Thilo Kellermann

Multidimensional assessment of empathic abilities: neural correlates and gender differences.

Empathy is a multidimensional construct and comprises the ability to perceive, understand and feel the emotional states of others. Gender differences have been reported for various aspects of emotional and cognitive behaviors including theory of mind. However, although empathy is not a single ability but a complex behavioral competency including different components, most studies relied on single aspects of empathy, such as perspective taking or emotion perception. To extend those findings we developed three paradigms to assess all three core components of empathy (emotion recognition, perspective taking and affective responsiveness) and clarify to which extent gender affects the neural correlates of empathic abilities. A functional MRI study was performed with 12 females (6 during their follicular phase, 6 during their luteal phase) and 12 males, measuring these tasks as well as self-report empathy questionnaires. Data analyses revealed no significant gender differences in behavioral performance, but females rated themselves as more empathic than males in the self-report questionnaires. Analyses of functional data revealed distinct neural networks in females and males, and females showed stronger neural activation across all three empathy tasks in emotion-related areas, including the amygdala. Exploratory analysis of possible hormonal effects indicated stronger amygdala activation in females during their follicular phase supporting previous data suggesting higher social sensitivity and thus facilitated socio-emotional behavior. Hence, our data support the assumption that females and males rely on divergent processing strategies when solving emotional tasks: while females seem to recruit more emotion and self-related regions, males activate more cortical, rather cognitive-related areas.

Gender differences in the cognitive control of emotion: An fMRI study.

The interaction of emotion and cognition has become a topic of major interest. However, the influence of gender on the interplay between the two processes, along with its neural correlates have not been fully analysed so far. In this functional magnetic resonance imaging (fMRI) study we induced negative emotion using negative olfactory stimulation while male (n=21) and female (n=19) participants performed an n-back verbal working memory task. Based on findings indicating increased emotional reactivity in women, we expected the female participants to exhibit stronger activation in characteristically emotion-associated areas during the interaction of emotional and cognitive processing in comparison to the male participants. Both groups were found to be significantly impaired in their working memory performance by negative emotion induction. However, fMRI analysis revealed distinct differences in neuronal activation between groups. In men, cognitive performance under negative emotion induction was associated with extended activation patterns in mainly prefrontal and superior parietal regions. In women, the interaction between emotion and working memory yielded a significantly stronger response in the amygdala and the orbitofrontal cortex (OFC) compared to their male counterparts. Our data suggest that in women the interaction of verbal working memory and negative emotion is associated with relative hyperactivation in more emotion-associated areas whereas in men regions commonly regarded as important for cognition and cognitive control are activated. These results provide new insights in gender-specific cerebral mechanisms.

Same or different? Neural correlates of happy and sad mood in healthy males

Emotional experience in healthy men has been shown to rely on a brain network including subcortical as well as cortical areas in a complex interaction, which may be substantially influenced by many internal personal and external factors such as individuality, gender, stimulus material and task instructions. The divergent results may be interpreted by taking these considerations into account. Hence, many aspects remain to be clarified in characterizing the neural correlates underlying the subjective experience of emotion. One unresolved question refers to the influence of emotion quality on the cerebral substrates. Hence, 26 male healthy subjects were investigated with functional magnetic resonance imaging during standardized sad and happy mood induction as well as a cognitive control task to explore brain responses differentially involved in positive and negative emotional experience. Sad and happy mood in contrast to the control task produced similarly significant activations in the amygdala-hippocampal area extending into the parahippocampal gyrus as well as in the prefrontal and temporal cortex, the anterior cingulate, and the precuneus. Significant valence differences emerged when comparing both tasks directly. More activation has been demonstrated in the ventrolateral prefrontal cortex (VLPFC), the anterior cingulate cortex (ACC), the transverse temporal gyrus, and the superior temporal gyrus during sadness. Happiness, on the other hand, produced stronger activations in the dorsolateral prefrontal cortex (DLPFC), the cingulate gyrus, the inferior temporal gyrus, and the cerebellum. Hence, negative and positive moods reveal distinct cortical activation foci within a common neural network, probably making the difference between qualitatively different emotional feelings.

Neural correlates of working memory dysfunction in first-episode schizophrenia patients: an fMRI multi-center study

Working memory dysfunction is a prominent impairment in patients with schizophrenia. Our aim was to determine cerebral dysfunctions by means of functional magnetic resonance imaging (fMRI) in a large sample of first-episode schizophrenia patients during a working memory task. 75 first-episode schizophrenia patients and 81 control subjects, recruited within a multi-center study, performed 2- and 0-back tasks while brain activation was measured with fMRI. In order to guarantee comparability between data quality from different scanners, we developed and adopted a standardized, fully automated quality assurance of scanner hard- and software as well as a measure for in vivo data quality. After these quality-control measures had been implemented, 48 patients and 57 controls were included in the final analysis. During attention-related processes, even when the performance between patients and controls was comparable, there was a recognizable emergence of cerebral dysfunctions with hypoactivations in the ventrolateral prefrontal cortex (VLPFC), in the superior temporal cortex and in the thalamus. During working memory performance, parietal hypoactivations, especially in the precuneus, were prominent and were accompanied by poorer performance in patients. A hyperfrontality emerged in the ventrolateral prefrontal cortex. Hence, results point to a dysfunctional ventrolateral prefrontal-parietal network during working memory in patients, suggesting impairments in basic functions such as retrieval, storage and maintenance. The brain activation pattern of this large and significant sample of first-episode schizophrenia patients indicates an imbalanced system failing to adjust the amount of brain activity required in the cerebral network involved in attention and working memory.

Increased neural response related to neutral faces in individuals at risk for psychosis.

OBJECTIVE The reliable discrimination of emotional expressions in faces is essential for adequate social interaction. Deficits in facial emotion processing are an important impairment in schizophrenia with major consequences for social functioning and subjective well-being. Whether neural circuits underlying emotion processing are already altered before illness onset is yet unclear. Investigating neural correlates of emotion processing in individuals clinically at risk for psychosis offers the possibility to examine neural processes unchanged by the manifest disorder and to study trait aspects of emotion dysfunctions. MATERIAL AND METHODS Twelve subjects clinically at risk for psychosis and 12 matched control subjects participated in this study. fMRI data were acquired during an emotion discrimination task consisting of standardized photographs of faces displaying different emotions (happiness, sadness, anger, fear) as well as faces with neutral facial expression. RESULTS There were no group differences in behavioral performance. Emotion discrimination was associated with hyperactivations in high-risk subjects in the right lingual and fusiform gyrus as well as the left middle occipital gyrus. Further, high-risk compared to control subjects exhibited stronger activation related to neutral faces relative to emotional faces in the inferior and superior frontal gyri, the cuneus, the thalamus and the hippocampus. CONCLUSIONS The present study indicates that individuals clinically at risk for psychosis show differences in brain activation associated with processing of emotional and--more pronounced--neutral facial expressions despite an adequate behavioral performance. The proneness to attribute salience to neutral stimuli might indicate a biological risk marker for psychosis.

Automated quality assurance routines for fMRI data applied to a multicenter study

Standard procedures to achieve quality assessment (QA) of functional magnetic resonance imaging (fMRI) data are of great importance. A standardized and fully automated procedure for QA is presented that allows for classification of data quality and the detection of artifacts by inspecting temporal variations. The application of the procedure on phantom measurements was used to check scanner and stimulation hardware performance. In vivo imaging data were checked efficiently for artifacts within the standard fMRI post‐processing procedure by realignment. Standardized and routinely carried out QA is essential for extensive data amounts as collected in fMRI, especially in multicenter studies. Furthermore, for the comparison of two different groups, it is important to ensure that data quality is approximately equal to avoid possible misinterpretations. This is shown by example, and criteria to quantify differences of data quality between two groups are defined. Hum Brain Mapp 25:237–246, 2005.

Estradiol Modulates Functional Brain Organization during the Menstrual Cycle: An Analysis of Interhemispheric Inhibition

According to the hypothesis of progesterone-mediated interhemispheric decoupling (Hausmann and Güntürkün, 2000), functional cerebral asymmetries (FCAs), which are stable in men and change during the menstrual cycle in women, are generated by interhemispheric inhibition of the dominant on the nondominant hemisphere. The change of lateralization during the menstrual cycle in women might indicate that sex hormones play an important role in modulating FCAs. We used functional magnetic resonance imaging to examine the role of estradiol in determining cyclic changes of interhemispheric inhibition. Women performed a word-matching task, while they were scanned twice during the cycle, once during the menstrual and once during the follicular phase. By use of a connectivity analysis we found that the inhibitory influence of left-hemispheric language areas on homotopic areas of the right hemisphere is strongest during the menses, resulting in a pronounced lateralization. During the follicular phase, due to rising estradiol levels, inhibition and thus functional cerebral asymmetries are reduced. These results reveal a powerful neuromodulatory action of estradiol on the dynamics of functional brain organization in the female brain. They may further contribute to the ongoing discussion of sex differences in brain function in that they help explain the dynamic part of functional brain organization in which the female differs from the male brain.

Neuronal Correlates of Facial Emotion Discrimination in Early Onset Schizophrenia

Emotion discrimination deficits represent a well-established finding in schizophrenia. Although imaging studies addressed the cerebral dysfunctions underlying emotion perception in adult patients, the question of trait vs state characteristics is still unresolved. The investigation of juvenile patients offers the advantage of studying schizophrenia at an age where influences of illness course and long-term medication are minimized. This may enable a more detailed characterization of emotion discrimination impairments and their cerebral correlates with respect to their appearance and exact nature. A total of 12 juvenile patients with early onset schizophrenia and matched healthy juveniles participated in this study. fMRI data were acquired during an emotion discrimination task consisting of standardized photographs of faces displaying happy, sad, angry, fearful, or neutral facial expression. Similar to findings in adult patients, juvenile patients exhibited reduced performance specificity whereas sensitivity was unaffected. Independent of the valence, their processing of emotional faces was associated with hypoactivations in both fusiform gyri and in the left inferior occipital gyrus. In addition, hyperactivations in patients were found in the right cuneus common to happy, angry, and fearful faces. Further, most distinct changes were present in juvenile patients when processing sad faces. These results point to a dysfunction in cerebral circuits relevant for emotion processing already prominent in adolescent schizophrenia patients. Regions affected by a decrease in activation are related to visual and face processing, similar to deficits reported in adult patients. These changes are accompanied by hyperactivations in areas related to emotion regulation and attribution, possibly reflecting compensatory mechanisms.

Differential brain activation during facial emotion discrimination in first-episode schizophrenia

BACKGROUND Aberrant brain activation during facial emotion discrimination has been described in chronic schizophrenia, while little is known about early stages of the illness. The aim of the current study was to investigate valence-specific brain activation of emotion discrimination in first-episode schizophrenia. These patients provide the advantage of lacking the effects of long-term medication and chronic illness course and can hence further enhance the understanding of underlying psychopathological mechanisms. METHODS Using event-related fMRI, we investigated 18 first-episode schizophrenia patients and 18 matched healthy subjects during an explicit emotion discrimination task presenting happy, sad and neutral monochromatic facial expressions. A repeated measure analysis of variance (ANOVA) with the factors Group (patients, healthy subjects), Gender and Emotion (happy, sad, neutral) was performed on behavioural and functional data. RESULTS Behavioural performance did not differ between groups. Valence-independent hypoactivations in patients were observed for the anterior cingulate and orbitofrontal cortex while hyperactivations emerged in the posterior cingulate and the precuneus. Emotion-specific group differences were revealed in inferior parietal and orbitofrontal brain areas and the hippocampus. CONCLUSIONS First-episode schizophrenia already affects areas involved in processing of both, emotions and primary facial information. Our study underlines the role of dysfunctional neural networks as the basis of disturbed social interactions in early schizophrenia.

Gender differences in the neural correlates of humor processing: Implications for different processing modes

Humor is a complex phenomenon of human social cognition with large inter-individual variability. Gender differences in emotion processing are a common finding in functional neuroimaging studies, and have been documented in behavioral studies of humor, but have received limited attention in functional neuroimaging studies on humor. Using blood oxygenation level dependent (BOLD) contrasts with high-field (3T) functional magnetic resonance imaging (fMR) we investigated 29 healthy subjects (14 female, 15 male) during the processing of humorous cartoons. In women, the ventral system implicated ín detection and appraisal of emotion was activated, including amygdala, insula, and Anterior Cingulate Cortex (ACC). Men showed activation in both the ventral and dorsal processing systems. The results indicate that women process humor though limbic reactivity, involving appraisal of its emotional features, while men apply more evaluative, executive resources to humor processing.