You are here:
Endophenotyping with fMRI: Genetic modulation and treatment response
Alcohol use disorders are up to 50% genetically driven and related to high relapse rates. To develop new therapeutic approaches, it is essential to extend our understanding of the genetic and biological underlying mechanisms. Therefore, we examine the influence of relevant genetic variations, which may increase the risk of developing alcohol dependence. We use functional magnetic resonance tomography to image specific brain processes, which are affected by chronic alcohol abuse, in 200 alcohol-dependent and 240 healthy individuals.
So far, we identified brain mechanisms, which indicated a decreased relapse risk in recently detoxified alcohol-dependent patients: less brain atrophy, increased connectivity between the neural reward system and the amygdala when alcoholic beverages were shown, increased activity in emotion-associated brain areas towards negative facial expressions, and compensatory neural activation during high task demand. These findings may represent resilience factors against relapse in alcohol-dependent individuals: a) an enhanced "warning signal" towards aversive aspects of alcohol, b) increased emotional control in social stressful situations, and c) engagement of intact neural resources to master challenging tasks.
Further, we investigated alcohol-associated "cue reactivity", which involves immediate reactions in alcohol-dependent patients. Thus, we found brain areas, which were associated with automatic attentional biases towards alcohol cues and with successful treatment processes. We also developed a paradigm for testing temptation resistance in alcohol-dependent patients, which engages cortical control areas that act on the neural reward system.
In future analyses we plan to investigate how risk genes modulate the observed brain mechanisms. This could help to develop new, more effective therapeutic interventions for the treatment of alcohol use disorders.
For further information, please see the website of the National Genome Research Network.
Imaging Genetics: Neural mechanisms of genetic risk factors for schizophrenia and affective disorders
The BMBF-funded, multicenter neuroimaging project "Neural mechanisms of genetic risk factors for schizophrenia and affective disorders" (MooDS) aims at two specific research goals: Firstly, the investigation of the effect of risk variants for affective and schizophrenic disorders on brain structure and function, and secondly, the investigation of shared and distinct mechanisms related to genetic risk for these disorders. A validated, reliable battery of neuroimaging structural and functional assessment sensitive to genetic variation that access major systems of executive cognitive control, memory, emotional regulation, reward processing and social cognition associated with affective and schizophrenic disorders was established. The main hypotheses of the project are that multimodal neuroimaging will identify neural mechanisms significantly linked to genetic risk for the disorders under study, that domain-specific neural processing abnormalities across diagnostic boundaries will map onto genetic associations with several traditional diagnostic categories, specifying both shared and distinct neurobiological mechanisms across the spectrum of psychotic and mood disorders, and finally that shared and distinct neural mechanisms associated with disease risk conferred by single genes will map on differences in brain structure and function in relatives of patients, vs. controls, establishing them as heritable intermediate phenotypes.
Validation of neuro-behavioral risk profiles regarding the development of harmful alcohol consumption in adolescents and adults (IMAGEN und eMed)
IMAGEN: IMAGEN is a European research project examining how biological, psychological, and environmental factors during adolescence may influence brain development and mental health. Using brain imaging and genetics, the project will help develop prevention strategies and improved therapies for mental health disorders in the future.
For further information, please see the website of the research project IMAGEN.
eMED: This consortium focusses on a systems-oriented approach to alcohol addiction with the aim to integrate all systems levels from genes to molecules to neuronal ensembles to large neuronal networks and finally to behavior. The mission is to better understand the ethiology of alcohol addiction, to define risk factors in young people for alcohol-use disorders later in life, and to provide better treatments to patients.
For further information, please see the website of the consortium SysMedAlcoholism.
Learning and Habitisation as Predictors of the Development and Maintenance of Alcoholism (DFG-Forschergruppe 1617)
Alcohol dependence is characterised by failures of choice. People drink despite severe negative consequences; other pleasures are hardly rewarding to them. A crucial unanswered question is the genesis of such choice anomalies. The question we wish to address in this work is the role learning mechanisms per se play in the aetiology of alcohol dependence. Our approach will rest on computational characterisations of learning mechanisms that have been highly successful in teasing apart separate neurobiological contributions by structures thought to be involved in the development and maintenance of addiction. At a first level, we will combine multimodal imaging techniques with computational measurements of behavioural changes consequent on rewards and punishments. We will assess the acquisition of Pavlovian values for stimuli, the effects of Pavlovian predictions on other types of choices and the habitisation of behaviour. The multimodal imaging techniques will allow both the localisation and neurochemical identification of learning mechanisms in addictive behaviours. At a second level, we acknowledge the abstract nature of reinforcement learning techniques. Thus we compare learning mechanisms in scenarios involving stimuli that are either relevant or irrelevant to the addictive behaviour. This involves learning about cues typically predictive of drugs and learning in the presence of the drug. Our long-term aim is to further improve treatment and prevention of alcohol dependence. Three factors will ensure maximal clinical impact. First, we examine these associations at a neurobiological and behavioural level in prospective investigations of (1) a representative at-risk population of young adults and (2) in a group of alcohol-dependent patients, both in a cross-sectional manner and in a longitudinal design aiming at the prediction of the emergence and recurrence of addictive behaviour. Second, based on a comprehensive cross-sectional and longitudinal neuropsychological and psychopathological characterisation of subjects/patients, we will link the neurobiological findings on learning mechanisms to specific cognitive, affective and behavioural dysfunctions and learning under the influence of alcohol. Third, all our work will be flanked by multivariate pattern analyses, which may help to refine both patient profiles for therapeutic interventions and neurobiological and neurochemical findings.
For further information, please see the website of the German Research Foundation.
Neurobiological correlates of behavioral addictions
In different projects we investigates the mechanisms of the development and maintenance of non-substance-related addictions (behavioral addictions), with an emphasis on gambling and internet use (e.g. computer games). The utilized research methods include imaging and psychophysiological measures, behavioral analyses, psychometric and epidemiological studies of different population samples, as well as research in therapy and healthcare. The main focus of our neurobiological research is on alterations in the mesocorticolimbic system of the brain. For further information on the phenomenon of gambling as well as excessive internet use, current research, and publications, see the webpage of the Research Group on Behavioral Addictions.
Effects of baclofen on neuronal correlates of cue reactivity, reward processing and executive functions in alcohol-dependent patients
The focus of this study is the investigation of the neurobiological correlates of a pharmacological treatment with Baclofen: cue-induced brain activation during the processing of alcohol-associated stimuli, executive functioning as well as reward processing will be assessed using functional imaging techniques in a group of alcohol-dependent patients. The major aim is to elucidate neural mechanisms that are crucially involved in individual treatment responses using this promising anti-craving agent.
The Meaning of socio-emotional and neurobiological factors in the school learning process (SELF)
Scientists of education, psychologists and neuroscientists examine the meaning of socio-emotional factors in the school learning process. Based on the extant research, this study is built upon two main research questions: (1) How are socio-emotional factors related to scholastic motivation? (2) Why are these factors only relevant for some students and not for others and what role does the type of motivation play? Due to the complexity of the relationship between socio-emotional factors and learning processes in school contexts a (1) quantitative data collection using questionnaires, (2) a neurobiological experimental design and (3) qualitative interviews are combined in a method triangulative procedure.
For further information, please see the website of the SELF project.
Imagination as individualized method of emotion induction in fMRI
In this project, the brain functional correlates of emotions are studied, in detail we applied fMRI imaging in different tasks of emotion processing and emotion induction. The used paradigms implicate a newly developed method of individualized emotion induction, which is based on methods of emotion induction in psychotherapy. The study aims at clarifying shared and distinct neuronal mechanisms in different types of emotion induction as well as the development of a valid method of individualized emotion induction in an fMRI setup, which will be used in further projects on emotion focused work in psychotherapy.
AERIAL: Addiction: Early Recognition and Intervention Across the Lifespan
Addictive disorders are among the most frequent and costly disorders in industrialized countries. While substantial research focused on treatment of single substance use disorders, most interventions do not address comorbid disorders sufficiently, are provided too late, do not reach the majority of addicted subjects and are not adjusted with respect to environmental stressors, affective comorbidity and age-specific contexts.
The main aim of the consortium is to improve the healthcare 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 substance use disorders, particularly alcohol- or tobacco-related, including as major target groups: 1) adolescents, 2) adults, and 3) older adults. We will use state-of-the-art basic science approaches to assess combinatorial effects of the different substances 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 from Adolescent Psychiatry and from a systematic assessment of 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.
Our research group cooperates with many research institutes in Berlin as well as with multiple national and international research units, e.g.:
- Central Institute for Mental Health, Mannheim (Andreas Meyer-Lindenberg, Falk Kiefer)
- Institute for Systemic Neuroscience, University Clinic Carl Gustav Carus, Clinic und Policlinic for Psychiatry and Psychiatry, Technical University Dresden (Michael Smolka, Hans-Ulrich Wittchen, Ulrich Zimmermann)
- Department of Neuroscience, University Pittsburgh, PA USA (Anthony A. Grace)
- Department of Nuclear Medicine and Research Center for Advanced Science and Technology, Tokyo University, Japan (Yoshitaka Kumakura)
- Department of Nuclear Medicine, Ludwig Maximilian University, Munich (Paul Cumming)
- Department of Psychology, Stanford University, CA, USA (Brian Knutson)
- Translational Neuromodeling Unit, Department of Biomedical Engineering, University of Zurich and ETH Zurich (Quentin Huys)
- Behavioural and Clinical Neuroscience Institute, Department of Psychiatry, University of Cambridge (Valerie Voon)
- Institute of Psychiatry, Psychology & Neuroscience, Centre for Population Neuroscience and Precision Medicine (PONS), King's College London, University of London (Gunter Schumann)