Viewing the personality traits through a cerebellar lens. A focus on the constructs of novelty seeking, harm avoidance, and alexithymia

The variance in the range of personality trait expression appears to be linked to structural variance in specific brain regions. In evidencing associations between personality factors and neurobiological measures, it seems evident that the cerebellum has not been up to now thought as having a key role in personality. This paper will review the most recent structural and functional neuroimaging literature that engages the cerebellum in personality traits, as novelty seeking and harm avoidance, and it will discuss the findings in the context of contemporary theories of affective and cognitive cerebellar function. By using region of interest (ROI)- and voxel-based approaches, we recently evidenced that the cerebellar volumes correlate positively with novelty seeking scores and negatively with harm avoidance scores. Subjects who search for new situations as a novelty seeker does (and a harm avoiding does not do) show a different engagement of their cerebellar circuitries in order to rapidly adapt to changing environments. The emerging model of cerebellar functionality may explain how the cerebellar abilities in planning, controlling, and putting into action the behavior are associated to normal or abnormal personality constructs. In this framework, it is worth reporting that increased cerebellar volumes are even associated with high scores in alexithymia, construct of personality characterized by impairment in cognitive, emotional, and affective processing. On such a basis, it seems necessary to go over the traditional cortico-centric view of personality constructs and to address the function of the cerebellar system in sustaining aspects of motivational network that characterizes the different temperamental trait

Cerebellar BDNF promotes exploration and seeking for novelty

Approach system considered a motivational system that activates reward-seeking behavior is associated with exploration/impulsivity, whereas avoidance system considered an attentional system that promotes inhibition of appetitive responses is associated with active overt withdrawal. Approach and avoidance dispositions are modulated by distinct neurochemical profiles and synaptic patterns. However, the precise working of neurons and trafficking of molecules in the brain activity predisposing to approach and avoidance are yet unclear

Interindividual variability in the dimensions of goaldirected behaviour and their neural correlates

Goal-directed behaviour is an instrumental action performed to control our environment in order to provide a satisfactory outcome. It has been shown that these actions do not solely depend on action-outcome contingencies, but are also strongly influenced by personality traits or psychiatric disorders. Personality aspects such as sensitivity to rewards and impulsivity, as well as schizophrenia, have been identified as prominent factors, though the exact relation still remains unclear. Therefore, the goal of this dissertation is to provide an additional specification of interindividual differences in goal-directed behaviour on a neural level. Using functional imaging, we employed 2 different paradigms to probe reward-related as well as inhibition-related neural activation in healthy subjects and patients with schizophrenia. Study I investigated the neural response during a monetary incentive delay task in 23 healthy subjects, relating the observed activations with psychometric assessed traits of behavioural approach/inhibition. We found that the tendency to approach reward-related situations leads to an elevated neural response to positive outcomes, and an attenuated response to omissions. Additionally, a high behavioural inhibition tendency led to an attenuated response to rewards. Study II applied the monetary incentive delay task on a group of 15 patients with schizophrenia, demonstrating a negative relation between striatal activation during the expectation of reward and the symptom of apathy, as well as negative relation between orbitofrontal activation during the receipt of a reward and the symptom of depression. Study III investigated the relation between the personality trait of impulsivity and brain activation during the inhibition of inappropriate responses. Results showed that impulsivity is positively related to activations of bilateral ventroprefrontal regions. The results illustrate the importance of frontal-subcortical networks in goal-directed behaviour in clinical and non-clinical populations. An orbitofrontal/striatal network is specifically related to behavioural approach and inhibition tendencies, whereas impairments in the ventral striatum can lead to symptoms of apathy and depression in patients with schizophrenia. Additionally, activity in ventrolateral prefrontal regions is related to motor inhibition during successful inhibition of unwanted responses. Providing exact definitions of the specific functions and dependencies of frontal-subcortical circuits can inform our understanding of cognitive and emotional functions, and support research dealing with psychiatric disorders

Neural Correlates of Approach and Avoidance Learning in Behavioral Inhibition

Behavioral inhibition is a temperamental trait characterized in infancy and early childhood by a tendency to withdraw from novel or familiar stimuli. Recent neuroimaging research indicates that BI individuals have atypical neural responses to information regarding reward and punishment in the striatum and amygdala--regions of the brain that receive information about salient stimuli and use it to guide motivated behavior. Activation to rewarding and punishing stimuli in these regions follows a "prediction error" pattern. My research examines whether behaviorally inhibited young adults display atypical prediction error responses, and whether these responses are specific to rewarding or aversive events. Prediction error signals are theorized to be critical for approach and avoidance learning, and a second study examined probabilistic approach and avoidance learning in the same sample, examining differences in approach and avoidance learning between behaviorally inhibited and non-inhibited individuals, and the relation between learning and neural prediction error signals to reward and punishment

Implications from social and non-social task-based and task-free neuroimaging studies

Research on the effects of oxytocin on social cognition and behavior is constantly growing. Moreover, oxytocin is already discussed to be used as a drug supporting common therapies for a range of disorders displaying deficits in social cognition. Although, the knowledge about its neurophysiological mechanisms lacks in particular regarding its functioning in the non-social domain of behavior, cognition and related brain responses. Therefore, the present thesis had the aim to explore whether the neuropeptide oxytocin has an effect on non-social cognitive processes and their underlying neural correlates, how the neural mechanisms of oxytocin are modulated by additional social input and which basal changes are driven by the effects of oxytocin. I addressed these questions by the use of functional magnetic resonance imaging (fMRI) with task-based and resting-state designs and with a neuroimaging genetics approach. Oxytocin is synthesized in subnuclei of the hypothalamus and was originally known for its involvement in inducing labor. The oxytocin receptor is distributed largely across the brain, covering areas of the mesolimbic system such as the ventral striatum (vStr), the ventral tegmental area (VTA) and the amygdala, but also frontal areas and regions which are not prominently involved in social cognition. Generally, oxytocin is thought to affect social behavior and cognition, including parenting, affiliative behavior, but also emotion-regulation. It is also assumed to be sensitive for context, gender and personality characteristics. Whereas many studies explored the impact of oxytocin on socio-emotional actions such as on emotion-processing in the amygdala, only very few studies focused on the non-socioemotional domain, as for example memory processing or reward-related decision-making. With regard to the aims of this thesis, two of the three experiments employed a non-social decision making paradigm to reveal effects of oxytocin on non-social behavior and related brain activity. Indeed, oxytocin also modulated neural circuits during non-social tasks and even during the resting-state paradigm in the third experiment. This indicates that a social context might not be required to observe changes in neural activity and connectivity by oxytocin. Several theories have been proposed to explain the mechanisms by which oxytocin might function. The social cognition theory suggests that oxytocin might modulate prosocial affiliative behaviors and self-referential processing, the fear/stress approach emphasized its anxiolytic and stress reducing effects, the general approach-avoidance hypothesis of oxytocin assumes that oxytocin acts on approach and avoidance motivation and the social salience hypothesis implies that oxytocin regulates the salience of social stimuli. In conclusion, currently there is no general theory accounting for all the social and non-social effects of oxytocin as described in the literature. In the same perspective, the overall results from the current thesis contradict aspects of each theory, while specific patterns of effects may be best reconciliated with the framework of the approach-avoidance theory and the social salience hypothesis. In the first study a neuroimaging genetics approach was applied to investigate whether common variants of the oxytocin receptor gene influenced behavior and neural responses in a non-social reward-based decision-making paradigm. Specifically, due to dopaminergic-oxytocinergic interactions oxytocin-induced changes were expected in bottom-up reward-related and in top-down cognitive control-related activity. Two of the three candidate single-nucleotide-polymorphism (SNP) of the oxytocin receptor gene (OXTR) were associated with a modulation of reward-related activity during desire and reason situations in the paradigm used. The desire context was formed by allowing to obtain a presented reward, whereas in the reason context the same reward had to be rejected. Participants who were homozygous for the major allele of the OXTR SNP rs1042778 expressed more bottom-up related activity in the vStr in the desire context. In contrast to this, minor allele carriers showed a greater suppression of the reward-related activity in the reason context. This might have led to better cognitive control and therefore to significantly better performance in the rejection of reward stimuli in reason situations. According to this, major allele carriers had a stronger coupling between the vStr and the VTA in desire contexts. Moreover, minor allele carriers displayed an enhanced connectivity between the vStr and the anteroventral prefrontal cortex (avPFC) in reason situations. For the OXTR SNP rs237897 an interaction of gender with the activity in the VTA could be detected. Female participants, homozygous for the major genotype, presented more activation in the left VTA compared to males. Altogether, this study could show that OXTR polymorphisms are able to modulate reward-related as well as control-related activity even in a non-social decision-making paradigm. In study 2 a neuroimaging experiment was performed with the application of intranasal oxytocin and a modified reward-based decision-making paradigm including non-social as well as social stimuli. The main question was whether exogenous oxytocin alters behavioral and neural processes during the non-social condition in this task. Additionally, I was interested in possible changes of oxytocin effects by the presentation of emotional stimuli. Furthermore, by the additional use of both positive and fearful stimuli, I wanted to shed light on the ongoing discussion whether oxytocin acts valence-dependent or irrespective of valence on the activity of the amygdala. An opposite modulation of activity and functional connectivity regarding non-social compared with social context was shown after oxytocin treatment. In the non-social desire situation oxytocin reduced bottom-up activity within the vStr, probably by enhancing top-down control due to strengthening the negative coupling to a frontal region. In contrast, in non-social reason contexts the vStr was less deactivated, maybe due to decreased top-down control. By presenting fearful faces in the social condition, the pattern of neural responses and functional connectivity reversed. In this condition, oxytocin increased the activation in the vStr in desire situations, while it reduced the activation in reason situations. This change in activity was paralleled by stronger positive coupling in the desire context and less coupling as well as negative coupling in the reason context. Furthermore, depending on valence oxytocin decreased amygdala activation for fearful faces and increased amygdala activation for positive faces. The altered activity within the reward system by oxytocin might be the reason for an impaired performance during both desire and reason trials. After oxytocin treatment participants were less accurate in selecting target stimuli than in rejecting the reward stimulus and vice versa for the placebo. This suggests rather an impaired working memory than disturbed stimulus-association learning. To sum up, the comparison between the effects of oxytocin in the non-social and social condition yielded that oxytocin influences corticomesolimbic regions in a context-sensitive manner. The last study used a resting-state fMRI technique with additional administration of intranasal oxytocin. Of particular interest was the possible alteration of functional connectivity within and between large-scale networks by oxytocin. The analysis focused on functional networks indicated to play a major role in salience processing (the salience network - CO), social cognition and self-referential processing (the default mode network - DM) and attention processing (the ventral attentional network - VA). Thereby, basal changes by which oxytocin might influence neuronal responses were shown providing results for the ongoing debate on the underlying function of oxytocin. Although, I expected significant changes of functional connectivity within the DM network. The modulation of the CO and the VA networks were seen. Indeed, oxytocin changed the functional connectivity within and between large-scale networks even without engagement in a task. Oxytocin mainly influenced the VA by decreasing the cross-talk to regions typically part of the DM nodes; and oxytocin strengthened the functional connectivity to the edges of the CO, involving regions linked to salience processing. Additionally, oxytocin directly impacted the functional connectivity within the CO. Therefore, one basic effect of oxytocin might be to redirect attention (VA) from self-referential processing (DM) to the external environment, preparing for reception of salient information (CO). Taken together, the purpose of the present thesis was to extend the knowledge about the effects of oxytocin as well as basic mechanisms of oxytocin’s influence on cognition, behavior and neural activation and connectivity in non-social, social and task-free conditions. The results clearly demonstrated effects on neural activation, functional connectivity and on behavior in all three studies; supporting the claim that oxytocin does not only play an important role in socio-emotional processing

The role of adult attachment in the risk pathways for psychosis: modulation on personality traits, emotional availability and neurobiology of emotion processing

Non applicabil

Individual Attachment Style Modulates Human Amygdala and Striatum Activation during Social Appraisal

Adult attachment style refers to individual personality traits that strongly influence emotional bonds and reactions to social partners. Behavioral research has shown that adult attachment style reflects profound differences in sensitivity to social signals of support or conflict, but the neural substrates underlying such differences remain unsettled. Using functional magnetic resonance imaging (fMRI), we examined how the three classic prototypes of attachment style (secure, avoidant, anxious) modulate brain responses to facial expressions conveying either positive or negative feedback about task performance (either supportive or hostile) in a social game context. Activation of striatum and ventral tegmental area was enhanced to positive feedback signaled by a smiling face, but this was reduced in participants with avoidant attachment, indicating relative impassiveness to social reward. Conversely, a left amygdala response was evoked by angry faces associated with negative feedback, and correlated positively with anxious attachment, suggesting an increased sensitivity to social punishment. Secure attachment showed mirror effects in striatum and amygdala, but no other specific correlate. These results reveal a critical role for brain systems implicated in reward and threat processing in the biological underpinnings of adult attachment style, and provide new support to psychological models that have postulated two separate affective dimensions to explain these individual differences, centered on the ventral striatum and amygdala circuits, respectively. These findings also demonstrate that brain responses to face expressions are not driven by facial features alone but determined by the personal significance of expressions in current social context. By linking fundamental psychosocial dimensions of adult attachment with brain function, our results do not only corroborate their biological bases but also help understand their impact on behavior

Punishment sensitivity modulates the processing of negative feedback but not error-induced learning

Accumulating evidence suggests that individual differences in punishment and reward sensitivity are associated with functional alterations in neural systems underlying error and feedback processing. In particular, individuals highly sensitive to punishment have been found to be characterized by larger mediofrontal error signals as reflected in the error negativity/error-related negativity (Ne/ERN) and the feedback-related negativity (FRN). By contrast, reward sensitivity has been shown to relate to the error positivity (Pe). Given that Ne/ERN, FRN, and Pe have been functionally linked to flexible behavioral adaptation, the aim of the present research was to examine how these electrophysiological reflections of error and feedback processing vary as a function of punishment and reward sensitivity during reinforcement learning. We applied a probabilistic learning task that involved three different conditions of feedback validity (100%, 80%, and 50%). In contrast to prior studies using response competition tasks, we did not find reliable correlations between punishment sensitivity and the Ne/ERN. Instead, higher punishment sensitivity predicted larger FRN amplitudes, irrespective of feedback validity. Moreover, higher reward sensitivity was associated with a larger Pe. However, only reward sensitivity was related to better overall learning performance and higher post-error accuracy, whereas highly punishment sensitive participants showed impaired learning performance, suggesting that larger negative feedback-related error signals were not beneficial for learning or even reflected maladaptive information processing in these individuals. Thus, although our findings indicate that individual differences in reward and punishment sensitivity are related to electrophysiological correlates of error and feedback processing, we found less evidence for influences of these personality characteristics on the relation between performance monitoring and feedback-based learning