Annual Report ruimte voor illustratie/beeld van het A-merk in blauw. MH&NS School for Mental Health & Neuroscience

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1 MH&NS School for Mental Health & Neuroscience Annual Report 2013 ruimte voor illustratie/beeld van het A-merk in blauw Maastricht University Faculty of Health, Medicine and Life Sciences & Health Institutes: Maastricht University Medical Centre + RIAGG Maastricht PMS Vijverdal Mondriaan Zorggroep Heerlen

2 Content Preface Professor Dr. Harry Steinbusch 3 1. Future directions of MH&NS and EURON 5 2. Organizational structure 8 3. Divisions Division I: Cognitive Neuropsychiatry and Clinical Neuroscience Division I: Research lines Division II: Mental Health Division II: Expert groups Division III: Neuroscience Division III: Research lines Facts and Figures Earning Power Research Staff Output results Aggregated results of the School Output Best publications PhD theses Master and PhD Educational Activities Master Programme PhD Programme 44 Annexes: I MH&NS / EURON PhD Educational Programme II Current PhD theses 49 III Publications 58 2 MH&NS Annual Report 2013

3 Preface Dear colleagues, Prof.dr. Harry W.M. Steinbusch Scientific Director I am pleased to provide you with our Annual Research Report It presents a full overview of the work and provides information concerning the School for Mental Health and Neuroscience (MH&NS) in the fields of research output, earning power, staff members and postdoctoral teaching activities in MH&NS has grown further not only regarding the number of publications as requested by the Faculty of Health, Medicine and Life Sciences (FHML) but more importantly also in the quality of the papers as indicated by an increase in the average impact factors. We were encouraged to increase the number of papers in particular in the top 10% and in general in the top 25% of the impact fields in which we are working. The increase in non-tenured staff members has resulted in a steady increase in the number of PhD theses to 24 in MH&NS currently hosts about 170 PhD students. The guidance of these students is a significant challenge that requires an enormous and coordinated effort of all our staff members, resulted always in two supervisors to guide one PhD student. In accordance with the performance contract with FHML we have focused on increasing more funding from NWO (Dutch Medical Research Council) and FP7- Horizon EU grants, which has resulted in depending less on grants obtained from other peer-reviewed agencies. Grants obtained from industrial contract research now represent a more limited component of our funding. However, it is worth noting that neuroscience research becoming less fragmented in the capital area. More intense cooperation among the different units is becoming more efficient. This restructuring has resulted in one division focused on Cognitive Neuropsychiatry and Clinical Neuroscience, one division on Environmental Psychiatry and the third one on Fundamental and Systems Neuroscience. In line with this, educational activities of the Master s programs correspond to these three divisions. The prime strength of MH&NS is a strict translational approach, e.g. division 1 concerns and combines neuroepidemiology and brain imaging, division 2 focuses on gene-environmental changes/interactions related to psychiatric disturbances such as psychoses, and division 3 uses animal and cellular models related to systems-level research. These lines of research at MH&NS will continue to find much synergy within collaborative projects and research networks, in the areas of Translational Neuropsychiatry, combined epigenetic studies and studies related to the disturbances of the Brain vasculature, leading to Vascular dementia and dysfunctioning of the Blood Brain Barrier, but also has further developed in closed relationships with Brains Unlimited and the Faculty of Psychology and Neuroscience. The proportion of foreigners on staff has been steadily increasing to approximately 28% for researchers in In conclusion, I would like to thank all members of MH&NS for contributing their knowledge and expertise to the School and students in the past years. Importantly, these changes and improvements that have been made will create new opportunities for the upcoming years. I look forward to new directions and challenges in the restructured academic environment in the coming years. Prof.dr. Harry W.M. Steinbusch Scientific Director School for Mental Health and Neuroscience 3 MH&NS Annual Report 2013

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5 Future directions of the School for Mental Health and Neuroscience (MH&NS) The mission of the School for Mental Health and Neuroscience at Maastricht University and the European Graduate School for Neuroscience, EURON, at the Euregional level, is threefold: 1. Focusing on a basic understanding of brain function and disease mechanisms, 2. Understanding the function of genes and proteins, cellular processes and neuronal networks in relation to human health, 3. Establishing reciprocal translational links between lab and clinic and reverse. This mission can be made possible by building on multidisciplinary approaches. Therefore, as a foundation we will continue to educate and train Master and PhD students to become independent researchers who are able to plan and execute cutting edge science and to function well in multidisciplinary research programs in academia and/or industry. We use as slogan Through Excellence in Education and Research towards Innovation and Translation. This will be achieved by sharing expertise and knowledge among not only within our School of Mental Health and Neuroscience but also in conjunction with our EURON partners and by stimulating mobility of Master and PhD students. In addition, we aim for uniformity or comparability of standards for PhD degrees among the four participating countries, i.e., the Netherlands, Belgium, Germany and France which ultimately should lead to double or joint degrees. Indisputably, the training of young competent PhD s in Neuroscience is crucial to maintaining the competitiveness of the European community in Neuroscience-based research. The new generation of our neuroscientists should be capable of integrating information across different levels of research. Similarly, they should be competent to participate in integrative projects as a next step in elucidating the complex interplay between multiple genetic and environmental factors in order to reveal how this interplay translates into normal brain function and/or disease. Strategic Goals for MH&NS The School will be facing in the immediate forthcoming period some important changes. However, we believe changes will also create opportunities. The first opportunity is related to the establishment of the Maastricht University Medical Centre (MUMC + ) and the fact that the MUMC + has decided to stimulate Translational Neuroscience, the clinical counterpart of MH&NS within MUMC +. The School will try to match this initiative with an amount of C0.5 million. The additional funding provided by MUMC + will be deployed with a view to put in effect and consolidate strategic choices for expansion and strengthen the positions of postdocs and researchers at the assistant professorship level. At present, all these positions are, unfortunately, non-tenured while what is really needed are tenure-track positions to support and recruit excellent career-oriented staff members from within or beyond. Another consideration regarding Strategic Goals for the years till 2020 is the implementation of Neuro-Innovation Centre (NIC) a Clinical Research Unit, headed by Prof.dr. J. van Os, Prof.dr. Y. Temel and Prof.dr. R. Stokroos. NIC will start in 2015 and will deal with all aspects of mental health related issues related to research, patient care and education in the Academic Hospital Maastricht. NIC and the School will jointly work together. As mentioned before this relationship has resulted in direct opportunities for translational research from bed to bench and vice-versa. Finally, we would like to provide some additional thoughts with respect to EURON. We have mentioned before that MH&NS is a fully integrated partner in EURON and moreover the coordinator. However, EURON comprises nine other universities in the Euregio as well. MH&NS has been taking the lead in all organizational aspects. Because 5 MH&NS Annual Report 2013

6 it already provides an excellent opportunity for networking, further Euregional activities and introducing an international or European Master in Translational Neuroscience have great potential, which we will incorporate in the next period. A further specific point deserving our attention is our partnership with the Faculty of Psychology and Neuroscience (FPN). In our School within Division 1, the Department of Psychopharmacology, (FPN) headed by Prof.dr. J. Ramaekers is already participating. In addition, there is a strong link with educational activities at the level of the Research Master Program Cognitive and Clinical Neuroscience in which the School is involved in 2 of the 4 tracks. Thus the FHML is the principal coordinator of two tracks of the Research Master. We would like to build further and even strengthen our partnership with other groups in FPN, such as the Neuroimaging group of Prof.dr. R. Goebels and the Neuroplasticity group of Prof.dr. P. De Weerd. These partnerships are important for research and educational exchanges and should result within the next period result into Centre for Interactive Neuroscience (CIN). The foundation of our future plans is that the research within MH&NS is divided into the three reorganized divisions. The choice for three divisions is based upon methodsrelated considerations: division 1 on patient care related cognitive neuropsychiatry and clinical neuroscience; division 2 on patient care-related gene environment investigations, and division 3 on animal models for neurodegenerative disorders. The research within MH&NS is based upon translational perspectives, in which the patient and related problems is the prime focus within the different clinical disciplines in particular Psychiatry and Neuropsychology and Neurology. The patient related studies or cohorts can be divided in patients with early life events problems (Division 2) or late-life event problems and aging (Division 1). Division 2 has an emphasis on gene-environment interactions in relation to neuropsychiatric and neurological disorders as studied in healthy and clinical human studies with as major clinical pictures schizophrenia and depression. The research of Division 1 is related to neuropsychiatric and neurological disturbances studied in healthy and clinical humans focused upon Alzheimer s disease and stroke. In the typical Maastricht University matrix structure towards both divisions, Division 3 is strategically positioned again from a translational perspective to perform animal experimental studies. The emphasis is upon cellular, molecular and behavioral processes underlying neurodegeneration and plasticity on animal models for Alzheimer s disease, Parkinson s disease, epilepsy, schizophrenia and pain. To summarize, MH&NS wants to move forward towards a Centre of Excellence. We are aiming together with the MUMC+ to formulate steps to increase our critical mass. We have already increased a variety of funding opportunities and we will continue to do so thereby increasing the number of Ph.D. students and postdocs. We intend to gain international recognition, showing this consistently on a translational level. In this way we clearly will distinguish ourselves within the national and international competition. To reiterate, the focus of MH&NS will be on three levels: 1. Research: three divisions working through a matrix model on joint translational neuroscientific clinical problems; 2. Education: expanding and strengthening Research Master, Ph.D. and postdoctoral activities; 3. Collaboration: further exploring the possibilities for a two faculty based Centre for Interactive Neuroscience 6 MH&NS Annual Report 2013

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8 Organizational structure MH&NS is managed by the Board of MH&NS. The board is the body where strategies issues are discussed and effectuated. It consists of five members: the scientific director, the managing director and the three division leaders. Dean of the Faculty Health, Medicine and Life Sciences Prof.dr. Albert Scherpbier Managing Director Laurent Louwies Scientific Director Prof.dr. Harry Steinbusch Cognitive Neuropsychiatry and Clinical Neuroscience Prof.dr. Frans Verhey Deputies Prof.dr. Robert van Oostenbrugge Prof.dr. Caroline van Heugten Psychiatry & Neuropsychology (section Neuropsychology) Movement Sciences General Practice Radiology Othorhinolaryngology Neurology Mental Health Prof.dr. Inez Myin-Germeys Deputy Dr. Koen Schruers Psychiatry & Neuropsychology (section Psychiatry) Neuroscience Dr. Bart Rutten Deputies Prof.dr. Yasin Temel Dr. Jos Prickaerts Psychiatry & Neuropsychology (section Neuroscience) Neurosurgery Anesthesiology Urology Ophthalmology Neurology Pediatrics Figure 2.1 Organogram of MH&NS: the contribution of the different Departments of FHML to the current three Divisions of MH&NS. Participating departments Core Departments Anesthesiology, Prof. Dr. W. Buhre Neurology, Prof. Dr. R. Van Oostenbrugge - Clinical Neurophysiology, Prof. Dr. W. Mess Neurosurgery, Prof. Dr. J. Van Overbeeke Ophthalmology, Prof. Dr. W. Webers Psychiatry & Neuropsychology, Prof. Dr. J. Van Os Urology, Dr. G. Van Koeveringe Non Core Departments General Practice, Prof. Dr. J. Metsemakers Human Movement Science, Prof. Dr. M. Hesselink Internal Medicine, Prof. Dr. C. Stehouwer General Practice, Prof. Dr. J. Metsemakers Pediatrics, Prof. Dr. L. Zimmerman Orthorhinolaryngology, Prof. Dr. B. Kremer Radiology, Prof. Dr. J. Wildberger 8 MH&NS Annual Report 2013

9 Members of EURON MH&NS is the coordinator of the European Graduate School of Neuroscience (EURON). EURON is a research and training network of 11 universities in four countries i.e. Belgium, Germany, France and the Netherlands. EURON MH&NS Belgium Université Libre de Bruxelles Universiteit Hasselt Katholieke Universiteit Leuven Université de Liège Université catholique de Louvain Germany RWTH Aachen University University of Bonn University of Cologne Saarland University, Homburg France Université Lille 1 Figure 2.2 EURON in relation to MH&NS. The Netherlands Maastricht University (MH&NS) 9 MH&NS Annual Report 2013

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11 Divisions Goals & Results 3.1 Division I: Cognitive Neuropsychiatry & Clinical Neuroscience Division Leader: Prof.dr. Frans Verhey Deputies: Prof.dr. Robert van Oostenbrugge Prof.dr. Caroline van Heugten Staff: Dr. Pauline Aalten Dr. Jos Adam Dr. Marjan van den Akker Prof.dr. Bert Aldenkamp Dr. Lucien Anteunis Dr. ir. Walter Backes Dr. Martin van Boxtel Dr. Saartje Burgmans Dr. Jeanette Dijkstra Dr. Annelien Duits Dr. Carin Faber Dr. Ed Gronenschild Dr. Paul Hofman Prof.dr. Raymond Hupperts Dr. Jaap Jansen Dr. Heidi Jacobs Prof.dr. Herman Kingma Dr. Sebastian Köhler Dr. Vivian Kranen van Mastenbroek Prof.dr. Bernd Kremer Dr. Abraham Kroon Dr. Albert Leentjens Prof.dr. Peter de Leeuw Prof.dr. Werner Mess Prof.dr. Job Metsemakers Prof.dr. Felix Mottaghy Prof.dr. Rudolf Ponds Dr. Inez Ramakers Dr. Jennifer Reijnders Dr. Olga Schiepers Dr. Pieter-Jelle Visser Dr. Marielle Vlooswijk Dr. Marjolein de Vugt Prof.dr. Joachim Wildberger Dr. Ieke Winkens Dr. Claire Wolfs Goals & Results CNP&CNS performs fundamental and applied research on brain-cognition relationships. CNP&CNS mission is to generate new insights into neurocognitive and neurobehavioural mechanisms, which help to improve the treatment and care for people with cognitive and other neurological disorders. Since 2009, clinical neuroscience researchers have been assigned to the Division 1 Cognitive Neuropsychiatry & Clinical Neuroscience (CNP&CNS), a name expressing the translational nature of the research program, and the multidisciplinary perspective. With respect to the medical core topics, the focus is upon neurodegeneration of the central nervous system, more specifically Alzheimer s disease and its prodromal phases, Vascular Cognitive Impairment / dementia, other related cognitive disorders, Parkinson s disease, peripheral nervous system disease, such as small fiber neuropathy, acquired brain damage, such as stroke, traumatic brain injuries, and epilepsy. Researchers in the division investigate the contribution of biological, neuropsychological and psychosocial factors, single and in combination, and the effects of ageing on the normal development of normal neurocognition and on mild to severe cognitive dysfunction. Research in Division 1 is typically conducted in a multi-disciplinary way, with contributions of scholars with a background in the departments of Psychiatry, Neuropsychology, Clinical neurology, Neuroradiology, Neurophysiology, and Otorinolaryngology. In 2013, we further pursued our studies into normal, successful and pathological ageing, with a great interest in translating basic insight into practical application. Collaboration between the departments of Psychiatry, Neurology and Neuroradiology were intensified. Studies that were carried out as part of the NWO/FES program on Center of Translational Molecular Medicine and Brain and Cognition are producing the first results and products. New grants were obtained from both national and international (EU) sources. 7 PhD students successfully defended their thesis. Below, several examples are presented of ongoing and recently started research projects that are at the core of the research in this division. 11 MH&NS Annual Report 2013

12 3.1.1 Division I Research lines Research line: Neurodegenerative disorders: mechanisms, early diagnosis and biomarkers PI: Prof dr FRJ Verhey/ Prof dr R van Oostenbrugge Research Staff: Dr. P. Aalten, Dr. M. Van Boxtel, Prof.dr. R. van Oostenbrugge, Dr. P. Hofman, Prof.dr.ir. W. Backes, Dr. J. Jansen, Dr. A. Leentjens, Dr. A. Duits, Dr. E. Gronenschild,, Dr. S. Köhler, Dr. P-J. Visser, Prof. dr. F. Verhey Postdocs: Dr. S. Burgmans, Dr. H. Jacobs, Dr I. Ramakers PhD-students: Drs. L. Clerx, Drs. L. Elias, Ir. H. van de Haar, Drs. R. Handels, Drs. M. Huijts, Drs. A. Moonen, Drs. S. Schievink, Drs. T. Van der Voort, Drs. S. Vos, drs W. Janssen, Drs R Hamel, Drs. B. Reijs, drs. E. Zhang, Drs A. Mertens Co-investigators European Alzheimer s Disease Consortium extern: Focus of research: Translational research into the early diagnosis of pathological ageing A large-scale national biobank, coordinated by MUMC and the VU-MC, formed the infrastructure for translational research into the early diagnosis of pathological ageing (Parelsnoer Neurodegeneratief), coordinated by Proven F. Verhey. Novel diagnostic technology for the early detection of Alzheimer s disease will be examined and evaluated in terms of Health Technology Assessment, i.e., with respect to its added value to existing diagnostic procedures (LeARN, CTMM). A project funded by VSB was started on the prediction of individual trajectories in cognitive disorders. Collaboration with the Departments of Neurology and Radiology was intensified, which has led to a new study on neurovascular mechanisms of cognitive disorders, and the interaction between vascular and neurodegenerative mechanisms. To assess brain microvascular pathology in the brain in vivo, novel imaging techniques are currently being developed. S. Burgmans and W. Backes started a pilot study on blood-brain barrier leakage in dementia (funded by an ISAO pilot award). They hypothesized increased bloodbrain barrier permeability in Alzheimer patients and developed a new dynamic contrast enhanced MRI scan. A new grant of was obtained by these researchers to expand this research line. On the European level, the research group has leading roles in projects on standardisation of biomarker assessment (JPND BIOMARKAPD) and the set-up of a European Medical information framework (IMI EMIF-AD), Collaboration between the departments of Psychiatry, Neurology and Radiology was intensified, which has led to a new study on neurovascular mechanisms of cognitive disorders, and the interaction between vascular and neurodegenerative mechanisms. To assess brain microvascular pathology in the brain in vivo, novel imaging techniques are currently being developed. S. Burgmans and W. Backes started a pilot study on blood-brain barrier (BBB) leakage in dementia (funded by an ISAO pilot award). They hypothesized increased blood-brain barrier permeability in Alzheimer patients and developed a new dynamic contrast enhanced MRI scan. A second BBBB project started up investigating the role of BBB leakage in patients with Vascular Cognitieve Impariment (Prof.dr. R. van Oostenburggen, Prof.dr. W. Backes). The VSB fonds/zonmw for a research program on successful psychosocial reintegration of patients and caregivers after stroke continued in 2013; at the moment all data are collected and follow-up measurements are being completed. In this program 4 PhD 12 MH&NS Annual Report 2013

13 students (Maastricht, Nijmegen and Utrecht) investigate the course and predictors of psychosocial functioning, costs of psychosocial care and effectiveness of two new psychosocial interventions for patients and caregivers aimed at self-management and cognitive behavioural therapy for post-stroke depression and anxiety. All projects will be finished in Research line: Neuroepidemiology: Course and determinants of normal, successful and pathological cognitive ageing PI: Dr. M. van Boxtel Research Staff: Prof.dr. F. Verhey, Prof.dr.ir. W. Backes, Dr. P. Hofman, Dr. J. Jansen, Prof.dr. R. van Oostenbrugge Postdocs: Dr. O. Schiepers, Dr. S. Koehler, Drs. J. Reijnders PhD-students: Drs. F. van Dooren, Drs. P. Spauwen, Drs. W. van Zwam, Ir. F. van Bussel, Drs. K. Deckers, ir. M.Wong, Focus of research: Insight into the prevention, etiology and treatment of cognitive dysfunction in the normal adult population Division staff members are active participants of the Maastricht Study (MS), a study to provide more insight into the prevention, aetiology and treatment of type 2 diabetes and other chronic diseases in relation to mental health. The MS illustrates the integrative approach we are aiming at, with multidisciplinary input from the departments of Psychiatry & Neurosychology, Neurology, Neuroradiology, and Neuro-ophthalmology. The FP7 funded 3-year s study into preventive strategies to ameliorate the individual dementia risk profile of middle-aged individuals (see has produced its first deliverables, more specifically, an evidence-based risk factor algorithm to estimate individual dementia risk. This product will be used in a multicentre European intervention study aimed to reduce the dementia risk profile in middle-aged individuals. The project by J. Jansen (VENI grant) on multi-parametric imaging of cerebral biomarkers of cognitive deterioration using MRI in diabetes type-2 in the context of the Maastricht Study has yielded its first results. This project encompasses a multi-disciplinary approach between the departments of Radiology, Internal Medicine and Psychiatry & Neuropychology. Furthermore, the NWO/FES program (0,9M) aimed at the development of internet-based low-level intervention strategies to support the cognitive ageing process in middleaged and older adults has rounded off the data-collection of a large intervention study. The Maastricht Ageing Study continuous to be a major source for new studies into determinants of cognitive ageing, including diabetes and hypertension. Collaborations with international partners in dementia epidemiology and prevention have been started and/or intensified (e.g. Dr. Launer, NIH; Prof. Brayne, U Cambridge; Prof. Yaffe, USCF). The Weijerhorst foundation supported (0,66M) further research of the blood-brainbarrier between the departments of Radiology and Neurology to develop MRI methods and apply these in patients with small vessel disease (SVD) to get more insight in the etiology of SVD and to link this with both pathological and normal ageing and cognitive decline. 13 MH&NS Annual Report 2013

14 Research line: Psychosocial interventions and cognitive rehabilitation PI: Prof.dr. C. van Heugten, Dr. M. de Vugt, Research Staff: Prof.dr. R. Ponds, Dr. M. van Boxtel, Prof.dr. F. Verhey Postdocs: Dr. I. Winkens, Dr Claire Wolfs, Dr. G. Wolters, PhD-students: Drs. B. Dandachi-Fitzgerald, Drs. B. Ament, Drs. L. Boots, Drs. I. Brands, Drs. J. Collet, Drs. M. van Eeden, Drs. M. Fens, Drs. R. van Knippenberg, Drs. B. ter Mors, Drs. V. Moulaert, Drs. S. Smeets, Drs. N. Tielemans, Drs. L. Willemstein, Drs. A. Dam Co-investigators International Interdem network extern: Focus of research: Cognitive rehabilitation and health service evaluation research. Interventions in cognitive and acquired brain disorders In this research line a strong focus is put on evidence-based neuropsychological interventions, psychosocial interventions, caregiver interventions, cognitive rehabilitation and health service evaluation research. Interventions are investigated in cognitive and acquired brain disorders. In addition, research is focussing on the development and evaluation of new instruments to measure outcome of treatment and on investigating factors which influence outcome. Innovative treatment techniques are being evaluated in this program, such as selfmanagement techniques and e-health interventions. The program on e-health intervention studies funded by Alzheimer Netherlands / Alzheimer Research Fund Limburg is well underway. Aim of the program is to support dementia patients and informal caregivers in their home environment. In this program 2 PhD students (L. Boots / R. van Knippenberg) study the feasibility and effectiveness of two newly developed e-health interventions. The programme was expanded with a third PhD student in 2013, developing a web-based tool to enhance social support. The NWO/FES Brain & Cognition program (0.9 Me) continued in 2013 studying the effectiveness of cognitive rehabilitation and factors influencing the success of cognitive rehabilitation. In 2013, new interventions for executive dysfunction in Parkinson patients (Groningen), errorless learning augmented Goal Management Training (Nijmegen), problem solving therapy for stroke patients (Rotterdam) and the ABC method for severe behavioural problems after acquired brain injury (Maastricht) have been developed, and recruitment for efficacy studies has started. In addition, factors influencing rehabilitation outcome are being studied: selfawareness (Maastricht), learning style and learning potential (Utrecht/Maastricht). Research line: Epilepsy PI: Prof.dr. A. Aldenkamp, Research Staff: Prof.dr. H. Vles, Prof.dr.ir. W. Backes, Dr. P. Hofman, Dr. M. Majoie, Dr. G. Hoogland, Dr. R. Rouhl, Dr. M. Vlooswijk Postdocs: Dr. J. Jansen PhD-students: Drs. E. Barendse, Drs. K. Beerhorst, Ir. R. Besseling, Drs. R. Binie, Drs. W. van Blarikom, Drs. N. Bodde, Drs. Z. Bouwman, Drs. H. Braakman, Dr. M. Buskermolen, Drs. S. Ebus, Drs. N. Gosens, Drs. M. Huijts, Drs. D. IJff, Drs. R. van der Kinderen, Drs. S. van der Kruijs, Drs. S. Klinkenberg, Drs. J. Peijnenborgh, Drs. J. van Tuijl, Ir. T. Veenendaal, Drs. S. Schipper. Focus of research: Chronic epilepsy In 2003, the central theme within the research topic Epilepsy was Chronic Epilepsy. A substantial grant from the National Epilepsy Fund (NEF) was preciously obtained 14 MH&NS Annual Report 2013

15 for this program (led by Prof.dr. A. Aldenkamp). One of the most severe consequences of chronic epilepsy concerns to the impairment of cognitive functions, including the general thinking, memory, language and problem-solving capabilities. The neuronal substrate that explains this co-morbidity is still largely unknown. The novel insight today is that epilepsy is more a network disease rather than a single focal abnormality of malfunction. Traditionally, epilepsy research utilizes different techniques and methods: measurement of brain waves (electro-ecephalogaphy, EEG), imaging (acquisition of anatomic and functional brain images with scanning devices) and neuropsychological assessment. Recent technological developemtns of MRI methods, in particular functional and diffusion MRI, provede possibilities to obtain new insights on the organization and integrity of cerebral networks which may lead to strategies that prevent chronic epilepsy and cognitive co-morbidity. Also, further efforts are taken to unravel the neuronal and physical substrates for Psychogenic Non-Epileptic Seizures. Next to this clinical line there is an established pre-clinical research program, which a.o. now aims at determining factors which are involved epileptogenesis and chronicity in epilepsy animal models, like epigenetics, extra-synaptic receptors and mitochondrial function. The current research program is a close collaboration between the Departments of Radiology and Neurology in the MUMC+ and the Epilepsy Institute Kempenheaeghe. In 2013 the formal process was started leading to the institution of the Academic Centre for Epileptology. Research line: Neuromuscular disorders PI: Dr. C. Faber, Dr. I.S. J. Merkies PhD-students: Drs M. Bakkers, Drs. E. Vanhoutte, Dr. M.C.E. Hermans, Dr. J.G.J. Hoeijmakers Focus of research: Myotonic dystrophy and (painful) neuropathy/small fiber neuropathy Research into neuromuscular disorders (led by Dr. C. Faber) targets myotonic dystrophy and (painful) neuropathy/small fibre neuropathy. A longstanding collaboration between the Maastricht UMC and Prof.dr. S. Waxman (Yale University) and dr. G. Lauria (Carlo Besta, Milan) has led to new developments in understanding the pathogenetic basis of neuropathic pain. This resulted in several papers in high-impact journals. Furthermore, grants from the European Union 7th Framework Programme (grant n ) and from the Prinses Beatrix Spierfonds (W.OR12-01) were obtained. The PeriNomS study resulted in an international consensus meeting on outcome measures in peripheral neuropathies in Naarden, guided by the European Neuromuscular Centre (February 2013). Research line: The sense of hearing and balance: advanced diagnosis and substitution PI: Prof.dr. R J Stokroos; Prof. dr. H. Kingma Research Staff: dr. L. J. C Anteunis, dr. J Brokx, dr. E. George PhD-students: Drs. Diane Smit, Drs. Guido Dees, Drs.Darius Henatsch, Drs. Raymond van de Berg, Drs Niels Guinand, Drs. Joke Debruyne, Drs. Remo Arts, Drs. Jasper Smit, Drs. Mark van Hoof, Drs. Sanne Wagemakers, Drs. Janny Hof, Drs. Elke Devocht, Drs Simone Schaefer, Drs. Tim Calon. Co-investigators Prof Dr E Formisano (FPN) Prof dr Yasin Temel, Prof Dr Ph Gyot extern: (universite de Geneve), Prof Dan Jiang (Londen), Prof Dr Boris Kramer, Dr D Kunst (KU Nijmegen) Prof Dr K van Overbeeke. Focus of research: Translational research into the etiology of disorders of the senses of hearing and balance and the effect of neuromodulation with neuroprosthetic devices. 15 MH&NS Annual Report 2013

16 Hearing and balance problems are among the most prevalent health problems in our population. Our research efforts are divided in three subcategories: Tinnitus Basic research aims to unravel central nervous mechanisms causing tinnitus by using FMRI and animal models and the potential of neuromodulation using deep brain stimulation. This translates into clinical application wherein a specific neuromodulatory device, a tinnitus suppression implant has been applied. This has attracted a great number of patients for which a care system was put in place which is systematically evaluated and improved further. Valorisation of this tinnitus care system is important since the new Dutch care standards are currently based on it. Hearing Optimizing the diagnostics of hearing loss at a very young age has been systematically studied, aimed at improving both measuring instruments and at early detection and intervention. Special attention has been addressed to basic mechanisms causing hearing damage in premature infants. Bilateral deafness treatment by cochlear implantation has been institutionalized at MUMC+. Research efforts are focused on optimizing coding strategies, on improving electrode placement using advanced fusion imaging, and on optimizing electrical and acoustic (bimodal) hearing. Single sided deafness is treated using bone conductive hearing. Research efforts are focused on optimizing abutmentskin interaction and at clinical evaluation of the Soundbite device (hearing via the teeth). Sensorineural hearing loss is treated with hearing aids. Hearing aid provision has been studied from a cost effectiveness point of view. Balance Advanced diagnosis and treatment possibilities of vestibular disorders have attracted many patients to our MUMC+. New medical and surgical treatment strategies became available for balance disorders, for example using the round window membrane as a pathway to the inner ear. However, for an important proportion of these patients, neuromodulatory devices remain the sole treatment option. In collaboration with Geneva and industrial partners a vestibular implant has been developed which substitutes a defect vestibular system and is currently evaluated and developed further. 16 MH&NS Annual Report 2013

17 3.2 Division II: Mental Health Division Leader: Prof.dr. Inez Myin-Germeys Deputies: Dr. Marieke Wichers Dr. Ruud van Winkel Staff: Prof.dr. Therese van Amelsvoort Dr. Maarten Bak Prof. dr. Philippe Delespaul Dr. Rob van Diest Dr. Marjan Drukker Prof.dr. Eric Griez Dr. Ed Gronenschild Prof.dr. Peter van Harten Dr. Gunter Kenis Prof.dr. Andries Korebrits Dr. Tineke Lataster Dr. Ritsaert Lieverse Dr. Richel Lousberg Dr. Machteld Marcelis Dr. Nancy Nicolson Prof.dr. Jim van Os Dr. Frenk Peeters Dr. Jan Schieveld Dr. Koen Schruers Prof dr. Jean-Paul Selten Dr. Ruud Severijns Dr. Jacqueline Strik Dr. Wolfgang Viechtbauer Prof.dr. Marten de Vries Dr. Marieke Wichers Dr. Ruud van Winkel Dr. Franz Wojciechowski Goals & Results As outlined in the SEP protocol, division II Mental Health is focusing on gene-environment research in mental health and illness, within a translational context, bringing together human and animal components of gene-environment interaction research as well as translating these findings to the clinic. The ultimate goal is to identify interactive determinants of reactive phenotypes at the level of lived experience relevant to mental health and resilience. In 2013, we worked on the following goals: 1) In order to improve G*E studies searching for the causes of complex diseases such as severe mental disorders, increasingly large sample sizes are urgently required. The EU- GEI study with 28 European partners, funded by a large FP7 grant, is almost reaching the end. The last consortium meeting in Barcelona in November 2013 demonstrated that the study is going well, with all centres being actively involved in data collection. Secondly, a large general-population study has been set up together with the Trimbos Institute. The NEMESIS II study is collecting genetic data as well as data on mental health in 7000 participants from the general population. Division II was specifically involved in collecting data on psychosis. The second wave of this study has been finished in Third, the third wave of data-collection in the national (Amsterdam, Utrecht, Groningen, Maastricht) GROUP study has been set up. This study is following up 1000 patients with psychosis, 1000 relatives and 1000 parents and 500 controls over a period of 10 years. The third wave has been finished in December Finally, the large data-set of real-life ESM data combined with genetic information has been finalized. 2) Division II has been strongly investing in neuro-imaging approaches (PET, SPECT, MRI, MRS, or fmri) alone, in multimodal imaging studies, or in combination with ESM. Combining imaging data with real-time and real-world person-environment interaction patterns is extremely powerful, since it provides ecological validity for the neuroimaging data, correlating real life behaviour with alterations in specific brain regions, and vice-versa, improves the understanding the neural mechanisms associated with real-life behaviour. Division II has been setting up a large cross-diagnosis study focusing on underlying mechanisms of reward, stress and aberrant salience, studied with experimental fmri paradigms as well as real-life ESM assessment. This large SMARTSCAN project has been started in In a second study, funded by an ERC consolidator grant, the neural effects of a psychological real-life intervention will be assessed in a combined ESM PET approach. This INTERACT study has started in the beginning of A multimodal imaging study (SMURF) looking at the neurobiological basis of cognition in psychosis, funded by a VIDI, has started around the same time. 3) In 2013, the PsyMate app has been developed as an assessment strategy of environmental exposures in relation to lived experience (reactive phenotytpes), relevant for mental 17 MH&NS Annual Report 2013

18 health and resilience. The PsyMate App for IPod and Android is now operational in 2013 and a web application to provide web-based feedback has been developed. 4) Division II is continuously working to develop the PsyMate as a therapeutic tool for mental illness, such as depression and psychosis. The division has focused on network analyses to improve our understanding of the mechanisms underlying psychiatric illness and potentially as a tool for personalized medicine. We also are conducting a clinical trial investigating a new PsyMate Acceptance and Commitment therapy, which will be applied both in the SMARTSCAN and INTERACT study. 5) Translational studies bringing together basic animal research and patient studies remain a core research line within division II. The translational expert-group has initiated a number of studies, translating human findings to animal models and vice versa. 6) Division II is actively involved in forming international networks to accelerate psychiatry research. The EURON Psychiatry Institute has been formed to formalize the intensive collaboration between the University of Leuven (UPC Kortenberg) and Division II of Maastricht University. This formal collaboration will also strengthen the clinical neuroscience within EURON. Second, members of division II are active partners in the European ROAMER project, aiming to set up a European Roadmap to Mental Health Research. The methodological expert groups within the division focus on 1) genetics, 2) Experience Sampling, 3) Neuroimaging, 4) Experimental approaches, 5) Epidemiology and Mental Health Services Research, and 6) Translational approaches Division II Expert groups Expert-group: Genetics Coordinator: Dr. R. van Winkel Staff: Prof.dr. J. van Os, Dr. B. Rutten, Dr. G. Kenis, Dr. W. Viechtbauer, Dr. M. Drukker, Dr. M. Wichers Postdoc: Dr. C. Simons, Dr. D. Collip PhD students: Drs. C. Hamels, Drs. M. Van Nierop, Drs. J. Decoster, Drs. C. Lothmann Focus of research: The design of genetic studies in the field of psychiatry as well as investigating the role of genetic variances and gene-environment interactions in the etiology, severity and course of psychopathology The genetics expert group coordinates the design of genetic studies in the field of psychiatry as well as the choice of various genetic methodologies, choice of SNPs and genes of interest for the different research lines. Furthermore, it offers a platform for bringing together several disciplines in order to conduct adequately designed, multidisciplinary and translational research to establish the role of genetic variances and gene-environment interactions in the etiology, severity and course of psychopathology and dimensions of psychological and psychiatric traits. The main focus is currently on developing polygenic risk scores. 18 MH&NS Annual Report 2013

19 Expert-group: Experience Sampling Coordinator: Drs. J. Bakker Staff: Dr. M. Wichers, Prof.dr. I. Myin-Germeys, Dr. T. Lataster, Dr. N. Nicolson, Dr. W. Viechtbauer, Dr. N. Jacobs Post doc: Dr. C. Simons, Dr. D. Collip, Dr. J. Lataster PhD students: Drs. C. Lothmann, Drs. J. Decoster, Drs. C. van Zelst, Drs. F. Smeets, Drs. I. Kramer, Drs. J. Hartmann, Drs. M. Janssens, Drs. M. Gevonden, Drs. M. van Winkel, Drs. T. Batink, Drs. Z. Kasanova, Drs. T. Vaessen, Drs. Y. Van der Steen, Drs. A. Klippel, Drs. H. Steinhart Focus of research: To guard and increase the quality of ESM data collections and analyses, as well as to increase statistical expertise and analytic possibilities The aim of the EXM expert group is to guard and increase the quality of ESM data collections and analyses, to examine the validity of the method and the items used in ESM and report on this in international peer-reviewed journals, as well as to increase statistical expertise and analytic possibilities, such as time-series analysis in ESM. Expert-group: Coordinator: Staff: Post doc/ PhD students: Networks in psychopathology Dr. M. Wichers Dr. W. Viechtbauer, Dr. M. Drukker, Dr. N. Jacobs, Dr. C. Simons Dr. H. Wigman, Drs. A. Klippel, Drs, J. Bakker, Drs. I. Lange, Drs. S. Michielse, Drs. S. Peeters, Drs. Y. van der Steen, Drs. L. Hasmi, Drs. Z. Kasanova, Drs. J. Hartmann Focus of research: To build and extend knowledge and expertise in the area of network analyses, to use brainstorms for new creative ideas for applications of network analyses and to build bridges and share knowledge on network applications across ESM and imaging fields of research. Expert-group: Neuro-imaging Coordinator: Dr. M. Marcelis (psychiatrist) Staff: Dr. K. Schruers, Prof.dr. I. Myin-Germeys, Dr. E. Gronenschild, Prof.dr. J. van Os, Dr. L. Ritsaert, Dr. M. Wichers, Prof. dr. T van Amelsvoort Collaborators: Dr. A. Roebroeck, Dr. M. van Kroonenburgh, Dr. P. Hofman, Prof.dr. R. Goebel, Prof.dr. K. van Laere, Prof.dr. F. Mottaghy, Dr. J. Suckling, Dr. J Jansen, Prof. dr. J Booij, Dr. M Caan Post doc: Dr. D. Collip, Dr. L. Goossens PhD students: Drs. P. Domen, Drs. Z. Kasanova, Drs. S. Michielse, Drs. I. Lange, Drs. C. Vingerhoets, Drs. G. Bakker, Drs. C. van der Leeuw, Drs. S. Peeters, Drs. D. Hernaus, Drs. A. Frissen Focus of research: To combine expertise on various neuroimaging modalities (eg. smri, DTI, fmri, PET, SPECT, MRS) and analysing techniques to examine brain structure and function in psychiatric disorders The expert group Neuro-imaging is a group of researchers that are using various neuroimaging modalities (e.g. smri, DTI, fmri, SPECT, PET, MRS) and analysing techniques to examine brain structure and function in psychiatric disorders, such as psychotic and anxiety disorder. Our main goals are to examine i) neurobiological pathways influencing psychopathology, ii) genetic and environmental determinants of brain phenotypes, and iii) neural mechanisms underlying therapeutic interventions. 19 MH&NS Annual Report 2013

20 Expert-group: Epidemiology and mental health services research Coordinator: Dr. M. Drukker Staff: Dr. W. Viechtbauer, Prof.dr. J. van Os, Dr. R. Lousberg, Dr. M. Drukker, Dr. M. Bak, Prof. Dr. Ph. Delespaul, Drs. G. Driessen, PhD students: Dr. F. van Dael, F Smeets, C Lothman, T Mentzel, S. Michielse, I. Lange, Z. Kasanova Focus of research: To discuss the correct use of research methods (epidemiology) and meta-analyses as well as to work on data of patient registers and monitors. In addition, this expert group is in charge of the Psychiatric Case Register South Limburg and the medication monitor (in Dutch AP monitor). 20 MH&NS Annual Report 2013