Projects: Systems Neuroscience in Psychiatry (SNiP)

An objectively measured and evaluated biomarker used as an indicator for a pathogenic process or pharmacological response needs to achieve analytical and clinical validity. The latter depends on qualifying measures linking peripheral biomarkers with a biological process and clinical endpoints of schizophrenia. Thus, biomarker signatures identified in subprojects (SP) 1 and SP2 will be evaluated and compared to schizophrenia-specific mechanistic endpoints in patient-derived neurons. Schizophrenia is a neurodevelopmental disorder characterized by developmental deficits such as impaired neuronal differentiation, reduced synapse densities in selected brain areas and dysfunctional neuronal network activity. Since brain samples from patients are not accessible for mechanistic biomarker validation in vitro, we apply neurons differentiated from patient-derived induced pluripotent stem cells (iPSC) which faithfully represent the genetic background of individual patients. To this end, iPSC clones from patients with schizophrenia will be delivered by partners LMU and CIMH. Diagnostic and imaging data as well as blood samples of the corresponding patients are at hand and serve for sequencing blood transcriptomes and the establishment of multi-modal disease signatures in SP1 and SP2. For biomarker validation, those iPSC specimens will be selected out of the available ones which display the most similar disease signature as compared to signatures obtained of the large scale patient cohorts in SP1 and SP2.

Although there has been much progress in the understanding of phantom limb pain (PLP), we still do not know which factors are antecedents and which are consequences of the pain and how central, peripheral and psychological factors interact. This project seeks to determine the development of phantom limb pain in a longitudinal fashion and will examine how central and peripheral changes as well as psychological factors develop over time. In addition, the role of central nervous system excitability and plasticity and the influence of use-dependent plasticity and body perception will be examined. Further, we will examine how evoked phantom pain is represented in the brain. Finally, we will employ high field imaging, neurofeedback using real time functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) to identify causal circuits for phantom pain.

We will develop and implement a mobile research infrastructure combining longitudinal assessments (A01) with two high-intensity measurement bursts (A04). MovisensXS will be used as a platform to assess e-diary items and track smartphone usage. Connected additional devices will capture physical activity and heart rate variability. All data will be sent via encrypted transmission to a secured server ensuring compliance with GDPR. Real-time analyses on all acquired data will allocate information on compliance and probability of phase changes. We will provide hard- and software interfaces to enable integration of apps (A02) and sensors (A03), as well as extensive training, ongoing support and troubleshooting.

The project will use ambulatory assessment and functional neuroimaging to identify triggers, modifying factors and intermediate neural mechanisms in alcohol use disorder (AUD) in course phases with a substantial increase or decrease in alcohol consumption, respectively. We will assess temporally highly resolved ambulatory assessment for six weeks to identify intraindividual differences in in the momentary effects of triggers and modifying factors on subjective craving, mood, impulsivity and alcohol consumption. We will further identify their neural correlates in brain circuits relevant for cognitive, affective and motivational processing and test the predictive value of the identified mechanisms for subsequent disease trajectories to critically inform novel prevention and intervention strategies.

More than any other area of medicine, psychiatry and psychotherapy depend on successful communication. Given that most refugees arriving in Germany in the 2last years speak languages such as Arabic that are not understood by the resident therapeutic community, interpreters are scarce and not available around the clock or in emergency situations, and no financing for language services is available for many hospitals, this presents a critical obstacle in providing mental health care for refugees. This consortium will leverage recent advances in machine learning, cross-lingual communication, portable communication technologies and crosscultural psychiatry to decisively address this problem. First, we will develop a portable, secure and extensible cross-lingual communication (including speech-tospeech, speech-to-text and text-to-text translation) system, based on smartphones, to be used on site during psychiatric diagnosis in Iraqi Arabic- and Levantine-speaking refugees. This will incorporate recent technological advances to enhance diagnosis of psychiatric disorders in refugees by characterizing stress levels and psychopathology through machine-learning based tools to characterize paralinguistic features (such as prosody and voice spectral analysis) and semantic features. Diagnostic assessment will be based on an electronic version of the M.I.N.I. (International Neuropsychiatric Interview), an established structured diagnostic interview with an administration time of approximately 15 minutes that is employed in more than 100 countries. Second, we will validate this tool against the gold standard of expert diagnosis with a human translator present, establishing feasibility, reliability and validity of our approach first regionally and then nationally through a network of health care systems delivering refugee services. Third, we will extend the use of the mobile platform through building a smartphone-based app to be used by the community for logging, therapist communication, and community building, and for monitoring client’s well-being outside the clinic using ecological momentary assessment (EMA). To ensure rapid and widespread implementation into clinical practice, we will produce the necessary information for BfARM approval as a medical device. Beyond the immediate goals, our approach has potential to benefit a wide range of therapeutic and diagnostic initiatives in refugees that depend on successful communication.

ACE have enduring effects on human stress regulatory circuits and promotes alterations in stress sensitivity and emotion regulation in later life. The likelihood of the sensitized neural system to (de)compensate is thereby shaped by adverse and protective social influences in everyday life, but the examination is methodologically challenging. The planned doctoral projects will tackle this problem and interrogate data on prior ACE, alterations in stress sensitivity and emotion regulation and real-life social environmental exposures to identify the intermediate neural mechanisms

We will conduct joint translational projects to test innovative interventions to (A) prevent conversion to schizophrenia in high-risk (HR) individuals, (B) enhance recovery in schizophrenia patients in the early phases of the illness, and (C) evaluate the outcome and efficacy of these interventions and implement them in clinical practice. (Aim A) For prevention of conversion in HR participants, we will conduct a randomized controlled trial (RCT) comparing two interventions with favorable risk-benefit ratios and clear translational rationale, a psychotherapy module aimed at improving social cognition, and a NMDA modulator/antioxidant (N-Acetyl Cysteine). (Aim B) To enhance recovery in patients after an acute episode, three harmonized RCTs will test the following add-on treatments: cannabidiol, mechanistically novel drug acting on the endocannabinoid system, actimetry-controlled physical exercise, and a psychotherapeutic intervention aiming at improving social cognition and social interaction. We will also perform a clinical experiment to test the hypothesis that transcranial direct current stimulation (tDCS) enhances the effects of cognitive training. (Aim C) We will evaluate treatment success for recovery, everyday function and stress reactivity, and quality of life. Using neuroimaging, we will examine neural systems related to gender and outcome. We provide costeffectiveness analyses both for experimental interventions and standardized inpatient treatment, and enhance transfer of successful results into practice.

Social neuroscience is a quickly evolving research discipline that aims at uncovering the cognitive and neural underpinnings of human social behavior. Difficulties in the social domain are a major risk for mental health and can be observed in a wide range of psychiatric conditions, in particular in developmental disorders such as autism. In order to understand the underlying pathophysiological mechanisms, one question is of particular importance: What are the changes in the brain that are responsible for the development of social abilities from childhood to adulthood? This question requires a developmental approach which allows to relate changes in neurobiology to changes in social abilities. Due to methodological challenges, such as the need for large sample sizes in a longitudinal design, this question remains unanswered. The current Habilitation project aims at filling this gap by characterizing the typical and atypical development of the so-called “social brain” in healthy individuals and individuals with autism from childhood to adulthood. Data were collected locally (project 1) and as part of the largest European multicenter study on autism (projects 2 and 3). By combining cross-sectional and longitudinal analyses of neuroimaging, behavioral and clinical data, detailed developmental trajectories of the social brain can be determined, along with their association with structural brain maturation, genetic influences and the acquisition of behavioral skills. With this Habilitation project, I will not only substantiate my expertise in the fields of social neuroscience and developmental psychiatry, but will also strengthen my methodological profile in the field of multimodal pediatric imaging.

Projektziel ist eine die Überprüfung eines Modells zur effektiveren Gesundheitsversorgung von jugendlichen und erwachsenen Flüchtlingen mit affektiven Störungen. Die zentrale Forschungsfrage lautet, ob sich mithilfe einer zielgruppenadaptierten, kultursensiblen Diagnostik, Indikationsstellung und Therapie innerhalb gestuften und partizipativen Versorgungsmodells (Stepped and Collaborative Care Modell, SCCM) die Versorgung dieser Patientengruppe effektiver gestalten lässt. Gleichermaßen soll überprüft werden, ob dieses Versorgungsmodell geeignet ist Menschen außerhalb von psychiatrischen Ambulanzen kosteneffektiver zu versorgen. Dabei ist die primäre Arbeitshypothese, dass das vorgeschlagene Versorgungsmodell im Vergleich zur Routineversorgung eine erhöhte Effektivität aufweist. Als Sekundärhypothese wird angenommen, dass das Versorgungsmodell in weiteren Effektivitätsparametern (Response, Remission, Lebensqualität) sowie hinsichtlich der Effizienz (direkte und indirekte Kosten, Kosten-Nutzwert-Relation, Kosten-Effektivitäts-Relation) überlegen ist. Explorativ sollen die aktiv gewonnenen Patientendaten dazu verwendet werden an fünf bundesdeutschen Standorten mit unterschiedlichen Versorgungssituationen Inzidenz und Prävalenz von psychischen Erkrankungen bei geflüchteten Jugendlichen und Erwachsenen zu erfassen

WP1 Neural correlates of aggression – human studies WP1 evaluates the neural substrates of impulsive and instrumental aggression by identifying neural, neurocognitive and biomarker mechanisms underlying aggressive/antisocial behaviour in high-risk children and adolescents (subjects with ADHD). Furthermore, a new sample of children with Conduct Disorder (CD), as well as of adolescents with CD is collected. In addition, this WP measures cognitive, physiological and motor components of empathy in children and adolescents with CD and examines whether different empathy components are differentially affected across the various aggression subtypes. Finally, WP1 integrates the findings of the different tasks and examines the common (cross-disorder) and the disorder-specific correlates of the aggressive/antisocial behaviour.

Selbstkontrolle ist eine basale menschliche Fähigkeit, die unter Alkoholeinfluss oder bei aggressivem Verhalten stark beeinträchtigt sein kann. Leichtsinniges Verhalten unter Alkoholeinfluss und aggressive Impulstaten können persönliches Leid und hohe gesellschaftliche Kosten nach sich ziehen. Kontrollverlust über das eigene Verhalten wird mit einem Ungleichgewicht zwischen präfrontal-limbischen Kontroll- und Emotionsnetzwerken sowie einer veränderten Belohnungsverarbeitung in Zusammenhang gebracht. Neben veränderten neuronalen Prozessen spielen bei erhöhtem Alkoholkonsum und aggressivem Verhalten auch genetische Prädispositionen sowie ungünstige Umweltfaktoren (z.B., sozialer Druck) eine Rolle. In dem vorliegenden Projekt zu „neurogenetischen Mechanismen und Umweltinteraktionen bei Störungen der Selbstkontrolle“ werden innovative experimentelle Methoden eingesetzt, um die Neuro-Gen-Umwelt Ebenen zu verknüpfen. Der Fokus liegt auf funktionellen neuronalen Markern emotionaler Reaktivität und inhibitorischer Kontrolle, die bei Störungen der Selbstkontrolle beeinträchtigt sind, sowie auf funktioneller „resting-state“ Konnektivität. Diese neuronalen Prozesse werden mittels funktioneller Magnetresonanztomographie (fMRT) in Menschen mit klinisch ausgeprägter reaktiver Aggressivität am Beispiel der „intermittierenden explosiblen Störung“ und in Gesunden mit und ohne genetische Risikovarianten gemessen. Der Einfluss von Gen-Umweltfaktoren auf neuronale Prozesse wird mittels Geno-typisierung von Risikopolymorphismen aggressiven Verhaltens und der Messung von Umweltfaktoren im tatsächlichen Lebensumfeld von Menschen mit Smartphone-basiertem „ecological momentary assessment“ (EMA) untersucht. Die Erforschung von Wechselwirkungen zwischen neuronalen Prozessen, genetischen Prädispositionen und ungünstigen Umweltfaktoren hat zum Ziel, funktionelle Bereiche für neue effiziente Präventions- und Therapieansätze zur Reduktion klinisch aggressiven Verhaltens und exzessiven Alkoholkonsums zu identifizieren.

Fragestellungen / Ziele - Persistieren die epigenetischen Merkmale von Geburt (Nabelschnurblut) oder 6 Monaten nach Geburt bis zum Alter von 4 Jahren? Sind psychosoziale Risiken der ersten 4 Lebensjahre mit spezifischen Veränderungen epigenetischer Marker assoziiert? - Lassen sich Auffälligkeiten in Verhaltenstests im Alter von 4 Jahren durch epigenetische Merkmale bei Geburt oder der Mutter-Kind-Interaktion im 6. Monat vorhersagen? - Können Stressoren in Schwangerschaft und früher Kindheit bzw. epigenetische Merkmale die Hirnentwicklung bis zum 4. Lebensjahr prognostizieren? - Stehen Auffälligkeiten in Verhaltenstests im Alter von 4 Jahren in Verbindung mit „Infektions-Historie“ (Antikörper im Speichel) oder der Darmflora?

1 Results of the first funding period Aim of IP3 is the identification of abnormal activity and connectivity in brain systems associated with trust in BPD by means of a rather new brain imaging method, hyperscanning. Hyperscanning permits the measurements of brain activity simultaneously in two people interacting socially. During the first funding period, we mainly focused on the development of a generalizable, robust and hypothesis-free analysis routine for hyperscanning data while collecting data from both healthy controls and patients. Method development was based on two independently recruited samples of healthy subjects, a sample of 26 subjects (13 pairs) including both sexes, and a sample of 50 female subjects (25 pairs), which also serves as control sample for our BPD patients. A Joint Attention (JA) task was chosen for first investigation, representing a fundamental developmentally early form of specifically human social interaction. Data from both investigated samples showed that during JA, coupling between brain systems does emerge, uniquely to truly interacting subjects, and temporally and spatially highly specific, i.e. based upon function of the right temporo-parietal junction (rTPJ). Remarkably, in our patient study we found that neural coupling parameters during JA were already affected by illness status, suggesting a disruption in fundamental processing of social information in BPD at early developmental and cognitive processing stages. Specifically, in 22 pairs, formed from one subject with BPD interacting with one healthy control participant, we found significantly lower coupling in dyads with a BPD subject during JA. Initial analysis of a multi-round trust game using the same methodology showed a comparable reduction in rTPJ coupling when BPD patients were involved in the interaction. 2 New questions and work schedule The surprising discovery of disrupted basic social information processing in BPD during JA raises several questions. First, since JA arises very early in development (during the first year of life) and is required for the emergence of higher-order social skills, it may predict social dysfunction in adult social interaction requiring those skills. In the coming funding period, we will therefore examine whether JA impairment is predictive of neural coupling during trust and deception in a hyperscanning framework. Secondly, impairment of JA could index a state or trait phenomenon, with differing implications for therapy. To test trait aspects, JA disruption will be related to early environmental exposure data as well as to genotype information available through the KFO, requiring a further buildup of sample size. To examine state properties of JA prediction, we will study the effects of a social interaction training battery, conducted in IP1, on neural synchrony before and after treatment, providing insights into the nature and biological importance of neural coupling parameters. This work should provide an assessment to which degree cross-brain rTPJ-coupling can serve as a predictive biomarker to standard therapy and contribute to the investigation of innovative treatments for baseline social cognition. Further toward this end, induced changes in oxytocin will be related to neural changes in hyperscanning and treatment effects. To achieve these gains in the coming funding period, our data set will be extended from currently female subjects and simple, cooperative interaction within JA to the inclusion of male patient- as well as control samples, an oversampling of early childhood adversity participants to examine the effects of early environmental risk. Our analysis methods will be further developed to characterize cross-brain connections and cross-task predictive interactions in a variety of social settings and according fMRI tasks.

1. Vorhabenziel Teilprojekt 2 (ZP2) verfolgt die Ziele der Identifikation von Phenotyp-Phänotyp-Assoziationen, der Bereitstellung von großen Patientenstichproben sowie der Ausweitung der Patientenressource des Konsortiums auf eine deutschlandweite multizentrische Kohorte. In TP4 und TP5 stehen die Identifizierung und Validierung neuer Marker (Bildgebung/Imaging, Genetik, Klinik, Umwelteinflüsse) für Schizophrenie (SCZ) sowie Unipolare und Bipolare Störung (MD) im Vordergrund. Es sollen computationale Netzwerk-Modelle zur Darstellung der dynamischen Abläufe im Gehirn, vor allem des präfrontalen Cortex, von Patienten mit SCZ und MD erarbeitet werden (TP10). Es ist folgende Gliederung einzuhalten: 1. Vorhabenziel, 2. Arbeitsplanung 2. Arbeitsplanung TP2: Identifizierung robuster Genotyp-Phänotypmuster mittels Genomsequenzierung und ggf. Patienten-Wiederbegutachtung. TP4 und 5: Etablierung der Bioinformatik-Infrastruktur, Marker-Identifizierung und –Validierung, Festlegen prädiktiver Marker. TP 10: Statistische Beschreibung zellulärer und synaptischer Transferfunktionen bei Kandidatengenen (CACNA1C, NCAN) und anschließende Netzwerk-Darstellung. 3. Ergebnisverwertung Ein vertieftes Verständnis der Pathophysiologie psychiatrischer Erkrankungen wir mittel- und langfristig zur Entwicklung von neuen und besser wirkenden Behandlungsstrategien und Medikamenten führen.

This grant examines previously unknown aspects of frontal-striatal plasticity, a crucial mechanism for the experience-dependent modification of brain circuits that is frequently disturbed in schizophrenia. This work is expected to advance our current neuroscientific knowledge on frontal-striatal plasticity and identify new genetic and neural systems-level biomarkers for plasticity disturbance and schizophrenia with high clinical potential. Over seven studies, the functional, structural and biochemical correlates of frontal-striatal plasticity will be quantified in vivo using multimodal magnetic resonance imaging (MRI) and established behavioral paradigms allowing for a robust induction of short- and long-term neural adaptation processes (Studies 1 und 2). The potential of these measures as biomarkers for disease vulnerability and severity is subsequently examined in neuroleptics-naïve patients with schizophrenia and their unaffected first-grade relatives (Study 3). The dopaminergic and glutamatergic mechanisms that modulate these processes will be examined using pharmaco-neuroimaging (Study 4). By combining neuroimaging and molecular genetics, the effects of important risk variants on frontal-striatal plasticity will be examined. Apart from the analysis of disease- and plasticity-related candidate genes (Studies 5 and 6) genome-wide association studies (GWAS) will be used to identify previously unknown risk variants (study 7).

In the previous funding period, repetitive transcranial magnetic stimulation (rTMS) was shown to induce plasticity in prefrontal circuits for executive function and working memory, and genome-wide significant variants for psychosis were found to impact on these circuits, as well as on prefrontal regulation of the limbic system. In the present project, plasticity in prefrontal circuits will be further dissected by three experiments: (a) a genetic association study examining the effects of genome-wide significant common variants for psychosis on modulation of prefrontal circuit plasticity by rTMS, (b) an experiment in healthy controls relating prefrontal plasticity to a direct cellular assay of synaptic and glutamatergic function by using neuronally-differentiated induced pluripotent stem cells (iPS cells) together with multimodal imaging and rTMS, and (c) an experiment in healthy controls to directly modulate prefrontal circuit (connectivity) features and dependent cognition through real-time-fMRI based neurofeedback. The experiments are independent, but subjects for experiments (b) and (c) will be subsamples of the group investigated in (a) If successful, these experiments will identify genetic variants linking prefrontal plasticity and risk for psychosis, establish a cellular model for systems-level plasticity in humans and provide a first cognitive approach to induce plasticity in connected brain circuits relevant for mental disorders.

Advancing treatment discovery in schizophrenia through functionally relevant neuronal intermediate phenotypes: a combined neuroimaging, genetics and human induced pluripotent stem cells approach The problem: Therapy development in schizophrenia is at an impasse: no fundamentally new drugs have been discovered in decades, treatment, especially for cognitive and negative symptoms, is unsatisfactory, and a massive disinvestment of industry in the last years highlights the urgent need to rethink the translational process1. As a consequence, schizophrenia remains one of the largest sources of disability, cost2 and burden3 in all of medicine. A major obstacle to psychiatric translation has been the inaccessibility of neuronal target tissue. This has now changed in principle through the availability of human induced pluripotent stem cells (hiPSC) that can be differentiated into neural lineages (hiPSCN), and studies have shown that hiPSCN exhibit morphological signatures found in schizophrenia brains4. These morphological features could be used for cellular imaging based high-throughput screening in drug discovery. However, to turn this assay into a pathway to translation it must be specified which morphological changes are functionally relevant, linked to the pathophysiology of the illness and ideally also to clinical course. Previous work: We have been active for a number of years defining neural systems-level intermediate phenotypes for schizophrenia using a combined genetic-neuroimaging approach 5-8. In work funded by the German Research Council, we have established a robust pipeline to differentiate neurons from hiPSC derived from genotyped healthy subjects into glutamatergic, GABAergic (figure 1, left) and dopaminergic lineages. We characterize their morphology and plasticity (neuronal growth, axon segment movement, calcium imaging, marker proteins, synapse density, monosynaptic connectivity), and obtain in-vitro electrophysiological recordings using patch-pipettes9 (figure 1, right). We have also created the world’s largest dataset of imaging data in whole-genome sequenced subjects carrying high-risk copy number variants for schizophrenia and autism in collaboration with Aventis/deCode Genetics, funded by the European Union Innovative Medicine Initiative (projects NEWMEDS and EU-AIMS). In the IMAGEMEND project, recently funded by the EU (FP7), we bring together neuroimaging and genetics information on over 13.000 subjects with clinical course and treatment information, enabling us to identify systems-level phenotypes relevant for illness progression. We are therefore in a good position to identify neuronal phenotypes that are linked to genetic/ expression profiles and heritable systems-level mechanisms of schizophrenia. Research proposal: In the research proposed here, we aim to systematically identify robust cellular and assembly-level phenotypes linked to genetic risk, systems-level dysfunction and course of schizophrenia (see figure 2). The focus on genetic risk is motivated by (a) the high heritability of the illness and (b) the fact that hiPSC generation entails large-scale epigenetic reprogramming. hiPSCN will be morphologically quantified as described above. In addition, assemblies of glutamatergic cells will be characterized using electrophysiology with established protocols that probe passive properties and instantaneous and steady-state f/I curves. Using a recently established efficient, fast, and predictive model-fitting framework 9, we will translate these recordings into physiologically valid neuron descriptors which can be embedded in anatomically and physiologically realistic models. To identify the subset of these features that is heritable, we will compare hiPSCN from healthy controls and patients with schizophrenia with subjects at increased formal genetic risk (first-degree relatives of patients from high-density families). All of these subjects are available from funded work. Following the intermediate phenotype (or “endophenotype”) concept, we will select measures that are abnormal in patients and show intermediate expression in genetic risk subjects. From heritable neuronal features that associate with assembly level function, we will then select features that are linked to systems-level intermediate phenotypes for schizophrenia, in particular dorsolateral prefrontal cortex (PFC) activation and PFC-HF connectivity, that have demonstrated heritability and are linked to course through IMAGEMEND data. We will verify that these features can be measured reliably in control experiments from hiPSCN derived from the same participants and exclude somatic de-novo mutations in the hiPSCN through sequencing. Deliverables: This project will for the first time identify morphological features in hiPSCN linked to assembly and systems level function relevant to heritable risk and course for schizophrenia. This will enable a new generation of high throughput drug discovery for schizophrenia. The link achieved in this project between the cellular, assembly and systems level also closes a critical gap in our understanding of how neuronal abnormalities, through changing systems-level function, lead to the complex symptomatology of schizophrenia. Finally, this unique joint genetic-neuronal-imaging dataset should be useful to provide parameters for innovative computational approaches to comprehensively model brain function, such as the Human Brain Project.

Phantom experiences occur in almost all amputees but are among the least understood sensory phenomena. Recently changes in the representation of body maps in the brain were found to be related to phantom pain and it has also been demonstrated that there are great similarities between non-painful phantoms and bodily illusions such as the rubber hand illusion. This research has also shown that the brain does not process the physical but the perceived reality, which opens the door to manipulations of the perceived reality in basic research and the treatment of phantom pain. Behavioural intervention methods such as prosthesis, sensory discrimination or mirror training influence phantom limb pain and alter brain function. Thus, phantom phenomena are an excellent tool to study the neural basis of somatosensory and specifically bodily perception and this can lead to new treatment methods such as brain-computer interfaces or virtual reality applications for phantom pain and similar pain states. The aim of this project is (1) an exact assessment and analysis of the interrelationship of various phantom phenomena such as phantom limb awareness, painful phantom sensation, telescoping, prosthesis use and proneness to bodily illusions or plasticity of body image in a large sample of amputees, (2) the analysis of the neural correlates of these phenomena in small subgroups of amputees using functional magnetic resonance imaging as well as transcranial magnetic stimulation, (3) the analysis of determinants and neural correlates of bodily illusions in healthy controls to identify potential common neural mechanisms and (4) use of prosthesis and virtual reality training early after amputation in order to understand how manipulations of the body image and sensory feedback alter the development and the brain correlates of phantoms.

On the regional level, Europe has one of the highest levels of resources for mental health care. Despite this, the high burden and impact of mental disorders in Europe is expected to rise. “ROAdmap for Mental health Research” (ROAMER) is designed to develop a comprehensive, consensus-based roadmap to promote and integrate mental health and well-being research in Europe. Research advances and innovations are to be devoted to decreasing the burden of mental disorders and increasing the mental health and well-being of Europeans. ROAMER will combine a neutral, fact-based methodology with extensive stakeholder involvement in consultation and dissemination. During the kick-off phase, the methodology (including comprehensive EU-wide indicators to assess the current state of the art, gaps and advances) and the desired situation (scoping and objectives) will be finalised. Secondly, the current state of the art will be examined, using these tools. In the third phase, the desired situation will be compared with the current situation to identify gaps and advances. Phase four prioritises these gaps and advances, as well as solutions. In the fifth phase, this information is translated into roadmaps covering infrastructures, capacity building and funding strategies for scientific areas relevant to mental health and well-being: biomedical, psychological, social, economic and public health. Geographical, interdisciplinary, developmental, gender and age perspectives will be taken into account. To achieve consensus among a broad group of scientists, service users, carers, government and funding institutions and other stakeholders, ROAMER uses web-based survey’s, scientific workshops, scientific advisory board meetings, stakeholder meetings, consensus meetings, and policy meetings. The consortium consists of leading experts in the field, and is well balanced in terms of geographical distribution and complementary expertises across all relevant aspects of mental health research.