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

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

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

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

Cognitive emotion regulation enhances aversive prediction error activity while reducing emotional responses

Cognitive emotion regulation is a powerful way of modulating emotional responses. However, despite the vital role of emotions in learning, it is unknown whether the effect of cognitive emotion regulation also extends to the modulation of learning. Computational models indicate prediction error activity, typically observed in the striatum and ventral tegmental area, as a critical neural mechanism involved in associative learning. We used model-based fMRI during aversive conditioning with and without cognitive emotion regulation to test the hypothesis that emotion regulation would affect prediction error-related neural activity in the striatum and ventral tegmental area, reflecting an emotion regulation-related modulation of learning. Our results show that cognitive emotion regulation reduced emotion-related brain activity, but increased prediction error-related activity in a network involving ventral tegmental area, hippocampus, insula and ventral striatum. While the reduction of response activity was related to behavioral measures of emotion regulation success, the enhancement of prediction error-related neural activity was related to learning performance. Furthermore, functional connectivity between the ventral tegmental area and ventrolateral prefrontal cortex, an area involved in regulation, was specifically increased during emotion regulation and likewise related to learning performance. Our data, therefore, provide first-time evidence that beyond reducing emotional responses, cognitive emotion regulation affects learning by enhancing prediction error-related activity, potentially via tegmental dopaminergic pathways. (C) 2015 Elsevier Inc. All rights reserved

How do you make me feel better? Social cognitive emotion regulation and the default mode network

Socially-induced cognitive emotion regulation (Social-Reg) is crucial for emotional well-being and social functioning; however, its brain mechanisms remain poorly understood. Given that both social cognition and cognitive emotion regulation engage key regions of the default-mode network (DMN), we hypothesized that Social-Reg would rely on the DMN, and that its effectiveness would be associated with social functioning. During functional MRI, negative emotions were elicited by pictures, and - via short instructions - a psychotherapist either down-regulated participants' emotions by employing reappraisal (Reg), or asked them to simply look at the pictures (Look). Adult Attachment Scale was used to measure social functioning. Contrasting Reg versus Look, aversive emotions were successfully reduced during Social-Reg, with increased activations in the prefrontal and parietal cortices, precuneus and the left temporo-parietal junction. These activations covered key nodes of the DMN and were associated with Social-Reg success. Furthermore, participants' attachment security was positively correlated with both Social-Reg success and orbitofrontal cortex involvement during Social-Reg. In addition, specificity of the neural correlates of Social-Reg was confirmed by comparisons with participants' DMN activity at rest and their brain activations during a typical emotional self-regulation task based on the same experimental paradigm without a psychotherapist. Our results provide first evidence for the specific involvement of the DMN in Social-Reg, and the association of Social-Reg with individual differences in attachment security. The findings suggest that DMN dysfunction, found in many neuropsychiatric disorders, may impair the ability to benefit from Social-Reg. (C) 2016 Elsevier Inc. All rights reserved