International Research Training Group

modulThe International Research Training Group (IRTG) is formed by scientists from JARA BRAIN, an initiative of the RWTH Aachen University and the Research Center Jülich, Germany, together with the University of Pennsylvania, USA. The IRTG will investigate a clinically and societally highly relevant topic: the neurobiology of pathological aggression and impulsivity. Applicants on both sides provide the optimal research and training environments, longstanding cooperation, and the required expertise and experience to address this topic. Clinicians frequently face pathological aggressive symptoms that pose major challenges for therapy.Impulsivity and aggression are multifactorial phenomena and understanding the underlying neurobiology is still in its infancy. The IRTG will examine circuit models based on imbalance among striatal, limbic and frontal networks. To address those questions, the IRTG will combine neuroimaging and behavioral research with neuropsychological, electrophysiological,neuroendocrinological, and molecular approaches in humans. Analogous research will also be conducted in animal models, providing a translational approach.

Human and animal studies will focus on two specific aims: 1) How factors such as environment, traumatic experiences, personality, gender, culture and (epi-)genetic factors influence impulsive and aggressive behavior, emphasizing effects on neural networks and neurotransmitters; 2) Ways to modulate and alter aggressive behavior and cerebral connectivity via neuromodulatory,psychological and psychopharmacological treatment.
Our overarching goal is to characterize and advance our understanding of the networks underlying aggression and impulsivity and to investigate new therapeutic clinical interventions. For this IRTG, faculty members have developed a comprehensive and unique qualification program centered on principles of clinically relevant research, international exchange, and synergy. Scientific excellence and independence is fostered while, at the same time, sufficient support is guaranteed. The qualification program emphasizes innovative aspects, such as the systematic integration of electronic media, enabling intensive US-German exchange. Students will be closely supervised by a US as well as a German supervisor, and associated to a postdoctoral and doctoral
US/German counterpart, enabling IRTG students to profit from a complementary research experience during the mobility period as well as from an elaborate mentoring program.
Hence, the IRTG strives to establish a productive and interdisciplinary environment for highlevel education of young scientists in the field of clinical and translational neuroscience.

Research Methods

Within this IRTG, we will employ a continuum of highly translational approaches, specifically neuroimaging studies, as our major methodological focus, conducting behavioral, electrophysiological and neuroendocrinological human studies. This core concept will be strengthened by also involving molecular and animal studies. Two research lines are pursued:

1) Investigation of major risk and influencing factors such as environment (e.g. stress, early trauma, harsh discipline,media, vicarious observation/learning, culture), personality or disposition (e.g. irritability, psychopathic traits, alexithymia, approachavoidance motivation), sex and gender (e.g. hormones, stereotypes) and genotype (e.g. MAOA, 5HTTLPR,GWAS) on impulsivity/aggression. We will focus on patients with mental disorders as well as on healthy individuals (including those with risk factors or specific psychopathological haracteristics) and investigate the effects of these influencing factors on neural networks and neurotransmitters. The effects of isolation, social defeat,stress and perceived danger on aggression using mouse models linked to mental disorders will also be examined.

2) Identification of ways to modulate and alter impulsivity and aggressive behavior by neuromodulatory (tDCS, neurofeedback, TMS), psychosocial
(emotion regulation), pharmacological means (see Figure 2) in humans and in rodents and analyze the effects on the underlying cerebral connectivity. This research relies on the complementary expertise of Penn and JARA-BRAIN researchers. Related concepts,such as addiction or stress, will be targeted only if related to impulsivity and aggression. Both research lines cover broad areas, thus giving rise to many PhD projects over a prolonged period. At the same time, both lines of research are well defined and focused, so that PhD projects will build a critical mass able to significantly advance the field. To adhere to these lines of research, we will define a guideline for each dissertation project. In particular, each project will cover at least one out of two elemental topics (see below) that define our core research areas, but have to tackle the area of aggression and impulsivity.

Qualification program

The qualification program rests on three columns of:

  • Shared structured curriculum
  • Interdisciplinary research training
  • Individualized supervision strategy

A) The structured curriculum includes several components:
Group specific courses
Internal group meetings, supervised by the speaker, represent the most regular and core component of the study program and are held bi-weekly. Here, students present their ongoing/planned projects at least twice a year. These meetings include two formal project presentations by doctoral students of their research project. These meetings alternate with external events, in which we will invite visiting national and international speakers (meetings are mandatory). Here, the students are given the opportunity to meet these experts and discuss scientific questions and their projects.

Electronic Learning Environment for Neuroscience of Aggression (ELENA) via learning management system (LMS): To strengthen and intensify the international educational interaction, our IRTG will implement electronic media and create an LMS. We will install a media library of recorded lectures held within the IRTG, thereby making them available to generations of students as well as across locations.

Online course modules
Students will receive a Penn ID at the beginning of their PhD training, required during Figure 3: Exemplification of the PhD education time line, course structure on both sides their mobility period. This will give them the unique chance to participate in the online CITI program, the Collaborative Institutional Training Initiative. The CITI offers web-based training materials in many curricular areas, which can be combined into a package that fits the needs of each subscriber, such as Biosafety and Biosecurity, Animal Care and Use, Good Clinical Practice, Human Subjects Research and Responsible
Conduct of Research, and others.

At Penn, the IRTG course structure includes regular IRTG meetings in the BBL (Brain Behavior Laboratory, supervision Ruben C. Gur). These are also work in progress seminars, open for all IRTG members to attend and present their work.

  • IRTG students will attend monthly seminars in the Silvio Conte Center (NIH-funded P50 Center grant, R.E. Gur, PI), and • The Center for Neurobiology and Behavior (CNB).
  •  IRTG students also attend bi-weekly seminars in the Clinical Neuroscience Training Program
    (CNST), which are made available via ELENA to students in Aachen.
  •  Weekly Grand Rounds are also available in the appropriate Departments (Psychiatry, Neurology, Radiology, Computer Science, also available via ELENA).
  • Regular ’soft skills’ workshops are offered at Penn throughout the year. The IRTG students
    also participate in the structured activities and meetings of their respective laboratories.

Individualized Development Plan (IDP)

Students will set up an IDP that meets the specific educational requirements for his/her research project. This individualized training will be discussed
and decided upon with both supervisors and within the thesis committee. Although the IDP will be set at the beginning of the first year it will be updated after 6 and 12 months.

Methodological workshops/lectures will provide training for important methodological skills. Students can choose workshops based on the relevance to their research subject. The workshops involve methods used by most of the students, ranging from statistics (connectivity (DCM, PPI), multivariate, resting state analyses) to basics in neuroimaging methods (joint fMRI-EEG, PET, NIRS, neurofeedback, tDCS), morphometry, behavioral epigenetics, mouse models, analysis techniques, basics in programming (Matlab, Presentation), as well as topics such as experimental design and special topics to be added based on the constellation of students within a given cohort.

Clinical workshops and lectures focus on clinical training (see clinical education) encompassing diagnostic skills, psychopathological assessment,
psychopharmacology, and knowledge on aetiology, neurobiological bases and symptomatology as well as current therapeutic approaches. These workshops will provide the necessary clinical background as well as the research skills needed for clinical projects.

Clinical rotation
The clinical rotation of 2 weeks (within the first 3 months within the IRTG) is obligatory for all students who have no prior experiences in a neuropsychiatric setting. This guarantees that students gain experience with patients and get an impression on the psychopathology of aggression and impulsivity. Students with experience in this field due to their educational background are not required to complete the clinical rotation. For those working in the methods or cellular section it provides valuable insight into the clinical domain and should provide a first step into translational research education.

Complementary courses

Modellstudiengang – School of Medicine, RWTH. The course of studies in the Medical Faculty will complement the qualification program of each IRTG member. The “Modell-Studiengang Medizin Aachen” aims (1) to implement modern strategies in learning (interdisciplinary approach centered on organs and systems, connecting preclinical and clinical topics, e-learning), (2) to shorten the preclinical part of the studies and acquire practical abilities
from the second semester on, and (3) to offer individual qualification profiles.
General Course Program – RWTH/Jülich. For members of the IRTG working on methodological questions, courses of the RWTH Masters program in Biomedical Engineering will be of special interest. For all students aiming at getting the “Dr. rer. medic.” at the Medical Faculty a course in medical terminology is obligatory (also offered in English). The program will be complemented by courses from medical statistics and the course program and lectures offered at the FZ Jülich.

General Course Program – Penn. In most American universities, PhD students are integrated into highly structured doctoral programs. This is also the case for the American students in the IRTG. They are therefore required to participate in a number of courses from the general course program to fulfill basic degree requirements. Of primary relevance for the American students of the IRTG is the Neuroscience Graduate Group (NGG). It is an interdisciplinary PhD program, part of the Biomedical Graduate Studies (BGS) program at the University of Pennsylvania and is closely associated with the Mahoney Institute of Neurological Sciences (MINS). Doctoral IRTG students will be authorized to participate in this program and take core and advanced courses in neuroscience and related courses in other disciplines. They also participate in extra-curricular courses.

Spring School.

The annual Spring Schools, held alternatively in Philadelphia or Aachen/Jülich, have been each year’s highlight within the IRTG 1328 with about 70-80 participants. They will be kept as a scientific conference experience. Here, the mutual scientific exchange between the partner universities takes place as well as one of the thesis committee meetings. German and US students give scientific presentations on their projects and get valuable feedback by their supervisors as a very important part of their scientific training. These meetings furthermore will lead to high group coherence and strengthen cooperation between researchers of both countries.

Environment of the Research Training Group

Research environment at RWTH Aachen/FZ Jülich- JARA-BRAIN

Since 2007, Germany’s Excellence Initiative strengthens the leading position of RWTH Aachen University and enhances its international competitiveness. The Forschungszentrum Jülich (FZJ), one of the 15 Helmholtz Research Centers in Germany, has gained high reputation and is recognized as a first-class institution at an international level. The FZJ Institute of Neuroscience and Medicine (INM) is devoted to brain research. The IRTG will more closely collaborate with Structural and Functional Organization of the Brain (INM-1), Medical Imaging Physics (INM-4) and Computational and Systems Neuroscience (INM-6). The INM has broad expertise in brain imaging and houses a unique 9.4-T MR-PET hybrid scanner and a 3-T MR-PET hybrid system in addition to 3T and 4T scanners as well as an animal 9.4T, animal PET and high-density whole-head MEG. The expertise in MR and PET physics for both maintenance and development of the necessary neuroimaging hardware and software will be a unique asset to the IRTG. JARA-BRAIN, a section of the Jülich Aachen Research Alliance (JARA, www.jara.org), is part of the Excellence Initiative. The collaboration between Aachen and Jülich is to be further stabilized by the funding of joint research institutes (JARA-BRAIN Institutes I and II, corresponding to INM-10 and -11), which will be integrated into both FZJ and RWTH Aachen (Directors among others: Habel, Konrad, Schneider, Shah, appointed in April).

JARA-BRAIN has always been dedicated to improving the translational aspect of neuropsychiatric research. It has named all eight (previous
and recent) JARA-BRAIN W1 junior professors “Clinician scientists”, thus giving them clinical and research responsibilities. Three of them are applicants of this proposal (former I.Vernaleken, K. Reetz; current T. Nickl-Jockschat). The long-standing close collaboration has resulted in many joint research projects, including Kompetenznetz Schizophrenia (KNS, BMBF), the Brain Imaging Centre West (BICW; BMBF), the Clinical Research Group 112 (KFO 112, DFG), and the Alliance for Mental Health in an Ageing Society (HelMA, Helmholtz).

More recently, the Human Brain Project as one of only two winners of a EU-wide competition and the BMBF multi-center project APIC “Antipsychotic induced structural and functional brain changes” (3,6 Mio. €, Schneider, Gründer, Mathiak, Vernaleken, Habel) and the coordinating database project PING (380 T€, Schneider). JARA-BRAIN scientists (Herpertz-Dahlmann, Konrad) are performing the largest international long-term study to date on
the causes of aggression in girls (FEMNAT-CD, eight EU member states, FP7-Health-2013-Innovation, €6 millions) as well as the multi-center “Teenage mother project” (BMBF) for “Understanding and Breaking the Intergenerational Cycle of Abuse (UBICA)”.

The IRTG will be located within the research priority “Clinical Neurosciences”, one of three focuses of the Medical Faculty. The Interdisciplinary Center for Clinical Research (IZKF Aachen) currently supports a consortium on “Alterations of neuronal connectivity” and funded another center grant on impulsivity and aggression between 2012-2014 (Vernaleken,Habel, Konrad, Mathiak, Reetz).
Workspaces for analyzing fMRI data as well as methodological expertise are provided by the Brain Imaging Facility of the IZKF Aachen. The Dept. of
Psychiatry focuses on imaging research in psychiatry. It has its own 3-T Prisma MR research scanner (plus simultaneous EEG system), as well as a HR+PET scanner. Further, equipment such as tDCS, EEG Feedback, TMS and Pathway pain stimulator is available.
This IRTG would fit perfectly into the existing research environments since it is the only structured graduate program in the research field of clinical neurosciences. As this is one of the research priorities of the Medical Faculty, it will considerably foster this research focus. It will also be a major component of JARA-BRAIN. The proposed IRTG would represent a model for the joint promotion of young scientists in brain research and on all stages of their career. Its additional value also lies in the special focus and promotion of translational research. The IRTG will furthermore strengthen the applicants’ research focus in the field of clinical neuroscience of aggression and impulsivity. It would further increase the internationality and international visibility of the doctoral students and with that, of the RWTH as well as its clinical neuroscientists. There is no other Research Training Group in this area or at the Medical Faculty at RWTH. There are also no competing cooperative arrangements with any Collaborative
Research Centers or Clusters of Excellence at RWTH. Similarly, no other graduate schools support scientists in this research area. The Medical Faculty offers only a MD/PhD program for physicians based on structured theoretical training. It is a three-year projectoriented post-graduate training with intensive personalized supervision. Only five physicians per year will be eligible for the Dr. rer. nat. The program consists of independent work on a
research project as well as structured theoretical training.
At the RWTH, the Center for Doctoral studies (CDS) is the university’s central unit providing continuing education and transferable skills training for doctoral candidates. The International Office provides support for international students and researchers. Child-care facilities and equality measures are provided (see 5.3). A central office “Strukturierte Doktorandenprogramme” has been installed that supports the establishment of structured doctoral programs.
The RWTH also fosters networks of doctoral students (“Doc.Net” and „DoktorandInnen-Forum“). If the maximum funding period for doctoral students is exceeded, the RWTH provides the possibility to apply for short-term extension grants.