Risk factors for internalizing symptoms: The influence of empathy, theory of mind, and negative thinking processes.

Internalizing symptoms such as elevated stress and sustained negative affect can be important warning signs for developing mental disorders. A recent theoretical framework suggests a complex interplay of empathy, theory of mind (ToM), and negative thinking processes as a crucial risk combination for internalizing symptoms. To disentangle these relationships, this study utilizes neural, behavioral, and self-report data to examine how the interplay between empathy, ToM, and negative thinking processes relates to stress and negative affect. We reanalyzed the baseline data of N = 302 healthy participants (57% female, Mage = 40.52, SDage = 9.30) who participated in a large-scale mental training study, the ReSource project. Empathy and ToM were assessed using a validated fMRI paradigm featuring naturalistic video stimuli and via self-report. Additional self-report scales were employed to measure internalizing symptoms (perceived stress, negative affect) and negative thinking processes (rumination and self-blame). Our results revealed linear associations of self-reported ToM and empathic distress with stress and negative affect. Also, both lower and higher, compared to average, activation in the anterior insula during empathic processing and in the middle temporal gyrus during ToM performance was significantly associated with internalizing symptoms. These associations were dependent on rumination and self-blame. Our findings indicate specific risk constellations for internalizing symptoms. Especially people with lower self-reported ToM and higher empathic distress may be at risk for more internalizing symptoms. Quadratic associations of empathy- and ToM-related brain activation with internalizing symptoms depended on negative thinking processes, suggesting differential effects of cognitive and affective functioning on internalizing symptoms. Using a multi-method approach, these findings advance current research by shedding light on which complex risk combinations of cognitive and affective functioning are relevant for internalizing symptoms.

Testing the monitor and acceptance theory: the role of training-induced changes in monitoring- and acceptance-related capacities after attention-based, socio-emotional, or socio-cognitive mental training in reducing cortisol stress reactivity.

Mindfulness-based interventions have become a popular means to reduce stress. However, the specific mechanisms driving observed stress reduction remain understudied. The Monitor and Acceptance Theory suggests that the cultivation of monitoring and acceptance skills are necessary moderators of practice-induced stress reduction. In the context of the ReSource Project, a large healthy adult sample underwent three 3-month mental training modules targeting either attentional (Presence module), socio-affective (Affect module) or socio-cognitive skills (Perspective module). In the current study, the development of a range of inter-individual differences in mindfulness-, interoception- and compassion-related traits - which mapped to either monitoring or acceptance categories - was tracked. The relationship of these training-induced changes with cortisol stress reactivity after the three distinct 3-month training modules was explored. We found that stress sensitivity was particularly modulated by a differential adaptivity of one cultivated attentional capacity - Attention regulation - which predicted higher cortisol reactivity after mere attention training (Presence) but was associated with lower stress-induced cortisol release after additional socio-affective and socio-cognitive practice (Affect and Perspective). However, this effect did not survive multiple comparisons correction, and analyses were limited by the sample size available. We conclude that our study provides preliminary support of the Monitor and Acceptance Theory, lending weight to the advantage of primary attentional increases in order to fully harness the beneficial effects of socio-affective training, ultimately leading to stress reduction. Although training-induced increases in acceptance were not directly shown to contribute to lowering cortisol stress reactivity, the data suggest an additional benefit of socio-affective and socio-cognitive training that is not directly captured within the current analyses. Our study corroborates the importance of going beyond the training of attention monitoring to foster stress resilience, and highlights that mental training relies on the co-development of several interacting processes to successfully attenuate stress. Further exploring the overarching concept of acceptance in future research may prove beneficial to the theoretical framework of MAT, and in understanding the processes by which stress reduction occurs.

Genetic predisposition for negative affect predicts mental health burden during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic was accompanied by an increase in mental health challenges including depression, stress, loneliness, and anxiety. Common genetic variants can contribute to the risk for psychiatric disorders and may present a risk factor in times of crises. However, it is unclear to what extent polygenic risk played a role in the mental health response to the COVID-19 pandemic. In this study, we investigate whether polygenic scores (PGSs) for mental health-related traits can distinguish between four resilience-vulnerability trajectories identified during the COVID-19 pandemic and associated lockdowns in 2020/21. We used multinomial regression in a genotyped subsample (n = 1316) of the CovSocial project. The most resilient trajectory characterized by the lowest mental health burden and the highest recovery rates served as the reference group. Compared to this most resilient trajectory, a higher value on the PGS for the well-being spectrum decreased the odds for individuals to be in one of the more vulnerable trajectories (adjusted R-square = 0.3%). Conversely, a higher value on the PGS for neuroticism increased the odds for individuals to be in one of the more vulnerable trajectories (adjusted R-square = 0.2%). Latent change in mental health burden extracted from the resilience-vulnerability trajectories was not associated with any PGS. Although our findings support an influence of PGS on mental health during COVID-19, the small added explained variance suggests limited utility of such genetic markers for the identification of vulnerable individuals in the general population.

Two systems for thinking about others' thoughts in the developing brain.

Human social interaction crucially relies on the ability to infer what other people think. Referred to as Theory of Mind (ToM), this ability has long been argued to emerge around 4 y of age when children start passing traditional verbal ToM tasks. This developmental dogma has recently been questioned by nonverbal ToM tasks passed by infants younger than 2 y of age. How do young children solve these tests, and what is their relation to the later-developing verbal ToM reasoning? Are there two different systems for nonverbal and verbal ToM, and when is the developmental onset of mature adult ToM? To address these questions, we related markers of cortical brain structure (i.e., cortical thickness and surface area) of 3- and 4-y-old children to their performance in novel nonverbal and traditional verbal TM tasks. We showed that verbal ToM reasoning was supported by cortical surface area and thickness of the precuneus and temporoparietal junction, classically involved in ToM in adults. Nonverbal ToM reasoning, in contrast, was supported by the cortical structure of a distinct and independent neural network including the supramarginal gyrus also involved in emotional and visual perspective taking, action observation, and social attention or encoding biases. This neural dissociation suggests two systems for reasoning about others' minds-mature verbal ToM that emerges around 4 y of age, whereas nonverbal ToM tasks rely on different earlier-developing possibly social-cognitive processes.

Boosting Empathy and Compassion Through Mindfulness-Based and Socioemotional Dyadic Practice: Randomized Controlled Trial With App-Delivered Trainings.

BACKGROUND: Contemplative trainings have been found to effectively improve social skills such as empathy and compassion. However, there is a lack of research on the efficacy of app-delivered mindfulness-based and dyadic practices in boosting socioaffective capacity. OBJECTIVE: The first aim of this study was to compare a novel app-delivered, partner-based socioemotional intervention (Affect Dyad) with mindfulness-based training to foster empathy and compassion for the self or others. The second aim of this study was to investigate the underlying mechanisms of these effects. METHODS: This randomized controlled trial included socioemotional and mindfulness-based interventions and a waitlist control group, which received socioemotional training after the postintervention assessment. We used linear mixed-effects models to test intervention effects on self-report measures and an ecologically valid computer task of empathy, compassion for the self and others, and theory of mind. Moderated mediation models were used to investigate whether changes in acceptance, empathic distress, empathic listening, interoceptive awareness, and mindfulness served as underlying psychological processes of intervention effects. RESULTS: In 218 participants (mean age 44.12, SD 11.71 years; 160/218, 73.4% female), we found all interventions to have positive effects on composite scores for compassion toward the self (ßsocioemotional=.44, P<.001; ßwaitlist socioemotional=.30, P=.002; ßmindfulness-based=.35, P<.001) and others (ßsocioemotional=.24, P=.003; ßwaitlist socioemotional=.35, P<.001; ßmindfulness-based=.29, P<.001). Compassion measured with the computer task did not change significantly but showed a trend toward increase only in socioemotional dyadic practice (ßsocioemotional=.08, P=.08; ßwaitlist socioemotional=.11, P=.06). Similarly, on the empathic concern subscale of the Interpersonal Reactivity Index, a nonsignificant trend toward increase was found in the socioemotional intervention group (ßsocioemotional=.17; P=.08). Empathy significantly increased in both socioemotional groups (ßsocioemotional=.16, P=.03; ßwaitlist socioemotional=.35, P<.001) and the mindfulness-based group (ßmindfulness-based=.15; P=.04). The measures of theory of mind did not change over time. In the mindfulness-based group, the increase in self-compassion was mediated by a decrease in empathic distress (indirect effect abmindfulness-based=0.07, 95% CI 0.02-0.14). In the socioemotional group, an increase in self-compassion could be predicted by an increase in acceptance (ßsocioemotional=6.63, 95% CI 0.52-12.38). CONCLUSIONS: Using a multimethod approach, this study shows that app-delivered socioemotional and mindfulness-based trainings are effective in fostering compassion for the self and others in self-report. Both low-dose trainings could boost behavioral empathy markers; however, the effects on behavioral and dispositional markers of compassion only trended after dyadic practice, yet these effects did not reach statistical significance. Training-related increases in self-compassion rely on differential psychological processes, that is, on improved empathic distress regulation through mindfulness-based training and the activation of a human care- and acceptance-based system through socioemotional dyadic training. TRIAL REGISTRATION: ClinicalTrials.gov NCT04889508; https://clinicaltrials.gov/ct2/show/NCT04889508.

Development of functional network architecture explains changes in children's altruistically motivated helping.

Childhood is marked by profound changes in prosocial behaviour. The underlying motivational mechanisms remain poorly understood. We investigated the development of altruistically motivated helping in middle childhood and the neurocognitive and -affective mechanisms driving this development. One-hundred and twenty seven 6-12 year-old children performed a novel gustatory costly helping task designed to measure altruistic motivations of helping behaviour. Neurocognitive and -affective mechanisms including emotion regulation, emotional clarity and attentional reorienting were assessed experimentally through an extensive task-battery while functional brain activity and connectivity were measured during an empathy for taste paradigm and during rest. Altruistically motivated helping increased with age. Out of all mechanisms probed for, only emotional clarity increased with age and accounted for altruistically motivated helping. This was associated with greater functional integration of the empathy-related network with fronto-parietal brain regions at rest. We isolate a highly specific neuroaffective mechanism as the crucial driver of altruistically motivated helping during child development.

Decreased emotional reactivity after 3-month socio-affective but not attention- or meta-cognitive-based mental training: A randomized, controlled, longitudinal fMRI study.

Meditation-based mental training interventions show physical and mental health benefits. However, it remains unclear how different types of mental practice affect emotion processing at both the neuronal and the behavioural level. In the context of the ReSource project, 332 participants underwent an fMRI scan while performing an emotion anticipation task before and after three 3-month training modules cultivating 1) attention and interoceptive awareness (Presence); 2) socio-affective skills, such as compassion (Affect); 3) socio-cognitive skills, such as theory of mind (Perspective). Only the Affect module led to a significant reduction of experienced negative affect when processing images depicting human suffering. In addition, after the Affect module, participants showed significant increased activation in the right supramarginal gyrus when confronted with negative stimuli. We conclude that socio-affective, but not attention- or meta-cognitive based mental training is specifically effective to improve emotion regulation capabilities when facing adversity.

Contemplative Mental Training Reduces Hair Glucocorticoid Levels in a Randomized Clinical Trial.

OBJECTIVE: This study aimed to investigate the effect of regular contemplative mental training on endocrine and psychological indices of long-term stress. METHODS: An open-label efficacy trial that comprised three distinct 3-month long modules targeting attention and interoception, socioaffective, or sociocognitive abilities through dyadic exercises and secularized meditation practices was conducted with healthy adults. Participants underwent the training for 3 or 9 months, or were assigned to a retest control cohort. Chronic stress indices were assayed at four time points: pretraining and after 3, 6, and 9 months. The main outcome measures were cortisol (HC) and cortisone (HE) concentration in hair and self-reported long-term stress. RESULTS: Of 362 initially randomized individuals, 30 dropped out before study initiation (n = 332; mean [SD] age = 40.7 [9.2] years; 197 women). Hair-based glucocorticoid assays were available from n = 227, and questionnaire data from n = 326. Results from three separate training cohorts (TC1-3) revealed consistent decreases in HC and HE levels over the first three (TC3) to 6 months (TC1 and TC2) of training, with no further reduction at the final 9-month mark (baseline to end of training differences, HC, TC1: t(355) = 2.59, p = .010, contrast estimate (est.) [SE] = 0.35 [0.14]; HC, TC2: t(363) = 4.06, p < .001, est. = 0.48 [0.12]; HC, TC3: t(368) = 3.18, p = .002, est. = 0.41 [0.13]; HE, TC1: t(435) = 3.23, p = .001, est. = 0.45 [0.14]; HE, TC2: t(442) = 2.60, p = .010, est. = 0.33 [0.13]; HE, TC3: t(446) = 4.18, p < .001, est. = 0.57 [0.14]). Training effects on HC increased with individual compliance (practice frequency), and effects on both HC and HE were independent of training content and unrelated to change in self-reported chronic stress. Self-reported stress, and cortisol-to-dehydroepiandrosterone ratios as an exploratory endpoint, were also reduced, albeit less consistently. CONCLUSIONS: Our results point to the reduction of long-term cortisol exposure as a mechanism through which meditation-based mental training may exert positive effects on practitioners' health.Trial Registration: ClinicalTrials.gov identifier: NCT01833104.

The neural basis of empathy.

Empathy--the ability to share the feelings of others--is fundamental to our emotional and social lives. Previous human imaging studies focusing on empathy for others' pain have consistently shown activations in regions also involved in the direct pain experience, particularly anterior insula and anterior and midcingulate cortex. These findings suggest that empathy is, in part, based on shared representations for firsthand and vicarious experiences of affective states. Empathic responses are not static but can be modulated by person characteristics, such as degree of alexithymia. It has also been shown that contextual appraisal, including perceived fairness or group membership of others, may modulate empathic neuronal activations. Empathy often involves coactivations in further networks associated with social cognition, depending on the specific situation and information available in the environment. Empathy-related insular and cingulate activity may reflect domain-general computations representing and predicting feeling states in self and others, likely guiding adaptive homeostatic responses and goal-directed behavior in dynamic social contexts.

Functional magnetic resonance imaging (fMRI) item analysis of empathy and theory of mind.

In contrast to conventional functional magnetic resonance imaging (fMRI) analysis across participants, item analysis allows generalizing the observed neural response patterns from a specific stimulus set to the entire population of stimuli. In the present study, we perform an item analysis on an fMRI paradigm (EmpaToM) that measures the neural correlates of empathy and Theory of Mind (ToM). The task includes a large stimulus set (240 emotional vs. neutral videos to probe empathic responding and 240 ToM or factual reasoning questions to probe ToM), which we tested in two large participant samples (N = 178, N = 130). Both, the empathy-related network comprising anterior insula, anterior cingulate/dorsomedial prefrontal cortex, inferior frontal gyrus, and dorsal temporoparietal junction/supramarginal gyrus (TPJ) and the ToM related network including ventral TPJ, superior temporal gyrus, temporal poles, and anterior and posterior midline regions, were observed across participants and items. Regression analyses confirmed that these activations are predicted by the empathy or ToM condition of the stimuli, but not by low-level features such as video length, number of words, syllables or syntactic complexity. The item analysis also allowed for the selection of the most effective items to create optimized stimulus sets that provide the most stable and reproducible results. Finally, reproducibility was shown in the replication of all analyses in the second participant sample. The data demonstrate (a) the generalizability of empathy and ToM related neural activity and (b) the reproducibility of the EmpaToM task and its applicability in intervention and clinical imaging studies.

Exploring the multidimensional complex systems structure of the stress response and its relation to health and sleep outcomes.

To gain a comprehensive understanding of the multidimensional complex systems structure of the stress response and related health outcomes, we utilized network analysis in a sample of 328 healthy participants in two steps. In a first step, we focused on associations between measures of basal hypothalamic-pituitary-adrenal axis functioning and subjective stress perceptions. In a second step, we linked these diverse stress-related measures to biomarkers and self-reports of health and sleep. Overall, measures clustered depending on their method of assessment, with high correlations between different saliva-based indices of diurnal cortisol regulation, between cortisol and cortisone levels in hair, between different biological health indicators (systemic inflammatory activity and body mass index), between state (experience sampling) and trait (questionnaire-based) self-reports of stress and wellbeing, and between different self-reports of sleep. Bridges between clusters suggested that if individuals perceive stress throughout their daily lives this is reflected in their total salivary cortisol output possibly contributing to long-term cortisol accumulation in hair. Likewise, earlier awakening time may contribute to cortisol accumulation in hair via an influence on awakening cortisol processes. Our results show that while meaningful connections between measures exist, stress is a highly complex construct composed of numerous aspects. We argue that network analysis is an integrative statistical approach to address the multidimensionality of the stress response and its effects on the brain and body. This may help uncover pathways to stress-related disease and serve to identify starting points for prevention and therapeutic intervention.

Cortisol stress resonance in the laboratory is associated with inter-couple diurnal cortisol covariation in daily life.

In laboratory environments individuals may display empathic cortisol stress responses merely from observing another experience psychosocial stress. Moreover, within couples, women synchronize their own to their partners' stress-induced cortisol release. We investigated whether a woman's tendency to experience such cortisol stress resonance in a controlled laboratory task is associated with the degree to which her and her partner's diurnal cortisol levels covary in a naturalistic environment. Such habitual cortisol covariation may be a pathway via which close relationships influence health outcomes. Forty-four men completed the Trier Social Stress Test while their female partners observed the situation, either via "real-life" (one-way mirror) or "virtual" (video) observation modality. Later, the couples collected diurnal cortisol samples over two weekdays. Hierarchical linear modeling indicated that the degree to which couples covaried in their daily cortisol secretion was associated with the female partner's cortisol stress resonance in the laboratory, and that this association was stronger if stress resonance was assessed in the "real-life" observation condition. Specifically, women with higher cortisol stress resonance were more closely linked to their partner's diurnal cortisol secretion. Neither momentary partner presence during sampling nor relationship duration or quality accounted for the association. By showing that covariation in the laboratory has ecological validity in naturalistic conditions, these results make an important methodological contribution to the study of dyadic processes. Given that close relationships exert immense influence over individual health outcomes, understanding the association between acute and chronic physiological linkage may provide important insight into the mechanisms by which close relationships impact well-being.

Socio-Cognitive Phenotypes Differentially Modulate Large-Scale Structural Covariance Networks.

Functional neuroimaging studies have suggested the existence of 2 largely distinct social cognition networks, one for theory of mind (taking others' cognitive perspective) and another for empathy (sharing others' affective states). To address whether these networks can also be dissociated at the level of brain structure, we combined behavioral phenotyping across multiple socio-cognitive tasks with 3-Tesla MRI cortical thickness and structural covariance analysis in 270 healthy adults, recruited across 2 sites. Regional thickness mapping only provided partial support for divergent substrates, highlighting that individual differences in empathy relate to left insular-opercular thickness while no correlation between thickness and mentalizing scores was found. Conversely, structural covariance analysis showed clearly divergent network modulations by socio-cognitive and -affective phenotypes. Specifically, individual differences in theory of mind related to structural integration between temporo-parietal and dorsomedial prefrontal regions while empathy modulated the strength of dorsal anterior insula networks. Findings were robust across both recruitment sites, suggesting generalizability. At the level of structural network embedding, our study provides a double dissociation between empathy and mentalizing. Moreover, our findings suggest that structural substrates of higher-order social cognition are reflected rather in interregional networks than in the the local anatomical markup of specific regions per se.

Experiencing meditation - Evidence for differential effects of three contemplative mental practices in micro-phenomenological interviews.

Despite increasing interest in effects of meditation, systematic in-depth research on how it qualitatively feels to engage in different kinds of contemplative practices is still missing. To fill this gap, we explore the validity of Micro-phenomenological Interviews (MpI) to assess experiences during breathing meditation (BM), observing-thought meditation (OTM), and loving-kindness meditation (LKM). We performed psycholinguistic analyses, quantitative ratings and qualitative explorations of 104 MpI (N = 57). All results reveal differential affective, bodily and sensorial fingerprints: BM-transcripts contain the most body-related vocabulary, specifically sensations in nose and abdomen. OTM-transcripts contain the most cognition-related vocabulary. OTM is experienced in head and face. LKM-transcripts contain the most vocabulary related to socio-affective processes. LKM is associated to love, sensations around the heart, and warmth. The LKM-outcomes were replicated with another independent set of MpI. These findings verify the merit of MpI as a scientific tool to gain reliable first-person data beyond questionnaires or rating scales.

Longitudinal evidence for 4-year-olds' but not 2- and 3-year-olds' false belief-related action anticipation.

Recently, infants younger than 2 years have been shown to display correct expectations of the actions of an agent with a false belief. The developmental trajectory of these early-developing abilities and their robustness, however, remain a matter of debate. Here, we tested children longitudinally from 2 to 4 years of age with an established anticipatory looking false belief task, and found a significant developmental change between the ages of 3 and 4 years. Children anticipated correctly only by the age of 4 years, and performed at chance at the ages of 2 and 3 years. Moreover, we found correct anticipation only when the agent falsely believed an object to be in its last rather than a previous location. These findings point towards the fragility of early belief-related action anticipation before the age of 4 years, when children start passing traditional false belief tasks.

Decoding the Charitable Brain: Empathy, Perspective Taking, and Attention Shifts Differentially Predict Altruistic Giving.

UNLABELLED: Altruistic behavior varies considerably across people and decision contexts. The relevant computational and motivational mechanisms that underlie its heterogeneity, however, are poorly understood. Using a charitable giving task together with multivariate decoding techniques, we identified three distinct psychological mechanisms underlying altruistic decision-making (empathy, perspective taking, and attentional reorienting) and linked them to dissociable neural computations. Neural responses in the anterior insula (AI) (but not temporoparietal junction [TPJ]) encoded trial-wise empathy for beneficiaries, whereas the TPJ (but not AI) predicted the degree of perspective taking. Importantly, the relative influence of both socio-cognitive processes differed across individuals: participants whose donation behavior was heavily influenced by affective empathy exhibited higher predictive accuracies for generosity in AI, whereas those who strongly relied on cognitive perspective taking showed improved predictions of generous donations in TPJ. Furthermore, subject-specific contributions of both processes for donations were reflected in participants' empathy and perspective taking responses in a separate fMRI task (EmpaToM), suggesting that process-specific inputs into altruistic choices may reflect participants' general propensity to either empathize or mentalize. Finally, using independent attention task data, we identified shared neural codes for attentional reorienting and generous donations in the posterior superior temporal sulcus, suggesting that domain-general attention shifts also contribute to generous behavior (but not in TPJ or AI). Overall, our findings demonstrate highly specific roles of AI for affective empathy and TPJ for cognitive perspective taking as precursors of prosocial behavior and suggest that these discrete routes of social cognition differentially drive intraindividual and interindividual differences in altruistic behavior. SIGNIFICANCE STATEMENT: Human societies depend on the altruistic behavior of their members, but teasing apart its underlying motivations and neural mechanisms poses a serious challenge. Using multivariate decoding techniques, we delineated three distinct processes for altruistic decision-making (affective empathy, cognitive perspective taking, and domain-general attention shifts), linked them to dissociable neural computations, and identified their relative influence across individuals. Distinguishing process-specific computations both behaviorally and neurally is crucial for developing complete theoretical and neuroscientific accounts of altruistic behavior and more effective means of increasing it. Moreover, information on the relative influence of subprocesses across individuals and its link to people's more general propensity to engage empathy or perspective taking can inform training programs to increase prosociality, considering their "fit" with different individuals.

Implicit and explicit false belief development in preschool children.

The ability to represent the mental states of other agents is referred to as Theory of Mind (ToM). A developmental breakthrough in ToM consists of understanding that others can have false beliefs about the world. Recently, infants younger than 2 years of age have been shown to pass novel implicit false belief tasks. However, the processes underlying these tasks and their relation to later-developing explicit false belief understanding, as well as to other cognitive abilities, are not yet understood. Here, we study a battery of implicit and explicit false belief tasks in 3- and 4-year-old children, relating their performance to linguistic abilities and executive functions. The present data show a significant developmental change from failing explicit false belief tasks at 3 years of age to passing them at the age of 4, while both age groups pass implicit false belief tasks. This differential developmental trajectory is reflected by the finding that explicit and implicit false belief tasks do not correlate. Further, we demonstrate that explicit false belief tasks correlate with syntactic and executive functions, whereas implicit false belief tasks do not. The study thus indicates that the processes underlying implicit false belief tasks are different from later-developing explicit false belief understanding. Moreover, our results speak for a critical role of syntactic and executive functions for passing standard explicit false belief tasks in contrast to implicit tasks.

Stimulus-Driven Reorienting Impairs Executive Control of Attention: Evidence for a Common Bottleneck in Anterior Insula.

A classical model of human attention holds that independent neural networks realize stimulus-driven reorienting and executive control of attention. Questioning full independence, the two functions do, however, engage overlapping networks with activations in cingulo-opercular regions such as anterior insula (AI) and a reverse pattern of activation (stimulus-driven reorienting), and deactivation (executive control) in temporoparietal junction (TPJ). To test for independent versus shared neural mechanisms underlying stimulus-driven and executive control of attention, we used fMRI and a task that isolates individual from concurrent demands in both functions. Results revealed super-additive increases of left AI activity and behavioral response costs under concurrent demands, suggesting a common bottleneck for stimulus-driven reorienting and executive control of attention. These increases were mirrored by non-additive decreases of activity in the default mode network (DMN), including posterior TPJ, regions where activity increased with off-task processes. The deactivations in posterior TPJ were spatially separated from stimulus-driven reorienting related activation in anterior TPJ, a differentiation that replicated in task-free resting state. Furthermore, functional connectivity indicated inhibitory coupling between posterior TPJ and AI during concurrent attention demands. These results demonstrate a role of AI in stimulus-driven and executive control of attention that involves down-regulation of internally directed processes in DMN.

Development of Behavioral Control and Associated vmPFC-DLPFC Connectivity Explains Children's Increased Resistance to Temptation in Intertemporal Choice.

Human civilization is based on the successful pursuit of long-term goals, requiring the ability to forego immediate pleasure for the sake of larger future rewards. This ability improves with age, but the precise cognitive and neural mechanisms underlying its development remain elusive. The developmental changes could result either from younger children valuing immediate rewards more strongly or because older children become better at controlling their impulses. By implementing 2 tasks, a choice-independent valuation task and an intertemporal choice task, both behaviorally and using fMRI in twenty 6- to 13-year old children, we show developmental improvements in behavioral control to uniquely account for age-related changes in temporal discounting. We show further that overcoming temptation during childhood occurs as a function of an age-related increase in functional coupling between value signals in the ventromedial prefrontal cortex and brain regions dedicated to behavioral control, such as left dorsolateral prefrontal cortex during choice. These findings can help to devise measures that reduce the substantial costs of impatience to society.

Study protocol of the ASD-Net, the German research consortium for the study of Autism Spectrum Disorder across the lifespan: from a better etiological understanding, through valid diagnosis, to more effective health care.

BACKGROUND: Autism Spectrum Disorder (ASD) is a severe, lifelong neurodevelopmental disorder with early onset that places a heavy burden on affected individuals and their families. Due to the need for highly specialized health, educational and vocational services, ASD is a cost-intensive disorder, and strain on health care systems increases with increasing age of the affected individual. METHODS: The ASD-Net will study Germany's largest cohort of patients with ASD over the lifespan. By combining methodological expertise from all levels of clinical research, the ASD-Net will follow a translational approach necessary to identify neurobiological pathways of different phenotypes and their appropriate identification and treatment. The work of the ASD-Net will be organized into three clusters concentrating on diagnostics, therapy and health economics. In the diagnostic cluster, data from a large, well-characterized sample (N = 2568) will be analyzed to improve the efficiency of diagnostic procedures. Pattern classification methods (machine learning) will be used to identify algorithms for screening purposes. In a second step, the developed algorithm will be tested in an independent sample. In the therapy cluster, we will unravel how an ASD-specific social skills training with concomitant oxytocin administration can modulate behavior through neurobiological pathways. For the first time, we will characterize long-term effects of a social skills training combined with oxytocin treatment on behavioral and neurobiological phenotypes. Also acute effects of oxytocin will be investigated to delineate general and specific effects of additional oxytocin treatment in order to develop biologically plausible models for symptoms and successful therapeutic interventions in ASD. Finally, in the health economics cluster, we will assess service utilization and ASD-related costs in order to identify potential needs and cost savings specifically tailored to Germany. The ASD-Net has been established as part of the German Research Network for Mental Disorders, funded by the BMBF (German Federal Ministry of Education and Research). DISCUSSION: The highly integrated structure of the ASD-Net guarantees sustained collaboration of clinicians and researchers to alleviate individual distress, harm, and social disability of patients with ASD and reduce costs to the German health care system. TRIAL REGISTRATION: Both clinical trials of the ASD-Net are registered in the German Clinical Trials Register: DRKS00008952 (registered on August 4, 2015) and DRKS00010053 (registered on April 8, 2016).