Bianca G. van den Bulk

Better than expected or as bad as you thought? The neurocognitive development of probabilistic feedback processing

Learning from feedback lies at the foundation of adaptive behavior. Two prior neuroimaging studies have suggested that there are qualitative differences in how children and adults use feedback by demonstrating that dorsolateral prefrontal cortex (DLPFC) and parietal cortex were more active after negative feedback for adults, but after positive feedback for children. In the current study we used functional magnetic resonance imaging (fMRI) to test whether this difference is related to valence or informative value of the feedback by examining neural responses to negative and positive feedback while applying probabilistic rules. In total, 67 healthy volunteers between ages 8 and 22 participated in the study (8–11 years, n = 18; 13–16 years, n = 27; 18–22 years, n = 22). Behavioral comparisons showed that all participants were able to learn probabilistic rules equally well. DLPFC and dorsal anterior cingulate cortex were more active in younger children following positive feedback and in adults following negative feedback, but only when exploring alternative rules, not when applying the most advantageous rules. These findings suggest that developmental differences in neural responses to feedback are not related to valence per se, but that there is an age-related change in processing learning signals with different informative value.

How stable is activation in the amygdala and prefrontal cortex in adolescence? A study of emotional face processing across three measurements

Prior developmental functional magnetic resonance imaging (fMRI) studies have demonstrated elevated activation patterns in the amygdala and prefrontal cortex (PFC) in response to viewing emotional faces. As adolescence is a time of substantial variability in mood and emotional responsiveness, the stability of activation patterns could be fluctuating over time. In the current study, 27 healthy adolescents (age: 12-19 years) were scanned three times over a period of six months (mean test-retest interval of three months; final samples N=27, N=22, N=18). At each session, participants performed the same emotional faces task. At first measurement the presentation of emotional faces resulted in heightened activation in bilateral amygdala, bilateral lateral PFC and visual areas including the fusiform face area. Average activation did not differ across test-sessions over time, indicating that at the group level activation patterns in this network do not vary significantly over time. However, using the Intraclass Correlation Coefficient (ICC), fMRI reliability demonstrated only fair reliability for PFC (ICC=0.41-0.59) and poor reliability for the amygdala (ICC<0.4). These findings suggest substantial variability of brain activity over time and may have implications for studies investigating the influence of treatment effects on changes in neural levels in adolescents with psychiatric disorders.

Aberrant resting-state functional connectivity in limbic and salience networks in treatment--naïve clinically depressed adolescents.

BACKGROUND Depression is prevalent and typically has its onset in adolescence. Resting-state fMRI could help create a better understanding of the underlying neurobiological mechanisms during this critical period. In this study, resting-state functional connectivity (RSFC) is examined using seed regions-of-interest (ROIs) associated with three networks: the limbic network, the default mode network (DMN) and the salience network. METHODS Twenty-six treatment-naïve, clinically depressed adolescents of whom 18 had comorbid anxiety, and 26 pair-wise matched healthy controls underwent resting-state fMRI. The three networks were investigated using a seed-based ROI approach with seeds in the bilateral amygdala (limbic network), bilateral dorsal anterior cingulate cortex (dACC; salience network) and bilateral posterior cingulate cortex (default mode network). RESULTS Compared to healthy controls, clinically depressed adolescents showed increased RSFC of the left amygdala with right parietal cortical areas, and decreased right amygdala RSFC with left frontal cortical areas including the ACC, as well as with right occipito-parietal areas. The bilateral dACC showed decreased RSFC with the right middle frontal gyrus, frontal pole, and inferior frontal gyrus in clinically depressed adolescents. No abnormalities in DMN RSFC were found, and differences in RSFC did not correlate with clinical measures. CONCLUSIONS The aberrant RSFC of the amygdala network and the dACC network may be related to altered emotion processing and regulation in depressed adolescents. Our results provide new insights into RSFC in clinically depressed adolescents and future models on adolescent depression may include abnormalities in the connectivity of salience network.

Reduced anterior cingulate gray matter volume in treatment-naïve clinically depressed adolescents.

Adolescent depression is associated with increased risk for suicidality, social and educational impairment, smoking, substance use, obesity, and depression in adulthood. It is of relevance to further our insight in the neurobiological mechanisms underlying this disorder in the developing brain, as this may be essential to optimize treatment and prevention of adolescent depression and its negative clinical trajectories. The equivocal findings of the limited number of studies on neural abnormalities in depressed youth stress the need for further neurobiological investigation of adolescent depression. We therefore performed a voxel-based morphometry study of the hippocampus, amygdala, superior temporal gyrus, and anterior cingulate cortex (ACC) in 26 treatment-naïve, clinically depressed adolescents and 26 pair-wise matched healthy controls. Additionally, an exploratory whole-brain analysis was performed. Clinically depressed adolescents showed a volume reduction of the bilateral dorsal ACC compared to healthy controls. However, no association was found between gray matter volume of the ACC and clinical severity scores for depression or anxiety. Our finding of a smaller ACC in clinically depressed adolescents is consistent with literature on depressed adults. Future research is needed to investigate if gray matter abnormalities precede or follow clinical depression in adolescents.

Amygdala activation during emotional face processing in adolescents with affective disorders: the role of underlying depression and anxiety symptoms.

Depressive and anxiety disorders are often first diagnosed during adolescence and it is known that they persist into adulthood. Previous studies often tried to dissociate depressive and anxiety disorders, but high comorbidity makes this difficult and maybe even impossible. The goal of this study was to use neuroimaging to test what the unique contribution is of depression and anxiety symptomatology on emotional processing and amygdala activation, and to compare the results with a healthy control group. We included 25 adolescents with depressive and/or anxiety disorders and 26 healthy adolescents. Participants performed an emotional face processing task while in the MRI scanner. We were particularly interested in the relation between depression/anxiety symptomatology and patterns of amygdala activation. There were no significant differences in activation patterns between the control group and the clinical group on whole brain level and ROI level. However, we found that dimensional scores on an anxiety but not a depression subscale significantly predicted brain activation in the right amygdala when processing fearful, happy and neutral faces. These results suggest that anxiety symptoms are a better predictor for differentiating activation patterns in the amygdala than depression symptoms. Although the current study includes a relatively large sample of treatment naïve adolescents with depression/anxiety disorders, results might be influenced by differences between studies in recruitment strategies or methodology. Future research should include larger samples with a more equal distribution of adolescents with a clinical diagnosis of depression and/or anxiety. To conclude, this study shows that abnormal amygdala responses to emotional faces in depression and anxiety seems to be more dependent on anxiety symptoms than on depression symptoms, and thereby highlights the need for more research to better characterize clinical groups in future studies.

Response to: ''the triadic model perspective for the study of adolescent motivated behavior''.

The triadic model by Ernst and colleagues is a foundational theory of brain development that proposes key linkages between adolescent brain function and emotional changes that accompany this phase of the lifespan. Not only has the triadic framework become a ‘modern classic’ in the field of developmental neuroscience, it has been highly influential in motivating empirical inquiry concerning the relationships between neurodevelopment, brain function, and adolescent behavior. Its importance to the field is undisputable. The triadic model proposes that adolescent emotion-guided behavior arises, in part, from key developmental shifts in the functional properties of three interacting neural systems: an approach system centered in the striatum, an avoidance system centered in the amygdala, and a control system centered in the prefrontal cortex. Indeed, the functional properties of these brain structures play a key role in shifts in adolescent motivated and emotional behavior, as supported by a broad empirical corpus. However, might recent advances in cognitive neuroscience warrant reconsideration of the proposed structure–function trichotomy? Since the original triadic model was put forth (Ernst, Pine, & Hardin, 2006), a wave of cognitive neuroscientific research has motivated a more complex, process-oriented view of the function of subcortical structures including the amygdala and striatum. Whereas the amygdala was classically conceptualized as a fear module that mediates avoidance behavior, contemporary work has demonstrated that amygdala responding is better predicted by emotional salience than by a given valence category (Costafreda, Brammer, David, & Fu, 2007). Similarly, early accounts of the striatum as a reward module have been expanded upon to highlight the key role of the striatum in coding not just reward properties of information, but of expectancy (Pagnoni, Zink, Montague, & Berns, 2002) in both appetitive and aversive contexts (Delgado, Li, Schiller, & Phelps, 2008). These and other findings have motivated theoretical shifts away from a modular view of valenced emotion centers of the brain (Lindquist, Wager, Kober, Bliss-Moreau, & Barrett, 2012) and toward a view that emphasizes the sensitivity of these systems to stimulus dimensions of salience and predictability. Recent advances in computational approaches have emphasized a functionalist perspective whereby emotion inputs – approach and avoidance cues – invoke learning mechanisms that associate environmental cues with positive and negative outcomes, which in turn support emotion-guided behavior. Interestingly, the proposed roles for the amygdala and striatum in learning are complimentary but distinct (Murray, 2007). While both the amygdala and striatum play interactive roles in facilitating emotion-guided learning, the amygdala response is best explained by associative learning computations whereas the striatum signal is tuned to prediction errors – discrepancies between predicted and actual outcomes (Li, Schiller, Schoenbaum, Phelps, & Daw, 2011). Thus, amygdala and striatal function stretches beyond detecting appetitive and aversive cues to guide emotional learning in complex ways. Importantly, the perspective sketched above remains compatible with empirical evidence suggesting that adolescent emotionguided behaviors (such as risk-taking and emotional lability) may result, in part, from sensitization of the amygdala and striatum. Cohen et al. (2010) reported exaggerated positive prediction error signaling in the adolescent striatum, which could serve to amplify the strength of positive outcomes on learning, facilitating risk-taking behavior. Though speculative, sensitized amygdala-based associative learning mechanisms could enhance appetitive and aversive associations, thereby strengthening emotional triggers during the adolescent years. In contrast with the valence-specific theories that remained prevalent until recently, the findings described above offer a contemporary viewpoint that holds the potential to refine extant accounts relating neurodevelopment with adolescent emotional behaviors. Our hope is that engaging in critical analysis of these and other perspectives will help to propel theoretical and empirical advances in the nascent and vibrant discipline of adolescent neuroscience.

The neural correlates of dealing with social exclusion in childhood

&NA; Observing social exclusion can be a distressing experience for children that can be followed by concerns for self‐inclusion (self‐concerns), as well as prosocial behavior to help others in distress (other‐concerns). Indeed, behavioral studies have shown that observed social exclusion elicits prosocial compensating behavior in children, but motivations for the compensation of social exclusion are not well understood. To distinguish between self‐concerns and other‐concerns when observing social exclusion in childhood, participants (aged 7–10) played a four‐player Prosocial Cyberball Game in which they could toss a ball to three other players. When one player was excluded by the two other players, the participant could compensate for this exclusion by tossing the ball more often to the excluded player. Using a three‐sample replication (N = 18, N = 27, and N = 26) and meta‐analysis design, we demonstrated consistent prosocial compensating behavior in children in response to observing social exclusion. On a neural level, we found activity in reward and salience related areas (striatum and dorsal anterior cingulate cortex (dACC)) when participants experienced inclusion, and activity in social perception related areas (orbitofrontal cortex) when participants experienced exclusion. In contrast, no condition specific neural effects were observed for prosocial compensating behavior. These findings suggest that in childhood observed social exclusion is associated with stronger neural activity for self‐concern. This study aims to overcome some of the issues of replicability in developmental psychology and neuroscience by using a replication and meta‐analysis design, showing consistent prosocial compensating behavior to the excluded player, and replicable neural correlates of experiencing exclusion and inclusion during middle childhood. HighlightsWe studied responses to observed and experienced social exclusion in childhood.Observing others social exclusion leads to prosocial compensating behavior.Experiencing inclusion was associated with activity in striatum and ACC.Experiencing exclusion was associated with activity in orbitofrontal cortex.Findings are robust in a replication and meta‐analysis design with three samples.

Amygdala habituation to emotional faces in adolescents with internalizing disorders, adolescents with childhood sexual abuse related PTSD and healthy adolescents

Highlights • A study investigating habituation patterns in the amygdala.• Compares adolescents with internalizing disorders and adolescents with CSA-related PTSD.• Initial heightened response and fast habituation in amygdala for the PTSD group.• No habituation of amygdala response in the internalizing group.• Possible difference in underlying neurobiological mechanisms for emotional face processing.

Hoe stabiel en betrouwbaar is hersenactiviteit in de amygdala en prefrontale cortex? Een longitudinale studie bij gezonde adolescenten

De laatste jaren wordt er steeds meer longitudinaal hersenonderzoek gedaan met behulp van fMRI (functionele magnetische resonantie imaging). Daarbij worden deelnemers over langere tijd gevolgd en wordt hersenactiviteit tijdens elke meting in kaart gebracht, bijvoorbeeld door de deelnemers in de MRI-scanner een taak te laten uitvoeren. Functionele MRI wordt onder andere toegepast bij onderzoek naar veranderingen in de hersenen die mogelijk samenhangen met de invloed van behandeling bij adolescenten met psychiatrische stoornissen (Maslowsky et al., 2010; Strawn et al., 2012).AbstractA growing number of studies use longitudinal designs to gather information about the developmental course of psychiatric disorders. For these kinds of studies it is important to know how stable and reliable brain activation patterns are over time in healthy individuals who constitute control group participants. However, not much is known about the stability and reliability of brain activation patterns, especially during adolescence. In the current study we investigated the stability and reliability of brain activation patterns in a group of healthy adolescents. All adolescents were scanned three times over a period of six months. The results show that brain activation patterns on a grouplevel do not vary significantly over time. However, on an individual level there is a lot of variability in brain activation patterns, suggesting that the activation patterns are not stable and reliable. This variability is more pronounced for subcortical brain areas than for cortical brain areas. Future research should take these results into account when they interpret findings in clinical samples and when they use a longitudinal study design.

Emotional face processing in adolescents with childhood sexual abuse-related posttraumatic stress disorder, internalizing disorders and healthy controls

a Curium-LUMC, Department of Child and Adolescent Psychiatry, Leiden University Medical Center, Leiden, The Netherlands b YOEP (Yulius Onderwijs zorg Expertise Partners), Warmond, The Netherlands c Leiden Institute for Brain and Cognition (LIBC), Leiden University, Leiden, The Netherlands d Department of Child and Family Studies, Faculty of Social Sciences, Leiden University, The Netherlands e Institute of Psychology, Leiden University, The Netherlands f Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands g Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands h School of Pedagogical and Educational Sciences, Erasmus University, Rotterdam, The Netherlands i VU Medical Center, Department of Child and Adolescent Psychiatry, Amsterdam, The Netherlands