Pretreatment characteristics associated with symptom reduction during group cognitive processing therapy versus exposure therapy for PTSD: an exploratory study of Veterans.

Exposure and cognitive-based therapies are both effective for PTSD, but knowledge of which intervention is best for which patient is lacking. This lack of knowledge is particularly noticeable for group treatments, as no study has examined whether responses to different group therapies are associated with different pretreatment characteristics. Here, we explored whether pretreatment levels of three types of psychological characteristics-PTSD symptom clusters, posttraumatic cognitions, and emotion regulation difficulties-were associated with symptom reduction during group-delivered cognitive versus exposure-based PTSD treatment. Participants were Veterans with PTSD drawn from two previous clinical trials: one of group CPT (GCPT; n = 32) and the other of group-based exposure therapy (GBET; n = 21). Growth curve modeling was used to identify pretreatment variables that predicted weekly PTSD symptom changes during each therapy. Higher posttraumatic cognitions at pretreatment predicted steeper PTSD symptom reduction during GCPT but not GBET. Additionally, symptom reduction during each therapy was associated with different pretreatment emotion regulation difficulties: difficulties with goal-directed behavior for GBET and lack of emotional clarity and limited access to emotion regulation strategies for GCPT. These findings suggest that assigning Veterans to a group PTSD therapy that better matches their pretreatment psychological profile might facilitate a better therapeutic response.

Noradrenaline tracks emotional modulation of attention in human amygdala.

The noradrenaline (NA) system is one of the brain's major neuromodulatory systems; it originates in a small midbrain nucleus, the locus coeruleus (LC), and projects widely throughout the brain.1,2 The LC-NA system is believed to regulate arousal and attention3,4 and is a pharmacological target in multiple clinical conditions.5,6,7 Yet our understanding of its role in health and disease has been impeded by a lack of direct recordings in humans. Here, we address this problem by showing that electrochemical estimates of sub-second NA dynamics can be obtained using clinical depth electrodes implanted for epilepsy monitoring. We made these recordings in the amygdala, an evolutionarily ancient structure that supports emotional processing8,9 and receives dense LC-NA projections,10 while patients (n = 3) performed a visual affective oddball task. The task was designed to induce different cognitive states, with the oddball stimuli involving emotionally evocative images,11 which varied in terms of arousal (low versus high) and valence (negative versus positive). Consistent with theory, the NA estimates tracked the emotional modulation of attention, with a stronger oddball response in a high-arousal state. Parallel estimates of pupil dilation, a common behavioral proxy for LC-NA activity,12 supported a hypothesis that pupil-NA coupling changes with cognitive state,13,14 with the pupil and NA estimates being positively correlated for oddball stimuli in a high-arousal but not a low-arousal state. Our study provides proof of concept that neuromodulator monitoring is now possible using depth electrodes in standard clinical use.

Do early responders and treatment non-responders offer guidance to make CPT group a more effective treatment?

BACKGROUND: Treatment dropout has been problematic with evidence-based treatments for posttraumatic stress disorder (PTSD), including cognitive processing therapy (CPT). This study sought to evaluate whether CPT group contributed to symptom improvement among treatment completers and non-completers. METHODS: Sixty-one Iraq and Afghanistan combat Veterans self-selected CPT group or treatment as usual (TAU) forming a convenience sample. Defining treatment completion as attending at least nine sessions: 18 completed treatment, 20 dropped-out (DOs); 20 completed TAU, 3 lost to TAU follow-up. RESULTS: Multiple Regression revealed significant pre-post-treatment improvement, the Clinician-Administered PTSD Scale (CAPS-IV, F(5, 40.1) = 2.53, p = 0.0436). Reviewing DOs' last available PTSD Checklist-Military Version scores before leaving treatment, six achieved clinically significant improvement of >10 points; seven a clinically reliable change of 5-10 points. CONCLUSION: These findings highlight that CPT group may be effective at reducing trauma-related symptoms among treatment completers and dropouts and point to the utility of a clinical definition of good treatment end-state.

Reinforcement Learning Disruptions in Individuals With Depression and Sensitivity to Symptom Change Following Cognitive Behavioral Therapy.

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 ß = -0.14; 95% credible interval [CrI], -0.12 to -0.03; outcome sensitivity: posterior mean regression ß = 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 ß = -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 ß = 0.15; 90% CrI, 0.001 to 0.41; loss outcome shift: posterior mean regression ß = 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.

Valuation of peers' safe choices is associated with substance-naïveté in adolescents.

Social influences on decision-making are particularly pronounced during adolescence and have both protective and detrimental effects. To evaluate how responsiveness to social signals may be linked to substance use in adolescents, we used functional neuroimaging and a gambling task in which adolescents who have and have not used substances (substance-exposed and substance-naïve, respectively) made choices alone and after observing peers' decisions. Using quantitative model-based analyses, we identify behavioral and neural evidence that observing others' safe choices increases the subjective value and selection of safe options for substance-naïve relative to substance-exposed adolescents. Moreover, the effects of observing others' risky choices do not vary by substance exposure. These results provide neurobehavioral evidence for a role of positive peers (here, those who make safer choices) in guiding adolescent real-world risky decision-making.

Opponent Effects of Hyperarousal and Re-experiencing on Affective Habituation in Posttraumatic Stress Disorder.

BACKGROUND: Aberrant emotion processing is a hallmark of posttraumatic stress disorder (PTSD), with neurobiological models suggesting both heightened neural reactivity and diminished habituation to aversive stimuli. However, empirical work suggests that these response patterns may be specific to subsets of those with PTSD. This study investigates the unique contributions of PTSD symptom clusters (re-experiencing, avoidance and numbing, and hyperarousal) to neural reactivity and habituation to negative stimuli in combat-exposed veterans. METHODS: Ninety-five combat-exposed veterans (46 with PTSD) and 53 community volunteers underwent functional magnetic resonance imaging while viewing emotional images. This study examined the relationship between symptom cluster severity and hemodynamic responses to negative compared with neutral images (NEG>NEU). RESULTS: Veterans exhibited comparable mean and habituation-related responses for NEG>NEU, relative to civilians. However, among veterans, habituation, but not mean response, was differentially related to PTSD symptom severity. Hyperarousal symptoms were related to decreased habituation for NEG>NEU in a network of regions, including superior and inferior frontal gyri, ventromedial prefrontal cortex, superior and middle temporal gyri, and anterior insula. In contrast, re-experiencing symptoms were associated with increased habituation in a similar network. Furthermore, re-experiencing severity was positively related to amygdalar functional connectivity with the left inferior frontal gyrus and dorsal anterior cingulate cortex for NEG>NEU. CONCLUSIONS: These results indicate that hyperarousal symptoms in combat-related PTSD are associated with decreased neural habituation to aversive stimuli. These impairments are partially mitigated in the presence of re-experiencing symptoms, such that during exposure to negative stimuli, re-experiencing symptoms are positively associated with amygdalar connectivity to prefrontal regions implicated in affective suppression.

In Cocaine Dependence, Neural Prediction Errors During Loss Avoidance Are Increased With Cocaine Deprivation and Predict Drug Use.

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.

The Interaction Between Punishment Sensitivity and Effortful Control for Emerging Adults' Substance Use Behaviors.

BACKGROUND: Within the dual systems perspective, high reward sensitivity and low punishment sensitivity in conjunction with deficits in cognitive control may contribute to high levels of risk taking, such as substance use. OBJECTIVE: The current study examined whether the individual components of effortful control (inhibitory control, attentional control, and activation control) serve as regulators and moderate the association between reward or punishment sensitivity and substance use behaviors. METHOD: A total of 1,808 emerging adults from a university setting (Mean age = 19.48; 72% female) completed self-report measures of reward and punishment sensitivity, effortful control, and substance use. RESULTS: Findings indicated significant two-way interactions for punishment sensitivity and inhibitory control for alcohol and marijuana use. The form of these interactions revealed a significant negative association between punishment sensitivity and alcohol and marijuana use at low levels of inhibitory control. No significant interactions emerged for reward sensitivity or other components of effortful control. CONCLUSIONS: The current findings provide preliminary evidence suggesting the dual systems theorized to influence risk taking behavior interact to make joint contributions to health risk behaviors such as substance use in emerging adults.

Associability-modulated loss learning is increased in posttraumatic stress disorder.

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.

Neural Interaction Between Risk Sensitivity and Cognitive Control Predicting Health Risk Behaviors Among Late Adolescents.

The developmental period of adolescence is characterized by increasing incidence of health risk behaviors (HRBs). Based on theoretical models that emphasize the moderating role of cognitive control, this study examined how neural correlates of cognitive control and risk sensitivity interact to predict HRBs among late adolescents (17-20 years). Neuroimaging data indicate that risk-related hemodynamic activity in the anterior insula during anticipation of uncertain outcomes predicts HRBs among late adolescents exhibiting greater dorsal anterior cingulate cortex (dACC) activity during a cognitive interference task but not among late adolescents requiring less dACC activity. These results present neural evidence for a significant moderating effect of cognitive control on the link between risk sensitivity and HRBs among late adolescents.

Executive functioning and substance use in adolescence: Neurobiological and behavioral perspectives.

The current review is guided by the theoretical perspective that emphasizes the regulating role of executive functioning (Carver et al., 2009) and presents studies that elucidate the ways that executive functioning (inhibition and working memory) explain individual differences in adolescent substance use independently or by regulating the reactive system (reward and punishment sensitivity). Behavioral studies indicate that main effects of executive functioning on adolescent substance use are often nonsignificant or weak in effect sizes. In contrast, emerging evidence suggests consistent and stronger regulating effects of executive functioning over reward and punishment sensitivity. Functional neuroimaging studies reveal significant associations between executive functioning task-related hemodynamic responses and substance use with strong effect sizes. There is also direct evidence from studies testing statistical interactions of the regulating effects of EF-related brain activation, and indirect evidence in studies examining functional connectivity, temporal discounting, and reinforced control. We note key future directions and ways to address limitations in existing work.

Valuation in major depression is intact and stable in a non-learning environment.

The clinical diagnosis and symptoms of major depressive disorder (MDD) have been closely associated with impairments in reward processing. In particular, various studies have shown blunted neural and behavioral responses to the experience of reward in depression. However, little is known about whether depression affects individuals' valuation of potential rewards during decision-making, independent from reward experience. To address this question, we used a gambling task and a model-based analytic approach to measure two types of individual sensitivity to reward values in participants with MDD: 'risk preference,' indicating how objective values are subjectively perceived, and 'inverse temperature,' determining the degree to which subjective value differences between options influence participants' choices. On both of these measures of value sensitivity, participants with MDD were comparable to non-psychiatric controls. In addition, both risk preference and inverse temperature were stable over four laboratory visits and comparable between the groups at each visit. Neither valuation measure varied with severity of clinical symptoms in MDD. These data suggest intact and stable value processing in MDD during risky decision-making.

Risky decision making in a laboratory driving task is associated with health risk behaviors during late adolescence but not adulthood.

Adolescence is characterized by increasing incidence of health risk behaviors, including experimentation with drugs and alcohol. To fill the gap in our understanding of the associations between risky decision-making and health risk behaviors, we investigated associations between laboratory-based risky decision-making using the Stoplight task and self-reported health risk behaviors. Given that there has been no examination of potential age differences in the associations between risky decision-making and health risk behaviors, we also examined whether the association of risky decision-making with health risk behaviors is consistent across adolescence and adulthood using two-group structural equation modeling (SEM). The results indicated significant differences across the two age groups: adolescents (17-20 year olds) who took more risks on the Stoplight task reported greater frequency and earlier onset of substance use, whereas stoplight performance was not associated with substance use frequency or onset among adults (31-61 year olds). Our findings suggest that a laboratory-based measure of risky decision-making is significantly related to health risk behaviors among adolescents but not among adults.

Social signals of safety and risk confer utility and have asymmetric effects on observers' choices.

Individuals' risk attitudes are known to guide choices about uncertain options. However, in the presence of others' decisions, these choices can be swayed and manifest as riskier or safer behavior than one would express alone. To test the mechanisms underlying effective social 'nudges' in human decision-making, we used functional neuroimaging and a task in which participants made choices about gambles alone and after observing others' selections. Against three alternative explanations, we found that observing others' choices of gambles increased the subjective value (utility) of those gambles for the observer. This 'other-conferred utility' was encoded in ventromedial prefrontal cortex, and these neural signals predicted conformity. We further identified a parametric interaction with individual risk preferences in anterior cingulate cortex and insula. These data provide a neuromechanistic account of how information from others is integrated with individual preferences that may explain preference-congruent susceptibility to social signals of safety and risk.

Diminished neural responses predict enhanced intrinsic motivation and sensitivity to external incentive.

The duration and quality of human performance depend on both intrinsic motivation and external incentives. However, little is known about the neuroscientific basis of this interplay between internal and external motivators. Here, we used functional magnetic resonance imaging to examine the neural substrates of intrinsic motivation, operationalized as the free-choice time spent on a task when this was not required, and tested the neural and behavioral effects of external reward on intrinsic motivation. We found that increased duration of free-choice time was predicted by generally diminished neural responses in regions associated with cognitive and affective regulation. By comparison, the possibility of additional reward improved task accuracy, and specifically increased neural and behavioral responses following errors. Those individuals with the smallest neural responses associated with intrinsic motivation exhibited the greatest error-related neural enhancement under the external contingency of possible reward. Together, these data suggest that human performance is guided by a "tonic" and "phasic" relationship between the neural substrates of intrinsic motivation (tonic) and the impact of external incentives (phasic).

Group psychotherapy's impact on trust in veterans with PTSD: a pilot study.

Interpersonal trust is fundamental for the recovery of trauma survivors and the effectiveness of group psychotherapy. Yet there is limited research on the relationship between interpersonal trust and group psychotherapy. Twenty-one male Vietnam combat veterans with posttraumatic stress disorder (PTSD) (6 in a long-term process group [LTP], 10 in a short-term cognitive processing therapy group [CPT], and 5 treatment-as-usual controls) were evaluated before and after group psychotherapy using the Posttraumatic Stress Disorder Checklist-Military Version (PCL-M) and an in-vivo measure of interpersonal trust, the Iterated Trust Game. Three (14.3%) of the veterans were African American, 9 were Caucasian (42.9%), and 9 were Hispanic (42.9%); they averaged 61.9 years of age (SD = 1.8 years). Change in PCL-M scores differed by group (controls: -1.0 ± 3.7; CPT: -15.5 ± 6.8; LTP: -1.3 ± 12.2; p = .003). CPT group subjects improved more than controls (p < .001) and trended toward more improvement than the LTP group (p = .081). Members of the LTP group, compared to nonprocess group participants, showed greater initial (p = .042), and posttherapy trust (p = .003). Posttreatment, interpersonal trust was significantly higher in the LTP than the CPT group (p < .001). These results suggest that CPT treatment may be better than LTP treatment for improving PTSD symptoms, but LTP therapy may be better than CPT therapy for improving interpersonal trust in veterans with PTSD. They suggest important roles for both group treatments and point to the value of interpersonal trust in successful recovery from PTSD.

Damage to dorsolateral prefrontal cortex affects tradeoffs between honesty and self-interest.

Substantial correlational evidence suggests that prefrontal regions are critical to honest and dishonest behavior, but causal evidence specifying the nature of this involvement remains absent. We found that lesions of the human dorsolateral prefrontal cortex (DLPFC) decreased the effect of honesty concerns on behavior in economic games that pit honesty motives against self-interest, but did not affect decisions when honesty concerns were absent. These results point to a causal role for DLPFC in honest behavior.

Social-cognitive, physiological, and neural mechanisms underlying emotion regulation impairments: understanding anxiety in autism spectrum disorder.

Anxiety is one of the most common clinical problems among children, adolescents, and adults with autism spectrum disorder (ASD), yet we know little about its etiology in the context of ASD. We posit that emotion regulation (ER) impairments are a risk factor for anxiety in ASD. Specifically, we propose that one reason why anxiety disorders are so frequently comorbid with ASD is because ER impairments are ubiquitous to ASD, stemming from socio-cognitive, physiological, and neurological processes related to impaired cognitive control, regulatory processes, and arousal. In this review, we offer a developmental model of how ER impairments may arise in ASD, and when (moderating influences) and how (meditational mechanisms) they result in anxiety.

Understanding interpersonal function in psychiatric illness through multiplayer economic games.

Interpersonal factors play significant roles in the onset, maintenance, and remission of psychiatric conditions. In the current major diagnostic classification systems for psychiatric disorders, some conditions are defined by the presence of impairments in social interaction or maintaining interpersonal relationships; these include autism, social phobia, and the personality disorders. Other psychopathologies confer significant difficulties in the social domain, including major depression, posttraumatic stress disorder, and psychotic disorders. Still other mental health conditions, including substance abuse and eating disorders, seem to be exacerbated or triggered in part by the influence of social peers. For each of these and other psychiatric conditions, the extent and quality of social support is a strong determinant of outcome such that high social support predicts symptom improvement and remission. Despite the central role of interpersonal factors in psychiatric illness, the neurobiology of social impairments remains largely unexplored, in part due to difficulties eliciting and quantifying interpersonal processes in a parametric manner. Recent advances in functional neuroimaging, combined with multiplayer exchange games drawn from behavioral economics, and computational/quantitative approaches more generally, provide a fitting paradigm within which to study interpersonal function and dysfunction in psychiatric conditions. In this review, we outline the importance of interpersonal factors in psychiatric illness and discuss ways in which neuroeconomics provides a tractable framework within which to examine the neurobiology of social dysfunction.

Depressive symptoms and mental health treatment in an ethnoracially diverse college student sample.

OBJECTIVES: To study (a) the prevalence of depressive symptoms and (b) the utilization of mental health treatment in an ethnoracially diverse sample consisting primarily of Asian Americans, European Americans, Native Hawaiians, and Pacific Islanders. PARTICIPANTS: Five hundred eighty-nine college students. METHOD: A questionnaire packet that included the Center for Epidemiological Studies Depression Scale (CES-D) was administered to students in introductory psychology courses. RESULTS: (a) There were no differences among ethnoracial groups in levels of depressive symptoms as measured by the CES-D; (b) 71% of participants with high levels of depressive symptoms had not received any mental health treatment in the previous 12 months; and (c) European Americans were 3.7 times more likely to have received mental health treatment in the previous 12 months than other students. CONCLUSION: Outreach efforts designed to improve utilization of mental health treatment services by depressed college students, especially by members of ethnoracial minority groups, should be increased.