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Investigating adolescents and young adults may provide a unique opportunity to understand developmental aspects of the neurobiology of depression. During adolescence, a considerable physiologic reorganization of both grey and white matter of the brain takes place, and it has been suggested that differences in grey-matter volumes during adolescence may reflect different maturational processes. We investigated grey-matter volumes in a comparatively large sample (n = 103) of adolescents and young adults (aged 12 to 27 years), 60 of them with a diagnosis of current depression. Replicating previous studies, we found a clear whole-brain effect of age: the older the participants, the lower their global grey-matter volumes, particularly in the paracingulate and prefrontal cortices. Contrasting depressed and healthy youth in a whole-brain approach, we found greater grey-matter volumes in the dorsolateral prefrontal cortex of those with depression. Furthermore, a region-of-interest analysis indicated lower grey-matter volumes in the hippocampus in participants with depression compared with healthy controls. The present study was limited because of a skewed sex distribution, its cross-sectional design and the fact that some participants were taking an antidepressant. During adolescence, restructuring of the brain is characterized by marked decreases in prefrontal grey-matter volumes, interpreted as a correlate of brain maturation. Findings of greater volumes in the prefrontal cortex, particularly in younger adolescents with depression, may suggest that these participants were more prone to delayed brain maturation or increased neuroplasticity. This finding may represent a risk factor for depression or constitute an effect of developing depression.

•Neural activation by primary and secondary rewards: commonalities and differences.•Task-based fMRI study on 42 healthy men, focusing on 12 reward-linked brain regions.•Calibrated Bayes factor permits categorization of effects from weak to decisive.•Common activation of VTA, amygdala, OFC, sgACC and vmPFC by reward outcome.•Stimulus-specific activations of reward centers for expectation and error prediction. According to their nature, rewarding stimuli are classified as primary (e.g., food, sex) and secondary (e.g., money) rewards. Neuroimaging studies have provided valuable insights in neural reward processing and its various aspects including reward expectation, outcome and prediction error encoding. However, there is only limited evidence of whether the two different types of rewards are processed in common or distinct brain areas, in particular when considering the different functions of reward processing. We analyzed a sample of 42 healthy, male participants using task-based functional magnetic resonance imaging (fMRI) during a variant of the monetary incentive delay task. We aimed to investigate the effects of three different rewarding stimuli—two primary (food and sex) and one secondary (money)—on the various functions of reward processing. To provide a thorough description, we focused on 12 brain regions of interest and utilized the Bayes factor bound (BFB) to express stimulus-related main effects and pairwise differences at different levels of evidence, ranging from weak to decisive. Our results revealed a dominance of sexually charged stimuli in engaging the brain's reward structures for all investigated aspects of reward processing. Nevertheless, the ventral tegmental area, amygdala, ventral caudate, ventromedial prefrontal cortex, subgenual anterior cingulate cortex, and lateral orbitofrontal cortex were activated by both primary and secondary reward outcomes. For other reward processing functions, i.e., reward expectation and the prediction error, effects of the different stimuli were weaker, and effects from one reward type cannot easily be generalized to the other.

The emergence of flow is a situation of high salience because externally oriented attention on the task and access to resources for goal-directed behavior are enhanced, while internally oriented or self-related cognition is decreased. The right anterior insula has been reported as a causal out-flow hub of the salience resting state network, orchestrating the engagement of the central executive network (CEN) and the disengagement of the default mode network (DMN) during a functional challenge. In the present study, we employed a combined task-based activation and connectivity analysis to investigate the role of the right anterior insula during the emergence of flow. A sample of 41 healthy male subjects was confronted with a functional challenge that permitted the emergence of flow during BOLD-based functional magnetic resonance imaging. Comparing connectivity changes of the right anterior insula during the flow condition against connectivity changes associated with control conditions of boredom and overload, relatively increased couplings were observed with left and right dorsolateral prefrontal cortex. Activation data for these regions did however not show the flow-typical inverted U-shaped response pattern. Relatively decreased functional couplings encompassed ventral aspects of the striatum, but neither the amygdala nor the medial prefrontal cortex. For the ventral striatum, activation data were consistent with the flow-typical U-shaped activation pattern, which supports the notion that under the high salience of autotelic situations the anterior insula is much less positively coupled with the ventral striatum than under boundary conditions of boredom and overload. Taken together, present functional connectivity results were in alignment with the assumed role of the right anterior insula under conditions of different salience. However, this particular region does not appear to mediate the most typical flow-associated activation patterns.

Flow refers to a positive, activity-associated, subjective experience under conditions of a perceived fit between skills and task demands. Using functional magnetic resonance perfusion imaging, we investigated the neural correlates of flow in a sample of 27 human subjects. Experimentally, in the flow condition participants worked on mental arithmetic tasks at challenging task difficulty which was automatically and continuously adjusted to individuals' skill level. Experimental settings of “boredom” and “overload” served as comparison conditions. The experience of flow was associated with relative increases in neural activity in the left anterior inferior frontal gyrus (IFG) and the left putamen. Relative decreases in neural activity were observed in the medial prefrontal cortex (MPFC) and the amygdala (AMY). Subjective ratings of the flow experience were significantly associated with changes in neural activity in the IFG, AMY, and, with trend towards significance, in the MPFC. We conclude that neural activity changes in these brain regions reflect psychological processes that map on the characteristic features of flow: coding of increased outcome probability (putamen), deeper sense of cognitive control (IFG), decreased self-referential processing (MPFC), and decreased negative arousal (AMY). •Flow was associated with increased activation in the inferior frontal gyrus and putamen.•Flow was associated with decreased activation of the amygdala and medial prefrontal cortex.•Individual flow experience correlated with changes in neural activation.

Anxiety- and trauma-related disorders are severe illnesses with high prevalence. Current treatment options leave room for improvement and the endocannabinoid system (ECS) has become a key target in psychopharmacological research. Rodent models suggest an anxiolytic effect of endocannabinoids and demonstrated that the ECS is involved in the modulation of fear learning and aversive memory consolidation. So far, one prominent target was inhibition of fatty acid amino hydrolase (FAAH), the degrading enzyme of the endocannabinoid anandamide (AEA). Research in humans remains scarce, but genetic studies have found that the single-nucleotide polymorphism (SNP) FAAH C385A (rs324420) is associated with lower catabolic performance of FAAH and increased levels of AEA. Translational research on the ECS in fear learning processes is rare, yet crucial to understand the mechanisms involved. To address this lack of research, we designed a fear conditioning, extinction learning paradigm with 51 healthy, male humans who underwent functional magnetic resonance imaging (fMRI) before analysing baseline and task-related changes of AEA, as well as the FAAH polymorphism (rs324420). The results indicate higher AEA levels in AC-heterozygotes than in CC-individuals (SNP rs324420), but no difference between the groups during extinction learning. However, neural activation of the anterior cingulate cortex and anterior insular cortex during extinction learning correlated positively with AEA baseline levels, and task-related changes in AEA were found particularly during fear extinction, with a modulatory effect on neural activation related to extinction learning. Results indicate a putative role for AEA in fear extinction learning. Pre-treatment with AEA-enhancing drugs could promote extinction learning during psychotherapeutic interventions.

Relational bullying in schools is one of the most frequent forms of violence and can have severe negative health impact, e.g. depression. Social exclusion is the most prominent form of relational bullying that can be operationalized experimentally. The present study used MR-based perfusion imaging (pCASL) to investigate the neural signatures of social exclusion and its relationship with individually different extent of previous bullying experience. Twenty-four teenagers reporting bullying experience at different extent were scanned during a virtual ball-tossing (Cyberball game). Our findings showed that social exclusion (relative to social inclusion) activated frontal brain areas: sub- and perigenual anterior cingulate cortex (sg/pgACC), left inferior frontal cortex (IFG), and dorsolateral prefrontal cortex. Positive relationship between exclusion-specific signal increase and individually different extents of prior bullying experience was for the first time observed in left IFG and sgACC. This suggests that more frequent prior experience has conditioned greater mentalizing and/or rumination, in order to cope with the situation. While this interpretation remains speculative, the present data show that the experience of being bullied partly sensitizes the neural substrate relevant for the processing of social exclusion.

Intraindividual intertrial variability has been suggested as an endophenotype of attention-deficit/hyperactivity disorder (ADHD). It is usually evaluated as response time variability (RTV) in reaction time tasks, and RTV has emerged as a robust and stable feature of ADHD. Among attempts to elucidate the neurobiological underpinnings of RTV, it has been suggested that alterations in white matter microstructure may explain RTV. We used diffusion tensor imaging (DTI) in a group of 53 adults with ADHD and 50 healthy controls. We obtained RTV parameters from a simple reaction-time task, in which participants were asked to respond to the appearance of white crosses on a screen using button presses. We observed significant between-group differences for the ex-Gaussian parameter τ, indicating that the mean of extremely slow responses was greater for adults with ADHD than controls. Fractional anisotropy (FA) derived from DTI was significantly different between groups in 2 clusters of the corticothalamic tract. In the ADHD group, relatively decreased FA values were significantly associated with the parameter τ, such that lower FA values in the corticothalamic tract predicted greater τ as an index of RTV. We did not observe this association in healthy controls. For comparison with previous studies, we used FA as a dependent variable of interest. However, although this metric is sensitive to white matter structural properties, there are ambiguities in its interpretation. Even in a simple reaction-time task, RTV proved again to be a stable feature of ADHD. It was associated with altered white matter structural properties of the corticothalamic tract in adults with ADHD.

Previous neuroimaging studies have suggested that the experience of flow aligns with a relative increase in activation of the dorsal raphe nucleus (DRN), and relative activation decreases of the medial prefrontal cortex (MPFC) and of the amygdala (AMY). In the present study, Dynamic Causal Modeling (DCM) was used to explore effective connectivity between those brain regions. To test our hypothesis that the DRN causally down-regulates activity of the MPFC and/or of the AMY, 23 healthy male students solved mental arithmetic tasks of varying difficulty during functional magnetic resonance imaging. A \"flow\" condition, with task demands automatically balanced with participants' skill level, was compared with conditions of \"boredom\" and \"overload\". DCM models were constructed modeling full reciprocal endogenous connections between the DRN, the MPFC, the AMY, and the calcarine. The calcarine was included to allow sensory input to enter the system. Experimental conditions were modeled as exerting modulatory effects on various possible connections between the DRN, the MPFC, and the AMY, but not on self-inhibitory connections, yielding a total of 64 alternative DCM models. Model space was partitioned into eight families based on commonalities in the arrangement of the modulatory effects. Random effects Bayesian Model Selection (BMS) was applied to identify a possible winning family (and model). Although BMS revealed a clear winning family, an outstanding winning model could not be identified. Therefore, Bayesian Model Averaging was performed over models within the winning family to obtain representative DCM parameters for subsequent analyses to test our hypothesis. In line with our expectations, Bayesian averaged parameters revealed stronger down-regulatory influence of the DRN on the MPFC when participants experienced flow relative to control conditions. In addition, these condition-dependent modulatory effects significantly predicted participants' experienced degree of flow. The AMY was down-regulated irrespective of condition. The present results suggest a causal role for the DRN in modulating the MPFC, contributing to the experience of flow.

Background: Due to the absence of robust biomarkers, and the low sensitivity and specificity of routine imaging techniques, the differential diagnosis between Parkinson’s disease (PD) and multiple system atrophy (MSA) is challenging. High-field magnetic resonance imaging (MRI) opened up new possibilities regarding the analysis of pathological alterations associated with neurodegenerative processes. Recently, we have shown that quantitative susceptibility mapping (QSM) enables visualization and quantification of two major histopathologic hallmarks observed in MSA: reduced myelin density and iron accumulation in the basal ganglia of a transgenic murine model of MSA. It is therefore emerging as a promising imaging modality on the differential diagnosis of Parkinsonian syndromes. Objectives: To assess QSM on high-field MRI for the differential diagnosis of PD and MSA. Methods: We assessed 23 patients (nine PDs and 14 MSAs) and nine controls using QSM on 3T and 7T MRI scanners at two academic centers. Results: We observed increased susceptibility in MSA at 3T in prototypical subcortical and brainstem regions. Susceptibility measures of putamen, pallidum, and substantia nigra reached excellent diagnostic accuracy to separate both synucleinopathies. Increase toward 100% sensitivity and specificity was achieved using 7T MRI in a subset of patients. Magnetic susceptibility correlated with age in all groups, but not with disease duration in MSA. Sensitivity and specificity were particularly high for possible MSA, and reached 100% in the putamen. Conclusion: Putaminal susceptibility measures, in particular on ultra-high-field MRI, may distinguish MSA patients from both, PD and controls, allowing an early and sensitive diagnosis of MSA.

Eye Movement Desensitisation and Reprocessing (EMDR) is a method in psychotherapy effective in treating symptoms of posttraumatic stress disorder. The client attends to alternating bilateral visual, auditory or sensory stimulation while confronted with emotionally disturbing material. It is thought that the bilateral stimulation as a specific element of EMDR facilitates accessing and processing of negative material while presumably creating new associative links. We hypothesized that the putatively facilitated access should be reflected in increased activation of the amygdala upon bilateral EMDR stimulation even in healthy subjects. We investigated 22 healthy female university students (mean 23.5 years) with fMRI. Subjects were scanned while confronted with blocks of disgusting and neutral picture stimuli. One third of the blocks was presented without any additional stimulation, one third with bilateral simultaneous auditory stimulation, and one third with bilateral alternating auditory stimulation as used in EMDR. Contrasting disgusting vs. neutral picture stimuli confirmed the expected robust effect of amygdala activation for all auditory stimulation conditions. The interaction analysis with the type of auditory stimulation revealed a specific increase in activation of the right amygdala for the bilateral alternating auditory stimulation. Activation of the left dorsolateral prefrontal cortex showed the opposite effect with decreased activation. We demonstrate first time evidence for a putative neurobiological basis of the bilateral alternating stimulation as used in the EMDR method. The increase in limbic processing along with decreased frontal activation is in line with theoretical models of how bilateral alternating stimulation could help with therapeutic reintegration of information, and present findings may pave the way for future research on EMDR in the context of posttraumatic stress disorder.