the final nail in the coffin of the immune-isolated CNS dogma.2,3 It took a new set of eyes, that of an immunologist, to re-examine the micro-structure of the CNS and bring an 6 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS

end to the dogma. A new era has begun in the field of neuroscience! Or, has it just begun? Along with commentary articles celebrating the landmark, seeking the answer to this has yielded additional, more intriguing results. Or troubling, should you look at the glass half empty. Publications dating back over half a century have reported the existence of lymphatic vessels in the CNS for the first time.4,5 Could it be that those studies failed to be investigated further because of their disagreement with the immune-isolated CNS dogma? Resistance to unpopular theories, driven by long-held biases, is not new in research. Yet, this story also highlights the importance of inter-disciplinary collaboration in the quest to answer century-long questions. This discovery necessitates a collaborative re-examination of the CNS, welcoming the emergence of such inter-disciplinary fields as neuroimmunology, psychoneuroimmunology, and neuroendocrinoimmunolgy. Nevertheless, inter-disciplinary science is not immune from dogmas, which may hurdle future discoveries. A fine balance should exist in the peer-review process: similar to the immune system, an overly tolerant review could result in an infectious pandemic of poorly-conducted science; while an overly

vigilant review may impede innovative thinking and re-examination of dogmas. Perhaps the focus should be placed on striving for publishing high-quality science, including that which may question an established idea. This new era in neuroscience opens the door for exciting research in the field, welcoming curiosity and innovation in exploring the relationship between the immune system and CNS. Most important, it empowers the notion that, so long as science is done rigorously, a debate over and re-examination of dogma should not be feared of. In the words of Marcel Proust, a “powerful idea communicates some of its strength to him who challenges it.” 6

References 1. Proust M. The Captive & The Fugitive: In Search of Lost Time, Vol. V. Enright DJ, editor. New York; London: Modern Library; 1999. 992. 2. Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015 Jul 16;523(7560):337–41. 3. Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, Detmar M, et al. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med. 2015 Jun 29;212(7):991–9. 4. Bucchieri F, Farina F, Zummo G, Cappello F. Lymphatic vessels of the dura mater: a new discovery? J Anat. 2015 Nov 1;227(5):702–3. 5. Mezey É, Palkovits M. Neuroanatomy: Forgotten findings of brain lymphatics. Nature. 2015 Aug 27;524(7566):415–415. 6. Proust M. Remembrance of Things Past. Vol.1. Wordsworth Editions; 2006. 1382.

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FEATURE

cochlear implant in children

An Interview with DR. KAREN

r. Karen Gordon is an Audiologist and the Director of Research in Archie’s Cochlear Implant Laboratory at The Hospital for Sick Children. She is an Associate Professor in the Department of Otolaryngology, and a Full Graduate Faculty Member in the Institute of Medical Science (IMS) at the University of Toronto. She is also affiliated with the Department of Speech Language Pathology. Dr. Gordon became the inaugural recipient of the Bastable-Potts Health Clinician Scientist Award in Hearing Impairment in 2014. She is presently examining ways to improve auditory development and hearing for children who are deaf by promoting binaural hearing with auditory prostheses including bilateral cochlear implants.

Please describe your education background and training. I completed my Bachelor of Science at the University of Toronto in 1991 and then received a clinical degree in audiology at Northwestern University in Evanston, Illinois in 1993. I worked as an audiologist at the Hospital for Sick Children for almost four years before starting my graduate studies through IMS at the University of Toronto in 1998. Those were wonderful and fun years as I became a mom (two daughters) and set up what is now Archie’s Cochlear Implant Laboratory at SickKids. How did you get involved in cochlear implant research and what did you find most appealing in this area? I was an audiologist in the cochlear implant program before going back to graduate school. At that time, cochlear implantation in children who were deaf was fairly new. There were so many questions about these unique devices and about how children who received one cochlear implant might learn to listen and communicate. 12 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS

Please give us some insight on unilateral and bilateral cochlear implant in children, and your research findings. In my PhD studies, I explored developmental changes along the auditory pathways in children who received one cochlear implant. We discovered changes in brainstem and thalamo-cortical function that were time-locked to the beginning of cochlear implant use. Rates of change in the auditory brainstem were remarkably similar to those in normal hearing children over the first years of life, indicating that development at this level of the auditory pathways requires stimulation. By contrast, changes in thalamo-cortical activity were more variable and dependent upon the age at implantation. It became clear that the auditory cortex was vulnerable to reorganization during a period of bilateral deafness which affected cochlear implant use. We wondered whether the auditory brainstem, which plays an important role in integrating sound information from our two ears, could be vulnerable to reorganization by unilateral stimulation and whether there were more central effects in the auditory cortex. At the same time, we were seeing

GORDON By Yekta Dowlati

that children using one cochlear implant were hearing and developing spoken language but that they were struggling in situations with multiple sounds and voices. This was due, in part, to a lack of hearing from both ears. We therefore embarked on studies of children provided with two cochlear implants. We compared children who had used one cochlear implant for months to years before receiving a second in the non-implanted ear (sequentially) to children who received bilateral cochlear implants simultaneously. The data revealed significant asymmetries in development along the bilateral auditory pathways in children implanted sequentially with a long delay. This sets up an “aural preference” for the first implanted ear, disrupting binaural hearing. By contrast, children implanted bilaterally with limited or no delays show more normal auditory development. What are the main impacts of your research work? Our early work revealed effects of deafness on the immature auditory system and the effectiveness of cochlear implant use to initiate development in the auditory

Photo by Tahani Baakdhah

FEATURE

brainstem and thalamo-cortex. More recently, we have identified the importance of bilateral hearing for children and defined a sensitive period during which bilateral hearing should be provided. We are now asking how best to stimulate bilateral pathways so children with bilateral cochlear implants can gain binaural/spatial hearing and hear better in difficult listening situations. We are also asking whether binaural hearing can be restored to children with asymmetric hearing loss. To answer this question, we are now providing a cochlear implant to children who meet candidacy for their worse ear but who have normal hearing or enough hearing to use a hearing aid in the other ear. This will mean that the auditory system has to integrate two very different inputs from each ear. What is the most rewarding part of your job? I have been very fortunate to watch children grow up with their cochlear implants. The experience of each child and family is so unique and it is a privilege for us to spend time with them. They inspire us and inform our specific research questions.

Karen Gordon, PhD Audiologist, Cochlear Implant Program Scientist, Neurosciences and Mental Health Full Member and Alumnus, Institute of Medical Science

Likewise, I work with an amazing group of clinicians and researchers who are always looking for innovative approaches to treating hearing loss in children.

listening and communication.

Whatâ&#x20AC;&#x2122;s on the horizon for this field?

Clinical research is incredibly stimulating and very rewarding but health research clinicians face challenges finding positions with secure funding. I am extremely thankful to my clinical departments, SickKids Research Institute, and the Bastable-Potts estate for their support.

At present, we cannot cure deafness. Rather, we attempt to provide the child or adult hearing system with the best information possible through hearing devices and hope that there is sufficient neuroplasticity to support optimal hearing. We have learned that children who use auditory prostheses may not recover or develop the same function as their normal hearing peers. This is because there are changes to the auditory brain during the period of sound deprivation and because hearing devices deliver imperfect representations of sound. Future efforts to improve hearing for children and adults with hearing loss must seek to identify and cure dysfunctions in the inner ear. At the same time, we will search for methods to limit maladaptive changes in the auditory system and promote development which best supports hearing. What we ultimately want is to remove the barriers that children and adults with hearing loss face in every day

What are some of the challenges that you have faced in your career as a researcher?

What words of wisdom do you have for graduate students? I advise graduate students at the outset to make sure that they feel connected and committed to their project. Youâ&#x20AC;&#x2122;ll probably have times during your training where you have doubts about what you are doing and why but these questions are more easily answered if you remember why you began this work and the potential impact it can have. I also encourage team work which is an important source of motivation and support.

IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS | 13

FEATURE

Photo credit Tahani Baakdhah

Martin Steinbach, PhD Senior Scientist, Toronto Western Research Institute and The Hospital for Sick Children Distinguished Research Professor Emeritus, York University Professor, Ophthalmology and Vision Sciences, University of Toronto Director, Ophthalmology Research, University of Toronto President, Vision Health Research Council of Canada Full Member, Institute of Medical Science

Left: Luminita Tarita-Nistor, Right: Taylor Brin

Treating Central and Peripheral Vision Loss:

More Than Meets the Eye An interview with Dr. Martin Steinbach on early detection and therapies for glaucoma and age-related macular degeneration. By Rachel Dragas

14 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS

mongst many of his notable designations, Dr. Martin Steinbach is a senior scientist at Toronto Western Hospital, Professor of Ophthalmology at the University of Toronto, and President of the Vision Health Research Council of Canada. For the past 5 decades, Dr. Steinbach’s renowned work on abnormal eye movements and visual processes, as well as his advocacy for vision health and research in Canada have stood as a true testament to his passion and dedication in the field. His contributions have been recognized nationally and internationally; most notably, he received the 2008 Carl Kupfer

Award from the Association for Research in Vision and Ophthalmology and has had the University of Toronto’s Department of Ophthalmology and Vision Sciences’ Annual Research Day Lecture named in his honour. Dr. Steinbach’s research not only focuses on plasticity of the developing visual system in patients with monocular eye enucleation, but also central and peripheral vision loss produced by diseases such as age-related macular degeneration (AMD) and glaucoma, respectively. His work is geared towards the development of effective techniques to measure residual visual acuity for patients with AMD as well as eye retraining strategies for utilization of

FEATURE functional retinal areas. More recently, his lab has also focused on early detection of impaired vection as an early indicator for glaucoma. I sat down with Dr. Steinbach to hear more about his passion for vision research and the progress of diagnostic applications and therapies for patients with retinal disease. Can you tell us a bit about your background, training, and what brought you to this particular field of research? I obtained my PhD from the Massachusetts Institute of Technology and have a degree in experimental psychology. I don’t identify as a psychologist, I identify as a systems neuroscientist—I do behavioural studies of the visual system. I came to Toronto in 1968 with a job offer at York University and, in 1971, while lecturing for an introductory psychology class, I noticed a student in the front row with eyes like Marty Feldman, the comedian. The condition he had is known as ‘alternating exotropia,’ a form of strabismus where both eyes are directed outward at alternate times. I hired the student as a research assistant and studied his eye movements. I soon realized that I couldn’t learn the clinical attributes of strabismus from books alone as I was always questioning the texts. After spending a year in San Francisco working with a famous eye muscle surgeon, I collaborated with another surgeon at The Hospital for Sick Children, where I looked at changes in the brains of patients with rotated eyes and how the brain stays informed about these movements. I was able to glean understanding on how vision works by understanding how it can go wrong. My collaboration with Dr. Brenda Gallie, who is world famous for treating unilateral retinoblastoma, enabled me to study the competition that occurs between the eyes during development—if it’s interrupted by a cataract, droopy lid, or unequal refractive error, for example, the child develops amblyopia (lazy-eye) and the brain doesn’t wire up properly. During development in enucleated children, the brain gets rewired to have the single eye take up space and computing energy that would normally be distributed between both eyes. Enucleated children have visual functions that are superior to those with monocular vision but equal to those with normal binocular vision. This is an example of sensory plasticity.

What rehabilitative strategies can be utilized by patients with macular degeneration? Macular degeneration is a condition where foveal or central vision becomes damaged and nonfunctional. Patients with this disease, however, retain function in their retinal periphery. In the absence of central vision, patients develop alternate points of fixation in eccentric parts of the retina, termed ‘preferred retinal loci.’ However, if a patient has a preferred retinal locus at the horizontal edge of a scotoma (blind spot with no photoreceptors), for example, they cannot read. If we can get these patients to change which part of the retina they use, essentially relocating their preferred retinal locus, they are able to read again and acquire better fixation stability. We train patients, using biofeedback methods, to move the fixation point to a position that would allow horizontal movement to seeing parts of retina. Unfortunately, this requires an expensive piece of equipment (a microperimeter), which is not readily available or easy to use. An alternative technique, called ‘perceptual learning’ is just as effective and has improved functioning in many patients. We ask patients to read text and encourage them to look above or below the script, allowing images to be picked up by a working part of the retina. They can develop a good point of fixation using this method. The challenge is getting this technique out into wider application given the time-consuming process of training patients, which is often impractical for most physicians and ophthalmologists. It would be ideal to create an online app for automation of these techniques, so that patients can train themselves in the comfort of their homes. Can you tell us more about the technology that you are utilizing for early detection of glaucoma? Contrast to macular degeneration, glaucoma is an eye disease that first affects peripheral vision. Despite this, most people don’t realize that their eyesight is impaired until their central vision is affected. The retinal periphery is necessary for orientation in space. Vection is a perceptual phenomenon where, when a large part of the visual field moves, the viewer feels like they have moved while the world remains stationary. Using Oculus

Rift virtual reality technology, our lab can extract information from peripheral visual function and test whether impaired vection is an early indicator for glaucoma. This provides an opportunity for early treatment and prevention of vision loss. What is the most rewarding part of your job? The most rewarding part of my job is training young scientists but also serving as a bridge between basic and clinical research. I’m trained as a basic scientist, but I’ve become sufficiently embedded in ophthalmology. For the past 11 years, I’ve written a bi-monthly column in the Canadian Journal of Ophthalmology called Cyclops. In every issue, there are 6 experimental studies that I briefly summarize and state the importance of for my ophthalmologist colleagues. There’s lots of interesting basic research that clinicians should be aware of so I’m particularly proud of Cyclops. In addition to this, I serve on the Canadian National Institute for the Blind research committee, I’m the Chair of Medical Advisories for the Foundation Fighting Blindness, and an advocate for vision research in Canada. What do you think is the future of research in vision science? Long term, the opportunity to see dead photoreceptor cells replaced through stem cells or gene transplants—this would cover a lot of diseases including macular degeneration and diabetic retinopathy. However, in the short term our efforts should also be focused on rehabilitation for patients currently experiencing vision loss, as there are still treatment strategies that can be implemented to prevent further vision loss and improve quality of life. What advice can you give to current graduates? Aside from following your dreams and enjoying your work, be open to opportunities that exist outside of academia. Appreciate the fact that you are acquiring numerous skills that have application outside of the academic world and that should give you optimism about being gainfully employed in the future.

IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS | 15

CURING

FEATURE

Dr. Vincent Lin

Development of New Treatment Strategies from Bench to Bedside

The Sonja N. Koerner Hearing Regeneration Initiative and Sunnybrook Cochlear Implant–Otology Research Program By Vincent Lin, MD, FRCSC and Nils Gritters, B.Sc (Hons)

I Nils Gritters Faculty affiliations: Associate Professor, Department of Otolaryngology–Head & Neck Surgery, Faculty of Medicine, University of Toronto Associate Scientist, Sonja N. Koerner Hearing Regeneration Initiative, Sunnybrook Research Institute

The Otology research program (http://sunnybrook.ca/ content/?page=otolaryngology-headneck-research) at Sunnybrook Health Sciences Centre has a bench to bedside philosophy for research into therapies 16 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS

for hearing restoration. The team’s clinical research involves trials for new pharmaceuticals to treat diseases of the ear as well as research into improving current cochlear implants and testing new cochlear implants. A cochlear implant is a device that receives sound through an external microphone worn over the ear which then transmits that sound, as an electrical signal, to an implanted electrode which directly stimulates the auditory nerve. The auditory nerve then sends the electronic signals to the brain where they are processed as sound. There is a large amount of variability in the outcomes of patients with cochlear implants as some patients achieve close to normal speech recognition and others receive almost no benefit from their cochlear implant.10 One area of research involves the measurement of the functional state of inner ear neurons by measuring electrophysiological responses to sound stimuli to determine the effect this may have on cochlear implant outcomes. Additionally, the team conducts trials for new programming methodologies and clinical indications for

Photos provided by Dr. Vincent Lin and Nils Gritters

Sunnybrook Cochlear Implant Program, Sunnybrook Health Sciences Centre Associate member, Institute of Medical Science

n humans, hearing loss is the most prevalent form of sensory impairment. In Canada, 19% of people aged 20 to 79 have some degree of hearing loss.1 This number increases to 65% for individuals aged 70-79.1 According to Speech-Language and Audiology Canada, the estimated cost of hearing loss to the Canadian economy is over $10 billion each year.2 Hearing loss can reduce quality of life by impacting communication potentially leading to withdrawal, social isolation, and depression.3,4 In addition, hearing loss has been associated with accelerated cognitive decline and dementia in elderly populations.5,6 Numerous studies have shown that the use of assisted hearing devices such as hearing aids or cochlear implants can significantly improve quality of life in individuals with hearing loss and their families.7-9

HEARING LOSS FEATURE

cochlear implants. Traditionally, cochlear implant surgery would eliminate any residual hearing thus only individuals with profound hearing loss would be implanted. We are currently investigating steroid treatments to prevent loss of hearing during surgery. Now we actively implant patients with residual hearing using our new soft surgery techniques. In addition, we are conducting research into the benefit of cochlear implants for patients with single sided deafness who are deaf in one ear, but have normal hearing in the other. Although these therapies may be effective at allowing patients to hear again, they do not fix or replace the damaged tissue that resulted in hearing loss. Cochlear implants instead bypass the damaged area giving patients a new way to hear. Hearing loss has been associated with increased risk for cognitive decline and dementia.5,6 With the large aging baby boomer generation, it is predicted that the percentage of Canadians above the age of 65 could rise from 15% in 2011 to 23% by 2031.11 As age is a large risk factor for both hearing loss and dementia, this association is of particular importance. We are therefore currently working to develop and validate a tool that can be used to screen for mild cognitive impairment in individuals with hearing loss because current tools can only be administered effectively to normal hearing individuals. There are three types of hearing loss: sensorineural, conductive, and mixed hearing loss. The most common form of hearing impairment is sensorineural hearing loss, which occurs when there is damage to sensory cells of the inner ear or damage to the auditory nerve.12 Acquired sensorineural hearing loss is often the result of damage or loss of the hair cells of the inner ear. Humans and other mammals are unable to regenerate these cells when they are damaged or lost unlike in birds, amphibians, or fish.13

Together with Dr. Alain Dabdoub, Director of the Sonja N. Koerner Hearing Regeneration Initiative and research scientist at the Sunnybrook Research Institute, we are interested in investigating generation and differentiation of inner ear neurons during development to ultimately design strategies to regenerate these cells. Our research is therefore attempting to find a biological solution to cure hearing loss. One area of interest is the Wnt signaling pathway in the inner ear. Wnt signalling is important for cochlear development, proliferation of prosensory cells, and cell fate determination and therefore may be a potential route for inner ear neuron regeneration and hearing restoration.14,15 Wnt signaling is different at different stages of development.14,16 We are currently identifying components of Wnt signalling pathways at various stages of development in vivo and in vitro to better understand their role in regenerating lost hair cells or neurons. Transcription factors, such as Atoh1, regulate hair cell formation during development. Atoh1 has been found to be necessary for maturation and survival of inner ear hair cells as well as neurogenesis in the cerebellum.17 At later stages of development, new hair cells are no longer generated in response to Atoh1.18 Another area of our research therefore involves attempting to investigate how Atoh1 activity changes in postnatal and adult tissue to understand how Atoh1 may be manipulated to regenerate hair cells.

References 1. Feder K, Michaud D, Ramage-Morin P, McNamee J, et al. Prevalence of hearing loss among Canadians aged 20 to 79: audiometric results from the 2012/2013 Canadian Health Measures Survey. Health Reports. 2015;26(7):18-25. 2. Speech-Language & Audiology Canada, Statistics on Communication disorders. [Cited March 10 2016]. http://sac-oac.ca/public/ information-sheets 3. Ciorba A, Bianchini C, Pelucchi S, et al. The impact of hearing loss on the quality of life in elderly adults. Clin Interv Aging. 2012; 7:159-63. 4. Canadian Hearing Society, Facts and Figures, 2013. [Cited March 10 2016] http://www.chs.ca/facts-and-figures 5. Lin FR, Yaffe K, Xia J,et al. Hearing Loss and Cognitive Decline in Older Adults. JAMA intern Med. 2013;173(4):293-99. 6. Lin FR, Metter J, O’Brien RJ, et al. Hearing Loss and Incident Dementia. Arch Neurol. 2011; 68(2):214-20. 7. Chen S, Karamy B, Shipp D, et al. Assessment of the psychosocial impacts of cochlear implants on adult recipients and their partners. Cochlear Implants Intl. 2016. epub ahead of print. 8. Vermeire K, Brokx JPL, Wutys FL, et al. Quality-of-Life Benefit from Cochlear Implantation in the Elderly. Otology & Neurotology. 2005;26(2):188-95. 9. Loeffler C, Aschendorff A, Burger T, et al. Quality of Life Measurements after Cochlear Implantation. The Open Otorhinolaryngology Journal. 2010;4:47-54. 10. Holden LK, Finley CC, Firszt JB, et al. Factors Affecting Open-Set Word Recognition in Adults With Cochlear Implants. Ear & Hearing. 2013;34:342-60. 11. Statistics Canada, Generations in Canada, 2015 [Cited March 10 2016] https://www12.statcan.gc.ca/census-recensement/2011/assa/98-311-x/98-311-x2011003_2-eng.cfm. 12. Muller U, Barr-Gillespie. New treatment options for hearing loss. Nat Rev Drug Discov. 2015; 14(5):346-65. 13. Corwin JT, Oberholtzer JC. Fish n’ Chicks: Model Recipes for HairCell Regeneration? Neuron. 1997;19(5):951-54. 14. Geng R, Noda T, Mulvaney JF, et al. Comprehensive Expression of Wnt Signaling Pathway Genes during Development and Maturation of the Mouse Cochlea. PLoS One. 2016;11(2):e0148339. 15. Munnamalai V, Fekete DM. Wnt Signaling during Cochlear Develoment. Semin Cell Dev Biol. 2013;24(5):480-89. 16. Shi F, Hu L, Jacques BE, et al. Β-Catenin Is Required for Hair-Cell Differentiation in the Cochlea. J Neurosci. 2014;34(19):6470-79. 17. Mulvaney JF, Amemiya Y, Freeman SD, et al. Molecular cloning and functional characterisation of chicken Atonal homologue 1: a comparison with human Atoh1. Biol Cell. 2015;107(2):41-60. 18. Stojanova ZP, Kwan T, Segil N. Epigentic regulation of Atoh1 guides hari cell development in the mammalian cochlea. Development. 2015;142(20):3529-36

Hearing loss is a significant issue that affects a large percentage of the Canadian population. With a growing elderly population, and age being the most common cause of hearing loss, the number of Canadians affected is likely to increase. Further research into methods of hearing restoration can have a massive impact on the quality of life of these individuals and their role in society. IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS | 17

FEATURE

HEARING THEEARS WITH

LISTENING WITH THE

BRAIN

By Bernhard Ross, PhD and Claudia Freigang, PhD (Post Doctoral Fellow) Faculty Affiliations: Senior Scientist, Rotman Research Institute, Baycrest Health Sciences Associate Professor, Department of Medical Biophysics, University of Toronto Full Member, Institute of Medical Science

ensory organs provide us with an interface to the environment. Specifically, hearing is crucial for speech communication, and not being able to hear properly has a huge impact on everyday life. Our ears receive pressure changes of sound travelling through the air, transform the sound into mechanical vibrations at the basilar membrane, and finally into electrical impulses at the auditory nerve. However for understanding a conversation or listening joyfully to a piece of music, we need the brain as an interpreter of what we hear. With our research we try to understand how the brain identifies elementary features of sound, separates sounds originating from different sources, and integrates pieces of sound into meaningful streams of speech and music. The brain has the spectacular ability to disentangle multiple simultaneously occurring sounds like those in everyday conversations and environments. We term this ‘auditory scene analysis’ and subsume the underlying brain actions as ‘central auditory processing’. We are investigating brain activity related to sensation and perception with electroencephalography (EEG) and magnetoencephalography (MEG), as both techniques record neural activity at fine time scales of millisecond resolution. With EEG and MEG we can identify

18 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS

brain activity at each stage of auditory processing. We use a battery of signal processing algorithms to extract auditory neural signals from ongoing brain activity. Each sound we hear elicits a sequence of neural responses along the auditory pathway, reflecting a hierarchy of information processing. Early responses are related to the analysis of the temporal and spectral structure of the sound, later responses may relate to combinations of sounds into a syllable or a word, and even later responses may indicate cognitive processes of decision-making or reacting based on the perceived sound. We focus our analyses on early and later brain responses. Early auditory responses are strictly time locked to the sound and can be identified by the temporal structure. Later brain responses are generated by the brain at more variable latencies, and we identify those signals based on their rhythmic structure using frequency analysis of brain activity. MEG additionally allows us to localize which brain area is involved in generating the neural response. Aging affects our sensory organs: the range of visual accommodation and tactile acuity is reduced and we lose sensitivity for hearing, specifically at higher frequencies. Hearing loss progresses gradually and becomes noticeable for most people in their 60s, when high frequency hearing loss reaches the frequency range of speech. Hearing loss can be compensated for

FEATURE by amplifying sound with hearing aids. However, older adults often experience difficulties in understanding speech in a noisy environment that cannot be compensated for by hearing aids alone. Our research in aging tries to determine which stages within the hierarchy of the auditory pathway are affected as we age and impact our ability to understand speech in noisy surroundings. One current hypothesis is that specifically the ability to combine sound elements and extract their meaning is affected, as reflected in a common complaint of older adults: â&#x20AC;&#x153;I can hear you, but I cannot understand what has been said.â&#x20AC;? The outcome of this research may inform future signal processing strategies for hearing aids or develop training programs for improving speech-in-noise understanding.

Sensory systems do not work in isolation but interact strongly which each other. We are interested in how we can employ the interaction between auditory and sensorimotor systems for improving rehabilitation after a stroke. We are conducting a randomized clinical trial that assigned chronic stroke patients with impaired arm and hand movement to either a conventional arm and hand training program or a music supported therapy in which patients were actively making music using percussion and keyboard instruments. Our hypothesis is that the interaction of auditory and sensorimotor networks during sound making facilitates neural recovery. We also hypothesize that perception of the rhythmic structures in music create an internal representation of timing,

which in turn supports the execution of movement. We are currently analyzing MEG data collected over the course of the study. Our results suggest that central auditory processing deficits may play a more important role in patients who suffered a stroke than previously thought. All patients in the study were able to hear sounds in both ears; however, their ability to make sense of the sounds was limited, as evident from impaired brain responses depending on the extent of the stroke injury. Thus, it is crucial to investigate hearing and central auditory processing to prevent undiscovered central auditory deficits which may have a negative impact on the success of recovery and the patientsâ&#x20AC;&#x2122; quality of life.

A: Photos of a stroke patient being engaged in music-supported rehabilitation (MSR) by playing e-drums and working closely together with the instructor. The photos show different ways of arm and hand training during MSR (left photo: using both hands, right photo: focusing on the affected hand by alternating between opened and closed hand).

Images provided by: Dr. Bernhard Ross

C: Typical MEG waveforms obtained for timelocked neural activity (top row) to a sound presentation (left plot) and to a button press (right plot) for left (blue lines) and right (red lines) brain hemispheres. The magnetic field distribution over the scalp of a participant typical for an auditory and motor task is shown in the middle plot. The lower row shows typical time-frequency distributions for sound presentation (left plot) and button press (right plot) obtained in MEG. B: MEG setup with a participant sitting in the MEG with task instructions projected on the screen in front of her.

IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS | 19

FEATURE

EARLY SURGICAL INTERVENTION

TO IMPROVE VISION OUTCOMES An interview with Dr. Agnes Wong

on developmental neuroplasticity and timing of surgical correction for pediatric strabismus

By Rachel Dragas

r. Agnes Wong, Ophthalmologistin-Chief at The Hospital for Sick Children as well as senior scientist and active staff physician at both SickKids and Toronto Western Hospital, is renowned for her research on the neural mechanisms underlying strabismus, abnormal eye movements, and amblyopia. She has received numerous prestigious awards in recognition of her work; most notably, a New Investigator Award from the Canadian Institutes of Health Research as well as an inaugural Young Investigator Award from the American Association of Pediatric Ophthalmology and Strabismus. Dr. Wong’s work is geared towards assessing neuroplasticity in the developing and mature visual system in both normal and diseased states, and identifying effective treatment strategies for these diseases. Her lab utilizes sophisticated techniques to measure visual function, eye movements, brain activity, and oculomotor behaviours. I sat down with Dr. Wong to hear more about her successful scientific career and treatment strategies for improving vision outcomes in patients with strabismus. Can you tell us a bit about your background and research on pediatric strabismus? I obtained my MD from McGill University and completed my residency in Ophthalmology at the University of Toronto where I also completed my PhD in Neuroscience with the Institute of Medical Science and clinical fellowship in Neuro-Ophthalmology. It was during my PhD and clinical research fellowship in Pediatric Ophthalmology 20 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS

at Washington University that I became interested in abnormal eye movements, strabismus (misalignment of the eyes either inwards or outwards), and amblyopia (lazy eye). My main area of research is on a specific form of strabismus called ‘infantile esotropia’ which is an inward misalignment of the eyes during infancy. Given the critical period that exists within the first 6 months of visual development, we hypothesize that early surgical correction of strabismus, specifically within 1 year of age, allows for normal development of the binocular visual pathway, ultimately improving vision outcomes. We’ve used a primate model to simulate infantile strabismus and have shown that early correction prevents abnormal development of the visual pathway. The standard timing for surgical correction of infantile esotropia in North America is 2 years of age or earlier; however, we are focusing our efforts on intervention as early as possible in life. Currently, we have an ongoing prospective clinical study evaluating vision outcomes in patients treated within the first year of life. Another area of research that we are working on is elucidating how amblyopia (lazy eye) affects the oculomotor system, motor system (hand-eye coordination), and auditory (speech) perception. What would you consider your most significant research accomplishment to date? I believe this has yet to be achieved, but a research program that I’m very satisfied with is the development of a clinical test for ‘skew deviation,’ a vertical form of strabismus. Typically arising

from damage to the brain stem or cerebellum, this condition manifests as one eye resting higher than the other. We showed that this misalignment is due to an imbalance in the vestibular system. Based on this pathophysiological knowledge, we were able to establish a simple but efficient clinical test capable of differentiating skew deviation from other forms of vertical strabismus such as peripheral trochlear nerve palsy. The test involves measuring vertical deviation while the patient is sitting up, then in a supine position (lying flat with face upward). We found that the vertical strabismus decreases significantly from upright to supine positions in patients with skew deviation, which is not the case in patients with peripheral trochlear nerve palsy. These changes are directly attributed to the specific pathophysiology of skew deviation, which is related to the vestibular system, ultimately serving as a gravity detector. This research accomplishment in particular was truly rewarding because it’s a perfect example of knowledge translation from bench to bedside; it has since been termed the ‘Upright Supine Test’ and is something that my colleagues and clinicians utilize to help make a diagnosis in the clinic. What is the most rewarding part of your job? The most rewarding part of my job is interacting with students. Being able to stimulate and learn from my students, guiding them in their research, and facilitating them to achieve their goals is truly a privilege.

Photo credit Chung Ho Leung

FEATURE

Agnes Wong, MD, PhD, FRCSC Ophthalmologist-in-Chief, The Hospital for Sick Children Senior Scientist and Ophthalmologist, Toronto Western Research Institute and The Hospital for Sick Children John and Melinda Thompson Chair in Vision Neurosciences, The Hospital for Sick Children and University of Toronto Professor, Ophthalmology and Vision Sciences, Neurology, and Otolaryngology, University of Toronto Full Member and Alumnus, Institute of Medical Science

What do you think is the future of research in vision sciences? The future of research in vision science is very exciting. Aside from my research, a lot of my colleagues are doing amazing work, whether it be genetics or gene therapy to treat various eye diseases, retinal prosthesis, or stem cell regenerative therapies for the optic nerve and cornea. What are some of the challenges that you’ve faced during your career as a clinician scientist? Some of the challenges have been learning to manage a big lab and striving to bring out the best in each person

while maintaining a constructive, collaborative, and multidisciplinary environment. It’s definitely something that needs to be learned. The primary purpose of the lab is to generate the best research knowledge for translation to the clinic, but I cannot emphasize enough that, equally important in my lab, is providing a nurturing environment where everyone learns and grows, ultimately achieving what they want to achieve in life. Tell us something you would like us to know about you that people don’t already know? I’m thinking of branching out into mindfulness research–how the brain

responds to mindfulness practice, and how physical and mental health benefit from being present, moment-tomoment, without judgment. What advice can you give to current graduate students? Choose a field that truly interests you—don’t look only at the job market. Also, keep an open mind; not everyone will become or enjoy being a principal investigator, and you don’t have to be a principal investigator in order to be a good scientist. Always follow your heart, enjoy what you do, and recognize that we are all making contributions to science and humanity in different ways. IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS | 21

FEATURE

Synaesthesia:

Sensing the world with a super-charged brain By Jonathon Chio

“Men ought to know that from nothing else but the brain come joys, delights, laughter and sports, and sorrows, griefs, despondency, and lamentations. And by this, in an especial manner, we acquire wisdom, and knowledge, and see and hear and know what are foul and what are fair, what are bad and what are good, and what are sweet and what are unsavory… In these ways I am of the opinion that the brain exercises the greatest power in the man.” – Hippocrates, On the Sacred Disease (Fourth century B.C.)

ippocrates’ pronouncement calls us to use our curiosity as fuel to explore how the 86 billion neurons in the human brain contribute towards human sensation.1 One model for sensation depicts sensory nerves (bundles of neurons) transmitting electrical impulses to sensory regions in the brain. Processing of afferent signals by the sensory brain regions determines subsequent efferent response. However, this mechanism is inadequate at explaining higher-order sensory processes. Studying synaesthetes, individuals with extraordinary sensory capabilities who can smell sounds, taste words and view numbers in color, may help to elucidate a more accurate mechanism. Background of synaesthesia and its different types Gustav Fechner made the first recorded description of synaesthesia.2 Currently with an estimated prevalence of 1/2000 individuals, synaesthesia is thought to be a consequence of aberrant cross-wiring among the brain’s neurons.3 Neuroimaging studies have revealed that altered neural connections exist in the white matter. The increased connectivity allows stimuli to activate atypical brain regions and trigger unexpected sensations. Although the possibility of synaesthesia in non-human animals can’t be completely discounted, research has suggested that synaesthesia is a human-specific phenomenon.⁴ Different types of synaesthesia have been named according to “X → Y” nomenclature. “X” is the inducer stimuli and “Y” is 22 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS

the atypical, concurrent and involuntarily elicited experience.5 Although not exhaustive, Table 1 describes the majority of known synaesthesia types.

Grapheme-color (most common)

Visual perception of numbers and letters in associated colors

Chromesthesia

Auditory stimuli evoke colors

Spatial sequence

Visual perception of numerical sequences in different spatial organizations/levels

Auditory-visual

Auditory stimuli lead to visual perceptions

Mirror-touch

Observing another person being touched and feeling the same sensation in self

Lexical-gustatory

Spoken and written language elicit tastes and smells

Table 1: Majority of known synaesthesia types, where left column is the inducer stimuli and the right column is the elicited experience.

Synaesthetes can be identified by testing for unique sensations. For instance, to test for grapheme-color synaesthesia, individuals are presented with a screen consisting of 2’s and 5’s as below; those without grapheme-color synaesthesia will see Panel (a), while grapheme-color synaesthetes will see Panel (b) in Figure 1.

Figure 1: Test used to determine presence of grapheme-color synaesthesia. Neuroimaging studies have also indicated that grapheme-color synaesthetes have abundant connections between the occipital lobe and temporal lobe’s fusiform gyrus (which processes color information).

FEATURE Probable causes of synaesthesia: immunology and genetics

TBRI

Development of the cerebral cortex

As synaesthetes’ brains have aberrant white matter connections, synaesthesia may be caused by abnormal brain development. A young (immature) brain contains an excessive number of synaptic connections.⁶ These links are selectively eliminated in a maturation process known as synaptic pruning, which occurs when an immature brain goes through “critical periods” of development.⁷ During the critical periods, neuronal networks are shaped by sensory stimuli;⁶ more active synapses and networks are kept and strengthened in favor of those less activated.⁷ This “survival of the fittest scenario” popularized the adages “Use it or lose it” and “Cells that fire together, wire together”.

SCN1A, SCN2A

Excitability threshold for neuronal networks (sodium channels)

GALNT13

Myelination of central nervous system through expression of neuronal sugar groups

GRIN2B

Long-term potentiation/ learning/memory

DPYSL3

Axona l growth, guidance, neuronal differentiation

Microglia, which are the resident immune cells of the central nervous system (CNS), are responsible for synaptic pruning.7,8 They represent 10-12% of all cells in the adult CNS. Although primarily known for their response towards CNS injury, research has revealed that microglia also perform synaptic pruning during critical periods. Microglial-dependent pruning is based on 2 main factors; directions from innate immune molecules to direct phagocytosis, and neuronal activation. If microglia were to perform irregular synaptic pruning, excess amounts of white matter could remain between different brain regions, creating an environment potentially primed for greater communication. Altered amounts of protein (white matter) are partially responsible for synaesthesia. As genes control protein production, researchers began to investigate possible genetic origins of synaesthesia. In 2009, Asher and colleagues performed the firstever whole-genome scan; albeit in only auditory-visual synaesthetes. As there are more female than male synaesthetes, synaesthesia was originally hypothesized to follow Mendelian genetics, have X-linked dominant mode of inheritance, and be controlled by a single loci.3 Contrary to X-linked gene expression, Asher and colleagues found chromosomes 2q24, 5q33, 6p12, and 12p12 were linked to auditory-visual synaesthetes. The genes in Table 2 showed the strongest correlations with neuronal communication.

Table 2: Genes that showed the strongest correlations with neuronal communication in Asher et al and their known function.

Side effects of synaethesia: Greater memory and empathy Synaesthetes have stronger memory and associated networks.9 For example, grapheme-color synaesthetes have more robust memory for words. However, the improvements occurred on a local level. Relative to non-synaesthetes, only visual long term memory and the parvo-cellular system (responsible for color and object input) were significantly better.9,10 Anatomically, this has been reflected to having less gray matter in the motion-specialized region of the orbital lobe.11 Given the great plasticity of synaesthetic brains, another phenomenon related to synaesthesia is phantom limb pain; which is the sensation of mild to extreme pain in the area where a limb had been amputated.12 Despite the limb not existing, nerve endings at the site of amputation continue transmission of pain signals to the brain. The presence of pain is explained by neuroanatomical reorganization; brain regions that continue to receive sensory input incorporate those regions deprived of sensory innervation. The extent of the incorporation correlates positively with the pain felt by the individual. Thus, given the plasticity that can occur after limb amputation, perhaps it is not surprising that one of three amputees develop mirror-touch synaesthesia.13

Mirror synaesthetic sensations generated were more intense when observing real (as opposed to inanimate) bodies being touched. Further, highly empathic individuals are predisposed to strengthening of existing neuronal pathways responsible for communication after observed and felt touch. Thus, while research on synaesthesia is still in its infancy, the findings have far-reaching implications. Conclusions In the human endeavour to understand the brain, studying synaesthetes offers great insight. As their brain circuitry is quite different from those without synaesthesia, synaesthetes can help advance our understanding of how the brain navigates through a world that constantly assaults our senses. By revealing how the brain segregates and integrates different sensations to construct our perception of consciousness, studying synaesthesia will facilitate our journey as we probe the organ that exercises the greatest power in man.

References 1. Azevedo F, Carvalho L, Grinberg L, et al. Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. The Journal of Comparative Neurology. 2009;513(5):532-541. 2. Swain F. Can synaesthesia be learnt? [Internet]. BBC. 2016 [cited 4 February 2016]. Available from: http://www.bbc.com/future/ story/20140611-can-synaesthesia-be-learnt) 3. Asher J, Lamb J, Brocklebank D, et al. A Whole-Genome Scan and Fine-Mapping Linkage Study of Auditory-Visual Synesthesia Reveals Evidence of Linkage to Chromosomes 2q24, 5q33, 6p12, and 12p12. The American Journal of Human Genetics. 2009;84(2):279285. 4. Terhune D, Rothen N, Cohen Kadosh R. Correcting misconceptions about synaesthesia. Neurobiology of Learning and Memory. 2013;103:1-2. 5. Ward J. Synesthesia. Annual Review of Psychology. 2013;64(1):4975. 6. Hensch T. The Power of the Infant Brain. Sci Am. 2016;314(2):6469. 7. Schafer D, Lehrman E, Kautzman A, et al. Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner. Neuron. 2012;74(4):691-705. 8. Witcher K, Eiferman D, Godbout J. Priming the Inflammatory Pump of the CNS after Traumatic Brain Injury. Trends in Neurosciences. 2015;38(10):609-620. 9. Ward J, Hovard P, Jones A, et al. Enhanced recognition memory in grapheme-color synaesthesia for different categories of visual stimuli. Frontiers in Psychology. 2013;4. 10. 1Rothen N, Meier B. Grapheme–colour synaesthesia yields an ordinary rather than extraordinary memory advantage: Evidence from a group study. Memory. 2010;18(3):258-264. 11. 1Banissy M, Stewart L, Muggleton N, et al. Grapheme-color and tone-color synesthesia is associated with structural brain changes in visual regions implicated in color, form, and motion. Cognitive Neuroscience. 2011;3(1):29-35. 12. Jutzeler C, Curt A, Kramer J. Relationship between chronic pain and brain reorganization after deafferentation: A systematic review of functional MRI findings. NeuroImage: Clinical. 2015;9:599-606. 13. Goller A, Richards K, Novak S et al. Mirror-touch synaesthesia in the phantom limbs of amputees. Cortex. 2013;49(1):243-251.

IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS | 23

BMC FEATURE

Atlas Beetle, Marina Spyridis, 1T6

BIOMEDICAL COMMUNICATIONS MASTER OF SCIENCE IN

24 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS

BMC FEATURE

Zika Virus, Meriem Benlamri, 1T6

Biomedical communications bridges disciplines (art, science, medicine and communication) to develop visual material for health promotion, medical education, and as part of the process of scientific discovery.

IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS | 25

PhD Tr a i n i n g

Around

VIEWPOINT

the World:

Are all degrees made equal?

hD graduates are highly mobile and are often willing to migrate around the world, seeking relevant positions and opportunities with the most talented individuals in their field. While very few professional degrees display this level of international recruitment, the limited PhD job market often encourages/forces many graduates to relocate. This type of employment diversity has unique limitations. As the training, education, and requirements of a PhD significantly varies among institutions and even more between countries,1,2 questions arise regarding the competency and qualifications of different doctoral graduates. I often hear colleagues claim that certain countries have “lower standards” and “shorter time requirements” that reduce the credibility of the

awarded PhD. In an attempt to evaluate these assertions, the IMS Magazine decided to explore the history of PhD education, how degree requirements vary, and how this confers degree quality.

The PhD – History, Origin, & Nomenclature The modern PhD, which incorporates original research, a final dissertation, and oral defense, stems from 19th century Germany.3 While many academic institutions in medieval Europe had awarded doctorates, such degrees were primarily knowledge-based and did not require the student to produce any original work/contributions in their field of study. Therefore, by being the first to

By Anna Badner

unify teaching and research in academia, Wilhelm von Humboldt initiated a radical educational reform and established a contemporary education model at the University of Berlin (currently known as Humboldt University).⁴ The institution’s structure and research-centric model of doctoral training quickly became the standard in Germany and was adopted by most Western countries shortly after. In 1861, Yale University awarded the first research-based PhD in the United States (US)⁵ and by the 1900s the degree had spread to Canada as well as several institutions in the United Kingdom (UK).⁶ Nonetheless, there are certain UK universities (such as Oxford and Sussex) that chose to retain the traditional DPhil nomenclature for their

Photo courtesy of istockphoto

26 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS

VIEWPOINT similarly re-structured research doctorate programs.⁷ The Doctor of Science (DSc/ScD) and Doctor of Letters (DLitt/LittD) present another example of nomenclature variation. Although the DSc and DLitt are PhD-equivalent degrees found in a majority of Asian as well as African countries, institutions within the Commonwealth and European Union regard this to be an academic qualification above the PhD on their educational hierarchy. As such, these degrees are only awarded for the most substantial and/ or sustained scientific contributions, requirements that are significantly beyond the expectations of a standard PhD. Moreover, certain institutions associate the DSc title with successful habilitation, which is a prominent academic qualification and often a stepping-stone to full university professorship in select universities.⁸ Habilitation can be achieved through frequent and independent (without a faculty supervisor) publications as well as the defense of a professorial thesis.⁹ This academic certification, somewhat comparable to tenure review in North America, continues to exist in many countries in Europe and Central Asia (including France, Italy, Switzerland, Germany, Austria, Poland, Czech Republic, Greece, Ukraine, and Russia).10

Photo courtesy of istockphoto

Through this very brief account of PhD history and the various nomenclature discrepancies, it is apparent that degree requirements have been—and continue— to be largely based on national or institutional conventions and the cultural environment. As there has been little effort to generate international standards, most academic centers are autonomous in program development. For this reason, there is considerable variability in average degree duration, student outcomes, and research contributions. With these issues in mind, there has been an increasing push for higher educational reform and standardization, with the Bologna Process as a leading example.11

Standardization of Higher Education in Europe–The Bologna Process In the hope of retaining high calibre students, European countries have become increasingly invested in improving the

overall quality and reputation of their higher learning institutions. The creation of a harmonized higher education space was sought to make European degrees more attractive and competitive on the international stage. Therefore, 30 countries opted to create the European Higher Education Area (EHEA) via the Bologna Declaration of June 19th 1999.12 The EHEA was meant to increase the compatibility and comparability of awarded degrees as to promote citizens' mobility within Europe.13 Since its official launch in 2010, the EHEA has grown to 47 member countries.9 Through the application of the European Credit Transfer and Accumulation System (ECTS), the EHEA aimed to standardize university credits and make degrees compatible. This system categorizes university education into three groups: first cycle (Bachelor's degree), second cycle (Master's program), and third cycle (PhD studies). Each “cycle” is associated with a specified number of credits, which are awarded based on an estimated average student workload. While this is fairly feasible for first and second cycle programs, PhD studies present unique barriers. Since each research project is different, no two PhDs are alike and workloads are not easily comparable. Further, degree structures inherently vary between disciplinary domains and individual subject areas. The “Dublin Descriptors” and the “Tuning program,” which provide a general outline for PhD outcomes/competences based on subject area, were designed to target this flexibility. An example of these third cycle (PhD) qualifications includes:14 1) a systematic understanding of a field of study and mastery of the skills and methods of research associated with that field; 2) the ability to conceive, design, implement, and adapt a substantial process of research with scholarly integrity; 3) original research contributions that extends the frontier of knowledge by developing a substantial body of work, some of which merits national or international refereed publication; 4) skills for critical analysis, evaluation, and synthesis of new and complex ideas; 5) effective communication with their peers, the larger scholarly community, and with society in general about their areas of expertise; and finally, 6) the ability to promote, within academic

and professional contexts, technological, social, or cultural advancement in a knowledge based society. While wide-ranging, these criteria are considerably accurate. Further, they lead me to realize that a PhD cannot be evaluated by a simplistic curriculum. Research is difficult. Each student is placed in a uniquely challenging environment with distinct mentorship and resources. Measures of time-to-degree completion, research publications, and journal impact may not be representative of degree or student quality. Statistics and norms do not truly capture the complexity of doctoral work, which (like research) can be fairly unpredictable. So, although different journeys can lead to the same destination—and we may be envious of a smilingly simpler path—the lessons, skills, and friends we make along the way are worth the effort. At least, we all hope so.

References 1. Cyranoski D, Gilbert N, Ledford H, et al. Education: The PhD factory. Nature. 2011; 472(7343): 276-9. 2. Powell S, Green H, editors. The Doctorate Worldwide. Maidenhead: Society for Research into Higher Education and Open University Press; 2007. 3. Taylor SE. Changes in doctoral education. Implications for supervisors in developing early career researchers. International Journal for Researcher Dev 2012; 3(2): 118-38. 4. Mueller-Vollmer K. Wilhelm von Humboldt. The Stanford Encyclopaedia of Philosophy (Internet). [cited 2016 Feb 13]. Available from: http://plato.stanford.edu/archives/win2014/entries/ wilhelm-humboldt/. 5. Yale Graduate School of Arts and Sciences [homepage on the Internet]. History of Yale Graduate School. [cited 2016 Feb 12]. Available from: http://gsas.yale.edu/about-gsas/history-yale-graduate-school 6. Rosenberg RP. The First American Doctor of Philosophy Degree: A Centennial Salute to Yale, 1861-1961. The Journal of Higher Education. 1961; 32(7): 387-94. 7. Department of Education, University of Oxford [homepage on the Internet]. DPhil (PhD) [cited 2016 Feb 12]. Available from: http:// www.education.ox.ac.uk/courses/d-phil/ 8. Balter M. Germany Tries to Break Its Habilitation Habit. Science.1999;285(5433):1525. 9. Hornborstel S. Postdoctoral Careers in Germany: Findings from the Evaluation of Young Research Group Leader Programs. Alexander von Humboldt-Stiftung/Foundation [cited 2016 Feb 18]. Available from: https://www.humboldt-foundation.de/web/31653.html 10. Schwarz S, Westerheijden DF, editors. Accreditation and Evaluation in the European Higher Education Area. Springer Netherlands: Springer Science+Business Media BV; 2004. 11. Usher R. A Diversity Of Doctorates: Fitness for the knowledge economy? Higher Education Research & Development. 2002; 21(2): 143-53. 12. European University Association. The European Higher Education Area and the Bologna Process [cited 2016 Feb 20]. Available from: http://www.eua.be/policy-representation/higher-education-policies/ the-european-higher-education-area-and-the-bologna-process 13. Brennan J, Naidoo R, Patel K, Kehm BM, Huisman J, Stensaker B, editors. The European Higher Education Area: Perspectives on a moving target. Sense Publishers; 2009. 14. European Commission/EACEA/Eurydice. The European Higher Education Area in 2015: Bologna Process Implementation Report. Luxembourg: Publications Office of the European Union; 2015.

IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS | 27

PhD enrolment

Canada: De

PhD Facts

Around the World

~45,000 students enrolled

Applicant age policy for some institutes

years old

published articles in peer-reviewed journals in an

eden & Fin

Private vs. Public

Japan:

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tio

Oral Ex am i

PhD enrolments.

years old

Minimum

largest

18-24

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United States has one of the

China:

B e f or e

VIEWPOINT

United Kingdom

Germany

Ireland

Finland

Sweden France

~30,000 Mexicans with PhD

Requirem

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Are you ready to pursue a PhD?

comp l et ion

Most countries require students to have an honours degree or a masterâ&#x20AC;&#x2122;s degree.

Typically, there is no formal oral examination in Australia

Common Qualities of Successful Candidates

1 2 3 4 5 Canada

$27,800

United States

$35,000 - 51,000

Mexico*

$15,100

Japan**

$6,300

China

$3,700 - 10,700

Australia

$16,700 - 34,400

Ireland

$6,600

United Kingdom

$7,300 $0

Sweden

Finland France

$700

Germany

60,000

50,000

40,000

30,000

20,000

Average Cost of Tuition per Year (CAD) 28 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS

10,000

Self-motivated Committment Curious to learn & passionate Cogency & ability to formulate & process scientific problems Financially stable

Minimum

= 1 year Maximum

Average Time-to-Degree (Years)

* Tuition costs reflect private institute only

** Minimum 5 years for direct entry & minimum 4 years after Masters degree

BOOK REVIEWS

The Brain That Changes Itself Stories of Personal Triumph from the Frontiers of Brain Science

By Norman Doidge, Penguin Books. 2007. 448 pages

he Brain That Changes Itself by Norman Doidge elucidates a significant paradigm shift that took place in the field of neuroscience when neuroplasticity was first observed. As a psychiatrist and psychoanalyst, Norman Doidge provides insight into the role of cognition in brain plasticity; he explores the underpinnings of neuroplasticity by drawing from the ideologies of scientists such as Luria and Freud and by highlighting the discoveries of others such as Merzenich. This book entails case studies of individuals who suffered from neurological disorders and mental illnesses, and were limited in their ability to function daily. For each case study, the author describes how the patient was able to overcome these impairments and rehabilitate through the power of neuroplasticity. In one case study, Doidge recounts the story of a woman with vestibular apparatus damage who learns to regain her balance though rehabilitation, illustrating the adaptability of the sensory cortex. Similarly, another chapter delineates how phantom pain can be overcome in amputees through plasticity-based approaches. Throughout these examples, Doidge emphasizes how these findings

“

Reviewed by Arunima Kapoor

terms and finding the balance between technical jargon and oversimplification. Concepts are clearly defined and ideas are well developed and supported. However, the accuracy of some of the associations drawn in this book has been challenged. Carmeli and Blass1 believe that neuroplasticity has no relevance to psychoanalysis, and that the connections made between the two are misleading. They also argue that Doidge portrays basic principles of learning as neuroscientific discoveries, and misapplies the notion of neuroplasticity to the explanation of therapeutic processes.

brought about a shift from localizationism‒ the idea that each part of the brain is specialized for a specific function‒to neuroplasticity. He weaves this concept throughout the chapters to illustrate the significance of this breakthrough. Doidge does an excellent job of explaining complex scientific experiments in layman’s

While Doidge is able to engage a reader with his writing and defend his views through case study examples, whether or not his interpretation of neuroplasticity and its correlation with psychoanalysis is valid is unsettled. Overall, this book provides a great overview of a major, recent paradigm shift in neuroscience and highlights interesting case studies that depict remarkable recoveries. Despite the critical reviews of Doidge’s interpretation, this book is worth reading for the fascinating case studies, and to gain one perspective on the relationship between psychology and neuroscience.

As a psychiatrist and psychoanalyst, Norman Doidge provides insight into the role of cognition in brain plasticity.

References 1. Carmeli Z, Blass R. The case against neuroplastic analysis: A further illustration of the irrelevance of neuroscience to psychoanalysis through a critique of Doidge’s The Brain that Changes Itself. Int. J. Psycho-anal. 2013; 94(2): 391-410.

IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS | 29

FACULTY SPOTLIGHT

Synergy

In conversation with

Dr. Jonathan Irish

Dr. Jonathan Crawford Irish, MD, FRCSC, MSc Core Lead, Institute for the Advancement of Technology for Health Chief, Department of Surgical Oncology, Princess Margaret Hospital Associate Member and Alumnus, Institute of Medical Science

By Adam Betel

hy is it that after the Beatles broke up, no individual member was able to rival the success achieved together as a group? Individually there’s no question that Paul McCartney, John Lennon, and George Harrison had incredible talent (and Ringo too, for all you Yellow Submarine fans out there). But what was it about being together that made them one of the most recognizable, successful, and influential music groups of the 20th century? It’s synergy and that’s what has been carrying Dr. Jonathan Irish and his GTx team at the Princess Margaret Hospital and the TECHNA Institute to make great strides in high-tech surgery. Dr. Jonathan Irish graduated from the Faculty of Medicine at University of Toronto (U of T) in 1984, before returning to U of T in the Institute of Medical Science (IMS) in 1991. Dr. Irish works concurrently as the Chief of Surgical Oncology at Princess Margaret Hospital and the Core Lead for the Guided Therapeutics core (GTx) at the TECHNA Institute, a division of the University Health Network. GTx refers to the combined use of robotic imaging, real time MRI tracking, and surgical navigation technology to guide 30 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS

and assist physicians during surgery. However, the success of GTx in treating patients extends beyond the surgeons and the operating room. Before application in the clinic, GTx technology is tested and refined in the GTX lab. Just like the Beatles had a studio to rehearse in, so does Dr. Irish and his team. Inside the MARS building on the 7th floor is the GTx lab, a space equipped with a pre-clinical model operating room, two 3D printers, as well as dedicated space for testing new technologies. Just as the Beatles spent hours rehearsing

in the studio and performing at Berlin nightclubs, the GTx team goes through rehearsal in the lab. The actual GTx Operating Room is located inside Toronto General Hospital in a large room fit with a cutting edge robotic CT scanner, in addition to large monitors and usual surgical equipment. The team’s efficiency in clinic is the result of the time and effort spent in the GTx lab. There they use the 3D printers to recreate and simulate patient anatomy for surgeons to practice on and for

Team from left to right: Harley Chan, PhD (Mechanical Engineer), Jonathan Irish, MD (Head & Neck Surgeon), Michael Daly (MSc (Biomedical Engineer & IMS PhD student), Robert Weersink, PhD (Medical Physicist)

Photo credit Shai Gil Photography Inc.

It’s all about

FACULTY SPOTLIGHT the whole team to reproduce studies. Reproducibility is key to innovation and making advances in medical research. The GTx team’s ability to innovate is matched by their mandate to translate and educate as well. This extends not only to engineers, surgeons, scientists, but to the public as well. “The GTx program is one of the pillars of the TECHNA Institute, which is a research institute dedicated to the development of new technologies and implementation,” explains Dr. Irish. “I like to view the GTx program as a U of T resource, not just a UHN resource […] we’re only as good as our human resource and our human resource includes our students.” Dr. Irish’s research team is unique as it brings scientists from different disciplines together. Just like John and Paul would often explore with other instruments, in the GTx lab and OR, clinicians, scientists, and engineers explore different roles within the team. For example, it’s not uncommon to see a doctor at work in the lab behind a computer, or an engineer in scrubs in the OR. This is the synergy. In addition to being a means of team collaboration, GTx has also become a means of institutional and departmental collaboration. For example, the GTx OR is shared quite frequently with the Peter Monk Cardiac Centre, part of the Toronto General Hospital. “The greatest possible compliment that you could get [is] when a world class […] program wants to use your resource,” says Dr. Irish.

Photo credit Shai Gil Photography Inc.

Dr. Irish credits much of his success to synergy. “This day and age there is no question that synergy and partnerships and collaborations are absolutely required to success,” he explains. “And I think that’s what has been the foundation of how I have been able to be reasonably successful in almost all of the fields that I’ve undertaken is the fact that I collaborate.” It’s easy for regular people to see how the technology will be helpful. “When people walk into our GTx lab or our GTx-OR, it has some immediate attractiveness because they can actually appreciate the tangibility of some of the things that we’re doing,” he says. “You can see real impact,

in a relatively short period of time and you can understand ‘ya, I get that’, there’s a coolness factor.” Some of the tangible research and innovation that Dr. Irish has been working on includes using contrast agents to mark cancer cells and live feedback dashboards to map and track surgery in real time. In addition, he’s utilized 3D modeling to predict and accentuate reconstruction after head and neck cancer surgery and hand-held spectroscope devices that allows for imaging over 3D volume. He also discussed using novel agents to replace traditional agents in areas like sentinel lymph node biopsies. The innovation coming from the GTx lab also goes through development quite rapidly, for medical research. “We’ve taken some of the technologies that we’ve developed in our GTx lab from proof of principle or a thought, to in-patient within two years. That’s kind of cool. There’s no drug that’s ever done that.” A pride Dr. Irish takes from his research is that it is disease agnostic. In other words, it can be translatable across all disciplines. Dr. Irish primarily uses GTx for head and neck cancers–his specialty– but the same technology and guiding

principles can be used to treat entirely different diseases. Dr. Irish’s advice to current IMS students is to stay broad, and not to specialize too early. Be multi-disciplinary and then focus your work. “Over time you will find your passion and you will explore and develop that foundation into areas of expertise that will take you forward,” he says. “But, it’s pretty clear that, at least in science and medicine, that engineering and technology and nanomedicines and nanotechnologies are going to play an increasingly stronger role in medical research.” The innovation and medical progress coming from Dr. Irish’s work comes from people working together, across faculties, institutions, and disciplines. This is a powerful message and an example of the incredible opportunity brought about through the IMS at U of T. Your journey has begun, and now, like Dr. Irish, you need to build up the right team to create your synergy and change the world. The Beatles may have sung it, but the GTx team definitely listened, “I get by with a little help from my friends.”

GTx-OR is unique in the world for having two highperformance CT scanners. This ‘porthole’ view is taken from inside one scanner (Siemens FLASH Dual-Energy CT) looking towards the second system (Siemens Zeego Cone-Beam CT).

IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS | 31

STUDENT SPOTLIGHT

DAVID QIXIANG CHEN By Melissa Galati

or some graduate students, identifying and following their passion is straightforward. For most of us, however, carving out a niche in scientific research is not as easy as it appears. We sometimes wonder where our experiences will take us or if our efforts will ever amount to anything. I sat down with David Chen to discuss how his background in computer science prepared him for neuroscience research and served as a conduit for his future success in the field of neuroimaging. David, born and raised in Chengdu, China, moved to Toronto at the age of 11. Throughout high school, he envisioned a career in graphic design, never intending on going to university. However, his parents, who valued education, encouraged him to pursue a postsecondary education. Consequently, he completed his bachelor’s degree in computer science at the University of Toronto (U of T), reasoning that he could appease his parents while simultaneously learning more about graphic design. During his third year, he interned for a 3D graphics technology company called Alias. It was 32 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS

only after this experience that David began to question his career goals. “You always think your life is going to go in one direction and you think you know what you want to do… the experience itself made me question what kind of value I wanted to create in my life.” After completing his computer science degree, David took on some freelance web development projects. “I sort of wandered

“

Hodaie, a neurosurgeon at Toronto Western Hospital (TWH). “She asked me if I would do research in neuroscience, so I thought—yeah I could do that. At this point I hadn’t touched biology since grade ten,” David smiled, “I had a lot of catching up to do.” While working for Dr. Hodaie as research associate (RA), David, who found that he enjoyed neuroscience immensely, decided that he wanted to pursue graduate studies. “By the time I started grad school,

The value of humans in knowledge creation is their creativity.

around for a while… a friend of mine, who was doing a summer studentship, mentioned that her boss needed a computer guy.” This is how David came to meet his future supervisor, Dr. Mojgan

I had a good idea of what my project would be.” David laughed as he reflected on his decision. “In retrospect, I think it was a good choice… I guess I should probably thank my parents for that.”

Photo credit Elizaveta Semechko

STUDENT SPOTLIGHT

David Qixiang Chen, 4th year PhD student Toronto Western Hospital Supervisor: Mojgan Hodaie

David is now a fourth year PhD student in the Institute of Medical Science (IMS). He studies Trigeminal Neuralgia (TN), a facial neuropathic pain syndrome typically caused by neurovascular compression of the fifth cranial (trigeminal) nerve. “People say it’s the worst pain that humans can experience because it’s a very sudden, shock-like, stabbing pain… it’s pretty horrendous,” remarks David. The trigeminal nerve, he points out, is a gateway to study pain. “It’s the primary sensory input of the face, but you get a very wide range of pain [sensations].” This includes TN-like pain that sometimes occurs in patients suffering from multiple sclerosis (MS). This spectrum of pain, arising from the perturbations of the same nerve, is what makes this structure interesting to study. David’s project involves comparing classical TN to TN secondary to MS (MS-TN) using diffusion magnetic resonance imaging (MRI)—a novel neuroimaging method that allows for better imaging of the trigeminal nerve (specifically the regions encompassed within the brain stem). David’s findings suggest that classical TN is caused by microstructure changes in the cisternal

portion of the trigeminal nerve, while MS-TN may be caused by lesions near the trigeminal nucleus—a structure contained within the brain stem. These results were recently published in Multiple Sclerosis. Data analysis using diffusion MRI images is incredibly time consuming if done manually, on a patient by patient basis. By employing his computer graphics intuition, David created a workflow to automate this process. 3D tractography data from many individuals can be combined to create an average, normalized brain in a way that retains the 3D model but prevents the loss of information. For the future, David hopes that this technology can be used to make tractography much more clinically relevant. Physicians, who normally have to wait a week for diffusion MRI images to be analyzed, can perform the analysis instantly. “If a machine can be precomputed [to tell you] how out of range your brain is from “normal”…this makes clinical diagnosis much faster.” When asked about his experience in the IMS, he reflects that the program has allowed him to interact with both basic

science and clinical researchers, both of whom have methods of problem solving that are different from computer scientists. By combining these strategies, David has been able to successfully apply his computer science background to accelerate neuroscience research. It is clear that David’s experience in the IMS has given him some valuable insight into what it takes to make it in scientific research. Students, he reasons, should be more involved in the design of experiments and interpretation of data. They should spend time discussing their projects and ideas with others. Although experiments are important for generating data, machines are replacing much of what we do in the lab. “The value of humans in knowledge creation is their creativity. They can interpret complexity in a different way.” He also advises new students to choose their mentors wisely. His supervisor, Dr. Hodaie, has been incredibly patient and supportive of him since he started as an RA in her lab. David’s story shows us that in order to find our passion, we sometimes have to be open to new opportunities. The experiences and skills we acquire can help us in ways we never anticipated. IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS | 33

STUDENT SPOTLIGHT

2nd year MSc Student Institute of Medical Science Keenan Research Centre for Biomedical Science St. Michaelâ&#x20AC;&#x2122;s Hospital Supervisors: Dr. Emil Schemitsch & Dr. Aaron Nauth

STUDENT SPOTLIGHT By Sarah Peters

34 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS

Photo credit Meital Yerushalmi

BRENT BATES

STUDENT SPOTLIGHT

f there is anyone who understands the principles of problem solving, it is Brent Bates: a second year Master’s student in the Institute of Medical Science (IMS) under the supervision of Dr. Emil Schemitsch and Dr. Aaron Nauth. As a varsity track coach, Brent’s unique ability to identify problems and implement suggestions for improvement has proved to be greatly beneficial both on the track as well as in his own area of research. Despite having practice-packed evenings, spending long days in the lab, and working on his final thesis, Brent found time to share his insights on academics, athletics, and crossovers between fields. Brent’s name may sound familiar: he leads the IMS Run Club, an organization often advertised in the IMS Students’ Association’s weekly emails. Believing this position to require a heavy time commitment, I was surprised to find out that in addition to this role, Brent also coaches the University of Toronto (U of T) Varsity track team. He certainly has the qualifications: as an undergraduate athlete at Western University, Brent played an integral role in securing Western’s Men’s Track and Field Team their first national title. Brent also placed 6th in Canada at the 2012 Olympic Track and Field Trials; with a smile, he remarked that his university’s win was more exciting. With his keen interest in sport and apparent Western pride, I wondered how Brent had found his way into research at U of T. “About 6 months after the Olympic trials, I injured my knee. Then I started thinking— well, maybe I can’t focus only on athletics.” In the same breath—and without showing any signs of discouragement—Brent went on to describe his injury as an inspiration to venture in a different direction, and the stellar reputation of graduate research at the IMS attracted him to Toronto. Having completed a 4th year thesis in a neurovascular physiology lab and a summer research project with a sports physician, Brent shifted his passion for biomechanics and kinesiology from the track to the lab, bringing with him important principles gleaned from years of competition. “People think that track is a very individual sport and all you do is run around

in circles, but when you run around in circles five days a week, you get used to… always pushing to go a little faster and a little farther.” This attitude is especially important when it comes to Brent’s research, which requires intricate manipulations and lots of patience. His lab at St. Michael’s Hospital focuses on developing endothelial progenitor cell (EPC) and mesenchymal stem cell (MSC) therapies for fracture healing. By treating bone defects with EPCs loaded onto a collagen scaffold, Brent and his colleagues have demonstrated their role in stimulating vasculature replenishment that ultimately aids in bone healing. Although his lab currently works with rodents, Brent’s team is rapidly approaching using larger models to understand how similar therapies can be used clinically to treat large, complex fractures. Due to the detailed nature of Brent’s research, I wondered about his thoughts on how these findings should be shared with target audiences. Drawing from his experience coaching high caliber athletes, Brent is well acquainted with the importance of effective communication. In orthopaedics specifically, publishing and presenting are great ways to foster collaboration between researchers; he adds that anything that can be applied without expert knowledge should be shared with the general public. However, Brent understands that in many cases it is most effective to communicate directly with clinicians and researchers whose practice could change as a result of scientific findings. Over the next few weeks, Brent will put this opinion into practice by presenting posters at both the Collaborative Program in Musculoskeletal Science Research Day and the Annual Meeting of the Orthopaedic Research Society. The journey from ethics proposals and study designs to interdisciplinary meetings and poster presentations can be strenuous, and Brent is familiar with certain challenges that can arise in research: he is currently handling a higher than usual number of animals due to a few setbacks faced during his first year in IMS. He expressed an opinion that it can be frustrating if research outcomes do not come to fruition after a first attempt, but these frustrations make research and

science unique: “That’s part of the whole process—trying to get things to work. You have to stay positive, keep trying, and [go] back to the literature a lot.” Brent’s attitude of persistence and dedication is partially attributed to his years of running and coaching, but also comes from connections he has made during his time at U of T. In niche areas of research, it is critical to forge connections with scientists in different areas who can offer varying perspectives on tough questions: “IMS is very unique because it [has] such a wide spectrum of researchers, scientists, and students. If you want to branch out to another area or…talk to someone about a different technique, you can.” With regards to the future, Brent hopes to pursue a career in medicine—but he is absolutely dedicated to continuing his involvement in research along the way. His personal experiences with athletics, injury, and orthopaedics have generated a keen interest in delving further into orthopaedic trauma, surgery, or sports medicine. Brent’s aspirations in research are analogous to his attitude as a track coach: practical and problem-oriented. As a coach, Brent works to identify minute technical details that require adjustment to achieve better results; as a future clinicianscientist, Brent hopes to spend time in clinical practice before delving into a PhD so that he can identify relevant problems to address in his research. After hearing about Brent’s clinical, academic, and athletic experiences, it is evident that he has the tools and the drive necessary to implement change in his field. He has found a comfortable balance between passion and skill; he strives to use his knowledge to constantly foster positive change in his team, his research techniques, and the medical field. Importantly, IMS has provided Brent with an appreciation for translational research: “Everything nowadays is multidisciplinary and you need to have connections in multiple areas in order to make a strong impact… Use the tools that IMS gives you to create a network for yourself—not just in your own field, but in other[s] as well.” IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS | 35

TRAVEL BITES

Society for Cardiovascular Magnetic Resonance Conference By Jessie Lim

or scientists and researchers, conferences are like field trips for school children: educational, awe-inspiring and—dare I say it—fun. However, it’s all fun and games until you have an oral presentation in a moderated competition against other more experienced research fellows and PhD candidates while you’re just an undergraduate. This is the position I found myself in when I attended my first conference for the Society for Cardiovascular Magnetic Resonance (SCMR) in Nice, France. Reflecting on this conference one year later, I realize that despite my less-than-perfect experience, it turned out to be a perfect segue into the research world and has made me a better graduate student. Let me explain why.

36 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS

and travelling to Europe than anything else. However, upon discovering that I would be involved in an oral competition, I suddenly realized that what I had to say mattered a lot more than dreaming of crème brûlée. Plus, I now worried that any confidence I had in presenting would wither away in the presence of worldrenowned cardiologists. Nonetheless, in the days leading to my presentation I was able to hold my anxiety at bay and enjoy the first few days of the conference. I sat in for other presentations and seminar talks about MRI physics, and as I observed others around me, I was enlightened by how passionately and professionally they spoke about their work. I became aware of the true purpose of conferences: to share ideas communally in hopes of solving questions and improving technology and medicine together. There was something humbling in the fact that all these professionals gathered to learn from each other—and even from me. This became important for me as a graduate student because the thought of becoming a mini-expert in our research niche is a major motivating force towards the success of our project. We all aspire to discover the unknown, and if we keep in mind the place we hold within our field, and the impact we have made to

help other academics, it will encourage us to be resilient in our work as we advance the field forward in our own way. After a few days of learning about cardiac function, the day of my presentation finally arrived as the morning sun crept through the tortuous peaks of the French Riviera. My supervisor’s key advice was to “go on a mountain or beach and practice your presentation over and over until you know it well”, but I didn’t have time to do either, so the public washroom had to do. A couple hours and a few last minute slide changes later, I presented and everything actually turned out well—I was even able to answer a question! But the best part was looking out into the audience and seeing all the members of my lab—including my supervisor who was front row—scattered amongst the people, supporting me and cheering me on. That was the second lesson I learned: that all things are made more rewarding with the support and encouragement from your peers and mentors. Guiding each other through the complex journey of research makes all triumphs collective. And after renting a house with them for the duration of the conference (that’s a whole other story), I can confidently say that we have each other’s backs for life! On to the next conference!

Photo credit Jessie Lim

SCMR is a prominent organization for physicians and scientists working with cardiovascular magnetic resonance imaging (CMR), and the annual conference is internationally known for showcasing novel imaging techniques for measuring cardiac function and improving diagnoses. When my abstract was accepted for this conference, I was ecstatic—but it was a bit misplaced. I was more excited about being able to mold my work into a comprehensive product,

A nice time in Nice

TRAVEL BITES

CANADIAN CONFERENCE ON DEMENTIA (CCD) From Social, Cultural and Ethical Issues to Dementia Care, Diagnosis, and Management

By Usman Saeed

he prevalence of dementia is on the rise and so is the awareness surrounding the many important issues related to dementia care, diagnosis, and management. The research in this area is exploding, so much so that it can be challenging to stay up-to-date with the cutting-edge developments, which may set the stage for future explorations. The Canadian Conference on Dementia (CCD) offers such a learning opportunity and a platform for physicians and researchers to communicate clinically relevant knowledge in dementia research. The most recent program was organized as a three-day event from October 1st to 3rd, at the heart of the capital city of Canada–a fabulous destination in its own right. The planning committee comprised of well-respected professionals, co-chaired by Dr. Sandra Black and Dr. Ron Keren. Needless to say, I was excited and honored to be one of the five selected to present at the ‘New and Notable–Oral Research Presentations’ session of the conference. The program covered a plethora of topics, which were offered to the registrants based on their individualistic interests. On the first day after the registration and opening remarks, the program began with a careful but optimistic talk by Dr. Stephen Salloway. The presentation covered exciting opportunities as well as challenges towards a treatment breakthrough in Alzheimer’s disease (AD). This was followed by a session on the theme of art and culture, including a research-based theatre production entitled ‘Cracked: a

new light on dementia.’ The play was the highlight of the day, as it featured honest impersonations of familial and social challenges faced by the dementia patients, with an undertone of poignancy and humor.

The second day of the conference was a busy one, with presentations on several social and ethical topics, including the role and impact of technologies in dementia care, place of genetic testing in dementia diagnosis, and issues surrounding the end-of-life decision making. Audience displayed considerable interest on topics related to the applicability of neuroimaging in dementia diagnosis and treatment. The presentations ended with an electric debate: Should cerebrospinal fluid biomarkers and amyloid positron

emission tomography be used in clarifying a diagnosis of AD in clinical practice? The debate saw Dr. Kenneth Rockwood and Dr. Stephan Salloway, two of the leading experts in aging research, on the opposing sides. The evening concluded was a delicious gala dinner and a performance by the band, ‘The Fundamentals.’ The third and final day focused on the Canadian initiatives related to neurodegeneration in aging, workshop sessions and students’ research presentations. The oral and poster presentations were of high quality and stimulated considerable interest and discussion among the attendees. My own presentation was well-received by the audience and focused on the association of apolipoprotein E ε4 allele, a major genetic risk factor of AD, with MRI-based hippocampal volumes across different dementia subtypes.1 Although CCD was my first out-of-city conference, the overall experience was spectacular and provided an invaluable opportunity to learn, gain experience, and network. The city of Ottawa itself is beautiful and some say that you may experience the best of Canada at one place due to its rich historical, cultural, and political importance. The hustle and bustle at daytime and the brightly lit downtown core at night are the two things hard to miss in this city. This remarkable mix of geographic prominence and exciting list of presentations may make for a perfect learning recipe. References 1. Oral Abstract Presentations at the 8th Canadian Conference on Dementia (CCD), Ottawa, October 2015. Canadian Geriatrics Journal. 2015;18(4):246-249.

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FUTURE DIRECTIONS

From Bench to Bedside:

Career Translation from

Science to Medicine S

By Petri Takkala

eeing patients and delivering babies are all in a day’s work for Dr. Joseph Gabriel, MD, MSc. As a first year resident in a rural family medicine program affiliated with the University of Toronto Family and Community Medicine program, Joe, as he likes to be called, has the daily opportunity to provide the first line of care to a diverse population of patients in various parts of Ontario.

that intravenous fluid loading in older participants could narrow the upper airway causing or exacerbating obstruction sleep apnea. This work led to a number of publications and has broadened our scientific understanding of this common sleep disorder. After defending his thesis in the summer of 2011, Joe only had a few weeks off before returning to Queen’s University to embark on his medical training.

Building Foundations in Biomedical Science

Clinical Training and Family Medicine

Growing up in rural Ontario, in the small town of Cobourg, east of Toronto, Joe knows first hand how important it is for rural communities to have access to family doctors. Joe began his training in science at Queen’s University where he completed his BSc in Life Science. He developed an interest in obstructive sleep apnea while working on his senior year research project in this area. Taking his interest in biomedical science further, he joined the Institute of Medical Science (IMS) at the University of Toronto to work towards his Master’s degree in the lab of Dr. Douglas Bradley, MD, a world leader in obstructive sleep apnea. Joe’s MSc thesis project examined the role of fluid retention on upper airway obstruction and the incidence of sleep apneas. In a unique set of experiments, normal healthy participants were given intravenous saline while sleeping and wearing compression stockings, causing fluid to accumulate rostrally. They found 38 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS

During medical school, students have the opportunity to explore a number of disciplines during their clinical rotations, however it was the 7-week rural family medicine rotation in Midland Ontario that really attracted Joe’s interest to becoming a primary care physician in a rural community. Delivering babies, performing minor surgical procedures, and being exposed to a lot of different situations was all very exciting for the young physician. The University of Toronto has a rural family medicine residency program in which doctors spend one year training in a hospital in Toronto, and the second year of training in Midland Ontario. As 1 of 8 doctors in the program, Joe is enthusiastic about the comprehensive medical education that the program offers for primary care physicians, and the services that he will be able to provide to communities around Ontario. A typical day for Joe runs from 8 am, occasionally to 7 am the next morning. During this time, he provides acute care to

patients, and gets exposure to a wide variety of specialties (e.g. obstetrics, pediatrics, internal medicine, emergency medicine, etc.), which is a great way to learn about medicine and appreciate the work of doctors in a diverse range of specialties. Joe is also looking forward to working on a quality improvement research project that is an integrated program requirement in year 1 of the residency program. Joe will rely foremost on the scientific tools and training he received at the IMS in assessing and evaluating ways to improve patient care. As part of a team and working with hospital administrators, one clinical research area of interest is in investigating whether prescription rates for proton pump inhibitors are in line with best practice guidelines for patient care, or whether changes can be made to optimize patient health and minimize complications. These are good drugs often prescribed for treatment of a variety of conditions including acid reflux, but have connections to a number of adverse effects. As a physician, the results of his research have a direct impact on the daily clinical experience of his patients. Maintaining a Healthy Work-Life Balance Finding time in such a busy life to pursue other personal interests is important for limiting stress and maintaining a positive outlook, but Joe advises that the extracurricular activities that students pursue during their studies must be sustainable.

FUTURE DIRECTIONS

Photo credit Dr. Joe Gabriel

During his MSc, Joe often took opportunities to explore Toronto to discover the vibrant culture that weâ&#x20AC;&#x2122;re all fortunate to be surrounded by. The big cityâ&#x20AC;&#x2122;s Indy and hip hop communities gave him the perfect opportunity to take his love of rap and hip hop and practice rapping in a small club to develop his hobby among a core group of regulars with a shared enthusiasm. As the talented rapper known as the Egyptian Prescription, Joe has since had the honour to open for his musical idol, Shad, been interviewed by the CBC, worked with producers and played shows in Toronto and Kingston, and is in the process of writing an album. For students currently thinking about pursing a career in medicine, Joe recommends that they apply broadly and be persistent. Take the time to develop yourself and have something interesting about you that makes you unique. Medicine is a life long and rewarding career that demands that physicians are constantly learning about new developments in biomedical science and patient care. Working well with colleagues and on a team are essential skills for physicians in any discipline. Joe emphasizes that the strong friendships and collegial environment of medical school and residency training have made both experiences a fantastic time. Joe is enthusiastic as he continues to develop his career and pursue his goals of providing care to patients in communities throughout Ontario.

Joseph Gabriel, MD, MSc Resident, University of Toronto Family and Community Medicine Institute of Medical Science Alumnus

IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS | 39

DIVERSIONS

40 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS

Photo credits: “Marriage vs. The Ph.D. by Jorge Cham, www.phdcomics.com” and “Correlation” by xkcd

www.xkcd.com

DIVERSIONS

In Their Own Words:

A Dumbed Down Version of PhD Thesis

“

Does music express emotions or just elicit them? Read the next 200 pages to not find out. - Welldogmycats

“

No idea if it’s important for anything. - Penguinpaige

“

Making new magnets from old magnets because we’re running out of magnets.

Sources from AskReddit (www.reddit.com)

- IAmAHiggsBoson

“

Little things stick together. Here’s a slightly easier way to calculate Two proteins touch each other in a their stickiness. specific place in the developing heart. - Born2bwire

“My experimental drug

does NOT cure addiction.

“

- NotSoCleverPork

We can take random pieces of bacterial DNA from beaver poop and put them into other bacteria to discover new things, like how to break wood down into biofuels. Yes, I had to dissect dead beavers and handle their poop. - Geneius

Girls take birth control. Girls then pee out unmetabolized estrogens from birth control. Pee goes to water treatment plant, estrogens not treated, male fish become female fish. - Altzul IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS | 41

DIVERSIONS

Declaration

A poem by Usman Saeed

I stood by you, When the storm thundered, And the lightening came crashing through, And when the fire raged roaring blue, Scorching away, slowly but mercilessly, The garden of beautiful memories. I understood you, In moments of agony and confusion, With your teary eyes, blank and cold otherwise, Searching for a glimmer of light in the lands of darkness, Akin to a wounded warrior silently fighting, The ultimate battle long lost. I admire you, For showing remarkable strength and resilience, And in those hours of fading existence, When the curtains fell and you subsumed within my memories, For we have shared these moments together, The moments to keep forever.

About the Poem: This poem is inspired by all those lovely and courageous individuals and their families, who are fighting Alzheimerâ&#x20AC;&#x2122;s and other neurodegenerative dementias on a daily basis. At this time, neurodegenerative dementias remain incurable. These verses are written to acknowledge the continuous emotional struggles and physical disabilities, and to highlight the sense of loneliness that many dementia patients experience during the course of their illnesses. I emphasize and declare that these individuals and their families are not alone in this battle. They may have lose their memories but these moments spent together and their identities will remain part of his lasting thoughts. I hope that future research will improve the quality of life and prognosis of patients suffering from these devastating disorders. 42 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS

PAST EVENTS

Past Events

IMS CAMH one brave night

Dodgeball Tournament

IMS Soccer Team

IMS Volleyball Team

IMSSA Outreach SciHigh and Visions of Science

IMSSA Events Success in Academia IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS | 43

READ IT ONLINE

IMSMAGAZINE

http://issuu.com/imsmagazine www.facebook.com/groups/imsmagazine/ @IMSMagazine

44 | IMS MAGAZINE SPRING 2016 SENSORY SYSTEMS