Decoding context memories for threat in large-scale neural networks.

Humans are often tasked with determining the degree to which a given situation poses threat. Salient cues present during prior events help bring online memories for context, which plays an informative role in this process. However, it is relatively unknown whether and how individuals use features of the environment to retrieve context memories for threat, enabling accurate inferences about the current level of danger/threat (i.e. retrieve appropriate memory) when there is a degree of ambiguity surrounding the present context. We leveraged computational neuroscience approaches (i.e. independent component analysis and multivariate pattern analyses) to decode large-scale neural network activity patterns engaged during learning and inferring threat context during a novel functional magnetic resonance imaging task. Here, we report that individuals accurately infer threat contexts under ambiguous conditions through neural reinstatement of large-scale network activity patterns (specifically striatum, salience, and frontoparietal networks) that track the signal value of environmental cues, which, in turn, allows reinstatement of a mental representation, primarily within a ventral visual network, of the previously learned threat context. These results provide novel insight into distinct, but overlapping, neural mechanisms by which individuals may utilize prior learning to effectively make decisions about ambiguous threat-related contexts as they navigate the environment.

The influence of aerobic exercise on model-based decision making in women with posttraumatic stress disorder.

Individuals with PTSD often exhibit deficits in executive functioning. An unexplored aspect of neurocognitive functions associated with PTSD is the type of learning system engaged in during decision-making. A model-free (MF) system is habitual in nature and involves trial-and-error learning that is often updated based on the most recent experience (e.g., repeat action if rewarded). A model-based (MB) system is goal-directed in nature and involves the development of an abstract representation of the environment to facilitate decisions (e.g., choose sequence of actions according to current contextual state and predicted outcomes). The existing neurocognitive literature on PTSD suggests the hypothesis of greater reliance on MF vs MB learning strategies when navigating their environment. While MF systems may be more cognitively efficient, they do not afford flexibility when making prospective predictions about likely outcomes of different decision-tree branches. Emerging research suggests that an acute bout of aerobic exercise improves certain aspects of neurocognition, and thereby could promote the utilization of MB over MF systems during decision making, although prior research has not yet tested this hypothesis. Accordingly, the current study administered a lab-based two-stage Markov decision-making task capable of discriminating MF vs MB decision making, in order to determine if moderate-intensity aerobic exercise (either shortly after or 30-minutes after the exercise bout has ended) promotes greater engagement in MB behavioral strategies compared to light-intensity aerobic exercise in adult women with and without PTSD (N=61). Results revealed that control women generally displayed higher levels of MB behavior that was further increased following immediate exercise, particularly moderate-intensity exercise. By contrast, the PTSD group generally displayed lower levels of MB behavior, and exhibited greater MB behavior when completing the task following moderate-intensity aerobic exercise compared to light-intensity aerobic exercise regardless of whether there was a short or long delay between exercise and the task. Additionally, women with PTSD demonstrated less impairment in MB decision-making compared to controls following moderate-intensity aerobic exercise. These results suggest that an acute bout of moderate-intensity aerobic exercise boosts MB behavior in women with PTSD, and suggests that aerobic exercise may play an important role in enhancing cognitive outcomes for PTSD.

Aerobic exercise after extinction learning reduces return of fear and enhances memory of items encoded during extinction learning.

Fear conditioning paradigms are widely used in laboratory settings to discover treatments that enhance memory consolidation and various fear processes (extinction learning, limit return of fear) that are relevant targets of exposure-based therapies. However, traditional lab-based paradigms often use the exact same conditioned stimuli for acquisition and extinction (typically differentiated with a context manipulation), whereas the opposite is true in clinical settings, as exposure therapy rarely (if ever) uses precisely the exact same stimuli from an individual's learning history. Accordingly, this study utilized a novel three-day category-based fear conditioning protocol (that uses categories of non-repeating objects [animals and tools] as conditioned stimuli during fear conditioning and extinction) to determine if aerobic exercise enhances the consolidation of extinction learning (reduces return of fear) and memory (for items encoded during extinction) during subsequent tests of extinction recall. Participants (n=40) completed a fear acquisition (day 1), fear extinction (day 2), and extinction recall (day 3) protocol. On day 1, participants completed a fear acquisition task in which they were trained to associate a category of conditioned stimuli (CS+) with the occurrence of an unconditioned stimulus (US). On day 2, participants were administered a fear extinction procedure during which CS+ and CS- categorical stimuli were presented in absence of the occurrence of the US. After completing the task, participants were randomly assigned to either receive moderate-intensity aerobic exercise (EX) or a light-intensity control (CON) condition. On day 3, participants completed fear recall tests (during which day 1, day 2, and novel CS+ and CS- stimuli were presented). Fear responding was assessed via threat expectancy ratings and skin conductance responses (SCR). During the fear recall tests, the EX group reported significantly lower threat expectancy ratings to the CS+ and CS- and exhibited greater memory of CS+ and CS- stimuli that were previously presented during day 2. There were no significant group differences for SCR. These results suggests that administration of moderate-intensity aerobic exercise following extinction learning contributes to reduced threat expectancies during tests of fear recall and enhanced memory of items encoded during extinction.

The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSD.

BACKGROUND: Posttraumatic Stress Disorder (PTSD) is commonly treated with exposure-based cognitive therapies that are based on the principles of fear acquisition and extinction learning. Elevations in one of the major endocannabinoids (anandamide) either via inhibition of the primary degrading enzyme (fatty acid amide hydrolase; FAAH) or via a genetic variation in the FAAH gene (C385A; rs324420) has resulted in accelerated extinction learning and enhanced extinction recall among healthy adults. These results suggest that targeting FAAH may be a promising therapeutic approach for PTSD. However, these effects have not yet been comprehensively examined in a PTSD population. METHODS: The current study examined whether genetic variation in the FAAH gene (CC [n = 49] vs AA/AC [n = 36] allele carriers) influences physiological (skin conductance), cognitive (threat expectancy), and neural (network and voxel-wise activation) indices of fear acquisition and extinction learning among a sample of adult women with PTSD (N = 85). RESULTS: The physiological, cognitive, and neural signatures of fear acquisition and extinction learning varied as a function of whether or not individuals possess the FAAH C385A polymorphism. For instance, we report divergent responding between CC and AA/AC allele carriers to CS + vs CS- in limbic and striatum networks and overall greater activation throughout the task among AA/AC allele carriers in several regions [e.g., inferior frontal, middle frontal, parietal] that are highly consistent with a frontoparietal network involved in higher-order executive functions. CONCLUSIONS: These results suggest that genetic variation within the FAAH gene influences physiological, cognitive, and neural signatures of fear learning in women with PTSD. In order to advance our understanding of the efficacy of FAAH inhibition as a treatment for PTSD, future clinical trials in this area should assess genetic variation in the FAAH gene in order to fully depict and differentiate the acute effects of a drug manipulation (FAAH inhibition) from more chronic (genetic) influences on fear extinction processes.