Jarrod A. Lewis-Peacock, Ph.D. - US grants

? DESCRIPTION (provided by applicant): The overall objective of the current project is to understand the neural mechanisms that allow us to remove information from our current thoughts. For the last half century, it has been known that we have a limited capacity to concurrently keep information in mind at one time, typically considered to be about 7 items. This capacity is often referred to as working memory. Surprisingly, what is not known, however, is how we remove information from working memory, so as to either allow other items in or to clear it entirely. Understanding how information is removed from working memory, and which brain systems allow one to do so, is important not only from the perspective of obtaining a better understanding of how the brain influences the way we think, but also because such an understanding has important implications for psychological disorders. Many psychological disorders are characterized by an inability to remove certain types of information from working memory. For example, individuals with obsessive-compulsive disorder have difficulty not thinking about what harm might befall them or others, and individuals with depression have difficulty not ruminating on negative ideas and feelings. One of the reasons that it has been so hard to understand how information is removed from working memory is the large challenge involved in determining what a person might be thinking of at a particular point in time, and/or knowing whether indeed thoughts have been cleared from working memory. The goal of this project is to leverage brain-imaging techniques to overcome this problem. Recent techniques drawn from computer science allow one to characterize the pattern of brain activity associated with particular items (e.g., apples, pears, grapes, melons) or particular categories of items (frui, tools, faces, buildings). The project will utilize such methods to verify, via a pattern of brain activity, on which occasions individuals have either cleared their mind of certain items, or replaced them with other thoughts (e.g., switched from thinking about an apple to thinking about a pear, switched from thinking about an apple to thinking about a hammer). Then, the study will test the hypothesis that a certain set of brain regions in the prefrontal cortex plays a central roe in successfully changing the nature of the information held in working memory. In addition, the proposed research will examine how these neural mechanisms vary depending on differences across individuals. In particular, the project is designed to gather information both on how much difficulty an individual reports in controlling his or her thoughts, and also on the topics and characteristics of an individual's everyday thoughts (e.g., they are usually about things that happened in the past, negative, vague in scope, etc.). It is predicted that individuals who have difficulty controlling their thoughts and who have vague and over general thoughts will have more difficulty removing information from working memory, and they will show less activity in brain regions that control such thoughts. If this hypothesis is confirmed, it could provide new avenues for therapeutic intervention for psychological disorders characterized by repetitive thought.

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.

PROJECT SUMMARY The overall objective of the current project is to understand how emotional thoughts can be removed from one's mind. Most psychiatric disorders are characterized by an inability to remove negative, intrusive, and maladaptive thoughts from mind. Previously examining whether an individual has purged a thought from mind has relied mainly on self-report measures (e.g., ?Yes, I stopped thinking about the car crash?). In the proposed research, the research team will use a combination of brain imaging approaches with machine learning techniques drawn from computer science to provide an objective neural marker of whether indeed a thought has been removed from mind. This approach builds on proven success with this technique pioneered by the research team. This prior work focused on the removal of (emotionally neutral) information from mind and demonstrated that suppressing a specific thought and clearing one's mind of all thought rely on different neural mechanisms. Moreover, the prior findings indicated that these mental operations differentially affect one's ability to take in new information after the old information has been removed. The focus of the proposed project will be to examine how emotional information is removed from current thought. The project will ask three main questions. First, it will examine whether the emotional valence of information affects the engagement and effectiveness of neural systems involved in removing information from mind. A series of parallel studies, one involving neuroimaging and the other examining people's behavior, are designed to examine whether these removal operations are affected by a) the emotional valence (positive, negative) of the information to be removed, b) the emotional valence of the information that should now be brought to mind and c) the match (e.g., positive, positive) or mismatch (positive, negative) between the valence of the information being removed and that which replaces it. Expectations are that negative information will be harder to remove and easier to be brought into current thought than positive information. Second, the project will examine whether the effectiveness of these removal operations varies across individuals. It will assess the degree to which individuals report that they have difficulty controlling their thoughts, the degree to which they have symptoms related to depression and anxiety, and their ability to hold and manipulate information in working memory. Expectations are that individuals who report difficulty in controlling their thoughts will have difficulty in removing information from mind, and that people with higher levels of depression will have specific difficulties in removing negative thoughts. Third, the project will examine whether individuals can be trained, using real-time feedback about brain function during neuroimaging, to effectively remove thoughts from mind by providing them with a sense of what it feels like to successfully remove a thought. The results of the proposed project will have important implications both for understanding the recurrent and intrusive thoughts that characterize psychopathology and for providing insights on how they might be reduced.