[Structures, aims and needs of early career scientists at the German Center for Mental Health]. / Strukturen, Ziele und Bedürfnisse der Early Career Scientists am Deutschen Zentrum für Psychische Gesundheit.

BACKGROUND: Early career scientists (ECS) are agents of change and driving forces in the promotion of mental health. The German Center for Mental Health (DZPG) is a powerful initiative to guide and support careers in the field of mental health. OBJECTIVE: The DZPG aims to make investments to educate, engage, excite, and empower ECS in an interdisciplinary and interinstitutional scientific community. STRUCTURES, TOPICS AND INITIATIVES: To achieve this, the ECS Board at the DZPG plays a central role and consists of 18 elected ECS representatives. The ECS culture gives members the right of voice and embraces bottom-to-top ideas and acknowledges autonomy and co-determination. The DZPG academy was developed to facilitate communication and networking and encourage collaboration among ECS members. The DZPG also navigates several key issues, such as equality, diversity, inclusion, family friendliness and work-life balance, which are essential for a functioning research landscape. The DZPG also extends opportunities to ECS to develop skills and competencies that are essential for contemporary ECS. It complements nationwide support for ECS with funding opportunities, mental health support at work, careers advice and guidance activities. Importantly, the ECS Board is committed to patient and public involvement and engagement, scientific communication and knowledge transfer to multiple settings. CONCLUSION: The DZPG will contribute to fostering ECS training programs for student and academic exchanges, collaborative research, and pooling of resources to acquire grants and scholarships. It will also support the establishment of hubs for ECS networks and promote the expansion of international competence of ECS in Germany.

[Working in a team and mental health]. / Arbeit im Team und psychische Gesundheit.

Humans have always naturally lived in groups, which has a significant impact on the well-being and mental stability of the individual. Various physiological processes are coregulated via the closeness of other persons. About one third of our adulthood is spent at work where social relationships often play an important role, because we are typically working with other individuals in groups or a team. In these situations, mutual support and successful cooperation can develop, which promotes the mental and physical health of the employees of a company ("social capital"). From various perspectives it becomes obvious that the quality of relationships at the workplace is a key factor for the satisfaction and health of individual employees as well as for the cohesion, resilience and performance of the entire team. This is confirmed by empirical findings that still need to be expanded, especially with respect to the neurobiological associations of the cooperation in teams and individual health.

Directed coupling in multi-brain networks underlies generalized synchrony during social exchange.

Advances in social neuroscience have made neural signatures of social exchange measurable simultaneously across people. This has identified brain regions differentially active during social interaction between human dyads, but the underlying systems-level mechanisms are incompletely understood. This paper introduces dynamic causal modeling and Bayesian model comparison to assess the causal and directed connectivity between two brains in the context of hyperscanning (h-DCM). In this setting, correlated neuronal responses become the data features that have to be explained by models with and without between-brain (effective) connections. Connections between brains can be understood in the context of generalized synchrony, which explains how dynamical systems become synchronized when they are coupled to each another. Under generalized synchrony, each brain state can be predicted by the other brain or a mixture of both. Our results show that effective connectivity between brains is not a feature within dyads per se but emerges selectively during social exchange. We demonstrate a causal impact of the sender's brain activity on the receiver of information, which explains previous reports of two-brain synchrony. We discuss the implications of this work; in particular, how characterizing generalized synchrony enables the discovery of between-brain connections in any social contact, and the advantage of h-DCM in studying brain function on the subject level, dyadic level, and group level within a directed model of (between) brain function.

Brain structural correlates of upward social mobility in ethnic minority individuals.

PURPOSE: Perigenual anterior cingulate cortex (pACC) is a neural convergence site for social stress-related risk factors for mental health, including ethnic minority status. Current social status, a strong predictor of mental and somatic health, has been related to gray matter volume in this region, but the effects of social mobility over the lifespan are unknown and may differ in minorities. Recent studies suggest a diminished health return of upward social mobility for ethnic minority individuals, potentially due to sustained stress-associated experiences and subsequent activation of the neural stress response system. METHODS: To address this issue, we studied an ethnic minority sample with strong upward social mobility. In a cross-sectional design, we examined 64 young adult native German and 76 ethnic minority individuals with comparable sociodemographic attributes using whole-brain structural magnetic resonance imaging. RESULTS: Results showed a significant group-dependent interaction between perceived upward social mobility and pACC gray matter volume, with a significant negative association in the ethnic minority individuals. Post-hoc analysis showed a significant mediation of the relationship between perceived upward social mobility and pACC volume by perceived chronic stress, a variable that was significantly correlated with perceived discrimination in our ethnic minority group. CONCLUSION: Our findings extend prior work by pointing to a biological signature of the "allostatic costs" of socioeconomic attainment in socially disadvantaged upwardly mobile individuals in a key neural node implicated in the regulation of stress and negative affect.

[The domain "social processes" in the system of research domain criteria: current state and perspectives]. / Die Domäne "soziale Prozesse" im System der Research Domain Criteria: aktueller Stand und Perspektive.

Social processes and their dysfunction, e.g. in autism spectrum disorders and psychotic disorders, have always been at the core of psychiatry. The last decades have led to impressive advances in our understanding of the underlying neurobiological mechanisms and also in the way we study and analyze social processes. Since their establishment, the research domain criteria have provided a powerful framework of how to operationalize and subdivide complex social processes in a way that it closely aligns to underlying neurobiological substrates while still enabling clinical approaches. In this article we summarize and discuss the most important findings for each of the four fundamental constructs of the social processes domain (a) binding and attachment, (b) social communication, (c) perception and understanding of self and (d) perception and understanding of others. We highlight the clinical relevance of the insights generated by the field of social neurosciences and discuss the resulting increasing importance of transdiagnostic concepts in applied research. Finally, we showcase three innovative research methods that build on the accelerating technological advances of the last decade and which will increasingly enable the study of complex social interactions in more realistic and ecologically valid settings.

Neural responses to social evaluative threat in the absence of negative investigator feedback and provoked performance failures.

Functional neuroimaging of social stress induction has considerably furthered our understanding of the neural risk architecture of stress-related mental disorders. However, broad application of existing neuroimaging stress paradigms is challenging, among others due to the relatively high intensity of the employed stressors, which limits applications in patients and longitudinal study designs. Here, we introduce a less intense neuroimaging stress paradigm in which subjects anticipate, prepare, and give speeches under simulated social evaluation without harsh investigator feedback or provoked performance failures (IMaging Paradigm for Evaluative Social Stress, IMPRESS). We show that IMPRESS significantly increases perceived arousal as well as adrenergic (heart rate, pupil diameter, and blood pressure) and hormonal (cortisol) responses. Amygdala and perigenual anterior cingulate cortex (pACC), two key regions of the emotion and stress regulatory circuitry, are significantly engaged by IMPRESS. We further report associations of amygdala and pACC responses with measures of adrenergic arousal (heart rate, pupil diameter) and social environmental risk factors (adverse childhood experiences, urban living). Our data indicate that IMPRESS induces benchmark psychological and endocrinological responses to social evaluative stress, taps into core neural circuits related to stress processing and mental health risk, and is promising for application in mental illness and in longitudinal study designs.

Bidirectional signal exchanges and their mechanisms during joint attention interaction - A hyperscanning fMRI study.

Social interactions are essential to our daily life. We tested the hypothesis that social interactions during joint attention (JA) require bidirectional communication, each with a different mechanism. We used a novel multivariate functional connectivity analysis, which enables obtaining directed pathways between four regions at each time-frequency point, with hyper-scanning MRI data of real-time JA interaction. Constructing multiple "4-regional directed pathways" and counting the number of times, regions engaged in feedforward or feedback processes in the 'sender' or the 'receiver brains, we obtained the following. (1) There were more regions in feedforward than in feedback processes (125 versus 99). (2) The right hemisphere was more involved in feedforward (74 versus 33), while the left hemisphere in feedback (66 versus 51). (3) The dmPFC was more engaged in feedforward (73 versus 44) while the TPJ in both (49 versus 45). (4) The dmPFC was more involved in the sending processes (i.e. initiation of feedforward and feedback) while the TPJ in the receiving processes. (5) JA interaction was involved with high MRI frequencies (0.04-0.1 Hz), while continues interactions by low MRI frequencies (0.01-0.04 Hz). (6) Initiation and responding to JA (i.e. IJA and RJA) evolved with composite neural systems: similar systems for pathways that included the dmPFC, vmPFC and the STS, and different systems for pathways that included the TPJ, vmPFC, PCC and the STS. These findings have important consequences in the basic understanding of social interaction and could help in diagnose and follow-up of social impairments.

Dynamic brain network reconfiguration as a potential schizophrenia genetic risk mechanism modulated by NMDA receptor function.

Schizophrenia is increasingly recognized as a disorder of distributed neural dynamics, but the molecular and genetic contributions are poorly understood. Recent work highlights a role for altered N-methyl-d-aspartate (NMDA) receptor signaling and related impairments in the excitation-inhibitory balance and synchrony of large-scale neural networks. Here, we combined a pharmacological intervention with novel techniques from dynamic network neuroscience applied to functional magnetic resonance imaging (fMRI) to identify alterations in the dynamic reconfiguration of brain networks related to schizophrenia genetic risk and NMDA receptor hypofunction. We quantified "network flexibility," a measure of the dynamic reconfiguration of the community structure of time-variant brain networks during working memory performance. Comparing 28 patients with schizophrenia, 37 unaffected first-degree relatives, and 139 healthy controls, we detected significant differences in network flexibility [F(2,196) = 6.541, P = 0.002] in a pattern consistent with the assumed genetic risk load of the groups (highest for patients, intermediate for relatives, and lowest for controls). In an observer-blinded, placebo-controlled, randomized, cross-over pharmacological challenge study in 37 healthy controls, we further detected a significant increase in network flexibility as a result of NMDA receptor antagonism with 120 mg dextromethorphan [F(1,34) = 5.291, P = 0.028]. Our results identify a potential dynamic network intermediate phenotype related to the genetic liability for schizophrenia that manifests as altered reconfiguration of brain networks during working memory. The phenotype appears to be influenced by NMDA receptor antagonism, consistent with a critical role for glutamate in the temporal coordination of neural networks and the pathophysiology of schizophrenia.

Information flow between interacting human brains: Identification, validation, and relationship to social expertise.

Social interactions are fundamental for human behavior, but the quantification of their neural underpinnings remains challenging. Here, we used hyperscanning functional MRI (fMRI) to study information flow between brains of human dyads during real-time social interaction in a joint attention paradigm. In a hardware setup enabling immersive audiovisual interaction of subjects in linked fMRI scanners, we characterize cross-brain connectivity components that are unique to interacting individuals, identifying information flow between the sender's and receiver's temporoparietal junction. We replicate these findings in an independent sample and validate our methods by demonstrating that cross-brain connectivity relates to a key real-world measure of social behavior. Together, our findings support a central role of human-specific cortical areas in the brain dynamics of dyadic interactions and provide an approach for the noninvasive examination of the neural basis of healthy and disturbed human social behavior with minimal a priori assumptions.

Differential responses of the dorsomedial prefrontal cortex and right posterior superior temporal sulcus to spontaneous mentalizing.

Previous research suggests a role of the dorsomedial prefrontal cortex (dmPFC) in metacognitive representation of social information, while the right posterior superior temporal sulcus (pSTS) has been linked to social perception. This study targeted these functional roles in the context of spontaneous mentalizing. An animated shapes task was presented to 46 subjects during functional magnetic resonance imaging. Stimuli consisted of video clips depicting animated shapes whose movement patterns prompt spontaneous mentalizing or simple intention attribution. Based on their differential response during spontaneous mentalizing, both regions were characterized with respect to their task-dependent connectivity profiles and their associations with autistic traits. Functional network analyses revealed highly localized coupling of the right pSTS with visual areas in the lateral occipital cortex, while the dmPFC showed extensive coupling with instances of large-scale control networks and temporal areas including the right pSTS. Autistic traits were related to mentalizing-specific activation of the dmPFC and to the strength of connectivity between the dmPFC and posterior temporal regions. These results are in good agreement with the hypothesized roles of the dmPFC and right pSTS for metacognitive representation and perception-based processing of social information, respectively, and further inform their implication in social behavior linked to autism. Hum Brain Mapp 38:3791-3803, 2017. © 2017 Wiley Periodicals, Inc.

Application of high-frequency repetitive transcranial magnetic stimulation to the DLPFC alters human prefrontal-hippocampal functional interaction.

Neural plasticity is crucial for understanding the experience-dependent reorganization of brain regulatory circuits and the pathophysiology of schizophrenia. An important circuit-level feature derived from functional magnetic resonance imaging (fMRI) is prefrontal-hippocampal seeded connectivity during working memory, the best established intermediate connectivity phenotype of schizophrenia risk to date. The phenotype is a promising marker for the effects of plasticity-enhancing interventions, such as high-frequency repetitive transcranial magnetic stimulation (rTMS), and can be studied in healthy volunteers in the absence of illness-related confounds, but the relationship to brain plasticity is unexplored. We recruited 39 healthy volunteers to investigate the effects of 5 Hz rTMS on prefrontal-hippocampal coupling during working memory and rest. In a randomized and sham-controlled experiment, neuronavigation-guided rTMS was applied to the right dorsolateral prefrontal cortex (DLPFC), and fMRI and functional connectivity analyses [seeded connectivity and psychophysiological interaction (PPI)] were used as readouts. Moreover, the test-retest reliability of working-memory related connectivity markers was evaluated. rTMS provoked a significant decrease in seeded functional connectivity of the right DLPFC and left hippocampus during working memory that proved to be relatively time-invariant and robust. PPI analyses provided evidence for a nominal effect of rTMS and poor test-retest reliability. No effects on n-back-related activation and DLPFC-hippocampus resting-state connectivity were observed. These data provide the first in vivo evidence for the effects of plasticity induction on human prefrontal-hippocampal network dynamics, offer insights into the biological mechanisms of a well established intermediate phenotype linked to schizophrenia, and underscores the importance of the choice of outcome measures in test-retest designs.

A social inference model of idealization and devaluation.

People often form polarized beliefs, imbuing objects (e.g., themselves or others) with unambiguously positive or negative qualities. In clinical settings, this is referred to as dichotomous thinking or "splitting" and is a feature of several psychiatric disorders. Here, we introduce a Bayesian model of splitting that parameterizes a tendency to rigidly categorize objects as either entirely "Bad" or "Good," rather than to flexibly learn dispositions along a continuous scale. Distinct from the previous descriptive theories, the model makes quantitative predictions about how dichotomous beliefs emerge and are updated in light of new information. Specifically, the model addresses how splitting is context-dependent, yet exhibits stability across time. A key model feature is that phases of devaluation and/or idealization are consolidated by rationally attributing counter-evidence to external factors. For example, when another person is idealized, their less-than-perfect behavior is attributed to unfavorable external circumstances. However, sufficient counter-evidence can trigger switches of polarity, producing bistable dynamics. We show that the model can be fitted to empirical data, to measure individual susceptibility to relational instability. For example, we find that a latent categorical belief that others are "Good" accounts for less changeable, and more certain, character impressions of benevolent as opposed to malevolent others among healthy participants. By comparison, character impressions made by participants with borderline personality disorder reveal significantly higher and more symmetric splitting. The generative framework proposed invites applications for modeling oscillatory relational and affective dynamics in psychotherapeutic contexts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Multimodal Associations of FKBP5 Methylation With Emotion-Regulatory Brain Circuits.

BACKGROUND: Understanding the biological processes that underlie individual differences in emotion regulation and stress responsivity is a key challenge for translational neuroscience. The gene FKBP5 is a core regulator in molecular stress signaling that is implicated in the development of psychiatric disorders. However, it remains unclear how FKBP5 DNA methylation in peripheral blood is related to individual differences in measures of neural structure and function and their relevance to daily-life stress responsivity. METHODS: Here, we characterized multimodal correlates of FKBP5 DNA methylation by combining epigenetic data with neuroimaging and ambulatory assessment in a sample of 395 healthy individuals. RESULTS: First, we showed that FKBP5 demethylation as a psychiatric risk factor was related to an anxiety-associated reduction of gray matter volume in the ventromedial prefrontal cortex, a brain area that is involved in emotion regulation and mental health risk and resilience. This effect of epigenetic upregulation of FKBP5 on neuronal structure is more pronounced where FKBP5 is epigenetically downregulated at baseline. Leveraging 208 functional magnetic resonance imaging scans during a well-established emotion-processing task, we found that FKBP5 DNA methylation in peripheral blood was associated with functional differences in prefrontal-limbic circuits that modulate affective responsivity to daily stressors, which we measured using ecological momentary assessment in daily life. CONCLUSIONS: Overall, we demonstrated how FKBP5 contributes to interindividual differences in neural and real-life affect regulation via structural and functional changes in prefrontal-limbic brain circuits.

Neural responses to instructed positive couple interaction: an fMRI study on compliment sharing.

Love is probably the most fascinating feeling that a person ever experiences. However, little is known about what is happening in the brains of a romantic couple-the central and most salient relationship during adult age-while they are particularly tender and exchanging loving words with one another. To gain insight into nearly natural couple interaction, we collected data from N = 84 individuals (including N = 43 heterosexual couples) simultaneously in two functional magnetic resonance imaging scanners, while they sent and received compliments, i.e. short messages about what they liked about each other and their relationship. Activation patterns during compliment sharing in the individuals revealed a broad pattern of activated brain areas known to be involved in empathy and reward processing. Notably, the ventral striatum, including parts of the putamen, was activated particularly when selecting messages for the partner. This provides initial evidence that giving a verbal treat to a romantic partner seems to involve neural reward circuitry in the basal ganglia. These results can have important implications for the neurobiological mechanisms protecting and stabilizing romantic relationships, which build a highly relevant aspect of human life and health.

Brain connectivity in psychiatric imaging genetics.

In the past decade, imaging genetics has evolved into a highly successful neuroimaging discipline with a variety of sophisticated research tools. To date, several neural systems mechanisms have been identified that mediate genetic risk for mental disorders linked to common candidate and genome-wide-supported variants. In particular, the examination of intermediate connectivity phenotypes has recently gained increasing popularity. This paper gives an overview of the scientific methods and evidence that link indices of neural network organization to the genetic susceptibility for mental illness with a focus on the effects of candidate genes and genome-wide supported risk variants on brain structure and function.

Genetic variation in CYP2D6 impacts neural activation during cognitive tasks in humans.

The drug metabolizing cytochrome P450 2D6 enzyme (CYP2D6) is highly expressed in brain and potentially involved in neurotransmitter biotransformation. Here, we report the effect of the CYP2D6 genotype on brain activation during a working memory and an emotional face matching task measured with fMRI. Subjects were taken from an ongoing large scale multicenter imaging genetic study. CYP2D6 genotyping of the alleles *2, *3, *4, *5, *6, *9, *10, *17, *35, *41 and the duplication was performed in N=114 healthy drug free individuals. All individuals had completed two tasks in functional brain imaging: an n-back working memory task and an implicit emotional face matching task. Contrast images were analyzed in second-level random effects models with CYP2D6 enzyme activity levels as regressor of interest and age, sex and scanning site as covariates. In the working memory task, a significant effect of CYP2D6 genotype was found in the fusiform gyrus and the precuneus. In the emotional face matching task, an effect was detected in the cuneus. No significant activation results were found in the thalamus. A conjunction analysis confirmed a significant joint effect of the CYP2D6 association in both regions. In both tasks activation increased with increasing CYP2D6 activity. In conclusion, we confirmed a central nervous system effect of CYP2D6 activity in a large independent sample using a different imaging modality, and provide evidence that basic cognitive processes related to such as alertness may be impacted.

Simulating the computational mechanisms of cognitive and behavioral psychotherapeutic interventions: insights from active inference.

Cognitive-behavioral therapy (CBT) leverages interactions between thoughts, feelings, and behaviors. To deepen understanding of these interactions, we present a computational (active inference) model of CBT that allows formal simulations of interactions between cognitive interventions (i.e., cognitive restructuring) and behavioral interventions (i.e., exposure) in producing adaptive behavior change (i.e., reducing maladaptive avoidance behavior). Using spider phobia as a concrete example of maladaptive avoidance more generally, we show simulations indicating that when conscious beliefs about safety/danger have strong interactions with affective/behavioral outcomes, behavioral change during exposure therapy is mediated by changes in these beliefs, preventing generalization. In contrast, when these interactions are weakened, and cognitive restructuring only induces belief uncertainty (as opposed to strong safety beliefs), behavior change leads to generalized learning (i.e., "over-writing" the implicit beliefs about action-outcome mappings that directly produce avoidance). The individual is therefore equipped to face any new context, safe or dangerous, remaining in a content state without the need for avoidance behavior-increasing resilience from a CBT perspective. These results show how the same changes in behavior during CBT can be due to distinct underlying mechanisms; they predict lower rates of relapse when cognitive interventions focus on inducing uncertainty and on reducing the effects of automatic negative thoughts on behavior.

Neural network-based alterations during repetitive heat pain stimulation in major depression.

The current study aimed to identify alterations in brain activation and connectivity related to nociceptive processing and pain sensitization in major depressive disorder (MDD), using repetitive heat pain stimulation during functional magnetic resonance imaging (fMRI) in 37 MDD patients and 33 healthy controls. Regional activation did not differ between groups, but functional connectivity was significantly decreased in MDD in a neural network connecting frontal, temporal and occipital areas (family-wise error-corrected pFWE = 0.045). Supporting analyses suggested a significant association between network connectivity and trait neuroticism (p = 0.007) but not with the clinical state or familiar risk of MDD (all p values > 0.13). Our data relate a network-based phenotype for altered pain processing and antinociceptive control to MDD and encourage future studies on the shared intermediate neural psychological risk architecture of MDD and chronic pain.

Deficient Amygdala Habituation to Threatening Stimuli in Borderline Personality Disorder Relates to Adverse Childhood Experiences.

BACKGROUND: Heightened amygdala response to threatening cues has been repeatedly observed in borderline personality disorder (BPD). A previous report linked hyperactivation to deficient amygdala habituation to repeated stimuli, but the biological underpinnings are incompletely understood. METHODS: We examined a sample of 120 patients with BPD and 115 healthy control subjects with a well-established functional magnetic resonance imaging emotional face processing task to replicate the previously reported amygdala habituation deficit in BPD and probed this neural phenotype for associations with symptom severity and early social risk exposure. RESULTS: Our results confirm a significant reduction in amygdala habituation to repeated negative stimuli in BPD (pFWE = .015, peak-level familywise error [FWE] corrected for region of interest). Post hoc comparison and regression analysis did not suggest a role for BPD clinical state (pFWE > .56) or symptom severity (pFWE > .45) for this phenotype. Furthermore, deficient amygdala habituation was significantly related to increased exposure to adverse childhood experiences (pFWE = .013, region of interest corrected). CONCLUSIONS: Our data replicate a prior report on deficient amygdala habituation in BPD and link this neural phenotype to early adversity, a well-established social environmental risk factor for emotion dysregulation and psychiatric illness.