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Projekte

Prof. Dr. Dr. h.c. Dr. h.c. Herta Flor

DFG - Deutsche Forschungsgemeinschaft : Die Rolle Pandemie-bezogener und individueller Variabilität in längsschnittlichen Kohorten über die Lebensspanne: Müssen wir die Modelle neurosoziobehavioraler Verläufe in einen Substanzmissbrauch weiterentwickeln?. 01/2021-01/2024.

Nees F. SFB 1158: B03 - The role of learning, stress and underlying brain circuits involving prefrontal-limbic interactions in the development of chronic back pain . 07/2019-06/2023.

Previous research led to the assumption that chronic pain may be related to emotional learning, however, little is known about the associated changes in brain structure and function that might predict persistent pain. This project seeks to determine brain circuits related to learning mechanisms in pain such as aversive and appetitive, operant and respondent learning as well as the role of stress to predict the transition from acute to chronic back pain and to identify risk and resilience factors.

Flor H, Vollstädt-Klein S. DFG - Deutsche Forschungsgemeinschaft : SFB TRR 265: Projekt C01: Modifikation des Ungleichgewichts zwischen kognitiver Kontrolle und habituellem Verhalten bei Suchterkrankungen. 07/2019-06/2023.

In dieser Studie untersuchen wir das Ungleichgewicht zwischen kognitiver Kontrolle und habituellem Verhalten bei Rauchern mit Behandlungswunsch, dessen neuronale Korrelate und wie dieses mit zwei Interventionen modifiziert werden kann. Bezüglich der ersten Intervention (kognitive Remediationstherapie, die auf die Verbesserung inhibitorischer Kontrolle und Exekutivfunktionen abzielt) wird angenommen, dass sie die Top-Down-Verarbeitung beeinflusst, wohingegen die zweite Intervention (ein lernbasierter Ansatz durch implizite Bahnung und Kontext-Modulation) Bottom-Up-Prozesse verändern sollte.

Andoh JA, Flor H. DFG - Deutsche Forschungsgemeinschaft SFB 1158: B 07 - Neural circuits involved in Phantom Limb Pain . 07/2019-06/2023.

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.

Reininghaus U, Flor H. BMBF - Bundesministerium für Bildung und Forschung 01EC1904B: perPAIN - Verbesserung der Behandlungsergebnisse chronisch muskuloskelettaler Schmerzerkrankungen durch einen personalisierten Therapieansatz. 05/2020-04/2023.

Chronische muskuloskelettale Schmerzen (CMSK) können durch kompensatorisches Verhalten, welches durch kurzfristige Schmerzreduktion und soziale Verstärkung aufrechterhalten bleibt, zu einer Chronifizierung der Schmerzen führen und werden durch Furcht vor den Schmerzen, komorbide Angsterkrankungen und Depression noch verstärkt. Ziel des Teilvorhabens ist es, eine auf Extinktions- und Expositionstraining basierende Therapie bei Patienten mit CMSK zu optimieren, zu implementieren und zu analysieren. Dieses Therapieverfahren wird im Vergleich zu einer auf die Reduktion emotionaler Belastung zugeschnittenen Behandlung oder einer Smartphone-basierten Minimalintervention untersucht. Ziel von Teilvorhaben 3 ist die Untersuchung von Schmerz auslösenden und aufrechterhaltenden Mechanismen, prognostischen Markern und behandlungs-bedingten Veränderungen im alltäglichen Leben durch Smartphone- und Sensoren-basiertes ambulatorisches Assessment sowie die Analyse der therapeutischen Effekte einer Minimal-Intervention mittels Smartphone-basiertem Aktivitätstagebuch in der personalisierten Behandlung bei Patienten mit CMSK. In Kooperation mit den Verbundpartnern wird ein Zuweisungsalgorithmus entwickelt und in einer Proof-of-Concept-Studie getestet und optimiert. Durch die frühe Personalisierung der Therapie für spezifische Subgruppen soll der Therapieeffekt bei gleichzeitiger Kostenreduktion deutlich verbessert werden.

TRR/1 TP C01: Losing and Regaining Control: TP Modifcation of the imbalance between goal-directed and habitual behavior. 07/2019-06/2022.

In this study, we aim to assess the imbalance between goal-directed and habitual behavior, its neural basis and how it can be differentially modified in treatment-seeking smokers, using two training interventions. The first intervention is cognitive remediation treatment (CRT), also known as cognitive enhancement therapy, focusing on improving inhibitory control and executive functions. The second intervention, a computer-based habit-modifying training focusing on implicit drug seeking ("implicit computer-based habit-modifying Training", ICHT) uses a conditioning approach through implicit priming and contextual modulation. We hypothesize that both interventions change the balance between goal-directed and habitual behavior but by different mechanisms. Whereas CRT should directly increase cognitive control, in contrast, ICHT should affect the early processing and the emotional valence of smoking and smoking cues.

BMBF - Bundesministerium für Bildung und Forschung : IMAC-Mind: Improving Mental Health and Reducing Addiction in Childhood and Adolescence through Mindfulness: Mechanisms, Prevention and Treatment. Project TP2 “Translation of neurobehavioral risk profiles into the development of screening and prevention . 10/2017-09/2021.

Flor H. DFG - Deutsche Forschungsgemeinschaft FL 156/41-1: Reinhart Koselleck Projekt: "Körperrepräsentation und sensomotorische Funktionen modulieren die Reorganisation des Gehirns und Verhaltensänderungen: Vom chronischen Schmerz zur lmmobilität und Demenz ". 07/2015-06/2020.

Brain circuits involved in pain processing and body representation are closely connected and interact more than previously thought. Somatosensory, visual, interoceptive and motor processes contribute to the formation of body perception and can be combined in treatments designed to reestablish normal body representation. Based on the development of novel psychological interventions targeting body representation in phantom limb pain, we devise new virtual and augmented reality-based training pro-cedures to reestablish normal body representation and improve sensory, motor and cognitive function. We apply these interventions in post-injury pain and motor dysfunction, where the counteracting of long-term immobility by feedback of movement should shorten recovery times and preserve muscle function. Another novel application is in chronic musculoskeletal pain, where the systematic shaping of intact body representation including interoception, should reduce pain and pain behaviors and alter maladaptive brain circuits. We expand this approach to early dementia, where the breakdown of sen-sorimotor processing and immobility may be important in disease progression. We employ novel im-plicit and explicit assessment methods of these perceptual and neuronal changes involving psycho-physics, computational modeling, physiological recordings and brain imaging methods. These studies are the basis for mechanistic treatment approaches and also advance basic research on body repre-sentation and multisensory integration.

Hector II Stiftung : FRAILBRAIN: Reversing maladaptive reorganization in frail brains: sensorimotor training, brain plasticity and the role of BDNF. 10/2016-09/2019.

DFG - Deutsche Forschungsgemeinschaft SFB 1158: B 07 - Neural circuits involved in Phantom Limb Pain . 07/2015-06/2019.

Flor H. BMBF - Bundesministerium für Bildung und Forschung 01EE1406C, AERIAL: Addiction: Early Recognition and Intervention Across the Lifespan . 02/2015-01/2019.

Addictive disorders are among the most frequent and costly disorders in industrialized countries. While substantial research focused on treatment of single substance use disorders (SUDs), most interventions do not sufficiently address comorbid disorders, are provided too late, do not reach the majority of addicted subjects and are not adjusted with respect to environmental stressors, affective comorbidity, gender and age-specific contexts. Focusing on alcohol use disorders (AUD), the main aim of the consortium is to improve the health care system by 1) assessing new access pathways including a wider range of healthcare professionals, and 2) evaluating existing and developing novel early assessment and intervention tools including e-health applications (computer/internet/smart phone-based). We will address patients suffering from the most prevalent SUDs, particularly alcohol, across the lifespan. We will use state-of-the-art basic science approaches to assess social stressors and comorbid affective disorders and we will adapt our approach to age-related differences in treatment needs. To adapt early interventions to modify risk and resilience factors across the lifespan, we will use existing cohorts such as the longitudinal IMAGEN sample of (now) young adults, representative data across the lifespan and from a systematic assessment of adolescent psychiatry, community and hospital general medical settings as well as observational data from studies on the mechanisms of addictive behavior. We will focus on proactive approaches for all primary medical care patients including general practices and hospitals. In all settings, we will assess comorbid mental disorders and gender and migration-specific factors such as social exclusion and discrimination.

Flor H, Bekrater-Bodmann R. DFG - Deutsche Forschungsgemeinschaft KFO 256, 2nd funding period: TP 04 Sensory-affective Interaction and Body Perception in BPD. 08/2015-07/2018.

BPD is characterized by dissociative symptoms that include intermittent somatosensory integration deficits and alterations in body perception. Frontoparietal dysfunctions, especially involving the temporoparietal junction (TPJ), may represent key mechanisms related to the processing of and interaction between the self and the environment. Our proposed project aims at the elucidation of psychobiological mechanisms of dissociative states and the evaluation of their importance for the psychopathology of BPD. In study 1, after the induction of dissociation or a neutral control condition, we will perform experiments that use of the processing of pain and pleasant touch as a tool to understand the perceptual mechanisms related to dissociative states. In study 2, we will facilitate or inhibit the activity of the TPJ or a control site using a neuronavigated transcranial magnetic stimulation (TMS) protocol. We will examine its effects on sensory integration associated with body perception and the processing of somatosensory stimuli with positive or negative valence, and their association with dissociation. By revealing the psychobiological basis and consequences of dissociative states, the results might enhance our understanding of the complex perceptual alterations in BPD.

Flor H. DGM F1/1: Lebensqualität, Schmerz und neuropsychologische Einschränkungen bei Patienten mit mitochondrialen Erkrankungen. 05/2015-04/2016.

Mitochondriale Erkrankungen sind Multisystemerkrankungen, bei denen es durch Genmutationen zu Defekten in den Mitochondrien kommt, die zu einer Vielzahl an Symptomen führen. Mitochondriale Erkrankungen sind phänomenologisch äußerst variabel, wobei allen Erkrankten eine starke Beeinträchtigung der Funktionalität und ein hoher Leidensdruck gemein ist. Trotzdem, oder vielleicht gerade deshalb, gibt es bisher keine systematische Beschreibung der somatischen, kognitiven und auch affektiv-emotionalen Beschwerden von Patienten mit mitochondrialen Erkrankungen. So treten, zum Beispiel, chronische Schmerzen bei vielen dieser Patienten auf, wird jedoch meist nicht als Teil der Erkrankung betrachtet, da der Schmerz nicht ursächlich durch die Defekte in den 2 Mitochondrien erzeugt wird. Eine systematische Erfassung von somatischen, kognitiven als auch affektiv-emotionaler Symptome ist dringend erforderlich und kann einen wichtigen Beitrag zum besseren Verständnis mitochondrialer Erkrankungen sowie zur Diagnosestellung und Therapie leisten. Zur Optimierung von Therapieempfehlungen, insbesondere unmittelbar anwendbarer und einfach umzusetzender Ansätze, müssen außerdem die Lebensqualität, Resilienzfaktoren und Bewältigungsstrategien erfasst werden. Eine solche systematische Erfassung an einer umfangreichen europaweiten Stichprobe von Patienten mit mitochondrialen Erkrankungen ist das übergreifende Ziel dieses Forschungsvorhabens. Um einen Beitrag zur Verbesserung von Diagnose und Therapie zu leisten, werden die erfassten Daten z.B. zu bekannten Diagnosen und Genmutationen in Beziehung gestellt. Das Projekt ist eine notwendige Pilotuntersuchung, um die Untersuchungsmethoden auszuwählen und zu optimieren. Dazu werden 200 Patienten und 50 Kontrollprobanden umfassend mittels validierter Fragebögen untersucht, sowie eine Subgruppe von 50 Patienten zusätzlich mit neuropsychologischen Test zu kognitiven Defiziten genauer getestet.

Flor H. DFG - Deutsche Forschungsgemeinschaft SFB 636: TP Z01: Zentrale Aufgaben. 01/2012-12/2015.

The SFB636 central services are responsible for the following tasks: Central bookkeeping of the SFB (monitoring and administration of the DFG funds, providing the annual financial reports), coordination the SFB personnel including the hiring of new personnel, handling the ordering of consumables and other materials needed in the SFB, preparing the meetings of the boards and committees of the SFB, organizing the visits of visiting scientists and colloquia presenters and organization of the SFB symposia. Further, the SFB office will take care of all correspondence of the SFB as well as organization and coordination of the SFB636 Graduate Program “Translational Neuroscience” and the involved students.

Flor H, Spanagel R. DFG - Deutsche Forschungsgemeinschaft SFB 636: TP MGK: Integriertes Graduiertenkolleg Translationale Neurowissenschaften. 01/2015-12/2015.

The overarching aim of the SFB Graduate Program "Translational Neuroscience" is to enable transfer of knowledge between basic and clinical sciences. All of our PhD and MD students shall gain insight into both areas of research by attending an interdisciplinary teaching program including electives in different interacting groups. We also provide a framework for regular advice to the students and individual support wherever techniques or knowledge are lacking. The international and interdisciplinary program accepts students from a wide variety of natural and social sciences as well as medical students. Much of the translational work within SFB 636 is done by junior scientists, mostly MD and/or PhD students. During the current funding period, the graduate program was instrumental in cross-linking different approaches and system levels within the SFB. All students were provided with a common knowledge base allowing them to understand the translational aspects of their own projects and to interact successfully with colleagues from other disciplines. The Graduate Program pursues its goals by offering a compact course (60 hours) in neurosciences which covers a large variety of relevant topics and methods (qualification concept). This core curriculum is taught on a regular basis and covers 4 hours/week (usually on Friday, with social events to follow). This introductory course ends with a written exam, ensuring a common knowledge base for all students. It is important that the program does not distract students from their own research projects. Therefore, the second part of the curriculum is individual, i.e. specifically adapted to the needs of individual students. This is supported by several measures: students have regular meetings with the members of the student advisory board; they can visit German and foreign laboratories, including those in industry, in order to acquire specific techniques; they can invite guest scientists. Most importantly, each student has to choose two special topics (major and minor) for extended studies throughout the PhD or MD course. Students with projects rooted in basic sciences chose a clinical minor and have to visit a clinical unit for an elective. Conversely, students with a clinical focus stay for some time in a laboratory. In-depth education in the major continues with courses of 2 hours/week throughout the entire period of the PhD or MD thesis work. In addition, we offer regular autumn schools focussed on selected topics in translational neuroscience. In order to represent the students' interests and to train their rganizational skills, these courses have been organized by the students themselves (with help of the board members of the Integrated Graduate Program). In addition, students have been offered specific training courses in “soft skills” such as presentation techniques or group work in cooperation with the Graduate Academy of Heidelberg University. The students choose one main laboratory and advisor with whom they are affiliated at the very beginning of the program. In order to foster the idea of translational research we have also encouraged the possibility to split the dissertation work between a basic/preclinical laboratory and a clinical unit. Accepted students thus chose one main laboratory and advisor and two additional advisors who have had regular meetings twice a year with the student and follow the progress of his or her work. We are strongly encouraging first-author publications by the students and allow for a short, cumulative version of the dissertation script after 1 or 2 articles have been accepted (depending on the extent of the work invested) and one additional article has been submitted at the time of the completion of the degree. The Graduate Program is run by a governing board that also involves student representatives. From our experience with the program so far, we found that both the scientists within SFB 636 and the students greatly profit from this structured program in advanced neuroscience teaching. It increases the students´ professional prospects in the growing area of translational neurosciences and it creates a platform for interdisciplinary dialogue within the SFB, thus fostering preclinical-clinical cooperations. In the new funding period we have kept the basic structure of the program but have added additional offers: mentoring can now be done by our international collaborators; there is more career counselling; recruitment efforts for medical students will be intensified; and additional self-organized activities of the students have been included.

Flor H. DFG - Deutsche Forschungsgemeinschaft SFB 636: TP C01: Lernen und Plastizität des Gehirns bei PTSD: Risikofaktoren und die Rolle der Konditionierung von Hinweisreizen und Kontexten. 01/2012-12/2015.

The goal of this study is the analysis of learning processes and plastic brain changes in the development and maintenance of posttraumatic stress disorder (PTSD). We hypothesize that enhanced cue and deficient context conditioning along with high stress sensitivity lead to an enhanced risk to develop PTSD after traumatic experience and suggest that these alterations in associative and non-associative learning are accompanied by enhanced amygdalar and reduced hippocampal activation during acquisition and deficient midfrontal-amygdalar and midfrontal-hippocampal connectivity during extinction. In addition, we believe that traumatic stress, which alters the brain structure in these regions and leads to altered stress reactivity of the ypothalamus-pituitary-adrenal axis (HPA), contributes to the occurrence of PTSD along with peritraumatic factors. In the last funding period we continued the longitudinal study and added another 125 students in schools for rescue workers to the original 120 subjects (we plan to have 300 complete cases by the end of 2011) and characterized them with psychometric, psychophysiological, neuroimaging, endocrine and genetic methods. Since we do not yet have enough subjects who converted to PTSD we focused on predictors of cue and context conditioning in this sample. We found that hippocampal volume predicts context conditioning and that larger amygdala volume is associated with better cue conditioning, whereas cue conditioning is reduced with larger hippocampal volume. We also found that polymorphisms related to the minor alleles of HPA axis-related genes predict enhanced amygdala activation during cue conditioning and reduced prefrontal activation and prefrontal-amygdala connectivity during extinction. A polymorphism on the neurogranin gene, which has been associated with high risk for schizophrenia and memory disturbance, was found to predict hippocampal activation during context conditioning. In addition, traumatized persons with and without PTSD and healthy controls participated in cross-sectional neuroimaging studies. We found enhanced stress sensitivity as indexed by higher stress analgesia in the patients with PTSD and this was linked to enhanced activation in the rostral anterior cingulate. We also observed better second order conditioning with trauma cues as unconditioned stimuli in the PTSD patients accompanied by amygdala deactivation, which was associated with delayed extinction and abnormal dorsolateral prefrontal activation. In the PTSD group renewal was enhanced and associated with reduced hippocampal activation. A study on reinstatement is still ongoing as is the assessment of the effects of exposure treatment on renewal and einstatement. We also observed enhanced hippocampal activation during simple contextual conditioning in the PTSD group. These data are in line with our hypothesis of deficient context conditioning as a core pathological factor in PTSD. In the new funding period we will complete the longitudinal study by adding another 150 subjects to arrive at a total of 450, will retest persons who developed PTSD symptoms and compare them to persons who were traumatized without developing the disorder and matched controls from the rescue worker samples. In addition to retesting these predefined subjects we will use regression analyses to predict symptoms from the baseline tests in the entire sample. In the cross-sectional study we will expand the analysis of the role of deficient contextual processing in PTSD. Study 1 will test the hypothesis that PTSD patients focus their attention more on emotional cues at the expense of contexts compared to traumatized persons without PTSD and controls and that this is an early attentional process related to the perception rather than the evaluation of the stimuli that also determines that cues are better remembered than contexts. The study combines electroencephalographic recordings and eye tracking. A second study will examine the relationship of cued and contextual fear by combining differential fear conditioning to cues and contexts in one study. The contexts will be more complex than previous contexts in order to be able to model configural versus single item processing. Extinction to cues, contexts and their combination will be tested on a separate day and in a third session the response to the cues and contexts will be reversed (the previous danger cue/context will signal safety and vice versa) and tested with and without a retrieval cue. This will permit to test the role of inhibitory mechanisms and safety signals and will provide the possibility to determine how easily aversive memories can be updated. Functional magnetic resonance imaging will be employed to study the role of medial prefrontal and orbitofrontal circuits in this task. In these studies the effects of exposure treatment will also be examined to test if the deficient processing of cue-context interactions is an enduring deficit or can be reversed by effective treatment. Finally, we will address the specificity of the altered onditioning mechanisms and the brain correlates by using comorbidity, medication effects and trauma load as covariates and by comparing our patient group to others in and outside the collaborative research center with respect to the specificity of alterations in context conditioning.

Flor H. Universität Heidelberg : Exzellenzcluster CellNetworks EcTop 3 Neuro. 01/2013-12/2015.

This project aims to study the representation of pain in the somatosensory cortex and elucidate neural circuit activity involved in nociceptive processing in humans using a combination of high resolution functional and structural magnetic resonance imaging at 7 Tesla and multivariate pattern analysis. We further plan to examine to what extent these somatosensory circuits are altered in neuropathic pain and in musculoskeletal back pain states and further extend these analyses to study neurochemical changes, such as GABAergic and glutamatergic modulation, using magnetic resonance spectroscopy. This interactive approach will unravel causal mechanisms in structural and functional plasticity by combining complementary studies in humans and animal models.

Flor H. : Robuste Rekonstruktion von Gesichts- und Körpermodellen mit Streifenlichtscannern. 10/2013-09/2015.

Ziel des Projeks ist die automatische Erzeugung sowohl dreidimensionaler Gesichts- als auch Körpermodellen aus 2,5D Streifenlichtscans. Hierbei soll ein solcher Scanner aus möglichst preiswerten Kameras und Projektoren in Kombination mit neuer Framegrabber-Technologie konstruiert werden. Dadurch wird die Komplexität der Modellerstellung statt durch besondere Hardware mit Hilfe von verschiedenen Algorithmen zur Rekonstruktion, Rauschentfernung und Modellerstellung gelöst. Daraus resultiert eine Reduktion der Gesamtsystemkosten. Ein weiterer Schwerpunkt in diesem Projekt ist, das Maß an Benutzerinteraktion bei der Modellerstllung so weit wie möglich zu reduzieren.

Flor H. BMBF - Bundesministerium für Bildung und Forschung VDI 16SV5851: BionikHand: Das Bionic basierte interaktive Assistenzsystem zur Unterstützung körperlicher Funktionen von Finger‐, Hand‐, Arm‐ und Oberarm Prothesenträgern. 08/2012-07/2015.

Ziel ist die Untersuchung von Einflussfaktoren auf die Steuerungsfertigkeit eines künstlichen Armes unter Zuhilfenahme neu entwickelter Lern- und Steuersoftware sowie des Einflusses einzelner Elemente des Prothesensystems auf den Einbau ins Körperbild. In AP 1 werden geeignete Amputationspatienten sowie gesunde Kontrollen rekrutiert und über Interviews und Fragebögen die Bedürfnisse der späteren Nutzer erfasst. In AP 4 wird geprüft, welche Umsetzung eines Feedbacksystems die größtmögliche Bindung zwischen Nutzer und Prothese ermöglicht, sowie die Evaluation dieser Systemvariante. AP 7 bildet die Umsetzung zu fMRT-Untersuchungen: Assistenzsystem und Feedback werden im Hinblick auf ihren Einfluss auf den Kortex der Nutzer untersucht. Hierbei wird Wert auf praxisnahe Einflussfaktoren auf den Prothesenumgang gelegt. In AP 9 wird die Anwendung des Gesamtsystems durch neu rekrutierte Versuchspersonen untersucht.

Flor H. BMBF - Bundesministerium für Bildung und Forschung 01GQ1003B: BCCN TP C6: HC-dependent cognitive functions. 05/2010-04/2015.

Flor H. DFG - Deutsche Forschungsgemeinschaft FL 156/34-1: PASCOM: Examination of a new transdisciplinary framework on pain and suffering by integrating philosophical, psychological, and neuroscientific perspectives. 02/2011-01/2015.

The aim of the PASCOM project, jointly financed by the Fonds National de la Recherche Luxembourg (FNR) and the German Research Foundation (DFG), is to use an innovative phenomenological conceptual approach combining psychological, neuroscientific and philosophical stances to better understand pain and suffering. This effort is pursued as a collaborative research between the Pain Research Laboratory at the University of Luxembourg, directed by Prof. Fernand Anton, and the Department of Cognitive and Clinical Neuroscience at the Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University Mannheim, Germany, directed by Prof. Dr. Herta Flor. The two groups consider that diverse interpretations in separated domains often limit our understanding and reduce our proficiency for alleviating pain. In this framework, the PASCOM project seeks to provide a novel transdisciplinary framework for research, with a strong scientific basis, which will give scientists and persons working in the humanities alike access to knowledge on pain and suffering from an integrative perspective. The philosophical approach, developed by Dr. Smadar Bustan, proposes to employ a diagrammatical reasoning, intersecting the sufferer’s inner world with his social world. In breaking down this global and theoretical methodology into smaller, experimentally testable versions, we wish to examine to what extend the experiences of pain and suffering are centered in the private experience or in a person’s social and cultural interaction with the others. Experimentally targeting the cases when the two worlds converge or diverge, the two groups will be able to constrain the different crossing points and better define the relation between Pain and Suffering by identifying pain stimulations methods and parameters that are appropriate for the induction of variable levels of pain on one hand and suffering on the other hand. Our continuous exchange will allow us to conduct additional 2 sets of studies in order to measure, quantitatively as well as qualitatively, to what extent the exchanges between the inner world of pain and the social realm connect them together or instead reinforce their divide.

Flor H. DFG - Deutsche Forschungsgemeinschaft FL 156/35-1: KFO 256 TP 4: Sensory-affective Interaction and Body Perception in BPD. 01/2012-12/2014.

BPD is characterized by an altered perception of the body that includes sensory deficits, such as reduced pain perception, which are related to dissociation and self-injurious behavior. However, it is unknown if these alterations, which occur primarily in aversive affective situations, are a core variable or some type of coping behavior related to the disorder. The specificity for the somatosensory system, the interaction between various sensory modalities, and their relationship to impaired body perception have not yet been investigated. In healthy subjects, a widely distributed neuronal network involving parietal and frontal brain regions is responsible for the integration of multimodal inputs and for the creation of a coherent feeling of one’s own body. In patients with BPD, this coherence might be impaired in some conditions (e.g., dissociative states) which suggests alterations in limbic-frontal interaction, as well as in interactions with parietal regions. Our project aims at specifying the alterations in sensory perception of BPD patients and to identify clinical and neural correlates of these alterations. Specifically, we propose that the sensory perception deficits are not only related to noxious sensory stimuli and that these deficits are enhanced by stress and dissociation. To allow for disorderspecific conclusions, a group of patients with fibromyalgia will be included. The results might ultimately pave the way for novel therapeutic approaches by revealing if and how simple illusory setups might be able to alter somatosensory integration and associated brain activity.

Flor H. EU - Europäische Union 230249: ERC PHANTOMMIND: Phantom Phänomene: Ein Fenster zu Geist und Gehirn. 01/2009-12/2014.

Obwohl nach der Amputation einer Gliedmaße fast immer Phantom Empfindungen, d.h. Empfindungen im nicht mehr vorhandenen Körperteil, auftreten ist dieses Phänomen noch nicht gut verstanden. Veränderungen der Repräsentation des Körpers im Gehirn wurden mit dem Ausmaß des Phantomschmerzes in Beziehung gesetzt. Außerdem gibt es große Ähnlichkeiten zwischen nicht schmerzhaften Phantomphänomenen und Körperillusionen wie z.B. der Gummihand-Illusion. Die Forschung konnte zeigen, dass das Gehirn nicht die tatsächliche, physischen sondern die empfunden Realität verarbeitet. Dies gibt sowohl in der Grundlagenforschung als auch bei der Behandlung von Phantomschmerz die Möglichkeit die erlebte Realität zu manipulieren. Verhaltenstherapeutische Interventionen wie ein Prothesentraining, ein sensorisches Diskriminationstraining oder ein Spiegeltraining beeinflussen den Phantomschmerz und verändern die Gehirnfunktionen. Das Ziel dieses Projektes ist (1) eine exakte Erhebung und Analyse der Beziehung verschiedener Phantomphänomene wie Phantomschmerz, Phantomempfindungen, Telescoping (die Wahrnehmung, dass sich das Phantomglied in seiner Länge verändert), Prothesennutzung, und Empfänglichkeit für Körperillusionen in einer großen Stichprobe durch zu führen, (2) die Analyse der neuronalen Korrelate dieser Phänomene in kleinen Subgruppen mittels der funktionellen Magnetresonanztomographie und der transkraniellen Magnetstimulation, (3) die Analyse der Determinanten und neuronalen Korrelate von Körperillusionen bei gesunden Personen um gemeinsame neuronale Mechanismen zu identifizieren und (4) ein virtuelles Training zur Nutzung der Prothese kurz nach der Amputation zu untersuchen um zu verstehen wie eine Manipulation des Körperschemas und sensorisches Feedback die Entstehung und die Korrelate der Phantome im Gehirn verändern.

Flor H. : IASP Collaborative Research Grant: Neural Correlates and the Role of Dopamine in the Interaction of Intrinsic and Extrinsic Reward with Pain Sensitivity. 06/2012-05/2014.

Wüst S, Flor H, Rietschel M. DFG - Deutsche Forschungsgemeinschaft WU392/7-1: Genetische Grundlagen des Phantomschmerzes: Aufbau einer nationalen Forschungsressource. 05/2010-04/2014.

Nach Amputation eines Körperglieds leidet die Mehrheit aller Patienten unter Phantomschmerzen und den damit einhergehenden erheblichen psychosozialen Folgen. Die neurobiologischen Grundlagen des Phantomschmerzes sind bisher nur in Ansätzen verstanden, man weiß jedoch, dass zentralnervösen Prozessen eine große Bedeutung zukommt. Die Erforschung des Phantomschmerzes hat unmittelbare klinische Bedeutung und ist auch ein Zugang zur Untersuchung der generellen neurobiologischen Grundlagen der Wahrnehmung des eigenen Körpers. Human- und Tierstudien weisen darauf hin, dass genetische Faktoren für die Entstehung von Phantomschmerzen bedeutsam sind, bislang stehen für die Erforschung der molekulargenetischen Grundlagen aber keine ausreichend großen und gut charakterisierten Patientenkollektive zur Verfügung. In dieser Situation bietet nun das im 7. Rahmenprogramm vom Europäischen Forschungsrat (ERC) geförderte „PHANTOMMIND“ Projekt (Leitung: Prof. Flor), in dem 6.000 Patienten mit Amputationen untersucht werden, eine einmalige Chance. Ziel des hier vorgeschlagenen „PHANTOMGENE“ Projektes ist die Erweiterung des PHANTOMMIND Projektes um den Aufbau einer DNA-Bank als nationaler Forschungsressource. Im Rahmen der Rekontaktierung der Patienten soll u.a. auch eine vertiefende Phänotypisierung erfolgen. Anschließend sind genomweite Untersuchungen zu den molekularen Ursachen von Phantomschmerzen geplant.

Flor H. BMBF - Bundesministerium für Bildung und Forschung 01EC1010D: LOGIN TP 5: Forschungsverbünde zu Muskuloskelettalen Erkrankungen: Localized and generalized musculoskeletal pain: psychobiological mechanisms and implications for treatment. 02/2011-01/2014.

-Besseres Verständnis der pathophysiologischen Mechanismen von Schmerzerkrankungen. Identifizierung von spezifischen Schlüssel-Mechanismen, die im Rahmen von muskuloskelettalen Schmerzen von Bedeutung sind (psychologische Aspekte (Angst, Depression, Traumatisierung), Endocannabinoides System, nerve growth factor, genetischer Variablen, Coping und Resilienz sowie die Rolle von Muskel, Faszie und Haut). -Identifikation von Risiko- und Schutzfaktoren für die Entwicklung chronischer muskuloskelettaler Schmerzen. -Etablierung einer mechanismen-basierten Subgruppenklassifikation von Patienten mit muskuloskelettalen Schmerzen unter der Berücksichtigung der Schlüssel-Mechanismen.

Flor H. Universitätsklinikum Heidelberg : Exzellenzinitiative II: Internationale Gastprofessur Prof. Dr. Z. Seltzer. 01/2013-12/2013.

Prof. Dr. Ze’ev Seltzer wird im Juni 2013 eine sechsmonatige Gastprofessur am Institut für Neuropsychologie und Klinische Psychologie (wissenschaftliche Direktorin: Prof. Dr. Herta Flor) antreten. Prof. Seltzer forscht seit 1976 schwerpunktmäßig im Bereich der Schmerzverarbeitung. Er untersuchte unter anderem die Mechanismen nach experimentaler Nervenverletzung und Verhaltenmuster chronischer Schmerzen bei Nagetieren, Verhaltensmuster postoperativer und posttraumatischer chronischer Schmerzen im Menschen und in den letzten zwei Jahrzehnten Schmerzgenetik bei Nagetieren und Menschen. Der aktuelle Fokus des Bewerbers liegt auf der Vorhersagbarkeit und Vererbbarkeit sowie auf nicht-genetischen Risikofaktoren chronischer Schmerzen. Gegenwärtig arbeitet und forscht Prof. Seltzer an der Universität von Toronto, Kanada. Während seines Aufenthalts am ZI Mannheim wird Prof. Seltzer Inhalte zur Schmerzphysiologie, Schmerzpathologie, Modellierung von Schmerz in Tiermodellen und Schmerzgenetik in bestehenden Bachelor‐, Master‐ und Doktorandenkursen der Universität Heidelberg vermitteln. Darüber hinaus wird er in Zusammenarbeit mit Prof. Dr. Marcella Rietschel (Genetische Epidemiologie in der Psychiatrie) große Datenmengen zur Schmerzgenetik analysieren, um unter anderem gemeinsame und unterschiedliche Risiko‐ und Schutzfaktoren bezüglich der Entwicklung chronischer Schmerzen zu identifizieren. Diese Ergebnisse könnten die Universität Heidelberg in den europäischen Fokus der Schmerzgenetikforschung stellen.

Flor H. EU - Europäische Union 037286: IMAGEN WP2: Reinforcement-related behaviour in normal brain function and psychopathology: Behavioural tasks in humans. 02/2007-07/2012.

The goal of this workpackage is the development, implemenatation and evaluation of behavioral tasks for functional magnatic resoance imaging as well as additional behavioral tasks and neuropsychological tests that capture the key constructs that will be addressed in the project. These include sensitivity to reward and punishment, impulsivity, novelty seeking, attentional capture, risk taking, reversal learning and pavlovian conditioning. The tasks have been closely modeled after the animal tasks used in workpackage 1 in order to permit a translational approach.

Flor H, Mann KF. EU - Europäische Union 037286: IMAGEN WP6: Reinforcement-related behaviour in normal brain function and psychopathology: Neuroimaging adolescents. 02/2007-07/2012.

To acquire a large integrated structural and functional MRI dataset to allow analysis of the structural-functional correlations within the dataset. Analysis will be conducted in cooperation with WP 07. This data will be acquired in an identical fashion from multiple sites and will require explicit standardization with the input of WP 05. Participants will be recruited in conjunction with WP 04. To relate findings in this dataset to external measures of adolescent development, environmental exposure (WP 04) and current neuropsychological performance on tasks which relate to impulsivity (WP 02) To relate findings to genetic information in a coordinated hypothesis testing approach using candidate genes identified from strategies developed in WP 01, 03, 08. Activities in this workpackage are also linked to training activities coordinated in WP 10. Initially each site will implement a comparable pulse sequence for BOLD sensitive functional imaging, for diffusion weighted imaging and for structural T1 weighed imaging. In addition each site will implement the agreed battery of tasks for fMRI scanning and test this set of paradigms. On this basis each site will conduct functional, structural and diffusion weighted imaging at a rate of approximately 100 subjects per year. This data will be analysed individually and then correlated with personality and genetic markers.


Zentralinstitut für Seelische Gesundheit (ZI) - https://www.zi-mannheim.de