Conflicts between long-term goals (e.g., maintaining health, achieving good grades) and immediate de-sires or strong habits (e.g., to smoke; eat a tasty dessert; to watch TV) are frequent in everyday life. Failures of self-control in such conflict situations are sources of a wide range of harmful behaviors including substance-related and addictive disorders (SAD), which incur immense personal and societal costs. The long-term aim of project C1 is to investigate whether impaired cognitive control, performance-monitoring, value-based decision-making and dysfunctional interactions between the underlying brain systems constitute vulnerability factors and/or mediating mechanisms underlying non-pathological daily self-control fail-ures (SCFs) as well as addictive behaviors. In the first funding period (07/2012-06/2016) project C1 launched a prospective cohort study using a multi-level approach that combines (i) a comprehensive clinical assessment, (ii) be-havioral task batteries assessing cognitive control and decision-making functions, (iii) task-related and resting state fMRI, and (iv) smartphone-based experience sampling of daily SCFs. In the first funding phase, from a representative community sample we recruited three groups of participants (each n = 100; age 20 - 26) with (a) symptoms of non-substance related and (b) substance-related addictive disorders and (c) syndrome-free controls. Hypothesis-driven cross-sectional analyses revealed that reduced error-related activity in brain areas involved in performance-monitoring and salience processing (anterior insu-la; aINS) and inhibitory control (right inferior frontal gyrus; IFG) as well as insufficient modulation of neural value signals in the ventromedial prefrontal cortex (vmPFC) by long-term goals predicted higher prone-ness to daily SCFs. Moreover, reduced conflict-related brain activity in performance-monitoring areas was associated with repeated unsuccessful attempts to quit smoking. These findings are consistent with a working model according to which deficient performance-monitoring, insufficient recruitment of cognitive control networks in response to conflicts or errors, and insufficient top-down modulation of value signals by long-term goals increase proneness to commit daily SCFs and show symptoms of SAD. Based on these encouraging results, in the second funding period project C1 will be expanded into a prospective-longitudinal cohort study with yearly clinical follow-up assessments and continued multi-level as-sessments 3 and 5 years after initial recruitment. This will provide the unique opportunity to examine with a cross-lagged panel design whether daily SCFs and SAD can be predicted by (a) cognitive control com-petencies as derived from latent variable analyses of our task battery and by (b) activity in brain areas involved in performance-monitoring, cognitive control, and value-based decision-making. This will not only allow us to investigate with sufficient statistical power (1) commonalities and differences in cognitive control functions between subgroups of SAD, but also (2) to address the central unresolved question whether cognitive control and performance-monitoring impairments are causally involved in the development of real-life SCFs and SAD.

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