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.

Decision-making for concurrent reward and threat is differentially modulated by trauma exposure and PTSD symptom severity.

Trauma exposure, particularly interpersonal violence (IPV) traumas, are significant risk factors for development of mental health disorders, particularly posttraumatic stress disorder (PTSD). Studies attempting to disentangle mechanisms by which trauma confers risk and maintenance of PTSD have often investigated threat or reward learning in isolation. However, real-world decision-making often involves navigating concurrent and conflicting probabilities for threat and reward. We sought to understand how threat and reward learning interact to impact decision-making, and how these processes are modulated by trauma exposure and PTSD symptom severity. 429 adult participants with a range of trauma exposure and symptom severities completed an online version of the two stage Markov task, where participants make a series of decisions towards the goal of obtaining a reward, that embedded an intermediate threat or neutral image along the sequence of decisions to be made. This task design afforded the possibility to differentiate between threat avoidance vs diminished reward learning in the presence of threat, and whether these two processes reflect model-based vs model-free decision-making. Results demonstrated that trauma exposure severity, particularly IPV exposure, was associated with impairment in model-based learning for reward independent of threat, as well as with model-based threat avoidance. PTSD symptom severity was associated with diminished model-based learning for reward in the presence of threat, consistent with a threat-induced impairment in cognitively-demanding strategies for reward learning, but no evidence of heightened threat avoidance. These results highlight the complex interactions between threat and reward learning as a function of trauma exposure and PTSD symptom severity. Findings have potential implications for treatment augmentation and suggest a need for continued research.

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.

Large-scale neural network computations and multivariate representations during approach-avoidance conflict decision-making.

Many real-world situations require navigating decisions for both reward and threat. While there has been significant progress in understanding mechanisms of decision-making and mediating neurocircuitry separately for reward and threat, there is limited understanding of situations where reward and threat contingencies compete to create approach-avoidance conflict (AAC). Here, we leverage computational learning models, independent component analysis (ICA), and multivariate pattern analysis (MVPA) approaches to understand decision-making during a novel task that embeds concurrent reward and threat learning and manipulates congruency between reward and threat probabilities. Computational modeling supported a modified reinforcement learning model where participants integrated reward and threat value into a combined total value according to an individually varying policy parameter, which was highly predictive of decisions to approach reward vs avoid threat during trials where the highest reward option was also the highest threat option (i.e., approach-avoidance conflict). ICA analyses demonstrated unique roles for salience, frontoparietal, medial prefrontal, and inferior frontal networks in differential encoding of reward vs threat prediction error and value signals. The left frontoparietal network uniquely encoded degree of conflict between reward and threat value at the time of choice. MVPA demonstrated that delivery of reward and threat could accurately be decoded within salience and inferior frontal networks, respectively, and that decisions to approach reward vs avoid threat were predicted by the relative degree to which these reward vs threat representations were active at the time of choice. This latter result suggests that navigating AAC decisions involves generating mental representations for possible decision outcomes, and relative activation of these representations may bias subsequent decision-making towards approaching reward or avoiding threat accordingly.

How reliable are amygdala findings in psychopathy? A systematic review of MRI studies.

The amygdala is a key component in predominant neural circuitry models of psychopathy. Yet, after two decades of neuroimaging research on psychopathy, the reproducibility of amygdala findings is questionable. We systematically reviewed MRI studies (81 of adults, 53 of juveniles) to determine the consistency of amygdala findings across studies, as well as within specific types of experimental tasks, community versus forensic populations, and the lowest- versus highest-powered studies. Three primary findings emerged. First, the majority of studies found null relationships between psychopathy and amygdala structure and function, even in the context of theoretically relevant tasks. Second, findings of reduced amygdala activity were more common in studies with low compared to high statistical power. Third, the majority of peak coordinates of reduced amygdala activity did not fall primarily within the anatomical bounds of the amygdala. Collectively, these findings demonstrate significant gaps in the empirical support for the theorized role of the amygdala in psychopathy and indicate the need for novel research perspectives and approaches in this field.

Test-retest reliability of fMRI during an emotion processing task: Investigating the impact of analytical approaches on ICC values.

Test-retest reliability of fMRI is often assessed using the intraclass correlation coefficient (ICC), a numerical representation of reliability. Reports of low reliability at the individual level may be attributed to analytical approaches and inherent bias/error in the measures used to calculate ICC. It is unclear whether low reliability at the individual level is related to methodological decisions or if fMRI is inherently unreliable. The purpose of this study was to investigate methodological considerations when calculating ICC to improve understanding of fMRI reliability. fMRI data were collected from adolescent females (N=23) at pre- and post-cognitive behavioral therapy. Participants completed an emotion processing task during fMRI. We calculated ICC values using contrasts and ß coefficients separately from voxelwise and network (ICA) analyses of the task-based fMRI data. For both voxelwise analysis and ICA, ICC values were higher when calculated using ß coefficients. This work provides support for the use of ß coefficients over contrasts when assessing reliability of fMRI, and the use of contrasts may underlie low reliability estimates reported in the existing literature. Continued research in this area is warranted to establish fMRI as a reliable measure to draw conclusions and utilize fMRI in clinical settings.

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.

Functional imaging correlates of childhood trauma: A qualitative review of past research and emerging trends.

Childhood trauma exposure is common and is associated with poor clinical outcomes in adolescence along with mental health and sociodemographic challenges in adulthood. While many strategies exist to investigate the biological imprint of childhood trauma exposure, functional neuroimaging is a robust and growing technology for non-invasive studies of brain activity following traumatic experience and the relationship of childhood trauma exposure with psychopathology, cognition, and behavior. In this review, we discuss three popular approaches for discerning functional neural correlates to early life trauma, including regional activation, bivariate functional connectivity, and network-based connectivity. The breadth of research in each method is discussed, followed by important limitations and considerations for future research. We close by considering emerging trends in functional neuroimaging research of childhood trauma, including the use of complex decision-making tasks to mimic clinically-relevant behaviors, data-driven techniques such as multivariate pattern analysis and whole-brain network topology, and the applications of real-time neurofeedback for treatment of trauma-related mental disorders. We aim for this review to provide a framework for understanding the relationship between atypical neural functioning and adverse outcomes following childhood trauma exposure, with a focus on improving consistency in research methods and translatability of research findings for clinical settings.