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.

Crisis response planning rapidly reduces suicidal ideation among U.S. military veterans receiving massed cognitive processing therapy for PTSD.

Posttraumatic stress disorder (PTSD) is common among U.S. military veterans and is associated with increased risk of suicidal thoughts and behaviors. Crisis response planning (CRP), a brief safety planning-type intervention, has been shown to rapidly reduce suicidal ideation and suicide attempts in emergency and acute care settings. CRP's effectiveness when combined with trauma-focused therapies remains unknown. In this randomized pragmatic clinical trial with one-year follow-up, 157 U.S. military personnel and veterans were randomly assigned to receive CRP or self-guided safety planning (SP) prior to beginning massed cognitive processing therapy (CPT) for PTSD. Among 51 (32.5 % of sample) participants endorsing suicidal ideation at baseline, reductions in the severity of suicidal ideation were significantly larger and faster in CRP (F(11,672)= 15.8, p < .001). Among 106 participants denying suicidal ideation at baseline, 8.5 % of CRP participants versus 11.9 % of SP participants (OR=0.69, 95 % CI=0.19-2.52) reported new-onset suicidal ideation during any follow-up assessment. PTSD symptoms significantly reduced over time with no differences between groups. Results support the effectiveness of CRP for rapidly reducing suicidal ideation and managing suicide risk during outpatient treatment for PTSD.

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.

Human ventromedial prefrontal cortex lesions enhance the effect of expectations on pain perception.

Pain is strongly modulated by expectations and beliefs. Across species, subregions of ventromedial prefrontal cortex (VMPFC) are implicated in a variety of functions germane to pain, predictions, and learning. Human fMRI studies show that VMPFC activity tracks expectations about pain and mediates expectancy effects on pain-related activity in other brain regions. Prior lesion studies suggest that VMPFC may instead play a more general role in generating affective responses to painful stimuli. To test whether VMPFC is required to generate affective responses to pain or is more specifically involved in expectancy-based pain modulation, we studied responses to heat stimuli in five adults with bilateral surgical lesions of VMPFC and twenty healthy adults without brain damage. All participants underwent a quantitative sensory testing procedure followed by a pain expectancy task in which cues predicting either low or high pain were followed by intermittent medium intensity heat stimuli. Compared to adults without brain damage, individuals with VMPFC lesions reported larger differences in expected pain based on predictive cues and failed to update expectations following the covert introduction of unexpected medium temperature stimuli. Consistent with observed expectancy differences, subjective pain unpleasantness ratings in the VMPFC lesion group were more strongly modulated by cue during thermal stimulation. We found no group differences in overall pain sensitivity, nor in relationships between pain and autonomic arousal, suggesting that VMPFC damage specifically enhances the effect of expectations on pain processing, likely driven by impaired integration of new sensory feedback to update expectations about pain. These results provide essential new data regarding the specific functional contribution of VMPFC to pain modulation.

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.

Uncertainty Potentiates Neural and Cardiac Responses to Visual Stimuli in Anxiety Disorders.

BACKGROUND: Intolerance of uncertainty and worry about future events are cardinal features of anxiety. However, the neurobiological and physiological mechanisms underlying these characteristics of anxiety remain to be fully elucidated. METHODS: Individuals with diagnosed anxiety disorders (n = 29, 22 female) and age-matched comparison subjects (n = 28, 17 female) completed a task in which pictures (aversive or neutral content) were preceded by cues indicating certainty or uncertainty about the emotional valence of the subsequent pictures. We assessed functional magnetic resonance imaging and heart rate activity with respect to the 1) cue period, 2) emotional valence of the pictures, and 3) modulatory effect of uncertainty on responses to subsequent pictures. RESULTS: Individuals with anxiety disorders and comparison subjects exhibited similar functional magnetic resonance imaging and cardiac activity during the cue period and for the aversive versus neutral picture contrast. However, individuals with anxiety disorders exhibited greater modulatory effects of uncertainty on their responses to subsequent pictures. Specifically, they displayed greater functional magnetic resonance imaging activity in a number of cortical regions (visual cortex, anterior cingulate cortex, superior temporal gyrus, and anterior insula), as well as significantly reduced cardiac deceleration to pictures preceded by the uncertainty cue. CONCLUSIONS: These findings suggest that heightened neural and autonomic reactivity to stimuli during conditions of uncertainty may be a key psychobiological mechanism of anxiety.

An Examination of the Association Between Subjective Distress and Functional Connectivity During Discarding Decisions in Hoarding Disorder.

BACKGROUND: Individuals with hoarding disorder (HD) demonstrate exaggerated subjective distress and hyperactivation of cingulate and insular cortex regions when discarding personal possessions. No prior study has sought to determine whether this subjective distress is associated with specific profiles of abnormal brain function in individuals with HD. METHODS: We used multimodal canonical correlation analysis plus joint independent component analysis to test whether five hoarding-relevant domains of subjective distress when deciding to discard possessions (anxiety, sadness, monetary value, importance, and sentimental attachment) are associated with functional magnetic resonance imaging-measured whole-brain functional connectivity in 72 participants with HD and 44 healthy controls. RESULTS: Three extracted components differed between HD participants and healthy control subjects. Each of these components depicted an abnormal profile of functional connectivity in HD participants relative to control subjects during discarding decisions, and a specific distress response profile. One component pair showed a relationship between anxiety ratings during discarding decisions and connectivity among the pallidum, perirhinal ectorhinal cortex, and dorsolateral prefrontal cortex. Another component comprised sadness ratings during discarding decisions and connectivity in the pallidum, nucleus accumbens, amygdala, and dorsolateral prefrontal cortex. The third component linked HD brain connectivity in several dorsolateral prefrontal cortex regions with perceived importance ratings during discarding decisions. CONCLUSIONS: The findings indicate that in patients with HD, the subjective intensity of anxiety, sadness, and perceived possession importance is related to abnormal functional connectivity in key frontal and emotional processing brain regions. The findings are discussed in terms of emerging neurobiological models of HD.

Unique neurocircuitry activation profiles during fear conditioning and extinction among women with posttraumatic stress disorder.

BACKGROUND: Neurocircuitry models of posttraumatic stress disorder (PTSD) suggest specific alterations in brain structures linked with fear conditioning and extinction. Most models assume a unitary pattern of neurocircuitry dysfunction in PTSD and little attention has focused on defining unique profiles of neurocircuitry engagement (i.e., biotypes), despite known clinical heterogeneity in PTSD. Here, we aim to address this gap using a data-driven approach to characterize unique neurocircuitry profiles among women with PTSD. METHODS: Seventy-six women with PTSD related to assaultive violence exposure competed a task during fMRI that alternated between fear conditioning, where a geometric shape predicted the occurrence of an electric shock, and fear extinction, where the geometric shape no longer predicted electric shock. A multivariate clustering analysis was applied to neurocircuitry patterns constrained within an a priori mask of structures linked with emotion processing. Resulting biotypes were compared on clinical measures of neurocognition, trauma exposure, general mental health symptoms, and PTSD symptoms and on psychophysiological responding during the task. RESULTS: The clustering analysis identified three biotypes (BT), differentiated by patterns of engagement within salience, default mode, and visual processing networks. BT1 was characterized by higher working memory, fewer general mental health symptoms, and low childhood sexual abuse, and lower PTSD symptom severity. BT2 was characterized by lower verbal IQ but better extinction learning as defined by psychophysiology and threat expectancy. BT3 was characterized by low childhood sexual abuse, anxious arousal, and re-experiencing symptoms. CONCLUSION: This data demonstrates unique profiles of neurocircuitry engagement in PTSD, each associated with different clinical characteristics, and suggests further research defining distinct biotypes of PTSD. Clinicaltrials.gov, https://clinicaltrials.gov/ct2/home, NCT02560389.

The Multifaceted Role of the Ventromedial Prefrontal Cortex in Emotion, Decision Making, Social Cognition, and Psychopathology.

The ventromedial prefrontal cortex (vmPFC) has been implicated in a variety of social, cognitive, and affective functions that are commonly disrupted in mental illness. In this review, we summarize data from a diverse array of human and animal studies demonstrating that the vmPFC is a key node of cortical and subcortical networks that subserve at least three broad domains of psychological function linked to psychopathology. One track of research indicates that the vmPFC is critical for the representation of reward- and value-based decision making, through interactions with the ventral striatum and amygdala. A second track of research demonstrates that the vmPFC is critical for the generation and regulation of negative emotion, through its interactions with the amygdala, bed nucleus of the stria terminalis, periaqueductal gray, hippocampus, and dorsal anterior cingulate cortex. A third track of research shows the importance of the vmPFC in multiple aspects of social cognition, such as facial emotion recognition, theory-of-mind ability, and processing self-relevant information, through its interactions with the posterior cingulate cortex, precuneus, dorsomedial PFC, and amygdala. We then present meta-analytic data revealing distinct subregions within the vmPFC that correspond to each of these three functions, as well as the associations between these subregions and specific psychiatric disorders (depression, posttraumatic stress disorder, addiction, social anxiety disorder, bipolar disorder, schizophrenia, and attention-deficit/hyperactivity disorder). We conclude by describing several translational possibilities for clinical studies of vmPFC-based circuits, including neuropsychological assessment of transdiagnostic functions, anatomical targets for intervention, predictors of treatment response, markers of treatment efficacy, and subtyping within disorders.