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.

Trust and childhood maltreatment: evidence of bias in appraisal of unfamiliar faces.

BACKGROUND: Child maltreatment is associated with poorer social functioning and increased risk of mental health problems in adolescence and adulthood, but the processes underlying these associations remain unclear. Although crucial for establishing and maintaining relationships, trust judgements have not been experimentally investigated in children who have experienced abuse and neglect. METHODS: A community-based sample of 75 children aged 8-16 years with maltreatment documented on the basis of social services records, and a group of 70 peers matched on age, gender, cognitive ability, socioeconomic status, and ethnicity took part in the study. Children completed a trustworthiness face-judgement task in which they appraised the trustworthiness of unfamiliar facial stimuli varying along a computationally modelled trustworthiness dimension. RESULTS: In line with clinical observations that childhood maltreatment is associated with an atypical pattern of trust processing, children with maltreatment experience were significantly less likely than their peers to rate unfamiliar faces as trustworthy. Moreover, they were more variable in their trust attributions than their peers. CONCLUSIONS: The study provides compelling experimental evidence that children with documented maltreatment perceive others as less trustworthy than their peers and are less consistent in their estimates of trustworthiness in others. Over time, alterations in trust processing may disrupt the development of social bonds and contribute to 'social thinning' (a reduction in the extent and quality of social relationships), leaving children more vulnerable to environmental stressors, increasing risk of mental health difficulties.

The burden attributable to headache disorders in children and adolescents in Lithuania: estimates from a national schools-based study.

BACKGROUND: We recently showed headache to be common in children (aged 7-11 years) and adolescents (aged 12-17) in Lithuania. Here we provide evidence from the same study of the headache-attributable burden. METHODS: Following the generic protocol for Lifting The Burden's global schools-based study, this cross-sectional survey administered self-completed structured questionnaires to pupils within classes in 24 nationally representative schools selected from seven regions of the country. Headache diagnostic questions were based on ICHD-3 beta criteria but for the inclusion of undifferentiated headache (UdH; defined as mild headache with usual duration < 1 h). Burden enquiry was conducted in multiple domains. RESULTS: Questionnaires were completed by 2505 pupils (1382 children, 1123 adolescents; participating proportion 67.4%), of whom 1858 reported headache in the preceding year, with mean frequency (±SD) of 3.7 ± 4.5 days/4 weeks and mean duration of 1.6 ± 1.9 h. Mean proportion of time in ictal state, estimated from these, was 0.9% (migraine 1.5%, probable medication-overuse headache [pMOH] 10.9%). Mean intensity on a scale of 1-3 was 1.6 ± 0.6 (mild-to-moderate). Symptomatic medication was consumed on 1.5 ± 2.8 days/4 weeks. Lost school time was 0.5 ± 1.5 days/4 weeks (migraine 0.7 ± 1.5, pMOH 5.0 ± 7.8) based on recall, but about 50% higher for migraine according to actual absences recorded in association with reported headache on the preceding day. More days were reported with limited activity (overall 1.2 ± 2.4, migraine 1.5 ± 2.2, pMOH 8.4 ± 8.5) than lost from school. One in 30 parents (3.3%) missed work at least once in 4 weeks because of their son's or daughter's headache. Emotional impact and quality-of-life scores generally reflected other measures of burden, with pMOH causing greatest detriments, followed by migraine and tension-type headache, and UdH least. Burdens were greater in adolescents than children as UdH differentiated into adult headache types. CONCLUSIONS: Headache in children and adolescents in Lithuania is mostly associated with modest symptom burden. However, the consequential burdens, in particular lost school days, are far from negligible for migraine (which is prevalent) and very heavy for pMOH (which, while uncommon in children, becomes four-fold more prevalent in adolescents). These findings are of importance to both health and educational policies in Lithuania.

The prevalence of headache disorders in children and adolescents in Lithuania: a schools-based study.

BACKGROUND: While the Global Burden of Disease (GBD) study reports headache disorders as the second-highest cause of disability worldwide, the headache data in GBD come very largely from adults. This national study in Lithuania was part of a global schools-based programme within the Global Campaign against Headache contributing data from children (7-11 years) and adolescents (12-17 years). METHODS: The methods followed the generic protocol for the global study. The basic study design was a cross-sectional survey. Self-completed structured questionnaires were administered, within classes, in 24 schools selected from seven regions of Lithuania to be nationally representative. Headache diagnostic questions were based on ICHD-3 beta criteria but for the inclusion of undifferentiated headache (UdH). RESULTS: Of 3714 potential participants, 2505 (children 1382 [55.2%], adolescents 1123 [44.8%]; males 1169 [46.7%], females 1336 [53.3%]) completed the questionnaire. Adolescents and males were therefore relatively under-represented, with non-participation (32.6%) due in most cases to lack of parental consent. Observed lifetime prevalence of headache was 92.2%. Gender- and age-adjusted 1-year prevalence was 76.6% (migraine: 21.4%; tension-type headache [TTH]: 25.6%; UdH: 24.0%; all headache on ≥15 days/month: 3.9%; probable medication-overuse headache: 0.8%). All headache types except UdH were more prevalent among females than males, and among adolescents than children. UdH showed a complex relationship with age, but represented 38.0% of all reported headache in children, 27.4% in adolescents. Headache yesterday (HY) was reported by 17.5%, almost double the 9.8% predicted from prevalence and headache frequency to have headache on any day. The reason was unclear. CONCLUSIONS: Findings were not very different from those reported in Turkey and Austria, but with more TTH. Headache has, therefore, again been shown to be common in children and adolescents, and UdH confirmed as a headache type that must be recognised and included in accounts of headache in these age groups.

Translation of the Child and Adolescent HARDSHIP (Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation) Questionnaire into the Lithuanian Language and Validation of Its HRQoL (Headache-Related Quality of Life) Scale.

Recently developed and originally published in English, the Child and Adolescent HARDSHIP (headache-attributed restriction, disability, social handicap and impaired participation) questionnaire is valid and acceptable for the global assessment of the burden of headache in children and adolescents. The present study aimed to translate, adapt and validate a Lithuanian version of this questionnaire. A total of 22 volunteers from 7 to 17 years of age completed the questionnaire with 24 h test-retest and a representative sample of 2505 schoolchildren of the same age participated in the main study. Test-retest reliability of the HRQoL (Headache Related Quality of Life) scale in the translated questionnaire showed substantial agreement (kappa: 0.604). Reliability and validity of the translated HRQoL scale were acceptable (Cronbach's alpha: 0.749; test-retest kappa: 0.604, test for discriminant validity demonstrated that quality of life decreased by severity of headache). Factorial analysis revealed the two-dimensional structure of the HRQoL scale with indices of good model fit to the collected data. A total of 92.2% of the surveyed children had experienced headache in their lifetime, 74.2% during the last year. Girls and older children experienced headache more often than participants from the other groups. The translated Lithuanian version of the questionnaire seems to be a valid, feasible and acceptable instrument to measure the extent of the burden of headache in large populations.

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.