Extending the concept of emotion regulation with model-based fMRI

Effective emotion regulation is essential for our social and emotional well-being. Yet, the concept of emotion regulation, as it is conventionally regarded in the field, does not take important aspects of emotions and emotion regulation into account. The overarching aim of the current thesis was to include such missing aspects and thereby expand the concept of emotion regulation. The expansion occurred in two directions: firstly, the definition of emotion within the field of emotion regulation was widened to include the motivational aspect of emotions in terms of value-based prediction errors and their neural implementation; and secondly, an underestimated type of emotion regulation – the social emotion regulation – and its neural underpinnings were investigated. Projects 1 and 2 of the current thesis expand the emotion part of emotion regulation. Project 1 investigated whether emotion regulation affects not only emotional response-related brain activity but also influences aversive prediction error-related activity, i.e., the motivation-related brain signal. We found that self- initiated reappraisal, a type of cognitive emotion regulation, indeed affected prediction error-related activity, such that this activity was enhanced in the ventral tegmental area, ventral striatum, insula and hippocampus, possibly via a prefrontal-tegmental pathway. Project 2 further examined the way emotion regulation affects emotions and prediction errors, by testing whether self- initiated reappraisal directly targets the brain network for motivated behaviour previously outlined by animal studies. We found that superior (in contrast to inferior) regulators affected the balance of competing influences of ventral striatal afferents on striatal aversive prediction error signals; they reduced the impact of subcortical striatal afferents (i.e., hippocampus, amygdala and ventral tegmental area), while keeping the influence of the prefrontal cortex on ventral striatal prediction errors constant. Inferior regulators, on the other hand, failed to supress subcortical inputs into the ventral striatum and instead counterproductively reduced the prefrontal influence on ventral striatal prediction error signals. Projects 3 and 4 of the thesis extend the regulation part of emotion regulation. Project 3 explored the neural correlates of social cognitive emotion regulation, specifically reappraisal, and directly compared them with those of self-initiated reappraisal. We found that regions of the anterior, the medial parietal, and the lateral temporo-parietal default mode network were specifically involved in social emotion regulation, and that social regulation success and the default mode network involvement during regulation were related to participants’ attachment security scores. Project 4 investigated social emotion modulation and its impact on two distinct types of emotional brain activity – emotional response- and aversive prediction error-related activity. We found – for the simple contrast of being with somebody versus being alone – a three-fold dissociation between signal types and insula subregions, including left and right anterior and posterior insula parts. Social emotion modulation reduced aversive stimulus-related activity in the posterior insula, while simultaneously increasing aversive prediction error-related activity in the anterior insula. Furthermore, the social effect on prediction error-related activity was positively associated with aversive learning in the right, but negatively in the left anterior insula. Altogether, by expanding the concept of emotion regulation, projects of the current thesis provide new insights into both the effects and the neural underpinnings of three distinct emotion regulation types. Considering that problems in both intrapersonal emotion regulation and social interaction are linked to affective disorders, our findings might contribute to a better understanding of these disorders and the disorder-specific emotional and social impairments

Extending the concept of emotion regulation with model-based fMRI

Effective emotion regulation is essential for our social and emotional well-being. Yet, the concept of emotion regulation, as it is conventionally regarded in the field, does not take important aspects of emotions and emotion regulation into account. The overarching aim of the current thesis was to include such missing aspects and thereby expand the concept of emotion regulation. The expansion occurred in two directions: firstly, the definition of emotion within the field of emotion regulation was widened to include the motivational aspect of emotions in terms of value-based prediction errors and their neural implementation; and secondly, an underestimated type of emotion regulation – the social emotion regulation – and its neural underpinnings were investigated. Projects 1 and 2 of the current thesis expand the emotion part of emotion regulation. Project 1 investigated whether emotion regulation affects not only emotional response-related brain activity but also influences aversive prediction error-related activity, i.e., the motivation-related brain signal. We found that self- initiated reappraisal, a type of cognitive emotion regulation, indeed affected prediction error-related activity, such that this activity was enhanced in the ventral tegmental area, ventral striatum, insula and hippocampus, possibly via a prefrontal-tegmental pathway. Project 2 further examined the way emotion regulation affects emotions and prediction errors, by testing whether self- initiated reappraisal directly targets the brain network for motivated behaviour previously outlined by animal studies. We found that superior (in contrast to inferior) regulators affected the balance of competing influences of ventral striatal afferents on striatal aversive prediction error signals; they reduced the impact of subcortical striatal afferents (i.e., hippocampus, amygdala and ventral tegmental area), while keeping the influence of the prefrontal cortex on ventral striatal prediction errors constant. Inferior regulators, on the other hand, failed to supress subcortical inputs into the ventral striatum and instead counterproductively reduced the prefrontal influence on ventral striatal prediction error signals. Projects 3 and 4 of the thesis extend the regulation part of emotion regulation. Project 3 explored the neural correlates of social cognitive emotion regulation, specifically reappraisal, and directly compared them with those of self-initiated reappraisal. We found that regions of the anterior, the medial parietal, and the lateral temporo-parietal default mode network were specifically involved in social emotion regulation, and that social regulation success and the default mode network involvement during regulation were related to participants’ attachment security scores. Project 4 investigated social emotion modulation and its impact on two distinct types of emotional brain activity – emotional response- and aversive prediction error-related activity. We found – for the simple contrast of being with somebody versus being alone – a three-fold dissociation between signal types and insula subregions, including left and right anterior and posterior insula parts. Social emotion modulation reduced aversive stimulus-related activity in the posterior insula, while simultaneously increasing aversive prediction error-related activity in the anterior insula. Furthermore, the social effect on prediction error-related activity was positively associated with aversive learning in the right, but negatively in the left anterior insula. Altogether, by expanding the concept of emotion regulation, projects of the current thesis provide new insights into both the effects and the neural underpinnings of three distinct emotion regulation types. Considering that problems in both intrapersonal emotion regulation and social interaction are linked to affective disorders, our findings might contribute to a better understanding of these disorders and the disorder-specific emotional and social impairments

Human threat circuits: Threats of pain, aggressive conspecific, and predator elicit distinct BOLD activations in the amygdala and hypothalamus

IntroductionThreat processing, enabled by threat circuits, is supported by a remarkably conserved neural architecture across mammals. Threatening stimuli relevant for most species include the threat of being attacked by a predator or an aggressive conspecific and the threat of pain. Extensive studies in rodents have associated the threats of pain, predator attack and aggressive conspecific attack with distinct neural circuits in subregions of the amygdala, the hypothalamus and the periaqueductal gray. Bearing in mind the considerable conservation of both the anatomy of these regions and defensive behaviors across mammalian species, we hypothesized that distinct brain activity corresponding to the threats of pain, predator attack and aggressive conspecific attack would also exist in human subcortical brain regions.MethodsForty healthy female subjects underwent fMRI scanning during aversive classical conditioning. In close analogy to rodent studies, threat stimuli consisted of painful electric shocks, a short video clip of an attacking bear and a short video clip of an attacking man. Threat processing was conceptualized as the expectation of the aversive stimulus during the presentation of the conditioned stimulus.ResultsOur results demonstrate differential brain activations in the left and right amygdala as well as in the left hypothalamus for the threats of pain, predator attack and aggressive conspecific attack, for the first time showing distinct threat-related brain activity within the human subcortical brain. Specifically, the threat of pain showed an increase of activity in the left and right amygdala and the left hypothalamus compared to the threat of conspecific attack (pain > conspecific), and increased activity in the left amygdala compared to the threat of predator attack (pain > predator). Threat of conspecific attack revealed heightened activity in the right amygdala, both in comparison to threat of pain (conspecific > pain) and threat of predator attack (conspecific > predator). Finally, for the condition threat of predator attack we found increased activity in the bilateral amygdala and the hypothalamus when compared to threat of conspecific attack (predator > conspecific). No significant clusters were found for the contrast predator attack > pain.ConclusionResults suggest that threat type-specific circuits identified in rodents might be conserved in the human brain

Amygdala functional connectivity as a longitudinal biomarker of symptom changes in generalized anxiety

Generalized anxiety disorder (GAD) is characterized by excessive worry, autonomic dysregulation and functional amygdala dysconnectivity, yet these illness markers have rarely been considered together, nor their interrelationship tested longitudinally. We hypothesized that an individual's capacity for emotion regulation predicts longer-term changes in amygdala functional connectivity, supporting the modification of GAD core symptoms. Sixteen patients with GAD (14 women) and individually matched controls were studied at two time points separated by 1 year. Resting-state fMRI data and concurrent measurement of vagally mediated heart rate variability were obtained before and after the induction of perseverative cognition. A greater rise in levels of worry following the induction predicted a stronger reduction in connectivity between right amygdala and ventromedial prefrontal cortex, and enhanced coupling between left amygdala and ventral tegmental area at follow-up. Similarly, amplified physiological responses to the induction predicted increased connectivity between right amygdala and thalamus. Longitudinal shifts in a distinct set of functional connectivity scores were associated with concomitant changes in GAD symptomatology over the course of the year. Results highlight the prognostic value of indices of emotional dysregulation and emphasize the integral role of the amygdala as a critical hub in functional neural circuitry underlying the progression of GAD symptomatology

Heterogenous mobile application development in RAD Studio 10 development environment

V diplomskemu delu smo raziskovali problem razvoja heterogenih aplikacij za pametne telefone. Obravnavali smo več različnih mobilnih naprav, ki uporabljajo različne operacijske sisteme. Za dosego večjega števila uporabnikov je potrebno podpreti čim več le-teh. Aplikacije se lahko razvijajo v domorodnih okoljih ali okoljih za navzkrižne platforme. Zanimalo nas je kvaliteta razvojnega okolja RAD Studio, če lahko nadomesti razvoj domorodnih aplikacij. Da bi to ugotovili, smo izdelali prototipno aplikacijo tako v domorodnih okoljih (Android Studio in Xcode) ter v RAD Studiu in jih na koncu primerjali med seboj. RAD Studio nudi manj udobja od domorodnih okolij.In the B.S. thesis we research the problem of development of heterogeneous applications for smart phones. We considered several different mobile devices that used different operational systems. Therefore one must produce applications for different operational system in order to reach several users. Applications can be developed in native environments or in cross platforms. We were interested in the quality of the development environment RAD Studio, whether it can replace development of native applications. To find this out we generated prototype application both in native environments (Android Studio and Xcode) and in RAD Studio and compared them at the end. RAD Studio offered less comfort than the native environments

Social reappraisal of emotions is linked with the social presence effect in the default mode network

Introduction: Social reappraisal, during which one person deliberately tries to regulate another’s emotions, is a powerful cognitive form of social emotion regulation, crucial for both daily life and psychotherapy. The neural underpinnings of social reappraisal include activity in the default mode network (DMN), but it is unclear how social processes influence the DMN and thereby social reappraisal functioning. We tested whether the mere presence of a supportive social regulator had an effect on the DMN during rest, and whether this effect in the DMN was linked with social reappraisal-related neural activations and effectiveness during negative emotions. Methods: A two-part fMRI experiment was performed, with a psychotherapist as the social regulator, involving two resting state (social, non-social) and two task-related (social reappraisal, social no-reappraisal) conditions. Results: The psychotherapist’s presence enhanced intrinsic functional connectivity of the dorsal anterior cingulate (dACC) within the anterior medial DMN, with the effect positively related to participants’ trust in psychotherapists. Secondly, the social presence-induced change in the dACC was related with (a) the social reappraisal-related activation in the bilateral dorsomedial/dorsolateral prefrontal cortex and the right temporoparietal junction and (b) social reappraisal success, with the latter relationship moderated by trust in psychotherapists. Conclusion: Results demonstrate that a psychotherapist’s supportive presence can change anterior medial DMN’s intrinsic connectivity even in the absence of stimuli and that this DMN change during rest is linked with social reappraisal functioning during negative emotions. Data suggest that trust-dependent social presence effects on DMN states are relevant for social reappraisal—an idea important for daily-life and psychotherapy-related emotion regulation

Human threat circuits

Threat processing, enabled by threat circuits, is supported by a remarkably conserved neural architecture across mammals. Threatening stimuli relevant for most species include the threat of being attacked by a predator or an aggressive conspecific and the threat of pain. Extensive studies in rodents have associated the threats of pain, predator attack and aggressive conspecific attack with distinct neural circuits in subregions of the amygdala, the hypothalamus and the periaqueductal gray. Bearing in mind the considerable conservation of both the anatomy of these regions and defensive behaviors across mammalian species, we hypothesized that distinct brain activity corresponding to the threats of pain, predator attack and aggressive conspecific attack would also exist in human subcortical brain regions

Common and specific large-scale brain changes in major depressive disorder, anxiety disorders, and chronic pain

Major depressive disorder (MDD), anxiety disorders (ANX), and chronic pain (CP) are closely-related disorders with both high degrees of comorbidity among them and shared risk factors. Considering this multi-level overlap, but also the distinct phenotypes of the disorders, we hypothesized both common and disorder-specific changes of large-scale brain systems, which mediate neural mechanisms and impaired behavioral traits, in MDD, ANX, and CP. To identify such common and disorder-specific brain changes, we conducted a transdiagnostic, multimodal meta-analysis of structural and functional MRI-studies investigating changes of gray matter volume (GMV) and intrinsic functional connectivity (iFC) of large-scale intrinsic brain networks across MDD, ANX, and CP. The study was preregistered at PROSPERO (CRD42019119709). 320 studies comprising 10,931 patients and 11,135 healthy controls were included. Across disorders, common changes focused on GMV-decrease in insular and medial-prefrontal cortices, located mainly within the so-called default-mode and salience networks. Disorder-specific changes comprised hyperconnectivity between defaultmode and frontoparietal networks and hypoconnectivity between limbic and salience networks in MDDlimbic network hyperconnectivity and GMV-decrease in insular and medial-temporal cortices in ANXand hypoconnectivity between salience and default-mode networks and GMV-increase in medial temporal lobes in CP. Common changes suggested a neural correlate for comorbidity and possibly shared neuro-behavioral chronification mechanisms. Disorder-specific changes might underlie distinct phenotypes and possibly additional disorder-specific mechanisms

Your presence soothes me: a neural process model of aversive emotion regulation via social buffering

The reduction of aversive emotions by a conspecific's presence-called social buffering-is a universal phenomenon in the mammalian world and a powerful form of human social emotion regulation. Animal and human studies on neural pathways underlying social buffering typically examined physiological reactions or regional brain activations. However, direct links between emotional and social stimuli, distinct neural processes and behavioural outcomes are still missing. Using data of 27 female participants, the current study delineated a large-scale process model of social buffering's neural underpinnings, connecting changes in neural activity to emotional behaviour by means of voxel-wise multilevel mediation analysis. Our results confirmed that three processes underlie human social buffering: (i) social support-related reduction of activity in the orbitofrontal cortex, ventromedial and dorsolateral prefrontal cortices, anterior and mid-cingulate; (ii) downregulation of aversive emotion-induced brain activity in the superficial cortex-like amygdala and mediodorsal thalamus; and (iii) downregulation of reported aversive feelings. Results of the current study provide evidence for a distinct neural process model of aversive emotion regulation in humans by social buffering

Cognitive emotion regulation modulates the balance of competing influences on ventral striatal aversive prediction error signals

Cognitive emotion regulation (CER) is a critical human ability to face aversive emotional stimuli in a flexible way, via recruitment of specific prefrontal brain circuits. Animal research reveals a central role of ventral striatum in emotional behavior, for both aversive conditioning, with striatum signaling aversive prediction errors (aPE), and for integrating competing influences of distinct striatal inputs from regions such as the prefrontal cortex (PFC), amygdala, hippocampus and ventral tegmental area (VTA). Translating these ventral striatal findings from animal research to human CER, we hypothesized that successful CER would affect the balance of competing influences of striatal afferents on striatal aPE signals, in a way favoring PFC as opposed to subcortical (i.e., non-isocortical) striatal inputs. Using aversive Pavlovian conditioning with and without CER during fMRI, we found that during CER, superior regulators indeed reduced the modulatory impact of subcortical striatal afferents (hippocampus, amygdala and VTA) on ventral striatal aPE signals, while keeping the PFC impact intact. In contrast, inferior regulators showed an opposite pattern. Our results demonstrate that ventral striatal aPE signals and associated competing modulatory inputs are critical mechanisms underlying successful cognitive regulation of aversive emotions in humans