The Ambiguous Cue Task: Measurement reliability of an experimental paradigm for the assessment of interpretation bias and associations with mental health.

Interpretation biases in the processing of ambiguous affective information are assumed to play an important role in the onset and maintenance of emotional disorders. Reports of low reliability for experimental measures of cognitive biases have called into question previous findings on the association of these measures with markers of mental health and demonstrated the need to systematically evaluate measurement reliability for measures of cognitive biases. We evaluated reliability and correlations with self-report measures of mental health for interpretation bias scores derived from the Ambiguous Cue Task (ACT), an experimental paradigm for the assessment of approach-avoidance behavior towards ambiguous affective stimuli. For a non-clinical sample, the measurement of an interpretation bias with the ACT showed high internal consistency (rSB = .91 - .96, N = 354) and acceptable 2-week test-retest correlations (rPearson = .61 - .65, n = 109). Correlations between the ACT interpretation bias scores and mental health-related self-report measures of personality and well-being were generally small (r ≤ |.11|) and statistically not significant when correcting for multiple comparisons. These findings suggest that in non-clinical populations, individual differences in the interpretation of ambiguous affective information as assessed with the ACT do not show a clear association with self-report markers of mental health. However, in allowing for a highly reliable measurement of interpretation bias, the ACT provides a valuable tool for studies considering potentially small effect sizes in non-clinical populations by studying bigger samples as well as for work on clinical populations, for which potentially greater effects can be expected.

Heightened response to positive facial cues as a potential marker of resilience following childhood adversity.

Background: Childhood maltreatment profoundly influences social and emotional development, increasing psychiatric risk. Alterations in the implicit processing of threat-related cues following early abuse and neglect represent a marker of mental health vulnerability. Less is known about how early adversity influences the perception of positive social cues, despite their central role in establishing and maintaining social interactions and their association with better mental health outcomes.Methods: The sample consisted of 42 children and adolescents with substantiated childhood maltreatment experiences and 32 peers (mean age 13.3), matched on age, pubertal status, gender, socioeconomic status, ethnicity, and cognitive ability. A computerised experimental task assessed the perceived emotional intensity of positive (happy) and negative (fearful) facial expressions. Mental health symptoms were measured via self- and parental reports, and perceived social support was self-reported.Results: The experience of abuse and neglect was associated with heightened perceived intensity of positive facial cues. Cross-sectional post-hoc moderation and mediation analyses, employing a model-building approach, revealed that in maltreatment-exposed participants: (i) their increased response to positive facial cues was associated with lower symptoms; (ii) the presence of social support accounted for their heightened perceived intensity of positive facial cues; (iii) the presence of social support putatively contributed to lower symptoms by increasing the perceived intensity of positive facial cues. No group differences in perceived intensity of negative expressions were observed.Conclusions: These findings provide fresh insight into how positive faces are processed following maltreatment experience in childhood. Maltreatment experience was found to be associated with heightened perceived intensity of happy faces, which in turn was associated with better mental health and greater levels of social support. This suggests that heightened saliency of positive emotions acts protectively in children with maltreatment experience.

The impact of childhood maltreatment on perceiving positive social cues, especially explicit emotional intensity appraisal, is less understood compared to the extensive focus on its role in processing threat-related cues and psychiatric risk.In this study, we found that maltreatment experience was associated with heightened perceived intensity of happy faces, which in turn was associated with better mental health and greater levels of social support.These findings suggest that heightened saliency of positive emotions may act protectively in children with maltreatment experience.

Atypical Interpersonal Problem-Solving and Resting-state Functional Connectivity in Adolescents with Maltreatment Experience.

BACKGROUND: Childhood maltreatment is associated with altered neurocognitive functioning, which is thought to reflect, in part, adaptation to early adverse environmental experiences. However, we continue to lack a precise mechanistic understanding linking atypical neurocognitive processing with social functioning and psychiatric outcomes following early adversity. OBJECTIVE: The present work investigated interpersonal problem-solving, resting-state functional connectivity (rsFC), and mental health symptoms in adolescents with documented maltreatment experience and explored whether altered neural function contributes in part to poorer social functioning. METHODS: Forty adolescents (aged 12-17) with documented experiences of abuse or neglect and a carefully matched group of 42 non-maltreated peers participated in this study that measured task-based interpersonal problem-solving skills and rsFC. RESULTS: Adolescents with maltreatment experience showed poorer interpersonal problem-solving performance, which partly accounted for their elevated mental health symptoms. Resting-state seed-based analyses revealed that adolescents with maltreatment experience showed a significant increase in rsFC between medial Default Mode Network (DMN) hubs, the medial prefrontal cortex (mPFC), with a posterior cluster, including the posterior cingulate cortex (PCC), precuneus (PCu), retrosplenial cortex (RSC), and lingual gyrus (LG). Moderation analyses revealed that maltreatment-related increased DMN rsFC partly accounted for poorer performance in interpersonal problem-solving. CONCLUSION: Poorer interpersonal problem-solving, partly accounted for by atypical coupling between DMN medial hubs, was associated with maltreatment exposure. Interventions tailored to enhance interpersonal problem-solving represents a promising avenue to promote resilience and reduce the likelihood of mental health disorder following maltreatment experience.

Altered reward and effort processing in children with maltreatment experience: a potential indicator of mental health vulnerability.

In this longitudinal study of children and adolescents with a documented history of maltreatment, we investigated the impact of maltreatment on behavioral and neural indices of effort-based decision making for reward and examined their associations with future internalizing symptoms. Thirty-seven children with a documented history of maltreatment (MT group) and a carefully matched group of 33 non-maltreated children (NMT group) aged 10-16, completed an effort-based decision-making task during functional magnetic resonance imaging (fMRI). Internalizing symptoms were assessed at baseline and again 18 months later. Computational models were implemented to extract individual estimates of reward and effort sensitivity, and neural signals during decision-making about different levels of reward and effort were analyzed. These were used to predict internalizing symptoms at follow-up. We identified lower effort-related activation in the anterior cingulate cortex (ACC), a prespecified region-of-interest, in the MT relative to the NMT group. No group differences were observed in the striatum, or in behavioral indices of reward and effort processing. Lower effort-related ACC activation significantly predicted elevated internalizing symptoms at follow-up in the MT group. These findings suggest that disrupted effort-related activation may index latent vulnerability to mental illness in children who have experienced maltreatment.

Brain Signal Variability Differentially Affects Cognitive Flexibility and Cognitive Stability.

Recent research yielded the intriguing conclusion that, in healthy adults, higher levels of variability in neuronal processes are beneficial for cognitive functioning. Beneficial effects of variability in neuronal processing can also be inferred from neurocomputational theories of working memory, albeit this holds only for tasks requiring cognitive flexibility. However, cognitive stability, i.e., the ability to maintain a task goal in the face of irrelevant distractors, should suffer under high levels of brain signal variability. To directly test this prediction, we studied both behavioral and brain signal variability during cognitive flexibility (i.e., task switching) and cognitive stability (i.e., distractor inhibition) in a sample of healthy human subjects and developed an efficient and easy-to-implement analysis approach to assess BOLD-signal variability in event-related fMRI task paradigms. Results show a general positive effect of neural variability on task performance as assessed by accuracy measures. However, higher levels of BOLD-signal variability in the left inferior frontal junction area result in reduced error rate costs during task switching and thus facilitate cognitive flexibility. In contrast, variability in the same area has a detrimental effect on cognitive stability, as shown in a negative effect of variability on response time costs during distractor inhibition. This pattern was mirrored at the behavioral level, with higher behavioral variability predicting better task switching but worse distractor inhibition performance. Our data extend previous results on brain signal variability by showing a differential effect of brain signal variability that depends on task context, in line with predictions from computational theories. SIGNIFICANCE STATEMENT: Recent neuroscientific research showed that the human brain signal is intrinsically variable and suggested that this variability improves performance. Computational models of prefrontal neural networks predict differential effects of variability for different behavioral situations requiring either cognitive flexibility or stability. However, this hypothesis has so far not been put to an empirical test. In this study, we assessed cognitive flexibility and cognitive stability, and, besides a generally positive effect of neural variability on accuracy measures, we show that neural variability in a prefrontal brain area at the inferior frontal junction is differentially associated with performance: higher levels of variability are beneficial for the effectiveness of task switching (cognitive flexibility) but detrimental for the efficiency of distractor inhibition (cognitive stability).

Stochastic Dynamics Underlying Cognitive Stability and Flexibility.

Cognitive stability and flexibility are core functions in the successful pursuit of behavioral goals. While there is evidence for a common frontoparietal network underlying both functions and for a key role of dopamine in the modulation of flexible versus stable behavior, the exact neurocomputational mechanisms underlying those executive functions and their adaptation to environmental demands are still unclear. In this work we study the neurocomputational mechanisms underlying cue based task switching (flexibility) and distractor inhibition (stability) in a paradigm specifically designed to probe both functions. We develop a physiologically plausible, explicit model of neural networks that maintain the currently active task rule in working memory and implement the decision process. We simplify the four-choice decision network to a nonlinear drift-diffusion process that we canonically derive from a generic winner-take-all network model. By fitting our model to the behavioral data of individual subjects, we can reproduce their full behavior in terms of decisions and reaction time distributions in baseline as well as distractor inhibition and switch conditions. Furthermore, we predict the individual hemodynamic response timecourse of the rule-representing network and localize it to a frontoparietal network including the inferior frontal junction area and the intraparietal sulcus, using functional magnetic resonance imaging. This refines the understanding of task-switch-related frontoparietal brain activity as reflecting attractor-like working memory representations of task rules. Finally, we estimate the subject-specific stability of the rule-representing attractor states in terms of the minimal action associated with a transition between different rule states in the phase-space of the fitted models. This stability measure correlates with switching-specific thalamocorticostriatal activation, i.e., with a system associated with flexible working memory updating and dopaminergic modulation of cognitive flexibility. These results show that stochastic dynamical systems can implement the basic computations underlying cognitive stability and flexibility and explain neurobiological bases of individual differences.

Touchscreen-paradigm for mice reveals cross-species evidence for an antagonistic relationship of cognitive flexibility and stability.

The abilities to either flexibly adjust behavior according to changing demands (cognitive flexibility) or to maintain it in the face of potential distractors (cognitive stability) are critical for adaptive behavior in many situations. Recently, a novel human paradigm has found individual differences of cognitive flexibility and stability to be related to common prefrontal networks. The aims of the present study were, first, to translate this paradigm from humans to mice and, second, to test conceptual predictions of a computational model of prefrontal working memory mechanisms, the Dual State Theory, which assumes an antagonistic relation between cognitive flexibility and stability. Mice were trained in a touchscreen-paradigm to discriminate visual cues. The task involved "ongoing" and cued "switch" trials. In addition distractor cues were interspersed to test the ability to resist distraction, and an ambiguous condition assessed the spontaneous switching between two possible responses without explicit cues. While response times did not differ substantially between conditions, error rates (ER) increased from the "ongoing" baseline condition to the most complex condition, where subjects were required to switch between two responses in the presence of a distracting cue. Importantly, subjects switching more often spontaneously were found to be more distractible by task irrelevant cues, but also more flexible in situations, where switching was required. These results support a dichotomy of cognitive flexibility and stability as predicted by the Dual State Theory. Furthermore, they replicate critical aspects of the human paradigm, which indicates the translational potential of the testing procedure and supports the use of touchscreen procedures in preclinical animal research.