Sensorimotor Feedback Control Dysfunction as a Marker of Posttraumatic Stress Disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is characterized not only by its direct association with traumatic events but also by a potential deficit in inhibitory control across emotional, cognitive, and sensorimotor domains. Recent research has shown that a continuous sensorimotor feedback control task, the rapid assessment of motor processing (RAMP) paradigm, can yield reliable measures of individual sensorimotor control performance. This study used this paradigm to investigate control deficits in PTSD relative to both healthy volunteer and a non-PTSD psychiatric comparison group. METHODS: We examined control processing using the RAMP paradigm in a sample of 40 individuals with PTSD, along with matched groups of 40 individuals with mood and anxiety (MA) complaints and 40 healthy controls (HC). We estimated Kp (drive) and Kd (damping) parameters using a proportion-derivative (PD) control modeling approach. RESULTS: The Kp parameter was lower in the PTSD group compared to the HC (Cohen's d = .86) and MA groups (Cohen's d = 0.63). After controlling for color-word inhibition, Kp remained lower in the PTSD group versus HC (Cohen's d = 0.79) and versus MA (Cohen's d = 0.62). Mediation analysis showed that Kd significantly mediated the relationship between PTSD and control deficits in the Kp parameter, with 96% of the effect mediated by Kd. CONCLUSIONS: These findings underscore the potential of using dynamic control paradigms to elucidate the control dysfunctions in PTSD and suggests that different psychiatric conditions may distinctly influence subcomponents of sensorimotor control.

Out of control: computational dynamic control dysfunction in stress- and anxiety-related disorders.

Control theory, which has played a central role in technological progress over the last 150 years, has also yielded critical insights into biology and neuroscience. Recently, there has been a surging interest in integrating control theory with computational psychiatry. Here, we review the state of the field of using control theory approaches in computational psychiatry and show that recent research has mapped a neural control circuit consisting of frontal cortex, parietal cortex, and the cerebellum. This basic feedback control circuit is modulated by estimates of reward and cost via the basal ganglia as well as by arousal states coordinated by the insula, dorsal anterior cingulate cortex, amygdala, and locus coeruleus. One major approach within the broader field of control theory, known as proportion-integral-derivative (PID) control, has shown promise as a model of human behavior which enables precise and reliable estimates of underlying control parameters at the individual level. These control parameters correlate with self-reported fear and with both structural and functional variation in affect-related brain regions. This suggests that dysfunctional engagement of stress and arousal systems may suboptimally modulate parameters of domain-general goal-directed control algorithms, impairing performance in complex tasks involving movement, cognition, and affect. Future directions include clarifying the causal role of control deficits in stress- and anxiety-related disorders and developing clinically useful tools based on insights from control theory.

Polygenic risk for neuroticism is associated with less efficient control in more difficult situations.

Neuroticism is a heritable trait and a risk factor for mental health due to its relevance to poor control of negative events. To examine the relationship between genetic propensity for neuroticism and control processing, we used the polygenic risk score (PRS) approach and a stop signal task during fMRI. We hypothesized that genetic propensity for neuroticism may moderate control processing as a function of control difficulty. PRSs for neuroticism were computed from a transdiagnostic group of individuals (n=406) who completed the stop signal task. The level of control difficulty was a function of the stop signal asynchrony: shorter asynchrony allows easier stopping whereas longer asynchrony makes stopping difficult. The relationship between PRS for neuroticism and neural activity for controlling responses was examined by the stop signal asynchrony. Although PRS for neuroticism did not relate to the overall inhibitory control, individuals with high PRS for neuroticism showed greater activity in left dorsal prefrontal cortex, middle temporal gyrus, and dorsal posterior cingulate cortex for difficult control. Thus, the genetic propensity for neuroticism affects neural processing in a difficult control context, which may help to explain why individuals with high levels of neuroticism exert poor control of negative events in difficult situations.

Neural substrates of continuous and discrete inhibitory control.

Inhibitory control dysfunctions play an important role in psychiatric disorders but the precise nature of these dysfunctions is still not well understood. Advances in computational modeling of real-time motor control using a proportion-integral-derivative (PID) control framework have parsed continuous motor inhibition into a preemptive drive component (signified by the Kp parameter) and a reactive damping component (signified by the Kd parameter). This investigation examined the relationship between inhibitory control processing during a stop signal task and continuous motor control during a simulated one-dimensional driving task in a transdiagnostic sample of participants. A transdiagnostic psychiatric sample of 492 individuals completed a stop signal task during functional magnetic resonance imaging and a simple behavioral motor control task, which was modeled using the PID framework. We examined associations between the Kp and Kd parameters and behavioral indices as well as neural activation on the stop signal task. Individuals with higher damping, controlling for a drive, on the driving task exhibited relatively less strategic adjustment after a stop trial (indexed by the difference in go trial reaction time and by stop trial accuracy) on the stop signal task. Individuals with higher damping, controlling for a drive, additionally exhibited increased activity in the frontal and parietal regions as well as the insula and caudate during response inhibition on the stop signal task. The results suggest that computational indices of motor control performance may serve as behavioral markers of the functioning of neural systems involved in inhibitory control.

Rapid, reliable mobile assessment of affect-related motor processing.

Mobile technologies can be used for behavioral assessments to associate changes in behavior with environmental context and its influence on mental health and disease. Research on real-time motor control with a joystick, analyzed using a computational proportion-derivative (PD) modeling approach, has shown that model parameters can be estimated with high reliability and are related both to self-reported fear and to brain structures important for affective regulation, such as the anterior cingulate cortex. Here we introduce a mobile version of this paradigm, the rapid assessment of motor processing (RAMP) paradigm, and show that it provides robust, reliable, and accessible behavioral measurements relevant to mental health. A smartphone version of a previous joystick sensorimotor task was developed in which participants control a virtual car to a stop sign and stop. A sample of 89 adults performed the task, with 66 completing a second retest session. A PD modeling approach was applied to compute Kp (drive) and Kd (damping) parameters. Both Kp and Kd exhibited high test-retest reliabilities (ICC .81 and .78, respectively). Replicating a previous finding from a different sample with the joystick version of the task, both Kp and Kd were negatively associated with self-reported fear. The RAMP paradigm, a mobile sensorimotor assessment, can be used to assess drive and damping during motor control, which is robustly associated with subjective affect. This paradigm could be useful for examining dynamic contextual modulation of affect-related processing, which could improve assessment of the effects of interventions for psychiatric disorders in a real-world context.

Mental Health Consequences of Traumatic Brain Injury.

Traumatic brain injury (TBI) is associated with a host of psychiatric and neurobehavioral problems. As mortality rates have declined for severe TBI, attention has turned to the cognitive, affective, and behavioral sequelae of injuries across the severity spectrum, which are often more disabling than residual physical effects. Moderate and severe TBI can cause personality changes including impulsivity, severe irritability, affective instability, and apathy. Mild TBI, once considered a largely benign phenomenon, is now known to be associated with a range of affective symptoms, with suicidality, and with worsening or new onset of several psychiatric disorders including posttraumatic stress disorder and major depressive disorder. Repetitive head impacts, often in athletic contexts, are now believed to be associated with a number of emotional and behavioral sequelae. The nature and etiology of mental health manifestations of TBI (including a combination of brain dysfunction and psychological trauma and interrelationships between cognitive, affective, and physical symptoms) are complex and have been a focus of recent epidemiological and mechanistic studies. This paper will review the epidemiology of psychiatric and neurobehavioral problems after TBI in military, civilian, and athletic contexts.

Inhibitory failures in cocaine use disorder: Not paying attention when there is a need to be cautious.

BACKGROUND: Stimulant use disorders, such as cocaine use disorder, are associated with significant impairment in inhibitory control, which has in turn been linked to difficulties maintaining abstinence following treatment. Here, we combine the Dynamic Belief Model (DBM) and a Hierarchical Drift Diffusion Model (HDDM) to examine whether individuals with cocaine use disorder have both strategic response updating and tactical speed accuracy trade-off problems during inhibitory control. METHODS: Twenty-seven individuals with cocaine use disorder and twenty-seven healthy control participants completed a Stop-Signal-Task (SST), in which one has to inhibit a motor response to a prepotent 2-alternative forced choice task on 25 % of the trials. RESULTS: Cocaine use disorder and control subjects did not differ on successful stopping behavior. In cocaine use disorder but not control subjects, higher likelihood of encountering a stop signal was associated with lower drift rate. Moreover, in cocaine use disorder subjects, a more negative relationship between likelihood of encountering a stop signal and drift rate was associated with lower accuracy on stop trials and slower stop reaction time. CONCLUSIONS: These results are consistent with a dysregulation between strategic and tactical processing during inhibitory control in cocaine use disorder. Specifically, these individuals are more likely to be less attentive to sensory evidence when the expectation of a stop signal is high.

Symptoms of Posttraumatic Stress Disorder are Associated with Exaggerated Neural Response to Surprising Errors.

Posttraumatic stress disorder (PTSD) is characterized by exaggerated salience of previously innocuous cues and associated with hyperactivity of salience-related brain regions. Recently, computational models have been deployed to operationalize salience more precisely regarding surprise-driven learning, leading to findings that such learning is altered in anxiety-related disorders. In the present study, a sample of 20 combat veterans completed a probabilistic learning task during fMRI scanning. We applied a computational model to generate a trial-by-trial surprise signal (i.e., unsigned prediction error or difference between the expected probability of an outcome and the actual observed outcome), which allowed us to examine the neural response to surprising events. We did not observe an association between PTSD symptoms and behavioral indices of learning in the task. Surprising errors were associated with increased activity in the left precuneus/inferior parietal lobule and right inferior parietal lobule, two parietal regions that are linked to salience processing. Additionally, PTSD symptom severity was positively associated with precuneus/inferior parietal lobule activation to surprising errors, r = .63, p = .004. Taken together, this pattern of results suggests that PTSD symptoms are specifically associated with an exaggerated response to surprising errors in salience-related regions of the brain. This altered pattern of neural activity could represent a target for intervention to improve PTSD symptoms.

A parallel accumulator model accounts for decision randomness when deciding on risky prospects with different expected value.

In decision-making situations individuals rarely have complete information available to select the best option and often show decisional randomness, i.e. given the same amount of knowledge individuals choose different options at different times. Dysfunctional processes resulting in altered decisional randomness can be considered a target process for psychiatric disorders, yet these processes remain poorly understood. Advances in computational modeling of decision-making offer a potential explanation for decisional randomness by positing that decisions are implemented in the brain through accumulation of noisy evidence, causing a generally less preferred option to be chosen at times by chance. One such model, the linear ballistic accumulator (LBA), assumes that individuals accumulate information for each option independently over time and that the first option to reach a threshold will be selected. To investigate the mechanisms of decisional randomness, we applied the LBA to a decision-making task in which risk and expected value (EV) were explicitly signaled prior to making a choice, and estimated separate drift rates for each of the four task stimuli (representing high and low EV and high and low risk). We then used the fitted LBA parameters to predict subject response rates on held-out trials for each of the 6 possible stimulus pairs. We found that choices predicted by LBA were correlated with actual choices across subjects for all stimulus pairs. Taken together, these findings suggest that sequential sampling models can account for decisional randomness on an explicit probabilistic task, which may have implications for understanding decision-making in healthy individuals and in psychiatric populations.

Computational Evidence for Underweighting of Current Error and Overestimation of Future Error in Anxious Individuals.

BACKGROUND: Real-time control of goal-directed actions requires continuous adjustments in response to both current error (i.e., distance from goal state) and predicted future error. Proportion-integral-derivative control models, which are extensively used in the automated control of industrial processes, formalize this intuition. Previous computational approaches to anxiety have separately addressed behavioral inhibition and exaggerated error processing, but a proportion-integral-derivative control approach that decomposes error processing into current and anticipated error could integrate these accounts and extend them to a real-time sensorimotor control domain. METHODS: We applied a simplified proportion-derivative control model to a virtual driving task in a transdiagnostic psychiatric sample of 317 individuals and computed a drive parameter (weighting of current error) and a damping parameter (weighting of the rate of change of error, enabling adjustment based on future error). RESULTS: Self-reported fear, but not negative affect, was selectively associated with lower drive and lower damping. Those individuals that were characterized by lower drive and damping also exhibited lower caudal anterior cingulate cortex, but not insula, volume in a structural magnetic resonance imaging analysis. CONCLUSIONS: The proportion-derivative control approach reveals that fear is specifically associated with reduced weighting of current error and overestimation of future error, resulting in both approach inhibition and overcorrecting overshoots around a goal state.

Where perception meets belief updating: Computational evidence for slower updating of visual expectations in anxious individuals.

BACKGROUND: Surprising events are important sources of internal model updating which adjusts expectations for both decision-making and perceptual processing circuits. Anxious individuals display relatively intact updating of internal models used to make decisions, however how these individuals update their perceptual expectations remains poorly understood. Based on previous work, we hypothesized that anxious individuals experienced exaggerated surprise to predictable events, which imbues them with undue salience. METHODS: To model the rate of updating of internal models for both decision-making and perceptual processing, we applied a hybrid Rescorla Wagner (RW)/Drift Diffusion Model (DDM) to a change point detection task in a transdiagnostic group of individuals with mood and anxiety disorders and examined the relationship between learning rates and anxiety and negative affect. RESULTS: Model comparison provided evidence that decision-making and perceptual processing rely on separate internal models with different learning rates. Anxiety and older age were associated with slower updating of models used in perceptual processing, but not those used in decision-making. LIMITATIONS: This was a cross-sectional study and lacked neural data to examine the role of specific brain circuits in updating of perceptual predictions. CONCLUSIONS: Anxious individuals display slower updating of internal models used in perceptual processing, but not those used in decision-making. This deficit could contribute to exaggerated salience of harmless stimuli in anxiety. The results have implications for the assessment and treatment of basic processing dysfunctions in anxiety.

Attention Deficit Hyperactivity Disorder and Risk of Posttraumatic Stress and Related Disorders: A Prospective Longitudinal Evaluation in U.S. Army Soldiers.

Cross-sectional associations between attention deficit hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) have been observed, but longitudinal studies assessing this association are lacking. This prospective study evaluated the association between predeployment ADHD and postdeployment PTSD among U.S. Army soldiers. Soldiers who deployed to Afghanistan were surveyed before deployment (T0) and approximately 1 month (T1), 3 months (T2), and 9 months (T3) after their return. Logistic regression was performed to estimate the association between predeployment ADHD and postdeployment (T2 or T3) PTSD among 4,612 soldiers with data at all waves and no record of stimulant medication treatment during the study. To evaluate specificity of the ADHD-PTSD association, we examined associations among predeployment ADHD, postdeployment major depressive episode (MDE), generalized anxiety disorder (GAD), and suicidal ideation. Weighted prevalence of ADHD predeployment was 6.1% (SE = 0.4%). Adjusting for other risk factors, predeployment ADHD was associated with risk of postdeployment PTSD, adjusted odds ratio (AOR) = 2.13, 95% CI [1.51, 3.00], p < .001, including incidence among soldiers with no predeployment history of PTSD, AOR = 2.50, 95% CI [1.69, 3.69], p < .001. ADHD was associated with postdeployment MDE, AOR = 2.80, 95% CI [2.01, 3.91], p < .001, and GAD, AOR = 3.04, 95% CI [2.10, 4.42], p < .001, but not suicidal ideation. Recognition of associations between predeployment ADHD and postdeployment PTSD, MDE, and GAD may inform targeted prevention efforts. Future research should examine whether treatment of ADHD is protective against PTSD and related disorders in trauma-exposed individuals.

The effect of single-dose methylphenidate on the rate of error-driven learning in healthy males: a randomized controlled trial.

RATIONALE AND OBJECTIVES: Norepinephrine mediates the adjustment of error-driven learning to match the rate of change of the environment, while phasic dopamine signals prediction errors. We tested the hypothesis that pharmacologic manipulation may modulate this process. METHODS: We administered a single dose of methylphenidate, a norepinephrine/dopamine reuptake inhibitor, or placebo in double-blind randomized fashion to 20 healthy human males, who then performed a probabilistic learning task. Each subject was tested in two sessions, receiving methylphenidate in one session and placebo in the other, in randomized order. Task performance was quantified by the percentage of trials on which subjects chose the most likely option, while learning rate was measured using a computational model-based parameter as well as with a behavioral analogue of this parameter. RESULTS: There was a substance-by-session interaction effect on behavioral learning rate and model-based learning rate, such that subjects receiving methylphenidate exhibited higher learning rates than those receiving placebo in session 1, with no difference observed in session 2, suggesting that subjects retained the increased learning rate across sessions. Higher behavioral learning rate was associated with both higher task performance and with the model-based learning rate. Higher learning rates were advantageous given the high rate of change on the task. Subjects receiving methylphenidate and placebo began the task in session 1 with a similar behavioral learning rate, but those receiving methylphenidate rapidly increased learning rate toward the optimal value, suggesting that methylphenidate accelerated the adaptation of learning rate based on the environment. CONCLUSIONS: The results suggest that methylphenidate may improve disrupted probabilistic learning in disorders involving noradrenergic or dopaminergic dysfunction.

Individual Differences in Subjective Utility and Risk Preferences: The Influence of Hedonic Capacity and Trait Anxiety.

Individual differences in decision-making are important in both normal populations and psychiatric conditions. Variability in decision-making could be mediated by different subjective utilities or by other processes. For example, while traditional economic accounts attribute risk aversion to a concave subjective utility curve, in practice other factors could affect risk behavior. This distinction may have important implications for understanding the biological basis of variability in decision-making and for developing interventions to improve decision-making. Another aspect of decision-making that may vary between individuals is the sensitivity of subjective utility to counterfactual outcomes (outcomes that could have occurred, but did not). We investigated decision-making in relation to hedonic capacity and trait anxiety, two traits that relate to psychiatric conditions but also vary in the general population. Subjects performed a decision-making task, in which they chose between low- and high-risk gambles to win 0, 20, or 40 points on each trial. Subjects then rated satisfaction after each outcome on a visual analog scale, indicating subjective utility. Hedonic capacity was positively associated with the subjective utility of winning 20 points but was not associated with the concavity of the subjective utility curve (constructed using the mean subjective utility of winning 0, 20, or 40 points). Consistent with economic theory, concavity of the subjective utility curve was associated with risk aversion. Hedonic capacity was independently associated with risk seeking (i.e., not mediated by the shape of the subjective utility curve), while trait anxiety was unrelated to risk preferences. Contrary to our expectations, counterfactual sensitivity was unrelated to hedonic capacity and trait anxiety. Nevertheless, trait anxiety was associated with a self-report measure of regret-proneness, suggesting that counterfactual influences may occur via a pathway that is separate from immediate counterfactual processing biases. Taken together, our results show that hedonic capacity but not trait anxiety affects risk-taking through a mechanism that appears independent of the shape of the subjective utility curve, while hedonic capacity and trait anxiety do not affect the influence of counterfactual outcomes on subjective utility. The results have implications for understanding the underlying mechanisms of variable decision-making and for developing interventions to improve decision-making.

Prevention of Trauma and Stressor-Related Disorders: A Review.

Posttraumatic stress disorder (PTSD) is a common, frequently chronic, and disabling condition which, along with acute stress disorder (ASD), is categorized as a trauma- and stressor-related disorder by the DSM-5. These disorders are unique in requiring exposure to a severe stressor, which implies that potential sufferers could be identified and helped before developing a disorder. Research on prevention strategies for stress-related disorders has taken a number of avenues, including intervention before and after trauma and the use of both psychosocial and somatic approaches. Despite advances in neurobiological understanding of response to trauma, clinical evidence for preventive interventions remains sparse. This review provides an overview of prevention approaches and summarizes the existing literature on prevention of ASD and PTSD, including clinical and preclinical studies. Given the potential benefits to trauma survivors and society, the development of effective preventive interventions should be given greater priority. Resources should be directed to adequately test promising interventions in clinical trials, and research should be conducted according to translational research principles in which preclinical research informs the design of clinical studies.

The neural basis of testable and non-testable beliefs.

Beliefs about the state of the world are an important influence on both normal behavior and psychopathology. However, understanding of the neural basis of belief processing remains incomplete, and several aspects of belief processing have only recently been explored. Specifically, different types of beliefs may involve fundamentally different inferential processes and thus recruit distinct brain regions. Additionally, neural processing of truth and falsity may differ from processing of certainty and uncertainty. The purpose of this study was to investigate the neural underpinnings of assessment of testable and non-testable propositions in terms of truth or falsity and the level of certainty in a belief. Functional magnetic resonance imaging (fMRI) was used to study 14 adults while they rated propositions as true or false and also rated the level of certainty in their judgments. Each proposition was classified as testable or non-testable. Testable propositions activated the DLPFC and posterior cingulate cortex, while non-testable statements activated areas including inferior frontal gyrus, superior temporal gyrus, and an anterior region of the superior frontal gyrus. No areas were more active when a proposition was accepted, while the dorsal anterior cingulate was activated when a proposition was rejected. Regardless of whether a proposition was testable or not, certainty that the proposition was true or false activated a common network of regions including the medial prefrontal cortex, caudate, posterior cingulate, and a region of middle temporal gyrus near the temporo-parietal junction. Certainty in the truth or falsity of a non-testable proposition (a strong belief without empirical evidence) activated the insula. The results suggest that different brain regions contribute to the assessment of propositions based on the type of content, while a common network may mediate the influence of beliefs on motivation and behavior based on the level of certainty in the belief.

Decision-Making Dysfunctions of Counterfactuals in Depression: Who Might I have Been?

Cognitive neuroscience enables us now to decompose major depressive disorder into dysfunctional component processes and relate these processes to specific neural substrates. This approach can be used to illuminate the biological basis of altered psychological processes in depression, including abnormal decision-making. One important decision-related process is counterfactual thinking, or the comparison of reality to hypothetical alternatives. Evidence suggests that individuals with depression experience exaggerated emotional responses due to focusing on counterfactual decision outcomes in general and regret, i.e., the emotion associated with focus on an alternative superior outcome, in particular. Regret is linked to self-esteem in that it involves the evaluation of an individual's own decisions. Alterations of self-esteem, in turn, are a hallmark of depression. The literature on the behavioral and neural processes underlying counterfactual thinking, self-esteem, and depression is selectively reviewed. A model is proposed in which unstable self-representation in depression is more strongly perturbed when a different choice would have produced a better outcome, leading to increased feelings of regret. This approach may help unify diverse aspects of depression, can generate testable predictions, and may suggest new treatment avenues targeting distorted counterfactual cognitions, attentional biases toward superior counterfactual outcomes, or increased affective response to regretted outcomes.