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Projects: Brain stimulation, neuroplasticity and learning

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.

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.

EFIC-Grünenthal-Grant (EGG): Circuits of pain memory in chronic pain patients. 01/2015-12/2016.

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.

Becker S. DFG - Deutsche Forschungsgemeinschaft BE 4309/51: Verstehen der Interaktionen und Konflikte zwischen Schmerz und Belohnung: Integration von Computermodellen und psychologischen Methoden". 02/2015-01/2016.

The aim of the project is to initiate and establish an international collaboration to study how the brain processes pain. The project focuses on a particular issue in pain neuroscience: how do we solve conflicts between pain and reward, termed ‘motivation-decision’ conflicts, which arise in everyday life? This is illustrated by the classic maxim ‘no pain, no gain’. The collaboration aims to develop a new approach to this problem by integrating two distinct disciplines: computational and engineering models of decision-making (Cambridge), and psychological and clinically-orientated approaches to understanding behaviour (Mannheim). The overall projects goals are to: a) develop a new model of pain-reward interactions that explains data from behavioural experiments, and; b) generate testable experimental predictions to identify how and where in the brain this interaction occurs. Our proposal involves three steps: (1) summarise the core experimental findings for painreward interactions to date (‘what needs to be explained’) and review key the computational models which can readily be applied to this data; (2) develop and simulate a new model and test its ability to account for these data (Cambridge) and make novel experimental predictions; (3) test these predictions in a newly designed behavioural experiment (Mannheim). At the end of the project, we aim to have a theoretically validated and behaviourally tested model of pain-reward interactions, which is both publishable in its own right, but more importantly supports a larger joint research proposal to study the neural basis of pain-reward interactions.

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. EU - Europäische Union 230249: ERC PHANTOMMIND: Phantom phenomena: A window to the mind and the brain. 01/2009-12/2014.

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.

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