PROJECT SUMMARY. The factors governing what we will remember and what we will forget from each day have a profound importance for our success in everyday life. Recent evidence suggests that moderate (vs. weak or strong) neural activation of a memory in visual processing regions of the brain can trigger inhibition that weakens the memory and leads to forgetting. The brain networks and cognitive factors involved in this process are poorly understood at this time. The overarching goal of this proposal is to understand the factors that influence activation-dependent forgetting, and to evaluate whether people can exploit this mechanism to improve their memory. The project will use functional magnetic resonance imaging (fMRI) and state-of-the-art analysis techniques (multivariate pattern analyses, neurofeedback) to measure memory activations from moment to moment and link this to behavior outcomes in tests of learning and memory. Specific Aim 1 will test whether memory activations can be biased intentionally to forget specific memories. We will also use fMRI neurofeedback – a procedure in which online feedback of neural activation is provided to the participant for the purpose of self-regulation – to evaluate whether people can learn to calibrate the strength of memory activation to selectively promote forgetting or remembering. Specific Aim 2 will test how contextual factors automatically bias memory activation and thereby influence learning and memory processes. Forgetting is adaptive when it helps us learn regularities in our environment, and we hypothesize that multiple aspects of context interact to bias memory activation to guide adaptive forgetting. Specific Aim 3 will test whether uncertainty about the behavioral relevance of information in working memory will bias neural activations and produce unintentional forgetting. Strategically reorganizing the contents of working memory in response to task demands causes the activation of memory items to wax and wane, and we will evaluate whether this produces memories that linger with moderate levels of activation and thus become vulnerable to weakening and forgetting. Understanding the deliberate and automatic factors that bias activation-dependent forgetting could change the field's view of both remembering and forgetting, and it could lay the foundation for neurologically inspired training and therapy.