Brain Center Bulletin

January 2020, 17th edition

Best Wishes

Rudolf Magnus Young Talent Fellowships 2019 for two couples

As part of its strategy, the UMC Utrecht Brain Center invests in junior scientific talent. The Rudolf Magnus Young Talent Fellowship (€200,000 to be shared between the two applicants) allows junior researchers to develop a strong and recognizable research profile and set up interdisciplinary collaborations. In 2019, different from previous years, two research couples are awarded to improve further collaboration within the UMC Utrecht Brain Center.

Jeroen Siero & Nikkie Dieleman

Jeroen Siero (MR physicist at the radiology department in the Cerebrovascular Imaging Group) and Nikki Dieleman (doctor at the neurology department and researcher at the radiology/neurology department) assess the impact of the (micro)vasculature on small vessel diseases progression in terms of cognitive decline and conventional markers of brain tissue damage 

Jeroen: “My specific expertise is on the development of acquisition methods and analysis approaches for both 3 and 7 tesla MRI. I aim to apply and develop MRI methods that target the cerebrovascular structure and function with high sensitivity and precision. Specifically I target the microvessels that directly feed the neuronal tissue. Microvessels are recognized to play a pivotal role in several neurological and cerebrovascular diseases. With my effort I hope to advance our understanding of the human brain in health and disease, even if it is only a little bit.”

Nikki: “During my PhD I have mainly focused on hunting down the causes of cerebral infarct using vessel wall imaging with (ultra) high MRI. My post-doctoral research is focusing on hypertension and its consequences on the brain and its vessels. There I combine brain tissue markers, vessel (wall) characteristics and cognitive outcome to further unravel the risk factors of stroke. With that I hope to be able to obtain a better understanding of the consequences of hypertension and find early intervention options before large damage has happened.”

Jeroen: “I believe that to push boundaries and avoid tunnel vision a multi-disciplinary approach and solid teamwork is the way to go. Combining expertise and data, we can broaden our research questions, and pose more far-reaching and fundamental hypotheses. Focussing on a single bio- or imaging marker usually does not allow this. In this fellowship project we will combine forces with the Internal Medicine, Neurology department and the Image Sciences Institute. We will use a wide-range of novel MRI-based markers together with patient risk factors to build a prediction platform on disease progression. Here we look at small vessel disease, which can lead to awful conditions such as stroke and dementia. Using machine-learning approaches we ultimately aim to see if and which MRI markers can early predict decline in cognition and larger brain tissue damage.”

Nikki: “Combining clinics and research is in my opinion of utmost importance to be able to optimize patient care and make individualized treatment possible. The position of both working in the clinic and as a physician makes it possible to address clinical questions directly from the clinic and translate this to research questions and scientific research. Together with a close collaboration with the Imaging Center, the translation from science to the clinic can made next. With this project we can find relevant markers of microvessel and brain function and structure using a multi-model 4D imaging prediction platform that can early predict consequences of SVDs. This will ultimate lead to early intervention and with that prevention, which is my main drive for doing research besides clinical work.”

Edwin van Dellen en Wim Otte

Edwin van Dellen (psychiatrist) and Wim Otte (neuroscientist) use the knowledge of brain network alterations in epilepsy to develop electroconvulsive treatment outcome predictors for depressive symptoms and cognitive functioning 

Edwin: “Will electroconvulsive treatment for depression improve my patient’s symptoms, or will it only induce severe cognitive impairment?” “Which elderly patient has a high risk of becoming delirious due to hospitalization, and needs preventive measures?” “Is it possible to predict non-response to antipsychotic medication for an adolescent suffering from a psychotic episode, so that we can skip treatment steps that are not effective?” As a young psychiatrist with a strong neuroscientific background, I am highly motivated to use electroencephalography (EEG) recordings, MRI, and computational modeling of brain activity for improvement of psychiatric treatment through precision medicine. During my clinical training as psychiatrist (2015-2019), I continued my research one day per week. I currently combine my clinical work as a psychiatrist with research on treatment outcome predictors in neuropsychiatric diseases.”

Wim: “My recent research activities have focused on translational brain imaging and connectivity modeling in relation to brain diseases, particularly in epilepsy and stroke. I have identified remote cerebral consequences of focal epilepsy on whole-brain networks in animal models and patients. I am currently trying to unravel the enigmatic functional–structural brain connectivity link and the dynamic nature of functional networks. In particular in relation to development and progression of different brain disorders.”

Edwin: “Many people with major depressive disorder may benefit from electroconvulsive therapy. However, it is currently unpredictable which people will truly benefit. Neither which people will suffer from lasting, therapy-induced cognitive side-effects. We therefore aim to develop two robust EEG-based predictors using a prospective intervention study. One personalized predictor will estimate electroconvulsive therapy outcome of depressive symptom relief. The other predictor will estimate cognitive functioning post electroconvulsive therapy.”

Wim: “We have an ideal set of overlapping and complementary expertise. We are both very familiar and experienced in a broad range of clinical neuroscience applications. Edwin has hands-on experience with conducting clinical intervention studies, whereas I am working on the forefront of deep learning and transfer function research.”

The Rudolf Magnus Young Talent Fellowship contains €200,000 to be shared between the two applicants in a couple. The couples form a multidisciplinary collaboration between one of laboratories of the UMC Utrecht Brain Center or between one of these laboratories and a clinical department (e.g. with clinicians or researchers in the fields of genetics, imaging, clinical care etc). The two awarded couples presented their proposal at the Research day at November 29, 2019.

Lieza Exalto investigates differences between men and women in vascular dementia

Dementia affects women twice as often as men. Women have a faster rate of decline after a diagnosis of Alzheimer’s Disease. In one out of six people with dementia, vascular injury is the main cause. More often, vascular damage occurs in the brain along with other causes of dementia. In cardiovascular disease relevant differences between men and women have been established. Yet, scientifically, little is known about male-female differences in vascular dementia. “Intriguing,” says Dr. Lieza Exalto. “We see so many differences between men and women. Not only physically, but also in dealing with an illness and treatment. And yet we treat everyone the same. As a doctor, I believe: we can’t ignore this”

Lieza recently received a grant from Alzheimer Nederland to investigate this further. “We know that vascular damage affects dementia. Cardiovascular disease and dementia come together in vascular dementia. In the cardiovascular field there is already much more insight into the differences between men and women. But not yet regarding vascular dementia. That is why I am happy to have the possibility to do this research. ”

Based on information from two large cohort studies, Lieza will provide insights in differences between men and women. “These insights, can lead to better prevention, diagnosis and treatment plans that are more personalized.”

Horizon 2020
Many people with vascular dementia have cardiovascular diseases such as high blood pressure, atrial fibrillation, diabetes or strokes. People with diabetes have on average twice as much risk of dementia as people without diabetes. Cognitive problems, can cause errors in medication use and lead to complications. Early recognition is therefore important. These patients do go to the ophthalmologist regularly, and this provides a surprising opportunity. The blood vessels in the retina of the eye have the same origin as the brain. A large European consortium (Recognised), will investigate retinal markers to identify persons at risk of dementia. The consortium, in which Lieza Exalto and Geert Jan Biessels participate, has received a Horizon 2020 grant for this. Lieza will be responsible for assessing cognitive testing and Geert Jan, together with Hugo Kuijf (division Beeld), will focus on brain imaging, including 7 Tesla MRI.

Evaluation of all research in UMC Utrecht

Similar as six years ago, the research of the UMC Utrecht is assessed according to the Standard Evaluation Protocol (SEP). An international committee of scientists visited the UMC Utrecht from the October 30 till November 1, 2019. The research is evaluated within the six strategic research programs.

“An excellent job,” says René van Lier about the quality and relevance of the research at the UMC Utrecht. The choice of the UMC Utrecht to focus its research in strategic research programs has led to concrete multidisciplinary research.

The UMC Utrecht Brain Center was complimented with their organization and scientific quality of both research and PhD program. However, there is also room for improvement regarding talent management and dedicated research time for clinical scientists. On behalf of Jeroen Pasterkamp and Marjolein Sneeboer, thank you all for your contribution!

Social Talk

Geert Ramakers wins Hijmans van den Bergh Education Prize

During a symposium on the occasion of the 150th birthday of professor Abraham Albert Hijmans van den Bergh, Geert Ramakers received the Hijmans van den Bergh Education Prize.

The UMC Utrecht values exceptional educational achievements. This year the prize went to Dr. Geert Ramakers (Translational Neuroscience and program coordinator of the master Neuroscience & Cognition) because of his exceptional commitment to education and his enormous involvement with students. What distinguishes Ramakers from the other candidates is primarily the complete vision of education on the basis of which study routes are created for students. Geert always keeps asking, seeks cooperation and cross-connections. He received the prize, a graphic work by artist Hans Laban, from drs. Cateautje Hijmans van den Bergh.

Four new Associate Professors


Four researchers from the Brain Center have been appointed as associate professors: Tristan van Doormaal, Marjolijn Ketelaar, Michael van Es and Jannie Wijnen.

Jannie Wijnen

Jannie Wijnen

“I am trained as a biomedical engineer and graduated on the topic of Magnetic Resonance Imaging (MRI). Ever since, the unlimited possibilities of MRI have intrigued me and pulled me into science. The mission of my research is to enable metabolic MRI in the diagnosis and treatment planning of children with metabolic disorders and cancer. I believe that direct measurement of tissue metabolism in the patient will lead to better understanding of the disease in the individual patient and can therefore faster translate to a change in treatment planning, to better help the patient. My goal is to develop advanced metabolic MRI methods and make them available for clinical research and diagnosis. To achieve this goal, I focus on finding new means to increase speed and robustness which is essential for successful clinical implementation.

From being an associate professor I expect to create an independent research position, build a stronger national network and push international collaborations forward.”

Marjolijn Ketelaar

“After I finished my study Human Movement Science with a focus on Rehabilitation and Psychology, and my PhD-research in the field of pediatric rehabilitation, I started as a researcher at De Hoogstraat Rehabilitation and UMC Utrecht. I am the leader of the research program on Family Empowerment in pediatric rehabilitation. Furthermore, I am a scientist at CanChild (www.canchild.ca), Center for Childhood Disability Research, McMaster University, Hamilton, Canada. On the national level I am the leader of the Dutch research program PERRIN (www.perrin.nl), studying the development of activities and participation of children and youths and adults with cerebral palsy. We do this in a consortium of university hospitals, patient association CP Nederland (BOSK), and many rehabilitation centers to support the implementation of knowledge by professionals and patients. Additionally, I co-founded CP-Net, a network of parents and persons with CP, clinicians and researchers (www.CP-Net.nl).

My research interests include family-centered services, and the role of the family in the development of children with disabilities, with a focus on Brain Based Developmental Disabilities (e.g., Cerebral Palsy) and neuromuscular diseases (e.g., SMA). Our main goal is to gain more insight in the process of parent empowerment, aiming to support the development of children with disabilities, by promoting health, well-being, confidence, and resilience of parents. In this field I collaborate with various research groups all over the world. Patients and families are involved throughout the research process, from idea to implementation, to optimize relevance and usefulness of research, and to improve clinical practice. There is a strong collaboration with patient associations.

I look forward starting new research projects with colleagues in other fields, such as neonatology, neurology, psychiatry and translational science. Moreover, I hope to inspire colleagues to take steps in the field of patient participation in research. Together we can make a difference in the lives of patients and their relatives.”

Tristan van Doormaal

Tristan van Doormaal

“I am a skull base and vascular neurosurgeon. I love my job because of the combination of challenging surgeries, teamwork and meaningful contacts with patients on very important moments in their lives. I like to be a compassionate doctor.  My research focusses on bench to bedside development of neurosurgical devices to make patient care and outcome of our treatment better.

Currently I am working on temporary basis as a staff neurosurgeon to further develop my technical and management skills for a year in Zürich, Switzerland. I will return in the UMC Utrecht in September 2020. Like all other neurosurgeons I am working mostly within multidisciplinary teams to deliver the best patient and disease centered care. My preclinical research is mainly centered in the Brain Technology Institute (BTI). BTI is a non-profit foundation to work also with external partners, perfect for implementation and valorization of our research. Part of my research is also performed in close cooperation with a UMC Utrecht spinoff I co-founded, AugmedIT. This is a medtech startup in which we develop new preoperative and intraoperative holographic tools to improve surgical outcome.

The main goal of my research is to further improve patient outcome. The devices we develop do this by preventing complications and make treatments easier. Examples are a ‘plaster’ we developed to prevent cerebrospinal fluid leakage, a new device we developed for vascular micro anastomoses and a new method of holographic surgical preparation and navigation.

Besides the continuous looking for new neurosurgical techniques, developments, ideas and possibilities my primary focus as associate professor will be our PhD students and master students from different programs. The goal is to motivate and inspire the team to work in a focused way towards our goals. If the team is motivated, focused and happy with a good work-life balance, results will come that ultimately will benefit patients.”

Michael van Es

Michael van Es

“I am a neuromuscular neurologist and researcher at the UMC Utrecht. My main focus is on ALS, neurodegenerative diseases and genetics. I studied medicine in Utrecht, followed by a PhD and neurology residency in the UMC Utrecht and subsequently became neuromuscular fellow (on a Veni grant) and staff member here. So with the exception of part of my medical internships (co-schappen) which I did in South Africa and my post-doc which I did at USCD, I have been in Utrecht for the last 20 years. So, Utrecht is my home professionally as well as personally.

The main focus of my research is on ALS and related disorders. ALS is a complicated disease with multiple subtypes, which forms a spectrum with frontotemporal dementia. The main goal of my research is to develop effective treatments for ALS by identifying subtypes (genetic, cognitive, etc) and performing targeted clinical trials.

I hope to further expand my research group and develop several promising collaboration, such as TRICALS, with KU Leuven and my work together with Tanja Nijboer on cognition.”

Research Day 2019

Cover Story

What is the story behind the thesis cover?

This time: Suzanne Lemstra

“My research focuses on the molecular pathways underlying neural connections. Specific protein families, called the Semaphorins and Plexins are important to ensure correct wiring of the brain and can result in neurodevelopmental disorders if perturbed. You can compare them to traffic signs, if they are wrongly placed, you will not reach your destination. Therefore it is crucial to understand how these proteins function.

On my cover I have placed a “growth cone”. This is a structure that nerve cells in the brain, the neurons, use to sample the environment for cues, like Semaphorins and Plexins. On my cover the growth cone pushes out a dent in a circle, which is inspired by Matt Might and his illustrated guide to a PhD. His circle represents all the knowledge in the world. During my PhD I have generated new information about Semaphorins and Plexins to the current knowledge circle, hence the growth cone created “a dent” in the circle”.

Watch the video:

Animated guide to a PhD

Publications

  • Goulay R, Mena Romo L, Hol EM, Dijkhuizen RM. From Stroke to Dementia: a Comprehensive Review Exposing Tight Interactions Between Stroke and Amyloid-β Formation. Transl Stroke Res. 2019 Nov 28. Pubmed
  • McDonald MW, Black SE, Copland DA, Corbett D, Dijkhuizen RM, Farr TD, Jeffers MS, Kalaria RN, Karayanidis F, Leff AP, Nithianantharajah J, Pendlebury S, Quinn TJ, Clarkson AN, O’Sullivan MJ. Cognition in stroke rehabilitation and recovery research: Consensus-based core recommendations from the second Stroke Recovery and Rehabilitation Roundtable. Int J Stroke. 2019 Oct;14(8):774-782. Pubmed
  • van Bodegraven EJ, van Asperen JV, Sluijs JA, van Deursen CBJ, van Strien ME, Stassen OMJA, Robe PAJ, Hol EM. GFAP alternative splicing regulates glioma cell-ECM interaction in a DUSP4-dependent manner. FASEB J. 2019 Nov;33(11):12941-12959. Pubmed
  • van Dijk BJ, Meijers JCM, Kloek AT, Knaup VL, Rinkel GJE, Morgan BP, van der Kamp MJ, Osuka K, Aronica E, Ruigrok YM, van de Beek D, Brouwer M, Pekna M, Hol EM, Vergouwen MDI. Complement C5 Contributes to Brain Injury After Subarachnoid Hemorrhage. Transl Stroke Res. 2019 Dec 6. Pubmed
  • Vonck BMD, Lammers MJW, van der Waals M, van Zanten GA, Versnel H, Cortical auditory evoked potentials in response to frequency changes with varied magnitude, rate, and direction. J Assoc Res Otolaryngol. 2019; 20:489-498. Pubmed
  • Rademaker MM, Stegeman I, Ho-Kang-You KE, Stokroos RJ, Smit AL. The Effect of Mindfulness-Based Interventions on Tinnitus Distress. A Systematic Review. Front  Neurol. 2019 Nov 1;10:1135. Pubmed
  • Nuijts MA, Degeling MH, Stegeman I, Schouten-van Meeteren AYN, Imhof SM. Visual impairment in children with a brain tumor: a prospective nationwide multicenter study using standard visual testing and optical coherence tomography  (CCISS study). BMC Ophthalmol. 2019 Nov 9;19(1):220. Pubmed
  • van der Hoek-Snieders HEM., van den Heuvel, AJML., van Os-Medendorp, H. Kamalski DMA., Diagnostic accuracy of fetal MRI to detect cleft plate: a meta analysis. Eur J Pediatr. 2019 dec. 3 epub ahead of print. Pubmed
  • Blijleven EE, Thomeer HGXM, Stokroos R, Wegner I. Protocol for a validation study of the translated stapesplasty outcome test 25 for measurement of disease-specific quality of life in Dutch patients with otosclerosis. BMJ Open. 2019 Dec 10;9(12):e030219. Pubmed
  • Yaz F, Ziylan F, Smeeing DPJ, Thomeer HGXM. Intratympanic Treatment in Menière’s Disease, Efficacy of Aminoglycosides Versus Corticosteroids in Comparison Studies: A Systematic Review.Otol Neurotol. 2020 Jan;41(1):1-10. Pubmed
  • Jonker, MA., Rijken, JA. et al. Estimating the penetrance of pathogenic gene variants in families with missing pedigree information. Stat Methods Med Res. 2019 Oct-Nov;28(10-11):2924-2936. Pubmed
  • Draaisma, Kaspar, et al. Molecular Evolution of IDH Wild-Type Glioblastomas Treated With Standard of Care Affects Survival and Design of Precision Medicine Trials: A Report From the EORTC 1542 Study. Asco

Grants & awards

  • Roger Adan was awarded with an ENW- KLEIN grant to study energy balance induced plasticity in neurons involved in reward signaling and eating behavior.
  • Elly Hol’s ALEXANDER consortium is granted. It is European joint program on rare diseases.The consortium is about GFAP mutations. Alexander is a white matter disorder, caused by astrocyte dysfunction. The consortium has members from Sweden, Israel, Spain, and Czech Republic and 2 patient organisations (Dutch and European patient organisation for white matter disorders).

Calendar

Public event – January 20

(update: sold out!)

The UMC Utrecht Brain Center organizes a public event in the evening of January 20, 2020. The theme of the event is data, artificial intelligence, and brain diseases. The event will be hold in TivoliVredenburg, Cloud Nine and is a collaboration between the UMC Utrecht Brain Center and New Scientist. The evening will be in Dutch.

X-Talks

The X-talks consist of a series of programs within the Brain Center. The X-talks attract both students and senior researchers and provide a forum for inspiring discussion, knowledge transfer, and by bridging boundaries drives novel combined research efforts for the future. X-talks are all held at 15.00-17.00 lecture hall David the Wied Stratenum 4th floor (STR. 4.112).

Next X-Talks:

  • February 7 – Developmental disorders
    Prof. dr. Ype Elgersma: From molecular mechanisms to clinical trials in neurodevelopment disordersYpe Elgersma (Erasmus MC, ENCORE expertise center, Rotterdam)  is an expert in the molecular mechanisms and genetics underlying various developmental disorders.
  • March 13 – Translational Approaches

Utrecht Brain Conference 2019

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