Exploring Sex Differences in the Neural Correlates of Self-and Other-Referential Gender Stereotyping.

While general self-referential processes and their neural underpinnings have been extensively investigated with neuroimaging tools, limited data is available on sex differences regarding self- and other-referential processing. To fill this gap, we measured 17 healthy women and men who performed a self- vs. other-appraisal task during functional magnetic resonance imaging (fMRI) using gender-stereotypical adjectives. During the self-appraisal task, typical male (e.g., "dominant," "competitive") and female adjectives (e.g., "communicative," "sensitive") were presented and participants were asked whether these adjectives applied to themselves. During the other-appraisal task, a prototypical male (Brad Pitt) and female actor (Julia Roberts) was presented and participants were asked again to judge whether typical male and female adjectives applied to these actors. Regarding self-referential processes, women ascribed significantly more female compared to male traits to themselves. At the same time both women and men indicated a stronger desire to exhibit male over female traits. While fMRI did not detect general sex differences in the self- and other-conditions, some subtle differences were revealed between the sexes: both in right putamen and bilateral amygdala stronger gender-congruent activation was found which was however not associated with behavioral measures like the number of self-ascribed female or male attributes. Furthermore, sex hormone levels showed some associations with brain activation pointing to a different pattern in women and men. Finally, the self- vs. other-condition in general led to stronger activation of the anterior cingulate cortex while the other- vs. self-condition activated the right precuneus more strongly which is in line with previous findings. To conclude, our data lend support for subtle sex differences during processing of stereotypical gender attributes. However, it remains unclear whether such differences have a behavioral relevance. We also point to several limitations of this study including the small sample size and the lack of control for potentially different hormonal states in women.

Cerebral and behavioural response to human voices is mediated by sex and sexual orientation.

Several studies report sex differences in sensitivity to gendered stimuli. We assume many of these to reflect differences as to the sex to which one feels attracted rather than to biological sex per se. Investigating voice perception, a function of high social relevance, we show that the behavioural and neural (BOLD) responses to male and female voices are mediated by sex and sexual orientation. In heterosexual men and women, we found an opposite-sex effect, reflected in higher classification accuracy for and a response bias towards voices of the other sex, while the effect became apparent as same-sex effect in homosexual men and women. Overall, sexual orientation had a greater impact in women than in men and homosexual women were closer to men in their behavioural responses to female voices. The activation patterns were similar for hetero- and homosexual men, both groups showing increased activation in response to male compared to female voices in regions distributed across the temporo-parietal and insular cortex. In contrast, women had increased activation in response to voices of the desired sex. It appears that both sex and sexual orientation impact on a function as basal as voice perception. Our results underline the need to assess sexual orientation in study participants if conclusions on sex differences shall be drawn. Many of the reported sex differences in behaviour and brain function might be mediated by sexual orientation and we encourage further research into the interplay between sex and sexual orientation.

Gender incongruence and the brain - Behavioral and neural correlates of voice gender perception in transgender people.

The phenomenon of gender incongruence is hypothesized to arise from a discrepant sexual development of the brain and the genitals, contingent on genetic and hormonal mechanisms. We aimed at visualizing transgender identity on a neurobiological level, assuming a higher functional similarity to individuals of the aspired rather than assigned sex. Implementing a gender perception paradigm featuring male and female voice stimuli, behavioral and functional imaging data of transmen were compared to men and women, and to transwomen, respectively. Men had decreased activation in response to voices of the other sex in regions across the frontoparietal and insular cortex, while the activation patterns of women and transmen were characterized by little or no differentiation between male and female voices. Further, transmen had a comparatively high discrimination performance for ambiguous male voices, possibly reflecting a high sensitivity for voices of the aspired sex. Comparing transmen and transwomen yielded only few differences in the processing of male compared to female voices. In the insula, we observed a pattern similar to that of men and women, the neural responses of the transgender group being in accordance with their gender identity rather than assigned sex. Notwithstanding the similarities found dependent on biological sex, the findings support the hypothesis of gender incongruence being a condition in which neural processing modes are partly incongruent with one's assigned sex.

Male-to-female gender dysphoria: Gender-specific differences in resting-state networks.

INTRODUCTION: Recent research found gender-related differences in resting-state functional connectivity (rs-FC) measured by functional magnetic resonance imaging (fMRI). To the best of our knowledge, there are no studies examining the differences in rs-FC between men, women, and individuals who report a discrepancy between their anatomical sex and their gender identity, i.e. gender dysphoria (GD). METHODS: To address this important issue, we present the first fMRI study systematically investigating the differences in typical resting-state networks (RSNs) and hormonal treatment effects in 26 male-to-female GD individuals (MtFs) compared with 19 men and 20 women. RESULTS: Differences between male and female control groups were found only in the auditory RSN, whereas differences between both control groups and MtFs were found in the auditory and fronto-parietal RSNs, including both primary sensory areas (e.g. calcarine gyrus) and higher order cognitive areas such as the middle and posterior cingulate and dorsomedial prefrontal cortex. Overall, differences in MtFs compared with men and women were more pronounced before cross-sex hormonal treatment. Interestingly, rs-FC between MtFs and women did not differ significantly after treatment. When comparing hormonally untreated and treated MtFs, we found differences in connectivity of the calcarine gyrus and thalamus in the context of the auditory network, as well as the inferior frontal gyrus in context of the fronto-parietal network. CONCLUSION: Our results provide first evidence that MtFs exhibit patterns of rs-FC which are different from both their assigned and their aspired gender, indicating an intermediate position between the two sexes. We suggest that the present study constitutes a starting point for future research designed to clarify whether the brains of individuals with GD are more similar to their assigned or their aspired gender.

Don't worry, be happy - Neural correlates of the influence of musically induced mood on self-evaluation.

Self-evaluation affects one's own mental state, social interactions and everyday life. Mood, in turn, has an impact on self-evaluation. However, the influence of mood on self-evaluation at the neural level has barely been examined. In this fMRI study, the interaction of mood and self-perception was investigated in 20 healthy participants. Happy, sad and neutral music was presented while participants were instructed to immerse themselves in the mood of the music and to rate how well presented traits characterized themselves. In a lexical control condition, subjects had to count a specific letter in the word. Behavioral data reflected successful mood induction. While self-ascription of positive traits was unaffected by mood, self-ascription of negative characteristics was decreased by negative affect. A positive correlation was found between self-worth scores and the difference in the amount of self-ascribed positive versus negative traits during negative mood induction. At the neural level, amygdalo-hippocampal, superior and middle temporal structures were differently involved in self-evaluation (vs. lexical processing) depending on the mood. While activation of the amygdalo-hippocampal complex was found during sad in comparison to both happy and neutral mood, superior/middle temporal gyrus (STG/MTG) activation was only found when contrasting sad vs. neutral mood. Further, a correlation analysis with self-worth ratings revealed a positive relation to STG activation during self-ascription of trait adjectives in sad compared to neutral mood. Our results underscore the importance of the current emotional state for self-evaluation and identify some neural correlates of this effect. Our findings in healthy research participants suggest a compensatory mechanism during sad mood induction to maintain a positive self-image, which is supported by activation of limbic and fronto-temporal cortex. Studies in clinically depressed populations could reveal whether this compensatory mechanism is aberrant.

Incidental Memory Encoding Assessed with Signal Detection Theory and Functional Magnetic Resonance Imaging (fMRI).

In functional magnetic resonance imaging (fMRI) studies that apply a "subsequent memory" approach, successful encoding is indicated by increased fMRI activity during the encoding phase for hits vs. misses, in areas underlying memory encoding such as the hippocampal formation. Signal-detection theory (SDT) can be used to analyze memory-related fMRI activity as a function of the participant's memory trace strength (d(')). The goal of the present study was to use SDT to examine the relationship between fMRI activity during incidental encoding and participants' recognition performance. To implement a new approach, post-experimental group assignment into High- or Low Performers (HP or LP) was based on 29 healthy participants' recognition performance, assessed with SDT. The analyses focused on the interaction between the factors group (HP vs. LP) and recognition performance (hits vs. misses). A whole-brain analysis revealed increased activation for HP vs. LP during incidental encoding for remembered vs. forgotten items (hits > misses) in the insula/temporo-parietal junction (TPJ) and the fusiform gyrus (FFG). Parameter estimates in these regions exhibited a significant positive correlation with d('). As these brain regions are highly relevant for salience detection (insula), stimulus-driven attention (TPJ), and content-specific processing of mnemonic stimuli (FFG), we suggest that HPs' elevated memory performance was associated with enhanced attentional and content-specific sensory processing during the encoding phase. We provide first correlative evidence that encoding-related activity in content-specific sensory areas and content-independent attention and salience detection areas influences memory performance in a task with incidental encoding of facial stimuli. Based on our findings, we discuss whether the aforementioned group differences in brain activity during incidental encoding might constitute the basis of general differences in memory performance between HP and LP.

More than just two sexes: the neural correlates of voice gender perception in gender dysphoria.

Gender dysphoria (also known as "transsexualism") is characterized as a discrepancy between anatomical sex and gender identity. Research points towards neurobiological influences. Due to the sexually dimorphic characteristics of the human voice, voice gender perception provides a biologically relevant function, e.g. in the context of mating selection. There is evidence for a better recognition of voices of the opposite sex and a differentiation of the sexes in its underlying functional cerebral correlates, namely the prefrontal and middle temporal areas. This fMRI study investigated the neural correlates of voice gender perception in 32 male-to-female gender dysphoric individuals (MtFs) compared to 20 non-gender dysphoric men and 19 non-gender dysphoric women. Participants indicated the sex of 240 voice stimuli modified in semitone steps in the direction to the other gender. Compared to men and women, MtFs showed differences in a neural network including the medial prefrontal gyrus, the insula, and the precuneus when responding to male vs. female voices. With increased voice morphing men recruited more prefrontal areas compared to women and MtFs, while MtFs revealed a pattern more similar to women. On a behavioral and neuronal level, our results support the feeling of MtFs reporting they cannot identify with their assigned sex.

Me, myself and I: temporal dysfunctions during self-evaluation in patients with schizophrenia.

Self-concept is deeply affected in schizophrenia. Positive symptoms in particular are related to disturbed self/other distinctions. The neural networks underlying self-evaluation in schizophrenia have barely been investigated. The study reported here involved 13 patients with schizophrenia and 13 matched controls. During functional MRI, participants decided in three conditions whether the presented positive and negative personality traits characterized themselves, an intimate person, or included a certain letter. Based on the responses, each experimental condition was designed using a flexible factorial model. Controls and patients showed a similar behavioral pattern during self-evaluation, with group comparison revealing decreased activation in patients in the left inferior temporal gyrus and both temporal poles during self-ascription of traits, and in the anterior medial prefrontal cortex during evaluation of an intimate person. In patients, positive symptoms correlated positively with brain activation in the left parahippocampus during trait self-ascription. Hence, while evaluating themselves, schizophrenia patients revealed decreased activation in areas related to self-awareness overlapping with networks involved in theory of mind, empathy and social knowledge. Moreover, patients' brain activation during self-reflection was affected by the current positive symptomatology. The close interaction between self and other highlights the clinical and social relevance of self-processing deficits in schizophrenia.

Evidence for gender-specific endophenotypes in high-functioning autism spectrum disorder during empathy.

Despite remarkable behavioral gender differences in patients with autism spectrum disorder (ASD), and growing evidence for a diminished male : female ratio for the putative "male disorder" ASD, aspects of gender are not addressed accordingly in ASD research. Our study aims at filling this gap by exploring empathy abilities in a group of 28 patients with high-functioning ASD and 28 gender-, age- and education-matched non-autistic subjects, for the first time by means of functional neuroimaging (fMRI). In an event-related fMRI paradigm, emotional ("E") and neutral ("N") video clips presented actors telling self-related short stories. After each clip, participants were asked to indicate their own emotion and its intensity as well as the emotion and intensity perceived for the actor. Behaviorally, we found significantly less empathic responses in the overall ASD group compared with non-autistic subjects, and inadequate emotion recognition for the neutral clips in the female ASD group compared with healthy women. Neurally, increased activation of the bilateral medial frontal gyrus was found in male patients compared with female patients, a pattern which was not present in the non-autistic group. Additionally, autistic women exhibited decreased activation of midbrain and limbic regions compared with non-autistic women, whereas there was no significant difference within the male group. While we did not find a fundamental empathic deficit in autistic patients, our data propose different ways of processing empathy in autistic men and women, suggesting stronger impairments in cognitive aspects of empathy/theory of mind for men, and alterations of social reciprocity for women.

Sex matters: Neural correlates of voice gender perception.

The basis for different neural activations in response to male and female voices as well as the question, whether men and women perceive male and female voices differently, has not been thoroughly investigated. Therefore, the aim of the present study was to examine the behavioral and neural correlates of gender-related voice perception in healthy male and female volunteers. fMRI data were collected while 39 participants (19 female) were asked to indicate the gender of 240 voice stimuli. These stimuli included recordings of 3-syllable nouns as well as the same recordings pitch-shifted in 2, 4 and 6 semitone steps in the direction of the other gender. Data analysis revealed a) equal voice discrimination sensitivity in men and women but better performance in the categorization of opposite-sex stimuli at least in men, b) increased responses to increasing gender ambiguity in the mid cingulate cortex and bilateral inferior frontal gyri, and c) stronger activation in a fronto-temporal neural network in response to voices of the opposite sex. Our results indicate a gender specific processing for male and female voices on a behavioral and neuronal level. We suggest that our results reflect higher sensitivity probably due to the evolutionary relevance of voice perception in mate selection.

The precuneus and the insula in self-attributional processes.

Attributions are constantly assigned in everyday life. A well-known phenomenon is the self-serving bias: that is, people's tendency to attribute positive events to internal causes (themselves) and negative events to external causes (other persons/circumstances). Here, we investigated the neural correlates of the cognitive processes implicated in self-serving attributions using social situations that differed in their emotional saliences. We administered an attributional bias task during fMRI scanning in a large sample of healthy subjects (n = 71). Eighty sentences describing positive or negative social situations were presented, and subjects decided via buttonpress whether the situation had been caused by themselves or by the other person involved. Comparing positive with negative sentences revealed activations of the bilateral posterior cingulate cortex (PCC). Self-attribution correlated with activation of the posterior portion of the precuneus. However, self-attributed positive versus negative sentences showed activation of the anterior portion of the precuneus, and self-attributed negative versus positive sentences demonstrated activation of the bilateral insular cortex. All significant activations were reported with a statistical threshold of p ≤ .001, uncorrected. In addition, a comparison of our fMRI task with data from the Internal, Personal and Situational Attributions Questionnaire, Revised German Version, demonstrated convergent validity. Our findings suggest that the precuneus and the PCC are involved in the evaluation of social events with particular regional specificities: The PCC is activated during emotional evaluation, the posterior precuneus during attributional evaluation, and the anterior precuneus during self-serving processes. Furthermore, we assume that insula activation is a correlate of awareness of personal agency in negative situations.

Neural correlates of moral reasoning in autism spectrum disorder.

In our study, we tried to clarify whether patients with autism spectrum disorder (ASD) reveal different moral decision patterns as compared to healthy subjects and whether common social interaction difficulties in ASD are reflected in altered brain activation during different aspects of moral reasoning. 28 patients with high-functioning ASD and 28 healthy subjects matched for gender, age and education took part in an event-related functional magnetic resonance imaging study. Participants were confronted with textual dilemma situations followed by proposed solutions to which they could agree or disagree. On a neural level, moral decision making was associated with activation in anterior medial prefrontal regions, the temporo-parietal junction and the precuneus for both groups. However, while patients and healthy controls did not exhibit significant behavioral differences, ASD patients showed decreased activation in limbic regions, particularly the amygdala, as well as increased activation in the anterior and the posterior cingulate gyrus during moral reasoning. Alterations of brain activation in patients might thus indicate specific impairments in empathy. However, activation increases in brain regions associated with the 'default mode network' and self-referential cognition also provide evidence for an altered way of patients' cerebral processing with regard to decision making based on social information.

The neural correlates of positive self-evaluation and self-related memory.

Humans tend to have a positive self-evaluation (PSE). To what extent positive self-perception is interacting with valenced self-related memories is debated. The underlying neural substrates are not adequately explained yet. To explore the cerebral correlates of PSE and its influence on memory, 24 healthy subjects were asked during fMRI to decide in two conditions whether presented positive and negative personality traits characterized their own selves (self-evaluation) or an intimate other (other-evaluation). A lexical condition served as control task. In a subsequent unannounced recognition task, trait adjectives had to be classified as old or new. Activation during positive self- vs positive other-evaluation was found in the medial ventral and dorsolateral prefrontal gyri, the parahippocampus and the supplementary motor area. Memory increased for positive personality traits and traits that had been referred to oneself or the other. In contrast to adjectives of the other-evaluation or lexical condition, recollection of negative vs positive traits of the self-evaluation condition specifically induced increased activation in the hippocampus and several prefrontal and temporal areas. Our data imply a specific network for PSE (although intimate others are perceived similarly). Moreover, memory for traits contradicting PSE resulted in activation increases indicating greater cognitive effort and emotional involvement.

Self-concept, emotion and memory performance in schizophrenia.

The "self-reference effect" describes better memory for material someone has related to one's self previously. Schizophrenia can affect aspects of the inner self such as own thoughts or actions. Schizophrenia symptoms, therefore, might not only have an influence on the self-concept, including the self-attribution of positive or negative personality traits, but also reduce the self-reference effect. 15 schizophrenia patients and 15 matched healthy controls were asked to decide on positive and negative personality traits across three separate conditions: self-evaluation, other evaluation (of an intimate person), and during a lexical control task, respectively. An unannounced recognition task followed. Patients revealed a negative bias in the evaluation of themselves and of the well-known other person. The reference to a person (oneself, close other) increased later recognition performance. However, patients with schizophrenia revealed an overall decreased recognition performance. The amount of patients' passivity symptoms, i.e., an increase in the permeability of their "self-other boundary", correlated negatively with their recognition performance for previously self-referred characteristics and traits referred to the intimate other. This was not the case for lexically processed stimuli or an increase of negative symptoms. Our data underline the necessity of taking into account symptom subgroups when dealing with specific cognitive dysfunctions in schizophrenia.

Neural correlates of emotion recognition in schizophrenia.

The following fMRI study aimed to characterize the neural correlates of explicit emotion discrimination in 17 patients with schizophrenia and 17 matched healthy controls. In patients, emotion recognition impairments were found to be paralleled by cerebral dysfunctions in the affective division of the anterior cingulate cortex, the bilateral dorsomedial prefrontal cortex, the right superior temporal gyrus and the right fusiform gyrus. While the patients' responses to emotional faces were characterized predominantly by hypoactivations, the neutral faces elicited hyperactivations mainly in the frontal and cingulate areas, and the basal ganglia, along with misattribution errors. The decreased activation in the fusiform face area during responses to both emotional and neutral stimuli may be indicative of general face processing deficits. Similar although less pronounced deficits have been observed in subjects at high risk of psychosis as well as in patients with early onset. In adult schizophrenia, the evidence of an imbalanced cerebral network appears early in the course of the illness, with the dysfunctions, as indicated by correlations here, becoming more pronounced in patients with longer illness duration.

Emotion-cognition interactions in schizophrenia.

OBJECTIVES: Negative emotion exerts a considerable influence on cognitive processes. This may have clinical implications in mental illnesses, such as schizophrenia, where negative emotions often prevail. Experimentally this influence can be studied by using olfactory emotion induction. METHODS: Fourteen schizophrenia patients and 14 healthy volunteers were investigated with functional magnetic resonance imaging with respect to the neural correlates of emotion-cognition interactions. Emotion was induced by odorants during an n-back working memory task. RESULTS: Similar detrimental effects of negative stimulation on working memory performance were observed in patients and control subjects. Among the neural correlates modulating this interaction a decreased activation emerged in patients in the anterior cingulate and the medial superior frontal cortex and increased activation in the medial orbitofrontal and middle frontal area. CONCLUSIONS: During emotion-cognition interaction hypoactivations were found in regions crucial for the monitoring/control of ongoing processes but also for emotion regulation. Decreased activations may reflect failure to adapt to higher task requirements. In contrast, increased activations could be indicative of a greater emotional response and irritation induced by the odour. These patterns may represent the neural correlates of an inefficient control of emotional influences on cognitive processes in patients with schizophrenia.

The interaction of working memory and emotion in persons clinically at risk for psychosis: an fMRI pilot study.

Subtle emotional and cognitive dysfunctions may already be apparent in individuals at risk for psychosis. However, there is a paucity of research on the neural correlates of the interaction of both domains. It remains unclear whether those correlates are already dysfunctional before a transition to psychosis. We used functional magnetic resonance imaging to examine the interaction of working memory and emotion in 12 persons clinically at high risk for psychosis (CHR) and 12 healthy subjects individually matched for age, gender and parental education. Participants performed an n-back task while negative or neutral emotion was induced by olfactory stimulation. Although healthy and psychosis-prone subjects did not differ in their working memory performance or the evaluation of the induced emotion, decreased activations were found in CHR subjects in the superior parietal lobe and the precuneus during working memory and in the insula during emotion induction. Looking at the interaction, CHR subjects, showed decreased activation in the right superior temporal gyrus, which correlated negatively with psychopathological scores. Decreased activation was also found in the thalamus. However, an increase of activation emerged in several cerebellar regions. Dysfunctions in areas associated with controlling whether incoming information is linked to emotional content and in the integration of multimodal information might lead to compensatory activations of cerebellar regions known to be involved in olfactory and working memory processes. Our study underlines that cerebral dysfunctions related to cognitive and emotional processes, as well as their interaction, can emerge in persons with CHR, even in absence of behavioral differences.

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.

Cerebral dysfunctions of emotion-cognition interactions in adolescent-onset schizophrenia.

OBJECTIVE: Schizophrenia is among the most severe of psychiatric disorders, leading to impairments of affective and cognitive abilities. These dysfunctions affect each other mutually. Adolescent-onset schizophrenia (AOS) constitutes a particularly severe form of the disorder. In this study, possible dysfunctions of the neural correlates underlying the interaction of negative emotion and working memory in AOS were investigated. METHOD: During functional magnetic resonance imaging, 12 patients with AOS and 12 non-AOS adolescents performed a verbal n-back task. Intermittently, negative and neutral emotions were induced by olfactory stimulation. Group differences in working memory, emotion, and their interaction were evaluated. RESULTS: In patients with AOS, lower performance sensitivity was observed, along with dorsolateral prefrontal, anterior cingulate, and inferior parietal hypoactivation during working memory demands. For negative versus neutral emotion induction, patients with AOS mainly showed increased brain activation compared with control subjects in widespread brain regions including the left orbitofrontal cortex and the medial frontal gyrus. Finally, during the interaction of emotion and cognition, altered patterns of activation in patients with AOS were found in the thalamocortical network, including the angular and the middle cingulate gyri extending to the precuneus. These activation differences were further decomposed by parameter estimates. CONCLUSIONS: Our results provide new insights into the neural correlates underlying the mutual influence of affective and cognitive symptoms in AOS. During the n-back task, areas typically associated with working memory performance were found hypoactivated in patients relative to the control subjects, including the dorsolateral prefrontal and parietal cortex and the anterior cingulate. However, patients with AOS mainly demonstrated increased activation in key areas of emotion processing, such as the left orbitofrontal cortex and medial frontal areas, during negative emotion induction. A dysfunctional thalamocortical network during the interaction mainly included regions involved in the integration of converging information--either on the subcortical (thalamus) or on a higher-order cortical level (comprising the angular gyrus). These findings point to dysfunctional emotion-cognition interactions in AOS, which may explain its poor prognosis.

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.