Periodic Reporting for period 4 - CCT (The psychology and neurobiology of cognitive control training in humans) Reporting period: 2020-05-01 to 2021-10-31 Summary of the context and overall objectives of the project Cognitive control regulates our thoughts and actions, helping us avoid impulsive behaviours that are inappropriate, costly or dangerous. In recent years, evidence has emerged that training in behavioural tasks that promote response inhibition or avoidance of specific stimuli can enhance cognitive control, reducing overeating and alcohol consumption. Despite the promising nature of cognitive control training (CCT), we know little about which CCT methods are most effective, how individual differences determine training outcomes, whether CCT produces benefits for real-life behaviour, and how CCT alters – and is determined by – the structure and function of the brain. My aim is to discover what works in CCT and how the effects of training relate to neurophysiology. Subproject 1 is the largest ever randomised trial on the effectiveness of different CCT methods for achieving weight loss, recruiting 36,000 participants worldwide to complete an app-based training programme. This study will reveal, with high statistical power, which CCT methods are the most effective and which individual differences are most important for producing real-life benefits. Subproject 2 is investigating how CCT influences neurobiology, and how individual differences in neurobiology influence CCT outcomes. In Subproject 2a, I focus on theoretically predicted changes to GABAergic systems in prefrontal and motor cortex, testing the effect of GABAergic brain stimulation on training outcomes. In Subproject 2b, I will use concurrent brain stimulation (TMS) and brain imaging (fMRI) to test how CCT alters top-down coupling between prefrontal cortex and remote regions that mediate reward and emotion. I will also study how CCT alters, and is altered by, white matter microstructure. This project promises to advance understanding of the causal determinants and moderators of CCT, with implications for its suitability as a clinical adjunct in addiction therapy and behaviour change. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far Work to date has focused on validation studies underpinning the launch of the smartphone app, as well as exploring mechanisms by which the policy implications of the wider project can be fully realised. To date the main achievements are1) The generation of results which question the assumption that transcranial direct current stimulation is positively effective in altering eating behaviour.2) The promising validation of affective priming as an assay of attitudes toward food stimuli, with this task be deployed in the smartphone app.3) Prominent coverage of our work in the BBC One programme, the Truth About Obesity, see https://twitter.com/RestrainProject/status/989863466432434176 which has led to over 3,800 participants signing up in advance for the large-scale study when it is launched in 2019. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) In the next phase of the project we will launch the smartphone app, revealing on a large scale which of several online forms of cognitive control training (CCT) are most effective in changing eating behaviour and cognition. We will then examine the association between any changes in behaviour caused by CCT and neurobiology, focusing in particular on changes in brain white matter, connectivity, and how individual differences in neurobiology influence CCT outcomes.