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Domain C: Specific interventions for impaired control and loss of control

The focus of Domain C is on modifying learning and control mechanisms in people with substance misuse. Interventions will begin by examining the modification of learning and the effects of physical activity on cognitive control. We will examine cognitive, emotional and behavioural training, as well as neurobiological interventions, such as brain stimulation or specific pharmacological therapies, directed at the mechanisms identified in Domain A and Domain B. To achieve this, domain C will use the information on risk and protective factors observed in domain A under real-life conditions, as well as the paradigms on learning processes and executive control from domain B and their computational modelling. Domain C will therefore be more and more able to identify the most efficient intervention strategies to strengthen control mechanisms and modify maladaptive learning mechanisms. This will then result in specific mechanism-based interventions for alcohol dependent individuals as well as for individuals suffering from other addictions.

C01: Modification of the imbalance between cognitive control and habitual behavior in addictive disorders

The current project investigates habitual and goal-directed decision-making behaviour in individuals with alcohol use disorders using behavioural experiments and functional imaging (fMRI). The focus is on the question to what extent the extent of habitual and goal-directed behaviour is related to the loss of control over alcohol consumption. Different behavioural measures of habitual and goal-directed behavioural control will be used to a) predict clinical trajectories from the A01/S01 cohort, b) examine the influence of addiction-specific reinforcers on behavioural control, and c) compare mechanisms of habit formation and motor routines. Project management: Prof. Dr. Tanja Endrass, Technical University of Dresden Prof. Dr. Florian Schlagenhauf, Charité - University Medicine Berlin Project collaborators: Viktoria Arndt, Dresden University of Technology Julia Berghäuser, Dresden University of Technology Claudia Ebrahimi, Charité - University Medicine Berlin Sophie Tragert, Charité - University Medicine Berlin

C02: Neuromodulation and mindfulness as therapeutic treatment in abstinent patients with AUD

Mindfulness-based interventions have been shown to effectively reduce cue reactivity and alcohol intake in individuals with alcohol use disorder (AUD), possibly by enhancing behavioral control and modulating prefrontal brain regions. Additionally, neuromodulation has been suggested as a treatment for AUD, as it can improve behavioral control through modulation of frontal midline theta (FMΘ) oscillations. C02 aims to investigate the effect of transcutaneous vagus nerve stimulation (tVNS) as an adjunct treatment to a mindfulness-based relapse prevention (MBRP) program in detoxified patients with AUD. In addition, we will uncover the causal role of FMΘ oscillations for MBI-related increase of behavioral control using closed-loop transcranial alternating current stimulation (cl-tACS), a novel method to directly enhance or suppress brain oscillations at specific frequencies. This will not only elucidate the causal role of FMΘ in MBRP, but also open up new avenues to specifically increase behavioral control in AUD using innovative neuromodulation techniques. Project Leaders: Prof. Dr. Anne Beck, HMU Health and Medical University Potsdam Prof. Dr. Nina Romanczuk-Seiferth, MSB Medical School Berlin Prof. Dr. Surjo R. Soekadar, Charité – Universitätsmedizin Berlin Project Collaborators: Dr. Annika Rosenthal, HMU Health and Medical University Potsdam, Charité – Universitätsmedizin Berlin Dr. Maria Garbusow, MSB Medical School Berlin - mit unter Team gelistet werden? Björn Apfel, Charité – Universitätsmedizin Berlin David Haslacher, Charité – Universitätsmedizin Berlin

C03: Modification of reactivity to alternative reinforcing stimuli and cognitive control through exercise therapy in human tobacco use disorder

This project will investigate whether acute and/or chronic stress exposure can exacerbate PIT effects and whether such effects influence the loss or regaining of control over substance use in currently non-detoxified, i.e. continuing users, with mild to moderate alcohol use disorder. Participants will be recruited from the A01/S01 cohort, providing the opportunity to track their substance use over one year. Currently active smokers with tobacco use disorder will also be studied using a general PIT paradigm to compare cognitive and neurobiological correlates in people with alcohol versus tobacco use disorder. Finally, a specific PIT paradigm for individuals with alcohol use disorder will be developed and its neurobiological correlates measured. Project management: Prof. Dr. Dr. Andreas Heinz, Charité - Universitätsmedizin Berlin PD Dr. Maximilian Pilhatsch, Technical University of Dresden Project collaborators: Matt Belanger, Dresden University of Technology Hao Chen, Dresden University of Technology Dr Claudia Ebrahimi, Charité - University Medicine Berlin Pascale Fischbach, Dresden University of Technology Dr. Maria Garbusow, Charité - University Medicine Berlin Angela Hentschel, Dresden University of Technology Carlotta Riemerschmid, Charité - University Medicine Berlin Prof. Dr. Michael N. Smolka, Dresden University of Technology

C04: Modifying cue reactivity using neurofeedback in people with AUD

We will use the alcohol deprivation effect (ADE) rat model to identify individual animals that develop alcohol dependence. For this, we will identify individual differences in the tendency to attribute particular value to those stimuli that predict reward. We will investigate whether this predicts the development of alcohol dependence. We will examine specific Pavlovian mechanisms including PIT. Building on these studies, we will apply neuromodulatory interventions to influence the attribution of special motivational value to alcohol stimuli and measure their molecular correlates. In a further step, we will investigate the preventive efficacy of neuromodulatory interventions against the development of dependent behaviour. Project management: Prof. Dr. Josef Priller, Charité - Universitätsmedizin Berlin Prof. Dr. Christine Winter, Charité - University Medicine Berlin Project collaborators: Dr. Chotima Böttcher, Charité - Universitätsmedizin Berlin Dr. Ravit Hadar, Charité - University Medicine Berlin Aileen Hakus, Charité - Universitätsmedizin Berlin

C05: Towards causal insights into contextual influences on substance use: Incorporating momentary interventions into everyday life

The purpose of project C05 is explained in a video.

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