Neurocognitive mechanisms of the negative retrieval bias in depression

About This Grant

PROJECT SUMMARY/ABSTRACT Major Depressive Disorder (MDD) is associated with emotional memory deficits that have substantial downstream consequences, but treatment is limited by poor understanding of the upstream mechanisms driving such behavior. Our recent work applying the Drift Diffusion Model (DDM) suggests that depression disrupts emotional memory by increasing “old” evidence accumulation for both old and new negative material, indicating a negative bias specific to retrieval. The DDM can account for the negative retrieval bias in depression via two mechanisms: increased familiarity, in which depression strengthens evidence for all negative memories—even false ones; or motivated retrieval, in which depression increases the propensity for judging all negative evidence as “old”—even if it is weak. Thus, it is unclear whether depression affects the quality of negative memories or the way they are acted upon, limiting both basic and applied depression research. The proposed work distinguishes the familiarity vs. motivated retrieval accounts via the Parceling Recognition Into Strength and Motivation (PRISM) task, which isolates memory strength from decision processes by generalizing single-item recognition behavior to forced choices between targets and lures. The logic is elegant: Though a motivation to respond “old” can bias single-item judgments, it cannot play a role when judging which of two items is old; thus, familiarity is implicated when differences in accumulation rates extend across tasks, and motivation is implicated when they do not. By extending the PRISM task to emotional memory in depression, the PI seeks to more precisely characterize the negative retrieval bias, with the primary goal of identifying false familiarity vs. motivated retrieval as potential targets for basic and applied research (Aim 1). Moreover, the PI will build expertise in model-based neuroimaging (Goal 1) and curate a practical skill set in clinical research (Goal 2) by running a functional magnetic resonance imaging (fMRI) version of the PRISM task to identify brain areas supporting retrieval that are affected by depression (Aim 2). With substantial research and training opportunities available at McLean Hospital/Harvard Medical School, the mentorship of Dr. Dan Dillon (a well-established clinical neuroscientist), Dr. Courtney Beard (an outstanding translational researcher and licensed clinical psychologist), and Dr. Michael J. Frank (a renowned computational neuroscientist), with consultation from Drs. Jeffrey Starns (developer of the PRISM task), Dr. David Badre (a leading cognitive neuroscientist with expertise in fMRI), and Dr. Avram Holmes (an expert in large-scale brain networks focusing on emotion and cognition), the applicant will receive advanced training in career development, model-based fMRI, and translational research. Together, the proposed research and training plans will launch the PI into an independent research career focused on identifying neurocognitive treatment targets for depression.