Browsing by Author "Brown, Vanessa M."

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    Associability-modulated loss learning is increased in posttraumatic stress disorder
    Brown, Vanessa M.; Zhu, Lusha; Wang, John M.; Frueh, B. Christopher; Casas, Brooks; Chiu, Pearl H. (eLife Sciences, 2018-01-09)
    Disproportionate reactions to unexpected stimuli in the environment are a cardinal symptom of posttraumatic stress disorder (PTSD). Here, we test whether these heightened responses are associated with disruptions in distinct components of reinforcement learning. Specifically, using functional neuroimaging, a loss-learning task, and a computational model-based approach, we assessed the mechanistic hypothesis that overreactions to stimuli in PTSD arise from anomalous gating of attention during learning (i.e., associability). Behavioral choices of combat- deployed veterans with and without PTSD were fit to a reinforcement learning model, generating trial-by-trial prediction errors (signaling unexpected outcomes) and associability values (signaling attention allocation to the unexpected outcomes). Neural substrates of associability value and behavioral parameter estimates of associability updating, but not prediction error, increased with PTSD during loss learning. Moreover, the interaction of PTSD severity with neural markers of associability value predicted behavioral choices. These results indicate that increased attention- based learning may underlie aspects of PTSD and suggest potential neuromechanistic treatment targets.
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    Behavioral Training of Reward Learning Increases Reinforcement Learning Parameters and Decreases Depression Symptoms Across Repeated Sessions
    Goyal, Shivani (Virginia Tech, 2023-12)
    Background: Disrupted reward learning has been suggested to contribute to the etiology and maintenance of depression. If deficits in reward learning are core to depression, we would expect that improving reward learning would decrease depression symptoms across time. Whereas previous studies have shown that changing reward learning can be done in a single study session, effecting clinically meaningful change in learning requires this change to endure beyond task completion and transfer to real world environments. With a longitudinal design, we investigate the potential for repeated sessions of behavioral training to create change in reward learning and decrease depression symptoms across time. Methods: 929 online participants (497 depression-present; 432 depression-absent) recruited from Amazon’s Mechanical Turk platform completed a behavioral training paradigm and clinical selfreport measures for up to eight total study visits. Participants were randomly assigned to one of 12 arms of the behavioral training paradigm, in which they completed a probabilistic reward learning task interspersed with queries about a feature of the task environment (11 learning arms) or a control query (1 control arm). Learning queries trained participants on one of four computational-based learning targets known to affect reinforcement learning (probability, average or extreme outcome values, and value comparison processes). A reinforcement learning model previously shown to distinguish depression related differences in learning was fit to behavioral responses using hierarchical Bayesian estimation to provide estimates of reward sensitivity and learning rate for each participant on each visit. Reward sensitivity captured participants’ value dissociation between high versus low outcome values, while learning rate informed how much participants learned from previously experienced outcomes. Mixed linear models assessed relationships between model-agnostic task performance, computational model-derived reinforcement learning parameters, depression symptoms, and study progression. Results: Across time, learning queries increased individuals’ reward sensitivities in depression-absent participants (β = 0.036, p =< 0.001, 95% CI (0.022, 0.049)). In contrast, control queries did not change reward sensitivities in depression-absent participants across time ((β = 0.016, p = 0.303, 95% CI (-0.015, 0.048)). Learning rates were not affected across time for participants receiving learning queries (β = 0.001, p = 0.418, 95% CI (-0.002, 0.004)) or control queries (β = 0.002, p = 0.558, 95% CI (-0.005, 0.009). Of the learning queries, those targeting value comparison processes improved depression symptoms (β = -0.509, p = 0.015, 95% CI (-0.912, - 0.106)) and increased reward sensitivities across time (β = 0.052, p =< 0.001, 95% CI (0.030, 0.075)) in depression-present participants. Increased reward sensitivities related to decreased depression symptoms across time in these participants (β = -2.905, p = 0.002, 95% CI (-4.75, - 1.114)). Conclusions: Multiple sessions of targeted behavioral training improved reward learning for participants with a range of depression symptoms. Improved behavioral reward learning was associated with improved clinical symptoms with time, possibly because learning transferred to real world scenarios. These results support disrupted reward learning as a mechanism contributing to the etiology and maintenance of depression and suggest the potential of repeated behavioral training to target deficits in reward learning.
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    In Cocaine Dependence, Neural Prediction Errors During Loss Avoidance Are Increased With Cocaine Deprivation and Predict Drug Use
    Wang, John M.; Zhu, Lusha; Brown, Vanessa M.; De La Garza, Richard II; Newton, Thomas F.; Casas, Brooks; Chiu, Pearl H. (Elsevier, 2018-08-03)
    Background: In substance-dependent individuals, drug deprivation and drug use trigger divergent behavioral responses to environmental cues. These divergent responses are consonant with data showing that short- and long-term adaptations in dopamine signaling are similarly sensitive to state of drug use. The literature suggests a drug state–dependent role of learning in maintaining substance use; evidence linking dopamine to both reinforcement learning and addiction provides a framework to test this possibility. Methods: In a randomized crossover design, 22 participants with current cocaine use disorder completed a probabilistic loss-learning task during functional magnetic resonance imaging while on and off cocaine (44 sessions). Another 54 participants without Axis I psychopathology served as a secondary reference group. Within-drug state and paired-subjects’ learning effects were assessed with computational model–derived individual learning parameters. Model-based neuroimaging analyses evaluated effects of drug use state on neural learning signals. Relationships among model-derived behavioral learning rates (α+, α−), neural prediction error signals (δ+, δ−), cocaine use, and desire to use were assessed. Results: During cocaine deprivation, cocaine-dependent individuals exhibited heightened positive learning rates (α+), heightened neural positive prediction error (δ+) responses, and heightened association of α+ with neural δ+ responses. The deprivation-enhanced neural learning signals were specific to successful loss avoidance, comparable to participants without psychiatric conditions, and mediated a relationship between chronicity of drug use and desire to use cocaine. Conclusions: Neurocomputational learning signals are sensitive to drug use status and suggest that heightened reinforcement by successful avoidance of negative outcomes may contribute to drug seeking during deprivation. More generally, attention to drug use state is important for delineating substrates of addiction.
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    Reinforcement Learning Disruptions in Individuals With Depression and Sensitivity to Symptom Change Following Cognitive Behavioral Therapy
    Brown, Vanessa M.; Zhu, Lusha; Solway, Alec; Wang, John M.; McCurry, Katherine L.; Casas, Brooks; Chiu, Pearl H. (American Medical Association, 2021-07-28)
    IMPORTANCE Major depressive disorder is prevalent and impairing. Parsing neurocomputational substrates of reinforcement learning in individuals with depression may facilitate a mechanistic understanding of the disorder and suggest new cognitive therapeutic targets. OBJECTIVE To determine associations among computational model–derived reinforcement learning parameters, depression symptoms, and symptom changes after treatment. DESIGN, SETTING, AND PARTICIPANTS In this mixed cross-sectional–cohort study, individuals performed reward and loss variants of a probabilistic learning task during functional magnetic resonance imaging at baseline and follow-up. A volunteer sample with and without a depression diagnosis was recruited from the community. Participants were assessed from July 2011 to February 2017, and data were analyzed from May 2017 to May 2021. MAIN OUTCOMES AND MEASURES Computational model–based analyses of participants’ choices assessed a priori hypotheses about associations between components of reward-based and loss-based learning with depression symptoms. Changes in both learning parameters and symptoms were then assessed in a subset of participants who received cognitive behavioral therapy (CBT). RESULTS Of 101 included adults, 69 (68.3%) were female, and the mean (SD) age was 34.4 (11.2) years. A total of 69 participants with a depression diagnosis and 32 participants without a depression diagnosis were included at baseline; 48 participants (28 with depression who received CBT and 20 without depression) were included at follow-up (mean [SD] of 115.1 [15.6] days). Computational model–based analyses of behavioral choices and neural data identified associations of learning with symptoms during reward learning and loss learning, respectively. During reward learning only, anhedonia (and not negative affect or arousal) was associated with model-derived learning parameters (learning rate: posterior mean regression β = −0.14; 95%credible interval [CrI], −0.12 to −0.03; outcome sensitivity: posterior mean regression β = 0.18; 95% CrI, 0.02 to 0.37) and neural learning signals (moderation of association between striatal prediction error and expected value signals: t₉₇ = −2.10; P = .04). During loss learning only, negative affect (and not anhedonia or arousal) was associated with learning parameters (outcome shift: posterior mean regression β = −0.11; 95% CrI, −0.20 to −0.01) and disrupted neural encoding of learning signals (association with subgenual anterior cingulate prediction error signals: r = −0.28; P = .005). Symptom improvement following CBT was associated with normalization of learning parameters that were disrupted at baseline (reward learning rate: posterior mean regression β = 0.15; 90% CrI, 0.001 to 0.41; loss outcome shift: posterior mean regression β = 0.42; 90% CrI, 0.09 to 0.77). CONCLUSIONS AND RELEVANCE In this study, the mapping of reinforcement learning components to symptoms of major depression revealed mechanistic features associated with these symptoms and points to possible learning-based therapeutic processes and targets.
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    Reinforcement learning processes as forecasters of depression remission
    Bansal, Vansh; McCurry, Katherine L.; Lisinski, Jonathan; Kim, Dong-Youl; Goyal, Shivani; Wang, John M.; Lee, Jacob; Brown, Vanessa M.; LaConte, Stephen M.; Casas, Brooks; Chiu, Pearl H. (Elsevier, 2024-09-11)
    Background: Aspects of reinforcement learning have been associated with specific depression symptoms and may inform the course of depressive illness. Methods: We applied support vector machines to investigate whether blood‑oxygen-level dependent (BOLD) responses linked with neural prediction error (nPE) and neural expected value (nEV) from a probabilistic learning task could forecast depression remission. We investigated whether predictions were moderated by treatment use or symptoms. Participants included 55 individuals (n = 39 female) with a depression diagnosis at baseline; 36 of these individuals completed standard cognitive behavioral therapy and 19 were followed during naturalistic course of illness. All participants were assessed for depression diagnosis at a follow-up visit. Results: Both nPE and nEV classifiers forecasted remission significantly better than null classifiers. The nEV classifier performed significantly better than the nPE classifier. We found no main or interaction effects of treatment status on nPE or nEV accuracy. We found a significant interaction between nPE-forecasted remission status and anhedonia, but not for negative affect or anxious arousal, when controlling for nEV-forecasted remission status. Limitations: Our sample size, while comparable to that of other studies, limits options for maximizing and evaluating model performance. We addressed this with two standard methods for optimizing model performance (90:10 train and test scheme and bootstrapped sampling). Conclusions: Results support nEV and nPE as relevant biobehavioral signals for understanding depression outcome independent of treatment status, with nEV being stronger than nPE as a predictor of remission. Reinforcement learning variables may be useful components of an individualized medicine framework for depression healthcare.
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    Threat-induced anxiety during goal pursuit disrupts amygdala-prefrontal cortex connectivity in posttraumatic stress disorder
    Sun, Delin; Gold, Andrea L.; Swanson, Chelsea A.; Haswell, Courtney C.; Brown, Vanessa M.; Stjepanovic, Daniel; LaBar, Kevin S.; Morey, Rajendra A.; Beckham, Jean C.; Brancu, Mira; Calhoun, Patrick S.; Dedert, Eric; Elbogen, Eric B.; Green, Kimberly T.; Kimbrel, Nathan; Kirby, Angela; McCarthy, Gregory; Moore, Scott D.; Runnals, Jennifer J.; Swinkels, Cindy; Tupler, Larry A.; Van Voorhees, Elizabeth E.; Weiner, Richard D. (2020-02-10)
    To investigate how unpredictable threat during goal pursuit impacts fronto-limbic activity and functional connectivity in posttraumatic stress disorder (PTSD), we compared military veterans with PTSD (n = 25) vs. trauma-exposed control (n = 25). Participants underwent functional magnetic resonance imaging (fMRI) while engaged in a computerized chase-and-capture game task that involved optimizing monetary rewards obtained from capturing virtual prey while simultaneously avoiding capture by virtual predators. The game was played under two alternating contexts-one involving exposure to unpredictable task-irrelevant threat from randomly occurring electrical shocks, and a nonthreat control condition. Activation in and functional connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC) was tested across threat and nonthreat task contexts with generalized psychophysiological interaction (gPPI) analyses. PTSD patients reported higher anxiety than controls across contexts. Better task performance represented by successfully avoiding capture by predators under threat compared with nonthreat contexts was associated with stronger left amygdala-vmPFC functional connectivity in controls and greater vmPFC activation in PTSD patients. PTSD symptom severity was negatively correlated with vmPFC activation in trauma-exposed controls and with right amygdala-vmPFC functional connectivity across all participants in the threat relative to nonthreat contexts. The findings showed that veterans with PTSD have disrupted amygdala-vmPFC functional connectivity and greater localized vmPFC processing under threat modulation of goal-directed behavior, specifically related to successfully avoiding loss of monetary rewards. In contrast, trauma survivors without PTSD relied on stronger threat-modulated left amygdala-vmPFC functional connectivity during goal-directed behavior, which may represent a resilience-related functional adaptation.