ANNUAL REPORT 2009 / 2010

Transcription

1 MHeNS School for Mental Health and Neuroscience ANNUAL REPORT 2009 / 2010 School for Mental Health and Neuroscience Faculty of Health Medicine and Life Sciences

2 Content Preface Professor Dr. Harry Steinbusch 5 1. Future directions of MHeNS and EURON 7 2. Organisation structure Divisions Division I Research lines Division II Expert groups Division III Research lines Facts and Figures Earning Power Research Staff Output results Output results of the School Output Best publications PhD theses Div I PhD theses Div II PhD theses Div III Master and PhD Educational Activities Master Programme PhD Programme 60 Annexes: 1. Overview Education PhD Programme Current PhD theses Publications

3 Preface 4 harry steinbusch scientific director I am pleased to provide our Annual Report It presents an overview of the work and full information concerning the School for Mental Health and Neuroscience in the fields of research output, earning power, staff members and postdoctoral teaching activities in The School has grown further not only regarding the number of publications as requested by the Faculty of Health, Medicine and Life Sciences but also in the quality of the papers as indicated by an increase in the average impact factors. The increase in non-tenured staff members has resulted in a steady increase in the number of PhD theses from 22 in 2009 to 30 in Our School now hosts about 170 PhD students. The guidance of these students is a significant challenge that requires an enormous and coordinated effort of staff members. In accordance with the performance contract with the Faculty of Health, Medicine and Life Sciences we have focused on establishing more funding from NWO (Dutch Medical Research Council) and FP7- 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. We are pleased to note that in this period several young investigators were successful in obtaining Mosaic, VENI or VIDI grants, such as those awarded to Drs. Temel, Rutten, Janssen and Germeys. Consequently, we can state that during this period we fully achieved all the goals of our performance contract. Another important event during this period was the application for re-accreditation of EURON and, thereby, implicated that of the School of Mental Health and Neuroscience. An evaluation of the External Research Committees (ERC) was carried in September 2009 when the committee visited the campus. In addition to the Research Director and the Division Leaders evaluated previously by the ERC, some Project Leaders, supported by competitive peer-reviewed financing, postdocs, Ph.D. students and the educational platform, were evaluated. All research groups were assessed as deserving continuous support. During this evaluation process, we received very valuable feedback regarding our strengths and weaknesses. These comments were used for our return visit at the ECOS (Evaluation Commission Research Schools) commission February 2010 at the Royal Dutch Academy of Arts and Sciences in Amsterdam. We were pleased that after the external research committee forwarded their positive comments to the ECOS commission, the KNAW decided by July 15th, 2010 to award us the official re-accreditation for another 6 years, In 2009, a discussion was started concerning the appropriate size for an Institute. In accord with its merits, MHeNS has been regarded as sufficiently large to act as an independent School within the university. Nonetheless, we would like to note that although we are one of the smaller Schools within the Faculty of Health, Medicine and Life Sciences, we still produce the largest number of high impact papers, Ph.D-students and a well-organized Master program. However, it is worth noting that neuroscience research is still quite fragmented in the capital area. This speaks to the need for closer cooperation among the different units. To this end, we have reorganized our clinical groups and divisions, although we will still have three divisions. Thus, one division will be clearly focused on Cognitive Neuropsychiatry and Clinical Neuroscience, one division will be on Environmental Psychiatry and the third one will focus on Fundamental and Systems Neuroscience. In with this, educational activities of the Master s programs corresponds to these subdivisions. The strength of MHeNS is in its translational approach. For example, division 1 concerns neuroepidemiology and brain imaging, division 2 focuses on gene-environmental changes/interactions related to psychiatric disturbances such as psychoses, and division 3 5

4 6 uses animal and cellular models related to systems-level research. These lines of research at MHeNS will continue to find much synergy within collaborative projects and research networks. The proportion of foreigners on staff has been steadily increasing from the inception of MHeNS in 2002, attaining approximately 26% for researchers in The Research Master Degree Program in Neuroscience EMN (The European Master in Neuroscience) was initiated (in early 2009) by EURON in cooperation with our partners. The first round of the teaching program will be implemented in September 2013 and the first student should graduate from the program in the middle of All research groups of our EURON partners will participate in teaching in EMN so that all major research areas of the Fundamental and Systems Neuroscience program will be covered. In this master we will bring together the best expertise available from all participating eleven universities, so that an excellent and stimulating program can be offered to the new students. In conclusion, I would like to thank all members of MHeNS 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. Harry W.M. Steinbusch Scientific Director School for Mental Health and Neuroscience chapter 1 Future directions of MHeNS and EURON

5 Future directions of MHeNS and EURON 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. This will be achieved by sharing expertise and knowledge among all EURON partners and by stimulating mobility of Master and PhD students. In addition, we will strive for uniformity or comparability of standards for PhD degrees among the three participating countries, i.e., the Netherlands, Belgium and Germany. Indisputably, the training of young competent PhD s in the Neurosciences 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. The mission of the School for Mental Health and Neuroscience European Graduate School of Neuroscience (EURON) at Maastricht University and the European Graduate As mentioned above EURON has been re-accredited by the School for Neuroscience, EURON, at the Euregional level is Royal Dutch Academy of Arts and Sciences (KNAW) from threefold: 2010 to The external review committee (ERC) has 1. focusing on a basic understanding of brain function made some clear observations concerning MHeNS in relation and disease mechanisms, to EURON. The report of the ERC identifies MHeNS as 2. understanding the function of genes and proteins, cellular the prime coordinator of EURON and states that MHeNS is processes and neuronal networks in relation to in a favourable position to continue to develop as a centre human health, of excellence in Europe. The shared expertise, knowledge 3. establishing reciprocal translational links between lab and infrastructure of EURON will facilitate this goal. The and clinic. ERC emphasizes that current leadership of MHeNS has 8 developed an excellent research training program, mak- 9 ing optimal use of the geographical Euregional location and opportunities for EU funded programs. The committee stated that the PhD program and the supervision is very good and of importance for PhD students on many levels, e.g., sharing expertise, knowledge transfer, mobility opportunities and opportunities for learning new techniques. In addition, EURON aims to produce uniform PhD degrees of the highest quality and to execute the Bologna process. The translational research focus of MHeNS to perform high impact translational neuroscience research fits very well with the mission of EURON to address research topics in a multidisciplinary approach. Strategic Goals for the School for Mental Health and Neuroscience at Maastricht University The School will be facing in the immediate forthcoming period some important changes. However, we believe change will also create opportunities. The first opportunity is related to the establishment of the Maastricht University Medical Center (MUMC) and the fact that the MUMC has decided to stimulate and invest an amount of H 2 million for the expansion of the research capacity of MHeNS. The School

6 has added to this from their own resources an additional H 0.5 million, which brings the total investment to H 2.5 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, nontenured while what is really needed is tenure-track positions to support and recruit excellent career-oriented staff members from within or beyond. Recently, an analysis of the five Schools by the MUMC Governing Board was conducted. As a result, it was decided that the criteria for carrying the certificate of Centre of Excellence include that a School should have sufficient critical mass to guarantee sufficient PhD-output and demonstrate the ability of staff to obtain VENI, VIDI and VICI, comparison with the other UMCs in the Netherlands, and 2) the wish that patients in both the short and long term should benefit from research. MHeNS also recognizes the need for a translational approach. Theme 1: Gene-Environmental Changes in Psychiatric Diseases In this research line participating groups are identifying A specific point deserving of attention is our partnership interactions between genes and environment, neuroimaging with the Faculty of Psychology and Neuroscience (FPN). In (i.e., identifying cerebral phenotypes for the study of our School within Division 1, the Department of Psychopharmacology, ecogenetics) and experimental psychology and psychopready (FPN) headed by Prof. Dr. J. Ramaekers alharmacology (i.e., identifying experimental psychological Thus, to summarize, the focus of MHeNS will be on various participates. In addition, there is a strong link with and psychopharmacological phenotypes for the study of levels: educational activities at the level of the Research Master ecogenetics). This will facilitate the early recognition and 1. Research: three divisions work on, two translational research Program Cognitive and Clinical Neuroscience in which the treatment of psychiatric disorders, in particular psychosis themes, bridging the boundaries between the School is involved in 3 of the 4 tracks. It should be noted and depression, leading ultimately to mental health services three divisions, 10 awards as well as grants from major organizations such as that the FHML is the principal coordinator of two tracks of research. 2. Education: further expanding and strengthening Re- 11 the Netherlands Foundation for Scientific Research (NWO). An analysis by the Board has revealed that MHeNS meets all these criteria. Another consideration regarding Strategic Goals for the next 4 years is the implementation of a ZKO, a Care Clinical Research Unit, headed by Prof. Dr. J. van Os. The MUMC is a fusion of the FHML with the Academic Hospital Maastricht which took place in This new ZKO Mental Health and Neuroscience initiative that started in 2009 will deal with all aspects of mental health related issues related to research, patient care and education in the Academic Hospital Maastricht. The ZKO is not formally integrated into the School but the two entities partly overlap with each other. 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 MHeNS is a fully integrated partner in EURON. However, EURON comprises nine other universities in the Euregio as well. MHeNS has been taking the lead in all organizational aspects. Currently only divisions 2 and 3 of MHeNS are participating within EURON. It should be expanded to other research areas. Because it already provides an excellent opportunity for networking, further Euregional activities and introducing an international or European Master in Experimental and Clinical Neuroscience have great potential, which we will incorporate in the next period. 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 could be a basis for a further growth towards a Neuroscience Campus Maastricht (NCM). The foundation of our future plans is that the research within MHeNS is divided into the three reorganized divisions. The choice for three divisions is based upon methods-related 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. However, all these three divisions will have a major focuses towards two translational themes: 1: Gene-Environmental Changes in Psychiatric Diseases and 2: Neurodegeneration and Plasticity as outlined below. This way, critical mass will be created and the research will acquire additional prominence within the MUMC. The specific focus on translational themes is in line with 1) the wish of MUMC to have a specific translational research focus in Theme 2: Neurodegeneration and Plasticity In this research line there is a direct link between clinical applied human research towards mechanistic approaches using transgenic mouse and rat models for neurodegeneration. Thus, participating fields within this translational line include quantitative neuromorphology, molecular neurobiology, behavioural neuroscience, neuroimmunology, neuroimaging and psychopharmacology. These involve clinical services for adult neurodegenerative disorders and developmental cognitive disorders, both from the point of view of early detection and intervention and from the point of view of health services research. In addition a large number of molecular neurobiological questions can be addressed. To summarize, MHeNS clearly wants to move forward and establish further its Center of Excellence level. To achieve this status we first need a critical mass. To a certain extent this is beyond our control and, therefore, should be encouraged/facilitated by the MUMC in the form of concrete rewards (financial support) as successive, specified goals are achieved. 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. However, to increase critical mass at the tenure-track level we need full cooperation and support by the MUMC and UM. We intend to garner international recognition of each of the two research lines, showing this consistently on a translational level. In this way we clearly will distinguish ourselves within the national competition. We are now ready for the next step. It is our hope that all members of MHeNS can join together on this in the time to come. search Master, Ph.D. and postdoctoral activities, 3. Collaboration: further exploring the possibilities for a two faculty based Neuroscience Campus Maastricht.

7 12 chapter 2 Organisation structure

8 Organisation structure MHeNS is managed by the Board of MHeNS. The board is the body where strategis 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. Martin Paul Managing Director Laurent Louwies Scientific Director Prof. Dr. Harry Steinbusch Cognitive Neuropsychiatry and Mental Health Neuroscience Clinical Neuroscience Prof.Dr. Frans Verhey Deputies Dr. Martin van Boxtel Dr. Caroline van Heugten FHML Psychiatry & Neuropsychology (section Neuropsychology) Prof.Dr. Inez Myin-Germeys Deputy Dr. Koen Schruers Psychiatry & Neuropsychology (section Psychiatry) Prof.Dr. Marc de Baets Deputies Prof.Dr. Martin van Kleef Dr. Yasin Temel Core departments: Psychiatry & Neuropsychology (section Neuroscience) * Restructuring of the divisions in Movement Sciences (2009)* General Practice Radiology Othorhinolaryngology (2010)* Neurology (2010)* FPN Neuropsychology & Psychopharmacology Clinical Neuropsychology (2010)* Neurosurgery Anesthesiology Urology Othorhinolaryngology (2009)* Ophthalmology Neurology (2009)* Non core departments: Clinical Neuropsychology (2009)* Pediatrics Internal medicine Figure 2.1 Organogram of MHeNS: the contribution of the different Departments of FHML to the current three Divisions of MHeNS.

9 Members of EURON MHeNS is the coordinator of the European Graduate School of Neuroscience [EURON]. EURON is a research and training network of 10 universities in the three countries Belgium, Germany and the Netherlands. 16 EURON MHeNS 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 The Netherlands Maastricht University (MHeNS) Radboud Universiteit Nijmegen (2009)* Figure 2.2 EURON in relation to MHeNS. * RU Nijmegen has withdrawn partnership in EURON since Dec chapter 3 Divisions

10 Divisions Goals & Results Division I: Cognitive Neuropsychiatry & Clinical Neuroscience Division Leader: Prof. Dr. Frans Verhey Deputies: Dr. Martin van Boxtel Dr. Carolien van Heugten Dr. Paulien Aalten Dr. Jos Adam Dr. Marjan van den Akker Prof. Dr. Bert Aldenkamp Dr. Lucien Anteunis Dr. Walter Backes Prof. Dr. Jan Willen Cohen Ter Vaart Dr. Jeanette Dijkstra Dr. Annelien Duits Dr. Carin Faber Dr. Ellen Gerrits Dr. Ed. Gronenschild Prof. Dr. Fred Hendrikse Dr. Paul Hofman Prof. Dr. Raymond Hupperts Dr. Vivian Kranen van Mastenbroek Prof. Dr. Herman Kingma Prof. Dr. Bernd Kremer Dr. Marc de Krom Dr. Abraham Kroon Dr. Albert Leentjens Prof. Dr. Peter de Leeuw Prof. Dr. Werner Mess Prof. Dr. Job Metsemakers Dr. Robert van Oostenbrugge Dr. Rudolf Ponds Dr. Sascha Rasquin Prof. Dr. Harry Uylings Dr. Wim van der Elst Dr. Pieter - Jelle Visser Prof. Dr. Hans Vles Dr. Marjolein de Vugt Dr. Wim E.J. Weber Prof. Dr. Joachim Wildberger 18 Dr. Claire Wolfs 19 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 in order to improve treatment and care for people with cognitive disorders, and other neurological disorders. Since 2009, clinical neuroscience researchers have been assigned to the Division 1 and the new name became Cognitive Neuropsychiatry & Clinical Neuroscience (CNP-&CNS), covering the translational nature of the Division 1 research program. With respect to the medical conditions, the focus is upon neurodegeneration in relation to neurodegenerative diseases of the central nervous system, such as Alzheimer s disease and its prodromal phases, Parkinson s disease, peripheral nervous system disease such as small fiber neuropathy, acquired brain damage such as stroke, traumatic brain injuries, and epilepsy. The general goal of the division is to develop new insights into the neurocognitive and neuro-behavioral mechanisms in order to improve treatment and care for people with such conditions. We investigate the contribution of biological, neuropsychological and psychosocial factors, single and in combination, and the effect of ageing on the development of normal neurocognition and mild to severe cognitive dysfunction. Research in Division 1 is conducted in a multi-disciplinary way, with contributions of researchers from neuropsychology, cognitive neuroscience, neuropsychiatry, clinical neurology, neuroradiology and neuro-epidemiology. In we continued to investigate normal, successful and pathological ageing, but with a greater emphasis on the translational focus. Programs and projects in the domains of neuroimaging and biomarkers were expanded by further adoption of HTA (Health Technology Assessment) approaches. The allocation of the clinical neuroscience researchers and radiologists in the division has strengthened the neuro approach of the division, enabling a strong research program in which cognitive and clinical neurosciences are integrated.

11 3.1.1 Divisie I Research lines, staff Research-Line: P.I.: Neurodegenerative disorders: mechanisms, early diagnosis and biomarkers Prof. Dr. F. Verhey, Dr. P-J Visser, Dr. P. Aalten, Dr. R. van Oostenbrugge, Dr. A. Leentjens, Dr. M. van Boxtel, Research-Line: P.I.: Neuropsychological interventions and cognitive rehabilitation Dr. C. van Heugten, Dr. M. de Vugt, Dr. R. Ponds, Dr. M. van Boxtel, Prof. Dr. F. Verhey PhD students: Drs. A. Colon, Drs. F. van Dooren, Post doc/ Drs. K. Beerhorst, Drs. R. Besseling, Dr. A. Duits Drs. O. Schiepers, Drs. P. Spauwen, PhD students: Drs. I. Brands, Drs. M. van Eeden, Drs. R. Binie, Drs. H. Braakman, PhD students: Drs. S. Aarts, Drs. L. Clerx, Drs. W. van Zwam Drs. M. Fens, Drs. E. de Joode, Drs. M. Hermans, Drs. S. van der Kruijs, drs. B. Dandachi-Fitzgerald, Focus of research: Insight into the prevention, etiology Drs. B. ter Mors, Drs. V. Moulaert, Drs. S. Stappenberg -Klinkenberg, Drs. R. Drijgers. Drs. L. Elias, and treatment of type 2 diabetes and Drs. S. Smeets, Drs. N. Tielemans, Drs. E. Vanhoutte, Drs. M. Vaessen, Drs. R. Handels, Drs. M. Huijts, other chronic diseases and mental Drs. D. van Vliet, Drs. L. Willemstein, Drs. M. Vlooswijk Drs. H. Jacobs, Drs. M. Legra, health Drs. G. Wolters, Focus of research: Chronic epilepsy 20 Drs. N. Vermunt, Drs. S. Vos Focus of research: Cognitive rehabilitation and health 21 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). 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 Department 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. Two Kootstra fellowships were obtained (Koehler, Burgmans). Research-Line: P.I.: Determinants of normal, successful and pathological cognitive ageing Dr. M. van Boxtel, Prof. Dr. F. Verhey, Dr. R. van Oostenbrugge, Dr. P. Hofman, Dr. W. Backes, Dr. T. van Berenschot Division staff members supported the initiation of the Maastricht Study (MS), a study to provide more insight into the prevention, etiology and treatment of type 2 diabetes and other chronic diseases and mental health. The MS is a good example of the integrative approach we are aiming at, with input from the departments of Psychiatry & Psychology, Neurology, Neuroradiology, and Neuro-ophtalmology). The central theme of the input from our division is the relation between cognitive function and (silent) cerebrovascular disease in type 2 diabetes, and the application of novel brain imaging methods for the early detection of cognitive dysfunction as well as cerebrovascular disease. A NWO/FES program (0,9Me) was obtained to develop internet-based low-level intervention strategies to support the development of the cognitive ageing process in middle-aged and older adults. service evaluation research. Interventions in cognitive and acquired brain disorders. A stronger focus was 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. Two large grants were received for research in this area. One was received from VSB fonds/zonmw for a research programme on successful psychosocial reintegration of patients and caregivers after stroke. In this programme 4 PhD students (Maastricht, Nijmegen and Utrecht) will investigate the course and predictors of psychosocial functioning, costs of psychosocial care and effectiveness of two new psychosocial interventions for patients and caregivers. The second grant is a NOW/FES Brain & Cognition grant. In this programme the effectiveness of cognitive rehabilitation and factors influencing the success of cognitive rehabilitation will be examined. Research-Line: P.I.: Post doc/ PhD students: Epilepsy/ neuropathy and myotonic dystrophy Prof. Dr. B. Aldenkamp, Dr. M. de Krom, Prof. Dr. H. Vles, Dr. C. Faber The central theme within the research topic Epilepsy is Chronic Epilepsy. This topic is studied in a translational design by means of animal studies, genetic studies (drug resistance), and studies in humans focussed on the impact on cognitive function in chronic epilepsy including brain imaging studies into the early detection of cognitive deterioration. A substantial grant from the National Epilepsy Fund (NEF) was obtained for this programme (led by Prof. Dr. B. Aldenkamp). Research into neuromuscular disorders (led by Dr. C. Faber) targets myotonic dystrophy and neuropathy, with a focus on small fibre neuropathy. In 2010, a formal international cooperation within this later field was established with Prof S. Waxman (Yale University). Furthermore, a PhD funded by the GBS CIDP Foundation International and a grant from a Baxter PNS Fellowship started a study on clinimetric aspects (outcome measures) in Small Fibre Neuropathy (SFN) within a large multi-dimensional international multi-centre collaboration project, captured under the umbrella PeriNomS Inflammatory Peripheral Neuropathy Outcome Measures Standardisation PeriNomS study, small fibre neuropathy (SFN) PeriNomS study). Furthermore, additional funding was obtained from the Talecris Talents programme.

12 3.2 Division II: Mental Health Division Leader: Prof. Dr. Inez Myin-Germeys Deputy: Dr. Koen Schruers Dr. Maarten Bak Dr. Philippe Delespaul Dr. Rob van Diest Dr. Marjan Drukker Prof. Dr. Eric Griez Dr. Ed Goenenschild Prof. Dr. Peter van Harten Dr. Gunter Kenis Prof. Dr. Andries Korebrits Dr. Tineke Lataster Dr. Richel Lousberg Dr. Machteld Marcelis Dr. Nancy Nicolson Prof. Dr. Jim van Os Dr. Frenk Peeters Dr. Bart Rutten Dr. Jan Schieveld 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 2) A second approach to improve G*E studies, is to improve focusing on gene-environment research in mental health the assessment strategy of environmental exposures in and illness, within a translational context, bringing together relation to live experience (reactive phenotytpes), relevant 22 human and animal components of gene-environment for mental health and resilience. In 2009, workers in divi- 23 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 2009 and 2010, we worked on the following goals: 1) In order to improve Gene-Environment (G*E) studies searching for the causes of complex diseases such as severe mental disorders, increasingly large sample sizes are urgently required. In 2009, Prof. van Os formed a European Consortium, funded by a large FP7 grant, bringing together 28 European partners to study the influence of G*E in the onset of the prodrome and the first episode of psychosis, the prevalence of psychosis as well as its course over time. The management team of this consortium is situated within Division II, as is the leader of workpackage 7, and collaborators within workpackage 2, 4 and 5. The first data are currently being collected by the 28 partners involved. A large effort has been made to pool together previously collected ESM data, resulting in a large data-set of real-life reactivity data which combined with genetic information offers a unique opportunity for G*E analyses. sion II developed a digital apparatus, the PsyMate, which allows investigating direct person-environment interactions in the realm of daily life lived experience. The software of this apparatus was patented, and it will be further developed for use within the FP7 European G*E study. Currently, the PsyMate is being used in studies of both psychosis and depression. Second, Division II has invested in the development of experimental tasks as tools to study how responses to experimental exposures are moderated by genotype. An experimental task assessing social defeat has been developed. 3) Different biological phenotypes as outcome variables of G*E studies have been identified using MRI, PET, and cortisol paradigms. 4) Complex designs using multimarker analyses require extensive statistical knowledge. Division 2 has invested in the further development of statistical approaches. A statistician has been appointed and close contacts with groups across Europe, Asia and the US have been further developed.

13 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. Bart Rutten obtained a VENIgrant to investigate resilience to trauma within a translational context, underscoring the national appreciation of this approach. 6) Finally, the PsyMate is in the process of being tested, in Zon-MW supported trials, in depression and psychosis for therapeutic effects, using feedback derived from information in the reality of daily life. Expert-group: Genetics Coordinator: Dr. R. van Winkel P.I.: Prof. Dr. J. van Os, Dr. B. Rutten, Dr. G. Kenis, Dr. W. Vichtbauer, Dr. M. Drukker, Dr. M. Wichers, Dr. C. Simons PhD students: Drs. D. Collip, Drs. C. Vangeneugten, Drs. M. Van Nierop, Drs. J. Decoster, Drs. N. Geschwind, 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 psycho- The management structure of Division II changed in In april 2009, Dr. Inez Myin-Germeys become the Division 24 leader of Division II. In addition, methodological expert pathology Drs. M. Gevonden, Drs. M. van Winkel, Drs. D. Hernaus 25 groups have been formed, enabling the joining of forces within the division, as well as providing excellent opportunities for training of junior team members. Expert groups on 1) Genetics, 2) Experience sampling, 3) Neuroimaging, 4) Experimental approaches, 5) Epidemiology and Mental Health Services Research, and 6) Translational approaches have been formed. Furthermore, division II welcomed two new full professors. Peter van Harten has become Professor of Movement Disorders in Psychosis. Inez Myin-Germeys has become Professor of Ecological Psychiatry Expert groups 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, multi-disciplinary 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. Expert-group: Coordinator: P.I.: Post doc/ PhD students: Experience Sampling Dr. M. Wichers Prof. Dr. I. Myin-Germeys, Dr. T. Lataster, Dr. R. van Winkel, Dr. Ph. Delespaul, Dr. N. Nicolson, Dr. W. Viechtbauer, Dr. N. Jacobs Dr. C. Simons, Drs. T. Driesen, Drs. M. Oorschot, Drs. N. Geschwind, Drs. D. Collip, Drs. R. Kuepper, Drs. J. Lataster, Drs. C. Lothmann, Drs. J. Decoster, Drs. C. van Zelst, Drs. F. Smeets, Drs. I. Kramer, Drs. J. Hartmann, Drs. M. Janssens, Drs. T. Batink. 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 expertgroup 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: P.I.: Collaborators: Post doc/ PhD students: Neuro-imaging Dr. M. Marcelis (psychiatrist) Dr. K. Schruers, Prof. Dr. I. Myin-Germeys, Dr. E. Gronenschild, Prof. Dr. J. van Os, Prof. Dr. E. Griez Dr. A. Roebroeck, Dr. V. van de, Dr. M. van Kroonenburgh, Prof. Dr. R. Goebel, Prof. Dr. K. van Laere, Prof. Dr. F. Mottaghy Drs. P. Habets, Drs. P. Domen, Drs. S. Peeters, Dr. L. Goossens, Drs. D. Collip, Drs. J. Lataster, Drs. R. Kuepper, Drs. N. Leibold, Focus of research: To combine expertise on various neuroimaging modalities (eg. smri, DTI, fmri, PET, 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, 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) genetic and environmental determinants of brain structure and function in these disorders, ii) neurobiological pathways influencing psychopathology and, iii) neurobiological effects of various therapeutic interventions.

14 Expert-group: Coordinator: P.I.: Post doc/ PhD students: Experimental Psychopathology Dr. T. Lataster Dr. K. Schruers, Prof. Dr. E. Griez Dr. C. Simons, Dr. L. Goossens, Drs. F. Smeets, Drs. M. Janssens, Drs. A. Shazad, Drs. K. de Cort, Drs. I. Knuts, Drs. D. Collip, Drs. J. Lataster Focus of research: To design novel experimental tasks assessing underlying (neuro)psychological and biological mechanisms that are implicated in the development, course and outcome of psychiatric disorders. Expert-group: Coordinator: P.I.: Post doc/ PhD students: Epidemiology and mental health services research Dr. M. Drukker* Dr. M. Bak, Dr. Ph. Delespaul*, Dr. W. Viechtbauer*, Prof. Dr. J. van Os, Drs. G. Driessen Drs. M. Heins, Drs. E. Deloore, Drs. C. Lothman*, Drs. I. Pipeleers, Drs. F. Smeets*, Drs. M. Oorschot, Dr. N. Gunther, Dr. G. Guilera Focus of research: To discuss the correct use of research methods (epidemiology) and metaanalyses as well as to work on data of patient registers and monitors. This expert group provides support to those researchers 26 designing novel experimental tasks assessing underlying *Active in meta-analysis subgroup approach. (neuro)psychological and biological mechanisms that are 27 implicated in the development, course and outcome of This expert group aims to analyse and develop in correct psychiatric disorders. The focus is on psychotic and affective use of research methods (epidemiology) and meta-analy- disorders. Our goal is to combine these experimental ses. Furthermore, this expert group works on the data of designs with the observational methods (for example the one register (Psychiatric Case Register) and two monitors Experience Sampling Method) that have been developed (Cumulative Needs for Care Monitor and Medication Monitor), within our department in order to improve validity of our as well as on data of healthy children, collected by the studies. youth health care division (YHCD) of the Public Health Service South-Limburg and the Infant Welfare Centre register. Expert-group: Coordinator: P.I.: Post doc/ PhD students: Translational and Cross-species Research Dr. B. Rutten Dr. G. Kenis, Dr. D. van den Hove, Prof. Dr. H. Steinbusch, Prof. Dr. J. van Os, Prof. Dr. K-P. Lesch, Prof. Dr. F. Verhey, Dr. K. Schruers, Dr. P-J. Visser Dr. B.e Machiels, Drs. E. Lambrichts, Drs. O. Peerbooms, Drs. L. Chouliaras, Drs. N. Leibold, Drs. S. Mafi Rad, Drs. C. Hammels, Drs. E. Pischva Focus of research: To support and stimulate innovative projects on translational research questions that require a cross-species The mission of this expert group / team is to support and stimulate innovative projects on translational research questions that require a cross-species approach. The research of its members aims to decipher molecular and cellular pathways that underlie sensitivity and resilience to environmental exposures, and gene-environment interactions in (neuro)psychiatric phenotypes. The ultimate goal is to identify molecular and cellular pathways that are causally involved in the etiologies of psychiatric disorders, to identify biologic markers that predict disease onset and course, to establish the reversibility of neurobiological changes, and to find novel preventive and therapeutic strategies.

15 3.3 Division III: Neuroscience Division Leader: Prof. Dr. Marc De Baets Deputies: Prof. Dr. Maarten van Kleef Dr. Yasin Temel Dr. Ronald Deumens Dr. Daniel van den Hove Dr. Danilo Gavilanes Dr. Govert Hoogland Dr. Bert Joosten Prof. Dr. Philip van Kerrebroeck Dr. Gommert van Koeveringe Dr. Boris Kramer Dr. Ellen La Heij Dr. Fred van Leeuwen Dr. Mario Losen Dr. Marco Marcus Dr. Piluca Martinez Prof. Dr. Koo van Overbeeke Dr. Jos Prickaerts Prof. Dr. Harry Steinbusch Prof. Dr. Veerle Visser-Vandewalle Prof. Dr. Hans Vles Dr. Lim Lee Wei Goals & Results The Division Neuroscience performs translational research with a strong emphasis on fundamental research. The translational research area can be subdivided into two parts: neurodegeneration and neuroplasticity. The results of the research efforts in division 3 are described by the different Principal investigators and expertise groups. 28 Its mission is to uncover the underlying mechanisms of 29 neurodegenerative and regenerative processes for neurological and psychiatric diseases to improve early diagnosis, health and treatment strategies. Thus, we aim to gain knowledge of physiological and pathophysiological mechanisms underlying affective, cognitive and motor disorders. Within this context, the role of neuroinflammation and pain is also studied as well as their link to developmental disturbances and neuro-urogenital control. Main research topics include cell signalling, brain plasticity, neurodegeneration, regeneration,genetics and epigenetics. Eventually, its aim is to translate relevant scientific findings into new neurotherapies including pharmacotherapy, antibodies or deep brain stimulation. The multidisciplinary staff consists of professionals from relevant disciplines within research and clinic. There are collaborations within world-wide international networks of research offering a strong environment to come up with new neurotherapeutical approaches.

16 3.3.1 Division III Signal Translation / Neuroplasticity Environment Epigenetics Signal Transduction Experimental Neurosurgery Pain: Transition from acute to chronic pain Modulation of chronic pain Urology 30 Neuroinflammation inflammation Translational neuro- nal transduction in affective processes/disorders, we have base tumours neuraxis, and are considered to be fundamental to the 31 Central Nervous System neuroinflammation Neonatology Epilepsy Alzheimer disease Research lines, staff Research lines: Signal Transduction P.I.: Dr. J. Prickaerts, Dr. Y. Temel, Prof. Dr. H. Steinbusch Post doc: Dr. T. Vanmierlo, Dr. M. van Duinen PhD students: Drs. O. Reneerkens, Drs. E. Bollen, Drs. A Sierksma, Drs. J. De Vry Focus of research: Cellular signal transduction in affective and cognitive processes in health and disease. The major aim is to unravel the mechanism of action of signaling pathways both in health and disease while at the same time exploring the therapeutic potential of key factors in the affected signaling pathway. With respect to sig- discovered that the mechanism of acute tryptophan depletion, which is a tool to challenge the serotonergic system in humans and animals to detect whether it is vulnerable to stress, is very likely not related to serotonin at all (Van Donkelaar et al., 2011). In the field of signal transduction in cognitive processes/disorders it has been shown that phosphodiesterase inhibitors improve memory in rats independently of cerebrovascular effects (Rutten et al., 2009). This is of major importance since this indicates that the second messengers camp and cgmp, which are normally degraded by phosphodiesterases, can be targets for new drugs to improve memory function directly. Recently, a proof of principle study funded by an obtained grant from ZonMW has started investigating the memory improving potential of a specific phosphodiesterase inhibitor in age-related cognitive impaired subjects. Finally, we have succeeded in setting up our unique method of microelectroporation as a non-viral approach for targeted gene delivery in specific brain areas of rodents (De Vry et al., 2010). This approach will be used in future experiments to directly influence the expression of genes implicated in signal transduction in either affective or cognitive processes. For this we received a grant from the Internationale Stichting Alzheimer Onderzoek (ISAO). The results of these studies will help us to find new therapeutic targets for affective and cognitive disorders. Research line: Experimental Neurosurgery P.I.: Dr. Y. Temel, Dr. G. Hoogland, Prof. Dr. V. Visser-Vandewalle and Prof. Dr. H.Steinbusch Post doc: Dr. LW. Lim PhD students: Drs. A. Jahanshahi, Drs. S. Hescham, Drs. M. Janssen, Drs. S. Tan, Drs. H. Vlamings,, Drs. Y. Yakkioui, Drs. D. Zeef Focus of research: Movement disorders and related psychiatric symptoms, biology of skull Our group is continuing to perform both clinical and experimental studies. In this respect, we have conducted studies to improve the surgical therapy for Parkinson s disease patients, by developing novel evaluation methods (saccadometry). In our experimental studies, we mainly focused on developing novel therapies in experimental models of Parkinson s disease (tailored neurostimulation) and Huntington s disease (neurostimulation and gene therapy). These lines of research are supported by grants from the NWO-Veni, Cure Huntington s Disease Intitiative (CHDI, New York, USA), and Hersenstichting Nederland. Research-Line: Transition from acute to chronic pain P.I.: Dr. B. Joosten, Dr. R. Deumens PhD students: Drs. S. van Gorp, Drs. R. Jaken, Drs. S. van Neerven, Drs. L. Knaepen, Drs. M. Theunissen Focus of research: Identification of predictors of chronic pain and investigating approaches aimed at prevention of chronic pain Chronic pain is associated with an enormous socio-economic burden and can result from a plethora of clinical conditions. In our research, we focus primarily on traumainduced neuropathies in the peripheral and/or central nervous system, which are a common cause of chronic pain. The initial pathological events at the site of nerve damage form the drive of pathological events higher up in the establishment of chronic of pain. We aim at understanding the processes of neurodegeneration and regeneration in relation to neuropathic pain. In a recently completed Ph.D. project we found that injury to peripheral nerves induces structural plasticity in the wiring of the spinal nociceptive network, a phenomenon which is likely long-lasting. In a collaboration with UMC Utrecht, we reported on immune-related molecular requirements for chronic pain in animal models of peripheral tissue inflammation and peripheral neuropathy. In two ongoing Ph.D. projects we are investigating predictors of neuropathic pain after spinal cord injury. As a strategy to prevent pain chronification after nerve injury, we aim to provide (1) repair of nerve injuries / damage, (2) immuno-modulatory therapies (Prof. Dr. M. De Baets, Dr. M. Losen, Dr. P. Martinez) and (3) functional training paradigms (e.g. enriched environment). Moreover, we are interested in understanding the pathological events by which pain-related insults during the neonatal period can have long-lasting effects on pain in adulthood (Dr. J. Pawluski, Prof. Dr. H. Steinbusch).

17 Research-Line: Modulation of chronic pain P.I.: Dr. B. Joosten Post doc: Dr. S. Janssen PhD students: Drs. M. Truin, Drs. H. Smits, Drs. W. Pluijms, Drs. K. van Boxem, Drs. R. Slangen Focus of research: The understanding and application of neuromodulatory techniques, in particular spinal cord stimulation and pulsed radiofrequency, in order to minimize chronic (neuropathic) pain. Pain Syndrome) and the other one in patients with Failed Back Surgery Syndrome (FBSS), both of which provide limited clinical evidence that SCS relieves neuropathic pain. We extend implementation of SCS in other NPP syndromes and designed and completed a pilot study on the clinical effect of SCS in painful diabetic polyneuropathy (PDP). As a follow-up, an RCT (Rachelle Slangen) on the effect of SCS in PDP is currently ongoing. In order to understand the underlying mechanism of action of SCS in PDP a rat model for PDP was developed in the laboratory and the effect of various stimulation parameters was analyzed. It is our intention to study the role of SCS in small fiber neuropathies experimentally as well as clinically in collaboration with Dr. C. Faber (Department of Neurology). From a basic scientific point of view the role of glial cells (as immune-regulatory cells) in the modulation of chronic pain (or plasticity of the nervous system) has our prime interest. Pulsed Radiofrequency as a minimally invasive therapy for treatment of chronic lumbar radicular pain (low back pain) is being studied based on an RCT (Koen van Boxem). In a rat model of lumbar radicular pain, the mechanism of action PRF is being studied. Research Line: Urology P.I.: Dr. G. Van Koeveringe Co investigators: Prof. Dr. J.I. Gillespie, Prof. Dr. Ph. E.BV. van Kerrebroeck, Dr. S.W. de Wachter Post doc: Dr. L. Herfst PhD students: Drs. S. Rahnamai, Drs. B. Biallosterski, Drs. V. Vennemann, Drs. R. Heeringa Focus of research: Neurourology: bladder signalling, control mechanisms and neuromodulation. The Urology Group performs a translational research program Today Spinal Cord Stimulation (SCS) is used in the treatment directed towards fundamental understanding of of intractable neuropathic pain (NPP). Despite the neurogenic and autonomic control mechanisms of the Research Line: Translational neuroinflammation existence of SCS as a pain therapy for over 40 years, up till bladder. The research involves neuronal bladder physiology P.I.: Prof. Dr. M. De Baets, now only two randomized clinical trials (RCT s) have been and pharmacology in relation to the origins of bladder dysfunction. Dr. P. Martinez, Dr. M. Losen and 32 Four projects are ongoing in order to study dif- Dr. P. Molenaar performed: one in patients with CRPS-1(Chronic Regional Research Line: Alzheimer disease; neurodegeneration PhD students: Drs. K. Vrolix, Drs. A. Gomez 33 and posttranslational modifications of Technicians: J. Endert, R. Schneider proteins Focus of research: Defining antigen-specific approaches to P.I.: Dr. F. Van Leeuwen, treatments in neurodegenerative and Prof. Dr. H. Steinbusch neuroimmunological diseases. Post doc: Dr. N. Kholod, Dr. J.-J. Cheng PhD students: Drs. F. Dennissen, Drs. R. Gentier ferent levels of bladder dysfunction in close collaboration with the neuroscience research school, clinical urological department and the Pelvic Care Centre Maastricht. Line 1, funded partly by an NWO-Mozaiek grant and an FP7-ITN Marie Curie EU grant, investigates the role of NO-cyclicG- MP and prostaglandin pathways in the bladder wall in relation to non-voiding activity and its role in the development of the overactive bladder syndrome. Both the NO-cyclicG- MP pathway and the prostaglandin pathway have been shown to play a role in the intrinsic control mechanism in the bladder wall. In addition, the way by which this mechanism is modulated by the central nervous system will be subject of the future afferent recording and tracer studies. Line 2, funded partly by the FP7-ITN Marie Curie EU grant, is a physiological and pharmacological study of non-voiding detrusor activity in animal models representing different mechanisms of diseases affecting bladder control such as a subvesical obstruction guinea pig model, an Alzheimer transgenic mouse model and a decerebrated rat model. The determination of the respective contribution of either bladder or brain/nerve dysfunction to these diseases will contribute to a better understanding of the clinical problems and (patho)physiological mechanisms. Line 3 investigates the perception of bladder sensations in humans and the relationship to voiding behaviour. A relationship of an existing overactive bladder syndrome with non-voiding activity is studied using high-resolution urodynamic measurements. A relationship is sought between psychological profile and the degree of bladder fullness perception.. Line 4 investigates the role of sacral neuromodulation in humans on complaints of overactive bladder and voiding dysfunction. In this research line both working mechanisms (using techniques and models described above) and an optimisation of the current neuromodulation treatment by means of determination of predictive factors and optimisation of techniques are the main subjects to be studied. Parts of the research lines 3 and 4 will be investigated in newly developed and ongoing clinical trials. Focus of research: Protein quality control in Alzheimer s disease. Efficient neuronal function depends on cellular homeostasis. Posttranslational modifications (e.g., ubiquitination) contribute to many functions such as control of short-lived proteins, transcription factors and degradation of aberrant proteins. These homeostatic control mechanisms are often flawed during aging and disease. Our research focuses on quality control mechanisms such as the ubiquitin-proteasome system (UPS). We have discovered that mutant ubiquitin (UBB +1 ) accumulates in the hallmarks of Alzheimer s disease, suggesting that it has a function in this multifactorial disease. Indeed, UBB +1 inhibits the UPS and results in neuronal dysfunction. In the past year we have fully characterized the enzyme Ubiquitin-C-terminal hydrolase L3 that is able to hydrolyse UBB +1 (in collaboration with N.Dantuma, Karolinska Institute, Stockholm, Sweden). In addition, we developed tools (e.g., transgenic animals) to study the effects of UBB +1 in vivo (Fischer et al., 2009, Dennissen et al., 2010). We are currently investigating anatomical (light and immunoelectron microscopy) and behavioral aspects ( e.g., Morris water maze and fear conditioning) in these UBB +1 mice as well as genetic crosses with the Alzheimer mouse model line (APP-Swe/PSEN1, Δ exon9).significantly, interactions between UBB +1 and Aβ plaque formation have already been shown, e.g., plaque load changes. We are working with a broad range of diseases from Myasthenia gravis to, Alzheimer s disease to Schizophrenia. Our goal is to define fine antigen-specificities of individual patients antibodies and their mechanisms of action and/ or individualised treatments based on this new knowledge. The project includes studies of inter-patient heterogeneity in the target autoantigens the autoantibodies and their pathogenic actions and immunological and tissue-specific factors that influence clinical presentation and severity. State of the art technology is used: mature (CD22 + ) B lymphocytes are isolated from peripheral blood or tissue and immortalized with EBV and the polyclonal B cell activator CpG After immortalization, B cell clones produce monoclonal antibodies. The screening of the antibodies is performed by immunohistochemistry or radioimmunoassay. We also test new approaches to explore the possibilities for treatment: We have demonstrated that Bortezomib

18 can improve MG symptoms and, therefore, proteasome inhibition is a promising therapeutic strategy to target plasma cells in antibody mediated autoimmune diseases. Research Line: Central Nervous System neuroinflammation P.I.: Dr. P. Martinez, Dr. M. Losen, Prof. Dr. H. Steinbusch, Prof. Dr. M. de Baets Post-doc: Dr. M. Gangolf PhD students: Drs. C. Mencarelli, Drs. G. Bode Focus of research: Understanding neuroinflammation in neurodegenerative diseases. The Epilepsy Research Group aims at translational research by organizing its projects around three central themes, i.e., epileptogenesis, diagnostics, and treatment. Febrile seizures are convulsions brought on by fever in infants and small children. Although the absolute risk remains very small, certain children who have febrile seizures face an increased risk of developing epilepsy. The epileptogenesis research studies the long-term influence of devel- We are studying the role of innate immunity in the pathogenic 34 mechanism involved in neurodegenerative diseases The topics were: 1) Fetal asphyxia (FA); our data support the opmental seizures on neuronal functions. These findings and the involvement of lipids in the early inflammatory prompted a new PhD-study that focuses on long-term 35 process. We are studying the function/dysfunction of danger functional changes of ionotropic receptors of hippocampal signal molecules e.g., Serum amyloid P component and granule cells (collaboration with prof. J-M Rigo and A. Swijs- the ceramide transporter in the neurodegenerative process. en, Hasselt University, Belgium; supported by transnational Moreover we also study the role of these proteins in ER and University Limburg). mitochondrial dysfunction, early pathogenic mechanisms in the neurodegenerative process. Passive immunization with human anti-abeta antibodies is a new therapeutic approach. However recent passive immunization trials have shown some adverse effects. Because antibodies can also exert inflammatory responses, the effector mechanisms of a therapeutic antibody need to be carefully controlled we are studying the contribution of these mechanisms to the therapeutic effect (plaque clearing and improvement of memory function) and possible side effects using pro-inflammatory mouse IgG2a and anti-inflammatory mouse IgG1 antibodies in an AD mouse model Research Line: Neonatology Developmental neuroscience P.I.: Dr. A. Gavilanes, Dr. B. Kramer, Prof. Dr. H. Steinbusch, Prof. Dr. L. Zimmermann, Prof. Dr. J. Vles Kootstra Postdoc: Dr. E Strackx PhD students: Drs.E. Vlassaks, Drs. K. Cox, Drs. R. Jellema, Drs. M. Seehaase, Drs. M. Gantert Associated Researchers: Dr. P. Martínez, Dr. D. van den Hove, Prof. Dr. M. De Baets Focus of research: Asphyxia and inflammation. We focused on the study of the impact of asphyxia and inflammation during fetal and neonatal CNS development. concept that severe FA has a critical role in neurodegeneration and aging. 2) Fetal asphyctic preconditioning; we report the development and characterization of a novel animal model of permanent neuroprotection due to sub-lethal FA. We believe that this model will serve as a useful tool to study the basic mechanisms underlying endogenous neuroprotection. 3) Fetal (LPS) inflammation; we documented for the first time morphological and electrophysiological evidence of a CNS compromise at preterm birth secondary to chorioamnionitis in the sheep. Furthermore, we showed cortical cerebellar changes that might account for the motor and non-motor deficits seen in neonates from compromised pregnancies. E. Strackx defended her PhD thesis, based on the first two described topics, in January Research Line: Epilepsy P.I.: Dr. G. Hoogland, Dr. M. Majoie, Prof. Dr. A. Aldenkamp, Prof. Dr. J. Vles Post doc: None PhD students: None In collaboration with: Focus of research: Molecular imaging of epileptogenesis. Accumulating evidence suggests that neuromodulation by electric currents can be a treatment option for epilepsy patients. However, the efficacy of this therapy is variable. The treatment research line explores mechanisms by which vagus nerve stimulation (VNS) may exert its antiepileptic effect. In 2011, we completed a PhD-study in which we developed a clinically relevant animal model that is suitable to study VNS-induced changes in the epileptic brain (Rijkers et al., Brain Res. 2010). In a follow-up PhD-study, supported by a Kootstra fellowship from Maastricht university, M. Aalbers is currently studying the role of neuroinflammation in epileptogenesis (in collaboration with dr. A. Vezzani, Mario Negri, Milano, Italy).

19 36 chapter 4 Facts and figures

20 Facts and figures 4.1 Earning Power In this section, we present information concerning resources and funding. Direct funding is provided mainly by the MUMC + and comes indirectly from the Dutch Ministry of Education, Culture and Science. Research Funding: funds received in competition from national and international science foundations. Contracts: funds from third parties. Direct Funding at Division level Div. Year Granted organisation Project Amount in e Acquired by Maastricht University Kootstra Talent Fellowship* (postdoc) S. Köhler 2010 Maastricht University Kootstra Talent Fellowship (postdoc) S. Burgmans SUBTOTAL CN&CN Maastricht University Kootstra Talent Fellowship (postdoc) L. Goossens Maastricht University Kootstra Talent Fellowship (postdoc) H. Lataster 39 SUBTOTAL Maastricht University Kootstra Talent Fellowship (PhD-student) M. Aalbers Maastricht University Kootstra Talent Fellowship (postdoc) Y. Brasnjevic Maastricht University Kootstra Talent Fellowship (PhD-student) A. Muris Maastricht University Kootstra Talent Fellowship (postdoc) E. Strackx SUBTOTAL TOTAL MHeNS * Kootstra Talent Fellowships: Awarded by the Faculty Health, Medicine and Life Sciences. Talented future PhD students: The fellowship is meant to bridge the time between graduation of a talented student in Medicine, Health or Life Sciences and the start of an official contract as a PhD-student. Talented future postdocs: The fellowship is meant to bridge the time between graduation of the PhD-student and the start of an official contract as a postdoc.